[Decreased glomerular filtration rate using the Cockckroft-Gault and MDRD formulas does not always predict cardiovascular morbidity and mortality in hypertensive primary care patients]. / El filtrado glomerular reducido según las fórmulas de Cockcroft-Gault y MDRD no siempre predice la morbimortalidad cardiovascular en los pacientes hipertensos atendidos en atención primaria.

BACKGROUND: A decrease in renal function is associated with cardiovascular morbidity and mortality. The aim of this study was to analyse the association of cardiovascular morbidity and mortality with baseline glomerular filtration rate (GFR), calculated according to the Cockcroft-Gault and MDRD formulas, with the incidence of major adverse cardiovascular events (MACEs) in a cohort of hypertensive individuals followed for 12 years. METHOD: We performed a prospective study of a random sample of 223 hypertensive patients free of MACEs, who were followed in an urban Primary Care Centre. GFR was estimated using both formulas. MACEs were considered as the onset of ischaemic heart disease, heart failure, heart attacks, peripheral vascular disease or cardiovascular death. Data were analysed using the life-table method and Cox regression modeling. RESULTS: The median follow-up was 10.7 (interquartile range, 6.5-12.1) years. Follow-up was completed in 191 participants (85.7%). The cumulative survival was 64.7% (95% Confidence Interval (CI), 57.9-71.6). The incidence of MACEs during the follow-up period was 3.6 (95% CI, 2.7-4.4) per 100 subject-years. The final multivariable model showed that the most predictive variables of MACEs in the study population were the presence of diabetes mellitus and the estimation of GFR ≥60 ml/min/1.73 m2 by MDRD equation. CONCLUSIONS: There was a relationship between the occurrence of MACEs and an estimated GFR by MDRD above 60 ml/min/1.73 m2 at study entry, inversely to what was expected. GFR estimated by the C-G formula was not associated with cardiovascular risk.

Respiratory muscle pressures in non-CF bronchiectasis: repeatability and reliability.

BACKGROUND: Respiratory muscle strength is used diagnostically in clinical practice and as an outcome measure in clinical trials in various chronic lung diseases. There is limited data on its repeatability in people with non-CF bronchiectasis. The aim of the present study was to assess the repeatability of maximal inspiratory (P( I)max) and expiratory pressures (P(E)max) in a group of patients with stable, moderate-to-severe non-CF bronchiectasis. METHODS: Twenty participants with stable moderate-to-severe non-CF bronchiectasis were recruited. Respiratory muscle strength measurements (three maximal inspiratory and expiratory pressures) were made on 2 separate days. A standard protocol was used, including practice tests, before obtaining three technically acceptable and reproducible readings with a difference of 10% or less between values. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00487149. RESULTS: The mean (SD) age of the non-CF bronchiectasis group was 63 (9) years. Maximal inspiratory pressures were repeatable with mean (SD) for highest P(I)max, Test 1 and Test 2, 75.90 (20) and 79.40 (19) cmH(2)O, and limits of agreement (mean difference +/- 2SD) -3.50 +/- 20 cmH(2)O, (p = 0.14). Maximal expiratory pressures differed significantly with mean (SD) for highest P(E)max, Test 1 and Test 2, 102.25 (27) and 112.30 (32) cmH(2)O, and limits of agreement (mean difference +/- 2SD) -10.10 +/- 35 cmH(2)O, (p = 0.02). The intraclass correlation coefficient (95% CI) for highest P(I)max and P(E)max was 0.93 (95% CI 0.82 to 0.97) and 0.90 (95% CI 0.76 to 0.96), respectively. CONCLUSION: Maximal inspiratory pressure measurements were repeatable during a period of clinical stability in moderate-to-severe non-CF bronchiectasis, suggesting this may be a useful outcome measure in non-CF bronchiectasis. Once a baseline has been established, a second visit is not required. P(E)max was not a repeatable measure and further study is necessary to ascertain how much practice testing is required to obtain an accurate value.

Síndrome nefrótico secundario a sífilis

El síndrome nefrótico se caracteriza por proteinuria importante, hipoalbuminemia, edema generalizado e hiperlipidemia. Según su etiología se clasifica en primario y secundario, siendo este último raramente encontrado en pediatría, cuyas causas pueden ser múltiples como enfermedades sistémicas, fármacos, neoplasias o enfermedades infecciosas. Se presenta el caso clínico de una adolescente femenina con síndrome nefrótico secundario a sífilis, quien recibió manejo antibiótico apropiado con resolución del cuadro clínico. (provisto por Infomedic International)

Nephrotic syndrome is characterized by significant proteinuria, hypoalbuminemia, generalized edema, and hyperlipidemia. According to its etiology, it is classified as primary and secondary, the latter being rarely found in pediatrics, whose causes can be multiple such as systemic diseases, drugs, neoplasms, or infectious diseases. A clinical case is presented of a female adolescent with nephrotic syndrome secondary to syphilis, who received appropriate antibiotic management with resolution of the clinical condition. (provided by Infomedic International)

Characterization of the European Sea Bass (Dicentrarchus labrax) Gonadal Transcriptome During Sexual Development.

The European sea bass is one of the most important cultured fish in Europe and has a marked sexual growth dimorphism in favor of females. It is a gonochoristic species with polygenic sex determination, where a combination between still undifferentiated genetic factors and environmental temperature determines sex ratios. The molecular mechanisms responsible for gonadal sex differentiation are still unknown. Here, we sampled fish during the gonadal developmental period (110 to 350 days post fertilization, dpf), and performed a comprehensive transcriptomic study by using a species-specific microarray. This analysis uncovered sex-specific gonadal transcriptomic profiles at each stage of development, identifying larger number of differentially expressed genes in ovaries when compared to testis. The expression patterns of 54 reproduction-related genes were analyzed. We found that hsd17ß10 is a reliable marker of early ovarian differentiation. Further, three genes, pdgfb, snx1, and nfy, not previously related to fish sex differentiation, were tightly associated with testis development in the sea bass. Regarding signaling pathways, lysine degradation, bladder cancer, and NOD-like receptor signaling were enriched for ovarian development while eight pathways including basal transcription factors and steroid biosynthesis were enriched for testis development. Analysis of the transcription factor abundance showed an earlier increase in females than in males. Our results show that, although many players in the sex differentiation pathways are conserved among species, there are peculiarities in gene expression worth exploring. The genes identified in this study illustrate the diversity of players involved in fish sex differentiation and can become potential biomarkers for the management of sex ratios in the European sea bass and perhaps other cultured species.

Physical training for cystic fibrosis.

BACKGROUND: Physical training may form an important part of the care package for people with cystic fibrosis. OBJECTIVES: To determine whether a prescribed regimen of physical training produces improvement or prevents deterioration in physiological and clinical outcomes in cystic fibrosis compared to no training. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of the most recent search: September 2007. SELECTION CRITERIA: All randomised and quasi-randomised controlled clinical trials in which a prescribed regimen of physical training is compared to no physical training in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, assessed methodological quality and extracted data. MAIN RESULTS: Of the 26 studies identified, seven studies which included 231 participants, met the inclusion criteria. This review does provide some limited evidence from both short- and long-term studies that aerobic or anaerobic physical training has a positive effect on primary outcomes (exercise capacity, strength and lung function) but improvements are not consistent between studies. AUTHORS' CONCLUSIONS: Conclusions about the efficacy of physical training in cystic fibrosis are limited by the small size, short duration and incomplete reporting of most of the studies included in this review. Physical training is already part of the care package offered to most people with cystic fibrosis and there is a lack of evidence to actively discourage this. The benefits obtained from including physical training in a package of care may be influenced by the type of training programme. Further research is needed to assess comprehensively the benefits of exercise programmes in people with cystic fibrosis and the relative benefits of the addition of aerobic versus anaerobic versus a combination of both types of physical training to the care of people with cystic fibrosis.

Non-invasive ventilation for cystic fibrosis.

BACKGROUND: Non-invasive ventilation (NIV) may be a means to temporarily reverse or slow the progression of respiratory failure in cystic fibrosis (CF). OBJECTIVES: To compare the effect of NIV versus no NIV in people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We searched the reference lists of each trial for additional publications possibly containing other trials. Most recent search: October 2006. SELECTION CRITERIA: Randomised controlled trials comparing a form of pressure preset or volume preset NIV to no NIV in people with acute or chronic respiratory failure in CF. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed trials for inclusion criteria and methodological quality, and extracted data. MAIN RESULTS: Fifteen trials were identified; seven trials met the inclusion criteria with a total of 106 participants. Six trials evaluated single treatment sessions only and one evaluated a six-week intervention. Four trials (79 participants) evaluated NIV for airway clearance compared with an alternative chest physiotherapy method and showed that airway clearance may be easier with NIV and people with CF may prefer it. We were unable to find any evidence that NIV increases sputum expectoration, but it did improve some lung function parameters.Three trials (27 participants) evaluated NIV for overnight ventilatory support. Lung function and nocturnal transcutaneous carbon dioxide were evaluated within two trials. Due to the small numbers of participants and statistical issues, there were discrepancies in the results between the RevMan and the original trial analyses. No clear differences were found between NIV compared with oxygen or room air except for exercise performance, which significantly improved with NIV compared to room air over six weeks. AUTHORS' CONCLUSIONS: Non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with CF who have difficulty expectorating sputum. Non-invasive ventilation, when used in addition to oxygen, may improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate to severe disease. These benefits of NIV have largely been demonstrated in single treatment sessions with small numbers of participants. The impact of this therapy on pulmonary exacerbations and disease progression remain unclear. There is a need for long-term randomised controlled trials which are adequately powered to determine the clinical effects of non-invasive ventilation in CF airway clearance and exercise.

Consequences of imperfect mixing the Gray-Scott model.

We study an autocatalytic reaction-diffusion scheme, the Gray-Scott model, when the mixing processes do not homogenize the reactants. Starting from the master equation, we derive the resulting coupled, nonlinear, stochastic partial differential equations that rigorously include the spatiotemporal fluctuations resulting from the interplay between the reaction and mixing processes. The fields are complex and depend on correlated complex noise terms. We implement a method to solve for these complex fields numerically and extract accurate information about the system evolution and stationary states under different mixing regimes. Through this example, we show how the reaction-induced fluctuations interact with the temporal nonlinearities, leading to results that differ significantly from the mean-field (perfectly mixed) approach. This procedure can be applied to an arbitrary nonlinear reaction diffusion scheme.

We think you can dance! A pilot randomised controlled trial of dance for nursing home residents with moderate to severe dementia.

OBJECTIVES: To evaluate the feasibility of a dance program for people with moderate to severe dementia living in nursing homeswith regards to recruitment and retention, assessment tools, intervention safety, attendance and engagement. DESIGN: Pilot randomised controlled trial with assessments at weeks 0, 16 and 32. SETTING: A nursing home in Sydney, Australia. INTERVENTIONS: Experienced dance teachers conducted dance groups (intervention) or music appreciation and socialisation groups (control) for 45min, three times a week for 16 weeks. MAIN OUTCOME MEASURES: Descriptive statistics for recruitment and retention, adverse events and attendance and engagement. RESULTS: Recruitment was smooth, attrition was17% over 32 weeks. Engagement during the sessions was high, and no serious falls or behavioural incidents occurred. Average attendance was poorer than anticipated for dance groups (67%) in comparison to music groups (89%). A ceiling effect on the Severe Impairment Battery and the logistical challenges of the Clinical Global Impression of Change meant they may not be optimal tools. CONCLUSIONS: It is feasible to conduct a study of group dance for people with moderate to severe dementia in residential care. Choice of attention control condition should be reconsidered.

Reconstruction of protein form with X-ray solution scattering and a genetic algorithm.

We have reconstructed, from experimental approximately 2 nm resolution X-ray solution scattering profiles, the corresponding shapes and sizes of myoglobin, troponin C, spermadhesin PSP-I/PSP-II, chymotrypsinogen A, superoxide dismutase, ovalbumin, tubulin, nitrite reductase, catalase, the structural change of troponin C upon dissociation of the two high affinity Ca(2+), and the solution model structure of a tandem pair of fibronectin type III cytoplasmic domains of integrin alpha6beta4 before determination of its crystal structure. To this purpose we have designed a new genetic algorithm which gradually explores a discrete search space and evolves convergent models made of several hundred beads (down to 0.3 nm radius) best fitting the scattering profile upon Debye calculation, without geometrical constraints or penalty for loose beads. This is a procedure of effective numerical transformation of the one-dimensional scattering profiles into three-dimensional model structures. The number of beads in models is correlated with the protein molecular mass (with one exception). The shape and approximate dimensions of each protein have been retrieved by a set of ten solution models, essentially superimposable with the available crystal structures.

Zonal expression of endothelial nitric oxide synthase in sheep and rhesus adrenal cortex.

There is mounting evidence that nitric oxide (NO) may inhibit adrenal steroidogenesis by binding to the heme group of P450 enzymes, particularly the rate-limiting steps cholesterol side-change cleavage P450, aldosterone synthase P450, and 17 alpha-hydroxylase/C(17/20)-lyase P450. Using immunohistochemistry, nitrotyrosine was detectable throughout the ovine adrenal cortex, and endothelial NO synthase (eNOS) was further identified in zona glomerulosa (ZG) and at a higher level throughout the zona fasciculata, increasing toward the medulla. Caveolin-1, 90-kDa heat shock protein, ERK-1/2, and Akt, all known and proposed regulators of eNOS activity, were detected throughout the ovine adrenal cortex. Western immunoblotting confirmed the identity of these proteins as well as the absence of neuronal NOS, inducible NOS, caveolin-2, and caveolin-3. Through dual immunostaining we further identified for the first time a zona intermedia without strong staining for 17 alpha-hydroxylase/C(17/20)-lyase P450 or angiotensin II type 1 receptor, but positive for eNOS. Rhesus adrenals also stained positively for eNOS, but staining was seen only in the ZG and zona reticularis. We conclude that eNOS may play a role in controlling zone-specific aldosterone synthase vs. 11 beta-hydroxylase activities of the single CYP11B gene in sheep. In the rhesus monkey, NO may modulate ZG aldosterone synthase, but it is not needed for control of the distinct 11 beta-hydroxylase in the zona fasciculata. In the zona reticularis, however, eNOS may control C(19) steroid production at the level of 17 alpha-hydroxylase vs. 17,20-lyase activity otherwise unopposed by 3beta-hydroxysteroid dehydrogenase.

Molecular target of endocrine disruption in human luteinizing granulosa cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin: inhibition of estradiol secretion due to decreased 17alpha-hydroxylase/17,20-lyase cytochrome P450 expression.

Estradiol (E2) production by human luteinized granulosa cells (hLGC) is inhibited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The molecular target of TCDD toxicity has not been identified. The decrease in E2 is ameliorated by androgen substrate addition and is not associated with changes in aromatase cytochrome P450 (P450arom) activity or protein expression. An antihuman 17alpha-hydroxylase/17,20-lyase cytochrome P450 (P450c17) antisera and a direct radiometric assay of 17,20-lyase activity were used to test the hypothesis that TCDD targets P450c17, thereby decreasing substrate availability for E2 synthesis by hLGC. P450c17 expression and 17,20-lyase activity were detected in hLGC with high levels of E2 secretion. Western immunoblot analysis demonstrated that TCDD treatment of hLGC decreased the expression of P450c17 by as much 50% (P < 0.05). TCDD exposure induced a 65% decrease in 17,20-lyase activity (P < 0.05), but no changes were seen in P450arom or in nicotinamide adenine dinucleotide phosphate (reduced)-cytochrome P450 oxidoreductase (reductase). Furthermore, the decreases in P450c17 and 17,20-lyase were proportional to the inhibition of E2 secretion. We conclude that the molecular target for endocrine disruption of hLGC by TCDD is P450c17, specifically decreasing the supply of androgens for E2 synthesis, and that it does not involve either P450arom or the redox partner protein reductase.

Regulation of microsomal P450, redox partner proteins, and steroidogenesis in the developing testes of the neonatal pig.

Testicular growth and plasma androgen concentrations increase markedly in the first weeks of neonatal life of pigs. The regulation of steroidogenesis through this period was examined by measuring total microsomal cytochromes P450 (P450), 17alpha-hydroxylase/17,20-lyase P450 (P450c17) and aromatase P450 (P450arom) enzyme activities, and the redox partner proteins nicotinamide adenine dinucleotide phosphate, reduced form (NADPH)-cytochrome P450 reductase (reductase) and cytochrome b(5) in testicular microsomes. Testes were collected from 1-24 d of age, and testicular development was suppressed by a GnRH antagonist in some animals from d 1-14. Both 17/20-lyase and aromatase activities increased from d 1-7 but not thereafter, and 17-20-lyase activity was always at least 200-fold higher than aromatase activity. Reductase decreased in wk 1, then increased to d 24. No changes were seen in cytochrome b(5) expression. GnRH antagonist treatment suppressed plasma LH, testosterone and testes growth to d 14. 17,20-Lyase and aromatase activities in testicular microsomes were reduced by 20% and 50%, respectively. Total microsomal P450 concentration was reduced by 50% on d 7, but there was no effect of treatment on reductase or cytochrome b(5) expression. These data support the hypothesis that the rise in neonatal testicular androgen secretion is more likely due to gonadotropin-stimulated gonadal growth, rather than specific P450c17 expression. Neither P450c17 nor P450arom can account for the decline in total microsomal P450. Reductase and cytochrome b(5) expression appears to be constitutive, but reductase levels saturate both P450c17 and P450arom.

Dopamine clearance in critically ill infants and children: effect of age and organ system dysfunction.

To learn if there are age-related differences in the pharmacokinetic behavior of dopamine, plasma dopamine clearance was determined in 27 acutely ill infants and children who were receiving a continuous intravenous infusion of the drug. Steady-state clearance was calculated from dopamine concentration in arterial blood. Dopamine clearance was 60.7 +/- 28.1 ml/kg/min. The age of the patient exerted an effect on clearance of dopamine (r = -0.63; p less than 0.05), and dopamine clearance was nearly twice as rapid in children younger than 2 years as it was in older children (82.3 +/- 27.7 ml/kg/min versus 45.9 +/- 17.0 mg/kg/min). Conjugated bilirubin exerted an age-independent effect on clearance of dopamine; clearance was 44.8 +/- 28.6 ml/kg/min in children with abnormal conjugated bilirubin (greater than or equal to 0.9 mg/dl) and 70.1 +/- 2.56 ml/kg/min in children with normal conjugated bilirubin (less than 0.9 mg/dl). Clearance was lowest (29.8 +/- 5.7 ml/kg/min) in the four children who had both hepatic and renal dysfunction. Age is an important determinant of dopamine clearance, explaining in part the clinical observation that infants and young children require higher infusion rates.

Gender differences in prostaglandin receptors of rat aorta.

The maximal contractile response to the prostaglandin endoperoxide H2 analogue U46619, prostaglandins E2, D2 and F2 alpha and the sensitivity of the superfused aorta preparation to these drugs (except PGF2 alpha) is greater in the male than the female rat. In contrast, gender differences were not observed in the response to noradrenaline of 5-hydroxytryptamine. In previous studies, testosterone unlike oestrogen or progesterone, increased the response of both rabbit and rat aorta to U46619. We conclude that prostaglandin receptors in rat thoracic aorta may be hormonally regulated.

Interruption of estradiol signal transduction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through disruption of the protein phosphorylation pathway in adipose tissues from immature and mature female rats.

At doses of 10-115 microg/kg, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreased body and adipose tissue weights of mature female rats. Doses below 10 microg TCDD/kg decreased body and adipose tissue weights of immature, but not mature females. Doses of 2 and 10 microg TCDD/kg decreased adipose tissue epidermal growth factor receptor (EGFR) binding activity 5 and 7 days later in immature and mature females, respectively. At these times, there was a decrease in the activities of tyrosine kinase (TK), mitogen-activated protein kinase (MAP2K), and protein kinase A (PKA). In mature females, estradiol (E2, 15 microg/kg) increased TK and PKA activities and decreased MAP2K activity. In immature females, E2 decreased TK and PKA activities but not MAP2K activity. TCDD abolished the stimulatory effect of E2 on TK and PKA in mature females, and in immature females TCDD potentiated the negative effect of E2 on all three kinases. TCDD decreased binding of [3H]E2 to cytosolic and nuclear estrogen receptors (ERs) of mature and immature females, and antagonized the stimulatory effect of E2 on ER binding activity. E2 increased DNA binding activity of the estrogen response element (ERE) and activator protein-1, and TCDD antagonized this effect. Geldanamycin, an inhibitor of Src tyrosine kinase, reduced the effects of TCDD on body and adipose tissue weights. Geldanamycin antagonized the effects of TCDD on EGFR binding activity and TK activity. In cell-free preparations, TCDD antagonized E2 action on TK activity in mature females, as well as E2 action on PKA activity in immature females. We hypothesize that TCDD antagonizes E2 action in female adipose tissues through disruption of common cytosolic signal transduction pathways.

The cellular immune response to immunization with zona pellucida antigens.

The cellular immune response of mice to porcine and rat zona pellucida and cynomolgus macaques to porcine zona pellucida antigens was evaluated. Mice mounted a vigorous cellular response to both antigens, as determined by the T cell proliferation response in vitro. There was poor cross-reactivity to murine zonae by T cells or serum antibodies from mice immunized with rat zona pellucida. Nevertheless, ovaries from the mice immunized with rat zona had significantly fewer antral follicles than adjuvant-treated controls, suggesting that the immune response to the zona antigen disrupted follicular development. T cells from two macaques that had been immunized with porcine zona pelludica proteins proliferated in vitro in response to this antigen. Both macaques also had strong antibody responses. The patterns of urinary steroid metabolites in these animals provided clear evidence of ovarian malfunction following immunization. The data indicate that a significant cellular immune response is generated upon immunization of animals with zona pellucida antigens regardless of whether the antigens are cross reactive with the host zona antigens. Whether impaired ovarian function and follicular development are related to the cellular response must be determined in future studies.

The effect of oxygen on the fibrinolytic enzyme system in vivo.

Arterial hypoxia has been accepted as a potent stimulus to increased fibrinolytic activity in vivo. This study has shown that significant levels of arterial hypoxaemia induced in healthy volunteers by breathing a hypoxic gas mixture have failed to induce changes in the fibrinolytic enzyme system.