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Biomedical subjects

N Brown

Publications and source records attributed to N Brown.

At least 145 records · Page 8Linked to original sources
PubMed1994

Climate change and human history. Some indications from Europe, ad 400-1400.

The influence of climate change on history is discussed in such a way as to take account of recent research while seeking to herald, rather than foreclose, the much more focussed and definitive debates that will become possible by the turn of the century. By then, much more elaborated time series of global climatic change over the last several millennia should be available. The period chosen for examination is the 1000 years or so following the collapse of Roman Europe. During this time, civilization seems to wane, wax and wane again, very much in phase with the climate deteriorating, improving and then deteriorating once more. What this overview high-lights is the great vulnerability to climatic perturbation of societies that are marginally poised for other reasons. In several major respects, the whole of world society will be marginal in the 21st century.

Journal Article↗
PubMed1994

Pharmacology of high-threshold calcium currents in GH4C1 pituitary cells and their regulation by activation of human D2 and D4 dopamine receptors.

1. The objective of this study was to characterize the pharmacology of calcium currents in GH4C1 pituitary cells and determine whether activation of heterologously expressed human dopamine receptors can regulate their function. Human D2(short), D3 and D4.2 receptor cDNA's were separately transfected into GH4C1 cells and whole cell calcium currents were recorded by use of nystatin-perforated patch clamp techniques. 2. High-threshold calcium currents were antagonized in a biphasic manner by the dihydropyridine, nisoldipine. The half-maximally effective concentration for each site was 0.2 nM (pIC50 = 9.78 +/- 0.21, n = 4) and 339 nM (pIC50 = 6.47 +/- 0.12, n = 4). The component of current inhibited by 10 nM nisoldipine was also blocked by omega-conotoxin GVIA (30 +/- 9% at 30 nM, n = 6) or by omega-agatoxin IVA (34 +/- 7% at 100 nM, n = 4). 3. Activation of either D2 or D4 receptors by dopamine (10 microM) or quinpirole (0.1 to 10 microM) reduced the peak calcium current by ca. 20% in the majority of cells studied. No inhibition was observed in control or D3 transfected GH4C1 cell lines. 4. The mobilisation of intracellular calcium by thyrotropin releasing hormone in hD4-GH4C1 cells was also studied using Fura-2 AM microspectrofluorimetry. Thyrotropin releasing hormone caused a concentration-dependent increase in calcium mobilisation with an EC50 of 7 nM. D4 receptor activation had no effect upon either basal or hormone-induced [Ca2+]i transients. 5. These results demonstrate that GH4C1 pituitary cells have at least two types of dihydropyridine sensitive high-threshold calcium currents and that like D2 receptors, human D4 receptors can also regulate calcium channel function.

Animals↗
PubMed1994

Epidemiology of vascular and Alzheimer's dementia among African Americans in Chicago, IL: baseline frequency and comparison of risk factors.

We compared demographic, medical, and other epidemiologic factors among 113 African-American Alzheimer's disease (AD) patients and 79 African-American vascular dementia (VaD) patients. The typical background profile of our AD and VaD patients who entered into the study was that of women who were born and raised on farms in the southeastern United States, currently lived in an apartment or home in Chicago with other family members, and were retired, widowed, and had some form of medical insurance. The following distinct patient profiles emerged: (1) African-American AD patients were generally older than their VaD counterparts, more likely to have a family history of AD, Parkinson's disease and dementia, a history of head injury with loss of consciousness and hip fracture, and more severe cognitive impairment and difficulty with instrumental activities of daily living. (2) African-American VaD patients had a higher frequency of cardiovascular disease risk factors and focal neurologic findings, more difficulty with activities of daily living, and a higher frequency of medication use. Differences in risk-factor profile may help explain differential susceptibility by dementia subtype. Since ethnic minorities will constitute a higher proportion of the United States population in the future, targeted epidemiologic research to better understand etiology and risk factors for the dementias of middle and later life among minorities is needed.

Black or African American↗
PubMed1994

Developing a maternity home care program.

Maternity patients are being discharged from hospitals earlier than ever. This maternity care program provides new mothers with comprehensive home care that ensures healthier mothers and babies.

Adult↗
PubMed1994

Cryptococcal meningitis in children in Papua New Guinea: a reminder.

Two young males from Central Province were referred to Port Moresby General Hospital with chronic headaches. In each case the initial impression of tuberculous meningitis needed revision in the light of strongly positive cryptococcal serology. Cryptococcal meningitis occurs with sufficient frequency in Papua New Guinea that it should be considered in cases of raised intracranial pressure, ataxia, cranial neuropathy and visual disturbances. Delay in treatment may be disastrous. In contrast to the developed world where fungal meningitides show a predilection for the immunosuppressed, the experience to date in Papua New Guinea is that the majority of cases in both adults and children occur in ostensibly immunocompetent individuals. The epidemiology, clinical course and current treatment of this potentially curable disease are discussed.

Amphotericin B↗
PubMed1994

Renal tubular acidosis in Papua New Guinea.

Unlike most other inborn errors of metabolism, which require advanced and expensive diagnostic techniques and complex drug and dietary management (often not feasible in developing countries), the renal tubular acidoses may be detected and treated both easily and cheaply. Diagnostic confusion is possible as this series demonstrates due to the protean clinical manifestations. Three recent cases from Port Moresby General Hospital are described and appropriate investigations and treatment discussed.

Acidosis, Renal Tubular↗
PubMed1993

Impedance matching at arterial bifurcations.

Reflections of pulse waves will occur in arterial bifurcations unless the impedance is matched continuously through changing geometric and elastic properties. A theoretical model is presented which minimizes pulse wave reflection through bifurcations. The model accounts for the observed linear changes in area within the bifurcation, generalizes the theory to asymmetrical bifurcations, characterizes changes in elastic properties from parent to daughter arteries, and assesses the effect of branch angle on the mechanical properties of daughter vessels. In contradistinction to previous models, reflections cannot be minimized without changes in elastic properties through bifurcations. The theoretical model predicts that in bifurcations with area ratios (beta) less than 1.0 Young's moduli of daughter vessels may be less than that in the parent vessel if the Womersley parameter alpha in the parent vessel is less than 5. Larger area ratios in bifurcations are accompanied by greater increases in Young's moduli of branches. For an idealized symmetric aortic bifurcation (alpha = 10) with branching angles theta = 30 degrees (opening angle 60 degrees) Young's modulus of common iliac arteries relative to that of the distal abdominal aorta has an increase of 1.05, 1.68 and 2.25 for area ratio of 0.8, 1.0 and 1.15, respectively. These predictions are consistent with the observed increases in Young's moduli of peripheral vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta, Abdominal↗
PubMed1993

Transformation of immortal, non-tumorigenic osteoblast-like human osteosarcoma cells to the tumorigenic phenotype by nickel sulfate.

Epidemiological studies have indirectly linked compounds of chromium, nickel and arsenic to human carcinogenesis. However, there is no evidence that metal compounds can transform human cells to the tumorigenic phenotype in culture. We show here that exposure to 36 microM NiSO4 for 48-96 h results in transformation of an immortal, nontumorigenic, osteoblast-like cell line, HOS TE85, to the tumorigenic phenotype. Continuous passaging following treatment leads to the formation of a few dense foci. The cells isolated and expanded from the foci are morphologically transformed, and form anchorage-independent colonies of the size and abundance comparable to that formed by Kirsten murine sarcoma virus transformed HOS TE85 cells. The transformed cells from tumors in nude mice, have enhanced levels of plasminogen activators and have lost the ability to form model bone matrix on extended culture in the presence of ascorbic acid and beta-glycerophosphate. A number of cell lines have been established from nude mouse tumors. Cytogenetic analysis reveals 16 marker chromosomes and an aberrant chromosome 16. This is the first report of the transformation of a human cell line to tumorigenic phenotype by a metal carcinogen.

Animals↗
PubMed1993

The effect of liquid fibre on gastric emptying in the rat and humans and the distribution of small intestinal contents in the rat.

A combination of the polysaccharide ethyl-hydroxyethyl-cellulose (EHEC) and the surfactant sodium-dodecylsulphate (SDS) has the extraordinary physical property of being liquid at room temperature but gelling firmly at 37 degrees C. It has been named 'liquid fibre' and its effect on gastric emptying has been tested in rats and humans, as well as its effect on intestinal distribution in rats. Rats were gavaged with 5 ml of radiolabelled liquid fibre, SDS in water, or water control. Subgroups were killed after 25, 50, 100, 200, and 300 minutes, the gut removed, and the distribution of radioactivity measured scintigraphically. Liquid fibre gelled in the stomach and spread exponentially down the small intestine before 25 minutes. This distribution was maintained for 200 minutes after which the stomach began to empty again. In the human study, 10 healthy men drank 250 ml liquid fibre and placebo labelled with 1.85 MBq technetium tin colloid on separate occasions. Gastric emptying was measured by gamma-camera. Half emptying time significantly increased from 17.7 to 55.8 minutes (means, p < 0.05). The time for 10% to empty (which includes any lag time) increased from 7.0 to 19.4 minutes (p < 0.05). Average emptying rate decreased from 4.49%/min for placebo to 1.60%/min for liquid fibre (p < 0.01). The dramatic delay in gastric emptying suggests liquid fibre may have clinical applications while its liquid formulation should improve acceptability.

Adult↗
PubMed1993

Acute streptococcal pharyngitis misdiagnosed as faucial diphtheria: a cautionary lesson.

A confirmed case of diphtheria has not been reported in Papua New Guinea for many years, though it should be considered dormant rather than extinct. Thus, most clinicians nowadays are unfamiliar with the classical features of the disease. We report a case of streptococcal pharyngitis which had several features of diphtheria leading to unnecessary and potentially harmful intervention. Some words of caution and various recommendations are made.

Acute Disease↗
PubMed1992

Determination of plicamycin in plasma by radioimmunoassay.

This article describes a method for the determination of plicamycin in plasma by radioimmunoassay. The anti-plicamycin antibody was produced against a plicamycin-bovine serum albumin conjugate prepared by using diazotized p-aminobenzoic acid as a cross-linker. The radiolabeled ligand, 125I-plicamycin, was prepared by the chloramine-T method. The linear plicamycin concentration range was 7-400 ng/ml. The coefficients of variation for intra- and interday variabilities were 7.5 and 15%, respectively. No interference was observed from either the structurally related chromomycin A or concomitantly used drugs hydroxyurea or allopurinol. With this method of testing, plicamycin levels in plasma could be determined in patients receiving small (0.85-1.0 mg/m2) therapeutic plicamycin doses. Preliminary pharmacokinetic data in humans indicate that the plasma drug disappearance curve was biphasic with a mean elimination half-life of 10.6 +/- 1.7 h, total clearance rate of 11.1 +/- 0.4 ml/min/m2, and area under the plasma drug concentration-time curve of 1,289-1,546 ng-h/ml. This assay method is clinically useful for pharmacokinetic studies of plicamycin and may be helpful in the design of rational therapeutic drug trials.

Antibody Specificity↗
PubMed1992

Ethanol-associated alterations in the kinetics of putrescine uptake and metabolism by the regenerating liver.

Biosynthesis of the polyamines, putrescine, spermidine, and spermine is required for DNA synthesis and liver regeneration after partial hepatectomy. We have previously reported that chronic ethanol consumption impairs polyamine synthesis and significantly retards liver regeneration after partial hepatectomy. In those studies, supplementation with putrescine restored hepatic DNA synthesis in ethanol-fed rats but exerted no effect in pair-fed controls. These differences in the response to putrescine treatment may have resulted from ethanol-associated differences in hepatic uptake, release, or metabolism of putrescine. To resolve these issues and define more completely how putrescine treatment affects DNA synthesis, we now assess the kinetics of putrescine uptake and metabolism after intraperitoneal or intravenous injection of radiolabeled putrescine (1.2 mmol/kg, specific activity 1 microCi/mmol) into rats fed 36% ethanol diets or isocaloric, nonethanol diets for 6 weeks prior to partial hepatectomy. After putrescine treatment, hepatic putrescine concentrations were greater in ethanol-fed rats than controls. Differences in post-treatment hepatic putrescine levels between ethanol and pair-fed groups could not be explained by differences in the rates of hepatic putrescine uptake or excretion into bile; residual de novo synthesis of putrescine from ornithine or metabolism of hepatic putrescine to its polyamine products, spermidine and spermine. Indeed, supplemental putrescine was not appreciably converted to spermidine or spermine in either ethanol or control rats. Hence, these latter polyamines are unlikely to be responsible for the treatment-associated improvement in DNA synthesis that has been noted in ethanol-fed rats. This suggests that putrescine itself acts to restore hepatic DNA synthesis in ethanol-fed rats.

Alcoholism↗