Tubular Dysfunction in Idiopathic Nephrotic Syndrome

Objectives: To evaluate the degree of tubular involvement in INS at various stage of the disease. Methods: 19 patients with INS were studied. 13 were steroid responders (group 1). 5 of them had biopsy which showed MCD. 6 patients were non responder to steroid or were steroid dependant with frequent relapses (group 2). Biopsies showed 3 FSGS and 3 MCD. They were treated with prednisone, ciclosporin and/ or mycofenolate mofetil. Protein, microalbumin (ALB), alpha-microglobulin (AMG), N-acetyl-beta-D-glucosaminidase (NAG) and creatinine (cr) were measured in each urine sample. Patients were considered in remission if prot/ cr ratio (g/mol) was < 20 (group 1a and 2a), and in relapse if the ratio was > 200 (group 1c and 2c). Some patients in group 1 had non nephrotic proteinuria (group 1b). Tubular dysfunction was defi ned by NAG/cr ratio (mg/mmol) > 0.86 or by AMG/cr ratio (mg/mmol) > 1.58. Results: Prot/cr ALB/cr NAG/cr AMG/cr Group 1a 10.3 ± 4.1 1.1 ± 1.0 0.19 ± 0.12 1.40 ± 0.97 Group 1b 60.4 ± 63.4 42.8 ± 66.7 0.39 ± 0.21 1.20 ± 0.56 Group 1c 713.3 ± 276.8 799.8 ± 534.9 2.25 ± 1.86* 4.25 ± 2.09* Group 2a 11.3 ± 6.1 4.7 ± 5.7 0.26 ± 0.19 1.18 ± 0.60 Group 2c 914.9 ± 718.6 682.9 ± 589.3 3.00 ± 2.72* 5.47 ± 4.30* Results are mean ± SD, p < 0.001 compared to group 1a and 2a No difference was observed between group 1 and group 2 neither in remission nor in relapse. Conclusions: These data indicate that tubular dysfunction occurs in INS but only in patients in relapse. In this population, tubular dysfunction was independent of the severity of the nephrotic syndrome, the treatment protocol and the histopathology.

Effect of a novel beta-adrenoceptor agonist (Ro 40-2148) on resting energy expenditure in obese women.

The aim of this single-blind, placebo-controlled study was to investigate the effects of the new beta-adrenergic compound Ro 40-2148 on resting energy expenditure (REE) at rest and after an oral glucose load in non-diabetic obese women before and after two weeks of treatment. After one week of placebo administration and after an overnight fast and one hour rest, REE and glucose and lipid oxidation rates were measured by indirect calorimetry (hood system) before and for 6 h after a single dose of placebo solution. A 75 g oral glucose tolerance test (OGTT) was performed during this period starting 90 min after the placebo administration. During the following two weeks, using a randomization design, six patients received Ro 40-2148 at a dose of 400 mg diluted in 100 ml water twice a day (i.e. 800 mg per day), while six others continued with the placebo administration. The same tests and measurements were repeated after two weeks, except for the treatment group which received the drug instead of the placebo. The 14-day period of drug administration did not increase REE measured in post-absorptive conditions. Similarly, there was no acute effect on REE of a 400 mg dose of Ro 40-2148. In contrast, glucose-induced thermogenesis was significantly increased after two weeks in the treatment group (means +/- s.e.m.: 3.7 +/- 1.3%, P = 0.047), while no change was observed in the placebo group (-0.8 +/- 0.7%, not significant). Since there was no significant change in the respiratory quotient, the increase in energy expenditure observed in the treatment group was due to stimulation of both lipid and glucose oxidation. The drug induced no variations in heart rate, blood pressure, axillary temperature or in plasma glucose, insulin and free fatty acid levels. In conclusion, this study shows that Ro 40-2148 activates glucose-induced thermogenesis in obese non-diabetic patients.

TBS discrimine les femmes avec ostéoporose fracturaire des femmes non ostéoporotiques indépendamment de la DMO, de l'âge et de l'IMC : Etude de la cohorte Ostéo-Mobile Vaud

Introduction. - « Ostéo-Mobile Vaud » est un projet pilote visant àinformer et promouvoir les mesures générales de prévention del'ostéoporose chez les femmes vaudoises de 60 ans et plus. Son butest également d'évaluer le risque de fracture dans cette populationen associant les facteurs de risque cliniques, la mesure de la DMOpar DXA de la colonne lombaire et du fémur proximal (Hologic Discovery),la recherche des fractures vertébrales préexistantes parVFA et une appréciation de la « qualité osseuse » par TBS. Une phaseprospective de 5 ans est prévue. Le Trabecular Bone Score (TBS) estun procédé qui consiste à appliquer un traitement informatique àl'image 2D de projection de la DXA basé sur la quantification desvariations locales de niveaux de gris. Un modèle mathématiquerelie le paramètre TBS avec des paramètres de microarchitecture 3Dtels la connectivité 3D, le nombre de travées et l'espace inter-trabéculaire.Ce modèle fait de TBS une mesure indirecte de microarchitectureosseuse.Résultats. - Fin juillet 2011, 510 femmes de ± 67 ans, IMC ± 26 kg/m2,ont été évaluées. Une ou plusieurs fractures de fragilité ont été rapportéeschez 72 femmes, parmi lesquelles 39 avec fractures vertébrales.TBS diminue avec l'âge (-0.005 par année, p < 0,001) etdiminue en fonction de l'IMC (- 0,011 par kg/m2, p < 0,001). La corrélationentre TBS et la DMO de la colonne lombaire est faible(r = 0,4, p < 0,001) et un grand pourcentage de la variabilité du TBSest indépendant de la DMO (> 84%). TBS discrimine les femmes avecfractures vertébrales des femmes sans fracture vertébrale et lesfemmes avec OP clinique (fractures de fragilité) de celles sans OPclinique. Ce pouvoir discriminatif est indépendant de la DMO de lacolonne lombaire ou du T-score le plus bas, après ajustement pourl'âge et l'IMC.Odd ratio (OR, 95 % IC) pour une diminution d'une déviation standarddu TBS, ajusté pour l'âge, l'IMC et la mesure de DMO :Conclusion. - TBS représente une plus-value par rapport à la DMOdans l'appréciation du risque de fracture chez les femmes vaudoisesde 60 ans et plus.

Spine Bone Texture Assessed by Trabecular Bone Score (TBS) to Evaluate Bone Health in Thalassemia Major.

Due to the increasing survival of thalassemic patients, osteopathy is a mounting clinical problem. Low bone mass alone cannot account for the high fracture risk described; impaired bone quality has been speculated but so far it cannot be demonstrated noninvasively. We studied bone quality in thalassemia major using trabecular bone score (TBS), a novel texture measurement extracted from spine dual-energy X-ray absorptiometry (DXA), proposed in postmenopausal and secondary osteoporosis as an indirect index of microarchitecture. TBS was evaluated in 124 adult thalassemics (age range 19-56 years), followed-up with optimal transfusional and therapeutical regimens, and in 65 non-thalassemic patients (22-52 years) undergoing DXA for different bone diseases. TBS was lower in thalassemic patients (1.04 ± 0.12 [range 0.80-1.30]) versus controls (1.34 ± 0.11 [1.06-1.52]) (p < 0.001), and correlated with BMD. TBS and BMD values correlated with age, indicating that thalassemia negatively affects both bone quality and quantity, especially as the patient gets older. TBS was 1.02 ± 0.11 [0.80-1.28] in the osteoporotic thalassemic patients, 1.08 ± 0.12 [0.82-1.30] in the osteopenic ones and 1.15 ± 0.10 [0.96-1.26] in those with normal BMD. No gender differences were found (males: 1.02 ± 0.13 [0.80-1.30], females 1.05 ± 0.11 [0.80-1.30]), nor between patients with and without endocrine-metabolic disorders affecting bone metabolism. Our findings from a large population with thalassemia major show that TBS is a valuable tool to assess noninvasively bone quality, and it may be related to fragility fracture risk in thalassemic osteopathy.

Attitudes towards morphine use among Swiss nurses and physicians

Background: There is little information regarding risk perception and attitudes on morphine use in Switzerland. Objectives: We aimed at assessing such attitudes in a sample of health professionals in the French-speaking part of Switzerland. Study design: Cross-sectional study. Setting: five non-university hospitals of the French-speaking canton of Valais, Switzerland. Methods: 431 nurses and 40 physicians (age range: 20-63). Risk perception and attitudes towards morphine use were assessed using a validated questionnaire. Results: Over half of participants showed a negative attitude regarding most adverse events related to morphine, while less than one third showed a similar attitude regarding other statements. On bivariate analyses, participants working in geriatrics showed a more negative attitude towards use of morphine than participants working in medicine and surgery. Non-Swiss participants also showed a more negative attitude than Swiss regarding use of morphine. Conversely, no differences were found between genders, profession (nurses or physicians), years of experience (<=14 and >14) and religion (catholic vs. others/no religion). These findings were further confirmed by multivariate adjustment. Limitations: possible selection bias due to responders only. Results limited to French speaking participants. Conclusion: Attitudes regarding morphine uses are mainly driven by its potential adverse effects and vary according to specialty and nationality. Educational measures directed at health professionals working in geriatrics or coming from abroad might reduce the high morphinophobia levels observed in these groups.

Can the trabecular bone score (TBS) be considered as a major clinical risk factor (CRF) of osteoporotic fractures? A meta-like analysis

Abstract: To have an added value over BMD, a CRF of osteoporotic fracture must be predictable of the fracture, independent of BMD, reversible and quantifiable. Many major recognized CRF exist.Out of these factorsmany of themare indirect factor of bone quality. TBS predicts fracture independently of BMD as demonstrated from previous studies. The aim of the study is to verify if TBS can be considered as a major CRF of osteoporotic fracture. Existing validated datasets of Caucasian women were analyzed. These datasets stem from different studies performed by the authors of this report or provided to our group. However, the level of evidence of these studies will vary. Thus, the different datasets were weighted differently according to their design. This meta-like analysis involves more than 32000 women (≥50 years) with 2000 osteoporotic fractures from two prospective studies (OFELY&MANITOBA) and 7 crosssectional studies. Weighted relative risk (RR) for TBS was expressed for each decrease of one standard deviation as well as per tertile difference (TBS=1.300 and 1.200) and compared with those obtained for the major CRF included in FRAX®. Overall TBS RR obtained (adjusted for age) was 1.79 [95%CI-1.37-2.37]. For all women combined, RR for fracture for the lowest comparedwith themiddle TBS tertilewas 1.55[1.46- 1.68] and for the lowest compared with the highest TBS tertile was 2.8[2.70-3.00]. TBS is comparable to most of the major CRF (Fig 1) and thus could be used as one of them. Further studies have to be conducted to confirm these first findings.

The predictive value of trabecular bone score (TBS) on whole lumbar vertebrae mechanics: an ex vivo study.

We investigated the association of trabecular bone score (TBS) with microarchitecture and mechanical behavior of human lumbar vertebrae. We found that TBS reflects vertebral trabecular microarchitecture and is an independent predictor of vertebral mechanics. However, the addition of TBS to areal BMD (aBMD) did not significantly improve prediction of vertebral strength. INTRODUCTION: The trabecular bone score (TBS) is a gray-level measure of texture using a modified experimental variogram which can be extracted from dual-energy X-ray absorptiometry (DXA) images. The current study aimed to confirm whether TBS is associated with trabecular microarchitecture and mechanics of human lumbar vertebrae, and if its combination with BMD improves prediction of fracture risk. METHODS: Lumbar vertebrae (L3) were harvested fresh from 16 donors. The anteroposterior and lateral bone mineral content (BMC) and areal BMD (aBMD) of the vertebral body were measured using DXA; then, the TBS was extracted using TBS iNsight software (Medimaps SA, France). The trabecular bone volume (Tb.BV/tissue volume, TV), trabecular thickness (Tb.Th), degree of anisotropy, and structure model index (SMI) were measured using microcomputed tomography. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies to assess failure load and stiffness. RESULTS: The TBS was significantly correlated to Tb.BV/TV and SMI (râeuro0/00=âeuro0/000.58 and -0.62; pâeuro0/00=âeuro0/000.02, 0.01), but not related to BMC and BMD. TBS was significantly correlated with stiffness (râeuro0/00=âeuro0/000.64; pâeuro0/00=âeuro0/000.007), independently of bone mass. Using stepwise multiple regression models, we failed to demonstrate that the combination of BMD and TBS was better at explaining mechanical behavior than either variable alone. However, the combination TBS, Tb.Th, and BMC did perform better than each parameter alone, explaining 79 % of the variability in stiffness. CONCLUSIONS: In our study, TBS was associated with microarchitecture parameters and with vertebral mechanical behavior, but TBS did not improve prediction of vertebral biomechanical properties in addition to aBMD.

Estructura del subsistema demersal durante el crucero de evaluación del recurso Merluza, BIC Humboldt 9705-06, Callao a Puerto Pizarro

Presenta la estructura especiológica, distribución, espacio temporal y captura de peces e invertebrados accesibles a redes tipo Granton 130/400 y Engel 998/400, empleadas durante el Crucero de Evaluación del recurso merluza BIC Humboldt 9705-06. Así como el análisis de comunidades de peces del fondo de la fauna acompañante. Se capturó 134 especies: 99 fueron peces, 19 crustáceos, 12 moluscos, 2 equinodermos, 1 cnidario, 1 sipuncúlido y un cordado. En comparación con los dos últimos cruceros BIC SNP-1 9505-06 y 9607-08, la diversidad íctica se incrementó hasta 43%, aún sin haberse constatado presencia de la típica diversidad íctica tropical costera y estuarina. Al sur de los 6°S se encontró distribuida más del 50% de la riqueza íctica. La captura total fue 45.368,59 kg, de los cuales 40.106,04 se obtuvo en 63 lances de fondo y 5.262,55 kg con 20 lances de media agua. El falso volador Prionotus stephanophrys y la merluza Merluccius gayi peruanus fueron las especies más frecuentes y abundantes con 21.259,21 kg y 14.190,51 kg de captura total, respectivamente.

Efficacy of garenoxacin in treatment of experimental endocarditis due to Staphylococcus aureus or viridans group streptococci.

The activity of garenoxacin was investigated in rats with experimental endocarditis due to staphylococci and viridans group streptococci (VGS). The staphylococci tested comprised one ciprofloxacin-susceptible and methicillin-susceptible Staphylococcus aureus (MSSA) isolate (isolate 1112), one ciprofloxacin-susceptible but methicillin-resistant S. aureus (MRSA) isolate (isolate P8), and one ciprofloxacin-resistant mutant (grlA) of P8 (isolate P8-4). The VGS tested comprised one penicillin-susceptible isolate and one penicillin-resistant isolate (Streptococcus oralis 226 and Streptococcus mitis 531, respectively). To simulate the kinetics of drugs in humans, rats were infused intravenously with garenoxacin every 24 h (peak and trough levels in serum, 6.1 and 1.0 mg/liter, respectively; area under the concentration-time curve [AUC], 63.4 mg. h/liter) or levofloxacin every 12 h (peak and trough levels in serum, 7.3 and 1.5 mg/liter, respectively; AUC, 55.6 mg. h/liter) for 3 or 5 days. Flucloxacillin, vancomycin, and ceftriaxone were used as control drugs. Garenoxacin, levofloxacin, flucloxacillin, and vancomycin sterilized >/=70% of the vegetations infected with both ciprofloxacin-susceptible staphylococcal isolates (P < 0.05 versus the results for the controls). Garenoxacin and vancomycin also sterilized 70% of the vegetations infected with ciprofloxacin-resistant MRSA isolate P8-4, whereas treatment with levofloxacin failed against this organism (cure rate, 0%; P < 0.05 versus the results obtained with the comparator drugs). Garenoxacin did not select for resistant derivatives in vivo. In contrast, levofloxacin selected for resistant variants in four of six rats infected with MRSA isolate P8-4. Garenoxacin sterilized 90% of the vegetations infected with both penicillin-susceptible and penicillin-resistant isolates of VGS. Levofloxacin sterilized only 22 and 40% of the vegetations infected with penicillin-susceptible S. oralis 226 and penicillin-resistant S. mitis 531, respectively. Ceftriaxone sterilized only 40% of those infected with penicillin-resistant S. mitis 531 (P < 0.05 versus the results obtained with garenoxacin). No quinolone-resistant VGS were detected. In all the experiments successful quinolone treatment was predicted by specific pharmacodynamic criteria (D. R. Andes and W. A. Craig, Clin. Infect. Dis. 27:47-50, 1998). The fact that the activity of garenoxacin was equal or superior to those of the standard comparators against staphylococci and VGS indicates that it is a potential alternative for the treatment of infections caused by such bacteria.

Analysis of patient physical restraints usage in a Swiss emergency service

Introduction: Emergency services (ES) are often faced with agitated,confused or aggressive patients. Such situations may require physicalrestraint. The prevalence of these measures is poorly documented,concerning 1 to 10% of patients admitted in the ES. The indications forrestraint, the context and the related complications are poorly studied.The emergency service and the security service of our hospital havedocumented physical restraint for several years, using specific protocolsintegrated into the medical records. The study evaluated the magnitudeof the problem, the patient characteristics, and degree of adherence tothe restraint protocol.Methods: Retrospective study of physical restraint used on adultpatients in the ES in 2009. The study included analysis of medical anddemographic characteristics, indications justifying restraint and qualityof restraint documentation. Patients were identified from computerizedES and security service records. The data were supplemented byexamination of patients' medical records.Results: In 2009, according to the security service, 390 patients (1%)were physically restrained in the ES. The ES computerized systemidentified only 196 patients. Most patients were male (62%). The medianage was 40 years (15-98 years; P90 = 80 years). 63 % of the situationsoccurred between 18h00 and 6h00, and most frequently on Saturday(19%). Substance or alcohol abuse was present in 48.7% of cases andacute psychiatric crisis was mentioned in 16.7%. In most cases,restraint was motivated by extreme agitation or auto / hetero-aggressiveviolence. Most patients (68 %) were restrained with upper limb andabdominal restraints. More than three anatomic restraints werenecessary in 52 % of the patients. Intervention of security guards wasrequired in 77% of the cases. 61 restraint protocols (31 %) were missingand 57% of the records were incomplete. In many cases, the protocolsdid not include the signature of the physician (22%) or of the nurse(43.8%). Medical records analysis did not allow reliable estimation ofthe number of restraint-induced complications.Conclusions: Physical restraint is most often motivated by majoragitation and/or secondary to substance abuse. Caregivers regularlycall security guards for help. Restraint documentation is often missing orincomplete, requiring major improvement in education and prescription.

Alimentación de la merluza peruana Merluccius Gayi Peruanus a comienzos del invierno 1998. Crucero BIC José Olaya Balandra 9806-07 de Puerto Pizarro a Huarmey

Se han analizado 169 estómagos de merluza peruana, colectados entre el 27 de junio y 13 de julio de 1998. El comportamiento alimentario presenta variaciones en función de la latitud, intervalos de talla y horas de alimentación, los cuales reflejan la disponibilidad y accesibilidad de las presas, evidenciando una segregación de las mismas como efecto de El Niño 1997-98. Es notoria la ausencia de anchoveta en la dieta, en comparación con años anteriores. La ictiofagia se incrementa con el tamaño, destacando el canibalismo a partir de los 40 cm. La merluza peruana ha manifestado un gran oportunismo trófico durante el periodo mencionado.

Quantitative monitoring of tamoxifen in human plasma extended to 40 metabolites using liquid-chromatography high-resolution mass spectrometry: new investigation capabilities for clinical pharmacology.

Liquid-chromatography (LC) high-resolution (HR) mass spectrometry (MS) analysis can record HR full scans, a technique of detection that shows comparable selectivity and sensitivity to ion transitions (SRM) performed with triple-quadrupole (TQ)-MS but that allows de facto determination of "all" ions including drug metabolites. This could be of potential utility in in vivo drug metabolism and pharmacovigilance studies in order to have a more comprehensive insight in drug biotransformation profile differences in patients. This simultaneous quantitative and qualitative (Quan/Qual) approach has been tested with 20 patients chronically treated with tamoxifen (TAM). The absolute quantification of TAM and three metabolites in plasma was realized using HR- and TQ-MS and compared. The same LC-HR-MS analysis allowed the identification and relative quantification of 37 additional TAM metabolites. A number of new metabolites were detected in patients' plasma including metabolites identified as didemethyl-trihydroxy-TAM-glucoside and didemethyl-tetrahydroxy-TAM-glucoside conjugates corresponding to TAM with six and seven biotransformation steps, respectively. Multivariate analysis allowed relevant patterns of metabolites and ratios to be associated with TAM administration and CYP2D6 genotype. Two hydroxylated metabolites, α-OH-TAM and 4'-OH-TAM, were newly identified as putative CYP2D6 substrates. The relative quantification was precise (<20 %), and the semiquantitative estimation suggests that metabolite levels are non-negligible. Metabolites could play an important role in drug toxicity, but their impact on drug-related side effects has been partially neglected due to the tremendous effort needed with previous MS technologies. Using present HR-MS, this situation should evolve with the straightforward determination of drug metabolites, enlarging the possibilities in studying inter- and intra-patients drug metabolism variability and related effects.