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Biomedical subjects

G Gitnick

Publications and source records attributed to G Gitnick.

At least 37 records · Page 2Linked to original sources
PubMed1996

Artificial liver support: state of the art.

Severe liver disease is very often life-threatening and dramatically diminishes quality of life. Liver support systems based on detoxification alone have proven ineffective because they cannot correct biochemical disorders. An effective artificial liver support system should be capable of carrying out the liver's essential processes such as synthetic and metabolic functions, detoxification, and excretion. It should be capable of sustaining patients with fulminant hepatic failure, preparing patients for liver transplantation when a donor liver is not readily available (i.e., bridge to transplantation), and improving the survival and quality of life for patients for whom transplantation is not a therapeutic option. Recent advances in cell biology, tissue culture techniques, and biotechnology have led the way for the potential use of isolated hepatocytes in treating an array of liver disorders. Isolated hepatocytes may be transplanted to replace liver-specific deficiencies or as an important element of an auxiliary hybrid, bioartificial extracorporeal liver support device, which are important therapeutic applications for treating severe liver disease. Although several hepatocyte-based liver support systems have been proposed, there is no current consensus on its eventual design configuration. Furthermore, application of tissue engineering technology, based on cell-surface interaction studies proposed by our group and others, has enhanced interest in the development of highly efficient hybrid, bioartificial, liver support devices.

Animals↗
PubMed1996

Health-related quality of life, patient outcome, and managed care: the road ahead.

The delivery of healthcare in the industrialized world is currently undergoing fundamental change due to a number of factors. These include market forces driving institutions to contain and reduce cost; the rapid emergence of new treatments; the recognition of unexplained regional variations in the delivery of care; and patients' increasing sophistication and involvement as consumers of healthcare resources. As a result, the practice of medicine is entering a new era of scrutiny. Demonstrating a treatment's safety and efficacy is no longer sufficient justification for its use. There is a need to evaluate the appropriateness of medical care based on both cost and patient outcomes measures, including health-related Quality of Life (HRQOL). This type of research is in the interests of healthcare provider organizations, physicians, and patients alike. Outcomes research in the GI diseases is expanding rapidly due to the potential for cost savings and increased quality of care. It is important that gastroenterologists become trained and take part in the design, conduct, and analysis of outcomes studies to maximize these gains.

Gastrointestinal Diseases↗
PubMed1996

Controlled release of endothelial cell growth factor from chitosan-albumin microspheres for localized angiogenesis: in vitro and in vivo studies.

Endothelial cell growth factor (ECGF) stimulates vascularization, however its relatively short half-life requires this angiogenic factor to be frequently administrated by non-specific and uncontrolled methods. This work describes the use of biocompatible chitosan, a polysaccharide having structural similarity to glycosaminoglycans, -albumin microspheres, as well as its fiber form, as a potential delivery system for the controlled and localized release of ECGF. Chitosan-albumin microspheres (400-600 microns) and fibers, formed in 0.5 M sodium hydroxide-methanol solution were incubated with ECGF. In vitro release was performed in PBS at 37 degrees C, under constant stirring. In vivo experiments were realized by implanting ECGF loaded matrices subcutaneously into rat groin fascia. After an initial ECGF burst of 1.32-1.62 mg (22-27%) within the first 2 hours, a daily release of 120-420 micrograms (2-7%) during the first, and 60-240 micrograms (1-4%) during the second week was observed from M(r) 70.000, 750.000, and 2,000.000 chitosan containing microspheres of 6 mg/ml loading. ECGF release rate of < 30 micrograms (0.5%)/day was maintained during the third week of experiments. By the increase in ECGF loading (12 mg/ml polymer), while the amount of release increased, percent release decreased. Chitosan-albumin fibers gave a ECGF release rate nearly similar to microspheres, and in vivo studies demonstrated a high degree of neovascularization for both types of implants, starting from 7 day-post implantation. Control animals that received ECGF injection did not show any significant neovascularization, after same period of time.

Animals↗
PubMed1995

Transplantation of microencapsulated hepatocytes for liver function replacement.

Recent advances in cell biology and biotechnology have lead the way for a greater understanding of cell function and the potential therapeutic use of transplanted cells for treating a wide array of illnesses. Treatment of disease by transplantation of normal healthy cells, for the replacement of specific biological deficiencies or as a form of auxiliary support for a failing organ, offers important therapeutic applications and also serves as a model for assessing cellular physiology. In the long-term, cell transplantation may also have potential in the development of artificial organ support systems for sustaining patients with severe and chronic diseases such as diabetes, liver failure, endocrine and exocrine disorders, neurological abnormalities, and congenital metabolic defects. Several groups have demonstrated the feasibility and efficacy of cell transplantation in providing specific function in various experimental animal models of human disease. However, without adequate immunosuppression, complications due to tissue rejection remain a significant problem. Microencapsulation of cells within a synthetic semipermeable membrane, prior to transplantation, has been proposed for circumventing immunological complications following transplantation. The microcapsule's semipermeable membrane allows permeant molecules to freely diffuse across while preventing the microencapsulated cells from escaping. This membrane also keeps unwanted substances, such as cells and antibodies, from entering the microcapsule. Thus, microencapsulation provides an innovative and unique technique for the transplantation of foreign tissue and cells without the need for immunosuppression.

Animals↗
PubMed1995

Hepatitis C in 1994.

Since the discovery of hepatitis C in 1989 its role in the development of acute and chronic liver disease has been carefully evaluated. Hepatitis C has a mean incubation period of between 6 and 8 weeks. It is often indolent and asymptomatic. Interferon may be helpful in chronically infected patients. After 6 months of therapy approximately 40-50% enter remission. Relapses are common however, up to 80% within 6 months. Effective long-term treatment has not yet been established.

Hepatitis C↗
PubMed1995

In vitro slow release profile of endothelial cell growth factor immobilized within calcium alginate microbeads.

Although a variety of angiogenic growth factors have been isolated, its appropriate in vivo delivery remains problematic due to nonspecific, uncontrolled delivery by conventional methods. We have investigated calcium alginate microbeads as a vehicle for the controlled slow-release of endothelial cell growth factor (ECGF). Three different microbead compositions, dependent on ECGF amount and alginate percentage were studied. Microbeads were incubated in a 1.5% calcium chloride solution and release of ECGF into solution was measured spectrophotometrically at specific timepoints. Our results show release rate and amount released after the first 2 hours are dependent on initial quick delivery of ECGF in the first 2 hours after which a sustained controlled release occurred for 4-5 days. Beyond this point, release at a slower rate was noted for at least approximately 2 weeks. Calcium alginate microbeads demonstrated a controlled and predictable rate of release and that the amount of ECGF delivered can be varied by varying the initial concentration of ECGF in the microbeads. Based on these observations we conclude that calcium alginate microbeads are a convenient and practical vehicle for sustained ECGF delivery.

Alginates↗
PubMed1995

Collagen and fibronectin immobilization on PHEMA microcarriers for hepatocyte attachment.

Polyhydroxyethylmethacrylate (PHEMA) microcarriers in a size range of 150-250 microns were prepared by a suspension polymerization in an aqueous phase containing magnesium oxide. The hydroxyl groups on the PHEMA microcarriers were activated by cyanogen bromide. In order to improve cell attachment, cell-adhesive proteins, namely, collagen and fibronectin were immobilized onto PHEMA microcarriers. The nonspecific adsorption values for collagen and fibronectin were 0.10 mg collagen/g PHEMA and 0.044 mg fibronectin/g PHEMA, respectively. Collagen and fibronectin immobilization on PHEMA microcarriers were studied at different pH by using single protein solutions containing different amounts of proteins, at a constant temperature of 20 degrees C. The maximum immobilizations were 0.85 mg collagen/g PHEMA (at pH: 9.5) and 0.52 mg fibronectin/g PHEMA (at pH: 7.4). Hepatocyte attachment onto these biologically modified PHEMA microcarriers was studied. Hydrophilic PHEMA microcarriers did not support cell attachment. High hepatocyte attachment yields (up to 75% surface coverage) were observed on collagen and fibronectin immobilized PHEMA microcarriers.

Animals↗
PubMed1994

Hepatitis infection in immunocompromised patients.

The current literature fails to address the long-term course of hepatitis infection in the immunocompromised patient, in large part because of the characteristically slow progression of this disease. An overview of the literature available fails to demonstrate evidence that immunosuppression per se promotes progression of hepatitis. In fact, many studies document a relatively low incidence of chronic active hepatitis or cirrhosis in immunocompromised patients; however, properly designed, prospective studies of sufficient numbers of patients with long-term follow-up are not available. Thus, no reliable conclusions are possible at this time.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Current views of the etiology of inflammatory bowel disease.

The cause or causes of Crohn's disease and of ulcerative colitis (UC) remain uncertain. Despite extensive investigations aimed at 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 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.

Child↗
PubMed1993

Non-A, non-B post-transfusion hepatitis. Looking back in the second decade.

OBJECTIVE: To determine the long-term course of non-A, non-B post-transfusion hepatitis. DESIGN: Follow-up in 1989 to 1992 of patients prospectively identified as having contracted non-A, non-B post-transfusion hepatitis between 1972 and 1980. SETTING: A university hospital. PATIENTS: Patients who were prospectively followed from receipt of blood products and in whom otherwise unexplained abnormalities in their serum alanine aminotransferase levels developed without serologic evidence of exposure to hepatitis A or B. MEASUREMENTS: The presence or absence of clinical evidence of liver failure or symptoms of chronic hepatitis. RESULTS: Of 90 patients identified in the 1970s, 80 were recontacted and evaluated between 1989 and 1992. Based on the current status of these 80 patients and on the last known status of the remaining patients, the following observations were made: 1) Although about 40% had some symptoms during the early phase of the disease, none subsequently experienced significant clinical problems related to hepatic inflammation; 2) eight patients (seven with chronic hepatitis) developed hepatic failure; and 3) life-table analysis showed that the probabilities of developing clinical evidence of cirrhosis after 16 years of disease in the entire cohort, in the subgroup who developed chronic hepatitis, in the patients who had hepatitis C, and in those with chronic hepatitis C were 18%, 21%, 17%, and 20%, respectively. CONCLUSIONS: For most of the study patients, non-A, non-B post-transfusion hepatitis was a biochemical and histologic disease that had not yet caused hepatic symptoms. If hepatic failure does occur, it is usually seen only after 10 or more years of disease. Before that time, many infected persons die due to other disease processes.

Adult↗
PubMed1993

Cryopreserved microencapsulated hepatocytes--transplantation studies in Gunn rats.

Hepatocyte transplantation has been shown to provide significant metabolic support in several animal models of liver diseases. However, for it to be a viable alternative for supplementation of liver function in disease, large quantities of isolated hepatocytes would be necessary. At the present time there are no inexpensive routine methods for cryopreservation of hepatocytes. Existing procedures are cumbersome and require expensive programmable freezers. Hepatocyte cultures are sensitive and easily damaged in handling. By utilizing techniques of microencapsulation and cryopreservation we have attempted to overcome these problems. We have developed a simple, convenient, and inexpensive technique for the long-term storage of hepatocytes. Biological activity of the nonfrozen isolated encapsulated hepatocytes (IEH) and cryopreserved IEH (cIEH) was assessed both in tissue culture and by transplantation in Gunn rats. Significant urea and protein syntheses were detectable during the 10-day culture period even in the 30-day cIEH. Additionally, transplanted IEH and cIEH significantly reduced hyperbilirubinemia in Gunn rats for up to 30 days posttransplantation. Control (empty) microcapsules did not lower serum bilirubin levels. Thus we conclude: (1) cryopreservation of IEH is a convenient and cost-effective method for preserving and storing hepatocytes; (2) cryopreserved IEH function as well as nonfrozen IEH both in vitro and in vivo; (3) microencapsulation may protect hepatocytes from the adverse effects of cryopreservation.

Animals↗
PubMed1993

A morphological and functional evaluation of transplanted isolated encapsulated hepatocytes following long-term transplantation in Gunn rats.

In this study we investigated the fate of microencapsulated hepatocytes following long-term (6 months) transplantation in Gunn rats. Isolated hepatocytes were microencapsulated with a collagen matrix within an alginate-poly L-lysine composite membrane. Isolated, encapsulated hepatocytes (IEH) or free (unencapsulated) isolated hepatocytes were intraperitoneally transplanted into homozygous Gunn rats that exhibit congenital hyperbilirubinemia. Control Gunn rats received empty microcapsules. Total serum bilirubin was measured at weekly intervals for one month post-IEH transplantation, every two weeks for the next month, and monthly thereafter for up to six months. IEH samples were biopsied from the Gunn rats at monthly intervals and analyzed by light and electron microscopy. A significant (p < 0.01) decrease in total serum bilirubin was observed in IEH transplanted animals during the first month of transplantation. Thereafter, total serum bilirubin levels gradually returned to pre-transplantation levels. A mild, transient decrease in total serum bilirubin was seen in animals transplanted with free (unencapsulated) hepatocytes. No decrease in total serum bilirubin levels was seen in the Gunn rats transplanted with control (empty) microcapsules. Transplanted IEH retained its normal ultrastructure for up to one month and intact microcapsules showed no evidence of hepatocyte rejection, at this time. Degenerative changes observed in the IEH beginning at 2 months post-transplantation, suggests that repeated transplantations may be necessary for long-term effectiveness of IEH therapy.

Animals↗
PubMed1993

Non-A, non-B posttransfusion hepatitis: comparing C and non-C hepatitis.

Using assays to detect antibodies against antigens (C-100, 5-1-1, C-22 and C-33) of the hepatitis C virus, we tested stored sera from 40 patients prospectively identified as having non-A, non-B posttransfusion hepatitis. The 28 patients who demonstrated seroconversion ("documented hepatitis C") had more severe initial disease; all 20 cases of chronic hepatitis occurred in this subgroup. Only 2 of the 12 patients who did not demonstrate such seroconversion even had symptoms. In the group of patients with documented hepatitis C, chronic hepatitis was more commonly seen in men (89%) than in women (40%). The patients in whom antibody to the C-100 antigen developed were younger and had received more blood than had those patients who had hepatitis C diagnosed by demonstration of antibodies to the 5-1-1, C-22 or C-33 antigen (or all three). The proportion of cases of posttransfusion hepatitis that could be associated with antibody sero-conversion decreased around the time that blood banks switched to an all-volunteer system. The hepatitis seen in patients who failed to demonstrate serological evidence of hepatitis C virus exposure was usually clinically unimportant; it may or may not have been due to viral infection.

Acute Disease↗
PubMed1992

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↗
PubMed1992

Improved function of microencapsulated hepatocytes in a hybrid bioartificial liver support system.

Conventional methods of microencapsulating isolated hepatocytes with Type I collagen matrix have provided metabolic liver support in experimental animal models of acute liver failure and congenital metabolic liver disease. We compared the biological function of transplanted microencapsulated hepatocytes cultured on standard Type I collagen (Vitrogen) and a commercially available liver basement-membrane-like extract from a mouse sarcoma (Matrigel). Isolated hepatocytes were microencapsulated with Matrigel and Vitrogen within an alginate-poly-L-lysine composite membrane. Isolated encapsulated hepatocytes (IEH) were transplanted intraperitoneally into homozygous Gunn rats that exhibit congenital hyperbilirubinemia. Control Gunn rats received empty or no microcapsules. Total serum bilirubin and conjugated bilirubin in bile were measured at weekly intervals for one month. Significant (p < 0.01) decreases in total serum bilirubin were observed in all IEH transplanted animals. No such decrease was seen in control animals. Gunn rats that received Matrigel had significantly (p < 0.05) lower serum bilirubin values and significantly (p < 0.05) higher conjugated bilirubin in bile than those that received Vitrogen. We conclude that hepatocytes microencapsulated with Matrigel functioned better than those with Vitrogen. This improved in vivo biological response underscores the importance of using the appropriate cell attachment substratum to enhance the function of a hybrid bioartificial liver support system based on transplanted hepatocytes.

Animals↗
PubMed1992

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↗
PubMed1992

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↗