Epidemiology and clinical pattern of hepatitis delta virus infection in Pakistan

BACKGROUND AND AIMS: The global epidemiology of hepatitis delta virus (HDV) infection is changing. This study was performed to determine the epidemiology and clinical impact of hepatitis delta in Pakistan. METHODS: Countrywide data was collected from 1994 to 2001. A total of 8721 patients were tested for hepatitis delta antibody. A subset of 97 hepatitis delta antibody reactive inpatients with chronic liver disease were compared to 97 patients admitted with liver disease due to hepatitis B alone. RESULTS: Of the 8721 patients tested, 1444 (16.6%) were reactive for hepatitis delta antibody. Most were males (87.4%, P < 0.001) and younger (mean age 31 years, P < 0.001) compared to HDV non-reactive patients. Prevalence of delta infection was highest in the rural (range 25-60%) compared to the urban population (range 6.5-11%). Analysis of the inpatient data showed that delta infected patients had significantly less severe clinical liver disease and a trend towards lesser development of hepatocellular carcinoma compared to delta negative patients. CONCLUSIONS: (i) HDV infection is present in 16.6% of hepatitis B infected patients in Pakistan, most commonly in younger males living in rural areas; and (ii) delta virus infected patients have less severe clinical liver disease compared to delta negative, hepatitis B patients.     

Effect of heptitis C virus core protein on cellular gene expression: specific inhibition of cyclooxygenase 2

Hepatitis C virus (HCV) core protein plays a significant role in the alteration of cellular gene expression. We expressed HCV core protein using a tetracycline-inducible expression system in HeLa cell lines. Profiles of gene expression in cells expressing the HCV core protein were compared with those in control cells by use of microarray analysis. Cells expressing the HCV core protein showed 86 down-regulated and 41 up-regulated genes, compared with control cells. One gene affected was cyclooxygenase 2 (COX-2). Levels of both COX-2 RNA and the Cox-2 protein were significantly inhibited after the expression of HCV core protein in HeLa cells. Similar results were obtained in hepatoma cells and in a functional assay that measured the production of the Cox-2 protein in response to a mitogenic stimulus. The inhibition of the Cox-2 protein could serve as a means of muting the cellular inflammatory response during HCV infection. Correlation of these findings with analysis of clinical specimens from chronically infected patients should lend further significance to the down-regulation of the inflammatory response via Cox-2.     

Decision-making for lung resection in patients with empyema and collapsed lung due to tuberculosis

OBJECTIVE: Collapsed lung with associated empyema is a different clinical entity from destroyed lung . A low perfusion rate of the diseased lung is usually considered an indication for pneumonectomy in patients undergoing thoracotomy for tuberculosis. Such a criterion may not adequately reflect the functional capacity of the underlying parenchyma when the lung is collapsed. METHODS: One hundred twenty-seven patients underwent thoracotomy for tuberculosis at our hospital between 1998 and 2003. Among these, 5 (4%) patients who had a collapsed lung for more than 3 months and pleural infection were the subjects of this study. Surgery was considered after at least a 3-month course of regular antituberculous treatment. Despite no perfusions in 2 patients and 8%, 10%, and 15% perfusion rates for the remaining 3 patients, decortication alone was intentionally performed, and any kind of resectional operation was avoided. RESULTS: The lung gradually filled the hemithorax between 5 and 12 days after surgery in 4 patients. The remaining patient required a thoracomyoplasty 8 weeks after the initial operation. Repeated perfusion scans 1 and 2 years after decortication continued to show no perfusion in patients who had had no preoperative perfusion. All patients were symptom free on regular follow-up between 10 months and 4.5 years. CONCLUSIONS: It seems that the outcome is unpredictable in terms of lung expansion after decortication, which is a relatively simple procedure compared with other surgical options. We think that the risk of rethoracotomy is acceptable, considering the devastating complications and high mortality rates of resectional surgery in the treatment of such patients.     

Sinonasal undifferentiated carcinoma: clinical and pathologic features and a discussion on classification, cellular differentiation, and differential diagnosis

Sinonasal undifferentiated carcinoma (SNUC) is an uncommon, highly aggressive, and clinicopathologically distinctive carcinoma of uncertain histogenesis. SNUC typically presents as a rapidly enlarging tumor mass involving multiple (sinonasal tract) sites, often with evidence of extension beyond the anatomic confines of the sinonasal tract. The light microscopic features include the presence of a hypercellular proliferation with varied growth patterns, including trabecular, sheet-like, ribbon, lobular, and organoid patterns. The tumor cells are medium to large sized and round to oval and have pleomorphic and hyperchromatic nuclei, inconspicuous to prominent nucleoli, varying amount of eosinophilic cytoplasm, high nuclear-to-cytoplasmic ratio, marked increase in mitotic activity frequently with atypical mitoses, tumor necrosis, and apoptosis. Adjunct analyses (eg, immunohistochemistry, electron microscopy, and molecular biologic studies) are often required in the diagnosis of SNUC and in differentiating it from other undifferentiated malignant neoplasms. The treatment of SNUC includes aggressive multimodality therapy, including surgical resection and adjuvant therapy (ie, radiotherapy, chemotherapy). The prognosis associated with SNUC is poor, and death due to disease often occurs within short periods following the diagnosis. We believe that the histologic definition of SNUC can be expanded to include tumors with limited differentiated foci (ie, squamous cell differentiation) predicated on the caveats that the clinical parameters (ie, rapidly enlarging and destructive sinonasal lesions) and the majority of the histologic findings (ie, undifferentiated pleomorphic cell population) match those features that have heretofore defined SNUC. The presence of squamous cell differentiation would correlate to origin in the Schneiderian epithelium, thereby conferring an ectodermal derivation to these tumors. Irrespective of its cell of origin and perhaps even in the face of differentiated foci in limited parts of the tumor, given its rather unique clinicopathologic characteristics, this tumor should be identified and classified as SNUC, thereby differentiating it from the other specific types of sinonasal carcinomas and nonepithelial malignant tumors.     

Atorvastatin reduces neurological deficit and increases synaptogenesis, angiogenesis, and neuronal survival in rats subjected to traumatic brain injury

Statins administered postischemia promote functional improvement in rats, independent of their capability to lower cholesterol. We therefore tested the effect of statin treatment on traumatic brain injury (TBI) in rats. Atorvastatin was orally administered (1 mg/kg/day) to Wistar rats starting 1 day after TBI for 7 consecutive days. Control animals received saline. Modified Neurological Severity Scores and Corner tests were utilized to evaluate functional response to treatment. Bromodeoxyuridine (BrdU, 100 mg/kg) was also intraperitoneally injected daily for 14 consecutive days to label the newly generated endothelial cells. Rats were sacrificed at day 14 after TBI, and the brain samples were processed for immunohistochemical staining. Atorvastatin administration after brain injury significantly reduced the neurological functional deficits, increased neuronal survival and synaptogenesis in the boundary zone of the lesion and in the CA3 regions of the hippocampus, and induced angiogenesis in these regions. The results suggest that atorvastatin may provide beneficial effects in experimental TBI.     

Maternal brain death, pregnancy and the foetus: the medico-legal implications for Ireland

This paper examines some of the medico-legal issues that arose as a result of a situation which occurred in May 2001 in Ireland when a woman who was a British citizen and who was fourteen weeks pregnant collapsed and suffered a brain haemorrhage. She was taken to hospital where she was placed on life support but declared brain-dead. As a result of the uncertainty regarding the hospital's obligation to the foetus, life-support was maintained until further opinion was sought. After two weeks the foetus died and life support was only then discontinued. In Ireland there currently exists neither medical guidelines nor legislation to regulate such areas of medical practice. Also, the courts have not had the opportunity to comment on this particular matter and thus there exists widespread concern as to how healthcare providers will act if such situation were to occur again in the future. This article examines the following difficult medico-legal implications that arise from the above situation and especially in light of the constitutional protection of the unborn child in Ireland.