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Malignant vascular tumours of the pleura in "asbestos" workers and endothelial differentiation in malignant mesothelioma.

BACKGROUND: Three cases of diffuse malignant vascular tumours of the pleura are described which mimicked malignant mesothelioma clinically and pathologically (so called "pseudomesothelioma"). All had occupational histories of exposure to asbestos. The relationship of these tumours to mesothelioma and asbestos exposure is discussed. METHODS: To examine the histogenetic relationship between mesothelioma and these three tumours an immunohistochemical analysis of vascular marker (CD31, CD34, and Von Willebrand factor) expression was undertaken in 92 cases of pleural mesothelioma, in addition to these three tumours. Electron microscopic fibre analysis of lung tissue was performed on each of the three cases to assess asbestos fibre content. RESULTS: Diffuse pleural epithelioid haemangioendotheliomas may closely resemble malignant mesothelioma clinically and pathologically but, of the 92 pleural mesotheliomas tested, none showed expression of CD31, CD34, and Von Willebrand factor. Although all three cases had claimed exposure to asbestos, ferruginous bodies typical of asbestos were only seen by light microscopy in case 2, and only in this subject was the asbestos fibre content raised in comparison with the range seen in a non-exposed background population. The latent period in the pleural epithelioid haemangioendotheliomas ranged from 18 to 60 years. CONCLUSIONS: Endothelial differentiation does not appear to occur in mesothelioma and therefore should be clearly separated from it. No definite association between pleural epithelioid haemangioendothelioma and exposure to asbestos can be made from this small series but further investigation is warranted.

Adult↗

Toxoplasmosis in the compromised host.

In 81 cases of toxoplasmosis in patients with neoplasia, collagen-vascular disorders, and organ allografts, the clinical manifestations were highly variable but neurologic syndromes consistent with diffuse encephalopathy, meningoencephalitis, or cerebral mass lesions predominated. Many concomitant infections with DNA viruses were seen. The diagnosis of toxoplasmosis was not made until postmortem examination in most cases. Biopsy of lymph nodes or brain and serologic tests needed for definitive diagnosis were done infrequently. Twenty patients received antitoxoplasma chemotherapy (pyrimethamine and sulfonamide), 16 (80%) showing marked clinical improvement or complete remission. In immunosuppressed hosts disseminated toxoplasmosis appears to result from defects in cellular immunity that permit recrudescence of latent infection. Because cell-mediated immunity to Toxoplasma gondii can be enhanced in animals by administration of adjuvants, immunotherapy may become a useful adjunct to chemotherapy in immunoincompetent humans suffering potentially lethal infection.

Animals↗

Neuropathology of HIV/AIDS with an overview of the Indian scene.

Neurological manifestations of HIV infection and AIDS are being recognized with a frequency that parallels the increasing number of AIDS cases. Next to sub-Saharan Africa, India has the second largest burden of HIV related pathology, essentially caused by HIV-1 clade C in both the geographic locales, in contrast to USA and Europe. But the true prevalence of HIV related neuroinfections and pathology is not available due to inadequate medical facilities, social stigma and ignorance that lead to underdiagnosis. Neurotuberculosis, followed by cryptococcosis and toxoplasmosis in various combinations are the major neuropathologies reflecting the endemicity and manifesting clinically by reactivation of latent infection. Discordance in the clinical prevalence of various infections, when compared to pathological studies highlight similarities in clinical, radiological modalities of diagnosis and inherent problems in establishing definitive diagnosis. Viral infections appear to be relatively rare. Inspite of heavy burden of HIV/AIDS, HIV associated neoplasia is infrequent, including primary CNS lymphomas. HIV encephalitis and HIV associated dementia are considered infrequent, though systematic studies have just been initiated in various centres. Peripheral neuropathy characteristically manifests with vasculitic neuropathy while diffuse infiltrative lymphocytosis syndrome (DILS) involving nerves has not been reported from India. Spinal cord pathology including vacuolar myelopathy is rare, even in asymptomatic cases. Till now the AIDS cases in India were drug naive but a new cohort of cases following initiation of HAART therapy as a national policy is soon emerging, altering the biology and evolution of HIV/AIDS in India. Lacunae in the epidemiology, diagnosis and study of biology of HIV/AIDS are outlined for future research.

Antiretroviral Therapy, Highly Active↗

[Thyroid cancers masked by hyperthyroidism. 12 cases].

The main object of this report was to attract again attention to the fact that obvious hyperthyroidism does not exclude the possibility of associated thyroid carcinoma, although this is an exceptional association. The 12 cases presented here may be added to about 30 cases found in the world literature. They were observed over a period of 13 years by the same surgical team and correspond to 0,3 p. 100 of all thyroid operations, 1 p. 100 of operated cases of hyperthyroidism and 3,6 p. 100 of cases of thyroid carcinoma. Contrary to most published cases, 11 or these cases out of 12, presented, clinically, mainly as hyperthyroidism the carcinotous lesion was either palpabale clinically in the form of a very small nodule (6 cases) or totally latent and discovered operation or even on histology as in 5 cases. Hyperthyroidism produced in 3 cases the classical picture of Graves' disease, in 6 cases that of toxic nodular goiter and, in 2 cases, that of a solitary toxic adenoma. The hyperplasia and the carcinoma were always in anatomically different areas. There is no apparent physiopahtological link and the classical notion of para-neoplastic hyperthyroidism seems debatable in most cases presented here, even in the cases of diffuse hyperfunctional hyperplasia. In any case, whatever the pathogenesis of this association, its possibility should be brought to mind in a case of hyperthyroidism. Surgery should always be advised in cases of toxic adenoma and in Graves' disease when the goiter is irregular and, especially, when a nodule is found. The course and prognosis seem to be mainly dictated by the histological type and the local spread or distant spread of the carcinoma, hyperthyroidism does not aggravate seriously the prognosis.

Adult↗

Cerebral glucose metabolism in five patients with Lennox-Gastaut syndrome.

Regional cerebral glucose metabolic rates were estimated by positron emission tomography, in parallel with electroencephalography and cranial computed tomography in 5 patients with Lennox-Gastaut syndrome. The 5 patients, 3 boys and 2 girls, ranged in age from 10-15 years. Computed tomography revealed no gross abnormalities. Each patient received 2-5 mCi of 2-(18F)-fluoro-2-deoxy-D-glucose (18F-FDG) intravenously. Averaged cerebral glucose metabolic rates were reduced in each cerebral region as compared with controls. Unilateral hypometabolism was present in 4 patients: one in the inferior frontal gyrus as well as the posterior portion of the superior temporal gyrus; one in the inferior frontal gyrus; one in the posterior portion of the superior temporal gyrus; and one demonstrated diffuse hemispheric hypometabolism including the inferior frontal and posterior portion of the superior temporal gyrus. The side of hypometabolism was the same as the epileptogenic focus on the electroencephalogram. No focal changes were demonstrated on the electroencephalogram of a patient whose positron emission tomography revealed hemispheric hypometabolism. Hypometabolism of the inferior frontal and posterior portion of the superior temporal gyrus may relate to the possible pathogenesis of Lennox-Gastaut syndrome. Positron emission tomography has the potential to reveal a latent focal or lateralized abnormality in some patients with non-localized electroencephalographic changes.

Blood Glucose↗

Cerebral microcirculation: heterogeneity of pial arterial network controlling microcirculation of cerebral cortex.

Analysis of the functional behaviour of pial arterial ramifications feeding small areas of the cerebral cortex of rabbits uncovered well-defined heterogeneity of vascular responses during development of functional hyperemia. In the network of the smaller pial arteries, under 100 microns in diameter, the most active segments, the sphincters of offshoots of smaller arterial branches from larger trunks and the precortical arteries just before their penetration as the radial arteries into the cerebral cortex, have been discovered. The frequency of their dilatation was found to be higher, the latent periods of the vascular responses significantly shorter, and the degree of vasodilatation greater than of the adjacent arterial segments. An abundant amount of cholinergic nerve plexuses (containing the cholinesterase) was found in the walls of these active vascular segments, and microapplication of atropine resulted in a considerable decrease of their dilatation. These experimental results indicate the involvement of the cholinergic neurogenic mechanism in the functional vasodilatation, as distinct from the largely accepted effect of the humoral mechanism accomplished by diffusion of active vasodilatory substances from tissue elements to the walls of the feeding arterial branches.

Animals↗

The nephroblastomatosis complex and its relationship to Wilms' tumor: a clinicopathologic treatise.

1. At least one third of all children with Wilms' tumors have evidence of aberrant metanephric differentiation, hamartomas, adenomas and nodules of blastema or Wilms' tumorlets in the subcapsular renal cortex. Only the presence of nodular renal blastema was found to correlate with younger age, suggesting that the other tumorlike lesions may be derivatives. 2. In our experience, all patients with bilateral and sequential bilateral Wilms' tumors have exhibited these characteristics in the "uninvolved" renal tissue removed at nephrectomy. 3. Pancortical (infantile), diffuse superficial (late infantile) and multifocal (juvenile) variants of nephroblastomatosis are defined. In the latter 2 forms of nephroblastomatosis the prognosis after modern therapy is at least as good as it is in patients with unilateral, unicentric Wilms' tumor arising in a histologically normal kidney. 4. The morphologic evidence presented strongly indicates that Wilms' tumor in patients with nephroblastomatosis develops either from nodular blastema or metanephric hamartomas. It is hypothetically possible that all Wilms' tumors develop from these precursors. The latent period between cessation of nephrogenesis and clinical presentation of Wilms' tumor is interpreted as favoring the hypothesis that carcinogenesis per se is the result of a postnatal event but that the substrate for tumor development, aberrant metanephric proliferation, has its inception during gestation.

Adenoma↗

Epstein-Barr virus (EBV)-associated smooth-muscle tumor arising in a post-transplant patient treated successfully for two PT-EBV-associated large-cell lymphomas. Case report.

The association of Epstein-Barr virus (EBV) with smooth-muscle tumors was recently reported in the setting of acquired immunodeficiency syndrome (AIDS) and post-transplantation. We report a case of an EBV-associated smooth-muscle tumor arising in a post-transplant (PT) patient who previously was treated successfully for two EBV-associated PT large-cell lymphomas. A 4-year-old girl required cardiac transplantation for dilated cardiomyopathy when she was aged 23 months. Her PT regimen included cyclosporine, azothiaprine, and diltiazem. At 16 months PT, she presented with anemia, guaiac-positive stools, and an abdominal mass diagnosed as diffuse large-cell lymphoma of B-cell phenotype. Immunosuppressive therapy was reduced, and interferon and i.v. immunoglobulin were initiated. She rapidly developed signs of rejection, and a cardiac biopsy was performed, revealing grade IIIB rejection. Subsequently, immunosuppressive therapy increased. At 23 months PT, a biopsy was done of a large pelvic mass that was diagnosed as immunoblastic large-cell lymphoma. After treatment with chemotherapy and retinoic acid, the size of the mass markedly decreased. Follow-up computed tomography scan revealed multiple liver nodules. A needle biopsy of the liver showed a smooth-muscle tumor of indeterminate grade. Both the lymphomas and the smooth-muscle tumor contained EBV within > 95% of tumor cells by Epstein-Barr (EBER1) in situ hybridization, were of strain type A by Epstein-Barr nuclear antigen-2 (EBNA-2) polymerase chain reaction (PCR) and contained an identical 30 base-pair deletion (amino acids 346-355) of the latent membrane protein (LMP)-1 oncogene by PCR analysis. Notably, the initial large-cell lymphoma and the subsequent immunoblastic lymphoma each contained a unique p53 mutation, suggesting that they were distinct. These data suggest that the same virus contributed to the pathogenesis of both the malignant lymphomas and the smooth-muscle tumor.

Abdominal Neoplasms↗

Basal ganglia injury as a complication of the ketogenic diet.

Movement disorders or basal ganglia injury have not been reported as complications of the ketogenic diet, an alternative treatment for intractable epilepsy. We report on a novel complication of the ketogenic diet manifesting as a severe extrapyramidal movement disorder and bilateral putaminal lesions. A single case is described. A video demonstrating the movement disorder is included. A 5-year-old girl with a cryptogenic epileptic encephalopathy developed focal dystonia, diffuse chorea, and ataxia after starting the ketogenic diet. Cranial magnetic resonance imaging (MRI) demonstrated bilateral putaminal lesions that were not present before starting the diet. MR spectroscopy showed a lactate peak in the basal ganglia, suggesting a failure of mitochondrial energy metabolism as the mechanism of cerebral injury. The radiographic abnormalities resolved after stopping the diet, although the movement disorder persisted. Basal ganglia injury and extrapyramidal movement abnormalities are potential complications of the ketogenic diet. Concomitant use of valproate or a latent inborn error of metabolism may be risk factors for these rare complications.

Ataxia↗

The role of moisture in the nest thermoregulation of social wasps.

Paper nests of social wasps are intriguing constructions for both, biologists and engineers. We demonstrate that moisture and latent heat significantly influence the thermal performance of the nest construction. Two colonies of the hornet Vespa crabro were investigated in order to clarify the relation of the temperature and the moisture regime inside the nest. Next to fairly stable nest temperatures the hornets maintain a high relative humidity inside the nest. We found that in consequence a partial vapor-pressure gradient between nest and ambient drives a constant vapor flux through the envelope. The vapor flux is limited by the diffusion resistance of the envelope. The driving force of vapor flux is heat, which is consumed through evaporation inside the nest. The colony has to compensate this loss with metabolic heat production in order to maintain a stable nest temperature. However, humidity fluctuations inside the nest induce circadian adsorption and desorption cycles, which stabilize the nest temperature and thus contribute significantly to temperature homeostasis. Our study demonstrates that both mechanisms influence nest thermoregulation and need to be considered to understand the thermodynamic behavior of nests of wasps and social insects in general.

Animals↗

[Orofacial herpes and other localizations (genital herpes and neonatal herpes excluded)].

BACKGROUND: Herpes is a pandemic infection in the human species. The purpose of this work was to conduct a critical analysis of the literature devoted to the pathophysiology and treatment of orofacial herpes an other localizations (genital herpes and neonatal herpes excluded). METHODS: We searched for articles in English and French devoted to orofacial herpes and other herpetic localizations indexed in Medline (1980-July 001), EmBase, and the Cochrane Library (1995-July 2001). Critical analysis was based on level of proof using the ANAES methodology. RESULTS: More than 700 articles were identified. One hundred four were selected for this report. Primary HSV1 infection usually occurred before adulthood and involved acute gingivo-stomatitis in the majority of the cases. Several primary HIV1 infections were asymptomatic or aspecific and non-recognized. After the primary infection, the virus remains in the ganglion of the trigeminal nerve in a latent state and can be reactivated sporadically. Reactivation is associated with viral excretion and can be symptomatic (herpetic recrudescence) or not (recurrence). Recrudescence of orofacial herpes is typically labial. No currently available vaccine can prevent acquisition of HSV1. Treatment of acute gingivostomatitis has been standardized and is based on aciclovir. Inversely, the effectiveness of aciclovir and other nucleoside analogs with anti-herpes activity has not been clearly established for prevention or cure of recrudescence of orofacial herpes. Other localizations (hand, anus, diffuse skin localizations in contact sports, Kaposi-Juliusberg syndrome) are much more exceptional. Treatment has not been standardized. DISCUSSION: Despite the abundance of the literature on orofacial herpes, consistent quality is lacking, particularly concerning therapeutic studies. The quality of these reports is generally inferior to those devoted to genital herpes. There has however been a general trend towards improved methodology over the last years. Very little has been reported on exceptional localizations of orofacial herpes.

Acyclovir↗

Detection of Eber-1 RNA in primary brain lymphomas in immunocompetent and immunocompromised patients.

Tissue from primary central nervous system lymphoma (PCNSL) which developed in five patients with acquired immuno deficiency syndrome (AIDS), nine patients without immunodeficiency, and two Epstein-Barr virus (EBV)-positive control cell lines (B95-8 and Raji) were examined for the presence of EBER-1 RNA. The tissues were hybridized with digoxigenin-labeled sense or anti-sense EBER-1 riboprobes. In all five AIDS-related PCNSLs, strong hybridization signals were found with the EBER-1 anti-sense probe. Signals could be eliminated by preincubation of the tissues with RNase-A. Hybridization with the EBER-1 sense probe showed no signal. All PCNSLs from immunocompetent patients (five paraffin-embedded, four frozen) showed no hybridization signals with EBER-1 sense or antisense probe but good hybridization signals with probes to immunoglobulin kappa or lambda light chain indicating RNA preservation. The paraffin-embedded B95-8-positive control cell-line showed positive hybridization in most cells with the anti-sense EBER-1 probe, and up to one percent of the cells had a weak signal with the sense probe. Most Raji cells showed a uniform signal with the anti-sense EBER-1 probe only. We conclude that, PCNSLs that arise in AIDS patients are associated with latent EBV infections, whereas PCNSLs from immunocompetent patients are not indicating a probable role for EBV in pathogenesis of these tumors.

Acquired Immunodeficiency Syndrome↗

[Large cell anaplastic lymphomas in the immunocompromised host].

Large cell anaplastic (LCA) lymphomas are a newly defined tumor entity, which has recently been integrated in the updated Kiel classification. The occurrence of CD30+ LCA lymphoma in the setting of renal transplant patients has so far been reported only once. This report describes two LCA lymphomas of B-cell phenotype in renal transplant patients. The clonal evolution and possible etiologic role of Epstein-Barr Virus (EBV) in LCA lymphoma was studied. Our findings give further evidence that clonal evolution of B-cell populations is a second event in lymphomagenesis and is, at least in the cases studied, preceeded by either reactivated latent or primary EBV-infection with clonal EBV proliferation.

Antigens, CD↗

Aldosterone regulation of sodium and potassium transport in the cortical collecting duct.

The aldosterone-induced up-regulation of Na absorption and K secretion in the CCD is complex and involves the regulation of numerous transport proteins. Some aspects of the response may be species dependent. For example, stimulation of Na and K transport in the rabbit CCD involves a marked up-regulation in the apical cell membrane Na and K conductances, the basolateral cell membrane K conductance, and the basolateral membrane NaK-ATPase activity. In the rat CCD, aldosterone causes a similar up-regulation in the NaK-ATPase and the apical membrane Na conductance, but supposedly has little influence on the apical and basolateral membrane K conductances as evaluated by indirect methods. Furthermore, the marked hyperpolarization of the basolateral membrane with long-term aldosterone treatment in the rabbit CCD is blunted or absent in the rat CCD. Other differences between the CCD of these two species have been outlined. Nonetheless, the basic responses of the CCDs from the two species show similar trends. The actions of aldosterone in the CCD principal cell are summarized in Figure 5. The initial steps have been described previously. Aldosterone (A) diffuse across the cell membrane and binds to a cytoplasmic receptor (R). The receptor complex moves into the nucleus and binds to an acceptor site on chromatin, initiating transcription and the subsequent synthesis of a myriad of new proteins referred to as aldosterone-induced proteins (AIP). The initial observed action of aldosterone is an upregulation of the apical membrane Na conductance during the early phase, which occurs within 1 to 2 hours. The increase in Na conductance likely reflects activation of preexisting latent Na channels and not synthesis of new channels, although activation does require protein synthesis. The increased Na influx during the early phase presents a larger Na load to the Na pump, which is likely reflected as a modest transient increase in intracellular Na activity. Based on kinetic considerations alone, this should cause an increased transport turnover of the pump with a greater Na extrusion rate and K uptake rate. The stimulated Na influx also causes a modest depolarization of the apical membrane during the early phase, which when combined with the increased K uptake via the pump and an apparent modest elevation in the intracellular K activity, results in a more favorable gradient for K secretion (increased driving force) into the tubule lumen.(ABSTRACT TRUNCATED AT 400 WORDS)

Aldosterone↗

[Clinico-diagnostic characteristics of autoimmune thyroiditis in children].

As many as 174 children (152 with autoimmune thyroiditis, 12 with thyroid diseases of non-autoimmune genesis and 10 with diffuse toxic goiter) underwent clinical and laboratory examinations with a purpose of delineating the clinical course and comparative assessments of the methods applied in the diagnosis of autoimmune thyroiditis. High risk for the disease in the pre- and pubertal age, the lack of a specific appearance, gradual disease development, uneventful course in many cases with a progressive development of hypothyrosis, and rare development of the grave patterns of hypothyrosis have been established. In clinically euthyroid conditions, the thyroliberin test revealed the predominance of latent or evident hypothyrosis in the majority of patients. Aspiration puncture of the thyroid accompanied by a cytological study of the punctate and detection of circulating immune complexes (increase of the content of medium-size circulating immune complexes) turned out to be of high diagnostic value. The measurement of the titer of antithyroid antibodies is of importance provided their level is high. Nevertheless the lack of antibodies does not allow one to exclude autoimmune thyroiditis. The scanning of the thyroid is of additional diagnostic significance, particularly in cases that require differentiation with nodular patterns of goiter and neoplasms.

Adolescent↗

Detection and characterization of Epstein-Barr virus in clinical specimens.

Epstein-Barr virus (EBV) is associated with a wide spectrum of benign and malignant diseases. Recent additions to the list include oral hairy leukoplakia; a subset of Hodgkin's lymphomas, particularly those with mixed cellularity histology or those occurring in underdeveloped countries; a subset of diffuse large cell/immunoblastic lymphoma in the immunocompromised, particularly primary central nervous system lymphoma; a subset of peripheral T cell lymphomas; and a subset of gastric carcinomas, particularly undifferentiated carcinomas. There are several distinctive aspects of the biology of the virus that are important in investigations of virus in clinical specimens. The presence of repeated elements in the genome facilitates detection of viral nucleic acids by a variety of hybridization techniques as well as the characterization of the clonality of virus-infected tissues. Latent viral infection is associated with several different patterns of viral gene expression in infected cells. Latent gene products are important because of their growth-regulating and -transforming properties as well as the potent cytotoxic T cell response they elicit. The abundant expression of the EBER RNA transcripts makes possible the sensitive detection of latent infection in EBV-associated tumors. Lytic infection can be inhibited by antiviral nucleoside analogues. Two lytic gene products are of special interest because of their homology to the cellular proteins BCL-2 and interleukin-10. Two viral biotypes or strains with different properties in terms of lymphocyte immortalization and transformation have recently been characterized. Current evidence suggests a differential biotype association with particular malignancies. Characterization of the association of EBV with various disease processes promises to be important for diagnosis and treatment as well as for a better understanding of the epidemiology and pathogenesis of these diabetes.

Herpesvirus 4, Human↗

Latent perianal Paget's disease associated with mucin-producing rectal adenocarcinoma. Report of two cases.

Two cases of latent perianal Paget's disease associated with mucin-producing papillary adenocarcinoma of the rectum are described. In both cases, the rectal tumors appeared as polypoid lesions located just above the dentate line. The adjacent anal squamous mucosa showed lateral invasion of alcianophilic mucin-containing Paget cells. Mucin histochemistry revealed the presence of O-acylated and non-O-acylated sialic acids in both neoplastic goblet cells in the adenocarcinomas and Paget cells in the anal mucosa. The Paget cells were immunoreactive diffusely for low-molecular-weight cytokeratin (CAM 5.2) and carcinoembryonic antigen, and focally for CA19-9, epithelial membrane antigen and CA15-3. All these substances were also expressed in the rectal adenocarcinomas but were negative or showed limited expression in the anal squamous epithelium. These findings indicated secondary epidermotropic infiltration of neoplastic goblet cells from the rectal adenocarcinomas.

Adenocarcinoma, Papillary↗

[A clinicopathologic study of CD30-positive sinusoidal large B-cell lymphoma].

OBJECTIVE: To explore the clinicopathologic features of CD30-positive sinusoidal large B-cell lymphoma (CD30 + SLBCL) and its relative correlation with Epstein-Barr virus (EBV). METHODS: Two cases of CD30 + SLBCL, a 65-year-old men and a 85-year-old women were morphologically and immunophenotypically analyzed. EBV status was also evaluated through not only the polymerase chain reaction (PCR) amplification to the EBV Bam HIW DNA sequence, but also an immunohistochemical detection of the latent membrane protein 1 (LMP1). RESULTS: The patients presented with similarly superficial lymphadenopathy. One of them died of the tumor within 10 months. Microscopically, both of the neoplasms were characterized by a cohesive sinus growth pattern and the monomorphic cytology of the tumor cells. Immunohistochemically, They were both positive for CD45, CD30, and CD20 or CD79alpha, whereas neither expressed EMA, ALK1, nor any histiocytic/T-lineage markers. No evidence of EBV-infection could be found either. CONCLUSIONS: CD30 + SLBCL is a morphologically and immunophenotypically distinctive variant of diffuse large B-cell lymphoma, which should be distinguished from T/null cell type anaplastic large cell lymphoma and some other nodal lesions with a predominantly sinusoidal infiltrative pattern. CD30 + SLBCL may not be correlation with EBV.

Aged↗