Biomedical subjects

S Vitols

Publications and source records attributed to S Vitols.

40 records · Page 3Linked to original sources

PubMed1984

Significance of the low-density lipoprotein (LDL) receptor pathway for the in vitro accumulation of AD-32 incorporated into LDL in normal and leukemic white blood cells.

The accumulation of the lipophilic cancer chemotherapeutic agent AD-32 as free drug and incorporated into low-density lipoprotein (LDL) (AD-32-LDL) has been studied in wbcs from normal subjects and from patients with acute myelogenous leukemia exhibiting high-affinity uptake and degradation of 125I-LDL. The rate of degradation of 125I-LDL in the leukemic cells was four to 25 times higher than that in normal wbcs. The accumulation of LDL-incorporated AD-32 was greater than that of the free drug and could be reduced by the addition of native LDL in excess. AD-32-LDL was as effective as native LDL in inhibiting the degradation of 125I-LDL. Preincubation of wbcs in a lipoprotein-deficient medium enhanced both the degradation of 125I-LDL and the cellular drug accumulation on incubation with AD-32-LDL. Heparin inhibited both the high-affinity degradation of 125I-LDL and the cellular accumulation of LDL-incorporated drug. However, comparison of the high-affinity degradation rate of 125I-LDL and the accumulation of LDL-incorporated AD-32 showed that the cellular drug accumulation markedly exceeded that which could be explained by high-affinity uptake and degradation of AD-32-LDL. Furthermore, saturation of the cellular uptake of LDL-incorporated drug occurred at higher LDL concentrations than saturation of 125I-LDL degradation. The results indicate that cellular uptake of AD-32-LDL is partly mediated by the LDL receptor pathway and partly by a nonspecific mechanism.

Aged↗

PubMed1984

Elevated low density lipoprotein receptor activity in leukemic cells with monocytic differentiation.

The receptor-mediated degradation of 125I-low density lipoprotein (LDL) was compared in normal white blood cells and leukemic cells. The cells were isolated from the peripheral blood and bone marrow of healthy subjects and patients with newly diagnosed leukemia. The cells from most of the 40 consecutive patients with acute myelogenous leukemia showed markedly higher degradation rates as compared to mononuclear cells and granulocytes from peripheral blood and nucleated cells from the bone marrow of healthy individuals. Leukemic cells from patients with monocytic (FAB-M5) or myelomonocytic leukemia (FAB-M4) exhibited the highest degradation rates. The rate of receptor-mediated degradation of 125I-LDL was also high in leukemic cells from all three patients with chronic myelogenous leukemia in blast crisis, as well as in two of three patients with acute undifferentiated leukemia. In contrast, leukemic cells isolated from two patients with acute lymphoblastic leukemia showed low rates. In most cases, there was little difference in LDL receptor activity between leukemic cells isolated from peripheral blood and those from bone marrow. Hypocholesterolemia was a frequent finding in the leukemic patients. There was an inverse correlation between the plasma cholesterol level and the rate of receptor-mediated degradation of 125I-LDL by the leukemic cells. Studies are now in progress to investigate the possibilities of using LDL as a carrier of cytotoxic drugs in the treatment of leukemia.

Acute Disease↗

PubMedDate not supplied

Feedback on prescribing rate combined with problem-oriented pharmacotherapy education as a model to improve prescribing behaviour among general practitioners.

OBJECTIVE: To develop a working model with which prescribing behaviour among general practitioners might be influenced. DESIGN: Intervention based on feedback on prescribing rates and problem-oriented educational outreach visits, using educational material and local opinion leaders. Randomised study with three parallel intervention groups of general practitioners, which also served as controls for each other. The pharmacotherapeutic fields chosen were hypertension, peptic ulcer/dyspepsia and depression. Prescription data were retrieved from the electronic patient records for periods of 1 year before and after the intervention. SETTING: Six health care centres and three continuing medical education groups in Stockholm. SUBJECTS: Forty general practitioners. MAIN OUTCOME MEASURES: Drug prescribing rates and patterns before and after the intervention. RESULTS: In the hypertension field, desired trends in fractional prescribing (favouring diuretics and beta blocking agents) were recorded, with a significant (P < 0.05) effect on prescriptions for agents acting on the renin-angiotensin system, despite a pre-existing prescribing behaviour already much in line with the goals. In the peptic ulcer/dyspepsia field, desired trends were recorded for both types of therapies addressed. The fractional prescribing rates for proton-pump inhibitors decreased from 61.0% to 52.6% in the intervention arm and increased from 68.1% to 76.0% in the control arm (not significant due to low power). The depression group focused on better general attention to the disease and only minor changes were registered. CONCLUSION: Feedback of individual prescribing rates, combined with problem-oriented educational outreach visits, is a promising model for the improvement of prescribing behaviour. Data from the electronic patient record were feasible for feedback on prescribing rates.

Education, Medical, Continuing↗

PubMedDate not supplied

Metabolism of lipoprotein remnants in humans. Studies during intestinal infusion of fat and cholesterol in subjects with varying expression of the low density lipoprotein receptor.

To study the possible importance of the low density lipoprotein (LDL) receptor in regulating the degree of postprandial lipemia, a cholesterol-rich fat emulsion was infused into the duodenum of subjects who were divided into four groups based on the expected variation in the expression of the LDL receptor: young men (n = 11), elderly men (n = 7), male patients on estrogen therapy (n = 5), and patients with familial hypercholesterolemia (n = 9). In familial hypercholesterolemia, fasting plasma levels of lipoproteins of d less than 1.006 g/ml, intermediate density lipoproteins, and LDLs were increased. During the fat infusion, the cholesterol and triglyceride contents in the d less than 1.006 g/ml fraction increased to a similar extent in all groups, whereas a concomitant reduction of LDL cholesterol levels was observed. The degree of the decrease in LDL cholesterol was positively correlated with the observed increase in triglycerides in the d less than 1.006 g/ml fraction. There were no signs of accumulation of intermediate density lipoproteins during infusion in any of the groups studied. The results indicate that the capacity for clearance of chylomicrons and chylomicron remnants is not affected by variation in LDL receptor expression.

Adult↗