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Biomedical subjects

G Gitnick

Publications and source records attributed to G Gitnick.

At least 55 records · Page 3Linked to original sources

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↗

Non-A, non-B hepatitis: etiology and clinical course.

It is currently believed that non-A, non-B hepatitis represents several different viral infections. Although the condition is clearly distinct from common cases of hepatitis A and B, new forms of non-A, non-B hepatitis have recently been found that share some characteristics with these diseases. Reliable serologic assays do not exist, but animal transmission and electron microscopic studies indicate the presence of more than one viral agent. The great risk of chronicity following post-transfusion non-A, non-B hepatitis contrasts with the infrequent chronicity of sporadic non-A, non-B disease. Chronic non-A, non-B hepatitis is usually clinically inapparent with mild biochemical abnormalities; nevertheless, it slowly but relentlessly progresses to cirrhosis and portal hypertension.

Antibodies, Monoclonal↗

The pursuit of hepatitis in dialysis units.

Chronic hemodialysis patients were prospectively followed at monthly intervals with hepatitis B serologic (HBsAg, anti-HBs, and anti-HBc) and aminotransferase determinations. Over this 1 year, 53/176 (30%) had two or more abnormal aminotransferase values. In at least 34 of these 53 patients, viral liver disease appeared to be the responsible factor. Although patients with anti-HBc were more likely to have abnormal aminotransferases, it is probable that most viral hepatitis in dialysis units is due to non-A, non-B hepatitis. After a further 2 1/2 years of follow-up, no clinical evidence of hepatic failure was seen in any of the patients with hepatitis. The ultimate course of this disease, however, is not yet established.

Alanine Transaminase↗

Ulcerative colitis and Crohn's disease tissue cytotoxins.

Bowel-wall tissue filtrates from patients with inflammatory bowel disease produce cytopathic effects in tissue culture. The cytopathic effects inducers have been reported to have the characteristics of a small RNA virus. Clostridium difficile toxin also produces cytopathic effects and has been found in the stools of patients with Crohn's disease and ulcerative colitis. The present study concerns the further characterization of the cytopathic inducers in tissues of inflammatory bowel disease patients. It was found that they are nonsedimentable at 148,000 g for 2 h and resistant to inactivation by UV light. They are proteins that are distinct from C. difficile toxin and are unique cytotoxins which are associated with the early cytopathic effects observed in Riff-free chick embryo and rabbit ileum cell cultures. These results suggest that the early cytopathic effects previously described are not produced by a virus. They do not explain the delayed cytopathic effects seen in rabbit ileum or WI-38 cells.

Animals↗