Search PubMed⌕ Search

Biomedical subjects

L Brown

Publications and source records attributed to L Brown.

At least 271 records · Page 15Linked to original sources

Transdermal delivery of drugs.

Transdermal drug delivery involves the continuous administration of therapeutic molecules through the skin. It has the advantage of maintaining constant drug plasma levels and improving patient compliance. Compared to the oral route, losses in bioavailability due to first-pass liver metabolism are reduced. This paper describes the theory of transdermal drug penetration, the role of the skin, in vitro testing, examination of currently available transdermal delivery systems, and recent developments in iontophoresis, prodrugs, and penetration enhancers.

Administration, Cutaneous↗

Utilization of inpatient services under shortened lengths of stay: a neonatal care example.

In the last several years many hospitals have experienced a significant reduction in average length of stay (LOS). We know relatively little about whether such reductions are likely to be accompanied by proportional reductions in the utilization of all inpatient services or whether services are merely condensed into a shorter time frame. Average patient severity may well rise as a result of shortened LOS, causing daily resource consumption to rise. In this paper, however, we hypothesize that patients with shorter LOS consume significantly fewer resources. Our empirical results support the hypothesis for some, but not all, of the services were examined.

Adult↗

Hospice care of the intravenous drug user AIDS patient in a skilled nurse facility.

We report on the initial experience in hospice care for a predominantly poor, black and Hispanic intravenous drug user AIDS population in New York City. Hospice care was provided in a skilled nursing facility with a certified hospice program delivering home care and inpatient care. A formal education program preceded patient admission to familiarize the staff and institution with AIDS issues. Between February 1986 and January 1988, 62 of 175 referred patients were accepted for hospice admission. The patients' mean age was 39 years and all had AIDS dementia complex. The mean length of stay was 35 days (range 1-280 days) and a total of 2011 days of hospice care was provided. Ninety-one percent of hospice days were spent on the inpatient unit; only 9% of hospice days were provided at home. Despite the requirement of expensive inpatient hospice care for most patient days, the estimated savings in decreased costs compared to acute hospital inpatient care was $751,488 for these 62 patients. Continuing fear of transmission among hospice staff was not a major problem; however, several unanticipated problems arose including (a) inability to provide home services, (b) continued drug abuse, (c) increased staff stress, (d) difficulty maintaining confidentiality, (e) difficult interactions with funeral directors, and (f) unsupportive and inappropriate funding requirements. Hospice care of AIDS patients is feasible, humane, and cost effective but problems of the intravenous drug using population require special attention and program modifications if hospice care is to be provided for this substantial and growing AIDS population.

Acquired Immunodeficiency Syndrome↗

Xyloside inhibits synthesis of the class II-associated chondroitin sulfate proteoglycan and antigen presentation events.

An alternative form of the human invariant chain exists as a chondroitin sulfate proteoglycan (CSPG) with invariant chain as the core protein. The selective inhibitor of proteoglycan synthesis, p-nitrophenyl beta-D-xyloside was used to study the role of this CSPG in class II biology. At xyloside concentrations of 2.5 and 5.0 mM, CSPG synthesis was completely inhibited with marginal inhibition of protein synthesis. The inhibitory effect on CSPG synthesis was completely reversible. The number of class II molecules on the cell surface was not affected by xyloside, but biosynthesis and appearance of newly synthesized class II molecules at the cell surface were both decreased by xyloside. Recognition of influenza virus-infected cells by class II-restricted, virus-specific cytotoxic T lymphocytes was not diminished by the presence of xyloside in the effector phase of the cytotoxicity assay. However, sensitization of target cells was markedly inhibited when target cells were exposed to virus in the presence of xyloside. These results are consistent with the hypothesis that the CSPG form of invariant chain has a role in antigen processing.

Antigen-Presenting Cells↗

In vitro and in vivo kinetics of regulated drug release from polymer matrices by oscillating magnetic fields.

The kinetics of drug release from polymer-drug matrices containing an embedded magnet was continuously monitored in vitro and in vivo. The application of an oscillating magnetic field increased the rate of drug release from the polymer matrices. Within the limits of detection the increase in release occurred immediately, remained stable for as long as the field was applied, and returned exactly to baseline upon withdrawal of the field. The increase in release was directly proportional to field amplitude. The same pattern of results were observed in vivo as in vitro, though higher strength fields were required in vivo to achieve the same effect observed in vitro.

Animals↗

Dobutamine: positive inotropy by nonselective adrenoceptor agonism in isolated guinea pig and human myocardium.

Positive inotropic responses to dobutamine have been examined using isolated myocardium from guinea pigs und humans. The potency (EC50) of dobutamine was 1.5 X 10(-6) mol/l on guinea pig papillary muscles, 1.8 X 10(-6) mol/l on guinea pig left atria and 2.5 X 10(-6) mol/l on human papillary muscle strips. In guinea pig cardiac muscles, Schild plots for the beta 1-selective antagonist, 1-practolol, using dobutamine as agonist, had slopes of less than unity. This suggested the involvement of other receptors in the inotropic response to dobutamine. The beta 2-selective antagonist, ICI 118,551, but not the alpha 1-selective antagonist, prazosin, attenuated the dobutamine response in guinea pig papillary muscles. Both ICI 118,551 and prazosin shifted the dobutamine concentration-response curve in guinea pig left atria. The positive inotropic response to dobutamine in human papillary muscles was antagonised by l-practolol and ICI 118,551 but not by prazosin. The maximal inotropic response to dobutamine was 90% that of calcium measured in the same guinea pig papillary muscles but only 37% that of calcium in human papillary muscle strips. This reduced maximal effect of dobutamine in human myocardium is probably a disease-induced change but species variations cannot be excluded.

Animals↗

Similar dose responsiveness of hepatic glycogenolysis and gluconeogenesis to glucagon in vivo.

This study was undertaken to determine whether the dose-dependent effect of glucagon on gluconeogenesis parallels its effect on hepatic glycogenolysis in conscious overnight-fasted dogs. Endogenous insulin and glucagon secretion were inhibited by somatostatin (0.8 micrograms X kg-1 X min-1), and intraportal replacement infusions of insulin (213 +/- 28 microU X kg-1 X min-1) and glucagon (0.65 ng X kg-1 X min-1) were given to maintain basal hormone concentrations for 2 h (12 +/- 2 microU/ml and 108 +/- 23 pg/ml, respectively). The glucagon infusion was then increased 2-, 4-, 8-, or 12-fold for 3 h, whereas the rate of insulin infusion was left unchanged. Glucose production (GP) was determined with 3-[3H]glucose, and gluconeogenesis (GNG) was assessed with tracer (U-[14C]alanine conversion to [14C]glucose) and arteriovenous difference (hepatic fractional extraction of alanine, FEA) techniques. Increases in plasma glucagon of 53 +/- 8, 199 +/- 48, 402 +/- 28, and 697 +/- 149 pg/ml resulted in initial (15-30 min) increases in GP of 1.1 +/- 0.4 (N = 4), 4.9 +/- 0.5 (N = 4), 6.5 +/- 0.6 (N = 6), and 7.7 +/- 1.4 (N = 4) mg X kg-1 X min-1, respectively; increases in GNG (approximately 3 h) of 48 +/- 19, 151 +/- 50, 161 +/- 25, and 157 +/- 7%, respectively; and increases in FEA (3 h) of 0.14 +/- 0.07, 0.37 +/- 0.05, 0.42 +/- 0.04, and 0.40 +/- 0.17, respectively. In conclusion, GNG and glycogenolysis were similarly sensitive to stimulation by glucagon in vivo, and the dose-response curves were markedly parallel.

Alanine↗

Hypothenar hammer syndrome: an occupational cause of Raynaud's phenomenon.

Hypothenar hammer syndrome is an uncommonly recognized, occupationally associated cause of Raynaud's phenomenon, induced by traumatic compromise of the vascular supply to the hand. Two patients are presented, one with preexisting Raynaud's phenomenon who sought attention after the development of cutaneous ulcers. The features of the syndrome are reviewed, and the importance of its recognition in the appropriate occupational setting as a potentially curable form of Raynaud's phenomenon is emphasized.

Adult↗

The red blood cell: a model for ouabain receptor regulation in the heart?

The assumption that the red blood cell can be used as a model for ouabain receptor regulation in heart muscle has been tested using isolated tissues from humans, guinea pigs, and chickens. The following results were obtained: The affinity of the ouabain receptor was similar in both human erythrocytes and right atrial appendage, but the density of binding sites was much lower on the erythrocytes. There was no correlation between the binding capacity in both tissues. Ouabain receptor occupation was closely correlated with inhibition of Na+/K+-transport in human erythrocytes and chick heart nonmuscle cells in culture. In contrast, in chick heart muscle cells, an occupation of 40% of the receptors decreased the Na+/K+-transport rate by only 10%. In hypokalemia, the ouabain binding capacity was increased in human and guinea pig erythrocytes but not in guinea pig heart muscle. Such increases were seen in chick heart nonmuscle cells in moderate hypokalemia but in heart muscle cells only after severe hypokalemia. Incubation of chick heart muscle cells in toxic but not in "therapeutic" ouabain concentrations increased the number of ouabain receptors. Increases in receptor number attenuated the positive inotropic and toxic actions of ouabain. These variations between ouabain receptor regulation in red blood cells and heart muscle of several species may be attributable to the lack of a "sodium pump reserve" in erythrocytes and heart nonmuscle cells. Such variations indicate that the human erythrocyte is not a suitable model for the ouabain receptor in the human heart.

Adolescent↗