Salt-dependent renal effects of an angiotensin II antagonist in healthy subjects.

This study was designed to evaluate in healthy volunteers the renal hemodynamic and tubular effects of the orally active angiotensin II receptor antagonist losartan (DuP 753 or MK 954). Losartan or a placebo was administered to 23 subjects maintained on a high-sodium (200 mmol/d) or a low-sodium (50 mmol/d) diet in a randomized, double-blind, crossover study. The two 6-day diet periods were separated by a 5-day washout period. On day 6, the subjects were water loaded, and blood pressure, renal hemodynamics, and urinary electrolyte excretion were measured for 6 hours after a single 100-mg oral dose of losartan (n = 16) or placebo (n = 7). Losartan induced no significant changes in blood pressure, glomerular filtration rate, or renal blood flow in these water-loaded subjects, whatever the sodium diet. In subjects on a low-salt diet, losartan markedly increased urinary sodium excretion from 115 +/- 9 to 207 +/- 21 mumol/min (P < .05). The fractional excretion of endogenous lithium was unchanged, suggesting no effect of losartan on the early proximal tubule in our experimental conditions. Losartan also increased urine flow rate (from 10.5 +/- 0.4 to 13.1 +/- 0.6 mL/min, P < .05); urinary potassium excretion (from 117 +/- 6.9 to 155 +/- 11 mumol/min); and the excretion of chloride, magnesium, calcium, and phosphate. In subjects on a high-salt diet, similar effects of losartan were observed, but the changes induced by the angiotensin II antagonist did not reach statistical significance. In addition, losartan demonstrated significant uricosuric properties with both sodium diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibiotics shaping bacterial genome: deletion of an IS91 flanked virulence determinant upon exposure to suinhibitory antibiotic concentrations

The nucleoid-associated proteins Hha and YdgT repress the expression of the toxin α-hemolysin. An Escherichia coli mutant lacking these proteins overexpresses the toxin α-hemolysin encoded in the multicopy recombinant plasmid pANN202-312R. Unexpectedly, we could observe that this mutant generated clones that no further produced hemolysin (Hly-). Generation of Hly- clones was dependent upon the presence in the culture medium of the antibiotic kanamycin (km), a marker of the hha allele (hha::Tn5). Detailed analysis of different Hly- clones evidenced that recombination between partial IS91 sequences that flank the hly operon had occurred. A fluctuation test evidenced that the presence of km in the culture medium was underlying the generation of these clones. A decrease of the km concentration from 25 mg/l to 12.5 mg/l abolished the appearance of Hly- derivatives. We considered as a working hypothesis that, when producing high levels of the toxin (combination of the hha ydgT mutations with the presence of the multicopy hemolytic plasmid pANN202-312R), the concentration of km of 25 mg/l resulted subinhibitory and stimulated the recombination between adjacent IS91 flanking sequences. To further test this hypothesis, we analyzed the effect of subinhibitory km concentrations in the wild type E. coli strain MG1655 harboring the parental low copy number plasmid pHly152. At a km concentration of 5 mg/l, subinhibitory for strain MG1655 (pHly152), generation of Hly- clones could be readily detected. Similar results were also obtained when, instead of km, ampicillin was used. IS91 is flanking several virulence determinants in different enteric bacterial pathogenic strains from E. coli and Shigella. The results presented here evidence that stress generated by exposure to subinhibitory antibiotic concentrations may result in rearrangements of the bacterial genome. Whereas some of these rearrangements may be deleterious, others may generate genotypes with increased virulence, which may resume infection.

Traumatic recurrent anterior dislocation of the shoulder: two- to four-year follow-up of an anatomic open procedure.

The purpose of this study was to evaluate the results of an anatomic open stabilization procedure. Twenty-three consecutive patients with traumatic, recurrent, anterior glenohumeral instability were managed with a modified open procedure. All had a Bankart lesion. A standardized, true anatomic capsulolabral reconstruction was performed with suture anchors. Two patients were lost to follow-up, and twenty-one were evaluated after 36 months [range, 24-49 months] by an independent observer. Shoulder stability and function were the principal outcome measures. None of the patients had subsequent dislocations. All returned to full working capacity, and 19 reached their previous level of sport activities. The mean loss in active abduction and flexion was 1 degrees, in internal rotation, one vertebral level, and in external rotation, 7 degrees (arm at 90 degrees of abduction). Two patients had a positive anterior apprehension test. No sign of shoulder osteoarthritis was observed. The open anatomic capsulolabral reconstruction provides excellent results and allows the restoration of stability with good function.

Oligoanalgesia in the emergency department: short-term beneficial effects of an education program on acute pain.

STUDY OBJECTIVE: Acute pain is the most frequent complaint in emergency department (ED) admissions, but its management is often neglected, placing patients at risk of oligoanalgesia. We evaluate the effect of the implementation of guidelines for pain management in ED patients with pain at admission or anytime during their stay in our ED. METHODS: This prospective pre-post intervention cohort study included data collection both before and after guideline implementation. Consecutive adult patients admitted with acute pain from any cause or with pain at any time after admission were enrolled. The quality of pain management was evaluated according to information in the ED medical records by using a standardized collection form, and its impact on patients was recorded with a questionnaire at discharge. RESULTS: Two hundred forty-nine and 192 patients were included during pre- and postintervention periods. Pain was documented in 61% and 76% of nurse and physician notes, respectively, versus 78% and 85% after the intervention (difference 17%/9%; 95% confidence interval [CI] 8% to 26%/2% to 17%, respectively). Administration of analgesia increased from 40% to 63% (difference 23%; 95% CI 13% to 32%) and of morphine from 10% to 27% (difference 17%; 95% CI 10% to 24%). Mean doses of intravenous morphine increased from 2.4 mg (95% CI 1.9 to 2.9 mg) to 4.6 mg (95% CI 3.9 to 5.3 mg); administration of nonsteroidal antiinflammatory drugs and acetaminophen increased as well. There was a greater reduction of visual analogue scale score after intervention: 2.1 cm (95% CI 1.7 to 2.4 cm) versus 2.9 cm (95% CI 2.5 to 3.3 cm), which was associated with improved patient satisfaction. CONCLUSION: Education program and guidelines implementation for pain management lead to improved pain management, analgesia, and patient satisfaction in the ED.

Post-Plutonic Magmatism: from the Source to the Emplacement of an Upper Crustal Dyke Swarm, Adamello Massif, Italy

Magmas of the arc-tholeiitic and calc-alkaline differentiation suites contribute substantially to the formation of continental crust in subduction zones. Different geochemical-petrological models have been put forward to achieve evolved magmas forming large volumes of tonalitic to granitic plutons, building an important part of the continental crust. Primary magmas produced in the mantle wedge overlying the subducted slab migrate through the mantle and the crust. During the transfer, magma can accumulate in intermediate reservoirs at different levels where crystallization leads to differentiation and the heat transfer from the magma, together with gained heat from solidification, lead to partial melting of the crust. Partial melts can be assimilated and mix with more primitive magma. Moreover, already formed crystal cumulates or crystal mushes can be recycled and reactivated to transfer to higher crustal levels. Magma transport in the crust involves fow through fractures within a brittle elastic rock. The solidified magma filled crack, a dyke, can crosscut previously formed geological structures and thus serves as a relative or absolute time marker. The study area is situated in the Adamello massif. The Adamello massif is a composite of plutons that were emplaced between 42 and 29 million years. A later dyke swarm intruded into the southern part of the Adamello Batholith. A fractionation model covering dyke compositions from picrobasalts to dacites results in the cummulative crystallization of 17% olivine, 2% Cr-rich spinel, 18% clinopyroxene, 41% amphibole, 4% plagioclase and 0.1% magnetite to achieve an andesitic composition out of a hydrous primitive picrobasalt. These rocks show a similar geochemical evolution as experimental data simulating fractional crystallization and associated magma differentiation at lower crustal depth (7-10 kbar). The peraluminous, corundum normative composition is one characteristic of more evolved dacitic magmas, which has been explained in a long lasting debate with two di_erent models. Melting of mafic crust or politic material provides one model, whereas an alternative is fractionation from primary mantle derived melts. Amphibole occurring in basaltic-andesitic and andesitic dyke rocks as fractionating cumulate phase extracted from lower crustal depth (6-7.5 kbar) is driving the magmas to peraluminous, corundum normative compositions, which are represented by tonalites forming most of the Adamello Batholith. Most primitive picrobasaltic dykes have a slightly steepened chondrite normalized rare earth elements (REE) pattern and the increased enrichment of light-REE (LREE) for andesites and dacites can be explained by the fractional crystallization model originating from a picrobasalt, taking the changing fractionating phase assemblage and temperature into account. The injection of hot basaltic magma (~1050°C) in a closely spaced dyke swarm increases the surface of the contact to the mainly tonalitic wallrock. Such a setting induces partial melting of the wall rock and selective assimilation. Partial melting of the tonalite host is further expressed through intrusion breccias from basaltic dykes. Heat conduction models with instantaneous magma injection for such a dyke swarm geometry can explain features of partial melting observed in the field. Geochemical data of minerals and bulk rock further underline the selective or bulk assimilation of the tonalite host rock at upper crustal levels (~2-3 kbar), in particular with regard to light ion lithophile elements (LILE) such as Sr, Ba and Rb. Primitive picrobasalts carry an immiscible felsic assimilant as enclaves that bring along refractory rutile and zircon with textures typically found in oceanic plagiogranites or high pressure/low-temperature metamorphic rocks in general. U-Pb data implies a lower Cretaceous age for zircon not yet described as assimilant in Eocene to Oligocene magmatic rocks of the Central Southern Alps. The distribution of post-plutonic dykes in large batholiths such as the Adamello is one of the key features for understanding the regional stress field during the post-batholith emplacement cooling history. The emplacement of the regional dyke swarm covering the southern part of the Adamello massif was associated with consistent left lateral strike-slip movement along magma dilatation planes, leading to en echelon segmentation of dykes. Through the dilation by magma of pre-existing weaknesses and cracks in an otherwise uniform host rock, the dyke propagation and according orientation in the horizontal plane adjusted continuously perpendicular to least compressive remote stress σ3, resulting in an inferred rotation of the remote principal stress field. Les magmas issus des zones de subduction contribuent substantiellement à la formation de la croûte continentale. Les plutons tonalitiques et granitiques représentent, en effet, une partie importante de la croûte continentale. Des magmas primaires produits dans le 'mantle wedge ', partie du manteau se trouvant au-dessus de la plaque plongeante dans des zones de subduction, migrent à travers le manteau puis la croûte. Pendant ce transfert, le magma peut s'accumuler dans des réservoirs intermédiaires à différentes profondeurs. Le stockage de magma dans ces réservoirs engendre, d'une part, la différentiation des magmas par cristallisation fractionnée et, d'autre part, une fusion partielle la croûte continentale préexistante associée au transfert de la chaleur des magmas vers l'encaissant. Ces liquides magmatiques issus de la croûte peuvent, ensuite, se mélanger avec des magmas primaires. Le transport du magma dans la croûte implique notamment un flux de magma à travers différentes fractures recoupant les roches encaissantes élastiques. Au cours de ce processus de migration, des cumulats de cristaux ou des agrégats de cristaux encore non-solidifiés, peuvent être recyclés et réactivés pour être transportés à des niveaux supérieures de la croûte. Le terrain d'étude est situé dans le massif d'Adamello. Celui-ci est composé de plusieurs plutons mis en place entre 42 et 29 millions d'années. Dans une phase tardive de l'activité magmatique liée à ce batholite, une série de filons de composition variable allant de picrobasalte à des compositions dacitiques s'est mise en place la partie sud du massif. Deux modèles sont proposés dans la littérature, pour expliquer la formation des magmas dacitiques caractérisés par des compositions peralumineux (i.e. à corindon normatif). Le premier modèle propose que ces magmas soient issus de la fusion de matériel mafique et pélitique présent dans la partie inférieur de la croûte, alors que le deuxième modèle suggère une évolution par cristallisation fractionnée à partir de liquides primaires issus du manteau. Un modèle de cristallisation fractionnée a pu être développé pour expliquer l'évolution des filons de l'Adamello. Ce modèle explique la formation des filons dacitiques par la cristallisation fractionnée de 17% olivine, 2% spinelle riche en Cr, 18% clinopyroxène, 41% amphibole, 4% plagioclase et 0.1% magnetite à partir de liquide de compositions picrobasaltiques. Ce modèle prend en considération les contraintes pétrologiques déduites de l'observation des différents filons ainsi que du champ de stabilité des différentes phases en fonction de la température. Ces roches montrent une évolution géochimique similaire aux données expérimentales simulant la cristallisation fractionnée de magmas évoluant à des niveaux inférieurs de la croûte (7-10 kbar). Le modèle montre, en particulier, le rôle prépondérant de l'amphibole, une phase qui contrôle en particulier le caractère peralumineux des magmas différentiés ainsi que leurs compositions en éléments en traces. Des phénomènes de fusion partielle de l'encaissant tonalitique lors de la mise en place de _lons mafiques sont observée sur le terrain. L'injection du magma basaltique chaud (~1050°C) sous forme de filons rapprochés augmente la surface du contact avec l'encaissante tonalitique. Une telle situation produit la fusion partielle des roches encaissantes nécessaire à l'incorporation d'enclaves mafiques observés au sein des tonalites. Pour comprendre les conditions nécessaires pour la fusion partielle des roches encaissantes, des modèles de conduction thermique pour une injection simultanée d'une série de filons ont été développées. Des données géochimiques sur les minéraux et sur les roches totales soulignent qu'au niveau supérieur de la croûte, l'assimilation sélective ou totale de l'encaissante tonalitique modifie la composition du liquide primaire pour les éléments lithophiles tel que le Sr, Ba et Rb. Un autre aspect important concernant la pétrologie des filons de l'Adamello est la présence d'enclaves felsiques dans les filons les plus primitifs. Ces enclaves montrent, en particulier, des textures proches de celles rencontrées dans des plagiogranites océaniques ou dans des roches métamorphiques de haute pression/basse température. Ces enclaves contiennent du zircon et du rutile. La datations de ces zircons à l'aide du géochronomètre U-Pb indique un âge Crétacé inférieur. Cet âge est important, car aucune roche de cet âge n'a été considérée comme un assimilant potentiel pour des roches magmatiques d'âge Eocène à Oligocène dans les Alpes Sud Centrales. La réparation spatiale des filons post-plutoniques dans des grands batholites tel que l'Adamello, est une caractéristique clé pour la compréhension des champs de contraintes lors du refroidissement du batholite. L'orientation des filons va, en particulier, indiqué la contrainte minimal au sein des roches encaissante. La mise en place de la série de filon recoupant la partie Sud du massif de l'Adamello est associée à un décrochement senestre, un décrochement que l'on peut lié aux contraintes tectoniques régionales auxquelles s'ajoutent l'effet de la dilatation produite par la mise en place du batholite lui-même. Ce décrochement senestre produit une segmentation en échelon des filons.

Intestinal and hepatic nitrogen balance in the rat after the administration of an oral protein load

The fate of a small oral dose of protein given to overnight-starved rats was studied. After 3 h, 62 per cent of the protein amino acids had been absorbed. Most of the absorbed N went into the bloodstream through the portal in the form of amino acids, but urea and ammonia were also present. About one-quarter of all absorbed N was carried as lymph amino acids. The liver was able to take all portal free ammonia and a large proportion of portal amino acids, releasing urea. The hepatic N balance was negative, indicating active proteolysis and net loss of liver protein.

Population demography of an endangered lizard, the Blue Mountains Water Skink.

BACKGROUND: Information on the age structure within populations of an endangered species can facilitate effective management. The Blue Mountains Water Skink (Eulamprus leuraensis) is a viviparous scincid lizard that is restricted to < 40 isolated montane swamps in south-eastern Australia. We used skeletochronology of phalanges (corroborated by mark-recapture data) to estimate ages of 222 individuals from 13 populations. RESULTS: These lizards grow rapidly, from neonatal size (30 mm snout-vent length) to adult size (about 70 mm SVL) within two to three years. Fecundity is low (mean 2.9 offspring per litter) and is affected by maternal body length and age. Offspring quality may decline with maternal age, based upon captive-born neonates (older females gave birth to slower offspring). In contrast to its broadly sympatric (and abundant) congener E. tympanum, E. leuraensis is short-lived (maximum 6 years, vs 15 years for E. tympanum). Litter size and offspring size are similar in the two species, but female E. leuraensis reproduce annually whereas many E. tympanum produce litters biennially. Thus, a low survival rate (rather than delayed maturation or low annual fecundity) is the key reason why E. leuraensis is endangered. Our 13 populations exhibited similar growth rates and population age structures despite substantial variation in elevation, geographic location and swamp size. However, larger populations (based on a genetic estimate of effective population size) contained older lizards, and thus a wider variance in ages. CONCLUSION: Our study suggests that low adult survival rates, as well as specialisation on a rare and fragmented habitat type (montane swamps) contribute to the endangered status of the Blue Mountains Water Skink.

First day of an oil spill on the open sea: early mass transfers of hydrocarbons to air and water.

During the first hours after release of petroleum at sea, crude oil hydrocarbons partition rapidly into air and water. However, limited information is available about very early evaporation and dissolution processes. We report on the composition of the oil slick during the first day after a permitted, unrestrained 4.3 m(3) oil release conducted on the North Sea. Rapid mass transfers of volatile and soluble hydrocarbons were observed, with >50% of ≤C17 hydrocarbons disappearing within 25 h from this oil slick of <10 km(2) area and <10 μm thickness. For oil sheen, >50% losses of ≤C16 hydrocarbons were observed after 1 h. We developed a mass transfer model to describe the evolution of oil slick chemical composition and water column hydrocarbon concentrations. The model was parametrized based on environmental conditions and hydrocarbon partitioning properties estimated from comprehensive two-dimensional gas chromatography (GC×GC) retention data. The model correctly predicted the observed fractionation of petroleum hydrocarbons in the oil slick resulting from evaporation and dissolution. This is the first report on the broad-spectrum compositional changes in oil during the first day of a spill at the sea surface. Expected outcomes under other environmental conditions are discussed, as well as comparisons to other models.

Influence of an inert electrolyte on the morphology of quasi-two-dimensional electrodeposits

The influence of an inert electrolyte (sodium sulfate) on quasi-two-dimensional copper electrodeposition from a nondeaerated aqueous copper sulfate solution has been analyzed. The different morphologies for a fixed concentration of CuSO4 have been classified in a diagram in terms of the applied potential and the inert electrolyte concentration. The main conclusion is the extension of the well-known Ohmic model for the homogeneous growth regime for copper sulfate solutions with small amounts of sodium sulfate. Moreover, we have observed the formation of fingerlike deposits at large applied potential and inert electrolyte concentration values, before hydrogen evolution becomes the main electrode reaction.

Library buildings : Selection of an architect ... A paper read before the Iowa Library Association at Grinnell, Iowa. October 30, 1902.

This leaflet, no. 7, by Grant C. Miller, of Patton & Miller Architects in Chicago, contains information on how to plan the erection of a new library building. It discusses how to select a librarian, architect, location and surroundings design and layout needed to best serve the library users.

Foodborne norovirus outbreak: the role of an asymptomatic food handler

Background: In July 2005 an outbreak of acute gastroenteritis occurred on a residential summer camp in the province of Barcelona (northeast of Spain). Forty-four people were affected among residents and employees. All of them had in common a meal at lunch time on 13 July (paella, round of beef and fruit). The aim of this study was to investigate a foodborne norovirus outbreak that occurred in the residential summer camp and in which the implication of a food handler was demonstrated by laboratory tests. Methods: A retrospective cohort study was designed. Personal or telephone interview was carried out to collect demographic, clinical and microbiological data of the exposed people, as well as food consumption in the suspected lunch. Food handlers of the mentioned summer camp were interviewed. Ten stool samples were requested from symptomatic exposed residents and the three food handlers that prepared the suspected food. Stools were tested for bacteries and noroviruses. Norovirus was detected using RT-PCR and sequence analysis. Attack rate, relative risks (RR) and its 95% confidence intervals (CI) were calculated to assess the association between food consumption and disease. Results: The global attack rate of the outbreak was 55%. The main symptoms were abdominal pain (90%), nausea (85%), vomiting (70%) and diarrhoea (42.5%). The disease remitted in 24-48 hours. Norovirus was detected in seven faecal samples, one of them was from an asymptomatic food handler who had not eaten the suspected food (round of beef), but cooked and served the lunch. Analysis of the two suspected foods isolated no pathogenic bacteria and detected no viruses. Molecular analysis showed that the viral strain was the same in ill patients and in the asymptomatic food handler (genotype GII.2 Melksham-like). Conclusions: In outbreaks of foodborne disease, the search for viruses in affected patients and all food handlers, even in those that are asymptomatic, is essential. Health education of food handlers with respect to hand washing should be promoted.

Development of an aggregation assay to screen FimH antagonists.

Alpha-D-mannopyranosides are potent FimH antagonists, which inhibit the adhesion of Escherichia coli to highly mannosylated uroplakin Ia on the urothelium and therefore offer an efficient therapeutic opportunity for the treatment and prevention of urinary tract infection. For the evaluation of the therapeutic potential of FimH antagonists, their effect on the disaggregation of E. coli from Candida albicans and guinea pig erythrocytes (GPE) was studied. The mannose-specific binding of E. coli to yeast cells and erythrocytes is mediated by type 1 pili and can be monitored by aggregometry. Maximal aggregation of C. albicans or GPE to E. coli is reached after 600 s. Then the FimH antagonist was added and disaggregation determined by light transmission over a period of 1400 s. A FimH-deleted mutant of E. coli, which does not induce any aggregation, was used in a control experiment. The activities of FimH antagonists are expressed as IC(50)s, the half maximal inhibitory concentration of the disaggregation potential. n-Heptyl alpha-D-mannopyranoside (1) was used as a reference compound and exhibits an IC(50) of 77.14 microM , whereas methyl alpha-D-mannopyranoside (2) does not lead to any disaggregation at concentrations up to 800 microM. o-Chloro-p-[N-(2-ethoxy-3,4-dioxocyclobut-1-enyl)amino]phenyl alpha-D-mannopyranoside (3) shows a 90-fold and 2-chloro-4-nitrophenyl alpha-D-mannopyranoside (4) a 6-fold increased affinity compared to 1. Finally, 4-nitrophenyl alpha-D-mannopyranoside (5) exhibits an activity similar to 1. As negative control, D-galactose (6) was used. The standardized aggregation assay generates concentration-dependent, reproducible data allowing the evaluation of FimH antagonists according to their potency to inhibit E. coli adherence and can therefore be employed to select candidates for experimental and clinical studies for treatment and prevention of urinary tract infections.