Testostérone et os: indications et limites [Testosterone and bone: indications and limitations].

Osteoporosis incidence increases exponentially with age in men and hypogonadism represents a risk factor. Sex steroids levels are correlated to bone mineral density and to fracture prevalence. Most studies demonstrate an improvement in bone mineral density in men with hypogonadism as a result of testosterone therapy. Nevertheless there are no data evaluating the effect of testosterone therapy on fractures in men. Approximately 20% of men older than 60 have a total testosterone level lower than the lower limit of the reference range but there is no true consensus on the definition of hypogonadism in older men. In older men we recommend to treat only if total morning testosterone levels are < 8 nmol/l or even < 6,9 nmol/l on several occasions in the absence of any reversible illness and if there is no contraindication for treatment.

Acquisitions thérapeutiques en médecine ambulatoire en 2011 [2011 findings from literature on general internal ambulatory medicine].

In 2011 several articles seemed significant for the practice of general medicine. Diagnosis of hypertension needs several measurements and may need 24-hour ambulatory blood pressure monitoring. Glycosylated hemoglobin is a reliable tool to diagnose diabetes mellitus. The ABCD2 score with neurological imaging help the triage of transient ischemic attacks. Pulmonary embolism can be treated as outpatient for low risk patients. Gluten-free diet may be tried in irritable bowel syndrome. Nitrofurantoin is a reasonable alternative for simple urinary tract infection in women, but antibiotics are not needed after drainage of an uncomplicated skin abscess. Subclinical thyroid dysfunction is a risk factor of osteoporosis in older men. Sequential use of MMSE and ACE scores is a promising approach to assess medical decision-making capacity.

Cardiac structure and function in the obese: a cardiovascular magnetic resonance imaging study.

BACKGROUND: Obesity is a major health problem in the Western world. Among obese subjects cardiac pathology is common, but conventional noninvasive imaging modalities are often suboptimal for detailed evaluation of cardiac structure and function. We investigated whether cardiovascular magnetic resonance imaging (CMR) can better characterize possible cardiac abnormalities associated with obesity, in the absence of other confounding comorbidities. METHODS: In this prospective cross-sectional study, CMR was used to quantify left and right ventricular volumes, ejection fraction, mass, cardiac output, and apical left ventricular rotation in 25 clinically healthy obese men and 25 age-matched lean controls. RESULTS: Obese subjects had higher left ventricular mass (203 +/- 38 g vs. 163 +/- 22 g, p < 0.001), end-diastolic volume (176 +/- 29 mL vs. 156 +/- 25 mL, p < 0.05), and cardiac output (8.2 +/- 1.2 L/min vs. 6.4 +/- 1.3 L/min, p < 0.001). The obese also had increased right ventricular mass (105 +/- 25 g vs. 87 +/- 18 g, p < 0.005) and end-diastolic volume (179 +/- 36 mL vs. 155 +/- 28 mL, p < 0.05). When indexed for height, differences in left and right ventricular mass, and left ventricular end-diastolic volume remained significant. Apical left ventricular rotation and rotational velocity patterns were also different between obese and lean subjects. CONCLUSIONS: Obesity is independently associated with remodeling of the heart. Cardiovascular magnetic resonance imaging identifies subtle cardiac abnormalities and may be the preferred imaging technique to evaluate cardiac structure and function in the obese.

Cardiovascular effects in patrol officers are associated with fine particulate matter from brake wear and engine emissions

Background: Exposure to fine particulate matter air pollutants (PM2.5) affects heart rate variability parameters, and levels of serum proteins associated with inflammation, hemostasis and thrombosis. This study investigated sources potentially responsible for cardiovascular and hematological effects in highway patrol troopers. Results: Nine healthy young non-smoking male troopers working from 3 PM to midnight were studied on four consecutive days during their shift and the following night. Sources of in-vehicle PM2.5 were identified with variance-maximizing rotational principal factor analysis of PM2.5-components and associated pollutants. Two source models were calculated. Sources of in-vehicle PM2.5 identified were 1) crustal material, 2) wear of steel automotive components, 3) gasoline combustion, 4) speed-changing traffic with engine emissions and brake wear. In one model, sources 1 and 2 collapsed to a single source. Source factors scores were compared to cardiac and blood parameters measured ten and fifteen hours, respectively, after each shift. The "speed-change" factor was significantly associated with mean heart cycle length (MCL, +7% per standard deviation increase in the factor score), heart rate variability (+16%), supraventricular ectopic beats (+39%), % neutrophils (+7%), % lymphocytes (-10%), red blood cell volume MCV (+1%), von Willebrand Factor (+9%), blood urea nitrogen (+7%), and protein C (-11%). The "crustal" factor (but not the "collapsed" source) was associated with MCL (+3%) and serum uric acid concentrations (+5%). Controlling for potential confounders had little influence on the effect estimates. Conclusion: PM2.5 originating from speed-changing traffic modulates the autonomic control of the heart rhythm, increases the frequency of premature supraventricular beats and elicits proinflammatory and pro-thrombotic responses in healthy young men. [Authors]

Hippocampal and amygdalar volume changes in elderly patients with Alzheimer's disease and schizophrenia.

Patients with Alzheimer's disease (AD) and schizophrenia display cognitive, behavioural disturbances and morphological abnormalities. Although these latter reflect progressive neurodegeneration in AD, their significance in schizophrenia is still unclear. We explored the patterns of hippocampal and amygdalar atrophy in those patients and their associations with clinical parameters. Structural magnetic resonance imaging was performed in 20 elderly schizophrenia patients, 20 AD and 19 healthy older controls. Hippocampal and amygdalar volumes were obtained by manual segmentation with a standardized protocol and compared among groups. In both schizophrenia and AD patients, left hippocampal and amygdalar volumes were significantly smaller. The hippocampus/amygdala ratio was significantly lower in schizophrenia compared to both AD cases [2.4 bilaterally, 95% C.I. 2.2 to 2.7] and healthy controls bilaterally [2.5, 95% C.I. 2.3 to 2.9 in left and 2.7, 95% C.I. 2.4 to 3.1 in right hemisphere]. In schizophrenia patients, a significant positive correlation was found between age at disease onset and the right hippocampus/amygdala volume ratio (Spearman rho=0.56). Negative symptoms correlated with higher right/left amygdala volume ratio (Spearman's rho=0.43). Our data show that unlike AD, the hippocampus/amygdala ratio is abnormally low and correlates with the age at onset in schizophrenia, being a neurodevelopmental signature of the disease.

Trends in cardiovascular risk factors (1984-1993) in a Swiss region: results of three population surveys.

BACKGROUND: This study attempted to assess the time trends in lifestyle and cardiovascular risk factors in the Swiss region of Vaud-Fribourg (population 784,000). METHODS: Three surveys (1984/1985, 1988/1989, and 1992/1993), based on independent representative samples (n = 3,300) of the population ages 25 to 74, were conducted within the framework of the international WHO-MONICA Project. RESULTS: The most favorable changes were observed in reported behaviors: increased physical activity in leisure time, healthier dietary habits (switch from unskimmed milk, butter, and meat to skimmed milk, margarine, and fish, with no change for fruits and vegetables), and lower prevalence of regular smoking among men (from 32 to 28%). Body mass index did not vary significantly, apart from an increase in the prevalence of obesity among men (from 11 to 15%). Total cholesterol varied only slightly, while the HDL cholesterol levels decreased steadily (from 1.37 to 1.19 mmol/L among men; from 1.59 to 1.51 among women). Average systolic blood pressure regressed among women (from 127.2 to 124.4 mm Hg), while the prevalence of untreated hypertension increased among older men. CONCLUSION: The self-reported changes in lifestyle were only partially reflected by favorable trends in objective measurements. Physical activity, even at moderate intensity, and consumption of fruits, vegetables, and fiber in general should be promoted.

Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium.

BACKGROUND: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. METHODS: We pooled data from 25 case-control studies and conducted separate analyses for adults ≤45 years old ('young adults', 2010 cases and 4042 controls) and >45 years old ('older adults', 17 700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI = 9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking = 5.3% (-11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR = 2.27 (95% CI = 1.26, 4.10)], but not in the older adults [OR = 1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (-2.41%, 5.80%) in older adults. CONCLUSIONS: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults.

Resting metabolic rate and protein turnover in apparently healthy elderly Gambian men.

Body composition, resting energy expenditure (REE), and whole body protein metabolism were studied in 26 young and 28 elderly Gambian men matched for body mass index during the dry season in a rural village in The Gambia. REE was measured by indirect calorimetry (hood system) in the fasting state and after five successive meals. Rates of whole body nitrogen flux, protein synthesis, and protein breakdown were determined in the fed state from the level of isotopic enrichment of urinary ammonia over a period of 12 h after a single oral dose of [15N]glycine. Expressed in absolute value, REE was significantly lower in the elderly compared with the young group (3.21 +/- 0.07 vs. 4.04 +/- 0.07 kJ/min, P < 0.001) and when adjusted to body weight (3.29 +/- 0.05 vs. 3.96 +/- 0.05 kJ/min, P < 0.0001) and fat-free mass (FFM; 3.38 +/- 0.01 vs. 3.87 +/- 0.01 kJ/min, P < 0.0001). The rate of protein synthesis averaged 207 +/- 13 g protein/day in the elderly and 230 +/- 13 g protein/day in the young group, whereas protein breakdown averaged 184 +/- 13 g protein/day in the elderly and 203 +/- 13 g protein/day in the young group (nonsignificant). When values were adjusted for body weight or FFM, they did not reveal any difference between the two groups. It is concluded that the reduced REE adjusted for body composition observed in elderly Gambian men is not explained by a decrease in protein turnover.

Metoprolol prevents sodium retention induced by lower body negative pressure in healthy men.

BACKGROUND: Lower body negative pressure (LBNP) has been shown to induce a progressive activation of neurohormonal systems, and a renal tubular and hemodynamic response that mimics the renal adaptation observed in congestive heart failure (CHF). As beta-blockers play an important role in the management of CHF patients, the effects of metoprolol on the renal response were examined in healthy subjects during sustained LBNP. METHODS: Twenty healthy male subjects were randomized in this double blind, placebo versus metoprolol 200 mg once daily, study. After 10 days of treatment, each subject was exposed to 3 levels of LBNP (0, -10, and -20 mbar) for 1 hour, each level of LBNP being separated by 2 days. Neurohormonal profiles, systemic and renal hemodynamics, as well as renal sodium handling were measured before, during, and after LBNP. RESULTS: Blood pressure and heart rate were significantly lower in the metoprolol group throughout the study (P < 0.01). GFR and RPF were similar in both groups at baseline, and no change in renal hemodynamic values was detected at any level of LBNP. However, a reduction in sodium excretion was observed in the placebo group at -20 mbar, whereas no change was detected in the metoprolol group. An increase in plasma renin activity was also observed at -20 mbar in the placebo group that was not observed with metoprolol. CONCLUSION: The beta-blocker metoprolol prevents the sodium retention induced by lower body negative pressure in healthy subjects despite a lower blood pressure. The prevention of sodium retention may be due to a blunting of the neurohormonal response. These effects of metoprolol on the renal response to LBNP may in part explain the beneficial effects of this agent in heart failure patients.

Thermogenic effect of amrinone in healthy men.

OBJECTIVES: The thermogenic effect of amrinone is unknown and its utilization in patients with severe cardiac failure could potentially increase oxygen requirements and therefore aggravate oxygen debt. Consequently, the present study was undertaken to assess the thermogenic response to amrinone at three different plasma concentrations under controlled conditions and to analyze amrinone's effects on various biochemical variables. DESIGN: A prospective, unblinded, controlled study. The initial control period was followed by three sequential, experimental treatments. SUBJECTS: Ten young, healthy, male volunteers with normal body weight. INTERVENTIONS: Three experimental periods. Amrinone was administered intravenously in progressive doses: a) 0.5 mg/kg followed by 5 micrograms/kg/min; b) 0.5 mg/kg followed by 10 micrograms/kg/min; and c) 1.0 mg/kg followed by 10 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Oxygen consumption (VO2) and CO2 production were continuously measured by means of a computerized indirect calorimeter. At the highest dose, amrinone produced a slight and significant (p < .01) increase in VO2 and in resting metabolic rate (+4.5% and +3.7%, respectively), while no change in CO2 production or in respiratory quotient occurred throughout the study. At the medium and high doses, amrinone increased plasma free fatty acid concentrations by 38% and 53%, respectively (p < .05). No variation in plasma glucose, lactate, insulin, norepinephrine, or epinephrine concentrations was observed during the study. CONCLUSIONS: Amrinone administered intravenously at therapeutic doses has minimal thermogenic and metabolic effects in humans without cardiac failure.

Performance of younger and older adults in lateralized right and left hemisphere asymmetry tasks supports the HAROLD model

The population of industrialized societies has increased tremendously over the last century, raising the question on how an enhanced age affects cognition. The relevance of two models of healthy aging are contrasted in the present study that both target the functioning of the two cerebral hemispheres. The right hemi-aging model (RHAM) assumes that functions of the right hemisphere decline before those of the left hemisphere. The Hemispheric Asymmetry Reduction in Older Adults (HAROLD) Model suggests that the contralateral hemisphere supports the normally superior hemisphere in a given task resulting in a reduced hemispheric asymmetry overall. In a mixed design, 20 younger and 20 older adults performed both a task assessing a left (lateralized lexical decisions) and a right (sex decisions on chimeric faces) hemisphere advantage. Results indicated that lateralized performance in both tasks was attenuated in older as compared to younger adults, in particular in men. These observations support the HAROLD model. Future studies should investigate whether this reduced functional hemispheric asymmetry in older age results from compensatory processes or from a process of de-differentiation

Effects of four-week high-fructose diet on gene expression in skeletal muscle of healthy men.

AIMS: A high-fructose diet (HFrD) may play a role in the obesity and metabolic disorders epidemic. In rodents, HFrD leads to insulin resistance and ectopic lipid deposition. In healthy humans, a four-week HFrD alters lipid homoeostasis, but does not affect insulin sensitivity or intramyocellular lipids (IMCL). The aim of this study was to investigate whether fructose may induce early molecular changes in skeletal muscle prior to the development of whole-body insulin resistance. METHODS: Muscle biopsies were taken from five healthy men who had participated in a previous four-week HFrD study, during which insulin sensitivity (hyperinsulinaemic euglycaemic clamp), and intrahepatocellular lipids and IMCL were assessed before and after HFrD. The mRNA concentrations of 16 genes involved in lipid and carbohydrate metabolism were quantified before and after HFrD by real-time quantitative PCR. RESULTS: HFrD significantly (P<0.05) increased stearoyl-CoA desaturase-1 (SCD-1) (+50%). Glucose transporter-4 (GLUT-4) decreased by 27% and acetyl-CoA carboxylase-2 decreased by 48%. A trend toward decreased peroxisomal proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) was observed (-26%, P=0.06). All other genes showed no significant changes. CONCLUSION: HFrD led to alterations of SCD-1, GLUT-4 and PGC-1alpha, which may be early markers of insulin resistance.

Interaction between dietary lipids an physical inactivity on insulin sensitivity and on intramyocellular lipids in healthy men

Résumé Interaction entre les lipides alimentaires et l'inactivité physique sur la sensibilité à l'insuline et les lipides intramyocellulaires chez le sujet masculin en bonne santé Ces deux dernières décennies, l'incidence de la résistance à l'insuline n'a cessé de progresser dans les pays industrialisés. Un grand nombre de travaux suggèrent que ce trouble métabolique joue un rôle important dans la pathogenèse de maladies propres au monde industrialisé, telles que le diabète, l'hypertension et les maladies cardiovasculaires. Malgré de nombreuses études, les mécanismes à l'origine de la résistance à l'insuline restent encore incomplètement élucidés. En plus d'une composante génétique, de nombreux facteurs environnementaux semblent impliqués parmi ces derniers, nous nous sommes intéressés à l'effet d'une alimentation riche en graisses associée à une période d'inactivité physique de courte durée. Nous nous sommes également penchés sur la corrélation décrite entre la résistance à l'insuline et la concentration de graisses présentes à l'intérieur des cellules musculaires squelettiques, appelées lipides intramyocellulaires. Pour ce faire, 8 volontaires masculins ont été étudiés à deux occasions. Après deux jours de diète équilibrée associée à une activité physique, les participants étaient confinés au lit strict pour 60 heures et devaient manger une alimentation soit riche en graisses saturées soit riche en hydrates de carbones. Pour évaluer l'effet de l'alimentation seule, 6 des 8 volontaires ont été réétudiés après deux jours de diète équilibrée suivie par 60 heures d'alimentation riche en graisses saturées associées à une activité physique contrôlée. Nous avons estimé la sensibilité à l'insuline par la technique du clamp hyperinsulinémique euglycémique alors que la concentration de lipides intramyocellulaires a été déterminée par spectroscopie par résonance magnétique. Après 60 heures d'inactivité physique associée à une alimentation riche en lipides, nous avons observé une diminution de l'utilisation de glucose dépendante de l'insuline (-24±6%; p<0.05), alors qu'aucune modification significative de ce même paramètre n'a été constatée lorsque l'inactivité physique était associée à une alimentation riche en hydrates de carbones (+19±10%). Ces deux conditions se sont accompagnées d'une augmentation des lipides intramyocellulaires (+32±7% et +17±8% respectivement). Bien que l'augmentation des lipides intramyocellulaires observée après 60 heures d'une alimentation riche en graisses saturées associée à une activité physique modérée fût d'une ampleur similaire à celle de la condition associant une alimentation riche en graisses et inactivité physique, l'utilisation de glucose induite par l'insuline n'a pas été modifiée de manière significative (-7±9%) Ces résultats indiquent que l'inactivité physique et une alimentation riche en graisses saturées semblent interagir, induisant une diminution de la sensibilité à l'insuline globale. La concentration de lipides intramyocellulaires a été influencée par les lipides issus de l'alimentation et l'inactivité physique, sans être toutefois corrélée à la résistance à l'insuline. Abstract OBJECTIVE - To assess the effect of a possible interaction between dietary fat and physical inactivity on whole-body insulin sensitivity and intramyocellular lipids (IMCLs). RESEARCH DESIGN AND METHODS - Eight healthy male volunteers were studied on two occasions. After 2 days of an equilibrated diet and moderate physical activity, participants remained inactive (bed rest) for 60 h and consumed either a high-saturated fat (45% fat, of which ~60% was saturated fat [BR-HF]) or a high-carbohydrate (70% carbohydrate [BR-HCHO]) diet. To evaluate the effect of a high-fat diet alone, six of the eight volunteers were restudied after a 2-day equilibrated diet followed by 60 h on a high-saturated fat diet and controlled physical activity (PA-HF). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and IMCL concentrations by H-magnetic resonance spectroscopy. RESULTS - Insulin-mediated glucose disposal was decreased by BR-HF condition (-24 ± 6%, P < 0.05) but did not change with BR-HCHO ( + 19 ± 10%, NS). BR-HF and BR-HCHO increased IMCL levels (+32 ± 7%, P < 0.05 and +17 ± 8%, P < 0.0011, respectively). Although the increase in IMCL levels with PA-HF (+31 ± 19%, P = 0.12) was similar to that during BR-HF, insulin-mediated glucose disposal ( -7 ± 9%, NS) was not decreased. CONCLUSIONS - These data indicate that physical inactivity and a high-saturated fat diet may interact to reduce whole-body insulin sensitivity. IMCL content was influenced by dietary lipid and physical inactivity but was not directly associated with insulin resistance.

Effects of dopamine on total oxygen consumption and oxygen delivery in healthy men.

The effect of acute intravenous dopamine (DA) administration at three sequential (but randomized) infusion rates was studied in eight young male volunteers. DA was infused at 2.5, 5, and 10 micrograms.kg-1.min-1. O2 consumption (VO2) and CO2 production (VCO2) were measured continuously by means of a computerized indirect calorimeter (blood system). In response to the 5- and 10-micrograms.kg-1.min-1 DA infusion rates, a significant increase (P less than 0.01) in VO2 corresponding to a 6% (range, 3-10) and 15% (range, 12-23) increase, respectively, of preinfusion values was observed. In contrast, at the low dose (2.5 micrograms.kg-1.min-1), DA induced no significant change in VO2. Cardiac output (Qc) increased significantly after the three DA administration rates [19% (range, 0-42), 34% (range, 17-71), and 25% (range, -3 to +47)] for the doses 2.5, 5, and 10 micrograms.-kg-1.min-1, respectively. The increase in O2 delivery (QO2) outweighed VO2 at all administration rates despite the relative drop in QO2 at the maximal DA administration rate. These results indicate that in humans DA improves net O2 supply to tissues proportionally more than it increases VO2 at all doses used in the present study.

Effects of the peroxisomal proliferator-activated receptor-gamma agonist pioglitazone on renal and hormonal responses to salt in healthy men.

Glitazones are used in the treatment of type 2 diabetes as efficient insulin sensitizers. They can, however, induce peripheral edema through an unknown mechanism in up to 18% of cases. In this double-blind, randomized, placebo-controlled, four-way, cross-over study, we examined the effects of a 6-wk administration of pioglitazone (45 mg daily) or placebo on the blood pressure, hormonal, and renal hemodynamic and tubular responses to a low (LS) and a high (HS) sodium diet in healthy volunteers. Pioglitazone had no effect on the systemic and renal hemodynamic responses to salt, except for an increase in daytime heart rate. Urinary sodium excretion and lithium clearance were lower with pioglitazone, particularly with the LS diet (P < 0.05), suggesting increased sodium reabsorption at the proximal tubule. Pioglitazone significantly increased plasma renin activity with the LS (P = 0.02) and HS (P = 0.03) diets. Similar trends were observed with aldosterone. Atrial natriuretic levels did not change with pioglitazone. Body weight increased with pioglitazone in most subjects. Pioglitazone stimulates plasma renin activity and favors sodium retention and weight gain in healthy volunteers. These effects could contribute to the development of edema in some subjects treated with glitazones.