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Archives of 

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ii 

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Archives of Iranian Medicine, Volume 15, Number 5, May 2012 

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Archives of Iranian Medicine, Volume 15, Number 5, May 2012 iii

• Editorial 

Hepatitis C in Iran. How Extensive of a Problem Is It? 

S. Merat, H. Poustchi 

When Are Patients with Common Bile Duct Stones Referred for Surgery? 

M. Khatibian, S. Merat 

• Original Articles 

High Prevalence of Hepatitis C Infection among High Risk Groups in 

Kohgiloyeh and Boyerahmad Province, Southwest Iran 

B. Sarkari, O. Eilami, A. Khosravani, A. Sharifi, M. Tabatabaee, M. Fararouei 

Assessment and Treatment of Choledocholithiasis when Endoscopic 

Sphincterotomy is not Successful 

A. Shojaiefard, M. Esmaeilzadeh, Z. Khorgami, R. Sotoudehmanesh, A. 

Ghafouri 

Reliability and Validity of the Modifiable Activity Questionnaire 

(MAQ) in an Iranian Urban Adult Population 

A. Momenan, M. Delshad, N. Sarbazi, N. Rezaei_Ghaleh, A. Ghanbarian, 

F. Azizi 

Efficacy of Harm Reduction Programs among Patients of a Smoking 

Cessation Clinic in Tehran, Iran 

H. Sharifi, R. Kharaghani, H. Emami, Z. Hessami, M.R. Masjedi 

Validity, Reliability and Factor Structure of Hepatitis B Quality of Life 

Questionnaire Version 1.0: Findings in a Large Sample of 320 patients 

A. Poorkaveh, A.H. Modabbernia, M. Ashrafi, S. Taslimi, M. Karami, M. 

Dalir, A. Estakhri, R. Malekzadeh, H. P. Sharifi, H. Poustchi 

A New Technical Approach to Cancers of the Cervical Esophagus 

N. Nikbakhsh, F. Saidi, H. Fahimi 

Severe Thrombocytopenia and Hemorrhagic Diathesis due to Brucellosis 

H. Karsen, F. Duygu, K. Yapıcı, A. İ. Baran, H. Taskıran, İ. Binici 

Acute Administration of Zn, Mg, and Thiamine Improves Postpartum 

Depression Conditions in Mice 

S. Nikseresht, S. Etebary, M. Karimian, F. Nabavizadeh, M. R. Zarrindast, 

H. R. Sadeghipour 

Microbial Susceptibility, Virulence Factors, and Plasmid Profiles of 

Uropathogenic Escherichia coli Strains Isolated from Children in Jahrom, 

Iran 

S. Farshad, R. Ranjbar, A. Japoni, M. Hosseini, M. Anvarinejad, R. Mohammadzadegan 

iv Archives of Iranian Medicine, Volume 15, Number 5, May 2012 

Table of Contents 

268 

269 

271 

275 

279 

283 

290 

298 

303 

306 

312 


268 

271

• Brief Report 

A Report of the Injuries Sustained in Iran Air Flight 277 that 

Crashed near Urmia, Iran 

A. Afshar, M. Hajyhosseinloo, A. Eftekhari, M. B. Safari, Z. 

Yekta 

• Report 

Advocacy Strategies and Action Plans for Reducing Salt Intake 

in Iran 

N. Mohammadifard, S. Fahimi, A. Khosravi, H. Pouraram, S. 

Sajedinejad, P. Pharoah, R. Malekzadeh, N. Sarrafzadegan 

• Case Reports 

A Rare Case of Perforated Meckel’s Diverticulum Presenting 

as a Gatrointestinal Stromal Tumor 

S. Sozen, Ö. Tuna 

Primary Adrenal Hydatid Cyst Presenting with Arterial Hypertension 

M. Mokhtari, S. Zeraatian Nejad Davani 

Primary Intrathoracic Biphasic Synovial Sarcoma 

Y.Tezcan, M. Koc, H. Kocak, Y. Kaya 

• Photoclinic 

M. F. jarmakani, M. R. Mohebbi 

• Excerpts from Persian Medical Literature 

317 

320 

325 

328 

331 


317 

320 

325 

333 

335 

Archives of Iranian Medicine, Volume 15, Number 5, May 2012 

v

268 Archives of Iranian Medicine, Volume 15, Number 5, May 2012 

Editorial 

Hepatitis C in Iran. How Extensive of a Problem Is It? 

See the pages: 271– 274 

Cite this article as: Merat S, Poustchi H. Hepatitis C in Iran. How extensive of a problem is it?. Arch Iran Med. 2012; 15(5):268. 

H 

epatitis B virus (HBV) used to be - and in many countries, 

still is - the most common cause of chronic viral hepatitis. 

Since the introduction of an effective vaccine against this 

virus, many countries have implemented neonatal HBV vaccination 

in their general health programs. We are beginning to observe 

the effects of this vaccination in most parts of the world, including 

Iran, where the prevalence of HBV infection is slowly declining. 1,2 

On the other hand, there is no effective vaccine against hepatitis C 

virus (HCV). The lack of an effective vaccine and increase in intravenous 

drug abuse, has led to a gradual increase in HCV infection 

in recent years. 3,4 It follows that sooner or later, HCV will replace 

HBV as the major cause of chronic viral liver disease. Currently, in 

many Western countries this already is the case. In Iran the rate of 

HCV infection in the general population is relatively low. Estimates 

are around 0.5%, while the latest estimates of HBV infection 

are around 2.5%. Thus it would be quite a while before HCV prevalence 

in the general population of Iran reaches that of HBV. 2,4 

Nevertheless, in high risk populations the prevalence of HCV infection 

is already alarming. In a report from Sarkari et al., published 

in this issue of the journal, 5 a rate of 8.6% is noted among 

over 2000 high-risk subjects. Other studies from Iran report rates 

as high as 31% in patients on chronic hemodialysis, 44.7% in thalassemia 

patients, 6 72% in hemophilia patients, 7 and up to 80% 

among intravenous drug abusers in prisons. 8 Numerous reports 

from Iran indicate a high prevalence of HCV infection in high-risk 

populations. How serious is the threat of HCV in Iran? 

Unlike HBV, there is a good chance for total eradication of 

HCVwith appropriate treatment. However this treatment is not inexpensive, 

nor is it well-tolerated. Genotype is one of the major 

factors effecting treatment and response. According to various reports 

from Iran, the difficult-to-treat genotypes (1 and 4) comprise 

about 40% – 60% of our cases which is less than reports from most 

Western countries. 9,10 Another peculiarity of Iranian HCV patients 

is that they appear to respond better to treatment, 11 although this 

better response might be partially explained by the recently described 

IL28B polymorphism. 12 This is fortunate as non-responders 

will probably require treatment with the expensive and poorly 

available protease inhibitors. 

It should be noted that the prevalence of HCV, as that of HBV, is 

not uniform throughout the country. Differences up to 6-fold have 

been observed. The prevalence among men is much higher than 

women, probably in the range of 10-fold. 4 

Another feature of HCV infection in Iran is that there is probably 

a less chance for chronicity. In a recent report from Iran, up to 38% 

of HCV infections spontaneously resolved. 13 

We need studies that will evaluate host factors in Iranian patients. 

It is conceivable that researchers may discover a genetic variation 

similar to IL28B which predicts response to treatment or spontaneous 

resolution. 

In Iran there is a low prevalence of HCV, a low ratio of difficultto-treat 

genotypes, a high rate of spontaneous resolution, and better 

response to treatment. However, with the improvement of general 

health awareness in Iran and the high prevalence of HCV infection 

among high-risk groups, we will soon face a large number of HCV 

patients who seek treatment for which we need to be prepared. 

Shahin Merat MD, Hossein Poustchi MD PHD 

Digestive Disease Research Center, Tehran University of Medical 

Sciences, Tehran, Iran. E-mail: merat@tums.ac.ir 

References 

S. Merat, H. Poustchi 

1. Merat S, Malekzadeh R, Rezvan H, Khatibian M. Hepatitis B in Iran. 

Arch Irn Med. 2000; 3: 192 – 201. 

2. Merat S, Rezvan H, Nouraie M, Jamali A, Assari S, Abolghasemi H, 

et al. The prevalence of hepatitis B surface antigen and anti-hepatitis B 

core antibody in Iran: a population-based study. Arch Iran Med. 2009; 

12(3): 225 – 231. 

3. Rezvan H, Ahmadi J, Farhadi M, Tardyan S. A preliminary study of 

prevalence of HCV infection in healthy Iranian blood donors. Vox 

Sang. 1994; 67(suppl 2): 149. 

4. Merat S, Rezvan H, Nouraie M, Jafari E, Abolghasemi H, Radmard 

AR, et al. Seroprevalence of hepatitis C virus: the first populationbased 

study from Iran. Int J Infect Dis. 2010; 14 (suppl 3):113 – 116. 

5. Sarkari B, Eilami O, Khosravani A, Sharifi A, Tabatabaee M, Fararoee 

M. High prevalence of hepatitis C infection among high risk groups in 

Kohgiloyeh and Boyerahmad province, Southwest of Iran. Arch Iran 

Med. 2012; 15(5): 271 – 274 

6. Hassanshahi G, Arababadi MK, Assar S, Hakimi H, Karimabad MN, 

Abedinzadeh M, et al. Post-transfusion-transmitted hepatitis C virus 

infection: a study on thalassemia and hemodialysis patients in southeastern 

Iran. Arch Virol. 2011; 156: 1111 – 1115. 

7. Mosavi SA, Mansouri F, Saraei A, Sadeghei A, Merat S. [Seroprevalence 

of hepatitis C in hemophilia patients refering to Iran Hemophilia 

Society Center in Tehran]. Govaresh. 2011; 16: 16 – 174. 

8. Mir-Nasseri MM, Mohammadkhani A, Tavakkoli H, Ansari E, Poustchi 

H. Incarceration is a major risk factor for blood-borne infection 

among intravenous drug users: Incarceration and blood borne infection 

among intravenous drug users. Hepat Mon. 2011; 11: 19 – 22. 

9. Zarkesh-Esfahani SH, Kardi MT, Edalati M. Hepatitis C virus genotype 

frequency in Isfahan province of Iran: a descriptive cross-sectional 

study. Virol J. 2010; 7: 69. 

10. Samimi-Rad K, Nategh R, Malekzadeh R, Norder H, Magnius L. Molecular 

epidemiology of hepatitis C virus in Iran as reflected by phylogenetic 

analysis of the NS5B region. J Med Virol. 2004; 74: 246 – 252. 

11. Jabbari H, Bayatian A, Sharifi AH, Zaer-Rezaee H, Fakharzadeh E, 

Asadi R, et al. Safety and efficacy of locally manufactured pegylated interferon 

in hepatitis C patients. Arch Iran Med. 2010; 13(4): 306 – 312. 

12. Mahboobi N, Behnava B, Alavian SM. IL28B SNP genotyping among 

Iranian HCV-infected patients: A preliminary report. Hepat Mon. 2011; 

11: 386 – 388. 

13. Poustchi H, Esmaili S, Mohamadkhani A, Nikmahzar A, Pourshams 

A, Sepanlou SG, et al. The impact of illicit drug use on spontaneous 

hepatitis C clearance: experience from a large cohort population study. 

PLoS One. 2011; 6:23830.

Editorial 

When Are Patients With Common Bile Duct Stones Referred for 

Surgery? 

See the pages: 275 – 278 

Cite this article as: Khatibian M, Merat S. When are patients with common bile duct stones referred for surgery? Arch Iran Med. 2012; 15(5): 269 – 270. 

I 

n this issue of the journal, Shojaiefard et al. report the results 

of surgery upon 186 patients in which endoscopic removal of 

common bile duct (CBD) stones had failed. 1 

Endoscopic Retrograde Cholangiopancreatography (ERCP) is 

considered the standard primary treatment for CBD stones in patients 

with previous cholecystectomy. Even in patients with gall 

bladders, ERCP together with cholecystectomy is a well-accepted 

method. 2 Laprascopic CBD exploration is time consuming, requires 

more expertize, and is associated with increased morbidity 

including biliray strictures.Thus, surgeons often prefer to have 

the CBD stones removed endoscopically either before or after 

cholecystectomy. 3A meta-analysis on non-cholecystectomiedsubjects 

with CBD stones looked at 7 trials comparing open surgery 

for removing both the gallbladder and the CBD stones vs. cholecystectomy 

and endoscopic removalof CBD stones. The results in 

terms of success rate, morbidity and mortality were no different 

between the two groups. Thus, the endoscopic method (followed 

by laparoscopic cholecystectomy), being less invasive and as successful 

as surgery was recommended as the therapeutic strategy of 

choice for CBD stones. 4 

When is surgery performed to remove CBD stones? Obviously, 

one occasion is when endoscopic treatment fails. Shojaiefard et 

al. report that among 1462 cases with CBD stones, 186 failed endoscopic 

treatment. 1 The success rate for removal of CBD stones 

with ERCPis 80 to 90%. Failures might be due to bile duct strictures, 

unusual anatomy such as duodenal diverticuli, stones being 

beyond the reach of wire basket, or stones being too large. 5 Failure 

of cannulation of ampulla occurs in 5% of ERCPs. The success rate 

is 76 and 80% at second and third attempt respectively. Although 

by expertise, the success rate might approach 100% on the second 

attempt. 6 Needle knife sphincterotomy increases the success rate 

by 25%. But occasionally, blocking of the endoscopic view due to 

bleeding might cause failure. 6 Needle-knife fistulotomy is another 

technique which might assist in difficult cases. 7 In patients with 

large CBD stones, mechanical lithotripsy can increase the success 

rate to 95%. If mechanical lithotripsy fails too, extracorporeal 

shock wave lithotripsy (ESWL) can be successful in another 80%. 8 

As discussed above, when initial ERCP fails, there is still a very 

good chance of success with repeated attempts using appropriate 

techniques. Nevertheless, sometimes patients are refered for surgury 

immediately after the first failure. 

A few other factors are involved in the decision of when to give 

up on non-surgical management. Endoscopists tend to refer patients 

with simultanious gallbladder and CBD stones for surgery 

earlier than those who have already had their gallbladder removed. 

When are patients with common bile duct stones referred for surgery? 

On the one hand, the former will eventually need surgery to remove 

the gallbladder, even if ERCP is successful in removing the 

CBD stones, so a second or third endoscopic attempt to remove the 

CBD stones might not be justified in light of the overloaded ERCP 

department with many emergency patientsin line. The relatively 

large number of non-cholecystectomied patients refered for surgery 

in this study (76%) might be a reflection of this fact. On the 

other hand, subjects who have already undergone cholecystectomy 

can be spared surgery if endoscopic treatment is successful. Thus, 

multiple attempts at removing the CBD stones endoscopically is 

well justified. 

It is also frequently observed that patients with less operative risk 

are more readily refered for surgery. 

In patients who are poor surgical risks, ERCP without cholecystectomy 

might lead to less morbidity and mortality. If the CBD 

stones cannot be removed, even after trying mechanical lithotripsy 

and ESWL, stenting of the CBD without removing the stones can 

still resolve symptoms in a majority of cases. 

A few newer techniques have also evolved. When ERCP is not 

performed before cholecystectomy, during surgery a standard 

ERCP cathter can be secured in the cystic duct instead of a T-tube. 

The cathter can be used to do cholangiography after surgery and 

if a stone is found, ERCP would be successful in removing the 

stone in 97% withan only 1% complication rate.Transcystic stenting 

of the CBD during cholecytectomy, or placing a guidewire via 

the cystic duct and using the so-called ʻrendezvouz technique’ are 

among other methods with promise. The ʻfacilitated ERCP’ performed 

after such surgeries has a much higher success rate of 95% 

and results in shorter hospital stay. 9 

Morteza Khatibian MD, Shahin Merat MD 

Digestive Disease Research Center, Tehran university of Medical 

Sciences, Tehran Iran. 

References: 

1. Shojaiefard AE, KhorgamiZ, SotoudehmaneshR, GhafouriA. Assessment 

and Treatment of Choledocholithiasis when Endoscopic Sphincterotomy 

is not Successful. Arch Iran Med. 2012; 15(5): 275 – 278. 

2. Adler DG, Baron TH, Davila RE, Egan J, Hirota WK, Leighton JA, et 

al. ASGE guideline: the role of ERCP in diseases of the biliary tract and 

the pancreas. Gastrointest Endosc 2005; 62(1): 1 – 8. 

3. Martin DJ, Vernon DR, Toouli J. Surgical versus endoscopic treatment 

of bile duct stones. Cochrane Database Syst Rev. 2006; 2: CD003327. 

4. Sikora SS. Common bile duct stones: endoscopy or surgery? Natl Med 

J India 2007; 20(1): 23 – 24. 

5. Tyagi P, Sharma P, Sharma BC, Puri AS. Periampullary diverticula and 

Archives of Iranian Medicine, Volume 15, Number 5, May 2012 269

technical success of endoscopic retrograde cholangiopancreatography. 

Surg Endosc. 2009; 23(6): 1342 – 1345. 

6. Kim J, Ryu JK, Ahn DW, Park JK, Yoon WJ, Kim YT, et al. Results 

of repeat endoscopic retrograde cholangiopancreatography after initial 

biliary cannulation failure following needle-knife sphincterotomy. J 

Gastroenterol Hepatol. 2012; 27(3): 516 – 520. 

7. Khatibian M, Sotoudehmanesh R, Ali-Asgari A, Movahedi Z, Kolahdoozan 

S. Needle-knife fistulotomy versus standard method for cannulation 

of common bile duct: a randomized controlled trial. Arch Iran 


M.Khatibian, S.Merat 

Med. 2008; 11(1): 16-20. 

8. Minami A, Hirose S, Nomoto T, Hayakawa S. Small sphincterotomy 

combined with papillary dilation with large balloon permits retrieval 

of large stones without mechanical lithotripsy. World J Gastroenterol. 

2007; 13(15): 2179 – 2182. 

9. Morino M, Baracchi F, Miglietta C, Furlan N, Ragona R, Garbarini 

A. Preoperative endoscopic sphincterotomy versus laparoendoscopic 

rendezvous in patients with gallbladder and bile duct stones. Ann Surg. 

2006; 244(6): 889 – 893.

Original Article 

High Prevalence of Hepatitis C Infection among High Risk Groups 

in Kohgiloyeh and Boyerahmad Province, Southwest Iran 

Bahador Sarkari PhD 1 , Owrang Eilami MD 2 , Abdolmajid Khosravani PhD• 2 , Asghar Sharifi PhD 2 , Marzieh Tabatabaee MD 2 , Mohammad 

Fararouei PhD 3 

See the pages: 268 

Abstract 

Background: Detection of Hepatitis C virus (HCV)-infected people in each community assists with infection prevention and control. This 

study aims to evaluate the prevalence of HCV infection among high risk groups in Kohgiloyeh and Boyerahmad Province, Southwest Iran. 

Methods: This was a cross-sectional study conducted from 2009-2010 in Kohgiloyeh and Boyerahmad Province. High risk groups for HCV 

were the subjects of this study. Blood samples were taken from 2009 individuals at high risk for HCV that included inmates, injecting drug 

users (IDUs), health care workers, patients on maintenance hemodialysis, hemophilic patients, and those with histories of blood transfusions. 

Patients were residents of Yasuj, Gachsaran, and Dehdasht (3 main townships in the province). Samples were analyzed by ELISA for anti- 

HCV antibodies. Demographic features of participants were recorded by a questionnaire during sample collection. Data were analyzed by 

SPSS version 13 software. 

Results: Of 2009 subjects, HCV antibodies were detected in 172 (8.6%). Rate of infection was higher in males (11.4%) compared to 

females (3.2%). Rate of infection in inmates was 11.7% while this rate was 42.4% in IDUs, 4.2% in health care workers, and 6.1% in thalassemic 

patients. Significant correlation was found between HCV infection, history of imprisonment, and thalassemia. 

Conclusion: Results of this study have provided epidemiologic features of HCV and its risk factors in Kohgiloyeh and Boyerahmad Province, 

Southwest Iran. This information may assist in preventing the spread of HCV infection in this and other similar settings in the region. 

The findings of this study may help in improving surveillance and infection control in the community through management and monitoring of 

infected individuals. 

Keywords: HCV, high risk group, Iran, prevalence, seroprevalence 

Cite this article as: Sarkari B, Eilami O, Khosravani A, Sharifi A, Tabatabaee M, Fararouei M. High Prevalence of Hepatitis C Infection among High Risk Groups in 

Kohgiloyeh and Boyerahmad Province, Southwest Iran. Arch Iran Med. 2012; 15(5): 271 – 274. 

Introduction 

H 

epatitis C is a global health problem affecting more than 

170 million people worldwide. 1 Hepatitis C virus (HCV) 

is mainly transmitted parenterally or in the course of blood 

contamination during medical procedures. 

Most who acquire acute HCV infection have no symptoms or 

have a mild clinical disease. However, chronic HCV infection develops 

in 75% – 85% of those acutely infected individuals. 2 HCVinfected 

people serve as a reservoir for transmission of the infection 

to others, including health care workers. 

It has been estimated that HCV accounts for 27% of cirrhosis 

and 25% of hepatocellular carcinoma (HCC) worldwide. HCV is 

a leading cause of liver failure and liver transplantation in adults. 2 

In Iran, it has been estimated that between 0.12% – 0.89% 

of the general population have anti-hepatitis C virus antibodies, 

Authors’ Affiliations: 1 Center for Basic Researches in Infectious Diseases, 

Shiraz University of Medical Sciences, Shiraz, Iran, 2 Faculty of Medicine, Yasuj 

University of Medical Sciences, Yasuj, Iran, 3 Faculty of Health, Yasuj University 

of Medical Sciences, Yasuj, Iran. 

•Corresponding author and reprints: Abdolmajid Khosravani PhD, Faculty 

of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran, E mail: 

khosravani2us@yahoo.com 

Accepted for publication: 7 September 2011 

HCV Infection in a Southwest Area of Iran 

which corresponds to as many as 0.5 million chronic carriers. 3 A 

higher seroprevalence of HCV has been reported in special groups 

(homeless or gypsies) in Iran. 4,5 The infection is emerging mostly 

due to the problem of intravenous drug abuse and needle-sharing 

in this country. 

In a recent population-based study by Merat et al. male sex, history 

of intravenous drug abuse, and imprisonment were attributed to 

HCV infection. 3 

Injection drug users (IDUs) constitute the largest group of persons 

at high risk for acquiring HCV infection in developed countries. 

The range of HCV infection among IDUs in Iran has been reported 

to be 38% to 47%. 6–8 

It is essential to assess the magnitude of HCV infection in each 

region of Iran. This assessment will assist health authorities in improving 

surveillance and prevention of HCV infection in the community 

through management and monitoring of infected individuals. 

High-risk populations for HCV infection are individuals involved 

in activities that include possible contact with contaminated blood, 

such as blood transfusions, medical or dental care, acupuncture 

and tattooing, IDUs, prison inmates, and healthcare workers. 

This study aims to evaluate the epidemiologic features of HCV 

and its risk factors among high risk groups in Kohgiloyeh and 


Table 1. Demographic characteristics of participants. 

Features 

Place of residence 

Frequency Percent 

Gachsaran 803 40 

Yasuj 802 39.9 

Dehdasht 

Sex 

404 20.1 

Male 1231 66.4 

Female 

Marital status 

621 33.6 

Single 692 39.7 

Married 

High risk groups 

1047 60.3 

Inmates 616 30.6 

Health care workers 212 10.5 

Injecting drug users (IDUs) 158 7.8 

Thalassemic 49 2.4 

Other† 

Age group (years) 

602 30 

1–20 166 9.5 

21–30 691 39.6 

31–40 472 27.1 

> 40 415 23.8 

Missing 265 - 

† Tattooing, history of surgery, dental care, having HCV-positive family member(s). 

High-risk groups Frequency HCV-positive Percent 

Inmates 616 72 11.7 

Health care workers 212 9 4.2 

Injection drug users (IDUs) 158 67 42.2 

Thalassemic 49 3 6.1 

Others† 602 47 7.8 

† Tattooing, history of surgery, dental practice, HIV-positive family members. 

Boyerahmad Province, Southwest Iran, where such data are not 

currently available. 

Materials and Methods 

This descriptive cross-sectional study was conducted from 2009 

– 2010 in Kohgiloyeh and Boyerahmad Province, Iran. High risk 

groups for HCV were the subjects of this study. After obtaining 

approval from the Ethics Committee of Yasuj University of 

Medical Sciences, blood samples were taken from 2009 individuals 

who were residents of Yasuj, Gachsaran, and Dehdasht (3 main 

townships in the province) that were at high risk for acquiring 

HCV. Participants were comprised of inmates (total inmates in 3 

main prisons in the province: 616), IDUs (158) health care workers 


Table 2. High-risk groups and HCV prevalence. 

B. Sarkari, O. Eilami, A. Khosravani, et al. 

Table 3. Risk factors associated with HCV seropositivity in high risk groups in Kohgiloyeh and Boyerahmad Province, Southwest Iran. 

Risk factor HCV positive HCV negative Total 

History of imprisonment 72 544 616 

History of drug use 67 91 158 

Transfusion 2 46 48 

Needle stick 9 213 222 

Thalassemia 3 46 49 

Unprotected sex 6 12 18 

Other† 47 555 602 

† Tattooing, history of surgery, dental practice, having HCV-positive family members. 

(222 in the 3 main townships, based on the population of health 

care workers in each township), and thalassemic patients (49). 

Participation in this study was voluntary and all participants were 

counseled about the study. Participants were requested to provide 

signed informed consents. Confidentiality of the details of the 

participants was guaranteed. 

Demographic features of participants were recorded using 

a questionnaire during sample collection. The questionnaire 

contained detailed questions regarding HCV-related risk behaviors 

such as injection of intravenous drugs, history of imprisonment, 

having received blood and/or blood products, unsafe sexual 

practice, and history of other risk factors such as receiving tattoos, 

body piercing, and history of surgery or dental care. 

A total of 5 ml of blood was taken from each subject and sera

High risk behavior Df Sig Odds ratio 

95% CI for Exp (B) 

Lower Upper 

History of drug use 1 0.105 1.603 0.906 2.838 

Thalassemia 1 0.000 3.761 1.909 7.409 

Transfusion/ hemophilia 1 0.907 1.101 0.221 5.487 

Needle stick 1 0.389 1.538 0.577 4.101 

History of imprisonment 1 0.033 8.231 1.191 56.884 

were tested for anti-HCV antibodies by an enzyme-linked 

immunosorbant assay (ELISA, DIALab, Austria). The sensitivity 

of this test (a third generation ELISA) is 99.55% and specificity is 

99.79%. 

Collected data were analyzed by SPSS version 13 software. 

Standard x 2 test was used to assess the univariate correlation of 

demographic and behavioral variables and HCV seropositivity. 

Results 

Of 2009 subjects, 802 (39.9%) were from Yasuj, 803 (40%) were 

from Gachsaran, and 404 (20.1%) were from Dehdasht. Males 

constituted 66.4% of subjects whereas 33.4% of participants were 

female. Most subjects (39.6%) were among the 21 – 30 year-old 

age group and most were married (60.3%). Table 1 shows the 

demographic characteristics of participants in this study. 

HCV antibodies were detected in 172 (8.6%) cases. Rate of 

infection was higher in males (11.4%) compared to females (3.2%). 

Rate of infection in inmates was 11.7% while this rate was 42.4% 

in IDUs, 4.2% in health care workers, and 6.1% in thalassemic 

patients. The highest prevalence of HCV (9.3%; 64/691) was 

found in the 21 – 30 year-old age group. Table 2 represents the 

prevalence of HCV infection in each high risk group in this study. 

Unemployed people were found to be the main victims of this 

disease. Significant correlation was found between marital status 

and HCV seropositivity. The rate of seropositivity in unmarried 

subjects was 11.4% compared with 6.4% for married individuals 

(P < 0.05). 

Significant correlation was found between HCV seropositivity 

and sex (more common in males), history of imprisonment, drug 

addiction, level of education (more common in illiterate and 

less educated subjects) and place of residence (more common 

in Gachsaran). No significant correlation (P > 0.05) was found 

between HCV seropositivity and age, history of needle stick, 

and employment. Table 3 shows the risk factors which might be 

associated with HCV seropositivity in this study. Multivariate 

analysis, using backward selection logistic regression, revealed 

a correlation between history of imprisonment, thalassemia and 

HCV positivity. Table 4 shows the details of this correlation. 

Discussion 

Approximately 3% of the world’s population are infected with 

HCV. 1 The high risk groups for HCV infection are those who practice 

activities such as blood transfusions, medical or dental care, 

acupuncture and tattooing, IDUs, imprisonment, and health care 

workers. HCV-positive individuals might expose their friends, 

families and general community to HCV infection. In this study 

we have evaluated the seroprevalence of HCV in high risk groups 

HCV Infection in a Southwest Area of Iran 

Table 4. Association between HCV positivity and risk factors in high risk groups in Kohgiloyeh and Boyerahmad Province, Southwest Iran. 

in Kohgiloyeh and Boyerahmad Province. The study was justified 

by the lack of information about HCV infection in this area. 

Prevalence of HCV antibody positivity among all participants 

of this study was 8.6%. Findings of this study demonstrated a 

relatively high prevalence of HCV in this area. Since the recruited 

subjects of this study were from selected high risk groups, 

therefore the rate of HCV in the entire population of the district 

might be different. Because of religious beliefs and possible lack 

of co-operation in answering questions related to sexual behaviors, 

many individuals did not properly answer this question. Such data 

was not considered in the statistical analysis. Self-reporting of 

behaviors such as sexual activity and drug use are other limitations 

of this study. 

It is worth mentioning that the seropositivity of HCV does not 

mean HCV infection since spontaneous resolution of HCV might 

occur in HCV-infected individuals. In such cases ELISA results are 

positive but the patient is not HCV-infected. 

Despite the low HCV seroprevalence in the Iranian general population, 

recent studies have shown a high prevalence of HCV infection 

among Iranian prisoners. Of 460 inmates in a prison in 

Guilan, 45.4% were HCV antibody positive. 7 In our study the 

rate of seropositivity in prisoners was lower (11.6%). Participants 

who spent more time in prison were significantly more likely to 

be positive for antibodies to HCV in our study. The current study 

found a positive correlation between being in prison and HCV 

seropositivity. Such connection has been reported in a study by 

Alizadeh et al. of prisoners in Hamedan, Iran where they reported 

a prevalence of 30% for HCV antibodies. 9 

The overall seroprevalence of HCV among Iranian blood donors 

has been estimated to be 0.12%. 10 The prevalence of anti-HCV 

antibodies among 7897 healthy voluntary blood donors in Shiraz, 

Iran was 0.59% in 1998. 11 This approximated the frequency of 

anti-HCV recently reported in a population-based study in Iran. 3 

Khedmat et al. reported a frequency of 2.07% for anti-hepatitis C 

among Iranian blood donors in 2009. 12 In our study, 4.1% of patients 

who had a history of transfusion were positive for anti-HCV 

antibodies. 

The prevalence of HCV infection in hemophilic patients in Iran 

has been reported to be 15.6% in Fars, 44.3% in Kerman, 29.6% 

in Zahedan, 59.1% in Hamadan, 71.3% in Guilan, and 76.7% 

in Northwest Iran. The overall estimate of HCV in these patients 

in the entire country is estimated to be 50%. 6,13–15 In our study the 

numbers of hemophilic patients were too few to draw any conclusion 

about prevalence of HCV in this high risk group in the region. 

Thalassemic patients are at high risk for hepatitis C infection; 

19.3% in 732 patients with beta-thalassemia from 5 provinces of 

Iran have been reported to be infected with HCV. 16 In our study 

6.1% of thalassemic patients were HCV-positive. 

HCV infection is a significant health problem in dialysis units 


in Iran. Seroprevalence of hepatitis C in hemodialysis patients in 

Guilan, northern Iran was reported to be 24.8%. 17 Recent studies 

have reported a decline in prevalence of HCV in hemodialysis patients 

in Iran from 14.4% in 1999 to 4.5% in 2006. 18 It has been 

shown that blood transfusion and duration of dialysis treatment are 

important risk factors for HCV infection in patients on maintenance 

hemodialysis. The more units transfused, the higher the risk for 

HCV infection. 

There is a wide range of HCV infection, 2 – 100%, in IDUs in 

different parts of the world. 19 

The findings of the current study have shown that 42.4% of IDUs 

are infected with HCV; thus they are a very important reservoir for 

the spread of HCV to others in the community. Alavi et al. have 

reported a higher seroprevalence of HCV (52.11%) in IDUs in Ahvaz, 

Iran. 20 

In conclusion, the findings of the present study have provided 

epidemiologic features of hepatitis C and its risk factors in 

Kohgiloyeh and Boyerahmad Province in Southwest Iran. This 

information contributes to our understanding of the worldwide 

prevalence of hepatitis C and may help to contain the spread of 

HCV infection in this and other similar settings in the region. The 

findings of this study may assist in improving surveillance and prevention 

of HCV infection in the community through management 

and monitoring of infected individuals. 

Acknowledgments 

This study was financially supported by the Governor of 

Kohgiloyeh and Boyerahmad Province. We thank the medical and 

nursing staff of Shahid Beheshti and Imam Sadjjad hospitals for 

their assistance with sample collection. We particularly express 

our appreciation to those who provided blood samples for this 

study. 

References 

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organized in collaboration with the Viral Hepatitis Prevention 

Board, Antwerp, Belgium. J Viral Hepat. 1999; 6: 35 – 47. 

2. Hoofnagle JH. Course and outcome of hepatitis C. Hepatology. 2002; 

36: 21 – 29. 

3. Merat S, Rezvan H, Nouraie M, Jafari E, Abolghasemi H, Radmard 

AR, et al. Seroprevalence of hepatitis C virus: The first population- 


B. Sarkari, O. Eilami, A. Khosravani, et al. 

based study from Iran. Int J Infect Dis. 2010; 14: 113 – 116. 

4. Vahdani P, Hosseini-Moghaddam SM, Family A, Moheb-Dezfouli R. 

Prevalence of HBV, HCV, HIV and syphilis among homeless subjects 

older than fifteen years in Tehran. Arch Iran Med. 2009; 12: 483 – 487. 

5. Hosseini Asl SK, Avijgan M, Mohamadnejad M. High prevalence of 

HBV, HCV, and HIV infections in gypsy population residing in Shahr- 

E-Kord. Arch Iran Med. 2004; 7: 20 – 22. 

6. Alavian SM, Fallahian F. Epidemiology of hepatitis C in Iran and the 

world. Shiraz E-Med J. 2009; 10(4): 162 – 172. 

7. Alavian SM, Adibi P, Zali MR. Hepatitis C virus in Iran: Epidemiology 

of an emerging infection. Arch Iran Med. 2005; 8: 84 – 90. 

8. Rahimi-Movaghar A, Razaghi EM, Sahimi-Izadian E, Amin-Esmaeili 

M. HIV, hepatitis C virus, and hepatitis B virus co-infections among 

injecting drug users in Tehran, Iran. Int J Infect Dis. 2010; 14: 28 – 33. 

9. Alizadeh AHM, Alavian SM, Jafari K, Yazdi N. Prevalence of hepatitis 

C virus infection and its related risk factors in drug abuser prisoners in 

Hamedan - Iran. World J Gastroenterol. 2005; 11: 4085 – 4089. 

10. Alavian SM, Gholami B, Masarrat S. Hepatitis C risk factors in Iranian 

volunteer blood donors: A case-control study. J Gastroenterol Hepatol. 

2002; 17: 1092 – 1097. 

11. Ghavanini AA, Sabri MR. Hepatitis B surface antigen and anti-hepatitis 

C antibodies among blood donors in the Islamic Republic of Iran. 

East Mediterr Health J. 2000; 6: 1114 – 1116. 

12. Khedmat H, Fallahian F, Abolghasemi H, Alavian SM, Hajibeigi B, 

Miri SM, et al. Seroepidemiologic study of hepatitis B virus, hepatitis 

C virus, human immunodeficiency virus and syphilis infections in Iranian 

blood donors. Pak J Biol Sci. 2007; 15: 4461 – 4466. 

13. Karimi M, Ghavanini AA. Seroprevalence of HBsAg, anti-HCV, and 

anti-HIV among haemophiliac patients in Shiraz, Iran. Haematologia. 

2001; 31: 251 – 255. 

14. Sharifi-Mood B, Eshghi P, Sanei-Moghaddam E, Hashemi M. Hepatitis 

B and C virus infections in patients with hemophilia in Zahedan, 

southeast Iran. Saudi Med J. 2007; 28: 1516 – 1519. 

15. Mansour-Ghanaei F, Fallah MS, Shafaghi A, Yousefi-Mashhoor M, 

Ramezani N, Farzaneh F, et al. Prevalence of hepatitis B and C seromarkers 

and abnormal liver function tests among hemophiliacs in 

Guilan (northern province of Iran). Med Sci Monit. 2002; 8: 797 – 800. 

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Zahedi MJ, et al. Epidemiology of hepatitis B, hepatitis C, and human 

immunodeficiency virus infections in patients with beta-thalassemia in 

Iran: A multicenter study. Arch Iran Med. 2006; 9: 319 – 323. 

17. Amiri ZM, Shakib AJ, Toorchi M. Seroprevalence of hepatitis C and 

risk factors in haemodialysis patients in Guilan, Islamic Republic of 

Iran. East Mediterr Health J. 2005; 11: 372 – 376. 

18. Alavian SM, Mahdavi-Mazdeh M, Bagheri-Lankarani K. Hepatitis B 

and C in dialysis units in Iran, changing the epidemiology. Hemodial 

Int. 2008; 12: 378 – 382. 

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among injecting drug users. Int J Drug Policy. 2007; 18: 352 – 358. 

20. Alavi SM, Alavi L. Seroprevalence study of HCV among hospitalized 

intravenous drug users in Ahvaz, Iran (2001-2006). J Infect Public 

Health. 2009; 2: 47 – 51.


Assessment and Treatment of Choledocholithiasis when Endoscopic 

Sphincterotomy is not Successful 

Abolfazl Shojaiefard MD 1 , Majid Esmaeilzadeh MD 2 , Zhamak KhorgamiMD• 1 , Rasoul Sotoudehmanesh MD 3 , Ali Ghafouri MD 1 

See the pages: 269 – 270 

Abstract 

Background: Choledocholithiasis exists in approximately 15% of patients with gallstones and is present in 3%-10% of those undergoing 

cholecystectomy. 

Methods: In this study, we retrospectively analyzed the outcome patients with choledocholithiasis that were managed by open common 

bile duct (CBD) exploration according to our center’s protocol. Endoscopic retrograde cholangiopancreatography (ERCP) was performed for 

CBD stone clearance. If ERCP and sphincterotomy were not successful, open surgical exploration of CBD was performed with T-tube insertion 

without routine intraoperative cholangiography (IOC). 

Results: We studied 1462 patients with choledocholithiasis. ERCP was successful in in 1276 (87.2%) patients. A total of 186 (12.8%) 

underwent surgery. Of these, 82 (45.2%) had CBD exploration and T-tube insertion without IOC. Choledochoduodenostomy was performed 

in 82 (44.1%) patients and choledochojejunostomy was performed in 20 (10.8%). Retained stones were found only in 4 cases which were 

treated by ERCP. 

Conclusion: ERCP is successful in most cases with choledocholithiasis. If ERCP fails, open exploration of CBD and T-tube insertion, or 

biliary-enteric anastomosis are acceptable ways for CBD drainage. The rate of retained stone is not more than expected, thus elective IOC 

is more acceptable than routine IOC. Routine IOC is time-consuming and particularly difficult in elderly patients and emergency conditions. 

Keywords: Choledochoduodenostomy, Choledochojejunostomy, Choledocholithiasis, ERCP 

Cite this article as: Shojaiefard A, Esmaeilzadeh M, Khorgami Z, Sotoudehmanesh R, Ghafouri A. Assessment and Treatment of Choledocholithiasis when Endoscopic 

Sphincterotomy is not Successful. Arch Iran Med. 2012; 15(5): 275 – 278. 


Choledocholithiasis is a medical condition that mandates surgical 

intervention. It may occur in 3% – 10% of patients 

with cholecystectomy, 1 and as high as 14.7% in some series. 

2 Generally, the prevalence of asymptomatic bile duct stones is 

reported between 5.2% and 12%. 3 

There are several diagnostic approaches for common bile duct 

(CBD) stones. These include: laboratory analysis, ultrasonography 

(US), computed tomography scans (CT scan), magnetic resonance 

cholangiopancreatography (MRCP), endoscopic ultrasonography 

(EUS), and endoscopic retrograde cholangiopancreatography 

(ERCP). Intraoperative cholangiography (IOC) during cholecystectomy 

can be performed routinely or selectively to diagnose 

choledocholithiasis. 4,5 Nowadays, 2 groups of interventions have 

a significant role in the management of patients with gallstone and 

CBD stones: pre- or post-cholecystectomy ERCP with endoscopic 

sphincterotomy (ES), which is a two-stage procedure, and surgical 

bile duct clearance and cholecystectomy by single open or 

laparoscopic surgery (one-stage procedure). Several randomized 

controlled trials have shown comparable effectiveness of these 

Authors’ Affiliations: 1 Department of Surgery and Research Center for Improvment 

of Surgical Outcomes and Procedures, Shariati Hospital, Tehran University 

of Medical Sciences, Tehran, Iran, 2 Department of General, Visceral and Transplantation 

Surgery, University of Heidelberg, Germany, 3 Digestive Diseases Research 

Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran . 

•Corresponding author and reprints: Zhamak Khorgami MD, Department of 

Surgery, Tehran University of Medical Sciences, Shariati Hospital, Kargar Ave, 

Tehran, Iran. Tel.: +98-21-84902450, Fax: +98-21-88633039, 

E-mail: khorgami@gmail.com. 

Accepted for publication: 21 October 2011 

modalities. 6,7 Other methods include electrohydraulic lithotripsy 

(EHL), extracorporeal shockwave lithotripsy (ESWL), laser lithotripsy 

and dissolving solutions that are advocated for special conditions. 

8,9 

Although, ERCP and laparoscopic CBD exploration are preferred 

methods in most centers, open CBD exploration should never be 

abandoned. Some studies have proposed choledochotomy with 

primary laparoscopic closure of the CBD which eliminates the 

need for a T-tube, thus reducing surgical time and postoperative 

morbidity. 10 However, open CBD exploration with T-tube insertion 

remains the standard procedure for most patients. 

In this study, we review the results of surgical management in 

186 out of 1462 patients with choledocholithiasis. We present our 

protocol for the management and treatment of choledocholithiasis, 

particularly in cases of unsuccessful ERCP and sphincterotomy. 


Treatment of Choledocholithiasis 

From June 2007 to March 2010, 1462 patients with choledocholithiasis 

referred to Shariati Hospital, Tehran University of Medical 

Sciences. After primary evaluation with laboratory tests and US, 

patients’ diagnoses were confirmed by EUS or MRCP. 

We performed ERCP and ES in confirmed cases to extract CBD 

stones. When ERCP was not successful the patient underwent surgery. 

We administered antibiotic therapy (ceftriaxone 1 gr/IV/BD 

and metronidazole 500 mg/IV/TDS) to patients with cholangitis 

and/or cholecystitis. This therapy continued for 5 – 7 days in patients 

with acute cholangitis and for 48 hours after elective surgeries 

in those without cholangitis. Surgical procedures included 


Frequency Percent (%) 

Main presentation 

Cholecystitis 98 52.7 

Cholangitis 62 33.3 

Biliary colic 15 8.1 

Pancreatitis 

Comorbid diseases 

11 5.9 

Diabetes mellitus 27 14.5 

Hypertension 22 11.8 

Ischemic heart disease 5 2.7 

Chronic obstructive pulmonary disease 3 1.6 

Other 

Type of surgery 

8 4.3 

CBD exploration and T-tube insertion 84 45.2 

Choledochoduodenostomy 82 44.1 

Choledochojejunostomy 20 10.7 

CBD exploration and T-tube insertion or biliary enteric anastomosis 

(choledochoduodenostomy and choledochojejunostomy). Figure 

1 shows the algorithmic approach to patients with choledocholithiasis 

at Shariati Hospital. 

In our center, laparoscopic cholecystectomy is the surgery of 

choice. However, due to insufficient experience in laparoscopic 

exploration of CBD and previous open cholecystectomy in some 

patients who had subsequent adhesions, we performed open surgery 

in these cases through a right subcostal or upper abdominal 

midline incision. We inserted a T-tube in the CBD when its diameter 

was less than 12 mm and in patients with cholangitis. In other 

patients that underwent elective surgery with CBD diameter more 

than 12 mm, we performed biliary-enteric anastomosis (choledochoduodenostomy 

or choledochojejunostomy). 

Routine IOC after T-tube insertion can determine retained stones. 

However, because IOC is time-consuming we did not perform this 

procedure if we could pass appropriate biliary dilators through the 

sphincter of oddi after stone extraction and certainty of CBD clearance. 

This timesaving approach was particularly important in older 

or critically ill patients. Then, after irrigation of the CBD with normal 

saline, we inserted a 14 or 16 Fr T-tube in the CBD and closed 

the choledocotomy with absorbable (Vicryl 3-0) separate sutures. 

Seven to eight days after surgery, T-tube cholangiography was performed. 

In cases without retained stones the T-tube was extracted 

14 to 21 days after surgery. 

Statistical analysis 

Statistical analysis was performed using SPSS for Windows version 

16.0 (SPSS Inc., Chicago, IL). For quantitative data, mean 

and ranges were calculated. Quantitative data were reported as 

relative frequencies and percentages. In this study, the significant 

variables analysis was entered into both the chi-square and t-tests. 

P values < 0.05 were considered statistically significant. 

Results 

There were 186 out of 1462 patients with choledocholithiasis 

who underwent surgery. Of these, 82 (44%) were women and 104 

(56%) were men. Patients’ mean age was 58.6 ± 15 years (range: 

21 – 78 years). The main presentations and comorbid diseases are 

shown in Table 1. Comorbidities of hypertension, diabetes mellitus, 

ischemic heart disease, and chronic obstructive pulmonary 

disease were present in 65 (34.9%) patients. 

Sixty-six (35.5%) patients had leukocytosis (wbc > 11,000/mm 3 ). 

Jaundice was present in 38 (20.4%) patients and the mean total 


A. Shojaiefard, M. Esmaeilzadeh, Z. Khorgami, et al. 

Table 1. Frequency of main presentation, comorbid disease, and type of surgery in 186 patients with choledocolithiasis. 

bilirubin was 2.7 ± 1.7 mg/dl. Alkaline phosphatase was greater 

than 300 U/dL in 96 (51.6%) patients. US showed a mean CBD diameter 

of 14.4 ± 6.4 mm; the mean stone size was 13.3 ± 4.8 mm. 

There was a history of previous cholecystectomy in 45 (24.2%) 

patients. 

ERCP was successful in 1276 of 1462 (87.3%) patients and 186 

(12.7%) underwent open surgical CBD exploration. Main reasons 

for ERCP failure were multiple stones, large stones (≥1.5 cm) and 

impacted stone in the distal portion of the CBD, among others. 

Existence of periampullary diverticulum (3 cases), bulbar deformity 

of the duodenum (1 case), and ampullary polyp (1 case) also 

prevented ERCP. 

In 84 (45.2%) out of 186 patients CBD exploration and T-tube 

insertion were performed. Of these, 40 (47.6%) had acute cholangitis, 

33 (39.3%) had cholecystitis, and 11 (13.1%) had pancreatitis. 

There were 4 cases with retained stones after T-tube insertion 

according to postoperative T-tube cholangiography. Endoscopic 

sphincterotomy and stone extraction were successfully performed 

to extract the retained stones. 

We performed biliary-enteric anastomoses in 102 (54.8%) patients 

whose surgical conditions were not urgent and had CBD 

diameters of 12 mm or more. Included in this group were patients 

with cholangitis who were responsive to antibiotic therapy. For 82 

(44.1%) patients, choledochoduodenostomy was performed and 

20 (10.7%) underwent choledochojejunostomy. The latter was 

performed when adhesions or deformity of the duodenum and difficulty 

in its mobilization were present. 

Mean surgery time was 128 ± 23 minutes. The length of hospitalization 

was 6.8 ± 3.8 days, which was less in patients who had 

T-tube insertions when compared with biliary-enteric anastomosis 

(6.4 ± 3.4 days vs. 8.5 ± 4 days, p = 0.02). The age of patients with 

T-tube insertion was less than those with biliary-enteric anastomosis 

(54.4 ± 14.4 vs. 63.7 ± 16.5 years, p = 0.01). 

A total of 33 (17.7%) patients were transferred to the intensive 

care unit (ICU) after surgery, mainly due to older age and comorbid 

diseases. The mean time in the ICU was 2.7 days (range: 1 – 5 

days). 

Postoperative complications were seen in 14 (7.5%) patients and 

included wound infection (8), pneumonia (3) and pancreatitis after 

surgery (3). Mortality occurred in 3 (1.6%) female patients, who 

were all over 50 years of age, as a result of sepsis (2) and myocardial 

infarction (1). 

Patients were followed at two weeks, one, three, and six months, 

and one year after surgery. Follow-up evaluations included physical 

examination, laboratory tests, and US. There were no cases of

ecurrent choledocholithiasis or any long-term complications. 

Discussion 

The management of choledocholithiasis has always been challenging. 

Nowadays, ERCP has essentially replaced open surgery 

for safe and effective CBD stone extraction. Open CBD exploration 

is an important surgical procedure when ERCP fails and expertise 

for laparoscopic CBD exploration is not available. 

The optimal method for performing open CBD exploration is 

unclear. 11 The routine use of IOC during laparoscopic cholecystectomy 

remains controversial. 12 Stuart et al. have performed IOC 

in 348 patients, of which it was abnormal in 17 (5%) cases. However, 

documented retained stones that existed in 5 patients were 

removed by CBD exploration or ERCP in that study. 13 Mir et al. 

did not perform IOC, and reported reductions in costs and hospital 

stay. 14 We did not perform IOC in order to reduce the surgical time. 

In our study, there were cases of 4 retained stones in patients with 

T-tube insertion that were successfully extracted by ERCP. Generally, 

ERCP is more feasible in this subgroup since postoperative 

T-tube cholangiography shows the anatomy of the biliary tree and 

large or impacted stones that have been extracted during surgery. 

Figure 1- Algorithmic approach at Shariati Hospital for choledocholithiasis 

Treatment of Choledocholithiasis 

The rate of retained CBD stones in our study was not greater than 

other studies. For this reason, we have proposed that routine IOC is 

not necessary after surgical CBD exploration and clearance. 

In our center, the appropriate surgical method was chosen based 

on the patient’s condition. In patients with sepsis due to cholangitis 

and accompanying diseases, it was necessary to shorten the time 

of surgery. In addition, biliary-enteric anastomosis increased the 

risk of complications. In such cases, the T-tube was inserted following 

CBD exploration. In cases with CBD diameters less than 

12 mm, the T-tube was used because of the high risk for anastomotic 

stricture 15 and subsequent complications. Most authors have 

preferred insertion of T-tube for CBD drainage, but some centers 

have utilized transcystic tubes (C-tube) or antegrade stenting with 

choledochorrhaphy for CBD drainage. 16 In patients with residual 

distal stone, ductal imaging in the postoperative period and provision 

of an access route for removal of residual CBD stones has 

been performed. 17 

The most commonly used choledochoenterostomy is side-toside 

choledochoduodenostomy, usually in the setting of a dilated 

CBD. 18 In cases where duodenal anastomosis was impossible, choledochojejunostomy 

was performed. 

Currently, many centers use laparoscopy for CBD surgeries. Ex- 


pert surgical teams have reported a CBD clearance rate of about 

97%. 19 The morbidity rate has been reported to be 9.5% and retained 

stone rate of 2.7% for exploratory laparoscopic CBD. 20 

Nevertheless, in comparison to open surgery, laparoscopic surgery 

is more time consuming, 21 yet has shorter postoperative hospitalization. 

Open surgery is still straightforward for management of 

choledocholithiasis and has a higher stone clearance rate. 

Conclusion 

Choledocholithiasis remains a challenging problem for clinicians. 

Currently, ERCP is used mainly for extraction of CBD stones, but 

surgery is the method of choice when ERCP fails. Performing 

an IOC assists in the detection of CBD stones but routine use of 

IOC remains controversial. Although ERCP and then laparoscopic 

CBD exploration are selective methods in most centers, open CBD 

exploration is the most effective method. Selection of treatment 

depends on physicians’ experience and available resources. 

References 

1. Schirmer BD, Witers KL, Edlich RF. Choledocholithiasis and cholecystitis. 

J Long Term Eff Med Implants. 2005; 15: 329 – 338. 

2. Riciarel R, Islam S, Canete JJ, Avcand PL, Stoker ME. Effectiveness 

and long term results of laparoscopic common bile duct exploration. 

Surg Endoscopy. 2003; 17: 19 – 22. 

3. Rosseland AR, Glomsaker TB. Asymptomatic common bile duct 

stones. Eur J Gastrentrol Hepatol. 2000; 12: 1171 – 1173. 

4. Freitas M, Bell R, Duffy A. Choledocholithiasis: Evolving standards 

for diagnosis and managements. World J of Gastroentrology. 2006; 12: 

3162 – 3167. 

5. Schwarz J, Simsa J, Pazdirek F. Our experience with preoperative choledochoscopy. 

Rozhl Chir. 2007; 86(4): 180 – 183. 

6. Clayton ESJ, Connor S, Alexakis N, Leandros E. Meta analysis of endoscopy 

and surgery versus surgery alone for common bile duct stones 

with the gallbladder in situ. Br J Surg. 2006; 93: 1185 – 1191. 

7. Martin DJ, Vernon DR, Toouli J. Surgical versus endoscopic treat- 


A. Shojaiefard, M. Esmaeilzadeh, Z. Khorgami, et al. 

ment of bile duct stones (Review). Cochrane Database Syst Rev. 2006; 

19(2): CD003327. 

8. Caddy GR, Tham TC. Symptoms, diagnosis and endoscopic management 

of common bile duct stones. Best Practice & Research Clinical 

Gastroenterology. 2006; 20: 1085 – 1101. 

9. Evans AJ, Branch MS. The recalcitrant bile duct stone. Techniques in 

Gastrointestinal Endoscopy. 2007; 9: 104 – 113. 

10. Ahmed I, Pradhan C, Beckingham IJ, Brooks AJ, Rowlands BJ, Lobo 

DN. Is a T-tube necessary after common bile duct exploration? World J 

Surg. 2008; DOI 10.1007/s00268-008-9475-2 

11. Gurusamy KS, Samrai K. Primary closure versus T-tube drainage after 

open common bile duct exploration. Cochrane Database Syst Rev. 

2007; 1: CD005640. 

12. Ciulla A, Aqnello G, Tomasello G, Castronovo G, Maiorana AM, 

Genova G. The intraoperative cholangiography during videolaparoscopic 

cholecystectomy. What is its role? Results of a non randomized 

study. Ann Ital Chir. 2007; 78(2): 85 – 89. 

13. Stuart AS, Simpson T, Alvord L, Williams M. Routine intraoperative 

laparoscopic cholangiography. Am J Surgery. 1998; 176: 632 – 637. 

14. Mir IS, Mohsin M, Kirmani O, Majid T, Wani K, Hassan MU, et al. Is 

intraoperative cholangiography necessary during laparoscopic cholecystectomy? 

A multicentre rural experience from a developing world 

country. World J Gastroenterol. 2007; 13(33): 4493 – 4497. 

15. Ramirez P, Parrilla P, Bueno FS, Abad JMP, Muelas MS, Candel MF, et 

al. Choledochoduodenostomy and sphincterotomy in the treatment of 

choledocholithiasis. Br J Surg. 1994; 81: 121 – 123. 

16. Isla AM, Griniatsos J, Karvounis E, Arbuckle JD. Advantages of laparoscopic 

stented choledochorrhaphy over T-tube placement. Br J Surg. 

2004; 91: 862 – 866. 

17. Petelin JB. Laparoscopic common bile duct exploration. Surg Endosc. 

2003; 17: 1705 – 1715. 

18. Hungness ES, Soper NJ. Management of common bile duct stones. J 

Gastrointestinal Surgery. 2006; 10(4): 612 – 619. 

19. Petelin JB. Laparoscopic common bile duct exploration. Surg Endosc. 

2003; 17: 1705 – 1715. 

20. Lien HH, Huang CC, Huang CS, Shi MY, Chen DF, Wang NY, et al. 

Laparoscopic common bile duct exploration with T-tube choledochotomy 

for the management of choledocholithiasis. J Laparoendosc Adv 

Surg Tech A. 2005; 15(3): 298 – 302. 

21. Mandry AC, Bun M, Ued ML, Iovaldi ML, Capitanich P. Laparoscopic 

treatment of common bile duct lithiasis associated with gallbladder lithiasis. 

Cir Esp. 2008; 83(1): 28 – 32.



(MAQ) in an Iranian Urban Adult Population 

Amir Abbas Momenan MD MPH 1 , Maryam Delshad BS 2 , Narges Sarbazi MD 1 , Nasrollah Rezaei_Ghaleh MD 2,3 , Arash Ghanbarian 

MD• 1 , FereidounAzizi MD 2 

Abstract 

Background: The purpose of this study is to evaluate the validity and reliability of a Persian translation of the Modifiable Activity Questionnaire 

(MAQ) in a sample of adults from Tehran, Iran. 

Methods: There were 48 adults (53.1% males) enrolled to test the physical activity questionnaire. A sub-sample included 33 participants 

(45.5% males) who assessed the reliability of the physical activity questionnaire.The validity was tested in 25 individuals (48.0% males). The 

reliability of two MAQs was calculated by intraclass correlation coefficients. The validation study was evaluated with the Spearman correlation 

coefficients to compare data between the means of 2 MAQs and the means of 4 physical activity records. 

Results: Intraclass correlation coefficients between 2 MAQs for the previous year's leisure time was 0.94; for occupational, it was 0.98;and 

for total (leisure and occupational combined) physical activity, it was 0.97. The Spearman correlation coefficients between the means of the 2 

MAQs and means of the 4 physical activity records was 0.39 (P = 0.05) for leisure time, 0.36 (P = 0.07) for occupational, and 0.47 (P = 0.01) 

for total (leisure and occupational combined) physical activities. 

Conclusions: High reliability and relatively moderate validity were found for the Persian translated MAQ in adults from Tehran. However, 

further studies with larger sample sizes are suggested to more precisely assess the validity of the MAQ. 

Keywords: Persian, physical activity, questionnaire, reliability, validity 

Cite this article as: Momenan AA, Delshad M, Sarbazi N, Rezaei_Ghaleh N, Arash Ghanbarian A, Azizi F. Reliability and Validity of the Modifiable Activity Questionnaire 

(MAQ) in an Iranian Urban Adult Population. Arch Iran Med. 2012; 15(5): 279 – 282. 


Recent interventions have been designed primarily to increase 

the level of physical activity in adults because the role of 

physical activity behavior has been confirmed as an important 

factor for health. 1 In large epidemiological studies, selecting 

the proper assessment tool is a challenging task for researchers 2 

and there are several different techniques used to assess physical 

activity, such as questionnaires, diaries, 7-day recall, movement 

sensors and doubly labeled water. 3 The gold standard method is the 

doubly labeled water that measure total energy expenditure, but it 

is not suitable for large population studies because that is complicated 

and expensive. 4 For practical reason and in the absence of 

inexpensive, readily available, relatively noninvasive, valid and 

reliable technology for measuring physical activity in large numbers 

of free-living humans, most epidemiological studies rely on 

questionnaires to assess physical activity. 4,5 Questionnaires are 

both comprehensive and easy to use in longitudinal studies, they 

are generally well accepted by individuals and easy to administer 

to a large number of study participants at a low cost so it is the most 

Authors’ Affiliations: 1 Prevention of Metabolic Disorders Research Center, Research 

Institute for Endocrine Sciences, Shahid Beheshti University of Medical 

Sciences, Tehran, Iran, 2 Endocrine Research Center, Research Institute for Endocrine 

Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 

3 Max Plank Institute for Biophysical Chemistry, Research Group Protein Structure 

Determination using NMR,Gottingen, Germany. 

•Corresponding author and reprints: Arash Ghanbarian MD, Prevention of 

Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, 

Shahid Beheshti University of Medical Sciences, Parvaneh St., Yaman St., Chamran 

Exp., Tehran, Iran. E-mail: ghanbarian@endocrine.ac.ir 

Accepted for publication: 13 July 2011 


widely used method to assess usual physical activity patterns in 

population studies. 6 

Physical activity includes multiple social domains (household, 

occupational, transportation related, leisure time), and recent researches 

have augmented the importance of assessing activities 

encountered in daily life. 7 The health risk associated with physical 

activity differs according to the different dimensions such as type 

of activity, duration and intensity. So, it is important that physical 

activity questionnaires assessing professional, domestic and 

leisure time activity, differentiate the intensity of activity and addressing 

the usual individual energy expenditure. 4 The Modifiable 

Activity Questionnaire (MAQ) assesses current (past year and past 

week) physical activity during occupation and leisure time, as well 

as extreme levels of inactivity due to disability. 6 This questionnaire 

was designed for easy modification to maximize the ability to assess 

physical activity in a variety of populations. 6 Because physical 

activity patterns and accuracy of self reports may differ across 

cultural/ethnic backgrounds or gender, it is necessary to use reliable 

and validated the instrument in each study population. 8 Few 

questionnaires have been tested on the Iranian urban adult population 

for evaluating physical activity. This paper describes the study 

of the validity and reliability of the Persian translated MAQ in a 

sample population of Tehranian adults. 

Methods 

Study population 

The Tehran Lipid and Glucose Study (TLGS) were designed in 

order to investigate the prevalence of non-communicable disorders 


and their risk factors in a sample of Iranian population. The participants 

of the present study were selected from the framework of 

the TLGS, a prospective study among urban population in district 

No. 13 of Tehran, Iran. 9 Based on the least sample size needed for 

validity 10 and an attrition rate of 30%, we invited 40 males and 40 

females, aged 19 years and over with Stratified Random Sampling. 

According to the following formula for reliability sample size, 

considering α = 0.05 and β = 0.1, the above mentioned sample size 

was satisfactory for reliability test, too. 

Forty eight adults (53.1% were males) accepted the invitation 

to fill the physical activity questionnaire in 2002 (response rate, 

60%). For validity, we excluded those who did not complete at 

least three physical activity records. So, of a total of 48 subjects, 

the validity of the physical activity questionnaire was assessed in 

25 individuals (48.0 % were males). The reliability was assessed 

in those same subjects who accepted the invitation. From those, 33 

participants (45.5% were males) were completed two MAQs and 

included for testing the reliability. 

The research ethical committee of Research Institute for Endocrine 

Sciences of the Shahid Beheshti University of Medical Sciences 

approved this study protocol and an informed written consent 

was obtained from each participant. 

Measurements 

The modifiable activity questionnaire 

The original version of the MAQ 11 was translated into Persian 

and then back-translated into the English. Based on Iranian culture, 

minor adaptations to fit in the current context in terms of usual 

leisure time physical activity performed by Iranian people were 

made. All the modifications, as well as translations, were approved 

by original MAQ author through email communication. Data were 

collected by the participants, assisted by trained interviewers when 

needed. Participants were asked to report the activities that they 

had participated at least 10 times during the past 12 months in their 

leisure times and then identified the frequency and duration for 

each leisure time physical activities. Total number of minutes per 

year, calculated for every physical activity were summed and then 

divided by 60 and 52 to estimate the hours per week of total leisure 

time physical activity. The calculation of MET-h/wk is summarized 

as below: 

MET-h/wk= (MET × months per year × time per month × minute 

per time) / (60×52) 

MET-h/wk of leisure time activity was calculated by multiplying 

the number of hours per week of each leisure time activity to 

metabolic equivalent (MET). One MET is set at 3.5 ml of oxygen 

consumed per kilogram body mass per minute (1kcal/kg/h) 

and represents the resting metabolic rate. The numbers of METs 

corresponding to each activity were calculated using the average 

metabolic cost for each activity. 12 

According to the questionnaire, individuals had to identify the 

number of month and hours participated in physical activity at 

work (standing, house work, work activities more intense than 

standing) over the past year. The assessment of occupational ac- 


tivity was based on using the number of hours per week of light, 

moderate and hard intensity activity, summed to express hours per 

week of occupational activity over the past year. Final occupational 

(MET-h/wk) activity was calculated by multiplying the number 

of hours per week of each three categories of occupational activity 

to MET values. 12 Total physical activities was expressed in hours 

of activity per week or MET-h/wk by adding leisure time physical 

activity to occupational activity. 

Reliability 

Participants completed the MAQ twice, with an interval of four 

weeks to evaluate the reliability. The standard time frame for testretest 

studies is one to two weeks. But, a four-week interval was 

chosen because of the practical issues. The subjects were a part of 

a large scale community-based study (the TLGS) and there were 

difficulties in recruiting them for shorter intervals. 

Validity 

All participants were asked to complete a weekly record form of 

physical activity and record all the activities in one typical week in 

every season, preferably in the middle of each season. They were 

trained how to record the activities. For convenience, the whole 

24-hours were divided into 3 intervals in our questionnaire; 8 – 14, 

14 – 22 and 22 to 8 am of next day. They were asked to record any 

activities during each interval, including leisure time and occupational 

activities.The physical activity record questionnaires completed 

in the middle of each season and were compared with mean 

of two MAQs to evaluate the convergent validity of the MAQ. 


Using the P-P plot test, the distribution of mean of MET-h/wk 

wasn’t normal, so we used non-parametric tests. Data from both 

MAQs and from the four physical activity records were reported 

as mean (± SD) values for age, weight, height, BMI (Body Mass 

Index), MET-h/wk. Mann-Whitney test was used to compare 

the means of two MAQs. Since there was no significant difference 

between two MAQs, we used the mean of two MAQs to be 

compared with four physical activity records. Intraclass Correlation 

Coefficients were used to calculate the reliability of the two 

MAQs. Intraclass Correlation Coefficients estimates ≥ 0.7 were 

considered asacceptable reliability. 13 To evaluate the convergent 

validity, Spearman Correlation Coefficients were used to compare 

means of two MAQs and means of four physical activity records. 

Results 

A.A Momenan, M. Delshad, N. Sarbazi, et al. 

The mean (± SD) values of age, weight, height, BMI and the percentage 

of sex and education levels for participants are presented 

in Table 1. The mean age of the participants was 39.5 ± 14.7 yr 

and 45.5% were men. Average BMI was 25.9 ± 4.7 kg/m 2 and the 

prevalence of normal weight, overweight and obesity were 35.5%, 

45.2% and 19.4%, respectively. All subjects were literate. Table 2 

shows the estimations of MET-h/wk measured by physical activity 

record questionnaires and two MAQs. Based on two MAQs, 

the mean of MET-h/wk for leisure time, occupational and total 

(leisure and occupational combined) physical activities were 23.4, 

52.3 and 75.7, respectively. Besides, the mean of total MET-h/wk 

was 86.3 MET-h/wk according to the data derived from physical 

activity records of four seasons. For past year leisure time, occupational 

and total (leisure and occupational combined) physical ac-

Measurement mean SD Minimum Maximum 

Age (year) 39.5 14.7 19.0 66.0 

Sex (men) * 45.5% - - - 

Weight (kg) 72.1 14.8 43.0 98.0 

Height (cm) 166.6 9.9 150 185 

BMI (kg/m2 ) 25.9 4.7 18.3 35.1 

Education (academic) † 9.1% - - - 

*= Sex presented as percentage; † = The percentage of individuals who were graduated from university. 

tivity, Intraclass Correlation Coefficients were 0.94, 0.98 and 0.97 

respectively. Spearman Correlation Coefficients between means 

of two MAQs and means of four physical activity recordsare presented 

in Table 2. The Spearman Correlation Coefficient was 0.39 

(p = 0.05), 0.36 (p = 0.07) and 0.47 (p = 0.01)for leisure time, occupational 

and total (leisure and occupational combined) physical 

activities, respectively. 

Discussion 

This is the first study to assess test-retest reliability and validity of 

the Persian translated MAQ in samples of males and females from 

an Iranian urban adults. We used four physical activity records to 

compare MET-h/wk from the MAQs and physical activity records. 

The reliability assessed by Intraclass Correlation Coefficient between 

the results of two MAQs with a one-month interval. Our 

results demonstrated excellent reliability and relatively moderate 

validity of the MAQ among an Iranian adult sample population. 

The MAQ, developed by Kriska, assesses current (past year and 

past week) physical activity level during both leisure and occupational 

time. 14–16 and it is a retrospective quantitative questionnaire 

that represents the most comprehensive form of physical activity 

recall survey. This questionnaire designed for easy modification 

to maximize the ability to assess physical activity in a variety of 

populations and it`s culture free. 16 Reliability and validity of the 

MAQ were previously reported in some other populations. 16,17 

Measurement of total energy expenditure by the doubly labeled 

water method demonstrated validity of the MAQ. 17 In Kriska et 

al. study, spearman correlation coefficients found 0.92 (ages 

21 – 36) and 0.88 (ages 37 – 59) for past year leisure time and 

for occupational and total (leisure and occupational combined) 

physical activity were 0.88 and 0.89 respectively. 14 Results from 

Schulz study showed that Spearman Correlation Coefficients for 

past-year leisure time (0.56) and total (0.74) physical activity 

were significantly related to total energy expenditure assessed by 

doubly-labeled water. 17 Evaluation of physical activity in middleaged 

women showed that both the leisure physical activity during 

the past month and the past week demonstrate good stability and 

convergent validity. 2 In our study, validity results for leisure time 

Table 1. Main characteristics of study population 


Table 2. Physical activity (MET-h/wk) measures obtained with the mean of two Modifiable Activity Questionnaires 

and the mean of four physical activity records 

Measurement 

Two MAQs 

(Mean ±S.D) * 

Four physical activity records 

(Mean ±S.D) 

ρ † P-value † 

Leisure time 23.41 ± 26.05 12.86 ± 13.81 0.39 0.050 

Occupational 52.32 ± 17.56 53.97 ± 52.58 0.36 0.070 

Total 75.73 ± 71.58 86.37 ± 63.55 0.47 0.017 

* = Standard error; † = ρ and P-value calculated by spearman correlation coefficients 

and total (leisure and occupational combined) physical activities 

presented relatively moderate correlation. 

Gabriel et al. based on MAQ, reported that leisure physical activity 

during the past month and the past week was reliable and 

associated with physical activity and physical fitness. 2 Our results 

suggested a high Intraclass Correlation Coefficients between two 

MAQs for leisure time (0.94), occupational (0.98) and total (leisure 

and occupational combined) (0.97) physical activity. 

As a conclusion and based on our results, the Farsi translated 

MAQ has a high reliability. However, the validity of the Persian 

version is in doubt because of our study limitations. Using four 

physical activity records may result in recall bias or have language 

and educational barriers and that cannot be gold standard to evaluate 

the exact validity of the MAQ. Objective activity monitors 

such as accelerometers, Vo 2 max, and the doubly labeled water 

technique have numerous advantages and provides a more precise 

way to validate the subjective method that estimate of energy 

expenditure. Since those methods are complicated and expensive 

and are not simple to do, we used physical activity record to estimate 

participants’ physical activity levels when those objective 

methods not provided. Furthermore, primarily and besides physical 

activity records, we had considered Vo 2 max as a gold standard 

and objective methods to evaluate the exact validity of the MAQ 

in our study. However, performing Vo 2 max measurement was not 

feasible in our study due to the lack of resources. On the other hand 

some previous epidemiological studies that used questionnaires 

have not been evaluated physical activity levels against objective 

measures. 18 

The small sample size of the present study and the moderately low 

participation rate are other limitations of this study. Moreover, we 

didn’t have any information about non responded to be reported. 

On the other hand, as it is shown, our data were from just young, 

over weight and mainly not having academic education subjects 

(Table 1). So, data from older subjects or people with normal 

weight or obese or even academic educated ones may show different 

results. 

In conclusion and considering that the original MAQ has an 

ability to assess the P.A. levels in a variety of different populations. 

The present study shows that the Persian translated version is 


eliable but can be used in the TLGS Tehranian population with 

caution because of relatively moderate convergent validity. It can 

be answered quickly and requires little cooperation by the patient. 

However, it is suggested to perform further studies with large 

sample size and better gold standard to assess the validity of this 

tool more precisely, if it is going to be used with no doubt and in 

other Iranian population. 

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Efficacy of Harm Reduction Programs among Patients of a 

Smoking Cessation Clinic in Tehran, Iran 

Hooman Sharifi MD MPH 1 , Roghieh Kharaghani MSc 1 , Habib Emami PhD• 1 , Zahra Hessami MD MPH 1 , Mohammad Reza Masjedi MD 2 

Abstract 

Background: Recently, harm reduction programs have been used to reduce mortality and morbidity among smokers. The main objective 

of this study was to evaluate the effect of harm reduction programs on the smoking patterns of subjects who presented to a smoking cessation 

clinic in Tehran, Iran. 

Methods: This observational study was conducted between September 2008 – September 2009 on 132 patients who were unable to quit 

smoking. Patients were enrolled by the first come first service method. During the study period, subjects were assigned to either group or 

individual visits every 15 days in conjunction with the use of nicotine gum. The main objective of this study was to evaluate at the third and 

sixth months of follow-up: the number of smoked cigarettes, level of expired carbon monoxide (CO), and numbers of nicotine gum used. Data 

were analyzed by the Wilcoxon rank, Fisher's exact, and Pearson's chi-square tests and SPSS version 17 software. 

Results: A total of 87.1% of the subjects were males. We noted decreases in the number of cigarettes smoked daily and the level of expired 

CO, whereas the amount of nicotine gum used significantly increased during the time interval between the first session and the third and sixth 

month follow-up visits (p

Variables Numbers Percent 

Sex (male) 

Age: 

115 87.1 

Males (years) 

37.3±10.7* 

_ 

Females (years) 

Education 

40.7±12.2* 

_ 

Illiterate and primary 

10 

7.5 

Guidance and high school 

31 

23.5 

Diploma and higher 

Social class 

91 

68.8 

Clerical or non-manual skilled 

65 

49.2 

Manual skilled 

47 

35.6 

Unskilled or semiskilled 

Tenure 

20 

15.2 

Owner occupied 

69 

52.3 

Rent/other 


63 

47.7 

Married 

85 

64.4 

Single 

35 

26.5 

Widowed, divorced or other 

12 

9.1 

* = Mean±standard deviation 

25 

20 

15 

10 

5 

0 

25 

20 

15 

10 

5 

22.19 22.19 

20.6 

able to quit completely. 13,14 

Nicotine replacement drugs contain small amounts of nicotine 

which is gradually released and somehow prevents cigarette craving. 

15 Use of these nicotine-containing products for a long time is 

not harmful and it is definitely superior to smoking cigarettes. 16,17 

Considering the prevalence of smoking, large number of exsmokers 

who relapse, and limited number of smoking cessation 

interventions in Iran, the present study has sought to determine if 

prolonged smoking cessation programs in which nicotine replacement 

products used by current smokers helped to decrease daily 

cigarette consumption and exhaled carbon monoxide (CO). This 

study was conducted to assess the efficacy of harm reduction programs 

for smoking cessation clinic patients. The main objectives 

of this study were to evaluate: i) the number of cigarettes smoked 

per day, ii) exhaled CO levels, and iii) number of nicotine gums 

used per day. 


Table 1. Baseline socio-demographic characteristics of participants. 

5.5 5.5 5.59 5.59 5.46 5.46 5.63 5.63 

3.34 

0 0.03 0.03 0.34 0.34 

Session Session 1 Session 1 Session 2 Session 2 Session 3 Session 3 Session 4 Session 4 Session 5 3-month 5 3-month 6-month 6-month 

f ollow-upf 

ollow-up f ollow-upf 

ollow-up 

Figure 1. Mean number of cigarettes smoked and number of nicotine gums used per day from 

baseline to 6-month follow up. Differences were all statically significant (p < 0.001). 


H. Sharifi, R. Kharaghani, H. Emami, et al. 

Number Mean Number of cigarettes of cigarettes smoked smoked per day per day 

Number Mean 

Number of nicotine of gums nicotine used gums per used day per day 

20.6 

15.57 15.5713.25 13.25 

12.12 12.12 

11.3 11.3 11.34 11.34 

3.34 

Study design 

This pre-post design interventional study was conducted at an 

inner-city smoking cessation clinic with approximately 1000 participants 

between September 2008 and September 2009 in Tehran, 

Iran. 

Sample selection 

The Tobacco Prevention and Control Research Center’s Smoking 

Cessation Clinic was considered as the main setting for sample 

selection. The inclusion criteria were: participants who had previously 

attended smoking cessation programs in this center, those 

who were unsuccessful in quitting smoking or relapsed after quitting, 

and those willing to participate in this study who offered their

(n) 

Figure 2. Expired carbon monoxide (CO) levels from baseline to 6-month follow up. 

Differences were all statically significant on Fisher’s exact test (p < 0.001). 

consent. The exclusion criteria were the inability to actively participate 

in the study or not having enrolled in a smoking cessation 

program. A total of 132 patients were enrolled. 

Data collection 

A questionnaire was designed according to International Union 

Against Tuberculosis and Lung Diseases (IUATLD) and WHOstructured 

questionnaires, pilot tested, and revised. The first two 

sections of the questionnaire were self-administered, whereas the 

third section was completed by counselors during the smoking cessation 

course. The questionnaire included demographic data, history, 

and pattern of smoking. Before beginning the course, in order to 

assess nicotine use, the Fagerström Test for Nicotine Dependence 

(FTND) was performed. 

The social status of the participants was determined based on the 

Registrar General Model of Social Classes, and participants were 

classified into 6 groups. 18 

The numbers of cigarettes smoked daily and consumed nicotine 

gums were recorded at every visit. 

There is no or little doubt about the reliability of the responses on 

questionnaires administered in the first visit of smoking cessation 

clinics, however many smokers mispronounce their situation during 

follow-up sessions. 19 In studying nicotine replacement therapies 

such as nicotine gum, cotinine cannot be used as a marker of 

cigarette abstinence, because cotinine is a metabolite of nicotine. 

Accordingly, cotinine’s first use for verification of self reports of 

abstinence during treatment is limited to non-nicotine containing 

medications. 20,21 

Since the determination of breath CO levels is noninvasive, inexpensive, 

and yields immediate results, it is the method of choice 

in research and clinical practice. 22 In this study, CO level was 

measured using a hand-held portable CO monitor (Bedfont Micro 

Smokerlyser, Kent, England) that had previously been shown to 

be effective in validating the participants’ self-reports regarding 

smoking status. 23,24 

CO has a 3 – 6 hour half-life, which depends on the level of exercise 

and environmental CO. Previous studies have shown that 

smoking within the past 24 hours generally results in elevated 

breath CO levels which are above the normal physiological range. 

However, this could depend on both the quantity of cigarettes 

smoked and the last time a cigarette was smoked. 25 One study has 

Harm Reduction in Smoking Cessation 

shown a strong, statistically significant relationship between level 

of reported smoking during the past 24 hours and breath CO levels. 

22 

Although presumed unsuitable for epidemiological studies that 

gather information during a single visit, breath CO testing could 

be a valuable tool for monitoring abstinence from smoking during 

cessation trials that have regular follow-up intervals. 26 

The Smokerlyzer measures breath CO levels in parts per million 

(ppm) based on the conversion of CO to CO 2 over a catalytically 

active electrode. On breath holding, the CO in the blood forms 

equilibrium with CO in the alveolar air; therefore, there is a high 

degree of correlation between breath CO levels and COHb concentration. 

This enables the Smokerlyser to accurately estimate 

the blood COHb concentration from the breath CO level. We have 

calibrated the Smokerlyzer weekly by using a mixture of 50 ppm 

CO in air. 

Procedures 

Patients were initially asked to participate in this study by phone 

contact using their previous records. Those who met the inclusion 

criteria were scheduled for their initial assessment visit following 

the first group therapy session. All 132 participants who consented 

to enroll in this study were divided into 10 groups of 5 – 15 participants 

each. Participants were visited approximately every two 

weeks, on weekdays, and a smoking counselor attended each session. 

Participants came to the Smoking Cessation Clinic at 2, 4, 6, 

8 and 10-week intervals following initiation of the study to participate 

in group therapy, and at 3 and 6 months for follow up assessments. 

In all sessions respiratory CO levels were assessed. 

The study protocol was approved by the Research Committee of 

the Tobacco Prevention and Control Research Center. 

Intervention 

No new intervention was implemented following the completion 

of all measurements. Subjects were monitored to achieve a certain 

percentage of reduction in smoking rate (at least 50%). Therefore, 

2 mg nicotine gums were administered to all subjects, the same as 

in the cessation program. 

The treatment procedure was started in a routinely conventional 

cessation program and categorized in three steps: i) one session 

as a baseline assessment; ii) two sessions for gradual reduction 


Variables Mean±standard deviation 

Age at smoking onset (years) 18.5±5.6 

Number of cigarettes smoked per day 22.1±10.4 

Expired carbon monoxide (CO) level 101 (76.5)** 

Number of nicotine gums used per day 0.03±0.43 

Pack of cigarettes smoked per year 22.3±16.9 

Q-MAT* score 14.9±4.1 

HAD† score 16.9±6.7 

FTND‡ score 5.9±2.8 

* Motivation to quit smoking; ** Number (percent); † Hospital anxiety and depression test; ‡ Fagerström Test for Nicotine Dependence; 

that used 2 mg nicotine gums; and iii) two maintenance sessions 

(steady amount of nicotine gum and cigarettes) following two 

maintenance sessions that aimed at further reduction or cessation 

of smoking. During the first session (baseline assessment), subjects 

precisely stated the mean number of cigarettes they smoked daily 

and their reduction amount for each day for 2 weeks, considering 

the counselor’s advice. Based on the recordings of the first session 

regarding smoking status, subjects were advised to decrease smoking 

over a 2-week period by 50% (reduction goal). In case of any 

difficulty following the schedule, the reduction pace was lessened. 

Upon achieving the 50% reduction goal, subjects were advised to 

further decrease their consumption or quit smoking completely. 

Outcome measures 

Outcome measures in this study included the decrease in the number 

of cigarettes smoked per day and the amount of nicotine gums 

used per day. Successful reduction was defined as a self-reported 

reduction by 50% in the number of cigarettes smoked per day. 

Data analysis 

First, the estimated prevalence was calculated for all variables 

through numbers, percentages, means and standard deviations. 

Second, in order to determine the efficacy of the intervention, the 


Table 2. Baseline smoking status, habits, and dependence. 

Figure 3. Percent abstinence after treatment from second session until 6-month follow up. 

Wilcoxon rank test was used since two outcome variables (number 

of cigarettes and nicotine gums used per day) did not have normal 

distributions as shown by the Kolmogorov-Smirnov test. Pearson’s 

chi-square test was used to determine the efficacy of intervention 

in decreasing CO levels. All data were analyzed using SPSS version 

17.0 software. Statistical tests used were two-tailed with 5% 

significance level. 

Results 


Characteristics of the subjects 

Among participants, 87.1% (n = 115) were men with a mean 

age of 37.33 ± 10.72 years and 12.9% (n = 17) were women 

with a mean age of 40.70 ± 12.24 years. A total of 64.4% (n = 

85) of the subjects were married, 26.5% (n = 35) were single, 

and the remainder were divorced, widowed or separated. Regarding 

their level of education, approximately 69.2% (n = 90) had 

a high school diploma or lower educational level. Homeowners 

comprised about 52.3% (n = 69) of subjects. All were from low 

class strata; most (49.6%, n = 65) were employed in clerical work 

or non-manual skilled labor, whereas 6.8% (n = 9) were unemployed 

(Table 1).

Smoking pattern and nicotine dependence 

The mean age of smoking initiation was 18.5 ± 5.6 years and the 

mean number of cigarettes smoked daily was 22.19 ± 1.03. The 

mean amount of expired CO for 76.5% (n = 101) of subjects was 

more than 20 ppm. According to FTND, the mean score of nicotine 

dependence was 5.9 ± 2.8. The mean score for readiness to 

quit smoking was 14.9 ± 4.1 based on motivation to quit smoking 

questionnaire (Questionnaire de motivation à l’arrêt du tabac) (Q- 

MAT) and according to the Hospital Anxiety and Depression test 

(HAD), the mean score for suffering from depression or anxiety 

was 16.9 ± 6.7 (Table 2). 

Treatment efficacy 

During the first 6 months, the number of cigarettes smoked daily 

significantly decreased; the number of nicotine gums used significantly 

increased. At the beginning of the study these rates were 

22.9 for number of smoked cigarettes and 0.03 for the number of 

nicotine gums used. This declined to 11.34 for the number of cigarettes 

smoked and 5.63 for number of nicotine gums used at the 

6-month follow up. All were statistically significant (p < 0.001; 

Figure 1). According to the chi-square test, differences in expired 

CO levels were statistically significant (p < 0.001 for all; Figure 2). 

In this study, 85 subjects (64.4%) decreased their number of daily 

cigarettes by a minimum of 50%. During the follow-up visits, the 

number of subjects who quit gradually increased. Finally at 3 and 

6-month follow-up visits, 17 subjects (12.9%) quit smoking (Figure 

3). After 4 weeks of observation there was a minimum of 50% 

reduction in daily cigarette consumption among the participants 

(Figure 4). 

Discussion 

Figure 4. Estimated survival curves for 50% reduction in daily cigarette consumption through 3 months. 

This study explained the feasibility of reduction and eventual cessation 

of cigarette smoking among Iranian people who previously 

failed to quit. The reduction in level of expired CO was statistically 

significant, even at the 6-month follow up, which validated the efficacy 

of smoking reduction programs in this study. 


Smoking reduction may encourage smoking cessation by allowing 

smokers to gradually take control of this habit. Similar studies 

that have aimed to decrease smoking in those trying to quit 

noted complete smoking cessation in a significant number of 

smokers. 27–31 In our study, the gradual reduction in smoking was 

followed by a 12.9% successful quit rate. 

One concern in harm reduction programs is that smokers who 

reduce the number of daily cigarettes may balance their intake of 

tobacco by smoking fewer cigarettes but more forcefully. In this 

study, reduction in expired CO levels and number of daily cigarettes 

is statistically significant. Therefore, even if this hypothesis 

is true, we have reached a significant reduction in expiratory CO 

levels due to the consumption of nicotine gums while participants 

still smoked. 

Some researchers suggest that high dose nicotine replacement 

therapy should be used to reduce the health risks due to compensatory 

smoking. 31 

Nicotine Replacement Therapy (NRT) increases lasting abstinence 

rates by 50% to 70%, irrespective of the method of prescription 

in smokers motivated to quit. 32 The 6-month abstinence rate 

in our study (12.9%) was the same as that observed in a number 

of previous studies on NRT products for smoking reduction (8% 

– 12%), 27–30 but lower than observed in a recent trial by Kralikova 

et al. which showed that 18.7% of participants quit smoking in an 

intervention group that used nicotine gums. 33 This was possibly 

due to the fact that Kralikova and colleagues recruited smokers 

who wanted to manage their smoking, which meant either decreasing 

cigarette consumption or immediate cessation; whereas, in the 

present study our participants were smokers who had failed to quit. 

The NRT-assisted reduction phase aims to promote cessation and 

engage smokers who are ready to quit in a time-limited course of 

structured reduction to reach a quitting endpoint. The reduce-toquit 

approach is not the only technique that uses NRT. A comparable 

approach, described as “cut down to quit”, encourages smokers 

who are not currently interested in quitting to use NRT for smoking 

reduction over a period of up to 12 months. The meta-analysis conducted 

by Wang et al. in 2008 have reported that this approach was 


successful but less cost effective than immediate cessation. The 

two approaches address different populations with different plans, 

making it difficult to compare the results. 34 

Our data suggest that although prolonged observation is not 

included in conventional smoking cessation programs, we could 

design our interventions for a longer period of time to address cessation 

in smokers. Moreover, a structured treatment on the first 

two months of the course with regular follow-ups could clearly 

enhance the quit rate. 

This study’s strengths include the presence of detailed data on 

smoking pattern and biochemical measures of smoke exposure. 

Another strong point is the report of smoking prevalence in a 

6-month period instead of point prevalence at the end of a conventional 

treatment, which is a less relevant outcome. 

In summary, this study shows that reduction in smoking can be 

achieved through prolonged counseling sessions and NRT. Smoking 

reduction in people unable to stop smoking immediately seems 

to be a step forward towards improved health and may finally proceed 

to complete smoking cessation. 

The results of this study support the efficacy of harm reduction 

programs. This is particularly useful for smoking cessation counselors 

to know that continuation of conventional programs can 

augment the success rate of quitting in smokers. We hope that the 

results of this study may be useful for tobacco control programs 

and policy making. Further studies are also recommended in this 

regard. 

Last but not least, similar studies in other regions and countries 

can help support and generalize our findin 


This article is based on a project supported and funded by the Tobacco 

Prevention and Control Research Center, Shaheed Beheshti 

Medical Science University. The author would like to thank all 

participants in this study and the staff who facilitated the process. 

Without their support and participation, this study would not have 

been performed. 

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DOI: 10.3310/hta12020. 

Mohtasham Garden in Rasht, Gilan Province - Iran, founded during Nasser al-Din Shah Qajar Period (1848 – 1896) 

(Photo by M.H. Azizi MD) 




Validity, Reliability and Factor Structure of Hepatitis B Quality of 

Life Questionnaire Version 1.0: Findings in a Large Sample of 320 

patients 

Atefeh Poorkaveh MSc 1,2 , Amirhossein Modabbernia MD 1,3 , Mandana Ashrafi MD 1 , Shervin Taslimi MD, MPH 1 , Maryam Karami BSN 1 , 

Mojtaba Dalir BSN 1 , Arezoo Estakhri MD 1 , Reza Malekzadeh MD 1 , Hassan Pasha Sharifi PhD 4 , Hossein Poustchi MD PhD• 1 

Abstract 

Background: Quality of life is of significant importance in chronic hepatitis B (CHBV). We aimed to assess the psychometric properties of 

the Hepatitis B Quality of Life Questionnaire v1.0 (HBQOL) in a large sample of 320 Iranian patients with CHBV. 

Methods: After adapting the Iranian version through forward-backward translation and expert panel discussion, we administered HBQOL 

together with Short-Form 36 (SF-36), Medical Outcome Study Social Support Questionnaire (MOS-SS), Hospital Anxiety and Depression 

Scale (HADS), and the Iowa Fatigue Scale (IFS) to 320 non-cirrhotic Iranian patients. We used principal component analysis with Varimax 

rotation to determine the factor structure. To evaluate the psychometric properties of HBQOL, test-retest and internal consistency reliabilities, 

divergent and convergent validity with other instruments, and discriminatory power were calculated. 

Results: Thirty-one questions loaded on to six factors (Anticipation anxiety, Stigma, Psychological well-being, Vitality, Transmissibility and 

Vulnerability) which explained 63.6% of total variance. Test-retest reliability was 0.66. Cronbach’s α was 0.94 for the overall scale and between 

0.7 and 0.9 for subscales, with the exception of the Vulnerability subscale. HBQOL and its subscales showed acceptable convergent 

and divergent validity with other instruments. Furthermore, Vulnerability subscale of HBQOL discriminated between patients with chronic 

active and chronic inactive hepatitis. 

Conclusion: The Iranian version of HBQOL is reliable, valid, and sensitive to the clinical conditions of the patients. This instrument has 

acceptable factor structure to measure several aspects of quality of life in patients with chronic HBV. 

Keywords: Anxiety, depression, factor analysis, fatigue, hepatitis B quality of life questionnaire version 1.0, reliability, validity 

Cite this article as: Poorkaveh A, Modabbernia AH, Ashrafi M, Taslimi S, Karami M, Dalir M, et al. Validity, Reliability and Factor Structure of Hepatitis B Quality 

of Life Questionnaire Version 1.0: Findings in a Large Sample of 320 patients. Arch Iran Med. 2012; 15(5): 290 – 297. 


I 

n recent years, health-related quality of life (HRQOL) has 

become a main measure of health and an important outcome 

in clinical trials. Although clinicians are more concerned with 

the biological outcomes of their patients, patients mainly worry 

about their quality of life. 1 Chronic diseases can negatively affect 

HRQOL and chronic hepatitis B (CHBV) is no exception. Several 

studies have shown impairment of HRQOL in patients with 

CHBV. 2–6 Instruments to assess HRQOL consist of two different 

categories: generic and disease-specific. Generic instruments can 

be used for all disease types and allow for comparison among diseases, 

whereas disease-specific instruments focus on a specific disease 

or a specific group of diseases, evaluating the condition in a 

more specific manner. 1 Two of the most important features of disease-specific 

questionnaires which make them useful outcome 

measure, particularly in clinical trials, are their capability to differentiate 

between different severities of the disease as well as their 

sensitivity to change in clinical condition over time. 7 

Authors’ Affiliations: 1 Digestive Disease Research Center, Shariati Hospital, 

Tehran University of Medical Sciences, Tehran, Iran, 2 Department of Counseling, 

Islamic Azad University, Tehran, Iran, 3 Department of Psychiatry, Roozbeh Psychiatric 

Hospital, Tehran University of Medical Sciences, Tehran, Iran, 4 Department 

of Psychology and Psychometrics, Islamic Azad University, Roodehen, Iran 

•Corresponding author and reprints: Hossein Poustchi MD PhD, Digestive 

Disease Research Center, Shariati Hospital, North Kargar Ave, Tehran, Iran , 

14117-13135. Tel: +98-21-82415141, Fax: +98-21-8241300, 

E-mail: h.poustchi@gmail.com. 

Accepted for publication: 6 July 2011 

A.Poorkaveh, A. Modabbernia, M. Ashrafi et al. 

Because biological outcomes or generic instruments may miss 

key disease-related components of HRQOL and overlook patients’ 

perceptions of their HRQOL, a disease-specific instrument 

seems necessary. 7 Until 2007, the measures used for evaluation of 

HRQOL in patients with CHBV were either generic [i.e., Short 

Form-36 (SF-36)] or liver-specific (but not CHBV-specific) quality 

of life questionnaires such as the Chronic Liver Disease Quality 

of Life Questionnaire (CLDQ) and the Liver Disease Quality of 

Life Questionnaire (LDQLQ). 8–10 

In 2007, Spiegel et al. 11 developed a disease-targeted quality of 

life questionnaire for non-cirrhotic patients with CHBV entitled 

the Hepatitis B Quality Of Life Instrument, version 1.0 (HBQOL 

v1.0). Their factor analysis showed the following six distinct factors: 

Psychological well-being, Anticipation anxiety, Vitality, 

Stigma, Vulnerability, and Transmissibility. An extra a priori-defined 

factor, related to Viral response, was also added which was a 

combination of Vulnerability and Transmissibility. They described 

high test-retest reliability, internal consistency, and discriminant 

validity for the questionnaire. However, after development of the 

HBQOL, no study evaluated the psychometric characteristics of 

the questionnaire. Additionally, this instrument has not been evaluated 

in different cultural contexts. CHBV is quite prevalent in 

Asian countries and the results from the English version cannot be 

generalized to other languages and cultures. 

To assess the psychometric properties of HBQOL in a larger 

sample of non-cirrhotic patients with CHBV and to evaluate the 

questionnaire in people with different cultural and language back-

Instrument 

Short-Form 36 

Medical 

Outcome Study 

Social Support 

Questionnaire 

Iowa Fatigue 

Scale 

Hospital Anxiety 

and Depression 

Scale 

Developers/year 

[reference 

number] 

Ware and 

Sherbourne/ 1992 13 

Sherbourne and 

Stewart /1991 13 

grounds, we administered HBQOL to Iranian patients with CHBV. 

Next, we performed a factor analysis and determined the questionnaire’s 

reliability. To ensure the convergent and divergent validity 

of HBQOL, we used several generic instruments. 


Number 

of items 

Subjects 

From March to September 2010, we evaluated 320 patients with 

CHBV who referred to a university clinic in Shariati Hospital, Tehran, 

Iran. Inclusion criteria were: confirmed CHBV diagnosis, age 

> 18 years, and ability to communicate. Co-infection with hepatitis 

C or HIV, severe psychiatric disorders and any other severe 

comorbid diseases were exclusion criteria. All patients read and 

signed an informed consent form. The Ethics Committee of the 

Digestive Disease Research Institute of Shariati Hospital approved 

the proposal. 

Data collection 

Two trained interviewers collected important baseline characteristics 

and clinical data in separate questionnaires. In addition to 

HBQOL, we administered several generic questionnaires to evaluate 

quality of life, social support, fatigue, depression, and anxiety 

with the intent to determine the convergent and divergent validity 

of HBQOL. Because of the large number of questions, we administered 

each instrument to a proportion of patients, so that each 

patient completed two or three questionnaires in addition to the 

HBQOL. All questionnaires were self-administered and interviewers 

were responsible for interviewing illiterate patients as well as 

supervising other patients as they completed the questionnaires. 

Assessment instruments 

HBQOL 11 consists of 31 questions. Each contains a 5-point Likert-type 

scale and is loaded onto six factors: Psychological wellbeing, 

Anticipation anxiety, Vitality, Stigma, Vulnerability, Transmission 

(plus a priori defined factor, Viral response). Cronbach’s 

α was 0.96 for the overall score and with a range of 0.75 – 0.9 for 

subscales. The scale showed high test-retest reliability and its related 

subscales showed high convergent validity with SF-36 MCS 

and PCS (mental and physical component summaries). Spiegel et 

al. 11 found high discriminatory power of the viral response item 

between viral responders and viral non-responders. 

Similar to the study by Spiegel et al. 11 ,we changed the total 

score of HBQOL (range: 31 – 155) to a 100-point scale with lower 

scores showing lower quality of life. We used forward-backward 

36 

19 

Hartze el al./ 2003 15 11 

Table 1. Instruments used in the validation of HBQOL. 

Subscales Cronbach’s α 

Mental and physical component 

summary (MCS and PCS) 

Emotional/Informational 

support, Tangible support, 

Affection, Positive interaction 

Cognitive, Fatigue, Energy, 

Productivity 

Zigmond and 

Snaith/ 1983 16 14 Anxiety, Depression 

Validity, Reliability and Factor Structure of HBQOL V1.0 

Adapting the 

Iranian version 

[Reference 

number] 

Cronbach’s α 

of the Iranian 

version 

> 0.85 Montazeri et al. 14 0.65– 0.9 

> 0.9 Our group 0.95 

0.9 Our group 0.81 

Anxiety: 0.8 

Depression: 

0.76 

Montazeri et al. 17 

Anxiety: 0.78 

Depression: 0.86 

translation recommended by World Health Organization to adapt 

the Persian version of the HBQOL. 12 

We used the following four generic questionnaires: i) SF-36, 13,14 

ii) Iowa Fatigue Scale (IFS), 15 Medical Outcome Study Social 

Support Questionnaire (MOS-SS), 13 and the Hospital Anxiety and 

Depression Rating Scale (HADS). 16,17 Table 1 provides a summary 

of these instruments. 

There are several “rules of thumb” for determining sample size 

in factor analysis. Many authors believe that a sample size of 10 

individuals per item, 50 individual per factor, or at least 300 is adequate. 

18 For the purpose of this study, we determined a sample 

size of 300, with an additional 20 subjects for possible missing 

data. Since the completed questionnaires were examined for completeness 

by the interviewer before the patient left the clinic, we 

considered a 7% loss of samples rather than the more routine 15%. 

The first 300 patients also completed other questionnaires based 

on a random block method. There were 13 blocks, each of which 

contained 23 individuals who were given the questionnaire. Based 

on another “rule of thumb” for bivariate correlation, a sample size 

of more than 100 (according to some, 104) is considered appropriate. 

However some authors consider numbers as low as 50 to be 

acceptable. 18,19 Thus, we have applied a ratio of 1.875 (15/8 in each 

block) and the overall MOS-SS was administered to 104 patients. 

The other patients received HADS and IFS questionnaires. Since 

SF-36 was the main measure of validity in our study, it was administered 

to as many patients as possible, unless time limitations of 

the clinic prevented us from doing so. 

Data analysis 

SPSS version 15.00 (Chicago, USA) was used for data analysis. 

We used exploratory factor analysis (principal component analysis) 

with Varimax rotation with Kaiser Normalization. 20 Factors 

with eigenvalues of more than one were retained for analysis. 

Items, which loaded more than 0.4 onto at least one factor and 

ranked first or second in the scale loadings, were retained in that 

factor. In addition, we determined the inclusion or exclusion of an 

item in a factor based on face validity (i.e., discussion with our 

expert panel). To evaluate the quality of sampling, we used Kaiser- 

Meyer-Olkin (KMO) and Bartlett’s test of sphericity. 

To report the score of our patients, we used the 100-point scale 

with higher scores showing better quality of life. Skewness was 

used to evaluate data distribution. To compare subgroups, the parametric 

tests was used for normally distributed data whereas the 

non-parametric tests were used for skewed data. Floor and ceiling 

effects were noted to be present if 15% of participants achieved the 


lowest or highest possible scores. 21 

To calculate test-retest reliability, we administered the HBQOL 

to a number of patients two weeks after the first administration and 

calculated the intraclass correlation coefficient. 22 To determine the 

internal consistency we calculated Cronbach’s α for each factor 

and for the overall HBQOL score. Cronbach’s α of 0.7 or more was 

considered acceptable. 

To determine questionnaire validity, we assessed content validity, 

construct validity, and discriminatory power of the questionnaire. 

23–25 Developers of the questionnaire had approved the content 

validity in their own study. Besides, we discussed the translated 

questionnaire with a number of experts in the fields of hepatology, 

psychology, and psychometrics to ensure its content validity. 

Construct validity determines how much a questionnaire measures 

the construct of interest. To determine construct validity, we 

evaluated both convergent and divergent validities. 23 There are 

many ways to assess these validities; all equally efficient. What is 

consistent among all studies for assessment of construct validity is 

correlational analysis. 

Convergent validity is the correlation of the questionnaire with 

other well-validated instruments that have the same construct 

(i.e., measuring the same thing). A correlation coefficient of 0.21 

to 0.4 is considered fair, 0.41 to 0.6 is good, 0.61 to 0.8 is very 

good, and more than 0.8 is excellent. 26 A good correlation coefficient 

was considered evidence of good convergent validity in our 

study. We hypothesized that MCS , depression, and anxiety should 

have at least good correlation with the mental-related subscales 

of HBQOL (most importantly Psychological well-being, and Anticipation 

anxiety), while PCS and IFS should have at least good 

correlation with the physical-related subscales of HBQOL (Vitality). 

In addition, these factors should be less correlated with other 

less-related subscales when compared with their correlation with 

more-related subscales. 

Divergent validity shows how much an instrument correlates 

with a construct that it should not measure. 23,25 We determined 

divergent validity by calculating the correlation of HBQOL and 

MOS-SS, each of which were designed to measure completely 

different constructs. Therefore, we hypothesized that HBQOL, although 

related to social support should have a fair correlation (0.2 

– 0.4) with MOS-SS. 

The discriminatory power of an instrument shows the ability of 

an instrument to discriminate between two clinically distinct conditions. 

Any outcome measure intended for health care purposes 

should be sensitive to changes in health status. In the study by 

Spiegel et al., this was determined as the capability of the Viral 

response subscale to distinguish between viral responders and 

nonresponders. Since the design of the present study was not longitudinal, 

we determined discriminatory power by a comparison 

of HBQOL and its subscale scores between patients with chronic 

active hepatitis (CAH) and patients with chronic inactive hepatitis 

(CIH). 

Results 

Sample characteristics and HBQOL scores 

A total of 320 patients (110 females and 210 males) with a mean 

± SD age of 39.6 ± 13.4 years participated in the study. No significant 

difference was observed in age, gender, marital status or 

educational level between patients who were administered a particular 

questionnaire and those who were not given that question- 


naire. Table 2 shows baseline characteristics of participants. Because 

of supervision at the time of administration of the questionnaires, 

none of the questionnaires had missing data. Mean time 

for completion of HBQOL was 6 (3 to 10) minutes. The overall 

score and scores of factors one to four on the percentile scale had 

a negative skewed distribution (better quality of life) while factors 

five to seven showed normal distribution. The mean ± SD score 

for HBQOL was 66.12 ± 20.90. Patients with recently diagnosed 

CHBV showed lower scores of HBQOL and its subscales (except 

Vulnerability) than the patients with previously diagnosed CHBV 

(P < 0.05 for Vitality, and P < 0.01 for overall scale and other 

subscales). Of patients, 0.9% achieved the highest possible score, 

whereas 0.9% also achieved the lowest possible scores which indicated 

the absence of floor and ceiling effects. The effects of several 

variables on scores of the HBQOL scale and its subscales are 

shown in Table 3. 

Table 2. Baseline characteristics of patients. 

Variable Value 

Male gender (%) 210 (65.6%) 

Age (mean ± SD) 39.63 ± 13.37 

Educational level 

Illiterate (%) 43 (13.5%) 

Less than diploma (%) 120 (37.5%) 

Diploma (%) 96 (30%) 

BS (%) 51 (15.9%) 

MS and over (%) 10 (3.1%) 

Residence 

Capital (%) 127 (39.7%) 

Other cities (%) 193 (60.3%) 


Single (%) 50 (15.6%) 

Married (%) 263 (82.2%) 

Divorced (%) 7 (2.2%) 

Widowed (%) 0 (0%) 

Habitual history 

None (%) 226 (70.6%) 

Cigarette (%) 67 (20.9%) 

Alcohol (%) 50 (15.6%) 

Illicit drug (%) 24 (7.5%) 

Comorbid conditions (%) 85 (26.5%) 

Possible transmission route 

Vertical (%) 68 (21.25%) 

Sex (%) 2 (0.6%) 

Blood-born (%) 32 (10%) 

Unknown (%) 218 (68.15%) 

Chronic active hepatitis (%) 72 (22.5%) 

Time since diagnosis (mean ± SD) 68.1 ± 68.6 (month) 

Recently (< 6 months) diagnosed patients (%) 59 (18.4%) 

SF-36 scores 

PCS (mean ± SD) 

MCS (mean ± SD) 


47.9 ± 9.1 

47.2 ± 11.5 

HADS scores 

Anxiety (mean±SD) 7.5±4.6 

Depression (mean±SD) 4.6±4.1 

IFS score (mean±SD) 26.8±8.3 

MOS-SS score (mean±SD) 73.6±17.7 

Factor analysis 

A six-factor solution emerged accounting for 63.6% of the total 

variance. The KMO test was 0.938 and Bartlett’s test of sphericity 

was significant at a level of P < 0.001, which showed high quality 

of the sampling. Anticipation anxiety, with eight items, explained 

15.5% of the variance followed by Stigma, Psychological well-being, 

Vitality, Transmissibility, and Vulnerability. We also included 

the Viral response factor, which consists of items of Transmissibility 

and Vulnerability (Table 4). After primary analysis, because 

Productivity (F12) loaded onto the Psychological well-being (it 

loaded onto Vitality in the study by spiegel et al.) we hypothesized

Variable 

Gender 

HBQOL components 

A n t i c i p a t i o n 

Stigma 

anxiety 

Psychological 

Vitality 

well-being 

Transmissibility Vulnerability Viral response HBQOL 

Female 57.5 ± 27.4 76.7 ± 24.3 68.8 ± 24.6 63.3 ± 27.9 56.8 ± 35.7 48.4 ± 30.9 52.6 ± 24.6 64.9 ± 20.9 

Male 62.7 ± 26.0 73.7 ± 24.5 71.7 ± 24.8 68.5 ± 26.7 52.6 ± 37.1 48.8 ± 30.2 50.7 ± 26.3 66.7 ± 20.9 

Age r = 0.062 r = 0.078 r = 0.100 r = 0.025 r = -0.030 r = 0.006 r = -0.013 r = 0.062 

Duration 

Diagnosis 

r = -0.069 r = 0.024 r = 0.072 r = -0.060 r = 0.057 r =-0.027 r = 0.043 r = 0.008 

Recent 52.5 ± 28.0** 67.7± 24.0** 56.8 ± 25.0** 58.7 ± 29.7* 41.5 ± 37.0** 43.2 ± 31.3 42.3 ± 26.5** 56.6 ± 20.1** 

Past 

Living in 

62.8 ± 25.9 76.4 ± 24.2 73.8 ± 23.6 68.5 ± 26.3 56.9 ± 36.0 49.9 ± 30.2 53.4 ± 25.1 68.2 ± 20.5 

Tehran 62.1 ± 28.0 75.4 ± 23.9 71.9 ± 25.2 66.4 ± 27.8 59.3 ± 36.0* 48.6 ± 30.2 53.9 ± 24.9 67.1 ± 21.4 

Other cities 

1Marital status 

60.2 ± 25.6 74.3 ± 24.8 69.9 ± 24.5 66.9 ± 26.9 50.6 ± 36.8 48.7 ± 30.7 49.7 ± 26.2 65.4 ± 20.5 

Single 63.3 ± 26.0 72.0 ± 24.8 67.5 ± 26.5 68.1 ± 30.7* 60.0 ± 35.1 47.7 ± 24.5 53.8 ± 23.0 65.7 ± 65.7 

Married 60.4 ± 26.6 75.1 ± 24.4 71.2 ± 24.3 67.2 ± 26.2 52.4 ± 36.9 49.1 ± 29.7 50.7 ± 26.3 66.1 ± 66.1 

Divorced 

Educational 

level 

61.1 ± 32.3 82.6 ± 25.9 73.2 ± 29.5 39.2 ± 25.1 75.0 ± 32.2 39.2 ± 27.4 57.1 ± 20.8 65.7 ± 65.7 

Less than 

diploma 

61.7 ± 27.6 72.4 ± 26.1 68.8 ± 26.8 64.5 ± 28.3* 54.2 ± 36.8 47.8 ± 29.3 51.0 ± 24.4 64.9 ± 21.9 

Diploma and 

over 

Comorbid 

disease 

61.8 ± 25.9 77.0 ± 23.3 73.5 ± 22.9 72.4 ± 25.2 56.7 ± 36.7 51.2 ± 31.9 54.0 ± 26.9 68.6 ± 20.2 

No 62.5 ± 26.1 74.4 ± 25.4 72.6 ± 24.6 70.8 ± 26.8** 57.3 ± 36.6 50.1 ± 30.9 53.7 ± 25.4 67.7 ± 20.9 

Yes 

Viral activity 

status 

59.5 ± 28.7 75.1 ± 23.6 66.8 ± 26.2 61.3 ± 27.0 50.1 ± 36.7 47.6 ± 30.0 48.9 ± 26.1 63.8 ± 21.5 

Active 60.7 ± 28.7 75.6 ± 24.6 71.4 ± 22.5 65.4 ± 27.2 56.9 ± 37.6 37.8 ± 27.4** 47.3 ± 25.6* 65.7 ± 19.8 

Inactive 61.0 ± 26.0 74.5 ± 24.5 70.5 ± 25.4 67.1 ± 27.2 53.2 ± 36.4 51.8 ± 30.6 52.5 ± 25.7 66.2 ± 21.2 

Values are presented as mean ± SD. * = P < 0.05; ** = P < 0.01; r = Spearman ranked correlation coefficient; 1Vitality scores differ between married and divorced, 

single and divorced patients. 

that patients may have different concepts of Productivity based on 

educational level. We found that in patients with lower educational 

levels, Productivity loaded more onto Vitality than other factors. 

Reliability, validity, and discriminatory power 

Testing of internal consistency showed satisfactory Cronbach’s 

α for five of the six main subscales (Anticipation anxiety = 0.9, 

Stigma = 0.86, Psychological well-being = 0.88, Vitality = 0.83, 

Transmissibility = 0.7, Vulnerability and Viral response = 0.55). 

HBQOL total scores had Cronbach’s α of 0.94. The Vulnerability 

subscale had a Cronbach’s α of < 0.6 which showed poor, but not 

‘unacceptable’ coefficient. 27 Substantial (defined as > 0.6) test-retest 

reliability was observed in 29 patients who were retested two 

weeks after the initial questionnaire administration (ICC = 0.660). 

Scores of MCS and PCS significantly correlated with HBQOL 

scores. However, the strength of correlation was higher for MCS 

(r = 0.616 for MCS and 0.399 for PCS; P < 0.001). In addition, 

among the subscales, the Psychological well-being factor had 

the highest correlation with MCS (r = 0.646, P < 0.001). Among 

the HBQOL subscales, Vitality had the highest correlation with 

both PCS and IFS (Table 5). As seen in Table 5, Anxiety had the 

strongest relation with Psychological well-being (r = -0.625, P < 

0.001) while depression had the highest correlation with Vitality 

(r = -0.621, P < 0.001). There was a significant correlation between 

HBQOL and MOS-SS scores (r = 0.322, P < 0.001). Of the 

HBQOL subscales, the strongest relation was between Vitality and 

MOS-SS (r = 0.422, P < 0.001) followed by Psychological well- 

Table 3. Effect of several variables on HBQOL and its subscales. 

being and MOS-SS (Table 5). 

Vulnerability and Viral response discriminated between patients 

with CAH and patients with CIH (defined by viral load and liver 

enzymes) and thus showed discriminatory power (P < 0.001 for 

Vulnerability and P < 0.05 for Viral response). 

Discussion 


The present study was the first, to our knowledge, which evaluated 

HBQOL after its development. Two of the main advantages of 

our study were its large sample size and the use of several instruments 

to validate HBQOL. Our results showed that the Vulnerability 

subscale was able to differentiate between patients with CAH 

and CIH. According to Spiegel et al. 11 the Viral response factor 

discriminated between viral responders and non-responders. While 

we found that the same factor was able to distinguish between patients 

with CAH and CIH, this was totally attributable to the Vulnerability 

subscale, which was a subset of the Viral response factor. 

Because the design of the present study was cross-sectional, we 

were unable to detect any “change” in our patients. The difference 

between patients with normal and abnormal liver functions 

has been shown in other studies that used different instruments. 

Lam et al. 5 and Ong et al. 4 showed that the Worry subscale of the 

CLDQ and MCS subscale of SF-36 were capable of differentiating 

between patients with normal and abnormal liver function, respectively. 

The recent diagnosis of CHBV significantly affected our patients’ 


Items 

Components 

1 

(Anticipation 

anxiety) 

2 

(Stigma) 

HRQOL. Patients who were diagnosed for longer durations might 

have adopted coping mechanisms which might have lowered the 

influence of CHBV on their HRQOL. 

Although the present study confirms the psychometric properties 

reported by the primary study, some points need clarification. 

For example, items F9 and C6 loaded onto Anticipation anxiety in 

our study (rather than Psychological well-being and Vitality in the 


Table 4. Factor structure of HBQOL v1.0. 

3 

(Psychological 

well-being) 

4 

(Vitality) 


5 

(Transmissibility) 

6 

(Vulnerability) 

C1: Concern failure 0.782 0.141 0.119 0.185 0.023 0.071 

C2: Concern cancer 0.719 0.280 0.091 0.187 0.187 -0.077 

C15: Concern worsen 0.660 0.203 0.216 0.126 0.296 0.165 

C5: Concern flare 0.653 0.236 0.100 0.076 0.404 0.157 

C12: Concern survival 0.622 0.249 0.204 0.146 0.371 0.131 

F9: Bad 0.608 0.214 0.468 0.086 0.056 0.015 

C6: Concern sick easily 0.606 0.133 0.092 0.185 0.306 0.192 

C9: Concern survival 0.504 0.326 0.322 0.207 0.190 0.170 

F2: Stigmatized 0.188 0.762 0.072 0.095 -0.075 0.046 

F1: Ashamed 0.164 0.625 0.334 0.009 0.048 0.074 

C14: Concern embarrassed 0.185 0.603 0.347 0.076 0.317 0.085 

C3: Concern boss 0.247 0.569 0.003 0.123 0.183 0.016 

F8: Isolated 0.188 0.565 0.451 0.138 0.149 0.012 

C11: Concern socially isolated 0.186 0.557 0.349 0.209 0.414 0.051 

C10: Concern self-conscious 0.209 0.554 0.446 0.101 0.362 0.088 

F4: Frustrated 0.216 0.532 0.492 0.224 -0.030 -0.055 

F3: Sad 0.408 0.486 0.422 0.128 -0.060 -0.017 

F10: Less enjoyable 0.203 0.286 0.684 0.195 0.108 0.051 

F11: Sex difficult 0.033 0.109 0.680 0.188 0.153 0.307 

F13: Scared 0.559 0.118 0.632 0.115 0.024 0.002 

F7: Angry 0.207 0.226 0.575 0.227 0.075 -0.050 

F6: Anxious 0.458 0.259 0.523 0.255 -0.027 -0.044 

F12: Unproductive 0.022 0.370 0.523 0.346 0.242 -0.067 

P3: Muscle aches 0.202 -0.003 0.152 0.796 0.031 0.075 

P1: Tiredness 0.215 0.249 0.212 0.787 0.018 0.043 

P2: Memory problems 0.125 0.069 0.182 0.733 0.128 0.048 

F5: Worn out 0.210 0.430 0.302 0.599 -0.090 0.089 

C4: Concern transmit child 0.208 0.079 0.071 -0.006 0.759 -0.027 

C7: Concern transmit sex 0.318 0.084 0.087 0.062 0.730 0.084 

C13: Concern eat 0.026 0.076 0.142 0.001 0.071 0.800 

C8: Concern medicines 0.239 0.015 -0.070 0.139 -0.001 0.771 

Rotated eigenvalues 4.8 4.1 4.0 2.8 2.2 1.5 

Variance explained (%) 15.5% 13.4% 13.1% 9.2% 7.3% 4.9% 

Table 5. Spearman’s ranked correlation coefficient (95% CI) between HBQOL and other instruments 

HBQOL components 

Instruments Anticipation 

anxiety 

Stigma 

Psychological 

well-being 

Vitality Transmissibility Vulnerability 

HBQOL total 

score 

PCS 

r = 0.340** 

(0.209 to 0.458) 

r = 0.230** 

(0.101 to 0.367) 

r = 0.402** 

(0.277 to 0.514) 

r = 0.544** 

(0.437 to 0.636) 

r = 0.057 

(-0.084 to 0.196) 

r = 0.082 

(-0.059 to 0.220) 

r = 0.399** 

(0.273 to 0.510) 

MCS 

r = 0.508** 

(0.396 to 0.605) 

r = 0.506** 

(0.393 to 0.603) 

r = 0.646** 

(0.556 to 0.721) 

r = 0.627** 

(0.534 to 0.705) 

r = 0.179* 

(0.040 to 0.312) 

r = 0.043 

(-0.098 to 0.182) 

r = 0.616** 

(0.521 to 0.696) 

IFS 

r = -0.544** 

(-0.636 to 

-0.437) 

r = -0.450** 

(-0.555 to -0.330) 

r = -0.608** 

(-0.689 to 

-0.511) 

r = -0.681** 

(-0.750 to 

-0.598) 

r = -0.215** 

(-0.345 to 

-0.077) 

r = -0.099 

(-0.237 to 0.042) 

r = -0.625** 

(-0.704 to 

-0.531) 

Anxiety 

r = -0.616** 

(-0.696 to 

-0.520) 

r = -0.511** 

(-0.608 to -0.400) 

r = -0.625** 

(-0.700 to 

-0.526) 

r = -0.620** 

(-0.700 to 

-0.526) 

r = -0.202** 

(-0.333 to 

-0.063) 

r = -0.171* 

(-0.304 to 

-0.031) 

r = -0.666** 

(-0.738 to 

-0.580) 

Depression 

r = -0.492** 

(-0.592 to 

-0.378) 

r = -0.435** 

(-0.542 to -0.314) 

r = -0.507** 

(-0.681 to 

-0.499) 

r = -0.621** 

(-0.701 to 

-0.527) 

r = -0.190** 

(-0.322 to 

-0.051) 

r = -0.090 

(-0.227 to 0.051) 

r = -0.587** 

(-0.672 to 

-0.487) 

MOS-SS 

r = 0.216* 

(0.024 to 0.392) 

r = 0.281** 

(0.094 to 0.449) 

r = 0.366** 

(0.187 to 0.522) 

r = 0.422** 

(0.249 to 0.568) 

r = 0.056 

(-0.138 to 0.246) 

r = -0.045 

(-0.235 to 0.149) 

r = 0.322** 

(0.138 to 0.485) 

* = P

Questionnaire Developer(year) 

Chronic 

Liver Disease 

Questionnaire 

Hepatitis Quality of 

Life Questionnaire 

Liver Disease 

Symptoms Index 

Liver Disease 

Symptoms Index 2.0 

Liver Disease 

Quality of Life 

Questionnaire 

Hepatitis B 

Quality of Life 

Questionnaire 1.0 

Table 6. Comparison of HBQOL with other liver disease-related HRQOL questionnaires. 

Younossi et al. 10 

(1999) 

Bayliss et al. 32 

(1998) 

Unal et al. 33 

(2001) 

Van der Plas et 

al. 34 (2004) 

Gralnek et al. 9 

(2000) 

Spiegel et al. 11 

(2007) 

Number of 

questions 

29(previous 

two weeks) 

69 

(previous 

four weeks) 

12 

(previous 

one week) 

18 

(previous 

one week) 

111 

(previous 

four weeks) 

Time 

needed to 

complete 

10 min 

with chronic conditions in developing countries is twice as high as 

developed countries. 28 Furthermore, while item F8 was considered 

an item of psychological well-being in the primary study, it was 

related to Stigma in the present work. In a study on HIV patients, 

Fife and Wright found four distinct dimensions for stigma: social 

rejection, financial insecurity, internalized shame, and social isolation. 

29 Of note, because in HBQOL at least three of these four 

dimensions (other than financial insecurity) are addressed, this tool 

may be considered a disease-specific tool for stigma. 

Eight items loaded on to Psychological well-being in our study, 

six of which were common between our study and the study by 

Spiegel et al. 11 Two items, sexual activity (F11) and productivity 

(F12), loaded on Psychological well-being, while in the primary 

study F11 loaded on to Transmissibility and F12 loaded on 

to Vitality. However, F12 was loaded on Vitality in less educated 

patients. Vitality mainly consists of items that describe physical 

function (as shown by its high correlation with PCS and IFS). Because 

educational level is regarded as a key item in socioeconomic 

status, it may be interpreted that patients with lower educational 

levels rely more on their physical function to do their jobs; so they 

consider their productivity as an important consequence of their 

physical function, rather than psychological well-being. Surprisingly, 

the item “I feel like sexual activity is difficult for me because 

of hepatitis B” loaded mostly on to Psychological well-being, than 

NA 

0.6 

Unrelated subscale: 

0.33 

Unrelated subscales: 

< 0.6 

Related subscales: 

0.52 – 0.8 

Worse HRQOL is 

associated with worse 

severity 

Related subscales: 

0.55 

Unrelated subscale 

< 0.4 

Transmissibility. However, in the primary study, the loading of this 

item differed only 0.05 between the Psychological well-being and 

Transmissibility factors. The highest correlation of this item with 

other items in the Psychological well-being was: “I feel my life 

is less enjoyable because of hepatitis B” (r = 0.528). Regarding 

these findings, it seemed that our patients’ main concern was less 

enjoyable life because of difficult sex rather than the transmission 

of the virus to another person. Since correlation is not necessarily 

indicative of causation, such interpretation is a hypothetical one 

and needs further investigation. 

Vitality highly correlated with IFS and PCS scores showing that 

this scale is mainly a measure of somatic aspect of the quality of 

life. High relation between Vitality and Depression scores may indicate 

a high relation between depression and somatization, particularly 

in Iranian patients. 30 As mentioned previously, somatic 

symptoms may be of major importance in patients with low educational 

levels. This may be the reason why our low-level educated 

patients had more impaired Vitality scores than the patients with 

high-levels of education. 

Low Cronbach’s α of the Vulnerability subscale can be interpreted 

in several ways. First, the low number of items in the subscales 

can affect this coefficient. Alternatively, it can reflect a low correlation 

between two items in the factor. Cronbach’s α of less than 

0.5 is considered unacceptable. 31 Because the Cronbach’s α did not 


each the unacceptable threshold and because this item showed 

high discriminatory power, we retained it in the final analysis of 

the questionnaire. The Viral response item was created by developers 

of the questionnaire using the combination of Transmissibility 

and Vulnerability. 11 Although this item also showed discriminatory 

power in our study, this was a result of the Vulnerability factor 

rather than the whole subscale. 

There are multiple liver (but not CHBV)-specific HRQOL instruments 

available in the literature. 9–11,32-34 The most important possible 

superiority of the HBQOL compared with other instruments 

is that it is CHBV-specific. Thereby as shown by Spiegel et al. 11 

and the present study, HBQOL is more likely to detect changes in 

health status in this subset of patients. This may justify its use in 

clinical trials, although this statement definitely requires more evidence. 

Because of its nature (i.e., being disease-specific), HBQOL 

is unable to address HRQOL in patients with other diseases; thus 

it cannot be used for comparison among the patients with diseases 

other than CHBV. Table 6 provides a comparison between 

HBQOL and other liver disease-related instruments. 

The present study had several strengths. The adequate sample 

size for this design minimized the probability of type II error, as 

mentioned in Materials and Methods. The adequate sample size 

was also confirmed by Bartlett’s test of sphericity and the KMO 

test. Supervision to ensure completion of questionnaires additionally 

strengthened our study. Another advantage of our study was 

the comparison of HBQOL and its subscales with several instruments 

that measured similar constructs, to ensure its convergent 

validity as well as the use of different constructs to ensure divergent 

validity. Exhaustive construct validation in the present study 

together with the extensive content validation process performed 

in the study by Spiegel et al. 11 provided substantial evidence for the 

validity of HBQOL. Moreover, both studies showed the HBQOL 

to be reliable in most of its dimensions by test-retest and Cronbach’s 

α. 

Our study had also some limitations. The cross-sectional design 

did not allow us to measure the change in the scores of HBQOL 

(i.e., responsiveness testing). Regarding generalizability, although 

the study was undertaken in one clinic, the sample size of this 

study could be considered a representative of Iranian patients, both 

because diverse ethnic groups live in Tehran and because our clinic 

is a referral center that accepts patients from throughout Iran. 14 

Conclusion 

The Iranian version of HBQOL v1.0 is a psychometrically sound 

measure with acceptable validity, reliability, and factor structure 

and can distinguish between different clinical conditions. Further 

studies for longitudinal assessment of this instrument, particularly 

in clinical trials, are warranted. In addition, studies in other cultures 

and languages can generalize the administration of HBQOL as a 

useful tool to assess the HRQOL in patients with CHBV. 

Conflict of interests: None 

Financial support: Digestive Disease Research Center, Tehran 

University of Medical Sciences, Tehran, Iran 

Acknowledgement 

We thank Dr. Ali Montazeri for his assistance in providing HADS 

and SF-36 questionnaires and his kind advice for improvement of 


the paper. 

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A view of Persepolis – Achaemenid Empire (c.550 – 331 BCE), around 60 Km northeast of Shiraz-Iran (Photo by M.H. Azizi MD) 




A New Technical Approach to Cancers of the Cervical Esophagus 

Novin Nikbakhsh MD• 1 , Farrokh Saidi MD, FACS, FRCS 2 , Hossein Fahimi MD 3 

Abstract 

Background: The aim of this study was to assess the possibility of a primary end-to-end pharyngoesophageal anastomosis after standard 

tumor resection of the cervical esophagus by acute flexion of the neck. 

Methods: A total of 34 consecutive patients with primary cervical esophageal cancer, none having received prior radio- or chemotherapy, 

were treated by two methods based on intraoperative findings. In 18 patients, reconstruction after esophageal resection was carried out by 

the standard gastric pull-through technique (control group). In 16 patients, acute flexion of the neck after tumor resection allowed for reconstruction 

by primary end-to-end pharyngoesophagostomy (experimental group). 

Results: There was no operative mortality in either group. The mean operative time for the experimental group was about 50 minutes less 

compared to the control group. Self-limited postoperative anastomotic leakage in the neck was twice as common in the experimental group. 

Postoperative dysphagia was about three times as common in the experimental group [5 patients (31%)] compared to the control group [2 

patients (11%)]. 

Conclusion: In selected cases, segmental resection of primary cervical esophageal cancers reconstructed by end-to-end pharyngoesophagostomy 

is technically feasible by bending the neck acutely forward during anastomosis and maintaining it in the flexed position during a 

postoperative period of about 7 days. The advantages are reduced scope and duration of the operation. The downside is doubling of the 

frequency of postoperative cervical leakage. 

Keywords: Cervical esophagus, esophageal cancer, squamous cell carcinoma 

Cite this article as: Nikbakhsh N, Saidi F, Fahimi H. A New Technical Approach to Cancers of the Cervical Esophagus. Arch Iran Med. 2012; 15(5): 298 – 302. 


About 6% of esophageal cancers arise from the cervical segment 

lying between the cricopharyngeus and the thoracic 

inlet; 1 the vast majority are squamous cell carcinomas. At 

presentation, one-third of patients have extension of the tumor beyond 

the confines of the esophagus and in one-fifth, the trachea or 

vocal cords are involved. 1,2 The reported operative mortality ranges 

from 5% to 31%, 3,4 and 7% to 37% of patients have postoperative 

anastomotic leakage. 3, 4 Neither mortality nor recurrence rates can 

be improved upon by removal of the entire length of the esophagus. 

5 Old reconstructive techniques consisted of fashioning a full 

thickness skin tube in the neck (Wookey procedure) or interposition 

of free jejunal grafts. Both procedures were time consuming 

and cumbersome, and have been abandoned. 3,6 

Surgical management of cervical esophageal cancer differs from 

that of other portions of the esophagus in two major aspects. Removal 

of the larynx with permanent loss of phonation is unavoidable, 

and reconstruction by gastric pull-up greatly expands the 

scope of the surgery. 

For these two reasons, chemo-radiotherapy has replaced surgery 

in many centers as the preferred treatment modality. Overall survival 

has not improved, however, nor has the rate of local recurrence 

diminished. 

A recent study has shown locoregional relapse-free survival be- 

Authors’ Affiliations: 1 Babol University of Medical Sciences, Babol, Iran, 2 Beheshti 

University of Medical Sciences, Tehran, Iran, 3 Mehr Hospital, Tehran, Iran. 

•Corresponding author and reprints: Novin Nikbakhsh MD, Department. of 

Thoracic Surgery, Beheshti Hospital, Babol University of Medical Sciences, 

Babol, Iran.Tel. +98-9111227003, Fax: +98-1113232665 

Accepted for publication: 24 August 2011 

tween 36% – 73% after curative chemoradiotherapy in a 2-year 

rate. 7 In these circumstances the management of local recurrence, 

furthermore, becomes hazardous and technically demanding because 

of prior radiotherapy. 8–11 Death occurs by suffocation or massive 

local bleeding and rarely because of distant metastases. 

The purpose of this study was to evaluate the practicality of an 

end-to-end esophageal anastomosis in the neck after tumor resection, 

thereby lowering the extent of surgical trauma associated with 

formal laparotomy, mobilization, and transfer of the stomach to 

the neck. There has been, unintentionally, refutation of the axiom 

against primary end-to-end anastomosis anywhere along the 

esophageal length. 

Patients and Methods 


Between March 2001 and September 2008, a total of 34 consecutive 

patients with primary, biopsy proven squamous cell carcinoma 

of the cervical esophagus were admitted to the teaching hospitals 

of Beheshti University of Medical Sciences, Tehran and Babol 

University of Medical Sciences, Babol, Iran. None of the patients 

(15 males and 19 females; age range: 56 to 74 years) that enrolled 

in the study had any co-morbidities or received prior chemoradiotherapy. 

Permission for the study was granted by the Institutional 

Review Board of the respective universities, and informed consent 

was obtained from all patients after full explanation of the two 

technical approaches being considered. The need for permanent 

tracheostomy was explained, the psychological impact of permanent 

aphonia lessened by demonstrating one of the currently available 

hand-held mechanical speech devices. 

The decision regarding the manner of reconstruction was deferred 

until the resection was completed, in the following manner:

Patient’s numbers 

Male 

Sex 

Female 

Age 

(mean±SD) 

Gastric bypass n=18 n=8 (44%) n=10 (56%) 64.5±8 

Neck flexion n=16 n=7 (44%) n=9 (56%) 65.3±9 

With the patient in the semi-sitting supine position, a mid-cervical 

collar incision allowed the lower skin flap to be opened enough 

to accommodate the permanent tracheostomy opening. The strap 

muscles were transected, and the exploratory finger inserted in the 

plane between the esophagus and anterior vertebral fascia. Obliteration 

of this space, which may not have been fully apparent on 

preoperative CT scans, meant unresectability of the lesion, as did 

gross involvement of the carotid vessels. The trachea was transected 

distal to the specimen in a beveled manner for tension-free 

accommodation to the skin aperture in the center of the lower skin 

flap. A prepared sterile endotracheal tube was inserted into the new 

tracheal opening (end- tracheostomy), which replaced the initial 

orally inserted endotracheal tube. 

Staying in the midline, the thyroid lobes and attached parathyroids 

were displaced laterally to avoid injury. The larynx and 

proximal trachea attached to the cervical portion of the esophagus 

where the tumor was located and mobilized in preparation for 

transection, superiorly at the level of the hyoid bone and inferiorly 

at a distance above the thoracic inlet. Having superiorly entered 

the pharynx and sacrificing the epiglottis, the specimen could be 

lifted off its base to allow for transection of the esophagus inferiorly 

above the thoracic inlet with a grossly tumor-free margin. 

Multiple biopsies were taken from the two open ends of the phar- 

Table 1. Patients’ characteristics 

Gastric bypass group (n=18) Neck flexion group (n=16) 

T statusa T1 ---- ---- 

T2 1 (6%) 2 

T3 10 (55%) 8 

T4 

N status 

7 (39%) 6 

a 

N0 5 4 

N1 

M status 

13 12 

a 

M0 18 16 

M1 

Stage 

---- ---- 

a 

I ---- ---- 

II 6 (35%) 4 (25%) 

III 11 (59%) 12 (75%) 

IV 

Residual disease 

1 (6%) ---- 

R0 16 (89%) 15 (94%) 

R1 2 (11%) 1 (6%) 

R0 = no residual tumor; R1 = microscopically residual tumor; a Table 2. Tumor characteristics in the two groups. 

According to the TNM system (AJCC, 2002) 

Table 3. Hospital morbidity and mortality. 

A New Technique in Cervical Esophagus Cancer 

Complications Gastric bypass Neck flexion P value 

Minor anastomotic leak a 2 (11%) 4 (25%) 0.387 

Major anastomotic leak b 1 (6%) 2 (13%) 0.591 

Cardiac arrhythmias 5 (28%) 1 (6%) 0.180 

Respiratory failure 0 0 ------- 

Blood transfusion required 2 (11%) 0 0.487 

Late stricture with dysphagia 2 (11%) 5 (31%) 0.214 

a Anastomotic leaks apparent after the seventh postoperative day; b Anastomotic leaks apparent before the seventh postoperative day. 

Table 4. Patterns of recurrence. 

Recurrence pattern Gastric bypass (n=18) Neck flexion group (n=16) P value 

Locoregional 2 (11%) 3 (19%) 0.648 

Distant 4 (22%) 3 (19%) 1.000 

Both 1 (6%) 2 (13%) 0.591 

ynx (above) and the esophagus (below) to ensure microscopically 

tumor-free edges. No attempt was made to mobilize any portion of 

the remaining distal esophagus, either laterally from its bed or inferiorly 

into the thorax. The only tension-releasing maneuver used 

consisted of gentle finger dissection around the open stump of the 

pharynx, allowing for about 2 to 3 centimeters of downward displacement 

of the pharyngeal opening to be used for anastomosis. 

Visible and palpable lymph nodes were removed, but no formal 

neck dissection was performed. 

With the specimen removed and the neck in the normal anatomic 

position, the resulting anatomic defect in the neck was measured 

with calipers. A gap of 8 centimeters or less suggested that a tension 

free, end-to-end anastomosis might succeed, but was verified 

by a somewhat more reliable maneuver, as follows: 

Pulling gently on two previously placed traction sutures on the 

sides of the pharyngeal opening (above) and the esophageal opening 

(inferior), an unscrubbed assistant would grasp the back of 

the patient’s head and gently flex it forward to a maximal, but not 

forced degree (Figures 1, 2). The degree of final tension that would 

be transferred on the anastomosis could subjectively assessed by 

noting how readily the traction sutures would come together while 

flexing the neck. If the caliper measured defect was greater than 8 

centimeters or the neck flexion maneuver indicated an intolerable 


Figure 1. Operative X-ray with neck in the neutral position showing a hemostat 

on the lower rim of the proximal remnant of the esophageal segment, 

with another hemostat on the sternal angle. 

tension at the anastomosis, a transhiatal gastric pull-up would be 

undertaken. Otherwise, primary end-to-end anastomosis was performed 

in the following manner: 

With the head brought back to its normal anatomic position, a 

posterior followed by an anterior row of interrupted 2-0 Vicryl ® 

sutures (0.5 centimeters apart) were placed and kept in sequential 

order, but not tied. The neck was fully flexed as described, essentially 

obscuring the site of anastomosis. Tying down the sutures, 

beginning with the posterior row, was carried out in a blind manner 

relying on the sense of touch in deciding the minimal degree 

of tension needed to bring the two open ends of the gullet together. 

If any doubt existed, the anastomosis was not completed, but reconstruction 

shifted to the gastric pull-up procedure. The anastomosis 

was not tested for leaks by either air or saline insufflations. 

At the end of the anastomosis, having maintained the head in the 

flexed position, the strap muscles were re-approximated and the 


Figure 2. Same patient. The neck has now been flexed about 45° forward, 

bringing the two hemostats much closer together. 

Figure 3. Overall survival curve. 


skin closed in two layers without drainage. A feeding jejunostomy 

was placed through a limited laparotomy incision, to be used on 

the first postoperative day. A stout chin suture further assured that 

the neck would be kept in the flexed position during the entire 

postoperative period of 7 days. The endotracheal tube, its balloon 

deflated, was kept in place for about 2 days to ensure access for 

the tracheobronchial toilet as needed. When signs of leakage such 

as cervical wound erythema or drainage were seen, we performed 

a dilute barium study to verify leakage. Its management was by 

cervical wound opening, dressing and nutrition via a jejunostomy 

tube. The mean duration of leakage in the neck flexion group was 

5 days for minor anastomotic leak (anastomotic leaks became apparent 

after the seventh postoperative day) and 10 days for major 

anastomotic leak (anastomotic leaks became apparent before 

the seventh postoperative day). During the leakage period, mouth 

washing with normal saline and oral intake of metronidazole syrup

was prescribed. After 5 days, in all leakage cases, oral nutrition 

was started with liquids and metronidazole syrup. Swallowing 

was achieved in all of these patients. 

Statistical analyses 

Survival analyses were performed using the Kaplan–Meier method. 

Comparisons of survival between groups were assessed by the 

log-rank test. Differences in clinicopathologic variables among 

various groups were calculated using the chi 2 test, Fisher exact 

test, and student t-test when appropriate. Multivariate analysis with 

a stepwise Cox regression model was conducted to evaluate the 

independent prognostic factors. A P value of less than 0.05 was 

considered significant. All analyses were performed with SPSS 

software version 11.0 (SPSS, Inc., Chicago, IL). 

Results 

A total number of 34 patients (55.9% female; mean age ± SD: 

64.9 ± 4.9; range: 56 – 74 years) were enrolled in the study during 

a 90 month period. The mean total surgical time ± SD was 196.6 

± 28.0 minutes. Patients and tumor characteristics are shown in 

Tables 1 and 2. 

There was no significant relationship between sex and the two 

surgery type groups (P = 0.9), nor was seen between the mean patients` 

age and two surgery type groups (P = 0.7). Analysis of patients’ 

process data also indicated that the mean surgical time(min) 

± SD in the standard gastric pull-through technique group was 

220.3 ± 14.0 and in the primary end-to-end pharyngoesophagostomy 

group, it was 170.0 ± 8.9, which was significant (P < 0.001). 

Overall, there was no significant relationship between sex and 

mean time (P = 0.9). 

A noticeable issue in this study was the weak reverse-correlation 

between duration of surgery and age of patients (Pearson correlation: 

-0.072), however this relationship was not significant (P = 

0.8). 

Outcome details for both the ‘gastric bypass’ and the ‘neck flexion’ 

techniques of reconstruction are summarized in Table 3. 

One patient in the gastric bypass group had a splenectomy because 

of inadvertent trauma to the spleen, and two patients required 

blood transfusions. The mean duration of hospital stay was 

similar for both groups, 15 days (10 – 30 days) in the neck flexion 

group and 12 days (10 – 20 days) in the standard method group. 

There was no mortality in either group. There was no need for 

conversion once the neck flexion technique had been decided 

upon at completion of resection. This lent weight to the reliability 

of simple inspection and palpation in assessing anastomotic tension. 

There was local tumor recurrence in 7 (39%) patients in the control 

group and 8 (51%) patients in the experimental group, with 

a mean delay of 16 months postoperatively (range: 3-80 months). 

Two patients in the control group developed tumor recurrence in 

the pulled-up stomach. Patterns of recurrence are depicted in Table 

4. Overall actuarial survival in both groups is shown in Figure 3. 

We could complete follow-up in all 34 patients. Of the 16 patients 

in the control group, 7 patients (40%) died of disease (locoregional 

and distant metastasis), 4 patients died from cardiovascular diseases, 

1 patient died due to a car accident and 4 patients were alive 

and disease free. In the experimental group, 8 patients (50%) died 

because of disease (locoregional and distant metastasis), 2 patients 

died because of cerebrovascular accident, 3 patients died because 

of cardiovascular disease, and 4 patients were alive without disease. 

The cause of death in the remaining patient was unknown. 

Discussion 

A New Technique in Cervical Esophagus Cancer 

This study showed the feasibility of primary pharyngoesophagostomy 

by neck flexion with overall lower morbidity than the 

standard method. As shown in Table 3, a doubling of postoperative 

anastomosis leakage and late stricture in our study was offset by 

significant saving of operative time and avoidance of complications 

with the gastric pull-up procedure. 

Most studies 12–16 prefer gastric transposition as the best surgical 

technique for restoring alimentary continuity after laryngopharyngectomy. 

Ayshford et al. have reported that 58% of British surgeons 

elected gastric pull-up as their favorite method 17 of restoring 

alimentary continuity after cervical esophageal reconstruction. The 

mortality rate ranged from 5% to 31% and anastomotic leakage 

rate ranged from 7% to 37%. Sullivan and associates have reported 

results of 32 consecutive pharyngogastric reconstructions with a 

12% mortality rate and anastomotic leakage rate of 31%. 18 

An unavoidable loss of the larynx has, understandably, swayed 

many surgeons towards chemoradiotherapy in managing primary 

cancers of the cervical esophagus. The benefits of chemoradiotherapy 

for lower-end esophageal cancers are being assessed, 19–21 but 

the results are not necessarily applicable to upper-end esophageal 

cancers. Any attempt, therefore, at ameliorating the plight of patients 

afflicted with cervical esophageal cancer would seem justified. 

Reverting to a completely surgical approach initially has the 

benefit of facilitating reoperations for local recurrence, something 

which would be technically difficult and hazardous after radiotherapy 

to the neck. Results of chemoradiation for cervical esophageal 

cancer by Burmeister et al. 22 among 34 patients has shown a failure 

rate of 12% for local control. Three patients (9%) died from persistent 

local disease and 2 (6%) patients died as a result of treatment 

[5 (15%)]. With well functioning, relatively inexpensive, handheld 

laryngeal voice devices now available, it is possible that there 

will be a reversal to surgical management of cervical esophageal 

cancers in the future. 

The neck-flexion maneuver, which allows for primary end-toend 

pharyngoesophagostomy, rightfully raises the question as to 

whether there might be some compromise with extent of cancer 

resection needed for a possible cure. The only way to avert this 

possibility would be to postpone the final decision regarding reconstruction 

until resection has been accomplished, according to 

oncological principles. The next problem is the maximal length of 

the final esophageal defect after resection that would allow for a 

successful primary end-to-end. One-half of the tracheal length is 

considered the maximum that can be removed and tracheal continuity 

restored by primary anastomosis. 23 No comparable measure 

exists for the esophagus, and the final decision rests on correct 

judgment. The length of the cervical portion of the esophagus varies 

according to body build of patients, which varies as does the 

degree of neck flexion tolerated by different individuals. Assigning 

a numerical value to the length of the esophageal defect that can be 

bridged by neck flexion would, therefore, be much less valuable 

than a visual and palpatory assessment of permissible tension, as 

described. The final results confirmed the reliability of this type of 

subjective assessment of the safety of performing an end-to-end 

anastomosis in the neck. The only tension releasing maneuvers 

permitted are limited to digitally freeing the pharynx in the neck. 


Any attempt at mobilizing the esophagus out of the thorax inferiorly 

should be resisted, the normal contractive pull of the freed-up 

esophagus making this maneuver counter-productive. End-to-end 

pharyngoesophagostomy runs counter to accepted surgical principles. 

Its execution in the neck, however, is made possible by the 

exceptional laxity brought about by neck flexion. This maneuver 

has also been used by Pirmoazen 24 in the management of long segment 

cervical esophageal strictures relieved by the Heineke–Mikulicz 

procedure, readily bringing together the two ends of the longitudinal 

incision. Maintaining the neck in the flexed position for 

a minimum of 7 days proved not to be a problem. A few patients 

voluntarily kept their head bent forward for an additional day or 2. 

Postoperative cervical anastomotic leakage was not as frequent 

or serious as expected, nor delayed strictures as severe as feared. 

The bent–neck posture was tolerated quite well by patients after 

tracheal resection for 7 or more days, and the same was observed 

for the neck flexion group in this study. The total number of cases 

in this study was not large enough to show whether, in the long 

run, the overall risk–benefit balance of the neck flexion maneuver 

manner of reconstruction after cervical esophageal resection surpasses 

that of the standard gastric pull-through procedure. 

Conclusion 

Resection of cervical esophageal cancer, based on oncological 

principles, with reconstruction carried out by primary end-to-end 

pharyngoesophagostomy is technically feasible, with no unacceptably 

high postoperative cervical leakage rates or local stricture formation. 


The authors thank the hospital authorities, and operation room 

and ICU staff. We express deep thanks to our patients. 

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Severe Thrombocytopenia and Hemorrhagic Diathesis due to 

Brucellosis 

Hasan Karsen MD• 1 , Fazilet Duygu MD 2 , Kubilay Yapıcı MD 3 , Ali İrfan Baran MD 3 , Huseyin Taskıran MD 4 , İrfan Binici MD 3 

Abstract 

Background: We aimed to examine cases of brucellosis that presented with severe thrombocytopenia and hemorrhagic diathesis. 

Methods: A total of 10 brucellosis cases with severe thrombocytopenia were included in this case-series study. Patients’ files were reviewed 

for their clinical and laboratory findings, as well as clinical outcomes and complications. Platelet counts of < 20000/mm³ were diagnosed as 

severe thrombocytopenia. 

Results: The lowest thrombocyte count was 3000/mm³ while the highest was 19000/mm³ (mean: 12000/mm³). Patients had the following 

symptoms: epistaxis (7 cases), petechia with epistaxis (4 cases), bleeding gums (3 cases), ecchymosis with epistaxis (2 cases), melena and 

renal failure (2 cases), and hematuria (1 case). Patients were given rifampicin and doxycycline along with supportive hematological therapy. 

All were treated successfully with no evidence of recurrence at follow-up visits. 

Conclusion: Since brucellosis is endemic in developing countries, it must be considered in the differential diagnosis of cases that present 

with severe thrombocytopenia and hemorrhagic diathesis. 

Keywords: Brucellosis, hemorrhagic diathesis, severe thrombocytopenia 

Cite this article as: Karsen H, Duygu F, Yapıcı K, Baran AI, Taskıran H, Binici I. Severe Thrombocytopenia and Hemorrhagic Diathesis due to Brucellosis. Arch Iran 

Med. 2012; 15(5): 303 – 305. 


Brucellosis is a multisystem disease with a wide variety of 

symptoms that include hematological abnormalities such as 

anemia, thrombocytopenia, pancytopenia and leucopoenia. 

Disseminated intravascular coagulation (DIC) and hemorrhagic 

diathesis are rarely seen. 1,2 In some studies, hematological findings 

ranging from mild anemia to pancytopenia are reported to be more 

than 50%. 3,4 Various rates of thrombocytopenia due to brucellosis 

have been reported; however, to the best of our knowledge, all 

published studies except for case-reports regarding severe thrombocytopenia 

due to brucellosis were pediatric case-series, until 

now. In this paper, 10 adults cases with severe thrombocytopenia 

and hemorrhagic diathesis due to brucellosis have been presented. 


This was a case-series study. Patients’ files were reviewed for 

their clinical and laboratory findings, symptoms, prognosis, age 

and gender as well as complications and clinical outcomes. The 

study protocol was approved by the local research committee for 

ethics. The Brucella Wright test; blood culture; complete blood 

count; erythrocyte sedimentation rate (ESR); C-reactive prote- 

Authors’ Affiliations: 1 Harran University Faculty of Medicine, Department of 

Infectious Diseases and Clinical Microbiology, Sanliurfa, Turkey, 2 Tokat State 

Hospital, Clinical Infectious Diseases, Tokat, Turkey, 3 Yuzuncu Yil University, 

Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, 

Van, Turkey, 4 Private Zirve Medical Center, Internal Medicine Clinic, Nizip, 

Turkey. 

•Corresponding author and reprints: Hasan Karsen MD, Harran University, 

Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, 

Sanliurfa, Turkey. Tel: +904143183000, E-mail: hasankarsen@hotmail.com. 


in (CRP); liver and renal function profiles; urinalysis; IgM anti- 

CCHF (Crimean-Congo hemorrhagic fever); as well as coagulation 

parameters such as prothrombin time (PT), activated partial 

thromboplastin time (aPTT), and fibrinogen levels were measured. 

Complete blood cell count was repeated when the results were abnormal 

or when indicated.. We also tested patients for enteric fever, 

malaria, acute viral hepatitis, and toxoplasmosis. 

Brucellosis was diagnosed by the presence of antibodies against 

brucella with a titer of ≥ 1:160 by the standard tube agglutination 

test (Brucella abortus antisera, Cromatest, Linear Chemicals, 

Barcelona, Spain) and/or by isolation of brucella from blood 

(BACTEC, Becton Dickinson, USA) in addition to clinical symptoms 

consistent with brucellosis. Anemia, thrombocytopenia, and 

leucopenia were defined as hemoglobin (Hb) levels of < 12 g/dL, 

a platelet count of < 150000/mm³, and leukocyte count of < 4000/ 

mm³, respectively. Platelet counts < 20000/mm³ were considered 

as severe thrombocytopenia. 5 

Results 

Severe Thrombocytopenia due to Brucellosis 

There were 4 male and 6 female patients with severe thrombocytopenia. 

Patients’ mean age was 35.24 ± 6.12 years (range: 18 to 

64 years). Standard agglutination test was positive in all patients, 

however B. melitensis was present in the blood cultures of only 3 

patients. 

Pancytopenia was present in 5 cases, bicytopenia (thrombocytopenia 

and anemia or thrombocytopenia and leucopenia) was seen 

in 4 cases, and there was only one case of isolated thrombocytopenia. 

The lowest thrombocyte count was 3000/mm³ while the 

highest was 19000/mm³ (mean: 12000/mm³). The mean Hb level 

was 9.17 g/dL and white blood cell level was 5720/mm³. Totally, 

the mean decrease in thrombocytes was 92% while it was 23.6% in 

Hb levels. There was no decrease in white blood cell count. 


As seen in Table 1, clinical symptoms were as follows: epistaxis 

(7 cases), petechia with epistaxis (4 cases), bleeding gums (3 cases), 

ecchymosis with epistaxis (2 cases), melena and renal failure 

(2 cases), and hematuria (one case). The following elevated laboratory 

abnormalities were present: ESR (6 cases), CRP (10 cases), 

PT (7 cases), PTT (2 cases), and PT together with aPTT and INR 

(one case). The one case which had elevated PT, aPTT and INR 

levels also had a low fibrinogen result. All patients were treated 

with rifampicin and doxycycline and platelet suspensions. Hb levels 

were < 8 gr/dL in 4 patients and each of them received whole 

blood transfusions. All cases were negative for CCHF, enteric fever, 

malaria, acute viral hepatitis, and toxoplasmosis. 

Discussion 

Table 1. The cases of thrombocyte, hemoglobin, and leukocyte values and clinical symtoms 

Case Number Platelet(/mm 3 ) Hb(g/dL) WBC(/mm 3 ) Complications seen in cases 

1 3000 12.4 9000 Epistaxis, petechia, neuropyschiatric symptoms 

2 7000 8.5 2700 Melena, gum bleeding 

3 9000 10.6 73000 Epistaxis, ecchymose 

4 10000 9.5 4900 Epistaxis, ecchymose, gum bleeding 

5 10000 5.5 3900 Melena, hematuria, renal failure, pyschiatric symptoms 

6 13000 7 3700 This case had no bleeding symptoms 

7 15000 7.8 7600 Neuropyschiatric symptoms 

8 16000 4.7 10900 Epistaxis, petechia, renal failure, pyschiatric symptoms 

9 18000 12.7 3700 Epistaxis, petechia, 

10 19000 13 3500 Epistaxis 

Mean±SD 12000±51 9.17±2.96 6800±2150.21 ------ 

Hb: Hemoglobin, WBC: White blood cell 

Mild hematological abnormalities such as anemia and leucopenia 

are common in the course of human brucellosis. Severe thrombocytopenia, 

acute hemolysis, DIC, hemorrhagic diathesis, immune 

thrombocytopenia, capillary leak syndrome (CLS), thrombotic 

thrombocytopenic purpura (TTP), and Evan’s syndrome are rarely 

seen. 6–10 In our study, the mainly affected blood elements were 

thrombocytes. The pathogenesis of thrombocytopenia in brucellosis 

remains obscure but several possible mechanisms, including 

hypersplenism, hemophagocytosis, granulomas, increased clearance 

of damaged thrombocytes with endotoxins, thrombocyte adherence 

to vascular surfaces, and bone marrow suppression due to 

septicemia may account for it. 11 In various studies, thrombocytopenia 

prevalence has been reported to be 3.4%-26%. 3,4,12–15 Severe 

thrombocytopenia and bleeding disorder due to brucellosis have 

generally been studied in children. The papers regarding adults are 

only case reports. 16–18 Although severe thrombocytopenia, bleeding 

disorder, DIC, and thrombotic thrombocytopenic purpura 

(TTP) are rarely seen in brucellosis, 4,6,15 in our study all cases had 

severe thrombocytopenia and bleeding disorders, 2 cases had TTP, 

and one case had DIC. 

According to a study by Kiki et al., a 19-year-old woman presented 

with complaints of headache, fever, sweating, malaise, and 

jaundice. Her clinical signs and laboratory findings were consistent 

with TTP. She received plasma exchange and antibiotic therapy. 17 

In a case presented by Erdem et al., a 51-year-old man had complaints 

of moderate confusion, depressed mood and dysarthria, fever 

(38.5°C), jaundice, and petechial-purpuric skin lesions. Laboratory 

tests showed white blood cell count of 9600/mm³, Hb 7.1 g/ 

dL, and platelets 18000/mm³. He received a plasma infusion and 

antimicrobial treatment. 19 

The clinical picture of our fifth case was as follows: confusion 

and speech disturbance, fever of 38.8°C, thrombocyte count of 


H. Karsen, F. Duygu, K. Yapıcı, et al. 

10000 /mm³, Hb of 5.5 mg/dL, creatinine level of 9.1 mg/dL (normal 

0.8 – 1.2), total bilirubin of 4.1 mg/dL (normal 0.2 – 1.2), and 

indirect bilirubin of 3.4 mg/dL (normal 0 – 0.75). He received 

thrombocyte infusion and antimicrobial treatment 

Our eighth case had the following clinical symptoms: convulsion 

and hallucinations, loss of consciousness, fever of 39.8°C, thrombocyte 

count of 16000/mm³, Hb of 4.7 mg/dL, creatinine level of 

2.52 mg/dL, total bilirubin level of 4.8 mg/dL, and indirect bilirubin 

level of 4 mg/dL. He received antimicrobial treatment, platelet 

suspensions and whole blood transfusions. 

Our third patient presented with DIC, whose laboratory findings 

were: PT 26 sec (normal 10 – 15), active partial thromboplastin 

time (aPTT) 59 sec (normal 26 – 41) and INR 1.8 (normal: 0.8- 

1.22), fibrinogen 67 mg/dL (normal: 150 – 400), and D-dimer 4.05 

ug/mL (normal: 0 – 0.4). He received antibiotics, platelet suspensions 

and fresh-frozen plasma. 

Bleeding disorders such as epistaxis and hematuria have rarely 

been reported. 19 We have not seen any case report of brucellosisinduced 

melena, gum bleeding, and ecchymosis in the literature. 

As mentioned in Table 1, in addition to severe thrombocytopenia, 

our cases had complaints of epistaxis, ecchymosis, melena, hematuria, 

gum bleeding, neuropsychiatric symptoms, and renal failure. 

The symptoms of our brucellosis cases were similar to those 

of hematologic malignancies and hemorrhagic viral diseases. 20,21 

Therefore, hematologists, ENT specialists, psychiatrists, dermatologists, 

dentists, urologists, and gastroenterologists should bear 

in mind the possibility of brucellosis in patients who present with 

bleeding. 

We agree with some authors who have suggested that thrombocytopenia 

is a result of immunological reactions. 16 In some of 

our cases thrombocytopenia had developed as a result of an immunological 

mechanism, which was the main reason for severe 

thrombocytopenia. Hemorrhage results from either a decrease in 

platelet counts or platelet dysfunction. Thrombocytopenia is rare; 

only in very rare cases of brucellosis is it severe enough to cause 

bleeding. 22 The high rates of bleeding in our cases (100%) warrant 

attention. After 4 days of treatment with antibiotics (rifampicin and 

doxycycline) and platelet suspensions, the hemorrhage stopped in 

all our cases with bleeding. Fortunately, the severe thrombocytopenia 

which occurs in brucellosis is responsive to antibiotics and 

hematological supportive therapy. 

Within 2 weeks, thrombocytopenia improved in the majority of 

cases. At the end of the third week, platelet counts were > 150000/ 

mm³ in all patients. At the end of the fourth week of treatment 

with anti-brucellosis drugs, hematological abnormalities as well as 

renal insufficiency, neuropsychiatric symptoms, and other symptoms 

had completely disappeared. Akdeniz et al. have reported that 

platelet counts returned to normal within 2 – 3 weeks of initiating

antibiotics. 2 Dilek et al. have reported restoration of thrombocytopenia 

to normal ranges within one week after initiation of antimicrobial 

therapy. 6 We have completed the antimicrobial treatment to 

6 weeks in all patients. 

All our patients were treated successfully then discharged. Patients 

were followed monthly for 12 months with clinical and 

laboratory findings. No recurrence of brucellosis was noted at 

follow-ups. 

Some authors have reported successful results with the administration 

of plasma, plasma exchange, intravenous gamma globulin, 

and steroids in conjunction with brucellosis treatment. 21,22 However, 

in our cases, those treatment modalities were not necessary. 

In conclusion, since brucellosis is endemic in developing countries, 

it must be considered in the differential diagnosis of viral 

hemorrhagic diseases and cases presenting with severe thrombocytopenia 

and bleeding disorders. Even with the development of 

severe thrombocytopenia and bleeding in patients with brucellosis, 

successful results can be obtained with antibiotics and hematologic 

supportive therapy. 

References 

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Lancet Infect Dis. 2007; 7: 775 – 786. 

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Acute Administration of Zn, Mg, and Thiamine Improves Postpartum 

Depression Conditions in Mice 

Sara Nikseresht MSc 1 , Sahabeh Etebary MSc 2 , Morteza Karimian PhD 1 , Fatemeh Nabavizadeh PhD 1 , Mohammad Reza Zarrindast 

PhD 3 , Hamid Reza Sadeghipour PhD• 1 

Abstract 

Background: Postpartum depression (PPD) affects approximately half of new mothers. Chronic exposure to progesterone during pregnancy 

and its withdrawal following delivery increases depression and anxiety. In addition, there are complex interactions between hormones, 

neurotransmitters, and trace elements. Zinc (Zn) and magnesium (Mg) influence the nervous system by impacting synaptic neurotransmission 

in the brain. Thiamine (Vit B 1 ) deficiency results in a high percentage of depressive behaviors. Elevated levels of reactive oxygen species 

in pregnancy are implicated in the pathogenesis of major depression. 

Methods: We examined the effects of different combinations of Zn, Mg, and Vit B 1 in an animal model of PPD. ZnCl, MgCl, and thiamine- 

HCl were administered to PPD-induced mice. Depression, anxiety-related behavior, and total antioxidant capacity (TAC) were assessed. 

Depression and anxiety-like behavior were evaluated by the forced swimming test (FST) and elevated plus-maze, respectively. 

Results: The acute combined administration of Zn, Mg, and Vit B 1 significantly decreased immobility time in FST, increased the percentage 

of both time spent in- and entries to open arms in the elevated plus-maze, and augmented TAC. 

Conclusion: Our data suggest that acute administration of combined treatment with Zn, Mg, and Vit B 1 on postpartum day 3 improves 

depressive symptoms and anxiety-like behaviors. Our evaluation of TAC is in accordance with behavioral results. 

Keywords: Anxiety, depression, magnesium, thiamine, Zinc 

Cite this article as: Nikseresht S, Etebary S, Karimian M, Nabavizadeh F, Zarrindast MR, Sadeghipour HR. Acute Administration of Zn, Mg, and Thiamine Improves 

Postpartum Depression Conditions in Mice. Arch Iran Med. 2012; 15(5): 306 – 311. 


A 

depressed mood is common during the postpartum period, 

affecting almost 50% of new mothers during the first days 

following delivery. This transient mood disturbance in vulnerable 

women may lead to more serious and persistent depression 

during subsequent weeks, finally fulfilling the diagnostic criteria 

for major depression, known as postpartum depression (PPD). 1,2 

Evidence suggests that maternal depression is harmful for new 

mothers, their infants, and family relationships. PPD can also impair 

the infant’s cognitive and social development. This situation 

can even lead to suicidal tendencies or infanticide. 3–5 

Rapid decline in hormone levels, in particular sex hormones, 

happens following delivery. Based on previous studies, withdrawal 

of progesterone has been proposed as a trigger for PPD symptoms 

and recent attention has been given to the possible mood effects of 

neuroactive metabolites and precursors of progesterone. Because 

depression is often accompanied by enhanced anxiety, chronic exposure 

to progesterone, followed by its withdrawal increases anxiety. 

6–10 It is possible that complex interactions between hormones 

and neurotransmitters are involved; because of this, alterations in 

ovarian steroids are associated with debilitating psychiatric and 

Authors’ Affiliations: 1 Department of Physiology, School of Medicine, Tehran 

University of Medical Sciences, Tehran, Iran, 2 Department of Midwifery, Shahid 

Beheshti University of Medical Sciences, Tehran, Iran, 3 Department of Neuroscience, 

School of Advanced Medical Technologies, Tehran University of Medical 

Sciences, Tehran, Iran. 

•Corresponding author and reprints: Hamid Reza Sadeghipour PhD, Department 

of Physiology, Tehran University of Medical Sciences, Poorsina Ave., Tehran, 

Iran. Tel: +98 21 64053281, Fax: +98 2166570435, 

E-mail: sadeghipour@sina.tums.ac.ir. 


S. Nikseresht, S. Etebary, M. Karimian, et al. 

neurological disorders that include premenstrual dysphoric disorder, 

premenstrual syndrome, menstrual migraine, PPD, and anxiety. 

Based on recent studies, trace elements such as zinc (Zn) and 

magnesium (Mg) also exert their antidepressant effects by acting 

on neurotransmitter pathways. 11–14 

Zn is a trace element, particularly abundant in the central nervous 

system (CNS). Zn is important as a signaling factor in synaptic 

neurotransmission in the brain. 15,16 Several studies have shown its 

potential antidepressant activity in humans and suggest that Zn 

may be involved in the mechanism of action of antidepressant 

therapy. In confirmation, anxiety-like behavior is increased in Zndeprived 

rodents. 17–19 In another study, the results have demonstrated 

a relationship between the severity of depressive symptoms and 

decreased serum Zn concentrations in humans with PPD. 20 

Mg is a trace element that acts primarily as an intracellular ion 

influencing the nervous system by its effects on the release and 

metabolism of neurotransmitters. 21,22 Mg has been proposed to 

participate in biochemical dysregulation that contributes to psychiatric 

disorders. The results of several studies indicate that Mg 

induces antidepressant and anxiolytic-like effects in mice without 

development of tolerance to these actions, which is suggestive of 

its potential antidepressant and anxiolytic activity. 9,23 The fetus and 

placenta absorb huge amounts of nutrients, particularly Mg, from 

the mother and loss of Mg is hypothesized to be a contributing factor 

in the development of PPD. 24 

Thiamine (Vit B 1 ) de 

and hyperemesis gravidarium. This condition shows a high percentage 

of aggressiveness, confusion, memory impairments, and 

depressive behaviors in animal models of Vit B 1 deficiency where 

antidepressants such as imipramine can suppress this depressive

ehavior. 25,26 

Oxidative stress is the imbalance between oxidative and antioxidative 

systems in favor of the former and has been implicated in 

the pathophysiology of several neuropsychiatric diseases, including 

major depressive disorder. A measurement of total antioxidant 

capacity (TAC) can provide information about overall antioxidant 

status which may include those antioxidants not yet recognized or 

not easily measured. 27,28 

Despite the high prevalence of PPD, up to half of the cases of 

postpartum disorders remain undiagnosed or untreated. 29 Although 

women with PPD may seek psychotherapy as an initial treatment, 

it is not always effective. Those with severe symptoms may need 

antidepressant therapy, but the high cost and side effects of antidepressant 

drugs remain important treatment obstacles for many. 30,31 

Many women choose nonpharmacological interventions, due to 

the potential transmission of drugs into breast milk and fear of addiction 

or drug dependence. 32 As mentioned above, a single administration 

of Zn and Mg improves depression and anxiety-related 

behavior. In addition, based on the literature and our pilot study, 

Vit B 1 has been shown to have antidepressant and anxiolytic effects. 

Therefore, the aim of the present study was to evaluate the 

therapeutic effects of different combinations of Zn, Mg, and Vit 

B 1 on an animal model of PPD. We assessed depressant-like and 

anxiety-like behaviors, as well as TAC. 


Figure 1. Percentage of time spent in open arms (A) and number of entries (%) into open arms (B) 

of the elevated plus-maze (EPM) measured during 5 minutes. 1: Saline, 2: Sesame oil, 3: PWD, 4: 

Zn+Mg, 5: Zn+Vit B 1 , 6: Mg+Vit B 1 , and 7: Zn+Mg+Vit B 1. Treatment doses are as follows: saline (2 

ml/kg); sesame oil (2 ml/kg); progesterone (5 mg/kg); Zn: (30 mg/kg); Mg (30 mg/kg); Vit B 1 (50 mg/ 

kg). Columns represent the mean±SEM (n=10 per group). P

Figure 2. Immobility time in the forced swim test (FST) of 7 groups of mice. Immobility time was 

measured over 4 minutes. 1: Saline, 2: Sesame oil, 3: PWD, 4: Zn+Mg, 5: Zn+Vit B1, 6: Mg+Vit 

B1, and 7: Zn+Mg+Vit B1. Treatment doses are as follows: saline (2 ml/kg), sesame oil (2 ml/kg), 

progesterone (5 mg/kg), Zn (30 mg/kg), Mg (30 mg/kg), and Vit B1 (50 mg/kg). Columns represent the 

mean±SEM (n=10 per group). P

Groups TAC (nmol/mg protein) 

Salineª 208 ± 0.032 

Sesame oilª 207 ± 0.021 

Progesterone b 169 ± 0.054 

Zn+Mg c 195 ± 0.052 

d Zn+Vit B1 184 ± 0.047 

d Mg+Vit B1 181 ± 0.043 

a Zn+Mg+Vit B1 206 ± 0.071 

Data are expressed as mean±SEM (n=10 per group). a-d: Different letters have statistically significant differences (P

Oxidative stress occurs as a consequence of an imbalance between 

the formation of oxygen-free radicals and inactivation of 

these species by an antioxidant defense system. 53 Oxidative stress 

has been found in pregnant mothers. It is well known that pregnancy 

is itself a state of oxidative stress arising from the increased 

metabolic activity in placental mitochondria and the reduced scavenging 

power of antioxidants. 54 Reactive oxygen species are implicated 

in the pathogenesis of various neuropsychiatric disorders, 

including major depression. 55 Major depression is associated with 

increased levels of serum superoxide dismutase (SOD), serum, 

and erythrocyte malondialdehyde (MDA), and decreased levels of 

plasma ascorbic acid. 56,57 Changes in antioxidative parameters can 

serve as a characteristic element of depression and help to assess 

the effects of pharmacological treatment. 58 

Antioxidant capacity can be defined as the ability of a compound 

to reduce pro-oxidant activity. It appears that TAC is tightly regulated 

in serum or plasma in neurological disorders, however, some 

studies have failed to demonstrate this. Sofic and colleagues did not 

find significant differences in total serum antioxidant capacity in 

patients with Parkinson’s and Alzheimer’s diseases, amyotrophic 

lateral sclerosis (ALS), depression and schizophrenia when compared 

to healthy control subjects. 59 In agreement with our results, 

Cumurcu and colleagues have reported that the serum total oxidant 

status (TOS) and oxidative stress index (OSI: ratio of TOS to TAC) 

were significantly higher along with a significantly lower TAC in 

the pre-treatment stage in major depressive disorder (MDD) patients 

compared to the healthy control group. Serum TOS and OSI 

significantly decreased, whereas TAC significantly increased in the 

post-treatment stage compared to the pre-treatment stage in MDD 

patients. 27 

Oxidative stress conditions can also induce excessive NO production 

by activating inducible NOS activity. NO reacts rapidly 

with reactive oxygen species (ROS) leading to protein nitration 

and vascular cell injury. 60 

PPD and anxiety are important concerns for the mother, infant, 

and family. Based on our findings, acute administration of combined 

Zn, Mg, and Vit B 1 3 days after delivery improved depressive 

symptoms and anxiety-like behavior. Our findings in the evaluation 

of TAC have confirmed this hypothesis. However we have 

investigated only TAC while more tests, such as SOD and MDA 

could have been performed to better analyze the changes in the 

antioxidant system. We suggest that oral administration of these 

elements along with other trace elements and vitamins should be 

investigated in future studies. The dosages in this study are for 

mice and their appropriateness for humans should be examined. 

Possible pharmacokinetic interactions between Zn, Mg, and Vit B 1 

need to be further investigated for safety considerations. 


The authors wish to express their appreciation to Drs. Shadan, 

Beckley, Dehpour, and Zandieh, in addition to Ms. Zaree and Ms. 

Fatehi for their kind help and Dr. Nategh for his cooperation. This 

study was supported by a grant from Tehran University of Medical 

Sciences, Tehran, Iran. 

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Microbial Susceptibility, Virulence Factors, and Plasmid Profiles 

of Uropathogenic Escherichia coli Strains Isolated from Children 

in Jahrom, Iran 

Shohreh Farshad PhD• 1 , Reza Ranjbar PhD 2 , Aziz Japoni PhD 1 , Marziyeh Hosseini MSc 1 , Mojtaba Anvarinejad MSc 1 , Reza Mohammadzadegan 

PhD 3 

Abstract 

Background: Urinary tract infections (UTIs), including cystitis and pyelonephritis, are the most common infectious diseases in childhood. 

Escherichia coli (E. coli) accounts for as much as 90% of the community-acquired and 50% of nosocomial UTIs. Therefore, identification 

of E. coli strains is important for both clinical and epidemiological implications. Understanding antibiotic resistance patterns and molecular 

characterization of plasmids and other genetic elements is also epidemiologically useful. 

Methods: To characterize uropathogenic strains of E. coli, we studied 96 E. coli strains recovered from urine samples of children aged 

1 month to 14 years with community-acquired UTIs in Jahrom, Iran. We assessed virulence factors (VFs), drug sensitivities, and plasmid 

profiles. 

Results: Drug sensitivities of the isolates were: 19.8% (ampicillin), 24% (trimethoprim-sulfamethoxazole), 29.2% ( tetracycline), 75.5% 

(nalidixic acid), 80.4% (cefixime), 84.6% (gentamicin), 91.4% (ciprofloxacin), 96.8% (nitrofurantoin), 96.8% (amikacin) and 100% (imipenem). 

Totally, 76 isolates harbored plasmids with an average of 5.5 plasmids (range: 1 – 10) in each strain. Plasmid profiling distinguished 22 different 

E. coli genotypes in all isolates that ranged in similarity from 50% to 100%. PCR showed that the prevalence of virulence genes ranged 

from 15.62% for hly to 30.2% for pap. 

Conclusion: These data mandate local monitoring of drug resistance and its consideration in empirical therapy of E. coli infections. Plasmid 

analysis of representative E. coli isolates also demonstrates the presence of a wide range of plasmid sizes, with no consistent relationship 

between plasmid profiles and resistance phenotypes. Plasmid profiles distinguished more strains than did the antimicrobial susceptibility 

pattern. 

Keywords: E. coli, plasmid, UTI, virulence genes 

Cite this article as: Farshad S, Ranjbar R, Japoni A, Hosseini M, Anvarinejad M, Mohammadzadegan R. Microbial Susceptibility, Virulence Factors, and Plasmid 

Profiles of Uropathogenic Escherichia coli Strains Isolated from Children in Jahrom, Iran. Arch Iran Med. 2012; 15(5): 312 – 316. 


Escherichia coli (E. coli) is one of the most important causes 

of community-acquired and human nosocomial infections. 

The organism is therefore of clinical importance and can be 

isolated from various clinical specimens. 1 Urinary tract infections 

(UTIs), including cystitis and pyelonephritis, are the most common 

infectious diseases in childhood. E. coli accounts for as much as 

90% of the community-acquired and 50% of the nosocomial 

UTIs. 2,3 

The pathogenic potential of E. coli strains is thought to be dependent 

on the presence of virulence factors (VFs), 4 which are located 

on large plasmids and/or in particular regions, called ‛pathogenicity 

islands’ (PAIs), on the chromosome. 5,6 Identification of E. coli 

strains is important for both clinical and epidemiological implica- 

Authors’ Affiliations: 1 Alborzi Clinical Microbiology Research Center, Shiraz 

University of Medical Sciences, Shiraz, Iran, 2 Molecular Biology Research Center, 

Baqiyatallah University of Medical Sciences, Tehran, Iran, 3 Interdisciplinary 

Nanoscience Center (INANO), Århus University, Århus, Denmark 

•Corresponding author and reprints: Shohreh Farshad PhD, Alborzi Clinical 

Microbiology Research Center, Shiraz University of Medical Sciences, Nemazee 

Hospital, Shiraz 71937-11351, Iran. Tel: +98 711 6474294, 

Fax: +98 711 6474303, E-mail:farshads@sums.ac.ir 


tions. Understanding antibiotic resistance patterns and molecular 

characterization of plasmids and other genetic elements is also 

epidemiologically useful. Antibiotic susceptibility is reported to be 

dynamic in bacteria, and it differs according to time and environment. 

7 Therefore, there is a need for periodic screening of common 

bacterial pathogens to determine their antibiotic susceptibility 

profiles in different communities. 1 Comparing plasmid profiles 

is a useful method to assess the possible relatedness of individual 

clinical isolates of a particular bacterial species for epidemiological 

studies. 8 

The present study isolated E. coli strains from clinical samples of 

patients with UTIs who resided in Jahrom, a city in southern Iran. 

Strains were isolated by culture methods and characterized by the 

appropriate biochemical, serological, and antibiogram tests. In this 

study, we performed molecular techniques such as plasmid profile 

analysis and PCR. This study also investigated the reliability of 

drug sensitivity patterns and plasmid profiles in the discrimination 

of E. coli strains isolated from UTI epidemics. 


S. Farshad, R. Ranjbar, A. Japoni , et al. 

Patients and bacterial isolation 

E. coli strains were isolated from urine samples of children aged 

l month to 14 years, who presented at Motahari Hospital, Jahrom,

Table 1. Antibiotic sensitivity of E. coli strains isolated from children with UTI 

Antibiotic Sensitivity n (%) 

Ampicillin 19 (19.8) 

Trimethoprim- Sulfamethoxazole 23 (24) 

Tetracycline 28 (29.2) 

Nalidixic acid 72 (75.5) 

Cefixim 77 (80.4) 

Gentamicin 81 (84.6) 

Ciprofloxacin 88 (91.4) 

Nitrifurantoin 93 (96.8) 

Amikacin 93 (96.8) 

Imipenem 96 (100) 

Table 2. Prevalence of virulence genes in E. coli strains isolated from different groups of children with UTI. 

Virulence genes 

Clinical findings (%) Kidney ultrasound (%) Sex (%) 

Pyelonephritis Cystitis Normal Abnormal Male Female 

pap 

+ (%) 

- (%) 

66.7 

46.5 

33.3 

53.5 

62.5 

54.5 

37.5 

45.5 

41.7 

33.3 

58.3 

66.7 

sfa 

+ (%) 

- (%) 

62.5 

50 

37.5 

50 

33.3 

59.3 

66.7 

40.7 

33.3 

35.9 

66.7 

64.1 

cnf-1 

+ (%) 

- (%) 

63.6 

48.7 

36.4 

51.3 

16.7 

72.4 

83.3 

27.6 

35 

35.7 

65 

64.3 

h ly 

+ (%) 

- (%) 

85.7 

47.1 

14.3 

52.9 

100 

61.8 

0 

38.2 

50 

333.3 

50 

66.7 

Iran. E. coli isolates were identified by standard methods. 9 The 

exclusion criteria were recent antibiotic use during the past 28 

days and nosocomial infections, defined as infections 48 h postadmission 

or within 4 weeks following a previous discharge. Positive 

urine cultures were defined by the growth of a single colony 

morphotype with counts > 10 5 colony forming unit/ml. 

Susceptibility testing 

Susceptibility of all the isolates to different antibiotics was determined 

by the disk diffusion method, as recommended by the 

National Committee for Clinical Laboratory Standards. 10 Commercial 

antimicrobial disks (Mast Co., UK) used in this study 

were: ampicillin (10 µg), nalidixic acid (30 µg), cefixime (5 µg), 

gentamicin (10 µg), nitrofurantoin (300 µg), ciprofloxacin (5 µg), 

amikacin (30 µg), and imipenem (10 µg). E. coli ATCC 25922 was 

used for quality-control purposes. 

Preparation of bacterial DNA 

DNA to be amplified was extracted from the whole organisms 

by boiling. Bacteria were harvested from 1.5 ml of an overnight 

Luria-Bertani broth culture, suspended in sterile distilled water, 

and incubated at 95 o C for 10 min. Following centrifugation of 

the lysate, the supernatant was stored at -20 o C as a template DNA 

stock. DNA from uropathogenic E. coli strain J96 was extracted 

and used as a positive control in our PCR reaction. 

Detection of virulence factors (VFs) 

Detection of pap, sfa, cnf-1, and hly genes was performed by 

gene amplification using Multiplex-PCR. The primer sequences 

were previously reported 11 and obtained from TIB MOLBIOL 

Syntheselabor GmbH (Berlin, Germany). Descriptions and sequences 

of the PCR primers used in this study are presented in 

Table 1. Other enzymes and chemicals were provided by Cinnagen 

Chemical Company (Tehran, Iran). The amplification steps 

were accomplished based on methods described by Yamamoto et 

Molecular characterization of E. coli 

al. using a thermal cycler (Eppendorf, Germany). 12 Negative control 

reactions with distilled water were performed with each batch 

of amplification to exclude the possibility of any contamination. 

Expected sizes of the amplicons were ascertained by electrophoresis 

in 1.5% agarose gel with an appropriate molecular size marker 

(100 bp DNA ladder, MBI, Fermentas, Lithuania). 

Plasmid DNA extraction 

Plasmid DNA was extracted from E. coli strains according to the 

alkaline lysis method by Brinboim and Doly (1979). 13 Extracted 

plasmid DNA was separated by horizontal electrophoresis in an 

0.8% agarose slab gel in tris-acetate EDTA (TAE) buffer at room 

temperature at 60 V for 4 h. Using ethidium bromide, the gel was 

stained after electrophoresis and video images were prepared by a 

gel documentation system. The molecular mass of the unknown 

plasmid DNA was assessed by comparing plasmid mobilities with 

the known supercoiled DNA ladder (Gibco-BRL, England). The 

Photo Capt Mw program was used to determine the molecular 

weight of plasmid bands and analyze plasmid profiles. 

Analysis of similarity among strains and construction of a dendrogram 

Similarities among the isolates as based upon plasmid profiles 

were analyzed by Numerical Taxonomy and Multivariate Analysis 

System software (NTSYS-PC ver. 2.02) for dendrogram construction. 

The matrix of similarity of coefficients was subjected to unweighted 

pair-group method analysis (UPGMA) to generate dendrograms 

using the average linkage procedure. 


Statistical analysis was performed using SPSS software for Windows, 

ver.15 (SPSS, IBM, USA). Chi-square was used to evaluate 

the variables correlation. P values less than 0.05 were considered 

significant. 


Results 

Patients and E. coli strains 

Totally, 96 strains of E. coli were isolated from children with 

UTI, aged 1 month to 14 years (mean 21.8 ± 26.9 months). There 

were 60 females (62.5%) and 36 males (37.5%). Among patients, 

46.6% had cystitis and 53.3% were diagnosed with acute pyelonephritis, 

which was more prevalent in girls (63.2% vs. 36.4%, p 

= 0.04). Only 37 patients underwent kidney sonography. Fourteen 

cases had abnormal findings that included reflux, UPJ stenosis, 

multicystic kidney, and single kidney. 

Antibiotic susceptibility analysis 

As shown in Table 1, drug sensitivities of the isolates were: 

19.8% (ampicillin), 75.5% (nalidixic acid), 80.4% (cefixime), 

84.6% (gentamicin), 91.4% (ciprofloxacin), 96.8% (nitrofurantoin), 

and 96.8% (amikacin). Sensitivity to imipenem was 100%. 

Multiple resistance to ampicillin, gentamicin, nalidixic acid, and 

cefixime were seen in 2.1% of the isolates, but no case of multidrug 

resistance to all drugs was detected. Only 12.5% of the strains 

were susceptible to all tested antibiotics. The remaining strains 

were resistant to one or more antibiotics. 

Detection of E. coli virulence genes by PCR assay 

PCR assay showed that the prevalence of virulence genes ranged 

from 15.62% for hly to 30.2% for pap. Of the studied toxin coding 

genes, cnf-1 (22.91%) was more prevalent than hly (15.62%). For 

the adhesion coding genes, pap (30.2%) was more prevalent than 

sfa (18.75%). There were 67 (69.8%) strains that were negative 

for the virulence genes. 

Figure 1. Plasmid patterns of some representative uropathogenic E. coli 

strains. 

Plasmid profile analysis 

Analysis of plasmid DNA revealed that, totally, 76 isolates harbored 

plasmids with an average of 5.5 plasmids (range from 1 – 

10) in each strain. Figure 1 shows the plasmid patterns of some 

representative strains of the isolates. Plasmid sizes ranged from 1 

to 33 kb in the isolates. The plasmids with the sizes of 4-5 kb were 


the most frequent plasmids, and were seen in about 28.94% of the 

isolates, while plasmids of 11 – 12 kb, 21 – 22 kb, 26 – 27 kb, and 

29 – 30 kb were detected in only 1.31% of the isolates. 

Genetic similarity among the isolates 

The genetic similarities among the 76 E. coli strains based on 

their plasmid patterns are represented by the dendrogram shown 

in Figure 2. 

Discussion 


Frequent irrational use of antibiotics changes the intestinal flora, 

leading to bacterial resistance. 14 In this study we observed a high 

incidence of antibiotic resistance among the uropathogenic Escherichia 

coli strains. Although resistance to tetracycline was high 

(70.8%), ampicillin (80.2%) was the most resistant, followed by 

trimethoprim-sulfamethoxazole (76%). High levels of resistance 

to tetracycline, ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol 

and sulphonamide have also been reported in other 

studies. 15–17 In a previous study in Shiraz, Iran, high levels of resistance 

to ampicillin (63%), trimethoprim-sulfamethoxazole (48%), 

and tetracycline (57%) were documented among E. coli strains obtained 

from urine samples. 18 However, the incidence of resistance 

to these antibiotics was higher in our UPEC strains compared to 

the Shiraz study. As Jahrom is a small city located southeast of 

Shiraz, the increase in antibiotic resistance observed in this study 

could be due to an irrational consumption of antibiotics and food 

from animals that have received antibiotics, transmission of resistant 

isolates among people, self-medication, and noncompliance 

with medication. 

No resistance to imipenem was observed in the studied isolates. 

A high sensitivity of E. coli strains to imipenem has been previously 

reported. 16,18–21 It seems this antibiotic can serve as a medication 

of choice for the treatment of UTI caused by E. coli. However, 

it should be noted that unlimited use of a medicine can gradually 

lead to rising antibiotic resistance. 

Resistance to nalidixic acid and chloramphenicol in our isolates 

was lower than that observed in studies performed in other parts of 

the world. 16,17 

In the present study, it has also been shown that resistance to ciprofloxacin 

(8.3%), norfloxacin (8.3%), nitrofurantoin (3.1%), and 

amikacin (3.1%) was low among the UPEC isolates. Shao et al. 22 

have shown that amikacin and nitrofurantoin are the most effective 

treatments in children with UTI in China, which could be explained 

by the low numbers of prescriptions of these antibacterial 

agents for UTI. Thus, they could be used as effective therapy for 

children in our area. 

A high incidence of multidrug resistant (MDR) strains was also 

detected among the present isolates. About 77% were resistant to 3 

or more tested antibiotics. The level of MDR among UTI isolates 

varies from country to country. For example, it was reported to be 

7.1% in the USA, 24,25 while 42% of the UPEC isolates in Slovenia 

in 2006 were MDR. 17 MDR causes major consequences such 

as empirical therapy of E. coli infections as well as possible coselection 

of antimicrobial resistance mediated by MDR plasmids. 

The WHO guidelines recommend trimethoprim-sulfamethoxazole 

and ampicillin as the first choice for UTI treatment. 26 In contrast, 

as revealed in the present study, these two antibiotics cannot serve 

as treatment of choice in our region.

Figure 2. Genetic similarities among 76 E. coli strains based on their plasmid patterns. 

Antibiotic resistance among bacteria can occur via plasmids. 

Transmission of specified characterization through plasmids (vertical 

and horizontal) is better than that through a particular bacterial 

clone. In this research, to reveal the clonality of UPEC strains 

isolated from community-acquired UTIs, the plasmid patterns of 

the isolates were investigated. 

The results showed that 76 (79%) of the isolates harbored an average 

of 5.5 plasmids. Other reported results agreed with our study. 

Woo-Joo et al. have reported that 87.5% and 72% of UPEC strains 

carried plasmids. 27 In another study undertaken by Fluit, the prevalence 

of plasmid in the isolates was 81%, which was also similar 

to our results. 28 

In the present study, the range of plasmids was 1-10 while Malkawi 

has reported the numbers of plasmids to be approximately 

1 – 6 in E. coli strains. 29 

Molecular weights of the plasmids were between 1-33 kb. In a 

research conducted by Malkawi, the plasmid sizes were from 1.5 

– 54 kb. 29 Tsen has reported a range of 2 – 22 kb for plasmid 

sizes. 30 Danbara et al. have also reported plasmid size variations 

between 3.9 kb and 50 kb in E. coli strains. 31 We detected plasmid 

weight ranges of 11 – 12 kb, 21 – 22 kb, 26 – 27 kb, and 

29 – 30 kb in only 1.31% of the isolates. Those with 4-5 kb were 

the most frequent plasmids, seen in about 28.94% of the isolates 

and among the strains resistant to the medicines under the study. 

These data show that the former plasmids have a lower stability 

in comparison with 4 – 5 kb plasmids. As ampicillin showed the 

most resistance, therefore we have suggested that the gene coding 

for ampicillin resistance could be located on this plasmid. On the 

other hand, 21% of our isolates have no plasmids, yet they were 

resistant to a large number of antibiotics. Possibly, some antibiotic 

resistance genes may not be located in the plasmid but may be 

on the bacterial chromosome. In order to prove the relationship 

between the plasmid and its resistance, additional studies such as 

plasmid curing and transferring of the plasmid to other known bac- 

Molecular characterization of E. coli 

teria should be performed. Similarity among isolates on the basis 

of the plasmid profile was also analyzed by NTSYS-PC ver. 2.02K 

software (Figure 2). As seen in the dendrogram, similarities ranged 

from 50% to 100%. Plasmid profiling could distinguish 22 different 

E. coli genotypes in all isolates named A1-A22. Pattern A1 has 

included 31 isolates with 100% similarity and pattern A2 has 14 

isolates with 100% similarity. It seems that patients with E. coli 

strains with each of these two models of plasmid patterns are likely 

to obtain the sources of the bacteria from a clone with a high incidence 

of bacterial gene transfer in the community. According to the 

data shown in Table 2, plasmid profiles distinguished more strains 

than did the antimicrobial susceptibility pattern. 

Saif and Umolu reported a high prevalence of plasmids in antibiotic 

resistant E. coli strains isolated from animals. 1,32 In Jahrom, 

most people are in close contact with animals, thus it could be suggested 

that animals may be a source for antibiotic resistant gene 

dissemination. 

In an attempt to investigate the prevalence of 4 important VFs, 

cnf-1, sfa, pap and hly, in resistant compared to susceptible uropathogenic 

E. coli strains isolated from urine samples of children 

with UTI, we found that pap operon was, as expected, the most 

prevalent virulence factor identified. Regarding pap, pooled results 

with the present data indicated a crucial role of this virulence factor 

in E. coli-associated UTI. 33,34 It has recently been shown that 

the transformation of E. coli with pap sequences is sufficient to 

convert it to a more potent host response inducer, with P fimbriae 

lowering the significant bacteriuria threshold. 35 The distribution of 

the sfa operon found among studied strains was also similar to previously 

reported data. The prevalence of hly among the collected 

clinical isolates also matched those reported by other investigators. 

4,35 However, in our study, the cnf-1 operon was more prevalent 

than in other studies. 4,11,35 Possibly, the cnf-1 gene played an 

important role in UTI in our study. 

In conclusion, the high incidence of MDR strains detected among 


the present isolates mandate local monitoring of resistance and its 

consideration in empirical therapy of E. coli infections, particularly 

those which cause UTIs. We found that pap operon was, as expected, 

the most prevalent virulence factor identified. Plasmid analysis 

of representative E. coli isolates also demonstrated the presence 

of a wide range of plasmid sizes, with no consistent relationship 

between plasmid profiles and resistant phenotypes. A common 

large plasmid with a molecular size of 28 kb was responsible for 

transferring partial resistance. In our study, plasmid profiles distinguished 

more strains than the antimicrobial susceptibility pattern. 


This work was supported by research grant #83-14 from Professor 

Alborzi Clinical Microbiology Research Center, Shiraz University 

of Medical Sciences. The authors wish to thank Dr. Fatemeh 

Emmamghorashi for her assistance with sample collection and Dr. 

Hassan Khajehi for his editorial assistance. 

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Brief Report 

A Report of the Injuries Sustained in Iran Air Flight 277 that 

Crashed near Urmia, Iran 

Ahmadreza Afshar MD• 1 , Majid Hajyhosseinloo MD 2 , Ali Eftekhari MD 2 , Mir Bahram Safari MD 1 , Zahra Yekta MD 3 

Abstract 

Background: On January 9, 2011 Iran Air Flight 277 crashed during approach to Urmia, Iran. Out of 105 passengers, 27 survived. This 

brief report presents a perspective of the passengers’ sustained injuries. 

Methods: We reviewed the recorded injuries of all passengers as provided by the Legal Medicine Organization authorities. The Injury 

Severity Score (ISS), an anatomical scoring system, was used to provide an overall code for those who survived with multiple anatomical 

injuries. 

Results: There were a total of 96 ISS body region injuries among those who survived. Facial injuries (83%) were the most frequent injuries 

noted among fatalities, which was statistically significant (P = 0.000). In those who survived, injuries to the head and neck (37%) and 

facial (33%) regions were relatively less frequent than other anatomical regions. The most serious injuries among survivors belonged to the 

extremity (85%) region, particularly lower limb fractures (62%). Differences in extremity injuries between the survivors and fatalities were not 

statistically significant. 

Conclusion: The findings of this study were similar to other studies where the most frequent serious injuries were fractures of the extremities, 

particularly the lower limbs. 

Keywords: Abbreviated injury scale, airplane crash during approach, injury severity score, mass casualty incidents 

Cite this article as: Afshar A, Hajyhosseinloo M, Eftekhari A, Safari MB, Yekta Z. A Report of the Injuries Sustained in Iran Air Flight 277 that Crashed near Urmia, 

Iran. Arch Iran Med. 2012; 15(5): 317 – 319. 


A irplane 

‛ 

crash during approach’ is defined as an emergency 

landing under circumstances where a normal landing is 

impossible. Usually the airplane is damaged, the circumstances 

are not under the pilot’s control and a runway is not available. 

1,2 Usually, because of extensive damage and fire, airplane 

crash accidents do not lend themselves to an extensive analysis of 

the occupants’ injuries. Therefore there is limited detailed analysis 

of such accidents. 3–6 

On January 9, 2011 Iran Air Flight 277, a Boeing 727, crashed 

during approach about 5 miles from the Urmia airport runway at 

19:40 pm local time. Fortunately, the airplane did not catch on fire; 

thus, this facilitated the identification and examination of victims. 

However, heavy snow and thick fog made the rescue activities difficult 

(Figure 1). 

This brief report presents a perspective of the flight passengers’ 

sustained injuries. 


Of the 105 passengers on this flight, 27 survived and 78 died. The 

Authors’ Affiliations: 1 Department of Orthopedics, Urmia University of Medical 

Sciences, Urmia, Iran, 2 Legal Medicine Organization, West Azarbaijan, Urmia, 

Iran, 3 Department of Community Medicine, Urmia University of Medical 

Sciences, Urmia, Iran. 

•Corresponding author and reprints: Ahmadreza Afshar MD, Urmia University 

of Medical Sciences, Department of Orthopedics, Imam Khomeini Hospital, 

Modaress Street, Ershad Boulevard, Urmia, Iran. Tel: +989123131556, 

Fax: +984413469939, E-mail: afshar_ah@yahoo.com. 


Injuries Sustained in Iran Air Flight 277 

legal medicine authorities examined all passengers and recorded 

their injuries. 

Autopsies were performed on the 3 cockpit crew who perished. 

However, passengers who died were not autopsied and X-ray examinations 

were not performed to detect occult skeletal fractures. 

The examinations of those killed were limited to the clinical appearance 

and obvious external body region injuries. Death certificates 

were issued because of multiple injuries. Injuries of the 

survivors were registered according to hospital in-patient records. 

We reviewed the documented examinations from the legal medicine 

authorities for all passengers. We used the Injury Severity 

Score (ISS), which is an anatomical scoring system, to provide an 

overall code for patients with multiple anatomical injuries. The 

ISS is a process by which complex and variable patient data is reduced 

to a single number. To calculate an ISS for an injured person, 

the body is divided into 6 ISS body regions, which are: head and 

neck (including cervical spine); face (including the facial skeleton, 

nose, mouth, eyes and ears); chest (including thoracic spine and 

diaphragm); abdomen or pelvic area (including abdominal organs 

and lumbar spine); extremities or pelvic girdle (including pelvic 

skeleton); and external (skin). Each injury in the body region is 

ranked according to the Abbreviated Injury Scale (AIS). AIS classifies 

each injury according to its relative severity on a 6 ordinal 

scale: 1 (minor), 2 (moderate), 3 (serious), 4 (severe), 5 (critical), 

and 6 [maximal (currently untreatable)]. We used only the highest 

AIS number for each body region. To calculate a final ISS code, 

the 3 most severely injured ISS body regions have their AIS score 

squared and added together to produce the ISS code. The ISS 

ranges from 1 to 75. Severity of each patient’s injuries is classified 

according to the ISS code: 1 – 8 (minor), 9 – 15 (moderate), and 16 


and above (serious). 7–9 

Fisher’s exact test was used to for data analysis and P values less 

than 0.05 were considered statistically significant. 

Results 

There were 27 survivors, of which all were adults. There were no 

pre-or in-hospital deaths. All passengers (survivors and fatalities) 

sustained multiple anatomical region injuries. Table 1 presents the 

AIS (range: 1 to 6) of the 6 ISS body regions and the ISS codes of 

the 27 survivors. Except for one individual, all survivors sustained 

more than one ISS body region injury and a total of 96 ISS body 

region injuries were recorded. The mean ISS code was 23 (1 to 41). 

Among survivors, 18 (67%) had severe injuries, 7 (27%) had 

moderate, and 2 (7%) had minor injuries according to the severity 

of the ISS codes. 

Of those who died, 65 (83%) out of 78 had facial injuries which 

were the most frequent obvious injuries. The difference in facial 

region injuries between survivors (33%) and fatalities (83%) was 

statistically significant (P = 0.000). Among survivors, injuries to 

the head and neck (37%) and facial (33%) regions were relatively 

less frequent than other anatomical regions. The most frequent 

injuries among survivors were external (100 %) and extremities 

(85%) body regions. However the external injuries consisted of 

swellings, bruises, abrasions, and superficial lacerations, all of 

which were minor injuries (AIS 1) that did not substantially impact 

the final ISS codes. From 27 survivors, 17 (62%) sustained lower 

limb fractures which were the most frequent site for extremities 

injuries. The difference in extremity body region injuries between 

the survivors and fatalities was not statistically significant. Among 

survivors, 16 (59%) out of 27 sustained fractures to their spinal 

columns, which were at different levels. Spinal injuries were included 

in the head and neck, abdominal, and thoracic ISS body 

regions. 

Only 4 out of the 27survivors sustained internal injuries to their 

abdominal organs. 

The 4 recorded abdominal injuries consisted of the 3 cockpit 

crew who were autopsied and one passenger who had extruded 

abdominal organs. Since fatalities were not autopsied, some fatal 


Figure 1. Cockpit of the Boeing 727 that crashed near Urmia on January 9, 2011. 

intra-abdominal, intra-thoracic, brain contusion and concussion injuries 

were not recorded. Therefore comparative analyses for these 

body regions were not an accurate reflection of this difference. The 

3 cockpit crew sustained the most severe and extensive injuries in 

all 6 ISS body regions. 

Discussion 

A. Afshar, M. Hajyhosseinloo, A. Eftekhari, et al. 

In airplane crashes, injuries are produced by horizontal, vertical, 

and transverse force axes. Head, neck, facial, and thoracic injuries 

occur when the transmitted horizontal deceleration force exceeds 

the limits of the human body’s tolerance to abrupt deceleration. 

The vertical deceleration force produces spinal fractures. Bending 

and torsional forces produce fractures in the extremities. However, 

combinations of different forces in 3-dimensional space produce 

many complex mechanisms for injuries. 4 

In 1968 Zanca reported an airplane crash accident in which 21 

of 66 occupants survived. In that accident the registered injuries 

among survivors in order of frequency were: abrasions, wounds 

and contusions, fractures, shock or impending shock, internal injuries, 

and concussions. Most fractures occurred in the lower limbs. 6 

Carter et al., in 1973, reported a total number of 203 injuries for 

all passengers of an airplane crash. Fractured extremities, which 

comprised 79 (39%) out of 203 total injuries, were the most frequent 

seen among victims. 4 

On February 25, 2009 Turkish Airline Flight 1951 crashed during 

approach to Schipol Airport, Amsterdam. Of the 135 passengers, 

9 including the 3 cockpit crew died, 11 had serious injuries, 22 had 

moderate injuries, 87 had minor injuries, and 6 were uninjured. A 

total of 297 ISS body region injuries were recorded, of which most 

were to the head, face, spine, and extremities. 3,5 

The findings of the current study were similar to previous reports 

on survivors 3–6 in which the most frequent serious injury was fracture 

of the extremities, especially in the lower limbs. 

In the current study, the cockpit crew who perished sustained 

extensive injuries in all 6 ISS body regions, which was similar 

to other reports. 3–6 It seems that the cockpit crew are at the most 

endangered position. Therefore, improvements in cockpit design 

might reduce and protect the crew from extensive injuries.

Table 1. AIS of 6 ISS body regions and final ISS codes in survivors. 

Cases Number 

ISS body regions 

Head and neck Face Chest Abdomen Extremity External ISS code 

1 3 0 0 0 0 1 10 

2 0 0 0 0 3 1 10 

3 0 0 0 3 3 1 19 

4 2 1 0 3 4 1 29 

5 0 0 0 0 3 1 10 

6 0 0 4 4 3 1 41 

7 0 1 3 0 3 1 19 

8 0 1 3 3 4 1 34 

9 2 0 3 0 4 1 29 

10 0 0 0 0 0 1 1 

11 4 1 3 3 0 1 34 

12 0 0 3 0 4 1 26 

13 0 0 4 3 3 1 34 

14 0 0 0 0 3 1 10 

15 3 0 0 0 0 1 10 

16 0 0 4 3 3 1 34 

17 0 0 0 0 2 1 5 

18 2 0 3 0 3 1 22 

19 1 2 4 4 3 1 41 

20 3 0 3 0 4 1 34 

21 0 1 0 3 4 1 26 

22 4 0 3 3 4 1 41 

23 0 0 0 0 3 1 10 

24 0 1 0 3 4 1 26 

25 4 3 4 3 3 1 41 

26 0 0 0 3 2 1 14 

27 0 1 0 3 3 1 19 

AIS: Abbreviated Injury Scale (1- minor; 2- moderate; 3- serious; 4- severe; 5- critical; 6- maximal); ISS: Injury Severity Score 

In the current study we did not evaluate the relation between seat 

locations, severity of the incurred injuries, and death because the 

seating positions of all occupants were not officially available to 

the authors of this study. In addition, since about two-thirds of seats 

were occupied, it was probable that some passengers had changed 

their seats during the flight and did not occupy their assigned seats. 

A major flaw of this study was that examinations of passengers 

who perished was limited to clinical appearance and obvious external 

injuries of the anatomical body regions. Therefore we were 

unable to compare the true differences between the head and neck, 

abdomen, and chest ISS body region injuries among survivors and 

fatalities. Doubtlessly those who perished had undetected intra-abdominal, 

intra-thoracic, and cranial injuries which were more than 

their registered injuries. Evaluations of skeletal injuries would have 

been completed and the number of skeletal fractures increased if 

X-rays had been taken from the bodies of those who died. Therefore, 

it might be reasonable to suggest that in such accidents autopsies 

should be regularly performed on those who expired. 

This study might hopefully provide an understanding of the survival 

aspect of airplane crash accidents that occur during approach. 

A study of these types of injuries may provide a resource for subsequent 

research and assist investigators to make recommendations 

that reduce the occurrence of similar injuries. 

Conflict of interest 

All data in this study was provided by the Legal Medicine Organization 

in Urmia, West Azarbaijan, Iran. 

References 

Injuries Sustained in Iran Air Flight 277 

1. Emergency landing. Available from URL: http://en.wikipedia.org/ 

wiki/Emergency-landing. (Accessed: 25 June 2011). 

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com/crash+landing . (Accessed: 25 June 2011). 

3. Crashed during approach, Boeing737-800, near Amsterdam Schiphol 

Airport, 25 February 2009. Available from URL: www.ntsb.gov/aviation/Netherlands/DSB_ENG_Report.pdf. 

(Accessed: 25 June 2011). 

4. Carter JH, Burdge R, Powers SR Jr, Campbell CJ. An analysis of 17 

fatal and 31 nonfatal injuries following an airplane crash. J Trauma. 

1973; 13: 346 – 353. 

5. Winkelhagen J, Bijlsma TS, Bloemers FW, Heetveld MJ, Goslings JC. 

Airplane crash near Schiphol Airport 25 February 2009: Injuries and 

casualty distribution. Ned Tijdschr Geneeskd. 2010; 154: A1064. 

6. Zanca P. Types of injuries in air plane crash survivors. South Med J. 

1968; 61: 1219 – 1222. 

7. Injury Severity Score. Available from URL: http://en.wikipedia.org/ 

wiki/Injury_Severity_Score. (Accessed: 2 July 2011). 

8. Baker SP, O’Neill B, Haddon W Jr, Long WB. The Injury Severity 

Score: A method for describing patients with multiple injuries and evaluating 

emergency care. J Trauma. 1974; 14: 187 – 196. 

9. Baker SP, O’Neill B. The Injury Severity Score: An update. J Trauma. 

1976; 16: 882 – 885. 



I 

t has been estimated that in 2008, non-communicable diseases 

(NCDs) accounted for 36 million death worldwide, 

contributing to 63 percent of all-cause global mortalities. 1 

Without any serious action, the NCD epidemic is projected to kill 

52 million people annually by 2030. 2,3 High blood pressure has 

been reported as the leading underlying cause of as many as 7.6 

million premature global deaths and 92 million disability adjusted 

life years (DALYs) in 2001. 4 Globally, 51 percent of deaths due to 

stroke (cerebrovascular disease) and 45 percent of deaths due to 

ischemic heart disease are attributable to high systolic blood pressure. 

At any given age, the risk of dying from high blood pressure 

in low- and middle-income countries is more than double that in 

high-income countries. In the high-income countries, only 7 percent 

of deaths caused by high blood pressure occur under age 60; 

in the African Region, this figure increases to 25 percent. 5 Nearly 

80 percent of current deaths due to non-communicable diseases 

occur in low- and middle-income countries, disproving the myth 

that non-communicable diseases are mostly affecting affluent societies. 

6 

There is abundant evidence on a causal relation between salt 

intake and high blood pressure. 7–10 In a meta analysis of salt reduction 

randomized clinical trials with the median duration of 

5 weeks (ranging from 4 weeks to 3 years), for each 100 mmol 


Report 

Advocacy Strategies and Action Plans for Reducing Salt Intake in Iran 

Noushin Mohammadifard MSc 1 , Saman Fahimi MD MPhil 2,3 , Alireza Khosravi MD 1 , Hamed Pouraram PhD 4 , Sima Sajedinejad MD 5 , 

Paul Pharoah MD PhD 3 , Reza Malekzadeh MD 2 , Nizal Sarrafzadegan MD• 6 

Cite this article as: Mohammadifard N, Fahimi S, Khosravi A, Pouraram H, Sajedinejad S, Pharoah P, et al. Efficacy Advocacy strategies and action plans for reducing 

salt intake in Iran. Arch Iran Med. 2012; 15(5): 320 – 324. 

Key words: Iran, national program, non-communicable diseases, salt reduction 

Authors’ Affiliations: 1 Department of Nutrition, Hypertension Research Center, 

Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, 

Isfahan, Iran, 2 Digestive Diseases Research Institute, Tehran University of 

Medical Sciences, Tehran, Iran, 3 Department of Public Health and Primary Care, 

University of Cambridge, Cambridge, UK, 4 Department of Nutrition, Under Secretary 

for Health, Ministry of Health & Medical Education, Tehran, Iran, 5 National 

Professional Officer, World Health Organization Office in Iran, Tehran, Iran, 6 Isfahan 

Cardiovascular Research Center, Isfahan Cardiovascular Research Institute, 

Isfahan University of Medical Sciences, Isfahan, Iran. 

•Corresponding author and reprints: Nizal Sarrafzadegan MD, Isfahan Cardiovascular 

Research Center, Isfahan Cardiovascular Research Institute, Isfahan 

University of Medical Sciences, Isfahan, Iran, Cardiovascular Research Center, 

Isfahan Cardiovascular Research Institute, Sedigheh Tahereh Research Center, 

Khorram St., Isfahan, Iran, P. O. Box: 81465-1148 . Tel: +98 311 3359696, Fax: 

+98 311 3373435, Email: nsarrafzadegan@gmail.com 

Accepted for publication: 26 March 2012 

N. Mohammadifard, S. Fahimi, A. Khosravi, et al. 

reduction in 24-hour urinary excretion of sodium, there was 3.99 

mmHg reduction in systolic blood pressure (95% CI: 2.93 – 5.05) 

and 1.92 mmHg reduction for diastolic blood pressure (95% CI: 

1.26 – 2.59). 11 The increase in blood pressure leads to an increased 

risk of cardiovascular disease. 12,13 In a meta-analysis of 19 independent 

cohort samples from 13 studies, with 177,025 participants 

and average follow up of 3 years (5 – 19 years) and over 11,000 

vascular events, a higher salt intake was associated with a greater 

risk of stroke (pooled relative risk 1.23, 95% confidence interval 

1.06 – 1.43, P = 0.007) and cardiovascular disease (pooled relative 

risk 1.14, 95% confidence interval 0.99 – 1.32, P = 0.07). 14 There 

is also substantive evidence suggesting that excessive salt intake 

is also causally associated with increased risk of gastric cancer. 15 

The UN high level meeting on NCD urged member states to 

adopt urgent preventive actions to tackle the NCD’s rapidly rising 

burden. 16 It has been estimated that reducing dietary salt intake 

across populations, as a single, inexpensive, cost effective 

measure, can hugely reduce the burden of cardiovascular disease 

(CVD). 17–19 According to the World Health Organization (WHO), 

reducing populations’ salt intake is by far the most effective preventive 

approach for all countries and in all settings. 20 It has been 

estimated that reducing the salt intake at a population level can reduce 

total mortality rate, on average, by 1 – 2 percent and increase 

mean life expectancy by 1.6 months. 21 

Iran is undergoing epidemiological transition and is facing a 

rapid increase in the burden of NCDs. 22 Based on a WHO report, 

NCDs are estimated to account for 72 percent of all deaths in Iran, 

24 percent of which happens under age 60. 23 The estimated age 

standardized prevalence of hypertension was 34 percent in the 

adult population (36 percent in men and 32 percent in women). It 

has been estimated that the circulatory system diseases contributed 

to about 1,500,000 Disability Adjusted Life Years Lost (DALYs) 

in Iran in 2003. 22 Cardiovascular diseases were responsible for 45 

percent of total national mortality, while communicable diseases, 

maternal, perinatal, and nutritional conditions together contributed 

to 13 percent of total mortality in Iran in 2008. 23 So far, compared 

to infectious diseases, chronic diseases have received less attention 

in the Iranian health care system. 24 However, recently the Iranian

Year Source population 

Sample 

size 

Age range 

(years) 

ministry of health has acknowledged tackling NCDs as one of its 

priorities. 25 A road map for reducing salt intake in Iran was proposed 

in the previous issue of this journal. 26 Here, we present the 

national advocacy strategies and action plans for implementing a 

nation-wide salt reduction program that was developed by Isfahan 

Cardiovascular Research Institute (ICRI) and proposed to the Iranian 

Ministry of Health. 27 

Main steps in designing a comprehensive national salt reduction 

plan 

Creating a national salt reduction task force 

As a first step, and after initial considerations by ICRI experts, 

a steering committee was formed in 2010 in order to set out the 

priorities and devising an action plan for reducing the salt intake 

in Iran. This committee encompassed a wide range of experts engaged 

with various aspects of NCD control in Iran and included 

ICRI senior members with expertise in cardiovascular preventive 

strategies and nutrition sciences, representatives from the Health, 

and “Food and Drug” deputies of Isfahan University of Medical 

Sciences and Institute of Standard and Industrial Research of Isfahan 

province, Director General of Nutrition Department in the 

Ministry of Health, and food technologies of Isfahan University 

of Technology, an officer from the NCD branch of WHO office in 

Tehran, and delegates from the food industry. In parallel an executive 

committee was formed in 2010 in order to define target groups 

and key messages based on the decisions made by the steering 

committee. The executive committee encompassed members of 

ICRI with a wide variety of expertise including its executive director 

and heads of nutrition group; education and training unit; evaluation, 

assessment and quality control group; and IT department. 

Estimating the current salt intake in Iran 

The next step was to get the best estimate for current salt intake 

in Iran. Details of the best methods for the estimation of populations 

salt intake and current estimates of salt intake in Iran, and 

its comparison to estimates from other countries was explained 

elsewhere. 26 In brief, there have been no studies that measured 24hour 

urinary sodium excretion in a nationally representative Iranian 

sample. However, there were three 24-hour urinary sodium 

excretion studies performed in representative adult population 

samples in the city of Isfahan. Equivalent 24-hour salt excretion 

values based on 24-hour urinary sodium excretions, in the years 

1999, 2002, and 2007, were 8.2, 12.5, and 10.6 g/d, respectively. 

28,29 Assuming that about 90 percent of sodium intake is excreted 

into the urine, they correspond to salt intakes of 9.1, 13.9, and 11.8 

g/d. These values are in line with most of the countries around the 

world, in which the intakes are higher than recommended daily 

Sampling method 

Equivalent 24-hour salt 

excretion based on 24hour 

urinary excretion 

values (g/d) 

Equivalent salt 

intake (g/d) * 

1999–2000 General urban adult population 1059 20–60 Multistage random sampling 8.2 9.1 

2001–2002 General urban adult population 374 +19 Multistage random sampling 12.5 13.9 

2007 General urban adult population 806 +19 Multistage random sampling 10.6 11.8 

* Assuming that 90 percent of sodium intake is excreted into the urine 

Advocacy Strategies and Action Plans for Reducing Salt intake in Iran 

Table 1. Twenty-four hour urinary salt equivalent excretion values based on 24-hour urinary sodium excretion studies in Isfahan 

intake. 26 

Table 1 provides further details of the 24-hour urinary sodium 

excretion studies in the city of Isfahan. 

There have also been dietary sodium studies that used food frequency 

questionnaire to estimate the salt intake in the cities of 

Rasht and Sari and those residing in “Ilam province” according to 

which the average intake for the population aged 2 – 79 were 7.2, 

7.7, and 10.3 g/d, respectively. 30,31 There is a general consensus that 

the dietary estimation of salt intake considerably under-reports the 

true salt intake; data from these studies support the notion that the 

salt intake of Iranians is high. 

Setting a salt intake target 

A joint WHO/FAO working group on Diet, Nutrition and the 

Prevention of Chronic Disease suggested reducing salt intake 

to less than 5.0 g/d. 32 In the UK, the recommended salt intake is 

to be less than 6 g/d in the British adult population. 33 However, 

more recently, the UK government’s health advisory agency, the 

National Institute for Health and Clinical Excellence (NICE), has 

recommended that by the year 2025 the population’s salt consumption 

should be reduced to less than 3 g/d. 34 In the USA, it is currently 

recommended salt intake should be reduced to less than 6 

g/d for adults, with an even further reduction to less than 4 g/d 

salt for those at higher risk of developing adverse effects including 

African Americans, those with hypertension, diabetes or chronic 

kidney disease, and all adults 51 years old and older. 35 The recommended 

daily salt intake in Iran was judged to be less than 5 g/d. 27 

Getting lessons from the experiences of other countries 

With revived interest worldwide on the importance of salt reduction 

as a tool for reducing the burden of salt intake, various 

countries of the world are in the development stages of theirs salt 

reduction plan. 26,36 Currently, only a few countries worldwide have 

successful operational salt reduction plans in place. They include 

countries such as the UK, Finland, and Canada. Such activities in 

the UK led to drop of about 10 percent in average populations salt 

intake, from 9.5 g/d in 2000 to 8.6 g/d in 2008. 37 Efforts were made 

to get the lessons from the experience of such countries as well as 

those of international action alliances such as World Action on Salt 

and Health (WASH). 

Choosing the key target groups 

Based on the experience from other countries and by considering 

the role that individuals and groups can potentially play, four key 

target groups were identified: First group were those who were engaged 

in decision making processes; they included the legislative 

authorities, policy makers, and the executive authorities. Engaging 

with the above mentioned authorities would help ensuring that ap- 


1 

Decision makers 

2 Beneficiaries 

3 Partners 

4 

Potential 

opposition 

Table 2. Targets groups with current or potential impacts on a national salt reduction plan 

Legislative 

Iranian parliament’s high council for health, food security and nutrition 

authorities 

Policy makers 

Executive 

forces 

Primary 

Secondary 

General 

population 

High risk 

groups 

propriate legislations and regulations would be put into place to 

incentivize the food industry to reduce foods salt content. Second 

group were the beneficiaries engaged with salt which itself comprised 

two major sub-groups: A primary beneficiary group which 

included : a) general population and b) the high risk groups and a 

secondary group that included institutions and organization such 

as universities of medical sciences, health insurance agencies, 

ʻeducation and training organization’, and ʻwelfare and social security 

organization’. The third target group consisted of those who 

can potentially act as partners and included bodies like the Iranian 

broadcasting corporation, religious authorities, and local as well as 


Iranian parliament’s; high council for health, food security and nutrition; Minister of health; 

Vice-chancellors in health and treatment affairs of the ministry of health; Food and drug 

organization; Nutrition improvement office; Institute of standard and industrial research; 

The ministry of agriculture; Ministry of industry, mining, and commerce; Governors of the 

provinces 

The ministry of Sciences; The welfare organization; The office for monitoring supply of 

flour and bread; The health, food and drug and treatment deputies of the Isfahan university of 

medical sciences; The medical education development center of Isfahan university of medical 

sciences; Institute of standard and industrial research of Isfahan province; The office for 

industries, mining, and commerce of Isfahan province; The office for agricultural of Isfahan 

province; Organizations that provide food for their employees; Food industries; The restaurant, 

bakeries sandwich, pizza shop and nuts unions 

Children; Adolescents; Adults; The elderly 


Individuals aged more than 40 years; Those suffering from high blood pressure, CVD, 

diabetes mellitus, renal disease, osteoporosis, or some types of cancer; First degree relatives 

of individuals with high blood pressure or suffering from CVD; Individuals with overweight 

or obesity 

Medical universities; Health insurance agencies; Ministry of education; Welfare organization; 

Organizations that provide food for their employees 

National Iranian broadcasting corporation; Religious authorities; Celebrities (actors, 

sportsmen); National and local media; Isfahan university of medical sciences; The Institute 

of standard and industrial research of Isfahan province; The office for agricultural of Isfahan 

province; The office for industries, mining, and commerce of Isfahan province; The office 

for monitoring supply of flour and bread; Health sector personnel; Non-governmental 

organizations 

Producers of processed foods with high salt content; Syndicate of restaurant owners; Syndicate 

of fast food shops; Syndicate of bakers; Individuals with wrong beliefs 

Core key messages 

High blood pressure is one of the leading causes of mortality and morbidity worldwide 

Excessive salt intake causes high blood pressure 

Reducing salt intake is the most cost-effective way for reducing blood pressure 

Iranian’s salt intake is more than twice recommended 

Up to two-thirds of salt intake of Iranians comes from processed foods , and salty snacks such as potato chips 

Secondary core messages * 

Table 3. Core key messages and some of the secondary key messages for communicating salt intake reduction plan 

High blood pressure, usually has no symptoms and is therefore also called “ a silent killer” 

The recommended daily intake for salt is less than 5 grams ( less than one large teaspoon) 

High blood pressure is the most important risk factor for CVD in Iran 

Reducing salt intake will lower the blood pressure levels and decreases the chance of CVD, diabetes, osteoporosis, and some types of cancers 

Bread and cheese are the main sources of salt intake of the Iranians 

Currently, the Salt intake in Iranians is more than twice the recommended intake 

Those suffering from high blood pressure should reduce their salt intake to less than 4 grams per day 

* A selection of the secondary core messages, the full list of the messages can be accessed at http://www.icrc.ir/pdf/advocacy.pdf 

national media. The last group was those who may oppose the salt 

reduction plan. Table 2 presents the different target groups whose 

views and actions has potential impacts on the success of a national 

salt reduction plan. 

Holding meetings with key stake holders 

Several meetings were held with a subset of the target groups in 

order to understand to their viewpoints and assess their beliefs and 

help clarify the mutual needs and priorities. These meetings helped 

identify the key messages for communicating the salt reduction 

plan.

Defining the key messages 

A set of key messages were chosen, by trying to put in an Iranian 

dietary pattern, the scientific facts on the harmful effects of excessive 

salt intake and the experience from other countries’ successful 

salt reduction programs. Accordingly, the messages were divided 

into those considered as “core key messages” and those regarded 

as “secondary key messages”. Table 3 presents the core key messages 

and some of the secondary key messages. 

Defining the methods for the communication of the national salt reduction 

plan 

Various methods for communication of the salt reduction plan were 

reviewed; Table 4 summarizes the different approaches proposed. 

Choosing the most appropriate key messages and their communication 

tools for different target groups 

The next task was to select and match those key messages (presented 

in Table 3) depending on the specific target groups (summarized 

in Table 2) by choosing the most effective communication 

tools (listed in Table 4). For instance, the main key message in 

communications with the general public was chosen to be through 

communication of the health effects of salt through various media; 

the cost-effectiveness of salt reduction planning could discussed in 

the meetings to be held with the authorities engaged in budget and 

health policy planning. 

Surveillance and monitoring 

Proper surveillance and monitoring is a vital element of any successful 

intervention program. Therefore, various steps were con- 

Table 4. Different methods for communication of salt reduction plan 

1 Regular contacts and meetings with the stakeholders 

2 Publication of booklets, pamphlets , and posters 

3 Initiating volunteer salt reduction campaign groups 

4 Holding debates on the health effects of salt on the national media 

5 Holding training courses, conferences and seminars 

6 Making documentaries, and animations on the importance of salt reduction 

7 Engaging the public through partnerships with popular figures, sportsmen and celebrities 

Stage of the intervention Elements to be assessed and monitored 

Processes 

Impacts 

Outcomes 

Existence and quality of educational programs and trainings provided through/at the time of: 

a) families attending health clinics 

b) attending mandatory continuing qualification courses for employees 

c) the meetings of “parents and teacher associations” 

d) TV programs 

e) bulletins 

f) competitions 

g) emails 

h) text messages 

i) attending health clinics specially for those suffering from obesity or diabetes 

a) public awareness and attitude towards harmful effects of excessive salt intake 

b) level of salt intake per capita 

c) the extent to which prepared food are used 

d) prevalence of taking salty snacks 

e) Consuming fast foods 

f) using discretionary salt at table 

a) Prevalence of hypertension 

b) Prevalence of controlled hypertension 

c) Average blood pressure level 

d) Incidence of cardiovascular disease 

e) Incidence of gastric cancer 

f) All-cause mortality rate 

g) Prevalence of obesity 

Advocacy Strategies and Action Plans for Reducing Salt intake in Iran 

Table 5. Surveillance and monitoring plan for evaluation and assessment the Iranian national salt reduction program 

sidered in order to evaluate and assess the “processes”, their “impacts”, 

and “outcomes” in each of the target groups; according to 

which the plan would be reviewed and revised. Multiple indicators 

were defined for each type of evaluation and its target population, 

place, time and frequency were explained in the full report. For instance, 

the success of interventions at the general population level 

will be assessed by: 

a) Assessing and evaluating the “processes” through which the 

intervention is communicated with the public (e.g. by assessing 

the existence and quality of education and training provided to the 

population on harmful effects of salt) 

b) Assessing and evaluating their “impacts” on general population 

by measures such as monitoring the trend in population’s salt 

intake 

c) Assessment and evaluation of the “outcomes”, for instance 

by monitoring the reductions in the level of blood pressure at the 

population level. 

Table 5 provides the details of the surveillance and monitoring 

plan for assessment of the success of the national salt reduction 

program in the general population. 


The study was supported by a grant from the Nutrition Department 

of Iranian Ministry of Health and Medical Education and the 

Office of World Health Organization in Iran. We thank Drs. Mansour 

Shiri, Katayoun Rabiei, Hasan Alikhasi Mohammad Badiei, 

and Soheila Kanani who cooperated in conducting this study. 

Conflict of interest: None to declare 


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non-communicable diseases through population-wide dietary salt reduction. 

2009. 

37. Consensus Action on Salt and Health, July 2009-10 Annual Report. 

2010.

Case Report 

A Rare Case of Perforated Meckel’s Diverticulum Presenting as a 

Gatrointestinal Stromal Tumor 

Selim Sozen MD• 1 , Ömer Tuna MD 1 

Abstract 

Meckel’s diverticulum is located on the antimesentric border of the ileum, approximately 45 to 60 cm proximal to the ileocecal valve, and 

results from incomplete closure of the omphalomesentric or viteline duct. Common complications presenting in adults include bleeding, obstruction, 

diverticulitis, and perforation. Tumors within Meckel’s diverticulum are a rare, but recognized complication. 

A 62year-old woman presented with peri-umbilical pain that had localized to the right iliac fossa. On examination, she was tender in the right 

iliac fossa, with localized peritonism. At surgery,a perforated Meckel’s diverticulum was found that was associated with free intra-abdominal 

fluid and hemorrhage. A 25 mm nodule was found at the apex of Meckel’s diverticulum.We resected 100 mm of the small bowel and a primary 

anastamosis was performed.Histopathological examination of the resected lesion revealed a mesenchymal tumor categorized as a 

gastrointestinal stromal tumor (GISTs). 

GISTs arising from Meckel’s diverticulum are an extremely rare, but recognized complication. Surgery is considered the standard treatment 

for non-metastatic GISTs with enbloc resection and clear margins. 

Keywords: Complications, gastrointestinal stromal tumor, Meckel’s diverticulum 

Cite this article as: Sozen S, Tuna O. A Rare Case of Perforated Meckel’s Diverticulum Presenting as a Gatrointestinal Stromal Tumor. Arch Iran Med. 2012; 15(5): 

325 – 327. 


Meckel’s diverticulumis located on the antimesentric border 

of theileum, approximately 45 to 60 cm proximal to the 

ileocecalvalve, and results from incomplete closure of the 

omphalomesentricor viteline duct. 1Common complications presentingin 

adults include bleeding, obstruction, diverticulitis, andperforation. 

Tumors within a Meckel’s diverticulum are a rare but 

recognized complication. Meckel’s diverticulumis surgically removed 

only when a complication arises ora neoplasia develops. 

The tumors are infrequent andobserved only in 0.5% – 3.2% of the 

Meckel’s diverticula.Of thesetumors, 12% are gastrointestinal 

stromal tumors(GISTs). 2 

GISTs occurs predominantly in adults at a median age of58 years. 

The majority of GISTs (60% to 70%) have been reported to arise 

in the stomach, whereas 20% to 30% originate in the small intestine, 

and less than 10% in the esophagus, colon, and rectum. GISTs 

also occur in the extra-intestinal abdominopelvic sites such as the 

omentum, mesentery, andretroperitoneum. 3,4 GISTs arising from 

Meckel’s diverticulum are extremely rare. 5 

Case Report 

A 62-yearold woman presented with peri-umbilical pain that had 

localized to the right iliac fossa. On examination, she was tender 

in the right iliac fossa with localized peritonism. Hematologic tests 

showed decreased hematocrit (Ht: 22%) and a platelet (PLT) count 

Authors’ Affiliations: 1 Kayseri Training and Research Hospital, Department of 

General Surgery. 

•Corresponding author and reprints: Selim Sozen MD, Kayseri Training and 

Research Hospital Department of General Surgery, Kayseri /Turkey. 

E-mail: selimsozen63@yahoo.com. 


of 114000/mL. Her Hiser white cell count was 15.2 × 10 9 (neutrophils 

12.1 × 10 9 ).On physical examination, there was abdominal 

tenderness, rebound, and increased bowel sounds in all quadrants. 

Plain abdominal X-rays were first obtained whenthe patient had 

acute symptoms, which revealed air-fluid levels that suggested intestinal 

obstruction(Figure 1). A palpable mass in the right lower 

quadrant was present.The patientunderwent surgery with a diagnosis 

of plastrone appendicitis. A McBurney incision in the abdomen 

was made;the appendix was normal. During surgery, a perforated 

Meckel’s diverticulum was found, which was associated with free 

intra-abdominal fluid and hemorrhage (Figure 2). A 25 mm nodule 

was found at the apex of Meckel’s diverticulum. Theperforation 

of the diverticulum was also not associatedwith the tumor nodule. 

At the subsequent laparotomy, 100 mm of small bowel was resected 

and primary anastamosis performed. Histology confirmed 

a Meckel’s diverticulum with a 12 mm area of perforation. The 

histopathological examination of the resected lesion revealed a 

mesenchymal tumor which was categorized as a GIST tumor. The 

stromal tumor demonstrated whirling sheets of spindle cells with 

a moderate level of pleomorphism and mitotic activity (6 – 7 mitoses/50 

HPF; H&E stain). No necrosis was observed. Immunohistochemical 

staining for CD117, a-smooth-muscle actin (SMA), 

and S-100 protein was positive, whereas staining for desmin and 

CD34 was negative(Figure 3). The labeling index for MIB-1, determined 

by counting positively stained nuclei, was about 5%.The 

postoperative period was unremarkable and she was discharged in 

good general condition. 

Discussion 

GIST 

Meckel’s diverticulum is the most commonly encountered congenital 

anomaly of the small intestine, occurring in approximately 


Figure 1. Plain abdominal X-rays were first obtained in patient with acute 

symptoms, which revealed air-fluid levels suggestive of intestinal obstruction. 

2% of the population. 6,7 GISTs, which arise primarily in the gut 

wall, are uncommon mesenchymal,malignant, or potentially malignant 

tumors affecting the gastrointestinal tract. GISTs are the 

most commonnon-epithelial tumors of the digestive tract, accounting 

for only 1% of all gastrointestinal malignancies. 8,9 Primary 

GISTs may occur anywhere along the gastrointestinal tract from 

the esophagus to the anus. 10 The most frequent site is the stomach 

(55%), followed by the duodenum and small intestine (30%), 

esophagus (5%), rectum (5%), colon (2%), and rare other locations.The 

incidence of tumors within Meckel’s diverticulm is 0.5% 

to 3.2%. 2 Most are commonly benign tumors such as leiomyomas, 

angiomas, and lipomas. Malignant neoplasms include adenocarcinoma 

(which commonly originate from the gastric mucosa), sarcoma, 

carcinoid tumor, and GISTs. 

The most common presentation of GISTs is acute or chronic gastrointestinal 

bleeding. They often present with nausea, vomiting, 

abdominal pain, metastatic disease, and bowel obstruction. In our 

case, the patient presented with bowel obstruction and perforation. 

In a large series of 1476 cases at the Mayo Clinic, Park et al. have 

reported the most common presentations of symptomatic Meckel’s 


Figure 2. A 25 mm nodule was found at the apex of Meckel’s diverticulum. 

Figure 3. Immunohistochemical staining for CD117, a-smooth-muscle actin (SMA), 

and S-100 protein was positive, whereas staining for desmin and CD34 was negative. 

S. Sozen, Ö. Tuna 

diverticula in adults to be bleeding (38%), obstruction (34%), diverticulitis 

(28%) and perforation (10%). 11 GISTs arise from the 

interstitial cells of Cajal, the pacemaker cells of the gastrointestinal 

tract. 8 GISTs strongly expresses the KIT (CD 117) protein and may 

harbor mutations of the type III tyrosine kinase receptorgene (either 

KIT or PDGFRA). 12 For many patients, detection of GISTs may be 

an incidentalfinding during evaluation of nonspecific symptoms. 

Symptoms tend to arise only when tumors reach alarge size or are 

in a critical anatomic location. Most symptomaticpatients present 

with tumors larger than 5 cm inmaximal dimension. Symptoms 

at presentation mayinclude abdominal pain, abdominal mass, nausea, 

vomiting,anorexia, and weight loss. There are little prognostic 

data regarding GISTs and current prognostic indicators are based 

on consensus guidelines. The most important adverse factors are 

thought to be a tumor diameter of greater than 5 cm and a high mitotic 

count exceeding 5 mitotic figures per 50 high powered fields 

on light microscopy. 12,13 Other suggested factors indicative of poor 

prognosisinclude tumor perforation, tumor necrosis, high cellularity, 

and marked pleiomorphism. 12 

Surgery is considered the standard treatment for non-metastatic

GISTs with enbloc resection and clear margins. The treatment of 

choice is the complete resection of the tumour. The surgeon’s approach 

in an actual case depends on factors such as: the exact anatomical 

site of the GISTs, the characteristics of the individual patient’s 

particular situation, and the specific location of the tumour 

relative to the blood supply of the involved organ. There is little evidence 

to support local/regional lymphadenectomy as GISTs rarely 

metastasize to lymph nodes. 12 Targeted therapy with imantinib, a 

KIT tyrosine kinase inhibitor, is considered the standard treatment 

for metastatic GISTs. 12 In our case, the outcome has shown that 

the location is very important in determining the prognosis. Patients 

with a small bowel localization do worse than those with 

stomach GISTs as reported by DeMatteo et al. 14 In a case of a MD 

(Meckel diverticulum) localization, treatment with imatinib mesylate 

has been reported by Khoury et al., 15 but the impact on the 

clinical behavior of the disease has not been described. The case 

reported by us has a low risk of recurrence based on characteristics 

of amaximum diameter of 2.5 cm, a low mitotic count of less than 

one mitotic figure in 10 × 40 high powered fields, and no evidence 

of necrosis. Importantly, the perforation of the diverticulum was 

also not associated with the tumor nodule. 

Conclusion 

GISTs arising from Meckel’s diverticulum are an extremely rare 

but recognized complication. 5 Surgery is considered thestandard 

treatment for non-metastatic GISTs with enblocresection and clear 

margins. 

References 

1. Dumper J, Mackenzie S, Mitchell P, Sutherland F, Quan ML, Mew D. 

Complications of Meckel’s diverticula in adults. Can J Surg. 2006; 49: 

GIST 

353 – 357. 

2. Yahchouchy E, Marano A, Etienne J, Fingerhurt A. Meckel’s diverticulum. 

J Am Coll Surg. 2001; 192: 658 – 662. 

3. DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan 

MF.Two hundred gastrointestinal stromal tumors: Recurrence patterns 

and prognostic factors for survival. Ann Surg. 2000; 231: 51 – 58. 

4. Miettinen M, Lacosta J.Gastrointestinal stromal tumors definition, 

clinical, histological, immunohistochemical and molecular genetic 

features and differential diagnosis. Arch Pathol Lab Med. 2006; 130: 

1466 – 1478. 

5. Hager M, Maier H, Eberwein M, Klingler P, Kolbitsch C, Tiefenthaler 

W, et al. Perforated Meckel’s diverticulum presenting as a gastrointestinal 

stromal tumor:A case report. J Gastrointest Surg. 2005; 9: 809 

– 811. 

6. Haber JJ.Meckel’s diverticulum. Am J Surg.1947; 73: 468 – 485. 

7. Harkins HN.Intussusception due to invaginated Meckel’s diverticulum. 

Ann Surg.1933; 98: 1070 – 1095. 

8. Nowain A, Bhakta H, Pais S, Kanel G, Verma S. Gastrointestinal stromal 

tumors: Clinical profile, pathogenesis, treatment strategies and 

prognosis. J Gastroenterol Hepatol. 2005; 20: 818 – 824. 

9. Eisenberg BL, Judson I. Surgery and imatinib in the management of 

GIST: Emerging approaches to adjuvant and neoadjuvant therapy. Ann 

Surg Oncol. 2004; 11: 465 – 475. 

10. Judson I. Gastrointestinal stromal tumors (GIST): Biology and treatment. 

Ann Oncol. 2002; 13: 4287 – 4289. 

11. Park J, Wolff B, Tollefson M, Walsh E, Larson D. Meckel diverticulum. 

The Mayo Clinic experience with 1476 patients (1950 – 2002). 

Ann Surg. 2005; 241: 529 – 533. 

12. Joensuu H. Gastrointestinal stromal tumor (GIST). Ann Oncol. 2006; 

10: 280 – 286. 

13. Chang M, Choe G, Kim W, Kim Y. Small intestine stromal tumors: 

A clinicopathological study of 31 tumors. Pathol Int. 1998; 48: 341 

– 347. 

14. Dematteo RP, Gold JS, Saran L, Gönen M, Liau KH,Maki RG, et al. 

Tumormitotic rate, size, and location independently predict recurrence 

after resection of primary gastrointestinal stromal tumor (GIST). Cancer. 

2008; 112(3): 608 – 615. 

15. Khoury MG, Aulicino MR. Gastrointestinal stromal tumor (GIST) 

presenting in a Meckel’s diverticulum. Abdom Imaging. 2007; 32: 78 

– 80. 



Hydatid disease is a parasitic disease most commonly caused 

by the larval stage of the tapeworm Echinococcus granulosus. 

1 Humans may become intermediate hosts through contact 

with a definitive host or by ingestion of contaminated water or 

vegetables. 2 

In humans, eggs hatch and embryos migrate through the intestinal 

mucosa before entering the portal circulation, causing hepatic 

hydatid disease. If embryos bypass the liver, they can reach the 

pulmonary circulation via the inferior vena cava, forming cysts in 

the lungs. 2–5 The most frequent sites of hydatid cyst involvement 

are the liver (45% – 75%) and lungs (10% – 50%). 4 Embryos may 

reach other organs or tissues in the body via the systemic circulation. 

These unusual sites include the brain, muscles, kidneys, heart, 

adrenals, and numerous other sites, all of which may cause preoperative 

diagnostic difficulties. 1 

The hydatid cyst wall has 3 layers of which the outermost layer 

is the pericyst, the middle layer is the laminated membrane, and 

the innermost layer is called the endocyst or germinal epithelium. 1 

Localization of the hydatid cyst in the adrenal glands is very rare 

(less than 1% of all cases). 4,5 Most reported cases have been discovered 

incidentally, but some adrenal hydatid disease has been 

reported to coexist with arterial hypertension. 4–9 There are a few 

reports of adrenal hydatid cyst presenting with symptoms suggestive 

of pheochromocytoma(episodes of headache, sweating, palpitations, 

and hypertension). 5 

Herein we report a case of primary adrenal hydatidosis,accompanied 

by arterial hypertension. 

Case report 

A 66-year-old female referred to the Surgical Department at 

Fasa University of Medical Scienceswith complaints of right flank 


Case Report 

Primary Adrenal Hydatid Cyst Presenting with Arterial 

Hypertension 

Maral Mokhtari MD• 1 , Sam ZeraatianNejadDavani MD 2 

Abstract 

Hydatid disease is an endemic illness in some countries. The main sites of involvement are the liver and lungs, but rarely,it can be seen in 

other organs as well. Herein, we report a case of primary adrenal hydatid cyst accompanied by arterial hypertension. 

Keywords:Adrenal gland, hydatid cyst, hypertension 

Cite this article as: Mokhtari M, ZeraatianNejad Davani S. Primary Adrenal Hydatid Cyst Presenting with Arterial Hypertension. Arch Iran Med. 2012; 15(5): 

328 – 330. 

Authors’ Affiliations: 1 Department of Pathology, Shiraz University of Medical 

Sciences, Shiraz, Iran, 2 Department of Surgery, Fasa University of Medical Sciences, 

Fasa, Iran. 

•Corresponding author and reprints:Maral Mokhtari MD, Pathology 

Department,Shiraz University of Medical Sciences, Shiraz, Iran. 

Fax: +987112301784, E-mail: maral_mokhtari@yahoo.com. 

Accepted for publication: 12 October 2011 

pain with radiation to her back. She had a 2-year history of arterial 

hypertension (systolic 150 – 170 and diastolic 95 – 105) and 

was on anti-hypertensive medications. Physical examination was 

unremarkable except for a blood pressure of 150/95. Laboratory 

examinations that included hematological and biochemical studies 

were within normal limits. As a part of the diagnostic workup, 

abdomeno pelvic computed tomography scan (CT scan) and plain 

chest X-ray were performed. Chest X-ray was unremarkable; however 

the abdominal CT scan showed a solitary lesion measured 5 

cm with coarse calcification in the right adrenal gland (Figure1). 

The other organs were unremarkable. Due to the possibility of 

pheochromocytoma,the urine catecholamine level was measured 

which was normal. The patient underwent open laparotomy and a 

right adrenalectomy was performed. 

Gross examination revealed a thick-walled, calcified cystic mass 

filled with an amorphous, fragile, creamy-white material measured 

5.5×5 cm(Figures 2 A,B). Microscopic study showed a calcified 

cyst that had a fibrous wall with no epithelial lining. The cyst was 

filled with a pink amorphous material that contained rare hooklet 

of echinococcus granulosus (Figures 3 A, B, C). 

The histologic diagnosis was primary adrenal hydatid cyst. 

The post-operative period was uneventful and the patient was 

discharged with normal blood pressure. Thus anti-hypertensive 

medications were discontinued.During the following 3 months, 

the patient remained normotensive. 

Discussion 


Hydatid disease is a parasitic disease, endemic in Iran and some 

countries. Cysts located in organs other than the liver and lungs are 

usually manifestation of generalized disease. 4 

Adrenal gland involvement may be due to secondary spread resulting 

from spontaneous or intra-operative rupture of a primary 

cyst, but the primary hydatid cyst of the adrenal gland is a rare 

event. 2 Cysts of the adrenal glands are usually unilateral (90%) and 

show no special predilection for either side. 4 

Adrenal hydatid disease is slow-growing, therefor it isusually an 

incidental discovery. When symptoms are present they are related 

to visceral compression. The most prominent features are flank 

pain, gastrointestinal symptoms (bloating, nausea, vomiting, con-

Figure 1. Abdominal CT scan shows a calcified mass in the right adrenal gland. 

stipation, and anorexia) and a palpable mass. 2,7 Rarely, hydatid cyst 

coexists with arterial hypertension and is referred to as Goldblatt’s 

phenomenon which may be caused by external compression of the 

renal artery by the cyst. 3 Some hypertensive patients have normal 

blood pressure after surgical removal of the hydatid cyst, as in 

our patient, however presence of adrenal hydatid cyst as the sole 

etiology of the hypertension is controversial .Some authors have 

reported that the hypertension may continue even after complete 

resection of the cyst. 9 

Nouria et al. 5 have reported a case of adrenal hydatid cyst with 

cardinal symptoms of pheochromocytoma and elevated Vanillylmandelic 

acid (VMA) level. They suggested that the elevation of 

catecholamine may be due to compression of the adrenal medulla 

by the cyst leading to catecholamine release. 

In our case the urine VMA was within normal limits so the pressure 

effect on the adrenal medulla was a remote possibility. Compression 

of the renal artery may be the responsible cause of hypertension 

because of normalization of blood pressure after surgery. 

Serological studies may help to diagnose hydatid cyst but they 

lack sensitivity and specificity. Imaging studies such as ultrasound, 

CT scan and MRI can assist with diagnosis, site of involvement, 

(A) (B) 

Figures 2 A,B. Large cystic adrenal mass filled with chalky white material. 

the number of cysts, and possible complications. 2 

In radiologic modalities calcification is seen in about 20% of hydatid 

cysts and its presence in an adrenal mass is suggestive of 

hydatid cyst. 2 

The complications of adrenal hydatid disease include rupture, fistula 

formation, hemorrhage, and anaphylactic shock. 2,7 

Differential diagnosis of an adrenal cyst include endothelial cyst, 

pseudocyst, cystic neoplasms such as lymphangioma, post-traumatic 

cyst, cystic pheochromocytoma, abscess, and other congenital 

or acquired cysts. 2,4 

Conclusion 

Primary adrenal hydatid cyst and arterial hypertension 

Primary hydatid cyst of the adrenal gland is a rare disease that 

may mimic many adrenal lesions, therefore it should be considered 

in the differential diagnosis of all adrenal cysts, particularly 

in endemic areas. This can be rarely accompanied by arterial hypertension 

as well as adrenal pheochromocytoma.Although imaging 

studies assist with diagnosis, however the exact nature of the 

adrenal hydatid cyst requires histologic examination. 


References 

(A) (B) 

Figures 3A,B. Fibrosed, calcified cyst wall with remnants of the adrenal cortex. H & E 100x, 400x. 

1. Yuskel M, Demirplat G, Sever A, Bakris S, Bulbuloglu E, Elmas 

N.Hydatiddisease involving some rare locations in the body: Apictorial 

essay. Korean J Radiol. 2007; 8: 531 – 540. 

2. Sallami S, Ben Rhouma S, Horanchi A. Primary adrenal hydatid cyst: 

A case report. Ibnosina J Med BS. 2010; 2(1): 38 – 41. 

3. Abdulmajed M, Resorlu B, Kara C, Turkolmez K. Isolated primary hydatidcyst 

of adrenal gland: A case report. Turkish Journal of Urology. 

2010; 36(2): 211 – 215. 

4. Dionigi G, Carrafiello G, Recaldini C, Sessa F, Boni L, Rovera F, et al. 

Laparoscopic resection of a primary hydatidcyst of the adrenal gland: 

A case report. J Med Case Reports. 2007; 1: 61 . 

5. Nouria Y, Benyounes A, Kbaier I, Attyaoui F, Horanchi A. Adrenal 


Figure3C. Hooklet of echinococcus granulosus.H & E, oil immersion. 


hydatid cyst presenting as a phaeochromocytoma. BJU International. 

2000; 86(6): 754. 

6. Escudero M, Sabater L, Calavete J, Camps B, Labios M, Liedo S. Arterial 

hypertension due to primary adrenal hydatid cyst. Surgery. 2002; 

132(5): 894 – 895. 

7. Ozarmagan S, Erbil Y, Barbaros U, Salmaslioglu A, Bozbora A. Primary 

hydatid disease in the adrenal gland: A case report. Braz J Infect 

Dis2006; 10 (5): 362 – 363. 

8. Gurbuz R, Guven S, Klinc M, AbasiyanikF, Gokce G, Peskin M. Primary 

hydatid cyst in adrenal gland: A case report. Int Urol Nephrol. 

2005; 37: 21 – 23. 

9. Safioleas MC, Moulakakis KG, Kostaksis A. Coexistence of primary 

adrenal hydatid cyst and arterial hypertension: Reports of a case and 

review of the literature. Acta Chir Belg. 2006; 106: 719 – 721.

Case Report 

Primary Intrathoracic Biphasic Synovial Sarcoma 

Yilmaz Tezcan MD• 1 , Mehmet Koc MD 1 , Husnu Kocak MD 2 , Yusuf Kaya MD 2 

Abstract 

Synovial sarcomas are most frequently observed in the extremities. Although synovial sarcomas are the third most common histological 

type of soft-tissue sarcomas of the extremities, primary mediastinal synovial sarcoma is extremely rare. Monophasic synovial sarcoma is the 

most commonly observed subtype. whereas the biphasic subtype is less common. We present our case which was diagnosed as biphasic 

synovial sarcoma located in the anterior mediastinum, which is considered to be a rare entity. The patient underwent surgical resection together 

with multimodal adjuvant radiotherapy and chemotherapy. 

Keywords: Chemotherapy, prognosis, radiotherapy, synovial sarcoma 

Cite this article as: Tezcan Y, Koc M, Kocak H, Kaya Y. Primary Intrathoracic Biphasic Synovial Sarcoma. Arch Iran Med. 2012; 15(5): 331 – 332. 

Case Report 

Our case was a 38-year-old married female who presented with 

complaints of cough, dyspnea, pain, and fatigue for 2 – 3 months. 

PA chest radiography revealed a mass in the anterior and left side 

mediastinum (Figure 1). A subsequent CT scan of the thorax 

showed a soft tissue mass, 13 – 14 cm in diameter, in the anterior 

and left side mediastinum (Figure 2). The same mass was verified 

by an MRI of the thorax (Figure 3). Following routine examinations, 

the patient underwent a left thoracotomy with complete excision 

of the mediastinal mass. 

The surgical procedure was as follows: the patient was placed 

on her right side with one arm raised. An incision was made on 

the skin of the rib cage. Muscle layers were cut and a rib removed 

to gain access to the cavity. Retractors were used to hold the ribs 

apart, exposing the tumor. The tumor and capsule were removed 

intact after which the layers of the skin, muscle, and other tissues 

were closed with stitches and staples. Next, the chest wall was 

closed. The left thoracotomy procedure was completed without 

complication. 

The pathology specimen consisted of a tumor that resembled 

encapsulated grey-white soft tissue, which macroscopically measured 

13×12×8 cm. There were groups of cells that had oval nuclei, 

fusiform cytoplasm, and malignant tumor that consisted of 

solid masses of epithelioid cells with wide eosinophilic cytoplasms 

and oval, pleomorphic nucleus . Focal necrosis was present in the 

tumor and mitotic activity was found to be 2/10 BBA. Tumor cells 

stained positive in solid epithelioid areas with cytokeratin; focal 

staining was observed with S100, CD99, and cytokeratin 7. Based 

on histomorphological and immunohistochemical findings, the 

case was diagnosed as biphasic synovial sarcoma. According to 

postoperative TNM staging, this case was staged as T2bN0M0. 

Authors’ Affiliations: 1 Selcuk University, Meram Faculty of Medicine, Department 

of Radiation Oncology, Konya, Turkey, 2 Mersin State Hospital, Department 

of Thoracic Surgery, Mersin, Turkey. 

•Corresponding author and reprints: Yilmaz Tezcan MD, Selcuk University, 

Meram Faculty of Medicine, Department of Radiation Oncology , 42090-Konya, 

Turkey. Tel: 0332-2236942 , Fax: 0332-2236182, 

E-mail: yilmaztezcan@yahoo.com. 

Accepted for publication: 16 November 2011 

Adjuvant radiotherapy was planned for the patient due to close 

surgical margins, young age, and tumor size (13 cm). A total of 66 

Gy adjuvant radiotherapy was applied to the primary tumor and 

consisted of an initial 50 Gy (Phase I) dose with a boost of 16 Gy 

(Phase II), followed by adjuvant chemotherapy with 4 cycles of ifosfamide 

and adriablastin. The treatments were well tolerated and 

the patient was observed each 3 months for follow up visits. A thorax 

CT performed 6 months after treatment end did not reveal any 

pathological findings (Figure 4). After approximately 36 months (3 

years), the patient was lost due to disease progression. 

Discussion 

Primary Intrathoracic Synovial Sarcoma 

Primary mediastinal synovial sarcomas are extremely rare in 

the thorax and lungs. Primary pulmonary sarcomas account for < 

0.5% of lung cancers. 1 However, an increase has been observed in 

these tumors in recent years. 2 Leiomyosarcomas, fibrosarcomas, 

and hemangiopericytomas are the most common types of primary 

pulmonary sarcomas. 3 Primary pulmonary and mediastinal synovial 

sarcomas are more aggressive than soft tissue synovial sarcomas. 

While biphasic synovial sarcomas arise in the pleural cavity, 4 

most are localized within the pulmonary parenchyma 5 and rarely 

extend into the bronchial structures. 6 Mediastinal lymphadenopathy 

is rare. 7 

Synovial sarcomas are histologically classified into four types: 

biphasic, monophasic fibrous, monophasic epithelial, and poorly 

differentiated. Monophasic synovial sarcoma is the most commonly 

observed subtype, and studies show that epithelial components 

of biphasic tumors are surrounded by pneumocytes. Direct chest 

radiography is used primarily for diagnosis where the lesion presents 

a typically uniform view with well-circumscribed rounded or 

lobulated borders. 7–8 Some patients have mediastinal shift. Bilateral 

pleural effusion is common. CT scan is more sensitive than 

chest radiography for detecting calcified tumor matrix and cortical 

destruction. 9 These tumors are less vascular and MRI imaging 

presents three findings (clear, dark, and grey) that reflect tumor, 

hemorrhage, and necrosis. 10 Clinically, patients may show varied 

symptoms such as cough, dyspnea, chest pain, and fatigue depending 

on the size and extent of the mass. 


Figure 1. PA chest radiography prior to treatment. 


Figure 2. CT scan of the thorax prior to treatment. 

Y. Tezcan, M. Koc, H. Kocak, et al. 

Figure 3. Thorax MRI prior to treatment. Figure 4. Thorax CT scan performed 6 months after the treatments 

CT-guided needle biopsy is adequate for diagnosis. Prognosis is 

related to the phase of the disease, and is generally poor. The fiveyear 

survival rate is between 36 – 76%. 3 

Tumor size (≥ 9 cm), male patients, over the age of 20 years, the 

presence of extensive tumor necrosis, high grade, large number of 

mitosis (> 9 – 10), neurovascular invasion, and in recent years, the 

presence of the SYT-SSX1 variant can be listed as poor prognostic 

factors. 11 Complete resection is mentioned as the most significant 

prognostic factor in a meta-analysis. This meta-analysis has shown 

that the application of adjuvant radiotherapy and adjuvant chemotherapy 

following complete surgical resection prolongs the time of 

local recurrence and survival without recurrence, and accordingly 

causes an increase in total survival rate. 12,13 

Synovial sarcomas are tumors which have moderate chemosensitivity, 

with about 50% response rates to regimens containing ifosfamide 

and doxorubicin. 14 Radiotherapy is recommended in cases 

with positive margins. 15 

In summary, we have presented a rare case of biphasic synovial 

sarcoma located in the anterior mediastinum. In these rarely observed 

cases, survival can be increased through complete resection 

and aggressive multimodal treatments. 

References 

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191 – 202. 

2. Roberts CA, Seemayer TA, Neff JR, Alonso A, Nelson M, Bridge JA. 

Translocation (X; 18) in primary synovial sarcoma of the lung. Cancer 

Genet Cytogenet. 1996; 88: 49 – 52. 

3. Etienne-Mastroianni B, Falchero L, Chalabreysse L, Loire R, Ranchere 

D, Souquet PJ, et al. Primary sarcomas of the lung: A clinicopathologic 

study of 12 cases. Lung Cancer. 2002; 38: 283 – 289. 

4. Gaertner E, Zeren EH, Fleming MV, Colbay TV, Travis WD. Biphasic 

synovial sarcomas arising in the pleural cavity. A clinicopathologic 

study of five cases. Am J Surg Pathol. 1996; 20: 36 – 45. 

5. Zeren H, Moran CA, Suster S, Fishback NF, Koss MN. Primary pulmonary 

sarcomas with features of monophasic synovial sarcoma: A 

clinicopathological, immunohistochemical, and ultrastructural study of 

25 cases. Hum Pathol. 1995; 26: 474 – 480. 

6. Essary LR, Vargas SO, Fletcher CD. Primary pleuropulmonary synovial 

sarcoma: Reappraisal of a recently described anatomic subset. 

Cancer. 2002; 94: 459 – 469. 

7. Duran Mendicuti A, Costello P, Vargas SO. Primary synovial sarcoma 

of the chest: Radiographic and clinicopathologic correlation. J Thorac 

Imaging. 2003; 18: 87 – 93. 

8. Zaring RA, Roepke JE. Pathologic quiz case. Pulmonary mass in a 

patient presenting with a hemothorax. Diagnosis: Primary pulmonary 

biphasic synovial sarcoma. Arch Pathol Lab Med. 1999; 123: 1287 – 

1289. 

9. Tateishi U, Gladish GW, Kusumoto M, Hasegawa T, Yokoyama R, 

Moriyama N. Chest wall tumors: Radiologic findings and pathologic 

correlation: Part 2. Malignant tumors. Radiographics. 2003; 23: 1491 

– 1508. 

10. Frazier AA, Franks TJ, Pugatch RD, Galvin JR. From the archives of 

the AFIP: Pleuropulmonary synovial sarcoma. Radiographics. 2006; 

26: 923 – 940. 

11. Trassard M, Le Doussal V, Hacène K, Terrier P, Ranchère D, Guillou L, 

et al. Prognostic factors in localized primary synovial sarcoma: A multicenter 

study of 128 adult patients. J Clin Oncol. 2001; 19: 525 – 534. 

12. Dennison S, Weppler E, Giacoppe G. Primary pulmonary synovial sarcoma: 

A case report and review of current diagnostic and therapeutic 

standards. Oncologist. 2004; 9: 339 – 342. 

13. Mankin HJ, Hornicek FJ. Diagnosis, classification, and management of 

soft tissue sarcomas. Cancer Control. 2005; 12: 5 – 21. 

14. Albritton KH, Randall RL. Prospects for targeted therapy of synovial 

sarcoma. J Pediatr Hematol Oncol. 2005; 27: 219 – 222. 

15. Al-Rajhi N, Husain S, Coupland R, McNamee C, Jha N. Primary pericardial 

synovial sarcoma: A case report and literature review. J Surg 

Oncol. 1999; 70: 194 – 198.

A 63-year-old female was admitted with complaints of pain in 

the lower abdominal quadrants. Her past medical history was significant 

for gangrenous small bowel resected 2 months prior to ad- 

Photoclinic 

Cite this article as: Jarmakani MF, Mohebbi MR. Photoclinic. Arch Iran Med. 2012; 15(5): 333 – 334. 

Morwan F. Jarmakani MD 1 , Mohammad R. Mohebbi MD• 2 

Authors’ affiliations: 1 Department of Rediology, Mercy Medical center, 2 Siouxland 

Medical Education Foundation-University of Iowa. 

•Corresponding author and reprints: Mohammad R. Mohebbi MD, Siouxland 

Medical Education Foundation-University of Iowa, 2501 Pierce Street, Sioux 

City, Iowa, 51104, USA. Tel: +1-712-294-5000, Fax: +1712-294-5092, 

E-mail: mohammad-mohebbi@uiowa.edu. 

Accepted for publication: 16 November 2011 

Figure 1. Hepatic portal venous gas (arrowheads). 

Figure 2. Air in the soft tissue around the sigmoid colon and rectum (arrows) consistent with 

pneumatosis intestinalis. 

mission, diabetes mellitus, chronic obstructive pulmonary disease, 

rheumatoid arthritis, coronary artery disease, and hypercholesterolemia. 

Laboratory results included a wbc count of 28150/mm 3 

with a significant left shift, Hgb of 9.6, BUN of 23 and Cr of 1.6. 

Abdominal CT scan showed evidence of air in the portal system 

and liver (Figure 1, arrowheads). 

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Photoclinic 


Photoclinic Diagnosis: Hepatic Portal Venous Gas in a Case of Ischemic Necrotic Colon 

Abdominal CT scan showed evidence of air in the soft tissue 

around the sigmoid colon and rectum (Figure 2, arrows) consistent 

with pneumatosis intestinalis. The patient underwent resection of 

the sigmoid colon which confirmed an ischemic, necrotic bowel. 

Air in the liver can be either in the portal venous system or the 

hepatobiliary tree. The appearance of gas in the portal venous system 

in adults is usually a sign of lethal conditions such as intestinal 

infarction. It has been described in association with a variety of 

pathologic conditions that include intestinal ischemia and necrosis 

(75%), ulcerative colitis (8%), and intra-abdominal abscess (6%). 1,2 

Patients with hepatic portal venous gas have an overall survival 

rate of less than 25%. 2 Portal venous gas has also been observed 

following endoscopic retrograde cholangiopancreatography and 

endoscopic sphincterotomy with a subsequent uneventful course. 3 

Gas in the portal venous system is carried by the centrifugal flow 

of blood in the periphery of the liver, appearing to extend to within 

2 cm of the hepatic capsule. Inversely, gas in the biliary tract moves 


with the centripetal flow of bile, thus appearing more centrally in 

the liver. 1 In our case, we believe that the gas in the portal vein 

was due to the ischemia and necrosis of the sigmoid colon with resultant 

mucosal damage and pneumatosis intestinalis. A repeat CT 

scan of the abdomen 2 weeks after resection of the necrotic colon 

did not show evidence of air in the portal system. 

References 

M.F. Jarmakani, M. R. Mohebbi 

1. Peloponissios N, Halkic N, Pugnale M, Jornod P, Nordback P, Meyer 

A, et al. Hepatic portal gas in adults: Review of the literature and presentation 

of a consecutive series of 11 cases. Arch Surg. 2003; 138: 

1367 – 1370. 

2. Liebman PR, Patten MT, Manny J, Benfield JR, Hechtman HB. Hepatic 

portal venous gas in adults: Etiology, pathophysiology, and clinical 

significance. Ann Surg. 1978; 187: 281 – 287. 

3. Simmons TC. Hepatic portal venous gas due to endoscopic sphincterotomy. 

Am J Gastroenterol. 1988; 83: 326.

Excerpts from Persian Medical Literature 

Excerpts from Persian Medical Literature 

Investigation of Periodontal Conditions in Patients with Rheumatoid Arthritis 

Periodontal disease with alveolar bone resorption and tooth loss is common in rheumatoid arthritis (RA). RA subjects show inadequate 

plaque control due to physical disabilities as well as a compromised immune response, both of which might result in a greater predisposition 

to periodontal disease in these subjects compared to the normal population. This study aims to evaluate the prevalence of periodontal 

disease among RA patients. 

Periodontal status (plaque, index, papillary bleeding index, and missing teeth) was examined in 70 individuals that included 35 patients 

with active RA and 35 healthy individuals as the control group. The results were analyzed using SPSS software and student’st-test. 

Patients with RAcomprised 31 females (88.6%) and 4 males (11.4%) with a mean age of 45 years. The healthy control group included 

26 females (74.3%) and 9 males (25.7%) with a mean age of 37 years. Patients with RA showed significant increases in plaque index 

(P=0.0001), papillary bleeding index (P=0.002),and number of missing teeth (P=0.03) compared to the control group. Three patients 

also had secondary Jorgen’ssyndrome. 

Patients with RA had more periodontal disorders compared to the control group. The effects of this chronic inflammatory disease and 

immune host deficiency could be attributed to the presence of a physical disability which precludes the maintenance of oral health and 

the gingival effects of anti-rheumatic medications. 

Authors:Taheri M, Saghafi M,Najafi MH,Radvar M, Marjani S, Javanbakht A, Baghani Z. 

Source: J Mash Dent Sch.2011; 35(4): 283 – 288. 

Effects of Stress Management Training on Glycemic Control in Women with Type 2 Diabetes 

Diabetes is a complicated disease which often leads to a number of psychological disorders such as stress, anxiety, and depression. 

Complete treatment of this disease requires psychological assessment and cognitive behavioral therapy. The purpose of this research is 

to study the effects of stress management training on glycemic control, stress, depression, and anxiety in women with type 2diabetes. 

The study population consisted of 46 type 2 diabetic women, aged 32–65 years, matched for age and additional criteria considered in 

this research. Subjects were randomly divided into two groups, experimental (n=23) and control (n=23). We assessed depression, anxiety, 

and stress by the DASS scale. HbA1c levels for all patients were measured prior to intervention. The experimental group underwent 12 

sessions of stress management based on the cognitive-behavior method, which was conductedfor 2 hours each week, after which patients 

were again assessed for DASS and HbA1c, and after 6 months as the follow up period in both groups. 

There was a significant difference between experimental and control groups in HbA1c levels. The rate of HbA1c in the experimental 

group significantly decreased compared to controls (P

336 

Archives of Iranian Medicine, Volume 15, Number 5, May 2012

In the Name of God

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