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Biomedical subjects

T W Meade

Publications and source records attributed to T W Meade.

At least 163 records · Page 9Linked to original sources

Haemostasis in normal pregnancy.

A study has been undertaken in 72 women to provide systematic information on the changes that occur in a wide range of haemostatic variables during and after pregnancy. Factors VII, VIII:C, VIIIR:Ag, X, fibrinogen and alpha 1-antitrypsin, rose markedly throughout pregnancy. Factors II and V and alpha 2 macroglobulin all rose early on but then decreased steadily. Antithrombin III:C and Ag fell slightly. There was a marked decrease in fibrinolytic activity from 11-15 weeks onwards. Levels of fibrin degradation products rose from 21-25 weeks onwards. The rise in coagulation factors that occurs could be due to increased synthesis or increased activation by thrombin, or to both. The findings are consistent with a mild degree of local intravascular coagulation from early on in pregnancy in some women.

Antigens↗

Fibrinopeptide A and sudden coronary death.

Fibrinopeptide A (FPA) concentrations were measured in blood taken by direct cardiac puncture from 31 patients who had died suddenly of ischaemic heart disease (IHD) and from 8 patients who had died suddenly of other causes. Mean FPA concentration in the IHD group was five times higher than that in the non-IHD group. This difference was almost entirely due to the high FPA level in the IHD subjects with a history of the disease. The FPA difference between the IHD and non-IHD groups is unlikely to have been due to differences in methods of resuscitation. A possible interpretation of the findings is that thrombin production causes or aggravates the course of events leading to sudden IHD death, particularly in subjects with a past history of IHD.

Aged↗

The prevention of ischaemic heart disease in flyers.

The question of secondary prevention in flyers arises only rarely, since those who have previously had episodes of ischaemic heart disease (IHD) are rarely allowed to resume flying. The strongest evidence on the effectiveness, or otherwise, of suggested primary preventive measures comes from randomized controlled trials, but the indications of observational studies should also be taken into account. A number of trials are due to report within the next few months or years and will strengthen the scientific basis for or against various recommendations. Meanwhile, evidence currently available suggests that the control of 'mild' hypertension may reduce the risk of IHD, though the evidence on this point is hardly strong enough to warrant any firm recommendation. There is more convincing, though not unassailable , evidence that dietary measures intended to reduce blood cholesterol levels are effective. In relative terms, the reduction of cigarette smoking is likely to have its greatest preventive impact in younger men but there is little good information on methods for persuading those who are at high risk of IHD to comply with preventive advice.

Adult↗

Haemostatic variables and the outcome of myocardial infarction.

In a study of 272 patients with myocardial infarction (MI) the 68 who died within 1 year had significantly higher levels of factor VIIIR:Ag, factor VIII:C, fibrinogen, alpha 1 antitrypsin and alpha 2 macroglobulin than those who survived. The mean white cell count (WCC) and peak creatine kinase (CK) were also significantly higher in those who died compared with the survivors. There was considerable intercorrelation between many of the haemostatic variables, WCC and CK as well as between many of the clinical predictors of outcome and the laboratory variables. The differences in haemostatic variables between those who died and those who survived may merely reflect the size of the infarct; alternatively, the haemostatic system may influence prognosis following an MI.

Antigens↗

Haemostatic changes following surgery.

Changes in factors V, VII and VIII and in fibrinogen were studied in 32 patients undergoing major abdominal surgery. Mean levels of factors V and VII were similar to population-based values preoperatively. Factor V fell following elective surgery and then rose above the mean pre-operative level before returning to it by the tenth post-operative day. Factor VII fell following both elective and emergency surgery and tended to remain depressed throughout the post-operative period. Pre-operative values of factor VIII and fibrinogen were higher than population-based values and higher in the emergency than in waiting-list patients. Both factor VIII and fibrinogen rose following elective surgery but no statistically significant change was seen following emergency surgery. The uncomplicated conditions leading to elective surgery, the acute complications leading to emergency surgery, and surgery itself may each have contributed to increases in factor VIII and fibrinogen levels, whereas the fall in factors V and VII was largely related to surgery itself. The findings may help in the interpretation of associations between clotting factors and thrombotic disease, particularly in the case of factor VII.

Aged↗

Hypertriglyceridaemia and hypercoagulability.

18 patients with severe hypertriglyceridaemia (mean fasting plasma triglyceride 5.7 mmol/l) had significantly higher concentrations of plasma fibrinogen and clotting factor Xc than did a normolipidaemic comparison group. Fibrinolytic activity was significantly lower in the hyperlipidaemic patients. Six months of treatment (diet or diet and clofibrate) lowered the patients mean plasma triglyceride to 3.1 mmol/l and caused a fall of clotting factors VIIc and Xc and a significant rise in fibrinolytic activity. None of these variables changed in the comparison group. Raised fibrinogen and factor VIIc concentrations are risk factors for cardiovascular mortality, and raised factor Xc and lowered fibrinolytic activity have both been found in groups at high risk of ischaemic heart-disease. Despite the fact that in population studies triglycerides do not consistently appear to be an independent risk factor for ischaemic heart disease, these data suggest that a pronounced increase in triglycerides warrants energetic therapy because it may be associated with a "hypercoagulable state".

Adult↗

Menopausal status and haemostatic variables.

The incidence of ischaemic heart disease (IHD) is higher in postmenopausal women than in premenopausal women of the same age. The difference may be partly explicable in terms of differences between premenopausal and postmenopausal women in haemostatic function. This possibility has been studied in 833 White women in the Northwick Park Heart Study (NPHS). Mean levels of factor VIIC, fibrinogen, and cholesterol were between 6% and 10% higher in postmenopausal women than in premenopausal women of the same age. When allowances were made for associations between these variables, the difference between the two groups in cholesterol was no longer evident. By analogy with NPHS data on men, the differences in factor VIIC, fibrinogen, and cholesterol would increase the risk of fatal IHD in postmenopausal women by about 40% compared with the risk in premenopausal women of the same age.

Age Factors↗

The epidemiology of plasma renin.

1. The epidemiological characteristics of plasma renin activity (PRA) were established in 1999 members of occupational groups in North and West London. 2. The main finding was that PRA was inversely associated with systolic blood pressure in men, the percentage fall in PRA (on a log scale) being 8.4% for each increase of one standard deviation in systolic blood pressure. There was a less obvious inverse relationship in women. 3. However, blood pressure accounted for less than 1% of the variance in PRA. 4. Mean PRA in both smokers and ex-smokers was about 20% higher than in non-smokers. 5. PRA fell with increasing age, was lower in women than in men and considerably lower in blacks (of either sex) than whites. 6. PRA was lower in the first quarter of the menstrual cycle than in the rest of the cycle. 7. Haemoglobin, blood cholesterol, leucocyte count and Factor VIII were positively correlated with PRA. 8. PRA was lower in men with diagnosed hypertension than in those without; there was no significant difference in the women. 9. PRA was lower in those who had had myocardial infarcts in the past than in those who had not. 10. The data as a whole suggest that it may be low, not high, levels of PRA which are associated with increased risks of cardiovascular disease in which hypertension is a predisposing factor. 11. The explanation may be a homoeostatic fall in PRA in response to a rise in blood pressure rather than a major causal role for PRA in the pathogenesis of essential hypertension and target-organ damage.

Adult↗

Predictors of mortality and disability in stroke.

The increasingly accurate prediction of survival and functional recovery in patients with stroke will be of value in planning both their individual management and the health and social services needed. To establish the independent predictive effects of a range of personal and clinical characteristics, data on 900 patients admitted to Northwick Park Hospital with stroke were analysed by stepwise multiple regression. Older patients who lose consciousness at the outset and show signs of multiple neurological deficits, abnormal pupils, and conjugate deviation of the eyes are more likely to die within a year than those without these characteristics. Those who survive the acute episode and are discharged alive are more likely to die within a year if they are old and have sensory loss with severe physical disability. Older female patients who are incontinent, lose consciousness at the onset of stroke, sustain extensive motor deficits in combination with other neurological deficits, and have residual disabilities from previous strokes are particularly likely to be severely disabled on discharge from hospital. Routinely collected clinical data enable useful forecasts about mortality and disability after stroke. The accuracy of these forecasts can probably be improved further.

Adult↗

Factor VII and ischaemic heart disease: epidemiological evidence.

High levels of factor VII are associated with an increased risk of death from cardiovascular disease, especially ischaemic heart disease (IHD). Theoretical considerations and experimental evidence, the latter including the results of clinical trials, suggest that the association may be one of cause and effect. The general epidemiology of factor VII also supports this view. Thus, characteristics such as increasing age, diabetes, obesity, the use of oral contraceptives and the occurrence of the menopause are each associated with raised factor VII levels as well as with an increased risk of IHD. Black ethnic group and vegetarianism, both apparently protective against IHD, are associated with low factor VII levels.

Adult↗

Common units for clotting factors assayed against different standards.

There are no generally accepted units for clotting factors except factor VIII. Results are usually expressed as percentages of the standards used in the assays and standards vary in their potency. Over a six year period, factors V, VII and VIII were measured in over 3000 participants in the Northwick Park Heart Study. Six different standards had to be used. For comparative purposes, all results were expressed in terms of the first standard (71/11). This paper describes how appropriate conversion values were derived. Three different methods were compared. One consisted of the assay of each standard against its replacement. Another was based on the use of a reference plasma spanning the use of two successive standards. The third was a population-based, or epidemiological method using the data from all the participants in the study. This method is based on the assumption that results would be the same in comparable groups of study participants. In order to ensure comparability, personal characteristics which affect clotting factor levels, such as age and degree of obesity, were taken into account. The three methods gave similar results but the population method was, in general, the most satisfactory for factor VIII as well as factors V and VII, and has been adopted for routine use.

Adolescent↗

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↗

Assay, kinetics and properties of plasma adenosine diphosphatase. The relationship to acid and alkaline phosphatase and variations in disease.

A rapid radioassay was used to characterise the adenosine diphosphatase (ADPase) activities in human plasma. There was a major peak at pH 9.3, 80% of whose activity was attributable to non-specific alkaline phosphatase, with the remaining 20% probably due to a specific ADPase. There was also a small peak of ADPase activity at pH 4.0. Inhibitor and chromatographic studies showed that whilst much of this activity was attributable to non-specific acid phosphatase, there was a discrete acid ADPase. Assays of plasma ADPase activities in vascular disorders, including myocardial infarction, peripheral vascular disease and diabetes mellitus, reveal no alterations from control values. Activities of alkaline ADPase were elevated in both chronic and acute liver failure. Acid ADPase was also increased in chronic liver disease and it is suggested that alterations in ADPase activities in liver disorders may contribute to the haemostatic problems observed in these patients.

Acid Phosphatase↗

Oral contraceptives, clotting factors, and thrombosis.

Oral contraceptives (OCs) raise the plasma levels of some clotting factors, especially factor VII. Until recently, however, there has been no evidence for a relationship between high levels of clotting factor and the onset of clinically manifest vascular disease. It has not been established, on a preliminary basis, that high levels of factors VII and VIII and of fibrinogen in men are associated with an increased risk of death from cardiovascular disease. There is a strong relationship between OC estrogen dose and the level of factor VII, a clotting factor with a number of other characteristics, suggesting that high levels would be thrombogenic. A strong relationship also exists between OC estrogen dose and the risk of thromboembolism. The thrombotic effects of OC are probably mediated, at least partly, through their effects on the coagulation system.

Animals↗