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81.
Diagnostic role of an immunoassay-detected polymorphism of factor IX for potential carriers of hemophilia B 总被引:3,自引:1,他引:3
In hemophilia B, assays based on a monoclonal antifactor IX specific for the Thr-148 variant of an exonic polymorphism have diagnosed carriers in selected families by either establishing linkage or by indicating the presence or absence of a given normal factor IX. The sensitivity of the immunoassays for detecting heterozygous women was explored by comparing results from immunoassays with solid-phase polyclonal v the monoclonal antifactor IXs. Factor IX with the normal Ala-148 variant gave a flat dilution curve, qualitatively distinct from factor IX with the Thr-148 variant in the monoclonal assay. The two were indistinguishable in the polyclonal assay. Mixtures of equal amounts of the two types gave an intermediate result, about half as reactive in the monoclonal as compared with the polyclonal assay system. Whereas mixtures with 10% Ala-148 and 90% Thr-148 factor IXs could not readily be distinguished from Thr-148 factor IX plasma, as little as 1% of the Thr-148 protein was detected in Ala-148 factor IX plasma. The frequency of the Ala-148 variant varied in individuals with different ethnic backgrounds; it was found in 29% of white, 12% of black, and none of Asian blood donors' factor IX genes in Seattle. Only 4% of samples from South African black men were nonreactive (ie, Ala- 148). The Thr/Ala-148 dimorphism is in strong linkage disequilibrium with Taql restriction fragment length polymorphisms (RFLPs). Three recombinations were noted in normal white genes and one in a normal black factor IX gene (less than 2% of those examined). In 34 white families with at least one woman being a possible carrier, genetically, the immunoassay results were informative in 18. RFLP analyses were informative in eight of the 15 families tested. In five families each, assignment of carrier status was made to a woman by only DNA or only immunoassay results, whereas the other approach was noninformative. The immunoassays provide a rapid, inexpensive screening test and complement DNA analysis in white women who are potential carriers of hemophilia B. 相似文献
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Objective
This study examined sex differences and eating disorder risk among psychiatric conditions, compulsive behaviors (i.e., gambling, suicide thoughts and attempts) and substance use in a nationally representative sample.Method
Data from participants of the Canadian Community Health Survey Cycle 1.2 who completed the Eating Attitudes Test (n= 5116) were analyzed. Sex differences were compared among psychiatric comorbidities according to eating disorder risk, binging, vomiting and dieting behavior. Poisson regression analysis provided prevalence ratios (PRs) of disordered eating adjusting for age, marital status, income, body mass index and recent distress.Results
Pronounced sex differences were associated with eating disorder risk (PRs 4.89–11.04; all P values < .0001). Findings of particular interest included significantly higher PRs for eating disorder risk in males associated with gambling (PR 5.07, P< .0001) and for females associated with steroid and inhalant use as well as suicide thoughts and attempts (PRs 5.40–5.48, all P values < .0001).Discussion
The findings from this detailed exploration of sex differences and eating disorder risk among psychiatric conditions, compulsive behaviors and substance use suggest that problem gambling, the use of inhalants and steroids and suicidal ideation in relationship to eating disorder risk warrant further investigation. 相似文献84.
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Andrew G. Matthew Shabbir M. H. Alibhai Tal Davidson Kristen L. Currie Haiyan Jiang Murray Krahn Neil E. Fleshner Robin Kalnin Alyssa S. Louis B. Joyce Davison John Trachtenberg 《Quality of life research》2014,23(8):2309-2317
Purpose
To identify the health-related quality of life (HRQoL) domains that radical prostatectomy (RP) impacts most negatively and to define the recovery of these domains over 30 months of observation.Patients and methods
A total of 1,200 RP patients completed the Patient-Oriented Prostate Utility Scale-Psychometric (PORPUS-P; range 0–100, higher is better), a prostate cancer-specific HRQoL measure, prior to RP and at 0–3 (T1), 3–9 (T2), 9–18 (T3) and 18–30 (T4) months post-RP. HRQoL changes were examined using paired t tests and a mixed-effect growth curve model. Multivariable analyses were performed to investigate demographic and treatment factors predicting the change in HRQoL.Results
Mean baseline PORPUS-P score, 83.1, fell to 66.5 (p < 0.001) at T1. Over time HRQoL improved but did not return to baseline (T4 mean 76.4, p < 0.001). Domain analysis revealed that sexual function (p < 0.001), sexual drive (p < 0.001), energy (p = 0.001) and bladder control (p < 0.001) failed to return to baseline at T4. Sexual function demonstrated the greatest impairment overall. The multivariable model revealed Black men experienced greater losses in global HRQoL compared with White men (coefficient ?2.77, 95 % CI ?5.00 to ?0.54, p = 0.015). High baseline HRQoL, pro-erectile aid use and bilateral nerve-sparing were significantly associated with smaller reductions in HRQoL post-RP.Conclusion
Overall HRQoL, sexual drive, sexual function, energy and bladder control do not return to preoperative levels within 30 months post-RP. Black patients experience the greatest reductions in HRQoL. HRQoL losses may be ameliorated by use of pro-erectile aids. These findings help to identify at-risk patient populations and inform survivorship programs. 相似文献86.
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88.
Adam Davison Kaspar Gierke Johann Helmut Brandsttter Norbert Babai 《Investigative ophthalmology & visual science》2022,63(3)
PurposeCone photoreceptors of the retina use a sophisticated ribbon-containing synapse to convert light-dependent changes in membrane potential into release of synaptic vesicles (SVs). We aimed to study the functional and structural maturation of mouse cone photoreceptor ribbon synapses during postnatal development and to investigate the role of the synaptic ribbon in SV release.MethodsWe performed patch-clamp recordings from cone photoreceptors and their postsynaptic partners, the horizontal cells during postnatal retinal development to reveal the functional parameters of the synapses. To investigate the occurring structural changes, we applied immunocytochemistry and electron microscopy.ResultsWe found that immature cone photoreceptor terminals were smaller, they had fewer active zones (AZs) and AZ-anchored synaptic ribbons, and they produced a smaller Ca2+ current than mature photoreceptors. The number of postsynaptic horizontal cell contacts to synaptic terminals increased with age. However, tonic and spontaneous SV release at synaptic terminals stayed similar during postnatal development. Multiquantal SV release was present in all age groups, but mature synapses produced larger multiquantal events than immature ones. Remarkably, at single AZs, tonic SV release was attenuated during maturation and showed an inverse relationship with the appearance of anchored synaptic ribbons.ConclusionsOur developmental study suggests that the presence of synaptic ribbons at the AZs attenuates tonic SV release and amplifies multiquantal SV release. However, spontaneous SV release may not depend on the presence of synaptic ribbons or voltage-sensitive Ca2+ channels at the AZs. 相似文献
89.
Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX‐AHF‐2 study 下载免费PDF全文
John R. Teerlink Adriaan A. Voors Piotr Ponikowski Peter S. Pang Barry H. Greenberg Gerasimos Filippatos G. Michael Felker Beth A. Davison Gad Cotter Claudio Gimpelewicz Leandro Boer‐Martins Margaret Wernsing Tsushung A. Hua Thomas Severin Marco Metra 《European journal of heart failure》2017,19(6):800-809
Patients admitted for acute heart failure (AHF) experience high rates of in‐hospital and post‐discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin‐2, a hormone with vasodilatory and end‐organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX‐AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF. Compared to placebo, serelaxin also reduced worsening heart failure (WHF) by 47% through day 5 and both all‐cause and cardiovascular mortality by 37% through day 180. RELAX‐AHF‐2 ( ClinicalTrials.gov NCT01870778) is designed to confirm serelaxin's effect on these clinical outcomes. RELAX‐AHF‐2 is a multicentre, randomized, double‐blind, placebo‐controlled, event‐driven, phase 3 trial enrolling ~6800 patients hospitalized for AHF with dyspnoea, congestion on chest radiograph, increased natriuretic peptide levels, mild‐to‐moderate renal insufficiency, and systolic blood pressure ≥125 mmHg. Patients are randomized within 16 h of presentation to 48 h intravenous infusions of serelaxin (30 µg/kg/day) or placebo, both in addition to standard of care treatments. The primary objectives are to demonstrate that serelaxin is superior to placebo in reducing: (i) 180 day cardiovascular death, and (ii) occurrence of WHF through day 5. Key secondary endpoints include 180 day all‐cause mortality, composite of 180 day combined cardiovascular mortality or heart failure/renal failure rehospitalization, and in‐hospital length of stay during index AHF. The results from RELAX‐AHF‐2 will provide data on the potential beneficial effect of serelaxin on cardiovascular mortality and WHF in selected patients with AHF. 相似文献
90.
Satit Janwanishstaporn Siting Feng John Teerlink Marco Metra Gad Cotter Beth A. Davison G. Michael Felker Gerasimos Filippatos Peter Pang Piotr Ponikowski Thomas Severin Claudio Gimpelewicz Thomas Holbro Chien Wei Chen Iziah Sama Adriaan A. Voors Barry H. Greenberg 《European journal of heart failure》2020,22(4):726-738