PubMed HealthSearch

Biomedical subjects

G Gitnick

Publications and source records attributed to G Gitnick.

14 recordsLinked to original sources

Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group.

BACKGROUND: Acute non-A, non-B hepatitis after blood transfusion often progresses to chronic hepatitis and sometimes culminates in cirrhosis or even hepatocellular carcinoma. However, the frequency of these sequelae and their effects on mortality are not known. METHODS: We traced patients with transfusion-related non-A, non-B hepatitis who had been identified in five major prospective studies conducted in the United States between 1967 and 1980. We matched each patient with two control subjects (identified as the first and second controls) who received transfusions but who did not have hepatitis. The mortality rates in the three groups were determined with use of data from the National Death Index and Social Security Death Tapes. Cause-specific mortality was determined by reviewing death certificates. RESULTS: Vital status was established for over 94 percent of the 568 patients who had had non-A, non-B hepatitis and the two control groups (526 first controls and 458 second controls). After an average follow-up of 18 years, the estimate by life-table analysis of mortality from all causes was 51 percent for those with transfusion-associated non-A, non-B hepatitis, as compared with 52 percent for the first controls and 50 percent for the second controls. The survival curves for the three groups were virtually the same. Mortality related to liver disease was 3.3, 1.1, and 2.0 percent, respectively, among the three groups (P = 0.033 for the comparison of the group with non-A, non-B hepatitis with the combined control group). Seventy-one percent of the deaths related to liver disease occurred among patients with chronic alcoholism. CONCLUSIONS: In this long-term follow-up study, there was no increase in mortality from all causes after transfusion-associated non-A, non-B hepatitis, although there was a small but statistically significant increase in the number of deaths related to liver disease.

Alcoholism

Mycobacteria in Crohn's disease: DNA probes identify the wood pigeon strain of Mycobacterium avium and Mycobacterium paratuberculosis from human tissue.

Mycobacterium paratuberculosis is known to cause Johne's disease, a granulomatous ileitis in ruminants, and may be involved in some cases of Crohn's disease. Like M. paratuberculosis, the wood pigeon strain of Mycobacterium avium may also show mycobactin dependence on primary isolation that is attenuated on further subculturing. A wood pigeon strain, M. avium restriction fragment length polymorphism (RFLP) type A/I, is also capable of causing granulomatous ileitis in experimental animal models but is not known to cause disease in humans. M. avium RFLP type A is associated with disease in immunocompromised hosts. Three DNA probes, pMB22 and the two subclones pMB22/S4 and pMB/S12, were found to be capable of distinguishing among M. paratuberculosis, M. avium type A, and M. avium type A/I (wood pigeon strain) on the basis of RFLPs. These DNA probes were used to identify two mycobacterial isolates (M. paratuberculosis and M. avium type A/I, wood pigeon strain) derived from the intestinal tissues of two patients with Crohn's disease. In addition, the wood pigeon strain of M. avium was identified from a patient with ulcerative colitis, and M. avium RFLP type A was identified from a patient with colonic carcinoma. This is the first time that M. avium A/I (wood pigeon strain) is known to have been isolated from human tissue. There are too few isolates to speculate about the etiological significance of mycobacteria and inflammatory bowel disease, but it is reasonable to conjecture that M. paratuberculosis may be responsible for some cases of Crohn's disease and that the wood pigeon strain of M. avium may also be an inflammatory bowel disease pathogen in humans.

Crohn Disease

Repeated transplantation of microencapsulated hepatocytes for sustained correction of hyperbilirubinemia in Gunn rats.

In previous studies we demonstrated that transplantation of microencapsulated hepatocytes could correct congenital hyperbilirubinemia in Gunn rats for 4 to 6 wks. Reduction in hyperbilirubinemia followed a single transplantation of isolated encapsulated hepatocytes (IEH). After 4 to 6 wks of transplantation IEH gradually lose their functionality. To sustain long-term supplementation of liver function we have investigated the efficacy of monthly IEH transplantation for 6 mo. Hepatocytes, isolated from young Wistar rats, were microencapsulated with a collagen matrix within an alginate-poly L-lysine composite membrane. We transplanted IEH intraperitoneally into homozygous Gunn rats at monthly (4-wk) intervals for 6 mo. Control Gunn rats received intraperitoneal transplantations of empty microcapsules. Total serum bilirubin was measured in the IEH-transplanted and control Gunn rats at weekly intervals for the duration of the 6-month study. A significant (p < 0.01) and sustained decrease (by nearly 50%) in total serum bilirubin levels was observed following monthly IEH transplantations in Gunn rats for the duration of the study. No such decrease in total serum bilirubin levels was seen in the controls. The Gunn rats exhibited good tolerance for the multiple IEH transplantations. Thus, repeated IEH transplantation may be one strategy for providing long-term supplementation of liver function in congenital metabolic liver disease.

Animals

Hepatocyte immobilization on PHEMA microcarriers and its biologically modified forms.

Polyhydroxyethylmethacrylate (PHEMA) based microcarriers with different bulk structures were prepared by a phase inversion polymerization technique. PHEMA surfaces were further modified chemically by glow-discharge treatment, and biologically by covalent attachment of fibrinogen and collagen. Hepatocytes were isolated from young male Wistar rats using an in situ portal vein collagenase perfusion technique. Freshly isolated hepatocytes were seeded at 6 x 10(5) cells/mL and microcarrier concentration was 10 g/L. Stationary microcarrier cultures were carried out in standard (nontissue culture) polystyrene petri dishes in a humidified 5% CO2 incubator at 37 +/- 0.5 degrees C. Cell attachment was followed by light microscopy by taking samples from the culture medium every 30 min. Urea and protein syntheses by microcarrier-attached hepatocytes were determined by standard techniques. Nonswellable (highly cross-linked) hydrophilic PHEMA microcarriers did not support cell attachment and viability. However, swellable (low cross-linked) PHEMA microcarriers (pretreated in FBS) allowed high attachment and cell spreading. PHEMA microcarriers treated in dimethylaminoethylmethacrylate (DMAEMA) glow-discharge plasma also improved the cell attachment characteristics of the PHEMA microcarriers. The highest attachment efficiencies (immobilization yields) were observed with the biologically modified PHEMA microcarriers, especially modified with fibronectin. Metabolic activity, as estimated by urea and protein syntheses, was also higher in these microcarriers.

Animals

Hepatitis C: what progress?

The new serologic assay for hepatitis C has made it possible to identify patients infected with this agent and to better characterize their clinical illness and its sequelae. As the clinical entity has become better recognized, our understanding of the infectious process has also progressed. Hepatitis C is a chloroform-sensitive RNA virus, only 30-60 nm in diameter, containing a lipid coat. Both erythrocytes and plasma can transmit infection. The viral genome consists of single-stranded linear RNA of approximately 10 kilobases. The first serologic assay developed was a radioimmunoassay, followed shortly by an enzyme-linked immunoassay. Secondary tests for specificity now exist. Blood donor populations may have a significant frequency of false positives on the antibody test, making it important that positive results be confirmed with a secondary assay. The antibody is only detected 2 months after infection, by means of currently available assays, and may not appear in many patients until 3 to 6 months after infection. Hepatitis C infection is commonly chronic. This may lead to an asymptomatic chronic carrier state without demonstrable liver disease, or to chronic progressive or non-progressive hepatitis.

Hepatitis C

Restoration of liver function in Gunn rats without immunosuppression using transplanted microencapsulated hepatocytes.

Microencapsulation of cells within synthetic semipermeable membranes is a novel technique that enables the transplantation of cell cultures without the need for immunosuppression. We have previously shown that transplanted isolated encapsulated hepatocytes can provide sufficient short-term metabolic support to improve the survival of animals with galactosamine-induced fulminant hepatic failure. Here we have demonstrated the feasibility of isolated encapsulated hepatocyte transplantation in providing long-term metabolic liver support in Gunn rats. Gunn rats have a congenital inability to conjugate bilirubin and thus exhibit lifelong hyperbilirubinemia. We studied the feasibility of isolated encapsulated hepatocyte transplantation in restoring this specific liver function. Free hepatocytes, isolated from male Wistar rats, were microencapsulated with collagen within a trilayered sodium alginate-poly-L-lysine-sodium alginate membrane using techniques developed in our laboratory. A total of 45 Gunn rats underwent intraperitoneal transplantation with free hepatocytes (5 x 10(7], isolated encapsulated hepatocytes (5 x 10(7], control (empty) microcapsules or no transplant (untreated controls). Serum bilirubin levels were monitored daily for 10 days after transplantation, and subsequent weekly samples were obtained for up to 1 mo. Microcapsules were studied by light and electron microscopy 1 mo after transplantation. During the first week after transplantation, the mean maximum reduction in serum bilirubin levels for the isolated encapsulated hepatocytes, free hepatocytes and control microcapsule transplanted groups was 45.7%, 18.6% and 14.3%, respectively. For up to 1 mo thereafter the mean reduction in serum bilirubin levels in these respective groups was 34.8%, 13.5% and 3.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance

Etiology of inflammatory bowel diseases: where have we been? Where are we going?

The cause or causes of Crohn's disease and of ulcerative colitis remain uncertain. In spite of extensive investigations, searching for immunologic or infectious causes, clear evidence suggesting an underlying etiology is lacking. Recent studies involving mycobacteria suggest that occasional patients thought to have Crohn's disease may indeed be infected with a mycobacterium. However, clear cause-and-effect relationships have not been established. Future efforts at trying to establish the relationship between environmental factors, including infectious agents, and immunologic mediators seem appropriate on the basis of available data. For the present, the causes or cause of these diseases remains obscure.

Colitis, Ulcerative

Hepatitis 1990.

In recent months newer concepts have evolved in our understanding of infection with the viruses that cause acute viral hepatitis. The natural course of hepatitis A has been described, and reliable diagnostics for its identification are now available. The early development of serologic assays for hepatitis B virus infection resulted in a rapid expansion of our knowledge of the serologic identification of this virus and of the natural course of the agent. Improved serologic tests have shown that infection with the virus is far more common than was appreciated in previous years. Its association with the development of chronic liver disease in up to 10% of infected patients is well documented. Among the most exciting events in our understanding of viral hepatitis has been the development of an assay to detect antibody to hepatitis C virus. This has enabled us to determine that posttransfusion hepatitis is usually due to a single hepatitis C viral agent. Unfortunately, the available antibody assay is associated with a high degree of false positivity and requires the utilization of a secondary test for specificity or a naturalization test to identify true positives. It is clear, however, that a person who has this antibody and who is also positive for a secondary test for specificity is likely to harbor an infectious agent in his or her blood. Hepatitis C is associated with an unusually high degree of chronicity, exceeding 50% in many studies. Second-generation assays have already been developed, and it is likely that we will shortly see a great expansion of our serologic diagnostic capabilities.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis A

Preliminary report on isolation of mycobacteria from patients with Crohn's disease.

Several investigators have recently described the isolation of slow growing mycobacteria from the tissues of patients with Crohn's disease (CD). The primary purpose of this study was to culture and identify mycobacteria from the intestines of patients with CD and other intestinal diseases (control tissues). The culture methods were designed to eliminate most rapid-growing mycobacteria and to enhance the isolation of slow growing mycobacteria. Eighty-two surgically resected intestinal tissue samples were cultured over a four-year period: 27 tissues were from CD patients and 55 from patients with other intestinal diseases. After 4-12 months of culture, five mycobacteria were isolated, but only two have been identified thus far. Both of these organisms appeared to have initially grown as spheroplasts, but revertant bacteria were cultivated after transfer into fresh media. Four of the mycobacteria were from CD tissues, and one isolate was from a control tissue. Two of the isolates have been identified as M. chelonei subsp. abscessus, strain 390 and M. paratuberculosis strain 410. This M. paratuberculosis is similar to the previously identified M. paratuberculosis strains isolated from other human intestinal tissues from patients with CD. Both strains 390 and 410 were inoculated into neonatal goats, but they failed to reproduce a CD-like disease. The isolation of four mycobacteria from 27 CD tissues and only one from 55 control tissues strengthens the findings of previous investigators and supports the hypothesis that mycobacteria may be etiologically associated with some cases of Crohn's disease.

Animals

Antibiotics and inflammatory bowel diseases.

In evaluating the medical literature dealing with antibiotics and inflammatory bowel diseases, I cannot help but recall the adage: "Those who have enthusiasm have no controls and those who have controls have no enthusiasm." There just are not enough data to justify the use of most antibiotics in the treatment of most patients with Crohn's disease or ulcerative colitis. An increasing body of data does support the use of metronidazole in selected patients with Crohn's disease, especially those with perianal disease or fistulae. However, this drug has important side effects that may preclude its long-term use. Other antibiotics have been inadequately tested and there is not adequate evidence to support their use.

Anti-Bacterial Agents

Famotidine in the USA: a review of efficacy studies.

Since its introduction into the USA, famotidine has been widely studied. A variety of studies has shown it to be a very potent H2-receptor antagonist; more potent and longer acting than cimetidine or ranitidine. It has been shown to be efficacious, cost-effective and relatively safe in the treatment of duodenal ulcers, benign gastric ulcers, in maintenance therapy, and when used intravenously in the critical care setting.

Anti-Ulcer Agents