Human insulin.
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Diabetes Mellitus, Type 1↗
Biomedical subjects
G Williams
Publications and source records attributed to G Williams.
Human insulin and hypoglycaemia: burning issue or hot air?
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Awareness↗
Human growth hormone and restoration of hypoglycaemia awareness.
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Awareness↗
Structural studies of the acidic transactivation domain of the Vmw65 protein of herpes simplex virus using 1H NMR.
We have overproduced and purified the carboxy-terminal transactivation domain of Vmw65 (VP16) of herpes simplex virus, and studied potential folding of the domain by 1H NMR. Two species of the acidic domain were obtained from the bacterial expression system, and we demonstrate that one of these represents read-through of the natural amber termination codon of the Vmw65 reading frame producing a larger polypeptide. Additional residues in the read-through product were identified by total amino acid analysis and by NMR. Study of the correctly terminated product by 1D NMR gave resonances which were clustered into groups around their random-coil chemical shift positions, and 2D NMR demonstrated that, even in mixed solvents containing up to 80% MeOH, there was very little evidence of secondary structure. Together these results indicate that the isolated acid domain has little if any alpha-helical content of any stable nature. We discuss these results with reference to the demonstrated activity of the acidic domain in a wide variety of polypeptide contexts.
Amino Acid Sequence↗
The effect of dexamethasone on neuropeptide Y concentrations in specific hypothalamic regions.
Neuropeptide Y (NPY) is a major hypothalamic peptide which is implicated in the regulation of energy balance and in the activation of the hypothalamo-pituitary adrenal axis. This study aimed primarily to determine the effects on regional hypothalamic NPY levels, of catabolism and weight loss induced in rats by the synthetic glucocorticoid, dexamethasone, injected daily at a dose of 0.4 mg/kg for 7 days. NPY concentrations were significantly raised in the paraventricular nucleus (PVN) of male Wistar rats (45%, p = 0.009; n = 10) compared with saline-injected controls (n = 10). Body weight (p less than 0.001) and food intake (p less than 0.001) were significantly reduced, plasma insulin concentrations were increased (p less than 0.001), but there was no change in glucose concentrations. Chronic dexamethasone treatment did not cause the marked NPY increases in the arcuate nucleus (ARC) and other hypothalamic regions which have been observed in other catabolic states causing weight loss. One possible explanation is the high insulin levels induced by dexamethasone, which may have prevented compensatory hyperphagia by suppressing an increase in hypothalamic NPYergic activity. We also examined the acute effects of a single dexamethasone injection on regional hypothalamic levels, to determine whether the drug had a direct action separate from that due to sustained weight loss. In the acute study, groups of rats (n = 7) were examined at 4 h after a single injection of dexamethasone or saline. NPY concentrations were significantly increased in the lateral hypothalamic area (LHA), (60%, p = 0.008) when compared with saline-injected controls, but there was no change in body weight or glucose or insulin concentrations during the 4h interval. Altered transport or release of NPY in the lateral hypothalamic area may be a result of acute feedback regulation by glucocorticoids on the hypothalamus.
Analysis of Variance↗
Child developmental delay and socio-economic disadvantage in Australia: a longitudinal study.
Socio-economic inequalities in adult and child health in Australia have been an issue of national concern. While a large body of data has discussed adult health, there have been relatively few Australian reports of socio-economic inequalities in child health. This occurs in a context where there have been increases in the proportion of Australian children living in poverty and where there has been an increased interest in child developmental delay as an indicator of child health status. This paper reports the result of a longitudinal study of pregnancy outcomes and one indicator of child health, namely child developmental delay. Three indicators of socio-economic status (chronic socio-economic disadvantage, mother's education, family income) were used to predict child developmental delays observed some 5 1/2 years after the study commenced. Mothers who had the lowest socio-economic status (using any of the indicators) had substantially higher rates of children manifesting developmental delays.
Australia↗
A recent reminder of botulism.
Botulism is a rare yet potentially common form of food poisoning that can be fatal. (1) Few documented cases of botulism exist in Australia (2,3,4) and New Zealand (5), emphasising how infrequently it is encountered. The recent admission to our Intensive Care Unit (ICU) of a man suspected of having botulism was a timely reminder of just how dangerous this condition can be. This paper will review the contemporary knowledge and interventions necessary in the management of botulism. It will also utilise anecdotes from our recent experience to illustrate some of the clinical scenarios and potentially fatal complications seen in this condition.
Australia↗
Attempts to accelerate glucagon absorption: effects of adding a vasodilator and of injection using a 'sprinkler' needle.
Glucagon injected subcutaneously or intramuscularly may take up to 30 min to reverse hypoglycaemia. We investigated whether glucagon absorption could be accelerated by two manoeuvres known to enhance insulin absorption: addition of a powerful local hyperaemic agent (10 nmole alpha-calcitonin gene-related peptide; CGRP), and injection using a multihole 'sprinkler' needle. Glucagon (1 mg) given by conventional injection to six normal subjects produced peak plasma glucagon concentrations of 1.48 +/- 0.23 (SEM) ng ml-1 after 20 min and a peak glycaemic response of 7.8 +/- 0.8 mmol l-1 at 25 min. Glucagon injected with CGRP or using the sprinkler needle did not produce any significant differences in plasma glucagon or glycaemia profiles, compared with conventional injection. Further studies demonstrated that glucagon is itself a powerful vasodilator, causing a 300-500% increase in local blood flow, comparable to that induced by CGRP. Because of its intense local hyperaemic action, the absorption of subcutaneously-injected glucagon may be optimal and seems unlikely to be accelerated by pharmacological or other means.
Absorption↗
Adult Wilms' tumour: review of 14 patients.
Wilms' tumour, or nephroblastoma, is the commonest renal neoplasm found in children, but is rarely found in adults, the world literature recording only approximately 200 cases. Individual case reports continue to be published but only within the last 10 years have definitive treatment regimes been suggested. In order to determine the UK experience of adult Wilms' tumour, members of the British Association of Urological Surgeons were circulated with a questionnaire, and from 141 replies, 13 members reported 17 cases. Critical review of the original histology slides excluded 3 of these; the 14 remaining cases are described and their management discussed in the light of current recommended treatment.
Adult↗
Are some animals more equal than others?
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Animals↗
The Liverpool Symposium on Human Insulin and Hypoglycemia.
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Diabetes Mellitus, Type 1↗
The products of the kdpDE operon are required for expression of the Kdp ATPase of Escherichia coli.
The expression of the Kdp system for K+ uptake in Escherichia coli requires the products of two genes, kdpD and kdpE. These genes constitute an operon adjacent to the kdpABC operon that encodes the three membrane protein subunits of Kdp. Both operons are transcribed in the same direction and overlap; the kdpDE promoter is in kdpC, the last gene of the kdpABC operon. Transcription of the kdpDE operon is at a low level when Kdp is not expressed; transcription increases about 10-fold when kdpABC is turned on, indicating significant read-through of the kdpDE operon by transcripts beginning at the promoter of kdpABC operon. The proximal region of the kdpD gene is the site of most mutations that lead to constitutive expression of the kdpABC operon.
Adenosine Triphosphatases↗
Malignant hyperpyrexia: a rare cause of postoperative death.
A middle aged man developed very high fever, status epilepticus, and terminal acute renal failure with myoglobinuria after surgery. A post mortem examination showed widespread muscle necrosis with hypercontraction bands. Muscle enzyme studies and electron microscopic examination disclosed central core disease, a condition closely related to malignant hyperpyrexia. This condition is a genetically inherited disorder which can be triggered by certain volatile anaesthetic agents or Suxamethonium. In this patient the condition may have been triggered by either the Isoflurane or the postoperative status epilepticus.
Humans↗
Exaggerated sensitivity to NE-induced vasoconstriction in IDDM patients with microalbuminuria. Possible etiology and diagnostic implications.
Increased urinary albumin excretion rate (AER) in the microalbuminuric phase of diabetic nephropathy has been attributed to intraglomerular hypertension. This could be caused by constriction of efferent glomerular arterioles, which carry alpha-adrenoceptors. We tested the hypothesis that insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria are hypersensitive to vasoconstriction induced by norepinephrine (NE). We studied 15 IDDM patients with microalbuminuria (AER 32-295 mg/24 h), 13 IDDM patients with normal AER (5-24 mg/24 h), and 9 nondiabetic subjects (AER 8-22 mg/24 h). All were normotensive. NE-induced vasoconstriction was measured in dorsal hand veins, which carry alpha-receptors similar to those of glomerular efferent arterioles. Vein diameter was measured with a linear displacement probe during a stepped NE infusion (1-32 ng/min) into the vein, and venoconstriction was expressed as a percentage of the maximum passively distended venous diameter. Microalbuminuric IDDM patients exhibited significantly greater vasoconstriction (P less than 0.005) at all NE infusion rates than both other groups. The NE infusion rate producing 50% of maximal venoconstriction (ED50) in the microalbuminuric IDDM group (median 1.1 ng/min, range 0.2-25.2 ng/min) was significantly less than in both the normoalbuminuric IDDM group (median 12.5 ng/min, range 4.9-40.5 ng/min, P = 0.00007) and the nondiabetic group (median 17.7 ng/min, range 5.9-42.2 ng/min, P = 0.0003). Dose-response curves and ED50 did not differ significantly between normalbuminuric IDDM and nondiabetic groups. IDDM patients with microalbuminuria are hypersensitive to NE-induced vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Why patients choose to purchase a hearing aid privately.
A questionnaire survey was undertaken of patients who had recently purchased a private hearing aid. They were asked their reasons for choosing a private aid in preference to an NHS aid. Cosmetic considerations and the failings of Health Service provisions were the most commonly cited reasons.
Aged↗
The prevalence of social-evaluative anxiety in opioid users seeking treatment.
The presence of social-evaluative anxiety in opioid users has been consistently recognized by clinicians, but as yet has not been systematically investigated. Scores on the Social Avoidance and Distress (SAD) Scale and the Fear of Negative Evaluation (FNE) Scale were obtained from the randomly selected files of 159 opioid users presenting for treatment at an inner city drug advisory service. Approximately one-quarter of the sample reported anxiety which may be considered psychologically and socially disfunctional. The prevalence of social-evaluative anxiety reported in this sample has implications for the provision of appropriate and effective treatment for this distressed population.
Adolescent↗
Assessing symptom improvement after elective prostatectomy for benign prostatic hypertrophy.
BACKGROUND: Elective surgery for benign prostatic hypertrophy requires estimates of likely improvement. METHODS: Data are from a prospective study of all patients without cancer who underwent transurethral prostatectomy. After eliminating patients for whom surgery was not elective, we examined symptom improvement. RESULTS: Surgery was effective in reducing symptoms for all but those with very mild preoperative symptoms. For the remainder, the average level of postoperative outcomes achieved was independent of the initial symptom severity. CONCLUSIONS: Elective prostatectomy is effectiveness for improving symptoms. The improvement is typically sustained, and for some symptoms improvement continues during the first year after surgery. Patients with severe symptoms were as likely to achieve the same level of postoperative improvement as were patients with less severe problems initially. However, patients with very mild symptoms benefited little or none from surgery.
Adult↗