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Biomedical subjects

P Roth

Publications and source records attributed to P Roth.

At least 145 records · Page 8Linked to original sources

Effects of high-dose cancer chemotherapy on the absorption of digoxin in two different formulations.

The oral absorption of digoxin in tablet form has been reported to be reduced after cancer chemotherapy and radiation therapy because of cancer treatment-induced damage to the intestinal epithelium. We investigated possible differences in the effects of high-dose cancer chemotherapy on the relative bioavailability of digoxin administered in tablet form (Lanoxin; Burroughs Wellcome Co.) and in solution-in-capsule form (Lanoxicaps; Burroughs Wellcome Co.). Each subject received a single oral dose of either 0.5 mg Lanoxin (six subjects) or 0.4 mg Lanoxicaps (seven subjects) both before and after chemotherapy. For Lanoxin, there was a significant reduction in the AUC after chemotherapy to 54.4% +/- 35.5% (mean +/- SD) of the value before chemotherapy (P = 0.02), whereas for Lanoxicaps there was an insignificant reduction in AUC to 85.1% +/- 42.7% of the value before chemotherapy. These findings show that changes in the oral dosage formulation of digoxin from a tablet to a solution-in-capsule form can overcome the adverse effects of high-dose cancer chemotherapy on drug absorption, and suggest a similar approach may be successful for other drugs.

Absorption↗

Interrelations of radiocalcium absorption tests and their clinical relevance.

Intestinal absorption of radiocalcium from an oral test dose was measured in 84 patients with various disorders of bone and calcium metabolism. In each subject, five different methods were used to assess intestinal absorption and the estimates obtained were compared inter- and intra-individually. The whole-body counting technique was chosen as reference method and as a basis for comparison of the other four estimates. Plasma levels of radiocalcium after oral administration seem to provide a simple and rapid test which may serve its purpose in various clinical situations. Fractional intestinal calcium absorption can be assessed equally well by the whole-body counting technique, the double-isotope method or the double-isotope deconvolution technique, since these methods yield comparable results. The deconvolution technique additionally provides a quantitative description of the absorptive process of calcium with respect to time.

Adult↗

Comparative physiologic performance of polymethyl methacrylate and gas-permeable contact lenses.

A short-term study of the physiologic response of the cornea to polymethyl methacrylate (PMMA) contact lenses and hard, gas-permeable contact lenses of different materials (polycon and Menicon 02), thicknesses, and fittings, was carried out on nine unadapted subjects using one eye as the experimental eye and the other as the control eye (no lens). Changes in corneal thickness were monitored at seven locations across the cornea using an electronic micropachymeter. It was found that gas-permeable lenses produced less corneal swelling than the PMMA lenses. However, lens thickness and the fit of the lens were still important control variables with these gas-permeable lenses. The thin gas-permeable lens produced less swelling than thicker lenses, and the flatter fitting gas-permeable lenses produced less swelling than the steeper fitting lenses. The swelling with all the hard lenses studied was confined primarily to the central 6 mm of the cornea.

Adult↗

Successful treatment of paroxysmal supraventricular tachycardia with MAST.

We have noted that inflation of the military antishock trousers (MAST) successfully converted five of six patients with paroxysmal supraventricular tachycardia to normal sinus rhythm. In all patients the usual "vagal" maneuvers were tried first and were unsuccessful. MAST inflation may be a safe and useful addition to the traditional vagal maneuvers used to treat paroxysmal supraventricular tachycardia.

Adult↗

Effects of propranolol in vitro and in vivo on platelet function and thromboxane formation in normal volunteers.

In vitro and ex vivo effects of propranolol on platelet aggregation, formation of thromboxane B2 (TXB2) and platelet sensitivity to prostacyclin were studied in healthy men. Propranolol, added in vitro to platelet rich plasma (PRP) inhibited platelet aggregation and TXB2 formation induced by ADP, 1-epinephrine, collagen and arachidonic acid. Concentrations of 20-100 microM propranolol were effective when ADP, 1-epinephrine and collagen were used as stimuli. Higher concentrations (250-500 microM) were needed to inhibit aggregation induced by arachidonic acid. Oral administration of propranolol either as a single dose (120 mg) or for one week (3 x 40 mg/day) did, however, not affect platelet aggregation, thromboxane formation and platelet sensitivity to prostacyclin. In addition, withdrawal of propranolol was without effect on these parameters. Although propranolol has potent effects on platelet function in vitro, it seems that the blood levels achievable by oral administration of propranolol are too low to affect platelet aggregation and TXB2 formation.

Adult↗

Plasma catecholamines, platelet aggregation and associated thromboxane formation after physical exercise, smoking or norepinephrine infusion.

To study the possible role of catecholamines in platelet activation, platelet aggregation stimulated by ADP, collagen, arachidonic acid and L-epinephrine, thromboxane B2 (TXB2) formation and plasma levels of catecholamines and renin were studied in healthy men both before and after 6 days of propranolol treatment (40 mg three times daily) under control conditions and during sympathoadrenergic stimulation by physical exercise (200 W) or smoking. Exercise markedly increased plasma norepinephrine from 128 +/- 28 to 998 +/- 418 pg/ml (+/- SD), and plasma renin activity from 1.0 +/- 0.5 to 4.2 +/- 1.8 ng AI/ml . hour. Smoking predominantly increased plasma epinephrine, from 47 +/- 25 to 154 +/- 76 pg/ml. Propranolol did not consistently influence these variables, but blunted the circulatory response to exercise and smoking. Despite the marked increases of plasma catecholamines after both stimuli with and without beta blockade, platelet aggregation stimulated by ADP, 1-epinephrine, collagen and arachidonic acid and associated TXB2 formation were not enhanced. Moreover, as already suggested by a trend toward reduced aggregability in these settings, plasma norepinephrine levels in the same range (745 +/- 368 pg/ml) due to infusion (5 micrograms/min) significantly reduced platelet aggregation with low-dose collagen (0.25-0.75 micrograms/ml), I-epinephrine (0.2-1.0 microM) and ADP (0.5-1.5 microM). These data do not support a role of endogenous catecholamines in initiating platelet activation and TXB2 formation.

Adult↗

A phorbol ester tumor promoter induces changes in the expression of immunoglobulins and DR antigens in human lymphoblastoid cells.

The present study indicates that 12-O-tetradecanoyl phorbol 13-acetate (TPA) can induce either increases or decreases in the relative expression of membrane-associated IgM and IgD as well as the expression of other markers of lymphocyte differentiation on human B lymphoblasts, depending on the clone studied. The changes in membrane Ig expression are apparent within 24 hr and are maximal at about 48 hr after the addition of the compound. In clone BL, TPA decreases the membrane IgM/IgD ratio as determined by the percentage of cells bearing these isotypes and by their densities on single cells. In clone MW-E, TPA has the opposite effect. Although these changes are followed by an increase in Ig secretion by MW-E cells, measured by immunofluorescence and the protein A plaque assay, there is no induction of Ig secretion in BL cells. In addition, TPA increases the expression in BL of an additional B lymphocyte marker, the D region-related (DR) antigens, while having the opposite effect in MW-E. In two sublines of Daudi, a membrane IgM-positive, IgD-negative, nonsecreting cell line, TPA treatment resulted in the expression of membrane IgD without the induction of Ig secretion. Thus, the TPA-induced changes in the IgM/IgD ratio and DR antigen expression are inversely related and are not due to differential proliferation of subpopulations. Taken together, it appears that, depending on the particular clone of B lymphoblasts studied, TPA can induce or inhibit a coherent program of B lymphocyte maturation.

Antibody-Producing Cells↗

Stimulated platelet aggregation, thromboxane B2 formation and platelet sensitivity to prostacyclin - a critical evaluation.

Platelets have been implicated in the development of atherosclerotic and thrombotic vascular diseases. Evaluation of platelet aggregation in relation to endogenously formed compounds which affect platelet function may provide information of clinical and pharmacological relevance. We describe a method in which thromboxane B2 (TXB2) formation was analyzed following stimulation of platelet-rich plasma (PRP) with ADP, 1-epinephrine, collagen, and arachidonic acid. In addition, we determined platelet sensitivity to prostacyclin following ADP- and collagen-induced platelet aggregation. The parameters under study were found to depend on the platelet count in PRP, on the type and dose of the aggregating agent used, and on the test time after blood sampling. By standardization of these variables, a reliable method was established which can be used in clinical and pharmacological trials.

Adenosine Diphosphate↗