Divergences in antihypertensive therapy in special situations in nephrology.

CONTEXT AND OBJECTIVE: The choice of an antihypertensive drug is based on several criteria and specific situations give rise to doubt and controversy. The aim here was to evaluate physicians approaches towards treatment with antihypertensive agents in specific situations. DESIGN AND SETTING: Cross-sectional study, at Universidade Federal de S?o Paulo, S?o Paulo. METHODS: A questionnaire was applied during a nephrology meeting to evaluate individual approaches towards each hypothetical clinical situation. The questionnaire consisted of five multiple-choice questions (clinical cases) concerning controversial aspects of antihypertensive therapy. RESULTS: A total of 165 questionnaires were analyzed. Most participants were nephrologists (93.2%). There was a preference for angiotensin-converting enzyme (ACE) inhibitors in at least two of the cases. Only 57.2% of the physicians were correct in choosing beta-blockers as the first-line drugs for patients with ischemic coronary disease. Moreover, 66.2% chose ACE inhibitors as the first-line drugs for patients with chronic kidney disease and proteinuria. About 5% of the physicians did not follow the current recommendations for the use of ACE inhibitors in diabetic patients with microalbuminuria. The most controversial question concerned the first-line drug for advanced chronic kidney disease. Most physicians were correct in choosing calcium channel blockers and avoiding ACE inhibitors in renovascular hypertension in the case of a patient with a single functioning kidney. CONCLUSIONS: Most physicians adopted the correct approach, but some had an alternative strategy for the same situations that was not based on evidence.     

Immunogenicity of a tetravalent meningococcal glycoconjugate vaccine in infants: a randomized controlled trial

Context  Immunization with a meningococcal tetravalent (serogroup ACWY) glycoconjugate vaccine is recommended for all US adolescents. However, the currently licensed vaccine is poorly immunogenic in infancy, when the highest rates of disease are observed. Objective  To determine the immunogenicity of a novel tetravalent CRM₁₉₇-conjugated meningococcal vaccine (MenACWY) in infants. Design, Setting, and Participants  Randomized, open-label, controlled study of 225 UK and 196 Canadian 2-month-olds from August 2004 to September 2006. Intervention  UK infants received a primary course of MenACWY (at 2, 3, and 4 months or 2 and 4 months) or Neisseria meningitidis serogroup C monovalent meningococcal glycoconjugate vaccine (MenC) (at 2 and 4 months). All received MenACWY at 12 months. Canadian infants received MenACWY at 2, 4, and 6 months or 2 and 4 months; at 12 months they received MenACWY, a plain tetravalent polysaccharide vaccine, or no vaccine. Main Outcome Measure  Percentage of infants with a human complement serum bactericidal activity (hSBA) titer 1:4 after a primary course of MenACWY and after a 12-month booster. Safety and reactogenicity of MenACWY were also assessed. Results  According to the prespecified per-protocol analysis, the percentages (95% CIs) of MenACWY 2-, 3-, and 4-month recipients with hSBA titers 1:4 after primary immunization were serogroup A, 93% (84%-98%); C, 96% (89%-99%); W-135, 97% (90%-100%); and Y, 94% (86%-98%). With a post hoc intention-to-treat analysis with imputed values for missing data, these values were unchanged for serogroups C and Y; for serogroup A, values were 92% (84%-97%), and for W-135, 97% (91%-99%). For the per-protocol analysis of MenACWY 2-, 4-, and 6-month recipients, the percentages (95% CIs) of responders were A, 81% (71%-89%); C, 98% (92%-100%); W-135, 99% (93%-100%); and Y, 98% (92%-100%). With the imputed value analysis, these values were A, 83% (74%-89%); C, 98% (93%-99%); W-135, 99% (94%-100%); and Y, 98% (92%-99%). At least 84% of MenACWY 2- and 4-month recipients achieved hSBA titers 1:4 for serogroups C, W-135, and Y after primary immunization, as did at least 60% for serogroup A (per-protocol and imputation analysis). At least 95% of primary and booster MenACWY recipients achieved hSBA titers 1:4 for serogroups C, W-135, and Y at 13 months, as did at least 84% for serogroup A (per-protocol and imputation analysis). During the primary immunization course, postimmunization pain on leg movement was observed in 2% of UK MenACWY 2- and 4-month recipients and 4% of MenC 2- and 4-month recipients; a temperature of 38°C or greater was observed in 4% and 2% in these groups, respectively. Conclusion  MenACWY is well tolerated and immunogenic in infancy. Trial Registration  clinicaltrials.gov Identifier: NCT00262002      

Muscle strength and power, maximum oxygen consumption, and body composition in middle-aged short-stature adults with childhood-onset growth hormone deficiency

BACKGROUND: Growth hormone (GH) replacement in adult GH-deficient (GHD) patients is reported to have a long-term beneficial effect on muscle mass and function, these effects being greater in young males and in adult-onset compared with those with childhood-onset GHD. To date, more discordant data are reported on the degree of muscle impairment in untreated GHD patients, due to the large heterogeneity of this syndrome. METHODS: Muscle maximum total isotonic strength (ST), lower limb maximum power output (W), maximum aerobic capacity (VO(2)max) and body composition (by tetrapolar bio-impedentiometry) were evaluated in seven short-stature adults with childhood-onset GHD and in seven age-matched normal-stature controls with comparable lifestyle and daily physical activity. RESULTS: Significant differences were found in body composition between control subjects and GHD patients, who presented higher adiposity (mean BMI+/-SD: GHD, 27.8+/-5.8 kg/m(2); controls, 22.1+/-0.8 kg/m(2); p=0.047), larger fat mass (GHD, 21.8+/-10.7 kg; controls, 8.8+/-3.5 kg; p=0.008), and lower fat-free mass (GHD, 65.8+/-11.4 %; controls, 87.0+/-6.5 %; p=0.002). In absolute terms, GHD patients attained significantly lower values in ST (GHD, 2479+/-493 N; controls, 4578+/-1476 N; p=0.008), W (GHD, 1092+/-452 W; controls, 1910+/-781 W; p=0.035) and VO(2)max (GHD, 1.68+/-0.40 l/min; controls, 2.67+/-0.84 l/min; p=0.035) than those attained by controls. The differences were still evident when the results were normalized by unit body mass, whereas they disappeared when the parameters were expressed per unit fat-free mass, suggesting for these patients the presence of an intrinsic muscle function in the same range as that of control subjects. CONCLUSIONS: Middle-aged and short-stature adults with childhood-onset GHD, who received discontinuous pit-GH substitution therapy only during childhood and have uncorrected long-lasting GHD, still retain a normal intrinsic muscle capability in attaining isotonic strength, generating anaerobic power as well as accomplishing oxidative processes. Nonetheless, it is not known which age-dependent evolution in motor dysfunction could be expected in this subgroup of GHD patients, when ageing processes add up to hormonal deficiencies.     

Ethanol-Induced Extracellular Signal Regulated Kinase: Role of Dopamine D1 Receptors

Background:  Addictive drugs activate extracellular signal regulated kinase (ERK) in brain regions critically involved in their affective and motivational properties. The aim of this study was to demonstrate the ethanol-induced activation of ERK in the nucleus accumbens (Acb) and in the extended amygdala [bed nucleus of the stria terminalis lateralis (BSTL) and central nucleus of the amygdala (CeA)] and to highlight the role of dopamine (DA) D₁ receptors in these effects.
Methods:  Ethanol (0.5, 1, and 2 g/kg) was administered by gavage and ERK phosphorylation was determined in the nucleus Acb (shell and core), BSTL, and CeA by immunohistochemistry. The DA D₁ receptor antagonist, SCH 39166 (SCH) (50 μg/kg), was administered 10 minutes before ethanol (1 g/kg).
Results:  Quantitative microscopic examination showed that ethanol, dose-dependently increased phospho-ERK immunoreactivity (optical and neuronal densities) in the shell and core of nucleus Acb, BSTL, and CeA. Pretreatment with SCH fully prevented the increases elicited by ethanol (1 g/kg) in all brain regions studied.
Conclusions:  The results of this study indicate that ethanol, similar to other addictive drugs, activates ERK in nucleus Acb and extended amygdala via a DA D₁ receptor-mediated mechanism. Overall, these results suggest that the D₁ receptors/ERK pathway may play a critical role in the motivational properties of ethanol.     

Seasonal variation of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) in endemic area of visceral leishmaniasis, Campo Grande, state of Mato Grosso do Sul, Brazil

The seasonal distribution of Lutzomyia longipalpis was studied in two forested and five domiciliary areas of the urban area of Campo Grande; MS, from December 2003 to November 2005. Weekly captures were carried out with CDC light traps positioned on ground and in the canopy inside a residual forest and on the edge (ground) of a woodland and in at least one of the following ecotopes in peridomiciles-a cultivated area, a chicken coop, a pigsty, a kennel, a goat and sheep shelter and an intradomicile. A total of 9519 sand flies were collected, 2666 during the first year and 6853 during the second. L. longipalpis was found throughout the 2-year period, presenting smaller peaks at intervals of 2-3 months and two greater peaks, the first in February and the second in April 2005, soon after periods of heavy rain. Only In one of the woodlands was a significant negative correlation (p<0.05) between the number of insects and temperature during the first year and the climatic factors (temperature, RHA and rain) was observed. In the domiciliary areas in four domiciles some positive correlations (p< or =0.05) occurred in relation to one or more climatic factors; however, the species shows a clear tendency to greater frequency (72%) in the rainy season than in the dry (28%). Thus, we recommend an intensification of the VL control measures applied in Campo Grande, MS, during the rainy season with a view to reducing the risk of the transmission of the disease.