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Biomedical subjects

P G Newrick

Publications and source records attributed to P G Newrick.

At least 19 recordsLinked to original sources
PubMed2005

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 8.7+/-0.6 years later. RESULTS: At baseline, neuropathic symptoms, neurological deficits, quantitative sensory testing, cardiac autonomic function and peripheral nerve electrophysiology showed minimal abnormality, which deteriorated at follow-up. Myelinated fibre density, fibre and axonal area, and g-ratio were normal but teased fibre studies showed paranodal abnormalities (p<0.001), segmental demyelination (p<0.01) and remyelination (p<0.01) without axonal degeneration. Unassociated Schwann cell profile density (p<0.04) and unmyelinated axon density (p<0.001) were increased and axon diameter was decreased (p<0.007). Endoneurial capillaries demonstrated basement membrane thickening (p<0.006), endothelial cell hyperplasia (p<0.004) and a reduction in luminal area (p<0.007). CONCLUSIONS/INTERPRETATION: The early pathological features of human diabetic neuropathy include an abnormality of the myelinated fibre Schwann cell and unmyelinated fibre degeneration with regeneration. These changes are accompanied by a significant endoneurial microangiopathy.

Axons↗
PubMed1993

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. 2. Two separate studies were performed. In study 1, superior mesenteric artery blood flow was measured by Doppler ultrasound in six normal subjects during either saline or glucagon infusion at 1, 3 and 6 ng min-1kg-1, which resulted in circulating glucagon levels within the physiological range. Mean superior mesenteric artery blood flow fell during the 3 and 6 ng min-1kg-1 glucagon infusions (3 ng min-1kg-1: -31.8%, range -20 to -56% of baseline; 6 ng min-1kg-1: -20.7%, range -8 to -53% of baseline; P < 0.05). 3. In study 2, superior mesenteric artery blood flow was measured during hypoglycaemia induced by an insulin infusion in 12 normal subjects. In six of these subjects the effect of suppression of glucagon release during hypoglycaemia was assessed by pretreatment with the somatostatin analogue octreotide (0.8 microgram/kg subcutaneously) given 30 min before the insulin infusion. 4. The nadir in blood glucose concentration at the hypoglycaemic reaction was similar in both groups and glucose recovery was complete by 60 min after the hypoglycaemic reaction. Plasma catecholamine concentrations rose in both groups after the hypoglycaemic reaction. 5. Superior mesenteric artery blood flow rose at the hypoglycaemic reaction in both groups despite suppression of glucagon release with octreotide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

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. Hypoglycaemic recovery was unaffected, despite effective suppression of plasma non-esterified fatty acid levels with acipimox. The results suggest that under these conditions activation of lipolysis may not be essential to recovery from hypoglycaemia.

Acetoacetates↗
PubMed1992

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. In the 15 patients with neuropathy and 3 without complications, who underwent biopsy of sural nerve, skin and muscle, associations were found between haemostatic variables and measures of nerve capillary pathology, notably: plasma fibrinogen and nerve capillary basement membrane thickness (r = 0.70, p < 0.001); thromboxane B2 production and nerve capillary basement membrane thickness (r = -0.61, p < 0.01); plasma fibrinolytic activity and endoneurial capillary lumen size (r = 0.60, p < 0.01) and endothelial cell outer perimeter (r = 0.65, p < 0.01). The main associations of skin and muscle capillary abnormalities were with measures of in vitro platelet aggregation, and the correlations found with nerve capillary measurements were not echoed in the overlying muscle and skin. The results are supportive of the involvement of haemostatic abnormalities in the pathogenesis of diabetic neuropathy.

Adult↗
PubMed1992

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. Such treatment may prove to be a preferable option to surgery.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

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. This patient is an additional case of acquired osmoregulatory dysfunction, whose features do not fall neatly into previously described categories.

Arginine Vasopressin↗
PubMed1991

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. 2. Blood glucose concentration fell from 4.5 (0.14) mmol/l basally to 1.5 (0.09) mmol/l [mean (SEM), P less than 0.003] at the hypoglycaemic reaction ('R') and recovered to baseline by 'R' + 60 min. There was an associated rise in plasma glucagon, adrenaline and noradrenaline levels. 3. Superior mesenteric artery blood flow rose at 'R' from a basal value of 532 (38) ml/min to a peak of 803 (73) ml/min at 'R' + 10 min [mean (SEM), P less than 0.005] and remained significantly elevated until 'R' + 40 min. Resistance in this vessel fell by 33% at 'R' + 10 min (P less than 0.005) and remained significantly low until 'R' + 40 min. 4. Cardiac output rose by 33% at 'R' (P less than 0.004) and returned to normal by 'R' + 20 min. This was associated with a 24% rise in pulse rate (P less than 0.03), but no change in stroke volume or mean arterial pressure. Total peripheral resistance fell by 21% at 'R' (P less than 0.005) and had returned to normal by 'R' + 20 min. 5. The sustained rise in splanchnic blood flow during hypoglycaemic recovery may be of homoeostatic importance by providing metabolic fuel to the liver for gluconeogenesis.

Adult↗
PubMed1991

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.

Adult↗
PubMed1990

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. After rectal administration, levels peaked at between 1 and 2 hours and persisted for 8 or more hours. Similar levels were achieved at 4 hours (about 1000 nmol/l) by both methods of administration. Self-treatment by rectal suppository may be useful in the prevention of Addisonian crises.

Administration, Rectal↗
PubMed1990

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.

Age Factors↗
PubMed1989

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. Endoneurial capillary density was significantly reduced in severely neuropathic diabetic patients (p less than 0.01) when compared with control subjects. Capillary basement membrane (p less than 0.002), endothelial cell (p less than 0.003) and total diffusion barrier (endothelial cell, pericyte, basement membrane) (p less than 0.001) thickness were significantly increased, and oxygen diffusing capacity was significantly reduced (p less than 0.001) in the nerves of patients with severe diabetic neuropathy when compared to control subjects. Endothelial cell profile number and luminal perimeter were significantly increased in asymptomatic (p less than 0.01), (p less than 0.05) and severely neuropathic (p less than 0.001), (p less than 0.05) diabetic patients respectively. However, endothelial cell outer perimeter, a measure of capillary size, showed no significant increase in diabetic patients when compared with control subjects. An association was observed between neurophysiological and neuropathological measures of neuropathic severity. There was no significant correlation between the duration of diabetes and HbA1 levels with capillary pathology or with neuropathic severity. Very few abnormalities of muscle and skin correlated with neuropathic severity. However, all measures of nerve capillary pathology correlated significantly with neurophysiological and neuropathological measures of neuropathic severity.

Adult↗
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

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. Peak flow was significantly reduced in neuropathic patients (2.3 +/- 1.4 (SD) volts) compared with control subjects (4.0 +/- 2.0 volts; p less than 0.03). The time for blood flow return to baseline was significantly prolonged in neuropaths (159 +/- 72 s) compared with normal subjects (93 +/- 18 s; p less than 0.01), with a significant delay also seen in non-neuropaths (151 +/- 38 s; p less than 0.0001 compared with normal).

Adult↗
PubMed1987

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. Most were taking benoxaprofen for osteoarthritis (53%) or non-specific musculoskeletal pain (39.9%). The issue of a prescription was not recorded in 19.6% of cases and 88% were on additional drugs. Greater precision in record-keeping is required to avoid problems similar to the experience with benoxaprofen.

Adolescent↗
PubMed1986

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 10.2) mm Hg. In all but one patient compared with none of four non-neuropathic subjects the mean nerve oxygen tensions were below dorsal foot vein values. This unphysiological state may have a role in the aetiology of diabetic neuropathy.

Adult↗
PubMed1985

Pain in motor neuron disease.

Twenty-seven of 42 patients with motor neuron disease had significant pain. The nature and duration of the pain are described along with an illustrative case-report. The aetiology and most effective treatment of this common complication of motor neuron disease remain unclear.

Aged↗