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Biomedical subjects

K B Shilkin

Publications and source records attributed to K B Shilkin.

At least 19 recordsLinked to original sources
PubMed1992

Carbamazepine hepatotoxicity: another cause of the vanishing bile duct syndrome.

Serious carbamazepine hepatotoxicity is being recognized more frequently and is usually manifest as an acute granulomatous hepatitis that is self-limiting if the drug is withdrawn. The case of a 59-year-old man who developed the vanishing bile duct syndrome after 2 months of treatment with carbamazepine for glossopharyngeal neuralgia is reported. The characteristic histological features of this syndrome may also be seen in primary biliary cirrhosis, primary sclerosing cholangitis, graft-vs.-host disease after allogeneic bone marrow transplantation, chronic liver allograft rejection, and other drug reactions. The progress of this patient to date suggests that irreversible liver injury resulting in chronic liver disease is likely, in keeping with the clinical course of the vanishing bile duct syndrome in most cases.

Bile Ducts↗
PubMed1992

The concept of mesothelioma in situ: implications for diagnosis and histogenesis.

The concept of mesothelioma in situ is explored by a detailed examination of seven patients, subsequently proven to have pleural malignant mesothelioma, who initially had no evidence of gross tumor and for whom biopsy material was available at this early presentation. The tissue was assessed by routine microscopy, the immunoperoxidase technique for epithelial membrane antigen and silver staining for nucleolar organizer regions. Tiny lesions of the pleura that merged with or were adjacent to microscopically flat monolayered or folded mesothelium with cytological atypia were observed. The atypical cells reacted positively to epithelial membrane antigen, and the nucleolar organizer region counts were elevated. These observations are considered to support the possibility of the presence of mesothelioma in situ. These findings are discussed in the light of the proposed concept of mesothelioma in situ, its histogenesis, and its possible clinical relevance.

Adult↗
PubMed1991

Nodular regenerative hyperplasia of the liver: the importance of combined macroscopic and microscopic findings.

A 40-year-old man with rheumatoid arthritis, splenomegaly and mild thrombocytopenia presented with gross ascites and a history of excess alcohol consumption. Oesophageal varices were documented endoscopically. Alcoholic cirrhosis was suspected and laparoscopy revealed a macronodular liver surface. Liver biopsy disclosed subtle microscopic structural variations which together with the laparoscopic findings were consistent with the diagnosis of nodular regenerative hyperplasia. The importance in diagnosis of macroscopic appearance combined with histological findings is emphasised. Clinically significant portal hypertension may be present at a histologically early stage of this condition.

Adult↗
PubMed1991

Diclofenac hepatitis.

We report five cases of biopsy-proven hepatitis developing between six and 20 weeks after administration of diclofenac. In one patient jaundice had previously developed following use of ibuprofen. In another the clinical, biochemical and histopathological features were those of chronic active hepatitis and treatment with corticosteroids was required. All patients recovered from their liver injury without sequelae. Resolution of symptoms occurred between three and 12 weeks following cessation of the drug, while liver function tests returned to normal between seven and 16 weeks after drug withdrawal, except in the patient with chronic active hepatitis who remained biochemically abnormal for eight months. Three of the five patients developed transient circulating autoantibodies, suggesting immune mechanisms may be important in the pathogenesis of this injury. The incidence of severe hepatic dysfunction related to the use of diclofenac appears low and is probably in the order of one case per 50-100,000 prescriptions.

Aged↗
PubMed1991

Miliary spread of malignant pleural mesothelioma without a clinically identifiable pleural tumour.

A 44-year-old man with past minor exposure to blue asbestos presented with supraclavicular lymphadenopathy and miliary shadowing on his chest radiograph. Cytology and electronmicroscopy on material obtained by fine needle aspiration from his cervical lymph node revealed malignant mesothelioma. Malignant mesothelioma cells were also present in bronchoalveolar lavage fluid and on transbronchial lung biopsy. At autopsy the right pleural cavity was studded with small tumour nodules. This case demonstrates that malignant mesothelioma may present as metastatic disease and without evidence on conventional investigations of a primary pleural tumour.

Adult↗
PubMed1991

Confirmation of the efficacy of hepatic tissue iron index in differentiating genetic haemochromatosis from alcoholic liver disease complicated by alcoholic haemosiderosis.

The hepatic tissue iron index proposed by Bassett et al was evaluated in 35 patients with homozygous genetic haemochromatosis, 67 patients with alcoholic liver disease, and 18 patients with other forms of chronic liver disease with and without cirrhosis. In patients with cirrhosis hepatic tissue iron concentration reliably differentiated alcoholic liver disease from genetic haemochromatosis. Although mean iron concentration was greater in patients with prefibrotic haemochromatosis than in those with prefibrotic alcoholic liver disease, some overlap occurred and complete differentiation of the two conditions was not possible. This overlap was particularly evident in some young patients with haemochromatosis in whom the tissue iron concentration grade fell in the range commonly seen in alcoholic haemosiderosis. Inability to differentiate early genetic haemochromatosis from alcoholic liver disease complicated by haemosiderosis was also a problem with standard Perls's staining. When the hepatic tissue iron index was calculated (hepatic tissue iron concentration/patient's age in years), clear differentiation of genetic haemochromatosis from both alcoholic liver disease and other forms of chronic liver disease was obtained in both cirrhotic and precirrhotic patients. This study confirms that the hepatic tissue iron index is a useful means of differentiating patients with genetic haemochromatosis from those with alcoholic liver disease. We suggest that biochemical estimation of tissue iron concentration and calculation of the tissue iron index in all patients in whom genetic haemochromatosis is a possible diagnosis will reduce the likelihood of misdiagnosing this as alcoholic liver disease.

Aging↗
PubMed1991

Histological and immunohistochemical study of the gall bladder lesion in primary sclerosing cholangitis.

The histological features and type of mononuclear cell infiltrate in gall bladders from six patients with primary sclerosing cholangitis were studied using routine staining techniques and immunohistochemistry. Control studies were performed using the gall bladders from six patients (age and sex matched) with chronic cholecystitis and four with primary biliary cirrhosis. A range of histological abnormalities was present in gall bladders from patients with primary sclerosing cholangitis including a mild to moderate degree of epithelial hyperplasia, pseudogland formation, and mononuclear cell infiltrate of the epithelium; moderate to severe chronic inflammatory cell infiltrate and fibrosis affecting the superficial and deep layers of the gall bladder wall; and minimal smooth muscle hypertrophy. These abnormalities were non-specific and were also present in gall bladders from patients with chronic cholecystitis and primary biliary cirrhosis. Vasculitis and granulomas were not present in the patients with primary sclerosing cholangitis. Immunohistochemistry showed that the superficial and deep mononuclear cell infiltrate in primary sclerosing cholangitis gall bladders was composed predominantly of lymphocytes, in contrast to chronic cholecystitis where macrophages were found in similar or greater numbers. Moreover, T lymphocytes (activated and resting) were present throughout the lymphocytic infiltrate and were apposed to the base and interdigitated between the biliary epithelial cells in significantly greater numbers than in chronic cholecystitis gall bladders. B lymphocytes were present only in lymphoid follicles. Comparative studies using liver biopsy specimens from three of the primary sclerosing cholangitis patients showed a similar T lymphocyte portal tract infiltrate. We conclude that a number of non-specific chronic inflammatory histological abnormalities were present in primary sclerosing cholangitis gall bladders. Immunohistochemistry found other features that were present in this disease - a predominantly lymphocytic mononuclear cell infiltrate of the superficial and deep layers of the gall bladder wall and the presence of T lymphocytes that infiltrated the biliary epithelial cells. These findings support the hypothesis that aberrant cell mediated immune mechanisms may play a role in the pathogenesis of both the intrahepatic and extrahepatic lesions in primary sclerosing cholangitis.

Adult↗
PubMed1990

Autoantibodies to isolated human hepatocyte plasma membranes in chronic active hepatitis. II. Specificity of antibodies.

The fine specificity of autoantibodies to human hepatocyte plasma membranes in autoimmune chronic active hepatitis was determined by one-dimensional immunoblotting. Sera from 12 patients with "classical" autoimmune chronic active hepatitis contained autoantibodies recognizing many human hepatocyte plasma membrane polypeptides in the 15 to 220 kD range. Many of these autoantibodies titrated beyond 1:80,000 and some may be potentially "pathological." In particular, one band with an apparent molecular weight of 60 kD was a dominant and consistent finding in all patients with autoimmune chronic active hepatitis by immunoblotting. Serum absorption studies showed this band to be predominantly liver-specific. Control sera from patients with chronic persistent hepatitis, nonhepatic autoimmune disease and normal healthy subjects possessed low titer reactivity that most likely represented "natural" autoantibodies. Anti-human hepatocyte plasma membranes in autoimmune chronic active hepatitis consisted of all three immunoglobulin isotypes (G,M and A) and their presence was not caused by nonspecific reactions as a consequence of hypergammaglobulinemia. Autoantibodies were shown to be specific by virtue of their absorption and exhaustion on titration. Many were directed at species nonspecific determinants, however, some autoantibodies recognized human-specific polypeptides. The majority of anti-human hepatocyte plasma membranes appeared to be organ-specific as sera from patients with autoimmune chronic active hepatitis reacted only weakly with polypeptides of kidney plasma membranes. Of the activity detected, few bands corresponded with those obtained using polypeptides of human hepatocyte plasma membranes. Our results show that patients with autoimmune chronic active hepatitis possess an array of liver-specific autoantibodies to polypeptide subunits of human hepatocyte plasma membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Autoantibodies to isolated human hepatocyte plasma membranes in liver disease. I. Specificity for chronic active hepatitis.

Circulating autoantibodies reacting with human hepatocyte plasma membranes (HHPM) were quantitated in acute and chronic liver disease using an enzyme-linked immunosorbent assay (ELISA). Anti-HHPM were found most frequently in patients with chronic active hepatitis (CAH), a disease postulated to result from autoimmune processes directed at organ-specific antigens on the surface of hepatocytes. The high incidence of anti-HHPM in CAH (75%) contrasted significantly with all other groups assayed, including primary biliary cirrhosis (44%), alcoholic liver disease (21%), acute viral hepatitis (17%), and chronic persistent hepatitis (8%). The titers of anti-HHPM in CAH were significantly greater than in other liver disease and control groups. Anti-HHPM quantitated by ELISA correlated with hepatocellular membrane staining by indirect immunofluorescence. Autoantibodies to HHPM were found with an equivalent frequency in three etiological subgroups of CAH: autoimmune CAH, hepatitis B virus (HBV)-related CAH, and CAH associated with excess alcohol consumption. Anti-HHPM of the IgG and IgA isotypes were found in the highest frequency. There was a trend for patients with a histologically more severe disease to have higher titers of anti-HHPM. Immunoblots of SDS-PAGE-separated HHPM showed antibodies to react with a number of polypeptides, some of which appeared human specific. These data suggest that isolated HHPM are a source of relevant hepatocellular membrane antigens. Further studies of the different antigenic specificities of anti-HHPM are required to define which of these may be of pathogenetic importance in chronic active hepatitis.

Autoantibodies↗
PubMed1989

'Corkscrew-like' bacteria associated with gastritis.

Gastric spiral bacteria morphologically unlike Campylobacter pylori have recently been described in patients with gastritis. We report an additional case. These organisms are as yet unnamed, remain uncultured and are morphologically similar to organisms present in the gastric mucosa of various mammalian species. Their possible role in the pathogenesis of gastritis is discussed.

Adult↗
PubMed1988

Lymphohistiocytoid mesothelioma: a rare lymphomatoid variant of predominantly sarcomatoid mesothelioma.

Of 394 "definite" mesotheliomas entered in the Australian Mesothelioma Surveillance Program, three bore a striking resemblance to malignant lymphoma by conventional light microscopy, and each was misinterpreted at some stage as lymphoma. The lymphoma-like morphology was a combined result of intense lymphoplasmacytic infiltration and the histiocytoid appearances of the underlying neoplastic cell population. Immunocytochemical analysis demonstrated cytokeratins coexpressed with vimentin within the tumor cells, whereas immunoreactivity for leukocyte common antigen was confined to the smaller lymphoid cells. Electron microscopy of two cases revealed a polymorphous population of fibrohistiocytic cells resembling those typical of malignant fibrous histiocytoma, admixed with lymphocytes and plasma cells, but sporadic cells expressed mesothelial properties in the form of sinuous villiform processes, intracytoplasmic neolumina lined by microvilli, and intermediate filaments that were aggregated into tonofilament bundles in some cells. The ultrastructural appearances, the localization of the tumors to the pleura, with effusion, and absence of anterior mediastinal mass lesions facilitated exclusion of lymphocyte-rich thymoma. In addition, a history of prior occupational exposure to asbestos was elicited in each instance. There was no apparent response to radiotherapy or chemotherapy, and the patients died at 4, 5, and 8 months after presentation. Our observations suggest that immunocytochemical or ultrastructural evaluation is mandatory for accurate diagnosis of all pleura-based lymphomatoid lesions with a mixed large and small cell pattern.

Aged↗
PubMed1986

Pleural fluid CEA levels in the diagnosis of malignant mesothelioma.

A study was undertaken to investigate whether the levels of carcino-embryonic antigen (CEA) in serous effusions helped distinguish between primary mesothelioma and metastatic adenocarcinoma in a body cavity. The investigation was designed to assess the role of the assay only when cytological analysis of the fluid had already shown the presence of malignant cells. No case of mesothelioma studied had levels of CEA above 2.9 ng/ml, whereas 67% of the adenocarcinomas tested were above 15 ng/ml. The test is helpful, therefore, in differentiating between these two types of malignant effusions.

Adenocarcinoma↗
PubMed1985

Trends in mortality from malignant mesothelioma of the pleura, and production and use of asbestos in Australia.

Annual mortality from malignant mesothelioma of the pleura (MMP) in Australia (as represented by ICD8 codes 163.0 and 212.4, and ICD9 codes 163 and 212.4) increased in men aged 30 years and older from about 0.5/100 000 in 1968-1970 to 2.1/100 000 in 1983. Corresponding rates in women varied from 0.1/100 000 to 0.2/100 000 between 1968 and 1980, then rose to 0.3/100 000 in 1983. The rise in MMP mortality in men probably corresponds to the increasing use of asbestos, particularly amosite, in Australia during and after World War II. That production and importation of amosite and crocidolite in Australia reached a peak in 1958 may mean that peak mortality from MMP will not be reached until the 1990s (allowing a 35-year lag period). Substantial increases in importation and later production, of chrysotile in the 1950s, 1960s and 1970s may lead to increases in the incidence of other asbestos-related cancers, not reflected in trends in the incidence of MMP.

Adult↗
PubMed1985

Premalignant epithelial lesions of the gall bladder: a prospective study of 120 cholecystectomy specimens.

One hundred and twenty gall-bladders obtained at cholecystectomy for gall bladder diseases formed the basis of a prospective study of premalignant epithelial lesions. Six cases displayed abnormal mucosa (5%); 4 had atypical hyperplasia (dysplasia) and 2 gall-bladders had carcinoma-in-situ; all were associated with chronic cholecystitis and lithiasis. These changes are considered premalignant and are probably precursors of gall-bladder carcinoma. It is impossible to predict which patient with chronic gall-bladder disease is likely to harbour premalignant epithelial changes. In any event, thorough histological examination of all gall bladders removed surgically is more than justified.

Adult↗
PubMed1984

Diagnosis of pleural malignant mesothelioma in life--a practical approach.

This review documents a practical approach to the pathological diagnosis of pleural malignant mesothelioma based on the closed needle biopsy and effusion cytology, thus avoiding the need to resort to open surgery. Tissue diagnosis is often difficult, and the pathologist's opinion may be influenced by a consideration of three factors: the clinical setting; the adequacy and availability of specimens; and the criteria for assessment and interpretation of these. The level of confidence with which a tissue diagnosis of mesothelioma can be established using limited material depends on there being an appropriate clinical background including a history of asbestos exposure. Without this, the diagnosis should be a qualified or tentative one. For an adequate tissue sample to be obtained, the closed needle biopsy procedure is best performed by an experienced operator. All aspirated pleural effusions should be forwarded for cytological evaluation. In addition to conventional morphological studies, adequate samples permit ancillary tests to be carried out. A combined interpretive approach utilizing both histopathology and cytology is recommended in order to increase the accuracy of the diagnosis.

Adenocarcinoma↗