Factors determining renal response to water immersion in non-excretor cirrhotic patients

Factors determining renal response to water immersion in non-excretor cirrhotic patients. Non-excretor cirrhotic patients, defined by their inability to normally excrete a standard water load, display variable responses to head–out water immersion. The hemodynamic, hormonal, and renal functional status of fifteen such patients were analyzed relative to water excretion during head-out water immersion. Group 1 patients (N = 7) all excreted less than 40% of the water load during immersion, whereas excretion was greater than 40% in all eight patients in Group 2. Group 1 patients, when compared with Group 2, had more ascites, more diuretic resistance, lower serum sodium concentration (125 ± 2 vs. 130 ± 1 mEq/liter, P < 0.05), and more impaired baseline water excretion (12.9 ± 1.2 vs. 35.9 ± 5.9% of water load in 5 hr, P < 0.005). Systemic hemodynamic responses to water immersion were similar in both groups. Glomerular filtration rate and renal plasma flow were significantly more impaired in Group 1 patients (inulin clearance 28 ± 6 vs. 62 ± 9 ml/min/1.73m2, P < 0.05; para-aminohippurate clearance 212 ± 35 vs. 357 ± 37 ml/min, P < 0.05). Concentrations of plasma vasopressin (1.7 ± 0.5 vs. 0.8 ± 0.1 pg/ml, P < 0.05), renin (8.6 ± 1.7 vs. 3.8 ± 0.9 ng/ml/hr, P < 0.05), aldosterone (82 ± 14 vs. 39 ± 10 ng/dl, P < 0.05) and norepinephrine (1155 ± 183 vs. 603 ± 126 pg/ml, P < 0.05) were all significantly higher in Group 1 than Group 2 patients during water immersion. Thus, non-excretor cirrhotic patients are not homogenous and appear to comprise a spectrum with those patients in whom water excretion is most impaired, having tense ascites, diuretic resistance, lower serum sodium concentrations, more impaired renal function, and more marked abnormalities in the hormonal markers of decreased effective blood volume

Valuing Transgenic Cotton Technologies Using a Risk/Return Framework

Stochastic Efficiency with Respect to a Function (SERF) is used to rank transgenic cotton technology groups and place an upper and lower bound on their value. Yield and production data from replicated plot experiments are used to build cumulative distribution functions of returns for nontransgenic, Roundup Ready, Bollgard, and stacked gene cotton cultivars. Analysis of Arkansas data indicated that the stacked gene and Roundup Ready technologies would be preferred by a large number of risk neutral and risk averse producers as long as the costs of the technology and seed are below the lower bounds calculated in this manuscript.cotton, financial risk, market value, SERF, transgenic, Agribusiness, Crop Production/Industries, Risk and Uncertainty, Q12, Q16,

Pharmacological Rationale for Targeting IL-17 in Asthma

Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway

Behavioral and Other Phenotypes in a Cytoplasmic Dynein Light Intermediate Chain 1 Mutant Mouse

The cytoplasmic dynein complex is fundamentally important to all eukaryotic cells for transporting a variety of essential cargoes along microtubules within the cell. This complex also plays more specialized roles in neurons. The complex consists of 11 types of protein that interact with each other and with external adaptors, regulators and cargoes. Despite the importance of the cytoplasmic dynein complex, we know comparatively little of the roles of each component protein, and in mammals few mutants exist that allow us to explore the effects of defects in dynein-controlled processes in the context of the whole organism. Here we have taken a genotype-driven approach in mouse (Mus musculus) to analyze the role of one subunit, the dynein light intermediate chain 1 (Dync1li1). We find that, surprisingly, an N235Y point mutation in this protein results in altered neuronal development, as shown from in vivo studies in the developing cortex, and analyses of electrophysiological function. Moreover, mutant mice display increased anxiety, thus linking dynein functions to a behavioral phenotype in mammals for the first time. These results demonstrate the important role that dynein-controlled processes play in the correct development and function of the mammalian nervous system

Severe hemolysis during primaquine radical cure of Plasmodium vivax malaria: two systematic reviews and individual patient data descriptive analyses

Primaquine (PQ) kills Plasmodium vivax hypnozoites but can cause severe hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We conducted two systematic reviews. The first used data from clinical trials to determine the variety of definitions and frequency of hematological serious adverse events (SAEs) related to PQ treatment of vivax malaria. The second used data from prospective studies and case reports to describe the clinical presentation, management, and outcome of severe PQ-associated hemolysis necessitating hospitalization. In the first review, SAEs were reported in 70 of 249 clinical trials. There were 34 hematological SAEs among 9,824 patients with P. vivax malaria treated with PQ, nine of which necessitated hospitalization or blood transfusion. Criteria used to define SAEs were diverse. In the second review, 21 of 8,487 articles screened reported 163 patients hospitalized after PQ radical cure; 79.9% of whom (123 of 154) were prescribed PQ at ≥ 0.5 mg/kg/day. Overall, 101 patients were categorized as having probable or possible severe PQ-associated hemolysis, 96.8% of whom were G6PD deficient (< 30% activity). The first symptoms of hemolysis were reported primarily on day 2 or 3 (45.5%), and all patients were hospitalized within 7 days of PQ commencement. A total of 57.9% of patients (77 of 133) had blood transfusion. Seven patients (6.9%) with probable or possible hemolysis died. Even when G6PD testing is available, enhanced monitoring for hemolysis is warranted after PQ treatment. Clinical review within the first 5 days of treatment may facilitate early detection and management of hemolysis. More robust definitions of severe PQ-associated hemolysis are required

[¹⁸F]FDG PET/CT Signal Correlates with Neoangiogenesis Markers in Patients with Fibrotic Interstitial Lung Disease Who Underwent Lung Biopsy: Implication for the Use of PET/CT in Diffuse Lung Diseases

The use of [¹⁸F]FDG PET/CT as a biomarker in diffuse lung diseases is increasingly recognized. We investigated the correlation between [¹⁸F]FDG uptake with histologic markers on lung biopsy of patients with fibrotic interstitial lung disease (fILD). // Methods: We recruited 18 patients with fILD awaiting lung biopsy for [¹⁸F]FDG PET/CT. We derived a target-to-background ratio (TBR) of maximum pulmonary uptake of [¹⁸F]FDG (SUVₘₐₓ) divided by the lung background (SUVₘᵢₙ). Consecutive paraffin-embedded lung biopsy sections were immunostained for alveolar and interstitial macrophages (CD68), microvessel density (MVD) (CD31 and CD105/endoglin), and glucose transporter 1. MVD was expressed as vessel area percentage per high-power field (Va%/hpf). Differences in imaging and angiogenesis markers between histologic usual interstitial pneumonia (UIP) and non-UIP were assessed using a nonparametric Mann–Whitney test. Correlation of imaging with angiogenesis markers was assessed using the nonparametric Spearman rank correlation. Univariate Kaplan–Meier survival analysis assessed the difference in the survival curves for each of the angiogenesis markers (separated by their respective optimal cutoff) using the log-rank test. Statistical analysis was performed using SPSS. // Results: In total, 18 patients were followed for an average of 41.36 mo (range, 5.69–132.46 mo; median, 30.07 mo). Only CD105 MVD showed a significantly positive correlation with [¹⁸F]FDG TBR (Spearman rank correlation, 0.556; P < 0.05, n = 13). There was no correlation between [¹⁸F]FDG uptake and macrophage expression of glucose transporter 1. CD105 and CD31 were higher for UIP than for non-UIP, with CD105 reaching statistical significance (P = 0.011). In all patients, MVD assessed with either CD105 or CD31 quantification on biopsy predicted overall survival. Patients with CD105 MVD of less than 12 Va%/hpf or CD31 MVD of less than 35 Va%/hpf had a significantly better prognosis (no deaths during follow-up in the case of CD105) than did patients with higher scores of CD105 MVD (median survival, 35 mo; P = 0.041, n = 13) or CD31 MVD (median survival, 28 mo; P = 0.014, n = 13). // Conclusion: Previous work has used [¹⁸F]FDG uptake in PET/CT as a biomarker in fILD. Here, we highlight a correlation between angiogenesis and [¹⁸F]FDG TBR. We show that MVD is higher for UIP than for non-UIP and is associated with mortality in patients with fILD. These data set the scene to investigate the potential role of vasculature and angiogenesis in fibrosis

Extreme Longitudinal Variability of Plasma Structuring in the Equatorial Ionosphere on a Magnetically Quiet Equinoctial Day

We investigate the extreme longitudinal variability of equatorial scintillation under quiet magnetic conditions during 22–23 March 2002. Scintillation Network Decision Aid (SCINDA) observations show intense activity in the South American–Atlantic sector during local evening hours, whereas an absence of scintillation is seen in the far east Asian sector. Ground- and space-based measurements from SCINDA, the Global Ultraviolet Imager (GUVI), TOPEX, and a chain of GPS receivers are used in combination with the Utah State University Global Assimilation of Ionospheric Measurements (USU-GAIM) model to explore the relationship between the large-scale ionization distribution and small-scale irregularities at low latitudes in both the scintillating and nonscintillating longitude sectors. Our analysis shows that there are significant differences in the evolution of the ionization distributions during the evening hours, which are likely the result of differences in the daytime and postsunset vertical plasma drift in the two sectors. This study demonstrates the importance of USU-GAIM as a new tool for investigating longitudinal as well as day-to-day variability that is observed in the large-scale distribution of the ionosphere and how this relates to the occurrence of scintillation

Areas of normal pulmonary parenchyma on HRCT exhibit increased FDG PET signal in IPF patients

Purpose: Patients with idiopathic pulmonary fibrosis (IPF) show increased PET signal at sites of morphological abnormality on high-resolution computed tomography (HRCT). The purpose of this investigation was to investigate the PET signal at sites of normal-appearing lung on HRCT in IPF. Methods: Consecutive IPF patients (22 men, 3 women) were prospectively recruited. The patients underwent 18F-FDG PET/HRCT. The pulmonary imaging findings in the IPF patients were compared to the findings in a control population. Pulmonary uptake of 18F-FDG (mean SUV) was quantified at sites of morphologically normal parenchyma on HRCT. SUVs were also corrected for tissue fraction (TF). The mean SUV in IPF patients was compared with that in 25 controls (patients with lymphoma in remission or suspected paraneoplastic syndrome with normal PET/CT appearances). Results: The pulmonary SUV (mean ± SD) uncorrected for TF in the controls was 0.48 ± 0.14 and 0.78 ± 0.24 taken from normal lung regions in IPF patients (p < 0.001). The TF-corrected mean SUV in the controls was 2.24 ± 0.29 and 3.24 ± 0.84 in IPF patients (p < 0.001). Conclusion: IPF patients have increased pulmonary uptake of 18F-FDG on PET in areas of lung with a normal morphological appearance on HRCT. This may have implications for determining disease mechanisms and treatment monitoring. © 2013 The Author(s)