2004 Summer Meeting - Amsterdam - The Pathological Society of ...

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Human Intestinal Astrovirus Infection in an
Immunocompromised Child Following Bone Marrow
Transplantation
NJ Sebire , M Malone , G Anderson , N Shah , HB Gaspar , WD
Cubitt
Great Ormond Street Hospital, London, United Kingdom
Introduction: Astroviruses are rare causes of diarrhoea and vomiting in infants
and the elderly, and may also cause symptoms in immune compromised
individuals. Despite its recognition using rt-PCR and immunofluorescence
methods in faecal samples, there is almost no data on their histopathological
features in humans. We report the first case describing the histopathological,
immunohistochemical and ultrastructural features of astrovirus infection in a
human immunocompromised patient.
Case Report. A 4 year old boy underwent bone marrow transplantation for
complications of intractable enterocolitis of infancy. Approximately 6 months
post-transplantation he presented with profuse diarrhoea. Investigation revealed
the presence of adenovirus and astrovirus in faecal samples. Gastrointestinal
biopsies were carried out to differentiate GVHD from infection as the cause of
the diarrhoea. The gastric biopsies were normal. The duodenal and jejunal
biopsies did not indicate GVHD, but showed villus blunting and irregularity of
surface epithelium with a mild lamina propria mixed inflammatory reaction and
no viral inclusions identified. Immunohistochemical staining for adenovirus
was negative but staining for astrovirus demonstrated strikingly positive
intestinal epithelial cells, predominantly located at the villus tips.
Ultrastructurally, intracytoplasmic crystalline viral arrays were identified in
surface enterocytes.
Conclusion. Astrovirus infection may be a cause of diarrhoea in
immunocompromised patients. Histopathological findings may be subtle and
diagnosis requires immunostaining and/or electron microscopy.
162
Spiral Artery Associated Restricted Growth (SPAARG):
Pathophysiology and Fetal Programming Implications
Resulting from Low Intervillous Pressure
NJ Sebire 1 , V Jain 2 , DG Talbert 2
1 Great Ormond Street Hospital, London, United Kingdom, 2 Imperial
College, London, United Kingdom
Introduction: Failure of adequate trophoblastic conversion of maternal spiral
arteries results in high flow resistance and consequent reduction in fetal oxygen
supply in intrauterine growth restriction (IUGR). In addition, raised spiral artery
resistance reduces placental intervillous pressure affecting maternofetal water
transfer. We examine the possible effects of reduced intravillous pressure using
a pathophysiological computer model.
Methods. A simulation of an experiment in which compression cuffs were
placed around each spiral artery to progressively restrict flow, while observing
various fetal and placental variables was carried out.
Results. In normal circumstances, water moved to the fetus in the
cotyledonary core villi, and to the mother in the outer villous layers. While the
fetus was able to match villous capillary pressure to changes in intervillous
pressure, net transplacental water movement was minimal. When spiral artery
resistance was increased sufficiently to cause mean intervillous pressure to fall
below that which the fetus could match, a net flow to the mother appeared
resulting in oligohydramnios and continuing until the resulting fetal blood
hemoconcentration produced a sufficient increase in colloid osmotic pressure to
restrict further loss.
Conclusion. Severe spiral artery flow restriction results in lowered mean
intervillous pressure, net water loss from the fetus and haemoconcentration.
Since systems within the developing feto-placental unit then operate in an
abnormal ionic environment, axes such as the renin-angiotensin set-point may
be affected. This may be a mechanism linking uteroplacental disease and IUGR
to the fetal origins of adult disease.
163
Alveolar Septal Collapse (ASC) in the Transitional Human
Lung: A Possible Common Mechanism in Sudden Unexpected
Death in Infancy (SUDI)
NJ Sebire 1 , DG Talbert 2
1 Great Ormond Street Hospital, Department of Paediatric Pathology,
London, United Kingdom, 2 Institute of Reproductive Science, Imperial
College, London, United Kingdom
Introduction: Sudden unexpected death in infancy (SUDI) is a category used to
represent the largest single group of infant deaths. We investigated a possible
biomechanical mechanism which may be common in SUDI and may provide an
explanation for the association of the known risk factors such as co-sleeping,
prematurity, prone sleeping position, overwrapping, overheating and maternal
smoking.
Methods: On the basis of previously published data on lung development,
surfactant function, connective tissue strength and elasticity, capillary pressures
and biomechanical functions, a dynamic computer simulation was constructed
to observe the consequences of altering various parameters.
Results: Alveolar septal collapse occurs when the balance between surface
tension causing them to collapse, (modified by surfactant function), is greater
than support provided by capillaries and connective tissue. The pressures
depend on both the surface tension itself and on the curvature of the surface
such that collapse is much more likely at low volumes, which may lead to
cyanosis and / or apnoea.
Conclusion: The fundamental developmental instability of the lung
predisposes to ASC, the risk being modified by other factors. SUDI may
represent either intrinsic abnormality in pulmonary development or surfactant
function, or, the combination of overheating, non-prone sleeping position and
partial airway obstruction may act synergistically to precipitate ASC and death.
Risk may be further modified by developmental factors such as prematurity and
environmental cigarette smoke. This hypothesis provides a plausible
biomechanical explanation linking many of the apparently unrelated
epidemiological risk factors for SUDI.
164
Surface Cautery and Contamination of Postmortem
Microbiological Samples: An Audit of Paediatric Autopsies
NJ Sebire 1 , M Malone 1 , J Hartley 2 , AD Ramsay 1 , RA Risdon
1
1 Department of Histopathology, Great Ormond Street Hospital, London,
United Kingdom, 2 Department of Microbiology, Great Ormond Street
Hospital, London, United Kingdom
Introduction: In our centre, paediatric post mortem examinations are carried out
according to a comprehensive protocol, which includes collection of
microbiology samples from CSF, blood, spleen and lung. Splenic and lung
samples are obtained using a sterile blade and forceps, with or without
preceeding surface cauterisation, according to pathologist preference.
Methods. During a five-month period the microbiology results of all cases of
non-forensic paediatric autopsies were reviewed and categorised according to
the method used to obtain the specimen.
Results. There were 70 reports reviewed. In all cases adequate microbiological
samples were obtained from multiple sites as per standard protocol, including
CSF, blood and tissue. In 21 cases surface spleen and lung cautery and splenic
swab was used (the practice of one pathologist), and in 49 cases sterile
instruments were used without prior surface cautery of spleen or lung. In seven
cases the cause of death was sepsis, with pathogenic organisms isolated from
multiple sites regardless of the technique used. The majority of spleen and lung
samples demonstrated growth of contaminents or commensals such as
coliforms, enterococci or upper respiratory tract commensals. Splenic samples
showed no growth in 10/21 (48%) following cautery and swab versus 12/49
(24%) with ‘sterile’ tissue biopsy only. (z=1.9, P=0.05), whereas lung samples
were sterile in 3/21 (14%) and 5/49 (10%) with and without cautery,
respectively.(z=0.5, P=0.6). There was no relation between contamination and
death to autopsy interval. (P=0.59)
Conclusion. Microbiological sampling can provide essential information
regarding cause of death in paediatric autopsies. Contamination is reduced
using swabs versus tissue biopsy but surface cautery per se does not further
reduce contamination risk.
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