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Biomedical subjects

M Small

Publications and source records attributed to M Small.

At least 127 records · Page 7Linked to original sources

Effect of insulin therapy on coagulation and platelet function in type II (non-insulin-dependent) diabetes mellitus.

Twenty type II (non-insulin-dependent) poorly controlled diabetics had tests of coagulation and platelet function performed while receiving high-dose sulphonylurea therapy and at 1 and 3 months following their conversion to insulin. Although no overall change in glycaemic control (assessed by glycosylated haemoglobin) was noted, a reduction in thrombin generation was observed, as judged by a significant fall in fibrinopeptide A concentrations. No changes in factor VIII coagulant activity (VIII:C), factor VIII-related antigen or antithrombin III were found. Glycosylated haemoglobin concentrations showed significant correlations with antithrombin III and factor VIII:C, suggesting that improved glycaemic control might lead to an improvement of antithrombin III function and lower factor VIII:C concentrations. No changes in platelet function were detected. The introduction of an insulin regimen that improves glycaemic control might lead to a reversal of the 'hypercoagulable state' found in type II diabetes.

Aged↗

Liver dysfunction in haemophilia.

Liver function was studied in 139 of 291 haemophiliacs known to a single Regional Haemophilia Centre including patients with classical haemophilia, Christmas disease and von Willebrand's disease. In 57 patients, six-monthly liver function tests over a five year period were also available. Thirty-nine of the 139 patients had had jaundice or hepatitis and 56 had a positive test for HBsAb in the blood although few of these had had an identifiable clinical illness. Fifty-eight haemophiliacs had elevated serum aminotransferases at the time of study, but the five year review revealed only six patients who had had persistently abnormal results, although none had clinically evident liver disease. Liver dysfunction was unrelated to a history of hepatitis, to a positive HBsAb test, or to age, type of haemophilia, factor level or frequency of factor replacement treatment. Abnormalities of liver function in haemophilia appear to be unrelated to past or present hepatitis B infection in most cases and may not be related to any single transmitted infectious agent.

Adult↗

Small bowel permeability in patients with nasal polyposis.

Small bowel absorption defects have been noted in a proportion of patients with atopic eczema. Eighteen patients with recurrent nasal polyps had the cellobiose/mannitol ratio test performed in order to assess their small bowel function. Evidence for atopy was found in 11 of 18 patients. Histologically the polyps were described as allergic but the cellobiose/mannitol ratio was normal in all cases. No evidence for a small bowel absorption defect was obtained.

Adult↗

Outcome of pregnancy in insulin-dependent (type 1) diabetic women between 1971 and 1984.

We have looked at the outcome of pregnancy in women with type 1 (insulin-dependent) diabetes mellitus who were confined at Glasgow Royal Maternity Hospital between 1971 and 1984. Of 134 pregnancies, 123 proceeded beyond 28 weeks' gestation and yielded 125 live infants. The perinatal mortality rate was 16/1000, due solely to congenital foetal malformation. Malformations were not related either to the severity of maternal diabetes (as graded by the White classification) or the glycaemic control in the first trimester (as judged by maternal glycosylated haemoglobin concentration). Over the period of study, there has been a marked reduction in the frequency of ketoacidosis during pregnancy and in the delivery of small-for-dates babies; more mature lecithin:sphingomyelin ratios have been obtained by amniocentesis; and better Apgar scores have been demonstrated in the infants at delivery. The Caesarean section rate has fallen from 83 to 30 per cent, and babies now spend less time separated from their mothers in paediatric units. These improvements largely reflect better diabetic treatment (improved insulin regimens and glycaemic control) and closer obstetric assessment. Foetal malformation occurred overall in 11.4 per cent of pregnancies and did not become less frequent over the period of study. Further major improvement in the outcome of diabetic pregnancy will only come from a reduction in the congenital malformation rate, which implies better diabetic control at and around the time of conception.

Adult↗

Comparison of oral glucose loading and intravenous glucagon injection as stimuli to C-peptide secretion in normal men.

In 10 healthy men, we have compared the respective effects of an intravenous injection of glucagon (1 mg) and an oral glucose load (75 G) in eliciting the release of C-peptide and insulin from the pancreas. Serum C-peptide and insulin concentrations increased respectively to median values of 190% and 500% at 6 minutes after glucagon injection, and 344% and 794% at 30 minutes and 268% and 278% at 60 minutes following glucose ingestion. The oral glucose load was as effective as glucagon injection in testing beta cell function and was free from the unpleasant side effects (nausea, vomiting, syncope) commonly associated with glucagon. We conclude that oral glucose loading is probably the test of choice to elicit C-peptide release when screening populations of normal subjects for adequacy of beta cell function.

Adult↗

Non-steroidal anti-inflammatory drugs in haemophilic arthritis. A clinical and laboratory study.

Non-steroidal anti-inflammatory drugs are theoretically contra-indicated in the haemophilias but might be useful for those patients with chronic arthritic pain, as long-term strong analgesics are also undesirable. We carried out studies of platelet function and coagulation in 8 normal controls and 7 haemophiliacs while they were taking sequentially benoxaprofen and salsalate. No significant alterations in platelet function, bleeding time or coagulation occurred with either drug. In a subsequent double-blind controlled clinical trial using ibuprofen and placebo 8 of 9 patients had a significant reduction in pain score whilst using ibuprofen without significant change in the frequency of bleeds or the amount of concentrate used. Laboratory measures of coagulation also failed to reveal any adverse effect of the active drug. Non-steroidal anti-inflammatory drugs may be beneficial and may be used with caution in haemophilia.

Adult↗

Serum oestradiol and ischaemic heart disease--relationship with myocardial infarction but not coronary atheroma or haemostasis.

Elevated oestradiol (E2) levels may be a risk factor for ischaemic heart disease in men, although the mechanisms for the elevation of oestrogen and for its adverse effects remain unclear. We have studied 100 Caucasian males undergoing elective coronary angiography for ischaemic chest pain and measured serum oestradiol, a profile of haemostatic tests, extent of coronary artery disease and evidence of previous myocardial infarction in order to assess any relationships which could explain the effect of elevated serum oestradiol levels. Levels were significantly higher in men with a history of myocardial infarction compared to those without (p less than 0.01), but were unrelated to the extent of coronary disease or to the haemostatic tests. These results suggest that the association of oestradiol with coronary events relates to myocardial infarction, not to atherogenesis, and is not due to any currently measurable alterations of haemostasis. Current beta-adrenoceptor blocker treatment was associated with lower oestradiol and thromboxane B2 concentrations (both, p = 0.06). These incidental findings suggest that further studies of the effects of beta-blockade on oestradiol and thromboxane metabolism are indicated.

Adrenergic beta-Antagonists↗

Culture of thymic epithelial cells from mice and age-related studies on the growing cells.

Culture of epithelial cells from the thymus of mice was achieved in a medium modified to favor epithelial growth while inhibiting proliferation of fibroblasts. Epithelial cells were identified by the presence of desmosomes in electron microscopic preparations and by antibody to intermediate filaments containing keratin. Morphologically, the cells thus positively identified displayed two main patterns: carpets of large flat cells resembling paving stones which are confluent along the length of their membranes, and networks of cells interconnected by long cytoplasmic processes. These two types of cells were dominant in cultures derived from mice of all ages tested (newborn to nine months) but the relative proportion of each type appeared to change with the age of the donor mice and also with the concentrations of cortisone in the culture medium. Autoradiography revealed that the cultured cells were dividing, and that (in the presence of cortisone) the rate of DNA synthesis was decreased in a portion of the epithelial cells derived from mice in which thymic involution was already underway.

Age Factors↗

Effect of stanozolol on delta-aminolaevulinic acid synthase and hepatic monooxygenase activity in man and rat.

Stanozolol is an anabolic steroid which is used in the treatment of aplastic anaemia and has been recently advocated for the prophylaxis of vascular thrombosis. Similar steroid substances stimulate the activity of delta-aminolaevulinic acid synthase (ALA S), the rate limiting enzyme of haem biosynthesis, in rat hepatocytes and chick embryo liver cell cultures and activate acute hepatic porphyria. In the present study stanozolol (10 mg daily for 14 days) has been shown to increase significantly leucocyte ALA S activity in 9 healthy male subjects. There was a concomitant rise in urinary ALA and total porphyrin excretion but no change in antipyrine kinetics or urinary 6 B hydroxycortisol excretion. In a complementary study in male Sprague Dawley rats, stanozolol administered intraperitoneally, produced a dose-dependent increase in hepatic ALA S activity without changing hepatic cytochrome P 450 content. Stanozolol has been clearly shown to elevate ALA S activity, probably directly, and thereby, porphyrin production without affecting hepatic monooxygenase activity. This porphyrinogenic effect may be relevant to the successful treatment of aplastic anaemia with anabolic steroids. Leucocyte ALA S activity may provide a human system for the study of drug porphyrinogenicity in vivo.

5-Aminolevulinate Synthetase↗

A method of calculating spinal cord transit time from potentials evoked by tibial nerve stimulation in normal subjects and in patients with spinal cord disease.

Somatosensory potentials were evoked by stimulation of the tibial nerve at the ankle and recorded over the spine and scalp in 16 normal subjects and 26 patients with known or suspected spinal cord disease, with the aim of developing a method of measuring spinal sensory conduction velocity using a tolerable number of stimuli, applied unilaterally to alert subjects. In normal subjects N21 was consistently recorded over L1 vertebra and in most subjects a complex, N27/N29/P33, was recorded over the cervical spine referred to the vertex. Constant latencies at different spinal levels and, in one subject, comparison with the latency of the ascending volley indicate that the complex was not derived from the spinal cord but from more rostral structures, and therefore only transit time, rather than velocity, could be measured. In patients with clinically definite multiple sclerosis, even with minimal clinical signs, the N27/N29/P33 complex was always abnormal. Abnormalities in this and other forms of spinal cord disease were commonly absence or distortion of the complex, prolonged transit time being rare. The clinical value of the method is limited by the very low amplitude of the responses.

Adolescent↗

Epistaxis and arterial ligation.

The management of severe epistaxis is discussed. Three groups of patients with severe epistaxis are studied retrospectively. The group which had early arterial ligation performed had a significantly reduced length of stay in hospital without increased risk. We conclude that early arterial ligation is the treatment of choice in severe epistaxis.

Adolescent↗

Sequential study of bacterial clearance in experimental cystitis.

Clearance of Escherichia coli in experimental cystitis was studied in the diuresing mouse model. Urine was collected daily; sediment was isolated by cytocentrifugation and either stained or treated with fluorescent antibodies directed against mouse immunoglobulins. During the initial phase of the infection the bacteria were either free and dispersed or adhering to epithelial cells but not generally to polymorphonuclear cells (PMNs). Subsequently, the bacteria adhered to each other, to epithelial cells and to PMNs, were phagocytosed by the latter and showed strong fluorescence. It is postulated that the appearance of opsonising and agglutinating antibodies in conjunction with activity of the PMNs is involved in bacterial clearance.

Adhesiveness↗

Alteration of hormone levels in normal males given the anabolic steroid stanozolol.

Anabolic steroids have widespread metabolic effects but, to date, their proven clinical indications have been limited. Recently the 17 alpha-alkylated steroid, stanozolol, has been shown to be of value in a variety of commonly occurring vascular diseases. Its endocrine effects have received little attention and we have investigated the effect of administering a 14 d course of stanozolol (10 mg orally per day) on a variety of important hormonal pathways in nine healthy male subjects. Significant changes occurred as follows: a 55% reduction in serum testosterone levels was noted and was accompanied by reductions in 'derived' free testosterone, sex hormone binding globulin and LH levels; total T4 and T3 levels fell in association with a decrease in thyroxine binding globulin, but no alteration was detected in TSH or free T4 levels. Changes in vitamin D status, with falls in 25-hydroxycholecalciferol and vitamin D binding globulin were also observed. These effects were reversible on stopping treatment. Stanozolol therapy therefore leads to a number of hormonal changes, probably by an action at both pituitary and hepatic levels.

Adult↗