Preservation of blood volume during edema removal in nephrotic subjects

Preservation of blood volume during edema removal in nephrotic subjects. During the gradual removal of edema with diuretics in 21 edematous patients with the nephrotic syndrome (NS) we monitored blood volume. For comparison, nine healthy subjects were studied after equilibration on diets containing 20, 200, and 1138mEq sodium. The initial extracellular fluid volume (ECFV) in the patients exceeded the final ECFV by 63.4 ± 8.4%. In 10 patients with a very low plasma oncotic pressure (8.2 ± 0.4mm Hg, Group 1), the blood volume changed little. In Group 2 (plasma oncotic pressure 13.4 ± 1.0mm Hg), it was 11.0 ± 2.5% higher at entry than after edema withdrawal. In the normal volunteers, the highest sodium intake raised the ECFV by 21.4 ± 4.1%. The accompanying rise in blood volume, 11.2 ± 3.0%, was larger than in the patients of Group 1 (2.4 ± 1.9%, P < 0.04), but not of Group 2 (8.1 ± 1.9%, NS) at similar degrees of expansion. There was no difference in blood volume between the edema-free patients and the normal subjects at low-sodium diet. The course of blood pressure and creatinine clearance during edema removal gave no evidence that functional hypovolemia was induced, but the plasma renin activity was higher than in the normal subjects at similar degrees of expansion. We conclude that the blood volume to ECFV relationship curve is flattened in the presence of hypoalbuminemia. Thus, the increase in blood volume that normally follows ECFV expansion is less in patients with the NS, but a drop below normal upon removal of edema is absent also

Functional relationships in the nephrotic syndrome

Functional relationships in the nephrotic syndrome. An analysis of 70 observations in patients with the nephrotic syndrome (NS) on a low sodium diet is presented. The following parameters were determined: plasma volume, plasma renin activity, plasma aldosterone concentration, serum albumin, urinary sodium and protein excretion, and creatinine clearance. In 41 instances glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined on the basis of 51Cr-EDTA and 125I-hippuran clearances, and the filtration fraction (FF) was calculated. The results in patients with minimal lesions (ML) and those with histological glomerular lesions (HL) were compared to determine whether these groups can be separated on the basis of signs of hypovolemia and primary renal sodium retention. Although a higher proportion of the ML patients showed extreme sodium retention and elevated plasma renin and aldosterone levels, these values tended to overlap and no differences were found for blood volume, blood pressure, and overall renal function between the groups. FF was markedly and equally depressed in both groups: 13.5 ± 1.6% in the ML and 14.2 ± 1.1% SEM in the HL group (NS). Analysis of the within-group relationships between the parameters under study revealed relatively few correlations, which supports the hypothesis that primary impairment of renal water and salt excretion is an important if not overruling factor in patients with the NS.Relations fonctionnelles au cours du syndrome néphrotique. Une analyse de 70 observations de malades atteintes de syndrome néphrotique (NS) en régime pauvre en sodium est présentée. Les paramètres suivants ont été déterminés: volume plasmatique, activité rénine plasmatique, aldostéronémie, albuminémie, natriurèse et protéinurie, et clearance de la créatinine. Dans 41 fois, le débit de filtration glomérulaire (GFR) et le débit plasmatique rénal efficace (ERPF) ont été déterminés par des clearances au 51Cr-EDTA et au 125I-hippuran, et on a calculé la fraction de filtration (FF). Les résultats des groupes de malades atteints de lésions minimes (ML) et de ceux atteints de lésions glomérulaires histologiques (HL) ont été comparés pour savoir s'il est possible de séparer ces groupes sur la base des signes d'hypovolémie et de rétention sodée d'origine rénale. Bien qu'une plus forte proportion de malades ML ait présenté une réntention sodée et une élévation des niveaux de rénine et d'aldostérone plasmatiques extrêmes, ces valeurs tendaient à se chevaucher et il n'a pas été trouvé de différence dans le volume sanguin, la pression artérielle et la fonction rénale globale entre les groupes. FF était diminuée de façon marquée et identique dans les deux groupes: 13,5 ± 1,6% dans le groupe ML et 14,2 ± 1,1% SEM dans le groupe HL (NS). Une analyse des interrelations à l'intérieur des groupes entre les paramètres étudiés a révélé relativement peu de corrélations, ce qui est en faveur de l'hypothèse que l'altération primitive de l'excrétion rénale d'eau et de sel est un facteur important, sinon capital chez les malades atteints de NS

Association between 8 P-glycoprotein (MDR1/ABCB1) gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia

Introduction: Hyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P-glycoprotein. Genetic variants of P-glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland. Aims: To investigate possible associations between MDR1/ABCB1 gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics. Methods: In total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross-sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8 MDR1/ABCB1 gene-polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone. Results: We did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic-induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone-induced hyperprolactinaemia. Conclusion: This study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone-induced hyperprolactinaemia

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least 4 m. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the 6.5 m James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 yr, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit