Value of perinatal necropsy examination.

In a retrospective study of 150 stillbirths and 150 neonatal deaths carried out between 1981 and 1985 the necropsy findings were compared with the clinical diagnoses, which had been obtained from the postmortem request form, and the case notes completed before the necropsy was performed. In all cases the necropsy comprised macroscopic findings and histological examination of all organs, with microbiology, radiology, and cytogenetics where appropriate. Clinically important differences between clinical and pathological diagnoses in 54 of 150 cases (36%) were noted in the cases of stillbirth. Of the neonatal deaths, examination showed clinically important information that had not been recognised during life in 66 cases (44%). Histological examination of tissues was essential for making or confirming the pathological diagnosis in 20% of all perinatal deaths.

Combined non-isotopic in situ hybridisation and immunohistochemistry on routine paraffin wax embedded tissue: identification of cell type infected by human parvovirus and demonstration of cytomegalovirus DNA and antigen in renal infection.

A method for combined immunohistochemistry using alkaline phosphatase antialkaline phosphatase (APAAP) and in situ hybridisation using biotinylated probes was developed. The method requires no change to either technique and no additional procedures between them. The procedure was able to show the cell types involved in parvovirus infection of the fetus. The efficiency of immunohistochemistry and in situ hybridisation for the detection of cytomegalovirus in kidney were also compared: occasional cells contained cytomegalovirus DNA but not antigen. The method is rapid, straightforward, and has wide applications in the study of viral infections, genes, and gene products in tissue sections because it permits the combined demonstration of antigen and nucleic acid on the same section in routine clinical material.

Fatal adenovirus 32 infection in a bone marrow transplant recipient.

A case of disseminated adenovirus type 32 infection causing severe hepatitis, gastrointestinal ulceration and also with respiratory involvement is reported in a bone marrow transplant recipient. Typical viral inclusions were seen in the postmortem histological sections and adenovirus infection was confirmed using in situ hybridisation and isolation of adenovirus type 32 from separate organs at necropsy. This is the first case in which adenovirus 32 was the cause of fatal disseminated disease in a bone marrow transplant recipient.

Parvovirus as a cause of hydrops fetalis: detection by in situ DNA hybridisation.

Lung tissue from 13 cases of unexplained non-immunological hydrops fetalis was examined by in situ hybridisation to detect parvovirus. Four specimens contained parvovirus DNA in cells in the blood vessel lumina and alveoli. Twenty six control cases were negative for parvovirus DNA. As there was no known epidemic of parvovirus infection during the study period, this suggests that parvovirus is a relatively common cause of non-immunological hydrops fetalis. In situ hybridisation may have a role in clinical medicine, particularly for retrospective investigations.

Adenovirus and intranuclear inclusions in appendices in intussusception.

AIMS: To examine the light and electron microscopic features of appendices removed at the time of surgical reduction of intussusception in children; and to confirm that the viral inclusions seen in some of them are due to adenovirus. METHODS: A series of 39 appendices from cases of intussusception and 15 control appendices were reviewed. Light microscopic examination of haematoxylin and eosin stained sections was performed on all of them and one appendix with large numbers of inclusions was examined by electron microscopy. Non-isotopic in situ hybridisation using a biotinylated DNA probe was carried out on sections of appendix from 30 of the cases of intussusception and from the 15 controls. RESULTS: Light microscopic examination showed viral inclusions in 19 of the appendices from the cases of intussusception and in none of the controls. Electron microscopic examination showed viral particles with the typical features of adenovirus. Most of the appendices with viral inclusions in the haematoxylin and eosin stained sections also contained adenovirus DNA as shown by in situ hybridisation. CONCLUSIONS: Viral inclusions seen in appendices from cases of intussusception are caused by adenovirus. Adenovirus DNA was not demonstrable in appendices from cases of intussusception without viral inclusions and the aetiological factors involved in intussusception in these children remain unknown.

Non-isotopic in situ hybridisation and immunophenotyping of infected cells in the investigation of human fetal parvovirus infection.

AIMS: To compare the use of biotinylated and digoxigenin labelled probes for diagnosis of human fetal parvovirus B19 infection in formalin fixed, paraffin wax embedded tissues; and to assess the cellular distribution of the virus in positive cases. METHODS: Sections of lung tissue from 23 cases of anatomically normal non-immune fetal hydrops presenting between 1984 and 1989, and from 13 control cases of hydrops due to chromosomal abnormality were probed for B19 DNA by in situ hybridisation using both biotinylated and digoxigenin labelled probes. The distribution of the virus was then investigated in all cases of fetal B19 infection confirmed in this laboratory to date (n = 11) by combining in situ hybridisation for viral DNA (using the digoxigenin system) with immunohistological labelling for a range of cellular antigens. RESULTS: Five unequivocal cases of B19 infection were identified among the 23 fetuses with unexplained hydrops using both probe labels. When combined with data from previous studies of the period 1974-1983, the results indicate that B19 infection was responsible for 27% of cases of anatomically normal non-immune hydrops and 8% of all cases, of non-immune hydrops presenting to this hospital over 15 years. False positive signal was seen in an additional three cases, using biotinylated probes. Digoxigenin labelled probes gave greater specificity and permitted detailed investigation of tissues high in endogenous biotin. Though most cells containing B19 DNA colabelled as erythroid precursors, viral DNA was frequently detected within mononuclear-phagocytic cells. In three cases viral signal was also found within occasional myocardial cells labelled by antibody to desmin. CONCLUSIONS: A relatively high proportion of cases of anatomically normal, non-immune hydrops are caused by B19 infection. Digoxigenin is a more reliable probe label than biotin for in situ hybridisation in archival fetal tissues. Double labelling for cellular antigens and viral nucleic acid is a powerful technique for investigating virus-host cell interactions, and provides evidence that cell types other than those of erythroid lineage may have a role in human fetal parvovirus infection.

The craft of urologic surgery: modern radical perineal prostatectomy.

Radical perineal prostatectomy (RPP) is the original approach used by urologists for removing the entire prostate for cancer treatment. From its original description approximately 100 years ago, it has gone through periods of increased and decreased popularity. RPP has not been performed as commonly in the United States since the late 1970s, with the introduction of the radical retropubic prostatectomy. With increased emphasis on reducing morbidity associated with radical prostatectomy by less-invasive techniques, however, more surgeons are revisiting RPP. As discussed in this article, RPP offers several advantages over the retropubic or laparoscopic approach for certain patients.

Parvovirus infection of the human fetus and newborn.

Human parvovirus B19 is a recently recognized cause of hydrops fetalis. It is a small, single-stranded DNA virus, which preferentially infects late erythroid precursors and produces red blood cell (RBC) aplasia, fetal anemia, and cardiac failure. Infection is accompanied by characteristic intranuclear inclusions in fixed and circulating RBC precursors. These inclusions have been shown to contain virus particles by electron microscopy and in situ hybridization. Infection of the fetus, mother, and newborn infant can be diagnosed by serological and molecular methods selected to match the stage of the infection. Recent work has shown that parvovirus B19 can infect cells other than erythroid precursors, and that additional mechanisms such as myocarditis may contribute to hydrops fetalis in some cases. Infected fetuses are not always hydropic. Maternal infection results in increased abortion and stillbirth even in the absence of transplacental transmission, which occurs in approximately one third of infected mothers. The overall risk of fetal loss following maternal exposure is much less than previously thought, and may be less than 3% in the first 20 weeks of gestation or approximately 10% if the mother is actually infected. Although parvoviruses are teratogenic in animals, there is no evidence that B19 is a significant teratogen in man. The long-term outlook of survivors of intrauterine infection, including those successfully treated by intrauterine blood transfusion, appears to be good, but requires further study.

Oculo-auriculo-vertebral spectrum with vascular ring and other unusual anomalies.

An infant with the oculo-auriculo-vertebral (OAV) spectrum is described with the previously unreported association of rectal agenesis with recto-urethral fistula. The patient died at the age of 14 weeks from respiratory obstruction. Autopsy revealed the cause of death to be tracheal compression from a pulmonary artery sling. Previous reports of vascular rings within the OAV spectrum are reviewed, and it is concluded that these malformations are an uncommon, but clinically important, complication of the disorder.

Laparoscopic hand-assisted nephrectomy for crossed fused ectopia with polycystic kidney disease.

Polycystic kidney disease occurring in individuals with crossed fused renal ectopia is an extremely rare occurrence. The treatment of individuals with this condition is a unique surgical challenge for the operating physician. Today's advances in laparoscopic techniques provide us with new and innovative ways of performing complex procedures while subjecting patients to relatively minimal surgical trauma. We describe the laparoscopic removal of a severely diseased polycystic crossed fused kidney.

Lethal arthrogryposis multiplex congenital (fetal akinesia deformation sequence, FADS).

Arthrogryposis multiplex congenital (AMC) is the presence at birth of multiple congenital contractures in an intact skeleton. The severity of the condition is highly variable and the possible underlying causes are numerous. Fetal immobility and lesions of the brain, spinal cord, peripheral nerves and muscle, along with mechanical restriction of the fetus in utero are the pathogenic mechanisms that need to be considered. Etiological factors that have been implicated in the development of AMC include genetic conditions, infections, drugs, toxins, maternal hyperthermia, and maternal illness. This review will concentrate on the severe end of the spectrum of AMC that results in disease that is lethal pre- or postnatally, and will discuss the pathology, pathogenesis, etiology, and practical approach to this diversely expressed condition.

Trisomy/partial monosomy 13 mosaicism associated with relatively mild clinical malformation.

A female fetus with a rare de novo chromosome abnormality involving mosaicism with two cell lines with trisomy 13 and presumptive partial monosomy 13 due to a Robertsonian translocation and ring chromosome, respectively, was prenatally diagnosed. On termination this case, together with apparently the only other three reported cytogenetically similar cases, was found to have much less severe clinical abnormalities than might have been predicted. The possibility in these cases that the effects of the trisomy and monosomy for the common segment of chromosome 13 may have counterbalanced each other at the tissue level in embryogenesis thereby resulting in less disturbance of morphogenesis than would be expected for each type of imbalance acting in isolation is considered.

Correlation of antenatal ultrasonography and pathological examinations in 153 malformed fetuses.

Findings in 153 abnormal fetuses diagnosed by antenatal ultrasound and subsequently examined by a pediatric pathologist were reviewed. The primary diagnoses in the 153 cases were 67 nervous system anomalies, 19 gastrointestinal system anomalies, 18 genitourinary system anomalies, 13 chromosomal abnormalities, 10 skeletal system anomalies, and 26 other abnormalities. Forty-six percent of the total number had multiple abnormalities. In 67 cases (44%), autopsy showed further anomalies or altered the ultrasonographic diagnosis. However, in only 36 (25%) were there autopsy findings that altered management. Errors in ultrasound diagnosis were most commonly associated with the presence of multiple anomalies and oligohydramnios. Expert pathological examination remains an essential tool in the management of fetal anomaly.

Clinical and histopathological features of parvovirus B19 infection in the human fetus.

OBJECTIVE: To provide a comprehensive description of the clinical and histopathological features associated with parvovirus B19 infection of the human fetus. SUBJECTS: All cases of parvovirus B19-related fetal death presenting to the John Radcliffe Hospital, Oxford, over a 16 year period. Diagnosis was confirmed retrospectively by non-isotopic in situ hybridization for parvovirus B19 DNA. RESULTS: The ten cases occurred in two clusters (1979-80 and 1988-89) and presented between 15 and 29 weeks gestation. In at least three cases maternal infection was asymptomatic. Nine fetuses were grossly hydropic at necropsy. Histological features common to all cases included the presence of typical intranuclear inclusions in erythroid precursor cells and evidence of vasculitis within placental villi. Inflammatory changes were also present in the myocardium of four cases, with evidence of subendocardial fibroelastosis in three. CONCLUSIONS: Histological features of fetal parvovirus B19 infection are similar across a range of gestational ages. The heart failure and hydropic state associated with fetal parvovirus infection may be of multifactorial aetiology, and not due to fetal anaemia alone.

Case selection and outcome of radical perineal prostatectomy in localized prostate cancer.

Radical prostatectomy continues to play a central role in the management of localized prostate cancer. The majority of patients diagnosed with prostate cancer will undergo radical prostatectomy. A decrease in the morbidity of this surgical procedure has been accomplished through an improved understanding of pelvic anatomy and a greater understanding of the natural history of prostate cancer. Recently, minimally invasive techniques have been applied to radical prostatectomy (laparoscopic prostatectomy) in order to further decrease the morbidity of this operation. What remains to be determined is whether this approach confers the same long term surgical outcomes as the open approach. One method which offers known long term outcomes coupled with decreased morbidity is the radical perineal prostatectomy. The purpose of this paper is to review the criteria for patient selection as well as outcomes of the radical perineal prostatectomy.

Nephrogenic rests and renal abnormalities in Brachmann-de Lange syndrome.

We report renal abnormalities found in four cases of Brachmann-de Lange syndrome (BDLS). In two there were nephrogenic tests and renal cortical cysts, a further case showed cortical cysts, and the fourth had dilated collecting ducts. The literature describing renal abnormalities in BDLS has been reviewed, and this includes a report of one individual with BDLS who developed Wilms tumor. The genetic basis of BDLS has not been elucidated, although a submicroscopic abnormality of chromosome 3 seems likely. Nephrogenic rests may be Wilms' tumor precursor lesions and are seen in syndromes associated with Wilms' tumors. Mutations of genes on chromosome 11 are the most common genetic abnormalities associated with Wilms' tumor, but other chromosomes have also been implicated. The frequency of renal abnormalities in the BDLS suggests that the involved gene may be important in renal development and also possibly in Wilms' tumors.

Placental lesions: is growth a predictor of bad outcome?

Placental lesions are difficult to assess because there is often a discrepancy between the ultrasound findings, clinical diagnosis and pathology. Large placental lesions especially when solid and echogenic on ultrasound may be associated with a high maternal serum alpha-fetoprotein, intrauterine growth retardation or uteroplacental insufficiency. We report three cases in which mainly solid placental lesions were noted to increase in size during the second trimester and the placental weights at birth were relatively heavy when compared to the fetal weight. In all cases there were serious pregnancy complications. Pathological examination showed infarction, haematoma or both. We suggest that the growth of placental lesions during pregnancy may be an important sign related to the severity of the disease and therefore poor outcome.

Direct gastrointestinal toxicity of flutamide: comparison of irradiated and nonirradiated cases.

PURPOSE: Gastrointestinal (GI) side effects of flutamide in cases treated for advanced prostate cancer are well documented. Proposed mechanisms for these side effects include increased serum blood levels, direct vehicle effects and/or local toxicity. If local toxicity, the focus of this study, mediates GI side effects of flutamide then cases exposed to external beam radiation (XRT) should have more symptoms. We hypothesize that GI side effects of flutamide are not a direct local toxic effect resulting in a similar side effect profile for irradiated and nonirradiated cases. Thus, the present study compares GI effects of flutamide in irradiated and nonirradiated cases. MATERIALS AND METHODS: We identified 106 of 440 cases from a prior flutamide dose comparison study as having undergone XRT (56 cases) or radical prostatectomy (50 patients). The prevalence of GI side effects (abdominal pain/distention, diarrhea, constipation, nausea/vomiting and anorexia) was tallied for each treatment group and/or dosing regimen, 250 mg every 8 hours or 500 mg daily. Chi-square analysis with Yates' correction was performed for statistical analysis. RESULTS: The overall prevalence in 106 cases of GI side effects with flutamide was 22%. Treatment specific differences revealed no differences between the XRT and radical prostatectomy groups at 21% and 22%, respectively. Furthermore, independent analysis of treatment groups for each distinct side effect and dosing regimen did not identify significant differences. CONCLUSIONS: Irradiated cases are not at greater risk for the development of GI side effects from flutamide, suggesting that drug induced local toxicity does not mediate GI distress.