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Biomedical subjects

M W Strachan

Publications and source records attributed to M W Strachan.

18 recordsLinked to original sources
PubMed2002

The treatment of a thyrotropin-secreting pituitary macroadenoma with octreotide in twin pregnancy.

TSH-secreting pituitary tumours are rare but difficult to treat due to a combination of refractory hyperthyroidism and low surgical cure rates. We describe the case of a 21-year-old woman who, despite twin pregnancy, became euthyroid and had dramatic tumour shrinkage on octreotide treatment. To our knowledge, this is the first description of the use of octreotide for a TSH-secreting pituitary adenoma throughout pregnancy.

Adenoma↗
PubMed2001

Acute hypoglycemia impairs the functioning of the central but not peripheral nervous system.

Acute hypoglycemia impairs functions of the central nervous system, but few controlled studies have assessed the impact of hypoglycemia on the function of the peripheral nervous system. Sixteen non-diabetic humans underwent two separate hyperinsulinemic glucose clamp procedures on different study days, in a counter-balanced fashion. On one occasion, euglycemia was maintained (blood glucose, 5.0 mmol l(-1)), and on the other occasion, hypoglycemia (blood glucose, 2.6 mmol l(-1)) was induced. During each condition, subjects performed a combined psychometric, cognitive-experimental and psychophysical test battery, and measures were made (in the dominant median and common peroneal nerves) of the motor nerve conduction velocities and the amplitudes of the motor action potentials. Hypoglycemia caused impaired performance of general cognitive and information processing tasks (P<.05), but nerve conduction velocities and the amplitudes of motor action potentials were unaffected. Conduction velocities of the common peroneal nerve decreased from baseline within each experimental condition, perhaps due to hyperinsulinemia. Overall, these results demonstrate that multiple levels of information processing in the brain may alter while peripheral nerve function remains intact, and imply that peripheral neurons do not have the same obligate requirement for glucose as a metabolic fuel as neurons of the central nervous system.

Acute Disease↗
PubMed2001

Cognitive function and information processing in type 2 diabetes.

AIMS: To determine whether uncomplicated Type 2 diabetes is associated with impairment of cognitive function and information processing ability. METHODS: Thirty-eight participants with uncomplicated Type 2 diabetes and 38 non-diabetic controls were studied. The two groups were comparable for age and premorbid intellectual ability, and did not have other medical disorders likely to affect cognitive function. An extensive battery of tests was administered which assessed different levels and domains of cognitive functions including verbal and visual memory, executive function, general mental ability and efficiency of information processing. RESULTS: No significant differences were found between the diabetic and control groups on any measure of cognitive function or information processing. The performance on these tests was not associated with recent glycaemic control (assessed by HbA1c). Duration of diabetes, however, correlated significantly with poorer performance on several measures of verbal memory. CONCLUSIONS: The results of the present study suggest that some aspect of Type 2 diabetes (as indexed by the estimated duration of the disorder) does relate significantly to cognitive function within the group with diabetes. However, other diabetes-related factors, such as macrovascular disease, hypertension and depression, may contribute more to previously observed cognitive decrements in Type 2 diabetes.

Age of Onset↗
PubMed2000

The care of students with insulin-treated diabetes mellitus living in university accommodation: scope for improvement?

Concern has been expressed about the welfare of young adults with Type 1 diabetes mellitus who leave home to attend university or college for tertiary education. This has been highlighted by the local experience in Edinburgh of two male students with Type 1 diabetes, both of whom died from metabolic complications of diabetes during their first term at universities distant from their homes. One student died following the development of cerebral oedema secondary to diabetic ketoacidosis, which was probably precipitated by prolonged coma after an episode of severe hypoglycaemia. Another student, who was found 'dead in bed', had a history of previous severe hypoglycaemia. At a Fatal Accident Inquiry in Edinburgh, held following the death of the first student, recommendations were made to improve the care and personal safety of students with diabetes living in university accommodation. Despite the report being circulated to all Scottish universities, the second student died within three years of the inquiry. Further efforts to protect the welfare of students with Type 1 diabetes who are attending centres for tertiary education away from their home environment may require the more active participation by diabetes healthcare professionals.

Adolescent↗
PubMed2000

Recovery of cognitive function and mood after severe hypoglycemia in adults with insulin-treated diabetes.

OBJECTIVE: Acute hypoglycemia in humans impairs cognitive functions and alters mood states. The time required for cognitive functions and moods to return to normal after an acute episode of severe hypoglycemia is unknown. RESEARCH DESIGN AND METHODS: Cognitive functions and moods were studied prospectively in 20 subjects with insulin-treated diabetes who had recently experienced a spontaneous episode of severe hypoglycemia ("hypo" subjects) and 20 matched control subjects with insulin-treated diabetes who had not experienced severe hypoglycemia during the preceding year. The hypo subjects had a history of a greater number of episodes of severe hypoglycemia (P = 0.000). Cognitive function tests and mood scales were administered at 1.5, 9, and 30 days after the severe hypoglycemia and at similar intervals for the control subjects. RESULTS: For most of the cognitive tests, no evidence of a "hangover" effect of the acute hypoglycemia on cognitive function was observed (P > 0.05). A trend was noted for levels of hedonic tone (P = 0.082) and energetic arousal (P = 0.053) to improve with time in the hypo subjects but not in the control subjects. However, the hypo subjects had chronically elevated levels of depression (P = 0.011) and anxiety (P = 0.049) and persistently performed more poorly in several cognitive tests, such as the Digit Symbol Test (P = 0.009) and the Stroop Task (P = 0.007). CONCLUSIONS: These results suggest that, in general, recovery from any acute cognitive decrement after severe hypoglycemia was complete by 1.5 days. The cognitive decrements and altered mood states noted in the hypo subjects may be persistent and may be a consequence of previous exposure to recurrent episodes of severe hypoglycemia.

Adult↗
PubMed1998

Effect of acute hypoglycemia on visual information processing in adults with type 1 diabetes mellitus.

Acute hypoglycemia in people with type 1 (insulin-dependent) diabetes mellitus causes general impairment in cognitive performance. The effects on more specific cognitive processes are less well defined. Acute hypoglycemia has been shown to impair visual information processing in nondiabetic human subjects and has now been examined in 16 adult subjects with type 1 diabetes. All subjects had normal visual acuity and no diabetic retinopathy, and their median (range) age was 24 (18-47) years with a median (range) duration of type 1 diabetes of 8 (2-18) years and a mean (SD) HbA1c of 8.5 (1.3)%. A hyperinsulinemic glucose clamp technique was used to maintain arterialized blood glucose at 5.0 mmol l(-1), and on separate test days, either euglycemia was continued or hypoglycemia (2.6 mmol l(-1)) was induced. During each condition subjects performed tests of visual processing and cognitive function. Hypoglycemia caused a significant disruption in general cognitive ability as assessed by digit symbol (p < 0.001) and trail-making B (p < 0.05) tasks. Conventional measures of visual acuity were unaffected by hypoglycemia, but visual information processing deteriorated significantly as indexed by inspection time (p < 0.005) and visual change detection (p < 0.01). Contrast sensitivity tended to deteriorate during hypoglycemia (p = 0.06). In conclusion, hypoglycemia impairs important aspects of early visual information processing and contrast sensitivity in adults with type 1 diabetes. Further research is needed to evaluate the functional relevance of such changes for everyday tasks that require the intake of visual information at speed and under conditions of low contrast.

Adolescent↗
PubMed1998

Seeing beyond retinopathy in diabetes: electrophysiological and psychophysical abnormalities and alterations in vision.

Contrast sensitivity testing, in common with color vision (another test of psychophysical function), demonstrates significant changes in diabetic subjects compared with nondiabetic controls, and there is some evidence for a relationship with grade of retinopathy. Changes in contrast sensitivity have been demonstrated in children and adults with diabetes of short duration, and some evidence exists for a correlation with poor glycemic control, although prospective studies are required to assess this relationship over a longer time period. Although both color vision and contrast sensitivity demonstrate similar patterns, studies that directly compare the two tests suggest that measurement of contrast sensitivity is the more sensitive and specific.

Adult↗
PubMed1998

Optimal time of administration of insulin lispro. Importance of meal composition.

OBJECTIVE: To compare the glucodynamics of pre- and postprandial administration of insulin lispro using test meals of differing composition. RESEARCH DESIGN AND METHODS: Twenty subjects with IDDM were studied on four separate occasions. Ten subjects ingested high-carbohydrate and high-fat breakfasts with a large liquid component, and 10 subjects ingested high-carbohydrate and high-fat breakfasts in a more solid form. With each meal, insulin lispro was injected 10 min preprandial on one occasion and 20 min postprandial on another. The magnitude and temporal pattern of postprandial glucose excursions were observed. RESULTS: With all meal types studied, postprandial blood glucose excursions were significantly smaller when insulin lispro was administered preprandially (P < 0.05). With both high-carbohydrate meals and the liquid high-fat meal, preprandial administration of lispro was associated with modest postprandial increments of blood glucose. With the solid high-fat meal, preprandial lispro produced a cumulative decline in postprandial blood glucose, whereas blood glucose rose when lispro was administered postprandially. CONCLUSIONS: For meals with a high carbohydrate content, the optimal time of administration of lispro is preprandial. However, for meals with a high solid fat content, postprandial administration of lispro may be preferable.

Adult↗
PubMed1997

Is type II diabetes associated with an increased risk of cognitive dysfunction? A critical review of published studies.

Type II (non-insulin-dependent) diabetes may be associated with impaired cognitive function. A detailed search of the literature has identified 19 controlled studies in which cognitive function in type II diabetes has been examined. The studies vary widely with respect to the nature of the diabetic populations studied and the psychological tests used. Thirteen studies demonstrated that the diabetic individuals performed more poorly in at least one aspect of cognitive function. The most commonly affected cognitive ability was verbal memory. Psychomotor ability and frontal lobe function were affected less consistently. The remaining six studies showed no differences in cognitive ability between subjects with type II diabetes and nondiabetic control subjects, but none had adequate statistical power to detect a between-group difference in cognitive ability of 0.5 of a standard deviation (a medium effect size). These findings are consistent with type II diabetes being associated with an increased risk of cognitive dysfunction. However, the widespread differences in methodology between the studies should lead to a cautious interpretation of their conclusions. The etiology of any cognitive decrement in type II diabetes is likely to result from an interaction between metabolic abnormalities intrinsic to diabetes, diabetes-specific complications, and other diabetes-related disorders.

Cognition Disorders↗
PubMed1991

Dose-dependent effects of angiotensin II, acetylcholine and vasopressin on the cytosolic concentration of Ca2+ in suspension primary cultures of zona fasciculata/reticularis cells from bovine adrenal cortex.

The effects of angiotensin II (AII), acetylcholine and vasopressin on the intracellular concentration of Ca2+ have been little studied in adrenocortical cells from the zona fasciculata/reticularis (ZFR). Primary cultures of bovine ZFR cells maintained in suspension cultured for 72 h produce cortisol in response to AII (0.1 microM), acetylcholine (0.1 mM) and vasopressin (1 microM). This response is accompanied by a breakdown of membrane phosphoinositides from [3H]inositol-prelabelled cells. Using cells loaded with the Ca2+ indicator fura-2, the intracellular concentration of Ca2+ was measured in response to increasing doses of all three agonists and found to increase in a graded fashion in each case. The basal intracellular concentration of Ca2+ was 75 +/- 3 nM (mean +/- S.E.M., n = 52), rising to a maximum 1.82 +/- 0.14-fold (n = 6) for AII (0.1 microM), 1.35 +/- 0.05-fold (n = 7) for acetylcholine (0.1 mM) and 1.27 +/- 0.10-fold (n = 6) for vasopressin (1 microM). In the case of AII and acetylcholine, agonists were added sequentially in medium of normal extracellular Ca2+ concentration (1.2 mM) or in medium in which the Ca2+ concentration was buffered to approximate to the intracellular concentration of Ca2+ (75-100 nM). Evidence was thereby obtained that both AII and acetylcholine mobilize a common intracellular pool of Ca2+. Our findings suggest that these three agonists, all of which stimulate phospholipase C, increase intracellular Ca2+ through a mechanism which depends, at least in part, on the release of Ca2+ from a common intracellular pool.

Acetylcholine↗
PubMed1990

Acetylcholine stimulates cortisol secretion through the M3 muscarinic receptor linked to a polyphosphoinositide-specific phospholipase C in bovine adrenal fasciculata/reticularis cells.

Zona fasciculata/reticularis (ZFR) cells, isolated from the bovine adrenal cortex, secreted cortisol in response to acetylcholine (AcCh). The response was present in freshly isolated cells and in cells maintained in primary culture, reaching a maximum after 48-72 h and thereafter declining. Cells maintained in primary culture for 72 h secreted cortisol with an ED50 at 1.2 x 10(-6) M. The potent inhibition of AcCh-stimulated secretion by atropine, and the relative ineffectiveness of nicotine or nicotinic antagonists, were consistent with a predominantly muscarinic response to AcCh in these cells. A selective M1-receptor agonist, McN-A-343, had no effect on cortisol secretion whereas the M3 antagonist, hexahydro-sila-difenidol, produced a dose-dependent inhibition of AcCh-stimulated cortisol secretion. These findings are consistent with AcCh mediating its effects on cortisol secretion through an M3 receptor. While AcCh had no effect on cAMP formation, a dose-dependent increase in [3H]phosphoinositols (identified using high-performance liquid chromatography (HPLC)) occurred in a manner that was not dependent on an influx of extracellular Ca2+. Detailed HPLC analysis of the formation of 3H-labelled phosphoinositols and glycerophosphoinositols from pre-labelled cells over the period 0-15 min showed that the earliest significant rise was in Ins(1,4,5)P3 at 5 s, followed by later rises in InsP1, InsP2 and Ins(1,3,4)P3. Additional studies using cells loaded with fura-2 indicator revealed a 1.6-fold increase in [Ca2+]i from a mean resting value of 75 nM in response to 10(-4) M AcCh. Furthermore, the rise in Ca2+ was not abolished by lowering extracellular Ca2+ to resting cytosolic levels, suggesting the mobilisation of an intracellular pool. These observations indicate that AcCh promotes rapid activation of a Ca2(+)-independent and polyphosphoinositide-specific phospholipase C, and that the Ins(1,4,5)P3 formed releases Ca2+ from an intracellular pool. The stimulation by AcCh of this signal transduction mechanism is consistent with our conclusion, based on the effects of the selective muscarinic agonist and antagonist on cortisol secretion, that the AcCh receptor is of the M3 subtype. We conclude that AcCh, acting through an M3 receptor coupled to phospholipase C, regulates cortisol secretion at the cellular level in bovine adrenal ZFR cells.

Acetylcholine↗
PubMedDate not supplied

Evaluation of serum markers of neuronal damage following severe hypoglycaemia in adults with insulin-treated diabetes mellitus.

BACKGROUND: Neurone-specific enolase (NSE) and protein S-100 (S-100) may be used as markers of acute neuronal damage in humans with neurological disorders. METHOD: To evaluate their use following a single episode of severe hypoglycaemia (defined as an episode requiring external assistance to aid recovery), serum concentrations of NSE and S-100 were measured following hypoglycaemia which had not caused persistent neurological impairment in 16 patients with insulin-treated diabetes (the 'hypo' subjects), and in three diabetic patients who died following severe hypoglycaemia. The serum proteins were also measured in 10 subjects with insulin-treated diabetes who had not experienced an episode of severe hypoglycaemia within the preceding year (the 'control' subjects). RESULTS: No differences in serum concentrations of NSE and S-100 were observed between the 'control' and the 'hypo' subjects at either 36 hours or seven days after the episode of severe hypoglycaemia (p>0.05). However, in two of the three subjects who died following hypoglycaemia, serum concentrations of the markers were markedly elevated. CONCLUSIONS: Any neuronal injury occurring during severe hypoglycaemia that is not associated with persistent neurological deficit is insufficient to provoke elevation of these serum markers. However, the measurement of serum concentrations of NSE and S-100 may have a prognostic role in evaluating clinical outcome following severe hypoglycaemia which is associated with neurological damage.

Adult↗
PubMedDate not supplied

Severe hypoglycaemia in patients with type 1 diabetes and impaired awareness of hypoglycaemia: a comparative study of insulin lispro and regular human insulin.

OBJECTIVE: To assess the potential of insulin lispro to limit the frequency of severe hypoglycaemia without compromising glycaemic control in a cohort of patients with type 1 diabetes who are at a high risk of severe hypoglycemia. Research design and methods An open-label, randomised, 12-month comparative crossover study of insulin lispro and regular human insulin was performed in 33 patients with type 1 diabetes with impaired hypoglycaemia awareness. The efficacy of each treatment was evaluated by glycaemic control (HbA(1c)), eight-point home blood glucose profiles, and the frequency and severity of hypoglycaemic episodes and quality of life. RESULTS: Eighteen (55%) patients experienced one or more episodes of severe hypoglycaemia in the 48 weeks of study. There was a trend to a lower incidence of severe hypoglycaemia during treatment with insulin lispro in comparison with regular human insulin (55 vs 84 episodes, p=0.087). This resulted principally from a 47% lower incidence of nocturnal severe hypoglycaemia with insulin lispro (25 vs 47 episodes, p=0.11). The lower frequency of severe hypoglycaemia associated with insulin lispro was not explained by differences in glycated haemoglobin between insulin treatments (HbA(1c) 9.1% insulin lispro vs 9.3% regular human insulin). CONCLUSIONS: In individuals with type 1 diabetes, who have impaired awareness of hypoglycaemia, treatment with insulin lispro may be associated with a lower incidence of severe hypoglycaemia manifested predominantly through less frequent nocturnal episodes. Insulin lispro may have a beneficial role in the management of patients with diabetes at risk of severe hypoglycaemia, although a larger study is required to confirm these findings.

Adult↗