Impact of estradiol, testosterone and their ratio on left and right auricular myofilament function in male and female patients undergoing coronary artery bypass grafting.

BACKGROUND: The impact of sex hormones on right and left auricular contractile apparatus function is largely unknown. We evaluated the impact of sex hormones on left and right heart contractility at the level of myocardial filaments harvested from left and right auricles during elective coronary artery bypass surgery. METHODS: 150 patients (132 male; 18 female) were enrolled. Preoperative testosterone and estradiol levels were measured with Immunoassay. Calcium induced force measurements were performed with left- and right auricular myofilaments in a skinned fiber model. Correlation analysis was used for comparison of force values and levels of sex hormones and their ratio. RESULTS: Low testosterone was associated with higher top force values in right-sided myofilaments but not in left-sided myofilaments for both sexes (p = 0.000 in males, p = 0.001 in females). Low estradiol levels were associated with higher top force values in right-sided myofilaments (p 0.000) in females and only borderline significantly associated with higher top force values in males (p 0.056). In females, low estradiol levels correlated with higher top force values in left sided myofilaments (p 0.000). In males, higher Estradiol/Testosterone ratio (E/T ratio) was only associated with higher top force values from right auricular myofilaments (p 0.04) In contrast, in females higher E/T ratio was associated with lower right auricular myofilament top force values (p 0.03) and higher top force values in left-sided myofilaments (p 0.000). CONCLUSIONS: This study shows that patients' comorbidities influence left and right sided contractility and may blur results concerning influence of sex hormones if not eliminated. A sex hormone dependent influence is obvious with different effects on the left and right ventricle. The E/T ratio and its impact on myofilament top force showed divergent results between genders, and may partially explain gender differences in patients with cardiovascular disease.

Individual and contextual determinants of the duration of diarrhoeal episodes in preschool children: a longitudinal study in an urban setting.

This study investigated individual and contextual factors associated with the duration of diarrhoeal episodes in 693 young children living in a large Brazilian city who were followed-up for at least 3 months. The outcome is analysed as a continuous variable, by means of a hierarchical conceptual model organizing the factors in meaningful blocks. A total of 2397 episodes were recorded (median duration 2 days, interquartile range 1-3 days). Low percentage of households connected to the sewerage system in the neighbourhood, low family purchasing power, high agglomeration, mother aged <19 years, low zinc content in child's diet, and episode severity were significantly associated with longer duration (0·26-0·69 days more). Purchasing power effect was largely mediated by environmental conditions, characteristics of the child, and hygienic behaviour. Environmental conditions acted as a possible effect modifier, enhancing the effect on duration of diarrhoea of the child not having being vaccinated against measles or breastfed for >6 months.

A simulation model for diarrhoea and other common recurrent infections: a tool for exploring epidemiological methods.

The measurement and analysis of common recurrent conditions such as diarrhoea, respiratory infections or fever pose methodological challenges with regard to case definition, disease surveillance and statistical analysis. In this paper we describe a flexible and robust model that can generate simulated longitudinal datasets for a range of recurrent infections, reflecting the stochastic processes that underpin the data collected in the field. It can be used to evaluate and compare alternative disease definitions, surveillance strategies and statistical methods under 'controlled conditions'. Parameters in the model include: characterizing the distributions of the individual disease incidence and the duration of disease episodes; allowing the average disease duration to depend on an individual's number of episodes (simulating a correlation between incidence and duration); making the individual risk of disease depend on the occurrence of previous episodes (simulating autocorrelation of successive episodes); finally, incorporating seasonal variation of disease.

Effect of HMG CoA reductase inhibitors on low-density lipoprotein cholesterol and C-reactive protein: systematic review and meta-analysis.

OBJECTIVE: HMG CoA reductase inhibitors (statins) have been claimed to decrease C-reactive protein (CRP), independent of their effect on low-density lipoprotein cholesterol (LDL-C). We conducted a systematic review and meta-analysis to investigate whether a relationship between the average effect of statins on LDL-C and CRP exists. DATA SOURCES: The literature search of the Medline and Cochrane databases between 1980 and August 2007 yielded 65 statin intervention studies with 94 treatment arms involving 16,260 patients reporting changes in both LDL-C and CRP. DATA EXTRACTION AND STATISTICAL METHOD: From each study relative changes in LDL-C and CRP were extracted. Random effects meta-analysis was used to obtain pooled summary estimates of the average study specific LDL-C and CRP reductions, in total and stratified by dose and type of statin. Weighted correlation analysis and metaregression analysis was used to investigate the relationship between the LDL-C and CRP changes adjusted for baseline values, type of statin and dose. RESULTS: Pooled summary estimates of statin-induced changes in LDL-C and CRP levels were -34.7% (95% CI: -37.7% to -31.8%) and -30.8% (95% CI: -39.4% to -22.3%), respectively. We found a positive correlation between the average LDL-C and CRP reduction (r = 0.49, p = 0.010) which increased when adjusting for pre-treatment concentrations (r = 0.79, p < 0.001). The effect of statins on CRP were strongly related to the changes in LDL-C and baseline concentrations, independent of the type and dose of statin used. CONCLUSION: Our meta-analysis shows a strong correlation between statin-induced reductions in LDL-C and CRP, which has not been evident from individual studies. Measuring CRP in addition to LDL-C in the monitoring of statin treatment is currently not warranted.

Early infection with Trichuris trichiura and allergen skin test reactivity in later childhood.

BACKGROUND: Allergic diseases cause a large and increasing burden in developed countries and in urban centres in middle-income countries. The causes of this increase are unknown and, currently, there are no interventions to prevent the development of allergic diseases. The 'hygiene hypothesis' has tried to explain the increase through a reduction in the frequency of childhood infections causing a failure to program the immune system for adequate immune regulation. Intestinal helminth parasites are prevalent in childhood in developing countries and are associated with a lower prevalence of allergen skin test reactivity and asthma. OBJECTIVES: To investigate whether children who had intestinal helminth infections during early childhood have a lower prevalence of allergen skin test reactivity later in childhood. METHODS: We re-visited a population of 1055 children from whom stool samples had been collected for detection of intestinal helminth infections for another study, and collected new stool samples and performed allergen skin prick testing. Information on potential confounding variables was collected. RESULTS: Children with heavy infections with Trichuris trichiura in early childhood had a significantly reduced prevalence of allergen skin test reactivity in later childhood, even in the absence of T. trichiura infection at the time of skin testing in later childhood. CONCLUSION: Early heavy infections with T. trichiura may protect against the development of allergen skin test reactivity in later childhood. Novel treatments to program immune-regulation in early childhood in a way that mimics the effects of early infections with T. trichiura may offer new strategies for the prevention of allergic disease.

Neonatal BCG protection against tuberculosis lasts for 20 years in Brazil.

Bacille Calmette-Guérin (BCG) efficacy against pulmonary disease is highly variable; until very recently there was no evidence of protection after 10 years. In the control arm of a trial of efficacy of revaccination of schoolchildren in Brazil we found substantial protection (39%; 95%CI 9-58) of neonatal BCG against all forms of tuberculosis (TB) 15-20 years after vaccination, much longer than previously believed. This confirms recent findings from an earlier trial, and must be considered in the design of trials of new TB vaccines and in policy decisions based on assumed lack of neonatal BCG protection with time.

Joint modelling of repeated transitions in follow-up data--a case study on breast cancer data.

In longitudinal studies where time to a final event is the ultimate outcome often information is available about intermediate events the individuals may experience during the observation period. Even though many extensions of the Cox proportional hazards model have been proposed to model such multivariate time-to-event data these approaches are still very rarely applied to real datasets. The aim of this paper is to illustrate the application of extended Cox models for multiple time-to-event data and to show their implementation in popular statistical software packages. We demonstrate a systematic way of jointly modelling similar or repeated transitions in follow-up data by analysing an event-history dataset consisting of 270 breast cancer patients, that were followed-up for different clinical events during treatment in metastatic disease. First, we show how this methodology can also be applied to non Markovian stochastic processes by representing these processes as "conditional" Markov processes. Secondly, we compare the application of different Cox-related approaches to the breast cancer data by varying their key model components (i.e. analysis time scale, risk set and baseline hazard function). Our study showed that extended Cox models are a powerful tool for analysing complex event history datasets since the approach can address many dynamic data features such as multiple time scales, dynamic risk sets, time-varying covariates, transition by covariate interactions, autoregressive dependence or intra-subject correlation.

Evaluation of five commercial enzyme immunoassays for the detection of human cytomegalovirus-specific IgM antibodies in the absence of a commercially available gold standard.

In the recent years the number of commercially available immunoassays for the detection of human cytomegalovirus (HCMV)-specific immunoglobulin M (IgM) antibodies has rapidly increased. The aim of the present study was to evaluate five commercial immunoassays for the serological diagnosis of HCMV-infection. These methods, namely the IMx CMV IgM assay, the AxSYM CMV IgM assay (both Abbott), the Gull CMV IgM, the CMV-IgM-ELA test PCS Medac and the Biotest Anti-HCMV recombinant IgM ELISA, were compared for their diagnostic effectiveness and interference with substances eventually producing cross-reactions with HCMV-IgM (Epstein-Barr-virus (EBV)-IgM, rheumatoid factor (RF)). In addition, repeated measurements on samples from kidney and heart transplant recipients with active HCMV infection were examined to compare the temporal development of the HCMV-IgM measured with the five assay systems. Since there is no commercially available gold standard, it was assumed that the true classification, of whether the patient sample is HCMV-IgM positive or negative, was unknown. Hence sensitivity and specificity were assessed based on a maximum likelihood approach using a "latent class" model. The cross-reactions were quantified by a Bayesian statistical model using prior information for the expected prevalences in the EBV-IgM and rheumatoid factor sample groups. The results of the study demonstrated that there are great differences in sensitivity and specificity as well as in cross-reactions with EBV-IgM and RF between the tested ELISAs.

Screening and diagnosis of congenital cytomegalovirus infection: a 5-y study.

Although cytomegalovirus infection is the most common infection transmitted via the placenta, there are no guidelines for routine screening to detect children congenitally infected with cytomegalovirus. From 1993 to 1997, maternal serum and cord vein blood of newborns was screened for HCMV-IgM (n = 21,183). Urine was examined for HCMV-excretion during the first postnatal week to prove HCMV infection in children who expressed HCMV-IgM in cord vein blood (n = 13) or who were born to mothers positive for HCMV-IgM in the serum (n = 234), or when both cord vein blood and maternal serum were positive for HCMV-IgM (n = 6). Congenital HCMV infection was detected in 17 newborns. To determine the incidence of congenital HCMV infection, only those mother/child pairs were selected in whom serum and cord vein blood were investigated (n = 5967 mother/child pairs). In this group 13 newborns were infected. The observed incidence for congenital HCMV infection is 0.21%. It is concluded that that this screening programme will detect those children at risk for congenital HCMV infection. These children have to be examined for virus excretion in the urine. Although the observed incidence is only 0.21%, congenital HCMV infection is a problem that can no longer be neglected because of its long-term sequelae.

Contrast-enhanced spiral CT of the head and neck: comparison of contrast material injection rates.

BACKGROUND AND PURPOSE: Contrast-enhanced spiral CT studies of the head and neck are performed frequently using contrast material volumes of approximately 30 g iodine and a scan delay of 30-45 seconds. Because little is known about the effects of contrast material injection rates on tissue enhancement, this was prospectively investigated in our study. METHODS: Ninety-seven patients underwent spiral CT of the head and neck. Each patient was assigned randomly to one of four groups who received 100 mL of nonionic contrast material (300 mg I/mL) at different monophasic injection flow rates with 1.5, 2, 3, and 4 mL/s. Scanning started after a constant delay of 35 seconds. The attenuation of the carotid artery, jugular vein, and sternocleidomastoid muscle was measured over time and the attenuation of the submandibular and thyroid gland was evaluated. Vascular attenuation of at least 150 HU was considered to be sufficient. RESULTS: The mean scan time was 33+/-5 seconds. The study, using an injection rate of 2 mL/s, showed the longest time of sufficient overall (arterial and venous) vessel attenuation (27+/-4 seconds, P< or =.008). The injection flow rate did not influence significantly muscular attenuation (mean enhancement during scan time: 9+/-7 HU). The 1.5 mL/s protocol showed the lowest attenuation values of the submandibular gland (81+/-12 HU) and the highest attenuation values of the thyroid gland (164+/-22 HU), but the attenuation of the thyroid gland was not statistically different from that revealed by the 2 mL/s protocol. CONCLUSION: Using 100 mL of intravenous contrast material with 300 mg I/mL for spiral CT studies of the entire head and neck, the optimal injection flow is 2 mL/s, whereas lower flow rates resulted in insufficient venous enhancement.