S18Y polymorphism in the UCH-L1 gene and Parkinson's disease: evidence for an age-dependent relationship.

We studied the relationship between Parkinson's disease (PD) and the S18Y polymorphism in the UCH-L1 gene and the effect on this relationship of age at onset, smoking, and pesticides. Patients requested free health coverage for PD to the Mutualité Sociale Agricole (MSA), the French health insurance organization for people whose work is related to agriculture. Controls requested reimbursement of health expenses to the MSA. A maximum of three controls were matched to each case. Analyses included participants with both parents born in Europe. There were no differences in S18Y genotypes between patients (n = 209; 67% SS, 32% SY, 1% YY) and controls (n = 488; 66% SS, 30% SY, 4% YY). The relationship between PD and S18Y was modified by age at onset (P = 0.03). The Y allele was inversely associated with PD for patients with onset before 61 years (odds ratio [OR] = 0.53; 95% confidence interval [CI], 0.29-0.99); there was no association for older patients (62-68 years: OR = 1.21; 95% CI, 0.67-2.20; >68 years: OR = 1.24; 95% CI, 0.67-2.31). Among patients, Y carriers had a later onset than noncarriers (P = 0.04). These findings were not modified or confounded by smoking and pesticides. In this community-based case-control study, carriers of the Y allele were at decreased risk of developing PD at a young age, independently of pesticides and smoking.     

Long-Term Outcomes After Percutaneous Closure of Ostium Secundum Atrial Septal Defect in the Young: A Nationwide Cohort Study

Objectives

This study sought to assess procedural characteristics, early clinical outcome, and long-term complications after transcatheter closure of atrial septal defect (ASD) in children.

Chronic Contamination of Rats with <Superscript>137</Superscript>Cesium Radionuclide: Impact on the Cardiovascular System

Cardiovascular system impairment has been observed in children and in liquidators exposed to the Chernobyl nuclear power plant accident. No experimental studies of animals have analyzed whether these disorders might be attributed to chronic ingestion of low levels of cesium 137 (¹³⁷Cs). Biochemical, physiological, and molecular markers of the cardiovascular system were analyzed in rats exposed through drinking water to ¹³⁷Cs at a dose of 500 Bq kg⁻¹ (6500 Bq l⁻¹). Plasma concentrations of CK and CK-MB were higher (+52%, P < 0.05) in contaminated rats. No histological alteration of the heart was observed, but gene expression was modified in the atria. Specifically, levels of ACE (angiotensin converting enzyme) and BNP (brain natriuretic peptide) gene expression increased significantly (P < 0.05). ECG analysis did not disclose any arrhythmia except ST- and RT-segment shortening (−9% and −11%, respectively, P < 0.05) in rats exposed to ¹³⁷Cs. Mean blood pressure decreased (−10%, P < 0.05), and its circadian rhythm disappeared. Overall, chronic contamination by an extreme environmental dose of ¹³⁷Cs for 3 months did not result in cardiac morphological changes, but the cardiovascular system impairments we observed could develop into more significant changes in sensitive animals or after longer contamination. Yann Guéguen and Philippe Lestaevel participated equally to this work.     

Effects of training in normoxia and normobaric hypoxia on time to exhaustion at the maximum rate of oxygen uptake

The effects of endurance training in normoxia or in hypoxia on time to exhaustion (T_lim) at the work rate corresponding to peak oxygen uptake (O_2peak) were examined at sea level in 13 healthy subjects. Before and after training the subjects performed the following: (1) incremental exercises up to exhaustion to determine peak oxygen uptake in normoxia (O_2peakN), the percentage of this value at the 4 mmol l^–1 blood lactate concentration (O₂4%N) and the work rate corresponding to O_2peakN (Pa_peakN), (2) a 5-min 90% Pa_peakN exercise followed by a 10-min passive recovery to determine the maximal blood lactate concentration (La_max) measured during the recovery, and (3) a T_lim at Pa_peakN. Training consisted of pedalling 2 h a day, 6 days a week, for 4 weeks. Five subjects trained in normobaric hypoxia [HT; partial pressure of inhaled oxygen (P_IO₂) 89 mmHg] and eight subjects trained at the same relative work rates in normoxia (NT; P_IO₂ 141 mmHg). The training-induced improvement of all the measured parameters were closely matched between the HT and the NT (P>0.05). Training increased T_lim by 59.7% [164(40) s]. The value of T_lim was related to O₂4%N and to La_max before and after training. Also, the training-induced improvement of T_lim was related to the concomitant decrease in La_max. It is concluded that: (1) endurance training including continuous high-intensity exercises improves T_lim for exercises performed at the same relative (higher absolute) work rate after training, (2) intermittent hypoxic training has no potentiating effect on T_lim as compared with training in normoxia, and (3) the intra-individual training-induced improvement of T_lim was associated with metabolic alteration in relation to lactate accumulation.     

Drosophila CAKI/CMG protein, a homolog of human CASK, is essential for regulation of neurotransmitter vesicle release

Vertebrate CASK is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. CASK is present in the nervous system where it binds to neurexin, a transmembrane protein localized in the presynaptic membrane. The Drosophila homologue of CASK is CAKI or CAMGUK. CAKI is expressed in the nervous system of larvae and adult flies. In adult flies, the expression of caki is particularly evident in the visual brain regions. To elucidate the functional role of CASK, we employed a caki null mutant in the model organism Drosophila melanogaster. By means of electrophysiological methods, we analyzed, in adult flies, the spontaneous and evoked neurotransmitter release at the neuromuscular junction (NMJ) as well as the functional status of the giant fiber pathway and of the visual system. We found that in caki mutants, when synaptic activity is modified, the spontaneous neurotransmitter release of the indirect flight muscle NMJ was increased, the response of the giant fiber pathway to continuous stimulation was impaired, and electroretinographic responses to single and continuous repetitive stimuli were altered and optomotor behavior was abnormal. These results support the involvement of CAKI in neurotransmitter release and nervous system function.     

Leg extensor power and dehydroepiandrosterone sulfate, insulin-like growth factor-I and testosterone in healthy active elderly people

We examined the association between quadriceps muscle function and serum levels of dehydroepiandrosterone sulphate (DHEAS), insulin-like growth factor I (IGF-I) and testosterone in a group of healthy elderly people. Fifty-three independent, community-dwelling elderly subjects (26 men and 27 women) aged from 66 to 84 years volunteered to participate in the study. Physical activity (PA) was evaluated by a questionnaire. Quadriceps maximal muscle power (W˙ _max) and optimal shortening velocity (v _opt) were measured on a friction-loaded non-isokinetic cycle ergometer. The W˙ _max is expressed in relation to body mass (W˙ _max/kg, W · kg⁻¹), and in relation to the mass of the two quadriceps muscles (W˙ _max/Quadr, W · kg_Quadr ⁻¹). In women, when adjusted for age, anthropometric measurements and PA indices, IGF-I correlated significantly with W˙ _max/kg (partial correlation: r=0.59; P=0.001), W˙ _max/Quadr (r=0.58; P=0.002) and v _opt (r=0.53; P=0.004), whereas DHEAS was correlated significantly with W˙ _max/kg (r=0.54; P=0.003) and W˙ _max/Quadr (r=0.58; P=0.002). No such correlation was found in men. These findings indicate that in healthy elderly women lower values for quadriceps muscle W˙ _max and v _opt are related, independently of age, anthropometric measurements and PA indices, to lower circulating levels of DHEAS and IGF-I. Accepted: 29 December 1999     

Cigarette smoking and Parkinson's disease: a case-control study in a population characterized by a high prevalence of pesticide exposure.

Epidemiological studies have been consistent in showing that cigarette smoking is inversely associated with Parkinson's disease (PD), whereas pesticide use is positively associated with PD. However, the relationship between PD and cigarette smoking remains poorly understood. Our objective was to study the relationship between cigarette smoking and PD in a population characterized by a high prevalence of pesticide exposure. This case-control study was carried out among subjects enrolled in the Mutualite Sociale Agricole, the French health insurance organization for workers connected to the agricultural world. We included 247 cases and 676 controls matched on age, sex, and region of residency. Information on smoking was obtained through in-person interviews. Pesticide exposure was assessed using a case-by-case expert evaluation procedure. We found an inverse relationship between ever cigarette smoking and PD (odds ratio [OR] = 0.6; 95% confidence interval [CI] = 0.4-0.9). The strength of this association increased with the number of pack-years. This relationship was present even when smoking was considered as long as 40 years before PD onset. An inverse association was also present among subjects professionally exposed to pesticides (OR = 0.5; 95% CI = 0.3-0.8) and was independent of the duration of exposure among men. We confirm the inverse association between cigarette smoking and PD in a population characterized by a high prevalence of professional pesticide exposure. The relationship between PD and cigarette smoking was not significantly modified or confounded by exposure to pesticides.     

The effects of parathyroid hormone fragments on bone formation and their lack of effects on the initiation of colon carcinogenesis in rats as indicated by preneoplastic aberrant crypt formation

The parathyroid hormone (PTH) and some of its fragments and analogs stimulate bone growth in various animal models and humans and one of them (hPTH-(1–34)) has been approved by the USFDA for treating osteoporosis. However, there are reports that PTH can stimulate the PI-3 kinase/mitogen-activated protein kinases-mediated proliferation of rat enterocytes and that primary hyperparathyroidism in humans is associated with an increased incidence of colon cancer. Here we have investigated the ability of two PTH fragments, hPTH-(1–34)NH₂ and [Leu²⁷]cyclo(Glu²²-Lys²⁶)hPTH-(1–31)NH₂ to initiate colon carcinogenesis or increase the initiatory activity of the widely used colon carcinogen azoxymethane (AOM). The initiation of colon carcinogenesis by AOM was indicated by the very early appearance of aberrant crypt foci. While both PTH peptides strongly stimulated femoral bone formation, they did not cause the appearance of ACFs or affect the number or the distribution along the colon of AOM-induced ACFs. Nor did AOM affect the PTHs’ ability to stimulate bone formation. Thus, a relatively short PTH treatment that is long enough to strongly stimulate bone formation does not initiate colon carcinogenesis in rats.     

Heart rate increment: an electrocardiological approach for the early detection of obstructive sleep apnoea/hypopnoea syndrome

The prevalence of OSAHS (obstructive sleep apnoea/hypopnoea syndrome) is high in developed countries and it is estimated that the vast majority of patients remain undiagnosed. On the basis of physiological evidence, we evaluated the frequency component of HRI (heart rate increment) as a simple and inexpensive screening tool for OSAHS detection in a first group of patients (group 1) and validated their discriminant capacity in a second group (group 2). The predictive accuracy of hourly %VLFI (frequency-domain HRI variable obtained from nocturnal ECG Holter monitoring) was analysed by comparison with an hour-by-hour respiratory disturbances index assessed by complete polysomnography in 28 consecutive clinically suspected OSAHS patients for group 1 and in 35 patients for group 2. OSAHS was present in 20 patients according to a mean hourly apnoea plus hypopnoea index >10 in group 1, and prevalence reached 77.1% in group 2. Sensitivity, specificity and positive and negative predictive accuracy were calculated and an ROC (receiver operating characteristic) curve was constructed for several polysomnographic threshold values. In group 1, hourly %VLFI appeared as an evident predictor of the apnoea/hypopnoea index (W=0.848, P<0.0001; where W is the area under the curve obtained using ROC curve analysis). Using an appropriate threshold (value > or =3.2%), %VLFI demonstrated a sensitivity of 78.1% and a specificity of 70.4%. These thresholds applied to group 2 yielded a sensitivity of 73.9% and a specificity of 76.6%. Frequency-domain analysis of the HRI appears to be a powerful tool for OSAHS prediction. The simplicity of its analysis and use makes of it a particularly well-suited variable for routine mass screening in high-risk populations undergoing ECG Holter monitoring.