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.

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.

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.

Hepatitis B core and surface antigens and delta agent in chronic liver disease in Kuwait.

Hepatitis B surface antigen was detected immunohistochemically in 25 out of 85 liver biopsies (29.4%) of chronic liver disease. Core antigen was also demonstrated in 9 of the 25 Hepatitis HBs Ag positive biopsies (36%). Delta agent however, was found in only one case of HBs positive chronic active hepatitis. The number of hepatocytes staining positively for HBc antigen was greater in those biopsies with the strongest staining for HBs antigen. The only case of chronic active hepatitis positive for delta agent showed that the positive staining was confined to the nuclei of few hepatocytes. The routine histology showed chronic active hepatitis with a moderate degree of inflammation. The present results confirm our previous reports that almost one third of chronic liver disease in Kuwait is associated with hepatitis B infection. Previous serological studies suggest that delta agent infection is also common; however, the present study suggest that delta agent may be a transient, and not a major, contributing factor in the progression of liver disease.

Immunohistochemical localization of collagens and fibronectin in human breast neoplasms.

Forty four specimens from neoplastic, hyperplastic and normal human breast tissues were studied for localization of collagens and fibronectin. Affinity purified antihuman type I, III and IV collagens and antifibronectins were utilized by the indirect immunoperoxidase technique on fixed and paraffin-embedded sections. 86% of the cell cytoplasm of infiltrating ductal and 83% of the lobular cancers were positively stained for collagen type I and III. Collagen type IV, however, was detected in 100% of infiltrating ductal and 83% of lobular carcinomas. Focal cytoplasmic staining is a predominant feature for all antigens in the intraduct carcinoma while a diffuse pattern is encountered in the infiltrating types. Intact basement membranes in various lesions always stained for type IV collagen and showed variable staining for type III collagen and fibronectin. Epithelia of normal, benign, hyperplastic breast and most medullary carcinoma were negative for the three collagen types. Our results are in favour of the view that infiltrating breast carcinoma cells produce inappropriately the majority of collagens and inconsistently other proteins such as fibronectin.

Immunohistochemistry of cytokeratin proteins in squamous and transitional cell lesions of the urinary tract.

Expression of low and high molecular weight cytokeratin proteins was investigated immunohistochemically in a variety of transitional and squamous epithelial lesions of the urinary tract with and without schistosomiasis. The monoclonal antibodies used were CAM 5.2 and NCL5D3 for low, PK 63 and 121 for high, and MAK 6 for a broad range of intermediate molecular weight cytokeratins. On staining with CAM 5.2 and NCL5D3, urothelial hyperplasias (n = 12) and grades 1 (n = 5) and 2 (n = 10) papillary transitional cell carcinomas showed labelling patterns quite distinct from carcinoma in situ (n = 4) and non-papillary grades 2 (n = 6) and 3 tumours (n = 3). Among squamous lesions only focal positivity was obtained in 14 of 22 moderate to poorly differentiated squamous cell carcinomas. By contrast, PK 63 and 121 stained squamous lesions exclusively. MAK 6 stained the whole range of urothelial and squamous lesions with the exception of squamous metaplasias. Polyclonal antikeratin adequately labelled spindle cell areas of high grade tumours. The distinctive staining patterns given by these or similar antibodies may help in the identification of squamous metaplasia and in diagnosing tumours of the urothelium.

Patterns of chronic liver disease in Kuwait with special reference to localisation of hepatitis B surface antigen.

Two hundred and fifty six consecutive liver biopsy specimens (without secondary malignancy) collected over five years were reviewed to characterise the pattern of liver diseases encountered in the Kuwait region. A relatively high proportion of chronic active hepatitis (19%) and cirrhosis (40%) was found. Localisation of HBsAg was carried out by the histochemical orcein method and the immunohistological peroxidase-antiperoxidase (PAP) procedure. The PAP technique was superior to orcein both in quality and quantity in addition to its specificity. Three immunohistological staining patterns were observed: diffuse pancytoplasmic , partial perinuclear, and peripheral cytoplasmic. The positivity rate of HBsAg in chronic hepatitis was 29% and 27%, in all cases of cirrhosis. The results of immunohistology and serology of HBsAg were compared in 52 patients in whom both tests were carried out; almost one third of chronic active liver diseases were positive by both methods. Our data clearly show the sensitivity of immunohistology and its value in detecting HBsAg, especially in retrospective studies where serology is not always available. Additionally, the data show that hepatitis B infection is often associated with the development of chronic liver disease in Kuwait.

Bacteroides fragilis is a silent pathogen in acute appendicitis.

The role of Bacteroides fragilis in the pathogenesis of acute appendicitis was studied in 135 patients in four patient groups: normal (17); phlegmonous appendicitis (17); gangrenous appendicitis (75); and septic complications of appendicitis (26). Aerobic and anaerobic bacteria were isolated from all groups and members of the 'B. fragilis group' were the most common anaerobic isolates. The rate of isolation of B. fragilis was similar from normal and inflamed appendices but was significantly higher from those with septic complications (p less than 0.01). Antibodies against B. fragilis were demonstrated in patients of all groups and occurred with similar frequencies in patients with normal and inflamed appendices but at a significantly higher rate in those with septic complications (p less than 0.01). Whereas patients in this latter group showed IgM-antibody responses to B. fragilis only, those with acute appendicitis had IgM antibodies against a wide range of organisms of the 'B. fragilis group' which suggests that B. fragilis does not play a significant role in acute appendicitis but may be a major cause of its septic complications.

Enzyme immunoassay of prostatic acid phosphatase after prostatic examination. Correlation with prostate size and immunopathology.

Variation in serum prostatic acid phosphatase (PAP) after prostatic digital examination was studied in 22 patients, 18 with benign prostatic hyperplasia (BPH), and 4 with prostatic carcinoma. Serum PAP was determined by enzyme immunoassay (EIA) and compared with standard enzymatic assay (EA). Prostatic tissue from transurethral resection (TUR) was subjected to routine pathologic examination and stained for PAP. PAP level increased above reference range and up to several-fold in 12 of 22 patients (54.5%) by EIA and in 22.7 percent by EA. The increase in PAP correlated positively with the prostate size estimated by digital palpation (R = 0.82, P less than 0.001). There was no definite correlation between the histologic parameters studied and the increase in PAP. No day-to-day variation in PAP level was detected in 8 other patients when samples were taken at 7 AM for three successive days. For proper comparison of PAP value, we suggest that sampling time should be fixed and specimens should be taken before prostatic manipulation.

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.

Schistosomiasis, metaplasia and squamous cell carcinoma of the prostate: histogenesis of the squamous cancer cells determined by localization of specific markers.

Histogenesis of squamous cell carcinoma in two prostates heavily affected by schistosomiasis was determined immunohistochemically by localization of two prostatic specific markers and keratin. The demonstration of prostatic specific antigen and keratin served to differentiate between metaplasia and squamous cell carcinoma associated with prostatic schistosomiasis from other prostatic and urinary bladder neoplasms.

Immunohistochemical localization of toxoplasma antigen in reactive and neoplastic lymph nodes.

Sixty-six formalin fixed, paraffin-embedded reactive and neoplastic lymph node biopsies were examined by the immunoperoxidase (PAP) procedure to localize toxoplasma antigen. 13:16 (81.25%) of the histologically suggestive toxoplasmic lymphadenitis and 4:8 (50%) of Hodgkin's lymphoma with histiocytic (epitheloid) cell infiltrates were positive. All other reactive and neoplastic biopsies were negative. Our data prove the usefulness of the PAP procedure as a specific and sensitive test to confirm the diagnosis of histologically suspicious toxoplasmosis. This study, however, is the first of its kind that demonstrates immunohistologically the association of toxoplasmosis with Hodgkin's lymphoma in the same lymph nodes. It also calls in question the nature of the histiocytes in lymphoid neoplasms and suggests the possibility that, at least in some lymphomas especially Hodgkin's, the histiocystic component may be due to the association of other conditions which are worth of further investigation.

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.

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.