[Type 2 diabetes and endocrine disrupting environmental chemical pollutants]. / Le diabète de type 2 et les polluants chimiques de l'environnement à effet perturbateur endocrinien.

Endocrine disruptors are chemicals or natural molecules able to interfere with the hormonal system of living organisms. These pollutants can promote the emergence of diseases of the endocrine system in humans or animals. In this publication, we will focus on certain families of endocrine disrupting chemicals that may contribute to the development of type 2 diabetes, a disease whose prevalence is increasing strongly in the world.

Les perturbateurs endocriniens sont des produits chimiques ou molécules naturelles capables d'interférer avec le système hormonal des organismes vivants. Ces polluants peuvent entraîner l'apparition de pathologies endocriniennes chez l'Homme ou chez l'animal. Dans cette publication, nous envisagerons le rôle possible de certaines familles de produits chimiques perturbateurs endocriniens sur l'apparition du diabète de type 2, pathologie dont la prévalence est en forte augmentation au niveau mondial.

How to achieve accurate blood culture volumes: the BD BACTEC FX blood volume monitoring system as a measuring instrument and educational tool.

Collecting adequate volumes of blood in blood culture bottles is crucial for sensitive detection of bacteremia and fungemia. Tools enabling easy collection of data on the degree of blood culture bottle filling at different hospital departments are an important step toward quality measurement and improvement. In this study, we verified the accuracy of a software tool for the monitoring of blood culture bottle filling developed by Becton Dickinson, BD blood volume monitoring system (BVMS) that was adjusted for use on plastic BACTEC bottles, and evaluated its ease of use in routine practice. In total, 538 negative plastic BD BACTEC Plus Aerobic/F blood culture bottles collected in two secondary care hospitals in Belgium were included in the study. The BVMS software demonstrated good performance, with an acceptable mean difference of - 0.3 mL or - 4.0% between the mean volume estimated by BVMS and the mean weight-based volume. Data (mean blood volume and standard deviation) and figures (box-and-whisker and histogram plots) on blood culture bottle filling are easily acquired. They provide information on the current situation in a hospital (department) and can be used as a tool for quality improvement measurements and follow-up. Caution is required when interpreting BVMS results for hospital wards where a substantial amount of the bottles collected come from patients with hematocrit values < 30%. This study demonstrated that BVMS is a reliable and easy to use tool which facilitates monitoring and coordination of optimization of blood culture bottles filling by the clinical laboratory.

Inefficacy of vancomycin and teicoplanin in eradicating and killing Staphylococcus epidermidis biofilms in vitro.

Biofilm-associated bacteria display a decreased susceptibility towards antibiotics. Routine assessment of antibiotic susceptibility of planktonic bacteria therefore offers an insufficient prediction of the biofilm response. In this study, in vitro biofilms of eight clinical Staphylococcus epidermidis strains were subjected to treatment with vancomycin, teicoplanin, oxacillin, rifampicin and gentamicin. In addition, the biofilms were subjected to combinations of an antibiotic with rifampicin. The effects on the biofilms were assessed by crystal violet staining to determine the total biofilm biomass, staining with XTT to determine bacterial cell viability, and microscopy. Combining these methods showed that treatment of S. epidermidis biofilms with glycopeptides increased the total biofilm biomass and that these antibiotics were not effective in killing bacteria embedded in biofilms. The decreased killing efficacy was more pronounced in biofilms produced by strains that were classified as 'strong' biofilm producers. Rifampicin, oxacillin and gentamicin effectively killed biofilm-associated bacteria of all tested strains. Combining antibiotics with rifampicin increased the killing efficacy without influencing the total biofilm biomass. When vancomycin or teicoplanin were combined with rifampicin, the increase in biofilm biomass was neutralised and also the killing efficacy was influenced in a positive way. We conclude that the combined methodology used in this study showed that glycopeptides were not effective in eradicating S. epidermidis biofilms but that combination with rifampicin improved the killing efficacy in vitro.

Reproductive status in adult male long-term survivors of childhood cancer.

BACKGROUND: This study assessed the long-term effects of cancer therapies on reproductive status in adult male childhood cancer survivors, evaluated the treatment-related risk factors for hypergonadotropic hypogonadism and assessed the association between the FSH levels and the later need for assisted reproductive techniques (ART). METHODS: The study cohort included adult male 5-year survivors of childhood cancer who were treated in our institution between 1966 and 2003. Data concerning patient and treatment characteristics, FSH, LH and testosterone levels and pregnancy outcome were collected. Multivariate regression analyses were performed to evaluate the treatment-related risk factors for disturbances in reproductive endocrine status. The diagnostic and predictive values of FSH and later need for ART were evaluated. RESULTS: Data on reproductive endocrine status were available for 488 survivors (86.4%) of the 565 male survivors who visited the outpatient clinic in adulthood. The median follow-up time from initiation of treatment to first visit to the outpatient clinic in adulthood was 15 years. The prevalence rates of elevated FSH levels and decreased testosterone levels were 33 and 12%, respectively. The use of procarbazine, cyclophosphamide, vinca-alkaloids, other alkylating agents, pelvic/abdominal irradiation, total body irradiation and testicular surgery were identified as treatment-related risk factors for elevated FSH levels. During the follow-up period, 73 men reported 120 conceptions, which resulted in 103 live births. Of these men, 56 (77%) were able to achieve conception naturally. All men whose partners conceived by assisted reproductive techniques (n = 13) had elevated FSH levels at their first visit after their 18th birthday (sensitivity: 100%; 95% CI: 71-100%) and all male survivors with a normal FSH level did not need assisted reproductive techniques (negative predictive value: 100%; 95% CI: 89-100%). CONCLUSIONS: One-third of young adult male survivors of childhood cancer has elevated FSH levels. FSH appears to be a very sensitive marker for the need of assisted reproductive techniques in male childhood cancer survivors.

Three-year prevalence of healthcare-associated infections in Dutch nursing homes.

From November 2007 for a period of three years (2007-2009), we conducted an annual one-day prevalence study of healthcare-associated infections (HAIs) among nursing home residents in the Nijmegen region of The Netherlands. In the absence of national HAI definitions applicable to the nursing home setting, we used modified definitions based on US Centers for Disease Control and Prevention criteria for bloodstream infection, lower respiratory tract infection, bacterial conjunctivitis, and gastroenteritis. For the surveillance of urinary tract infection (UTI), criteria established by the Dutch Association of Elderly Care Physicians were used. Resident characteristics were recorded and data collection was performed by the attending elderly care physicians. For the three-year period, 1275, 1323, and 1772 nursing home residents were included, resulting in a prevalence of HAIs of 6.7%, 7.6% and 7.6%, in 2007, 2008 and 2009, respectively. The demographics with respect to age (mean 81 years) and sex (31% men, 69% women) were almost identical in all three years. UTI was the most prevalent HAI with 3.5%, 4.2%, and 4.1% respectively. Most HAIs occurred among residents of rehabilitation units. The prevalence of HAIs varied by nursing home (range: 0.0-32.4%). We present the results of the first prevalence study of HAIs in Dutch nursing homes. Point prevalence studies of HAIs, as part of a quality improvement cycle, are an important cornerstone of infection control programmes in nursing homes, allowing us to further increase patient safety efforts in this setting.

Quality of life, reproduction and sexuality after stem cell transplantation with partially T-cell-depleted grafts and after conditioning with a regimen including total body irradiation.

Thirty-four men and 36 women (median age 43 and 45 years, respectively) underwent stem cell transplantation (SCT) for acute leukaemia in first complete remission or chronic myelogenous leukaemia in first chronic phase between 1981 and 2001 from HLA-identical siblings. The conditioning regimen included TBI and all grafts were partially depleted of T cells. Changes in quality of life (QOL), reproduction and sexuality were studied using a questionnaire, and the previously given information related to these problems was assessed. In addition, endocrine status was assessed and semen analysis was performed. After SCT, patients reported less energy (n=50) and a deterioration in the job situation (n=31). Patients experienced a negative change in sexual relations (n=41). Important problems of sexual dysfunction were vaginal dryness in women (n=19) and erectile dysfunction in men (n=16). None of the patients was fertile based on their gonadotrophin levels, sperm concentrations and reproductive outcomes. Women experienced climacteric symptoms (n=24). Quality of life was negatively influenced by these changes. One-fifth of the patients were not satisfied with the information given with regard to reproduction, premature menopause and sexual problems.

Supernormal left ventricular diastolic function in triathletes.

We studied the structural and functional heart adaptations of 52 male triathletes compared with those of 22 active, nonathletic men, by 2-dimensional Doppler echocardiography. Left ventricular diastolic function was evaluated by recording transmitral flow velocities. To exclude the influences of preload, left atrial pressure, and aortic pressure, left ventricular diastolic function was also evaluated by pulsed Doppler tissue imaging. Significant differences in cardiac structure and function were observed between the 2 groups. In the triathletes, the left ventricular diastolic function was completely normal, despite signs of mixed eccentric and concentric left ventricular hypertrophy, and this function was better than that in the control group. We measured 2 aspects of the late passive diastolic filling period in the triathletes: ASEAC value (the amplitude of excursion of the interventricular septal endocardium at the end of left ventricular diastole just after atrial contraction); and the time between onset of the P wave on the electrocardiographic tracing and onset of systolic septal movement on M-mode echocardiography. Pulsed Doppler tissue imaging confirmed these results. The E/A ratios (peak early left ventricular diastolic motion velocity divided by the peak atrial systolic motion velocity), measured by pulsed Doppler tissue imaging, yielded even more evidence for supernormal left ventricular diastolic function in the triathletes. Left ventricular relaxation and filling properties were measured along the longitudinal and transverse axes by pulsed Doppler tissue imaging, which was useful for evaluating left ventricular diastolic function. We determined that triathletes may develop supernormal left ventricular diastolic function with increased diastolic reserves.

Importance of determining the percentage body fat in endurance-trained athletes.

A triathlete has to complete a hard endurance effort in aerobic circumstances. This requires important cardiovascular, haemodynamic and metabolic adaptations which alter the percentage body fat. This study included 52 triathletes and 22 control persons. The anthropometric data of the two groups were similar. All the subjects underwent the same extensive non-invasive cardiac exploration with two-dimensional cardiac echo-doppler examination. Maximal incremental exercise tests with determination of lactate and the ventilatory threshold were done on bicycle and on treadmill. Three different methods determined the percentage of body fat: 4 and 12 skin fold method, bioelectrical impedance analysis and dual energy X-ray absorptionmetry. The results showed important structural and functional heart changes in the triathletes. These changes caused distinct heamodynamic adaptations so that the maximal performing capacity and the aerobic capacity could be forced up largely. The haemodynamic adaptations were connected with changes in the percentage body fat in triathletes. The determination of the 12 skin fold measurements enabled us to distinguish the triathletes with better competition results from the inferior triathletes. It is concluded that the method of 12 skin fold measurements gives the most reliable results and requires only a limited instrumentarium. Moreover, this examination can be performed correctly and easily in all circumstances.

Echocardiographic and physiological performance characteristics of triathletes.

BACKGROUND: Endurance sports require a variety of physiological adaptations. OBJECTIVE: To examine the structural and functional heart adaptations and their hemodynamic implications in triathletes. PATIENTS AND METHODS: A group of 52 male triathletes was compared with a control group of 22 healthy male nonathletes. All of the subjects were given a bidimensional cardiac Doppler echocardiography examination and administered maximal exercise tests with lactic acid determinations, on a bicycle ergometer and a treadmill. RESULTS: The triathletes showed clear structural and functional heart adaptations with concentric and eccentric hypertrophy with evidence of a supernormal diastolic left ventricular function. The performance capacity of the triathlete differed significantly from that of the control subject. The maximal oxygen consumption and the maximal oxygen consumption per kilogram on the bicycle and on the treadmill were significantly higher in the triathletes. The same results and conclusions were obtained concerning aerobic capacities and power outputs on a bicycle ergometer at blood lactate concentrations of 2, 3 and 4 mmol/L. The heart rate 6 min after the start of exercise is a significant parameter for the evaluation of the physical condition of a subject. The lactic acid determinations during the recovery phase enabled important conclusions to be drawn about the physical condition of the subjects. CONCLUSIONS: The triathletes showed evidence of important structural and functional heart adaptations with hemodynamic implications. The maximal performing capacities, on the bicycle as well as on the treadmill, were distinctly higher in the triathlete group. Furthermore, the aerobic and anaerobic capacities were significantly different between the groups. In this context, the heart rate 6 min after the start of exercise and the blood lactate concentrations 20 min after the maximal exercise test were significant parameters. It was not always the best triathletes who had the most significant structural cardiac adaptations. Thus, the 'athletic heart' syndrome as a physiological entity is questioned.

Changes in mortality of acute myocardial infarction as a function of a changing treatment during the last two decades.

Forty years ago, after the establishment of coronary care units, a significant decrease in mortality of acute myocardial infarction was noted. Twenty years ago, the break-through of thrombolysis realized once again a significant decrease in mortality. In this study we compare, in a rather small community hospital, the mortality and safety of thrombolytic therapy in acute myocardial infarction with a more conventional, conservative medical therapy. We examined all cases of acute myocardial infarction between 1978 up to 1998 inclusive, concerning treatment and mortality rate after a six month period. To be included in the study, acute myocardial infarction had to fulfill particular inclusion criteria. A total of 1863 cases of acute myocardial infarction were included. The mortality rate of patients with acute myocardial infarction treated with thrombolytic agents was strikingly lower and statistically very significantly different (p < 0.001) in comparison with the mortality rate of patients treated with heparin or coumarine derivatives. The mortality rate dropped from 10.57% in the coumarine group and from 14.95% in the heparin group to 5.41% in the alteplase group, to 4.95% in the anistreplase group and 4.00% in the streptokinase subgroup. The complications directly connected to the treatment did not seem to be different between the five groups, and they were also not more frequent by using thrombolytic agents. In the last 20 years, better preventive measures (life habits, diet, medication) and trials to better control the risk factors have not influenced greatly the average amount of cholesterol in patients with an acute myocardial infarction. Also the percentage of patients with high blood pressure has hardly decreased over the last 20 years. The mortality associated with acute myocardial infarction has decreased significantly with the use of thrombolytics. In most cases, thrombolytics are administered routinely and safely. In this way, they are the first choice therapy for myocardial infarction in smaller hospitals. To obtain excellent coronary patency, thrombolytic agents with a long half-life and with PAI-1 resistance are required in the future. The current measures and medical therapies seem to be insufficient to control the risk factors for coronary atherosclerosis.

Physiological or pseudophysiological ECG changes in endurance-trained athletes.

"Sudden cardiac death" in seemingly healthy, active, and asymptomatic people has always been a tragic fact and is now occurring more frequently. Thus, the preventive detection of "subjects at risk" becomes a priority. A traditional resting electrocardiogram can sometimes give useful indications. Fifty-two competitive triathletes were compared with 22 control persons with similar anthropometric parameters. All subjects underwent the same noninvasive cardiac exploration with electrocardiography, bidimensional echo-Doppler examination, and maximal spiroergometric exercise tests, on a stationary bicycle as well as on a treadmill. In the triathletes we noted manifest signs of eccentric as well as concentric left ventricular hypertrophy with arguments for a supernormal diastolic left ventricular function, with important hemodynamic adjustments and with consequences on the resting electrocardiogram. We described "ten commandments" in evaluating the resting electrocardiogram of healthy competitive athletes. We suspect that the occurrence of ventricular premature beats at peak load of a maximal exercise could be the first expression of a pathological cardiac adaptation to sports activities. The resting electrocardiogram can show interesting details in detecting the "subjects at risk" for problems such as possible lethal arrhythmias and "sudden cardiac death." The analysis of the four subgroups of triathletes compels us to feel dubious about the "athletic heart syndrome" as a physiological entity. In several cases the "athletic heart" is possibly a transitional situation to a pathological hypertrophic and dilated cardiomyopathy.

Structural heart adaptations in triathletes.

OBJECTIVE: To perform a triathlon in aerobic conditions, a variety of cardiovascular, haemodynamic and metabolic adaptations are required. The heart is the central concern and also the most important limiting factor. In this study we investigate the structural and functional heart adaptations of a group of triathletes. METHODS AND RESULTS: A group of 52 male triathletes was divided into 4 subgroups in function of their athletic results and compared with a control group of 22 healthy, very active but no athletic men. The groups had comparable anthropometric and general physical characteristics. Very significant differences in cardiac structure and cardiac function were observed between the groups. In the triathletes, we registered distinct signs of significantly mixed eccentric and concentric hypertrophy. Unlike the findings in a pathological left ventricular hypertrophy, the diastolic left ventricular function in triathletes was completely normal and even better than in the control group. The late passive diastolic filling period of the triathlete, in particular, seemed to have specific characteristics. The comparison between the subgroups of triathletes shows us that genetic factors probably play an important role in the cardiac adaptations in triathletes. CONCLUSIONS: In our opinion the "athletic heart" in triathletes is not a specific "physiological entity" but is a transitional phase to a dilated hypertrophic cardiomyopathy. Our study yields some arguments for the following proposition: "People are born as elite athletes, with specific characteristics of the left ventricle and with a specifically supernormal diastolic left ventricular function."

Eimeria refractile body proteins contain two potentially functional characteristics: transhydrogenase and carbohydrate transport.

cDNA encoding an immunogenic protein from partially sporulated oocysts of Eimeria acervulina was cloned and used to search for the homologous counterpart in Eimeria tenella. Monospecific antibodies were raised against the recombinant expression product. Using these antibodies, the parasite proteins were found to be localised in the refractile bodies. The derived amino-acid sequences were compared by computer using the SWISSPROT protein database. In addition to high homology between the Eimeria species, extensive similarity was found with pyridine nucleotide transhydrogenase from Escherichia coli. Comparison with the sugar signature database also resulted in a possible sugar binding domain present only in the Eimeria proteins. It is possible that the corresponding parasite proteins play a role in the recently discovered mannitol cycle of Eimeria.

Avian herpesvirus as a live viral vector for the expression of heterologous antigens.

Control of Marek's disease in the poultry industry has been successfully achieved for several decades by large-scale vaccination of day-old chickens with live herpesvirus of turkeys (HVT) strains. Several features of this virus including lack of pathogenicity and long-term immune protection due to a persistent viraemic infection made us decide to use HVT as a live viral vector for the expression of foreign antigens. Potential sites for the integration of foreign DNA in the unique short region of the HVT genome were identified by the insertion of a beta-galactosidase expression cassette. Vaccination trials with recombinant virus strains indicated that the marker gene was expressed and stably maintained during animal passage. Based on an insertion site mapping in one of the open reading frames of the unique short region, a general recombination vector was designed for the integration of foreign genes into HVT. Recombinant virus-directed expression of individual antigens from Newcastle disease virus was driven by a strong promoter element derived from the lung terminal repeat sequence of Rous sarcoma virus.

Are the various thrombolytic agents equally effective in the treatment of acute transmural myocardial infarction?

While it is no longer possible to imagine the treatment of an acute transmural myocardial infarction without the use of thrombolytic agents, some discussion still exists as to the choice of the thrombolytic agent. Our study concerns a group of 160 patients with an acute transmural myocardial infarction, 60 of whom were treated with anistreplase, 52 with streptokinase and 48 with alteplase. Statistically, the administration of anistreplase was associated with a significantly higher frequency of ventricular arrhythmias in comparison to the other thrombolytic agents, whereas after subsequent coronary angiography, the anistreplase group revealed a significantly lower number of completely occluded coronary arteries. The data from this study demonstrate that anistreplase is a very valuable thrombolytic agent. It may even be more effective than streptokinase and alteplase in the treatment of acute myocardial infarction when the patency of the coronary arteries 1 month after the acute coronary event is considered the primary endpoint.

Interventional intra-arterial ultrasonography as an exclusive method of exploration to determine atherosclerotic lesions of the arterial wall at a preclinical stage.

Intravascular ultrasonography of the peripheral arterial system was applied following coronarography in 56 patients with one or several critical stenoses of the coronary arteries. Even though the clinical vascular examination and the subsequent noninvasive examination of the peripheral arterial system of all these patients turned out to be completely normal, intra-arterial ultrasonography was able to reveal important atherosclerotic alterations in the wall of the abdominal aorta and of the iliac-femoral arterial system in 51 of these patients. Intra-arterial ultrasonography appears to be a very sensitive method of exploration, permitting atherosclerotic changes of the arterial wall to be detected at a very early preclinical stage, long before these deviations could have caused symptoms.

Detection of silent arteriosclerotic lesions by intra-arterial ultrasonography.

OBJECTIVES: The aim of this study was to detect arteriosclerotic changes in the arterial wall at a preclinical stage. That is at a moment when these arteriosclerotic lesions are still fully asymptomatic and when the usual non-invasive vascular investigation techniques do not show any abnormalities. METHODS: Fifty-six patients with one or more critical stenoses of the coronary arteries, but with a completely normal peripheral vascular examination, were submitted to intravascular ultrasonography of the peripheral arterial system following coronary arteriography. Sonicath Ultrasound catheters were used and images were created with a Diasonics Imaging System. RESULTS: Although these 56 patients, after a profound noninvasive investigation, were classified as having perfectly normal peripheral arteries, we found severe arteriosclerotic wall abnormalities of the abdominal aorta and/or the iliac arterial system in 5% of the subjects. In addition, this exploration technique was used to evaluate the nature and the structure of the registered degenerative arteriosclerotic lesions. CONCLUSIONS: Intra-arterial ultrasonography obviously is a very sensitive investigation method which allows tracing arteriosclerotic changes of the arterial wall in a very early preclinical stage. The external ultrasound exploration techniques still have several important limitations, which, of course, do not hinder the intravascular application. The remaining disadvantage of the intra-arterial ultrasonography is however its invasive character.

Molecular cloning and sequence analysis of the genome of chicken anaemia agent.

The replicative form (RF) DNA of chicken anaemia agent (CAA) was isolated and cloned into bacterial plasmids. After religation of the cloned CAA DNA and transfection into MDCC-MSB1 cells, the DNA could induce c.p.e. characteristic of that caused by CAA, and an antigen was produced which gave positive immunofluorescence when detected with an anti-CAA serum. Sanger sequencing of the 2298 bp genome revealed several open reading frames (ORFs); the major ORF encoded a polypeptide of 51.8K. In SDS-PAGE of CAA viral particles a 50K protein has been reported as the only detectable viral protein. The genomic region downstream of the major ORF had several predicted GC-rich inverted repeats, a poly(A) signal and four copies of an 18 bp repeat element. Database searches did not reveal any sequence with homology to the viral genomic DNA, nor to the amino acid sequence of any of the ORFs, apart from the N-terminal 40 amino acids of the major ORF which showed a limited similarity to the structure of protamines.

Inhibition of Marek's disease virus DNA transfection by a sequence containing an alphaherpesvirus origin of replication and flanking transcriptional regulatory elements.

A co-transfection method was used to identify regions of the Marek's disease virus (MDV) genome that inhibit plaque formation when introduced along with total DNA from MDV-infected chicken embryo fibroblasts into secondary chicken embryo fibroblasts. Co-transfections involving MDV plasmids containing the BamHI-D or BamHI-H regions of the genome inhibited plaque formation more than 10-fold. The inhibitory region was localized to a 222-base-pair region that contains a sequence homologous to the consensus origin of replication of alphaherpesviruses. The region also contains several potential transcriptional regulatory elements, including two CCAAT boxes, one Sp1 binding site, and an octamer element. The sequence of this region has been reported previously. Transfection inhibition was also observed for the BamHI-I2 region, although the effect was weaker.

The intra-arterial ultrasonography as an exclusive exploration method to determine atherosclerotic lesions of the arterial wall in a preclinical stage.

An intravascular ultrasonography of the peripheral arterial system was applied following on the coronarography to 56 patients suffering from one or several critical stenoses on the coronary arteries. Though the clinical vascular examination and the subsequent noninvasive examination of the peripheral arterial system of all these patients turned out to be completely normal, the intra-arterial ultrasonography was able to reveal important atherosclerotic alterations in the wall of the abdominal aorta and of the iliac arteries in the case of 51 of these patients. The intra-arterial ultrasonography appears to be a very sensitive method of exploration, permitting atherosclerotic changes of the arterial wall to be detected at a very early pre-clinical stage, even long before these anomalies could have caused a specific pattern of complaints.