Volume 36 Number 1&2 December 2010

medicinemosul.uomosul.edu.iq

Volume 36 Number 1&2 December 2010

Annals of

the College

of Medicine

Mosul

Volume 36 Number 1&2 December 2010

Editorial Board

Professor Hisham A. AL‐ATRAKCHI

Professor Elham K. AL‐JAMMAS

Professor Raad Y. AL‐HAMDANI

Dr. Bedoor A. K. AL‐IRHAYIM

Dr. Kahtan B. IBRAHEEM

Dr. Rami M. A. AL‐HAYALI

Dr. Mazin M. FAWZI

Editor

Member

Member

Member

Member

Member

Member & Manager

Professor Taher Q. AL‐DABBAGH

External editor

Miss Faiza A. ABDULRAHMAN

Administration

A publication of the College of Medicine (since 1966), University of Mosul, Mosul,

Iraq.

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Annals of

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Annals of

the College

of Medicine

Mosul

Volume 36 Number 1&2 December 2010

CONTENTS (1)

Demographic and causal pattern of acute upper gastrointestinal bleeding in Mosul

Khaldoon Th. Al-Abachi………………………………...….………………………………….…...…….…...… 1-7 1 - 7

Prevalence of upper gastro intestinal endoscopy findings in endoscopy referred patients at

Mosul city, a ten years retrospective study

Makkie A.K. AL-Youzbaki ….…………………………………...……….….……………………………...…. 8-11 8 -11

Waist circumference: a better predictor for lung ventilation than body mass index

Amjad F. Ahmad, Rajaa A. Yonis, Hazim M. Al-Habib….………………………………………......….….12-17 12-17

The effect of physical training program on body composition and body mass index

Bashar Jasim AL-juwari, Hussam Qahtan …………………………………………………………..….…..18-25 18-25

Fever of unknown origin: A prospective study in Northern Iraq

Rami M. Adil Khalil, Rafe' H. Al-Kazzaz, Humam Ghanim, Dhia J. Al-Layla ……………………….….. 26-35 26-35

Effect of hydrochlorothiazide with amiloride on serum lipid profile and malondialdehyde in

hypertensive women

Faris A. Ahmed……………………………………………………………………………………….………. 36-40 36-40

Measurement of lipid profile parameters in hypertensive patients using atenolol or captopril

Ahmed Yahya Dallal Bashi, Rawaa Khazal Jaber, Mohammed Khalid Al. Hamo…………………..…. 41-48 41-48

Accuracy of clinical scores in differentiating stroke subtypes in Mosul

Hakki Mohammed Majdal, Khalid Gh. Hameed Al-Abachi, Mahmood Mal-Allah………………….…… 49-55 49-55

The effects of pulse pressure on left atrium and left ventricle geometry in hypertensive

patients

Arwa M. Fuzi Alsaraf………………………………………..…………………………………….……….….. 56-62 56-62

Bone marrow trephine in some hematological and non-hematological disorders

Mohammed S. Saeed, Nazar M. Jawhar……………………………………………………….………....…63-71 63-71

Serum ferritin level in transfusion dependent β-thalassaemia patients in Mosul

Faris Y. Bashir, Omar A. Sadoon…………………………………………………………………….…....… 72-78 72-78

Value of IgA human recombinant tissue transglutaminase antibody test in diagnosis of

symptomatic celiac disease in children

Nashwan M. Al-Hafidh, Khaldoon Th. Al-Abachi………………………………………………………....… 79-85

(ΙΙΙ)


Annals of

the College

of Medicine

Mosul

Volume 36 Number 1&2 December 2010

CONTENTS (2)

Non CNS pediatric malignancies in Mosul

Khalil I. Mahmood, Likaa Fasih Al-Kzayer, Sahar K. Omar..………………………………..…..………… 86-91

-91

Soft tissue tumors - Histopathological study of 93 cases

Bashar A. Hassawi, Abdulkarem Y. Suliman, Intisar S. Hasan…………………………..………....….... 92-98

-98

The role of aerobic and anaerobic Bacteria in non gonococcal urethritis (NGU) in men

Haitham M. Al-Habib, Haitham B. Fathi……………………………………………….……………..…….. 99-105

-105

Bacterial etiology of chronic osteomyelitis involving anaerobes

Haitham M Al-Habib, Mahmood A Aljumaily………………………………………………..……...…..….106-113

Effects of dietary supplementation on bone healing in bisphosphonate treated rabbits

Mahmood A. Aljumaily, Kassim S. Ibrahim, Hazim Al-allaf ...………………………………………..…..114-120

Factors affecting success of trial of labour after previous one lower segment caesarean

section

Raida M. Al-Wazzan………………………………………………………………………………….……....121-129

Immunohistochemical detection of estrogen receptor α in endometrial carcinoma

Abeer H. Ahmed, Wahda MT Al- Nuaimy……………………………………………………………....….130-137

Comparative study of Olopatadine 0.1% and Lodoxamide 0.1% in treatment of

seasonal allergic conjunctivitis

Azzam A. Ahmed …………………………………………………………………………………….…...….138-145

Case report: Hydatid cyst in the scrotum: a case report and review of literature

Nashwan K. Mahjob…………………………………………………………….………….……...……...….146-148

Case report: Management of transverse vaginal septum in a neonate (case report and

review of literature)

Majid Khalid Al-Sultan………………………………………………….………………………….…….…..149-152

Case report: Congenital epulis (congenital gingival granular cell tumor)

Mohammed S. Saeed, Moutaz Al Ani……………………………………………………………….….….153-156

Printing of this issue was completed in September, 2011.

(ΙV)


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Demographic and causal pattern of acute upper

gastrointestinal bleeding in Mosul

Khaldoon Th. Al-Abachi

Department of Medicine, Nineveh College of Medicine, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 1-7).

Received: 29 th Jun 2009; Accepted: 9 th Jun 2010.

ABSTRACT

Objectives: To assess the age and sex distribution of 200 patients presented with acute upper

gastrointestinal bleeding (AUGIB) in Al-Salam General Hospital in Mosul, and to identify the causes of

bleeding through endoscopic examination.

Patients and methods: This is a case series study of 200 patients with (AUGIB) at the endoscopy

unit in Al-Salam general hospital in Mosul, during the period from April 1999 to January 2009. The

endoscopic findings, causes of bleeding and the patients' age and gender were recorded, analysed

and the results were compared with other similar studies.

Results: The mean age of the patients was 43.68 ± 19.11 years; those aged 60 years and above

constituted 25.5% (51/200). Male:female ratio was ~ 2:1 (135 male, 65 female). Gastroduodenitis with

erosions and duodenal ulcer (DU) were the main causes of (AUGIB) constituting 42.5% and 30.5%

respectively. Actively bleeding (DU) constituted 36.1% (22/61) while actively bleeding erosions

constituted 16.5% (14/85) which is a significant difference (p=0.008). Non-steroidal anti-inflammatory

drugs (NSAIDs) were associated with bleeding in 9% of the cases (18/200).

Conclusions: In this sample from Mosul city, (AUGIB) afflicted a relatively younger age group

compared with western studies, while male: female ratio was nearly similar (2:1).

Gastroduodenitis with erosions dominated the causes of bleeding and (DU) came next in frequency,

while (DU) is the main cause in most western studies. The results of this study coincide more with the

results from some developing countries.

Keywords: Acute upper gastrointestinal bleeding, gastroduodenitis, non-steroidal anti-inflammatory

drugs.

الخلاصة

الأهداف:‏ التعرف على عمر وجنس ٢٠٠ مريض مصابين بنزف حاد من أعلى القناة الهضمية تم فحصهم بواسطة الناظور

في مستشفى السلام العام في مدينة الموصل،‏ وآذلك لمعرفة أسباب هذا النزف.‏

المرضى وطريقة البحث:‏ تم دراسة حالات متسلسلة لمئتي مريض مصابين بنزف حاد من أعلى القناة الهضمية في وحدة

الناظور في مستشفى السلام العام في الموصل خلال الفترة من نيسان لغاية آانون الثاني تم تسجيل وتحليل

نتائج الفحص الناظوري وأسباب النزف وأعمار المرضى وجنسهم ومقارنة النتائج مع دراسات أخرى مشابهة.‏

سنة.‏ شكل المرضى اللذين هم في عمر سنة وأآثر نسبة

النتائج:‏ آان متوسط عمر المرضى

نسبة الذآور إلى الإناث آانت مقاربة ل ذآر و أنثى).‏ شكلت التأآلات والالتهابات

المعدية-الأثني عشرية وقرحة الأثني عشري الأسباب الرئيسية للنزف بنسب و على التوالي.‏ شكل

ومن التأآلات المعدية-الأثني عشرية نسبة

النزف الفعال من قرحة الأثني عشري نسبة

%١٦,٥

.٢٠٠٩

٦٠

%٣٠,٥

٦٥

%٤٢,٥

١٩٩٩

١٣٥) ١:٢

(٢٢/٦١)

١٩,١١

%٣٦,١

±٤٣,٦٨

.(٥١/٢٠٠) %٢٥,٥

© 2010 Mosul College of Medicine 1


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

وهو فرق مهم من الناحية الإحصائية ارتبط استعمال الأدوية المضادة للالتهابات الغير ستيرويدية

من الحالات.‏

الاستنتاج:‏ في العينة التي تمت دراستها في مدينة الموصل تبين بأن متوسط عمر النازفين من أعلى القناة الهضمية هو

أصغر نسبيا من مثيله في الدول الغربية بينما نسبة النازفين الذآور إلى الإناث آانت متقاربة وهي . ١:٢ شكل النزف نتيجة

التأآلات والالتهابات المعدية-‏ الاثني عشرية السبب الرئيسي للنزف الحاد من أعلى القناة الهضمية تلاه في التسلسل النزف

من قرحة الأثني عشري والذي هو السبب الأآثر شيوعا للنزف في معظم الدراسات الغربية.‏ نتائج هذه الدراسة تنسجم أآثر

مع نتائج بعض دراسات الدول النامية.‏

.(p=٠,٠٠٨)

(١٤/٨٥)

بنسبة % ٩ (١٨/٢٠٠)

A

cute upper gastrointestinal bleeding

(AUGIB) is a common medical

emergency that results in significant morbidity

and mortality (1) . It is defined as gastrointestinal

blood loss that originates proximal to the

ligament of Treitz

(2) . Clinically (AUGIB)

manifests as haematemesis and, or melaena

and rarely haematochezia with or without

haemodynamic compromise

(3) . Endoscopy

has a sensitivity of 92% for identification of the

site of (AUGIB), with a specificity that

approaches 100% (4) , especially if it is done

within the first 24 hour of (AUGIB) (5) . The age

distribution varies depending on the studied

population with significant frequency affecting

the elderly population in the west (6,7) . The

male:female ratio for (AUGIB) in some

European countries and the United States is

approximately 2:1 (8,9) . In the west, peptic ulcer

is the most common cause of (AUGIB),

accounting for up to 50% of cases (10) . Multiple

studies showed variable contribution of

gastroduodenal erosions (GDE) to (AUGIB)

with a range of (2-20%) (10,11,12) . Exposure to

aspirin carries a definite risk of gastroduodenal

injury (13) . Some 15-30% of patients exposed to

(NSAIDs) develop gastroduodenal ulcers (14) ,

the risk of bleeding increases with older age

(15) .

There is regional variation regarding the

frequency of causes of (AUGIB) depending on

the demographic characteristics of the studied

population, risk factors of bleeding, timing of

the study and pathological classifications. In

our region there is paucity of published reports

about the epidemiology, demography, causes,

and complications of upper gastrointestinal

tract lesions.

The aim of this study is to elucidate the

demographic features of (AUGIB) in a sample

of 200 patients from Mosul city, identifying its

causes, and comparing our results with others.

Patients and methods

This study was conducted in the endoscopy

unit of Al-Salam General Hospital in Mosul

during the period from April 1999 to January

2009.

All patients presenting with haematemesis

and, or melaena were included in this study.

Two hundred patients were collected, most of

the patients were referred from the casualty

department and inpatient wards after receiving

proper resuscitation, others were referred from

outpatient or private clinics and they were

haemodynamically stable. Informed Consent

was taken from all patients or their families.

Some patients were in a fasting state while

others have recently vomited their stomach

contents. The following data were obtained

from every patient and registered on a usual

form of endoscopic examination which

included age, gender, date, site of referral,

short relevant history and intake of

medications. The endoscopic findings were

documented on the same form including

biopsies of suspicious lesions. The tools of

diagnosis were Japanese Olympus GIF

endoscope type XP40 (1999) and Olympus

endoscope with videoscope GIF SP-20 (2007).

All patients underwent endoscopic

examination within the first 2-48 hours of

admission. Patients with significant bleeding

were supported with nasogastric tube suction

prior to endoscopy. The diagnosis was based

on endoscopic criteria of each lesion.

Gastroduodenitis and (GDE) implied the

presence of different grades of mucosal

congestion and oedema in different patterns

with or without visible erosions; such lesions

© 2010 Mosul College of Medicine 2


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

might be confined to the stomach and or the

duodenum. Signs of bleeding included actively

bleeding lesion, lesion covered by blood clot,

visible blood vessel at ulcer base, and

presence of fresh blood or coffee ground

material inside the stomach.

Statistical analysis

Data analysis was done by Minitab statistical

soft ware program version 13.20. Descriptive

statistics were used to describe the mean age

of the sample. T-test unpaired two means and

Z-two proportion were also applied. Statistical

significance was set at 5%.

Results

The patients' age range was 6-92 year. The

mean age was around 43 year for males,

females, and collectively.

Patients who were 60 year or above formed

25.5% of the group under study. The mean

age of patients with (AUGIB) due to (NSAIDs)

use was significantly higher than all other

patients (57.9 year Vs 42.3 year, p=0.001).

Male:female ratio (135:65) was ~2:1 (table 1).

Gastroduodenitis and (GDE) constituted

42.5% (85/200) and was the main cause of

(AUGIB), followed by (DU) with frequency of

30.5% (61/200) (table 2).

Actively bleeding (DU) formed 36.1% (22/61)

while actively bleeding (GDE) formed 16.5%

(14/85), with significant difference between

both frequencies (p=0.008) (table 3).

Six patients of bleeding due to tumours were

detected, five cases with adenocarcinoma of

the stomach and one case of cancer invading

the duodenum. We encountered a 15-year-old

female with measles having extensive (GDE).

Low dose aspirin and other (NSAIDs) were

associated with 9% (18/200) of (AUGIB),

erosions were the main lesions in (72.2%,

13/18) while associated duodenal ulcers

formed 22.2% of the patients (4/18) and one

patient showed no lesion (5.6%, 1/18).

Warfarin use was associated with only three

patients of (AUGIB). One patient developed

(AUGIB) due to gastroduodenitis after oral

corticosteroids. Alcohol consumption was

associated with (MWT) in one patient and with

(GDE) in another.

Table (1): Age and sex distribution of 200

patients with (AUGIB).

Age group

(year)

Males

Females

0-9 2 0

10-19 7 7

20-29 22 13

30-39 27 12

40-49 24 4

50-59 19 12

60-69 15 8

70-79 15 7

80-89 4 1

90-99 0 1

Total 135 65

Table (2): Endoscopic findings and frequency

of (AUGIB).

Source of bleeding

Gastroduodenitis and

(GDE)

Number of

patients

n=200

Duodenal ulcer 61

Frequency

%

85 42.5

30.5

٭ (0.001=p)

Oesophageal varices 13 6.5

Oesophagitis and

oesophageal erosions

13 6.5

Tumours 6 3

Mallory-Weiss tear

(MWT)

Vascular

malformations

Source of Excess

bleeding unidentified

2 1

2 1

3 1.5

Normal endoscopy 15 7.5

Z-two proportion (compared with frequency ٭

of GDE).

Table (3): State of (DU) and (GDE) with their

frequencies.

Lesion

(DU)

n=61

(GDE)

n=85

Active

bleeding

Blood clot

Clean base

22(36.1%) 19(31.1%) 20(32.8%)

14 (16.5%) 6 (7%) 65(76.5%)

© 2010 Mosul College of Medicine 3


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Discussion

Age

In this study The mean age was 43.7 year with

25.5% of the patients being over 60 year;

similar or close results were reported from

Kuwait, Turkey, Saudi Arabia, and Pakistan

where majority of patients were under 60 year

(12,16-18) . In Western studies the mean age was

>60 year and those above 60 year made 50-

70٪ of the total

(19-21) . In the developed

countries the percentage of older patients

suffering from (AUGIB) has been increasing

rapidly over the last years; the main reasons

are the increase in the life expectancy and the

increased consumption of many drugs such as

(NSAIDs) (7) . In the present study the mean

age of those who bled while using low dose

aspirin and other (NSAIDs) was significantly

higher than the mean age of the rest of the

sample ( 57.9 Vs 42.3 respectively p = 0.001),

this can be due to the higher prevalence of

cardiovascular and rheumatological conditions

in the elderly necessitating the use of such

drugs. In our locality which is part of a

developing country (AUGIB) afflicts younger

age groups which may be explained on the

basis of the following risk factors: higher

prevalence of H.pylori infection starting from

childhood period, increasing rate of smoking in

youth, environmental stressors, nutrition, and

probably infection by other pathogens.

Gender

The male: female ratio was ~ 2:1 which is

similar to the ratio of some European countries

and the United States (8,9) . Worldwide male

patients have higher prevalence.

Causes of (AUGIB)

The main causes of (AUGIB) are different

throughout the world depending on variation in

the risk factors present in the studied

populations. In this study gastroduodenitis with

erosions was the most frequently encountered

lesion followed by (DU) making 42.5% and

30.5% respectively. Different studies showed

that peptic ulcer disease was the main cause

(10-12,16) (table).

Table: Causes of (AUGIB), a comparative table.

Source of

bleeding

Frequency٪

Mosul

n=200

Peptic ulcer 30.5

Gastroduodenitis

with erosions

Esophageal

varices

Esophagitis and

esophageal

erosions

42. 5

Frequency٪ Frequency٪ Frequency٪ Frequency٪ Frequency٪

n=215 (16) n=11567 (22) n=336 (12) n=1830 (11) n>1000 (4,10)

Kuwait Egypt Turkey Malaysia West

61.8

(P= 0.0001) * 24.9

6.97

(p=0.0001) * 41.7

48.2

(p= 0.0001) * 64 31-59

9.3

(p= 0.0001) * 16.5 2-20

6.5 23.7 53.3 22 6.4

5-20

6.5 21.5 1-15

Tumours 3 1.39 3.9 3.6 1-7

Mallory-Weis tear 1 2.3 5-15

Vascular

malformations

Normal

endoscopy

Excess bleedingno

source

identified

1 1.86 0-7

7.5 9 8-14

1.5

* Compared with results of the present study (Z-two proportion).

© 2010 Mosul College of Medicine 4


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Two studies were done in Saudi Arabia and

Egypt showed that oesophagogastric varices

was the most frequent cause of (AUGIB) (17,22) .

Another five studies from Egypt, Jordan, and

Pakistan found that bleeding due to

gastroduodenitis and acute gastric mucosal

lesions was commoner than bleeding due to

peptic ulcer (18,22-25) . More recent data suggest

that the proportion of cases caused by peptic

ulcer disease has declined. Peptic ulcers were

responsible for only 21% of episodes of

(AUGIB) among 7822 patients included in a

national, United States database between

1999 and 2001, the most common cause was

nonspecific mucosal abnormalities (26) . A big

epidemiological study was done in Germany

which found that the incidence of bleeding

peptic ulcer among younger patients is

decreasing due to improved medical treatment

through eradication of H.pylori infection while

such incidence is increasing in the elderly

patients due to a higher intake of (NSAIDs) (27) .

Over the last two decades, Mosul physicians

are increasingly using H.pylori eradication

regimens which may have an impact on

lowering the incidence of bleeding (DU).

H.pylori infection has been implicated as a risk

factor of bleeding from peptic ulcer, whether

the same factor is operating in bleeding from

erosions is a matter that needs to be

confirmed by further studies. (NSAIDs) is an

established risk of bleeding from erosions and

peptic ulcers. Other types of infection and

stress may be operating in bleeding from

mucosal erosions but more work is needed to

unmask these adverse factors. In the present

study bleeding benign gastric ulcer is not

encountered, probably due to its low incidence

compared to (DU) while in the western series it

might account for up to 20% (28) .

Actively bleeding (DU) is significantly more

common than bleeding erosions (36.1% Vs

16.5% - p=0.008) which might be attributed to

more active arterial bleeding from (DU)

compared with capillary oozing from erosions.

Alcoholism, as a cause of (AUGIB), is rare in

the current study due to religious and social

restrictions; it is a more frequent cause in the

west.

Drugs and (AUGIB)

Despite the limited number of patients with

(AUGIB) due to the associated use of low dose

aspirin and other (NSAIDs), the study showed

that the use of such drugs was mainly

associated with bleeding erosions (13/18,

72.2%) compared with duodenal ulcer (4/18,

22.2%). It is well recognized that (NSAIDs) use

is associated with an increased risk of gastric

or duodenal ulcer; antral erosions are present

within 1 to 2 days in virtually all individuals

taking (NSAIDs) (29,30) .

The gastrointestinal tract is the most common

site of significant bleeding in patients receiving

long-term oral anticoagulant therapy (31) .

This study has got its own limitations; the

studied sample was relatively small over this

long period which might be ascribed to security

problems making most of the patients shift to

other hospitals. The results of this study will be

more precise if other city hospitals were

involved.

Conclusions

In this sample of 200 patients from Mosul,

(AUGIB) afflicted a relatively younger age

group which is consistent with the mean age in

developing countries, but the sex ratio

(male:female 2:1) was similar to studies from

western and developed countries.

Gastroduodenitis with erosions and (DU) were

major causes of (AUGIB) which differs from

western studies but coincides with results from

some developing countries.

Analytical studies on larger scales are

needed to identify the causes of

gastroduodenitis with erosions and to explain

the rarity of bleeding gastric ulcers.

Acknowledgement

I would like to thank the medical endoscopy

staff of Al-Salam general hospital for their

assistance and express my gratitude to Dr.

Bedoor AK. Al-Irhayim (Department of

pathology, Mosul college of Medicine) and Dr.

Humam Gh. Haj Zubeer (Department of

Community Medicine, Mosul College of

Medicine) for their valuable remarks.

© 2010 Mosul College of Medicine 5


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

References

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2. Fallah MA, Prakash C, Edmundowicz S .

Acute gastrointestinal bleeding. Med Clin

North Am 2000; 84(5):1183-208.

3. Palmer KR. British Society of

Gastroenterology Endoscopy Committee.

Non-variceal upper gastrointestinal

haemorrhage: guidelines. Gut 20t 2:51

(supplement Iv): 1-6.

4. David J.Bjorkman, Gastrointestinal

haemorrhage in: Arend, Armitage,

Clemmons, Drazen, Griggs, LaRusso.

Cecil Medicine, 33 rd edition USA;

Saunders, 2008, p 978.

5. Thoeni et al. A critical look at the accuracy

of endoscopy and double-contrast

radiography of the upper gastrointestinal

tract in patients with substantial UGI

haemorrhage. Radiology 1980; 135: 305-

308.

6. Church NC, Palmer KR. Non-variceal

gastrointestinal haemorrhage. In:

Evidence-based Gastroenterology and

Hepatology- McDonald JWD, Burroughs

AK, Feagan BG, eds. (2004) 2 nd ed.

Blackwell publications.139-159.

7. Pilotto A. Aging and upper gastrointestinal

disorders. Best Pract Res Clin

Gastroenterol 2004; 18 suppl: 73:81.

8. Meaden C, Makin AJ. Diagnosis and

treatment of patients with gastrointestinal

bleeding. Curr Anaesthesia Crit Care

2004; 15: 123-32.

9. Yavorski RT, Wong RK, Maydono C,

Battin LS, Furnia A, Amundson DE.

Analysis of 3294 case of upper

gastrointestinal bleeding in military

medical facilities. Am J Gastroenterol, Apr

1995; 90(4): 568-73.

10. Laine L. Gastrointestinal bleeding. In:

Braunwald E, Fausi A, Kasper D, eds.

Harrison's principles of internal medicine.

17 th edition. New York; McGraw-Hill; 2008:

257-258.

11. Cheng JLS, Gunn A, Menon J,

Arokiasarny J, Ong P, Long SY, Oommen

C, Damodaran A. Aetiology of Acute

Upper Gastrointestinal Bleeding in East

Malaysia. Med J Mal 2001; 56 (supp A)

D31.

12. Sezgln O, Altintas E, Tombak A. Effects

of seasonal variation on acute upper

gastrointestinal bleeding and its

aetiology. The Turkish Journal of

Gastroenterology 2007; 18(3): 172-176.

13. Sorensen HT, Mellemkjaer L, Blot WJ et

al. Risk of upper gastrointestinal bleeding

associated with the use of low-dose

aspirin. Am J Gastroenterol 2000; 95:

2218-2224.

14. Laine L. Approaches to non-steroidal antiinflammatory

drug use in the high-risk

patient. Gastroenterology 2001; 120:594-

606.

15. Hemandez Diaz S et al. Association

between non-steroidal anti-inflammatory

drugs and upper gastrointestinal tract

bleeding /perforation: an overview of

epidemiologic studies published in 1990s.

Arch Int Med 2000; 160:2093-9.

16. Khajah AY, Hassan F, Al-Kalaoui M, Al-

Nakib B. Acute Upper Gastrointestinal

Bleeding in Kuwait- 1995. Kuwait Medical

Journal 2001; 33(2): 144-147.

17. Qari FA. Major Causes of Upper

Gastrointestinal Bleeding at King Abdul

Aziz University Hospital (Jeddah). Kuwait

Medical Journal 2001; 33(2): 127-130.

18. Khurram M, Khaar HT, Hasan Z et al. A 12

years audit of upper gastrointestinal

endoscopic procedures. Journal of the

College of Physicians and Surgeons-

Pakistan 2003; 13(6): 321-324.

19. Konstantinos C Thomopoulos,

Konstantinos P Mimidis, George J

Theocharis, Anthie G Gatopoulou,

Georgios N Kartalis, Vassilik N

Nikolopoulou.Acute upper Gastrointestinal

bleeding in patients on long-term oral

anticoagulant therapy. World J

Gastroenterol 2005; 11(9): 1365-1368.

20. Kenneth R. McQuaid, Gastrointestinal

disorder in: Stephen J. McPhee, Maxine A.

Papudakis. Current medical diagnosis

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

and treatment 47 th edition, New York,

McGraw Hill 2008; 487- 488.

21. Van Leerdam ME et al. Acute upper

gastrointestinal bleeding between

1993/1994 and 2000. Am J Gastroenterol

2003; 98: 1494-1499.

22. Gouda MK. Acute upper gastrointestinal

bleeding in Kaser El-Aini gastrointestinal

endoscopy unit in the last 10 years (1991-

2000). Cairo University, MSc Thesis 9896,

2002.

23. Banisalamah AA, Mraiat ZM. Upper

Gastrointestinal Bleeding in Irbid, Jordan.

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24. Chaudhary AW, Tabassum HM,

Chaudhary MA. Pattern of Upper

gastrointestinal bleeding at Rahim Yar

Khan. Ann King Edward Med Coll Jul-Sep

2005; 11(3): 282-3.

25. Khurram M, Javed S, Khaar HTB, Goraya

F, Hasan Z. Endoscopic evaluation of

2484 patients with upper GI Hemorrhage.

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26. Boonpongmanee S, Fleischer DE,

Pezzullo JC, et al. The frequency of peptic

ulcer as a cause of upper gastrointestinal

bleeding is exaggerated. Gastrointest

Endosc 2004;59:788.

27. Ohmann CH, Imhof M, Ruppert CH, Janzik

U, Vogt CH, Frieling CH, et al. Time-trends

in the epidemiology of peptic ulcer

bleeding. Scandinavian Journal of

Gastroenterology 2005; 40:914-920.

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Gastrointestinal Haemorrhage, British

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Effect of aspirin on the human stomach in

normals: endoscopic comparison of

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2 weeks after administration. Scand J

Gastroenterol Suppl 1981; 67:211-4.

30. Larkai EN, Smith JL, Lidsky MD, Graham

DY. Gastroduodenal mucosa and

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Gastroenterol 1987; 82:1153-8.

31. Choudri CP, Palmer KR. Acute

gastrointestinal haemorrhage in patients

treated with anticoagulant drugs. Gut

1995; 36:483- 484.

© 2010 Mosul College of Medicine 7


ج

Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Prevalence of upper gastro intestinal endoscopy findings in

endoscopy referred patients at Mosul city, a ten years

retrospective study

Makkie A.K. AL-Youzbaki

Endoscopy Unit, Department of Medicine, Al-Salam Teaching Hospital, Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 8-11).

Received: 15 th Nov 2009; Accepted: 9 th Jun 2010.

ABSTRACT

Objectives: To analyze the findings of upper GI endoscopic examination carried out in order to

assess the prevalence of upper GI disorders in the examined patients.

Design and setting: A retrospective clinical case series study done over a 10 years period from the

1 st of October 1998 to the 1 st of October 2008, at the Endoscopy Unit of Al Salam Teaching General

Hospital during which a total of three thousand seven hundreds and nineteen upper GI endoscopic

examinations were performed and analyzed.

Results: The mean age of our patients was 39.8 years and male to female ratio was 1.29:1 (males

56% and females 44%). Out of the total number of patients (3719), a sum of 1322 (35.5%) patients

were typed as normal on endoscopic assessment while 2397 (64.5%) patient were found to retain

abnormal findings with the duodenal lesions being the commonest 64%, followed by esophageal one

19%, then gastric lesions 17%. Duodenal ulcer was the most frequently recovered pathology [689

(29%) patients] followed by duodenitis [483 (20%) patients], then by gastroesophageal reflux disease

[363 (15%) patients] that is followed by gastritis [312 (13%) patients].

Conclusions: Upper GI lesions are frequent in Mosul population. The upper GI endoscopy is a

valuable mean in the assessment of upper GI symptomatology.

Keywords: GI, gastrointestinal.

الخلاصة

الأهداف:‏ لتحليل نتائج تنظير الجهاز الهضمي العلوي الذي تم إجراؤه في شعبة التنظير لتقييم أنواع انتشار أمراض الجهاز

الهضمي العلوي للمرضى المحالين.‏

التصميم والاعداد:‏ تم إجراء دراسة لسلسلة من الحالات السريرية الاسترجاعية والتي امتدت لفترة عشر سنوات ابتداءا من

في شعبة التنظير التابعة لمستشفى السلام التعليمي العام

ولغاية الأول من شهر تشرين أول شهر تشرين أول حيث تم خلال هذه الفترة فحص وتحليل ثلاثة آلاف وسبعمائة وتسعة عشر حالة.‏

والإناث

‏(الذآور سنة وبلغت نسبة الذآور الى الاناث آان متوسط عمر المرضى النتائ آانت طبيعية أثناء

من المجموع الكلي لعدد المرضى البالغ (٣٧١٩)، وتم تصنيف ما مجموعه منها

آانت حالات مرضية آما يلي،‏ أمراض ألاثني

الفحص،‏ في حين وجد بان باقي المرضى البالغ عددهم

وأخيرا أمراض المعدة وبلغت نسبتها

تليها أمراض المريء وآانت نسبتها عشري آانت الأآثر شيوعا يليها التهاب

قرحة ألاثني عشري آانت هي الأآثر انتشارا حيث آان عدد المرضى المصابين بها

ويليها أخيرا أمراض

ويليها المرضى المصابين برخاوة الفتحة الفؤادية

ألاثني عشري

التهاب المعدة حيث بلغ عددهم

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٢٠٠٨

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:

.(%١٧)

© 2010 Mosul College of Medicine 8


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

الاستنتاجات:‏ تعتبر أمراض الجهاز الهضمي العلوي شائعة ومنتشرة بين المرضى في مدينة الموصل.‏

تنظير الجهاز الهضمي العلوي أحد أهم الوسائل في تقييم مرضى الجهاز الهضمي العلوي.‏

ويعتبر فحص

T

he endoscopy of upper GI tract is a safe

and easily carried out procedure of both

high diagnostic and valuable therapeutic

benefits with relatively low incidence of

morbidity and low cost.

The era of endoscopy made the information

about the prevalence of upper GI disorders

available in various world countries (1-5) .

The number of patients attending the

endoscopy unit complaining of broad array of

upper GI symptoms is increasing. The upper

GI endoscopy that is now performed as the

first initial examination instead of contrast

studies is carrying a high diagnostic yields in

evaluating the explored symptoms (6-8) .

The aim of the study

To analyze the findings of upper GI

endoscopic examinations within Mosul

population.

Patients and methods

During the period between the 1 st of October

1998 and the 1 st of October 2008, 3719

patients underwent upper GI endoscopic

examination and analyzed. Patients were

referred from out-patients department,

medical wards, surgical wards, and private

clinics. The procedure was performed on an

overnight fasting patients using lignocaine

spray or jelly. Diazepam was rarely used in

excited patients in a dose of 5-10 mg.

Olympus (GIF endoscope, Japan) was used to

proceed through the distal second part of

duodenum then stomach, with careful

assessment of mucosa of upper GI tract was

achieved. Biopsies were taken from suspected

malignant lesions; antral biopsies for

helicobacter pylori detection were performed,

also biopsies taken from 2 nd part of duodenum

for suspected malabsorption. The over all

examination was done by one endoscopist,

and diagnosis of different pathologies was

done according to the American society of

gastroenterology criteria. Examination notes

were documented and archived properly.

Numbers and percentages plus means were

calculated using SPSS software.

Results

Out of the total number of patients (3719), a

sum of 1322 (35%) patients were typed as

normal on endoscopic assessment while 2397

(65%) patient were found to retain abnormal

findings.

The mean age of our patients was 39.8

years and male to female ratio was 1.29:1

(males 56% and females 44%). The duodenal

lesions were the commonest 64%, followed by

esophageal one 19%, then gastric lesions

17% table (1). Duodenal ulcer was the most

frequently recovered pathology [689(29%)

patients] with a male predominance (M:F=

2.1:1), followed by duodenitis [483(20%)

patients] that also showed male predominance

(M:F= 1.4:1) table (2), then by

gastroesophageal reflux disease [363 (15%)

patients] predominantly among males (M:F=

1.6:1) table (3), followed by gastritis [312

(13%) patients] that was more predominant

among females (F:M= 1.05:1) table (4).

Table (1): Showing the prevalence of regional

endoscopic findings, with percentages

calculated within the total No. of patients.

Type of endoscopy No. %

Normal results 1322 35.5

Abnormal results:

1. Duodenum

2. Esophagus

3. Stomach

2397

1527

464

406

64.5

41.05

12.47

10.91

Total No. 3719 100

© 2010 Mosul College of Medicine 9


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Table (2): Demonstrates the duodenal array of

disorders found on endoscopy.

Disease No. %

Duodenal

ulcer

Male

%

Female

%

Mean

age

689 45.1 67.9 32.1 37

Duodenitis 483 31.6 59.6 40.4 34

Celiac

disease

Bleeding

duodenal

ulcer

Operated

duodenal

ulcer

35 2.3 37.1 62.9 12

50 3.3 76 24 41

34 2.2 73.5 26.5 45

Deformity 79 5.2 64.6 35.4 38

Pyloric

obstruction

Multiple

duodenal

ulcers

Healed

duodenal

ulcer

Total No. 1527 64

37 2.4 75.7 24.3 45

53 3.4 62.3 37.7 36

67 4.3 65.7 34.3 34

Table (3): Shows the esophageal disorders

found on endoscopy.

Disease No. %

Gastroesophageal

reflux disease

Male

%

Female

%

Mean

age

363 78 61.7 38.3 41

Varix 37 8 75.6 24.4 44

Foreign body 2 0.4 100 ------ 40

Inflammation 29 6.2 68 32 39

Tumors 11 2.4 54.5 45.5 57

Hiatus hernia 18 4.4 61 39 51

Mallory Weiss

tear

Total No. 464 19

4 0.6 50 50 25

Table (4): Demonstrates the gastric lesions

found on endoscopic examination.

Disease No. %

Male

%

Female

%

Mean

age

Gastritis 312 76.8 48.7 51.3 37

Tumors 72 17.7 54.2 45.8 57

Gastric ulcer 4 1 75 25 58

Active Bleeding 10 2.5 70 30 48

Previous

Operation

5 1.2 20 80 53

Osler weber

rendu

2 0.5 ------ 100 25

Trichobezoar 1 0.2 ------ 100 25

Total No. 406 17

Discussion

This study demonstrated that 2397 (65%) of

the examined patients had visible endoscopic

findings, the most common lesions observed

were duodenal (64%) followed by esophageal

and gastric, (19%) and (17%) respectively.

The commonest lesion was duodenal ulcer

(29%). This is higher than that found by Sarkis

at Basrah (22.8%) (9) , Sudan (17%) (4) , and

Saudia Arabia (14%) (10) .

The duodenal ulcer was found to be

predominant in males (M:F= 2.1:1) as

compared to Sarkis study at Basrah (9) (M:F=

3:1) and a study from Sudan (M:F= 4.5:1) (4) .

Benign gastric ulcer was uncommon finding

(0.16%) when compared to duodenal ulcer

(29%), this was documented also by Sarkis (9)

and other studies held at southern Iraq (5) ,

Kuwait (11 ) and Sudan (4) .

Conclusions

It is concluded that upper GI disorders are

prevalent in Mosul population with duodenal

ulcer being the commonest pathology followed

by duodenitis then by gastoesophageal reflux

disease and gastritis respectively.

The upper gastrointestinal endoscopy has a

high diagnostic value in investigating upper GI

symptoms.

Recommendations

Since that the upper GI endoscopy is not

costly and easily performed, hence we

recommend it as the procedure of choice in

investigating the upper GI symptomatology.

© 2010 Mosul College of Medicine 10


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

References

1. Fedail S. Araba B, Homeida M, et al.

Upper gastrointestinal fibreoptic

endoscopy experience in sudan. Lancet

1993; 2:897-899.

2. Al Moagel M, Al Faraji M, Al Mofarreh.

Endoscopy of the gastrointestinal tract in

Riyadh central hospital. Proceeding of the

seventh suadi medicine meeting king

faisal university, dammam, 2-6 august

1982.

3. Laajam M, Al Mofleh I, Al Faleh Fz. et al.

upper gastrointestinal fibreoptic

endoscopy in Suadi Arabia, analysis of

6386 procedures. Quarterly Journal of

medicine, new series 1980; 66:21-25.

4. Shoboksh O, Al Sakffizy, Zahrani JY.

prevalence of endoscopic findings, Saudi

Medical Journal 1994;15: 372-388.

5. Al Hilly h, Alsikafy H, Bakes S, et al.

endoscopy in the diagnosis of dyspeptic

patients in Basrah region. Medical Journal

of Basrah University 1990; 9:93-99.

6. Tedesco FJ. Endoscopy in the evaluation

of upper gastrointestinal symptoms

indications, expectations and

interpretation. J. Clini. Gastro enterol.

1981; 3(2): 67-71.

7. Health and public committee, American

College of Physicians, Philadelphia,

Pennsylvania, clinical competence in

diagnostic OGD. Annals of Internal

Medicine 1987; 937-39.

8. The working party of the clinical services

committee of the British Society of

Gastroenterology. Provision of GI

endoscopy and relevant services for

district general hospital. GUT.1991; 32:95-

100.

9. Sarkis K. Upper gastro intestinal

endoscopy findings in patients with

dyspeptic symptoms in Basrah. Iraqi

Journal of Gastro Enterology 2002; 3(1):

45-48.

10. Al karawi M, Ali A, Mohamed A, et al.

Upper gastro intestinal endoscopy findings

at Riyadh armed forces hospital. Saudi

Medical Journal 1999; 20(8): 598-601.

11. Al Nakib B, Al Liddawin. Upper gastro

intestinal endoscopy experience in Kuwait

analysis of 1019 cases. Gastroenterologic

endoscopy. 1981; 23:605-08.

© 2010 Mosul College of Medicine 11


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Waist circumference: a better predictor for

lung ventilation than body mass index

Amjad F. Ahmad, Rajaa A. Yonis, Hazim M. Al-Habib

Department of Physiology, College of Medicine, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 12-17).

Received: 16 th Feb 2010; Accepted: 7 th Jul 2010.

ABSTRACT

Objective: To evaluate the relationship between waist circumference, as a measure of central fat

distribution, and lung ventilation function in both sexes among different weight categories in

comparison with body mass index (BMI).

Subjects and Methods: One hundred healthy adults from both sexes were volunteered in this

observational-cross-sectional study (53 males aged 19-69 years and 47 females aged 19-51 years).

Subjects were recruited from Mosul Medical College students, teaching as well as administration staff.

After collecting personal and health information necessary for the study, all subjects underwent

anthropometric measurements (height, weight, and waist circumference) before spirometry test using

computerized spirometer. The study was conducted in the Department of Medical Physiology-Mosul

Medical College.

Results: All spirometric data were within 80-120% of the normal predicted values, thus excluding the

possibility of any asymptomatic airway disease. A consistent negative correlation between, both waist

circumference and BMI, with FVC and FEV1 were clearly observed in both sexes. Unlike BMI, waist

circumference revealed stronger and significant negative correlation with lung function especially in

male subjects. The significant negative correlation between waist circumference and FVC and FEV1

was more evident in overweight and obese subjects.

Conclusion: Waist circumference, as a measure of body fat distribution, seems more reliable

predictor of poor lung function, secondary to overweight and obesity, than BMI. This might be

attributed to the fact that BMI relies only on body weight and height without consideration to the

distribution of body fat, muscle and bone mass which might possess a more significant role.

Keywords: Waist circumference, body fat distribution, lung function tests.

الخلاصة

هدف البحث:‏ لتقييم العلاقة بين محيط الخصر،‏ آمقياس لتوزيع الدهون في الجسم،‏ ووظائف الرئة في آلا الجنسين

ولمختلف الفئات الوزنية و ذلك بالمقارنة مع مقياس آتلة الجسم.‏

طريقة البحث:‏ شمل البحث مئة متطوع من الأصحاء البالغين من طلبة آلية طب الموصل ومنتسبيها من آلا الجنسين.‏

بعد أخذ آافة المعلومات الشخصية والطبية المتعلقة بالبحث،‏ تم قياس الطول والوزن وآذلك محيط الخصر لجميع عينة

البحث وذلك قبيل إجراء فحص وظائف الرئة باستخدام جهاز فحص وظائف التنفس الالكتروني ‏(السبايروميتر)‏ وقد تمت

الدراسة في فرع الفسلجة الطبية في آلية طب الموصل.‏

نتائج البحث:‏ أظهرت نتائج البحث ان جميع أفراد العينة آانوا ضمن المديات الطبيعية المتوقعة لقياسات وظائف الرئة

لاستبعاد إمكانية وجود اي أمراض تنفسية.‏ وقد أشارت النتائج ايضا الى وجود علاقة عكسية بين آل من

محيط الخصر ومقياس آتلة الجسم مع حجم الزفير القسري الكلي وحجم الزفير القسري في الثانية الاولى في آلا الجنسين.‏

(%١٢٠-٨٠)

© 2010 Mosul College of Medicine 12


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

الا ان هذه العلاقة العكسية آانت أقوى وذات دلالة احصائية بالنسبة لمحيط الخصر خصوصا لدى الذآور وآذلك مجموعة

الأشخاص ذوي الوزن الزائد والأشخاص ذوي السمنة.‏

استنتاجات البحث:‏ ان محيط الخصر،‏ آمقياس لتوزيع الدهون في الجسم،‏ أآثر قدرة على توقع التأثيرات السلبية لزيادة

الوزن والسمنة على وظائف الرئة بالمقارنة مع مقياس آتلة الجسم والذي يعتمد على وزن الجسم وطوله فقط دون الأخذ

بنظر الاعتبار توزيع الدهون في أنحاء الجسم وآذلك آتلة العضلات والعظام والتي ربما لها الدور الأهم.‏

I

t is well known in medical practice that

prediction of lung function is largely

dependent on body anthropometry especially

body height, weight, and body surface area.

Body mass index (BMI), a measure of body

weight in relation to height, is currently used to

determine how thin or fat a person is.

However, some argue that the error in the BMI

is significant and it is not generally useful in

evaluation of health (1,2) . Professor Eric Oliver

from University of Chicago for political science

says "BMI is a convenient but inaccurate

measure of weight, and should be revised (3) .

The National Institute of Health had recently

reported some shortcomings of BMI. Because

the BMI is dependent only upon weight and

height, it makes simplistic assumptions about

distribution of muscle and bone mass, and

thus may overestimate adiposity on those with

more lean body mass (e.g. athletes) while

underestimating adiposity on those with less

lean body mass (e.g. the elderly). A further

limitation relates to loss of height through

aging. In this situation, BMI will increase

without any corresponding increase in

weight (4) .

Current studies on obesity revealed that

health may be negatively affected when

excess body fat has accumulated to a certain

extent. Respiratory system involvement

included obstructive sleep apnea, obesity

hypoventilation syndrome and asthma. Several

studies have reported a negative correlation

between BMI and forced vital capacity (FVC)

"a measure of the total volume of air that can

be forcefully exhaled" and the forced

expiratory volume in one second (FEV1), "a

measure of the maximum volume of air

expired in one second (5,6,7) . Although the

influence of obesity on pulmonary function

tests (PFTs) has been examined, there are

limited studies to evaluate the association

between body fat distribution and pulmonary

function tests in overweight and moderate

obesity (8) . This study was attempted to

evaluate the relationship between waist

circumference "as a measure of central

obesity in terms of body fat distribution" and

pulmonary ventilation among different body

weight groups in both sexes, in comparison

with BMI.

Subjects and methods

One hundred healthy adults (53 males and 47

females) among Mosul Medical College

students, teaching and administration staff

volunteered in the present study. Details of

age and anthropometric measurements are

shown in table (1).

Table (1): The anthropometric characteristics of subjects according to gender. Values are expressed

as range (mean± SD).

Parameter

Total (n=100) Male (n=53) Female (n=47)

Age (year)

Height (Cm)

Weight (Kg)

Body mass index

Waist circumference (cm)

19-69

33.75±12.74

150-183

166.64±9.43

44-123

80.41±18.42

18.5-40

29.33±5.98

58-133

95.67±18.13

19-69

36.64±13.71

150-183

172.01±8.17

47-123

88.23±16.97

19-40

30.41±5.88

64-133

102.45±15.98

19-51

30.48±10.79

150-179

160.57±6.71

44-110

71.59±15.96

18.5-40

28.11±5.93

58-126

88.02±17.48

© 2010 Mosul College of Medicine 13


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Subject data sheet included all personal and

health information necessary for the study.

Our study group fulfilled the following criteria:

1. No history of any significant pulmonary or

cardiac diseases. Never smoker.

2. Clear chest on physical examination.

3. Absence of any neuromuscular or

musculoskeletal disorders which could

affect spirometry test.

Anthropometric measurements: Height,

weight and waist circumference were

measured by using standard techniques as

follows: height to within 0.5 cm, without shoes;

weight to within 100 g, without heavy clothing;

and waist circumference to within 0.1 cm by

using plastic measuring tape, with the waist

defined as midway between the lowest rib and

the iliac crest as the participant breathed out

gently (9) .

Spirometry: Forced vital capacity (FVC) and

forced expiratory volume in 1 second (FEV1)

were measured by using electronic spirometer

(Discovery-2 version 8B Futurmed-America

Inc.-Granada Hills, USA). Standard procedure

were adopted following the recommendations

of the American Thoracic Society (ATS) (10) .

The forced expiratory vital capacity procedure

was described and demonstrated to the

subject before the test, emphasizing the tight

fit between lips and tongue and encouraging

the subject to breathe out as long and

forcefully as possible. The best of three

technically satisfactory maneuvers was

recorded. The SPSS statistical package

(windows version 8.0) was used to analyze the

data.

Results

Table (1) shows the anthropometric data of

subjects distributed according to gender. The

study groups included normal weight,

overweight as well as obese subjects for both

sexes.

The percent predicted values for lung

function parameters in both sexes are given in

table (2). As expected, all spirometric

parameters were well within the normal

predicted range (80-120%) insuring the

absence of any asymptomatic airway disease:

thus subjects perfectly fulfilled the criteria for

inclusion in the study.

Table (3) revealed a consistent negative

correlation between both waist circumference

and BMI with FVC and FEV1in both sexes.

Unlike BMI, waist circumference revealed

stronger and significant negative correlation

with lung function especially in male subjects.

Table (4): waist circumference and BMI

continued to show negative correlation with

lung function parameters FVC and FEV1 after

redistributing the study group through different

weight categories (normal weight, overweight

and obese). The relationship was weaker and

not significant in the normal weight group

compared to that of overweight and obese

groups. On the other hand, the relation

between spirometric parameters and BMI was

weak and not significant among all body

weight categories.

Table (2): Spirometric parameters according to gender. Percent predicted values are given expressed

as range (mean±SD).

Parameter

Total (n=100)

Male (n=53)

Female (n=47)

FVC

FEV1

FEV1%

PEF

FMF

82-116

(96.97±15.55)

87-120

(93.19±15.77)

83-115

(98.33±12.31)

80-110

(95.96±9.08)

88-111

(99.63±9.2)

88-116

(93.66±13.59)

90-120

(94.49±16.87)

88-115

(101.35±8.23)

86-110

(97.38±9.57)

90-111

(101.6±9.7)

82-110

(88.7±13.88)

87-110

(91.72±14.46)

83-99

(94.91±15.07)

80-95

(94.36±8.29)

88-102

(97.41±8.12)

FVC=Forced Vital Capacity, FEV1=Forced Expiratory volume in the first second, FEV1%= Percent Forced

Expiratory volume in the first second, PEF=Peak Expiratory Flow rate, FMF=Forced Midexpiratory Flow.

© 2010 Mosul College of Medicine 14


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Table (3): Correlation between waist

circumference and BMI regarding their

relationship with FVC and FEV1 according to

gender.

FVC FEV1

r p R P

Total

(n=100)

-0.44 ** -0.32 **

Waist

circumference

Body mass

index

Male

(n=53)

Female

(n=47)

Total

(n=100)

Male

(n=53)

Female

(n=47)

-0.50 ** -0.46 **

-0.33 * -0.32 *

-0.15 NS -0.14 NS

-0.12 NS -0.16 NS

-0.09 NS -0.13 NS

FVC=Forced Vital Capacity, FEV1=Forced

Expiratory volume in the first second.

** correlation is significant at the 0.01 level (2-

tailed).

* correlation is significant at the 0.05 level (2-tailed).

Table (4): Correlation between waist

circumference and BMI regarding their

relationship with FVC and FEV1 according to

body weight.

FVC FEV1

r p r P

Normal

weight -.15 NS -.13 NS

Waist

circumference

Body mass

index

(n=28)

Overweight

(n=31)

Obese

(n=41)

Normal

weight

(n=28)

Overweight

(n=31)

Obese

(n=41)

-.45 * -.42 *

-.39 * -.31 *

-.17 NS -.04 NS

-.15 NS -.06 NS

-.23 NS -.07 NS

FVC=Forced Vital Capacity, FEV1=Forced

Expiratory volume in the first second

* correlation is significant at the 0.05 level (2-tailed).

Discussion

Waist circumference and (BMI) are indirect

ways to assess body composition. Body mass

index (BMI) has long been used as a simple

means of assessing whether someone's

weight put their health at risk. But increasingly,

the value of this familiar measure is being

called into question because it has been found

that measurement of body fat and its

distribution may be more important (6,9) . Waist

circumference measurement has been

increasingly related to ill health (9) . It reflects

total and abdominal fat accumulation and is

not greatly influenced by height (11) . However,

other studies have shown that abdominal

adiposity is an important indicator of reduced

lung function in men; however, among women,

the relationship is less clear

(12,13) . In

accordance with previous studies, our results

in table (3) show a consistent negative

correlation between BMI and waist

circumference with both FVC and FEV1 in

both sexes

(12,14) . The reason for this

significant negative association is not entirely

clear, but it seems likely that a large waist

circumference could have mechanical effects

on lung function, that is, at least partially

affecting movement of the diaphragm and

chest wall. However, a large waist

circumference is associated with fat, a

metabolically active tissue, and other biologic

effects cannot be ruled out (5) . Apart from

other spirometric parameters measured in the

present study, only FVC and FEV1 was

considered owing to their stronger predictive

power for restrictive impairment of lung

function currently observed in obesity (15,16) .

Referring back to table (3), waist

circumference revealed stronger and

significant relation with FVC and FEV1 in both

sexes especially males (r = -0.50 for FVC and

-0.46 for FEV1 for waist circumference

compared to –0.12 for FVC and –0.16 for

FEV1 for BMI). This is in accordance with

RaidaI et al study (7) which reported that body

fat distribution has independent effect on lung

function that were more prominent in men than

women. In an Australian study of the effects of

body composition and fat distribution on

ventilatory function, Lazarus et al. (17)

investigated a single measurement, FVC only,

and observed that it was significantly

negatively correlated with waist circumference

in men but not in women. On the other hand,

© 2010 Mosul College of Medicine 15


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

the predominance of waist circumference over

BMI might be partially explained by the study

of Han et al in 1997 (11) who concluded that

height and age had limited influences on the

differences in waist among Caucasian subjects

of different stature and waist alone may be

used to indicate adiposity or to reflect

metabolic risk factors. In contrast, the

influence of height on body weight, and

consequently on BMI, was important. The

present study also enquired whether the

negative relation of BMI and waist

circumference with lung function is maintained

through different body weight categories For

that reason, subjects were regrouped into

different weight categories according to the

international classification of obesity for Asian

populations (18) as follows:

1. Normal weight group: BMI=18.5-25.

2. Overweight group: BMI=25-30.

3. Obese group (class I, class II): BMI=30-40.

Subjects with BMI ≥ 40 (class III obesity)

were excluded from the study because

measurement of waist circumference in this

category adds little to the predictive power of

BMI as most individuals with this BMI have an

abnormal waist circumference (8) . In addition to

difficulty collecting such obese subjects.

Data given in table (4) reveal that the

negative relation of BMI and waist

circumference with lung function continued

through different body weight categories.

However, the relationship was stronger and

significant with waist circumference, rather

than BMI, in the overweight and obese groups.

This finding agrees with previous studied on

different lung function parameters in relation to

body fat distribution on men and women

separately which concluded that lung volumes

(Forced vital capacity FVC, Total lung capacity

TLC, Functional residual capacity FRC, and

Expiratory reserve volume ERV) were all

substantially affected in overweight and obese

subjects. Apart from impact of obesity on lung

volumes, other studies mentioned an effect of

obesity on lung diffusion as well. Prefault et al

(19)

showed a reduced DLCO and carbon

monoxide transfer coefficient in 20% of obese

persons, and it was related to the disorder in

ventilation distribution and significant decrease

in closing volume at the end of expiration;

however, Rubinstein et al

(20)

found an

increase in CO diffusion.

Conclusion

Lung ventilation function is affected in

overweight and obese persons in relation to

body fat distribution especially in men.

Therefore, pulmonary function tests, especially

lung volumes, must be interpreted carefully in

this population. Accordingly, it seems

reasonable to consider the waist

circumference measurement before

interpreting the spirometry report of obese

subjects.

References

1. "Do You Believe in Fairies, Unicorns, or

the BMI?". Mathematical Association of

America. 2009-05-01. http://www.maa.org/

devlin/devlin.

2. "Is obesity such a big, fat threat?" 2004-

08-30. http://www.rockymounttelegram.

com / featr / content/shared / health/stories

/BMI.

3. "Oliver blames 'obesity mafia' for American

weight scare" (April 26, 2005). http://

thedartmouth.com/2005/04/26/news/oliver.

4. "Aim for a Healthy Weight: Assess your

Risk". National Institutes of Health. 2007-

07-08. http:// www.nhlbi.nih.gov/health/

public/heart/obesity/lose_wt/risk.htm#limita

tions.

5. Ruoling C, Hugh T, Caroline B-, Mary K. H

and Caroline M. Association of Dietary

Antioxidants and Waist Circumference

with Pulmonary Function and Airway

Obstruction. American Journal of

Epidemiology 2001;153; 2 : 157-163.

6. Lazarus R, Sparrow D, Weiss ST. Effects

of obesity and fat distribution on ventilatory

function: the normative aging study. Chest

1997;111:891-898.

7. Raidal I, Harik-Khan RI, Wise RA, Fleg JL.

The effect of gender on the relationship

between body fat distribution and lung

function. J Clin Epidemiol 2001;54:399-

406.

8. Chen Y, Rennie D, Cormier YF, et al.

Waist circumference is associated with

pulmonary function in normal-weight,

© 2010 Mosul College of Medicine 16


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

overweight, and obese subjects. Am J Clin

Nutr 2007; 85:35-39.

9. Lean MEJ, Han TS, Seidell JC.

Impairment of health and quality of life in

people with large waist circumference.

Lancet 1998; 351:853–856.

10. Official Statement of the American

Thoracic Society: single-breath carbon

monoxide diffusing capacity (transfer

factor); recommendations for standard

technique-1995 update. Am. J. Respir.

Crit. Care. Med. 1995; 152: 2185-2198.

11. Han TS, Seidell JC, Curral JEP, et al. The

influence of height and age on waist

circumference as an index of adiposity in

adults. Int J Obes 1997;21:83–98.

12. Bray GA. Complications of obesity. Ann

Intern Med 1985;103:1052-1062.

13. Canoy D, Luben R, Welch A, et al.

Abdominal obesity and respiratory function

in men and women in the EPIC-Norfolk

Study, United Kingdom. Am J Epidemiol

2004;159:1140-1149.

14. Sue DY. Obesity and pulmonary function:

more or less? Chest 1997;111:844-845.

15. Collins LC, Hoberty PD, Walker JF, et al.

The effect of body fat distribution on

pulmonary function tests. Chest

1995;107:1298-1302.

16. Jenkins SC, Moxham J. The effects of mild

obesity on lung function. Respir Med

1991;85:309-311.

17. Lazarus R, Gore CJ, Booth M, et al.

Effects of body composition and fat

distribution on ventilatory function in

adults. Am J Clin Nutr 1998; 68:35–41.

18. WHO expert consultation. Appropriate

body-mass index for Asian populations

and its implications for policy and

intervention strategies. The Lancet 2004;

157-163.

19. Prefaut C, Ramonatxo M, Monnier L, et al.

Mechanical effects of obesity on lung

function. Pathol Biol 1980;28:149-154.

20. Rubinstein I, Zamel N, DuBarry L, et al.

Airflow limitation in morbidly obese,

nonsmoking men. Ann Intern Med

1990;112:828-832.

© 2010 Mosul College of Medicine 17


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

The effect of physical training program on

body composition and body mass index

Bashar Jasim AL-juwari, Hussam Qahtan

Nursing College, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 18-25).

Received: 5 th Apr 2010; Accepted: 30 th Jan 2011.

ABSTRACT

Objectives: To evaluate the effect of physical training program on body composition and body mass

index, and to evaluate the body mass index as predictor of body fat in young adults.

Material and methods: Prospective was done at the College of Physical Education – University of

Mosul, first year students (100) male and (22) female were participated in this study. A physical

training program of 2 hours (aerobic exercise) daily for 4 days per week for 4 months. Medical height

and weight scales (Detector) and bio-electrical impedance analysis measurements device(Quantum

П) were used for measurements.

Results: Physical training program has significant effect on body weight, BMI and free fat mass, but

has no significant effect on fat mass.

Conclusions: Physical training program increase BMI and free fat mass but has no significant effect

on fat mass. BMI is a specific test for overweight and obesity but it is not a sensitive test.

Keywords: BMI, physical training program, body composition.

الخلاصة

الأهداف:‏ تقييم تأثير برنامج التدريب الجسدي على ترآيبة الجسم ومؤشر آتلة الجسم وتقييم آفاءة مؤشر آتلة الجسم آدالة

على نسبة الدهون لدى الشباب.‏

طريقة العمل:‏ دراسة استباقية أجريت في جامعة الموصل آلية التربية الرياضية على طلبة السنة الأولى آلية التربية

الرياضية من الذآور من الإناث.‏ تم تطبيق برنامج التدريب الجسدي لمدة ساعتين يوميا"‏ وعلى مدى أربعة

أيام في الأسبوع ولأربعة أشهر وتم استخدام جهاز قياس الطول والوزن وجهاز تحليل المقاومة الكهربائية الحيوية.‏

النتائج:‏ لبرنامج التدريب الجسدي تأثير معنوي على وزن الجسم ومؤشر آتلة الجسم والكتلة الخالية من الدهون ولم يظهر

له تأثير على آتلة الدهون.‏

الاستنتاجات:‏ برنامج التدريب الجسدي له تأثير معنوي على مؤشر آتلة الجسم والكتلة الخالية من الشحوم وليس له تأثير

معنوي على آتلة الشحوم.‏ مؤشر آتلة الجسم هو فحص خاص لزيادة الوزن ولكن غير حساس.‏

الكلمات المفتاحية:‏ مؤشر آتلة الجسم،‏ ترآيبة الجسم،‏ برنامج التدريب الجسدي.‏

(٢٢)

(١٠٠)

O

besity is a world wide public health

problem, and its great increase is

mainly due to the increases in energy

consumption owing to availability of food of

high caloric density and to the reduction of

energy expenditure by regular physical

activities 1-6 . Observational and experimental

studies have shown beyond doubt the growing

prevalence of obesity. Obesity occurs in an

individual when body fat is very high relative to

the lean body mass and is defined as a body

mass index (BMI)≥(30 Kg / m 2 ) (7,8) .

Absolute prevalence has been observed

across the globe over the past few decades (9) .

© 2010 Mosul College of Medicine 18


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

The WHO estimates that over a billion

adults are over-weight and over 30٠ millions

are obese world wide. We are facing a global

obesity crisis (10,11) .

Obesity means having too much body fat. It is

different from being over weight which means

weighing too much, the weight comes from

muscle, bone, fat and / or body water. Both

terms mean that a person’s weight is greater

than what’s considered healthy for his or her

height (12,13) .

The national Health and Nutrition

Examination Survey (NHANES) reports that

the prevalence of obesity has doubled over the

last 25 years, based on direct height and body

– weight measurements (14,15) .

Obesity is a cause of major morbidity and

mortality (16,17) ; it is associated with numerous

co-morbidities such as cardiovascular disease,

type 2 diabetes, hypertension, certain cancers,

sleep apnea, osteoarthritis and reduced life

expectancy (18-21) .

BMI is a calculation based on height, weight

and gender specific in adults. It does not

directly measure the percentage of body fat,

but it is a more accurate indicator of over

weight and obesity that relying on weight alone

(22) .

Bioelectrical impedance analysis is another

method of assessing body fat percentage.

There is a variety of body composition and

body fat analyzer and scales available that

provide more than just total weight

measurements. It determines total weight

measurements, the percent and amount of

body fat, muscle mass, water and even bone

mass (23) .

Eating disorder clinics and fitness centers

use more sophisticated tests such as

bioelectrical impedance analysis that calculate

lean body mass, body fat, and total body water

based on changes in conduction of all applied

electrical current (24) .

When weight is lost too rapidly or by

significant reductions in energy intake, lean

muscle mass will be lost, which can affect

performance negatively (25,26) .

The National Institute of Health recommends,

that a healthy adult male’s body should have

between 13-17% fat , a healthy female’s body

should be composed of 25% fat (27) .

Objectives: To evaluate the effect of physical

training program on body composition and

body mass index, and to evaluate the body

mass index as predictor of body fat in young

adults.

Methods

The data were collected prospectively using

experimental design. A simple stratified

sample consists of 122 students (100 males

and 22 females) from first year of the College

of Physical Education– University of Mosul.

The pre test started at 1 st Dec. 2008 for one

month, standard scale (medical Decto scale,

USA origin) is used for measuring the height

and weight of adults, was used in order to

identify the BMI levels. The weight was

measured in kilograms and the height was

measured in meters.

Using the following formula to calculate the

BMI:

Body composition was examined by using of

Bio – electrical impedance analysis device

(Quantum П – USA origin); available at

Nursing College and College of Physical

Education– University of Mosul. The following

circumferences in the body were measured,

neck, chest, abdomen, hip, right arm, right

thigh, right calf circumferences.

Body composition measurements

a. Fat percentage.

b. Fat weight (kg).

c. Free fat percentage.

d. Free fat weight.

e. BMI.

The results of Segal study 1998 confirms the

validity of BIA and indicate that the precision of

predicting LBM and FFM from impedance, can

be enhanced by sex and fatness-specific

equations (28) .

© 2010 Mosul College of Medicine 19


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

The following guideline were applied before

Bio–electrical impedance analysis

measurement:

1- No eating or drinking within 4 hours of the

test.

2- No exercise within 12 hours of the test.

3- Urinate within 30 minutes of the test.

4- No alcohol consumption within 48 hours.

5- No Diuretic within 7 days.

The BIA test starts by lying the student on

testing table, and electrodes are connected to

the hands and feet, electrolyte gel is applied,

then a current of 50 KH2 is introduced.

Selecting the appropriate equation to

determine the quality of the results and

minimize variables. Average time for

conducting this test is about 10 minutes BIA

is used to determine body weight, BF%, free

fat mass.

According to the College of Physical

Education curriculum; a physical training

program of 2 hours of aerobic exercise with

strength training (moderate practice at the

beginning and increased gradually) for 4 days

a week for 4 months is practiced. The post test

started on the 1 st April 2009, BMI and BIA was

also examined in the same manner for one

month.

Results

Table (1) shows significant difference of

physical training program on mean body

weight, BMI and free fat but no significant

difference on fat mass.

Table (2) shows anthropometric measurements

in male pre and post physical training

program by using BMI, and bio electrical

impedance analysis to determine BF%.

Table (1): The effect of physical training program.

BMI classify 82% of students within normal

range, while actually 42% of them are within

normal range by using BIA for estimating of

body fat . After physical training program (post

test) there is an increase of the over weight

and obese students, while there in decrease in

the number of over weight and obese students

by using BIA for estimating body fat. The mean

BMI is (22) and mean body fat is (21) in pre

physical training program while the mean BMI

is (23) and mean body fat is (16) in post

physical training program.

Table (3) shows the anthropometric

measurements in female pre and post physical

training program BMI, BF%.

It shows that 68% of females are within

normal range of weight by using of BMI, while

28% only are within normal range by using of

BIA, in contrast to 18% are overweight by

using BMI and 45% are over weight by using

BIA.

No great difference is seen in post training

program by the use of BMI and BIA, and the

mean BMI is (22) in pre and post physical

training program.

The mean body fat is (47) in pre physical

training program while it is (38) in post physical

training program by using of bio electrical

impendence analysis.

Table (4) shows the sensitivity and specificity

of BMI.

It represent the sensitivity and specificity of

BMI in males and females according to WHO

criteria. The mean specificity is 87.5% in males

compared with 84.9% in females, while mean

sensitivity is 30.2% in males and 32% in

females, it indicate that BMI is a specific test

but it is not a sensitive test for overweight and

obesity.

Categories Physical training program No. X SD t.cal P. Value

Body weight

BMI

Fat mass

Fat free

mass

df= 121, t. critical = 2.6, X= mean weight in kilograms

Pre 122 64.94 9.6

0.05

2.9

Post 122 65.81 9.9 Sig

Pre 122 22 9

0.05

3.6

Post 122 23 10.4 Sig

Pre 122 12.3 5.6

0.05

1.5

Post 122 11.35 5.8 N.S

Pre 122 80.2 11.9

0.05

3.5

Post 122 83.6 7.4 Sig

© 2010 Mosul College of Medicine 20


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Table (2): Male anthropometric measurements

in pre and post physical training program.

Pre physical

training program

BMI

Body fat

no % no %

underweight 1 1 4 4

normal 82 82 42 42

overweight 13 13 32 32

obese 4 4 22 22

X- SD 22-7.5 2-3.6 21-3.8 13-0.6

Post physical

training program.

BMI

Body fat

no % no %

underweight 4 4 2 2

normal 73 73 57 57

overweight 15 15 24 24

obese 8 8 17 17

X-SD 23-1.55 2-3 16-6.5 9-0.7

Table (3): Female anthropometric

measurements in pre and post physical

training program.

Pre physical

BMI

Body fat

training program. no % no %

underweight 1 4 0 0

normal 15 68 6 28

overweight 4 18 10 45

obese 2 10 6 27

X-SD 22-4.4 3-2.9 47-5.2 18-0.6

Post physical

BMI

Body fat

training program. no % no %

underweight 2 10 0 0

normal 13 59 6 28

overweight 4 18 11 49

obese 3 13 5 22

X-SD 22-5.2 3-12 38-5.9 15-3.6

Table (4): The sensitivity and specificity of BMI in male and female.

Male

Female

BMI Specificity Sensitivity Specificity Sensitivity

30.0 92.5% 4.3% 84.5% 15%

Mean 87.5% 30.2% 84.9 % 32.1%

Discussion

Obesity is a cause of major morbidity and

mortality. It is a chronic condition associated

with increased cardio metabolic risk as well as

number of obesity – related co morbidities.

Achieving and maintaining weight reduction

can have numerous positive effects , on overall

health (29) .

There is universal support for the use of

physical activity to decrease overweight and

promote improved health (30,31) . An increase in

physical activity is an important part of weight

management program. Most weight loss

occurs because of decreased caloric intake.

Sustained physical activity is most helpful in

preventing weight regain (32) .

There are reasons to become more informed

about body composition:

- To develop complete physical fitness profile

for clients.

- To monitor body fat loss and muscle growth

resulting from exercise.

- To provide baseline data for nutritional

counseling and treatment of obesity.

- To describe changes due to growth,

development, maturation and aging.

- To maximize the performance of

athletes (33) .

Table (1) shows significant difference of

physical training program on body weight , BMI

and free fat mass, but no significant difference

on fat mass.

© 2010 Mosul College of Medicine 21


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Physical activity has been shown to be

inversely associated with BMI in numerous

cross-sectional studies, and obese subjects

have been observed to be physically less

active than non-obese. However, in some

studies No association between physical

activity and BMI has been found or an inverse

association has been observed only in

women (34,35) .

Table (2) shows anthropometric

measurements in males pre and post physical

training program by using BMI, and bio

electrical impedance analysis to determine

BF%.

The athlete’s weight should typically fall

between the 25 th and 75 th percentile of weight

for height for age (by Nationals center for

health statistics guidelines), although some

athletes weigh more because of increase

muscles mass, the use of BMI in athletes

is not recommended (36,37) .

BMI demonstrates low or no correlation with

other methods for assessing overweight and

obesity, BMI identifies fewer obese subjects

than other methods (38) .

WHO suggest the use of BMI as a method of

choice to determine over weight, it is an

adequate method, its index ranges from

malnutrition to grade Ш obesity, However, fat

content, which is the most important factor in

terms of associated chronic disease may

oscillate widely within the same BMI value (39) .

Table (3) shows the female anthropometric

measurements in pre and post physical

training program. Significantly higher

associations exist in each gender between

BMI and BF% in the upper BMI textile than in

the lower BMI textile. In the lower BMI textile,

the correlations between BMI and FFM were

approximately twice as large as those between

BMI and BF%, the BMI correctly identified 44%

of obese men and 52% of obese women,

when obesity was determined from BF%, BMI

is an uncertain diagnostic index of obesity (40) .

Average men have more skeletal muscles

than average women and average women

have more fat than average men (41,42) .

Jackson 2002 study show there is an

average BMI gap of 2.3 kg/m 2 between men

and woman, body fat 25% for men, 33% for

woman (43) , while Deureberg 2001 study shows

overweight women tend to have higher BMI

values than over weight men (44) .

The mean BMI in men is not necessarily that

different from BMI in women; body

composition does vary by gender, men have

more skeletal muscle than women – both in

absolute terms and relative to body mass. The

differences have been found to be greater in

the upper body (45) .

Table (4) represents the sensitivity and

specificity of BMI in males and females

according to WHO criteria. It indicates that BMI

is a specific test but it is not a sensitive test for

overweight and obesity. This result is in

agreement with Dietiz study 1998 which show

that the BMI has a poor sensitivity to screen

for overweight (46) .

Sensitivity is given more importance than

specificity since false positive overweight is not

considered as serious as a false negative

overweight (47) .

The use of BMI to screen for overweight /

obesity can generate a high percentage of

false positive male and even higher

percentage of false negative female, a more

universal approach to using anthropometric

measure to screen for overweight / obesity

should be developed (40) .

BMI a number tested a formula for calculating

weight for height is significantly associated

with total body fat content and should be used

to monitor changes in body weight or to

assess overweight or obesity, the calculated

BMI is a common clinical Index of obesity or

altered body fat distribution. A well accepted

scale has been developed to calculate by

gender using weight-to-height ratios (48) .

BMI continues to serve well for many

purposes, but the time is now right to initiate a

gradual evolution beyond BMI toward

standards, based on actual measurement of

body fat mass (49) .

Conclusions

Increased physical activity has significant

effect on body weight, so sustained physical

activity is most helpful in the prevention of

weight regain.

Anthropometry has the advantage of being a

measuring tool involving less time and

© 2010 Mosul College of Medicine 22


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

operational costs than other more complex

methods, However, BMI fails to distinguish

between lean body mass and fat, thus the

relationship between BMI and body fatness

varies according to body composition

properties.

BIA is a method of choice to determine body

fat . One draw back of using BIA method is the

equipment is relatively expensive ($3,500).

Recommendations

• Physicians should understand body

composition measurement, and be willing

to educate athletes, about nutritional

consultation and physical training

programs.

• Results are consistent with published data

showing the need to consider the age and

sex as an open defining the prevalence of

obesity with BMI.

• BIA should be considered as a method of

choice to determine overweight and obese

people according to fat mass.

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Fever of unknown origin: A prospective study in Northern Iraq

Rami M. Adil Khalil*, Rafe' H. Al-Kazzaz**, Humam Ghanim***, Dhia J. Al-Layla*

* Department of Medicine, College of Medicine, University of Mosul; ** Department of Medicine, Ibn Sina

Teaching Hospital; *** Department of Community Medicine, College of Medicine, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 26-35).

Received: 9 th Jun 2010; Accepted: 9 th Feb 2011.

ABSTRACT

Objectives: A wide variety of diseases are likely causes of fever of unknown origin (FUO). No fixed

guidelines exist to direct the workup in these cases. We followed a diagnostic protocol to study the

causes of FUO in Iraq, and to evaluate the contribution of clinical assessment and various

investigations in making the final diagnosis.

Methods: From March 2002 to September 2009, fifty five consecutive patients with FUO were

admitted in a tertiary referral centre in Mosul, Iraq. The patients underwent a series of clinical and

diagnostic evaluation in a prospective study, in an attempt to diagnose the underlying cause of fever.

The benefit of history taking and clinical examination as directors of the diagnostic workup and the

yield of various laboratory and imaging techniques were assessed.

Results: Infections were the commonest causes of FUO (32.7%), followed by non-infectious

inflammatory diseases (NIID) (25.4%), malignancies (16.4%) and miscellaneous causes (5.4%). No

diagnosis was made in 20% of cases. Of infections, tuberculosis was the most important single cause

of fever, while various vasculitides and non-Hodgkin's lymphoma were the commonest NIID and

malignant disease, respectively. Symptoms of the patients were of little benefit in directing

subsequent investigations, but the physical signs were more useful; finding enlarged lymph nodes

was significantly associated with malignant diseases (p=0.009). Anaemia, high ESR and elevated

liver enzymes were common and bear no significant association with any disease category. Chest

radiograph and abdominal ultrasound were helpful initial imaging studies. CT scan of the chest was

shown a useful diagnostic procedure.

Conclusion: Together with infections, NIID are important causes of FUO in Iraq. Careful physical

examination and a systematic approach on investigations are usually rewarding in reaching the

diagnosis.

الخلاصة

الأهداف:‏ أمراض مختلفة قد تكون سببا للحمى مجهولة المصدر.‏ لا توجد خطوط هادية محددة لتوجيه العمل التشخيصي

في مثل هذه الحالات.‏ اتبعنا منهجا تشخيصيا لدراسة حالات الحمى مجهولة المصدر في العراق،‏ ولتقييم ما تسهم به

العلامات السريرية ومختلف الفحوصات في التوصل إلى التشخيص النهائي.‏

الطريقة:‏ بين آذار وأيلول تم إدخال خمسة وخمسين مريضا متعاقبا مصابين بحمى مجهولة المصدر الى

مرآز إحالة من المرتبة الثالثة في الموصل شمالي العراق.‏ خضع المرضى لسلسلة من الفحوصات السريرية والمختبرية

في دراسة مستقبلة لمحاولة تشخيص سبب الحمى.‏ تم تقييم فائدة المعومات التي يعطيها المريض والفحص السريري

آموجهات للعمل التشخيصي وحصيلة مختلف الفحوصات المختبرية والتصويرية التي تجرى في محاولة الكشف عن

التشخيص النهائي.‏

النتائج:‏ آانت الأخماج السبب الأعم للحمى مجهولة المصدر تبعتها الأمراض الالتهابية غير الخمجية

ثم أسباب متفرقة ولم يتم التوصل إلى تشخيص في

والأمراض الخبيثة

٪٢٠

،(٪٣٢,٧)

.(٪٥,٤)

،٢٠٠٩

‏(السرطانية)‏ (١٦,٤٪)

٢٠٠٢

(٪٢٥,٤)

© 2010 Mosul College of Medicine 26


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

من الحالات.‏ آان السل أهم الأسباب الخمجية للحمى،‏ ومختلف التهابات الأوعية الدموية والورم اللمفاوي غير هوجكن أهم

الأمراض الالتهابية غير الخمجية والأمراض السرطانية،‏ على التوالي.‏ آانت أعراض المريض ذات فائدة قليلة في توجيه

الفحوصات المختبرية،‏ إلا أن الفحص السريري آان أآثر فائدة،‏ حيث أن تضخم العقد اللمفاوية آان علامة دالة على

احتمال تشخيص مرض خبيث ‏(ب=‏‎٠,٠٠٩‎‏).‏ آان آل من فقر الدم وارتفاع سرعة ترسيب الدم وزيادة نسبة أنزيمات الكبد

ملاحظات عامة آثيرة الحدوث في جميع الأصناف ولم تميز صنفا عن غيره إذا قيست إحصائيا.‏ آانت أشعة الصدر

وفحص البطن بالأمواج فوق الصوتية دراستين تشخيصيتين مفيدتين.‏ ظهر مفراس الصدر آإجراء تشخيصي فعال في مثل

هذه الحالات.‏

الاستنتاج:‏ إضافة إلى الأخماج،‏ آانت الأمراض الالتهابية غير الخمجية سببا مهما للحمى مجهولة المصدر في العراق.‏

الفحص السر يري المتأني والتعامل المنهجي مع الفحوصات يؤدي إلى التشخيص النهائي في أآثر حالات الحمى مجهولة

المصدر.‏

F

ever of unknown origin (FUO) is one of

the most challenging problems that can

face a physician during his clinical practice.

The earliest work on this subject was

published by Petersdorf and Beeson in 1961 (1) .

They defined FUO as fever of at least 3 weeks

duration exceeding 38.3˚C on several

occasions, with no established diagnosis after

one week of evaluation in hospital.

Considering the increased cost of in-hospital

care and advances in investigative techniques

that accelerated the pace of exploration, Durak

and Street (2) (agreed by Petersdorf (3) ) revised

the conventional definition in 1991, limiting the

hospital stay to 3 days or more than two

outpatient's visits. They also divided FUO into

four groups: classic, neutropenic, nosocomial

and HIV related FUO.

The spectrum of diseases responsible for

FUO varies in different geographical locations

and changes over time in the same locality (4,5) .

The aim of our work was to study the causes

of classic FUO in Iraq and to evaluate the

contribution of clinical assessment and various

investigations in making the diagnosis.

Patients and methods:

From March 2002 to September 2009, we

gathered a series of consecutive patients with

prolonged fever presented to Ibn Sina

Teaching Hospital in Mosul Medical City

(Mosul, Iraq), and admitted under the care of

one of the first two authors. Patients were

referred from general practitioners and family

physicians. Some of them presented directly

without referral, or came to our attention after

consultations from other physicians. Patients

were included in the study if they fulfilled the

Durak and Street's revised criteria of classic

FUO. Accordingly, patients should be at least

10 years old, and have documented fever of

38.3˚ C or more, which was repeated on more

than one occasion, for more than 3 weeks,

with no diagnosis after 3 days of hospital

admission or two outpatients' visits.

Patients were excluded from the study if the

diagnosis was already established before

referral. Patients whose fever has developed

in hospital (nosocomial), had severe

neutropenia (defined as WBC count < 1.0 ×

10 9 / L, or granulocyte count < 0.5 × 10 9 / L) or

HIV infection were also excluded.

Fifty five (55) patients met the above criteria,

and after taking their informed consent, they

were included in a prospective study

considering the final diagnosis as the main

outcome measure.

The final diagnosis was either made during

hospital admission or during the follow up

period. Only diagnoses that were sufficiently

validated were retained. The test most

convincingly ascertained the final diagnosis in

each case was determined. Patients were

labelled as "no diagnosis" if they died during

the evaluation period or remained

undiagnosed during their hospital stay and

subsequent follow up period, which was open

until the end of the study.

The causes of FUO were classified into 4

categories: 1. infection, 2. malignancies, 3.

non-infectious inflammatory diseases (NIID) (a

category coined by de Kleijn et al in 1997 that

© 2010 Mosul College of Medicine 27


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

comprises connective tissue diseases,

vasculitis and granulomatous diseases (6) ) and

4. miscellaneous causes which do not fit in any

of the above categories.

A comprehensive review of history was done,

stressing on the presence of localizing

symptoms, with careful consideration of past

medical and surgical history, details of travel,

occupation and animal exposure. Careful

clinical examination was conducted by the

authors themselves. Some patients were

referred for clinical evaluation by specialists in

other fields; namely, surgeons, otolaryngologists,

ophthalmologists, dermatologists,

neurologists and gynaecologists. Patients

were re-examined daily during their admission

and on each follow up visit for possible

appearance of new signs that may help in

reaching the diagnosis. Any available records

of examination, medications or investigations

were reviewed. All patients underwent an initial

diagnostic evaluation (step 1 investigations).

These are mentioned in table 1.

If the diagnosis had not been established

after the initial clinical and laboratory

evaluation, investigations from the second

diagnostic set were started (step 2

investigations (table 2)). No rigid protocol was

followed, as no published guidelines exist on

the approach of FUO (7) . The strategy

suggested by Knockaert in 1992 was

considered (8) . Selection of step 2

investigations was based on the presence of

potentially diagnostic clues from history,

examination and step 1 investigation. Much

weight was given to exclude the common

diseases in the community.

If the diagnosis was still illusive after this

step, a third stage investigation was

considered (step 3 investigations (table 2)).

These included invasive procedures (like liver

biopsy, laparoscopy or surgical exploration) or

therapeutic trials. The latter were only

conducted when the patient was otherwise

deteriorating; the choice was dictated by

clinical suspicion, this mostly involved antituberculosis

therapy for suspected cryptic

tuberculosis and corticosteroid therapy when

certain NIID was highly likely in the absence of

diagnostic laboratory test (such as the case

with Still disease).

Table (1): Step 1 obligatory investigations.

Step 1 investigations

1. Complete blood picture and ESR.

2. General urine examination.

3. Serum urea, creatinine and electrolytes.

4. Liver function tests (bilirubin, alanine and

aspartate transaminases, alkaline

phosphatase and albumin).

5. Blood and urine culture.

6. Brucella agglutination test, Widal test and

hepatitis serology.

7. Antinuclear antibodies, rheumatoid factor.

8. Chest X-ray.

9. Ultrasound of the abdomen and pelvis.

Table (2): Step 2 and 3 investigations.

Step 2 investigations

1. Other biochemical tests: prostate specific

antigen (PSA), acid phosphatase, T3, T4,

TSH, protein electrophoresis, creatine

kinase, troponins.

2. Serological tests: antiDS antibodies,

antineutrophil cytoplasmic antibodies

(ANCA).

3. Blood film for malaria.

4. Bone marrow aspirate (or biopsy) and

culture.

5. CT scan of the chest, abdomen and pelvis.

6. lumbar puncture and CSF examination.

7. MRI of the brain, spine or abdomen.

8. Echocardiography.

9. Endoscopy (gastroscopy, colonoscopy or

bronchoscopy).

10. Biopsy from pathological specimens

(pleural, endoscopic, lymph nodes... etc.).

Step 3 investigations

1. Liver biopsy.

2. Laparoscopy.

3. Surgical exploration.

4. therapeutic trial.

© 2010 Mosul College of Medicine 28


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

The data were tabulated and analyzed using

MiniTab version (13.20). Z two – proportions

with 95% confidence interval was used in

comparing different proportions. P – value <

0.05 was considered significant throughout the

study.

Results

Of the 55 patients included in the study, 27

were males and 28 were females (49.1% and

50.9% respectively). The patients mean age

was 42.76 ± 19.29 years, ranging from 10 – 76

years. Excluding 5 patients with long history

(>6 months) of intermittent fever, the mean

duration of fever was 43.28 ± 34.35 days.

Infection was the most common cause of

FUO, responsible for 18 cases (32.7%). NIIDs

were diagnosed in 14 patients (25.4%) and

malignancies in 9 patients (16.4%).

Miscellaneous causes were found in 3 patients

(5.4%). No diagnosis was made in 11 patients

(20%); four (4) of them died during evaluation

(table 3).

Tuberculosis was the infection most

frequently responsible for FUO in our study.

Only one of the 4 patients had pulmonary

tuberculosis, in whom a faint apical cavitary

lesion was overlooked in the earlier films. The

others had cryptic tuberculosis (diagnosed

after therapeutic trial), disseminated disease

(affecting lumbar spines, meninges and

ovaries) and pericardial disease. Typhoid and

brucellosis were diagnosed in 3 patients each.

All the typhoid patients had received multiple

courses of antibiotics before presentation and

their blood cultures were negative. All of them

had splenomegaly and two had neutropenia.

The diagnosis was confirmed by bone marrow

culture in one patient and by rising titre of

Widal test, exclusion of other diseases and a

response to treatment in the other two.

splenomegaly was noticed in two out of the

three patients with brucellosis. The diagnosis

was established by a positive brucella

agglutination test (which was negative on preadmission

testing). Two patients were

diagnosed as infective endocarditis confirmed

by a positive blood culture (growing

Staphylococcus aureus in both cases) and

echocardiographic evidence of vegetations. In

two patients, urinary tract infection was

determined to be the cause of fever. Both had

pyuria on urine examination, with

ultrasonographic features of acute

pyelonephritis. Urine culture was positive for E.

coli in one of them only (the diagnosis was

supported by a positive response to treatment

in the other). A woman with ovarian abscess

was diagnosed after surgical exploration for

suspected ovarian tumour. Malaria was

confirmed by a positive blood film after two

negative results. An elderly woman with

inconclusive chest X-ray was diagnosed with

basal pneumonia on CT scan of the chest, and

a young man had infectious mononucleosis.

Table (3): Causes of fever of unknown origin in

55 patients.

1. Infections

Tuberculosis

Typhoid fever

Brucellosis

Infective endocarditis

Pyelonephritis

Pneumonia

Malaria

Ovarian abscess

Infectious mononucleosis

2. Non-infectious inflammatory diseases

Systemic lupus erythematosus

Wegener's granulomatosis

Polyarteritis nodosa

Microscopic polyangiitis

Temporal arteritis

Behçet's syndrome

Mixed connective tissue disease

Adult onset Still disease

Ulcerative colitis

Crohn's disease

Familial Mediterranean fever

Subacute thyroiditis

3. Malignant diseases

Non-Hodgkin's lymphoma

Carcinoma of the prostate

Hodgkin's disease

Carcinoma of the colon

Multiple myeloma

Liver metastases (unknown primary)

4. Miscellaneous causes

Liver cirrhosis (hepatitis B)

Migraine

5. No diagnosis

Persistent fever

Death

18 (32.7%)

4 (7.3%)

3 (5.5%)

3 (5.5%)

2 (3.6%)

2 (3.6%)

1 (1.8%)

1 (1.8%)

1 (1.8%)

1 (1.8%)

14 (25.4%)

2 (3.6%)

2 (3.6%)

1 (1.8%)

1 (1.8%)

1 (1.8%)

1 (1.8%)

1 (1.8%)

1 (1.8%)

1 (1.8%)

1 (1.8%)

1 (1.8%)

1 (1.8%)

9 (16.4%)

3 (5.5%)

2 (3.6%)

1 (1.8%)

1 (1.8%)

1 (1.8%)

1 (1.8%)

3 (5.4%)

2 (3.6%)

1 (1.8%)

11 (20%)

7 (12.7%)

4 (7.3%)

© 2010 Mosul College of Medicine 29


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Systemic lupus erythematosus was

responsible for the FUO in two patients and

mixed connective tissue disease in a third one.

Adult onset Still disease was diagnosed in a

patient with one year of prolonged intermittent

fever, generalized lymphadenopathy (including

intra-abdominal lymph nodes), splenomegaly

and skin rash. After negative lymph node

biopsy, the patient dramatically responded to

corticosteroid therapy albeit with recurrent

relapses over three years follow up.

Vasculitides (including Behçet's syndrome)

were responsible for six cases. Two patients

were proved to have ANCA positive

Wegener's granulomatosis (one presented

with biopsy confirmed granulomatous mastitis

and pulmonary cavitary lesions missed as

tuberculosis, and one with cavernous sinus

thrombosis, pulmonary infiltrate and pleural

effusion). A woman was treated empirically

with corticosteroids after extensive cavitating

nodular lesion was diagnosed as vasculitis on

CT scan. Complete resolution and long time

remission on immunosuppressive therapy was

noticed. Polyarteritis nodosa was diagnosed

on clinical basis in a young man with

hypertension, mononeuritis multiplex, skin

nodules, vaculitic skin rash and ischaemic

stroke. Prolonged remission (4 years) was

attained on steroids and immunosuppressants.

After unexplained fever, Behçet's syndrome

was diagnosed when a patient developed

oligoarthritis and posterior uvietis on follow up

visits, Pethargy test was also positive. The

sixth case of vasculitis was an elderly woman

with temporal arteritis associated with

polymyalgia rheumatica. Two cases of

inflammatory bowel disease were diagnosed;

one with mild diarrhoea, in whom ulcerative

colitis was diagnosed by colonoscopy and

biopsy; and the second with Crohn's disease

suspected on clinical and radiological grounds

and proved after exploration for colonic

perforation. In a patient with prolonged

episodic fever and hepatosplenomegaly, liver

biopsy diagnosed amyloidosis, with retrograde

diagnosis of familial Mediterranean fever. A

woman with fever, high ESR and mild

thyrotoxicosis was diagnosed as subacute

thyroiditis by needle aspiration of the thyroid,

with dramatic response to corticosteroids.

Lymphoma was the main malignancy

responsible for FUO in our cohort. All four

cases were confirmed by lymph node biopsy.

Non-Hodgkin's lymphoma was found in three

patients, two with mixed small and large cell

type B cell lymphoma, and one with

angioimmunoblastic T cell lymphoma (formally

angioimmunoblastic lymphadenopathy). The

fourth was a patient with Hodgkin's disease

who was diagnosed quite late, as initial

evaluation wrongly suggested infective

endocarditis, but the patient failed to respond

to antibiotic therapy. One month later cervical

lymphadenopathy appeared and permitted the

correct diagnosis to be made. Unusually two of

our patients were shown to have carcinoma of

the prostate with bone metastases (one of

them discovered by CT scan). Acid

phosphatase was markedly elevated in both,

but prostate specific antigen was abnormal in

one of them only. Carcinoma of the colon was

diagnosed by colonoscopy after prolonged

fruitless investigation of a patient with fever,

abdominal pain and constipation, but

otherwise negative imaging studies. Fever was

caused by multiple myeloma and by

metastases to the liver and spleen of unknown

primary in two other patients.

Another patient with prolonged history of

paroxysmal fever in association with headache

and neck pain was clinically diagnosed as

migraine. The diagnosis was confirmed by

durable response to propranolol prophylaxis

and recurrent relapses on its withdrawal.

Unexpectedly, two patients were found to have

liver cirrhosis due to hepatitis B infection. The

first had negative laparoscopic liver biopsy

despite nodular liver on MRI and CT scan.

Gastroduodenoscopy has been initially

normal, but the patient bled heavily from

oesophageal varices few months later. The

other one presented with hepatosplenomegaly

and abnormal liver function tests in association

with fever. The diagnosis was established

when further evaluation disclosed ascites and

oesophageal varices.

Beyond fever and associated constitutional

symptoms of fatigue, malaise, sweating and

© 2010 Mosul College of Medicine 30


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

generalized aches, 19 patients (34.6%)

described symptoms that potentially localize

the source of fever. In only 6 of these patients

(31.6%), their symptoms really led to the true

diagnosis.

No finding apart from fever was noticed on

clinical examination of 10 patients (18.2%),

while positive findings were demonstrable in

the remaining 45 patients (81.8%). In 11

patients, new clinical signs appeared during

hospital stay or follow up visits. In 6 of them,

discovery of these signs contributed to the final

diagnosis. Diagnosis was made in 38 out of 45

patients with positive clinical examination

(84.4%), and in 6 out of 10 patients with

negative clinical examination (60%) (95

percent confidence interval, (0.177 to 1.06;

P=0.136). Finding lymph node enlargement on

physical examination was significantly

associated with subsequent diagnosis of

malignant disease (p=0.009). No similar

relationship was noticed with splenomegaly

(p=0.131).

None of the obligatory biochemical

investigations revealed the diagnosis by its

own; however, many of these tests were

helpful as potentially diagnostic clues.

Elevated serum urea and creatinine pointed to

renal impairment that was relevant four out of

five times. Uraemia was an initial marker of

amyloidosis, vasculitis, carcinoma of the

prostate and multiple myeloma.

Transaminases and alkaline phosphatase

were elevated in 12 (21.8%) and 17 (31%)

patients, respectively, but they did not show a

particular association with any diagnostic

category.

The majority of patients were anaemic

(69.1%). All (except two with hypochromic

anaemia) were having normochromic

normocytic anaemia. Malignancy was more

commonly diagnosed among anaemic patients

than among those without anaemia (21.1%

versus 5.9%) (95 percent confidence interval, -

0.019 to 0.322; p=0.082). Mean ESR was not

significantly different between the diagnostic

groups. Although an ESR of 100 mm/h or

higher was more commonly noticed in patients

with malignancy and NIID (44.4% and 41.7%

respectively) than in patients with infections

(22.2%), this difference was not statistically

significant (95 percent confidence interval,

(0.400 to 0.455; p=0.899).

Blood culture was diagnostic in two cases of

staphylococcus aureus infective endocarditis,

but positive cultures were misleading in 6

patients (growing staphylococci and α

haemolytic streptococci) in patients ultimately

found to have unrelated diagnosis. On the

other hand, bone marrow culture diagnosed

one patient with typhoid fever and supported

positive blood culture result in a patient with

infective endocarditis.

Chest X-ray and ultrasound examination of

the abdomen and pelvis were ordered

routinely as step 1 investigation. Chest X-ray

was abnormal in 15 (27.3%) patients, and

provided useful findings that led to the correct

diagnosis in 7 of them (diagnostic yield of

12.7%), while ultrasound showed abnormal

findings in 36 patients (65.6%), and truly

contributed to the final diagnosis in 16 patients

(diagnostic yield of 29%). CT scan of the

abdomen (ordered in 16 patients) added

useful information beyond ultrasound findings

in 2 cases only, while CT of the chest was

diagnostically useful beyond chest X-ray in 4

out of 5 patients (80%).

Discussion

Despite the enormous improvement in the

diagnostic abilities provided by the new

techniques of investigations, the percentage of

undiagnosed cases of FUO has steadily

increased over the last decades, rising from a

mean of 17.2% in 1970s to 30% in 1990s (9) .

One explanation is that patients nowadays

tend to seek medical advice early and that a

diagnosis is frequently established before 3

weeks elapsed (10) . Only the difficult, hard to

diagnose cases would remain. Moreover,

advanced diagnostic techniques helped to

diagnose many cases which were previously

considered as FUO, with selection of difficult to

diagnose cases, mostly self limiting or benign

fevers. The percentage of undiagnosed cases

in our study is intermediate among those of

recent studies (table 4).

We followed a diagnostic protocol that made

use of the previous experience in this field,

with two considerations regarding infectious

© 2010 Mosul College of Medicine 31


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

disease investigations: 1. We avoided blind

microbiological serological screening because

such strategy was associated with a very low

diagnostic yield (11) . 2. Studies in many

countries have shown that the spectrum of

infections presenting as FUO in a community

is a mirror reflection of the endemic infections

in that community. Among infections, Q fever

was an important cause of FUO in France (12) ,

leishmaniasis in India (13) , melioidosis in

Taiwan (14) and brucellosis in Jordan (15) and

Turkey (16) . Accordingly, we adapted the study

algorithm to the epidemiological status in Iraq

and included brucella agglutination test and

Widal test in the initial diagnostic workup.

Until recently, it was almost a constant finding

in all studies of FUO that infections represent

the major category of cases. In series from

more developed countries (USA and Europe

3,6,10,-12 ), the proportion of cases diagnosed as

infections has gradually declined over the last

four decades, with a parallel rise in NIID. In

some countries, like France (12) and Belgium (10) ,

these diseases are now the leading cause of

FUO. Infection is still the dominating category

in FUO series from developing

countries (13,14.16-19) . Comparing the distribution

of FUO cases in the different categories in

studies published over the last 5 years (table

4), the proportion of infections in our present

study was less than that of other developing

countries and nearer to the figures of

European studies.

As much as high percentage of infectious

diseases reflects the high prevalence of

infection in that community, it is also true that a

high rate of infectious diseases presenting as

FUO indicates a diagnostic problem at the

outpatient level as far as most cases represent

atypical presentation of common diseases (1,10) .

The early consideration of diseases like

typhoid fever and brucellosis by general

practitioners has probably contributed to the

relatively small number of cases due to

infection in our study. Tuberculosis was the

leader among infections that were responsible

for FUO in developing countries (ranging from

35.5% - 45.2% of all infections (13,15,22,23) ).

Although it was the commonest infection in our

series, the proportion of these cases (22.2%)

was less than other studies showed. Taking in

consideration that tuberculosis is highly

endemic in Iraq, this was an unusual finding. A

possible explanation is the trend toward early

introduction of anti-tuberculosis therapy for any

difficult to explain febrile illness before

referring them as FUO.

The group of diseases not caused by

infection or neoplasm had different

nomenclature in FUO series: inflammatory,

connective tissue diseases, collagen vascular

disease. . etc. Since the adoption of the name

"non infectious inflammatory diseases (NIID)"

by de Kleijn et al (6) , subsequent studies have

used this term in their work. Similar to other

studies, NIID has emerged as an important

cause of FUO in Iraq, with a particularly high

percentage of cases caused by a variety of

vasculitides which comprised 10.9% of overall

cases.

In the diagnostic category of malignancy,

non-Hodgkin's lymphoma was the main cause

of FUO, a finding that is shared by most other

studies in the field (6,10,13,15-17,22,24) . Although

carcinoma of the prostate has been reported

to cause FUO (25) , such cases are rare, and it

was strange to diagnose two cases in one

series.

Table (4): The percentage of patients with FUO by cause in the most recent studies.

Italy

(Mansueto) 20

China

(Zheng) 21

France

(Zenone) 12

Iraq

(Present

study)

Taiwan

(Chin) 14

India

(Kejariwal) 13

Mexico

(Avec-

Salinas) 17

Turkey

(Coplan) 16

Infections 31.8 49.1 22.9 32.7 57.4 53 42.2 45.1

NIID 12.2 7.8 26.4 25.4 7.8 11 26.7 26.8

Malignancy 14.2 7.8 9.7 16.4 8.5 17 17.8 14.1

Miscellaneous 9.2 8.8 15.3 5.4 8.5 5 1.2 5.6

Undiagnosed 31.8 26.5 25.7 20 17 14 11 8.5

© 2010 Mosul College of Medicine 32


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Although many studies stressed on the

importance of careful history and clinical

examination in directing FUO workup (5-7) ,

symptoms described by the patients were

potentially localizing in only one third of cases.

These proved falsely localizing in 69.4% of

cases, and did not lead to the correct

diagnosis. This misleading symptomatology

was probably one factor that contributed to

delayed diagnosis in these patients. Careful

physical examination on the other hand can be

rewarding. Diagnosis was more likely to be

made when there were positive clinical signs

that would direct the subsequent investigations

(successful diagnosis in 84.4% of patients with

positive clinical examination versus 60% in

those without). De Kleijn was able to diagnose

70% of patients (6) with potentially diagnostic

clues and 60% of those lacking such clues.

But the difference was not statistically

significant, neither in our study, nor in De

Kleijn's. The presence of enlarged lymph

nodes was found a predictor of subsequent

diagnosis of malignant disease, supporting

similar notice made by Coplan et al (16) .

However, the association between

splenomegaly and malignancy as a cause of

FUO has not been confirmed in this study.

Liver function tests (manifested as serum

transaminases and/or alkaline phosphatase)

were abnormal in 38.2% of cases. Such

changes were not related to a particular

disease category and they represented a real

liver disease in only one patient (1.8%). Other

studies also noticed non-specific elevation of

liver enzymes in 50% of cases (11) . In a second

study (16) , high serum aspartate transaminase

(AST) was found to be associated with NIID.

Such relationship was not confirmed in our

study.

Regardless to the diagnostic category, most

of our patients were anaemic (69.1%); with

normochromic normocytic blood picture.

Similar percentage of anaemia was found by

de Kleijn et al (70%) (6) , while 97.5% of Gupta

et al patients were anaemic (26) .

In agreement with Coplan et al (16) , mean ESR

was not statistically different between the

groups. An ESR equal to or exceeding 100

was not found a statistically significant pointer

of a particular aetiology.

The diagnostic yield of chest X-ray and

ultrasound of the abdomen and pelvis were

high enough to include them in the initial step

of evaluation. Although CT scan of the

abdomen has been reported to have a

diagnostic yield of 19% in the workup of

FUO (9) , ultrasound of the abdomen possessed

a similar ability to detect local pathology. In a

recent study, standardized ultrasound

examination correctly diagnosed the cause of

fever in one third of FUO cases (27) , a result that

is comparable to our findings. Considering the

costs of the two studies and the risk of

radiation associated with CT scan, ultrasound

was a logical starting investigation, which can

be supplemented by CT scan in case of

negative or indeterminate results.

CT scan of the chest has not been studied

well in the investigation of FUO cases. Out of

five times this test was ordered, useful

diagnostic findings were obtained in four of

them. These findings support the

recommendation of Lopez et al to include CT

scan of the chest as well as the abdomen in

the investigation strategy of FUO (28) .

It is important to note that polymerase chain

reaction (PCR) is gaining increasing utility in

the diagnosis of many infectious diseases that

may present as FUO. Of particular interest

was the ability of PCR to diagnose malaria in

patients with low parasitaemia and thus

negative blood film (29) . PCR in samples of

bone marrow aspirate diagnosed tuberculosis

in 33% of patients clinically suspected to have

the disease, despite negative bone marrow

culture. Subsequent improvement on antituberculosis

drugs was shown in 85% of these

patients (30) . Nested PCR (nPCR) targeting the

flagellin gene (fliC) of salmonella typhi was

carried out on DNA extracted from the buffy

coat layer of blood samples. The test had

sensitivity and specificity of 100% and 97.5%,

respectively. In a study from rural India, nPCR

diagnosed typhoid fever in 4.2% of cases of

FUO, while concomitant blood culture (using

completely automated blood culture system)

diagnosed the disease in 2% of cases only (31) .

© 2010 Mosul College of Medicine 33


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Conclusion

Although infections are still the commonest

cause of FUO in Iraq, NIIDs are important

causes and should always be considered.

Systematic approach for the diagnosis of

cases of FUO is usually rewarding.

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HH, Lin WR, Huang CK, Tsai HC, Kao CH,

Yen MY, Liu YC. Fever of unknown origin

in Taiwan. Infection. 2006;34(2):75-80.

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North Jordan. Trop Doct. 2006;36:251-3.

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Cevik M, Erin S, Bodur H. Fever of

unknown origin: Analysis of 71

consecutive cases. Am J Med Sci. 2007;

334: 92-96.

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Villaseñor-Ovies P, Muro-Cruz D.

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22. Sipahi OR, Senol S, Arsu G, Pullukcu H,

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Effect of hydrochlorothiazide with amiloride on serum lipid

profile and malondialdehyde in hypertensive women

Faris A. Ahmed

Department of Physiology, Nineveh College of Medicine, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 36-40).

Received: 11 th May 2010; Accepted: 27 th Oct 2010.

ABSTRACT

Objectives: To study the effect of hydrochlorothiazde with amiloride on serum lipid profile and

malondialdehyde (MDA) in hypertensive women.

Methods: A case-control study was carried out in the Outpatient Department in Ibn-Sina General

Hospital, Mosul, during the period from November 2005 to May 2006. Thirty hypertensive women

treated with 50 mg hydrochlorothiazide and 5 mg amiloride per day in a single dose. The duration of

treatment was between 1-5 years. Thirty mild hypertensive women (newly diagnosed, before

treatment) were also included as a control group. Blood samples were taken from both the treated

patients and controls and analysed for serum lipid profile and MDA. Non-paired 't-test was used to

compare between parameters.

Results: Hydrochlorothiazide with amiloride did not change serum lipid profile significantly in the

hypertensive women compared with the control group, although serum lipid profile was in the upper

normal value. The combination therapy decreased serum MDA significantly (P‏ مصل المالوندالدهايد مقارنة

مع المجموعة الضابطة.‏

٥٠

(

٥-١

٠,٠٥)

٥

٢٠٠٥

© 2010 Mosul College of Medicine 36


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

الاستنتاج:‏ إن الاستعمال المزمن للعلاج التوافقي لعقار هايدروآلوروثايزايد مع عقار اميلورايد لم يؤثر معنويا على واجهة

الدهون في النساء المصابات بفرط الدم الشرياني لكن هذا العلاج التوافقي قلل معنويا من زناخة الدهون.‏ إن زناخة الدهون

هي نتيجة وليست سبب ارتفاع ضغط الدم الشرياني.‏

T

hiazides are moderately potent diuretics

that increase urine flow, sodium and

potassium excretion (1) . Hydrochlorothiazide

has important effect on hypertension as a

single therapy (2) . However, no trials have been

done for evaluating the efficacy of amiloride,

the potassium sparing diuretic, as a blood

pressure lowering monotherapy (3) . The

combination of hydrochlorothiazide and

amiloride is used for the treatment of

hypertension and the rational for combination

is to spare potassium and magnesium loss

through the kidney (4) .

Hydrochlorothiazide caused significant

increase in serum triglycerides (TG) (5) . Moser (6)

found that the rate of dyslipidaemia was higher

with thiazide diuretics than loop diuretics.

However, these disturbances in lipid profile

were negligible at half standard dose of

thiazide diuretics (7) . The potassium sparing

diuretic, spironolactone, exerted no relevant

effect on lipid profile (8) . There is well defined

relationship between thiazide and

dyslipidaemia but not with spironolactone (9) .

Lipid peroxidation of cell membrane was

associated with a number of pathological

conditions including atherosclerosis and

thrombosis (10) . Essential hypertension was

also associated with increased oxidative stress

and reduced antioxidant status (11) . In addition,

antihypertensive drugs and some diuretics

exerted a positive effect on the imbalance

between peroxide on lipid and antioxidant

defense system (12) .

Usually, hydrochlorothiazide and amiloride

are used in combination for the treatment of

hypertension. Therefore, this study was

conducted to evaluate the effect of this

combination of drugs on serum lipid profile and

lipid peroxidation presented by serum

malondialdehyde (MDA).

Patients and methods

This study received approval from Nineveh

Directorate of Health (Medical Research

Ethical Committee, consents of patients were

taken for this study). The study was carried out

in the Outpatient Department in Ibn Sina

Teaching Hospital in Mosul, from November

2005 to May 2006. Two groups of 30 female

patients for each group were studied (under

supervision of cardiologist). Patients of the first

group received 50 mg hydrochlorothiazide with

5 mg amiloride per day in a single dose. The

age of the treated patients ranged between

43-74 years (mean±SD: 51.8±7.6 years). The

duration of treatment was between 1-5 years.

The second group included mild hypertensive

patients (early diagnosed before treatment).

Their ages ranged between 45-74 years

(mean ± SD: 51.6±7.6 years). Patients with

other diseases or receiving medication other

than the studied drugs were excluded from this

study.

Six ml of blood were collected from each

patient, after overnight fasting. The sera were

separated for the analysis of lipid profile and

MDA. Determination of serum TC (total

cholesterol), trigycerides (TG) and high density

lipoprotein cholesterol (HDL-C) were

performed by enzymatic methods (13-15) . Serum

low density lipoprotein cholesterol (LDL-C)

was calculated using Friedewald formula. (16)

Serum MDA was estimated by the method of

Buege and Aust (17) .

Data are presented by mean±SD and were

analysed using unpaired t-test.

Results

In hypertensive patients treated with

hydrochlorothiazide and amiloride, serum TC,

TG, LDL-C, VLDL-C, HDL-C and ratio

TC/HDL-C were not significantly different

compared with the results in the non-treated

patients (controls) (Table 1). However, values

for serum lipid profile in the treated patients

were in the upper normal limit based on the

recommendation of British Hyperlipidaemia

Association (1998) (18) .

Serum MDA was decreased significantly

(P


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Table (1): Serum lipid profile and malondialdehyde in the control group and treated patients with

hydrochlorothiazide and amiloride.

Hypertensive

subjects

Controls

N = 30

Treated

patients

N = 30

TC

mmol/L

4.08

±1.59

TG

mmol/L

1.30

±0.67

LDL-c

mmol/L

2.18

±1.52

VLDL-C

mmol/L

0.59

±0.34

HDL-C

mmol/L

1.3

±0.34

TC

mmol/L

3.53

±3.14

MDA

µmol/L

0.204

±0.125

4.99

±1.85

1.66

±0.59

3.09

±1.9

0.75

±0.27

1.15

±0.39

4.87

±2.38

0.134*

±0.069

TC: total cholesterol; TG: triglycerides; LDL-c: low density lipoprotein cholesterol; VLDL-c: very low density

lipoprotein cholesterol; MDA: malondialdehyde. *P


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

3. Heran BS, Chen JM, wang JJ, Wright JM.

Blood pressure lowering efficacy of

potassium–sparing diuretics (that block the

epithelial sodium channel) for primary

hypertension. Cochrane Database System

Rev 2010; 20: CD008167

4. Fluster D. When do combinations of

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5. Nandeesha H, Payithran P, Madanmohan

T. Effect of antihypertensive therapy on

lipids in newly diagnoses essential

hypertensive women. Angiology 2009; 60:

217-20.

6. Moser M. Why are physians not

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management of hypertension? JAMA

1998; 279: 1813-16.

7. Law MR, Wald NJ, Morris JK, Jordan RE.

Value of low dose combination treatment

with blood pressure lowering drugs:

Analysis of 354 randomized trials. BMJ

2003; 326: 1427-30.

8. Weidmann P, de Courten M, Ferrari P,

Bohlen L. Serum Lipoproteins during

treatment with antihypertensive drugs. J

Cardiovase Pharmacol 1993; 22 supp 6:

S98-105.

9. Suter PM, Vetter W. Metabolic effects of

antihypertensive drugs. J Hypertens suppl

1995; 13: S11-7.

10. Polidori MC, Pratico D, Parente B, Mariani

E, Cecchetti R, Yao Y, et al. Elevated lipid

peroxidation biomarkers and low

antioxidant status in atherosclerotic

patients with increased carotid or

iliofemoral intima media thickness. J

Investig Med 2007; 55: 163-7.

11. Tandon R, Sinha MK, Garg H, Khana R,

Khanna HD. Oxidative stress in patients

with essential hypertension. Nati Med J

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12. Serkova VK, Burdeinaia LV. Effect of

antihypertensive therapy on indices for

lipid peroxidation and antioxidant system

in patients with hypertensive heart. Liak

Sprava 2002; (5-6): 12-16.

13. Allian CC, Poon LS, Chan CS, Richmond

W, Fu PC. Enzymatic determination of

total serum cholesterol. Clin Chem 1974;

20: 470-5.

14. Fossati J, principe L. Serum triglycerides

determined colorimetrically with an

enzyme that produce hydrogen peroxide.

Clin Chem 1982; 28: 2077-80.

15. Lopes-Virella MF, Stone P, Ellis S, Colwell

JA. Cholesterol determination in high

density lipoproteins separated by three

different methods. Clin Chem 1977; 23:

882-4.

16. Friedewald WT, Levy RI, Fredrickson DS.

Estimation of the concentration of low

density lipoprotein cholesterol in plasma

without use of the preparative ultra

centrifuge. Clin Chem 1972; 18: 499-502.

17. Buege JA, Aust SD. Microsomol lipid

peroxidation. Methods Enzymol 1978; 52:

302-10.

18. Wood D. Joint British recommendations on

prevention of coronary heart disease in

clinical practice. Heart 1998;51: 1-29.

19. Nandeesha H, Pavithran P, Madanmohan

T. Effect of antihypertensive therapy on

serum lipids in newly diagnosed essential

hypertensive men. Angiology 2009; 60:

217-20.

20. Ott SM, LaCroix AZ, Ichikawa LE, Scholes

D, Barlow WE. Effect of Low-dose thiazide

diuretics on plasma lipids: results from a

double-blind, randomized clinical trail in

older men and women. J Am Geriatr Soc

2003; 51: 340-7.

21. Rao RA, Hegde BM, Bhat EK,

Vidyavathiu, Rao RR. Lipid profile studies

in long term thiazide treated

hypertensives. Postgrad Med J 1991; 67:

652-4.

22. Lakshmann MR, Reda DJ, Metersen BJ.

Diuretic and β-blockers do not have

adverse effects at layer on plasma lipid

and lipoprotein profile in men with

hypertension. Arch Intern Med 1999; 159:

551-8.

23. Ferrari P, Rasman J, Weidmann P.

Antihypertensive agents, serum

lipoproteins and glucose metabolism. Am

J Cardiol 1991; 67: 26-35.

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

24. Weir MR, Moser M. Diuretics and betablockersr

is there a risk for dyslipidemia?

Am Heart J 2000; 139: 174-184.

25. Neutel JM. Metabolic manifestations of low

dose diuretics. Am J Med 1996; 100: 71-

82.

26. Chrysant SG, Luu TM. Effect of amiloride

on arterial pressure and renal function. J

Clin Pharmacol 1980; 20: 332-7.

27. Sahu S, Abraham R, Vedahalli R, Daniel

M. Study of lipid profile, lipid peroxidation

and vitamin E in pregnancy induced

hypertension. Indian J Physiol Pharmcol

2009; 53: 365-9.

28. Kedziora-kornatowska K, Czuczeiko J,

Pawluk H, Kornatowski T, Motyl J,

Szadujkis-Szadurski L, et al. The marker

of oxidative stress and activity of

antioxidant system in the blood of elderly

patients with essential arterial

hypertension. Cell Med Biol Lett 2004; 9:

635-41.

29. Khanna HD, Sinha MK, Khanna S, Tandon

R. Oxidative stress in hypertension:

associated with antihypertensive

treatment. Indian J Physiol Pharmacol

2008; 52: 283- 7.

30. Touyz RM, Schiffrin EL. Oxidative stress in

arterial hypertension: oxidative stress and

hypertension. In: Atherosclerosis and

oxidant stress- A new prospective Ed.

Jordan L Holtzman, Springer USA

2008;51-78.

© 2010 Mosul College of Medicine 40


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Measurement of lipid profile parameters in hypertensive

patients using atenolol or captopril

Ahmed Yahya Dallal Bashi*, Rawaa Khazal Jaber**, Mohammed Khalid Al. Hamo***

* Department of Medical Biochemistry, College of Medicine; ** Specialist in Clinical Biochemistry,

Al-Khansa Maternity Hospital; *** Department of Medicine, College of Medicine, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 41-48).

Received: 19 th Sept 2010; Accepted: 9 th Feb 2011.

ABSTRACT

Objectives: To study the effects of atenolol and captopril on lipid profile parameters including total

cholesterol (TC), triglycerides (TG), High density lipoprotein cholesterol (HDL-c), Low density

lipoprotein cholesterol (LDL-c) and atherogenic index (AI) in serum. Moreover to compare the effects

of these drugs on the above parameters with each other.

Patients and Methods: One hundred hypertensive patients were involved in this study which were

divided into two groups each of 50 patients. Patients in the first group were on atenolol and the

patients in the second group were on captopril. All of the cases of hypertension were of the primary

type (essential) as the patients were diagnosed by specialist physicians. The patients included were

not chronically using any other drugs, nor having family history of hyperlipidemia, and not suffering

from any other chronic disease.

The ages of the patients in the first group ranged from 35-74 years with a mean of 55±5.02 years,

while the ages of the second group ranged from 36-80 years with a mean of 57±6.0 years. Another

group of 50 normal individuals participated in this study as a control group, with ages ranged from 35-

72 years with a mean of 53±4.4 years.

Results: The results of this study showed that serum TG and AI were significantly higher in atenolol

using group in comparison with the control group, while serum HDL-c concentration was significantly

lower. Whereas, the remaining lipid profile parameters studied were not significantly different from the

control group. Serum LDL-c concentration was significantly low in captopril using group compared

with the control group whereas the remaining lipid parameters studied were not significantly changed

in this group. Further analysis of the results of the present study indicated significant decreases of

serum TG and AI in captopril using group in comparison with Atenolol using group. Whereas, serum

HDL-c concentration was significantly higher in captopril using group.

Conclusion: The overall analysis of the lipid profile parameters studied might suggest that atenolol

has certain undesirable effects on these parameters while captopril has less undesirable effects. This

might indicate that captopril seems to be more suitable antihypertensive agent than atenolol for

patients with lipid profile abnormalities.

Keywords: Serum, lipid profile, triglyceride, total cholesterol, HDL-c, LDL-c, atherogenic index,

hypertension.

الخلاصة

الأهداف:‏ لمعرفة تأثير عقاري الاتنولول والكابتوبريل على بعض فحوصات واجهة الشحوم في مصل الدم تشمل ترآيز

الكوليستيرول،‏ الدهون الثلاثية،‏ البروتين ألشحمي عالي الكثافة،‏ البروتين ألشحمي واطئ الكثافة،‏ ودليل التصلب الشرياني

في مصل الدم).‏

)

© 2010 Mosul College of Medicine 41


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

المرضى والطرق:‏ أجريت هذه الدراسة على مائة مريض مصابين بفرط ضغط الدم.‏ وقد تم تقسيم المرضى إلى مجموعتين

آل مجموعة تتكون من خمسين مريضا.‏ المجموعة الأولى يتناولون عقار الاتنولول وتتراوح أعمارهم من عاما

وبمعدل عاما أما المجموعة الثانية فيتناولون عقار الكابتوبريل لمعالجة فرط ضغط الدم وتتراوح أعمارهم من

عاما وبمعدل عاما.‏ آما شارك في هذه الدراسة مجموعة أخرى تتكون من خمسين شخصا من

الأصحاء الذين لا يتناولون أي عقار وتتراوح أعمارهم من عاما وبمعدل عاما وهم يمثلون مجموعة

الضبط.‏ جميع المرضى المشمولين بهذه الدراسة مصابين بضغط الدم الابتدائي ومشخصين من قبل الأطباء الاختصاصيين

ويتناولون إما عقار الاتنولول أو عقار الكابتوبريل ولا يتناولون أي عقار أخر وليس لديهم إصابة بفرط تدسم الدم في عائلته

ولا يعانون من أي مرض أخر مزمن غير فرط ضغط الدم.‏

النتائج:‏ وجد أن ترآيز الدهون الثلاثية ودليل التصلب الشرياني في مصل الدم أعلى في مجموعة المصابين بفرط ضغط

الدم الذين يتناولون عقار الاتنولول بينما آان ترآيز البروتين ألشحمي عالي الكثافة في مصل الدم اقل في هذه المجموعة

عند مقارنتها بمجموعة الضبط.‏

أما بالنسبة لمجموعة المرضى الذين يتناولون عقار الكابتوبريل فقد آان ترآيز البروتين ألشحمي واطئ الكثافة في مصل

الدم أقل في هذه المجموعة عند مقارنتها بمجموعة الضبط إلى جانب ذلك فقد تمت مقارنة نتائج فحوصات مجموعة

المرضى الذين يتناولون عقار الاتنولول مع مجموعة المرضى الذين يتناولون عقار الكابتوبريل إحصائيا وقد أظهرت هذه

المقارنات أن ترآيز الدهون الثلاثية ودليل التصلب الشرياني في مصل الدم أقل بفرق معنوي في مجموعة المرضى الذين

يتناولون عقار الكابتوبريل مقارنة بمجموعة المرضى الذين يتناولون عقار الاتنولول.‏ من جهة أخرى فان ترآيز البروتين

ألشحمي عالي الكثافة اظهر زيادة إحصائية ذات معنى في مجموعة المرضى الذين يتناولون عقار الكابتوبريل مقارنة

بمجموعة مرضى الاتنولول.‏

الاستنتاج:‏ إن التحليل الإحصائي الكلي لهذه الدراسة يوضح أن عقار الاتنولول له بعض التأثيرات الجانبية غير المرغوبة

على نسب الدهون في الدم،‏ بينما عقار الكابتوبريل فأن تأثيراته الجانبية أقل وانه مناسب أآثر من عقار الاتنولول لمرضى

فرط ضغط الدم خاصة المصابين بخلل في تراآيز الدهون في مصل الدم.‏

٧٤-٣٥

٥٣±٤,٤

٧٢ -٣٥

٥٧

±٦,٠

٥٥ ±٥,٠٢

٨٠-٣٦

A

n elevation of the systolic and/or

diastolic blood pressure increases the

risk of developing heart diseases, kidney

diseases, hardening of the arteries, eye

damage, and even stroke (brain damage)

might happen (1) .

The objective of treating a systemic arterial

hypertension is to reduce the risk of

complications and to improve survival (2) .

The commonly used anti hypertensive drugs

include a lot of drugs with different mechanism

of action. In this study the two most popular

antihypertensive drugs were chosen which are

atenolol and captopril (3) .

Atenolol, a synthetic, β1-selective (cardio

selective) adreno receptor blocking agent is

prescribed for patients with high blood

pressure (4) . Nowadays, the use of beta

blockers was downgraded as antihypertensive

therapy from the first line treatment to the

fourth line as they perform less well than other

new drugs, particularly in elderly (5) .

Captopril is characterized by the presence of

sulfhydryl group in its structure, it is an ACE

inhibitor (6) . The mechanism of action is by

blocking the rennin angiotensin system, that

inhibit the conversion of the inactive

angiotensin I to the powerful vasoconstrictor

and stimulator of aldosterone release,

angiotensin II. This effect results in decrease

of peripheral vascular resistance and also a

reduction in the level of the sodium retaining

hormone aldosterone (7) .

The aim of this study is to find the effects of

atenolol and captopril on certain lipid profile

parameters including serum; total cholesterol

(TC), triglycerides (TG), High density

lipoprotein cholesterol (HDL-c), Low density

lipoprotein cholesterol (LDL-c) and atherogenic

index (AI). Moreover to compare the results of

the effects of the drugs studied on the above

parameters with each other in order to assess

the relative safety of each in comparison to the

other.

© 2010 Mosul College of Medicine 42


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Patient and methods

Patients

This study was approved by ethical committee

in the College of Medicine and Local Health

Authority. One hundred hypertensive patients

of both sexes were included in this study

during a period of 8 months from October 2007

till June 2008. Half of the patients were

controlled using the antihypertensive drug

"captopril" in doses ranging from 25-150

mg/day. The duration of treatment ranged from

6 months to 15 years and their ages ranged

from 36 – 80 years with a mean of 57 years.

The other half of patients were controlled by

using the antihypertensive drug "Atenolol" in a

dose ranging from 50 – 100 mg/day. The

duration of treatment ranged from 6 months to

20 years and their ages ranged from 35 – 74

years with a mean of 55 years.

Patients with a history of hepatic, cardiac or

any other diseases which may interfere with

this study were excluded. Also any patient who

takes drugs other than captopril or atenolol

were also excluded. Moreover diabetic

patients, alcoholics, and those with a family

history of hyperlipidemia were also excluded

from the study.

Control

Fifty apparently healthy individuals aged 35 –

72 years with a mean of 53±4.4 years of both

sexes were included in this study as a control

group (the consent of each volunteer was

taken to give a sample of his blood to be used

as a control). All factors which might interfere

with the study were excluded just like that of

the patient's groups.

Specimens and methods

Overnight fasting blood samples were

obtained from all subjects included in this

study by antecubital venepuncture.

Five milliliters (5 ml) of venous blood sample

from each patient were collected in a plain

tube, allowed to clot for 15 minutes in a water

bath at 37 ºC. Serum was separated by

centrifugation at 3000 rpm for 15 minutes to

ensure complete separation of the serum.

Each sample of serum was used for the

measurement of certain lipid profile

parameters as mentioned. The samples were

stored at – 20 ºC until analysis was done on

daily basis. For accuracy and reproducibility

internal quality control (QC) of pooled serum

was used within the run and within the batch

through out the study.

All biochemical analysis was performed at the

laboratory of higher study in the Department of

Biochemistry, Mosul Collage of Medicine,

University of Mosul.

Serum Total cholesterol (TC) concentration

was determined by enzymatic method (8) , using

a kit supplied by Biomerieux company

(France).

Serum triglycerides (TG) was estimated by

enzymatic method (9) , using a kit supplied by

Biomerieux company (France).

Serum high density lipoprotein cholesterol

(HDL-c) was determined by enzymatic

method (10) , using a kit supplied by Biomerieux

company (France).

Serum low density lipoprotein cholesterol

(LDL-c) is calculated according to the following

equation (11) :

LDL-c= total cholesterol- (HDL-c)-TG/5 (mg/dl)

Atherogenic index (AI) was calculated by the

following equation (12) :

AI = Total serum cholesterol / HDL-c .

Statistical analysis

The experimental data were subjected to

Analysis of Variance, Duncan Multiple Range

Tests, and Trend Analysis using Statistical

Analysis System (SAS) according to Littlell et al.,

(13) .

Results

Table (1) and figure (1) show the results of

comparing lipid profile parameters between the

control group and each of the other groups of

hypertensive patients using atenolol or

captopril.

TC: No significant decrease was observed by

comparing the means of total serum

cholesterol between the group using atenolol

and the control group. The same results found

when comparing total cholesterol in the group

using captopril and the control group (Table 1,

Fig 1).

HDL-c: The mean of serum HDL-c in atenolol

using group showing a highly significant

decrease (P


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

showing no significant decrease in captopril

using group in comparison with the control

group (Table 1, Fig 1).

LDL-c: The mean of serum LDL-c showing a

no significant change in atenolol using group

in comparison with the control group, while in

captopril using group there is a significant

decrease in the mean of serum LDL-c

(P≤0.05) (Table 1, Fig 1).

AI: In the comparison of AI in atenolol using

group with control group there is a significant

increase in atenolol using group (P


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Discussion

In this study, the value of serum total

cholesterol is found to be within normal level in

patient's group using atenolol in comparison

with control group. This result is in agreement

with the result of the study reported by another

author (14) who studied the effects atenolol on

hypertensive patients and found that there is

no significant change in TC in patients who

used atenolol.

In other words, prolonged administration of

atenolol in the recommended dose by

hypertensive patients has no adverse effects

on TC, meaning that atenolol has no effect on

cholesterol metabolism. The mechanism of

this action for β-blockers on lipid parameters is

still not understood (15) .

The result of the present study showed that

HDL-c is significantly lower in patient's group

using atenolol in comparison with control

group. This result agrees with that of many

authors who found that β-blockers cause

decrease in serum HDL-c (15,16,17) .

The decrease in serum HDL-c might be

accounted to be due to the inhibitory effect of

β- blockers on lipoprotein lipase (18) . LPL is

essential for the transfer of phospholipids and

apo-lipoproteins to HDL-c (19) . Others

suggested that atenolol might decrease serum

apo-lipoprotein type AI which is the principle

constituent of HDL-c that is associated with

enhanced reflux of cholesterol from arterial

wall (20) .

When serum LDL-c concentration is

compared between the patient's group using

atenolol and the control group, it is found that

there is an increase in the mean of serum

LDL-c in atenolol using patient's group in

comparison with the control group but this

increase does not reach to significant level.

This result agrees with that of other studies

where atenolol indicated to has no significant

effect on LDL-c (15,17) .

On the other hand, the present result

disagrees with certain study where it is found

that serum LDL-c concentration increased

significantly in patients used β- blockers. This

difference might be attributed to the long

period of treatment in those patients (18) .

The slight increases in the level of serum

LDL-c concentration might be explained by the

effect of atenolol on serum apo-lipoprotien B

which is suggested to be increased by atenolol

administration (21) .

The level of AI is significantly higher in

Atenolol using patient's group in comparison

with the control group. This result is in

agreement with the result obtained by other

authors who found that atenolol causes a

significant increase in total cholesterol / HDL-c

ratio( i.e. AI) (22) , that might be explained by the

significant change in serum HDL-c level by

atenolol in the present study.

The comparison of serum TG level in

patient's group using atenolol with the control

group shows that there is a significant increase

in serum TG level in those using atenolol. This

result is in agreement with that result of other

authors where they found that atenolol causes

hypertriglyceridemia (18, 23) .

On the contrary, the result of this study is in

contrast with results obtained by others who

found that atenolol has no significant effects

on TG (14) . The effect of atenolol on serum TG

may be accounted by that the blockage of β-

adrenergic receptor might affect serum

lipoproteins and the plasma enzymes involved

in the metabolism of serum lipoproteins like

lipoprotein lipase, hepatic lipase and lecithin

cholesterol acyl transferase (16, 18, 24) . A more

clear account suggested that as LPL is a ratelimiting

enzyme in the lipolysis of plasma TGrich

lipoproteins and is bound to

glycosaminoglycans on the surface of the

endothelium in muscles and adipose tissues.

The hydrolytic function of LPL is essential for

the processing of TG-rich lipoproteins and

VLDL to remnant particles and for transfer of

phospho-lipids and apo-lipoprotiens to HDL-c

(25, 26) .

Another opinion that the effects of β-blockers

in inhibiting LPL activity could be due to

altered LPL gene transcription and / or

translation of lipoprotein lipase mRNA or could

be an effect at the protein level of the gene (19) .

Captopril and lipid profile

The value of serum TC in patient's group using

captopril shows no significant difference in

comparison with the control group. This means

© 2010 Mosul College of Medicine 45


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

that captopril has no adverse effect on serum

total cholesterol. The result of the present

study agrees with many other studies which

indicate that captopril causes no change in

serum TC level (27, 28) .

In contrast, the result of the present study

disagree with the result of studies reported that

treatment with captopril caused significant

decrease in serum total cholesterol level (29) .

This difference may be due to the difference in

the sample size.

The result of the present study shows no

significant difference in serum HDL-c level

between captopril using patient's group and

the control group. The effects of captopril on

lipid profile were studied by many

investigators; all showed a similar result to the

present study (27, 30) .

In the present study, the result of serum LDLc

concentration is compared between patient's

group using captopril and the control group. It

shows a significant reduction in serum LDL-c

concentration. This result agrees with that of

others where they found a significant reduction

in serum LDL-c level in captopril using

patient's group when compared with control

(30) . The decrease in serum LDL-c level may be

accounted to be due to an increase in LDL

receptor numbers (30) , or may be due to that

various substances containing thiol group (-

SH) such as glutathione, acetyl cystein or

ACEI (captopril and zofenopril) can inhibit the

free radicals production in atherogenesis

leading to improving the situation of lipids in

the body (31) .

The level of atherogenic index (AI) of

captopril using patient's group shows no

significant difference from the control group.

This result agree with that of Alves et al., (30) ,

who found that there was no significant

decrease in the ratio of serum total cholesterol/

serum HDL-c in patients shared in their study,

this difference may be due to that in their study

the serum TC was significantly decreased by

captopril treatment.

The comparison of serum triglycerides level

in patient's group using captopril with the

control group shows that no significant

difference was found. This result is in

agreement with the results of the following

study done by Scemama et al., (32) .

Nevertheless, the result of the present study

disagrees with that of other investigators who

found that captopril reduced serum TG level

(33, 34) .

This effect on serum TG may be accounted

for that converting enzyme inhibitors have

beneficial effects on insulin and glucose levels

that could be expected to favorably influence

lipids (35, 36) .

Conclusion

The findings, in this study indicate that

Atenolol has some undesirable effects on the

metabolism of lipids whereas Captopril has

less undesirable effects on the metabolism of

lipids. Accordingly Captopril may be regarded

more suitable antihypertensive drug for

patients with hyperlipidemia than Atenolol. We

recommend that patients who are on Atenolol

treatment should have periodic measurements

and follow up of lipid profile parameters.

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gastrointestinal therapeutic system in the

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

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Triglyceride stability in whole blood

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Cholesterol determination in HDL

separated by three different methods. Clin

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ultracentrifuge. Clin Chem. 1972; 18: 499-

502.

12. Schulpis K, Karikas GA. Serum

Cholesterol and Triglyceride Distribution in

7767 School-aged Greek Children.

Pediatric. 1998; 101( 5): 861-4.

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Linear Models, 4 th ed. Cary NC; SAS

Institute Inc: USA; 2002.

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Kardasz I, Huang Y, Taddoi S. Salvetti

A. Different effect of Antihypertensive

Drugs on Conduit Artery Endothelial

Function, Hypertension. 2003; 41: 1281- 6.

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Adrenoceptor antagonist drugs. Basic and

Clinical Pharmacology 10 th ed. New York,

USA: McGraw Hill Company; 2007.

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Short-term effects of beta-blockers

atenolol, nadolol, pindolol, propranolol on

lipoprotein metabolism in normolipidemic

subjects. J Clin Pharmacol. 2007; 17: 475-

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17. Middeke M, Richter WO, Schwandt P,

Beck B, Halzgreve H. Normalization of

lipid metabolism after withdrawal from

antihypertensive long-term therapy with

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Assoc. 2001; 10: 145-7.

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adrenergic receptor blockers on lipid

during antihypertensive drug treatment. J

Clin Pharmac. 2000; 33(3): 286-9.

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Reymer BSC, Eric G. Genetic variant

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on lipoprotein lipase activity. Circulation.

2000; 95: 2628-35.

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Haenni A, Byberg L, Lithell H. Induction of

insulin resistance by β-blockade but not

ACE-Inhibition:long-term treatment with

atenolol ortrandolapril. J Hum Hypertens.

2000; 14(3): 175-80.

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Effect of losartan, compared with atenolol,

on endothelial function and oxidative

stress in patients with type 2 diabetes and

hypertension. J Hypertension. 2007; 25(4):

785-91.

22. Chopra HK, Krishna CK, Ravinder

SS,Komal KK. Non-cardiac effects of

atenolol. Supplement of JAPI. 2009; 57:

26-8.

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Loukianos S, Necolas H, Alex D. LDL sub

fraction in patient with myocardial

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313-8.

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Olivecrona G. Lipoprotein lipase enhances

the binding of chylomicrons to low density

lipoprotein receptor related protein. Proc

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25. Lalouel JM, Wilson DE, Iverius PH.

Lipoprotein lipase and hepatic triglyceride

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Lipoprotein lipase and hepatic lipase. Curr

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Rilmenidine in the hypertensive type 2

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an innovative antihypertensive treatment.

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Kalil N, Thomas A. Effects of

antihypertensive therapy on serum lipids.

An Intern Med. 2000; 122: 133- 41.

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

30. Alves RJ,Diament J, Amancio RF, Forti N,

Maranhae R. Lack of effect of captopril on

the metabolism of an artifical lipid

emulsion similar to chylomicrons in

hypertensive hypercholestrolemic patients.

Arq Bras cardiol. 2004; 83(6): 512-5.

31. Wojciech W, Jan G, Krzysztof S. The

influence of ACE inhibitors on aorta elastin

metabolism in diet induced

hypercholesterolemia in rabbits. J Renin –

Angiotens- Aldost Sys. 2001; 1: 37- 41.

32. Scemama M, Fevrier B, Beucler I and

Divon F. Lipid profile and antihypertensive

efficacy in hyperlipidemia hypertensive

patient comparison of rilmenidine and

captopril. J Cardiovas Pharmacol. 1996;

26: 34-9.

33. Kost CK, Rominski BR, Herzer WA,

Jakson EK, Toforic SP. Persistent

improvement of cardiovascular risk factor

in spontaneously hypertensive rats

following early short term captopril

treatment. Clin Exp Hypertens. 2000; 22:

127- 43.

34. Robert WC. Effects of beta blockers on

blood lipid levels. Am Heart J. 2001; 132:

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35. Berne C. Metabolic effects of ACE

inhibitors. J Intern Med. 2000; 239: 119-

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36. Paolisso G, Gambardella A, Verza M,

Amor A, Sgambato S, Varricchio M. ACE

inhibitors improve insulin sensitivity in

aged insulin resistant hypertensive

patients. J Hum Hypertens. 2002; 16: 175-

9.

© 2010 Mosul College of Medicine 48


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Accuracy of clinical scores in differentiating

stroke subtypes in Mosul

Hakki Mohammed Majdal*, Khalid Gh. Hameed Al-Abachi**, Mahmood Mal-Allah***

* Neurologist, ** Interventional cardiologist, *** Consultant Cardiologist, Ibn-Sina Teaching Hospital.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 49-55).

Received: 17 th Nov 2009; Accepted: 9 th Feb 2011.

ABSTRACT

Objectives: To study the validity of clinical scores in differentiating intracerebral hemorrhage and

ischemic stroke and to see which of them is more applicable in our hospitals.

Methods: A prospective study of 100 consecutive patients with acute neurological deficit admitted as

inpatient to the neurological unit in Ibn-Sina Teaching Hospital in the city of Mosul, evaluated with

computed tomography and Allen and Siriraj scores to determine the pathological type of stroke

during the period from September 15 th 2008 and January 28 th 2009.

Results: The prevalence of hemorrhage (diagnosed with computed tomography) was 19%. Allen

scores were "uncertain" in 13 cases and Siriraj scores in 17 cases; Sensitivity, specificity, positive and

negative predictive values, for haemorrhage were 0.53, 0.96, 0.77 and 0.90, for Allen scores and

0.79, 0.97, 0.88, and 0.95 for Siriraj scores; such values for infarction were 0.91, 0.89, 0.97, and 0.71

for Allen scores and 0.80, 0.95, 0.98 and 0.53 for Siriraj scores.

Conclusion: When CT-Scan is not immediately available and the clinician wishes to start

antithrombotic treatment, the Siriraj score (and possibly the Allen score) can be useful to identify

patients at low risk of intracerebral hemorrhage and The Siriraj score is simple, cheap, reliable and

practical method which can be used immediately after the stroke.

Keywords: Ischemic stroke IS, intracerebral hemorrhage ICH, computerized tomography (CT-Scan),

Allen Hospital score (AS), Siriraj stroke Score (SS).

الخلاصة

الهدف من البحث:‏ لدراسة مصداقية المقاييس السريرية في التفريق بين السكتة الدماغية التعطشية والنزف داخل المخ،‏

ومعرفة أي من المقاييس أآثر عملية للتطبيق في مستشفياتنا.‏

الوسائل:‏ الدراسة شملت مريض آانوا يعانون من خلل عصبي حاد،‏ أدخلوا وحدة الإمراض العصبية في مستشفى

ابن سينا التعليمي في الموصل للفترة من ‎٢٠٠٨/٩/٢٥‎م ‎٢٠٠٩/١/٢٨‎م،‏ وأجري لهم فحص مفراس الدماغ وقيمت

حالاتهم بواسطة آلا المقياسين ألين وسيريراج لتحديد نوع السكتة الدماغية أهي تعطشية أم نزف داخل المخ.‏

النتائج:‏ نسبة حدوث النزف داخل المخ ‏(المشخص بواسطة جهاز المفراس)‏ آانت مقياس ألين آان غير واضح في

من الحالات،‏ بينما مقياس سيريراج آان غير واضح في من الحالات بينما آانت الحساسية والدقة والقيمة

على التعاقب،‏ بينما آانت

التنبؤية الموجبة لحالات النزف داخل المخ حسب مقياس ألين هي

أما لحالات السكتة الدماغية التعطشية فكانت

حسب مقياس سيريراج هي

(٠,٩٧) حسب مقياس ألين على التعاقب وآانت حسب مقياس سيريراج

الاستنتاجات:‏ في حالة عدم التمكن من إجراء فحص المفراس بصورة فورية للمرضى وعند رغبة الطبيب المعالج بإعطاء

علاج مانع التخثر،‏ مقياس سيريراج ‏(ومن الممكن أيضا مقياس ألين)‏ يمكن أن يكون مفيدا لتحديد المرضى ذو الخطورة

.%١٩

%١٧

(٠,٧٧) (٠,٩٦) (٠,٥٣)

(٠,٨٩) (٠,٩١)

(٠,٨٠) (٠,٩٥) (٠,٩٨) على التعاقب.‏


.(٠,٨٨) (٠,٩٧) (٠,٧٩)

١٠٠

%١٣

© 2010 Mosul College of Medicine 49


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

الأقل للإصابة بنزف داخل المخ.‏ مقياس سيريراج هو مقياس بسيط،‏ غير مكلف،‏ عملي ومن السهل استعماله مباشرة بعد

حصول السكتة الدماغية

.

S

troke was defined as rapidly developing

clinical signs of focal disturbance of

cerebral function, lasting more than 24 hours

or leading to death with no apparent cause

other than that of vascular origin (WHO

definition (1) ).

It is not possible for all stroke patients in Iraq

to have a computed tomography scan (CT

scan) immediately, (even sometimes not

obtainable at all), for two reasons: first, lack of

this tool in most of our hospitals; second -

especially at the time being - transporting

patients between hospitals may be hazardous

or not allowed because of curfew. The ability

to classify stroke would improve understanding

of the nature of stroke and provide clues to its

etiology which would be useful for potential

interventions in the acute stage. In such

situations, the clinical diagnosis is often the

only way to differentiate between hemorrhagic

and ischemic stroke. Considering the

unreliability of clinical assessment in

diagnosing the type of stroke. (2 - 5) , scoring

systems were devised to assist physicians

without easy access to CT scanning facilities

to improve the accuracy of the clinical

diagnosis of acute stroke.

The two scoring protocols produced by

Allen (6) (also known as Guy's Hospital score

(AS)) in 1983 and Poungvarin et al (Siriraj

Stroke Score (SS)) in 1991 (7) are the common

ones that are currently used in clinical practice

and have been validated against both

postmortem and CT scan results. They are

designed to give an objective score based on

clinical variables shown to be significantly

different between hemorrhagic and ischemic

strokes. (8) (Appendix)

These two scores require the least testing

and investigation and appear to be simple to

use. The SS only requires a history and clinical

examination, whereas the AS requires a chest

x-ray and electrocardiogram in a addition.

The aim of this study is to validate the above

mentioned clinical scores in acute stroke

patients, and to compare their applicability in

our practice.

Patients and methods

This study was approved by ethical committee

in the Local Health Authority. A prospective

study which included 129 consecutive patients

with an acute neurologic deficit studied during

the period between September 15 th 2008 and

January 28 th 2009. The patients were

admitted as inpatients to neurology unit in Ibn

Sina Teaching Hospital in Mosul. Consent was

taken from all patients and their relatives after

explanation.

Patient's assessment included careful history

and thorough physical and neurological

examination including proper evaluation by a

cardiologist.

The following investigations were made for

each patient: CBP and ESR, FBS, renal and

liver function tests, serum electrolytes, serum

lipid profile, ECG, CXR, and

echocardiography. Both scores were

calculated for each patient. The final clinical

diagnosis was determined before any imaging

is made. CT scans taken were within 15 days

of the event were included in the study to

eliminate the possible misdiagnosis of

resolving intra cerebral hemorrhage as

ischemic stroke (9) .

Twenty nine patients were excluded from the

study; 25 of them, due to inability to perform a

CT-scan (3 of them died before doing CT

scan), two proved to have brain tumor, one

found to have focal deficit due to

hypoglycemia and another one due to

brucellosis. We combined subarachnoid

hemorrhage (SAH) and cerebral hemorrhage

as “intracerebral hemorrhage (8,10) .

The scores were compared in terms of

"certain" results (i.e. percentages of cases in

which the scores predicted ischemia or

hemorrhage, according to the cut offs

suggested in the original papers (6,7) ). A result

was considered to be certain when the Allen

score was 24 or the Siriraj score was


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

1 or >1. The two scores were compared with

the results of computed tomography, and

sensitivity, specificity, positive predictive value,

negative predictive value, and likelihood ratio

were calculated using standard formulas and

significances determined by using z-test of two

proportion (11) .

We included the “uncertain” results, i.e. The

results that did not yield a definite answer of

ICH or IS, in the analysis, as negative because

both sensitivity and specificity may be

increased by excluding these results (8) .

Results

A wide range of ages was found (32 to 88

years), with a mean age for all patients of 64.3

years ± 10.43 (men, 63 years ± 11.35;

women, 65.5 ± 9.25 years); male (58 cases) to

female(42 cases) ratio was 1.38.

CT scan showed IS in 81% of cases, and ICH

in 19% of patients (2 cases had SAH).

In comparison with the CT scan result,

applying the recommended optimum cutoff

points for each scale, the cases with definitive

diagnoses were classified by the AS and SS

scales as probable ICH (13% and 17%,

respectively) or probable IS (76% and 66%,

respectively). The remainder were classified

as uncertain as seen in (table1).

As seen in table 2, after excluding uncertain

cases, percentage of true infarction for both

scores were more than 97% in comparison to

brain CT scan result and differences in the

diagnosis made by the above two methods

(between scores and CT scan) was

insignificant.

The results for the AS score as shown in

table 3 had a sensitivity of 53% and a

specificity of 96% for ICH. The positive

predictive value for ICH was 77%). For IS, the

AS score had a sensitivity of 80%, a specificity

of 96%, and a positive predictive value of 99%.

The results for ICH in SS score had a

sensitivity of 79%, a specificity of 98%, and a

positive predictive value of 88%. For ischemic

stroke, the SS score had a sensitivity of 80%,

a specificity of 90%, and a positive predictive

value of 97%.

Table (1): Predicting ICH and IS With the AS

and SS in comparison with CT scan.

Infarction Hemorrhage Uncertain

SS 66 (66%) 17 (17%) 17 (17%)

AS 76 (66%) 13 (17%) 11 (17%)

CT result 81 (81%) 19 (19%)

Table (2): Percentage of true and false result in both methods of certain cases only compared with CT

scan.

True IS False IS CT Results p-value True ICH False ICH CT Results p-value

AS 74 (97.6%) 2 (2.6%) 76 =0.155* 10 (76.9%) 3 (23.1%) 13 =0.066*

SS 65 (98.5%) 1 (1.5%) 66 =0.315* 15 (88.2%) 2 (11.7% ) 17 =0.145*

* = insignificant

Table (3): Performance of the SS and AS in diagnosing Intracranial hemorrhage compared with the

brain imaging.

sensitivity

specificity

positive

predictive

value

negative

predictive

value

Positive

likelihood

ratio

negative

likelihood

ratio

ICH (AS) 0.53 0.96 0.77 0.90 13.2 0.5

ICH (SS) 0.79 0.97 0.88 0.95 31.6 0.05

IS (AS) 0.91 0.89 0.97 0.71 9 0.1

IS (SS) 0.80 0.95 0.98 0.53 15 0.2

© 2010 Mosul College of Medicine 51


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Discussion

The conventional bedside diagnosis of stroke

subtypes is said to be inaccurate (11) . It raised a

lot of conflicts. Aring and Merrit, Dalsgaad

Nielson, Heasman and Lipworth, Schaafsma,

and Harrison all reported conflicting results

about the clinical features that distinguish

cerebral hemorrhage from infarction (12-16) . On

the other hand the scoring methods are said

to be more accurate (6) but our study as others

shows that these scores do not diagnose the

cases as being certain infarction or certain

hemorrhage. Since missing diagnosis of ICH

has more grave consequences than that of

infarction in acute treatment of stroke (first of

all do not harm the patient) (8) . Using both

scores may slightly increase the accuracy,

however the Allen score can be calculated only

after 24 hours.

The findings suggest that these two

commonly used, validated clinical scoring

systems have sufficient sensitivity to allow

classification of stroke into the two main types,

hemorrhagic or ischemic, although the

sensitivities for the detection of hemorrhage

were 53% and 79% for the GHS and SHS

scores, respectively.

The SS performed marginally better than the

GHS and had a much higher sensitivity for

detecting ICH. Reversely GHS more sensitive

in diagnosing IS (91% vs 80%).

We have compared our findings with those

found in other regions of the world (7,8,11,17-26)

and values were similar to the results of the

some studies but differed from others. A

higher sensitivity, specificity, and positive

predictive value for the SS in detecting

intracranial hemorrhage was shown in the

study than was found in most of other

population. This was despite the high

proportions of intracranial hemorrhage

especially in those studies from Africa (47% ,

59%,32%) (17,18,26) , compared with our study

(17%). This probably reflects patient selection

and the limitations of a retrospective study

design rather than a true difference in the

performance of the SS, where missing

variables in the calculations were adjusted to

zero and score will over diagnose infarction.

The other reason may relate to that the

scoring systems are for epidemiological

classification (as occur in retrospective study)

or for clinical trials in which the intention is to

eliminate hemorrhagic strokes. Exclusion of

“uncertain” cases as seen in studies from

Thailand (7) and Hong Kong (China) (23) , they

have better sensitivity than our study because

both sensitivity and specificity will increase by

excluding these results (8) .

The most appropriate studies for comparison

with our study are those from Malaysia (24) and

SouthAfrica (26) . They were also prospective

studies that included “uncertain” results in the

analysis. We found the SS had a higher

sensitivity and positive predictive values for

detecting intracranial hemorrhage from both of

them, but the specificity were nearly similar in

above mentioned two studies.

Although the AS has shown a high specificity

and a fair positive predictive value in the

diagnosis of intracranial hemorrhage, the

sensitivity was low. Together with studies from

Italy (19) , SouthAfrica (26) and New Zealand (8)

they found the lowest sensitivity (0.31, 0.34 to

0.38) respectively for detecting intracranial

hemorrhage using the AS. It has been

suggested that the AS was developed with

relatively young patients with stroke (under the

age of 76 years) and therefore AS had low

sensitivity in a population with a higher

prevalence of intracranial hemorrhage (8) .

In our study, the SS was more accurate at

diagnosing IS than in Nigeria (17) , Ethiopia (18)

and New Zealand

(8) . Our findings for

sensitivity, specificity, and positive predictive

value are remarkably consistent with those

found in studies from Pakistan, India, and

Hong Kong.

The accuracy of the AS in diagnosing

ischemic stroke in our study was good when

compared with previous studies. The AS score

places far more emphasis on measures of

atherosclerosis than the SS does. Perhaps it

performs better in populations in which

atherosclerosis is an important cause of

ischemic stroke.

The limitations of the scoring system should

be understood. If a patient or his relatives

cannot give a clear description of the

symptoms of the ictus, the score will tend to

© 2010 Mosul College of Medicine 52


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

overestimate the likelihood of infarction. Many

of the symptoms used in the score as being in

favor of ICH (loss of consciousness at onset,

early headache, vomiting) may develop later

in IS due to brain edema. If the time onset of

such symptoms was not accurate, patients

with IS wrongly diagnosed as ICN (8) . Also

patients with brainstem infarction tend to have

symptoms which may suggest hemorrhage (8) .

On the other hand patients with small deep

hematomas may present under the clinical

guise of cerebral infarction (8) . This occur in 2

cases of our study.

In conclusion, for great areas of Iraq,

thrombolytic and anticoagulation are available

only for few patients. A score that excluded

significant intracranial hemorrhage would

encourage doctors in remote areas to initiate

aspirin therapy early. It is unlikely that any

score will replace brain imaging, and we would

encourage investment in CT scanners. Where

this is impossible and the treatment of stroke

therefore limited, scoring system is the second

best means (after CT or MRI) in differentiating

cerebral hemorrhage from infarction in Iraqi

patients. The Siriraj score is simple, cheap,

reliable and practical method, and can be used

immediately after the stroke, (but the Allen

score can be calculated only after 24 hours)

and has a 98% positive predictive value for

ischemia. When clinicians wish to start

antiplatelet antithrombotic treatment (aspirin or

heparin) while waiting for the scan results, they

can rely on the Siriraj score.

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11. Beaglehole R, Bonita R, Kjellström T.

Basic Epidemiology. Geneva, Switzerland:

World Health Organization; 1993.

12. Aring GCD, Merrit MH. Differential

diagnosis between cerebral hemorrhage

and thrombosis. Arch Intern Med 1935; 56:

435-456.

13. Dalsgaard,Nielson T.Survey of 1000 cases

of apoplexia cerebri. Acta Neurol Scand

1956; 30:160-185.

14. Heasman MA, Lipworth L. Accuracy of

Certification of Causes of Death. London:

HMSO,1966.

15. SchaafsmaS.On the Differential diagnosis

between cerebral hemorrhage and

infarction Neurol Sci 1968;7:83-95.

16. Harrison MJG. Clinical distinction of

cerebral hemorrhage and cerebral

infarction. Postgrad Med J 1980; 629-623.

© 2010 Mosul College of Medicine 53


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

17. Ogun SA, Oluwole SOA, Oluremi A,

Fatade AO, Ojini F, Odusote KA. Accuracy

of the Siriraj Stroke Score in differentiating

cerebral haemorrhage and infarction in

African Nigerians. African Journal of

Neurological Sciences. 2001; 20:21–26.

18. Zenebe G, Asmera J, Alemayehu M. How

accurate is Siriraj Stroke Score among

Ethiopians? A brief communication. Ethiop

Med J. 2005;43:35–38.

19. Celani MG, Righetti E, Migliacci R,

Zampolini M, Antoniutti L, Grandi FC, Ricci

S. Comparability and validity of two clinical

scores in the early differential diagnosis of

acute stroke. BMJ. 1994;308:1674–1676.

20. Badam P, Solao V, Pai M, Kalantri SP.

Poor accuracy of the Siriraj and Guy’s

Hospital stroke scores in distinguishing

haemorrhagic from ischaemic stroke in a

rural, tertiary care hospital. Natl Med J

India. 2003;16:8–12

21. Kochar DK, Joshi A, Agarwal N, Aseri S,

Sharma BV, Agarwal TD. Poor diagnostic

accuracy and applicability of Siriraj Stroke

Score, Allen score and their combination

in differentiating acute haemorrhagic and

thrombotic stroke. J Assoc Physicians

India. 2000;48:584–588.

22. Shah FU, Salih M, Saeed MA, Tariq M.

Validaty of Siriraj Stroke Scoring. J Coll

Physicians Surg Pak. 2003;13:391–393.

23. Hui AC, Wu B, Tang AS, Kay R. Lack of

clinical utility of the Siriraj Stroke Score.

Intern Med J. 2002;32:311–314.

24. Kan CH, Lee SK, Low CS, Velusamy SS,

Cheong I. A validation study of the Siriraj

Stroke Score. Int J Clin Pract. 2000; 54:

645–646.

25. Akpunonu BE, Mutgi AB, Lee L, Khuder S,

Federman DJ, Roberts C. Can a clinical

score aid in early diagnosis and treatment

of various stroke syndromes? Am J Med

Sci. 1998;315:194–198.

26. Connor D, Modi G, Charles P. Accuracy of

the Siriraj and Guy’s Hospital Stroke

Scores in Urban South Africans. Stroke

2007; 38;62-68.

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Appendix

Calculation of Siriraj score

*Consciousness (x2.5) (Alert 0, Drowsy or stupor 1, Semicoma or coma 2)

*Vomiting (x2) (No 0, Yes 1)

*Headache within two hours (x2)( No 0,Yes 1)

*Diastolic blood pressure (x0.1)

*Atheroma markers (x3) Diabetes, angina, intermittent claudication(None 0, One or

more 1

*Constant -12

Hemorrhage (>89% certainty), score greater than +1; ischemic stroke (>93% certainty), score less than -1; and

uncertain, score of -1 to +1.

Calculation of Allen score

*Apoplectic onset: Loss of consciousness, Headache within two hours, Vomiting

Neck stiffness (None or one 0, Two or more 21.9)

*Level of consciousness (24 hours after admission)

( Alert 0, Drowsy 7.3, Unconscious 14.6)

*Plantar responses Both flexor or single extensor 0, Both extensor 7.1

*Diastolic blood pressure(x0.17)

*Atheroma markers Diabetes, angina, intermittent claudication(None 0,One or more-

3.7)

*History of hypertension Not present 0, Present -4.1

*Previous event TIA (None 0 , Any number of previous events -6.7)

*Heart disease None O, Aortic or mitral murmur -4.3 , Cardiac failure -4.3,

Cardiomyopathy -4.3, Atrial fibrillation -4.3, Cardiomegaly -4.3, Myocardial

infarct within six months -4.3)

*Constant -12

Hemorrhage (>90% certainty), score greater than +24; ischemic stroke (>90% certainty), score less than +4; and

uncertain, score of +4 to +24.

© 2010 Mosul College of Medicine 55


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

The effects of pulse pressure on left atrium and

left ventricle geometry in hypertensive patients

Arwa M. Fuzi Alsaraf

Department of Medicine, College of Medicine, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 56-62).

Received: 13 th Oct 2010; Accepted: 9 th Feb 2011.

ABSTRACT

Objectives: An increased pulse pressure (PP) suggests aortic stiffening. New evidence suggests that

(PP) is more sensitive measure of cardiac risk than other indexes of blood pressure.

We aim to study the effect of pulse pressure in hypertensive patients on left atrial and left ventricle

diameters (LAD, LVD), left ventricle geometry [wall thickness (WT), left ventricle mass (LVM), regional

wall thickness (RWT)] and the effects of age and sex on the PP.

Methods: Echocardiography study of LAD, LVD, left ventricle end diastolic diameter (LVEDD), aortic

root diameter (ARD), ratios and left ventricle geometry was performed on 92 patients (61 female & 31

male). A correlation analysis between these variables and pulse pressure was done. Patients were

grouped into high PP >60 mmHg and normal PP p

الطبيعي p

٥٢

© 2010 Mosul College of Medicine 56


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

C

urrent guidelines for the diagnosis and

management of hypertension have

defined cardiovascular risk by the elevation of

systolic blood pressure (SBP) and/or the

elevation of diastolic blood pressure (DBP) (1,2) .

Recently research has focused on the relation

between cardiovascular diseases and elevated

pulse pressure (PP) which apparently reflects

increased large artery stiffness (3,4) . The

principal components of blood pressure (BP)

consist of both a steady component (mean

arterial blood pressure MAP) and a pulsatile

component (pulse pressure PP). Major

determinants of MAP are ventricular ejection

and peripheral vascular resistance (1,5) . PP, the

difference between SBP and DBP, is also

made up of two major components one due to

ventricular ejection and the elastic properties

of the large arteries (direct) and the other due

to wave reflection (indirect). The rise in SBP

and DBP in middle aged and elderly subjects

is due primarily to an increase in large artery

stiffness and an associated increase in wave

reflection amplitude (1) .

In older people, observational studies have

commonly found U or S shaped relationship of

BP with mortality especially for DBP; in some

studies, individuals with the lowest BP had the

highest mortality. It is possible that the PP is

the measure of BP most strongly related to

cardiovascular risk in elderly people. Several

prospective studies have found that elevated

PP is associated with risk of myocardial

infarction, congestive heart failure and

cardiovascular total mortality. It also increases

the risk of stroke as a consequence of arterial

stiffness and left atrial dilatation and

subsequent risk of atrial fibrillation (6-8) .

As shown in the study (pulse pressure and

mortality in older people 2000), PP appears to

be the best single measure of BP in predicting

mortality in older people (6) .

The exponential rise in atrial fibrillation

incidence with age parallels a rapid age

related increase in aortic stiffness (9) . The

concomitant increase in PP adds to pulsatile

load on the heart (10) , thereby promoting

ventricular hypertrophy (9,11,12) , impaired

ventricular relaxation (13,14) and increased left

atrial (LA) size (11) . This all together may lead to

fibrosis and electrical remodeling in the

atrium (9) , leading to atrial fibrillation. Consistent

with this causal pathway, echo measures of

abnormal left ventricle (LV) geometry and

diastolic dysfunction are associated with

increased risk of atrial fibrillation (15,16) .

Increased LAD/LVD ratio was observed in

subjects with hypertension, diabetes and LV

hypertrophy (17) . Increased ratio predicted

worse exercise capacity. These data are

consistent with the hypothesis that this ratio is

a non invasive marker of LV diastolic pressure

– volume relationship (17) .

It is shown that PP is an independent

predictor of increased incidence of coronary

heart disease and congestive heart failure (18) ,

accordingly, the PP may represent an easily

measured and potentially modifiable risk factor

for cardiovascular risks.

Our objective is to measure the pulse

pressure in hypertensive patients with different

ages and sex and to study its effect on left

atrium diameter (LAD), left ventricle geometry

{including left ventricle diameter (LVD), left

ventricle wall thickness (WT), left ventricle

mass (LVM) and regional wall thickness

(RWT)}, the ratio between LAD and both aortic

root and LV diameters.

Patients and methods

This is a patient based cross section

correlation and case control study. It began in

October 2009 and ended in May 2010. One

hundred twenty hypertensive males and

females aged between 30 and 78 year old

were enrolled.

Study sample and data collection

From October 2009 until May 2010 we

recruited 120 patients with history of

hypertension or receiving anti-hypertensive

medications for 3 years or more, visiting the

echography clinic in Ibn Sina Teaching

Hospital in Mosul for different medical and preoperative

checking indications.

Thorough history was taken including history

of hypertension or antihypertensive medication

for the last 3 years.

After taking a written consent from the

patients, recordings of SBP and DBP were

taken in the supported right arm of lying

© 2010 Mosul College of Medicine 57


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

subject, after 5 minutes of quiet rest, using a

mercury column sphygmomanometer.

Readings were recorded to the nearest even

number. SBP was recorded at the first

appearance of Korotkoff sounds and palpation

was used to check auscultatory systolic

readings. DBP was recorded at the

disappearance (phase 5) of Korotkoff sounds.

Baseline SBP and DBP each were the

average of two separate measurements taken

by the examining physician.

A standardized 2- dimensional guided M-

mode echocardiogram was performed at

baseline examination. The following data were

obtained: diastolic LAD, aortic root diameter

(ARD), LV end diastolic diameter (LVEDD),

septal thickness (ST), posterior wall thickness

(PWT) and ejection fraction (EF).

A standard 12 leads ECG was taken.

The patients with EF less than 55% and

those with evidence of acute coronary

ischemia or previous myocardial infarction

were excluded from the study; the remaining

92 patients were included.

The mean of ST and PWT for each patient

was calculated, and considered as WT, normal

(< 12.5 mm). The LAD was measured, normal

(


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Table (1): Comparison of normal and abnormal values of both PP groups.

WT

RWT

LVM

LAD

LVEDD

LAD//ARD

LAD/LVEDD

Pulse pressure

60 mmHg

(%)

increased 19 (51%) 36(65%)

normal 18 (49%) 19(35%)

increased 21 (56%) 38 (69%)

normal 16 (44%) 17 (31%)

increased 15 (40%) 43 (78%)

normal 22(60%) 12 (22%)

increased 9 (24%) 36 (65%)

normal 28 (76%) 19 (35%)

small 23 (62%) 38 (69%)

large 14 (38%) 17 (31%)

increased 14 (38%) 31 (56%)

normal 23 (62%) 24 (44%)

increased 17 (46%) 32 (58%)

normal 20 (54%) 23 (42%)

p-value

0.176

0.226

0.00*

0.26

0.49

0.08

0.24

Chi- square test used

*p-value considered significant

Table (2): Correlation analysis between pulse

pressure and other variables.

Pulse

pressure

correlated

with

(r)= correlation coefficient

* = significant at 0.05

Mean Std (r)

P value

Sig (2-

tailed)

Age 52.3 10.96 0.390 0.00*

LAD 29.39 3.89 0.169 0.106

LVEDD 44.29 3.79 0.39 0.714

WT 12.94 1.69 0.236 0.024*

LAD/ARD 1.193 0.19 0.016 0.881

LA/LVEDD 0.662 0.091 0.252 0.121

LVM 216.92 50.2 0.249 0.017*

RWT 0.582 0.09 0.185 0.078

From the high PP group 36 pt (65%) had

enlarged LA. Compared to 9 pt (24%) from low

PP group, (p value =0.29) (table 1). Although

there was higher percentage of pt with high PP

have enlarged LA, this was statistically

insignificant. Furthermore the correlation

analysis showed no significant correlation

between PP & LAD. P value= 0.106 (table 2).

Thirty eight patients (69%) of high PP had

small ventricles, compared to 23 (62 %) of low

PP (P value= 0.491) (table 1).

The LAD/ARD ratio appears to be higher in

high PP group but it is statistically insignificant,

(p value = 0.08) (table 1). Correlation study

also shows no significant correlation, (p

value=0.88) (table 2).

The LAD/LVEDD ratio was studied. Of high

PP group 32pt (58%) had high ratios,

compared to 17 pt (46%) of low PP group. (P

value =0.24), (table1). No significant

correlation was found between PP and this

ratio by correlation analysis (p value =0.25)

(table 2).

No significant correlation was found between

PP & RWT, (p value> 0.05) (table 1, table 2).

The correlation analysis between the PP and

each of the above studied variables is shown

in (table 2). There is a positive correlation

between PP and age, WT, LVM in total and

LVM in female. There is no correlation

between PP and LAD, LAD/ARD ratio,

LAD/LVEDD ratio, and PP with RWT.

There was a significant positive correlation

between SBP and RWT, (p value= 0.0116). No

significant correlation was found between SBP

and the other parameters.

© 2010 Mosul College of Medicine 59


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

There was significant negative correlation

between DBP and age (p value =0.004).

Although there was negative correlation of PP

with WT, LAD/ARD, LAD/LVEDD, LVM, LA, LV

and RF, but it was statistically not significant (p

value > 0.05), also there was insignificant

positive correlation with RWT, (p value 0.156)

(table 4).

The SBP was positively correlated with both

DBP and PP, (p value< 0.05) (table 3).

Table (3): Correlation analysis between SBP

and other variables

SBP correlated with (r) P value

Age 0.185 0.077

LAD 0.126 0.231

LVEDD 0.011 0.917

WT -0.172 0.101

LAD/ARD -0.061 0.563

LAD/LVEDD 0.086 0.415

LVM 0.144 0.170

RWT 0.262 0.011*

PP 0.828* 0.00*

DBP 0.532* 0.00*

(r)= correlation coefficient

* = significant at 0.05

Table (4): Correlation analysis between DBP

and other variables.

DBP correlated with (r) P value

Age -0.297* 0.004*

LAD -0.098 0.352

LVEDD -0.031 0.769

WT -0.037 0.726

LAD/ARD -0.131 0.213

LAD/LVEDD -0.061 0.56

LVM -0.036 0.73

RWT 0.149 0.156

PP -0.021 0.84

(r)= correlation coefficient

* = significant at 0.05

Table (5): Correlation analysis between LVM

and other variables.

LVM correlated with (r) P value

LAD 0.478 0.00*

LVEDD 0.405 0.00*

WT 0.082 0.43

LAD/ARD 0.282 0.006*

LAD/LVEDD 0.218 0.03*

RWT 0.340 0.00*

Age 0.275 0.007*

(r) = correlation coefficient.

* = significant at 0.05

Discussion

This study shows significant positive

correlation between age and PP, (p value =

0.000), and negative correlation between DBP

and age (p value= 0.004). Although the SBP

has positive correlation with age, but it is

statistically insignificant (p value = 0.07).

As large artery stiffness increases in middle

aged and elderly, SBP rises and DBP falls,

with a resulting increase in PP (26) . The

normally present higher gradient of peripheral

to central arterial PP (amplification) found in

young subjects gradually decreases with aging

as a result of the augmentation of central PP

by early wave reflection (27) .

As shown in table 3 & 4 the SBP was

significantly positively correlated with both

DBP&PP (p value=0.000). DBP was negatively

correlated with PP, but it was an insignificant

correlation (p value= 0.84). So in our study the

PP is mainly determined by the high SBP

rather than low DBP.

As vascular resistance rises, there is

proportional increase in SBP and DBP in

young individuals. With the onset of middle

age, however, SBP rises more than DBP,

resulting in elevation of PP (26,28) . Thus, DBP

rises with increased peripheral arterial

resistance and falls with increased central

artery stiffness; the relative contributions of

these 2 opposing forces determine DBP and

ultimately PP. Normally, PP & SBP are highly

correlated because both BP components rise

with increases in vascular resistance and large

artery stiffness (1) . Determinants of PP include

© 2010 Mosul College of Medicine 60


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

ventricular ejection and stroke volume, but the

age dependent increase in PP is largely

determined by the increase in stiffness in large

arteries (21) . Recently, it was shown that

telomeres, the ends of chromosomes, which

serve as clocks of cellular aging, are inversely

related to PP (21,22,23) . Therefore, pp might serve

as a phenotype of chronological and biological

aging (21) .

The WT is positively correlated with PP (p

value


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

4. Psaty BM, Furberg CD, Kuller LH, et al.

Association between blood pressure level

and the risk of myocardial infarction,

stroke and total mortality. Arch Intern Med.

2001; 161:1183-1192.

5. Nicholas WW, O' Rourk MF, McDonald' s.

blood flow in arteries. Philadelphia, Pa:

Lea and Fibiger; 1998.

6. Robert J, Glynn, et al, pulse pressure and

mortality in older people, Arch Intern Med.

2000; 160: 2765-2772.

7. Franklin SS, Khan SA, Wong ND, Larson

MG, Levy D. is pulse pressure useful in

predicting risk for coronary heart disease?

The Framingham Heart Study. American

Heart Association, Circulation. 1999; 100:

354-360.

8. Lanteleme P, Laurent S, Besnard C, et al.

Arterial stiffness is associated with left

atrial size in hypertensive patients. Arch

Cardiovasc Dis. 2008; 101:9-10.

9. Gary F, Mitchell MD, et al. pulse pressure

and risk of new onset atrial fibrillation,

JAMA. 2007; 297: 709.

10. Mitchell GF, Parise H, Benjamin EJ, et al.

Changes in arterial stiffness and wave

reflection with advancing age in healthy

men & women. The Framingham Heart

Study. Hypertension. 2004; 43: 1239-

1245.

11. Tigan K, Karaahet T, Fotbolen H, et al.

The influence of dipper and non dipper

blood pressure patterns on left ventricular

functions in hypertensive patients: a tissue

Doppler study. Turk Kardiyol Dern Ars.

2009; 37:101-106.

12. Libhaber E, Woodiwiss AJ, Libhaber C, et

al. Gender specific brachial artery blood

pressure independent relationship

between pulse wave velocity and left

ventricle mass index in a group of African

ancestry. J Hypertens, 2008; 26:1619-

1628.

13. Aqoston CL, Mocan T, Bober C. arterial

stiffness and left ventricle diastolic function

in the patients with arterial hypertension.

Rom J Intern Med. 2008; 46: 313-321.

14. Hundiy WG, Kitzman DW, Morgan TM, et

al. Cardiac cycle dependent changes in

aortic area and distensibility are reduced

in older patients with exercise intolarence.

J Am Coll Cardiol. 2001; 38:796-802.

15. Tsang TS, Gersh RT, Appletion CP, et al.

Left ventricular diastolic dysfunction as a

predictor of the first diagnosed non

valvuler atrial fibrillation in 840 elderly men

and women. J Am Coll Cardiol. 2002; 40:

1636- 1644.

16. Vasan RS, Larson MG, Levy D, Galders

M, Wolf PA, Benjamin EJ. Doppler

transmitral flow indexes and risk of atrial

fibrillation , the Framingham Heart Study.

Am J Cardiol. 2003; 91: 1079- 1083.

17. Sperack DM, Blum L, Malhotra D, et al.

Ratio of left atrial to left ventricle size: an

anatomical marker of the diastolic left

ventricular pressure – volume relationship.

Echography 2008; 25:366-373.

18. Viola V, Thedore RH, Harkin MK. Pulse

pressure and risk for myocardial infarction

and heart failure in the elderly. J Am Coll

Cardiol. 2000; 36:130-138.

19. Echocardiographic Evaluation of Left and

Right ventricular Systolic Function. In Text

Book of Clinical Echocardiology, editor

Catherine MO: USA, 2000; P 104.

20. Echocardiography: a Practical Guide for

Reporting, Editor Helen R, Jhon PC, 2007

inform UK ltd, P 30-31.

21. Nawrot TS, Steassen JA, Thijis L, et al.

Should pulse pressure become part of the

Framingham Risk Score? Journal of

Human Hypertension 2004; 18: 279-286

22. Aviv A, Aviv H. Telomeres and essential

hypertension. 1999; 12:427-432

23. Benetos A, Telemer length as an indicator

of biological aging: the gender effect and

relation with pulse pressure and pulse

wave velocity. Hypertension. 2001; 37:

381-385.

24. Chea CU, Pfereffer MA, Glynn RJ,

Mitchell GF, et al. increased pulse

pressure and risk of the heart failure in the

elderly. JAMA. 1999; 281:634-639.

25. Robert J, Glynn CU, Chae JM, et al. Pulse

pressure and mortality in older people.

Arch Intern Med. 2000; 160:2765- 2772.

26. Berne RM, Levy MN. Cardiovascular

physiology. St Louis, Mo: CV Mosby 1992;

113-144.

27. Benetos S, Laurent S, Hoeks AD,

Boutouyrie PH, Safar ME. Arterial

alterations with aging and high blood

pressure. Arterioscler Thromb. 1993; 13:

90-97.

28. Franklin SS, Gustin WG, Wong ND,

Lerson MG, et al. Hemodynamic patternes

of age related changes in blood pressure:

the Framingham Heart Study. Circulation

1997; 96:308-315.

© 2010 Mosul College of Medicine 62


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Bone marrow trephine in some hematological

and non-hematological disorders

Mohammed S. Saeed*, Nazar M. Jawhar**

*Department of Pathology, College of Medicine; ** Department of Pathology, Nineveh College of

Medicine, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 63-71).

Received: 11 th Nov 2009; Accepted: 19 th May 2010.

ABSTRACT

Objective: To evaluate the frequency, age distribution and document the histological pattern of

various hematological disorders reported in bone marrow biopsy.

Methods: A retro and prospective study carried out from 2000 to 2007 at pathology laboratory of Irbil

Razkary Hospital. A total number of 117 cases were investigated. The biopsy was taken from

posterior superior iliac spine by the clinician. A length of 0.5 to 2 cm of marrow element was obtained,

put overnight in 10% formalin for fixation, followed by decalcification in 5% nitric acid. Then processed

in usual manner. Sections were examined by 2 pathologists independently.

Results: the mean age of patients was 46.16 years ranging from 2 years to 76 years. The male to

female ratio was 1.49:1. The commonest presenting clinical features of patients underwent bone

marrow biopsy were pallor (91.4%), followed by body weakness (59.0%). The most frequent

histological diagnoses in order of frequency were unremarkable bone marrow (28.20%), lymphoma

(11.1%), acute leukemia, chronic myeloproliferative disorders (9.40%), chronic leukemia, (5.12%),

multiple myeloma (3.42%), metastatic tumor (2.56%), myelodysplastic syndrome and megaloblastic

anemia equally reported (1.71%), pure red cell aplasia and granulomatous inflammation were present

in (0.85%).

Acute leukemia was encountered mostly in 1 st and 2 nd decades of life. Lymphoma, chronic leukemia,

chronic myeloproliferative disorders occur in 4 th and 5 th decades. Myelodysplastic syndrome

presented in older age group 5 th and 6 th decades. Multiple myeloma and metastases were seen in 6 th

and 7 th decades of life. Other disorders were randomly distributed.

Conclusion: Bone marrow trephine biopsy is an invasive procedure with few known complications,

but is a valuable diagnostic tool in the diagnosis, staging, management and follow up of various

conditions both neoplastic and non-neoplastic. High percentage of cases in our study showed normal

marrow finding, this may reflect overindication of marrow biopsy, such finding urge for more

clinicopathological coordination and data analysis.

Keywords: Bone marrow trephine biopsy, lymphoma, leukemia, myeloproliferative disorders,

myelodysplastic syndrome, multiple myeloma.

الخلاصة

الأهداف:‏ لغرض تقييم التردد وتوزيع الأعمار وتثبيت النمط النسيجي لاضطرابات الدم المختلفة مع موجودات خزع نخاع

العظم.‏

الطرق:‏ أجريت دراسة راجعة ومستقبلية للفترة من سنة ولغاية في مختبر الإمراض مستشفى رازآاري

في اربيل.‏ ولقد تم فحص وقد أخذت الخزع من شوآة الحرقفة الخلفية العلوية من قبل الطبيب ألسريري.‏ ولقد تم

الحصول على إلى سم طولا من مادة النخاع ووضعت في فورما لين للتثبيت ثم اتبعت بإزالة الكلس بمادة


٢٠٠٧

%١٠

٢٠٠٠

١١٧ حالة

٢

© 2010 Mosul College of Medicine 63

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

حامض النتريك ومن ثم مررت بالطريقة الاعتيادية.‏ ولقد تم فحص المقاطع النسيجية من قبل اثنان من اختصاصي

علم الإمراض وبصورة مستقلة.‏

النتائج:‏ لقد آان المتوسط العمري للمرضى سنة وبتراوح بين سنة.‏ وآانت نسبة الذآور إلى الإناث

إن الإمراض السريرية للمرضى الخاضعين إلى خزعة نخاع العظم آانت شحوب بنسبة يتبعها الوهن

الجسمي بنسبة لقد آان التشخيص النسجي وحسب الترداد آالآتي:‏ نخاع عظم عادي في و ورم لمفي في

أبيضاضات حادة في واضطرابات نخاعية تكاثرية في أبيضاضات مزمنة في ورم

نقي متعدد في و نقائل الأورام في ومتلازمة خلل تنسج النخاع وفقر الدم الضخم الارومات لكل

منها ولا تنسج خلايا الحمر النقي ‏(الخالص)‏ وآذلك التهابات حبيبية ٠,٨٥% لكل منهما.‏

ولقد ترافقت الابيضاضات الحادة وعلى الأغلب في الحقب الأولى والثانية من العمر وتواجدت الأورام اللمفية و

الابيضاضات المزمنة واضطرابات النخاع التكاثرية في الحقب الرابعة والخامسة وتواجدت متلازمة خلل تنسج النخاع في

حقب الأعمار الأآبر إي الخامسة والسادسة.‏ لقد شوهدت ورم نقي متعدد ونقائل الأورام في الحقب السادسة والسابعة.‏ فيما

تناثرت الاضطرابات الأخرى بصورة عشوائية.‏

الاستنتاج:‏ إن خزع نخاع العظم هي وسيلة عدوانية مع احتمالية القليل من المضاعفات المعروفة ولكن لها قدرات

تشخيصيه عالية وأهمية في علاجات ومتابعة مختلف الحالات الورمية واللامرضية.‏ نسبة عالية من الحالات في هذه

الدراسة أظهرت نخاع عظمي سليم هذا يظهر الدلالة المفرطة لعمل خزعة نخاع العظم.‏ هذا يؤآد على أهمية التواصل

ألسريري المرضي وتحليل المعطيات والبيانات لكل حالة.‏

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B

one marrow trephine was first performed

in 1903 by Piance who punctured the

epiphysis of the femur by trocar. Arikin

recommended the use of needle for bone

marrow examination in 1929 and thereafter

open biopsies were abandoned. This allows

complete assessment of marrow architecture

and the pattern of distribution of any abnormal

infiltrate and for the detection of focal bone

marrow lesions (1,2) .

For bone marrow interpretation, pathologist

should be provided with the history, clinical

finding, peripheral blood picture and bone

marrow aspirate examination (3) . The

pathologist also should be familiar with the

normal marrow histology to understand the

pathological process (4) .

A bone marrow trephine biopsy is an

uncomfortable procedure for the patient and

carries few adverse effects. The complications

of bone marrow biopsy that may be

encountered are excessive hemorrhage,

infection and breaking of the needle within the

bone (5,7) . Therefore it should be performed

only when there is a clear clinical indication

(5,6) . Such indications include inadequate or

failed aspirate as in cases of dry aspirate,

need for accurate assessment of marrow

cellularity as to determine the extent of bone

marrow damage in patients exposed to

radiation, drugs, chemical or other myelotoxic

agents, in suspected bone marrow fibrosis, in

cases that need studying bone marrow

architecture and determination of the pattern

of infiltration (5) , monitor the efficacy of

treatment of certain conditions, assessment of

the stage or progression of certain diseases

and tumors including lymphomas and certain

non-hematopoietic malignancies as neuroblastoma

and other childhood tumors (7) , to

monitor the recovery process in patient

undergoing bone marrow transplantation or

marrow-ablative chemotherapy, and lastly it is

also an important diagnostic procedure in

cases of fever of unknown origin (8,9) .

Trephine biopsy is usually carried out from

the posterior superior iliac spine, with the

patient in the left or right lateral position and

the knee drawn up. The alternative site is just

below the anterior superior iliac spine with the

patient in supine position (5) . These sites

carried out successfully in children and adult,

while for neonate, a modified technique

applicable to the tibia has been described (10) .

There are different types of trephine bone

marrow needle, example Jamshidi needles,

Goldenberg SNARECOIL Bone marrow biopsy

needle, ISAN and ACRI bone marrow biopsy

© 2010 Mosul College of Medicine 64


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

needles, Monoject bone marrow aspiration

and biopsy needles, Lee Lok Bone Marrow

Biopsy and Harvest Needle, Core-Lock Bone

Marrow Biopsy Systems (11) .

The biopsy should contain at least 5 to 6

intertrabecular spaces and should be at least

2-3 cm (1) . 1.5-2 cm is also acceptable length

for adequate marrow biopsy (12-14) .

The aim of the study is to evaluate the

frequency, age distribution and document the

histological pattern of various hematological

disorders reported in bone marrow biopsy.

Material and methods

This is a retrospective and prospective study in

which trephine bone marrow biopsies had

been collected from Razkary hospital in Irbil

from 2000 to 2007. The biopsies were

performed for different clinical and laboratory

indications. The relevant information and

demographic data were collected from the

laboratory request forms.

The retrospective cases were retrieved from

laboratory archive. Blocks were re-cut, stained

and reexamined. While the prospective cases

started from 2004 in which the trephine

biopsies had been carried out by the clinicians.

The site of the biopsies was the posterior

superior iliac crest. The average length of the

biopsies were 0.5 to 2 cm. Biopsies were fixed

in 10% formalin solution, kept for 24 hours

then decalcified in 5% nitric acid for 3 to 4

hours, processed in automated tissue

processor, then stained by routine hematoxylin

and eosin stain.

The results were analyzed according to the

number and percentage of different

parameters.

Results

Bone marrow trephine biopsies of 117 cases

were included in this study. There were 70

(59.83%) male and 47 (40.17%) females. The

overall male to female ratio was 1.49:1. The

mean age of patients who underwent trephine

biopsy was 46.16 year with a range between 2

to 76 years. Majority of cases were in the 4 th

and 5 th decades. The detailed distribution of

age group and sex are shown in table (1).

Table (1): Age and sex distributions of the

study sample.

Age

Male

No %

Female

No %

Total

No %

0 – 10 3 (2.56) 0 (0.0) 3 (2.56)

11 – 20 4 (3.41) 7 (5.98) 11 (9.40)

21 – 30 8 (6.83) 8 (6.83) 16 (13.67)

31 – 40 10 (8.54) 5 (4.27) 15 (12.82)

41 – 50 12 (10.25) 8 (6.83) 20 (17.09)

51 – 60 13 (11.11) 11 (9.40) 24 (20.5)

61 – 70 13 (11.11) 6 (5.12) 19 (16.23)

71 – 80 7 (5.98) 2 (1.70) 9 (7.69)

Total 70 (59.83) 47 (40.17) 117 (100)

The commonest indication for bone marrow

biopsy was pallor, which was seen in 107

(91.4%) of cases, followed by generalized

body weakness, seen in 69 (59.0%) of cases,

followed by other clinical and laboratory

indications, as illustrated in table (2).

Table (2): Distribution of the study sample

according to the main clinical and laboratory

indications of bone marrow biopsy.

Clinical and lab

indications

No of cases

% of cases

Pallor 107 (91.4)

Body weakness 69 (59.0)

Fever 51 (43.6)

Splenomegaly 35 (29.9)

Hepatomegaly 17 (14.5)

Lymphadenopathy 16 (13.6)

Bleeding 15 (12.8)

Increase ESR 15 (12.8)

Staging of

malignancy

14 (11.9)

Pancytopenia 13 (11.1)

Blast in peripheral

blood

12 (10.2)

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

The biopsies were examined by 2

pathologists independently with emphasis on

the adequacy of the specimen, cellularity,

proportion of hematopoietic cells, presence of

atypical cells, abnormal proliferative process,

presence of granuloma or microorganism, and

abnormal infiltration of marrow biopsy.

The biopsies were adequate for

establishment of diagnosis in 106 samples

(90.6%), while in 11 samples (9.4%) the

biopsies were inadequate, composed mainly

of fibrocartilagenous tissue with no marrow

elements. Few cases were due to processing

or staining artifact.

The most frequent final diagnoses were

malignancy of varying types (lymphoma,

leukemias, chronic myeloproliferative

disorders, multiple myeloma, metastasis and

myelodysplastic syndrome) which was seen in

50 (42.7%), followed by normal bone marrow

biopsy as it was seen in 34 (29.05%) of the

biopsies. Others are illustrated in table (3).

Regarding the age distribution of different

bone marrow diseases: in acute leukemia,

majority of cases were seen in young age

groups (1 st and 2 nd decades), whereas the

chronic myeloproliferative disorders (including

CML), chronic leukemias and lymphomas were

identified in 4 th and 5 th decades of life.

Myelodysplastic syndrome occurs in higher

age groups, 5 th and 6 th decades, while the

metastatic deposits and multiple myeloma

were seen in 6 th and 7 th decades. Other

disorders were distributed randomly in different

age groups (table 4).

Table (3): Distribution of the number of cases according to the final diagnosis.

Diagnosis No % Sub typing No %

Lymphomas 13 11.1

Lymphoplasmocytic

Mixed small & large

Small cell

Non classified

4

4

2

3

3.42

3.42

1.71

2.56

Chronic myeloproliferative

disorders

11 9.40

CML

Myelofibrosis

Essential Thrombocythaemia

CMPD unclassifiable

6

3

1

1

5.12

2.56

0.85

0.85

Acute leukemia 11 9.40

AML

ALL

Unclassified

5

3

3

4.27

2.56

2.56

Chronic leukemia 6 5.12

CLL

Hairy Cell Leukemia

Prolymphocytic leukemia

3

2

1

2.56

1.71

0.85

Multiple myeloma 4 3.42

Metastatic focus 3 2.56

Prostate

Breast

GIT

1

1

1

0.85

0.85

0.85

Myelodysplastic syndrome 2 1.71

Refractory anemia

Refractory anemia with excess blasts

1

1

0.85

0.85

Normal bone marrow 34 29.05

Insufficient for diagnosis 11 9.40

Hyperplastic bone marrow 9 7.69

Aplastic anemia / Hypoplastic

bone marrow

9 7.69

Megaloblastic anemia 2 1.71

Pure red cell aplasia 1 0.85

Granulomatous inflammation 1 0.85

Total 117 100

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Table (4): Age group distribution according to the final diagnosis.

Diagnosis 0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 Total %

Lymphomas 2 2 2 5 2 13 (11.11)

Chronic myeloproliferative disorder 1 4 5 1 1 11 (9.40)

Acute leukemia 1 3 5 1 1 11 (9.40)

Chronic leukemia 2 1 3 6 (5.15)

Multiple myeloma 2 2 4 (3.42)

Metastatic 2 1 3 (2.56)

Myelodysplastic syndrome 1 1 2 (1.70)

Normal bone marrow 1 4 3 3 7 8 4 3 34 (29.05)

Insufficient for diagnosis 3 4 3 1 11 (9.40)

Hyperplastic bone marrow 2 1 2 2 1 1 9 (7.69)

Aplastic anemia / Hypoplastic bone

marrow

1 2 2 3 1 9 (7.69)

Megaloblastic anemia 1 1 2 (1.70)

Pure red cell aplasia 1 1 (0.85)

Granulomatous inflammation 1 1 (0.85)

Total 3 9 16 15 20 24 19 9 117 (100)

Discussion

Bone marrow trephine biopsy is an

indispensable tool for the diagnosis of various

hematological diseases. To provide optimal

results, the finding should be correlated with

pertinent clinical and laboratory information. It

can be performed in different age groups. In

this study, various age groups were included;

the mean age of this study was 46.16 year,

reflecting the predominant age groups which

are the 4 th and 5 th decades. This finding was

higher than other studies (15-17) , probably due

to the relatively high number of hematological

malignancies in this study. Regarding the

gender, there was a male predominance with a

ratio of 1.49:1 female. Slightly lower results

were seen in other studies (15,16,18) .

Pallor was the most common clinical feature

of patients who underwent bone marrow

trephine biopsy (seen in 91.4% of cases),

solely or associated with other features. This

agrees with other studies (15,16,19) . Generalized

body weakness ranked the second frequent

symptom and was present in 59.0% of cases.

The latter was the main presenting symptom in

another study (18) . The least common clinical

feature was bleeding, which was the

presenting symptom in 12.8% of cases. This is

similar to another study (18) .

Regarding the final diagnosis, the reporting of

a normal bone marrow was reached in 29.05%

of the biopsies. This is a relatively high percent

in comparison with another study (18) and may

reflect the overindication of marrow biopsy in

our locality probably related to lack of proper

clinicopathologic coordination.

Lymphoma was the second diagnostic report

seen in 11.1%. This is similar to another study

which shows the highest percent of

lymphoma (16) . All were non-Hodgkin's

lymphoma. The majority of these cases were

lymphoplasmocytic lymphoma 4 (3.42%)

cases and mixed small and large cell

lymphoma 4 (3.42%) cases. They show a

predominant diffuse and, to less extend,

nodular pattern of infiltration. Similar results

were reported by others (20-22) . In 3 (2.56%)

cases the specific type of lymphoma could not

be achieved and further immunohistochemical

stains were recommended.

Acute leukemias ranked third by 9.40% of

biopsies. The majority of those patients were

in 1 st and 2 nd decades and mostly acute

myeloid leukemia 5 (4.27%). While cases of

acute lymphoblastic leukemia were seen in

only 3 (2.56%). However; in 3 cases definitive

typing of acute leukemia cannot achieved by

bone marrow trephine biopsy alone. Similar

findings were reported by other studies

© 2010 Mosul College of Medicine 67


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

(18,19,23,24)

and slightly higher finding by others

(15) .

The chronic myeloproliferative disorders

(CMPDs) are another group commonly

diagnosed on histopathological examination

of trephine bone marrow biopsies. The 2001

WHO classification system of chronic myeloid

neoplasms classified chronic

myeloproliferative disorders into the four

classical MPDs (chronic myelogenous

leukemia (CML), polycythaemia vera, essential

thrombocythemia and chronic idiopathic

myelofibrosis) as well as chronic neutrophilic

leukemia (CNL), chronic eosinophilic

leukemia/hypereosinophilic syndrome

(CEL/HES) and CMPD unclassifiable. The

central and shared feature in CMPDs is

effective clonal myeloproliferation (that is

peripheral blood granulocytosis,

thrombocytosis or erythrocytosis) which is

devoid of dyserythropoiesis, granulocytic

dysplasia or monocytosis (25) .

As for CML cases the histological picture

shows hypercellular marrow with granulocytic

hyperplasia and loss of fat cells. Reticulin is

increased and may be confused with primary

myelofibrosis (17) . In our study CML was

diagnosed in 6 (5.12%) patients. Regarding

myelofibrosis in which bone marrow aspirate

usually shows “dry tap” and so trephine biopsy

is the ultimate diagnostic tool in this condition.

In our series, 3 (2.56%) cases were diagnosed

as myelofibrosis, comparable to that of other

studies (18,26,27,28) . We encountered 2 (1.71%)

cases that were labeled as unclassified

myeloproliferative disorders.

Chronic leukemia, including 3 cases of

chronic lymphocytic leukemia (2.56%), 2 cases

of hairy cell leukemia (1.71%), and 1 case of

prolymphocytic leukemia (0.85%). All

represent 5.12% of the studied group. This is

similar to another study (18) .

Myelodysplastic syndrome (MDS) is a

heterogeneous group of clonal stem cell

disorders which generally occur in older adults

but may affect children. Myelodysplastic

syndrome is characterized by ineffective

hematopoiesis, morphological cell dysplasia

(dyserythropoiesis; dysgranulopoiesis;

dysmegakaropoiesis), peripheral blood

cytopenias, progressive bone marrow failure

and a tendency to progress to acute

myelogenous leukemia (29,30) . According to the

French-American-British (FAB) classification

which was published in 1976 and revised in

1982 and WHO classification in late 1990s,

cases were classified into 5 categories. These

are refractory anemia (RA), refractory anemia

with ringed sideroblasts (RARS), refractory

anemia with excess blasts (RAEB), refractory

anemia with excess blasts in transformation

(RAEB-T), and chronic myelomonocytic

leukemia (CMML) (31) . In our study we reported

myelodysplastic syndromes in 2 (1.71%) of

cases, one is refractory anemia and the other

is refractory anemia with excess blasts. The

bone marrow findings were either hyper or

hypocellular with multilineage dysplasia. This

was similar to others (15,26) .

As for bone marrow aplasia/ hypoplasia, we

reported 9 cases (7.69%) and was seen in

different age groups suggesting the variety of

underlying causes. This is similar to other

studies (18,20) , but is lower than 2 other

studies (19,26) . Determination of whether the

aplasia was primary or secondary cannot be

achieved by bone marrow biopsy alone; it

needs clinical coordination.

Pure red cell aplasia was seen in 0.85% of

cases. This is similar to other studies (24,32) .

Bone marrow hyperplasia was encountered

in nine cases (7.69%), 3 of them showed

erythroid hyperplasia alone (as a result of the

hemolytic process) and the rest showed pan

hyperplasia of all three elements (probably

due to hypersplenism). Megaloblastic anemia

was diagnosed in 1.70% of cases. These

numbers are lower than in another study (18) .

The diagnosis of multiple myeloma in marrow

biopsy depends upon extent of plasma cell

infiltration, pattern of infiltration and cytological

features of plasma cells (1,33) . Trephine biopsy

in this disorder is an essential investigation.

However; in cases in whom an aspirate

permits a definitive diagnosis, the trephine

biopsy is important as a baseline for

comparison with repeated biopsies during

follow up (5) . In our study 3.42% of cases were

diagnosed as multiple myeloma. This is similar

to two other studies (15,18) .

© 2010 Mosul College of Medicine 68


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

The bone marrow biopsy is considered a

sensitive technique for detecting metastatic

tumors. It is also performed for staging

purposes at the time of diagnosis in a number

of solid tumors such as neuroblastoma in

children and tumors of breast, stomach, colon,

kidney, prostate, lung and lymphoma in adults

(2,34) . The problems and pitfalls in the

interpretation of metastatic deposits on bone

marrow biopsy could arise because of some

normal components of bone marrow like

megakaryocytes, crushed erythroid cells,

osteoblasts, osteoclasts, macrophages and

fibroblasts may resemble with the tumor

deposits (1) . In our study 3 (2.56%) known

cases of solid body tumor were found to have

metastatic deposits of adenocarcinma

(prostate, breast and gastrointestinal tract).

This finding coincides with other

studies (15,17,35) .

Granulomatous lesion was the least common

pathological diagnosis which was present in

0.85% of cases. This histological finding is

seen in a variety of conditions including

tuberculosis, sarcoidosis, Hodgkin’s disease,

cat scratch disease, Q fever, brucellosis,

leprosy, syphilis and typhoid fever (5,36-39) .

There are no characteristic morphological

features which allow reliable etiologic

diagnosis of bone marrow granulomas (40,41) .

This is similar to two other studies which show

infrequent granuloma finding in bone marrow

trephine biopsy (40,41,42) , but unlike two other

studies which show preponderance of

granulomatous inflammation (17,18) .

Inadequate biopsies were seen in 9.40% of

cases. These were due mainly to absence of

bone marrow element, or due to processing

and staining artifact which obscured the

histological picture. This is comparable to

another (18) .

Conclusion

Bone marrow trephine biopsy is an invasive

procedure with few known complications, but

is a valuable diagnostic tool in the diagnosis,

staging, management and follow up of various

types of conditions both neoplastic and nonneoplastic.

High percentage of cases in our

study show normal marrow finding, this may

reflect overindication of marrow biopsy, such

finding urge for more clinicopathological

coordination and data analysis.

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and bone marrow granulomas. Inter Med.

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39. Miller AC, Chacko T, Rashid RM, et al.

Fever of unknown origin and isolated

noncaseating granuloma of the marrow:

could this be sarcoidosis. Allergy Asthma

Proc. 2007 Mar-Apr: 28(2): 230-235.

40. Bodem CR, Hamory BH, Taylor HM et al.

Granulomatous bone marrow disease. A

review of literature and clinicopathologic

analysis of 58 cases. Medicine

(Baltimore). 1983 Nov; 62(6): 372-383.

41. Vijnovich Baron IA, Barazzutti L, Tartas N,

et al. Bone marrow granulomas. Sangre

(Barc). 1994 Feb; 39(1): 35-38.

42. Basu D, Saravana R, Purushotham B, et

al. Granulomas in bone marrow- a study of

fourteen cases. Indian J Pathol Microbiol.

2005 Jan; 48(1): 13-16.

© 2010 Mosul College of Medicine 71


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Serum ferritin level in transfusion dependent

β-thalassaemia patients in Mosul

Faris Y. Bashir, Omar A. Sadoon

Department of Pathology, College of Medicine, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 72-78).

Received: 10 th Jan 2010; Accepted: 10 th Nov 2010.

ABSTRACT

Objectives: To establish a correlation between serum ferritin and different clinical, biochemical and

haematological parameters and to determine the efficacy of chelation therapy using desferrioxamine

measured by serum ferritin.

Patients and Methods: A case-series of one hundred patients with transfusion dependent

β-thalassaemia were included in the study during a period of one year (Nov. 2007-Nov.2008). The

study included clinical evaluation, routine haematological tests and serum ferritin level.

Results: Mean value of serum ferritin in our patients was 1886.74 ng/ml. It was found that serum

ferritin was higher in older patients, those who received higher number of blood transfusions to date

and those of higher annual blood consumption. β-thalassaemic patients with serum ferritin level equal

or higher than 2500 ng/ml were older, of shorter stature, had higher percentage of splenectomy,

higher number of blood transfusions to date and higher annual blood consumption than patients with

serum ferritin level less than 2500 ng/ml. It was found that patients with good compliance to chelation

therapy with desferrioxamine had lower mean serum ferritin than patients with poor compliance. Thirty

seven percent of our patients had growth retardation regarding weight for age and 57% were low in

height for their age.

Conclusions: Serum ferritin was higher in older patients, those with higher annual blood

consumption and those with poor compliance to desferrioxamine therapy when compared to patients

with good compliance. Patients with serum ferritin equal to or more than 2500 ng/ml were older and of

shorter stature for their age than patients with serum ferritin less than 2500 ng/ml.

الخلاصة

الاهداف:‏

إيجاد قيم حديدين المصل في مرضى الثلاسيميا نوع بيتا المعتمدين على نقل الدم في الموصل.‏

تم تطبيق ارتباط بين حديدين المصل ومختلف القياسات السريرية والمخبرية ‏(الدموية والكيماوية).‏

قياس آفاءة دواء الدسفريوآسامين في القدرة على طرح عنصر الحديد من الجسم باستخدام حديدين المصل.‏

الحالات والطرق:‏ شملت الدراسة مريض بالثلاسيميا نوع بيتا المعتمدين على نقل الدم خلال الفترة الممتدة من

‏(تشرين الثاني تشرين الثاني تضمنت الدراسة تقييماً‏ سريرياً‏ وفحص الدم الكامل بالإضافة إلى فحص

حديدين المصل.‏

النتائج:‏ معدل حديدين المصل لدى مرضانا هو ١٨٨٦,٧ نانوغرام/مللتر.‏ وجد أن حديدين المصل آان أعلى عند المرضى

الأآبر سناً‏ وأولئك الذين استلموا العدد الأعلى من قناني الدم حتى وقت أجراء الفحص وأولئك الذين يكون استهلاك الدم

السنوي لديهم عالياً.‏ وجد أيضاً‏ أن مرضى الثلاسيميا نوع بيتا المعتمدين على نقل الدم الذين آان لديهم حديدين المصل

مناظراً‏ أو أعلى من نانوغرام/مللتر آانوا أآبر سناً‏ وأقصر قامة ولديهم نسبة أعلى من عمليات رفع الطحال

وأستلموا عدداً‏ أآبر من قناني الدم حتى وقت اجراء الفحص واستهلاآهم السنوي للدم آان أعلى من أولئك الذين آان لديهم

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© 2010 Mosul College of Medicine 72




Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

حديدين المصل أقل من نانوغرام/مللتر.‏ وجد أيضاً‏ أن المرضى الذين آان لديهم التزام جيد بعلاج الدسفريوآسامين

فان حديدين المصل عندهم أوطأ من أولئك المرضى الذين لا يلتزمون بالعلاج بصورته الصحيحة.‏ من مرضانا

المعتمدين على نقل الدم آان لديهم تأخر في النمو عند قياس وزنهم بالنسبة لعمرهم و‎٥٧‎‏%‏ منهم آانوا قصيري القامة

بالنسبة لعمرهم.‏

الاستنتاجات:‏ حديدين المصل آان أعلى عند المرضى الأآبر سناً‏ والذين يكون استهلاك الدم السنوي لديهم عالياً‏ والمرضى

الذين لا يلتزمون جيداً‏ بعلاج الدسفريوآسامين عند مقارنتهم بالمرضى الملتزمين بالعلاج.‏ آما أن المرضى الذين لديهم

حديدين المصل مساوياً‏ أو أعلى من نانوغرام/مللتر هم أقصر قامة وأآبر سناً‏ من المرضى الذين لديهم حديدين

المصل اقل نانوغرام/مللتر.‏

%٣٧

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من ٢٥٠٠

T

halassaemia is the commonest single

gene disorder in man, characterized by a

lack or decreased synthesis of one or more of

the globin subunits of haemoglobin molecule

(1) . β-thalassaemia is classified into β 0

thalassaemia with complete absence of β

globin chain and β + thalassaemia in which the

production of β globin chain is reduced (2) . Iron

overload causes most of the morbidity and

mortality associated with thalassaemia. (3)

Two factors are responsible for iron overload

in β- thalassaemia:

1- Increased intestinal absorption of iron due

to erythroid hyperplasia despite tissue iron

overload.

2- Transfusional siderosis with up to 200 mg

iron is added per packed RBC unit. (4)

The iron storage protein, ferritin, plays a key

role in iron metabolism.

Its ability to sequester the iron gives ferritin

the dual function of iron detoxification and iron

reserve. (5)

Annual blood consumption was measured by

calculating total intake of packed RBC in one

year divided by body weight in kilograms, and

the resultant unit is ml of packed RBC/ kg body

weight/year, it had been regarded as a good

indicator of iron overload, transfusion scheme

and hypersplenism, in which amount in excess

of 200 ml/kg/year is an indication for

splenectomy . (6,7)

Patients with thalassaemia major in the early

transfusional period need to have serum

ferritin levels determined every 1–2 months in

order to have a baseline value of iron load to

initiate iron chelation therapy which should be

started when serum ferritin levels exceeds

1000 ng/ml and periodic monitoring of serum

ferritin every 3 months should be done for

patients on iron chelation therapy. (8)

Aims of the study

1- To assess serum ferritin in transfusion

dependent β-thalassaemic patients in

Mosul.

2- To establish a correlation between serum

ferritin and different clinical, biochemical,

and haematological parameters.

3- To determine the efficacy of chelation

therapy using desferrioxamine measured

by serum ferritin.

Patients and methods

A total of 100 transfusion dependent β-

thalassaemia patients attending at

thalassaemic centre in Ibn-Al Atheer paediatric

hospital in Mosul, 52% were males and 48%

were females for regular blood transfusions

from November 2007 to November 2008 were

studied.

History and examination were done for all

patients.

The patients were divided into three groups:

1- Patients with good compliance to

desferrioxamine therapy (37 %) who took

desferrioxamine at a dose of (20 mg/kg

/day), four times weekly or more by

subcutaneous infusion using a special

pump.

2- Patients with poor compliance to

desferrioxamine therapy (36%) who took

less than four times weekly with variable

dose either by subcutaneous infusion or

by other route.

3- Patients who didn’t receive

desferrioxamine therapy at all (27 %).

No WBC filter was used in all of our patients.

© 2010 Mosul College of Medicine 73


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Ten ml of venous blood were obtained from

each patient immediately before the next blood

transfusion.

Three ml were added to EDTA containing

tubes and used for doing complete blood

picture and blood film.

The remaining 7 ml of blood sample were

collected in a plain tube for serum separation,

serum is stored at - 20 degrees centigrade for

estimation of serum ferritin and performing

hepatitis screen later.

All investigations were done according to

standard methods. (9)

Results

Age of patients was in the range of (2-29)

years with a mean age of 8 years, 72% of

patients were 10 years or younger.

Regarding weight for age distribution of our

patients, compared to 5 th % of the general

population, 37% of our patients were found to

be under weight (p


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Figure (4): Scatter diagram shows that

increased annual blood consumption is directly

associated with increased serum ferritin level

(p< 0.05 ) and (r =0.212).

Table (1): On grouping of patients according

to serum ferritin level into 2 groups, those

below 2500 ng/ml and those equal to or more

than 2500 ng/ml and comparison between

them, it was found that patients with serum

ferritin equal to or above 2500 ng/ml were

older than those below 2500 ng/ml, and had

significantly short stature for their age when

compared to patients with serum ferritin less

than 2500 ng/ml.

Figure (5): Diagram shows distribution of

patients compliance to desferrioxamine with

regard to serum ferritin with higher serum

ferritin in patients with poor compliance when

compared to patients with good compliance (p

< 0.05).

Mean serum ferritin in all patients using

desferrioxamine was 2043 ng/ml with a mean

Serum ferritin (ng/ml)

age of (9.44) years, and significantly (P< 0.05)

higher than mean serum ferritin in patients not

started using desferrioxamine with a very

young age, the mean age was (3.4) years and

serum ferritin mean was 1462.96 ng/ml.

9000

8000

7000

6000

5000

4000

3000

2000

1000

r = 0.212

p = < 0.05

0

0 50 100 150 200 250 300 350 400 450 500

Annual blood consumption(ml/kg/year)

Figure (4): Scatter diagram between serum

ferritin level and annual blood consumption.

Table (1): Grouping of patients with transfusion dependent β-thalassaemia according to S. ferritin

level and comparison between their different parameters.

Serum ferritin (ng/ml)

Parameters

< 2500

No. of patients (79)

≥2500

No. of patients (21)

P-value

Range 380 – 2460

Mean ± SD 1369.80 ± 510.09

Range 2740 – 7990

Mean ± SD 3831.43±1285.31

Age(years)

Range

Mean ± SD

2 – 21

7.18 ± 4.13

2.5 – 29

11.32 ± 6.64


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Figure (5): Distribution of patients compliance to desferrioxamine with regards to S. ferritin level (Total

no. of patients on desferrioxamine was 73).

Regarding some of the complications, 2 male

patients were diabetics, aged 16 and 29 years

and both were splenectomised.

They were both on insulin, but their random

blood glucose was within normal range, serum

ferritin of one of them was 1740 ng/ml, the

other patient serum ferritin was 3400 ng/ml.

Table (2): This table shows a statistically

significant increased hepatitis C infection in

our patients compared to normal Iraqi

population (p< 0.001).

Table (2): Comparison of hepatitis between

patients in the study and Iraqi population.

Patients in

the study %

Prevalence in

Iraqi

population

(%)

* Reference 10

** Reference 11

Hepatitis

B

(HBsAg)

Hepatitis C

(HCV

Antibodies)

Concomitant

Hepatitis B

and C

1 16 1

2-3* 0.5* 0**

Discussion

Results of serum ferritin were significantly

correlated with both advancing age of the

patients (figure 2) and increased number of

blood transfusion to date (figure 3) which is

comparable to those of Shanna study. (12)

Carnelli et al and Cario et al studies also

found that serum ferritin values correlates to

total amount of blood transfusions. (13,14)

Close to our results, Cario et al found that

(75%) of patients younger than 10 years had

serum ferritin less than 1800 ng/ml while

(52%) of thalassaemic patients who were older

than 10 years had serum ferritin above 2500

ng/ml. (14)

Short stature was found in 71.43% of

transfusion dependent β-thalassaemia patients

with serum ferritin equal or above 2500 ng/ml

compared to (53.16%) of short stature in

patients with serum ferritin below 2500 ng/ml,

similar findings were repeated in Moayeri et al

study who showed that short stature is

common in thalassaemic patients with serum

ferritin above 2000 ng/ml; he relates this to

suboptimal chelation therapy leading to high

serum ferritin level with iron deposition and

damage to hypothalamic pituitary axis and

growth failure. (15)

© 2010 Mosul College of Medicine 76


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Also Shalitin et al suggested that a cutoff

point of 3000ng/ml serum ferritin during the

first decade of life predict final short stature. (16)

Mean serum ferritin is lower in patients with

good compliance to desferrioxamine (DFO)

when compared to patients with poor

compliance (p < 0.05) (figure 4) indicating the

beneficial effect of proper chelation therapy in

reducing mean serum ferritin level.

The same was found by Kattamis et al (17)

and Richardson et al . (18)

Patients not started using DFO had

significantly lower mean serum ferritin values

1462.96 ng/ml compared to both groups on

DFO therapy those with good compliance to

DFO (mean serum ferritin of 1701.19 ng/ml)

and those with poor compliance to

desferrioxamine therapy with a mean serum

ferritin of 2395.28 ng/ml.

The probable cause for this lower mean

serum ferritin value in the group of patients not

started using desferrioxamine was the younger

mean age of these patients compared to other

groups on desferrioxamine therapy (3.4 years

mean age of patients not use desferrioxamine

versus 9.4 years in patients with compliance

and 9.49 years in patients with poor

compliance to desferrioxamine respectively).

Many studies showed that 2500 ng/ml serum

ferritin is a cut point of prognosis with higher

incidence of cardiac complication and

shortened survival in those above 2500 ng/ml

compared to those below 2500 ng/ml. (19,20)

Short stature was found in 71.43% of

transfusion dependent β-thalassaemia patients

with serum ferritin equal or above 2500 ng/ml

compared to 53.16% of short stature in

patients with serum ferritin below 2500 ng/ml,

similar findings were reported in Moayeri et al

study who showed that short stature is

common in thalassaemic patients with serum

ferritin above 2000ng/ml, he relates this to

suboptimal chelation therapy leading to high

serum ferritin level with iron deposition and

damage to hypothalamic pituitary axis and

growth failure. (15)

In the current study splenectomised patients

have higher ferritin mainly because those

patients were older than non splenectomised

and received more units of total blood

transfusion.

Annual blood consumption is significantly

higher in transfusion dependent β-

thalassaemia patients with serum ferritin

above 2500 ng/ml when compared to those

below 2500 ng/ml, because increased blood

intake per body weight is associated with

increased iron overload.

Because of early accelerated schedule for

hepatitis B vaccination which starts at the time

of registration in thalassaemic centre and

administration of booster doses of hepatitis B

vaccine, the prevalence of hepatitis B in our

patients is even less than those of general

population.

However, up to 16% of our patients were

infected by hepatitis C.

This result was similar to that of Dawaj study

on thalassaemic patients in Mosul 2007, where

he found that 17% of patients had hepatitis C

infection. (21)

These results of hepatitis C infection in

thalassaemic patients were high when

compared to 0.5 % incidence of hepatitis C in

Iraqi population. (22)

It appears clearly that the unavailability of

vaccination to hepatitis C and the use of non

screened blood bags during sanction against

Iraq in the nineties of the previous century till

2003 increased the incidence of hepatitis C in

our thalassaemic patients.

Conclusions

1. Growth retardation regards weight for age

and height for age was found in 37% and

57% of our patients respectively.

2. Increasing age of the patients, number of

blood transfusions to date and annual

blood consumption were found to be

associated with increased serum ferritin

level.

3. By grouping patients into two groups those

with serum ferritin below 2500 ng/ml and

those with serum ferritin equal or above

2500 ng/ml, it was found that patients with

serum ferritin equal or more than 2500

ng/ml were of shorter stature, had greater

percentage of splenectomy, received

higher number of blood transfusions and

were of higher annual blood consumption

© 2010 Mosul College of Medicine 77


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

than patients with serum ferritin less than

2500 ng/ml.

4. Compliance of patients to chelation

therapy was directly correlated to serum

ferritin level with higher serum ferritin in

patients with poor compliance.

5. Patients not using desferrioxamine had

lower mean age and lower mean serum

ferritin than patients using

desferrioxamine.

References

1. David HK. Thal for thal?, Blood 2007; 110

(8): 2788.

2. Provan D. ABC of clinical haematology,

2 nd ed., BMJ books 2003;11.

3. Gardenghi S, Marongiu MF, Ramos P, et

al. Ineffective erythropoiesis in β-

thalassemia is characterized by increased

iron absorption mediated by downregulation

of hepcidin and up-regulation of

ferroportin, Blood 2007;109(11): 5035.

4. Rund D, Rachmilewitz E. β-thalassemia, N

Eng J Med. 2005; 353: 1135-1139.

5. Hoffbrand AV, Catovsky D, Tudenham

EG. Postgraduate haematology, 5 th ed.,

Blackwell publishing 2005; 88-90.

6. Al-Awamy BH. Thalassemia syndromes in

Saudi Arabia, meta-analysis of local

studies, Saudi Med J 2000; 21(1): 13.

7. Origa R, Bina P, Agus A, et al. Combined

therapy with deferiprone and

desferrioxamine in thalassemia major,

Haematologica 2005; 90:1309.

8. Angelucci E , Barosi G, Camaschella C, et

al. Italian society of hematology practice

guidelines for the management of iron

overload in thalassemia major and related

disorders, Haematologica 2008;93(5): 742.

9. Lewis SM and Bain BJ, Dacie and Lewis

practical haematology, 9 th ed., Churchill

Livingstone 2004; 34-39,44,60.

10. Hepatitis C in Iraq, Ministry of health,

Center of disease control, Bulletin of

endemic disease, 2004; 31: 1.

11. Awad MH. Homozygous beta

thalassaemia in Mosul, Ph.D thesis in

pathology (haematology), college of

medicine, Mosul, Iraq,1999; 31-33.

12. Shaana RK. Relationship between serum

ferritin and number of blood transfusions in

minimally chelated thalassaemia patients

in the Erbil city of Iraq, 2007, A thesis of

fellowship of Iraqi board of medical

specialization in pathology : 22.

13. Carnelli V, D’Angelo E, Pecchiari M, et al.

Pulmonary dysfunction in transfusiondependent

patients with thalassemia

major, Am J Respir Crit Care Med 2003;

168: 180-183.

14. Cario H, Stahnke K, Sander S, et al.

Epidemiological situation and treatment of

patients with thalassemia major in

Germany: Results of the german

multicenter β-thalassemia study,Ann

Hematol 2000; 79(1):7.

15. Moayeri H, Oloomi Z. Prevalence of

growth and puberty failure with respect to

growth hormone and gonadotropins

secretion in beta-thalassemia major, Arch

Iranian Med 2006; 9 (4): 329.

16. Shalitin S, Weintrob D, Carmi N, et al.

serum ferritin level as a predictor of

impaired growth and puberty in

thalassemia major patients, Eur J

Haematol 2005;74:93.

17. Kattamis A, Dinopoulos A, Ladis V, et al.

Variations of ferritin levels over a period of

15 years as a compliance chelation index

in thalassemic patients, American J

hemat 2001; 68(4):221.

18. Richardson ME, Matthews RN, Alison JF,

et al. Prevention of heart disease by

subcutaneous desferrioxamine in patients

with thalassaemia major, Aust N Z J

Med1993; 23(6):656.

19. Silvilairat S, Sittiwangkul R, Pongprot Y,

et al. Tissue doppler echocardiography

reliably reflects severity of iron overload in

pediatric patients with β thalassemia, Eur J

Echocardiogr 2008; 9(3):368.

20. Olivieri NF, Nathan DJ, MacMillan JH, et

al. Survival in medically treated patients

with homozygous β-thalassemia, N Eng J

Med1994; 331(9):609.

21. Dawaj MH, Prevalence of hepatitis C in

thalssaemic patients in Mosul, Ph.D.

thesis in Microbiology, College of Science,

University of Mosul, Iraq, 2007;76.

22. Hepatitis C in Iraq, Ministry of health,

Center of disease control, Bulletin of

endemic disease, 2004; 31: 1.

© 2010 Mosul College of Medicine 78


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Value of IgA human recombinant tissue transglutaminase

antibody test in diagnosis of symptomatic celiac disease in

children

Nashwan M. Al-Hafidh, Khaldoon Th. Al-Abachi

Department of Medicine, Nineveh College of Medicine, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 79-85).

Received: 22 nd Jun 2010; Accepted: 12 th Jan 2011.

ABSTRACT

Objective: To identify the value of serological examination in diagnosis of celiac disease in children.

Patients and methods: A prospective case series study was conducted at private clinics in Mosul

city during the period from 30th of October 2007 to 30 th of October 2009. A total of 40 patients (29

males, 11 females) aged more than 6 months on gluten containing diet presented with symptoms

suggestive of celiac disease were screened by serological testing using second generation ELISAs

IgA human recombinant tissue transglutaminase antibody. Multiple duodenal biopsies were performed

for every patient enrolled in this study regardless of the results of serology. Statistical methods were

used to indicate sensitivity, specificity, negative and positive predictive values of serological test in

comparison to biopsy results.

Results: A total of 16 (40%) out of 40 symptomatic patients with mean age of 51 months,

demonstrated both positive IgA anti-tissue transglutaminase antibody test and biopsy results for celiac

disease, the remaining 24 patients (60%) displayed negative results for both serology and biopsy. IgA

anti-tissue transglutaminase antibody test had (100%) specificity, sensitivity, positive predictive value,

and negative predictive value in relation to biopsy results.

Conclusion: Our results provide additional support to the concept that IgA anti-tissue

transglutaminase antibodies can be used as a diagnostic serologic marker for celiac disease.

الخلاصة

هدف الدراسة:‏ معرفة قيمة الفحص المصلي في تشخيص الجواف لدى الاطفال.‏

طريقة البحث والمشارآون:‏ هذه دراسة مستقبلية لحالات متتالية،‏ أجريت في العيادات الخاصة في مدينة الموصل،‏ خلال

مريضا

العينة المدروسة ضمت تشرين الأول عام ولغاية تشرين الأول عام الفترة من ذآرا،‏‎١١‎ أنثى)‏ تجاوزت أعمارهم أآثر من ستة أشهر.‏ الكل آان يتناول قبل الدراسة طعاما يحتوي على الغروين ولديهم

أعراضا موحية بالجواف.‏ خضع آل أفراد العينة للفحص المصلي الذي يمثل الجيل الثاني لفحص الأجسام المضادة من نوع

تم إجراء الفحص الناظوري لأعلى الجهاز الهضمي وأخذ خزعات

متعددة من الأثني عشري لكل أفراد العينة وبغض النظر عن نتيجة الفحص المصلي.‏ أستخدمت الوسائل الإحصائية لتقييم

الفحص المصلي المذآور من ناحية الحساسية والنوعية والقيمة التكهنية الموجبة والسالبة ومقارنتها مع نتائج الفحص

النسيجي للخزع.‏

من العدد الكلي للمرضى والذي

مريضا والذين شكلوا نسبة النتائج:‏ آانت نتيجة الفحص المصلي موجبة لدى شهرا،‏ وعند إجراء فحص الخزعة لهؤلاء المرضى تبين بأن النتيجة آانت موجبة أيضا.‏ أما بقية

بلغ معدل أعمارهم من العدد الكلي،‏ فكان آلا الفحصان المصلي والنسيجي لديهم

مريضا ونسبتهم أفراد العينة والبالغ عددهم سالبا.‏

٢٩)

(٤٠)

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© 2010 Mosul College of Medicine 79

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٣٠

.(ELISAs IgA human recombinant tTG)

(١٦)

%٦٠

(٢٤)

(٥١)


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

إن الفحص المصلي المذآور حقق نسبة فيما يخص الحساسية والنوعية والقيمة التكهنية الموجبة والسالبة بالمقارنة

مع نتائج فحص الخزعة.‏

من الممكن استخدامه

الاستنتاج:‏ نتائج هذه الدراسة تعطي دعما إضافيا لفكرة أن الفحص المصلي

آمؤشر مصلي تشخيصي للجواف.‏

(IgA anti-tTG)

%١٠٠

T

he North American Society for Pediatric

Gastroenterology, Hepatology, and

Nutrition (NASPGHAN) recommended that

children and adolescents with symptoms of

celiac disease (CD) or an increased risk for

CD have a blood test for antibody to tissue

transglutaminase (anti-tTG) to identify

individuals for whom the biopsy is indicated (1) .

Despite the increasing importance of

serological methods, the diagnosis of CD is

still based on histological criteria (1, 2) , followed

by a therapeutic response to a gluten free diet

(GFD) (3) .

Second generation ELISAs that detect antitTG2

IgA using human recombinant or human

purified tTG2 antigen have sensitivity and

specificity values ranging from 91% to 97%

with the manufacturer-recommended cut-off

values and are easy to perform (4-7) . As this

type of analysis can be automatized, it is a

valid tool in screening programs, and also is

recommended for monitoring CD patients on

GFD (4) . Failure of the anti-tTG level to decline

over a period of 6 months after starting the

GFD suggests continued ingestion of gluten or

related products (1) . IgA anti-tTG antibody test

can be falsely negative with IgA deficiency,

which is associated with an increased

incidence of CD. Measurement of serum IgA

concentration is mandatory to assure that

false-negative results in IgA-deficient

individuals are excluded (8) . Newer assays

incorporating synthetic deamidated gliadinrelated

peptides or other TG isoenzymes as

antigen, enhances the sensitivity for detecting

gluten sensitivity among non-IgA- deficient,

anti-tTG seronegative patients with CD-like

enteropathy (9) . A positive serological test in an

individual with normal small intestinal histology

may represent a false positive serological test,

milder disease or a more sensitive test that

identifies latent CD before mucosal injury (1) . It

is important to set the lower limit of antibody

titers high enough to avoid false-positive

results (8). In children with CD (87%) younger

and (96%) older than 2 years showed high

serum levels of anti-tTG2 (10) .

Definitive diagnosis of CD requires small

intestinal biopsy (8) . The mucosal involvement

can be patchy and varies in severity, so

multiple biopsies must be obtained (1, 3,11) . The

histologic findings in celiac disease are

characteristic but not specific; indeed, celiac

disease is not the only cause of villous atrophy

(12) . Marsh classified the histologic changes of

CD as Type 0 (normal), Type 1 (increased

intraepithelial lymphocytes), Type 2 (Type 1+

hyperplastic crypts), Type3 (Type 2 + variable

degree of villous atrophy) and Type 4 (total

villous atrophy with crypt hypoplasia) (1) .

Based on these facts investigators inquired

the possibility of obviating the need for small

intestinal biopsy which is invasive, time

consuming, not free of complications, and not

accepted by all patients, by assessing the

value of serological test in diagnosis of CD.

Studies concerning different aspects of CD are

rare in our locality and to the best of our

knowledge no similar study has been

conducted in Mosul.

Patients and methods

This study was approved by ethical committee

in Nineveh College of Medicine and Local

Health Authority. This prospective study has

been conducted at private clinics in Mosul city

during the period from 30 th of October 2007 to

30 th of October 2009. Patients with suspected

CD presenting with anorexia, failure to thrive,

abdominal distention, and chronic diarrhea (in

various combinations) who were aged more

than 6 months and on gluten containing diet

were selected.

A total of 40 patients (29 males, 11 females)

with mean age of 51 months, were

serologically screened by measuring IgA

© 2010 Mosul College of Medicine 80


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

antibody to human recombinant tTG which

was done by commercially available kit

(AESKULISA tTG-A 3503/ Germany) a new

generation of a solid phase enzyme

immunoassay employing human recombinant

tTG cross linked with gliadin-specific peptides

display neo-epitopes of tTG. The cut-off value

of the kit for a positive result is more than 15

U/ml.

For the purpose of achieving the objective of

evaluation of serological data in comparison to

biopsy results, and also because of

unavailability of IgA level measurement for

those with negative IgA anti- tTG2, all patients

were subjected to duodenal biopsy regardless

of the results of serology. Consents of parents

of all patients were taken prior to laboratory

and endoscopic examination. Upper

gastrointestinal endoscopy was done in Al-

Salam General Hospital in Mosul city where

three biopsies from different sites of

duodenum were taken from every patient.

Histopathologic reports were analyzed

according to Marsh criteria (6) .

The validity of the serologic test and the

mean age were computed through using

Statistical Package for Social Sciences (SPSS,

version 14).

Results

IgA anti- tTG2 test of the used kit was positive

in 16 patients (40%), all of them displayed a

positive biopsy suggestive of CD, including

three patients aged ≤ 2 years, where as the

remaining 24 patients (60%) manifested

negative serology test and normal biopsy

results at the same time (Table 1). All patients

with positive serology displayed March 3

histopathologic grading. In this study the

lowest level of IgA anti- tTG2 that was

associated with positive biopsy of CD was

15.05 U/ml, whereas the maximum level

associated with negative biopsy was 12.75

U/ml.

Positive biopsy reports of all patients with CD

showed variable degree of villous atrophy

consistent with the definition of Marsh type 3

histological grading.

Follow up of CD patients after starting GFD

showed that IgA anti-tTG2 levels declined to

normal in 14(87.5%) patients after 6 months of

starting GFD. The remaining 2(12.5%) female

patients, in spite of stressing on importance of

strict adherence to GFD, their IgA-anti tTG2

levels remained positive after 6 months and

their repeated biopsy was positive too (Table

2).

Table (1): Sensitivity, specificity, and predictive

values of IgA anti- tTG2 in comparison to

results of duodenal biopsy.

IgA anti- tTG2

Test positive >15U/ml

Test negative≤15U/ml

Sensitivity = 100%

Specificity = 100%

Positive

biopsy

16

0

Negative

biopsy

0

24

Predictive value of positive test result = 100%

Predictive value of negative test result = 100%

Table (2): Clinical, serological, and histological follow up of 2 CD patients with persistent abnormal

IgA-anti tTG2 level.

Age

(year)

Symptoms

(6 months after GFD)

Initial

IgA anti-tTG2 (U/ml)

6 months after

GFD)

7 months after

GFD)

Biopsy

6 months after GFD

9

Abdominal pain

25.45

29.50

positive

12

Asymptomatic

38.70

43.75

86.76

positive

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Discussion

The newly developed ELISA tests for IgA antitTG

antibodies are now available and are

easier to perform, less expensive than the

immunofluorescence assay that is used to

detect anti-endomysium IgA antibody (anti-

EMA); it is not subjected to inter-observer

variation being investigator-independent (13-16) .

The diagnostic accuracy of anti-tTG

immunoassays has been improved by the use

of human tTG instead of nonhuman tTG

preparations (13) . It has a high sensitivity and

specificity in CD, comparable to (anti-EMA)

antibodies (17) . The serologic tests with the

highest overall diagnostic accuracy were the

tTG and the EMA, addition of HLA-DQ typing

did not add to increase the diagnostic

accuracy of these two tests (18) .

Our study confirms the excellent specificity

(100 %) of the IgA anti-tTG2 test reported by

previous studies (4, 14, 19-21) , and the excellent

(13, 19,

sensitivity (100%) found in other studies 22-24) . Up to 100% positive predictive value was

also registered (4, 14) , which is identical to our

finding. In the current study, the negative

predictive value of IgA anti-tTG2 test was

100%, which was similar to Carroccio A et al

study result (22) . The fact that IgA anti-tTG2

titer has a good relationship with the severity

of the mucosal damage of the small

bowel (23,25) , may explain the 100% sensitivity

of this test in relation to Marsh 3

histopathological grading in our patients. The

sensitivity of this test appears to be lower than

reported when milder histologic grades are

used to define CD (26) .

In some studies high positive tTG level

antibody results has not always been

associated with final diagnosis of CD (27-29) .

This may be attributed to false negative

duodenal biopsy, probably due to patchy

histopathological lesion or using guinea pig

tTG which lacks specificity, and although tTG

antibody positivity may appear in

gastrointestinal and liver inflammatory

disorders, to date, strong positive results have

not been described for such conditions; in

addition many of these patients may have

coexistent CD (30) .

The human tTG-based ELISA is the method

of choice for easy and noninvasive screening

and diagnosis of CD (19) .The presence of

human anti-tTG is a reliable indicator for the

diagnosis and follow-up of CD (2) . In patients

with symptomatic CD, the presence of

circulating anti-EMA or anti-tTG antibodies is

highly predictive (97%–100%) of biopsy

changes of CD

(31) . Serologic testing is

important not only for screening but also for

confirmation of CD (32) .

In children


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

to 1 year, even if the patient remains on a strict

GFD (34). Refractory CD occurs in

approximately 5% of patients with CD (12) and

is defined by persistent or recurrent

malabsorptive symptoms and villous atrophy

despite strict adherence to a GFD for at least

6-12 months in the absence of other causes of

non-responsive treated CD and overt

malignancy, and require additional laboratory

and therapeutic intervention besides a GFD (35-

38) .

Though our study is limited by its relatively

small sample size and being a private clinic

based rather than hospitals or community

based, the study clearly showed that anti-tTG

antibody test is a highly sensitive and specific

marker for CD diagnosis and biopsy might not

always be needed to confirm it.

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disease in Libyan children: antigliadin,

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anticalreticulin antibodies. j pediatr

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© 2010 Mosul College of Medicine 85


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Non CNS pediatric malignancies in Mosul

Khalil I. Mahmood*, Likaa Fasih Al-Kzayer**, Sahar K. Omar***

* Department of Medicine, Nineveh College of Medicine, University of Mosul; ** Pediatric oncologist in

Ibn Al-Atheer Pediatric Hospital;*** Department of Pediatrics, College of Medicine, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 86-91).

Received: 30 th Sept 2009; Accepted: 9 th Feb 2011.

ABSTRACT

Objectives: To find out the types of pediatric malignancies in patients from Mosul, their age and sex

distribution as well as the death rate among these diseases with special emphasis on acute

lymphoblastic leukaemia.

Patients and methods: A survey which was conducted in Mosul pediatric wards of oncology in

Alsalam, Ibn Sina general hospitals and Ibn Alatheer hospital for pediatric diseases on 228 children of

both sexes, their ages were less than 12 years from year 2001-2007. The clinical data were taken

from their case sheets regarding age, sex, clinical presentation at time of admission and the lab tests

including tissue biopsy as well as bone marrow examination.

Results: The commonest 3 types of these malignancies were acute lymphoblastic leukaemia (ALL)

(43.4%), lymphoma (19.5%) and neuroblastoma (7.9%). The mean age of presentation was 65

months; the majority of cases were between 13 months - 6 years. Males predominate in a ratio of

1.28/1. Regarding ALL the main clinical features at presentation were fever, pallor, bone pain and

bleeding. All cases were treated as inpatients. Death rate was high (35.08 %), the commonest causes

were sepsis, bleeding and progressive disease.

Conclusion: There were different types of malignancies in children in Mosul, the commonest were

ALL, Lymphoma and neuroblastoma, with high death rate.

Keywords: Pediatric, malignancies.

الخلاصة

أهداف البحث:‏ لمعرفة أنواع الأمراض السرطانية عند الأطفال في الموصل آذلك الأعراض السريرية لكل نوع مع تشديد

خاص على ابيضاض الدم.‏

التصميم والمشارآون:‏ دراسة وصفية أجريت على طفلا في ردهات الأطفال في مستشفيات السلام وابن سينا وابن

وأخذت

الأثير والتي تعالج فيها سرطانات الأطفال لكلا الجنسين وأعمارهم أقل من سنة بين عامي

المعلومات من سجلات المرضى فيما يخص العمر،‏ والجنس والأعراض السريرية وقت دخول المستشفى مع الفحوصات

المختبرية التي أجريت ومن ضمنها الخزعة النسيجية وفحص نخاع العظم.‏

النتائج:‏ تبين ان الأمراض السرطانية الثلاثة الأآثر انتشارا عند الأطفال هي:‏ ابيضاض الدم السرطانات

اللمفاوية وسرطان الغدد الكظرية وآان معدل عمر الأطفال وقت الدخول الى المستشفى هو ٦٥ شهرا

ومعظم الأعمار آانت تتراوح بين شهرا سنوات ومعظم الحالات آانت من الذآور بنسبة الذآور\الإناث

بالنسبة لابيضاض الدم آانت أهم الأعراض السريرية وقت الدخول الى المستشفى هي الحمى،‏ الشحوب،‏ ألم في

العظام والقابلية على النزف.‏ جميع الأطفال المرضى بالسرطان أدخلوا المستشفى وعولجوا فيه.‏ آانت نسبة الوفيات عالية

وأهم أسباب الوفيات آانت خمج الدم،‏ النزف،‏ متلازمة تحلل الورم وتقدم المرض.‏

١.٢٨)

.٢٠٠٧-٢٠٠١

،(%٤٣,٤)

١٢

٢٢٨

(%٧,٩)

٦-

١٣

(%١٩,٥)

.(١\

(%٣٥,٠٨)

© 2010 Mosul College of Medicine 86


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

الاستنتاج:‏ أهم الأمراض السرطانية عند

الكظرية.‏ نسبة الوفيات آانت عالية.‏

الأطفال

في الموصل هي ابيضاض الدم،‏

السرطانات اللمفاوية وسرطان الغدد

C

ancer in children is not common. Around

1 child in 500 develops cancer by 15

years of age and each year there are 120-140

new cases per million children aged under 15

years (1) .

While in adults about 80% of cancerous

diseases pertain to the respiratory,

gastrointestinal and reproductive organs; only


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

4- Study the percentage of death among

treated patients and the causes of their

death.

Patients and methods

A random sample of 228 children with

different malignant diseases, other than C.N.S

malignancies, who were from Mosul city and

registered in pediatric oncology wards in

Alsalam, Ibn Sina and Ibn Alatheer Hospitals

between January 2001 and December 2007

were included in this study. They were

admitted to the centre and managed as

inpatient for the purpose of diagnosis and

treatment, at least in the phase of induction of

remission. The data taken from all patients and

recorded in isolated files. The case records

were analyzed, including age, sex, signs and

symptoms at the time of presentation and the

final diagnosis of each patient. Z1 proportion

test was used to study the significance in the

difference of male/female ratio and a test value

of more than 1.96 is considered to be

significant.

Acute lymphoblastic leukemia (ALL) was

taken as prototype for studying the clinical

features at the time of presentation. Required

investigations for each case were done

according to the disease type, such as

complete blood picture, E.S.R, different types

of imaging studies, bone marrow aspiration

and biopsy, tumor markers….etc and the

histological diagnosis was confirmed by

pathologists in all cases.

C.N.S neoplasms were excluded from the

study because they were managed in a

different centres; however histiocytosis - X and

connective tissue tumors of borderline

malignancy were also included in this study.

Results

The most common malignancy was acute

lymphoblastic leukemia and it accounted for

43.4 % of all cases. The least common were

retinoblastoma and malignant fibrous

histiocytoma, and each accounted for 0.4 % of

all cases as shown in table 1.

The mean age of presentation of all patients

was 65.16 months, the oldest age group were

those presented with germ cell tumor (132.5

months), while the youngest was that found to

have retinoblastoma (16 months) as shown in

table 1.

The majority of cases had an age range of

13 months - 6years (131 patients) (57.45%).

No case had been diagnosed in the neonatal

period, there were 7 patients between 2-12

months (3%) and there were 90 patients more

than 6 years (39.5%)

Males were 128 while females were 100

(1.28/1), that is a higher male ratio, the male

ratio was clearly higher in the first four

common diseases which were a statistically

significant differences as calculated by Z1

proportion test, however the female ratio is

higher for the less common diseases as shown

in table 1.

Fever was the most common presenting

complaint among patients with acute

lymphblastic leukemia, and was present in

61.6% of patients at the time of diagnosis,

followed by pallor (45.45%), bleeding tendency

(33.33%), abdominal pain (35.35%),

lymphadenopathy, (30.30%), hepatomegaly

and/or splenomegaly (22.22%), fatigue and

weight loss (18.18%) as shown in table 2.

Eighty patients (35.08%) died of all

malignancies due to different causes. Serious

infections (like pneumonia, gastroenteritis and

septicemia), bleeding (mainly intracranial),

progressive disease (resistance to treatment,

metastasis and development of complications

despite treatment) and tumor lysis syndrome

were the major causes of death, however

sepsis was the leading cause of death in 46

patients (57.5%) followed by other causes as

shown in table 3.

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Table (1): Types of malignancies, mean age of presentation and gender of patients.

Malignancy

Table (2): Signs and symptoms of patients with ALL.

Signs and symptoms No of patients %

Fever 61 61.61%

Pallor 45 45.45%

Bleeding tendency (nasal, cutaneous and intracranial) 33 33.33%

Bone pain 35 35.35%

Abdominal pain 31 31.31%

Lymphadenopathy 30 30.30%

Hepato and/or splenomegaly 22 22.22%

Fatigue and weight loss 18 18.18%

Table (3): Causes of death of patients.

Number of

patients

Disease Bleeding Sepsis

Progressive

disease

Tumor lysis

syndrome

1 Acute lymphoblastic leukemia 11 (39%) 16 (57%) 1 (14%) 28

2 Non Hodgkin lymphoma 1 (5%) 14 (74%) 2 (10.5%) 2 (10.5%) 19

3 Neuroblastoma 2 (40%) 3 (60%) 5

4 Hodgkin’s lymphoma 1 (50%) 1 (50%) 2

5 Acute myelogenous leukemia 2 (18.18%) 7 (63.6%) 2 (18.18%) 11

6 Wilms tumor 2 (40%) 3 (60%) 5

7 Rhabdomyosarcoma 1 (25%) 3 (75%) 4

8 Histiocytosis 1 (100%) 1

9 Chronic myeloid leukemia 0

10 Osteogenic sarcoma 1 (100%) 1

11 Hepatoblastoma 1 (100%) 1

12 Germ cell tumor 0

13 Unclassified leukemia 0

14 Primitive neuroectodermal tumor 2 (100%) 2

15 Retinoblastoma 0

16 Malignant fibrous histiocytoma 1 (100%) 1

Total 15 (18.75%) 46 (57.5%) 14 (17.5 %) 5 (6.25%) 80(100%)

© 2010 Mosul College of Medicine 89

%

Mean age in

months

males

females

1 Acute lymphoblastic leukemia 99 43.4 66 63 (63.6%) 36 (36.4%)

2 Non Hodgkin lymphoma 45 19.5 64 26 (57.7%) 19 (42.3%)

3 Neuroblastoma 18 7.9 39.27 13 (72.2%) 5 (27.8%)

4 Hodgkin’s lymphoma 16 7.0 76.25 9 (56.25%) 7 (43.75%)

5 Acute myelogenous leukemia 14 6.1 68.28 5 (35.7%) 9 (64.3%)

6 Wilms tumour 10 4.4 60.80 3 (30%) 7 (70%)

7 Rhabdomyosarcoma 6 2.4 42.33 3 (50%) 3 (50%)

8 Histiocytosis 4 1.8 41.50 1 (25%) 3 (75%)

9 Chronic myeloid leukaemia 3 1.3 68.66 1 (33.3%) 2 (66.6%)

10 Osteogenic sarcoma 3 1.3 94 1 (33.3%) 2 (66.6%)

11 Hepatoblastoma 2 0.9 17 1 (50%) 1 (50%)

12 Germ cell tumour 2 0.9 132.50 0 (0%) 2 (100%)

13 Unclassified leukaemia 2 0.9 87 0 (0%) 2 (100%)

14 Primitive neuroectodermal tumor 2 0.9 108 0 (0%) 2 (100%)

15 Retinoblastoma 1 0.4 16 1 (100%) 0 (0%)

16 Malignant fibrous histiocytoma 1 0.4 61.00 1 (100%) 0 (0%)

Total 228 100 128 (56.14%) 100 (43.86%)

Total


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Discussion

Malignancy is a serious problem, and after

excluding C.N.S tumors, the relative frequency

of different malignancies was nearly similar to

that of other localities and among the total

pediatric patients treated in Mosul as reported

by Mosul cancer registry in year 2008, with

acute lymphoblastic leukemia was the most

frequent one among all other malignancies (2,5-

8,15) . But this study disagrees with another

study done by AL-Jumaily which found that

lymphoma was the commonest type of

malignancy during the period 1991-1998; a

difference that is probably due to the effect of

prohibited weapons used against Iraq at that

time as that study showed (16) .

In general, malignancies were more common

in male children than in females in Mosul and

this was especially true for leukemias,

lymphomas and neuroblastom. The first 5

years of age was the most common age of the

presentation of cancers in Mosul children and

this age requires particular attention when

such diagnosis is considered and this finding

was similar to that found by others . (8,9)

The clinical presentation of malignant

disease in Mosul children was more or less the

same as that written in text books (10,11) , this

was largely because the pathogenesis of the

clinical picture was the same anywhere, and

this was especially true for acute lymphoblastic

leukemia, where fever was the commonest

complaint followed by pallor, bone pain and

bleeding.

The death rate in all cases was 35.08%

compared to less than 30% found by others (2)

and if acute leukemia was taken as a

prototype, the death rate was significantly

higher than that in developed countries (2,13,14) ,

and this was explained by the difficulties

related to management including availability

of diagnostic equipments, chemotherapeutic

agents, effective radiotherapy machines and

lack of stem cell transplantation as well as

difficulties related to follow up of patients.

Sepsis and bleeding were the major causes

of death especially in leukemias and

lymphomas and this was the same as that

found by other studies (12,14) , while another

study found that chemotherapy related toxicity

and resistant disease where the major causes

of death (13) and this is due to improvement in

the diagnosis and treatment of sepsis with this

latter group.

Conclusion

1- Leukemia is the most common malignancy

among Mosul children and it accounted for

43.4% of all cases followed by Non-

Hodgken lymphoma (19.5%) and

neuroblastoma (7.9%).

2- Age and sex distribution in malignant

diseases and clinical features were more

or less similar to those elsewhere.

3- The death rate in general was high, which

was due to the difficulties related to

management and follow up of patients,

and the commonest causes of death were

sepsis, bleeding and progressive disease.

References

1. Lissauer. T, Clayden. G. Illustrated text

book of pediatrics. Third edition, Mosby,

2007. chapter 21, Malignant Diseases:

347-360.

2. P. Imbach· T. Kühne· R. Arceci. Pediatric

Oncology. Second Edition, 2004. Springer-

Verlag Berlin Heidelberg New York.

Introduction, Incidence and Management

of Childhood Cancer : 3-6.

3. Nina S. Kadan-Lottick: Epidemiology of

Childhood and Adolescent Cancer. In:

Robert M. Kliegman, Richard E.

Behrman, et al editors: Nelson Text Book

of Pediatrics,18 th ed, W B Saunders, 2007:

1105-1109.

4. Malcolm A. Smith and Lynn A. Gloeckler

Ries: Childhood Cancer: Incidence,

Survival, and Mortality. In: A. Pizzo, David

G. Poplack: Principles and Practice of

Pediatric Oncology, 4 th Edition , Lippincott

Williams & Wilkins Publishers, 2001:7.

5. Thomas W. McLean Marcia M. Wofford:

Oncology. In: Robert M. Kliegman,

Richard E. Behrman: Nelson Essentials Of

Pediatrics, 5 th ed, W B Saunders, 2006:

725-726.

6. Parkin DM, Stiller CA, Drapper GJ, Bieber

CA. The international incidence of

childhood cancer. Int J Cancer 1988; 42:

511-520.

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

7. Gurney JG, et al: Incidence of cancers in

children in the united states. Cancer

1995; 75:2186.

8. Yacoub AAH, Al-Sadoon IO, Hassan GG

and Al-Hemadi M: Incidence and pattern

of malignant disease among children in

Basrah with specific reference to leukemia

during 78 the period 1990- 1998. Medical

journal of Basrah University 1999;17:33.

9. Kusumakumary P., Rojimon Jacob, Rema

Jothirmayi, M.K. Nair. .Profile of

malignancies: A ten years study. Indian

Pediatrics 2000;37: 1234-1238.

10. Donald H. Mahoney, Jr. acute

lymphoblastic leukemia. In: Julia A.

McMillan , Catherine D et al editors: Oski's

Pediatrics: Principles and Practice,3rd

Edition, Lippincott Williams & Wilkins

Publishers,1999:327.

11. Judith M. Sondheimer, MD. Current

Essentials Pediatrics. first Edition, The

McGraw-Hill Companies, 2008. Chapter 8,

Oncology: p.149.

12. Slats A M, et al: Causes of death in

childhood acute lymphoblastic (ALL) and

myeloid leukemia. Archives of Disease in

Childhood 1992; 67:1378-1383.

13. Ulla M. Saarinen-Pihkala, Carsten

Heilmann, et al: Pathways Through

Relapses and Deaths of Children With

Acute Lymphoblastic Leukemia. Journal of

Clinical Oncology 2006; 24(36): 5750-

5762.

14. Bo Lantz, Jan Adolfsson, Bengt Lagerlöf,

Peter Reizenstein: Causes of Death in

Leukemia and Lymphoma with Modern

Treatment.: Acta Haematol 1980;63:61-67

15. Al-Ramadhani A.H. and Ismail A.M.:

Cancers in children:Cancers in Mosul

2008; 17:31-65.

16. Al-Jumaily S .The prohibited weapons and

malignant disease of children in north of

Iraq: Annals college of medicine Mosul

2000;26 (1 and 2):35-40.

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Soft tissue tumors - Histopathological study of 93 cases

Bashar A. Hassawi*, Abdulkarem Y. Suliman*, Intisar S. Hasan**

*Department of Pathology, College of Medicine, University of Mosul;

**Department of Pathology, College of Medicine, University of Dohuk.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 92-98).

Received: 22 nd Dec 2009; Accepted: 9 th Jun 2010.

ABSTRACT

Objective: Histopathological and immunohistochemical examination of soft tissue tumors to assess

the value of these techniques in verifying the primary diagnosis and their classification.

Methods: A prospective study of 93 consecutive soft tissue biopsies that reached the department of

histopathology, central labs, Dohuk, and application of immunohistochemical markers on 27 biopsies.

Results: Out of 93 soft tissue tumors, 70 (75.2%) were benign with mean age 27.6 y. and 23 cases

(24.8 %) were malignant with mean age 39.1 y.. Immunohistochemistery was performed in 27 cases;

21 (77.7%) cases of malignant tumors and 6 (22.3%) benign cases. The most common benign tumors

were Lipoma, Haemangioma, Neurofibroma, while malignant muscle tumors (leiomyosarcoma and

Rhabdomyosarcoma) and malignant round cell tumors (Ewing’s sarcoma/ PNET) were the major

groups .

Conclusion: High quality H and E stained section, remain the best method for establishing the

primary diagnosis of soft tissue tumors, but immunohistochemical examination proved extremely

helpful in sub classifying them, where 7 out of 9 cases of gastrointestinal tumors (GISTs) showed

strong immunoreactivity with (c – kit proteins) CD 117 , CD 34 , while other (non GISTs) tumors were

negative.

الخلاصة

الهدف:‏ استعمال الفحوصات النسيجية والكيمياوية النسيجية المناعية للتوصل الى التشخيص النهائي وتصنيف أورام

الأنسجة الرخوة.‏

الطريقة والنموذج المستخدم:‏ دراسة مستقبلية ل خزعة نسيجية مأخوذة من أورام الأنسجة الرخوة واستعمال

الفحوصات النسيجية الكيمياوية المناعية ل ٢٧ حالة تطلب استعمالها لتثبيت تشخيصها النهائي وتصنيفها.‏

النتائج:‏ مثلت حالات الأورام الحميدة من الأنسجة الرخوة حوالي حالة وآان معدل العمر سنة،‏ و

من سرطانات الأنسجة الرخوة مع معدل عمر ٣٩,١ سنة وآانت أورام الأنسجة الرخوة الحميدة من

هي الأآثر

هي الأآثر شيوعا.‏ وسرطان الأنسجة الرخوة للعضلات،‏

انتشارا.‏

الاستنتاج:‏ الصبغة النسيجية من نوع H and E هو أفضل طريقة وتمثل حجر الزاوية للتشخيص النهائي لأورام الأنسجة

الرخوة.‏

٢٧,٣

و round cell

(%٧٥,٨)

(٧٠)

٩٣

(٢٣) حالة (%٢٤,٨)

نوع lipoma و haemangioma

S

oft tissue tumors (STTs) are defined as

mesenchymal proliferations that arise in

the extra skeletal nonepithelial tissue of the

body exclusive of the viscera, coverings of the

brain and lymphoreticular system (1) . STTs are

classified according to the tissue that they

recapitulate or principally based on line of

differentiation of tumors, rather than the type of

tissue from which they developed. They

include tumors of voluntary muscle, fat, fibrous

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

tissues, tumors of vessels serving them and

peripheral nervous tissues. However, in some

STTs, no corresponding normal counterpart is

known (2) .

Soft tissue tumors (STTs) are infrequent

neoplasms with the exception of skeletal

neoplasms, However, benign tumors

outnumber their malignant counterpart at least

100:1 due to their rarity as well as the variation

and frequent overlap in their histopathological

features, accurate diagnosis of STTs is a

constant challenge to pathologists (2, 3) .

Over the years, the role of one of these

ancillary diagnostic procedures

(Immunohistochemistery IHC) has greatly

enhanced our capability to properly diagnose

these tumors, from these markers (actin,

desmin, vimentin, S - 100 protein, neuron

specific enolase (NSE), cytokeratin, CD 99 ,

CD 117 , EMA, myoglobulin, AFP) (table 1).

Soft tissue tumors (STTs) arise anywhere in

the body, about (50%) occur in the extremities

(arm, legs, hands or feet), (40%) occur in the

trunk (chest, hips, back, shoulders and

abdomen) and (10%) occur in the head and

neck (4) .

Soft tissue tumors (STTs) usually affects old

persons as about 40% of the affected are 55

years old or older and only 15% are younger

than 15 years (2) . Certain prognostic factors for

(STTs) should be taken in consideration in

order to predict the outcome of tumor which

include the age at presentation, size and site

of the tumors, tumors' grade and histological

subtype (5, 6) , and factors associated with poor

prognosis including old patient (> 60 years)

tumor size (>5 cm) and high grade histology

with deep seated tumors (7) .

Aims of the study

1. To assess the relative frequency of soft

tissue tumors.

2. To assess the role of

immunohistochemical markers in the

primary diagnosis and subclassification of

soft tissue tumors.

Materials and methods

During a period of one year (from 2007 –

2008) a 93 cases of soft tissue tumor were

collected from Azadi Teaching Hospital. Data

collected from each patient includes age, sex,

cheif complaint, site of lesion and history of

trauma.

The following histopathological and

immunohistochemical techniques were used:

1. Routine H and E staining method was

applied for primary diagnosis and

subtyping of soft tissue tumors were

performed on each case.

2. Standard Avidin - biotin peroxidase

complex (ABC) and the following

immunohistochemical markers (actin

(smooth muscle actin), desmin, vimentin,

S - 100 protein, neuron specific enolase

(NSE), cytokeratin, CD 99 , CD 117 , EMA,

myoglobulin, AFP). (table 1) were applied

on 27 cases as needed.

Result

During a period of one year, 93 cases of soft

tissue tumors were collected. There were (70)

cases 75.2 % of benign soft tissue tumors with

mean age of 27.6 y. and (23) cases (24.8 %)

malignant one with mean age of 39.1 y. (table

2).

The most frequent benign tumors were:

lipoma, hemangioma and neurofibroma, while

the malignant muscle tumors

(Leiomyosarcoma and Rhabdomyosarcoma)

and malignant round cell tumor (Ewing’s

sarcoma / PNET) were the major group of

sarcomas (table 3).

Table (1): Markers most commonly used to

correlate with histogenesis.

Histogenesis

1- Mesenchymal

(general)

2- Epithelial

3- Smooth muscle

4- Skeletal muscle

5- Fibrohistiocytic

6- Melanocytes

7- Neuronal

8- Endothelial

9- Neuroendocrine

Ewing’s

sarcoma / PNET

Vimentin

Markers

Cytokeratin, Epithelial

Membrane Antigen (EMA)

Desmin, actin (smooth

muscle actin)

Myoglobin

Vimentin, CD68, factor XΙΙΙa

HMB45. S – 100 protein

S – 100 protein, glial fibrillary

acidic protein

Factor VIII, CD 34 , factor XIIIa

Neuron-specific enolase

(NSE), chromogranin,

synaptophysin CD 99

PNET = primitive neuroectodermai tumor

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

The immunostaining was used in 27 cases

depending on the differential diagnosis which

was highlighted by H & E staining where 7

cases of gastrointestinal stromal tumors out of

9 cases show positive immunoreactivity for

CD 117 , CD 34 ((c – kit proteins)) (table 4).

Table (3): Histological types of soft tissue tumors.

Table (2): Type and number of soft tissue

tumors with mean age.

Type of

Men

Number Percentage

tumor

age / yr.

Benign

tumors

70 76.3 % 27.6

Malignant

tumors

23 23.6 % 39.1

Total 93

Histological types

Benign tumors

Total

number

Malignant tumors

Total

number

Tumor like lesions 16 16

Adipose tumors lipoma 20 Liposarcoma 3 23

Vascular tumors

Fibrohistiocytic tumors

Neuronal tumors

Smooth and skeletal

muscle tumors

others

Hemangioma &

glomus tumor

Giant cell tumor of

tendon sheath

Neurofibroma

& schwannoma

Rhabdomyoma

& leiomyomas

Total

22 Kaposi sarcoma 1 23

2

Malignant fibrous

histiocytoma

2 4

8 Malignant schwannoma ----- 8

2

Rhabdomyosarcoma

& leiomyosarcomas

Synovial sarcoma

PENT / Ewing's tumor

11 13

total 70 23 93

Table (4): Histological types and its immnuoreactivity.

1

5

1

5

Type of tumour

NO. of cases

vimentin

S –100 protein

Actin

Desmin

myoglobin

keratin

CD 99

NSE

AFP

CD117+

EMA

Ewing’s sacrcoma / PNET 5 + + + +

Rhabdomyo sarcoma 3 + + +

Synovial sarcoma 1 +

Schwannoma 2 +

Neurofibroma 1 +

Leiomyosarcoma 1 + + +

Gastrointestinal stromal tumor

(GIST)

MFH 2 +

Liposarcoma 1 +

Spindle cell lipoma 1

Glomus tumor 1 + + +

Total 27

9 + +

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Discussion

Soft tissue tumors (STTs) constitute a large

and heterogeneous group of neoplasm that

involves muscles, fat, fibrous tissue with their

supplying vessels and peripheral nerves.

Soft tissue sarcoma is a disease of the adult,

occurring most commonly in persons between

30 and 60 years of age, except few types like

embryonal, and botryoid rhabdomyosarcoma

occur in young children. The mean age was

39.1 yr; a finding compatible with others (table

2) (8) .

Although clinical information regarding age,

site, size of the lesions are critical for the

diagnosis of STTs, but histological

examination remains the cornerstone for their

diagnosis. However, certain complementary

methods like EM and immnunohistochemical

examination (IHC) may be needed to confirm

the diagnosis and to establish their

classification (9) .

The IHC should be applied after careful H &

E examination in order to limits the number of

markers selected in every specific case. In this

study many markers were applied for

confirmation of diagnosis.

Vimentin is the most known broad spectrum

marker for detection of mesenchymal tumors.

It is an intermediate filament protein where the

desmin and cytokeratin belong to this group of

cytoskeleton. In general vimentin reacts with

fibroblasts, Endothelial cells and smooth

muscle of leiomyoma of the uterus (but not

with that arising in the gastrointestinal tract)

(10,11) .

This wide variation in immunoreactivity of

vimentin makes it of limited diagnostic value.

In this study many benign and malignant

tumors were positive for vimentin (table 4).

Due to the lack of specific markers for

fibrohistiocytic tumors, Vimentin is known as

the only marker positive in fibrohistiocytic

tumors, that is why the diagnosis of these

tumors is based on the absence of markers of

other lineages (12) . In this study there were two

cases of MFH showing strong

immunoreactivity for vimentin.

S-100 protein is widely distributed in

peripheral (Schwann cells) and central

nervous system (Astrocytes and

oligodendrocytes) as well as melanocytes

indicates that these cells are both considered

to arise from neural crest, the result of this

study confirms this correlation (13) , but it is also

appeared in other tumor that does not show

neuronal differentiation like glomus tumor

(table 4) .

Actin is a marker which is expressed in

tumors that arise from striated and smooth

muscle fibers like leiomyoma, rhabdomyoma,

rhabdomyosarcoma and leiomyosarcoma as

well as few types of vascular tumors like

glomus tumor and hemangiopericytoma; these

contractile proteins are classified as alpha

(skeletal, cardiac and smooth muscle) and

beta (cytoplasmic) and gamma (smooth

muscle and cytoplasmic) (14) . In this study actin

was positive with the above mentioned tumors

except for rhabdomyosarcoma because we

use smooth muscle actin where the specificity

of smooth muscle actin is more restricted (it

doesn't detect skeletal and cardiac muscle

actin). These results were compatible with

others (15-16) .

Desmin is intermediate filament markers for

skeletal, cardiac and smooth muscle; it is

expressed in 95 % of Rhabdomyosarcoma and

variable smooth muscle tumor Fig. (1 A, B ).

Other tumors may share this reactivity like

MFH (17) , this expression of conventional

markers of muscle fiber tumors in some cases

of MFH may raise the questions about the

nature of this tumor and its histogenesis.

Myoglobin represents a specific marker for

neoplastic striated muscle cells, i.e.

"Rhabdomyosarcoma" which includes different

histological subtypes (i.e., embryonal, botryoid,

alveolar, pleomorphic) (18,19) . In the current

study 3 cases of rhabdomyosarcoma were

positive for Myoglobin.

Myxoid liposarcoma in this study was

negative for all markers, although few cases of

liposarcomas express focal reactivity for S-100

protein (20) ; a finding compatible with others Fig

(2 A, B ).

Gastrointestinal stromal tumors (GISTs)

comprise the largest subset of mesenchymal

tumors of the gastrointestinal tract, they are

characterized by expression of tyrosine kinase

growth factor receptors (c-Kit antigen). These

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

neoplasms differ immunohistologically and

behaviorally from other mesenchymal tumors

such as leiomyosarcoma which does not

express Kit antigen. Most GISTs express CD 34

and CD 117 (c-kit protein) but not desmin (21) . In

the current study there were 9 cases of GISTs

(8 malignant and one benign), 7 cases were

positive for CD 117 and CD 34 , which was

compatible with others (22) .

Both cell surface antigen P30/ 32 (CD 99 ) and

NSE are markers of tumors that express a

neural differentiation (23) . These include Ewing's

sarcoma of bone and soft tissue (Fig. 3) and

primitive neuroectodermal tumor (PNET)

where molecular studies have recently

revealed that (PNET) and Ewing's sarcoma

entities that once considered unrelated, are

perhaps best considered as members of the

same family (24,25) . In this study there were 5

cases all were positive for these markers, a

result matched with other studies (26) .

In this study the malignant tumors constitute

about quarter of all STTs, and this result does

not reflect the accurate incidence of malignant

tumors, because not all benign tumors are

excised and rarely sent for histopathological

examination.

Finally the IHC is a good tool in the

differentiation between large numbers of soft

tissue tumors and it is an indispensable

procedure for the solution of the diagnostic

challenges facing the pathologist.

Figure (1-B): Desmin in leiomyosarcoma.

Figure (2-A): Synovial sarcoma exhibiting a

classic biphasic spindle cell and gland – like

histologic appearance.

Figure (2-B): “Epithelial Membrane Antigen”

(EMA) In Synovial sarcoma.

Figure (1-A): Leiomyosarcoma. This tumor

consists of elongated cells with a cigar –

shaped nucleus and eosinophilic cytoplasm,

with several mitosis.

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Figure (3): Ewing's sarcoma (H and E stain)

sheets of small round cells slightly larger than

lymphocytes.

Conclusion

1. H and E stained sections remain the best

method for establishing the primary

diagnosis of soft tissue tumors.

2. Immunohistochemistry is of great help in

accurate categorization of both benign and

malignant tumors particularly (c-kit protein)

CD 117 , CD 34 in GISTs .

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soft tissue tumors. Am J Pathol. 1988;

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17. Truong LD, Rangdaeng S, Cagle P, et al.

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

The role of aerobic and anaerobic bacteria in

non gonococcal urethritis (NGU) in men

Haitham M. Al-Habib*, Haitham B. Fathi**

* Department of Microbiology, ** Department of Medicine, College of Medicine, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 99-105).

Received: 17 th Oct 2010; Accepted: 9 th Feb 2011.

ABSTRACT

Objectives: To identify causative microorganisms of nongonococcal (NGU) urethritis in men.

Methods: A descriptive comparative study included 240 male patients with urethritis and 40 agematched

males free from urethritis was carried out. The urethral swabs were inoculated on different

culture media and incubated both aerobically and anaerobically.

Results: A 153 patients were considered as NGU cases. From them, 18 genera of aerobic and

anaerobic microorganisms were isolated. Aerobic bacterial isolates were two times the anaerobic

bacterial isolates. The type of growth was heavy among patients in comparison to scanty growth

among controls. The most common microorganism in each group were Staph. epidermidis,

Gardnerella vaginalis, and Bacteroides species.

Conclusion: Aerobic and anaerobic microorganisms are associated with urethritis in men. The

confluent growth and dramatic response after treatment by appropriate antibiotics confirm the roles of

the isolated bacteria in development of NGU in men.

Key words: Urethritis, nongonococcal urethritis, aerobic & anaerobic bacteria.

الخلاصة

الأهداف:‏ تشخيص أنواع الجراثيم المسببة لخمج الاحليل غير السيلاني وغير الكلاميدي عند الرجال.‏

طريقة البحث:‏ أجري البحث بالطريقة المسحية المقارنة على عينة مكونة من مريضا مصابا بخمج الاحليل.‏ قورنت

النتائج مع نتائج الفحص ل متطوعا مطابقين للمرضى في العمر ولا يعانون من خمج الاحليل.‏ أخذت مسحات من

الاحليل وزرعت على أوساط مختلفة لزرع الجراثيم تحت ظروف هوائية ولا هوائية.‏

النتائج:‏ أظهرت نتائج الدراسة الحالية أن مريضا آانوا يعانون من خمج الاحليل غير السيلاني وغير آلاميدي.‏ تم

عزل جنسا مختلفا من الجراثيم الهوائية واللاهوائية وآانت الجراثيم من النوع الهوائي ضعف الجراثيم من النوع

اللاهوائي.‏ آان النمو الجرثومي آثيفا في عينة المرضى مقارنة مع النمو المتفرق والشحيح عند الأصحاء من العينة

الضابطة.‏ أن أآثر أنواع الجراثيم شيوعا في آل مجموعة هي المكورات العنقودية الجلدية،‏ الكاردنيريلا المهبلية وجراثيم

الباآتيرويدس.‏

الخلاصة:‏ أن الجراثيم الهوائية واللاهوائية التي عزلت من مسحة الاحليل في الدراسة الحالية لها علاقة سببية وثيقة مع

الإصابة بخمج الاحليل عند الرجال ويدعم هذا الرأي نتائج النمو الجرثومي الكثيف للجراثيم المعزولة من المرضى وآذالك

الاستجابة الجيدة للمرضى بعد إعطائهم المضاد الحيوي المناسب.‏

٢٤٠

١٠٦

٤٠

١٨

U

rethritis is a common sexually

transmitted disease in men (1) . Around

half of the cases are caused by Chlamydia

trachomatis and Neisseria gonorrhea and the

second half are caused by other microbes (2,3,4) .

The latter is called nonchlamydial

nongonococcal urethritis (NCNGU). The NGU

is a common condition frequently diagnosed in

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

sexually transmitted diseases clinics all over

the world (3) . It is the most common condition

diagnosed and treated in men who attend

departments of genitourinary medicine in the

United Kingdom (5) . Despite the extensive

studies, its prevalence among urethritc group

and the etiology remain controversial (6) . In

addition to the causative bacterial pathogens

associated with NGU, it has been

demonstrated that there was a significant

relationship of Mycoplasma genitalium with

acute NGU (7) . The major effort applied to

identify novel pathogens have employed

culture methods mainly (8,9) . However,

molecular techniques have believed that

documented cultured microorganisms to date

represent fraction of the total pathogens (10) .

Because information regarding NGU is lacking

in our locality, this study was conducted aiming

the determination of the causative bacteria of

NGU.

Patients and methods

This study was approved by the Scientific

Research Committee at the College of

Medicine, University of Mosul. Formal consent

was taken from all patients and control

subjects after careful explanation.

The present study includes 240 males

presented with signs and symptoms of

urethritis who attended the Dermatology and

Venereology Clinics at Mosul Teaching

Hospital or referred from private clinics to the

Department of Microbiology, College of

Medicine, University of Mosul, during the

period from April, 2007 to March 2009. The

age of the patients ranged from 18 to 52 years

with mean and standard deviation of

(26.3±7.9) years, while that of the control

subjects varied from 22 to 45 years with mean

and standard deviation of (24.5±5.8) years.

The patients who used antibiotics during the

last two weeks, those with visible urethral

deformities such as hypospadias, stricture,

surgical interference or others, and patients

who refused to participate in the study were

excluded. A total of 240 patients were enrolled

in the current study. The patients were

suffering from penile irritation, urethral

discharges and/ or dysuria. The urethral

meatus of each patient was washed with a

sterile gauze soaked in sterile distilled water,

then a 30 ml of first voided urine was collected

into sterile tubes. The urethritis was confirmed

microscopically on the basis of >6

polymorphonuclear leukocytes (PMNs) per ml

in sediments of urine samples (1) . In addition

urethral swabs were obtained for diagnostic

purposes.

The patients were treated with the

appropriate antibiotics namely ciprofloxacin

500 mg twice daily for one week and / or

doxycycline 500 mg twice daily for one week.

A control subjects of 40 male volunteers with

no signs and symptoms of urethritis who

matched the patients by age (22 to 45 years)

were asked to participate in this study. The

inclusion criteria included married, absence of

urethral discharge after urethral squeezing and

have


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Results

Among the examined 240 urethral discharge

specimens, 87 (36.2%) were positive for

Neisseria gonorrhea by both gram stain and

culture. The remaining 153 (63.8%) were

considered as non gonococcal urethritis

(NGU). Among them 106 (69.3%) yielded a

positive bacterial growth, while the remaining

47 patients (30.7%) showed a negative

growth. Different 18 genera of aerobic and

anaerobic microorganisms were detected from

the patients and controls (Tables 1, 2, and 3).

Some cases yielded a single microorganism,

while other cases showed a mixed bacterial

growth. The ratio of aerobic to anaerobic

microorganisms was 2:1 and the ratio of

aerobic gram positive to gram negative

microorganism was 1.6: 1. The most common

isolates of aerobic gram positive bacteria were

Staph. epidermidis (26.4%), Corynebacterium

species (17.0%) and lactobabacilli (15.1%). G.

vaginalis (13.2%) and Escherichea coli (9.4%)

represent the most frequent gram negative

isolates. Bacteroides species (15.0%),

Peptostreptococcus (13.2%), and Prevotella

melaninogenicus (11.3%) were the dominant

anaerobic isolates. Also, 11 isolates of

Mycoplasma and 6 isolates of Candida

albicans were detected. The difference in

Staph. epidermidis and total aerobic Gram's

positive bacterial isolates between patients

and controls was statistically significant, while

the rest of differences were statistically nonsignificant.

Overall the type of growth of the

isolated microorganisms were heavy growth

(+++) among patients in comparison to scanty

growth isolates among control subjects. This

means that the number of isolated colonies

obtained from studied patients was greater

than that resulted from control group. Among

the tested 40 control subjects, only 34 of them

showed a positive culture growth while

negative growth was obtained from the

remaining 6 individuals.

Table (1): Percentage of aerobic gram positive bacteria isolated from patients with NGU and control

group.

Microorganism

* (+) scanty, (++) moderate, (+++) heavy growth ** χ 2 test, df=1

Table (2): Percentage of aerobic gram negative bacteria isolate from with NGU and control group.

NGU

Control

N=106

N=40

Microorganism

No. %

No. %

NGU

N=106

Type of

growth*

Type of

growth

No. %

No. %

Control

N=40

Type of

growth

Type of

growth

NGU

vs.

control

NGU

vs.

control

P-value**

Staph. epidermidis 28 26.4 +++ 4 10.0 + 2.6:1 0.02

Corynebacterium 18 17.0 +++ 6 15.0 + 1.1:1 0.49

Lactobacilli 16 15.1 +++ 8 20.0 + 1:1.3 0.31

α-h.streptococci 12 11.3 ++ 3 7.5 + 1.5:1 0.36

Ent.faecalis 8 7.5 + 2 5.0 + 1.5:1 0.45

Staph.saprophyticus 2 1.9 + 2 5.0 + 1:2.6 0.30

Total 84 79.2 25 62.5 1.2:1 0.03

P-value

G. vaginalis 14 13.2 ++ 4 10.0 + 1.3:1 0.41

Esch. coli 10 9.4 +++ 4 10.0 + 1:1.1 0.56

Acinetobacter 8 7.5 +++ 2 5.0 + 1.5:1 0.45

Klebsiella 7 6.6 ++ 4 10.0 + 1:1.5 0.35

P. aeruginosa 4 3.8 +++ 2 5.0 + 1:1.3 0.52

Proteus sp. 4 3.8 +++ 4 10.0 + 1:2.6 0.14

H. parainflunzae 3 2.8 + 0 00.0 - - -

H. influnzae 1 0.9 + 0 00.0 - - -

Total 51 48.1 20 50.0 1:1 0.49

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Table (3): Percentage of anaerobic gram positive and gram negative bacteria isolate from patients

with NGU and control group.

NGU

Control

N=106

N=40 NGU vs.

Microorganism

P-value

Type of

Type of control

No. %

No. %

growth

growth

Peptostreptococcus 14 13.2 +++ 3 7.5 + 1.8:1 0.25

P. melaninogenius 12 11.3 +++ 2 5.0 + 2.2:1 0.20

Prop. acne 10 9.4 ++ 6 15.0 + 1:1.6 0.24

Lactobacilli 10 9.4 ++ 8 20.0 + 1:2.1 0.07

B. corodons 8 7.5 ++ 1 2.5 + 3:1 0.23

B. fragilis 8 7.5 ++ 2 5.0 + 1.5:1 0.45

Eubacterium 6 5.6 ++ 1 2.5 + 2.2:1 0.38

Total 68 64.1 23 57.5 1.1:1 0.29

Discussion

Regarding the etiology of NGU in males, it is

appropriate to distinguish between acute and

chronic disease. This study included only

acute cases of urethritis. The etiology of NGU

is multifactorial (10,11) . Both aerobic and

anaerobic bacteria were isolated from almost

all sexually active non-urethritis (NU) men and

males with NGU (12) . This corresponds well with

this study where different genera of aerobic

and anaerobic bacteria were obtained. In the

current study, except for staph. epidermidis, no

significant differences were noted among

different aerobic and anaerobic isolates

between patients and control subjects. This is

in agreement with results of other groups who

had examined the urethral flora of males with

and/or without urethritis (13-15) and mentioned

that no differences between NGU patients and

NU men. Moreover, Bowie et al. (12) reported

that aerobic lactobacilli, G. vaginalis, alphahaemolytic

streptococci, and Bacteroides were

isolated significantly more frequently from the

NU group than NGU patients. However some

investigators had low isolate rate for

aerobes (13) . In another study at least one

aerobe was isolated from 93% or more of

individuals (12) . Mehta etal isolated few Staph.

epidermidis, but many Staph. aureus (14) . Also,

Helmholz in USA (16) reported isolation of

Staph. aureus which has not been obtained in

more recent studies including the present

study. Staph. epidermidis and other coagulase

negative staphylococci are normal

commensals of the skin, but increasing

importance of these microorganisms as human

pathogens has been recognized over the past

25 years (17) . Many studies confirmed rising

frequency of infections caused by these

microorganisms (18) . In the current work Staph.

epidermidis constituted the dominant aerobic

gram positive isolate (26.4%) followed by

Corynebacterium species (17.0%) which was

in agreement with other studies (12) who

reported that Staph. epidermidis was isolated

from 96% of patients with Chlamydia

trachomatis positive NGU and in 88% of

individuals with C. trachomatis negative NGU.

These high isolation percentages of Staph.

epidermidis and that recorded in the current

study are attributed to the great ability of this

microorganism to attach firmly on biot or abiot

surfaces which is facilitated by its natural

hydrophobic nature. In addition Staph.

epidermidis produces a viscous extracellular

polysaccharide slim as biofilm which provides

additional adhesion to the epithelial surfaces

of urethra and resistance to multiple

antimicrobial agents (19) . Davis etal reported a

relatively high recovery of corynebacterium

species, but there was a nonsignificant

difference between men with or without

NGU (15) . Also, the rate of isolation of so-called

NGU corynbacteria by Furness et al was the

same for normal as for patients with NGU (20) .

G. vaginalis constituted 13.2% out of the total

isolates of gram negative bacteria which was

quite different from the finding in other studies

who recovered G. vaginalis in percentage of

4.6% and 6.9% respectively (12,21) . However,

other investigators proposed that G. vaginalis

was the cause of some cases of NGU (22) .

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Riemersma et al reported that Pseudomanslike

bacterial species were identified relatively

frequently. Really many of the gram negative

bacilli recovered by Ambrose and Taylor (23)

were Pseudomonas aeruginosa which was

also detected in the current study in

percentage of 3.8%. The detection of diversity

of Pseudomonas-like bacterial species

suggests that there is much to explore in the

bacterial flora of the male urethra. Whereas

the detection of bacterial species that

disappear upon disease development may

have important implication to the therapy of

NGU. The prevalence of NGU and the

pathogenic potential of these bacterial species

need to be defined more precisely. This

requires the development of diagnostic tests

for these elusive microorganisms that allow

larger group of patients to be screened. In

addition, various species of the genus

Haemophilus have been implicated in NGU (24) .

In the present study H. parainflunzae (2.8%)

and H. influenzae (0.9%) were isolated from

NGU patients but were not encountered

among healthy controls. This is unsuitability

with results of other investigators (1) .

Acinetobacter (7.5%) appeared as a distinct

causative agent of NGU in our results, which

was also confirmed by other workers (12) .

In the current study different genera of

anaerobes were detected from both NGU

patients and controls (Table 3). This result

goes with that of other workers who suggested

that anaerobes could be recovered from both

patients with NGU and healthy people, hence

they are part of normal urethral flora (12) .

However other investigators have either failed

to isolate anaerobes from patients with NGU

and/or men without urethritis (13,25) . In addition,

other investigators recovered them in small

fraction. In contrast to other studies, Hafiz et al

reported a great correlation between NGU and

urethral infection with Clostridium difficile (26) . In

this study no single isolate of C. difficile was

seen in both gram stain and anaerobic culture.

The Bacteroides species were recovered from

(15.0%) of the total cases which is really

somewhat higher than the results of other

workers who reported percentages of 12.5%

and 3.9% respectively (27,18) . However other

investigators didn't isolate Bacteroides species

from any case of NGU (28) . The high isolation

rates of Peptostreptococcus (13.2%) and

Prevotella (11.3%) among anaerobes were in

agreement with the finding of other

investigators (12) .

Mycoplasma genitalium is one of the

pathogens of male urethritis and is usually

transmissible (29) . Recent data by Bjornellius et

al revealed that M. gentitalium could be

detected in more than 36% of patients (11) . The

study done by Totten, et al showed a strong

association of M. genitalium and NGU in 22%

of patients and 4% of control group (5) . In 1996,

Jensen, et al reported that four M. genitalium

strians were isolated from urethral swab of

men with NGU (30) . In the current study

Mycoplasma species constituted 10.4% out of

the total 106 growth positive cases and in

3.8% of the control group. This somewhat low

isolation rate of Mycoplasma may be due to

the need of further sophisticated identification

procedures which are not available in our

department at the meantime. The increasing

evidence of the association of M. genitalium

with urethritis in men implies the need for

further studies assessing the potential

treatment and prevention strategies. Moreover,

clinical diagnostic molecular test such as PCR

could be helpful for detection of M. genitalium

in both men and women.

The recorded 47 negative cases may be

attributed to other causes such as Chlamydia

trachomatis, Herpes simplex viruses,

adenoviruses, or Trichomonas vaginalis.

In conclusion, most of the isolated bacteria in

the current study represent part of the normal

flora of urethra of patients and control group.

But, the heavy growth of different pathogens

obtained from patients in contrast to the scanty

type noted in control subjects may indicate the

capability of these bacteria to adhere firmly to

epithelial surfaces of urethra which lead to

infection. Another important evidence confirms

the involvement of these bacteria in urethritis

was the good response obtained in patients

after treatment with the appropriate antibiotics

where there was no urethral discharge and

symptoms of dysuria and itching subsided.

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Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

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Gonorrhea and Vener. Dis. 1953; (37):

501-513.

26. Sturm AW. Haemophilus influenzae and

Haemophilus parainfluenzae in nongonococcal

urethritis. J. Infect. Dis. 1986;

(153): 165–167.

27. Justesen T, Nielson M L, Hattel T.

Anaerobic infections in chronic prostatitis

and chronic urethritis. Med. Microbiol.

Immunol. 1973; (158): 237-248.

28. Hafiz S, McEntegart M G, Morton R S, et

al. Clostridium difficile in the urogenital

tract of males and females. Lancet. 1975:

420-421.

29. Swartz SL, Kraus SJ, Herrmann KL, et al.

Diagnosis and etiology of nongonococcal

urethritis. The journal of infectious

diseases. 1978; 138 (4): 445-454.

30. Hallen A, Ryden AC, Schwan A, et al. The

possible role of anaerobic bacteria in the

etiology of nongonococcal urethritis in

men. British Journal of Venereal Disease.

1977; (53): 368-371.

31. Hamasuna R, Osada Y, Jensen JS.

Isolation of Mycoplasma genitalium from

First-Void Urine Specimens by Coculture

with Vero Cells. J. Clin. Microbiol. 2007:

847–850.

32. Jensen JS, Hansen H T, Lind K. Isolation

of Mycoplasma genitalium strains from the

male urethra. J. Clin. Microbiol. 1996; (34):

286–291.

© 2010 Mosul College of Medicine 105


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Bacterial etiology of chronic osteomyelitis involving anaerobes

Haitham M Al-Habib*, Mahmood A Aljumaily**

*Department of Microbiology, **Department of Surgery, College of Medicine, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 106-113).

Received: 21 st Jul 2010; Accepted: 12 th Jan 2011.

ABSTRACT

Objective: To identify common bacterial causes in chronic osteomyelitis, to verify the role of

anaerobic microorganisms in chronic osteomyelitis, and to assess the reliability of swab from

discharging sinuses, and from abscess aspirate in chronic osteomyelitis.

Material and Methods: The study included 184 patients suffering from chronic osteomyelitis, 141

males and 43 females, ranging in age between 4-78 years with mean 40.5 years. The patients

presented with chronic discharging sinus in 152 patients or acute flare up in 32 patients; they were

divided according to causes into two broad categories haematogenous in 52 patients and exogenous

in 132 patients. Specimens were taken from infected bone debridement during surgery, other

specimens taken from sinus discharge or aspirated from bone abscesses. All specimens were

inoculated on different culture media and incubated both aerobically and anaerobically.

Results: The majority of cases of chronic osteomyelitis involved long bones specially the femur and

tibia (64.6%). Aerobic microorganisms were found in 134 patients (73%), staph. aureus and

pseudomonas were the commonest aerobic isolates. In fifty cases (27%), the causative

microorganisms were anaerobic. Anaerobes were found to be mixed with aerobes in 34 cases (68%),

while pure anaerobes were obtained in 16 cases (32%). Peptostreptococcus and Bacteroides were

the dominant anaerobic isolates. The reliability of culture of abscesses aspirate in comparison with

bone debridement culture is 93.3%. The reliability of culture of sinus discharge in comparison with

bone debridement culture is 42.7%, while for anaerobic infection is 26%.

Conclusion: Chronic osteomyelitis commonly affect adult males in long bones. The exogenous

causes were the commonest. Aerobic isolates were the major cause, and anaerobic bacteria were an

important other causative agents. Anaerobes usually isolated in prolonged persistent infection and

pure anaerobes in older patients. The cultures of aspirate from bone abscesses were reliable way in

diagnosis, while cultures from discharging sinuses had low diagnostic reliability and lower for

anaerobic infection.

Keywords: Osteomyelitis, chronic, aerobic, anaerobic, microorganisms.

الخلاصة

الأهداف:‏ تحديد الأنواع الشائعة من البكتريا في التهاب العظم المزمن والتأآيد على دور البكتريا اللاهوائية في التهاب

العظم ولتحديد درجة الثقة في العزلات من الجيوب الفارزة ومن قيح الخراجات المسحوبة أثناء العملية الجراحية في

تشخيص البكتريا المسببة.‏

المرضى والطريقة:‏ شملت الدراسة حالة من التهاب العظم المزمن وردوا ولديهم جيوب فارزة أو مصابين بالتهاب

حاد عقب الالتهاب المزمن للعظم.‏ تم تقسيم المجموعة حسب السبب إلى عقب التهاب دموي المنشأ أو خارجي المنشأ ثم

أخذ عينات من فتات العظام الملتهبة وزرعت في أوساط زرعية مختلفة هوائية ولا هوائية.‏ آما أخذت عينات زرعية من

إفراز الجيوب ومن الخراجات.‏

١٨٤

© 2010 Mosul College of Medicine 106


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

النتائج:‏ شملت الدراسة من الذآور و‎٤٣‎ من الإناث وآان معدل أعمارهم سنة وآان عمر معظم المصابين

فوق الثلاثين عام.‏ وآانت أآثر الإصابات في العظام الطويلة وبالأخص عظم الفخذ وقصبة الساق.‏ آانت أخماج البكتريا

الهوائية وأعطت عزلات مختلطة في وعزلات نقية في وآانت البكتريا الأآثر في العزلات المكورات

الذهبية تليها الزائفات ثم الايشريشياآولاي.‏ وجدت البكتريا اللاهوائية في حالة أي وآانت العزلات مختلطة في

حالة وآانت نقية في حالة آانت الببتوستربتوآوآس والبكترويد هي أآثر العزلات شيوعا،‏ أظهرت

زراعة فتات العظام الملتهبة نموا في آل الحالات،‏ وآانت تطابق مع الزرع من إفرازات الجيوب في حالة من

حالة وآان الزرع من الخراجات متطابقا في ٣٠ حالة من ٣٢ حالة.‏

الخلاصة:‏ أن التهاب العظم المزمن أآثر شيوعا في الذآور البالغين وفي العظام الطويلة وهي غالبا خارجية المنشأ عقب

الكسور المفتوحة والعمليات الجراحية.‏ وأن البكتريا الهوائية هي المسببات الأآثر لالتهاب العظم المزمن وبالأخص

المكورات العنقودية الذهبية والزائفات وهي الأآثر في العزلات.‏ إن البكتريا اللاهوائية سبب مهم في التهاب العظم المزمن

وان الببتوستربتوآوآس تليها البكترويد هي الأآثر شيوعا في التهاب العظم المزمن اللاهوائية،‏ إن زرع السائل المسحوب

من الخراج أو من تجويف العظم طريقة موثوقة في تشخيص المسبب البكتيري وإن ثقة الزرع من الجيوب الفارزة لبكتريا

قليلة واقل في حالة البكتريا اللاهوائية.‏

١٥٢

٦٥

%٢٧

٤٠,٥

%٢٢

٥٠

%٧٨

.%٣٢

١٦

١٤١

١٣٤

%٦٨

٣٤

O

steomyelitis is an infection of bone and

bone marrow that may be caused by

direct inoculation of open fractures or surgical

procedures (exogenous), or blood born

organism (haematogenous) (1) . Osteomyelitis

could be acute or chronic although distinction

between the two types may not be clear either

clinically or on morphologic examination of

tissue (2, 3) . Chronic osteomyelitis used to be

the dreaded sequel of acute haematogenous

osteomyelitis; nowadays it more frequently

follows open fractures or postoperative (4) .

Chronic osteomyelitis is difficult to eradicate

completely, systemic symptoms may subside,

but one or more foci in the bone may contain

purulent material, infected granulation tissues

or a squestrum (5) . Intermittent acute

exacerbations may occur for years (5) .

Culture of material taken from a bone biopsy

is needed to identify the specific pathogens,

alternative sampling methods such as needle

puncture or surface swabs are easier to

perform (6) . the usual aerobic organisms in

chronic osteomyelitis are Staph. aureus,

Escherichia coli, Streptococcus pyogenes,

Proteus, and Pseudomonas (4) .

Anaerobic bacteria are recognized

increasingly as an important cause of

osteomyelitis. The first case of anaerobic

osteomyelitis was reported by Vone

Lanyebeck (7) . Purely anaerobic osteomyelitis

resulting from haematogenous spread is rare

(1,2,3) . The most frequent anaerobic isolates

from cultures are Bacteroides species or the

gram positive anaerobic cocci

Peptostreptococcus (8) . Osteomyelitis caused

solely by a clostridial species in pure culture is

uncommon (9) . Anaerobic osteomyelitis of the

feet is usually associated with diabetes

mellitus, severe trauma or other underlying

diseases causing vascular insufficiency (10) .

The aim of this study was to identify bacterial

isolates from infected bone debridement

cultures of chronic osteomyelitis including the

anaerobes, and to assess the reliability of

cultures taken from discharging sinuses, and

those obtained by aspiration from

subperiosteal and medullary abscesses.

Patients and methods

This study was approved by the scientific

research committee at the College of

Medicine, University of Mosul. Formal consent

was taken from all patients after careful

explanation. The current study was conducted

at Al-Jumhori Teaching Hospital in Mosul and

the department of microbiology, College of

Medicine, University of Mosul, during the

period from October 2003 to April 2010. One

hundred and eighty four (184) cases of chronic

pyogenic osteomyelitis were investigated for

causative microorganisms including anaerobic

bacteria by culturing infected bone

debridement taken during surgery. There were

141 males and 43 females; males to females

© 2010 Mosul College of Medicine 107


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

ratio was 3.3:1, their mean age was 40.5;

(range 6-78 years). The age and sex

distribution of the patients are presented in

(table 1). The cases were divided clinically

according to the causes into chronic

osteomyelitis following acute haematogenous

osteomyelitis (haematogenous) in 52 patients

(28.3%), and exogenous (posttraumatic and

postoperative) in 132 patients (71.7%). In 152

patients, the presentation was chronic

discharging sinuses, samples of pus for

cultures were taken before surgery from

sinuses, in addition to the samples obtained

from infected bone debridement during

surgery. In 32 cases, the presentation was

acute on chronic osteomyelitis, sample of pus

aspirated during surgery by sterile disposable

syringe from subperiosteal abscesses or

medullary abscesses, in addition to the

samples taken from infected bone

debridement during surgery. Antibiotic stopped

at least for three days before surgery and

sample collection.

Microbiological methods

Each specimen was inoculated directly on to

chocolate agar plate and blood agar base

plate containing 5% sheep blood that had

been held in anaerobic jar with gas pak

generating kit (Oxoid, U.K.). Another blood

agar plate (incubated aerobically in 5% CO2

atmosphere) and MacConkey , s agar were

used for isolation of other aerobic

microorganism. In addition other culture media

were employed for the isolation of anaerobic

bacteria, namely sodium thioglycolate broth,

cooked meat medium, and brain heart

infusion. The inoculation of the appropriate

culture media was attempted immediately at

the site of specimen collection in operating

theaters and then incubated under aerobic and

anaerobic conditions without using a transport

medium. All the inoculated culture media were

held at a temperature between 35 C˚ - 37 C˚

for 24 hours, and with further 48 hours

incubation if growth negative.

Identification of the isolates was relied on

their colonial morphology, gram stain, and

standard biochemical tests (11) .

Table (1): The age and sex distribution of 184

patients with chronic osteomyelitis.

Age

(years)

< 15

15-30

> 30

Total

Gender

males females

No % No %

28

32

81

141

15.2%

17.3%

44%

76.6%

15

7

21

43

8.1%

3.8%

11.4%

23.4%

No

43

39

102

184

Total

Statistical analysis

Results are reported as mean ± standard

deviation. The unpaired student (t) test used to

calculate the differences between two means.

The p value was considered significant if it was

less than 0.05. The reliability calculated by 2x2

table; the reliability = A + D/ Total × 100.

Statistical analysis were conducted by using

the: Statistical Package for Social Sciences

for window, version 11 (SPSS Inc. Chicago

Illinois USA).

Results

Highest incidence of the disease was seen in

patients over 30 years (55.5%). The majority of

the current cases of chronic osteomyelitis were

involve the long bones specially femur and

tibia (64.6%); as shown in (table 2). Chronic

osteomyelitis follow posttraumatic or

postoperative infection (exogenous) in 132

patients (71.7%), and follow acute

haematogenous osteomyelitis (haematogenous)

in 52 patients (28.3%), (Table 3). In 152

patients (83%), the presentation was chronic

discharging sinuses, and in 32 cases (17.4%),

the presentation was acute on chronic

osteomyelitis, (table 3).

Aerobic infections were detected in 134

patients ( 72.8 %), give 222 isolates ( mixed in

78% and pure in 22%). The commonest

microorganisms detected were Staph. aureus

in 65 isolates (29.3%), followed by

Pseudomonas in 41 isolates (18.5%), E. coli in

35 isolates (15.8%), Staph. epidermidis in 31

isolates (14%), Proteus in 22 isolates (9.9%),

and other microorganisms in 27 isolates

(12.6%), (table 4).

%

23.3%

21.2%

55.5%

100%

© 2010 Mosul College of Medicine 108


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Table (2): The distribution of anatomical location of different types of chronic osteomyelitis

involvement.

Bone affected

Aerobic infection

Anaerobic infection

Pure

Mixed

Total

Femur

Tibia

Foot bones

Humerus

Radius

Ulna

Pelvic bones

Fibula

Other bones *

Total

No

48

42

14

15

9

3

1

3

2

134

%

26.1%

22.8%

7.6%

6.5%

4.8%

1.6%

0.54%

1.6%

1.1%

No

6

4

2

2

0

0

1

0

1

16

%

3.3%

2.2%

1.1%

1.1%

0.54%

0.54%

No

11

8

3

1

4

2

2

1

2

34

%

6%

4.3%

1.6%

0.54%

2.2%

1.1%

1.1

0.54%

1.1%

No

65

54

19

15

13

5

4

4

5

184

%

35.3%

29.3%

10.3%

8.2%

7.0%

3.0%

2.0%

2.0%

3.0%

100 %

*Clavicle, patella, metacarpal.

Table (3): Distribution of clinical presentation according to the cause of chronic osteomyelitis.

Cause of chronic

osteomyelitis

Acute on chronic

No. (%)

Chronic discharging

sinus

No. (%)

No.

Total

(%)

haematogenous

14

7.6%

38

20.7%

52

28.3%

exogenous

18

9.8%

114

61.9%

132

71.7%

Total

32

17.4%

152

82.6%

184

100%

Table (4): Distribution of aerobic isolates from culture of infected bone debridement.

Type of aerobic

microorganism

Staph. aureus

Pseudomonas

E.coli

Acute on chronic osteomyelitis

Following

*A.H.O

Exogenous

No. (%) No. (%)

2 0.9 10 4.5%

2 0.9% 7 3.15%

1 0.45% 7 3.15%

Chronic discharging sinus

Following

*A.H.O

Exogenous

No. (%) No. (%)

6 2.7% 47 21.1%

6 2.7% 26 11.7%

5 2.25% 22 9.9%

total isolates

No. (%)

65 29.3%

41 18.5%

35 15.8%

Staph.

epidermidis

2

0.9%

6

2.7%

7

3.15%

16

7.2%

31

14%

Proteus

1

0.45%

3

1.35%

5

2.25%

13

5.85%

22

9.9%

Other microorganisms

2

0.9%

4

1.8%

6

2.7%

16

7.2%

28

12.6%

total

10

4.5%

37

16.7%

35

15.8%

140

63%

222

100%

*A.H.O is acute haematogenous osteomyelitis

Anaerobic organisms were detected in 50

cases (27.2%) out of the total 184 cases of

chronic osteomyelitis, and 58 different

anaerobic bacterial isolates were recovered.

Peptostreptococcus; represented the most

frequent isolate (34.9%), followed by

Bacteroides (22.1%) Prevotella.

melaninogenicus (17.2%) Propionibacterium.

© 2010 Mosul College of Medicine 109


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

acne (12.1%) Fusobacterium (5.2%)

Clostridium. perfringens (3.4% ), Eubacterium

(3.4% ) and Viellonella (1.7%), (table 5).

Out of the 20 patients with acute on chronic

osteomyelitis following acute haematogenous

osteomyelitis, only 2 of them were infected

with anaerobic bacteria which yielded 3

bacterial isolates. Among the 14 patients with

acute on chronic osteomyelitis following

exogenous osteomyelitis, anaerobes were

present in 4 cases only and yielded 6

anaerobic isolates. Regarding the 38 patients

with chronic discharging sinus following acute

haematogenous osteomyelitis, anaerobic

bacteria were detected in 14 cases and gave

14 anaerobic isolates, while out of the 114

patients with chronic discharging sinus

following exogenous osteomyelitis, 30

revealed anaerobic infections and yielded 33

anaerobic isolates (table 3).

The duration of illness in patients with aerobic

infection was 178 days ± 121, while that in

patients with anaerobic was 890 days ± 625,

as shown in (Table 6). The difference between

the two durations was statistically very highly

significant (p


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Table (6): Comparison of duration illness in aerobic and anaerobic infection.

Type of isolates

Aerobic

microorganisms

Anaerobic

microorganisms

Mean duration

(days )

178

890

Standard

deviation

121

625

p- value

0.0001

significance

Very highly

significant

Table (7): Comparison between age of patients with pure anaerobic and mixed anaerobic isolates.

Type of isolates

Mixed anaerobic

Pure anaerobic

Mean of patients

age in years

38.4

57.3

Standard

deviation

11.1

8.6

p-value

0.001

Significance

Highly

Significant

Table (8): Type of cultures according to causes of chronic osteomyelitis.

Source of osteomyelitis

Haematogenous

18

Type of culture

Pure

Mixed

9.8% 34 18.5%

52

Total

28.3 %

Exogenous

54

29.3%

78

42.4%

132

71.1 %

Total

72

39.1%

112

60.9%

184

100 %

Table (9): The 2 x 2 table of reliability of bones abscesses pus cultures in comparison with bone

cultures.

Bone cultures

Total

Positive Negative

No. (%)

No. (%)

No. (%)

Discharging sinus Positive 28 (93.3%) 0 (0%)

28 (93.3%)

pus cultures Negative 2 (6.7%)

0 (0%)

2 (6.7%)

Total: No. (%)

30 (100%)

0 (0%)

30 (100%)

Table (10): The 2 x 2 table for reliability of discharging sinus pus cultures in comparison with bone

cultures.

Bone cultures

Total

Positive

Negative

No. (%)

No. (%)

No. (%)

Discharging sinus Positive 65 (42.7%) 0 (0%) 65 (42.7%)

pus cultures Negative 87 (57.3%) 0 (0%) 87 (57.3%)

Total: No. (%)

152 (100%)

0 (0%)

152 (100%)

Table (11): The 2 x 2 table for reliability of discharging sinus pus cultures of anaerobic infections in

comparison with bone cultures.

Positive

No. (%)

Bone cultures

Negative

No. (%)

Total

No. (%)

Discharging sinus Positive

13 (26%) 0 (0%) 13 (26%)

pus cultures Negative 37 (74%) 0 (0%) 37 (74%)

Total: No .(%)

50 (100%)

0 (0%)

50 (100%)

© 2010 Mosul College of Medicine 111


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Discussion

The literature contain variable reports on

causative organisms of chronic osteomyelitis.

The gold standard etiologic diagnosis of

chronic osteomyelitis is bone specimens

cultures (5, 12) . In the current study the ratio of

male to female was 3.3:1, this finding may be

due to male frequent exposure to accidents,

missile injuries, trauma, and fractures. Highest

incidence of chronic osteomyelitis was

recorded in patients over 30 years (55.5%)

which could be partly attributed to their high

hazard of exposure to missile injuries, trauma

and infections, as well as the slower healing of

fractures compared to younger age groups.

The high rate of chronic osteomyelitis follow

exogenous causes (posttraumatic or

postoperative) in 132 patients (72%), which

means that there was poor control to infections

after open fractures and in operating theaters,

and the high prevalence of wars injuries in our

community following multiple wars. Our finding

is similar to that reported in Turkey

(13) ,

Germany (14) and Switzerland (15) , while the

reverse reported in African community (16) .

In the current study, anaerobic organisms

were isolated from 50 patients (27.2%) out of

184 cases with pyogenic osteomyelitis, a result

that differs from that reported by Malik who

reported anaerobes in 2.6% of chronic

osteomyelitis (17) , and from that reported by

Naumenko et al too, who found anaerobes in

65% of chronic osteomyelitis (18) . This May be

explained by differences in climate,

environment, community, development,

medical services and techniques of bacterial

isolation. In the current study, the high

incidence of anaerobes indicates the important

role of anaerobes in development and

persistent of the purulent inflammatory process

in chronic osteomyelitis. In a series from Mayo

clinic, 40 of 182 patients have surgery for

osteomyelitis was found to be anaerobic

bacteria in the cultures (4) . Anaerobic infection

reported in 19% of osteomyelitis in drug

abuser (19) , while was no drug abuse detected

in our patients. Anaerobic bacteria are

increasingly recognized as a potential

pathogen in non haematogenous osteomyelitis

(20) .

The distribution of aerobic isolates in this

study was different from that reported by Malik,

who reported that the common isolates

belongs to Enterobacteriaceae (32.8%)

followed by Staph. aureus in 29.5%,

Pseudomonas (15.5%), anaerobes (2.6%) and

miscellaneous in (19.3%), which might

explained by different community and

environment (17) . The distribution of aerobic

and anaerobic isolates in the current study is

different from that reported by Brook and

Zuluaga et al , this might explained by different

medical facilities, techniques of bacterial

isolation, level of development in community

and environment (12, 21) . Some investigators

describe the isolation of a strictly anaerobic

strain of Staphylococcus epidermidis in pure

culture from the site of an infected prosthesis ,

(20)

, in our patients we didn’t detect this strain.

The cultures of aspirate from bone abscesses

is a reliable way in diagnosis, this made

aspiration of abscesses a proper way in

diagnosis of causative microorganisms and in

detecting drug sensitivity. While cultures from

discharging sinuses had low diagnostic

reliability and it had lower reliability for

anaerobic infection. This finding are

comparable with that of Zuluaga et al who

confirmed that the appropriate diagnosis of

chronic osteomyelitis requiring microbiological

cultures of the infected bone and non bone

specimens are not valid for appropriate

diagnosis in chronic osteomyelitis (12, 22) .

The duration of illness in patients with aerobic

infections was significantly shorter than that in

with anaerobic infections , which indicates that

as the duration of chronic osteomyelitis

prolonged, the anaerobic microorganism

become predominating. Some investigators

mentioned that as the duration of chronic

osteomyelitis lengths, the number of isolated

species of anaerobes increases (5,10, 23) . Pure

anaerobic growth was more frequent in older

patients than their counterparts with mixed

aerobic and anaerobic isolates , this may be

due to poor circulation in older age which

favored anaerobic infection (5,10, 24) .

We conclude that, chronic osteomyelitis

commonly affects adult males in long bones.

The exogenous causes are the commonest.

© 2010 Mosul College of Medicine 112


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Aerobic isolates are the common causes,

Staph. aureus and Pseudomonas represent

the most frequent etiological agents in aerobic

osteomyelitis. Anaerobic bacteria are

important other cause, Peptostreptococcus

and Bacteroides represent the most frequent

etiological agents in anaerobic osteomyelitis.

Anaerobic culture should be performed

routinely for all patients with osteomyelitis.

Mixed infection is common. Anaerobes usually

isolated in prolonged persistent infection and

in older patients. The cultures of aspirate from

bone abscesses is reliable way in diagnosis,

while cultures from discharging sinuses had

low diagnostic reliability and even lower for

anaerobic infection.

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2. Kumar V, Abbas AK, Fausto N, Mitchell

RN. Robbins Basic Pathology. 8 th ed.

Saunders Elsevier. 2007; 810- 11.

3. Brooks GF, Butel JS, Morse SA. Jawetz .

Melnick and Adelberg

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© 2010 Mosul College of Medicine 113


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

Effects of dietary supplementation on bone

healing in bisphosphonate treated rabbits

Mahmood A. Aljumaily*, Kassim S. Ibrahim**, Hazim Al-allaf***

* Department of Surgery, ** Department of Pathology, *** Department of Imaging and Radiology,

College of Medicine, University of Mosul.

(Ann. Coll. Med. Mosul 2010; 36 (1 & 2): 114-120).

Received: 10 th May 2010; Accepted: 27 th Oct 2010.

ABSTRACT

Objective: The aim of this study was to evaluate the effect of the daily oral administration of vitamin

D, calcium, fluoride and vitamin C as dietary supplementation on bone healing in bisphosphonate

treated experimental animals (rabbits).

Material and methods: Eight young male rabbits divided into two groups after induction of open ulnar

osteotomy, both groups received weekly 1 mg/ kg BW of alendronic acid (alendron) orally starting 6

days before osteotomy for five weeks, the experimental group received daily dose of vitamin D,

calcium, fluoride and vitamin C as dietary supplementation from the second post operative day for

four weeks. The control group received ordinary diet. At the end of the fifth week the animals'

sacrificed and the specimens taken for radiological and computerized tomography (CT) scan

densimetry and histomorphometric evaluation carried out for the callus at site of osteotomy.

Results: All ulnar bone osteotomies in both groups united at the end of the fifth week macroscopically

and radiologically. The callus density was measured in site of osteotomy by CT scan densimetry, its

mean in the experimental group was 681 ± 219 and in the control group was 492 ± 233. The

difference between the experimental and control group was significant, (P value


Annals of the College of Medicine Vol. 36 No. 1 & 2 2010

الكالسيوم وفيتامين دي والفلوريد وفيتامين سي لمدة أربعة أسابيع فيما آانت المجموعة عينة ضابطة.‏ وبعد