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Biomedical subjects

F Negro

Publications and source records attributed to F Negro.

At least 127 records · Page 7Linked to original sources

Hepatitis delta virus (HDV) and woodchuck hepatitis virus (WHV) nucleic acids in tissues of HDV-infected chronic WHV carrier woodchucks.

The molecular forms of genomic and antigenomic hepatitis delta virus (HDV) RNA and of woodchuck hepatitis virus (WHV) DNA and WHV RNA were studied in nonneoplastic liver (NL) tissues, hepatocellular carcinoma (HCC) tissues, and several extrahepatic tissues of chronic WHV carrier woodchucks acutely (two animals) and chronically (six animals) superinfected with HDV. HDV was shown to replicate in all NL and HCC tissues but not in any of the extrahepatic tissues analyzed, which included spleen, peripheral blood lymphocytes, kidney, ovary, testis, thymus, lung, and stomach. HDV RNA was present as species with molecular weights consistent with those of monomers, dimers, and trimers of both strand polarities, supporting the rolling circle model proposed for HDV RNA replication. WHV DNA levels in NL, HCC, spleens, and serum were 10- to 100-fold lower than the levels typically observed in chronic WHV carrier woodchucks not infected with HDV. WHV DNA replicative intermediates were rarely observed and only at very low levels, representing less than 10% of the total WHV DNA. By contrast, WHV RNA transcription was not significantly depressed and both primary WHV RNA transcripts, 2.3 and 3.6 kilobases, were observed in NL, HCC, spleens, and in one of the kidney tissues. In addition, a 2.6-kilobase WHV RNA transcript was found in the majority of the NL tissues.

Animals↗

Enterocutaneous fistulas: effect of nutritional management and surgery.

Records of 38 consecutive patients affected by enterocutaneous fistulas were reviewed concerning etiology, site, management, results and prognostic factors. Thirtyfive fistulas resulted from surgical complications, 2 from Crohn's disease and one from pancreatic blunt trauma. Thirty (78.9%) out of 38 fistulas were treated successfully: 22 (57.8%) healed after nutritional treatment, 8 (21.3%) required definitive surgical repair. A significant difference (p = 0.007) in the incidence of medical closure was observed between upper gastrointestinal tract and small bowel fistulas (73.1%) and those located in the large bowel (25%). Large bowel fistulas required definitive surgical repair in 53.8% of cases. Eight patients died prior to fistula resolution; sepsis constituted the major cause of death. Results suggest that the treatment of enterocutaneous fistulas should include early control of infections and appropriate nutritional support. An earlier surgical approach for patients with large bowel fistulas is suggested.

Adult↗

Evidence for replication of hepatitis delta virus RNA in hepatocyte nuclei after in vivo infection.

Examination of a naturally infected human liver and experimentally infected chimpanzee and woodchuck livers by in situ hybridization showed that hepatitis delta virus (HDV) RNA was restricted to hepatocytes. Genomic RNA was 20-30 times more abundant than antigenomic RNA and was predominantly single-stranded while antigenomic RNA was predominantly double-stranded. In acute delta hepatitis, viral RNA was a more reliable marker of virus infection in single cells than hepatitis delta antigen (HDAg) while in chronic hepatitis both markers were usually present in the same cell. In all cases, viral antigen and RNA were localized predominantly to the nuclei of infected cells. Thus, replication of HDV RNA is closely associated with HDAg expression at the cellular and intracellular level and it is likely that this new class of defective animal RNA viruses replicates in the nucleus of the infected cells.

Animals↗

Chronic HDV (hepatitis delta virus) hepatitis. Intrahepatic expression of delta antigen, histologic activity and outcome of liver disease.

The expression of intrahepatic delta antigen (HDAg) was studied in relation to the morphologic features of HDV hepatitis and the outcome of liver disease. The study was performed in 101 patients followed up for an average of 12 years; one or more liver biopsies were available from each patient, giving a total of 167 specimens. The histologic features were assessed using numerical scores. A significant positive relation was observed between the number of HDAg-positive cells and the extent of portal inflammation (Spearman's rank coefficient 0.75). The highest degree of inflammation and intrahepatic expression of HDAg was found before the elimination of the virus, while the outcome of HDV disease was unrelated to the severity of the initial morphologic lesion. These results suggest that the individual immune response may play an important role in the pathogenesis of HDV hepatitis.

Adolescent↗

Chronic hepatitis D virus (HDV) infection in hepatitis B virus carrier chimpanzees experimentally superinfected with HDV.

Chimpanzees that were chronic hepatitis B virus carriers and that were superinfected with hepatitis D virus (HDV) apparently developed acute, self-limited type D hepatitis. Reevaluation with a sensitive hybridization-based assay using RNA probes specific for the HDV genome, however, demonstrated that greater than 50% of these animals still had detectable signs of ongoing HDV replication an average of 2.4 y (range, 1-6.4 y) after inoculation. The only positive marker for the presence of HDV was serum HDV RNA; HDV antigen was undetectable in both serum and the liver by an immunoblot assay and immunofluorescence, respectively. Because the detected amount of viral genome was very low, the previous failure to identify the chronic HDV carrier state in the chimpanzee can be attributed to the lower sensitivity of previously described assays.

Animals↗

Preoperative parenteral nutrition of malnourished surgical patients.

Malnutrition is associated with increased incidence of surgical complications and mortality. The efficacy of preoperative parenteral nutrition in preventing septic states and mortality was evaluated in malnourished patients undergoing gastrointestinal surgery. The patients were allocated to three groups according to criteria of malnourishment. In all groups parenteral nutrition decreased the incidence of septic complications and serious sepsis as compared with control patients.

Clinical Trials as Topic↗

Nutritional monitoring in the ICU: rational and practical application.

The metabolic response to injury can induce a state of hypermetabolism that results in the rapid loss of the body nitrogen, so that a critical reduction in lean body mass that affects morbidity and mortality can occur in a short period of time. The process also induces a redistribution of the body nitrogen away from the skeletal mass and toward the viscera and areas of increased metabolic activity, such as the surgical wound, the zone of inflammation, and toward cells producing mediators. Exogenously administered nitrogen is not very effective in reducing the rate of catabolism. It can, however, increase the rate of protein synthesis. In so doing, the rate of net catabolism is reduced. The modified amino acids appear to be much more effective in achieving these ends than do the standard amino acid formulas. Visceral protein synthesis is difficult to use as an index of visceral protein malnutrition in the settings where the metabolic response to injury is also present. These proteins and the acute-phase reactants may not have the sensitivity and specificity to discriminate between visceral protein malnutrition and the changes induced by the metabolic response to injury. The practical clinical endpoint, then, in managing the nitrogen economy during the metabolic response to injury is to provide adequate nitrogen intake, achieving 2 to 4 gm of positive nitrogen balance whenever possible. Caloric (energy) equilibrium can be achieved. Calories in excess of demand or glucose in excess of the ability to effectively oxidize, however, can have detrimental effects in some settings. Expired gas analysis can be useful in this context. Achieving caloric equilibrium does not appear to be essential. The reduction in malnutrition as a cofactor in morbidity and mortality appears to come from achieving nitrogen equilibrium. These alterations in metabolism induced by metabolic stress and the changes in nutrient requirements have been called metabolic support and are summarized in Table 3. The end-points of metabolic support, whenever possible, become 2 to 4 gm of positive nitrogen balance with an amino acid load that will achieve that balance; support of visceral protein synthesis as judged by acute-phase reactant and hepatic protein (e.g., transferrin) synthesis; and avoiding complications of excess VCO2 and urea production (BUN less than 110 mg per cent) (Fig. 5).

Carbohydrate Metabolism↗

Liver transplantation in hepatitis delta virus disease.

Seven patients with hepatitis delta virus (HDV) cirrhosis underwent liver transplantation. In every case the HDV infection was florid but accompanied by an inactive hepatitis B virus (HBV) infection. The patients were given anti-HB surface antigen (HBsAg) serum globulins and HBV vaccine. Two patients cleared the HBsAg and the HDV, and are alive and well 14 and 15 months, respectively, after transplantation. HDV infection recurred in the other five patients: hepatitis developed in three, another died, and the fifth was re-transplanted for causes unrelated to viral hepatitis (reinfection was shown by the presence of HD antigen in the graft). Liver transplantation is feasible in patients with HDV disease but involves a high risk of HDV reinfection that cannot be predicted by the virological pattern of the native HBV infection or prevented by conventional HBV prophylaxis.

Adult↗

[Cefotiam, a new cephalosporin. Microbiological research, preliminary evaluation of its effect on phagocytosis and clinical multicenter research].

After a brief review of the data on cefotiam in the literature the report presents the results of microbiological research, a preliminary study into the drug's possible actions on phagocytosis and a polycentric clinical study of 93 cases of broncho-pleuro-pulmonary pathology and one sinusitis of the jaw. In vitro cefotiam was found to have an excellent inhibitory effect on gram positive and gram negative bacteria with MICs50 and 90 respectively 0.2 and 0.8 mcg/ml V. Staph. aureus, Str. pyogenes. E. Coli, K. pneumoniae and Pr. mirabilis. A dose-dependent increase in phagocytosis was noted. The clinical response was excellent with 90.43% (88/94) of the cases achieving clinical and radiological cure or very much improved. Cefotiam was very well tolerated with the appearance of 2/94 skin rashes (2.12%). The liver and kidney parameters showed no change at the end of treatment. No increase in enzymuria was noted during treatment with cefotiam.

Absorption↗

Detection of HBV-DNA by in situ hybridization using a biotin-labeled probe.

A biotin-labeled DNA probe specific for hepatitis B virus (HBV) nucleotide sequences was hybridized in situ to liver tissue of 20 patients; 16 were chronic carriers of hepatitis B surface antigen (HBsAg) and 4 had no markers of HBV infection. HBV-DNA was also analyzed in the serum and the liver of these patients by spot and Southern blot hybridization, respectively. Liver specimens from six carriers were positive for HBV-DNA both by in situ and Southern blot hybridization; ten carriers were negative by in situ hybridization, and two of these were positive by Southern blot technique. The staining was granular, mainly cytoplasmic, limited to liver specimens containing replicative forms of HBV-DNA, and associated with detection of HBcAg in hepatocytes by immunofluorescence. The sensitivity of this technique was not sufficient to detect few copies of integrated HBV-DNA. The hybridization procedure was specific, as results were constantly negative in liver specimens of patients without markers of HBV infection, and no reaction was observed using DNA probes lacking HBV-DNA sequences. Detection of HBV-DNA by in situ hybridization, using a biotinylated probe, is a rapid, reproducible, and specific histochemical method. Currently available biotinylated probes are advantageous when absolute sensitivity is not the limiting factor, and they also facilitate studies of the cellular and subcellular distribution of HBV nucleic acids.

Autoradiography↗