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Biomedical subjects

R Taylor

Publications and source records attributed to R Taylor.

At least 451 records · Page 25Linked to original sources

Progressive myopathy in hyperkalemic periodic paralysis.

A progressive degenerative myopathy has been well described in hypokalemic periodic paralysis but is not as widely recognized in hyperkalemic periodic paralysis. We studied four families with the latter disease in which some members developed a progressive myopathy. Episodes of paralysis were prolonged, lasting for months in some cases, and in one case paralysis was sufficiently severe to require ventilatory support. The progressive myopathy tended to develop at a time when attacks of paralysis were decreasing in frequency. Muscle biopsy specimens showed variability in fiber size, internal nuclei, and fibers with vacuoles. Electron microscopy showed myofibrillary degeneration and tubular aggregates. An abnormal biopsy specimen was more common in older patients. Our experience suggests that a progressive myopathy is as common in hyperkalemic periodic paralysis as it is in the hypokalemic disorder.

Adolescent↗

Rising cholesterol levels in children with familial hypercholesterolaemia.

Reference ranges (5th to 95th percentile) for fasting total serum cholesterol concentration were calculated for 571 unrelated children aged 4-19 years, without known predisposition to hypercholesterolaemia. Values were 3.31-5.81 mmol.l-1 for boys and 3.20-5.66 mmol.l-1 for girls, without significant differences between sexes at any age, compared to our laboratory reference ranges for men (3.46-6.87 mmol.l-1) and women (3.00-6.38 mmol.l-1). A further 85 children, each with a first degree relative with Familial Hypercholesterolaemia (FH), were studied. Initially, 39 had high cholesterol concentrations suggestive of FH. Repeated serial measurements were carried out in 18 of the 46 apparently unaffected children. Seven of these showed marked increases in serum cholesterol over 1-7 years, reaching concentrations above the 95th centiles of the appropriate reference ranges. The annual rate of increase was significantly higher than in the 11 who remained normocholesterolaemic. In 3 of these 7 children, diagnosis of FH was confirmed retrospectively, using recombinant DNA technology to show that each had inherited the defective allele of the LDL-receptor gene from an affected parent. Thus, serial cholesterol measurements may be needed to confirm or exclude FH in potential heterozygotes, while DNA studies can be used for definitive diagnosis in some families.

Adolescent↗

Lung function in patients with diabetes mellitus.

Lung function was assessed in 35 nonsmoking adults with insulin dependent diabetes mellitus and 34 matched control subjects. The tests included spirometry, lung volumes, CO transfer factor and maximum respiratory pressures. Additionally, in subjects under 35 years of age (20 patients and 18 controls) measurements of CO transfer factor were obtained during exercise at three different workloads. Random blood glucose and glycosylated haemoglobin were measured and each patient's diabetic history was recorded. The total lung capacity (TLC) in the patients was lower than those recorded for the controls (P less than 0.05) but there were no significant differences in respiratory muscle strength between the groups. In the young group of patients (less than 35 years) the transfer factor for CO (TLCO) was similar but the volume corrected transfer coefficient (KCO) was higher at rest than in the controls (P less than 0.02). The KCO remained high in these patients during exercise. The older patients (greater than 35 years) showed a lower TLCO (P less than 0.01) with a similar KCO to the controls. The association of a reduction in TLC and higher KCO in the young patients suggests an extrapulmonary mechanism of lung volume restriction. This is not attributable to muscle weakness but might be due to limited expansion of the rib cage. In older patients any tendency for KCO to rise may be masked by disease-related changes in the pulmonary microvasculature.

Adult↗

Effects of intensive dietary treatment on insulin-stimulated skeletal muscle glycogen synthase activation and insulin secretion in newly presenting type 2 diabetic patients.

Ten newly presenting, untreated, Europid Type 2 diabetic patients were studied before and after 8 weeks treatment with intensive diet alone. Nine normal control subjects were also studied. The degree of activation of skeletal muscle glycogen synthase (GS) was used as an intracellular marker of insulin action, prior to and during a 240-min insulin infusion (100 mU kg-1 h-1). Fasting blood glucose decreased from 12.1 +/- 0.9 (+/- SE) to 9.2 +/- 0.8 mmol l-1 (p less than 0.01), but there was no change in fasting insulin concentrations, 9.9 +/- 2.3 vs 9.3 +/- 2.1 mU l-1. Fractional GS activity did not increase in the Type 2 diabetic patients during the insulin infusion either at presentation (change -1.5 +/- 1.9%) or after treatment (change +0.9 +/- 1.8%), and was markedly decreased compared with the control subjects (change +14.5 +/- 2.8%, both p less than 0.001). Glucose requirement during the clamp was decreased in the Type 2 diabetic patients at presentation (2.2 +/- 0.7 vs 7.3 +/- 0.6 mg kg-1 min-1, p less than 0.001), and despite improvement following dietary treatment to 3.3 +/- 0.6 mg kg-1 min-1 (p less than 0.01) remained lower than in the control subjects (p less than 0.001). Fasting plasma non-esterified fatty acid (NEFA) concentrations were elevated at presentation (p less than 0.05), and failed to suppress normally during the insulin infusion. After treatment fasting NEFA concentrations decreased (p less than 0.05) and suppressed normally (p less than 0.05). Insulin secretion was assessed following an intravenous bolus of glucose (0.5 g kg-1) at euglycaemia before and after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Morphology of palpably abnormal injection sites and effects on absorption of isophane(NPH) insulin.

The absorption of isophane(NPH) insulin (Human Insulatard) from palpably abnormal thigh insulin injection sites was determined in 10 C-peptide negative diabetic patients. Absorption was compared with a control day study when the insulin was injected into normal thigh. Standard meals were given 30 and 240 min after the injection. Within 2 weeks the tissue morphology and adipose tissue depths at both injection sites were assessed by ultrasound scanning. Absorption of isophane(NPH) insulin was markedly defective from the abnormal compared with the normal injection sites (area under the free insulin curve to 10 h 115 +/- 15 vs 188 +/- 21 mU l-1 h; p less than 0.01). The area under the blood glucose curve from 270 min to the end of the study at 600 min was significantly greater after injection into the palpably abnormal injection site compared with normal thigh (80.4 +/- 5.2 vs 61.2 +/- 7.0 mmol l-1 h; p less than 0.05) representing a 22% improvement in blood glucose control on the normal injection site afternoon. The depth of abnormal injection site tissue was significantly greater than the depth of adipose tissue at the control site (17 +/- 6 vs 5 +/- 4 mm; p less than 0.001) and considerable disruption of the normal anatomy observed. These results demonstrate defective absorption of isophane(NPH) insulin from palpably abnormal injection sites and describe the morphology of the abnormal tissue.

Absorption↗

Encoding preferences in memory in dementia.

Encoding preferences in memory were examined in 22 subjects with presumed dementia of the Alzheimer type (DAT), 22 subjects with presumed multi-infarct dementia (MID), and 19 elderly depressed subjects by means of multiple-choice recognition testing of memory for word lists where target words appeared in choice arrays amongst semantic, acoustic and unrelated distractor words. Performance was worse in dementia than in depression. Subjects with dementia tended to make many unrelated error choices, and in DAT this tendency was stronger in more impaired subjects; but there were no significant differences between groups in the proportions of different types of errors made.

Aged↗

Relationships between cognitive test performance and everyday cognitive difficulties in multiple sclerosis.

Cognitive test performance and rated everyday cognitive difficulties were compared in 29 subjects with multiple sclerosis. Modest relationships between test and questionnaire measures were found. The correlation between test and everyday measures was higher when informants' ratings of everyday problems were used rather than subjects' own ratings. The size of the discrepancy between subject and informant ratings was related to subjects' performance on tests considered sensitive to frontal lobe dysfunction.

Activities of Daily Living↗

DNA probes show genetic variation in cyanobacterial symbionts of the azolla fern and a closer relationship to free-living nostoc strains than to free-living anabaena strains.

Twenty-two isolates of Anabaena azollae derived from seven Azolla species from various geographic and ecological sources were characterized by DNA-DNA hybridization. Cloned DNA fragments derived from the genomic sequences of three different A. azollae isolates were used to detect restriction fragment length polymorphism among all symbiotic anabaenas. DNA clones were radiolabeled and hybridized against southern blot transfers of genomic DNAs of different isolates of A. azollae digested with restriction endonucleases. Eight DNA probes were selected to identify the Anabaena strains tested. Two were strain specific and hybridized only to A. azollae strains isolated from Azolla microphylla or Azolla caroliniana. One DNA probe was section specific (hybridized only to anabaenas isolated from Azolla ferns representing the section Euazolla), and five other probes gave finer discrimination among anabaenas representing various ecotypes of Azolla species. These cloned genomic DNA probes identified 11 different genotypes of A. azollae isolates. These included three endosymbiotic genotypes within Azolla filiculoides species and two genotypes within both A. caroliniana and Azolla pinnata endosymbionts. Although we were not able to discriminate among anabaenas extracted from different ecotypes of Azolla nilotica, Azolla mexicina, Azolla rubra and Azolla microphylla species, each of the endosymbionts was easily identified as a unique genotype. When total DNA isolated from free-living Anabaena sp. strain PCC7120 was screened, none of the genomic DNA probes gave detectable positive hybridization. Total DNA of Nostoc cycas PCC7422 hybridized with six of eight genomic DNA fragments. These data imply that the dominant symbiotic organism in association with Azolla spp. is more closely related to Nostoc spp. than to free-living Anabaena spp.

Journal Article↗

Outcome of congestive heart failure, dilated cardiomyopathy, hypertrophic hyperkinetic disease, and ischemic heart disease in dialysis patients.

Congestive heart failure in dialysis patients is associated with dilated cardiomyopathy, hypertrophic hyperkinetic disease and ischemic heart disease. To determine the natural history of these four diseases, 150 dialysis patients were prospectively followed for 3-5 years. The 2-year cumulative survival rate was 33% in those with recurrent or persistent congestive heart failure vs. 80% in dialysis patients without. Survival was significantly worse in patients with an echocardiographic diagnosis of dilated cardiomyopathy compared to patients with normal echo-cardiogram (2-year survival rate 67 vs. 90%). In hypertrophic hyperkinetic disease the 2-year survival rate was 30% after entry into the study, and 43% after first admission with congestive heart failure. Symptomatic ischemic heart disease did not have an adverse impact on mortality when compared to those without ischemic heart disease. We conclude that congestive heart failure in dialysis patients has a bad prognosis. Its associated disorders include dilated cardiomyopathy and hypertrophic hyperkinetic disease, the latter being associated with a high mortality. As the prognosis for patients with overt ischemic heart disease was not different from patients without, it is likely that the underlying cardiomyopathy directly influenced survival.

Cardiomegaly↗

The clinical course of left ventricular hypertrophy in dialysis patients.

To determine the clinical and echocardiographic outcome of left ventricular hypertrophy a prospective study was undertaken of 104 nondiabetic dialysis patients without dilated cardiomyopathy, who were followed for 3-5 years. 33% of patients had normal echocardiogram, 41% mild and 27% severe hypertrophy (left ventricular wall thickness greater than or equal to 1.4 cm in diastole). In the first 2 groups 16% progressed to severe hypertrophy, 23% were admitted with congestive heart failure after starting dialysis therapy, and 2-year cumulative survivals were 97 and 85%. In the group with severe hypertrophy 88% already had severe hypertrophy on starting dialysis therapy, it was persistent in 87%, 50% were admitted at least once with congestive heart failure, and the 2-year cumulative survival was 53%. 71% of those who died in the severe group died from cardiac or cerebrovascular causes compared to none of those with normal echocardiogram, which accounted for the significantly worse (p = 0.001) survival. We conclude that severe left ventricular hypertrophy occurs frequently in dialysis patients, is often present at the start of end-stage renal disease therapy, is persistent, may predispose to congestive heart failure, and is associated with a high mortality.

Cardiomegaly↗

Benign autosomal dominant syndrome of neuronal Charcot-Marie-Tooth disease, ptosis, parkinsonism, and dementia.

We present a kindred with a previously undescribed combination of neuronal Charcot-Marie-Tooth disease, ptosis, parkinsonism, and mild dementia. The propositus, a 72-year-old man, had pes cavus, peripheral neuropathy, ptosis, parkinsonism, hyperreflexia, orthostatic hypotension, central hypoventilation, and mild dementia. Peripheral electrophysiologic studies showed features of an axonal neuropathy. The electroencephalogram showed intermittent 2 to 4 Hz activity symmetrically in the hemispheres. Several family members in 3 generations had pes cavus, neuropathy, ptosis, parkinsonism, and dementia although not all of the features were consistently present. Survival past the 7th decade was common. Autopsy in 2 affected members revealed the neuropathy to be axonal in type and showed mild to moderate loss of anterior horn cells in the spinal cord and pigmentary loss with gliosis in the substantia nigra. This is a unique, benign, autosomal dominant syndrome which shows complete penetrance, variable expression, and both central and peripheral nervous system involvement.

Adult↗

Lowering of plasma glucose concentrations with bezafibrate in patients with moderately controlled NIDDM.

The goal of this study was to investigate whether treatment with bezafibrate improves glucose tolerance in non-insulin-dependent diabetes mellitus (NIDDM). The study included 37 NIDDM patients with HbA1 concentrations greater than 8.5% and normal kidney and liver function who were being treated with diet alone or diet together with a sulfonylurea drug. One patient withdrew because of constipation. At randomization and after 3 mo of treatment, patients were given a standard mixed-test-meal tolerance test (MTT; 500 cal) after an overnight fast, and plasma glucose, insulin, C-peptide, metabolite, nonesterified fatty acid (NEFA), and triglyceride concentrations were measured at 15- to 30-min intervals. Serum lipid, HbA1, and fructosamine concentrations were measured at monthly intervals. Glucose, NEFA, and triglyceride concentrations were significantly lower throughout the second MTT in bezafibrate patients (P less than 0.01-0.001) but not in the placebo group. Fasting serum insulin and C-peptide levels, but not postprandial concentrations, were reduced only in bezafibrate patients (P less than 0.05). After 3 mo, mean fasting serum triglyceride concentrations fell from 2.2 to 1.4 mM (P less than 0.001), total serum cholesterol concentrations from 6.3 to 5.5 mM (P less than 0.001), and low-density lipoprotein cholesterol concentrations from 4.2 to 3.5 mM (P less than 0.001) in bezafibrate patients. There were no changes in serum lipid concentrations in the placebo group. Treatment of patients with moderately controlled NIDDM with bezafibrate improves glucose tolerance and the serum lipid profile. Bezafibrate treatment may be a useful adjunct to hypoglycemic therapy in patients with NIDDM.

Bezafibrate↗

Signal-detection analysis of nonverbal recognition memory in dementia.

A signal-detection analysis was applied to performance on two non-verbal recognition memory tasks for 21 subjects with presumed dementia of the Alzheimer type, 19 subjects with presumed multi-infarct dementia, and 19 elderly depressed subjects. Performance was best for the depressed and worst for the Alzheimer subjects. Response bias did not differ significantly among groups. Within the depressed group, more impaired and older subjects were more conservative on one test. Correlations suggested that the sensitivity and response-bias measures may depend on the type of material used and so have limited generality.

Aged↗

Effect of bezafibrate on metabolic profiles in non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by hyperglycemia secondary to increased hepatic glucose output and impaired extrahepatic insulin sensitivity. Many NIDDM patients also have raised serum triglyceride and low-density lipoprotein (LDL) cholesterol levels, which may require drug therapy, as well as increased plasma nonesterified fatty acid concentrations. Some hypolipidemic agents such as bezafibrate lower fatty acid levels as well as LDL cholesterol and triglycerides. It has been suggested that raised fatty acid levels may be responsible in part for the increased hepatic glucose output and insulin insensitivity of NIDDM. Several groups have therefore sought to examine the effects of fibrates on glycemic control in NIDDM. In our own studies, we used bezafibrate (200 mg t.i.d.) in a double-blind, placebo-controlled design for 3 months. Fasting blood glucose, serum insulin, C-peptide, plasma nonesterified fatty acids, blood lactate and alanine, serum triglycerides, and LDL cholesterol were all lowered. HbA1 showed no significant change. Meal hormone and metabolite profiles were all improved although this reflected mainly the lower premeal values. The results of our and other studies are sufficiently encouraging to suggest that bezafibrate could provide alternative first-line drug therapy in hyperlipidemic NIDDM patients when diet alone has failed.

Bezafibrate↗

American way.

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Adolescent↗

Blood transfusion and surgery: the effect on growth of a syngeneic sarcoma.

The effects of blood transfusion, blood components, and surgical trauma on the growth of an experimental sarcoma have been examined. Recipient animals were inbred adult female WAB rats, which received allogeneic transfusions from inbred adult female PVG rats, syngeneic blood from inbred colony-mates, or saline infusions. Small volume transfusions (1-4 ml) of whole blood had no effect on tumour growth, but growth of the MC7 sarcoma was significantly enhanced following allogeneic transfusions of 5 ml whole blood, or when 4 ml was combined with sham laparotomy. Maximal enhancement of tumour growth occurred when 4 ml transfusions of allogeneic washed cells were given, but allogeneic plasma was also able, to a lesser degree, to enhance tumour growth. These data confirm that blood transfusion may enhance growth of the MC7 sarcoma, that the effect may be dose dependent, and synergistic with the immunosuppression of surgery. Many components of an allogeneic transfusion may be responsible for this effect.

Animals↗

Insulin sensitivity in experimental cirrhosis.

To investigate insulin action in muscle and adipose tissue in hepatic cirrhosis, a recently described animal model was used. Dimethylnitrosamine administration induced histologically proven cirrhosis. Contrary to expectation, muscle strips from cirrhotic rats displayed increased insulin sensitivity both with respect to glycogen synthesis (ED50 0.11 +/- 0.01 vs 0.23 +/- 0.04 nmol/l; p less than 0.03) and glucose oxidation (ED50 0.36 +/- 0.07 vs 0.97 +/- 12 nmol/l; p less than 0.02). As the cirrhotic rats had failed to gain weight normally, it is postulated that a state of relative starvation accounted for the enhanced insulin sensitivity. These data demonstrate that the severe insulin resistance characteristically associated with cirrhosis is reversible. Control of nutritional state in future studies upon DMNA induced cirrhosis should permit detailed examination of the cellular mechanisms controlling insulin sensitivity in hepatic cirrhosis.

Adipose Tissue↗