Biomedical subjects
Publications and source records attributed to F Qureshi.
In a family at risk for Langer mesomelic dwarfism, we document the onset of disproportionate growth in the second trimester by sonographic biometry. Midtrimester pathologic correlation of this condition demonstrates primary changes in the growthplate in the regions of proliferating cartilage and hypertrophic and degenerative chondrocytes.
A case of the chronic type of placental polyp, occurring in a 37-year-old woman approximately 9 years after abortion of her last known pregnancy, is reported. The placental polyp was predominantly composed of necrotic and hyalinized chorionic villi without identifiable lining trophoblast; however, some villi showed a thin rim of apparently viable syncytiotrophoblast that exhibited focal strong positivity for human chorionic gonadotropin by immunohistochemical studies. Intermediate trophoblast, especially abundant within the intervillous fibrin, appeared most viable and showed strong positivity for human placental lactogen (hPL); syncytiotrophoblast also showed focal positivity for hPL. The basal aspect of the polyp was composed of abundant decidua that contained dilated and ectatic blood vessels. This study demonstrates the presence of cytoplasmic markers for pregnancy in a chronic type of placental polyp, apparently of 9 years' duration, and draws attention to an entity that may be encountered more frequently due to the current prevalence of induced abortions.
Human herpesvirus 6 (HHV-6) is a recently discovered virus which has not been causally linked to any particular disease. In order to investigate the possible role of this virus in the pathogenesis of lymphoid malignancies, we examined tissue samples from 117 patients for the presence of HHV-6-specific DNA sequences. Two cases of non-Hodgkin's lymphoma were found to be positive. One patient had a T cell lymphoma and a preceding history of angioimmunoblastic lymphadenopathy; the other had a B cell lymphoma occurring in the context of Sjögren's syndrome. HHV-6 has been isolated previously from a patient with angioimmunoblastic lymphadenopathy, and viral sequences have been identified in another patient with Sjögren's syndrome and B cell lymphoma. The relationship between HHV-6 and these conditions therefore warrants further investigation.
Mast cell proteinases are known to be released in response to helminth infection, and are, in particular, characteristic of the immune rejection of intestinal nematode parasites. In intestinal mucosal tissue the relevant enzyme is rat mast cell proteinase II (RMCP II) and that of other tissues, including the lung, is rat mast cell proteinase I (RMCP I). The function of these enzymes is unknown, and we have examined the possibility that they directly attack the parasites. This was done by examining the cleavage patterns produced by both proteinases on 125I-labelled excretory/secretory (ES) products of two intestinal nematodes (the infective larva of Ascaris suum, and adult Nippostrongylus brasiliensis) and one which has a pulmonary migration route (the third/fourth stage larva of A. suum). It was first established that all the labelled molecules were proteinaceous, by their susceptibility to broad spectrum proteinases, and that none were host components carried over into culture, by their antigenicity to infected hosts. All the nematode ES products were found to be remarkably resistant to RMCP I and II, only one major component of the infective larva of A. suum being cleaved by both enzymes. This was not found to reflect a resistance to serine proteinases in general, since selected ES components were cleaved by chymotrypsin and trypsin. This would, therefore, argue that, if the enzymes play any direct role in the immune expulsion of nematodes, it is unlikely to be successfully directed at their secretions.
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It is widely accepted that the major cause of visceral larva migrans (VLM) in man is Toxocara canis infection. This has been largely based on the detection of antibodies to this species. We have compared the antigens of T. canis and Toxocara cati in order to establish whether assay for the former might be compromised by infection with the latter. Comparisons were made by radioiodination of the surface and excretory/secretory (ES) glycoproteins of the infective larvae of both species, immunoprecipitation with poly- and monoclonal reagents, and SDS-PAGE. The SDS-PAGE profiles of surface antigens of the two species showed few similarities, whereas that of the ES material indicated considerable homology. Serum from infected animals and a human VLM patient exhibited complete cross reactivity, although there was evidence in the mouse of a specific response to one of the components of T. cati ES. Testing of ES against a panel of monoclonal antibodies (MoAbs) confirmed the similarity; all but one of the MoAbs recognized several of the components of both sources of ES. The only exception was MoAb Tcn-2, which did not react with T. cati surface, somatic or ES antigens. This antibody is known to recognize a carbohydrate determinant which is widespread on T. canis glycoproteins. This species-specific determinant, therefore, represents a reversal of the consensus that peptide determinants tend to be the more specific. Finally, the MoAbs were used to examine the exposure of shared epitopes on the surface of intact larvae of T. cati. Again, fine differences in binding by anti-carbohydrate monoclonals were observed when the two species of Toxocara were compared, reflecting a distinction in exposure or orientation of surface molecules on these nematodes. Moreover, these epitopes were absent or variably present on the surface of freshly hatched larvae, and full exposure did not occur until about 24 h post-hatching. This delay in the presentation of epitopes might have implications for the process of infection in sensitized hosts. In conclusion, it is probable that the serological response in man to T. canis is, by current serological methods, indistinguishable in specificity from that induced by T. cati infection, and that the MoAb which we describe could be used to permit discrimination.
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The materials released in vitro by the tissue-parasitic larval stages of the large roundworm of man, Ascaris lumbricoides, were analysed by radio-iodination, immunoprecipitation, and SDS-PAGE. The antigens were found to be heterogeneous, ranging in molecular weight from 14 to 410 kD, and were found to alter radically during the parasites' migration to the lungs. The antigens secreted by the infective and lung-stage larvae of the pig homologue, Ascaris suum, were compared with those of the human worms. This revealed a remarkable degree of homology between the products of the two, at both the molecular and immunological levels. The two species could be discriminated, however, on the basis of the SDS-PAGE profiles of the antigens secreted by both developmental stages of the parasites examined. Finally, antiserum to the canine ascarid infective to man, Toxocara canis, was found to precipitate a significant proportion of Ascaris-secreted molecules. These studies, therefore, confirm the potent antigenicity of excretory/secretory materials, and their potential for use in immunodiagnosis, but predict serious difficulties for seroepidemiology and the specific detection of ascariasis in man.
The excretory/secretory (ES) antigens of the infective (L2) and lung-stage (L3/4) larvae of Ascaris have been characterized by radio-iodination, immunoprecipitation, and SDS-PAGE. These antigens were found to be heterogeneous, ranging in apparent molecular weights from 14,000 to 410,000, were stage-specific and were the targets of considerable antibody responses mounted in infected hosts. A major contaminant of the ES of L3/4 recovered from the lungs of host animals was found to be serum albumin, which appeared to have been processed in some way by the worm or its secretions. A comparison between the humoral responses of three species of experimental animals showed that rabbits recognized all ES components, while mice and rats responded to distinct subsets of these. The mouse was distinguished by non-recognition of a major 14,000 MW antigen that was common to both L2 and L3/4 ES. The body fluid of adult Ascaris worms (ABF) was similarly characterized, and the antibody response to this was inferior to that of ES materials in discriminating between infected and non-infected animals. The major constituent of ABF was a 14,000 MW molecule homologous to that of larval ES products. The variability in host responsiveness to Ascaris antigens, revealed by the disparate responsiveness of three species of experimental animal, and the potential of ES for serodiagnosis, might prove of significance to immunological studies of ascariasis in man. Moreover, the heterogeneity of ES components questions the assertion of previous workers that the allergenic, IgE-potentiating, and protective activities of larval ES can be ascribed to one molecular species.
Vasectomy has become a popular method of family planning in recent years in Australia. The relatively simple procedure is effective, has few complications and usually does not require hospitalisation.
The female breast is a delicate organ which is prone to infection during lactation. Although the treatment plan outlined by the author appears simple we do not recommend routine treatment by the occasional operator. The breast should be treated with the utmost care and respect because irreversible distortion can result from the chronic inflammation and persistent discharge associated with delayed or inadequate drainage of the abscess.
A patient who received an oral dose of iodine-131 for the treatment of metastatic thyroid carcinoma unexpectedly died with a large total-body retention of the radioiodine. An autopsy was required and the family requested the body to be transported out of state to their home town. Since the radiation intensity near the surface of the cadaver was above 200 mR/hr, advanced planning and special precautions were necessary in order for the autopsy to proceed safely. This required the immediate cooperation of the pathologists, nuclear medicine physicians, health physicists, an endocrine oncologist, and other hospital staff. As a result of team efforts, personnel radiation exposures were kept as low as reasonably achievable, contamination of the autopsy room was minimal, and the radiation level of the cadaver was adequately reduced for safe transport and burial.
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We report on 32 cases of Candida funisitis and describe the associated clinicopathologic features. The Candida funisitis was characterized grossly by small, circumscribed, yellow-white nodules on the umbilical cord surface and, microscopically, by subamnionic microabscesses in which fungal organisms were demonstrable. Chorioamnionitis was present in all cases. Twenty-four (75%) of the 32 infants were premature. There were 7 perinatal deaths, all in immature fetuses. Five (16%) of the 32 fetuses had congenital candidiasis. Five (16%) of the mothers had a history of intrauterine foreign body, including intrauterine contraceptive device in three and cervical cerclage in two. The diagnosis of Candida funisitis should prompt a careful examination for fetal infection, even though it is associated with congenital candidiasis in only a minority of the cases.
Choriocarcinoma arising in the placenta, or intraplacental choriocarcinoma, has seldom been reported, particularly in the absence of maternal metastases. Reluctance to diagnose choriocarcinoma in the presence of chorionic villi can delay diagnosis; however, timely diagnosis of choriocarcinoma is prognostically important, both for the mother and infant. We report the clinicopathologic findings in five mothers and infants in whom choriocarcinoma was identified in the placenta. None of the mothers had a history of gestational trophoblastic disease in previous pregnancies. Three placentas were similar with a single small lesion grossly suggesting a small infarct; microscopically these consisted of infarcted areas surrounded by choriocarcinoma. These three mothers were unusual in that none had metastatic choriocarcinoma; two were treated with chemotherapy and remained disease-free; the third was lost to follow-up shortly following delivery. The remaining two mothers had known pulmonary metastases at time of delivery. One of these latter two placentas contained a large marginal lesion microscopically identified as choriocarcinoma. The fifth placenta had rare microscopic foci of choriocarcinoma, and sheets of necrotic choriocarcinoma were identified in "blood clot" submitted with the placenta. In four of the five cases the choriocarcinoma appeared to be arising from otherwise normal chorionic villi, and in no case was there invasion of the villous stroma. All of the infants survived, and none had evidence of choriocarcinoma. These cases support the concept that choriocarcinoma associated with otherwise normal pregnancy arises in the placenta and may be more common than reported.
We describe extensive placental involvement by hepatoblastoma in a 2600 g, 33-week estimated gestational age (EGA) hydropic female fetus with the hepatoblastoma otherwise limited to the liver. The placenta weighed 1190 g and histopathologic examination revealed diffuse tumor emboli in chorionic villous vessels. The placental tumor exhibited a cytologic appearance similar to the primary tumor and showed strong alpha-fetoprotein staining. Although unusual, other congenital tumors, including neuroblastoma and leukemia, have also been described metastatic to the placenta. This case emphasizes the important role of careful histopathologic examination of the placenta which, combined with immunohistochemistry and clinicopathologic correlation, may establish a diagnosis and possibly obviate the need for invasive neonatal diagnostic procedures.
The objectives of this study were to test the hypotheses that antibiotic therapy will alter the histologic appearance of fetal membranes in preterm premature rupture of membranes (pPROM), and that the membrane histology will demonstrate distinct differences between term and preterm rupture of membranes. We also wished to test interobserver variability of pathologists. Placental membranes were sampled from 268 women participating in a randomized placebo-controlled trial of antibiotic therapy for pPROM at 24-32 weeks of gestation (cases) and from 4 control groups who were not in the randomized trial: (1) preterm labor without pPROM (n = 21), (2) term labor (n = 65), (3) term PROM (n = 21), and (4) term cesarean section (n = 27). The cases and controls were scored for 40 histologic features by pathologists blinded to the identity of each sample (case or control). pPROM histology of samples from patients receiving antibiotics and those receiving placebo was compared using a chi-squared test and with control groups using logistic regression. There were no histological differences between pPROM cases treated with antibiotic and those receiving placebo, nor with respect to duration of membrane rupture greater or less than 48 h. Concordance among pathologists was low for features other than acute inflammation. Logistic regression analysis controlled for race and pathologist, and demonstrated that all of the control groups had significantly fewer common markers of acute inflammation when compared with the pPROM cases. This study suggests that histopathologic evidence of infection is seen more frequently with pPROM than in preterm or term controls. The histologic features used in this study cannot be used to determine the effectiveness of antibiotic therapy.