The Viral Activation Transfusion Study (VATS): rationale, objectives, and design overview.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
A Collier
Publications and source records attributed to A Collier.
Sodium status, corticosteroid metabolism and blood pressure in normal human subjects and in a patient with abnormal salt appetite.
1. A patient with severe hypertension was found to have mildly impaired 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity on the basis of urinary steroid metabolite ratios, low plasma aldosterone, angiotensin II and renin levels and marginally low levels of plasma potassium. 2. The patient also had a compulsively high salt intake. 3. We tested the hypothesis that high salt intake may affect 11 beta-HSD activity. 4. High salt intake in normal subjects did not significantly alter either blood pressure or 11 beta-HSD activity. 5. We suggest that the potentially small hypertensive effect of the partial enzyme deficiency in our patient, also reported in patients with essential hypertension, has been markedly amplified by the very high salt intake.
Adrenal Cortex Hormones↗
[Internuclear bilateral pseudo-ophthalmoplegia and dermatomyositis].
A 60 year-old woman complaining of diplopia presents an ocular motility disturbance mimicking internuclear ophthalmoplegia. Idiopathic dermatomyositis is diagnosed by the help of clinical, biological, electrophysiological and histological data. The outcome is favorable under corticotherapy. Ocular muscle involvement is rare in dermatomyositis. An overlap syndrome with another auto-immune disorder like myasthenia should be excluded in this kind of manifestation.
Dermatomyositis↗
Development and testing of improved suicide functions for biological containment of bacteria.
We have developed very efficient suicide functions for biological containment based on the lethal Escherichia coli relF gene. The suicide functions are placed in duplicate within a plasmid and arranged to prevent inactivation by deletion, recombination, and insertional inactivation. The efficiency of this concept was tested in a plasmid containment system that prevents transfer of plasmids to wild-type bacteria. Protection against plasmid transfer was assayed in test tubes and in rat intestine. Protection was efficient and refractory to inactivation by mutation and transposons. The efficiency of the suicide system was also tested in soil and seawater. We show that unprecedented suicide efficiency can be achieved in soil and seawater after suicide induction by IPTG (isopropyl-beta-D-thiogalactopyranoside). More than 7 orders of magnitude reduction in suicide bacteria was achieved.
Animals↗
Neutrophil count and activation in vascular disease.
An elevated peripheral leucocyte count is associated with an increased risk of myocardial infarction and progression of coronary artery disease. The aim of this study was to determine neutrophil count and activation, measured as an increase in plasma neutrophil elastase, in patients with stable ischaemic heart disease, insulin-dependent diabetes mellitus and essential hypertension compared with a comparable group of control subjects. Neutrophil count and neutrophil elastase were raised significantly for patients with ischaemic heart disease (p less than 0.005; p less than 0.002), diabetes mellitus (p less than 0.001; p less than 0.01) and hypertension (p less than 0.05; p less than 0.0001) respectively compared to the control subjects. Neutrophil elastase did not correlate with subject age or leucocyte count. This study confirms the association between leucocyte count and vascular disease, and is consistent with neutrophil activation contributing to the progression of vascular disease.
Adult↗
Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria.
In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA'] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (B beta 15-42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA' was elevated in the microalbuminuric patients compared with control subjects (P less than 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P less than 0.05) and control subjects (P less than 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P less than 0.01). Except for B beta 15-42, all the hemostatic variables were increased (P less than 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P less than 0.03) and t-PA (P less than 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Plasma endothelinlike immunoreactivity levels in IDDM patients with microalbuminuria.
OBJECTIVE: To determine whether plasma endothelin, a potent vasoconstrictor and growth factor for vascular smooth muscle, is elevated in microalbuminuric insulin-dependent diabetes mellitus patients. RESEARCH DESIGN AND METHODS: Plasma endothelinlike immunoreactivity was measured by radioimmunoassay in 15 microalbuminuric diabetic patients, 12 normoalbuminuric diabetic patients, and 12 control subjects. RESULTS: The mean levels of plasma endothelinlike immunoreactivity were raised in the normoalbuminuric patients (8.4 pM [range 4.8-12.7 pM]; P less than 0.01) and the microalbuminuric patients (10.2 pM [range 5.6-31.1 pM]; P less than 0.001) compared with control subjects (6.1 pM [range 4.5-7.6 pM]). Plasma endothelinlike immunoreactivity was also higher in the microalbuminuric patients compared with the normoalbuminuric patients (P less than 0.05). CONCLUSIONS: The increase in plasma endothelinlike immunoreactivity further confirms endothelial dysfunction in diabetes and this increase in plasma endothelin may contribute to the vascular disease prevalent in diabetes.
Adult↗
Alterations in monocyte receptor function in type 1 diabetic patients with ketoacidosis.
The level of expression of three monocyte cell surface receptors was studied in seven patients with Type 1 (insulin-dependent) diabetes admitted to hospital with ketoacidosis. After recovery of metabolic control the monocyte carbohydrate-binding ('lectin-like') receptors that recognize bacterial cell wall sugars and receptors for complement components were reduced in the patients compared with normal control subjects. This was in contrast to the expression of the receptor for the Fc portion of immunoglobulin which remained unaltered. Compared with the control subjects the level of 'lectin-like' receptors was reduced by 22.8 +/- 6.5% (p less than 0.05) on admission to hospital and 12.1 +/- 1.7% (p less than 0.001) 6 weeks later when metabolic control had been established. The expression of complement receptors was 33.8 +/- 8.1% (p less than 0.01) lower than normal subjects when the diabetic patients suffered from ketoacidosis and 8.6 +/- 1.6% (p less than 0.01) lower than control subjects when patients had recovered metabolic control. The increased susceptibility to infection seen in diabetic patients, and the high incidence of infection in patients with ketoacidosis, may be partially the result of these changes in monocyte recognition mechanisms.
Adult↗
The role of the polyol pathway in diabetes mellitus.
The mechanism by which hyperglycaemia leads to diabetic complications has not been fully elucidated. Non-enzymatic glycosylation leads to considerable functional and structural alteration of proteins. Hyperglycaemia also induces changes in intracellular metabolites, particularly in the polyol pathway. Aldose reductase inhibitors, which block the polyol pathway, have been shown to prevent complications in animal models, and this provides the rationale for the large scale trials that are presently being conducted.
Aldehyde Reductase↗
Retroperitoneal fibrosis in two patients with Parkinson's disease treated with bromocriptine.
Retroperitoneal fibrosis has been observed in two patients with Parkinson's disease treated with bromocriptine. The patients complained of abdominal or lower back pain and presented with various degrees of renal insufficiency, with anuria in one. Laboratory evaluation furthermore showed an increased sedimentation rate and inflammatory anemia. Computerized tomography disclosed marked retroperitoneal thickening, and biopsy was performed in one patient. The symptoms appeared eighteen months and five years after treatment was started, at doses of 20 and 22.5 mg of bromocriptine daily. The medication was discontinued in both patients and steroid therapy was initiated, with resolution of all clinical, biological and radiological evidence of disease. This potential but rare complication of a widely prescribed drug warrants monitoring of renal function and sedimentation rate in patients undergoing bromocriptine treatment.
Aged↗
Felodipine in type II diabetes mellitus.
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Aged↗
Effects of felodipine on atrial natriuretic peptide in hypertensive non-insulin dependent diabetes mellitus.
Eighteen patients with non-insulin dependent diabetes mellitus and hypertension were treated during two 4 week periods with the calcium antagonist felodipine or placebo in a double-blind, randomised, cross-over study. Mean systemic blood pressure was significantly lower on felodipine, without producing a deleterious effect on diabetic control. Felodipine was associated with an increment in plasma renin concentration but plasma aldosterone and the renal outputs of sodium and dopamine were similar on both treatments. Plasma atrial natriuretic peptide levels were significantly reduced following felodipine treatment.
Aged↗
Free radical activity in type 2 diabetes.
Free radical activity has been implicated in the development of diabetic vascular complications in Type 1 diabetes. The aim of the present study was to investigate the levels of free radical scavengers, particularly erythrocyte superoxide dismutase, plasma and erythrocyte lysate thiol, and caeruloplasmin in 22 Type 2 diabetic patients clinically free of complications, and 15 comparable non-diabetic control subjects. The concentration (median (range] of both superoxide dismutase (23 (10-39) vs 45 (25-75) mumol l-1; p less than 0.001) and plasma thiol (374 (172-523) vs 460 (386-595) mumol l-1; p less than 0.01) were reduced in the diabetic group. There were no significant differences in the concentration of erythrocyte lysate thiol (199 (114-520) vs 188 (114-328) mumol l-1) or plasma caeruloplasmin (18 (9-31) vs 24 (6-50) mumol l-1) between the groups. This reduction in superoxide dismutase and the imbalance in the redox status of the plasma and lysate thiol demonstrated is consistent with an increase in free radical activity in Type 2 diabetes.
Blood Glucose↗
Relationship between urinary excretion of sodium and dopamine in type 1 diabetic patients with an without microalbuminuria.
The relationship between urinary sodium and dopamine excretion was investigated in 40 normal males and in 48 normotensive, Type 1 diabetic males, 11 with microalbuminuria and 37 with normal albumin excretion. In all three groups a significant correlation was demonstrated and the regression lines were similar. Thus, no evidence was found that a defect in dopamine mobilization contributes to the early renal pathophysiological changes of Type 1 diabetes.
Adult↗
Leucocyte mobilization and release of neutrophil elastase following acute insulin-induced hypoglycaemia in normal humans.
Insulin-induced hypoglycaemia in humans is associated with the rapid mobilization of leucocytes in peripheral blood. The aim of the present study was to determine whether neutrophil activation, manifested in plasma by neutrophil elastase concentration, occurs in response to insulin-induced hypoglycaemia. Acute hypoglycaemia (mean blood glucose 1.3 +/- 0.2 mmol l-1; mean +/- SD) was induced with intravenous insulin in 15 normal human subjects, and provoked an increase in the neutrophil count from 3.4 (range 1.9-6.5) to 10.7 (9.4-16.3) X 10(9) l-1 (p less than 0.001), and in the total leucocyte counts from 5.7 (4.1-8.1) to 12.8 (11.3-18.6) X 10(9) l-1 (p less than 0.001), with associated elevations in plasma neutrophil elastase concentration from 21 (12-34) to 29 (14-70) micrograms l-1 (p less than 0.05), and in total neutrophil elastase concentration from 5.90 (3.13-8.20) to 25.20 (23.00-52.00) mg l-1 (p less than 0.001). As neutrophil elastase is implicated in the development of vascular disease, this rise in response to hypoglycaemia may be of pathological importance in insulin-treated diabetic patients.
Adult↗
Comparison of intramuscular glucagon and intravenous dextrose in the treatment of hypoglycaemic coma in an accident and emergency department.
Hypoglycaemia remains a serious and much feared complication of insulin therapy. In this study, patients attending an accident and emergency department in hypoglycaemic coma were randomized to treatment with either intravenous dextrose (25g) or intramuscular glucagon (1mg), administered into the right thigh. Restoration of normal conscious level was slower after glucagon than dextrose (9.0 vs 3.0 min, P less than 0.01), although the average duration of hypoglycaemic coma was 120 min. Two patients in the glucagon-treated group, who failed to show satisfactory recovery after 15 min, required additional treatment with intravenous dextrose. On questioning following recovery, all except two patients reported loss of awareness of the onset of hypoglycaemia Intramuscular glucagon is valuable in the treatment of severe hypoglycaemia outwith hospital and, although the slightly slower and less predictable recovery may appear to make it a less attractive option than intravenous dextrose in the accident and emergency department, this must be balanced against the advantages of ease of administration and a lower incidence of serious adverse effects.
Diabetes Mellitus, Type 1↗
Fund raising in the multi-institutional environment.
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Financial Management↗
Plasma hepatic glutathione S-transferase concentrations after insulin-induced hypoglycaemia in normal subjects and diabetic patients.
Plasma glutathione S-transferase basic isoenzyme (GST B1) concentrations have been measured by specific radioimmunoassay in Type 1 diabetic patients and in normal subjects, before and after controlled insulin-induced hypoglycaemia, and in a further group of Type 1 diabetic patients in hypoglycaemic coma. The activities of alanine aminotransferase (ALT), aspartate amino-transferase (AST), and gamma-glutamyl transferase (gamma GT) were also measured. GST B1 concentrations were significantly increased 3 h after controlled insulin-induced hypoglycaemia, both in the diabetic patients (p less than 0.02) and in the normal group (p less than 0.05), but the magnitude of the rise did not differ between these two groups. Four of the 9 patients presenting in hypoglycaemic coma had a GST B1 concentration above the reference range. ALT, AST, and gamma GT activities did not rise following hypoglycaemia in any of the groups.
Adolescent↗