Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A further series of 41 adult patients with late-onset hepatic failure was investigates with respect to aetiological factors, particularly hepatitis C and E, which have been identified since our earlier report of this condition. The increased use of transplantation and its impact on survival overall is assessed. Comparison is made with 64 patients admitted over the same period with fulminant hepatic failure of non-A, non-B aetiology. Screening for the hepatitis viruses revealed three cases of hepatitis A and one case of Epstein Barr virus hepatitis. There were no cases of hepatitis C or hepatitis E virus detected by enzyme immunoassay and reverse transcriptase/polymerase chain reaction techniques, although three patients had positivity for IgG anti-hepatitis E virus, demonstrating previous exposure. Serum autoantibodies in a titre greater than or equal to 1:40 were present in 29% of samples tested and in three cases, titres of SMA or ANF were greater than 1:320. In a further five cases, a potentially hepatotoxic agent had been given within 3 months of the onset of symptoms, leaving the majority of patients (29) with no identifiable cause for their disease. The frequency of symptoms, however, including nausea, abdominal discomfort with the subsequent development of ascites, encephalopathy and renal impairment suggest a similar disease process in these patients. Analysis of liver biopsy material showed similar patterns on all cases of map-like necrosis with nodular regeneration and without other additional features of aetiological significance. Differences in clinical and histological changes for the non-A, non-B fulminant hepatic failure comparison group reflect the tempo of disease process rather than the nature and cause of the liver damage. The introduction of transplantation has led to a marked improvement in survival (39% overall in the earlier series). In the 21 patients in whom transplantation was carried out, the 1-year actuarial survival is currently 55%. Treatment of late-onset hepatic failure with corticosteroids and the use of Prostaglandin E1 and interferon in individual cases has been disappointing, and the emphasis in management should be placed on teh early referral of such patients to a centre offering transplantation.
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PMID:Late-onset hepatic failure: clinical features, serology and outcome following transplantation. 865 52

Saquinavir is an HIV protease inhibitor which, formulated as a hard-gel capsule (HGC), was the first drug of its class to become available for the treatment of patients with HIV infection. Despite the beneficial effects that saquinavir HGC-containing combination regimens have shown in the treatment of patients with HIV infection, the HGC formulation has limited oral bioavailability and has shown only modest antiviral activity in vivo. To overcome this limitation (with the aim of improving antiviral efficacy), a soft-gel capsule (SGC) formulation of the drug has been developed. At the recommended dosage of 1200 mg 3 times daily, the SGC formulation of saquinavir achieves plasma concentrations > 8 times higher than those in patients receiving saquinavir HGC 600 mg 3 times daily. Initial results of trials evaluating the therapeutic efficacy of saquinavir SGC-containing combination therapy in patients with moderate to advanced HIV infection are promising. In patients who were previously antiretroviral therapy-naive or -experienced, short term (< or = 36 weeks) treatment with saquinavir SGC in combination with > or = 2 nucleoside reverse transcriptase inhibitors (NRTIs), or nelfinavir, or 2 NRTIs plus nelfinavir led to marked improvements in virological and immunological markers of HIV disease. In comparative trials, saquinavir SGC showed improved antiviral activity compared with the HGC formulation in terms of reducing viral load. Furthermore, saquinavir SGC in combination with 2 NRTIs was as effective as indinavir plus 2 NRTIs in antiretroviral-naive or -experienced patients. Available data suggest that saquinavir SGC-containing combination therapy may be of greatest benefit in patients naive to previous antiretroviral therapy. The SGC formulation of saquinavir appears to be generally well tolerated by adults with HIV infection. Gastrointestinal adverse events, notably diarrhoea, abdominal discomfort, nausea and dyspepsia, are the most common adverse events occurring during treatment with the drug. Initial results of several trials that used surrogate markers to assess treatment efficacy indicate that the SGC formulation of saquinavir, administered in combination with other antiretroviral drugs, is an effective and well-tolerated treatment for patients with moderate or advanced HIV infection. Although further data are required before definitive conclusions can be drawn regarding the comparative efficacy and tolerability of the SGC and HGC formulations, it appears likely that the SGC formulation will replace the conventional formulation as a component of combination regimens for the treatment of patients with HIV infection.
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PMID:Saquinavir soft-gel capsule formulation. A review of its use in patients with HIV infection. 953 May 49

Hyperlactataemia is seen in 8-18.3% of HIV-infected patients taking nucleoside-analogue reverse transcriptase inhibitors (NRTIs). Recent epidemiological studies suggest that most episodes are transient and subclinical. However, symptomatic and occasionally life-threatening cases accompanied by metabolic acidosis and hepatic steatosis (ie, lactic acidosis syndrome) have also been described. Though yet to be fully elucidated, the proposed mechanism is NRTI-induced inhibition of mitochondrial DNA polymerase culminating in derangements in oxidative phosphorylation and lactate homeostasis. Signs and symptoms range from mild hyperlactataemia accompanied by nausea, abdominal discomfort, and weight loss to severe, intractable lactic acidosis complicated by coma and multi-organ failure. Significant progress has recently been made with regard to the natural history of NRTI-related hyperlactataemia. However, other important aspects of the disorder, such as its pathogenesis, predisposing conditions, and management, remain poorly understood. This article reviews the current published work on these issues, identifies areas of controversy, and addresses directions for future research.
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PMID:Hyperlactataemia syndromes associated with HIV therapy. 1452 59

Mixed epithelial and stromal tumor of the kidney is a recently described neoplasm that predominantly affects perimenopausal women. Although typically benign, few cases with malignant features have been reported. Here, we report the second male case of malignant mixed epithelial and stromal tumor of the kidney with sarcomatous transformation. The patient presented with abdominal discomfort and right flank pain. Computed tomography (CT) of the abdomen revealed a large mass arisen from the right kidney with solid and focal cystic components. The patient underwent right radical nephrectomy. Histologic sections showed benign and malignant components. The benign component consisted of multiple tubules and variably sized cysts lined by benign epithelium. The malignant component was predominantly composed of undifferentiated cellular spindle cell sarcoma. By immunohistochemical studies, the epithelial component was positive for cytokeratins and epithelial membrane antigen (EMA). The stromal component displayed strong immunohistochemical expression of vimentin, CD-99, bcl-2; and was negative for cytokeratins, desmin, SMA, S-100, estrogen receptor (ER) and progesterone receptor (PR). Analysis by reverse transcriptase polymerase chain reaction (RT-PCR) failed to identify the SYT-SSX1 or SYT-SSX2 fusion transcripts characteristic of synovial sarcoma. Subsequently adjuvant chemotherapy was given. The patient developed a local recurrent tumor 9 months after operation.
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PMID:Malignant mixed epithelial and stromal tumor of the kidney: the second male case and review of literature. 2496 82

Mixed epithelial and stromal tumor of the kidney is a recently described neoplasm that predominantly affects perimenopausal women. Few cases with malignant features have been reported. Here, we report the case of malignant mixed epithelial and stromal tumor of the kidney with sarcomatous transformation arising in a 27-year-old female. She presented with abdominal discomfort. Computed tomography of the abdomen revealed a large compressive mass arisen from the left kidney with solid and focal cystic components. The patient underwent left radical nephrectomy. Histologic sections showed benign and malignant components. The benign component consisted of multiple tubules and variably sized cysts lined by benign epithelium. The malignant component was composed of undifferentiated cellular spindle cell sarcoma. By immunohistochemical studies, the epithelial component was positive for cytokeratins and epithelial membrane antigen (EMA). The stromal component displayed strong immunohistochemical expression of vimentin, CD99, bcl2; and was negative for cytokeratins, desmin, SMA, S-100, estrogen receptor (ER) and progesterone receptor (PR). Analysis by reverse transcriptase polymerase chain reaction (RT-PCR) failed to identify the SYT-SSX1 or SYT-SSX2 fusion transcripts characteristic of synovial sarcoma.
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PMID:[About a rare tumor of the kidney: Malignant mixed epithelial and stromal tumor]. 2572 64