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Biomedical subjects

B M Fisher

Publications and source records attributed to B M Fisher.

At least 55 records · Page 3Linked to original sources

Splenic responses to acute insulin-induced hypoglycaemia in humans.

1. The effects of acute hypoglycaemia on the spleen were examined in normal humans using radioisotopic techniques, complemented by ultrasonic examination of the spleen. Hypoglycaemia had a modest effect on splenic area, measured by ultrasonography, which declined to 62 +/- 6% (mean +/- SEM) of the basal value after the onset of the acute hypoglycaemic reaction. 2. Hypoglycaemia had a pronounced effect on the splenic radioactivity, which decreased significantly to a mean of 10 +/- 7% of basal radioactivity at 15 min after the onset of hypoglycaemia. The splenic image completely disappeared at some time after hypoglycaemia in all subjects. 3. The reduction of splenic radioactivity was abolished during non-selective alpha-adrenergic blockade with phentolamine, but was unaffected by beta-adrenergic blockade with propranolol, or cholinergic blockade with atropine, which suggests that the response of vessels perfusing the spleen is mediated by alpha-adrenoceptors.

Adult↗

The relationship between colonisation, secretor status and in-vitro adhesion of Candida albicans to buccal epithelial cells from diabetics.

This study investigated whether oral candida infection in diabetics and adhesion of Candida albicans to buccal epithelial cells in vitro were related. Buccal cells from 50 patients with diabetes mellitus showed a significant increase in adhesion of C. albicans strain CDS 88 compared with those collected from 50 non-diabetic controls matched for age, sex and denture status. Oral candida carriage, candida infection and secretor status were also investigated in both groups. The frequency of carriage was increased, but not significantly, and there was a significantly higher incidence of candida infection in diabetic patients compared with controls. Diabetic patients who were non-secretors had a significantly increased frequency of oral candida carriage.

Candida albicans↗

The effect of alpha-adrenergic blockade on responses of peripheral blood cells to acute insulin-induced hypoglycaemia in humans.

Acute hypoglycaemia provokes rapid changes in peripheral blood cell counts. To examine possible adrenergic mechanisms modulating these changes, counts of peripheral blood cells including lymphocytes, granulocytes and erythrocytes were measured in response to acute hypoglycaemia in a group of six normal subjects in control conditions (study 1), and during alpha-adrenergic blockade with phentolamine (study 2). In study 1 hypoglycaemia provoked a biphasic leucocyte response, with an early rise in lymphocyte count and a later rise in granulocyte count. The erythrocyte count increased modestly following hypoglycaemia. During alpha-adrenergic blockage, the rise in total leucocyte count was diminished, with the rise in the lymphocyte count being greatly obtunded. These findings suggest that the increments of peripheral lymphocyte and erythrocyte counts in response to acute insulin-induced hypoglycaemia are mediated via alpha-adrenoreceptors.

Adult↗

Secretion of epidermal growth factor in parotid saliva in diabetic patients: role of autonomic innervation.

Parotid saliva was collected over a 12-min period from 24 insulin dependent diabetic patients with varying degrees of autonomic neuropathy and 12 age and sex matched non-diabetic controls. Epidermal growth factor (EGF) concentrations in saliva were measured by radio-immunoassay. The EGF concentrations in diabetics with no autonomic neuropathy or with combined autonomic neuropathy were equivalent but secretion of EGF was significantly elevated at the 6- and 12-min periods of collection in diabetic patients with early or established autonomic neuropathy. It is postulated that when parasympathetic autonomic neuropathy is present a relative "over-activity" of the sympathetic innervation promotes release of salivary EGF. This sympathetic predominance may maintain salivary EGF concentration despite the elevated salivary flow and volume which is associated with parasympathetic autonomic neuropathy.

Autoimmune Diseases↗

Cardiac responses to acute insulin-induced hypoglycemia in humans.

The effects of acute hypoglycemia on the heart and cardiovascular system were examined in humans using radioisotopic techniques, complemented by measurement of heart rate and blood pressure. The heart rate increased from 62 +/- 3 to 87 +/- 3 beats/min in response to hypoglycemia; this increase was accompanied by a significant increase in systolic blood pressure, a fall in diastolic blood pressure, with no change in the mean arterial blood pressure. The left ventricular ejection fraction increased from 47 +/- 3 (SE) to 72 +/- 5% in response to hypoglycemia. The increases in heart rate and ejection fraction were abolished during parenteral nonselective beta-adrenergic blockade with propranolol but were unaffected by either alpha-adrenergic blockade with phentolamine or cholinergic blockade with atropine. During beta-adrenergic blockade, there were significant increases in diastolic and mean arterial blood pressure in response to hypoglycemia. During alpha-adrenergic blockade the systolic, diastolic, and mean arterial pressures fell significantly after hypoglycemia. The blood pressure responses to hypoglycemia were unaffected by cholinergic blockade. Thus the increases in ejection fraction and in heart rate in response to hypoglycemia are mediated by beta-adrenoreceptors, whereas the blood pressure responses to hypoglycemia are mediated by alpha- and by beta-adrenoreceptors.

Acute Disease↗

Usefulness of cardiovascular tests of autonomic function in asymptomatic diabetic patients.

A group of five cardiovascular tests of autonomic neural function was studied in 115 asymptomatic insulin-dependent diabetic patients and nine patients with symptoms of diabetic autonomic neuropathy. In the asymptomatic group, 34 patients had one or more abnormal test. R-R variation during deep breathing was most frequently abnormal, but reliance on this test alone to examine parasympathetic function would have missed 12 of the 34 abnormal patients. The two abnormal responses to isometric exercise in this group were probably false-positive results caused by poor patient effort. In the symptomatic patients, R-R variation during deep breathing was abnormal in all nine, the blood pressure response to standing was abnormal in seven, and the response to isometric exercise was abnormal in three. The blood pressure response to isometric exercise is uncomfortable, requires special equipment, and should probably be confined to the assessment of symptomatic patients in a specialist setting.

Adolescent↗

The role of cortisol in the peripheral granulocyte response to insulin-induced hypoglycaemia in man.

Peripheral blood leukocyte counts and plasma hormonal changes in response to acute insulin-induced hypoglycaemia were examined in 16 patients undergoing assessment of pituitary function. Eight subjects had a normal cortisol secretory response (Group 1), and 8 patients had definite hypopituitarism in whom the cortisol responses were deficient or absent (Group 2). An equivalent degree of hypoglycaemia was achieved in both groups. In Group 1a biphasic rise in leukocyte count occurred following hypoglycaemia, with an early rise in lymphocytes at 15 minutes after the acute hypoglycaemic reaction, and a later rise in granulocytes. A similar rise in lymphocytes was observed in Group 2, but the rise in the granulocyte count was attenuated, increasing from a basal value of 3.6 +/- 0.6 x 10(9) cells/L to a peak of 7.4 +/- 1.1 x 10(9) cells/L, compared with a peak of 11.7 +/- 1.2 x 10(9) cells/L in Group 1 (P less than 0.05). The usual increment in plasma cortisol in response to hypoglycaemia occurred in Group 1, but plasma cortisol did not rise in Group 2. A correlation was observed between the magnitude of the granulocyte rise and the increment in plasma cortisol in individual subjects (r = 0.64, P less than 0.02). This suggests that the rise in peripheral granulocytes following insulin-induced hypoglycaemia in man is mediated by cortisol released from the adrenal gland, following activation of the hypothalamic-pituitary-adrenal axis.

Blood Glucose↗

Endomyocardial biopsy pathology in insulin-dependent diabetic patients with abnormal ventricular function.

We have previously shown impaired ventricular function in asymptomatic middle-aged type 1 (insulin-dependent) diabetic patients who had no evidence of coronary artery disease. The diabetic patients had normal coronary angiograms but reduced ventricular ejection fraction on exercise. To examine the possible contribution of small vessel disease to this functional abnormality, we compared endomyocardial biopsies from seven symptom-free type 1 diabetic patients with biopsies from seven age- and sex-matched non-diabetic subjects. Interstitial fibrosis was present in three diabetic patients, arteriolar hyalinization in three patients and arteriolar thickening was observed in five patients. Morphometry performed on electron micrographs showed no significant difference in the thickness of the capillary basal lamina between diabetics and controls. While the functional significance of the abnormalities on light microscopy is unclear, our findings indicate that the abnormality of cardiac function described in diabetes is not associated with thickening of the myocardial capillary basal lamina.

Adult↗

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↗

Non-invasive evaluation of cardiac function in young patients with type 1 diabetes.

Cardiac function was evaluated in 40 Type 1 diabetic patients aged less than 30 years and compared with 20 age- and sex-matched control subjects using resting and exercise electrocardiography, and echocardiography. The duration of diabetes was from 0.25 to 25 years (mean 10 years), and few patients had microvascular complications. Left ventricular end-diastolic and end-systolic diameters were similar in both groups, with no significant differences between the groups in mean thickness of the intraventricular septum and the posterior wall of the left ventricle. Fractional shortening and mean velocity of circumferential fibre shortening as indices of ventricular function were similar in both groups. Left ventricular hypertrophy (Minnesota Code 3,1) was observed in the resting electrocardiogram of 22 patients and 12 control subjects (NS), but no other significant abnormalities were observed. One diabetic patient developed asymptomatic ST segment depression during exercise electrocardiography. In conclusion, the chamber size, wall thickness, and systolic function of the left ventricle are normal in most young Type 1 diabetic patients who have few microvascular complications.

Adolescent↗

Arginine vasopressin and oxytocin responses to insulin-induced hypoglycemia in type 1 (insulin-dependent) diabetes.

In normal humans, arginine vasopressin and oxytocin are released acutely from the posterior pituitary gland in response to hypoglycemia, and their release may assist counterregulation. The responses of these hormones to insulin-induced hypoglycemia were measured in 16 insulin-dependent diabetic patients with no autonomic neuropathy (8 patients who had been diabetic less than 5 yr and 8 patients who had been diabetic greater than 15 yr) and in 6 normal subjects. The time of the onset of hypoglycemia and the mean blood glucose nadirs were similar in all groups, but the blood glucose recovery was delayed in the diabetic patients. In the normal subjects plasma arginine vasopressin rose from a mean basal value of 0.4 +/- 0.2 (+/- SE) pmol/L to a maximum of 1.3 +/- 0.6 pmol/L, and plasma oxytocin rose from 0.7 +/- 0.1 pmol/L to a maximum of 1.2 +/- 0.2 pmol/L 30 min after the onset of hypoglycemia. The plasma arginine vasopressin and oxytocin concentrations after hypoglycemia were significantly higher in both of the diabetic groups compared with those in the normal group. Arginine vasopressin and oxytocin rose in all control subjects after hypoglycemia. The individual hormonal profiles in the diabetic patients were variable, with an exaggerated rise of oxytocin in some diabetic patients and no rise in others. The arginine vasopressin responses were exaggerated in all of the diabetic patients. There was no correlation between the hormonal responses and the duration of diabetes. The exaggerated plasma arginine vasopressin and oxytocin responses to hypoglycemia in diabetic patients may indicate the failure of a normal inhibitory mechanism which modulates hormonal secretion or a compensatory response to impaired glucose recovery.

Adolescent↗

Counterregulatory hormonal responses to hypoglycaemia in type 1 (insulin-dependent) diabetes: evidence for diminished hypothalamic-pituitary hormonal secretion.

Acute insulin-induced hypoglycaemia in humans provokes autonomic neural activation and counterregulatory hormonal secretion mediated in part via hypothalamic stimulation. Many patients with Type 1 (insulin-dependent) diabetes have acquired deficiencies of counterregulatory hormonal release following hypoglycaemia. To study the integrity of the hypothalamic-pituitary and the sympatho-adrenal systems, the responses of pituitary hormones, beta-endorphin, glucagon and adrenaline to acute insulin-induced hypoglycaemia (0.2 units/kg) were examined in 16 patients with Type 1 diabetes who did not have autonomic neuropathy. To examine the effect of duration of diabetes these patients were subdivided into two groups (Group 1: 8 patients less than 5 years duration; Group 2: 8 patients greater than 15 years duration) and were compared with 8 normal volunteers (Group 3). The severity and time of onset of hypoglycaemia were similar in all 3 groups, but mean blood glucose recovery was slower in the diabetic groups (p less than 0.01). The mean responses of glucagon, adrenaline, adrenocorticotrophic hormone, prolactin and beta-endorphin were similar in all 3 groups, but the mean responses of growth hormone were lower in both diabetic groups than in the normal group (p less than 0.05). The mean increments of glucagon and adrenaline in the diabetic groups were lower than the normal group, but these differences did not achieve significance; glucagon secretion was preserved in several diabetic patients irrespective of duration of disease. Various hormonal responses to hypoglycaemia were absent or diminished in individual diabetic patients, and multiple hormonal deficiencies could be implicated in delaying blood glucose recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Secretor status, candidal carriage and candidal infection in patients with diabetes mellitus.

One hundred and nine patients with diabetes mellitus and 100 age-, sex- and denture-status-matched, non-diabetic individuals were investigated prospectively. Comparison was made of oral candidal carriage, clinical infection and inherited ability to secrete blood group antigens in saliva. Diabetic patients had a significantly higher prevalence of oral candidal carriage and infection (P less than 0.001) than non-diabetic individuals, but the candidal load between the 2 groups, was not significant. A comparable proportion of insulin-dependent, non-insulin dependent and control groups were secretors of blood group antigens, and there was no difference in the oral candidal carriage and infection rates between secretors and non-secretors.

ABO Blood-Group System↗

Responses to acute insulin-induced hypoglycaemia in diabetic patients: a comparison of short-acting human and porcine insulins.

A comparison was made of the metabolic, hormonal, haemodynamic and symptomatic responses to acute hypoglycaemia induced by short-acting porcine and human insulins in 16 fasting, insulin-dependent diabetic patients, 8 of whom had diabetes for less than 5 years (Group A) and 8 of whom had diabetes for greater than 15 years (Group B). Each patient received an intravenous injection of 0.2 units/kg of insulin on two separate occasions. No differences were found between the groups in the rate of fall of blood glucose or the blood glucose nadir with either insulin, but in Group B, glucose recovery was more rapid after human insulin (p less than 0.01). No differences in the responses of blood lactate, plasma free fatty acids, glucagon or prolactin were observed between the groups. In Group B the rises of growth hormone and cortisol occurred more rapidly following human insulin (p less than 0.01), while the rise in adrenaline was greater following porcine insulin. Haemodynamic changes were identical following each species of insulin in both diabetic groups. A questionnaire was used to score 18 symptoms of hypoglycaemia on a 7 point scale. No significant differences were found in the mean scores of each symptom of hypoglycaemia or in the total symptom score. Thus recovery of blood glucose from hypoglycaemia was slightly more rapid after administration of human insulin to diabetic patients of long duration, but it is unlikely that these marginal differences would confer any clinical advantage in this subgroup.

Adolescent↗

Cardiovascular effects of training for a marathon run in unfit middle aged men.

The effects of a 30 week exercise programme on serum lipid values, blood pressure, and cardiac function were assessed in a group of sedentary men aged 35-50 training for their first marathon. Mean serum cholesterol concentration (n = 33) fell by 12% from 6.54 (SE 0.18) to 5.76 (0.15) mmol/l (mean fall 0.78 mmol/l; 95% confidence interval 0.52 to 1.04 mmol/l), serum triglyceride concentration (n = 33) by 22% from 1.56 (0.17) to 1.21 (0.09) mmol/l (mean fall 0.34 mmol/l; 95% confidence interval 0.12 to 0.56 mmol/l), and mean blood pressure (n = 27) by 10% from 102 (2) to 92 (2) mm Hg (mean fall 10 mm Hg; 95% confidence interval 7 to 13 mm Hg). These changes were not explained by changes in body composition. Peak exercise left ventricular end diastolic volume (n = 16) increased with training; as a result of this and an increased exercise left ventricular ejection fraction peak exercise cardiac output increased from 19.9 (1.2) to 23.1 (3.0) l/min (mean rise 3.2 l/min; 95% confidence interval 1.5 to 5.0 l/min). Maximum oxygen consumption increased from 33.9 (1.6) to 39.0 (1.3) ml/kg/min (mean rise 5.0 ml/kg/min; 95% confidence interval 1.8 to 8.2 ml/kg/min). This study showed favourable effects on coronary risk factors and cardiac function and supports the place of regular exercise in coronary prevention programmes.

Blood Pressure↗