Beta-blockers in heart failure.
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Biomedical subjects
Publications and source records attributed to J Yudkin.
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Functional sequence changes in the promoter of a gene may have a direct effect on the rate of transcription and thus on cellular or plasma levels of the protein. For both the beta fibrinogen gene and the plasminogen activator inhibitor-1 (PAI-1) gene such functional variations have been described. For the fibrinogen gene a G/A sequence variation has been detected at position -455 of the promoter, with carriers of the A allele, representing roughly 20% of the population, consistently having 7-10% higher fibrinogen levels than those with the genotype G/G. For the PAI-1 gene we have detected a run of four or five Guanidine residues (4G/5G polymorphism), and in several published studies those homozygous for the 4G allele (25% of the population) having levels of PAI-1 roughly 30% higher levels than 5G5G individuals. The magnitude of both of these genotype effects indicates that they are likely to be of biological significance in causing an elevated risk of thrombosis and reduced fibrinolysis. However the magnitude of these effects are modulated by several environmental factors and data will be presented to demonstrate interaction between genotype and presence of ischaemic disease and physical exercise, in the determination of an individual's plasma fibrinogen levels and of triglycerides and diabetes in determining levels of PAI-1.
Human proinsulin and 32-33 split proinsulin have been measured in the peripheral circulation by immunoradiometric assays (IRMAs) and have been shown to be elevated in impaired glucose tolerance and non-insulin-dependent diabetes mellitus (NIDDM). The IRMA for 32-33 split proinsulin did not discriminate between this molecule and des-32 or des-31,32 split proinsulin. We describe the comparison of IRMA for human plasma proinsulin and 32-33 split proinsulins with assays combined with high-performance liquid chromatography (HPLC), which can discriminate between 32-33 split, des-32 split, and des-31,32 split proinsulin. Subjects were those with normal glucose tolerance (n = 8) and those with NIDDM (n = 17), who were studied while fasting and 30 min after a glucose load. After collection, blood was centrifuged promptly, and the serum/plasma was stored frozen until assay. Both IRMA and HPLC methods were calibrated against synthetic peptides. Interassay coefficients of variation for the IRMA for proinsulin and 32-33 split proinsulin were < 13% over the ranges 3.8-65 pmol/l and 6.4-65 pmol/l, respectively. The following regression lines were obtained: proinsulin IRMA = -0.143 + 1.066 HPLC, r = 0.860; 32-33 split proinsulin IRMA = 0.048 + 1.051 HPLC; and des-31,32 split proinsulin, r = 0.814. For both analytes, there was no significant difference in the relationship of IRMA to HPLC results between the various subject groups and various time points. Thus, the IRMA for proinsulin has been validated by an independent method.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To evaluate the effectiveness and acceptability of centrally organised prompting for coordinating community care of non-insulin dependent diabetic patients. DESIGN: Randomised single centre trial. Patients allocated to prompted care in the community or to continued attendance at hospital diabetic clinic (controls). Median follow up two years. SETTING: Two hospital outpatient clinics, 38 general practices, and 11 optometrists in the catchment area of a district general hospital in Islington. PATIENTS: 181 patients attending hospital outpatient clinics. NULL HYPOTHESIS: There is no difference in process of medical care measures and medical outcome between prompted community care and hospital clinic care. RESULTS: 14 hospital patients failed to receive a single review in the clinic as compared with three patients in the prompted group (chi 2 = 6.1, df = 1; p = 0.013). Follow up for retinal screening was better in prompted patients than in controls; two prompted patients defaulted as against 12 controls (chi 2 = 6.9, df = 1; p = 0.008). Three measures per patient yearly were more frequent in prompted patients: tests for albuminuria (median 3.0 v 2.3; p = 0.03), plasma glucose estimations (3.1 v 2.5; p = 0.003), and glycated haemoglobin estimations (2.4 v 0.9; p < 0.001). Continuity of care was better in the prompted group (3.2 v 2.2 reviews by each doctor seen; p < 0.001). The study ended with no significant differences between the groups in last recorded random plasma glucose concentration, glycated haemoglobin value, numbers admitted to hospital for a diabetes related reason, and number of deaths. Questionnaires revealed a high level of patient, general practitioner, and optometrist satisfaction. CONCLUSIONS: Six monthly prompting of non-insulin treated diabetic patients for care by inner city general practitioners and by optometrists is effective and acceptable.
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1. Diene-conjugated fatty acids are one of the products of free-radical attack upon lipids and therefore have been used as markers of such attack. The major diene-conjugated fatty acid in human tissue and serum is an isomer of linoleic acid (9,12-octadecadienoic acid), namely 9,11-octadecadienoic acid. Diet may be another source of this isomer, raising questions as to its value as a free-radical marker. The aim of this study was to determine the importance of diet as a source of 9,11-octadecadienoic acid in phospholipid esterified fatty acids in human serum. 2. Foodstuffs rich in 9,11-octadecadienoic acid were identified. Fourteen subjects volunteered to alter their diets, either increasing ('high diet') or decreasing ('low diet') their intake of these foodstuffs for 3 weeks. Where subjects undertook both diets, a washout period of at least 3 weeks was allowed between phases. 3. Seven-day diet histories were kept and scored with respect to their content of 9,11-octadecadienoic acid. The concentrations of 9,11-octadecadienoic acid and linoleic acid in serum phospholipids were measured by h.p.l.c. with u.v. detection. 4. The percentage molar ratio of 9,11-octadecadienoic acid to linoleic acid was calculated. The percentage molar ratio rose significantly on the 'high diet' [1.3(0.4) versus 1.9(0.7), P = 0.01, mean (SD)] and fell significantly on the 'low diet' [1.6(0.4) versus 1.1(0.4), P = 0.004, means (SD)]. There was a significant correlation between the change in dietary intake of 9,11-octadecadienoic acid and the change in the percentage molar ratio (r = 0.829, P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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Male and female Sprague-Dawley rats were fed purified diets in which the carbohydrate component was either starch or refined sugar (sucrose). The addition to these diets of the ash prepared by the incineration of unrefined muscovado sugar prevented the deficiencies of Factor R seen in the offspring when the diets were not supplemented with ash. Analysis by neutron activation showed that the ash from the unrefined sugar significantly increased the proportion of iron, cobalt, manganese, caesium and rubidium in the diets. The addition of chlorides of all five mineral elements to the diet containing refined sugar also prevented the development of signs of deficiency of Factor R in the pups. However the addition of cobalt chloride alone, or of cobalt and manganese chlorides, did not prevent the deficiency. It is likely that what we have called reproductive Factor R is iron, caesium or rubidium.
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Following the report from Hawaii (Heilbrun et al., 1986) of relationships between tea consumption and respectively rectal cancer (positive) and prostate cancer (negative), these questions were examined using data from a prospective mortality study of London men initiated in 1967. The small numbers of men who did not usually drink any tea prevented a reliable study of this sub group. Nevertheless no evidence of a dose-response relationship was found for rectal, colon or prostate cancer. Significant relationships were found, however, between tea consumption and deaths from stomach, lung and kidney cancers. In the case of stomach and lung cancer, these were partly due to the effects of social class and smoking, and possible reasons are considered for the residual relations.
The dietary sugar of 15 young men was reduced from their habitual approximately 150 g/day to about 55 g/day. After 3 weeks, the concentration of oestradiol in their plasma fell by about 25%. Resumption of their habitual intake of sugar for 2 weeks restored the oestradiol concentration to its previous value. The results provide further evidence that dietary sugar can be one of the causes of coronary heart disease, and support the view that the underlying mechanism producing the disease is a disturbance in hormone balance.
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The effects on the biochemistry and physiology of the human body of diets differing only in the ratio of the two major carbohydrates, starch and sugars are discussed and related to the epidemiology of coronary heart disease and diabetes.