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Biomedical subjects

R G Hanson

Publications and source records attributed to R G Hanson.

At least 19 recordsLinked to original sources

Randomized trial of chlorambucil for primary biliary cirrhosis.

Twenty-four patients with primary biliary cirrhosis were entered into a prospective, randomized trial of chlorambucil therapy. Thirteen patients received chlorambucil (0.5-4 mg/day) and 11 patients received no therapy; all have been followed for 2-6 yr (mean, 4.1 yr). Two control but no treated patients died. Average serum bilirubin, serum aspartate aminotransferase activities, and albumin levels improved or remained unchanged in treated patients but worsened in controls. Serum alkaline phosphatase levels did not change in either group. Immunoglobulin M levels decreased and became normal in all treated patients but in only 3 control patients. Liver biopsy histology revealed an improvement in inflammatory cell infiltrate in treated patients in comparison with controls, but no significant change in degree of fibrosis or the histologic stage of disease. Side effects of therapy included bone marrow suppression necessitating discontinuation of the drug in 4 patients. These findings indicate that chlorambucil therapy may retard the progression of primary biliary cirrhosis. Whether such therapy will ultimately decrease morbidity and improve survival in this disease can only be demonstrated by large-scale, placebo-controlled trials.

Adult↗

Anticomplement receptor activity in the serum of patients with primary biliary cirrhosis.

Patients with primary biliary cirrhosis have a defect in the receptor mediated clearance of complement coated erythrocytes by fixed macrophages of the reticuloendothelial system. To investigate the probable mechanism of this defect peripheral blood monocytes were isolated from nine patients with primary biliary cirrhosis and seven control subjects and the ability of these cells to form rosettes with complement coated, IgM-sensitised sheep erythrocytes was assessed. Primary biliary cirrhosis peripheral blood monocytes formed rosettes to the same extent as control peripheral blood monocytes (71.0 +/- 7.1% [SEM] versus 73.3 +/- 4.3%) suggesting normal complement receptor function of primary biliary cirrhosis peripheral blood monocytes. When primary biliary cirrhosis or control peripheral blood monocytes were preincubated with primary biliary cirrhosis serum, however, the per cent of peripheral blood monocytes that formed rosettes was decreased: 2.4 +/- 0.8 and 3.1 +/- 1.3 fold respectively. To study this phenomenon further, fractions containing IgG or IgM synthesised by cultures of control or primary biliary cirrhosis lymphocytes were prepared. Rosette formation was not affected by exposure to fractions containing control or primary biliary cirrhosis IgG or control IgM, but was markedly inhibited (6.0 +/- 4.8 fold) by exposure to fractions containing primary biliary cirrhosis IgM. Similar results were obtained when freshly isolated peripheral blood monocytes or peripheral blood monocytes that had been cultured for 7-10 days--that is, macrophages, were used. Assuming that one can draw inferences concerning the status of fixed macrophages from data obtained using peripheral blood monocytes, the results of this study suggest that the complement specific defect in reticuloendothelial system clearance function in primary biliary cirrhosis is not caused by abnormality in the functional status of complement receptors on fixed macrophages but rather by a factor present in the serum of patients with primary biliary cirrhosis that has the capacity to inhibit the adherence of complement coated erythrocytes to complement receptors present on the surface of fixed macrophages. This serum factor does not appear to be a complement component but rather a product of peripheral blood mononuclear cells, other than IgG.

Cells, Cultured↗

A short course of prednisolone in chronic type B hepatitis. Report of a randomized, double-blind, placebo-controlled trial.

Fifteen patients with chronic type B hepatitis were treated with corticosteroids in a randomized, double-blind, placebo-controlled trial lasting 28 days. Ten patients received prednisolone, 60 mg/d for 2 weeks, then 30 mg/d for another 2 weeks; 5 patients received placebo. Serum aminotransferase levels decreased significantly during prednisolone therapy but 4 to 10 weeks after abrupt withdrawal of the drug, they rebounded to levels greater than those before treatment. This exacerbation of disease lasted for several months and was prolonged and symptomatic in 3 patients. Hepatitis B virus levels did not change substantially during treatment. Follow-up examinations showed no improvement in biochemical or serologic features of the disease in any of the 15 patients; follow-up liver biopsies showed a worsening in 4 of 7 treated patients but in 0 of 5 control patients. Thus, a 28-day course of prednisolone produced no beneficial effects in patients with mild-to-moderate chronic type B hepatitis; on the contrary, such treatment may be harmful.

Adult↗

Treatment of chronic type B hepatitis with multiple ten-day courses of adenine arabinoside monophosphate.

Ten patients with chronic type B hepatitis were treated with three courses of adenine arabinoside monosphosphate (Ara-AMP). The drug was given intramuscularly at a dosage of 10 mg/kg/day in ten-day courses during each of three sequential months. The patients were all men, aged 31-61 years, who were known to have had chronic hepatitis for one to four years. Each of the ten-day courses of Ara-AMP was accompanied by a marked inhibition in the serum levels of hepatitis B virus (HBV) DNA and DNA polymerase activity. However, HBV-DNA remained detectable in every patient during treatment and invariably rebounded to pretreatment levels soon after each course was stopped. One patient developed severe, and two patients developed mild neuromuscular side effects. During a 12-18-month follow-up period, only one of the ten patients has had a sustained clinical, serum biochemical, and serological remission. In this patient, serum HBeAg, HBV-DNA, and DNA polymerase became undetectable three months after the final course of treatment; serum aminotransferase levels subsequently fell into the normal range; and a follow-up liver biopsy showed a diminution in the chronic inflammatory cell activity and a disappearance of intrahepatic hepatitis B core antigen reactivity. Thus, multiple ten-day courses of Ara-AMP do not induce a high rate of remissions in this disease and are associated with appreciable neuromuscular toxicity. Ara-AMP is a potent inhibitor of serum levels of hepatitis B virus, but Ara-AMP therapy has not been shown to have long-term beneficial effects in chronic type B hepatitis.

Adult↗

Randomized controlled trial of adenine arabinoside monophosphate for chronic type B hepatitis.

Twenty patients with chronic type B hepatitis were entered into a randomized, controlled study of adenine arabinoside monophosphate. Before entry, all patients were documented to have stable levels of hepatitis B surface antigen, hepatitis B e antigen, serum hepatitis B virus deoxyribonucleic acid, and deoxyribonucleic acid polymerase activity. Ten patients received adenine arabinoside monophosphate and 10 received no treatment. The two groups were well matched with respect to age, sex, known duration of hepatitis B surface antigen, presence of symptoms, serum aminotransferase levels, and hepatic histopathology. During the 4 wk of therapy, serum levels of hepatitis B virus fell dramatically. However, serum hepatitis B virus-deoxynbonucleic acid or deoxyribonucleic acid polymerase activity, or both, remained detectable, and levels of hepatitis B virus invariably rose once therapy was stopped. From 2 to 9 mo after therapy, 4 of the 10 treated patients became hepatitis B e antigen or hepatitis B virus-deoxyribonucleic acid and deoxyribonucleic acid polymerase negative, or both, and the results of routine serum biochemical tests improved. However, 2 of these 4 patients later relapsed. In the control group, 2 patients became seronegative for hepatitis B virus-deoxyribonucleic acid and deoxyribonucleic acid polymerase and manifested improvement in serum biochemical results by 18-24 mo after randomization. Thus, long-term improvements in clinical and serologic features of disease occurred in 20% of both treated and control patients. Side effects of adenine arabinoside monophosphate therapy were common, and 3 patients developed a severe and prolonged neuropathic pain syndrome. These results suggest that a 4-wk course of adenine arabinoside monophosphate therapy does not induce an increased rate of long-term remissions in chronic type B hepatitis.

Adult↗

Cell-mediated immunity to hepatitis B surface antigen in man.

An aqueous preparation of hepatitis B virus (HBV) vaccine was used as an intradermal skin test antigen to assess delayed hypersensitivity to hepatitis B surface antigen (HBsAg). Thirty-five persons were tested including 10 individuals seronegative for all HBV markers, 10 positive for HBsAg (chronic carriers) and 15 positive for antibody to HBsAg (anti-HBs), five of whom had received the HBV vaccine. All patients were also studied for lymphocyte blastogenic responses to phytohaemagglutinin, concanavalin A, pokeweed mitogen and purified HBsAg. Only one individual had a positive delayed skin test reaction to HBsAg. This person had received the HBV vaccine and had high titres of anti-HBs in serum. However, neither this individual nor any other subject exhibited a positive lymphocyte blastogenic response to HBsAg in vitro. Thus, delayed hypersensitivity skin test reactivity to HBsAg was not detected after natural infection with HBV and was rarely present in hyperimmunized individuals. In vitro assays of immune responsiveness failed to demonstrate cellular immunity to HBsAg even in hyperimmunized persons. These studies provide no evidence that cell-mediated immunity to HBsAg plays a role in the immunopathogenesis of acute or chronic type B hepatitis.

Carrier State↗

Pipetter's thumb.

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Allied Health Personnel↗

High-pressure liquid chromatographic determination of cimetidine in plasma and urine.

An assay is described for the determination of the H2-receptor antagonist, cimetidine, in human plasma and urine. Alkalinized plasma or urine was extracted with methylene chloride, the organic phase was evaporated, and the reconstituted residue was analysed by high-pressure liquid chromatography (HPLC) using a reversed-phase prepacked plastic column housed in a radial compression module. The metabolite, cimetidine sulfoxide, was identified but could not be quantitated due to interference from the solvent front. The sensitivity limit of the assay was 25 ng/ml. The assay was applied to the measurement of plasma and urine samples in a pilot pharmacokinetic study. Cimetidine was substantially absorbed and rapidly eliminated (plasma elimination half-life of 112-130 min). Plasma cimetidine concentrations could be measured to 12 hr after a 200-mg dose (iv or oral), but they were below the sensitivity of the assay by 24 hr. Urinary excretion of unmetabolized cimetidine accounted for 40-50% of the administered dose in the first 12 hr. This assay is simpler and more sensitive than those previously described, and it is suitable for the measurement of cimetidine in plasma and urine of subjects receiving doses appropriate for clinical use.

Chromatography, High Pressure Liquid↗

Pharmacokinetic and gastric secretory studies of ranitidine in man.

A sensitive and specific high pressure liquid chromatographic procedure for ranitidine estimation is described and pharmacokinetic studies in six healthy volunteers reported. Each subjects received 20 mg of ranitidine i.v.; 20 mg, 40 mg and 100 mg orally having fasted overnight and 100 mg with a standard meal. Following the i.v. dose, ranitidine plasma concentrations fell biexponentially with a distribution half-life of 6.1 +/- 0.9 min and a terminal elimination half-life of 1.9 +/- 0.1 h. The volume of distribution was 115 +/- 7 1 and the systemic plasma clearance 709 +/- 62 ml/min. After 20 mg oral doses the systemic availability was high (88 +/- 10%). Bioavailability was unaffected by food and AUC increased linearly with dose to 100 mg. Renal excretion of unchanged ranitidine was between 50 and 70% and a further 1-3% was excreted as desmethylranitidine. In separate studies, the inhibitory action of cimetidine and ranitidine on pentagastrin stimulated gastric acid output was compared in seven duodenal ulcer patients. Results so far indicate that ranitidine 150 mg i.v. produces a more pronounced and more prolonged suppression of pentagastrin stimulated gastric acid output than cimetidine 200 mg i.v. (p less than 0.001). Ranitidine produced a sustained near total (greater than 90%) suppression in acid output in the period 60 to 120 min after drug administration, whereas acid output with cimetidine was less and fell from 82 to 54% in the same period.

Administration, Oral↗

Equity and balance.

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Education, Medical↗

Considering "social nutrition" in assessing geriatric nutrition.

"Social nutrition" is of great importance to the well-being of elderly people, who often are socially isolated and hungry for interaction with others. The physician should be sensitive to this need and explore the geriatric patient's social situation. The physician's suggestions have significant impact on elderly patients, and a social prescription often enhances a medical regimen. It is important to suggest to these patients attainable goals, such as social contacts at mealtimes. Even the Meals on Wheels program may help meet their social needs.

Aged↗

An operational model for teaching geriatric medicine in a family practice residency program.

Increased concern for our aging population has necessitated an evaluation of the role of gerontology and geriatric medicine in both undergraduate and graduate medical education programs. The instructional model developed for the Family Practice Residency Program at the University of Minnesota Medical School emphasizes removing barriers to health care for the aged and modifying attitudes of physicians toward normal aging. Three general components make up the Geriatric Medicine Program: (1) clinical rotations in geriatric medicine in ambulatory residential facilities, in multilevel long-term care facilities, and in an acute care hospital; (2) geriatric case conferences; and (3) a seminar in gerontology and geriatric medicine. Evaluation of these components by the residents indicates a high degree of satisfaction with the experience and belief in its applicability to future practice.

Aged↗