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Biomedical subjects

G Kafiri

Publications and source records attributed to G Kafiri.

14 recordsLinked to original sources
PubMed2006

Evaluation of the prognostic and predictive value of p53 and Bcl-2 in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy.

PURPOSE: To assess the prognostic and predictive significance of p53 and Bcl-2 protein expression in high risk patients with breast cancer treated with dose-dense sequential chemotherapy. PATIENTS AND METHODS: From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m2 followed by three cycles of paclitaxel (P) 250 mg/m2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) or to four cycles of E, followed by four cycles of CMF. p53 and Bcl-2 expression was investigated by immunohistochemistry in 392 and 397 patients respectively. RESULTS: Positive expression of p53 was detected in 104 (26.5%) patients and was significantly associated with negative hormonal status, worse histologic grade, higher incidence of disease relapse and higher rate of death. p53 positive expression was a significant negative predictor of overall survival (OS) (P = 0.002) and disease-free survival (DFS) (P = 0.001). Negative expression of Bcl-2 was detected in 203 (51%) patients and was significantly associated with negative hormonal status. Multivariate analysis revealed that, positive p53 expression, higher number of positive nodes and worse tumor grade were related to significantly poorer OS and DFS. CONCLUSIONS: For both treatments, p53 positive expression was a significant negative prognostic factor for OS and DFS while Bcl-2 was not. No predictive ability of p53 status or Bcl-2 status for paclitaxel treatment was evident.

Adult↗
PubMed2006

Diabetes mellitus in chronic hepatitis B and C: prevalence and potential association with the extent of liver fibrosis.

Diabetes mellitus has been reported to have an increased prevalence and to be associated with more severe fibrosis in patients with chronic hepatitis C. We evaluated the prevalence of diabetes mellitus in patients with chronic hepatitis B or C as well as the possible association between presence of diabetes and extent of liver fibrosis. In total, 434 consecutive patients with histologically documented hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (n = 174) or chronic hepatitis C (n = 260) were studied. The relationships of diabetes and epidemiological, somatomorphic, laboratory and histological patient characteristics were evaluated. Liver histological lesions were blindly evaluated according to the Ishak's classification. Diabetes was present in 58 (13%) patients, without any difference between those with chronic hepatitis B (14%) or C (13%). Diabetes was observed significantly less frequently in patients with fibrosis score 0-2 (7.7%) than 3-4 (10.4%) than 5-6 (29.2%) (P < 0.001). The presence of diabetes was independently associated with higher gamma-glutamyl-transpeptidase (GGT) levels and more severe fibrosis or presence of cirrhosis (P < 0.001) as well as with presence of hepatic steatosis and increased serum triglycerides levels (P < 0.02). In the noncirrhotic patients, diabetes was significantly associated with older age and higher GGT levels, but not with the extent of fibrosis. In conclusion, diabetes mellitus is observed in more than 10% of patients with either HBeAg-negative chronic hepatitis B or chronic hepatitis C. The presence of diabetes is strongly associated with more severe liver fibrosis, but such an association may be related to the high prevalence of diabetes in patients with cirrhosis.

Alanine Transaminase↗
PubMed2002

Post-infantile giant cell hepatitis associated with autoimmune hepatitis and polyarteritis nodosa.

We report the case of a patient with corticosteroid-responsive giant cell hepatitis associated with typical manifestations and changes of polyarteritis nodosa from the kidney and central nervous system. Initially, the patient presented with transient right hemiparesis, followed by spontaneous remission without any abnormalities on computed tomography scan, magnetic resonance imaging and cerebrospinal fluid examination. A few months later he was admitted to our clinic because of icterus, peripheral oedema and abdominal distension. He was found to have clinical signs of active cirrhosis. Serological tests for hepatitis B, C and HIV virus were negative. Serum ceruloplasmin. a1-AT and ferritin levels were within normal limits. Antinuclear antibodies were positive (1: 160). Liver biopsy showed micronodular cirrhosis with many eosinophils in the portal tracts and giant hepatocytes with multiple nucleoli in the lobule. Fulfilling the diagnostic criteria for autoimmune hepatitis, he was started on treatment with prednisolone and azathioprine, resulting in both clinical and biochemical responses. Four years later he presented with severe pain at the right costovertebral angle. Ultrasonography revealed a haematoma at the right kidney, and selective angiography of the abdominal aorta, renal arteries and hepatic artery documented microaneurysms in both kidney and liver arteries. Because of severe haemorrhage, right nephrectomy was performed. Histology of kidney specimen showed characteristic lesions of polyarteritis nodosa. Several months later, while on treatment with prednisolone and cyclophosphamide, the patient experienced a fatal episode of brain haemorrhage. An association between autoimmune hepatitis, polyarteritis nodosa and postinfantile giant cell hepatitis has not been reported previously.

Adult↗
PubMed2000

Gliclazide-induced acute hepatitis.

There are few reports in the literature related to sulfonylurea-induced hepatotoxicity. We describe the case of acute hepatitis induced by gliclazide, a second generation sulfonylurea. A 60-year-old woman with diabetes mellitus (type 2) developed an acute icteric hepatitis-like illness 6 weeks after the initiation of gliclazide therapy. Other causes of acute hepatocellular necrosis were excluded. Liver histology showed marked portal inflammation with lymphocytes, monocytes and eosinophils, associated with lobular inflammation (indicative of a histological pattern consistent with drug-induced hepatitis). The drug was immediately withdrawn and the patient was given glibenclamide. The patient recovered clinically and, in less than 4 weeks, her serum bilirubin and aminotransferases returned to normal levels. We believe that this is the first description of acute hepatitis caused by an idiosyncratic adverse reaction to gliclazide or to one of its metabolites. In conclusion, this case strongly suggests that gliclazide can induce acute icteric liver necro-inflammation which may be misdiagnosed clinically as acute viral hepatitis. In patients who show abnormal liver function tests, the immediate discontinuation of gliclazide is recommended.

Chemical and Drug Induced Liver Injury↗
PubMed1999

Fulminant hepatic failure as a presenting paraneoplastic manifestation of Hodgkin's disease.

Malignancies may uncommonly present as fulminant hepatic failure and, due to the rarity of such an occurrence, they may easily be overlooked as one of its possible causes. An unusual case of Hodgkin's disease presenting as a fulminant hepatic failure is reported. A 34-year-old man presented with an acute onset of liver failure characterized by jaundice, ascites, encephalopathy and bleeding diathesis. Chemotherapy was initiated, resulting in a dramatic improvement not only in the patient's level of consciousness, but also in prothrombin time. Unfortunately, he succumbed shortly after to disseminated candidiasis. A post-mortem needle liver sample revealed massive hepatocellular necrosis, but no liver infiltration by the neoplastic disease. We conclude that in Hodgkin's disease, involvement of the liver can be manifested as a syndrome of paraneoplastic fulminant hepatic failure. In such cases, liver transplantation is an absolute contraindication but urgent chemotherapy under antifungal surveillance can be life saving.

Adult↗
PubMed1998

Core variability does not affect response to interferon alpha in HBeAg negative chronic hepatitis B.

BACKGROUND/AIMS: The pre-core stop codon variant (A 1896) of hepatitis B virus (HBV) has been associated with chronic active liver disease with acute exacerbations and a high relapse rate after an initial response to alpha-interferon (IFN-alpha) therapy. Poor sustained response has been correlated with a high prevalence of mutations in the core region, potentially enabling escape from the immune system. The aim of this study was to analyse the predictive factors of response to IFN-alpha in such patients. METHODS: We studied the baseline clinical, biochemical, histological, serological and virological parameters in 30 hepatitis B s antigen positive (HBsAg-positive)/hepatitis B e antigen negative (HBeAg-negative) Greek patients with chronic liver disease. The patients were selected from a cohort who received IFN-alpha for 24 weeks. These were divided into three groups of ten sequential patients: those with no response to IFN-alpha treatment, those who relapsed after an initial response, and those with a sustained response. Serum HBV DNA was measured by a liquid hybridisation method, and the anti-HBc IgM was quantitated by the IMx analyser. The amino-acid sequence of core protein residues 40-89, a region where a clustering of mutations has been detected previously in severe hepatitis, was compared with a sequence from an HBeAg positive patient with chronic liver disease. RESULTS: Multiple logistic regression analysis showed that the initial response to IFN-alpha could be predicted by pre-treatment absence of HBcAg staining in the liver and high ALT values, but no parameter could predict sustained response. The pre-treatment extent and pattern of aminoacid substitutions in the core region sequenced was similar in all groups studied and was not associated with IFN-alpha response. CONCLUSIONS: In HBsAg-positive/HBeAg-negative patients with chronic liver disease, response to IFN-alpha therapy was not correlated with genomic variability of the core region. Other parameters such as pre-treatment HBcAg positivity in the liver and alanine aminotransferase values indicative of disease activity before treatment were associated with initial IFN-alpha response.

Adult↗
PubMed1997

Biochemical and virological outcome of patients with chronic hepatitis C treated with interferon alfa-2b for 6 or 12 months: a 4-year follow-up of 211 patients.

To compare two interferon (IFN) schedules for the treatment of chronic hepatitis C, we followed 211 patients who received 3 million units IFN-alpha2b thrice weekly for either 6 months (group 1; 85 patients) or 12 months (group 2; 126 patients), with a median follow-up of 3.4 (0.1-8.4) and 4.2 (0.7-8.7) years, respectively. The biochemical and virological responses at the end of treatment were 34.1% and 16.5% versus 62.7% and 41.2% for the 6- and the 12-month regimens, respectively. Late biochemical responses (after the third month of treatment) occurred in 30.6% of responding patients, and they were not particularly associated with an adverse long-term treatment outcome. In a multivariate analysis, patients with a primary response were significantly more frequently infected with a non-1b HCV genotype (relative risk [RR]: 14.4), had been treated for 12 months (RR: 6.0), and had an early stage of liver fibrosis (RR: 5.2). Baseline serum HCV-RNA and ferritin levels also bore a significant, though weaker, association with a primary response. Using a set of pretreatment variables in a model of discriminant analysis, we could correctly predict the long-term virological outcome in 86.6% of the individual cases. At the end of follow-up, a biochemical and virological sustained response was observed in 14.1% and 11.8% versus 40.5% and 31% of groups 1 and 2, respectively. Significant predictors of a virological sustained response were a virological primary response (RR: 41.2) and the pretreatment level of serum HCV-RNA (RR: 10.3 per each 10(6)-Eq/mL decrease). Patients with a "good treatment profile," including an early stage of liver fibrosis, a non-1b genotype and serum HCV-RNA <0.35 x 10(6) Eq/mL, had a 66.7% rate of observed virological SR, compared with a zero response for those with the opposite, a "bad treatment profile." We conclude that a 12-month IFN treatment, along with a non-1b genotype and the absence of advanced stage of fibrosis, are the main determinants for the induction of a virological primary response in chronic hepatitis C. Such response, along with a low pretreatment serum HCV-RNA level, are the main predictors for a 4-year virological response to IFN.

Adolescent↗
PubMed1996

Reversal of liver failure in sickle cell vaso-occlusive crisis.

A severe but unusual complication of sickle cell vaso-occlusive crisis is acute liver failure related to intrahepatic cholestasis. The outcome is usually fatal in adults. A case of reversible acute liver failure in a patient with s/beta+ thalassemia is reported. The patient was admitted to the intensive care unit because of major organ failure related to vascular occlusion phenomena. After blood-plasma transfusion and supportive therapy for acute liver failure, complete recovery was noted. A liver biopsy performed at the stage of recovery was compatible with intrahepatic cholestasis and sickling. Even though patients with s/beta+ thalassemia usually manifest milder symptoms, they rarely develop major organ failure such as acute liver failure.

Acute Disease↗
PubMed1996

Sclerosing lymphocytic lobulitis in the male breast.

Sclerosing lymphocytic lobulitis is an inflammatory disorder of the breast that is well recognised in women. It has only been reported previously in two men; two further men with the condition are described here. Both presented with a breast mass, and one was an insulin dependent diabetic. Biopsy specimens from both patients showed circumscribed perivascular and, to a lesser extent, periductal collections of B and T lymphocytes. Sclerosing lymphocytic lobulitis in the female breast shows predominantly perilobular inflammation. The predominantly perivascular distribution in men is consistent with the relative paucity of epithelium in the male breast. Interlobular fibrosis with epithelioid fibroblasts was also present.

Biopsy↗
PubMed1995

Multiple systems organ failure from organophosphate poisoning.

A 68-year-old man was admitted to an intensive care unit after a suicidal ingestion of dimethoate with organophosphate poisoning. Despite temporary improvement, the patient's condition progressively deteriorated with the development of adult respiratory distress syndrome and acute renal failure. Hemodynamic measurements substantiated the evidence of non cardiogenic pulmonary edema, while renal indices the presence of acute tubular necrosis. Despite vigorous organ specific support the patient died on the 12th hospital day. An autopsy confirmed the presence of adult respiratory distress syndrome and acute tubular necrosis. Organophosphate poison can be added to the list of toxins that caused adult respiratory distress syndrome and acute tubular necrosis and provoked the development of multiple systems organ failure.

Aged↗
PubMed1992

Over-expression of p53 nuclear oncoprotein in colorectal adenomas.

p53 is a nuclear phosphoprotein which controls normal cell growth. Normal p53 protein is undetectable by standard immunohistochemical staining and the over-expression found in neoplastic cells correlates with the presence of point mutations of evolutionary conserved regions of the p53 gene. We examined the expression of p53 protein in a series of 36 colorectal adenomas (13 tubular, 17 tubulovillous, 6 villous) showing different degrees of dysplasia (11 mild, 19 moderate, 6 severe), 11 moderately differentiated adenocarcinomas (6 Duke's A, 4 Duke's B, 1 Duke's C) and 5 metaplastic polyps using the polyclonal antibody CM1 which recognises p53 protein in conventionally fixed and processed histological material. We found that 15 out of 36 colorectal adenomas showed p53 immunoreactivity, although in 4 positive cases (26%) the staining was very focal (less than 0.1% positive cells). More than 80% of severely dysplastic adenomas showed strong p53 immunoreactivity and this over-expression was correlated with increased cell proliferative rate as detected by the proliferating-cell-nuclear-antigen (PCNA) staining. p53 nuclear staining was also seen in 8 out of 11 (65%) colorectal adenocarcinomas as previously shown. Our data suggest that the p53 gene mutation, with the subsequent over-expression of the protein, occurs in colorectal adenomas and may therefore be a fundamental genetic event underlying the dysplasia and loss of proliferative control that are characteristic of adenomas with malignant potential.

Adenoma↗
PubMed1992

p53 expression is common in malignant mesothelioma.

The p53 tumour suppressor gene has been shown to be frequently mutated in a wide range of human neoplasms. This is accompanied by increased levels of p53 protein which become immunologically detectable in pathological material. We have investigated the possibility that the differential diagnosis between reactive and neoplastic mesothelium might be resolved using a polyclonal serum raised to human p53 protein, CM-1. None of 20 cases of reactive mesothelial proliferation showed p53 immunoreactivity while 70% (14 of 20) of cases of malignant mesothelioma showed p53 staining. We can thus infer that abnormalities of p53 appear to be a common event in malignant mesothelioma and that p53 immunostaining may be of value in the distinction of malignant mesothelioma from reactive hyperplasia.

Adult↗
PubMedDate not supplied

Combined hepatocellular-cholangiocarcinoma presented with massive pulmonary embolism.

A 30-year-old HBsAg-positive woman was admitted to the hospital because of 6 days of progressive shortness of breath. She was in severe respiratory distress with circulatory collapse. She had an enlarged liver but no stigmata of chronic liver disease or signs of cirrhosis. She had rapidly developed respiratory arrest and was transferred to intensive care unit. Heart ultrasonography and Doppler scan showed right heart straining and high pulmonary artery pressure. Despite cardiovascular and respiratory support she died a few hours after admission. Autopsy revealed combined hepatocellular-cholangiocarcinoma infiltrating the entire liver, metastatic invasion of lung blood vessels and absence of right ventricular hypertrophy. The incidence of hepatocellular-cholangiocarcinoma, a variant of hepatocellular carcinoma, is roughly 2-3% and the presenting symptoms are abdominal pain, weight loss, jaundice, fever or decompensation of liver disease. Associated HBsAg positivity and cirrhosis are reported in 20-30% and 60% of patients, respectively. Metastases to lungs are relatively frequent but this is the first report of hepatocellular-cholangiocarcinoma presented with acute respiratory distress due to massive pulmonary embolism.

Adult↗