Unconventional T-H phase diagram in the noncentrosymmetric compound Yb2Fe12P7.

The temperature-(T-)magnetic-field (H) phase diagram for the noncentrosymmetric compound Yb(2)Fe(12)P(7), [corrected] determined from electrical resistivity (ρ), specific heat (C), and magnetization (M) measurements on single crystal specimens, is reported. This system exhibits a crossover from a magnetically ordered non-Fermi-liquid (NFL) phase at low H to another NFL phase at higher H. The crossover occurs near the value of H where the magnetic ordering temperature (T(M)) is no longer observable in C(T,H)/T and ρ(T,H), but not where T(M) extrapolates smoothly to T=0 K at a possible quantum critical point (QCP). This indicates the occurrence of a quantum phase transition between the two NFL phases. The lack of a clear relationship between the extrapolated QCP and NFL behavior suggests an unconventional route to the NFL ground states.

Esophageal injury from thoracic pedicle screw placement in a polytrauma patient: a case report and literature review.

The authors present a case report illustrating a visceral complication that may occur as result of thoracic pedicle screw placement. The case describes the previously unreported occurrence of esophageal impingement secondary to anterior vertebral body perforation by a pedicle screw at the third thoracic vertebra. This case highlights the challenge of thoracic pedicle screw placement and the importance of preoperatively measuring the maximum anterior-posterior dimension of the vertebral body.

Platelets in the prediction of thrombotic risk.

A study is reported which tries to identify those members of the general population who may be at increased risk of vascular disease. It is probable that patients who have had previous thrombotic episodes are inherently more at risk of further episodes and that a thrombus many months ago will not affect current tests. Accordingly we carried out a number of tests involving platelets on 'controls', and on patients with a past history of either myocardial infarction or deep vein thrombosis (DVT) and patients suffering from intermittent claudication who also are assumed to be at higher risk than the controls. Differences were demonstrated between controls and patient groups and these differences were utilized to develop statistical functions with the ability to discriminate between the groups. The functions were then tested using a second set of data from similar groups. Those designed to discriminate between myocardial infarction patients and controls and between patients with claudication and controls were validated. The heparin thrombin clotting time was found to be the prime predictor variable; the platelet count, platelet volume, platelet factor 3 clotting time and the bleeding time have some predictive value. The antithrombin clotting time, platelet aggregation and platelet adhesiveness tests as measured were not found to have discriminating potential. It is suggested that these appropriate risk functions could be of practical value in identifying members of the general population who may be at greater risk than average. The discriminate functions for DVT patients and controls could not be validated, suggesting differences in platelet involvement in arterial and venous thrombosis.

Gender and employment grade differences in blood cholesterol, apolipoproteins and haemostatic factors in the Whitehall II study.

In the first Whitehall study, plasma cholesterol was a strong predictor of coronary heart disease (CHD) but it showed a positive association with grade of employment: the higher the grade the higher the level. Because it could not explain the higher rate of CHD in lower employment grades, further investigation of biochemical CHD risk factors has been conducted with data from the baseline examination of the Whitehall II cohort in 1985-88. These data also allow investigation of gender differences and the effect of menopause. Serum cholesterol (6860 men and 3374 women) and apolipoproteins A-I and B (apo AI and apo B) were measured in those aged 35-55 working in the London offices of twenty Civil Service departments. Plasma fibrinogen and factor VII were determined in 45-55 year olds. The apo B/apo AI ratio (95% confidence interval) after age adjustment is lowest in premenopausal women: 0.557 (0.549-0.565), intermediate in postmenopausal women: 0.601 (0.589-0.613) and highest in men: 0.703 (0.698-0.709). After age adjustment fibrinogen is higher in postmenopausal (2.90 (2.85-2.95) g/l) than in premenopausal women (2.78 (2.71-2.84) g/l), who have higher levels than men (2.64 (2.62-2.67) g/l). A positive association with employment grade is seen for apo AI and a negative association is seen for fibrinogen, apo B (women only) and the apo B/apo AI ratio, after age adjustment. These patterns are consistent with the higher rates of CHD in lower grades. Cholesterol and factor VII show no gradient with our sensitive measure of social position. After adjusting for the effects of smoking rates, alcohol consumption, exercise and dietary pattern, as well as age, ethnicity, body mass index and report of symptoms, the regression coefficient for apo AI on employment grade is reduced by 43% in men and 70% in women. Corresponding reductions for fibrinogen are 53% and 65%. These attenuations suggest that a considerable part of the social gradients in apo AI and fibrinogen are explained by variations in health related behaviours. The remaining gradients may represent effects independent of these behaviours.

Effects of a fish oil supplement on serum lipids, blood pressure, bleeding time, haemostatic and rheological variables. A double blind randomised controlled trial in healthy volunteers.

Sixty male volunteers were randomised to take 10-16 ml of a fish oil supplement (MaxEPA) or 10-16 ml of olive oil for a period of 3-6 weeks. A fall in serum triglyceride of 54% (P less than 0.01) and a fall in diastolic blood pressure of 7% (P less than 0.05) was attributable to taking fish oil supplements. The bleeding time was prolonged by 12%, but this did not reach conventional levels of statistical significance. A global test of heparin-neutralising activity, the heparin thrombin clotting time, increased by 14% (P = 0.05) but there was no demonstrable effect on thrombin time, fibrinogen or (intraplatelet) platelet factor 4. A fall in red cell pore transit time of 23% was attributable to fish oil, but was not statistically significant. There was no convincing evidence of an effect of fish oil supplementation on total serum cholesterol, HDL-cholesterol, blood counts or platelet aggregation. A beneficial effect of fish oil on the cardiovascular risk profile was confirmed in this study. However, with this regime changes in total cholesterol, HDL-cholesterol and platelet aggregation are of unlikely clinical importance.

The heparin-mobilisable pool of platelet factor 4: a comparison of intravenous and subcutaneous heparin and Kabi heparin fragment 2165.

Some clinical advantages are claimed for low molecular weight heparin so the mobilisation of platelet factor 4 (PF 4) from the endothelial pool by the heparins may be relevant. Unfractionated (UF) heparin has been compared with Kabi heparin fragment 2165. A single intravenous (i.v.) injection of 60 iu/kg heparin was compared with 5000 anti-Xa units of Kabi-2165. Less PF 4 was mobilised by Kabi-2165 and some apparently remained in the pool and was released when the pool was subsequently challenged by giving i.v. heparin. Subcutaneous (s.c.) injections of 5000 iu heparin twice daily were compared with 5000 anti-Xa units of Kabi-2165 once daily, each given for a week. The plasma PF 4 was never raised yet when finally challenged with i.v. heparin the pool was "empty" or refractory after the s.c. heparin but some PF 4 remained after the s.c. Kabi-2165. The two glycosaminoglycans (GAGs) had widely differing half-lives but the t/2 of the PF 4 mobilised by the two GAGs was similar even though the PF 4 is apparently bound to the GAG.

Intra-platelet platelet factor 4 (IP.PF4) and the heparin-mobilisable pool of PF4 in health and atherosclerosis.

Some patients with clinical evidence of atherosclerosis and others with diabetes were compared with appropriate controls. The intraplatelet level of platelet factor 4 (PF4) was significantly decreased in the arteriopaths and was lower in the diabetics when compared with controls. Patients with transient ischaemic attacks and stroke have even lower values. Intravenous heparin liberates large amounts of PF4 from an unknown reservoir, perhaps the endothelium, into the plasma. Arteriopaths liberated significantly more PF4 than the controls and the diabetics most. If a second heparin injection is given 24 hr after the first, the resultant plasma PF4 level was on average half that achieved after the first injection and again the patients had higher levels than the controls. Thus the reservoir originally "emptied" of PF4 by the heparin had been partially refilled in 24 hr and the reservoir in the atherosclerotic patients then contained more than the controls. Patients with atherosclerosis and especially diabetics differ from controls in the PF4 content of their platelets and in their response to heparin and in the rate of refill of the "heparin-mobilisable pool of PF4".

The effect of ICI 55,897 and clofibrate on platelet function and other tests abnormal in atherosclerosis.

There is considerable evidence that the quantity or quality of plasma lipids influences platelet function tests, and clofibrate reduces high plasma lipids and alters some platelet tests. Clofibrate was accordingly given to patients with vascular disease who were at risk of thrombosis. The heparin thrombin clotting time (HTCT), initially short and thus possibly reflecting increased activation, was regularly returned to normal after about a month's delay. The fibrinogen was also normalized but the initially abnormal anti-thrombic activity became more abnormal. ICI 55,897, an analogue of clofibrate, also normalized the HTCT and the fibrinogen and had no adverse effect on the anti-thrombin levels. This compound has no effect on plasma lipids. If it can be shown that the correction of abnormal tests conveys clinical benefit these findings suggest that ICI 55,897 might clinically be more beneficial than clofibrate. However, direct comparison of clofibrate and ICI 55,897 suggests that clofibrate is more effective in normalizing the HTCT. The mechanism underlying these drug-induced changes are unknown but they cannot be directly related to lipid changes.

Platelet function in acute myocardial infarction patients compared with controls.

A considerable number of tests were carried out comparing 33 patients with acute myocardial infarction (MI), 13 patients with chest pain (CP) and 47 controls. There was some evidence that the plasma platelet factor 4 (PF4) was different in the three groups. The heparin neutralizing activity (HNA) of platelet poor plasma was increased in the MI patients relative to the controls and the intra-platelet HNA was decreased. Malondialdehyde (MDA) formation by platelets maximally stimulated by thrombin was decreased in MI whilst the plasma 5-hydroxyindoles (5HIs) in MI was greatly increased. The acute phase proteins alpha 1 acid glycoprotein and fibrinogen were significantly raised in MI. The results in the CP group were intermediate between the MI and the controls. These findings define more precisely the changes in acute MI and are relevant to the concept of exhausted platelets.

The association of platelet and red cell count with platelet impedance changes in whole blood and light-scattering changes in platelet rich plasma: evidence from the Caerphilly Collaborative Heart Disease Study.

This epidemiological study was undertaken to explore possible relationships among various haematological indices, prevalent ischaemic heart disease and platelet "function" as measured by two rather different methods. ADP-induced platelet impedance changes in whole blood were strongly associated with prevalent ischaemic heart disease in a general population of 49-66 year men at increased risk. Adenosine diphosphate (ADP) induced platelet aggregation in platelet rich plasma (PRP) at a constant platelet count and also the whole blood platelet count and red cell (RBC) count were strongly and independently related to ADP-induced platelet impedance changes. Both platelet count and platelet aggregation in PRP assessed by changes in optical density were directly related to increasing platelet "sensitivity" as measured by impedance changes in whole blood but RBC count was inversely related. Positive independent relationships between platelet impedance changes and plasma viscosity and fibrinogen were markedly attenuated when platelet count was taken into account, but this finding does not discount a role for these factors in platelet aggregation. No relationship was noted between white blood cell (WBC) count and platelet impedance changes; however, a significant inverse relationship was noted with platelet aggregation in PRP. These findings indicate that laboratory-based experimental findings can be observed in population based studies, and that these haematological factors may be important indicators of ischaemic disease in the population.

Some effects of mucopolysaccharide stains on platelet aggregation.

FIVE MUCOPOLYSACCHARIDE STAINS INHIBIT PLATELET AGGREGATION INDUCED BY SEVERAL AGGREGATING AGENTS: with two stains inhibition is competitive. Alcian blue, 0.05 mg/ml, added to platelet-rich plasma potentiates ADP-induced aggregation. Alcian blue, 0.5 mg/ml, itself produces platelet aggregation, probably causing the release reaction. Three of these stains produce aggregation of red cells. They also bind heparin, and so may influence heparin-neutralizing sites (platelet factor 4) and probably the charge on the platelet membrane. The only known common factor to these stains is their ability to bind onto the mucopoly-saccharides. It is suggested that when platelets are ;stained' the surface mucopolysaccharide is altered and that this alteration can influence platelet aggregation.

A comparison of an effect of different anti-inflammatory drugs on human platelets.

Different doses of aspirin, indomethacin, paracetamol, benorylate, and sodium salicylate were taken by four volunteers. The minimal dose that altered a platelet function test and the persistence of this alteration at different dose levels were studied. Minute doses of indomethacin (0.035 mg/kg) were effective but the effect of even a large single dose did not persist. A tenth of the therapeutic dose of aspirin (1 mg/kg) was effective, and higher doses altered the platelets' function for several days. Benorylate in a high therapeutic dose gave aspirin-like results. Paracetamol and sodium salicylate were relatively inactive. The persistence of the aspirin effect may be related to the acetyl group. These findings are surveyed in relation to a general theory of the action of anti-inflammatory drugs.

Some interactions between human platelets and glass: von Willebrand's disease compared with normal.

If native or heparinized blood is passed slowly through a column of glass beads at room temperature, the number of platelets removed from the initial drop emerging from the column is less than that removed from the final drop. At 4 degrees C. this difference disappears. If the blood is passed rapidly through such columns at room temperature fewer platelets are removed, but the initial-final difference persists. Von Willebrand's platelets are removed normally at slow speeds; at fast speeds abnormally few platelets are removed. Platelets emerging from all such columns are in aggregates. On adding glass beads to normal heparinized plasma, the platelets at once become more rounded and after about 50 seconds' delay they aggregate: the delay and rate of aggregation can be quantitated. Aggregation occurs best at 20 to 30 degrees C. and is not inhibited by the addition of some enzyme inhibitors. In von Willebrand's disease all these glass-induced aggregation phenomena occur normally and aggregation in response to adenosine diphosphate (ADP), serotonin creatinine sulphate (5-HT), adrenaline, collagen, and glass is also normal.

Effect of aggregating agents and their inhibitors on the mean platelet shape.

The ;swirling' seen when platelet-rich plasma is stirred is caused by the average asymmetry of the platelets and a technique for recording the swirling is reported. After the addition of adenosine diphosphate, 5-hydroxytryptamine, thrombin, and collagen, platelets become rounded and more symmetrical immediately before they become sticky. Monoiodo-acetate and adenosine prevent both the change in shape and sticking whereas E.D.T.A. and p-tosyl arginine methylester prevent sticking but the shape still changes. Adrenaline produces sticking but no change in shape. The effects of temperature and E.D.T.A. are also reported. All these findings are discussed and diagrammatic representations of some reactions are tentatively proposed.

Comparison of the effect of heparin and citrate on platelet aggregation.

When whole blood was passed through a column of glass beads, heparinized and native blood gave similar results. With citrated blood far fewer platelets were lost on the column. Thus citrate inhibits this test and heparin has no effect.Platelet-rich plasma (PRP) was prepared from citrated and heparinized blood and the responses in a number of aggregation tests were compared. With added adenosine diphosphate and adrenaline (first wave), the response in heparin PRP was greater than that in citrate PRP and was proportional to the amount of free calcium ions. With added collagen and adrenaline (second wave) the response was worse in heparin than in citrate platelet-rich plasma. It is concluded that heparin has no effect on the adhesive forces but inhibits the release mechanism. This may be of therapeutic importance.

Changes in the heparin neutralising activity of platelet poor plasma after immunisation.

Acute myocardial disease, which may be associated with abnormal platelet activity, has been reported after routine immunisation. Thirty-two army apprentices undergoing immunisation were studied for changes in the heparin neutralising activity (HNA) of platelet poor plasma. HNA increased after immunisation. This increase in HNA may represent an increase in platelet activation but may also relate to changes in acute phase proteins. These changes were not observed in elderly subjects undergoing immunisation with influenza vaccine.

Heparin neutralizing activity test in the diagnosis of acute myocardial infarction.

We have previously shown in patients after recovery from a myocardial infarct (post-MI) that the heparin neutralizing activity (HNA) in the plasma is raised and that this activity may come from platelet factor 4 derived from activated platelets. This report concerns 89 patients admitted with acute chest pain; in 54, with evidence of acute infarction, the level of HNA is much higher than in a post-MI group or controls. Over the ensuing weeks the HNA decreases to the post-MI level. In 34 patients the evidence subsequently collected excluded a diagnosis of infarction; in these there were almost always normal amounts of HNA and little overlap with the results from the patients with infarcts. This easy test is therefore likely to prove clinically useful. Its significance is discussed. The platelet count and platelet volume are both abnormal in patients with acute infarction and also in the chest pain group so these tests do not help to discriminate.

Some long term effects of smoking on the haemostatic system: a report from the Caerphilly and Speedwell Collaborative Surveys.

Data from two community studies on men from South Wales and the west of England suggest that the effects of smoking on the haemostatic system remain for many years after giving up. Long term correlations between several variables, including plasma fibrinogen and white cell count, and the length of time after giving up were seen in ex-smokers. Dose response relations were apparent in current smokers in terms of the white cell count and two haematological variables, the packed and mean cell volumes. These long term correlations probably reflect the toxicity of other agents in tobacco smoke besides nicotine and carbon monoxide, which act only in the short term. Identification of these agents may further our understanding of the mechanism by which cigarette smoking is associated with atherosclerotic disease.

Platelet aggregation and incident ischaemic heart disease in the Caerphilly cohort.

BACKGROUND: Platelets are involved in myocardial infarction but evidence of prediction of infarction by measures of platelet function are sparce. METHODS: Platelet aggregation to thrombin and to ADP in platelet rich plasma was recorded for 2176 men aged 49-65 years in the Caerphilly cohort study. RESULTS: Results from 364 men were excluded, 80 of whom had not fasted before venepuncture; most of the others were excluded because antiplatelet medication had been taken shortly before the platelet tests. During the five years following the platelet tests 113 ischaemic heart disease (IHD) events which fulfilled the World Health Organisation criteria were identified--42 fatal and 71 non-fatal. No measure of platelet aggregation was found to be significantly predictive of incident IHD. The possibility that platelet function is predictive for only a limited time after it is characterised, and that prediction falls off with time, was tested. When IHD events are grouped by their time of occurrence after aggregation had been measured, the test results show a gradient suggestive of prediction of early IHD events. Thus, 24% of the men who had an event within 500 days of the test had had a high secondary response to ADP while only 12% of those whose IHD event had been 1000 or more days after the test had shown a high platelet response at baseline. The trend in these proportions is not significant. CONCLUSIONS: Platelet aggregation to thrombin and ADP in platelet rich plasma was recorded in the Caerphilly cohort study. No measure of aggregation was found to be predictive of IHD.

A pilot study of the effect of Gemfibrozil on some haematological parameters.

In a double-blind 13 week study the effects of Gemfibrozil were compared with placebo. Gemfibrozil was given to 10 patients with evidence of severe atherosclerosis; four similar patients acted as controls. As expected, in the treated group, total cholesterol and triglycerides decreased significantly and HDL cholesterol increased. The Fibrinogen did not change although the ESR increased markedly and the heparin neutralizing activity (HNA) of the plasma decreased (p = 0.01). The antithrombic activity increased. The change in the HNA correlated weakly to the total cholesterol both before and during treatment. These findings show that some of the effects of Gemfibrozil on atherosclerotic humans are similar to those of Clofibrate but others are different.