Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids.

Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure. Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study. Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12-18 months. Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.

Effectiveness and Safety of Acupuncture and Moxibustion in Pregnant Women with Noncephalic Presentation: An Overview of Systematic Reviews.

BACKGROUND: Breech presentation at the time of delivery is 3.8-4%. Fetuses that maintain a noncephalic presentation beyond 32 weeks will have a lower probability of spontaneous version before labor. Given the increasing interest in exploring the use of complementary medicine during pregnancy and childbirth, the moxibustion technique, a type of traditional Chinese medicine, could be another option to try turning a breech baby into a cephalic presentation. OBJECTIVES: To review the evidence from systematic reviews (SR) on the efficacy and safety of acupuncture and moxibustion in pregnant women with noncephalic presentation. MAIN RESULTS: Our SR synthesizes the results from five clinical trials on pregnant women with a singleton noncephalic presentation. There is evidence that moxibustion reduces the number of noncephalic presentations at the time of birth compared with no treatment. The adverse effects that acupuncture and moxibustion can cause seem to be irrelevant. Most SRs agree that there are no adverse effects directly related to acupuncture and moxibustion. CONCLUSIONS: Even though the results obtained are positive and the five reviews conclude that moxibustion reduces the number of noncephalic presentations at birth (alone or combined with postural techniques or acupuncture), there is considerable heterogeneity between them. Better methodologically designed studies are required in the future to reaffirm this conclusion.

Aronia-citrus juice (polyphenol-rich juice) intake and elite triathlon training: a lipidomic approach using representative oxylipins in urine.

In the present study, we examined whether particular urinary oxylipins (isoprostanes (IsoPs), leukotrienes (LTs), prostaglandins (PGs), and thromboxanes (TXs)) in 16 elite triathletes could alter during 145 days of training. Within this time span, 45 days were dedicated to examining the effects of the intake of a beverage rich in polyphenols (one serving: 200 mL per day) supplemented in their diet. The beverage was a mixture of citrus juice (95%) and Aronia melanocarpa juice (5%) (ACJ). Fifty-two oxylipins were analyzed in the urine. The quantification was carried out using solid-phase extraction, liquid chromatography coupled with triple quadrupole mass spectrometry. The physical activity decreased the excretion of some PG, IsoP, TX, and LT metabolites from arachidonic acid, γ-dihomo-linolenic acid, and eicosapentaenoic acid. The ACJ also reduced the excretion of 2,3-dinor-11ß-PGF2α and 11-dehydro-TXB2, although the levels of other metabolites increased after juice supplementation (PGE2, 15-keto-15-F2t-IsoP, 20-OH-PGE2, LTE4, and 15-epi-15-E2t-IsoP), compared to the placebo. The metabolites that increased in abundance have been related to vascular homeostasis and smooth muscle function, suggesting a positive effect on the cardiovascular system. In conclusion, exercise influences mainly the decrease in oxidative stress and the inflammation status in elite triathletes, while ACJ supplementation has a potential benefit regarding the cardiovascular system that is connected in a synergistic manner with elite physical activity.

Targeting γ-secretases protect against angiotensin II-induced cardiac hypertrophy.

OBJECTIVE: The Notch pathway has been linked to pulmonary hypertension, but its role in systemic hypertension and, in particular in left ventricular hypertrophy (LVH), remains poorly understood. The main objective of this work was to analyse the effect of inhibiting the Notch pathway on the establishment and maintenance of angiotensin II (Ang-II)-induced arterial hypertension and LVH in adult mice with inducible genetic deletion of γ-secretase, and to test preclinically the therapeutic efficacy of γ-secretase inhibitors (GSIs). BASIC METHODS: We analysed Ang-II responses in primary cultures of vascular smooth muscle cells obtained from a novel mouse model with inducible genetic deletion of the γ-secretase complex, and the effects of GSI treatment on a mouse cardiac cell line. We also investigated Ang-II-induced hypertension and LVH in our novel mouse strain lacking the γ-secretase complex and in GSI-treated wild-type mice. Moreover, we analysed vascular tissue from hypertensive patients with and without LVH. MAIN RESULTS: Vascular smooth muscle cells activate the Notch pathway in response to Ang-II both 'in vitro' and 'in vivo'. Genetic deletion of γ-secretase in adult mice prevented Ang-II-induced hypertension and LVH without causing major adverse effects. Treatment with GSI reduced Ang-II-induced hypertrophy of a cardiac cell line 'in vitro' and LVH in wild-type mice challenged with Ang-II. We also report elevated expression of the Notch target HES5 in vascular tissue from hypertensive patients with LVH compared with those without LVH. CONCLUSION: The Notch pathway is activated in the vasculature of mice with hypertension and LVH, and its inhibition via inducible genetic γ-secretase deletion protects against both conditions. Preliminary observations in hypertensive patients with LVH support the translational potential of these findings. Moreover, GSI treatment protects wild-type mice from Ang-II-induced LVH without affecting blood pressure. Our results unveil the potential use of GSIs in the treatment of hypertensive patients with LVH.

Potentially inappropriate prescribing in institutionalised older patients in Spain: the STOPP-START criteria compared with the Beers criteria / Prescripción potencialmente inapropiada en ancianos institucionalizados en España: los criterios STOPP-START comparados con los criterios de Beers

Objective: The aims of this study were to identify potentially inappropriate prescribing using the Beers and STOPP criteria. The START criteria were applied to detect prescription omission in the geriatric population. We compared the utility of these criteria in institutionalised older people. Methods: Descriptive study reviewing the medication and clinical records of 81 residents (aged 65 years and more) by pharmacists in a nursing home in the Lleida region (Spain). Results: The mean patients’ age was 84 (SD=8) years, with an average of 5 drugs per resident (total prescriptions: 416 medicines). The Beers criteria identified potentially inappropriate medication use in 25% of patients and 48% of patients used at least 1 inappropriate medication according to STOPP criteria. The most frequent potentially inappropriate medications for both criteria were long-acting benzodiazepines and NSAIDs. START detected 58 potential prescribing omissions in 44% of patients. Calcium-vitamin D supplementation in osteoporosis was the most frequent rule (15%), but omissions corresponding to the cardiovascular system implied 23% of patients. Conclusion: The STOPP-START criteria reveal that potentially inappropriate prescribing (PIP) is a highly prevalent problem among Spanish nursing home residents, and a statistically significant positive correlation was found between the number of medicines prescribed and the number of PIP detected in this study. The STOPP criteria detect a larger number of PI medications in this geriatric population than the Beers criteria. The prescribing omissions detected by the START criteria are relevant and require intervention. Pharmacists’ review of medications may help identify potentially inappropriate prescribing and, through an interdisciplinary approach, working with physicians may improve prescribing practices among geriatric residents of nursing homes (AU)

Objetivo: Este estudio está orientado a identificar la prescripción potencialmente inapropiada usando los criterios de Beers y STOPP. Las omisiones de prescripciones se detectan en esta población geriátrica aplicando los criterios START. Se compara la utilidad de estos criterios en ancianos institucionalizados. Métodos: Estudio descriptivo de revisión de la medicación y las historias clínicas por farmacéuticos, de 81 pacientes (con 65 o más años) ingresados en una residencia en la provincia de Lleida (España). Resultados: La media de edad de los pacientes fue de 84 años (DE=8), con cinco medicamentos de promedio de tratamiento por residente (prescripciones totales: 416 medicamentos). Los criterios de Beers detectaron el uso de medicación potencialmente inapropiada en el 25% de los pacientes. Los criterios STOPP identificaron una posible medicación inapropiada en el 48% de los pacientes. La mayor frecuencia de uso de medicamentos potencialmente inapropiados para ambos criterios correspondió a las benzodiacepinas de larga duración y los AINE. Los criterios START detectaron 58 prescripciones potencialmente omitidas en el 44% de los pacientes. Entre ellas, la ausencia de suplementos de Calcio-vitamina D en osteoporosis fue la regla más frecuentemente implicada (15% de los pacientes); sin embargo, las omisiones relacionadas con el sistema cardiovascular asociadas a elevado riesgo cardiovascular son las que implicaron hasta un 23% de pacientes. Conclusión: La aplicación de los criterios STOPPSTART ha detectado una elevada proporción de prescripciones potencialmente inapropiadas en pacientes ancianos en una residencia sanitaria en España, con una significativa correlación positiva entre el número de medicamentos prescritos al paciente y el número de prescripciones potencialmente inapropiadas. Los criterios STOPP identificaron más medicación potencialmente inapropiada que los criterios de Beers. Las omisiones detectadas por los criterios START son relevantes y requiere una intervención. La revisión de la medicación por un farmacéutico puede ayudar a identificar potenciales prescripciones inapropiadas y, con un abordaje interdisciplinario, en colaboración con los médicos se podría mejorar la prescripción en pacientes ancianos de residencias geriátricas (AU)

Potentially inappropriate prescribing in institutionalised older patients in Spain: the STOPP-START criteria compared with the Beers criteria.

OBJECTIVE: The aims of this study were to identify potentially inappropriate prescribing using the Beers and STOPP criteria. The START criteria were applied to detect prescription omission in the geriatric population. We compared the utility of these criteria in institutionalised older people. METHODS: Descriptive study reviewing the medication and clinical records of 81 residents (aged 65 years and more) by pharmacists in a nursing home in the Lleida region (Spain). RESULTS: The mean patients''age was 84 (SD=8) years, with an average of 5 drugs per resident (total prescriptions: 416 medicines). The Beers criteria identified potentially inappropriate medication use in 25% of patients and 48% of patients used at least 1 inappropriate medication according to STOPP criteria. The most frequent potentially inappropriate medications for both criteria were long-acting benzodiazepines and NSAIDs. START detected 58 potential prescribing omissions in 44% of patients. Calcium-vitamin D supplementation in osteoporosis was the most frequent rule (15%), but omissions corresponding to the cardiovascular system implied 23% of patients. CONCLUSIONS: The STOPP-START criteria reveal that potentially inappropriate prescribing (PIP) is a highly prevalent problem among Spanish nursing home residents, and a statistically significant positive correlation was found between the number of medicines prescribed and the number of PIP detected in this study. The STOPP criteria detect a larger number of PI medications in this geriatric population than the Beers criteria. The prescribing omissions detected by the START criteria are relevant and require intervention. Pharmacists' review of medications may help identify potentially inappropriate prescribing and, through an interdisciplinary approach, working with physicians may improve prescribing practices among geriatric residents of nursing homes.

[Palliative and support care at home in primary care]. / Atención sanitaria paliativa y de soporte de los equipos de atención primaria en el domicilio.

OBJECTIVES: To estimate the proportion of people requiring palliative and support care at home in primary care and to describe their characteristics. METHODS: A descriptive study was carried out by five Spanish sentinel networks between October 2007 and March 2008 in 282,216 people attended by 218 general practitioners and nurses. Patients receiving comprehensive, active and continued care at home were included if the aim was not to prolong life but to achieve the best quality of life for the patient, the family and the carers. A standard form was used to collect data on age, sex, type of patient, underlying diseases and other variables related to the process. Crude and age-adjusted rates were estimated. RESULTS: Of the 400 men and 792 women registered, 12% were strictly terminal. The mean age was 82.4 years and was higher in patients with functional disability (82.9 years) than in terminally-ill patients (78.9 years) (p<0.01). The estimated prevalence was 422.3 per 100,000 inhabitants aged 14 years or more (95% CI: 398.7-447.0) and was much higher in women than in men (553.9 versus 287.3, p<0.01). The estimate for the entire Spanish population was 309.0 per 100,000 inhabitants (95% CI: 286.0-332.0). CONCLUSIONS: The prevalence of palliative and support care in Spain is around three cases per 1,000 inhabitants and is higher in elderly populations. More than 85% of patients needing palliative or support care have a life expectancy of over 6 months and thus represent the majority of persons using this type of medical and social support. The most susceptible groups are women and the oldest-old.

Impacto pronóstico de una estrategia invasiva en el síndrome coronario agudo sin elevación del segmento ST según la presencia o no de disfunción sistólica / Effect of invasive treatment on prognosis in non-ST-segment elevation acute coronary syndrome with or without systolic dysfunction

Introducción y objetivos. Escasa evidencia respalda la implantación de una estrategia invasiva (EI) en pacientes con síndrome coronario agudo sin elevación del segmento ST (SCASEST) y disfunción sistólica (DS). El objetivo de este trabajo es evaluar el impacto pronóstico atribuible a una EI en sujetos con SCASEST según tengan DS o no. Métodos. Se incluyó a 972 pacientes consecutivos ingresados por SCASEST (descenso del segmento ST y/o elevación de troponina I). Se definió la DS como fracción de eyección < 50% mediante ecocardiografía transtorácica. El objetivo principal fue la muerte o infarto a largo plazo. Se analizó el impacto pronóstico atribuible a una EI mediante regresión de Cox. Resultados. El 23,4% presentó DS. Un total de 303 (31%) pacientes alcanzaron el objetivo primario, hecho que fue más frecuente en los pacientes con DS (el 49,8 frente al 25,5%; p < 0,001). La realización de coronariografías y procedimientos de revascularización fue similar entre pacientes con DS y pacientes con fracción de eyección ≥ 50% (el 59 frente al 63,4%; p = 0,239 y el 38,3 frente al 38,8%; p = 0,9). Tras un minucioso ajuste multivariable que incluyó un índice de propensión, se observó un impacto pronóstico diferencial atribuible a la realización de una coronariografía según hubiera DS o no (interacción, p = 0,01). Así, el beneficio del cateterismo fue evidente en los pacientes con DS ( hazard ratio [HR] = 0,47; intervalo de confianza [IC] del 95%, 0,3-0,75; p = 0,001), pero no en aquellos con fracción de eyección ≥ 50% (HR = 0,9; IC del 95%, 0,63-1,29; p = 0,567). Conclusiones. La presencia de DS permite la identificación de los SCASEST que más se benefician de aplicar una EI (AU)

Introduction and objectives. Few data are available on the use of invasive treatment in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) and systolic dysfunction. The aim of this study was to determine the effect of invasive treatment on the prognosis of patients with NSTEACS, with or without systolic dysfunction. Methods. The study included 972 consecutive patients admitted for NSTEACS (i.e. ST-segment depression or an elevated troponin-I level). Systolic dysfunction was defined as an ejection fraction <50 on transthoracic echocardiography the primary long-term endpoint was death or myocardial infarction effect of invasive treatment prognosis evaluated by cox regression analysis results overall 23 4 patients had systolic dysfunction and 303 31 2 reached which more frequent in those with 49 8 vs 25 5 p <.001). Usage of coronary angiography and revascularization procedures were similar in patients with systolic dysfunction and those with an ejection fraction ≥50% (59% vs. 63.4%; P=.239; and 38.3% vs. 38.8%; P=.9; respectively). Detailed adjusted multivariate analysis, including the use of a propensity score, demonstrated that coronary angiography had a differential effect on prognosis depending on the presence or absence of systolic dysfunction (interaction, P=.01). Catheterization was clearly beneficial in patients with systolic dysfunction (hazard ratio [HR]=0.47; 95% confidence interval [CI], 0.3-0.75; P=.001) but not in those with an ejection fraction ≥50% (HR=0.9; 95% CI, 0.63-1.29; P=.567). Conclusions. The presence of systolic dysfunction identifies those patients with NSTEACS who will benefit most from invasive treatment (AU)

High-spatiotemporal-quality petawatt-class laser system.

We have developed a femtosecond high-intensity laser system that combines both Ti:sapphire chirped-pulse amplification (CPA) and optical parametric CPA (OPCPA) techniques and produces more than 30 J broadband output energy, indicating the potential for achieving peak powers in excess of 500 TW. With a cleaned high-energy seeded OPCPA preamplifier as a front end in the system, for the compressed pulse without pumping the final amplifier, we found that the temporal contrast in this system exceeds 10(10) on the subnanosecond time scales, and is near 10(12) on the nanosecond time scale prior to the peak of the main femtosecond pulse. Using diffractive optical elements for beam homogenization of a 100 J level high-energy Nd:glass green pump laser in a Ti:sapphire final amplifier, we have successfully generated broadband high-energy output with a near-perfect top-hat-like intensity distribution.

Effect of porins and plasmid-mediated AmpC beta-lactamases on the efficacy of beta-lactams in rat pneumonia caused by Klebsiella pneumoniae.

The in vivo activities of imipenem, meropenem, and cefepime were studied in a model of rat pneumonia caused by a plasmid-mediated AmpC beta-lactamase ACT-1-producing Klebsiella pneumoniae strain (K. pneumoniae strain 12) and a derivative porin-deficient mutant (K. pneumoniae strain 12dp). No differences between these activities were seen with K. pneumoniae 12. Only meropenem showed an activity slightly better than that of imipenem with K. pneumoniae 12dp.

Aspectos etiológicos da pancreatite crônica no ambulatório de gastroenterologia da Santa Casa de Misericórdia de São Paulo / Etiologic aspects of chronic pancreatitis at gastroenterology clinic of the Santa Casa de Misericórdia Hospital in São Paulo

Objetivo: Analisar a etiologia das pancreatites crônicas(PC) do Ambulatório da Clínica de Gastroenterologia do Departamento de Medicina da Santa Casa de Misericórdia de São Paulo. Casuística e métodos: Foram avaliados, retrospectivamente, dados dos pacientes do setor de Afecções Pancreáticas, no período de 1986 a 2001.Os critérios diagnósticos para PC foram baseados em: história clínica, amilasemia, lipasemia, amilasúria de 24 horas, presença de síndrome de má absorção e diabetes melitus, ultra-sonografia abdominal, tomografia computadorizada do abdome e ecoendoscopia do pâncreas com achados compatíveis com PC.A análise estatística foi realizada pelo teste exato de Fisher.Resultados: A PC foi diagnosticada em 101 pacientes, sendo 79(78,2 por cento) do sexo masculino e 22(21,7 por cento) do feminino.A idade variou entre 22 e 87 anos, com mediana de 54,5 anos.As etiologias encontradas foram: alcoólica em 80(79,2 por cento) pacientes,obstrutiva em dois(1,9 por cento)pacientes e idiopática em 19(18,8 por cento)pacientes.A distribuição da etiologia no sexo masculino foi a seguinte:alcoólica em 76(96,2 por cento)casos,obstrutiva em um (1,2 por cento)caso e idiopática em dois (2,5 por cento)casos.No sexo feminino a etiologia foi obstrutiva em um (4,54 por cento)caso,alcoólica em quatro(18,18 por cento)casos e idiopática em 17(77,27 por cento)casos.Vale ressaltar que em seis pacientes mulheres com diagnóstico de PC idiopática,foram encontrados seis casos de microlitíase.Conclussão:A maior parte dos pacientes portadores de PC encontra-se na faixa etária entre 40 e 50 anos de idade.A principal etiologia evidenciada no total dos casos foi o consumo alcoólico,principalmente no sexo masculino.Das causas não relacionadas com álcool,as idiopáticas assumem a maioria,sendo nesta o principal contingente representado pelo sexo feminino