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Biomedical subjects

R J Corrall

Publications and source records attributed to R J Corrall.

At least 55 records · Page 3Linked to original sources

Aldose reductase inhibition in diabetic neuropathy: clinical and neurophysiological studies of one year's treatment with sorbinil.

In a double-blind placebo-controlled trial the effect of Sorbinil (250 mg daily) on diabetic neuropathy was examined. After a 2-month run-in placebo period (with three major assessments) 21 patients were randomized to Sorbinil and 10 to placebo, and all were studied for a further 12 months with neurophysiological measurements at 3-month intervals of nerve conduction velocity in multiple nerves, autonomic function tests, vibration thresholds as well as clinical examination and an extensive self-assessment of symptoms. Two subjects on Sorbinil treatment developed a hypersensitivity reaction and were withdrawn. Metabolic control and severity of neuropathy was not significantly different between groups. There were no changes in symptoms as judged by self-assessment scores. No patient entered the trial with neuropathic ulcers but ulceration developed in 4 patients during Sorbinil treatment and in 1 of the placebo group. No beneficial effect of Sorbinil was demonstrated on either the clinical manifestation or on the neurophysiological measurements made in these neuropathic diabetic patients over 12 months of treatment.

Aldehyde Reductase↗

Bone scintigraphy and radiography in the early recognition of diabetic osteopathy.

Twenty-seven diabetic patients with clinical evidence of neuropathy were investigated by foot radiography, two-phase bone scintigraphy, biothesiometry and cardiovascular autonomic function testing. Typical signs of diabetic osteopathy on radiography were found in 10 subjects (37%), the degree of radiographic abnormality correlating with the severity of neurological impairment. Furthermore, all diabetics with evidence of severe neuropathy showed some evidence of osteopathy on foot radiographs. In all 10 cases of diabetic osteopathy diagnosed radiographically, abnormalities were shown on scintigraphy. In addition, five other patients showed scintigraphic abnormalities, without corresponding changes on radiography, and in this group the neurological impairment was less severe. Although confirmatory longitudinal studies are necessary, it seems likely that the earliest changes of diabetic neuropathic osteopathy may thus be recognized on bone scintigraphy, at a time when conventional radiographs are normal. This stage of diabetic osteopathy is associated with a lesser degree of neurological impairment.

Adult↗

The relationship of the renin-angiotensin-aldosterone system to atrial natriuretic peptide and the natriuresis of volume expansion in diabetics with and without proteinuria.

Atrial natriuretic peptide (ANP) and the renin-angiotensin-aldosterone system are important regulatory hormones in sodium homeostasis. We have measured these hormones during volume expansion produced by water immersion in diabetic subjects without and with microalbuminuria or frank proteinuria and compared the response with normal controls. Diabetic subjects excreted about half the amount of sodium that was excreted by the normal subjects (39 vs 21 mmol) over 4 h. Diabetic subjects and normal ones showed a twofold rise in ANP during immersion and a marked suppression of both plasma renin activity and aldosterone. There was no difference in the hormonal response between diabetic and normal subjects or between those diabetic subjects with and those without incipient (microalbuminurics) or established nephropathy.

Adult↗

Haemodynamic changes in man during immersion in water at different temperatures.

1. Stroke volume and cardiac output were measured using the Doppler ultrasound technique in 16 normal subjects immersed to the neck in water at 33 degrees C, 35 degrees C, 37 degrees C and 39 degrees C. A standard aortic diameter was assumed and results were expressed as percentage changes from pre-immersion resting values. 2. Cardiac output rose progressively at higher temperatures, increasing by 30% at 33 degrees C and by 121% at 39 degrees C. At thermoneutral temperatures (33 degrees C and 35 degrees C) this was achieved by an increase in stroke volume of 50% despite a significant decrease in heart rate. There was a further rise in stroke volume and pulse rate at higher temperatures and a mean tachycardia of 109 +/- 4 beats/min was noted at 39 degrees C. Calculated peripheral resistance reduced progressively with increasing temperature of immersion. 3. This non-invasive and simple technique may provide a non-exercise-related cardiovascular stress test to study cardiovascular responses in a variety of pathophysiological states.

Adult↗

A comparative study of once daily insulin injection regimes in the treatment of elderly diabetics.

A randomised crossover trial of Insulatard, Lentard and Mixtard insulins as once daily therapy was undertaken in 10 diabetics who had been on long term insulin and in 7 patients who were poorly controlled on oral hypoglycaemic agents and had not previously received insulin. The glycaemic control of those patients with prior insulin therapy was very similar under these 3 insulin regimes. In patients previously on oral hypoglycaemic agents the mean (+/- SEM) blood glucose (10.0 +/- 0.8 mmol/l), log "M" value (1.78 +/- 0.10) and area under the glucose curve (192 +/- 16 mmol . hr/l) were all lower on Insulatard than when on Lentard (13.0 +/- 0.9, 2.03 +/- 0.08 and 258 +/- 17 respectively; p less than 0.05 in each case). Mixtard values were intermediate (11.2 +/- 1.3, 1.83 +/- 0.19 and 258 +/- 17). Furthermore blood glucose values were within the physiological range of 3-7 mmol/l in 20% of patients on Insulatard, in 16% on Mixtard but in only 2% on Lentard. Significant hypoglycaemia (blood glucose less than 3 mmol/l) in both groups of patients was noted more commonly with Mixtard (7 episodes) than with Lentard (3 episodes) or Insulatard (2 episodes). There was no significant difference in the free insulin levels between these insulin regimes but mean log total insulin levels were higher (p less than 0.005) when the patients were taking Lentard (2.33 +/- 0.13) in comparison with both Insulatard (1.99 +/- 0.14) and Mixtard (1.92 +/- 0.13). The mean insulin binding rose 4.9% during Lentard treatment and fell slightly by 0.6% on Insulatard and 0.9% on Mixtard (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Atrial natriuretic peptide: physiological release associated with natriuresis during water immersion in man.

Thermoneutral water immersion produces a physiological increase of thoracic blood volume, raises central venous pressure and increases urinary sodium excretion by a hitherto ill-understood mechanism. We have investigated whether this enhanced sodium excretion could be mediated by the recently discovered natriuretic factor, atrial natriuretic peptide (ANP). During water immersion there was a highly significant (P less than 0.001) twofold increase of the mean plasma ANP concentration and a doubling of the mean urinary sodium excretion. Both were unchanged during the control experiments. These results are consistent with the hypotheses that ANP is released into plasma in response to central blood volume expansion and that it functions as a natriuretic hormone in normal man under physiological conditions.

Adult↗

Impaired sodium excretion in response to volume expansion induced by water immersion in insulin-dependent diabetes mellitus.

The renal response to volume expansion produced by water immersion to the neck at 35 degrees C was examined in eight young normotensive uncomplicated insulin-dependent diabetic subjects and in eight matched normal control subjects. Both the diabetic and normal subjects manifested a renal response of natriuresis and kaliuresis on immersion, but the natriuretic response was reduced in the diabetic group. Thus the induced excretion of sodium over the 4 h of immersion was 40 +/- 5 mmol (mean +/- SEM) in the normal group compared with 22 +/- 4 mmol in the diabetic group (P less than 0.02). In the normal subjects creatinine clearance did not change during immersion compared with pre-immersion control values while in the diabetic group it rose from pre-immersion control values of 112 +/- 11 ml/min to a mean value of 127 +/- 11 ml/min during immersion (P less than 0.01). The diabetic subjects thus excreted less sodium despite an increased filtered load during water immersion. Fractional excretion of sodium was significantly reduced in the diabetic subjects compared with the normal control subjects (P less than 0.05). The suppression of plasma renin and aldosterone was similar in normal and diabetic groups. Tubular sodium retention could be an early functional change in the diabetic kidney, and be implicated in the development of diabetic nephropathy.

Aldosterone↗

Plasma catecholamine levels during water immersion in man.

In ten normal subjects thermoneutral neck-out water immersion produced a highly significant natriuresis and diuresis mediated via an induced central hypervolaemia. During immersion suppression of plasma noradrenaline and adrenaline was observed but no change occurred in plasma dopamine levels. No correlation was found between the suppression of noradrenaline and the diuresis and natriuresis. The reduction in plasma noradrenaline observed may reflect a widespread diminution of sympatho-adrenal activity during water immersion. This reduction could be a consequence of the cardiovascular changes of immersion and may not be directly involved in the mechanism of the renal response.

Adult↗

Abnormal circadian rhythm of melatonin in diabetic autonomic neuropathy.

The circadian rhythm of melatonin secretion from the pineal body is entrained to the light-dark cycle and is controlled via sympathetic fibres originating from the superior cervical ganglia. We have therefore examined plasma melatonin profiles in diabetics with and without evidence of autonomic neuropathy and in normal matched controls. The physiological increase in nocturnal plasma melatonin concentration was not observed in diabetics neuropaths. There was no consistent pattern in the diabetics without neuropathy; only three out of the eight subjects in this group had a sustained nocturnal increase in melatonin. Normal diurnal variation of plasma cortisol was present in all groups of subjects. The present study shows that diabetic patients with evidence of autonomic neuropathy lack the normal circadian changes of plasma melatonin concentration. This provides confirmation for the control of pineal function via the sympathetic nervous system in man. The impaired melatonin profiles observed in diabetic patients without apparent autonomic neuropathy suggest that a subclinical state of sympathetic denervation may exist in this group of diabetics.

Aged↗

Does melatonin deficiency cause the enlarged genitalia of the fragile-X syndrome?

Melatonin profiles were studied in five males with cytogenetic and clinical features of the fragile-X syndrome including megalo-orchidia and macrogenitosomia. In comparison with age-matched normal controls, the fragile-X group showed lower melatonin values and a significant impairment of the nocturnal rise in this hormone. Melatonin deficiency may thus be responsible for some of the phenotypic features of this disorder.

Aged↗

Heart rate variability in healthy subjects: effect of age and the derivation of normal ranges for tests of autonomic function.

The diagnosis of autonomic neuropathy frequently depends on results of tests which elicit reflex changes in heart rate. Few well-documented normal ranges are available for these tests. The present study was designed to investigate the effect of age upon heart rate variability at rest and in response to a single deep breath, the Valsalva manoeuvre, and standing. A computerised method of measurement of R-R interval variation was used to study heart rate responses in 310 healthy subjects aged 18-85 years. Heart rate variation during each procedure showed a skewed distribution and a statistically significant negative correlation with age. Normal ranges (90% and 95% confidence limits) for subjects aged 20-75 years were calculated for heart rate difference (max-min) and ratio (max/min) and standard deviation (SD). Heart rate responses were less than the 95th centile in at least one of the four procedures in 39 (12.6%) out of the 310 subjects, and were below this limit in two or more tests in five (1.6%) subjects. In view of the decline in heart rate variation with increasing age, normal ranges for tests of autonomic function must be related to the age of the subject.

Adolescent↗

Factitious Cushing's syndrome.

In this report we describe a patient who produced the clinical and laboratory features of Cushing's syndrome by injecting himself for many months with hydrocortisone. Factitious Cushing's syndrome is a variant of the Münchausen syndrome and should be considered if tests used to establish the diagnosis of Cushing's syndrome appear incongruous particularly in subjects with access to medical intelligence and drugs.

Adult↗

Sodium retention in response to saline infusion in uncomplicated diabetes mellitus.

The response to a 21 infusion of physiological saline infusion was studied in 7 male uncomplicated insulin-dependent diabetics and in 7 non-diabetic male controls. The urinary sodium excretion in the diabetics in each of the 4 hr following the infusion was approximately half that of the controls. The total induced sodium excretion in controls was 34 +/- 4 mmols (mean +/- SEM) but only 14 +/- 4 mmols in the diabetics (p less than 0.005). The hourly creatinine clearance rate was higher in diabetics than in controls indicating a mechanism of reduced sodium excretion via enhanced tubular reabsorption rather than impaired filtration. This propensity to sodium retention in diabetics may play a role in the tendency to cardiovascular and renal complications.

Blood Glucose↗