Physiological coagulation is dependent on the formation of a powerful thromboplastin within the blood. It is well recognized that coagulation defects, such as that in haemophilia, are due to a failure of the normal thromboplastin mechanism, but lack of knowledge has hitherto prevented any precise or detailed study of these abnormalities. Biggs, Douglas, and Macfarlane (1953a) have shown that three components, normal plasma treated with AI(OH)3, platelets, and normal serum, react to form thromboplastin. Further analysis has shown that two essential substances, antihaemophilic globulin and factor V, occur in the Al(OH)3-treated plasma, while serum contains two factors, factor VII and the Christmas factor, both of which are required for thromboplastin formation (Biggs, Douglas, and Macfarlane, 1953b). These five components-platelets, antihaemophilic globulin, the Christmas factor, and factors V and VII-react together in the presence of CaCl2 to form a labile thromboplastin as powerful as any so far described. A lack of any one of the five produces a coagulation defect associated with abnormal thromboplastin formation.Factors V and VII are usually thought of as " accelerators " of prothrombin conversion because they are necessary for the rapid conversion of prothrombin to thrombin in the presence of brain thromboplastin. This conception is valid because brain extract does not contain a complete thromboplastin ; it replaces part of the normal intrinsic thromboplastin system, but is incomplete because it lacks factors V and VII (Biggs, Douglas, and Macfarlane, 1953b (Merskey, 1950(Merskey, , 1951, and after transfusion with normal blood the clotting time of haemophilic patients may be restored to normal while the defect must remain uncorrected because the haemorrhage continues.In spite of the number of factors involved and the apparent complications of the reactions which produce thromboplastin, the thromboplastin generation test (Biggs, Douglas, and Macfarlane, 1953a) is simple to carry out and to interpret. Using this test together with the one-stage "prothrombin " time, it is possible readily to distinguish between deficiencies in the various factors which react to form thromboplastin. It is the purpose of this communication to describe the application of the thromboplastin generation test to the study of various coagulation abnormalities. Factor V was present in normal amounts in the blood of all of the patients studied. Factor V deficiency is not considered in this investigation. TechniqueCollection of Blood.-Venous blood is collected from a normal subject and the patient under investigation. Part of each sample is citrated by adding 1 part of 3.8% sodium citrate to 9 parts of blood. The plasma is separated after centrifuging at 2,000 r.p.m. for 15 minutes. Five millilitres of blood will suffice for the thromboplastin-generation test.

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The ability to measure cyclic changes in myocardial sarcomere lengths and orientations during cardiac ejection and filling would improve our understanding of how the cellular processes of contraction relate to the pumping of the whole heart. Previously, only postmortem sarcomere measurements were possible after arresting the heart in one state and fixing it for histology. By combining such histological measurements with direct observations of the deformation experienced by the same myocardial region while the heart was beating, we have developed a method to reconstruct sarcomere lengths and orientations throughout the cardiac cycle and at several transmural layers. A set of small (1 mm) radiopaque beads was implanted in approximately 1 cm3 of the left ventricular free wall. Using biplane cineradiography, we tracked the motion of these markers through various cardiac cycles. To quantify local myocardial deformation (as revealed by the relative motion of the markers), we calculated the local deformation gradient tensors. As the heart deforms, these describe how any short vectorial line segment alters its length and orientation relative to a reference state. Specifically, by choosing the reference state to be the arrested and fixed heart and by measuring the sarcomere vector in that state, we could then use the deformation gradient tensors to reconstruct the sarcomere vector that would exist in the beating heart. As ventricular chamber volume varied over its normal range of operation, the range of reconstructed sarcomere lengths (approximately 1.7-2.4 microns) was comparable to other histological studies and to measurements of sarcomere length in excised papillary muscles or trabeculae. The pattern of sarcomere length changes was markedly different, however, during ejection vs. filling.

Study objective -Seasonality of coronary heart disease (CHD) was examined to determine whether fatal and non-fatal disease have the same annual rhythm. Design -Time series analysis was carried out on retrospective data over a 10 year period and analysed by age groups (<45 to >75 years) and gender. (under 45 years) admitted to hospital there was a dominant spring peak and an autumn trough. A bimodal pattern of spring and winter peaks was evident for hospital admissions in older male age groups: with increasing age the spring peak diminished and the winter peak increased. In contrast, female hospital admissions showed a dominant winter/summer pattern of seasonal variation. In male and female CHD deaths seasonal variation showed a dominant pattern of winter peaks and summer troughs, with the winter peak spreading into spring in the two youngest male age groups. CHD incidence in women showed a winter/summer rhythm, but in men the spring peak was dominant up to the age of 55. Conclusions -The male, age related spring peak in CHD hospital admissions suggests there is an androgenic risk factor for myocardial infarction operating through an unknown effector mechanism. As age advances and reproduction becomes less important, the well defined winter/summer pattern of seasonal variation in CHD is superimposed, and shows a close relationship with the environment, especially temperature, or the autumn and early winter fall in temperature. (J Epidemiol Community Health 1995;49:575-582) Studies of seasonal variation in coronary heart disease (CHD) are almost entirely based on data derived from national registers of deaths. Studies based on seasonal variation of CHD hospital admissions are few. Dunnigan et all found a bimodal pattern of seasonal variation with spring and winter peaks in a study of 47 281 admissions to all Scottish hospitals in 1962-66 in the diagnostic category ICD 420

Background -In Western societies there is a winter peak in mortality, largely accounted for by respiratory and cardiovascular deaths. In view of the known seasonal variation in vitamin D, and of the postulated link between tuberculosis and vitamin D deficiency, a study was undertaken to examine whether the presentation of tuberculosis had the same seasonal rhythm as other pulmonary infections. Methods -Using cosinor analysis the presence or absence of seasonality was determined for 57 313 tuberculosis notifications for England and Wales. OPCS data in four weekly notifications over a 10 year period were examined as two quinquential sets (1983-7 and 1988-92 (Thorax 1996;51:944-946)