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Biomedical subjects

C Fischer

Publications and source records attributed to C Fischer.

At least 19 recordsLinked to original sources

Alterations in the disposition of differently cleared drugs in patients with cirrhosis.

We have compared the disposition of antipyrine orally (15 mg/kg) and the new antiarrhythmic drug lorcainide intravenously (1.5 mg/kg) in 8 patients with alcoholic cirrhosis. Antipyrine (AP) serves as a model drug for drugs which are eliminated independently of liver blood flow and lorcainide (L) elimination as a model for drugs which depend on liver blood flow. Since in healthy subjects elimination half-life (t 1/2) of L increased with age (r = 0.68, p less than 0.01) due to parallel change in the volume of distribution (r = 0.52, p less than 0.05), its disposition had to be compared to age-matched controls. Elimination of both AP and L was impaired in cirrhotic patients, expressed either in terms (mean +/- SD) of t 1/2 (AP = 26.8 +/- 15.0 hr and 12.3 +/- 1.8; L = 12.5 +/- 4.5 hr and 7.7 +/- 2.2 hr, p = 0.002) or of clearance (Cl) (AP = 21.9 +/- 7.9 ml/min and 41.7 +/- 5.5 ml/min; L = 814 +/- 144 and 1002 +/- 304 ml/min, p = 0.06). While the alterations in plasma Cl were great for AP, they were smaller for L. This suggests that elimination of drugs in cirrhotic patients is associated with relatively more impairment of enzyme activity than of hepatic blood flow. The slightly decreased Cl of L in patients with alcoholic cirrhosis would suggest that L should be carefully handled in patients with dysfunction of the liver.

Acetanilides

[Prevention of reinfarction with acetylsalicylic acid].

A report is presented on the prospective trial for prophylaxis of myocardial reinfarction by means of acetylsalicyclic acid. For the first time it was organized on the basis of population. 1,340 patients were treated with acetylsalicylic acid or placebo respectively for 22 months on an average. There were 24 cases of reinfarction in the group of treatment and 51 in the placebo group. The difference is significant.

Adult

Hemodynamic studies, acid-base status and osmolality in different hemodialysis procedures.

Three patients on maintenance dialysis were each treated with three different procedures: A) twenty-liter recirculation dialysis with bicarbonate buffering, B) recirculation-adsorption dialysis and C) single-pass dialysis. Hemodynamic parameters were measured invasively and procedures A, B and C were compared for each patient. In this intraindividual comparative study, the authors attempted to establish a relationship between the varying hemodynamic parameters and the changes in osmolality and acid-base status. There were indications of some causal relationship to circulatory stability: in A and B, there were peripheral resistance increases of 24.5% and 38.4%, respectively, with stable circulation; in C, there was a 6.1% increase and unstable circulation. Additionally, the influence of acidosis is shown in B, with disproportionately strong reductions of cardiac output (21.9%) and pulmonary artery pressure (44.9%); In spite of a decrease of osmolality (A: 15.6 mOsm/L), stable circulation could be achieved if the peripheral resistance was substantially increased and acid-base status was equalized.

Acid-Base Equilibrium

The identification and measurement of a folate-binding protein in human serum by radioimmunoassay.

Antiserum raised in rabbits against the FBP obtained from CML cells, and the purified binder labeled with 125I, have been used for an RIA which can measure an immunologically similar protein in human serum. The concentration of the binding protein in normal serums ranged from 1.2 to 9.3 ng/ml, with a mean +/- S.E.M. of 3.8 +/- 0.4 ng/ml. Elevated values of the binder protein were measured in the serums from patients with folate deficiency, vitamin B12 deficiency, liver disease, uremia, myeloproliferative disease, chronic lymphocytic leukemia, and various types of cancer and in the serum from pregnant women. The concentration of the binder protein and the capacity of the serum to specifically bind isotopically labeled PGA correlated poorly, indicating that the binding protein concentration and degree of saturation by endogenous serum folate vary independently in many instances.

Antigen-Antibody Complex

A direct ligand-binding radioassay for the measurement of methotrexate in tissues and biological fluids.

A direct ligand-banding radioassay for methotrexate (MTX) has been developed using dihydrofolate reductase, contained in the lysate of L1210 leukemia cells, as the binding determinant. The procedure is a two-phase reaction system where standard MTX concentrations or the sample being assayed in incubated with the reagent lysate in the first phase, and [3H]MTX is then added in the second phase to titrate the remaining unoccupied binding sites on the enzyme. This method eliminates the need for measuring the residual catalytic activity of the enzyme. The sensitivity of the radioassay is limited only by the specific activity of the [3H]MTX and how approximates 10 pg of the drug. Folic acid, methyltetrahydrofolate, formyltetrahydrofolate, and dehydrofolate in concentrations that are physiological do not interfere in the radioassay. Both mercaptoethanol and reduced nicotinamide andnine dinucleotide phosphate increase the binding capacity of the lysate for MTX; but the reduced nucleotide also increases the affinity of the enzyme for the inhibitor. MTX added to serum can be assayed without extraction if the concentration is greater than 500 pg/ml and recovery of the drug added to serum is about 92%. MTX has been assayed in serum, spinal fluid, and urine of patients who were treated with this drug. It has also been assayed in the lysates of L1210 cells from C57BL X DBA/2 F1 mice treated with MTX. The procedure is simple, rapid, and accurate and should permit better correlation of the therapeutic and toxic effects of MTX with blood concentrations over long-term treatment periods.

Animals