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Biomedical subjects

W R North

Publications and source records attributed to W R North.

At least 37 records · Page 2Linked to original sources

Variation between batches in clotting factor assays.

Differences in factor V, VII and VIII potency between the standards used in the Northwick Park Heart Study (NPHS) are described in the previous paper. This paper discusses the variation from batch to batch within each standard. In every case there was significant variation between batches, the standard deviation of batch means being between a third and a half of that within batches. Some of this variation could be attributed to drifts over time, but most of the "batch effect" was not easily accounted for. It is relatively simple to correct for steady drift, but there is no satisfactory way of allowing for unexplained batch variation.

Adolescent↗

Multicentre trial of physiotherapy in the management of sciatic symptoms.

Four treatments for sciatic symptoms--traction, exercises, manipulation, and corset--were assessed in a randomised controlled trial in 322 outpatients. The design was factorial. There were thus sixteen treatment groups, enabling a comparison of combinations of methods as well as of individual methods. Treatment lasted for four weeks. Patients were reviewed at the end of this period and at four and sixteen months after entry to the trial. Progress was measured by the patient's account of symptomatic improvement or deterioration and by return to work or normal activities. At four weeks each of the treatments was associated with a small degree of benefit over and above the high rate of spontaneous improvement. For manipulation, the benefit was statistically significant on one of the scales used to measure progress. There was a significant increase in symptomatic improvement with increasing numbers of treatments used in combination. This was complemented by a clear tendency for those who had received fewer types of treatment during the trial to have further treatment in the ensuing three months. There were no beneficial effects of treatment detectable at four or sixteen months. In the short-term, active physiotherapy with several treatments appears to be of value in the outpatient management of patients with sciatic symptoms, but it does not seem to confer any longer-term benefit.

Adult↗

Are fibre supplements really necessary in diverticular disease of the colon? A controlled clinical trial.

Fifty-eight patients with uncomplicated diverticular disease of the colon took bran crispbread, ispaghula drink, and placebo for four months each in a randomised, cross-over, double-blind controlled trial. Assessments were made subjectively, using a monthly self-administered questionnaire, and objectively, by examining a seven-day stool collection at the end of each treatment period. In terms of a pain score, lower bowel symptom score (the pain score and sensation of incomplete emptying, straining, stool consistency, flatus, and aperients taken), and total symptom score (belching, nausea, vomiting, dyspepsia, and abdominal distension) fibre supplementation conferred no benefit. Symptoms of constipation, however, when assessed alone, were significantly relieved. Both fibre regimens produced the expected changes in stool weight, consistency, and frequency. It is concluded that dietary fibre supplements in the commonly used doses do no more than relieve constipation. Perhaps the impression that fibre helps diverticular disease is simply a manifestation of Western civilisation's obsession with the need for regular frequent defecation.

Adult↗

Haemostatic function and cardiovascular death: early results of a prospective study.

Components of the haemostatic system which may be involved in the pathogenesis of ischaemic heart disease (IHD) were measured in the Northwick Park Heart Study. Of 1510 white men aged 40-64 at recruitment, 49 have since died. 27 died from cardiovascular disease (IHD in all but 3), 18 from cancer, and 4 from other causes. The mean recruitment levels of factor VIIc, factor VIIIc, and fibrinogen were significantly higher in those who died of cardiovascular disease than in those who survived. The independent associations of factor VIIc and fibrinogen with cardiovascular death were at least as strong as the association of blood cholesterol with cardiovascular death. A clustering of two or three high clotting-factor values (factor VIIc, factor VIIIc, and fibrinogen) was present at recruitment in 63% of those who died of cardiovascular disease, compared with 23% of those who survived. The clotting-factor results appeared to be specific for cardiovascular disease: there was no evidence that high levels of factor VIIc, factor VIIIc, and fibrinogen were associated with death from cancer. The general epidemiology of factor VIIc, factor VIIIc, and fibrinogen is consistent with their having a role in the pathogenesis of IHD.

Adult↗

The ICTH/WFH study of the partial thromboplastin time in mild haemophilia.

A study has been carried out in two stages to compare the sensitivity of different Partial Thromboplastin Time (P.T.T.) methods to partial deficiencies of factor VIII. In Stage 1, 63 laboratories throughout the world compared their own methods with a reference method, all using samples of the same three mild haemophilic plasmas. Wide variation was found between laboratories using the same method, especially for those methods which were not well standardised. There was fairly good agreement for the reference method. All methods correctly diagnosed the three mild haemophilic plasmas, but their factor VIII levels were rather low. Stage 2 was restricted to seven laboratories in Great Britain, comparing seven well-standardised commercial methods and the same reference method. A much wider range of abnormal plasmas was tested, and a variety of normal ones. P.T.T.'s for all plasmas (factor VIII levels from 5 to 58 iu/dL) fell outside the normal range by all methods, with a few exceptions. It was not possible to rank the methods in any order.

Blood Coagulation Tests↗

Haemostatic variables associated with diabetes and its complications.

To study the possible role of an "increased thrombotic tendency" in the vascular complications of diabetes several tests of haemostatic function were carried out on 91 men and 63 women with diabetes aged 35-54 years and the results compared with findings in 686 men and 393 women of the same age in the Northwick Park Heart Study. Mean values for factors VII and X, fibrinogen, and platelet adhesiveness were higher in the diabetics, but mean fibrinolytic activity and whole blood platelet counts were lower. Antithrombin III values were also higher in the diabetics, which may have constituted a protective response to other changes favouring the onset of vascular disease. Diabetics with retinopathy had higher factor VII and antithrombin III values, and those with proteinuria had higher values for factor VII, fibrinogen, and platelet adhesiveness than those without these complications. These findings suggest a potentially important association between a thrombogenic tendency and vascular disease in diabetes. Nevertheless, prospective data are needed to clarify whether the haemostatic abnormalities precede the onset of clinically manifest vascular complications or are a consequence of them.

Adult↗

Characteristics affecting fibrinolytic activity and plasma fibrinogen concentrations.

As part of a study to determine the extent to which the haemostatic system is implicated in the onset of clinically manifest ischaemic heart disease, characteristics influencing fibrinolytic activity (FA) and plasma fibrinogen concentrations were examined in 1601 men aged 18-64 and 707 women aged 18-59 in several occupational groups in North-west London. In men FA noticeably decreased till the age of about 58, when there was a small rise. In women a small increase in FA between 18 and about 40 was followed by a slightly larger fall between 40 and 59. There was a pronounced negative association of FA with obesity. FA was significantly less in smokers than non-smokers, though the effect was not large. FA increased with alcohol consumption. FA in men appeared to be greatest in the lower social classes, and men on night shift had poorer FA than those on day work. FA was greater in women using oral contraceptives than in those not using these preparations. In both sexes FA increased with exercise, but there were no associations between any of the characteristics studied and the increase. Plasma fibrinogen concentrations increase with age and obesity, are higher in smokers than non-smokers, and fall with alcohol consumption. In women the concentrations are higher in those using oral contraceptives. The general epidemiology of FA and plasma fibrinogen concentrations suggests that they may well be implicated in the pathogenesis of ischaemic heart disease.

Adolescent↗

Mean cell volume in a working population: the effects of age, smoking, alcohol and oral contraception.

The effects of mean cell volume (MCV) of age, smoking habit, alcohol consumption, menopausal status, and use of oral contraceptives have been studied as appropriate in 1596 white men and 892 white women in working populations in North-West London. In men, increasing age, smoking and alcohol consumption each make an independent contribution to MCV. In women, the effect of smoking is similar to that in men; the effect of alcohol is less obvious, possibly because of the low stated alcohol intake in women. The effect of alcohol on MCV in the population studied is not as marked as in hospital patients who admit to excessive alcohol consumption; this may partly be due to differences in methods of eliciting intake. There is a small increase in MCV following the menopause. Women on oral contraceptives show a rise in MCV with increasing age; this is not seen in women not on oral contraceptives. There is a strong inverse association between MCV and red blood cell count, which may be part of a mechanism to ensure constant oxygen carrying capactiy.

Adolescent↗

Relationship of air temperature to various chemical, haematological, and haemostatic variables.

Results for biochemical and haematological variables have been correlated with data on atmospheric temperature in order to identify possible mechanisms through which low environmental temperature may increase mortality from myocardial infarction and cerebrovascular disease. With the exception of cholesterol, there were no associations in the case of several clinical chemistry variables, or of haemoglobin and related indices. With varying degrees of consistency among the sex and age groups studied, temperature was positively correlated with factor VII, antithrombin III, and cholesterol, and negatively correlated with fibrinolytic activity. The correlations were all low but may offer some clues to mechanisms whereby air temperature influences ischaemic heart and cerebrovascular disease mortality.

Adolescent↗

The effect of plasma fibrinogen levels on measures of fibrinolytic activity.

It has been claimed that lysis time methods may be inappropriate as measures of fibrinolytic activity on the grounds that they are largely determined by plasma fibrinogen levels. The dilute blood clot lysis time (DBCLT) has therefore been measured in 103 subjects; fibrinolytic activity (expressed as 100/DBCLT) has been compared with the fibrin plate area (FPA) lysed by the euglobulin fraction, the latter method being, of course, virtually independent of plasma fibrinogen. Plasma fibrinogen levels have also been measured; they ranged from 167 to 416 mg%. Results have been analysed by the technique of multiple regression. The incorporation of plasma fibrinogen levels in the regression equation relating 100/DBCLT to FPA does not result in a significant increase in the proportion of the variance in 100/DBCLT that can be explained. It is concluded that there is no evidence that DBCLT is influenced by plasma fibrinogen levels within the physiological range.

Female↗

Automation of two-stage factor VIII assay.

Two automated methods for two-stage factor VIII assays have been compared with one another, and evaluated in practice. The Depex method records the clotting time when an electric circuit is completed by the formation of a fibrin thread across a hook-type electrode; the Electra method is based on an optical density technique of clot detection. The two methods gave comparable results for measured levels of factor VIII when haemophilic or "normal" plasmas were assayed. Results from the two methods in practice also suggest that both are valid at low and "normal" factor VIII levels. The Electra method is also probably suitable for assays of concentrates; however, the Depex method appears to give falsely high values in these circumstances, and experimental findings suggest that the reason may be that increased viscosity due to the high fibrinogen levels in factor VIII concentrates causes premature closure of the circuit between the two ends of the Depex electrode. The main advantage of the Depex method is that, provided 3 or 4 machines are available, a given number of assays can be completed more quickly than on Electra. The main advantages of Electra are that it is probably subject to less laboratory error than Depex, and that it is suitable for assaying concentrates as well as haemophilic and "normal" plasmas.

Automation↗

Haemostatic, lipid, and blood-pressure profiles of women on oral contraceptives containing 50 microgram or 30 microgram oestrogen.

In 15 women on oral contraceptives containing 30 microgram oestrogen, mean values for factors II, VII, and X, fibrinogen, fibrinolytic activity, antithrombin III, cholesterol, and fasting triglycerides were intermediate between values for 63 women on preparations containing 50 microgram oestrogen and those for 243 premenopausal women not on oral contraceptives. Mean blood-pressure levels, however, were higher in women on 30 microgram than in those on 50 microgram preparations. In 28 women on 50 microgram preparations containing 3 mg or 4 mg norethisterone, mean values of factor VII, fibrinogen, fibrinolytic activity, cholesterol, fasting triglycerides, and systolic blood-pressure were higher than in 15 women whose preparations contained only 1 mg of norethisterone. A less consistent picture was found in women on 30 microgram oestrogen preparations containing either 250 microgram (10 women) or 150 microgram (5 women) d-norgestrel. It is concluded that 30 microgram oestrogen preparations probably result in smaller hemostatic and lipid changes than 50 microgram preparations but that they may have a blood-pressure-raising effect attributable to the particular progestagen, d-norgestrel, used in 30 microgram preparations. The safety of these 30 microgram oestrogen preparations may thus depend partly on the balance between these two sets of effects. It is also concluded that norethisterone may have effects similar to those attributed to oestrogens.

Adult↗

Lipid and lipoprotein concentrations in 1604 men and women in working populations in north-west London.

Serum lipid and lipoprotein concentrations in men and women vary with age, and so-called "normal" limits should take account of this. Serum cholesterol, triglyceride, and phospholipid concentrations were measured in 1027 men and 577 women in five working populations in north-west London, and lipoprotein electrophoresis and quantitative analyses of lipoprotein concentrations were also performed. In men the best fit between serum cholesterol, triglycerides, and phospholipids, on the one hand, and age, on the other, was given by a curvilinear relationship expressed as a quadratic regression. In women the best fit was given by a linear regression. White men had higher serum cholesterol and triglyceride concentrations than Black men, and these differences were reflected in the distributions of the lipoproteins. There were no differences between values in White and Black women. Young women on oral contraceptives had lipid concentrations similar to those of older women not on these preparations. These data suggest that the adoption of concentrations of serum cholesterol (275-300 mg/100 ml (7-1-7-8 mmol/l) and triglycerides (175-200 mg/100 ml (2-0--2-3 mmol/l) recommended by a recent report on the prevention of coronary disease as limits above which special attention should be given to the management of hyperlipidaemia could result in as few as 2% of younger men or as many as 31% of older men being selected for treatment.

Adolescent↗