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Biomedical subjects

R J Corrall

Publications and source records attributed to R J Corrall.

At least 37 records · Page 2Linked to original sources

Increases in plasma lysosomal enzymes in type 1 (insulin-dependent) diabetes mellitus: relationship to diabetic complications and glycaemic control.

Lysosomal enzymes degrade membrane glycoconjugates, and increased circulating enzyme activity may be an important mechanism in the pathogenesis of diabetic microangiopathy. We have assayed a profile of seven lysosomal enzyme activities (nmol.h-1.ml-1) in platelet-free plasma from 54 Type 1 (insulin-dependent) diabetic subjects (median age 31 years) and 42 matched normal control subjects. A significant increase in median (interquartile range) enzyme activity was measured in diabetic compared to control subjects for beta-D-glucuronidase, 121 (97.7-171) vs 88.8 (62.8-113), p less than 0.001; beta-D-Nacetylglucosaminidase, 693 (568-799) vs 568 (462-686), p less than 0.001; alpha-D-mannosidase, 23.8 (16.7-28.9) vs 14.5 (10.1-20.0), p less than 0.001; and beta-D-galactosidase, 6.94 (6.11-9.99) vs 6.66 (4.78-8.33), p less than 0.04. In contrast, alpha-L-fucosidase, alpha-D-galactosidase and beta-D-mannosidase activities were similar in diabetic and control subjects. None of the enzyme activities differed significantly (p less than 0.05) between 24 diabetic patients with clinical complications and 30 complication-free diabetic patients with similar glycaemic control which does not support the hypothesis that enzyme increases in diabetes arise simply by leakage from damaged tissues. In the diabetic subjects HbA1, median (interquartile range) 9.10 (7.40-10.60), was significantly related to beta-D-glucuronidase (rs = 0.56, p less than 0.001) and beta-D-Nacetylglucosaminidase (rs = 0.55, p less than 0.001). We have therefore demonstrated in diabetic subjects an increase in certain lysosomal glycosidases, that correlates with glycaemic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

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↗

Failure of blood mononuclear cells from human donors with autoimmune haemolytic anaemia to reconstitute severe combined immunodeficient mice.

The use of severe combined immunodeficient (SCID) mice to study humoral responses by peripheral blood mononuclear cells (PBMC) from patients with autoimmune haemolytic anaemia (AIHA) was assessed. Upon transfer to SCID mice, PBMC from normal donors and patients with autoimmune thyroid disease (AITD) produced substantial levels of immunoglobulin (Ig), detectable in the plasma of recipient SCID mice. In contrast, the majority of PBMC from AIHA donors did not produce Ig in recipient mice. The capacity of PBMC to reconstitute SCID mice was not related to the donor's age. In one case, remission of AIHA allowed the donor's PBMC to successfully reconstitute SCID mice, despite the fact that the donor had developed immune thrombocytopenic purpura (ITP). AIHA PBMC were viable by dye exclusion and contained cells in various states of activation, as judged by their IgG secretion profiles when cultured in vitro. The proportions of leukocytes in AIHA PBMC (T to B cell ratios, CD4+ to CD8+ cell ratios and monocytes) were highly variable compared to non-AIHA PBMC. To determine the effect of abnormal lymphocyte proportions on SCID reconstitution, depletion experiments were carried out on normal and AITD PBMC. This work demonstrated a requirement for high T cell numbers, especially CD4+ cells, and minimal B cell numbers for successful reconstitution. CD8+ depletion of PBMC led to increased levels of Ig production in some instances. It is considered that PBMC from AIHA patients have a defect different from that of other autoimmune disorders, which renders them incapable of reconstituting SCID mice.

Adolescent↗

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↗

Fasting and post-prandial splanchnic blood flow is reduced by a somatostatin analogue (octreotide) in man.

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.

Adult↗

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↗

Autonomic and sensory nerve function in diabetic foot ulceration.

Peripheral sensory and autonomic nerve dysfunction are thought to be crucial factors in the pathogenesis of diabetic foot ulceration. However, their relative importance is not known. In this study we have compared peripheral sensory nerve function and cardiac autonomic reflexes in 51 diabetics with a history of foot ulceration and 480 diabetic control subjects. In the diabetics with ulceration ankle reflexes were absent or impaired and vibration perception threshold reduced in 96.1% and 82.4%, respectively, compared with 40.8% and 25.8%, respectively, in control subjects (P less than 0.001). Cardiac autonomic tests were abnormal more frequently in the diabetics with ulceration and an autonomic score derived from four tests was abnormal in 62.8% of those with ulceration compared with 13.5% of those without ulceration (P less than 0.001). Discriminant analysis of the two groups of diabetes showed that an abnormal autonomic score was the best predictor of foot ulceration in diabetic patients.

Diabetic Neuropathies↗

Underwater medicine: a neglected area in Accident and Emergency specialist training.

We have evaluated the available medical care to sports divers by a postal questionnaire sent to consultants and senior registrars in Accident and Emergency medicine in the UK, assessing their training in underwater medicine. Replies were received from 60 of 96 consultants (63%) and 32 of 58 (55%) senior registrars. Thirty-two per cent of consultants and 50% of senior registrars had previous personal experience in managing an underwater diving accident. Thirty per cent of consultants and only 19% of senior registrars had prior formal postgraduate training in underwater medicine. Twenty-seven per cent of consultants and 13% of senior registrars replying did not know the pattern of referral for specialist advice nor where the nearest recompression chamber was to be found. We believe that more formal postgraduate training in underwater medicine is needed by A and E medical staff. Furthermore, clear guidelines about emergency management and patterns of referral for diving accidents should be displayed prominently in all A and E departments.

Decompression Sickness↗

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↗

The influence of autonomic neuropathy on mortality in insulin-dependent diabetes.

Five-year survival was investigated in 506 randomly selected patients with insulin-dependent diabetes mellitus screened for autonomic neuropathy with a series of cardiac autonomic function tests. Of the 484 diabetics traced, 44 (9 per cent) had died. The cumulative 5-year mortality rate was increased more than five-fold in those with autonomic neuropathy: 27 per cent vs. 5 per cent in those with normal autonomic function. Discriminant analysis of survivors and non-survivors showed that autonomic neuropathy was the most important independent predictor of death. Among those who died, autonomic neuropathy was associated with an increased frequency of retinopathy and peripheral neuropathy and a slightly lower frequency of macrovascular disease. Autonomic neuropathy was associated with an increased mortality rate from renal failure, but not from any other causes.

Adolescent↗

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↗

The importance of distinguishing familial hypocalciuric hypercalcaemia from asymptomatic primary hyperparathyroidism prior to neck exploration.

The increasing detection of asymptomatic hypercalcaemic patients by biochemical screening has led to an increase in the number of patients referred for neck exploration. Familial Hypocalciuric Hypercalcaemia (FHH) has emerged as an important condition to distinguish from primary hyperparathyroidism as a cause of hypercalcaemia. Patients with FHH are usually asymptomatic, have similar biochemical findings to primary hyperparathyroidism, but fail to respond to parathyroid surgery. We have studied 15 members of a large kindred with FHH. The initial diagnosis was made in the propositus after a failed neck exploration for presumed primary hyperparathyroidism. Of the 7 affected members, 2 had recurrent acute pancreatitis and 2 had incidental malignant disease with no evidence of bony involvement. Measurement of the calcium: creatinine clearance ratio provides a good method of identifying hypercalcaemic patients who might have FHH. A ratio of less than 0.013 is an indication to screen first-degree relatives before considering neck exploration.

Adolescent↗

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↗

Hormonal response to blood volume expansion in diabetic subjects with and without autonomic neuropathy.

The hormonal and renal response to volume expansion, produced by water immersion for 4 h, was studied in 14 insulin-dependent diabetic subjects (seven without complications, seven with autonomic neuropathy) and in 14 age-and-sex-matched normal control subjects. The diabetic subjects showed an impaired natriuretic response to volume expansion (total amount of sodium excreted 21 mmol compared to 39 mmol in normals, P less than 0.01) but the response did not differ in those with and without autonomic neuropathy. There was no significant difference in the suppression of plasma renin or aldosterone during immersion in either group. Plasma catecholamines suppressed on immersion in all groups. Basal values were lowest in the group with autonomic involvement. Atrial natriuretic peptide levels showed a twofold rise (from 4.8 to 9.6 pmol/l, P less than 0.01) on immersion. There was no significant difference in the levels of this hormone between diabetic patients and normal subjects or between those diabetics with and those without autonomic neuropathy. The present study confirms that diabetic subjects retain sodium avidly during volume expansion. This enhancement cannot be ascribed to any measurable difference in the levels of circulating hormones known to be involved in natriuresis and is not influenced by the presence of autonomic neuropathy.

Adult↗

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↗