Treatment-resistant nephrotic syndrome is a rare form of glomerular disease that occurs in children and adults. No Food and Drug Administration-approved treatments consistently achieve remission of ...proteinuria and preservation of kidney function. CD80 (B7-1) can be expressed on injured podocytes, and administration of abatacept (modified CTLA4-Ig based on a natural ligand to CD80) has been associated with sustained normalization of urinary protein excretion and maintenance of glomerular filtration rate in experimental and clinical settings.
In this report, we describe the rationale for and design of a randomized, placebo-controlled, clinical trial of abatacept in patients with treatment-resistant nephrotic syndrome caused by focal segmental glomerulosclerosis or minimal change disease. The design is a hybrid of a parallel-group and crossover design (switchover) with the primary objectives assessed in the first period of the study and the secondary objectives assessed using data from both periods. All participants will receive the active agent in 1 of the periods. The duration of treatment will be 4 months per period.
The primary outcome will be improvement in nephrotic-range proteinuria to subnephrotic range, that is, reduction from baseline to 4 months in urine protein:creatinine ratio ≥ 50% and to a level < 3. The projected sample size is 90 patients, which has 80% power to detect a treatment difference of 28%.
This study advances efforts to validate CD80 as a therapeutic target for treatment-resistant nephrotic syndrome, and implements a precision medicine-based approach to this serious kidney condition in which the selection of a therapeutic agent is guided by the underlying disease mechanism operating in individual patients.
Abstract Study Objectives To determine 1) which proportion of academic departments have policies concerning older anesthesiologists, 2) whether departments with such policies, particularly those ...related to call, had characteristics such as departmental size and proportions of older anesthesiologists that differed from departments without these policies, 3) if departments routinely screened their older members for problem behaviors, and 4) if departments provided nonclinical roles for older anesthesiologists. Design Survey instrument. Setting Academic medical centers. Measurements An anonymous, web-based questionnaire that included questions on demographics and specific policy-related issues was sent to chairpersons of all academic anesthesia departments in the ASA database. Main Results No department directly addressed every issue listed in the survey. Department size and the number of anesthesiologists over 60 years of age were unrelated to whether that department had one or more policies for older anesthesiologists. Twenty percent of programs stopped night call at age 60 years. Most departments did not exempt older anesthesiologists of any age from call responsibilities. Almost all departments tracked critical incidents and errors in technique and/or judgment. Almost three quarters tracked substance abuse, and over half of the responding departments tracked physical and emotional impairment and fixation errors. A third of departments tracked all 6 types of problem behavior. Only 12% had specific assessment tools for tracking problem behaviors in the clinic, and no department used these tools specifically for older anesthesiologists. While only 17% of departments directed older anesthesiologists into nonclinical roles, older clinicians had teaching, mentoring, and administrative roles within most of the departments. Conclusions Relatively few departments had specific policies for older anesthesiologists that addressed the issues raised in the survey. Further research is needed to determine whether departments should decrease ambiguity of their policies, formulate explicit policies for older anesthesiologists, especially in regard to call, and assess problem behaviors more directly.
We have previously described the cloning of a group of novel cellular immediate-early response genes whose expression in human umbilical vein endothelial cells is induced by tumor necrosis factor α ...in the presence of cycloheximide. These genes are likely to participate in mediating the response of the vascular endothelium to proinflammatory cytokines. In this study, we further characterized one of these novel gene products named B61. Sequence analysis of cDNA clones encoding B61 revealed that its protein product has no significant homology to previously described proteins. Southern analysis suggested that B61 is an evolutionarily conserved single-copy gene. B61 is primarily a hydrophilic molecule but contains both a hydrophobic N-terminal and a hydrophobic C-terminal region. The N-terminal region is typical of a signal peptide, which is consistent with the secreted nature of the protein. The mature form of the predicted protein consists of 187 amino acid residues and has a molecular weight of 22,000. Immunoprecipitation of metabolically labeled human umbilical vein endothelial cell preparations revealed that B61 is a 25-kilodalton secreted protein which is markedly induced by tumor necrosis factor.
Recently PHOBOS has focused on the study of fluctuations and correlations in particle production in heavy-ion collisions at the highest energies delivered by the Relativistic Heavy Ion Collider ...(RHIC). In this report, we present results on event-by-event elliptic flow fluctuations in Au + Au collisions at √s NN =200 GeV. A data-driven method was used to estimate the dominant contribution from non-flow correlations. Over the broad range of collision centralities, the observed large elliptic flow fluctuations are in agreement with the fluctuations in the initial source eccentricity.
Pleural effusions and pulmonary hypoplasia Castillo, R A; Devoe, L D; Falls, G ...
American journal of obstetrics and gynecology,
11/1987, Letnik:
157, Številka:
5
Journal Article
Recenzirano
Nine cases of fetuses with pleural effusions are presented in which the diagnosis was made by ultrasound before the thirtieth week of gestation. A ratio of lung span to hemithorax diameter was ...calculated and ranged from 0.44 to 0.77 (mean 0.60). At autopsy, pulmonary hypoplasia was confirmed in all cases by criteria based on the ratio of lung weight to total body weight. Because pleural effusions occurring in the midtrimester can be detected and may lead to pulmonary hypoplasia, consideration should be given to definitive in utero therapy when no other major fetal abnormality is detected.
There has been considerable interest in the benefits and risks of eating Great Lakes fish, particularly with regard to reproductive health. We report the results of a survey conducted from 1993-1995 ...among Michigan anglers. The survey was designed to identify a reproductive-aged cohort of persons who consume high or low levels of Great Lakes fish in order to study the impact of polyhalogenated biphenyl (PHB) compounds and other toxins on human reproduction outcomes. Using fishing license data obtained from the Michigan Department of Natural Resources, we identified anglers of early reproductive age (18-34 years) in ten Michigan counties. The screening survey ascertained demographic, behavioral, fish consumption, and reproductive history information on anglers and their partners. Over 4,000 angler households were contacted. One thousand nine hundred fifty questionnaires were returned from 1,168 households. The median age of respondents was 30 years; 58% were male and 64% reported being married. Slightly more than one-half the respondents had attended or graduated from college, and less than 10% had not completed high school. In the past year, most respondents (46%) reported having eaten sport-caught fish 1-12 times, while 20% reported having eaten no sport-caught fish; 20% had consumed 13-24 meals. More sport-caught fish was consumed in the spring and summer than in the fall and winter, and males reported eating more fish than females. About 43% of our respondents reported that they intend to have one or more children in the next five years. Of these respondents, 287 couples had no identified impairments to reproduction and therefore would be eligible to participate in the future reproductive study.
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