Glucagon is absorbed from the rectum but does not hasten recovery from hypoglycaemia in patients with type 1 diabetes.

Aims: A failure to secrete glucagon during hypoglycaemia is near universal in patients with type 1 diabetes 5 years after disease onset and may contribute to delayed counter-regulation during hypoglycaemia. Rectal glucagon delivery may assist glucose recovery following insulin-induced hypoglycaemia in such patients and has not been previously studied.

Methods: Six male patients (age 21-38 years) with type 1 diabetes (median duration 10 years) without microvascular complications, were studied supine after an overnight fast on two separate occasions at least 14 days apart.

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy.

Aims/hypothesis: The early pathological features of human diabetic neuropathy are not clearly defined. Therefore we quantified nerve fibre and microvascular pathology in sural nerve biopsies from diabetic patients with minimal neuropathy.

Methods: Twelve diabetic patients underwent detailed assessment of neuropathy and fascicular sural nerve biopsy at baseline, with repeat assessment of neuropathy 8.

A role for helix 3 of the TRbeta ligand-binding domain in coactivator recruitment identified by characterization of a third cluster of mutations in resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) has hitherto been associated with thyroid hormone beta receptor (TRbeta) mutations which cluster in two regions (alphaalpha 310-353 and alphaalpha 429-461) of the hormone-binding domain and closely approximate the ligand-binding cavity. Here, we describe a third cluster of RTH mutations extending from alphaalpha 234-282 which constitute a third boundary of the ligand pocket. One mutant, T277A, exhibits impaired transactivation which is disproportionate to its mildly reduced ligand affinity (Ka).

Prolonged remission of hypercalcaemia due to parathyroid carcinoma with pamidronate.

Parathyroid carcinoma is rare and the associated hypercalcaemia is often resistant to all treatment. A case is described in which prolonged control of hypercalcaemia has been achieved by infrequent infusions of pamidronate despite continuing hypersecretion of parathyroid hormone.

Evidence against a putative role for glucagon as a physiological splanchnic vasodilator in man.

1. Previous studies have suggested that glucagon in supraphysiological doses may mediate postprandial and hypoglycaemia-induced splanchnic vasodilatation in man and experimental animals. There are no reported studies investigating the role of glucagon in doses producing circulating concentrations within the physiological range.

Suppression of lipolysis in normal man does not inhibit recovery from insulin-induced hypoglycaemia.

Pharmacological suppression of lipolysis is being increasingly used in the treatment of diabetic hyperlipidaemia. Although theoretical hazard of such treatment is that recovery from hypoglycaemia might be impaired. Seven normal subjects were therefore studied on two occasions, following treatment with a single dose of either acipimox 250 mg or placebo.

Relationships between haemostatic factors and capillary morphology in human diabetic neuropathy.

We have examined haemostatic factors in 15 diabetic patients with peripheral neuropathy and 10 diabetic patients without clinical complications. Plasma and blood viscosity, fibrinogen, factor VIIIc, von Willebrand factor activity, spontaneous platelet aggregation and fibrinolytic activity were not significantly different between diabetic patients without clinical complications and diabetic patients with peripheral neuropathy. Platelet aggregation was enhanced in diabetic patients with neuropathy compared with those without complications.

Primary renal renin secretion responding to angiotensin converting enzyme inhibition.

A case of primary renal renin secretion of probable neoplastic origin is reported. Investigation demonstrated renin secretion to be incompletely autonomous with suboptimal suppression to posture and hypervolaemia. Easy control of the hypertension and hypokalaemia was achieved with an angiotensin converting enzyme inhibitor.

Studies of acquired sustained hypernatraemia occurring in a diabetic patient.

We describe studies undertaken in a diabetic patient with acquired sustained severe hypernatraemia. Arginine vasopressin levels and thirst scores were grossly subnormal in the presence of marked hypernatraemia but arginine vasopressin increased normally under the influence of negative pressure-induced hypovolaemia. Despite very low levels of arginine vasopressin, polyuria was not a feature suggesting acquired renal hyper-responsiveness.

Splanchnic haemodynamic changes during acute hypoglycaemia in man.

1. Splanchnic haemodynamic changes were studied in seven healthy subjects during hypoglycaemia induced by the intravenous infusion of insulin. Superior mesenteric artery blood flow and cardiac output were examined noninvasively by a Doppler ultrasound technique.

Do in-vivo suppression and stimulation of lipolysis influence thyroid hormone levels in man?

To determine whether increases in non-esterified fatty acids alter free thyroid hormone and TSH levels, the effect of endogenous activation of lipolysis by insulin-induced hypoglycaemia was examined in seven healthy volunteers pretreated with placebo or acipimox. Whilst levels of non-esterified fatty acid were very different in the two groups, levels of free thyroxine, tri-iodothyronine and TSH were unchanged. Thus, within the range of non-esterified fatty acid levels likely to be seen in clinical practice, any effect on thyroid hormone measurements can be safely ignored.

Parotid salivary secretion in diabetic autonomic neuropathy.

Parotid salivary flow rates and amylase concentrations were measured in three groups of eight subjects each (normal control, non-neuropathic diabetic, and neuropathic diabetic). Flow rates were significantly reduced in neuropathic diabetic patients as compared with normal controls (p less than 0.001) and non-neuropathic diabetic patients (p less than 0.

Autonomic denervation may be a prerequisite of diabetic neuropathic foot ulceration.

Studies using visceral (cardiovascular) autonomic function testing have left doubt as to the importance of autonomic neuropathy in the development of diabetic neuropathic foot ulceration. A test for peripheral autonomic denervation has been developed (acetylcholine sweatspot test), dependent on intradermal acetylcholine causing secretion by innervated sweat glands, detected by starch/iodine discoloration. The response is photographed and quantified using a grid (normal score = 0 or 1; abnormal = 5 to 60).

Relationship between longevity and lifeline: a manual study of 100 patients.

The relationship between length of lifeline and age at death has been evaluated in 100 consecutive autopsies. A highly significant association between the two was discovered which was strengthened further when hand size was controlled for. We feel that a powerful new prognostic sign may thus be within grasp.

Self-management of adrenal insufficiency by rectal hydrocortisone.

An alternative to intramuscular hydrocortisone self-injection was evaluated in healthy controls and in patients with adrenal insufficiency. Plasma cortisol concentrations were assayed after administration of 200 mg hydrocortisone by intramuscular injection (10 healthy subjects) or after insertion of an identical dose by rectal suppository (12 healthy subjects, 3 patients with adrenal failure). Plasma cortisol concentrations peaked at 1 hour (about 4000 nmol/l) following intramuscular injection and declined thereafter.

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.

Microangiopathy in human diabetic neuropathy: relationship between capillary abnormalities and the severity of neuropathy.

Clinical, electrophysiological and ultrastructural morphometric observations were made in 5 diabetic non-neuropathic patients, 5 diabetic patients with mild neuropathy and 11 diabetic patients with severe neuropathy. Capillary abnormalities were assessed in simultaneous nerve, muscle and skin biopsies and compared with results from 6 age-matched, non-diabetic control subjects. Nerve capillaries demonstrated markedly greater pathology than skin and muscle capillaries.

Reduced hyperaemic response under the diabetic neuropathic foot.

Diabetic neuropathic ulcers typically occur at high pressure sites. Microvascular blood flow has been assessed on the plantar surface of the foot in three matched groups each of 12 subjects free from macrovascular disease: (a) patients with diabetic neuropathy with abnormal foot pressures and previous neuropathic ulceration; (b) non-neuropathic diabetic patients; (c) non-diabetic control subjects. Resting flow was measured at the highest pressure point under the metatarsal heads (defined by pedobarograph) using laser doppler flowmetry, and the hyperaemic response was assessed at the same site following 3 min standing.

Nerve ischaemia-resistance: an early abnormality in diabetes.

Vibration perception threshold (VPT) has been measured before and 30 min after limb ischaemia in 17 newly diagnosed non-insulin-dependent diabetic patients and matched controls. Mean baseline VPT was higher in the diabetics than in controls (14 vs 11, p less than 0.01) while VPT at 30 min was lower (25 vs 30, p less than 0.

Abnormalities of foot pressure in early diabetic neuropathy.

Dynamic foot pressure has been studied in 44 diabetic subjects of mean age 52 years with no clinical evidence of neuropathy and in an age and sex matched non-diabetic control group. Vibration perception threshold (VPT), sensory (SCV), and motor conduction velocities (MCV) were also measured in the diabetic subjects. Sixteen diabetic subjects (Group A) had abnormally high pressures under the metatarsal heads (greater than 10 kg/cm2), whereas the remaining 28 diabetic subjects had normal results (Group B).

Benoxaprofen--adverse reactions and monitoring in general practice.

We report on the pattern of use of benoxaprofen (Opren) in a single group practice for a period which included the complete clinical life of the drug. One hundred and seventy-two patients of the 6495 practice patients had been prescribed benoxaprofen, but 55% had only a small exposure (less than 20 g). Recorded adverse reactions, of which none was serious, appeared in 25 patients.

Sural nerve oxygen tension in diabetes.

Peripheral nerve oxygen tensions were assessed in vivo by using microelectrodes to measure endoneurial oxygen tension in exposed sural nerve. In 11 diabetic patients with chronic sensorimotor neuropathy the mean endoneurial oxygen tension was 39.7 (SD 10.

The distribution of diabetic neuropathy in a British clinic population.

A survey of over 1,000 diabetic patients attending a routine hospital clinic clinic in a British city revealed 104 with neuropathic symptoms or foot ulceration. Patients could be assigned to one of four clinical neuropathy groups: chronic sensorimotor, predominantly sensory, proximal motor and mononeuropathy. Only duration of diabetes differed significantly between the groups, with the longest duration in the chronic sensorimotor group.