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Biomedical subjects

I A O'Brien

Publications and source records attributed to I A O'Brien.

At least 19 recordsLinked to original sources
PubMed1995

The prevalence of autonomic and peripheral neuropathy in insulin-treated diabetic subjects.

The prevalence of autonomic and peripheral neuropathy was examined in 506 diabetic subjects treated with insulin, mean age 43 years, diabetes duration 15 (range 1-54) years. Autonomic neuropathy was present if two or more (of four) cardiovascular autonomic function tests were abnormal using age-related ranges derived from 310 normal control subjects. Peripheral neuropathy was defined as a vibration threshold > 95th centile for age combined with absent/impaired ankle reflexes. Eighty-four (16.6%) of diabetic subjects had abnormal autonomic function and 119 (23.5%) peripheral neuropathy, concordant in 44/506 (8.7%). Of the diabetic subjects with autonomic neuropathy 40/84 (47.6%) did not have peripheral neuropathy and only 44/119 (37.0%) with peripheral neuropathy had abnormal autonomic function (p < 0.001). The prevalence of both neuropathies increased in relation to diabetes duration (both p < 0.001). Autonomic neuropathy was more common in subjects diagnosed < 20 years of age (18.2%) vs age > 40 years (11.1%) (p < 0.05). In contrast peripheral neuropathy was more common with older age at diagnosis (< 20 years 13.5% vs 36.8% > 40 years, p < 0.001). The age-related prevalence of autonomic neuropathy peaked at age 40-49 years while peripheral neuropathy increased progressively with age (p < 0.001). The prevalence of peripheral exceeded autonomic neuropathy 20 years after diagnosis (40.2% vs 30.7%, p < 0.001).

Adult↗
PubMed1993

Emergency serum creatine kinase MB isoenzyme concentration in patients with suspected acute myocardial infarction.

We report the results of the introduction of a service which offered emergency measurement of serum creatine kinase MB isoenzyme concentration in patients admitted to hospital with suspected acute myocardial infarction and a non-diagnostic electrocardiogram. A retrospective study suggested that in such patients, a single admission measurement would have a diagnostic sensitivity of 70% and specificity of 100%. A prospective study employed a protocol which included repeat measurement after two hours where the initial measurement was low in samples taken less than six hours after the onset of symptoms. The prospective study showed that the service was welcomed by physicians, who employed the measurements appropriately as a supplement to, rather than substitute for, clinical judgement. In a continuing audit, 228 patients had an emergency measurement according to the agreed protocol. 79 of these had a discharge diagnosis of acute myocardial infarction. The diagnostic sensitivity and specificity of our emergency strategy were both 94%. The strategy led to the treatment with thrombolytic drugs of 73 patients who would not otherwise have been treated, 69 with a discharge diagnosis of acute myocardial infarction, and four with some other discharge diagnosis. The median time taken from requesting the analysis to reporting the result was 34 minutes. The costs and potential benefits of our strategy are discussed.

Adult↗
PubMed1991

Autonomic and sensory nerve function in diabetic foot ulceration.

Peripheral sensory and autonomic nerve dysfunction are thought to be crucial factors in the pathogenesis of diabetic foot ulceration. However, their relative importance is not known. In this study we have compared peripheral sensory nerve function and cardiac autonomic reflexes in 51 diabetics with a history of foot ulceration and 480 diabetic control subjects. In the diabetics with ulceration ankle reflexes were absent or impaired and vibration perception threshold reduced in 96.1% and 82.4%, respectively, compared with 40.8% and 25.8%, respectively, in control subjects (P less than 0.001). Cardiac autonomic tests were abnormal more frequently in the diabetics with ulceration and an autonomic score derived from four tests was abnormal in 62.8% of those with ulceration compared with 13.5% of those without ulceration (P less than 0.001). Discriminant analysis of the two groups of diabetes showed that an abnormal autonomic score was the best predictor of foot ulceration in diabetic patients.

Diabetic Neuropathies↗
PubMed1991

The influence of autonomic neuropathy on mortality in insulin-dependent diabetes.

Five-year survival was investigated in 506 randomly selected patients with insulin-dependent diabetes mellitus screened for autonomic neuropathy with a series of cardiac autonomic function tests. Of the 484 diabetics traced, 44 (9 per cent) had died. The cumulative 5-year mortality rate was increased more than five-fold in those with autonomic neuropathy: 27 per cent vs. 5 per cent in those with normal autonomic function. Discriminant analysis of survivors and non-survivors showed that autonomic neuropathy was the most important independent predictor of death. Among those who died, autonomic neuropathy was associated with an increased frequency of retinopathy and peripheral neuropathy and a slightly lower frequency of macrovascular disease. Autonomic neuropathy was associated with an increased mortality rate from renal failure, but not from any other causes.

Adolescent↗
PubMed1989

Impaired sweating in the diabetic neuropathic foot and its influence on skin flora.

Three groups each of 10 subjects, were defined by clinical and neurophysiological studies: diabetic with neuropathy (Group A), diabetic without neuropathy (Group B) and normal control (Group C). Sweating on the foot was quantified and the bacterial flora on the dorsum of the foot and deltoid area were examined. There were no significant differences in type of density of bacterial species found on either foot or deltoid regions between any of the three groups. Diabetics free of clinical infection have a similar skin microbial flora to non-diabetics even when sweating is seriously impaired. It is therefore unlikely that a change in the resident microbial flora is involved in the propensity of diabetic neuropathic patients to foot ulceration and infection.

Actinomycetales↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

The prevalence of autonomic neuropathy in insulin-dependent diabetes mellitus: a controlled study based on heart rate variability.

Autonomic function was investigated by tests of heart rate variation in 506 unselected insulin-dependent diabetics aged 12 to 85 years. Heart rate variability was measured by a computerised technique during rest and in response to a single deep breath, the Valsalva manoeuvre and standing. Changes in heart rate were compared with age-related normal ranges derived from 310 non-diabetic control subjects aged 18 to 87 years. Heart rate responses were found to be below the 5th centile control value in 13 to 23 per cent of diabetics. Impaired heart rate variability occurred more frequently in response to a single deep breath than to the other procedures. Results from all four procedures were combined in each subject to give an 'autonomic score', varying from 0 to 4. This score was greater than 1 in only five of 310 (1.6 per cent) non-diabetic control subjects. A score of 2 or more was therefore defined as abnormal and indicative of cardiac autonomic denervation. Abnormal autonomic scores were found in 84 diabetics (16.6 per cent). In diabetic subjects the autonomic score correlated most closely with heart rate variability at rest and in response to a single deep breath. Abnormal autonomic scores correlated significantly with duration of diabetes (p less than 0.0001) but not with age (p = 0.06). The frequency of abnormal autonomic scores was greatest in diabetics aged 40 to 49 years (24.5 per cent) and those with diabetes of 20 or more years duration (30.7 per cent).

Adult↗
PubMed1985

Hypoglycemia during adrenergic beta-blockade: evidence against mediation via a deficiency of lactate for gluconeogenesis.

Acute hypoglycemia was induced using intravenous inulin in three groups of normal volunteers: (1) seventeen control subjects, (2) six subjects under beta-adrenergic blockade with propranolol, and (3) eight subjects given propranolol plus sodium lactate as an exogenous substrate for gluconeogenesis. Under propranolol blockade the recovery from hypoglycemia was significantly impaired. This impairment was not prevented by the infusion of sodium lactate despite the production of an adequate elevation of blood lactate concentrations. These findings suggest that the impaired recovery from hypoglycemia during beta-adrenergic blockade is not mediated via a deficiency of lactate as substrate for hepatic gluconeogenesis.

Adult↗
PubMed1985

Factitious diabetic instability.

Factitious diabetic instability is described in four patients. In three the predominant problem was recurrent hypoglycaemia. The fourth presented with apparent insulin resistance and episodes of ketoacidosis. The methods used to make the diagnosis are described, and the factors which contribute to this type of diabetic instability are discussed.

Adult↗
PubMed1984

Papilloedema in diabetes: an ischaemic optic mononeuropathy.

Five diabetic patients had acute visual impairment due to papilloedema, which was bilateral in two patients. The clinical features and subsequent course were compatible with ischaemic optic mononeuropathy presumed to result from ischaemia in a posterior ciliary artery. This cause should always be considered in the differential diagnosis of papilloedema in a diabetic patient to avoid the instigation of inappropriate and invasive investigations. In general the condition has a good prognosis.

Adult↗