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Biomedical subjects

C A Hirsch

Publications and source records attributed to C A Hirsch.

At least 19 recordsLinked to original sources

Adjusted-dose continuous-infusion cyclosporin A to prevent graft-versus-host disease following allogeneic bone marrow transplantation.

Graft-versus-host disease (GVHD) remains a major obstacle to allogeneic bone marrow transplantation. We administered cyclosporin A (CsA) by continuous intravenous infusion for prophylaxis against GVHD and adjusted the dose to maintain a constant whole blood level. Forty-five patients, ranging in age from 16 to 56, mean 39.5 years, undergoing allogeneic transplantation for various hematological malignancies received CsA as a continuous intravenous infusion. CsA was started on day -1 and continued until day +22 when oral CsA was initiated. The whole blood level of CsA was determined and the dose adjusted to maintain a fixed level. Methotrexate 15 mg/m2 i.v. was given on day +1, followed by 10 mg/m2 on days +3 and +6. CsA administered as a continuous infusion was well tolerated. All patients required multiple adjustments of the infused dose of CsA to maintain the targeted whole blood level. The mean rise in creatinine was 0.89 mg/dl. There was an association between the concomitant administration of amphotericin B and CsA and the development of nephrotoxicity. Hypertension developed in 30/45 patients, and all responded to oral nifedipine. Tremors were noted in 16/45 patients. None of the patients developed serious neurological side effects. Greater than grade-I acute GVHD developed in only 13% of the patients. We conclude that administering CsA as an adjusted dose by continuous intravenous infusion is well tolerated and effective in preventing acute GVHD in patients undergoing allogeneic bone marrow transplantation.

Adolescent↗

Pediatric reference ranges for serum aldolase.

Most investigators have found that serum aldolase levels normally are higher in children than in adults. Although several earlier studies have included sufficient subjects to establish statistically reliable reference ranges, pediatric reference ranges have not been made available for the now widely used assay method of Pinto and associates (Clin Chem 1969;15:349-360.). The authors present age-related ranges determined by this method.

Adolescent↗

Spurious serum creatinine elevations in ketoacidosis.

Diabetic ketoacidosis is usually accompanied by volume depletion and prerenal azotemia. However, the case reported here and a chart review of 10 patients with diabetic ketoacidosis showed creatinine concentration to be disporportionately elevated compared to the blood urea nitrogen level on admission, compatible with true renal insufficiency. Investigation showed most of this elevation in creatinine to be artifactual and due to interference of acetoacetate in the automated methods for measuring creatinine. A manual method that excluded noncreatinine interfering chromagens showed no interference. This manual method should be used to measure creatinine in patients admitted with ketoacidosis to exclude the possibility of coexistent renal insufficiency.

Acetoacetates↗

Fenoprofen: drug form selection and preformulation stability studies.

Several fenoprofen salts were prepared to obtain the most acceptable form for an oral dosage formulation. Thermal analysis techniques were used to compare stabilities of the water of hydration in different salt forms and to assess the effects of the water of hydration on compatibility with propoxyphene and codeine salts. Photodegradation products of fenoprofen were isolated and identified, and their relevance to product formulation was evaluated.

Amines↗

Substitued 5-nitro-1, 3-dioxanes: correlation of chemical structure and antimicrobial activity.

Various derivatives of 5-nitro-1, 3-dioxane were synthesized to determine the relative effect of chemical substitution in the 2-and 5-positions on broad spectrum antimicrobial activity. Each compound was evaluated quantitatively by calculation of a microbiocidal index, which measured the time to kill several different microorganisms. This test system indicated that 5-bromo-5-nitro substitution was essential for significant activity. Optimal activity was effected by 2-methyl substitution in the alkyl series and 2-hydroxy-phenyl substitution in the aryl series. The antimicrobial activity of the substituted dioxanes was not related directly to water solubility or hydrolysis to microbiocidal diols or aldehydes.

Anti-Infective Agents, Local↗

The isolation of large polysomes in high yield from unfractionated tissue homogenates.

It was found that if large quantities of both exogenous RNA and Mg-2+ were present during gentle tissue homogenization, the subsequent addition of deoxycholate to the whole homogenate produced a viscous mass from which polysomes could be isolated in large yields. These polysomes were substantially less degraded than those isolated by previous methods. In the case of rat liver, 15 ribosomes per mRNA was the species present in highest concentration. The parameters of this method were investigated and optimized. About 80 percent of the rRNA in the homogenates was recovered in the polysomes. Omission of deoxycholate permitted the isolation of less-degraded free polysomes as well. In the liver of fed rats these represented one-fourth of the total polysomes, in good agreement with results obtained by an independent approach. Using the method to isolate polysomes from the liver of starving rats, it was found that only about one percent of the large amount of monomers and dimers present resulted from polysome breakdown during isolation. It was further shown that random RNAase hydrolysis of polysomes could not produce the patterns of liver polysomes seen during starvation. Polysomes isolated by this procedure were quite stable in solution and were very active in cell-free protein synthesis. Application of this method without adaptation to eight other tissues also permitted the isolation of large polysomes in high yields.

Animals↗