1,124 research outputs found

    Human pharmacokinetics and CSF penetration of clavulanic acid

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    Clavulanic acid, a product of Streptomyces clavuligerus with β-lactam structure, is a potent inhibitor of several β-lactamases. To study its pharmacokinetic and CSF penetration in patients without meningeal inflammation, a single oral dose of 250 mg of clavulanic acid was given to 21 patients. One patient was studied in a multiple dose schedule. Fifteen of these 21 patients had a diagnostic lumbar puncture and 3 neurosurgical patients had a continuous CSF drainage. Serum and urine concentrations of clavulanic acid were available from 22 patients. The mean peak serum concentration was 4·3 mg/l and individual peak serum concentrations ranged from 0·1-9·5 mg/i between 40 and 60 mm after ingestion of clavulanic acid. Urinary recovery between 300 and 400 mm ranged from 0·8-54·3% of the administered dose. The mean absorption half life was 0·26 h and the mean elimination half life was 0·9 h. Considerable degradation of clavulanic acid occurred in vitro at 37°C. In pooled human serum, phosphate buffer pH 7 and 5, an hourly loss of activity of about 10, 7 and 10% respectively, was observe

    Mosaics of canopy openness induced by tropical cyclones in lowland rain forests with contrasting management histories in northeastern Australia

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    Tropical Cyclone 'Rona' crossed the coast of the Daintree lowlands of northeastern Australia in 1999. This study reports on its impact on forest canopy openness at six lowland rain forest sites with contrasting management histories (old-growth, selectively logged and regrowth). Percentage canopy openness was calculated from individual hemispherical photographs taken from marked points below the forest canopy at nine plots per site 3±4 mo before the cyclone, and at the same points a month afterwards. Before the cyclone, when nine sites were visited, canopy openness in old-growth and logged sites was similar, but significantly higher in regrowth forest. After the cyclone, all six revisited sites showed an increase in canopy openness, but the increase was very patchy amongst plots and sites and varied from insignificant to severe. The most severely impacted site was an old-growth one, the least impacted a logged one. Although proneness to impact was apparently related to forest management history (old-growth being the most impacted), underlying local topography may have had an equally strong influence in this case. It was concluded that the likelihood of severe impact may be determined at the landscape-scale by the interaction of anthropogenic with meteorological, physiographic and biotic factors. In the long term, such interactions may caution against pursuing forest management in cyclone-prone areas

    Fertilización de pasturas de alfalfa y su efecto sobre propiedades fisícoquímicas de un suelo degradado de la Región Semiárida Pampeana Central

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    En un suelo clasificado como Haplustol éntico se realizaron dos ensayos, cuyos objetivos fueron: a) Evaluar el efecto de la fertilización a la siembra y postergada con N, P YS a partir de diferentes fuentes, sobre la producción y composición botánica de pasturas asociadas en base a alfalfa. b) Evaluar el efecto de las pasturas con y sin fertilización, sobre algunas características físicas y químicas del suelo, bajo condiciones de pastoreo. Los resultados pusieron de manifiesto que los mayores rendimientos de materia seca se encontraron en los tratamientos que incluyeron N, P Y S, siendo la combinación más favorable Super Fosfato Triple (SFT) y Sulfato de Amonio (S A), la cual presentó a su vez, la menor incidencia de maleza. La fertilización a la siembra presentó la mayor producción de la pastura debido a una mayor eficiencia al incorporar el fertilizante. En éste caso tuvieron mejor respuesta los tratamientos fertilizados con altas dosis de SPT combinado con SAo No se observó cambios significativos de las propiedades físicas (Resistencia a la penetración del suelo, densidad aparente, estabilidad estructural en seco y en húmedo) y químicas (MO y N K) analizadas. Esto se atribuyó a que el suelo se encontraba muy degradado y a que se requerirla un mayor tiempo de duración de las pasturas para mejorar dichas propiedades. En fertilización a la siembra con altas dosis de SPT se logró aumentar el nivel de P asimilable del suelo luego de dos años y medio de pastura.Director: Ing. Agr. Daniel Buschiazzo. Cátedra de Edafología, Manejo, y Conservación y Fertilidad del sueloCodirector: Ing. Agr. Alfredo Bono. Cátedra de Edafología, Manejo, y Conservación y Fertilidad del suel

    Long-term (10 years) prognostic value of a normal thallium-201 myocardial exercise scintigraphy in patients with coronary artery disease documented by angiography

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    In order to assess the prognostic significance of normal exercise thallium-210 myocardial scintigraphy in patients with documented coronary artery disease, we studied the incidence of cardiac death and non-fatal myocardial infarction in 69 symptomatic patients without prior Q wave myocardial infarction, who demonstrated one or more significant coronary lesions (stenosis ≤70%) on an angiogram performed within 3 months of scintigraphy (Group 1). These patients were compared to a second group of 136 patients with an abnormal exercise scintigram, defined by the presence of reversible defect(s) and angiographically proven coronary artery disease (Group 2), and to a third group of 102 patients with normal exercise scintigraphy without significant coronary lesions (stenosis ≥30%) or with normal coronary angiography (Group 3). In contrast to coronary lesions observed in Group 2, patients in Group I presented more frequently with single- vessel disease (83% vs 35%, P>0·0001) and with more distal lesions (55% vs 23%, P>0·0001). Over a mean follow-up period of 8·6 years, one fatal and eight non-fatal cases of myocardial infarction were observed in Group 1. The majority of patients in Group 1 were treated medically: only 24 (35%) underwent myocardial revascularization, usually by coronary angioplasty. There was no significant difference in the incidence of combined major cardiac events (cardiac death, non-fatal myocardial infarction) in patients with normal exercise scintigraphy, with or without documented coronary artery disease (Groups 1 and 3), while the incidence was higher in Group 2. However, while the mortality remained very low in Group 1, the incidence of non-fatal myocardial infraction was not different from that of Group 2, where most patients underwent revascularization procedures. In conclusion, patients with coronary artery disease and a normal exercise thallium-201 myocardial scintigram usually have mild coronary lesions (single-vessel disease, distal location) and good long-term prognosis, with a low incidence of cardiac deat

    Meningeal defects alter the tangential migration of cortical interneurons in Foxc1hith/hith mice

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    <p>Abstract</p> <p>Background</p> <p>Tangential migration presents the primary mode of migration of cortical interneurons translocating into the cerebral cortex from subpallial domains. This migration takes place in multiple streams with the most superficial one located in the cortical marginal zone. While a number of forebrain-expressed molecules regulating this process have emerged, it remains unclear to what extent structures outside the brain, like the forebrain meninges, are involved.</p> <p>Results</p> <p>We studied a unique <it>Foxc1 </it>hypomorph mouse model (<it>Foxc1<sup>hith/hith</sup></it>) with meningeal defects and impaired tangential migration of cortical interneurons. We identified a territorial correlation between meningeal defects and disruption of interneuron migration along the adjacent marginal zone in these animals, suggesting that impaired meningeal integrity might be the primary cause for the observed migration defects. Moreover, we postulate that the meningeal factor regulating tangential migration that is affected in homozygote mutants is the chemokine Cxcl12. In addition, by using chromatin immunoprecipitation analysis, we provide evidence that the <it>Cxcl12 </it>gene is a direct transcriptional target of Foxc1 in the meninges. Further, we observe migration defects of a lesser degree in Cajal-Retzius cells migrating within the cortical marginal zone, indicating a less important role for Cxcl12 in their migration. Finally, the developmental migration defects observed in <it>Foxc1<sup>hith/hith </sup></it>mutants do not lead to obvious differences in interneuron distribution in the adult if compared to control animals.</p> <p>Conclusions</p> <p>Our results suggest a critical role for the forebrain meninges to promote during development the tangential migration of cortical interneurons along the cortical marginal zone and Cxcl12 as the factor responsible for this property.</p

    Anterior implant restorations with a convex emergence profile increase the frequency of recession: 12-month results of a randomized controlled clinical trial

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    AIM To test whether the emergence profile (CONVEX or CONCAVE) of implant-supported crowns influences the mucosal margin stability up to 12 months after insertion of the final restoration. MATERIALS AND METHODS Forty-seven patients with a single implant in the anterior region were randomly allocated to one of three groups: (1) CONVEX (n = 15), implant provisional and an implant-supported crown both with a convex profile; (2) CONCAVE (n = 16), implant provisional and an implant-supported crown both with a concave profile; (3) CONTROL (n = 16), no provisional (healing abutment only) and an implant-supported crown. All patients were recalled at baseline, 6, and 12 months. The stability of mucosal margin along with clinical, aesthetic, and profilometric outcomes as well as time and costs were evaluated. To predict the presence of recession, multivariable logistic regressions were performed and linear models using generalized estimation equations were conducted for the different outcomes. RESULTS Forty-four patients were available at 12 months post-loading. The frequency of mucosal recession amounted to 64.3% in group CONVEX, 14.3% in group CONCAVE, and 31.4% in group CONTROL. Regression models revealed that a CONVEX profile was significantly associated with the presence of recessions (odds ratio: 12.6, 95% confidence interval: 1.82-88.48, p = .01) compared with the CONCAVE profile. Pink aesthetic scores amounted to 5.9 in group CONVEX, 6.2 in group CONCAVE, and 5.4 in group CONTROL, with no significant differences between the groups (p = .735). Groups CONVEX and CONCAVE increased the appointments and costs compared with the CONTROL group. CONCLUSIONS The use of implant-supported provisionals with a CONCAVE emergence profile results in a greater stability of the mucosal margin compared with a CONVEX profile up to 12 months of loading. This is accompanied, however, by increased time and costs compared with the absence of a provisional and may not necessarily enhance the aesthetic outcomes. TRIAL REGISTRATION German Clinical Trials Register; DRKS00009420

    Restorative angle of zirconia restorations cemented on non-original titanium bases influences the initial marginal bone loss: 5-year results of a prospective cohort study

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    AIM: To assess radiographic, restorative, clinical and technical outcomes as well as patient satisfaction of directly veneered zirconia restorations cemented on non-original titanium bases over 5 years. MATERIAL AND METHODS: Twenty-four patients with a single missing tooth in the aesthetic zone were recruited. All patients received a two-piece implant with a screw-retained veneered zirconia restoration cemented extraorally on a titanium base abutment. Marginal bone levels (MBL), marginal bone changes, technical complications, patient satisfaction and clinical parameters including probing depth, bleeding on probing and plaque index were assessed at crown delivery (baseline), at 1 year (FU-1) and 5 years (FU-5) of follow-up. To investigate the relationship between restorative angle and MBL as well as marginal bone changes (bone loss/bone gain), correlation tests and linear regression models were carried out. RESULTS: Twenty-two patients were available for re-examination at 5 years. The mean MBL amounted to 0.54 ± 0.39 mm at baseline, and to 0.24 ± 0.35 at FU-5 (=bone gain) (p  .05). At distal sites, no correlations or associations between the restorative angle and MBL or marginal bone changes were found regardless of the time point. During the 5-year follow-up, 5 technical complications occurred, mainly within the first year and mostly chippings. All patients were entirely satisfied with their implant-supported restoration at 5 years. CONCLUSION: Within the limitations of the present study, the restorative angle of implant-supported crowns on non-original titanium bases might influence the initial marginal bone loss but without affecting their favourable long-term clinical performance. A restorative angle of <40° may limit the initial marginal bone loss at implant-supported crowns with titanium bases

    Enantiospecific pharmacokinetics of intravenous dexmedetomidine in beagles

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    The goal of this study was to investigate the pharmacokinetic (PK) behaviour of dexmedetomidine in dogs administered as a pure enantiomer versus as part of a racemic mixture. Eight unmedicated intact purpose-bread beagles were included. Two intravenous treatments of either medetomidine or dexmedetomidine were administered at 10- to 14-day intervals. Atipamezole or saline solution was administered intramuscularly 45&nbsp;min later. Venous blood samples were collected into EDTA collection tubes, and the quantification of dexmedetomidine and levomedetomidine was performed by chiral LC–MS/MS. All dogs appeared sedated after each treatment without complication. Plasma concentrations of levomedetomidine were measured only in the racemic group and were 51.4% (51.4%–56.1%) lower than dexmedetomidine. Non-compartmental analysis (NCA) was performed for both drugs, while dexmedetomidine data were further described using a population pharmacokinetic approach. A standard two-compartment mammillary model with linear elimination with combined additive and multiplicative error model for residual unexplained variability was established for dexmedetomidine. An exponential model was finally retained to describe inter-individual variability on parameters of clearance (Cl1) and central and peripheral volumes of distribution (V1, V2). No effect of occurrence, levomedetomidine or atipamezole could be observed on dexmedetomidine PK parameters. Dexmedetomidine did not undergo significantly different PK when administered alone or as part of the racemic mixture in otherwise unmedicated dogs
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