Stress ulcer prophylaxis in non-critically ill patients: a prospective evaluation of the practice in a surgical ward

Introduction The benefit of stress ulcer prophylaxis (SUP) in noncriticallyill patients has not been proved. Over-prescription of SUP isnot devoided of risks (i.e. drug-drug interactions, adverse events).This prospective study aimed to evaluate the use of proton pumpinhibitors (PPIs) for SUP in a visceral surgery ward.Materials & Methods Data collection was performed prospectivelyduring a 8-week period on patients hospitalized in a visceral surgeryward (58 beds). Patients with a PPI prescription for the treatment ofulcers, gastroesophageal reflux disease, esophagitis or epigastralgiawere excluded as well as patients hospitalized twice during the studyperiod. The American Society of Health-System Pharmacists guidelineson SUP were used to assess the appropriateness of de novo PPIprescriptions.Results Among 255 patients in the study, 138 (54.1%) received aprophylaxis with PPI, of which 86 (62.3%) were de novo PPI prescriptions.93.5% of patients received esomeprazole (according to thehospital drug formulary) mainly orally at 40 mg qd. 79.1% of patientshad no risk factors for SUP. 17.9% and 3.0% had one and two riskfactors, respectively. 95% of the patients with PPI were not hospitalizedin the intensive care unit (ICU) before their stay in the visceralsurgery ward. At discharge, PPI therapy was continued in 34.2% ofpatients with a de novo PPI prescription.Discussion & Conclusion This study highlights the over-utilizationof PPIs in non-ICU patients and the inappropriate continuation of PPIprescriptions at discharge. The PPI dosage prescribed for prophylaxiswas probably too high compared with the data of the literature.Treatment recommendations for SUP are needed to restrict PPIuse for justified indications.

The V-ATPase proteolipid cylinder promotes the lipid-mixing stage of SNARE-dependent fusion of yeast vacuoles.

The V-ATPase V(0) sector associates with the peripheral V(1) sector to form a proton pump. V(0) alone has an additional function, facilitating membrane fusion in the endocytic and late exocytic pathways. V(0) contains a hexameric proteolipid cylinder, which might support fusion as proposed in proteinaceous pore models. To test this, we randomly mutagenized proteolipids. We recovered alleles that preserve proton translocation, normal SNARE activation and trans-SNARE pairing but that impair lipid and content mixing. Critical residues were found in all subunits of the proteolipid ring. They concentrate within the bilayer, close to the ring subunit interfaces. The fusion-impairing proteolipid substitutions stabilize the interaction of V(0) with V(1). Deletion of the vacuolar v-SNARE Nyv1 has the same effect, suggesting that both types of mutations similarly alter the conformation of V(0). Also covalent linkage of subunits in the proteolipid cylinder blocks vacuole fusion. We propose that a SNARE-dependent conformational change in V(0) proteolipids might stimulate fusion by creating a hydrophobic crevice that promotes lipid reorientation and formation of a lipidic fusion pore.

Seleção de variáveis em modelos matemáticos dos parâmetros de cultivo do camarão marinho Litopenaeus vannamei

O objetivo deste trabalho foi selecionar as variáveis de manejo do camarão marinho Litopenaeus vannamei que mais influenciaram nas variáveis-respostas ao cultivo (produção, produtividade, peso final e taxa de sobrevivência), em modelos matemáticos. O banco de dados foi composto por 83 cultivos, realizados no período de 2003 a 2005, obtidos de uma fazenda comercial localizada no litoral sul de Pernambuco. Para estimar os parâmetros dos modelos, utilizou-se a técnica dos mínimos quadrados. A seleção das variáveis foi realizada com o processo "backward elimination" associado ao método de transformação de Box e Cox. A adequação das equações e os pressupostos de normalidade e homocedasticidade, para os erros, foram analisadas com base na análise de variância e análise de resíduo. É possível relacionar essas variáveis e estabelecer predições com as equações.

Cation Transport Coupled to ATP Hydrolysis By the (Na, K)-ATPase : an integrated, animated model

An Adobe (R) animation is presented for use in undergraduate Biochemistry courses, illustrating the mechanism of Na+ and K+ translocation coupled to ATP hydrolysis by the (Na, K)-ATPase, a P-2c-type ATPase, or ATP-powered ion pump that actively translocates cations across plasma membranes. The enzyme is also known as an E-1/E-2-ATPase as it undergoes conformational changes between the E-1 and E-2 forms during the pumping cycle, altering the affinity and accessibility of the transmembrane ion-binding sites. The animation is based on Horisberger's scheme that incorporates the most recent significant findings to have improved our understanding of the (Na, K)-ATPase structure function relationship. The movements of the various domains within the (Na, K)-ATPase alpha-subunit illustrate the conformational changes that occur during Na+ and K+ translocation across the membrane and emphasize involvement of the actuator, nucleotide, and phosphorylation domains, that is, the "core engine" of the pump, with respect to ATP binding, cation transport, and ADP and P-i release.

Small access (30F) clinical central venous smart cannulation: is it adequate?

OBJECTIVES: To assess the performance of 45F vs. 36F smartcanula in CPB with gravity drainage alone. METHODS: Twenty patients were randomly assigned to two groups receiving for venous drainage a smartcanula which is collapsed over a mandrel for trans-atrial insertion into the inferior vena cava and expanded in situ to either 45F or 36F. RESULTS: Valve replacement/repair was realized in 7/10 and/or CABG in 6/10 for 36F (69+/-13 years) vs. 5/10 and 5/10, respectively, for 45F (63+/-11 years: NS). Body weight and surface area (BSA) were 83+/-9 kg (1.9+/-0.2 m2, max 2.2 m2) for 36F vs. 79+/-6 kg: NS (1.9+/-0.1 m2 (NS), max 2.1 m2) for 45F. Insertion and access orifice diameter (area) was 6 mm and 10 mm (78.5 mm2) for the 36F vs. 6 mm and 13 mm (132 mm2) for the 45F (+69%). Calculated target pump flow (2.4 l/min/m2) was 4.7+/-0.4 l/min for 36F vs. 4.5+/-0.3 l/min for 45F. Achieved pump flow accounted for 5.0+/-0.3 l/min for 36F (8% above target) vs. 4.8+/-0.3 l/min for 45F (8% above target): NS. The water balance during the pump run (clear volume added minus hemofilter and urine output) was 2.2+/-0.3 l for 36F vs. 2.0 l for 45F: NS. CONCLUSION: Due to its 'open' wall (the vena cava provides the seal), its reduced wall thickness (range: 0.0-0.4 mm), and its self-expanding design, the 36F smartcanula requiring a 30F access orifice has sufficient drainage capacity by gravity alone for full CPB in adults with a BSA up to 2.2 mm2.

Receptor occupancy vs. induction of Na+-K+-ATPase and Na+ transport by aldosterone.

In the urinary bladder of the toad Bufo marinus aldosterone (between 0.8 and 100 nM) stimulates Na+ transport [half-maximal induction concentration (K1/2) = 6.5 nM]. At low hormone concentrations (0.8-8 nM), the increase of Na+ transport between 0.75 and 2.5 h is accompanied by a fall in transepithelial resistance (R). Higher hormone concentrations (30-800 nM) induce an additional resistance-independent fraction of Na+ transport within 2.5-8 h. From 6 h on, aldosterone (between 0.2 and 20 nM) stimulates in the same tissue the biosynthesis rate of the alpha- and beta-subunits of Na+-K+-ATPase (K1/2 = 3 and 1.5 nM, respectively). New pump synthesis is thus not a prerequisite for the early mineralocorticoid response but might be linked to the late transport event. The mineralocorticoid response is usually ascribed to interaction with the higher affinity type 1 receptor. In the present study we show, however, that at least 55% of the overall Na+ transport response is linked to nuclear occupation of the lower affinity type 2 receptors [dissociation constant (Kd) = 50 nM, maximum number of binding sites (Nmax) = 315 fmol/mg protein]. Distinct aldosterone effects, such as the fall in R and the increase in Na+-K+-ATPase synthesis, are more closely related to occupation of type 1 receptors (Kd = 0.3 nM, Nmax = 23 fmol/mg protein). At maximal induction of these latter parameters, only about 20% of type 2 receptors are occupied. These results suggest that both types of aldosterone receptors are involved in the mediation of the full mineralocorticoid response: type 1 in the early and late and type 2 particularly in the late tissue response.

Relationships among endogenous ouabain, alpha-adducin polymorphisms and renal sodium handling in primary hypertension.

OBJECTIVE: The basolateral Na pump drives renotubular reabsorption. In cultured renal cells, mutant adducins, as well as sub-nanomolar ouabain concentrations, stimulate the Na-K pump. METHODS: To determine whether these factors interact and affect Na handling and blood pressure (BP) in vivo, we studied 155 untreated hypertensive patients subdivided on the basis of their plasma endogenous ouabain or alpha-adducin genotype (ADD1 Gly460Trp-rs4961). RESULTS: Under basal conditions, proximal tubular reabsorption and plasma Na were higher in patients with mutated Trp ADD1 or increased endogenous ouabain (P = 0.002 and 0.05, respectively). BPs were higher in the high plasma endogenous ouabain group (P = 0.001). Following volume loading, the increment in BP (7.73 vs. 4.81 mmHg) and the slopes of the relationship between BP and Na excretion were greater [0.017 +/- 0.002 vs. 0.009 +/- 0.003 mmHg/(muEq min)] in ADD1 Trp vs. ADD1 Gly carriers (P < 0.05). BP changes were similar, whereas the slopes of the relationship between BP and Na excretion were lower [0.016 +/- 0.003 vs. 0.008 +/- 0.002 mmHg/(muEq min)] in patients with low vs. high endogenous ouabain (P < 0.05). In patients with high endogenous ouabain, volume loading increased the BP in the ADD1 Trp group but not in the Gly group (P < 0.05). Thus, patients with ADD1 Trp alleles are sensitive to salt and tubular Na reabsorption remains elevated after volume expansion. CONCLUSION: With saline loading, BP changes are similar in high and low endogenous ouabain patients, whereas tubular Na reabsorption increases in the high endogenous ouabain group. Saline loading unmasks differences in renal Na handling in patients with mutant adducin or high endogenous ouabain and exposes an interaction of endogenous ouabain and Trp alleles on BP.

Rivascolarizzazione miocardica con arteria radiale: tecniche chirurgiche a confronto e risultati a breve termine [Myocardial revascularization and radial artery: different surgical strategies and short-term results]

BACKGROUND: The radial artery is routinely used as a graft for surgical arterial myocardial revascularization. The proximal radial artery anastomosis site remains unknown. In this study, we analyzed the short-term results and the operative risk determinants after having used four different common techniques for radial artery implantation. METHODS: From January 2000 to December 2004, 571 patients underwent coronary artery bypass grafting with radial arteries. Data were analyzed for the entire population and for subgroups following the proximal radial artery anastomosis site: 140 T-graft with the mammary artery (group A), 316 free-grafts with the proximal anastomosis to the ascending aorta (group B), 55 mammary arteries in situ elongated with the radial artery (group C) and 60 radial arteries elongated with a piece of mammary artery and anastomosed to the ascending aorta (group D). RESULTS: The mean age was 53.8 +/- 7.7 years; 55.5% of patients had a previous myocardial infarction and 73% presented with a satisfactory left ventricular function. A complete arterial myocardial revascularization was achieved in 532 cases (93.2%) and 90.2% of the procedures were performed under cardiopulmonary bypass and cardioplegic arrest. The operative mortality rate was 0.9%, a postoperative myocardial infarction was diagnosed in 19 patients (3.3%), an intra-aortic balloon pump was used in 10 patients (1.7%) and a mechanical circulatory device was implanted in 2 patients. The radial artery harvesting site remained always free from complications. The proximal radial artery anastomosis site was not a determinant of early hospital mortality. Group C showed a higher risk of postoperative myocardial infarction (p = 0.09), together with female gender (p = 0.003), hypertension (p = 0.059) and a longer cardiopulmonary bypass time. CONCLUSIONS: The radial artery and the mammary artery can guarantee multiple arterial revascularization also for patients with contraindications to double mammary artery use. The four most common techniques for proximal radial artery anastomosis are not related to a higher operative risk and they can be used alternatively to reach the best surgical results

Quantum Hall Phases of two-component bosons

The recent production of synthetic magnetic fields acting on electroneutral particles, such as atoms or photons, has boosted interest in the quantum Hall physics of bosons. Adding pseudospin 1/2 to the bosons greatly enriches the scenario, as it allows them to form an interacting integer quantum Hall (IQH) phase with no fermionic counterpart. Here we show that, for a small two-component Bose gas on a disk, the complete strongly correlated regime, extending from the integer phase at filling factor ν = 2 to the Halperin phase at filling factor ν = 2 / 3, is well described by composite fermionization of the bosons. Moreover we study the edge excitations of the IQH state, which, in agreement with expectations from topological field theory, are found to consist of forward-moving charge excitations and backward-moving spin excitations. Finally, we demonstrate how pair-correlation functions allow one to experimentally distinguish the IQH state from competing states, such as non-Abelian spin singlet (NASS) states.

Prolonged fluconazole exposure leads to a shift to Candida species with decreased susceptibility in breakthrough candidemia: prospective survey of the Fungal Infection Network of Switzerland

Objectives: To compare the clinical characteristics, species distribution and antifungal susceptibility of Candida bloodstream isolates (BSI) in breakthrough (BTC) vs. non-breakthrough candidemia (NBTC) and to study the effect of prolonged vs. short fluconazole (F) exposure in BTC.Methods: Candida BSI were prospectively collected during 2004- 2006 from 27 hospitals (seven university, 20 affiliated) of the FUNGINOS network. Susceptibility to F, voriconazole (V) and caspofungin (C) was tested in the FUNGINOS mycology reference laboratory by microtitre broth dilution method with the Sensititre YeastOneTM test panel. Clinical data were collected using standardized CRFs. BTC was defined as occurring during antifungal treatment/prophylaxis of at least three days duration prior to the candidemia. Susceptibility of BSI was defined according to 2010/2011 CLSI clinical breakpoints.Results: Out of 567 candidemia episodes, 550 Candida BSI were available. Of these, 43 (7.6%) were from BTC (37/43, 86% were isolated after F exposure). 38 BTC (88.4%) and 315 NBTC (55.6%) occurred in university hospitals (P < 0.001). The majority of patients developing BTC were immunocompromised: higher proportions of haematological malignancies (62.8% in BTC vs. 47.1% in NBTC, P < 0.001), neutropenia (37.2% vs. 11.8%, P < 0.001), acute GvHD (14% vs. 0.2%, P < 0.001), immunosuppressive drugs (74.4% vs. 7.8%, P < 0.001), and mucositis (32.6% vs. 2.3%, P < 0.001) were observed. Other differences between BTC and NBTC were higher proportions of patients with central venous catheters in the 2 weeks preceding candidemia (95.3% vs. 83.4%, P = 0.047) and receiving total parenteral nutrition (62.8% vs. 35.9%, P < 0.001), but a lower proportion of patients treated with gastric proton pump inhibitors (23.3% vs. 72.1%, P < 0.001). Overall mortality of BTC and NBTC was not different (34.9% vs. 31.7%, P = 0.73), while a trend to higher attributable mortality in BTC was found (13.9% vs. 6.9%, P = 0.12). Species identification showed a majority of C. albicans in both groups (51.2% in BTC vs. 62.9% in NBTC, P = 0.26), followed by C. glabrata (18.6% vs. 18.5%), C. tropicalis (2.3% vs. 6.3%) and C. parapsilosis (7.0% vs. 4.7%). Significantly more C. krusei were detected in BTC versus NBTC (11.6% vs. 1.6%, P = 0.002). The geometric mean MIC for F, V and C between BTC and NBTC isolates was not significantly different. However, in BTC there was a significant association between duration of F exposure and the Candida spp.: >10 days of F was associated with a significant shift from susceptible Candida spp. (C. albicans, C. parapsilosis, C. tropicalis, C. famata) to non-susceptible species (C. glabrata, C. krusei, C. norvegensis). Among 21 BTC episodes occurring after £10 days of F, 19% of the isolates were non-susceptible, in contrast to 68.7% in 16 BTC episodes occurring after >10 days of F (P = 0.003).Conclusions: Breakthrough candidemia occurred more often in immunocompromised hosts. Fluconazole administered for >10 days was associated with a shift to non-susceptible Candida spp.. Length of fluconazole exposure should be taken into consideration for the choice of empirical antifungal treatment.

ERK1/2 controls Na,K-ATPase activity and transepithelial sodium transport in the principal cell of the cortical collecting duct of the mouse kidney.

The collecting duct of normal kidney exhibits significant activity of the MEK1/2-ERK1/2 pathway as shown in vivo by immunostaining of phosphorylated active ERK1/2 (pERK1/2). The MEK1/2-ERK1/2 pathway controls many different ion transports both in proximal and distal nephron, raising the question of whether this pathway is involved in the basal and/or hormone-dependent transepithelial sodium reabsorption in the principal cell of the cortical collecting duct (CCD), a process mediated by the apical epithelial sodium channel and the basolateral sodium pump (Na,K-ATPase). To answer this question we used ex vivo microdissected CCDs from normal mouse kidney or in vitro cultured mpkCCDcl4 principal cells. Significant basal levels of pERK1/2 were observed ex vivo and in vitro. Aldosterone and vasopressin, known to up-regulate sodium reabsorption in CCDs, did not change ERK1/2 activity either ex vivo or in vitro. Basal and aldosterone- or vasopressin-stimulated sodium transport was down-regulated by the MEK1/2 inhibitor PD98059, in parallel with a decrease in pERK1/2 in vitro. The activity of Na,K-ATPase but not that of epithelial sodium channel was inhibited by MEK1/2 inhibitors in both unstimulated and aldosterone- or vasopressin-stimulated CCDs in vitro. Cell surface biotinylation showed that intrinsic activity rather than cell surface expression of Na,K-ATPase was controlled by pERK1/2. PD98059 also significantly inhibited the activity of Na,K-ATPase ex vivo. Our data demonstrate that the ERK1/2 pathway controls Na,K-ATPase activity and transepithelial sodium transport in the principal cell and indicate that basal constitutive activity of the ERK1/2 pathway is a critical component of this control.

Mesoscale numerical analysis of the historical November 1982 heavy precipitation event over Andorra (Eastern Pyrenees)

From 6 to 8 November 1982 one of the most catastrophic flash-flood events was recorded in the Eastern Pyrenees affecting Andorra and also France and Spain with rainfall accumulations exceeding 400 mm in 24 h, 44 fatalities and widespread damage. This paper aims to exhaustively document this heavy precipitation event and examines mesoscale simulations performed by the French Meso-NH non-hydrostatic atmospheric model. Large-scale simulations show the slow-evolving synoptic environment favourable for the development of a deep Atlantic cyclone which induced a strong southerly flow over the Eastern Pyrenees. From the evolution of the synoptic pattern four distinct phases have been identified during the event. The mesoscale analysis presents the second and the third phase as the most intense in terms of rainfall accumulations and highlights the interaction of the moist and conditionally unstable flows with the mountains. The presence of a SW low level jet (30 m s-1) around 1500 m also had a crucial role on focusing the precipitation over the exposed south slopes of the Eastern Pyrenees. Backward trajectories based on Eulerian on-line passive tracers indicate that the orographic uplift was the main forcing mechanism which triggered and maintained the precipitating systems more than 30 h over the Pyrenees. The moisture of the feeding flow mainly came from the Atlantic Ocean (7-9 g kg-1) and the role of the Mediterranean as a local moisture source was very limited (2-3 g kg-1) due to the high initial water vapour content of the parcels and the rapid passage over the basin along the Spanish Mediterranean coast (less than 12 h).

Identificação de marcadores microssatélites relacionados ao escurecimento de grãos em feijão

O objetivo deste trabalho foi identificar marcadores microssatélites ligados ao loco de características quantitativas (QTL) responsável pelo escurecimento tardio do tegumento de feijões do tipo carioca, a fim de reduzir o tempo de avaliação necessário para seleção quanto a essa característica. Foram utilizados dados de avaliação fenotípica de 185 progênies F2:3 derivadas do cruzamento VC-3 x 'BRSMG Majestoso', para o estudo do controle genético do escurecimento dos grãos. Com esses dados, foram confeccionados dois "bulks" segregantes de DNA, empregados para a avaliação de 444 pares de primers SSR. Os aplicativos computacionais GQMOL e Sisvar foram utilizados para avaliar as segregações, confeccionar um grupo de ligação e realizar análises de marca simples e de regressão múltipla pelo método "backward". Oito marcadores apresentaram polimorfismo nos "bulks". Seis desses marcadores foram agrupados em um grupo de ligação de 80,49 cM, e destes, três mostraram-se estreitamente ligados ao QTL responsável pelo escurecimento tardio dos grãos. O marcador PVM02TC116 cossegregou com o QTL em questão, e os marcadores PVESTBR-98 (2,00 cM) e PV176 (12,24 cM) flanqueiam essa região, o que sugere elevada eficiência para possível uso na seleção assistida.

Pirosi: avete la scelta per la presa a carico a breve termine!: revisione Cochrane per il medico di famiglia.

Cet article présente les résultats de la revue systématique: van Pinxteren B, Sigterman KE, Bonis P, Lau J, Numans ME. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database of Systematic Reviews 2010, Issue 11, Art. No.: CD002095. DOI: 10.1002/14651858.CD002095.pub4. PMID: 21069670.

Influence of infusion line compliance on drug delivery rate during acute line loop formation.

OBJECTIVE: To determine whether infusion line compliance contributes to irregular drug delivery during vertical displacement of syringe pumps. DESIGN: Five different commercially available infusion lines were studied at infusion rates of 0.5, 1.0, and 1.5 ml/h. Zero drug delivery time was measured after acute line loop formation (70 cm) using an electronic balance. Compliance of each infusion line was calculated using a pressure transducer and measurement of the occlusion release bolus at 300 mmHg occlusion pressure. Finally, the influence of infusion line compliance on drug delivery during acute lowering of the syringe pump was studied using low- and high-compliance infusion lines. RESULTS: Acute line loop formation resulted in zero drug delivery time from 5.1 +/- 1.5 to 44.0 +/- 6.8 s at flow rates of 0.5 ml/h. Increased flow rates significantly reduced loop-induced flow variability. A close correlation was found between zero drug delivery time and calculated infusion line compliance at 0.5 ml/h (linear regression R2 = 0.79). Lowering of the syringe pump 50 cm prolonged zero drug delivery time from 295.8 +/- 20.7 s with the low-compliance tube to 463.3 +/- 24.0 s with the high-compliance infusion line. CONCLUSIONS: Infusion line compliance contributes to irregular drug delivery associated with vertical displacement of syringe pumps. Siphoning of the infusion line during patient care should be avoided, and flow rates of 1 ml/h or higher are recommended. Low-compliance infusion lines are indicated whenever highly short-acting vasoactive drugs at low delivery rates are administered.