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

An unusual case of acute cerebral edema as part of the syndrome of portal systemic encephalopathy in an individual with established chronic liver disease is reported. Several episodes of edema occurred with clinically important increases in the blood ammonia level.

Assuntos

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The objective of this study was to define the severe neurological complications that occur in recipients of an orthotopic liver transplantation, receiving FK 506 as their primary immunosuppressive agent. To accomplish this, 100 consecutive orthotopic liver transplantation patients were followed prospectively from the time of their transplant until the date of their initial post-orthotopic liver transplantation discharge from hospital. All major neurological complications occurring during this period were recorded and assessed. The frequency of severe neurological complications occurring in these severely ill transplant recipients was 34%. Delirium was noted in 16, coma in 9, seizures in 4, and 5 developed focal motor deficits associated with the finding of a brain abscess, transient ischemic attack or central pontine myelinolysis. At the time at which a major neurologic complication was noted, the blood level of FK 506 was recorded. No direct relationship between FK 506 blood levels and the presence or absence of major neurologic complications of orthotopic liver transplantation could be demonstrated. Based upon this series, it can be concluded that although FK 506 may contribute to the pathogenesis of minor neurological complications seen after orthotopic liver transplantation such as tremors and headaches, the pathogenesis of most of the major neurologic complications occurring after orthotopic liver transplantation is multifactorial and cannot be ascribed solely to FK 506 toxicity.

Assuntos

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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

A study of the histopathological abnormalities in a case of alopecia universalis was accompanied by immunohistochemical analysis of the expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin (formerly known as endothelial leukocyte adhesion molecule-1) within the skin. ICAM-1 expression on follicular epithelium co-localized with intraepithelial mononuclear cells (MNC) positive for the interleukin-2 receptor alpha-chain (IL-2R) or HLA-DR. Aberrant expression of E-selectin was observed on dermal endothelium. Although restricted to one case, these new observations concerning the expression of E-selectin and IL-2R in alopecia universalis are consistent with the view that extravascular trafficking of MNC into follicular epithelium may play a key role in the pathogenesis of alopecia universalis and that use of agents that interfere with this process may be an effective therapeutic strategy.

Assuntos

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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

FK 506 is a new immunosuppressive agent with a similar molecular action to cyclosporin A. We have investigated immunohistochemical changes in lesional biopsies of seven patients with severe recalcitrant chronic plaque psoriasis receiving systemic FK 506 therapy. Within 4 weeks of start of treatment, there was a striking reduction in psoriasis area and severity index (mean reduction 87.4%), accompanied by marked reductions in dermal and epidermal CD4+ and CD8+ cells. Investigation of biopsies obtained 4-8 weeks after start of treatment revealed a significant fall in the numbers of activated mononuclear cells expressing CD25 (IL-2 receptor alpha-chain), HLA-DR, or CD11a (lymphocyte function-associated antigen-1, LFA-1 alpha chain). In contrast, the number of epidermal CD1+ (Langerhans) cells increased in response to FK 506 therapy. Study of leukocyte adhesion-related epitopes in active disease revealed strong expression of CD54 (intercellular adhesion molecule-1, ICAM-1) and E-selectin (previously known as endothelial leukocyte adhesion molecule-1) both on microvascular endothelial cells and of ICAM-1 on infiltrating mononuclear cells; ICAM-1 was also expressed weakly on epidermal keratinocytes. Vascular cell adhesion molecule-1 (VCAM-1) was either absent or expressed rarely on vascular endothelium. In response to FK 506 treatment, both ICAM-1 and E-selectin expression on blood vessels was reduced consistently but nevertheless persisted, even in individuals exhibiting total clearance of psoriatic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Assuntos

Assuntos

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BACKGROUND: Cirrhosis is associated with a chronic low-grade hepatic encephalopathy and disturbances in quality of life. This study investigated the extent to which severity of hepatic encephalopathy before orthotopic liver transplantation correlated with quality of life. METHODS: A battery of neuropsychological tests was administered to nonalcoholic patients to quantify severity of hepatic encephalopathy. The Sickness Impact Profile was administered before and after surgery to document quality of life across multiple health and psychosocial dimensions. RESULTS: There was substantial improvement from the pretransplant to the posttransplant periods across almost all dimensions of quality of life. Neuropsychological test scores explained up to 20% of the variance in magnitude of change from pre (before) to post (after) surgery. CONCLUSION: Severity of hepatic encephalopathy (particularly with respect to static ataxia and fine motor control) is associated with posttransplantation improvement in quality of life.

Assuntos

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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