Biomedical subjects
Publications and source records attributed to L Franklin.
This paper describes the devastating outcome of a neonate who presented with severe late onset group B beta-haemolytic streptococcal (GBS) disease. There were extensive infarcts of the brain and gangrene of the toes. The purpose of this report is to alert healthcare workers of the unusual presentation and that fatal late onset group B beta-haemolytic streptococcal disease may occur despite early and effective management.
Considerable knowledge exists concerning the events mediating neuron death following a necrotic insult; prompted by this, there have now been successful attempts to use gene therapy approaches to protect neurons from such necrotic injury. In many such studies, however, it is not clear what sequence of cellular events connects the overexpression of the transgene with the enhanced survival. We do so, exploring the effects of overexpressing the Glut-1 glucose transporter with an adenoviral vector in hippocampal cultures challenged with the excitotoxin kainic acid (KA). Such overexpression enhanced glucose transport, attenuated the decline in ATP concentrations, decreased the release of excitatory amino acid neurotransmitters, and decreased the total free cytosolic calcium load. Commensurate with these salutary effects, neuronal survival was enhanced with this gene therapy intervention. Thus, the neuroprotective effects of this particular gene therapy occurs within the known framework of the mechanisms of necrotic neuronal injury.
The alkaloid derivative vinpocetine (14-ethoxycarbonyl-(3alpha,16alpha-ethyl)-14,15-eburnamine; Cavinton) has a well known beneficial effect on brain function in hypoxic and ischemic conditions. While it increases CNS blood flow and improves cellular metabolism, relatively little is known about vinpocetine's underlying molecular mechanisms on the single cell level. Since apoptotic and necrotic cell damage is always preceded by an increase in [Ca2+]i, this study investigated the effect of vinpocetine on [Ca2+]i increases in acute brain slices. Sodium influx is an early event in the biochemical cascade that takes place during ischemia. The alkaloid veratridine can activate this Na+ influx, causing depolarization and increasing [Ca2+]i in the cells. Therefore, it can be used to simulate an ischemic attack in brain cells. Using a cooled CCD camera-based ratio imaging system and cell loading with fura 2/AM, the effect of vinpocetine on [Ca2+]i changes in single pyramidal neurons in the vulnerable CA1 region of rat hippocampal slices was investigated. Preperfusion and continuous administration of vinpocetine (10 microM) significantly inhibited the elevation in [Ca2+]i induced by veratridine (10 microM). When the drug was administered after veratridine, it could accelerate the recovery of cellular calcium levels. Piracetam, another nootropic used in clinical practice, could attenuate the elevation of [Ca2+]i only at a high, 1 mM, concentration. We have concluded that vinpocetine, at a pharmacologically relevant concentration, can decrease pathologically high [Ca2+]i levels in individual rat hippocampal CA1 pyramidal neurons; this effect might contribute to the neuroprotective property of the drug.
Glucocorticoids (GCs), the adrenal steroids secreted during stress, can compromise the ability of hippocampal neurons to survive numerous necrotic insults. We have previously observed that GCs worsen the deleterious effects of gp120, the glycoprotein of the acquired immune deficiency syndrome virus, which can indirectly damage neurons and which is thought to play a role in the neuropathological features of human immunodeficiency virus infection. Specifically, GCs augment gp120-induced calcium mobilization, ATP depletion, decline in mitochondrial potential, and neurotoxicity in fetal monolayer cultures from a number of brain regions. In the present report, we demonstrate a similar gp120/GC synergy in adult hippocampal and cortical explants. We generated explants from rats that were either adrenalectomized, adrenally intact, or intact and treated with corticosterone to produce levels seen in response to major stressors. Metabolic rates in explants were then indirectly assessed with silicon microphysiometry, and cytosolic calcium concentrations were assessed with fura-2 fluorescent microscopy. We observed that basal levels of GCs tonically augment the disruptive effects of gp120 on metabolism in the CA1 cell field of the hippocampus and in the cortex. Moreover, raising GC concentrations into the stress range exacerbated the ability of gp120 to mobilize cytosolic calcium in a number of hippocampal cell fields. Finally, we observed that the synthetic GC prednisone had similarly exacerbating effects on gp120. Thus, GCs can worsen the deleterious effects of gp120 in a system that is more physiologically relevant than the fetal monolayer culture and in a region-specific manner.
Medical workforce data have a profound impact on health policy formulation, but derived doctor population ratios (DPR) are often more relevant to plotting national trends than providing a detailed regional or local workforce perspective. Regional workforce data may be more useful if national approaches are augmented by local information. In developing a detailed workforce analysis for one region of Australia, the authors encountered several challenging methodological issues, including the accuracy of medical workforce databases, clarity of definition of community boundaries, interpretation of workforce definitions and the difficulty accounting for local community needs. This paper discusses the implications for regional workforce research.
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Psychosocial support is vital for women with breast cancer. The breast care nurse performs a crucial role in this support.
Penicillin concentrations in cerebrospinal fluid (CSF) were measured at various hours and days of treatment in 163 infants undergoing therapy for congenital syphilis. The CSF levels were compared for three treatment regimens. Aqueous penicillin G (A-PEN), 100,000 U/kg per day, was used in 23 infant, and a dosage of 200,000 U/kg per day was used in 40 patients; procaine penicillin G (P-PEN), 50,000 U/kg per day, was used in 100 children. Mean CSF penicillin levels were 0.416, 0.493, and 0.077 microgram/ml, respectively, in the three treatment groups. The mean CSF penicillin concentration among the 63 infants treated with either of the A-PEN regimens (0.465 microgram/ml) was significantly greater than the mean concentration (0.077 microgram/ml) among those treated with P-PEN (p < 0.001). Among those who received A-PEN, the difference in dosage was not associated with a significant difference in mean CSF penicillin concentration (p = 0.68). All the specimens obtained from patients who received A-PEN, but only 82% of those from patients who received P-PEN, had treponemicidal concentrations (> or = 0.018 microgram/ml). However, 33.3% (9/27) of specimens from infants who received P-PEN, tested between 18 and 24 hours after a dose, had CSF penicillin concentrations < 0.018 microgram/ml. These data suggest that administration of A-PEN may be the preferred therapy if CSF levels > 0.018 microgram/ml are desired, especially for infants with severe disease or congenital neurosyphilis.
As the first phase of a major programme to develop epidemiologically derived recreational water quality criteria for South Africa, a preliminary epidemiological-microbiological study was conducted in Cape Town during February and March 1990. Serial trials were carried out at a clean and at a relatively polluted beach over weekends. Participants were recruited at the beach, at which time information on swimming status and sociodemography was obtained. This provided for a beach-going but non-swimming control group. Symptoms which developed subsequent to the beach visit were obtained by follow-up telephone interviews conducted 3-4 days later. Water samples collected on trial days both before and during maximum swimming activity, were analysed for enterococci, faecal coliforms, staphylococci, coliphages and F-male-specific bacteriophages. Significant differences in the indicator levels at the beaches were observed. An excess in gastro-intestinal, respiratory and skin symptoms were found among swimmers relative to non-swimmers at the polluted beach. Although not statistically significant, the results are suggestive of a relationship between swimming-associated illness and water quality. The study demonstrated the feasibility of the methodology and the results of the overall programme will form the basis for the development of epidemiologically derived recreational water quality criteria for South African beaches.
The effects of 1 year of growth hormone (GH) therapy were studied in 10 subjects with subnormal spontaneous secretion of GH, whose ages ranged from 6.5 to 12.4 years. Height, weight, body fat percentage, total body potassium (TBK), and extracellular water (ECW) were measured prior to initiating the treatment, and thereafter at 6 months (period 1) and 12 months (period 2). Height velocity almost doubled during the year of treatment: 7.8 +/- 0.8 and 7.1 +/- 0.7 cm/yr (P less than .0001) during periods 1 and 2, respectively, as compared with 3.9 +/- 0.6 cm/yr pretreatment. Body fat percentage decreased during period 1 to 18.2% +/- 4.9%, versus 16.3% +/- 4.5% (P less than .02), but stabilized thereafter (16.3% +/- 4.9%). Mid-arm muscle circumference (MAMC) and TBK increased in accordance with the predicted values for age. Body mineral density (BMD) increased both in absolute and standardized terms. No changes were found in ECW during treatment. We concluded that GH treatment in children with subnormal spontaneous secretion of GH has mainly a lipolytic effect on body composition, and that resistance to the lipolytic effect develops during the course of therapy.
The present studies were designed to characterize the behavior of Maudsley reactive (MR/Har) and nonreactive (MNRA/Har) rats in a modification of the Geller-Seifter operant conflict paradigm. Food-restricted (85% of free-feeding weights) female MR/Har and MNRA/Har rats were trained to lever press for food reinforcement in a multiple-schedule operant conflict paradigm. In the absence of a tone, a fixed ratio-30 (FR-30) schedule for reinforcement only was in effect (i.e., every 30th lever press resulted in the delivery of a 45-mg food pellet). During the presence of a tone, a fixed ratio-1 (FR-1) schedule of both reinforcement (food) and punishment (0.20 mA footshock applied for 500 ms) was in effect (i.e., each lever press resulted in both food and shock delivery). The tone periods were 27 s in duration and were presented on a variable interval (VI)-120-s schedule (approximately 20 tones/40-min session). Behavioral testing was conducted 5 days/week for 35 weeks. Initially, punished responding between the MR/Har and MNRA/Har rat strains did not differ dramatically. However, over the course of many weeks of conflict testing, rats of the MNRA/Har strain came to accept significantly more shocks than did subjects of the MR/Har strain. A direct examination of footshock sensitivity in these rats revealed that this difference in conflict behavior over time was not due to strain differences in shock sensitivity. The mechanism for this time-dependent difference in conflict behavior between the MR/Har and MNRA/Har rats remains undetermined.
Previous reports that central administration of arginine vasopressin (AVP) increases turnover of brain catecholamines raise the possibility that the pressor responses which follow central administration of AVP may be mediated, in part, by central catecholamines. To test this hypothesis, rats were given intraventricular injections of vehicle, or of the neurotoxin, 6-hydroxydopamine, which resulted in significant depletions of hypothalamic and medulla oblongata noradrenalin and hypothalamic dopamine, but not of medullary dopamine or of hypothalamic and medullary 5-hydroxytryptamine. Following a one week recovery, these conscious rats, fitted with indwelling arterial catheters, were given intraventricular injections of AVP; the increases in arterial pressure and heart rate were significantly reduced in the catecholamine-depleted animals. These data support the hypothesis that the pressor and tachycardia responses to intraventricular AVP are mediated, in part, by central catecholamine-containing neurons.
Saturated fatty acids and cholesterol in the diet raise the plasma cholesterol concentration, and a reduction in these constituents is recommended widely. However, there is not general agreement as to which nutrients should replace saturated fatty acids. Several different substitute nutrients are possible. In this study, three cholesterol-lowering diets were compared in nine men living in a domiciliary. On a typical American diet at baseline, cholesterol levels were in the normal range. One replacement diet was high in polyunsaturated fatty acids (High Poly); another had 30% fat and corresponded to the American Heart Association's (AHA) recommended diet for the general public (AHA phase I); the third diet had 20% fat, equivalent to the AHA phase III diet for treatment of hypercholesterolemia. Compared with baseline levels, all diets caused similar reductions in total cholesterol and low-density lipoprotein cholesterol levels, but the High Poly and AHA phase III diets lowered the high-density lipoprotein cholesterol level more than the AHA phase I diet. Thus, for the limited number of patients in this study, the diet recommended for the general public appeared as effective for lowering of cholesterol levels as diets containing more polyunsaturates or more carbohydrates.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.