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J Crawley

Publications and source records attributed to J Crawley.

At least 37 records · Page 2Linked to original sources

Clinical features and outcome of severe malaria in Gambian children.

The clinical and laboratory features of severe falciparum malaria in 180 Gambian children were studied between 1985 and 1989. Of the 180 children, 118 (66%) presented with seizures, 77 (43%) had cerebral malaria, 35 (20%) had witnessed seizures after admission, 29 (16%) were hypoglycemic, and 27 (15%) died. Respiratory distress was a common harbinger of a fatal outcome. The differences in admission parasite counts in the blood, hematocrit, and opening cerebrospinal pressures for patients who died and survivors were not significant. A multiple logistic regression model identified neurological status (coma, particularly if associated with extensor posturing), stage of parasite development on the peripheral blood film, pulse rate of > 150 or respiratory rate of > 50, hypoglycemia, and hyperlactatemia (plasma lactate level, > 5 mmol/L) as independent indicators of a fatal outcome. Biochemical evidence of hepatic and renal dysfunction was an additional marker of a poor prognosis, but, in contrast to severe malaria in adults, none of these children with severe malaria had acute renal failure.

Adult↗

Interobserver variation in respiratory signs of severe malaria.

Respiratory abnormalities are common presentations of malaria and acute respiratory tract infection, both of which are major causes of childhood mortality and morbidity in sub-Saharan Africa. Appropriate management depends on accurate assessment of disease severity which for the majority of children must be based on clinical signs alone. Choosing which signs best serve this purpose remains a considerable problem particularly in malaria endemic areas. As part of a prospective study to define clinical signs indicative of life threatening malaria video recordings were used to examine the level of agreement between clinicians for potentially important respiratory signs in 51 children. Overall agreement was good for recession, severe recession, and nasal flaring (kappa = 0.57, 0.50, and 0.60 respectively) and substantial for deep breathing and the summary impression of respiratory distress (kappa = 0.70 and 0.69 respectively). However, within this substantial variation in interpretation was apparent between individual observers from slight to almost perfect agreement (kappa values 0.10-0.92). Video is a useful tool to demonstrate interobserver variation and it may also allow training in recognition of signs and a means of standardising clinical signs between centres.

Child↗

The management of severe malaria in children: a review.

We have attempted to summarise an approach to management of severe malaria from our experience and that of others from published data in this review. This represents our current state of knowledge and practices which may change as research continues in this field. It also represents what we feel should be the minimum aim in treating severe malaria even at district hospital level. It focuses on practical issues encountered when admitting such patients: initial assessment, immediate supportive management, use of transfusion, appropriate anti-malarial treatment and ongoing management.

Child↗

Glycerol metabolism in severe falciparum malaria.

Gluconeogenesis and liver blood flow (LBF) in severe falciparum malaria were assessed from the clearance and metabolic response to intravenously administered glycerol (0.3 g/kg) and Indocyanine Green ([ICG] 0.4 mg/kg), respectively. Fasting baseline blood glycerol concentrations (mean +/- SD) were significantly higher in acute malaria (133 +/- 65 mumol/L, n = 14), than in convalescence (65 +/- 31 mumol/L, n = 9, P = .01), but basal triacylglycerol concentrations were similar. Estimated glycerol turnover was also more than twice as high in acute malaria compared with convalescence (1.36 +/- 0.87 v 0.54 +/- 0.15 mumol.min-1.kg-1, P = .015). The increment in plasma glucose (AUC0-55 min) following glycerol infusion was greater during acute malaria compared with convalescence (median [range], +31.6 [-0.9 to +107.6] v +14.5 [-103 to +27.1] mmol.min-L-1, P < .05), but the insulin increments were similar (P = .9), indicating reduced tissue insulin sensitivity. The increment in venous lactate (AUC0-55 min) was higher in severely ill patients (17.2 [-7.8 to +53.4] mmol.min.L-1, n = 10) compared with patients with moderately severe malaria (-3.1 [-8.7 to 3.2] mmol.min-L-1, n = 4, P = .01). LBF estimated from ICG clearance was lower during acute illness than in convalescence (mean +/- SD, 15.5 +/- 2.3 v 18.6 +/- 2.9 mL.min-1.kg-1, P = .007) and correlated inversely with the basal venous lactate concentration (rs = .53, P < .05). LBFs less than 15 mL.min-1.kg-1 were associated with hyperlactatemia, and all four fatal cases had LBFs of less than 12 mL.min-1.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Comparison of artemether and chloroquine for severe malaria in Gambian children.

Artemether is an oil-soluble methyl ether of artemesinin (qinghaosu). It has been studied extensively in China, where it has been shown to be rapidly effective in severe falciparum malaria. Nearly all the patients studied previously were adults. We have investigated the efficacy of artemether in children with moderate or severe falciparum malaria. In the preliminary study of moderately severe malaria, 30 Gambian children were randomised in pairs to receive either intramuscular artemether (4 mg/kg loading dose followed by 2 mg/kg daily) or intramuscular chloroquine ('Nivaquine') 3.5 mg base/kg every 6 h. Both drugs were well tolerated and rapidly effective. The times to parasite clearance were significantly shorter in the artemether recipients (mean 36.7 [SD 11.3] vs 48.4 [16.8] h, p less than 0.05). 43 children with severe malaria were then randomised to receive intramuscular treatment with the same regimens of artemether (n = 21) or chloroquine (n = 22) as used in the preliminary study. 8 children (19%) died. There were no significant differences between the two groups in the clinical, haematological, biochemical, or parasitological measures of therapeutic response in survivors and there was no evidence of local or systemic toxicity. Despite similar parasite counts on admission, clearance times overall were longer in severe malaria than in moderate malaria. Artemether is a well tolerated and rapidly effective parenteral treatment for severe malaria in children, and would be especially valuable in areas with chloroquine-resistant P falciparum.

Animals↗

Clinical validation of a miniature nuclear probe system for continuous on-line monitoring of cardiac function and ST-segment.

A new, miniature cesium iodide/photodiode nuclear probe (the "Cardioscint") has been developed for continuous on-line measurement of left ventricular function and the ST-segment. Ejection fraction (EF) measurements in 77 patients were compared with gated equilibrium radionuclide ventriculograms. The probe was positioned over the left ventricle by first using a blind positioning algorithm and then by using the gamma camera. Background was measured both manually and automatically. There was good correlation between probe (positioned blind) and gamma camera EF with both manual (r = 0.80, n = 65) and automatic (r = 0.78, n = 66) backgrounds. Use of the gamma camera did not significantly alter the results. Correlation between the probe stroke counts and thermodilution-derived stroke index during atrial pacing in six subjects was also satisfactory (r = 0.69, n = 102). Thus, the Cardioscint is able to provide a reliable estimate of EF and can track rapid changes in cardiac volumes.

Cardiac Pacing, Artificial↗

N-terminal galanin-(1-16) fragment is an agonist at the hippocampal galanin receptor.

The galanin N-terminal fragment [galanin-(1-16)] has been prepared by solid-phase synthesis and by enzymic cleavage of galanin by endoproteinase Asp-N. This peptide fragment displaced 125I-labeled galanin in receptor autoradiography experiments on rat forebrain and spinal cord and in equilibrium binding experiments from high-affinity binding sites in the ventral hippocampus with an IC50 of approximately 3 nM. In tissue slices of the same brain area, galanin-(1-16), similarly to galanin, inhibited the muscarinic agonist-stimulated breakdown of inositol phospholipids. Upon intracerebroventricular administration, galanin-(1-16) (10 micrograms/15 microliters) also inhibited the scopolamine (0.3 mg/kg, s.c.)-evoked release of acetylcholine, as studied in vivo by microdialysis. Substitution of [L-Trp2] for [D-Trp2] resulted in a 500-fold loss in affinity as compared with galanin-(1-16). It is concluded that, in the ventral hippocampus, the N-terminal galanin fragment [galanin-(1-16)] is recognized by the galanin receptors controlling acetylcholine release and muscarinic agonist-stimulated inositol phospholipid breakdown as a high-affinity agonist and that amino acid residue [Trp2] plays an important role in the receptor-ligand interactions.

Animals↗

Ethanol and the GABA receptor complex: studies with the partial inverse benzodiazepine receptor agonist Ro 15-4513.

Ethanol potentiates GABA-receptor-mediated Cl- ion flux in vitro and, at similar concentrations, has anxiolytic and intoxicating properties in vivo. The imidazobenzodiazepine, Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-meth-6-oxo-4H- imidazo(1,5-a)(1,4)benzodiazepine-3-carboxylate), is a potent partial inverse agonist of the benzodiazepine/GABA receptor which can antagonize the in vitro actions of ethanol in potentiating GABA receptor-mediated Cl- ion flux. Moreover, several of the behavioral effects of ethanol are also antagonized by Ro 15-4513, and these effects can be demonstrated in several paradigms at doses of Ro 15-4513 that do not produce opposite behavioral effects. In contrast, in our studies, other benzodiazepine receptor antagonist and inverse agonists, including Ro 15-1788, FG-7142, and beta-CCE were not able to antagonize these biochemical or behavioral effects of ethanol at doses that were without intrinsic effects. However, both Ro 15-1788 and beta-CCE blocked the antagonism of ethanol's effects by Ro 15-4513, suggesting a role for the GABA receptor complex in the actions of ethanol. These studies provide further evidence that GABAergic neurones may mediate at least some of the behavioral and biochemical actions of low-to-moderate doses of ethanol.

Alcoholic Intoxication↗

Chronic corticosterone administration in rats: behavioral and biochemical evidence of increased central dopaminergic activity.

Chronic corticosteroid treatment in humans in frequently complicated by behavioral changes. The present study suggests that chronic steroid administration in rats has distinct neurochemical consequences which are behaviorally relevant. Ten male Sprague-Dawley rats received 7 daily injections of corticosterone, following which they exhibited increased caudate homovanillic acid as well as an attenuated decline in vertical and ambulatory movement (functional measures of dopamine activity) compared to placebo-treated rats. A subgroup of steroid-treated rats which was more behaviorally responsive to corticosterone also showed increased caudate 5-hydroxyindole acetic acid and decreased prefrontal cortex dopamine and serotonin. These results are discussed in relation to the known behavioral side effects of chronic corticosteroid administration in man and the psychiatric manifestations of naturally occurring states of hypercortisolemia.

Animals↗

Factors influencing the feeding of first-born infants.

Influences on the choice and use of an infant feeding method by primigravidae were studied from late pregnancy until six months after delivery. Data were collected by home interviews and postal questionnaires, and from hospital case-notes. Three-quarters of the women had chosen a method before their first hospital visit and most adhered to their choice. Mothers named midwives and health visitors more often than other health professionals as appropriate for discussions about feeding. However, there was little evidence of the influence of health professionals apart from an association between hospital feeding practices and duration of breast feeding. The major influences on mothers were socio-cultural. Findings suggest that breast feeding can be encouraged by a wide dissemination of information, by enabling mothers to discuss feeding with their preferred professional, by respecting an early choice of method, and by encouraging demand feeding which should begin soon after delivery.

Attitude↗

A novel chemically induced animal model of human anxiety.

The ethyl ester of beta-carboline-3-carboxylic acid (beta-CCE) has a high affinity for benzodiazepine receptors and can antagonize some of the pharmacologic actions of benzodiazepines in rodents. Administration of beta-CCE (2.5 mg/kg) to chair-adapted, male rhesus monkeys (7-9 kg) elicited a behavioral syndrome characterized by extreme agitation, head and body turning, distress vocalization and other behaviors which might be termed 'anxious'. Concomitant increases in plasma cortisol, epinephrine, norepinephrine, heart rate, and mean arterial blood pressure were observed. Pretreatment of animals with the benzodiazepine receptor antagonist Ro 15-1788 (5 mg/kg) antagonized the behavioral, endocrine, and somatic changes produced by beta-CCE, but did not elicit any significant changes in these parameters when administered alone. Thus, administration of beta-CCE to primates may be a reliable and reproducible model of human anxiety and, as much, may prove valuable for studying the postulated role of 'stress' or 'anxiety' in a variety of human disorders. In toto, these results strongly suggest that benzodiazepine receptors not only mediate the pharmacologic actions of benzodiazepines, but may also subserve both the affective and physiologic expression of anxiety.

Animals↗

Antagonism of the anxiolytic action of diazepam and chlordiazepoxide by the novel imidazopyridines, EMD 39593 and EMD 41717.

The imidazopyridines EMD 35993 and EMD 41717 antagonized the anticonflict actions of diazepam and chlordiazepoxide in rodent models which are predictive for anxiolytic action in man. In contrast to other described benzodiazepine antagonists, these compounds did not antagonize either the anticonvulsant or muscle relaxant properties of either benzodiazepine. Both EMD 39593 and EMD 41717 competitively inhibit the binding of [3H]diazepam to brain membranes, but do not exhibit regional differences in potency. These observations suggest that both EMD 39593 and EMD 41717 display some selectivity in antagonizing the anxiolytic properties of benzodiazepines, and as such may be useful tools in identifying neuronal substrates of anxiety.

Animals↗

Hyperaemia and swelling of a limb upon release of a tourniquet.

Using monkeys, a quantitative study was carried out to measure the effect of a tourniquet on the lower limb on peak flow, the amount of acute swelling and the time for it to recover. The disappearance of acute swelling is related to the duration of the period of ischaemia. No significant change in peak flow was demonstrated as the duration of the tourniquet was increased.

Animals↗