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Biomedical subjects

C M Leevy

Publications and source records attributed to C M Leevy.

At least 55 records · Page 3Linked to original sources

A randomized, double blind controlled trial of the efficacy of immune serum globulin for the prevention of post-transfusion hepatitis. A Veterans Administration cooperative study.

A double blind, randomized, controlled trial has been conducted in 11 Veterans Administration hospitals during a 49-month period to compare the relative efficacies of immune serum globulin (ISG) and an albumin placebo for the prevention of post-transfusion hepatitis (PTH). A total of 2204 patients, of whom 1094 received ISG, participated in the study. The results indicate that ISG significantly reduced the incidence of icteric type non-B hepatitis only (inferred to be also type non-A hepatitis). Adverse reactions were rare, and the ISG did not significantly alter the incubation period or duration of the disease. The data suggest, however, that a similar reduction in type non-A, non-B hepatitis would have occurred had commercial blood been excluded from use. Analysis of the 241 patients who developed hepatitis indicates that type B hepatitis constituted less than 20% of the cases each year of the study. Furthermore, the efficacy of the ISG, manufactured in 1944, against apparent type non-A, non-B hepatitis suggests that this overlooked disease has existed from at least that time. Host- and transfusion-related factors that might have modified the development of PTH were examined. The use of commercial blood was observed to be the most important risk factor. It is concluded that the PTH incidence can be most effectively reduced by eliminating commercial donor blood, and continuing to screen volunteer donors for hepatitis B surface antigen (HBsAg) by sensitive procedures. Of prime importance is the need to define the agent(s) responsible for type non-A, non-B hepatitis.

Adult↗

Lymphocyte cytotoxicity in alcoholic hepatitis.

Studies were undertaken to evaluate the cytotoxicity of peripheral lymphocytes obtained from patients with alcoholic hepatitis. Lymphocyte cytotoxicity to Chang liver cells was investigated by a microcytotoxicity test, and that to autologous liver cells obtained by percutaneous liver biopsy was studied using a 51Cr release assay. Lymphocytes from patients with alcoholic hepatitis were found to be highly cytotoxic to Chang liver cells and autologous liver cells when compared to those of healthy subjects (P is less than 0.001). Cell-free supernatant fluid of lymphocytes from patients with alcoholic hepatitis incubated with purified alcoholic hyalin for 5 days was significantly cytotoxic to Chang liver cells (P is less than 0.01), indicating that a cytotoxic factor is elaborated by sensitized lymphocytes. A significant reduction in cytotoxicity was noted with disappearance of clinical features or direct addition of a purified isolate of alcoholic hyalin or its preincubation with lymphocytes. Preincubation of sensitized lymphocytes with acetaldehyde increased cytotoxicity for autologous liver beyond that obtained by the combined effects of lymphocytes alone and acetaldehyde alone (P is less than 0.001), interpreted as evidence that ethanol toxicity and hyperactivity of lymphocytes independently and collectively contribute to development of cirrhosis in patients with alcoholic hepatitis who continue to imbibe alcohol.

Acetaldehyde↗

Alcoholic hyalin antigen (AHAg) and antibody (AHAb) in alcoholic hepatitis.

Complement fixation (CF) and immune adherence (IA) hemagglutination tests demonstrate antigen (Ag) and antibody (Ab) to alcoholic hyalin (AH) in serum of patients with alcoholic hepatitis. Immunoglobulins from postmortem liver of patients dying of alcoholic hepatitis show antibody activity against AH. Isolated purified AH was used to produce AHAb in rabbits. Rabbit antiserum was added to heat-inactivated human serum to detect AHAg; purified AH was added to serum and tissue elutes to detect AHAb. AHAg was present in serum of each of 15 patients with early phase alcoholic hepatitis in CF titers of 8 to 64 and IA titers of 16 to 2048. AHAg became negative within 3 to 5 weeks with abstinence from alcohol and was followed by transient appearance of AHAb. AHAb was present in 11 patients with advanced phases of alcoholic hepatitis in CF titers of 8 to 640 and IA titers of 16 to 4096. Four patients in this group exhibited concomitant AHAb and AHAg. Investigations of liver tissue elute reveal that patients with advanced alcoholic hepatitis or active alcoholic cirrhosis have AHAg-reactive immune complexes containing IgG and IgA immunoglobulins.

Animals↗

Chemical nature of alcoholic hyalin.

Alcoholic hyalin was prepared from postmortem livers of patients with alcoholic liver disease. Alcoholic hyalin was purified by discontinuous sucrose density gradient ultracentrifugation. The purified protein preparation contained about 12% reducing sugar, the remainder being protein. Gel filtration on Sephadex 4B column showed the presence of three peaks. Each peak material thus obtained contained acetylglucosamine, hexosamine, and deoxysugar (calculated as rhamnose). That these protein components followed by scanning the gels at 280 nm, and at 520 nm after staining the gels with periodic acid-Schiff base reagent for the presence of carbohydrate.

Antigens↗

Lymphocyte proliferation inhibitory factor (PIF) in alcoholic liver disease.

Lymphocyte proliferation inhibitory factor (PIF) was determined in the supernatants of PHA-stimulated lymphocytes from patients with alcoholic liver disease. PIF was assayed by determining inhibition of DNA synthesis in WI-38 human lung fibroblasts. A two-fold greater inhibition in thymidine incorporation into DNA by lung fibroblasts was observed in supernatants of PHA stimulated lymphocytes from patients with alcoholic hepatitis or active Laennec's cirrhosis as compared with that found in control subjects or patients with fatty liver. It is suggested that decreased liver cell regeneration seen in some patients with alcoholic hepatitis may be due to increased elaboration of PIF.

Alcoholism↗

Alcoholic hepatitis. Cell-mediated immunological response to alcoholic hyalin.

Immunological reactivity in alcoholic hepatitis has bben attributed to alcoholic hyalin, the histological hallmark of this disease. A purified isolate of alcoholic hyalin with electron microscopic, biochemical, and serological characteristics documented previously was added to lymphocytes from healthy subjects and patients with alcoholic hepatitis or other hepatic disorders. Production of migration inhibition factor (MIF) in response to this material was used as an index to lymphocyte reactivity. MIF was significantly increased in lymphocytes obtained from patients with alcoholic hepatis, as compared to the healthy controls (P less than 0.001), and persons with other liver diseases (P less than 0.005). These observations indicate that immunological hyperreactivity to alcoholic hyalin occurs in patients with alcoholic hepatitis; such activity may be of key importance in the pathogenesis or sequelae (or both) of this disease.

Alcoholism↗

Alcoholic hepatitis.

Alcoholic hepatitis is the precursor of cirrhosis. Susceptibility is independent of amount and duration of ethanol intake or of diet. Centrilobular hyalin, the key morphologic abnormality, sensitizes lymphocytes to secrete factors which may account (in part) for necrosis, liver cell destruction, increased collagen synthesis and development of cirrhosis. Diagnosis may be facilitated by detection of alcoholic hyalin antigen (AHAg) and antibody (AHAb) in serum of patients with alcoholic hepatitis. Treatment requires abstinence. Steroids have not reduced mortality rates. Measures to improve immunologic reactivity may be helpful. Persons unable to abstain should be enrolled in a surveillance group.

Alcoholism↗

Efficacy of hepatitis B immune serum globulin after accidental exposure. Preliminary report of the Veterans Administration Cooperative Study.

A randomised, double-blind, controlled trial has been undertaken to compare the efficacy of hepatitis B immune globulin (H.B.I.G.) with that of immune serum globulin (I.S.G.) for the prophylaxis of viral hepatitis. Participants in the trial were individuals exposed accidentally to material infectious for hepatitis (primarily viral B hepatitis). Preliminary evaluation of the first 302 of the 561 individuals entered into the study indicates that H.B.I.G. significantly reduced the frequencies of both clinical and subclinical hepatitis during the first 3--4 months after the injection. Less than 10% of H.B.I.G. recipients had detectable anti-HBs at the sixth month after the injection, suggesting that H.B.I.G. might need to be given every 3--4 months to continually exposed individuals. Further long-term evaluation is required in order to define more clearly those most likely to benefit from H.B.I.G.

Clinical Trials as Topic↗

Liver disease of the alcoholic.

Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis.

Alcoholism↗

Inability of chronic alcoholics with liver disease to use food as a source of folates, thiamin and vitamin B6.

Absorption of folates, thiamin, vitamin B6, pantothenate and riboflavin from a natural food source--yeast--and their respective synthetic forms was studied in 37 patients with liver disease due to alcoholism, and 12 healthy, nonalcoholic subjects. All alcoholics absorbed riboflavin and pantothenate but had a significantly lowered absorption of thiamin and vitamin B6 from yeast. Alcoholics absorbed synthetic vitamin B6, but not thiamin. Ingested folylpolyglutamates (the predominant folates in yeast) could not serve as a source of folate for the alcoholics, but synthetic folylmonoglutamate served. We suggest that the folate, vitamin B6, and thiamin deficits so common in alcoholic liver disease ensue from inability to absorb these specific vitamins from foods.

Adult↗

The community and medical education: organization and function of a board of concerned citizens.

A Board of Concerned Citizens was organized in 1971 to facilitate the resolution of problems between the College of Medicne and Dentistry of New Jersey at Newark and the community in which it is located. The board has provided an orderly imput by consumers, representatives of community organizations and nonfaculty employees into decisions on policies and programs of the medical and dental schools. It has aided in the resolution of employee grievances and student problems, given support needed to assist the development of quality health care services, helped improve the climate for clinical research, and served as an intermediary between the community and college on issues of special concern to local residents. An opinion poll conducted 3 1/2 years after its organization shows c ontinued support by citizenry, nonfaculty employees, faculty, and students for a Board of Concerned Citizens. Experiences of the board indicate that investigations and recommendations of a properly organized and motivated group of community residents and leaders can provide an effective bridge between a community and a medical or dental school.

Community Participation↗

Collagen biosynthesis in liver disease of the alcoholic.

Percutaneous liver biopsies obtained from patients with a history of chronic alcoholism and normal liver, fatty liver, alcoholic hepatitis, or active cirrhosis were incubated with tritiated proline to determine the pattern of collagen biosynthesis in these conditions. Incorporation of labeled proline and hydroxyproline into salt-soluble and insoluble fractions of collagen was evaluated by radiochemical analysis and tissue localization documented by autoradiography. Biopsy specimens of alcoholic hepatitis and cirrhosis exhibit a significant increase in the amount of radioactive proline and hydroxyproline in salt-soluble and insoluble collagen. Marked accumulation of radioactivity occurred over bile ducts, fibroblasts, and collagen fibers in the portal area and over hepatocytes, fibroblasts, and collagen fibers in the centrilobular area. Fatty liver is associated with an increase in uptake of proline and hydroxyproline in the salt-soluble fraction of collagem; silver grains appear in the periphery of fat-laden cells and in areas of focal inflammation. Digestion by collagenase indicates that labeling over fibroblasts and collagen reflects active synthesis, whereas, entry of proline into the cell protein pool is responsible for accumulation of radioactivity in other sites. In vitro ethanol causes a significant increase in the incorporation of proline and hydroxyproline into collagen in biopsy specimens of alcoholic hepatitis or active cirrhosis, but has no effect on collagen synthesis by normal or fatty liver.

Alcoholism↗