SUMMARY 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.

HNF-1alpha MODY diabetic subjects are more sensitive to sulphonylureas than Type 2 diabetic subjects and this is seen in different families, with different mutations and may continue up to 13 years from diagnosis. This is an example of pharmacogenetics, with the underlying aetiological genetic defect altering the pharmacological response to treatment. The present cases suggest that in HNF-1alpha MODY patients: (i) sulphonylureas can dramatically improve glycaemic control and should be considered as initial treatment for patients with poor glycaemic control on an appropriate diet; (ii) hypoglycaemia may complicate the introduction of sulphonylureas and therefore very low doses of short acting sulphonylureas should be used initially; and (iii) cessation of sulphonylureas should be undertaken cautiously as there may be marked deterioration in glycaemic control.

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.

Peripheral white and red blood cell changes were studied in response to acute insulin-induced hypoglycaemia in six normal, six splenectomized and five sympathectomized (tetraplegic) subjects. The normal subjects were restudied during beta (propranolol) and beta 1-selective (metoprolol) adrenergic blockade. In the normal subjects a lymphocytosis immediately followed the acute hypoglycaemic reaction (R) with a neutrophilia 2 h later. The early lymphocytosis was absent in sympathectomized subjects (P less than 0.001) and reduced under beta blockade (P less than 0.02) in normal subjects, indicating mediation via an adrenergic mechanism. The later neutrophilia from R + 60 min was not abolished by adrenergic blockade or preceding sympathectomy; the enhanced response with propranolol was associated with an elevated plasma cortisol. Haemoglobin, packed cell volume and total erythrocyte count rose maximally at R in all groups except the sympathectomized subjects in whom all parameters declined progressively from basal values. These peripheral erythrocytes changes appear to be mediated via an adrenergic mechanism which is unaffected by beta adrenergic blockade and which does not involve splenic contraction.

1. The effects of the subcutaneous administration of a long-acting somatostatin analogue (octreotide) or of placebo on the splanchnic blood flow response to a mixed solid meal has been examined in eight normal subjects by using a transcutaneous Doppler ultrasound technique. Each subject was studied on two occasions more than 1 week apart. 2. On the control day, feeding had a pronounced effect on both superior mesenteric artery and portal venous blood flows, causing a peak rise of 82% in superior mesenteric artery blood flow at 15 min and of 75% in portal venous blood flow at 30 min post-prandially (P less than 0.001). Blood flows remained elevated 2 h after the meal. Pulse and blood pressure showed no significant changes from baseline. 3. Octreotide reduced fasting superior mesenteric artery blood flow by 59% (P less than 0.05) and portal venous blood flow by 49% (P less than 0.01) and blunted the normal post-prandial rise. Pulse and blood pressure did not change in response to either the injection or the ingestion of the meal. 4. Octreotide suppressed the release of insulin, glucagon and pancreatic polypeptide in response to feeding and resulted in post-prandial hyperglycaemia. 5. The mechanism of action of octreotide on splanchnic blood flow is uncertain. It may be mediated via a direct vascular effect or it may act via suppression of vasoactive intestinal hormones.

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