Lipid composition of serum lipoproteins in relation to gonadal hormones during the normal menstrual cycle

Twenty-two normally menstruating women were studied during one menstrual cycle. Blood was collected on 4 occasions and was analysed for free and total cholesterol and triglycerides and phospholipids in the lipoprotein fractions, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Fluctuations in lipid parameters were correlated to serum levels of estradiol-17β, progesterone, androstenedione, testosterone and sex-hormone-binding globulin (SHBG).Elevated concentrations of SHBG and HDL-cholesterol and a suppression of LDL-cholesterol were found during the luteal compared to the follicular phase and these findings were interpreted as an estrogenic influence. Consequently the ratio LDL-cholesterol/HDL-cholesterol was depressed during the luteal phase. Triglycerides in serum and VLDL reached a peak at midcycle. When effects on lipid metabolism induced by endogenous steroids were compared to lipoprotein fluctuations exerted by exogenous hormones a parallelism was found in certain variables. However, obvious discrepancies were also found in effects on lipid metabolism, especially for hormones with androgenic properties.The present data underline the necessity of defining in which menstrual phase blood has been collected when lipid metabolism is studied in women of fertile age. Knowledge about metabolic events induced by exogenous sex steroids does not allow conclusions concerning the effects exerted by corresponding endogenous hormones.     

Enhanced systolic myocardial function in elite endurance athletes during combined arm-and-leg exercise

The aim here was to employ color tissue velocity imaging (TVI), to test the hypothesis that highly trained endurance athletes exhibit enhanced systolic function of the left ventricular (LV) myocardium both at rest and during combined arm-and-leg exercise in comparison with untrained subjects. For each of the ten elite male (EG) and ten matched control participants (CG), LV dimensions and systolic function were assessed at rest using echocardiography. Subsequently, these subjects exercised continuously on a combined arm-and-leg cycle ergometer for 3 min each at 50, 60, 70, 80, 90 and 100% of VO_2max. Oxygen uptake, heart rate, systolic blood pressure (SBP) and peak contraction systolic velocities of the LV myocardium (PSV) were recorded in the end of each level. At rest, the trained and untrained groups differed with respect to LV dimensions, but not systolic function. At 60–100% VO_2max, the EG group demonstrated both higher PSV and SBP. The observation that the EG athletes had higher PSV than CG during exercise at 60–100% VO_2max, but not at rest or at 50% of VO_2max, suggested an enhanced systolic capacity. This improvement is likely to be due to an enhanced inotropic contractility, which only becomes apparent during exercise.     

Cost-effectiveness of pharmacogenetics in anticoagulation: international differences in healthcare systems and costs

Genotyping patients for CYP2C9 and VKORC1 polymorphisms can improve the accuracy of dosing during the initiation of anticoagulation with vitamin K antagonists (coumarin derivatives). The anticipated degree of improvement in the safety of anticoagulation with coumarins through genotyping may vary depending on the quality of patient care, which varies both with and among countries. The management and the cost of anticoagulant care can therefore influence the cost-effectiveness of genotyping within any given country. In this article, we provide an overview of the cost-effectiveness of pharmacogenetics-guided dosing of coumarin derivatives. We describe the organization of anticoagulant care in the UK, Sweden, The Netherlands, Greece, Germany and Austria, where a genotype-guided dosing algorithm is currently being investigated as part of the EU-PACT trial. We also explore the costs of anticoagulant care for the treatment of atrial fibrillation in these countries.     

Pennation angle dependency in skeletal muscle tissue doppler strain in dynamic contractions

Tissue velocity imaging (TVI) is a Doppler based ultrasound technique that can be used to study regional deformation in skeletal muscle tissue. The aim of this study was to develop a biomechanical model to describe the TVI strain’s dependency on the pennation angle. We demonstrate its impact as the subsequent strain measurement error using dynamic elbow contractions from the medial and the lateral part of biceps brachii at two different loadings; 5% and 25% of maximum voluntary contraction (MVC). The estimated pennation angles were on average about 4° in extended position and increased to a maximal of 13° in flexed elbow position. The corresponding relative angular error spread from around 7% up to around 40%. To accurately apply TVI on skeletal muscles, the error due to angle changes should be compensated for. As a suggestion, this could be done according to the presented model.     

High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23

Objective: Iron isomaltoside (Monofer^®) is a high-dose intravenous iron preparation with good tolerability and efficacy in inflammatory bowel disease (IBD) patients with iron deficiency anaemia (IDA). This trial evaluates the safety and efficacy, including effect on intact fibroblast growth factor 23 (iFGF23) of a high single dose and cumulative doses of iron isomaltoside in IBD patients with IDA.

Materials and methods: The trial was a prospective, open-label, multi-centre trial conducted in IBD patients with IDA. Based upon haemoglobin (Hb) levels at baseline and weight, the patients received 1500, 2000, 2500 or 3000?mg of iron isomaltoside infused in single doses up to 2000?mg. The outcome measurements included adverse drug reactions (ADRs) and changes in haematology and biochemistry parameters.

Results: Twenty-one IBD patients with IDA were enrolled, receiving 1500 (seven patients), 2000 (eight patients), 2500?mg (four patients) or 3000 (two patients) mg of iron. No serious ADRs were observed. Four patients experienced nine mild to moderate ADRs (hypersensitivity, pyrexia, vomiting, constipation, abdominal pain, dyspepsia (two events) and eye allergy (two events)). In total, 15 (75%) patients had an increase in Hb of ≥2.0?g/dL during the trial, with normalisation of ferritin. No changes in iFGF23 or clinically significant hypophosphataemia were found.

Conclusion: Rapid infusions of high-dose iron isomaltoside, administered as single doses up to 2000?mg and cumulative doses up to 3000?mg, were without safety concerns and were efficacious in increasing Hb levels in IBD patients. Iron isomaltoside did not induce profound phosphate wasting via increased iFGF23 levels.     

Long-term QALY-weights among spouses of dependent and independent midlife stroke survivors

Purpose

The aim of this study was to investigate whether the dependency of midlife stroke survivors had any long-term impact on their spouses’ QALY-weights.

Method

Data on stroke survivors, controls, and spouses were collected from the 7-year follow-up of the Sahlgrenska Academy Study on Ischemic Stroke. Health-related quality of life was assessed by the SF-36, and the preference-based health state values were assessed with the SF-6D. Spouses of dependent and independent stroke survivors were categorized according to their scores on the modified Rankin Scale. An ordinary least squares regression analysis was used to evaluate whether the dependency of the stroke survivors had any impact on the spouses’ QALY-weights.

Result

Cohabitant dyads of 247 stroke survivors aged <70 at stroke onset and 245 dyads of controls were included in the study. Spouses of dependent stroke survivors (n = 50) reported a significant lower mean QALY-weight of 0.69 in comparison to spouses of independent stroke survivors (n = 197) and spouses of controls, (n = 245) who both reported a mean QALY-weight of 0.77. The results from the regression analysis showed that higher age of the spouse and dependency of the stroke survivor had a negative association with the spouses’ QALY-weights.

Conclusion

The QALY-weights for spouses of dependent midlife stroke survivors were significantly reduced compared to spouses of independent midlife stroke survivors. This indicates that the inclusion of spouses’ QALYs in evaluations of early treatment and rehabilitation efforts to reduce stroke patients’ dependency would capture more of the total effect in dyads of stroke survivors.

     

Wave intensity wall analysis: a novel noninvasive method to measure wave intensity

Wave intensity analysis is a concept providing information about the interaction of the heart and the vascular system. Originally, the technique was invasive. Since then new noninvasive methods have been developed. A recently developed ultrasound technique to estimate tissue motion and deformation is speckle-tracking echocardiography. Speckle tracking-based techniques allow for accurate measurement of movement and deformation variables in the arterial wall in both the radial and the longitudinal direction. The aim of this study was to test if speckle tracking-derived deformation data could be used as input for wave intensity calculations. The new concept was to approximate changes of flow and pressure by deformation changes of the arterial wall in longitudinal and radial directions. Flow changes (dU/dt) were approximated by strain rate (sr, 1/s) of the arterial wall in the longitudinal direction, whereas pressure changes (dP/dt) were approximated by sign reversed strain rate (1/s) in the arterial wall in the radial direction. To validate the new concept, a comparison between the newly developed Wave Intensity Wall Analysis (WIWA) algorithm and a commonly used and validated wave intensity system (SSD-5500, Aloka, Tokyo, Japan) was performed. The studied population consisted of ten healthy individuals (three women, seven men) and ten patients (all men) with coronary artery disease. The present validation study indicates that the mechanical properties of the arterial wall, as measured by a speckle tracking-based technique are a possible input for wave intensity calculations. The study demonstrates good visual agreement between the two systems and the time interval between the two positive peaks (W1–W2) measured by the Aloka system and the WIWA system correlated for the total group (r = 0.595, P < 0.001). The correlation for the diseased subgroup was r = 0.797, P < 0.001 and for the healthy subgroup no significant correlation was found (P > 0.05). The results of the study indicate that the mechanical properties of the arterial wall could be used as input for wave intensity calculations. The WIWA concept is a promising new method that potentially provides several advantages over earlier wave intensity methods, but it still has limitations and needs further refinement and larger studies to find the optimal clinical use.     

Stunting,recovery from stunting and puberty development in the MINIMat cohort,Bangladesh

Aim

This paper aimed to analyse the association between small for size at birth, stunting, recovery from stunting and pubertal development in a rural Bangladeshi cohort.

Methods

The participants were 994 girls and 987 boys whose mothers participated in the Maternal and Infant Nutrition Interventions in Matlab trial. The birth cohort was followed from birth to puberty 2001-2017. Pubertal development according to Tanner was self-assessed. Age at menarche was determined and in boys, consecutive height measurements were used to ascertain whether pubertal growth spurt had started. The exposures and outcomes were modelled by Cox’s proportional hazards analyses and logistic regression.

Results

There was no difference in age at menarche between girls that were small or appropriate for gestational age at birth. Boys born small for gestational age entered their pubertal growth spurt later than those with appropriate weight. Children who were stunted had later pubertal development, age at menarche and onset of growth spurt than non-stunted children. Children who recovered from infant or early childhood stunting had similar pubertal development as non-stunted children.

Conclusion

Infant and childhood stunting was associated with a later pubertal development. Recovery from stunting was not associated with earlier puberty in comparison with non-stunted children.

     

Changes in Systolic and Diastolic Function Indexes Throughout Dobutamine Stress Echocardiography in Healthy Volunteers and Patients with Ischemic Heart Disease

BACKGROUND AND HYPOTHESIS: Dobutamine stress echocardiography is a well-established diagnostic method for investigating patients with suspected ischemic coronary disease. A positive test result is based on systolic parameters, but left ventricular filling parameters also are affected by myocardial ischemia. The aim of the present study was to study changes in both systolic and diastolic left ventricular variables throughout the test, including the period following it. METHODS AND RESULTS: Seven healthy control subjects (group I), 10 patients with chest pain but without significant coronary stenosis (group II), and 17 patients with significant coronary stenosis (group III) were entered in the study. Dobutamine stress echocardiography was performed according to a preset standardized protocol. Two-dimensional echocardiography and transmitral pulsed-Doppler images were stored for later analysis at rest, low dose, peak dose, and 5 minutes after termination of the dobutamine infusion. The wall motion score index increased from rest to low dose by 6.7% +/- 6.4% (P < 0.05) and to the peak dose by 39.1% +/- 9.9% (P < 0.001) in all three groups. The increase from rest to peak dose was significantly higher in groups I and II than in group III (P < 0.01). There was a significant increase in the atrial velocity-time integral (A-VTI) at peak dose in groups I and II (64.8% +/- 52.1% and 103.8% +/- 68.7%, respectively; P < 0.05 and <0.001), but no change in group III was noted. At the peak dose, A-VTI was significantly greater in groups I and II than in group III (P < 0.05). Among the 17 patients with proved coronary stenosis, 15 (88.2%) had a positive systolic response and 14 (82.3%) had a positive diastolic response, expressed as an A-VTI increase of 相似文献   

Paper discs impregnated with capillary blood. A sampling technique for immunoassays by means of DIG-ELISA and DIG-TIA

A modification of the diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA) and the diffusion-in-gel thin layer immunoassay (DIG-TIA) using paper discs impregnated with blood or serum as source of diffusion is described. Using a BSA-anti-BSA model system the suitability of this sampling and assaying technique for simple and accurate quantitation of antibodies has been demonstrated. Paper discs impregnated with blood or serum and subsequently dried could be stored at temperatures between +4 degrees C and +37 degrees C for at least six weeks without significant loss of antibody activity. Application of paper disc DIG-ELISA was exemplified by assaying anti-BSA antibodies in rabbits immunized with BSA as well as antibodies against both soluble egg antigen and adult worm extract in mice experimentally infected with Schistosoma mansoni cercariae. The simplicity and good reproducibility of this technique should make it an attractive alternative in serological screening of large population groups. Definite advantages of this technique are the possibilities to analyse quantitatively antibodies in capillary blood, rather than serum from venous blood samples, and to store sampled material for a considerable time even under such climatic conditions as often prevail in tropical countries.