Guided waves-based damage identification in plates through an inverse Bayesian process.

The use of guided waves to identify damage has become a popular method due to its robustness and fast execution, as well as the advantage of being able to inspect large areas and detect minor structural defects. When a travelling wave on a plate interacts with a defect, it generates a scattered field that will depend on the defects geometry. By analysing the scattered field, one can thus characterize the type and size of the plate damage. A Bayesian framework based on a guided waves interaction model for damage identification of infinite plate for the first time is presented here. A semi-analytical approach based on the lowest order plate theories is adopted to obtain the scattering features for damage geometries with circular symmetry, resulting in an efficient inversion procedure. Subsequently, ultrasound experiments are performed on a large aluminium plate with a circular indentation to generate wave reflection and transmission coefficients. With the aid of signal processing techniques, the effectiveness and efficiency of the proposed approach are verified. A full finite element model is used to test the damage identification scheme. Finally, the scattering coefficients are reconstructed, reliably matching the experimental results. The framework supports digital twin technology of structural health monitoring.

Limb blood flow in treated hyperlipoproteinaemic patients with peripheral vascular disease. A preliminary report.

Fourteen patients with hyperlipoproteinaemia and peripheral vascular disease have been investigated to determine the effect on limb blood flow of hypolipidaemic therapy. Satisfactory lowering of serum lipoprotein levels was achieved in the treated group. There was a significant deterioration in peak reactive blood flow measurements in the placebo group compared with the treated group. Treatment of hyperlipoproteinaemia may, therefore, be of value in preventing the progression of peripheral atherosclerosis.

Regulation of cholesterol synthesis in the hyperlipoproteinaemias. Polymorphonuclear leucocyte abnormality specific to familial type II hypercholesterolaemia.

A simple procedure has been devised to give virtually pure preparations of polymorphonuclear leucocytes. This has permitted study of the regulation of cholesterol biosynthesis at cell level. Freshly isolated cells from donors with various forms of hyperlipoproteinaemia have been shown to have very low levels of cholesterol synthesis, presumably due to high circulating levels of apoprotein-B in donor plasma [1]. The activity of the rate-limiting enzyme for cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase, rapidly increases as the cells are incubated in lipoprotein-deficient medium, until, by 12 h, cells from patients heterozygous for familial type IIa hypercholesterolaemia are clearly distinguished from other hyperlipoproteinaemias. The possible significance of this finding is discussed in relation to the causation and treatment of atherosclerotic disease.

The effects of cholestyramine on high density lipoprotein metabolism.

This study on 4 type II hyperlipoproteinaemic subjects examines the effects of pharmacologic doses (8 g twice daily) of the bile acid sequestrant cholestyramine on the plasma distribution and chemical composition of the high density lipoprotein subfractions, HDL2 and HDL3, and describes the influence of the drug on the metabolism of the major HDL aporoteins, apolipoprotein A-I and A-II. Cholestyramine lowered plasma low density lipoprotein cholesterol (32%; P less than 0.05) without affecting the level of that lipid in very low density or high density lipoproteins. However, the plasma HDL2/HDL3 ratio and apolipoprotein A-I concentration rose significantly on treatment, while apolipoprotein A-II remained unchanged. The rise in apolipoprotein A-I derived from an increase in its synthetic rate and produced a relative enrichment of the protein with respect to apolipoprotein A-II in both HDL subfractions. These results demonstrate the cholestyramine treatment affects HDL metabolism in a way which, according to current concepts, may prove beneficial to the recipient.

Beta-adrenoreceptor blockade in hypertension.

There is good evidence from many sources that beta-adrenoreceptor blockade is an effective form of therapy in mild, moderate and severe hypertension either alone or in combination with other antihypertensive agents. Although a number os such beta blocking compounds are now available, they appear to have a hypotensive effect of approximately equal magnitude. This hypotensive effect is obtained in both the supine and standing positions thus avoiding postural hypotension. The maximum hypotensive effect may take some time to become apparent. Despite considerable work the mode of action remains uncertain, reduction in cardiac output, resetting of baroreceptors, reduction in plasma renin and a central nervous system effect have been suggested but remain unproved. There is evidence to suggest that these compounds can control, to some degree, the surges in blood pressure resulting from either mental or physical stress. A low incidence of serious side effects has been reported by many workers. Only the long-term use of these compounds in comparison with other antihypertensive agents will determine their place in the management of hypertension.

Acylated streptokinase--plasminogen complex in patients with acute myocardial infarction.

BRL 26921 is the p- anisoyl derivative of the primary streptokinase-human plasminogen complex in which the acyl group is specifically located at the catalytic centre of the enzyme. Doses of BRL 26921 ranging from 5 mg to 25 mg were given intravenously or into a coronary artery to 12 patients with acute myocardial infarction. The complex was well tolerated and produced no serious bleeding. Coronary artery reperfusion was demonstrated angiographically in three patients. In most patients, fibrinogen, plasminogen, alpha 2 antiplasmin and alpha 2 macroglobulin levels fell and the level of fibrinogen degradation products increased acutely post treatment indicating systemic fibrinolytic activation. The degree of this activation was variable but was profound in some. It appeared to be dose related and modified by the presence of streptokinase antibodies. BRL 26921 appears less "selectively" thrombolytic in patients than had been expected from animal models.

Increased plasma fibrinogen and platelet-aggregates in type II hyperlipoproteinaemia.

Plasma fibrinogen and platelet-aggregates (method of Wu and Hoak) were measured in 21 patients with familial Type II hyperlipoproteinemia and 21 matched control subjects. Patients with hyperlipoproteinaemia had increased levels of fibrinogen and platelet-aggregates (p less than 0.01). Young patients with hyperlipoproteinaemia had prematurely high fibrinogen levels, and the normal rise in fibrinogen during adult life was abolished. There were no statistically significant correlations within the patient group between fibrinogen, platelet-aggregates, and plasma lipids. High fibrinogen and platelet-aggregate levels may play a part in the development of the premature arterial disease associated with Type II hyperlipoproteinaemia, or may be markers of arterial injury.

The effects of propranolol and acebutolol on left ventricular function and coronary haemodynamics in the conscious dog with myocardial ischaemia.

1 The cardiovascular effects of the beta-adrenoceptor blocking drugs, propranolol and acebutolol, on regional coronary blood flow and left ventricular function have been investigated in the conscious dog with developing myocardial infarction. 2 Propranolol (1 to 1.5 mg/kg) or acebutolol (4 to 5 mg/kg) were administered intravenously 2 to 3 h after occlusion of the left anterior descending coronary artery. 3 Propranolol or acebutolol administration resulted in a relative increase in flow to the ischaemic area of the myocardium, particularly to the subendocardium. 4 Propranolol produced a greater reduction in heart rate and myocardial contractility than acebutolol. 5 These results demonstrate that beta-adrenoceptor blocking drugs reduce myocardial oxygen consumption and increase coronary flow to the ischaemic area of the myocardium after coronary artery occlusion in the conscious dog.

The effects of a new beta-adrenoceptor blocking compound, tolamolol, on haemo-dynamics and myocardial function in man.

1 The effects of tolamolol on haemodynamics and myocardial contractility were investigated in two groups of six patients undergoing diagnostic cardiac catheterization.2 The intravenous administration of tolamolol (0.15 mg/kg) produced a significant fall in heart rate from a control value (87 +/- 7 to 62 +/- 3 beats/min) 5 min after administration and a concomitant fall in cardiac output from 4.7 +/- 0.9 to 3.5 +/- 0.8 litres/minute. There was no significant change in systemic blood pressure, pulmonary artery blood pressure or stroke volume.3 There was no change in left ventricular end diastolic pressure after tolamolol. There was a fall in the maximum rate of rise of the left ventricular pressure (LV dp/dt(max)) and the derived index of the left ventricular contractile state (V(max)).4 These results suggest that tolamolol has a predominantly negative chronotropic but also a lesser negative inotropic action on the heart.

Hypothalamo-pituitary-thyroid axis function during cardiopulmonary bypass.

Marked alterations in levels of circulating thyroid hormone were found in patients undergoing cardiopulmonary bypass with a rise in the free thyroxine and a fall in the free triiodothyronine levels. Studies using thyrotropin-releasing hormone during bypass demonstrated a blunted response to this stimulus. This reduced response is related to changes in thyroid hormone levels and it is suggested that bypass surgery may have a direct inhibitory action on thyroid-stimulating hormone release at the hypothalamo-pituitary level. The potential significance of these hormonal changes is discussed.

Study of the pedigree of a patient with type 3 hyperlipoproteinaemia and sinking prebeta lipoprotein.

A 49-year-old woman, suffering from peripheral vascular disease, was found to have two lipoprotein abnormalities, namely, type III hyperlipoproteinaemia and sinking prebeta lipoprotein. Twenty-one members of the kindred were investigated in an attempt to determine the pattern of inheritance of both of these abnormalities. In a 21-year-old son of the proband plasma electrophoresis was in keeping with a type V hyperlipoproteinaemia. It is suggested that this may be a stage in the development of the characteristic type III pattern. If this is so it is consistent with previous suggestions of an incompletely penetrant single autosomal allele. Sinking prebeta lipoprotein was found in the plasma of two other members of the family. If this abnormality is also inherited as a single autosomal allele it must have a very low penetrance and the possibility that the abnormality is acquired cannot be excluded.

Low density lipoprotein metabolism in a family of familial hypercholesterolemic patients.

A low-density lipoprotein turnover study was performed on six heteroxygous familial hypercholesterolemic subjects and five control subjects. The diagnosis of the condition was clear-cut on biochemical, clinical, and genetic grounds. Kinetic analysis of the plasma decay curves gave the following mean values: (1) The plasma concentration of low density lipoprotein apoprotein (apoLDL) in the affected subjects was 247 mg/dl, a 2.5-fold increase over control values (98 mg/dl). (2) The calculated fractional catabolic rate of the intravascular apoLDL pool in the dyslipo-proteniemics was reduced with respect to control data (16.4%/day versus 31.2%/day), and the half-life of the apolipoprotein was correspondingly increased (6.07 days versus 3.63 days). (3) The absolute catabolic rate of the apoLDL was 15.6 mg/kg/day in contrast to the lower value of 11.6 mg/kg/day in the control group. (4) A strong negative correlation was observed between the plasma apoLDL concentration and the fractional catabolic rate (r = 0.96). We conclude from our data that increased apoLDL synthesis coupled with a defective or saturated catabolic mechanism is implicated in the pathogenesis of familial hypercholesterolemia.

Relationship of plasma uric acid to plasma lipids and lipoproteins in subjects with peripheral vascular disease.

Hyperuricaemia and hyperlipidaemia (elevated fasting plasma cholesterol or triglycerides) were frequently found in 219 males and 63 females with peripheral vascular disease (PVD). The subjects were divided into sexes and the uric acid, cholesterol and triglyceride concentration adjusted for the effects of age and obesity by multiple regression analysis. Followig this no significant relationship was found between uric acid and cholesterol or triglyceride. When the males with PVD were divided into lipoprotein types it was found that those who were normo-lipoproteinaemics or who had type IV hyperlipoproteinaemia (HLP) had a significantly higher mean uric acid level. The other types had a mean uric acid concentration similar to that found in 25 healthy normolipoproteinaemic males. The discrepancy between this result and the lack of correlation between uric acid and triglyceride noted above is presumably due to the complex effects of age and obesity. In the females no significant increase in the mean uric acid concentration was found in any of the lipoprotein groups.

Plasma apolipoprotein A levels in healthy human adults.

The apolipoprotein A concentration in the plasma of ten healthy human subjects was measured immunologically on three occasions at monthly intervals and the following results recorded. 1. There was no difference between fasting and non-fasting apoprotein A concentrations. 2. Apoliportein A levels were higher in females than in males (p less than 0.001). 3. The correlation coefficient calculated for high density lipoprotein cholesterol and apolipoprotein A was 0.62. 4. The apoprotein values varied widely between subjects and ther were considerable concentration differences from month to month in the plasma of each individual.

Lipoprotein concentrations in untreated adult onset diabetes mellitus and the relationship of the fasting plasma triglyceride concentration to insulin secretion.

Plasma lipoprotein concentrations in 64 untreated adult onset diabetics were compared to the lipoprotein levels found in non diabetics. No significant difference was found. The relationship of the fasting plasma triglyceride concentration to the plasma immunoreaction insulin response to 50 g glucose orally was investigated. Using correlation analysis a significant and insulin response in the non diabetics but not in the diabetics.

The relationship between the cholesterol content and subfraction distribution of plasma high-density lipoproteins.

High density lipoprotein subfractions (HDL2 and HDL3) were separated from the plasma of 25 healthy volunteers (13 males, 12 females) rate zonal ultracentrifugation. The rotor elution profile, measured at 280 nm, was used with the specific extinction coefficient for each subfraction (HDL2, 0.60 +/- 0.11 mg protein/A280nm, HDL3, 0.86 +/- 0.10 mg protein/A280nm (n=25) to calculate their plasma concentration. Their protein and lipid composition were also determined by chemical analysis. Plasma lipids, lipoprotein cholesterol, apolipoprotein A-I, apolipoprotein A-II and apolipoprotein B levels were measured in the same subjects and correlated with the HDL subfraction concentrations. HDL cholesterol and apolipoprotein A-I concentrations correlated significantly (p less than 0.01 and 0.02 respectively) with plasma HDL2, but not with HDL3. Indeed, the significantly higher levels of HDL cholesterol and apolipoprotein A-I in the female group could be attributed entirely to an increase in circulating HDL2. This data supports the proposal that the latter subfraction is the major contributor to the anti-atherogenic role of plasma HDL.

Oestrogens and progestogens for preventing and treating postnatal depression.

BACKGROUND: Postnatal depression, with a prevalence of at least 10%, is probably the most common complication of the puerperium. A deficiency or imbalance of sex hormones has repeatedly been suggested as a cause. OBJECTIVES: The objective of this review was to evaluate the role of oestrogens and progestogens in the prevention and treatment of postnatal depression. SEARCH STRATEGY: The register of clinical trials maintained and updated by the Cochrane Pregnancy and Childbirth Group. SELECTION CRITERIA: All trials were considered in which pregnant or postpartum women (up to 18 months) were randomised to receive postpartum oestrogen or progestogen or placebo for the treatment or prevention of postnatal depression. DATA COLLECTION AND ANALYSIS: Two published randomised placebo controlled trials were identified for inclusion in the analyses for this review. One study was excluded. MAIN RESULTS: Depot norethisterone enanthate given within 48 hours of delivery and lasting 8-12 weeks was associated with significantly higher postpartum depression scores than placebo. Oestrogen therapy in severely depressed women was associated with a greater improvement in depression scores than placebo. REVIEWER'S CONCLUSIONS: There is no place for synthetic progestogens in the prevention of treatment of postnatal depression. Long-acting norethisterone enanthate is associated with an increased risk of postnatal depression. It and other long-acting progestogen contraceptives should be used with caution in the postnatal period, especially in women with a history of depression. The role of progesterone in the prevention and treatment of postnatal depression has yet to be evaluated in a randomised placebo-controlled trial. Oestrogen therapy may be of modest value at a late stage of severe postnatal depression. Its role in the prevention of recurrent postnatal depression has not been evaluated. Further research on its value is unlikely for ethical reasons.

Long-term comparison of metoprolol and methyldopa in the treatment of hypertension.

The effect of the cardioselective beta-adrenoreceptor blocking compound, metoprolol, was compared with methyldopa in the long-term management of hypertension. Thirty patients given metoprolol and twenty-six given methyldopa were treated for 2 years. The maximum dose of metoprolol was 200 mg twice daily (average 308 mg) and of methyldopa 1,000 mg twice daily (average 1,120 mg). Blood pressure was similar at entry to the study (metoprolol 177/110 mmHg and methyldopa 181/111 mmHg). After 2 years of treatment the blood pressure levels were again similar (metoprolol 149/91 mmHg and methyldopa 148/91 mmHg). Erect pressures were lower in the methyldopa group, but there was no difference between supine and erect blood pressure levels in those on metoprolol. At an exercise load of 300 and 600 kpm the increase in systolic pressure was significantly less in the metoprolol group. The proportional increase in systolic and diastolic pressure in response to a standardized stress situation was reduced by treatment with metroprolol but not by methyldopa. Tolerance to therapy did not develop in either group. The main difference between metoprolol and methyldopa was in the incidence and severity of side effects. Four patients were withdrawn from the metoprolol group. Seventeen were withdrawn from the methyldopa mainly because of side effects including drowsiness, depression, skin rash, and impotence. Six patients on metoprolol and seventeen on methyldopa continued on therapy although side effects were present. It is concluded that metoprolol and methyldopa lower blood pressure to the same extent, but metoprolol is advantageous because of a lower incidence of side effects.