Contribution of bacteriology and virology in sudden unexpected death in infancy.

OBJECTIVE: To appraise the inter-agency protocol used in sudden unexpected death in infancy (SUDI) cases in South Yorkshire, UK. DESIGN: A retrospective audit of 121 postmortems carried out over a 3-year period was completed to assess adherence to local guidelines introduced in 2005 specifying the required microbiological specimen set to be collected at postmortem in cases of SUDI. Data on organisms isolated was also collated and assessed for significance. SETTING: Sheffield Children's Hospital Histopathology Department is the South Yorkshire referral centre for SUDI. Post-mortem samples were processed by Sheffield Teaching Hospital's microbiology and virology departments. PATIENTS: All postmortems of SUDI in children less than 2 years of age performed between January 2004 and December 2007. RESULTS: 116/121 cases had samples sent for microbiological and/or virological investigation: 90% of cases had a blood culture and 68% had a cerebrospinal fluid sample taken. Of the 116 cases, 49% had a potentially pathogenic organism isolated, 73% had post-mortem flora and 10% had no organisms isolated (32% had both post-mortem flora and a potential pathogen). 27% of cases were found to have middle ear exudate requiring sampling, from 48% of which a potentially pathogenic organism was isolated. CONCLUSIONS: Our finding of a potential pathogen in 57/116 (49%) of our cases, although not necessarily the cause of death, confirms the relevance of performing multisite and virology investigations in all cases of SUDI. Standardised protocols with agreed definitions are necessary for a consistent approach.

A sensitive mutation-specific screening technique for GNAS1 mutations in cases of fibrous dysplasia: the first report of a codon 227 mutation in bone.

AIMS: To report on the mutation-specific restriction enzyme digest (MSRED) method using paraffin-embedded tissue as a means of detecting GNAS1 mutations in fibrous dysplasia (FD), and to determine if any of the reported GNAS1 mutations in endocrine neoplasms, not previously documented in FD, can be found in FD. METHODS AND RESULTS: Sixty-seven cases of extragnathic FD were analysed as two groups, 1997-2002 and 2003-06, chosen because tissue fixation and decalcification methods were more accurately recorded in the latter. MSRED revealed that between 2003 and 2006, 93% of 28 'in house' extragnathic cases harboured a GNAS1 mutation, compared with 75% of 32 cases before 2003. Fixation times of no more than 48 h and decalcification in ethylenediamine tetraacetic acid gave the best results. Of the 56 mutations detected (five gnathic, 51 extragnathic), 32 (57%) were R201H, 21 (38%) were R201C and three (5%) were Q227L. Two Q227L extragnathic cases had unusual clinical/radiological findings. No mutations were detected in osteofibrous dysplasia. CONCLUSION: Detection of GNAS1 mutations by MSRED is a valuable adjunct to the histopathological diagnosis of FD. This is the first report of a Q227L mutation in FD, although it has been previously documented in pituitary adenoma.

The role of perinatal pathological examination in subclinical infection in obstetrics.

Infectious agents are associated with a wide range of obstetric complications and pathological processes affecting the placenta, membranes and fetus. In some cases there will be associated maternal symptoms and signs indicating an infectious aetiology, but in the majority such infection is subclinical, and specific diagnosis or confirmation is achieved following pathological examination of the delivered placenta and/or fetus. There are two major groups of microorganism-related mechanisms associated with significant perinatal morbidity and mortality. First, ascending genital-tract infection, almost always bacterial, which ranges from localized choriodecidual inflammation to frank chorioamnionitis with fetal sepsis; this is a major cause of mid-trimester miscarriage and severe preterm delivery, and more recent data suggest that it may also have potentially important effects via cytokine release mediating neonatal cerebral injury. Second, haematogenous spread of maternal systemic infection--bacterial, viral or parasitic--which may result in isolated placental effects or transmission to the fetus with associated developmental abnormalities and neonatal complications. In many cases distinctive histopathological findings are described, and in addition a wide range of techniques is now available for culture and microscopy to confirm these diagnoses; such techniques include highly specific immunohistochemical markers and sensitive molecular diagnostic techniques such as the polymerase chain reaction. It is likely that with increasingly widespread availability of these investigative approaches to obstetric pathology, a greater understanding of the role of infectious agents in obstetric complications will become apparent.

Histopathological reporting of paediatric cutaneous vascular anomalies in relation to proposed multidisciplinary classification system.

BACKGROUND: The terminology applied to vascular anomalies has been variable in previously published literature making interpretation suboptimal. The International Society for the Study of Vascular Anomalies (ISSVA) has proposed a revised classification based on clinical features and histopathological findings. This classification is increasingly being accepted as clinically useful and a platform for future studies. AIMS: To examine the extent to which the ISSVA classification can be practically applied to diagnostic histopathological specimens. METHODS: Cutaneous vascular lesions received in a single paediatric pathology unit during a 2-year period (2004-5) were reviewed, including glucose transporter protein 1 (GLUT1) immunostaining where required, and lesions were reclassified according to the ISSVA classification. RESULTS: 144 specimens were identified. Appropriate full clinical information was provided in only 17% of cases at submission. Infantile haemangiomas comprised 46% of cases, 18% of which were regressive type, initially inaccurately identified as vascular malformations before GLUT1 immunostaining. 30% of lymphatic malformations and all lymphovenous malformations were previously classified as vascular malformations, not otherwise specified. CONCLUSIONS: The ISSVA classification of vascular anomalies provides a useful framework for histopathologists to classify vascular anomalies. However, meaningful and appropriate use of such a system is dependent on the adequacy of clinical information provided and routine use of immunohistochemical markers.

Interchange between collagenous and lymphocytic colitis in severe disease with autoimmune associations requiring colectomy: a case report.

BACKGROUND: Collagenous colitis and lymphocytic colitis present with a similar clinical picture. Whether these conditions are separate entities or whether they represent different pathological stages of the same condition is an unresolved issue. PATIENT: This is a case of collagenous colitis following a fulminant course in which a colectomy was necessary. In the operative specimen the thickened collagen plate, which had been present only two weeks preoperatively had been lost and the pathology was of a lymphocytic colitis. Six months postoperatively this patient developed a CREST syndrome and primary biliary cirrhosis. CONCLUSIONS: This case shows the lability of the collagen plate and the common ground between collagenous and lymphocytic colitis, and presents evidence that these two conditions are different manifestations of the same disease. It also describes for the first time an association between collagenous colitis and CREST syndrome and primary biliary cirrhosis.

Cholestatic jaundice induced by spontaneous disruption of an oestrogen implant.

OBJECTIVE: To describe the case of a women with cholestatic jaundice induced by the spontaneous fragmentation of an oestrogen implant. PATIENT: A 48-year-old woman, who presented with jaundice, pruritus and a flu-like illness 2 weeks after the insertion of a 100 mg oestradiol implant into her right buttock. INTERVENTIONS: At presentation the implant was removed and found to be fragmented. Investigations revealed an oestradiol level of 1548 pmol/l and an oestrogen-induced cholestatic jaundice. RESULTS: After removal of the implant and progesterone therapy, the patients symptoms resolved. CONCLUSION: This is the first reported case of cholestatic jaundice induced by a subcutaneous oestrogen implant.

Improvement in allograft survival of islets of Langerhans by pretreatment with deoxyguanosine.

In vitro pretreatment of isolated islets of Langerhans prior to transplantation with deoxyguanosine (dGuo) was found to be effective in improving the survival in fully allogeneic diabetic rats (Wistar----PVG). Post transplant immunosuppression was not used. Islets pretreated with various concentrations of dGuo, 1, 1.35, 1.5 and 2 microM dGuo per islet showed a graft survival of 9, 36, 9 and 14% respectively.

Prolongation of allograft survival in diabetic rats treated with cyclosporine by deoxyguanosine pretreatment of pancreatic islets of Langerhans.

In vitro pretreatment of islets of Langerhans with deoxyguanosine (dGuo) has been shown to be effective for the prolongation of islet allograft survival in rats. [This study evaluates the effect of pretreatment of islets with dGuo transplanted into CsA-treated recipients.] Transplantation of dGuo-treated islets from Wistar rats into diabetic hooded (PVG) rats resulted in 36% graft survival without immunosuppression (dGuo-group) and 89% islet survival after a short course of cyclosporine was used in recipients (dGuo + CsA group). In contrast, transplantation of untreated islets into rats without immunosuppression (controls) and with CsA (CsA group) immunosuppression resulted in 0 and 56% survival, respectively. The differences in graft survival between dGuo versus control group (P less than 0.001), (dGuo + CsA) versus control group (P less than 0.0001), and CsA versus control group (P less than 0.002) are statistically significant. Donor-strain skin-graft challenge failed to induce rejection of transplanted normoglycemic rats in (dGuo) and (dGuo + CsA) groups. The results indicate that a state of immunologic unresponsiveness may have been induced in the recipients of dGuo-treated islets, and further treatment with CsA synergistically prolongs islet survival in fully mismatched rats.

Collagen of the dystrophic hamster diaphragm.

The collagen content of the diaphragm was measured in normal and dystrophic hamsters aged 130 and 270 days. The diaphragm collagen content was greater in dystrophic hamsters than in control hamsters of the same age. The effect was greater in the older hamsters whether the collagen content was expressed in terms of the percentage of dry weight, in relation to surface area, or as total collagen. This increase was apparently at the expense of muscle tissue and may be a major factor contributing to respiratory muscle weakness as dystrophy advances.

Primary gastrointestinal non-Hodgkin's lymphoma: a study of 35 patients.

In a retrospective study of 35 patients (29 men, 6 women) with primary non-Hodgkin's lymphomas of the gastrointestinal tract, 13 of the tumours were located in the stomach, 21 in the small bowel and one in the colon. Various radiological findings were detected, and the majority of tumours (23) had high grade histology. Three patients had immunoproliferative small intestinal disease. Only tumours in stages I and II were included in the study, and the majority (25) were in stage IIA. All patients except one had undergone resection of the neoplasm. This was followed by combined chemotherapy in 25 patients, and chemotherapy followed by radiotherapy in three cases. There were two (5.7%) hospital mortalities. Two- and 5-year survival rates were better in those patients with low stage and low grade tumours. The overall 5-year survival rate was 38%.

Transplantation of islets of Langerhans isolated by Trowell's T8 medium in outbred rats: effect of cyclosporine.

This study was carried out to investigate the efficacy of cyclosporine to prolong islets isolated by collagenase in Trowell's T8 medium and Ficoll gradient separation. Our results demonstrate that a short course of cyclosporine is effective in minimizing rejection of transplanted islets in outbred rats.

Differential immunohistochemical localization of cytokeratins and collagen types I and III in experimentally-induced cirrhosis.

Liver cirrhosis was induced in male Wistar rats by subcutaneous injection (1 ml of 30 g/l) of an aqueous solution of thioacetamide. Using the indirect immunoperoxidase technique, high molecular weight keratins were localized in bile ducts and ductules. Low molecular weight cytokeratins were present in regenerating hepatocytes in active cirrhosis; bile ducts were unstained. These results suggest that cytokeratin staining may be useful in distinguishing bile duct epithelium and hepatocytes in hepatobiliary diseases. Anticollagen type III antibody stained hepatocytes and thin connective tissue fibres, while anticollagen type I antibody stained thicker fibres and some sinusoidal cells but not hepatocytes. Collagens were usually undetectable in normal liver cells. It is suggested, therefore, that hepatocytes may play a major role in collagen type III production which precedes the deposition of collagen type I. By contrast, collagen type I may be produced by fibroblasts and some cells along sinusoids (e.g. perisinusoidal fat-storing cells) after liver injury.

Structural changes in glomeruli and proteinuria in streptozotocin diabetic rats.

In streptozotocin induced diabetes in rats, excretion of urinary protein fractions were studied in relation to structural changes in the renal glomeruli, using light and transmission electron microscopy. After six weeks of induced diabetes only beta 1 and beta 2 plasma globulins were significantly elevated. The amount of excreted proteins and degree of glomerular changes were not proportional. In the initial stages (1-2 weeks) glomerular structural changes were very mild and were accompanied by significantly elevated proteinuria. This progressed (4-8 weeks) to moderate to prominent structural changes with intermittent proteinuria except for the fractions beta 1 & beta 2 which were elevated throughout the duration of the experiment. The amount of proteinuria was not proportional to changes in the plasma protein levels. The following conclusions may be made: 1) The mild early glomerular abnormalities seem to be mainly due to acute metabolic disturbances. 2) An early indication of diabetic nephropathy is provided not only by albuminuria, but may also be an elevated excretion of beta-globulin fractions. 3) Decrease of albuminuria in the later stages of diabetes may be related to the deposition of albumin as a basement membrane-like material in the mesangium.

Takayasu's arteritis and nephrotic syndrome in a patient with crossed renal ectopia.

A male patient with nephrotic syndrome, crossed renal ectopia, and extensive Takayasu's arteritis (TA), involving one of the renal arteries, is described. Renal histology showed amyloidosis. After reviewing the literature and considering the finding of raised serum amyloid protein A levels, it was concluded that TA had probably caused the amyloidosis. The crossed renal ectopia must have been a purely coincidental finding.