[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.

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.

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.

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.

Randomised trial comparing sequential methotrexate (or 5-FU), vinblastine and ifosfamide to vincristine, adriamycin and ifosfamide in advanced lung cancer.

A randomised trial has compared the sequential administration of ifosfamide (with its urinary antidote mesna) combined with methotrexate (or 5-FU in adenocarcinomas) and vinblastine (protocol I) or combined with adriamycin and vincristine (protocol II) in advanced lung cancer. In 29 evaluable cases the results were not influenced by the protocol nor by the histology of the tumors (oat cell v non-oat cell) or the clinical stage (limited v extensive). An overall response rate of 58.6% was obtained (100% in the oat cell and anaplastic carcinomas, 44% in adenocarcinomas, 50% in squamous cell carcinomas) with a clear prolongation of survival in responding groups, whatever the clinical stage.

Comparative effects of doxazosin and hydrochlorothiazide on serum lipids and blood pressure in essential hypertension.

The efficacy and safety of doxazosin (mean dosage 6.9 mg, range 1 to 16) in the treatment of essential hypertension were compared in a double-blind study with those of hydrochlorothiazide (HCTZ) (mean dosage, 84.6 mg, range 25 to 100) in 104 hypertensive patients treated once daily for 6 months. Thirty-five patients were also assessed for comparative effects of the 2 agents on serum lipid parameters. Doxazosin produced potentially favorable changes from baseline in the concentrations of serum lipid fractions (total triglycerides, total cholesterol, high density lipoprotein [HDL] cholesterol and the derived HDL/total cholesterol ratio) compared with HCTZ. The decreases in total triglyceride and total cholesterol concentrations and an increase in the HDL/total cholesterol ratio were significantly different (p less than 0.006) from the opposite changes observed with HCTZ. Clinically relevant decreases from baseline in supine and standing blood pressures at 24 hours after administration did not significantly differ between the 2 agents. The incidence and severity of side effects were similar for both drugs. Three patients receiving doxazosin and 6 receiving HCTZ were withdrawn due to drug-related clinical side effects including 2 patients receiving HCTZ who were withdrawn because of laboratory test abnormalities. Eight HCTZ- and 1 doxazosin-treated patients developed hypokalemia and 6 HCTZ-treated patients developed hyperuricemia. These findings indicate that doxazosin and HCTZ provide comparable antihypertensive efficacy after 6 months of treatment using a once-daily regimen, but doxazosin produces a beneficial effect on the serum lipid profile as well as fewer biochemical aberrations.

Distribution of actin isoforms in sarcomas: an immunohistochemical study.

The actin immunophenotype of eight benign mesenchymal tumors, 14 nonsarcomatoid tumors, and 46 sarcomatoid tumors was studied, using monoclonal antibodies (MoAb) specific for alpha-smooth muscle actin (clone 1A4), alpha- and gamma-smooth muscle actin (designated CGA7), and muscle actin (designated HHF35) on frozen sections. Tumor cells of nonsarcomatoid tissues were not reactive, but all leiomyomas and five of the seven leiomyosarcomas reacted with the three MoAbs. One leiomyosarcoma was immunoreactive for the MoAb 1A4 only. One of the six malignant schwannomas showed staining for muscle actin (HHF35). The 22 malignant fibrous histocytomas (MFH) expressed these actin isoforms in various degrees. One case immunoreacted with all three MoAbs, three reacted with 1A4 only, seven reacted with CGA7 and HHF35, and two reacted with HHF35 only. Nine MFHs were not immunoreactive for any of the MoAbs specific for (smooth) muscle and actin. In addition, the expression of desmin and collagen type IV was investigated for the group of leiomyosarcomas and MFHs. Desmin was found in five leiomyosarcomas and in two MFHs. Collagen type IV was seen in all leiomyosarcomas, and was seen weakly in a few small areas in four MFHs. When we take into account the expression of all markers tested [( smooth] muscle actin, desmin, and collagen type IV), then six of the 22 MFHs were unreactive for all these markers. Five of these six tumors were located intramuscularly, whereas only half of the total number of MFH cases had an intramuscular location. The fact that 15 of 22 MFHs displayed one or more markers linked with (smooth) muscle differentiation suggests that some of the MFHs may be classified as poorly differentiated leiomyosarcomas, and that MFH is not a unique entity.

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.

Neurological toxicity of vindesine used in combination chemotherapy of 51 human solid tumors.

The authors treated 51 patients with solid tumours with vindesine 4 mg/m2, generally every third week, in combination chemotherapy protocols scheduled according to diurnal variability of kinetics. No dose-related sensory disorders were observed: On the contrary, motor toxicity appeared cumulative: 1) Early depression of osteotendinous reflexes from the first course onward, with progressive deterioration. No more normal reflexes could be evoked after 55 mg; 2) Early appearance of neurogenic pattern in the electromyograph after 5-10 mg. Progressive alteration with no normal detection recordings after 45 mg; 3) Late slowing down of conduction speeds (normal in 50% of cases up to 55-60 mg). Improvement or even complete recovery of neuropathy was documented following reduction of the unit dose, increased time interval between doses, or discontinuation of the treatment. The drug had to be withheld in only three patients: in two cases a low dosage related to individual sensitivity was being used.

Phase II trial with high-dose ifosfamide and mesna given in a 24-h infusion for advanced GI tract cancer.

In all, 26 patients with advanced GI tract cancer (among whom 23 had liver metastases) were treated in a phase II trial with a 24-h infusion of high-dose ifosfamide and mesna (5 g/m2). Two PR, 1 CR and 4 NC were evidenced among 23 patients evaluable for response. The toxicity was significant and mainly expressed in the hair, digestive tract, granulocytes and CNS. One patient died from CNS and kidney toxicities. Only patients with good clinical indices, normal serum albumin and creatinine levels and without pelvic involvement seemed to be candidates to benefit from the treatment.

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.

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.

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."

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.

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.