RESUMO

Neonatal hepatitis is a syndrome of unknown etiology occurring in children with viral liver disease, as well as children with unidentified disorders of bile salt synthesis and other poorly understood metabolic diseases. It is characterized by jaundice, giant cell hepatitis and rare liver failure necessitating liver transplantation. In the present investigation, the outcome of liver transplantation performed in 16 children with neonatal hepatitis at the investigators' institution was determined from 1 January 1989 to 31 December 1991. The results were compared to those obtained in 288 children transplanted for biliary atresia and 66 children transplanted for recognized metabolic liver disease. The children transplanted for neonatal hepatitis (4.1 +/- 1.3 years) and metabolic liver disease (5.8 +/- 0.6 years) were older than those transplanted for biliary atresia (3.3 +/- 0.2 years) (p < 0.01), but did not differ in terms of sex, ABO type, UNOS status or year in which the transplant procedure was performed. Interestingly, first allograft survival was equal in the children with neonatal hepatitis (74%) and those with metabolic liver disease (74%), but was greater than that for children transplanted for biliary atresia (68%) (p < 0.01). Despite this significant difference in first graft survival, no differences in 5-year survival were seen for the three groups (81% for neonatal hepatitis, 68% for biliary atresia and 79% for metabolic liver disease).(ABSTRACT TRUNCATED AT 250 WORDS)

Assuntos

RESUMO

In patients with end-stage liver disease complicated with hypersplenism, neutropenia and thrombocytopenia are risk factors for systemic sepsis and spontaneous bleeding. Granulocyte-macrophage colony-stimulating factor is a naturally occurring cytokine that promotes proliferation and differentiation of granulocyte and monocyte progeny cells. In addition, it is reported to promote the proliferation of megakaryocytes. Its use as an intravenous infusion is Federal Drug Authority (USA) approved for the enhancement of myeloid recovery following autologous bone-marrow transplantation. The present study was initiated to determine whether granulocyte-macrophage colony-stimulating factor could be used to increase the white blood cell and platelet count in patients with cirrhosis and hypersplenism and to determine whether the more convenient subcutaneous route can be used with the same efficacy as the recommended intravenous route. Nine patients with cirrhosis and hypersplenism manifested by a reduced absolute neutrophil count (mean value of 1300 +/- 200/mm3) were studied. In eight patients, Indium white blood cell splenic sequestration scans were obtained before and after the administration of granulocyte-macrophage colony-stimulating factor intravenous infusion or subcutaneously for 7 days. One patient had to discontinue the therapy due to a reaction to granulocyte-macrophage colony-stimulating factor. Following intravenous infusion of granulocyte-macrophage colony-stimulating factor, the mean absolute neutrophil count increased to 2600 +/- 1100/mm3. Following subcutaneous administration, the mean absolute neutrophil count increased to 4100 +/- 200/mm3. No significant change in platelet count occurred with either route of administration. Indium scans obtained before and after the treatment period revealed no significant difference in the splenic uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Assuntos

RESUMO

Seventy-nine subjects (19 women and 60 men) with chronic viral hepatitis were studied to determine the role of hepatic iron and its biochemical correlates in determining response to interferon alpha therapy. Each subject was treated for 6 months with interferon alpha. A total of 45 (57%) subjects achieved either a full or partial response. No differences between responders and non-responders were evident for the type of hepatitis, age, initial alanine aminotransferase, serum iron, total iron binding capacity, %sat, or ferritin. In contrast, the hepatic iron content of non-responders was almost twice that of responders (1156 +/- 283 micrograms/g dry weight vs. 638 +/- 118; p < 0.05). Hepatic iron correlated with total iron binding capacity (r = 0.435) and ferritin (r = 0.585). This study showed that: 1) the hepatic iron content of responders is less than that of non-responders, 2) the relationships of hepatic iron with %sat and ferritin in patients with viral hepatitis are weak, and 3) hepatic iron content predicts a response to interferon therapy.

Assuntos

RESUMO

Using a rat model, the effect of pre-treatment with FK 506 on hepatic ischemia/reperfusion injury was investigated. All control animals died within 72 h of the ischemia/reperfusion injury. Pre-treatment of the animals with FK 506 (0.3 mg/kg in 0.5 ml saline) administered intravenously improved survival. The most striking protection against fatal ischemia/reperfusion injury was achieved in rats that were given FK 506 6 and 24 h prior to the induction of the hepatic ischemic insult (70% and 80% 10-day survival rates, respectively). The hepatoprotective effect of FK 506 was assessed further in a second experiment in which the serum levels of tumor necrosis factor (TNF) and interleukin 6 (IL-6) were measured. These results suggest that a 60-min period of hepatic ischemia and subsequent reperfusion triggers the release of both TNF and IL-6, and that FK 506 pre-treatment (6 h before the ischemic episode) significantly inhibits the production and/or release of these two cytokines compared to untreated controls. These data provide additional information concerning the immunosuppressive and hepatoprotective activities of FK 506. Based upon these data, it is probable that FK 506 attenuates hepatic ischemia/reperfusion injury, at least in part, by reducing TNF and IL-6 levels.

Assuntos

RESUMO

Two estrogenic substances of plant origin have been identified in beer using gas chromatography/mass spectrometry. These phytoestrogens, daidzein and genistein, have previously been shown to be biologically active in animals. Confirming the presence of biologically active phytoestrogens in beer and their possible presence in other beverages, suggests that there may be clinically significant effects related to sustained exposure to phytoestrogens contained in alcoholic beverages.

Assuntos

RESUMO

The prevalence and bacteriology of bacteriuria was studied in 140 patients with cirrhosis of the liver, referred to the University of Pittsburgh Medical Center for evaluation for liver transplantation (72 males and 68 females; mean age 46 years). Urine samples were obtained for cultures within 24 h after admission. Significant bacteriuria (SB) (> 10(5) bacteria/ml) was present in 25 patients (18%), the most common being E. coli (36%) and coagulase-negative staphylococcus (20%). SB was more common in females than in males (32 vs. 4%, p < 0.001), and was seen in every category of cirrhosis. The occurrence of bacteriuria did not correlate with the severity of the underlying liver disease or with the age of the patient. Based upon these results, it can be concluded that: (1) bacteriuria is common in patients with advanced liver disease and occurs in approximately 20% of the cases; (2) it is more common in females than in males; and (3) its prevalence in patients with primary biliary cirrhosis is similar to that in other types of chronic advanced liver disease.

Assuntos

RESUMO

A system consisting of isolated rat hepatocytes immobilized in agarose threads continuously perifused with oxygenated Krebs-Henseleit (KH) solution has been found to maintain cell viability with excellent metabolic activity for more than 6 h. The hepatocytes were monitored by phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy at 4.7 Tesla, by measurement of oxygen consumption and by the leakage of lactate dehydrogenase (LD) and alanine aminotransferase (ALT). The data obtained were comparable to those found for an isolated perfused whole liver in vitro. The effects of allyl alcohol (AA), ethanol, and 4-acetaminophenol (AP) were examined. A solution of 225 microM AA perifused for 90 min caused the disappearance of the beta-phosphate resonance of adenosine triphosphate (ATP) in the 31P-NMR spectra, a 7-fold increase in LD leakage and a 70% reduction in oxygen consumption. Ethanol (1.0 M) perifused for 90 min reduced the beta-ATP signal intensity ratio by 20%, the phosphomonoester (PME) signal by 50% and inorganic phosphate (Pi) by 33% (P less than 0.05). AP (10 mM) caused only mild liver-cell damage. The results demonstrate that perifused immobilized hepatocytes can be used as a liver model to assess the effects of a wide range of chemicals and other xenobiotics by NMR spectroscopy.

Assuntos

Assuntos

RESUMO

The feminization seen in alcoholic male cirrhotics, in whom circulating levels of estrone and estradiol are normal or only moderately elevated, is not fully understood. Conceptualization of the puzzle has heretofore focused on the ethanol component of alcoholic beverages. In addition to ethanol, however, alcoholic beverages contain a myriad of substances which are collectively termed congeners. To examine the possibility that the congeners of alcoholic beverages include substances which are capable of producing an estrogenic effect, the congeners of bourbon were prepared and administered to ovariectomized rats. Exposure to bourbon congeners produced a dose response in both the mass of the uterus plus fallopian tubes and in plasma levels of luteinizing hormone. These findings provide evidence that the congeners of at least one alcoholic beverage are capable of eliciting responses which are consistent with a hypothesis that alcoholic beverages contain estrogenically active substances.

Assuntos

RESUMO

There is considerable evidence that several plant metabolites have estrogenic properties. Given that many alcoholic beverages are made from plants which have been shown to possess estrogenic activity, we considered the possibility that alcoholic beverages may contain estrogenically active substances. To evaluate this hypothesis we first extracted and then used gas chromatography/mass spectrometry to identify two phytoestrogens, biochanin A and beta-sitosterol in the bourbon extracts. Based on these findings we suggest that the feminization observed in chronic male alcoholics with liver disease may reflect, at least in part, the presence of biologically active phytoestrogens in the alcoholic beverages they consume.

Assuntos