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71.
Omrana?PashaEmail author Shivaprasad?S?Goudar Archana?Patel Ana?Garces Fabian?Esamai Elwyn?Chomba Janet?L?Moore Bhalchandra?S?Kodkany Sarah?Saleem Richard?J?Derman Edward?A?Liechty Patricia?L?Hibberd K?Michael?Hambidge Nancy?F?Krebs Waldemar?A?Carlo Elizabeth?M?McClure Marion?Koso-Thomas Robert?L?Goldenberg 《Reproductive health》2015,12(Z2):S11
Background
During the post-partum period, most women wish to delay or prevent future pregnancies. Despite this, the unmet need for family planning up to a year after delivery is higher than at any other time. This study aims to assess fertility intention, contraceptive usage and unmet need for family planning amongst women who are six weeks postpartum, as well as to identify those at greatest risk of having an unmet need for family planning during this period.Methods
Using the NICHD Global Network for Women’s and Children’s Health Research’s multi-site, prospective, ongoing, active surveillance system to track pregnancies and births in 100 rural geographic clusters in 5 countries (India, Pakistan, Zambia, Kenya and Guatemala), we assessed fertility intention and contraceptive usage at day 42 post-partum.Results
We gathered data on 36,687 women in the post-partum period. Less than 5% of these women wished to have another pregnancy within the year. Despite this, rates of modern contraceptive usage varied widely and unmet need ranged from 25% to 96%. Even amongst users of modern contraceptives, the uptake of the most effective long-acting reversible contraceptives (intrauterine devices) was low. Women of age less than 20 years, parity of two or less, limited education and those who deliver at home were at highest risk for having unmet need.Conclusions
Six weeks postpartum, almost all women wish to delay or prevent a future pregnancy. Even in sites where early contraceptive adoption is common, there is substantial unmet need for family planning. This is consistently highest amongst women below the age of 20 years. Interventions aimed at increasing the adoption of effective contraceptive methods are urgently needed in the majority of sites in order to reduce unmet need and to improve both maternal and infant outcomes, especially amongst young women.Study registration
Clinicaltrials.gov (ID# NCT01073475)72.
Joshua M. Goldenberg Julio Cárdenas-Rodríguez Mark D. Pagel 《Molecular imaging and biology》2018,20(4):575-583
Purpose
We sought to determine if the synergy between evaluations of glucose uptake in tumors and extracellular tumor acidosis measured with simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) can improve longitudinal evaluations of the response to metformin treatment.Procedures
A standard 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET protocol that evaluates glucose uptake in tumors, and a standard acidoCEST MRI protocol that measures extracellular pH (pHe) in tumors, were simultaneously performed to assess eight vehicle-treated (control) mice and eight metformin-treated mice 1 day before treatment, 1 day after initiating daily treatment with metformin, and 7 days after initiating treatment. Longitudinal changes in SUVmax and extracellular pH (pHe) were evaluated for each treatment group, and differences in SUVmax and pHe between metformin-treated and control groups were also evaluated.Results
MRI acquisition protocols had little effect on the PET count rate, and the PET instrumentation had little effect on image contrast during acidoCEST MRI, verifying that [18F]FDG PET and acidoCEST MRI can be performed simultaneously. The average SUVmax of the tumor model had a significant decrease after 7 days of treatment with metformin, as expected. The average tumor pHe decreased after 7 days of metformin treatment, which reflected the inhibition of the consumption of cytosolic lactic acid caused by metformin. However, the average SUVmax of the tumor model was not significantly different between the metformin-treated and control groups after 7 days of treatment, and average pHe was also not significantly different between these groups. For comparison, the combination of average SUVmax and pHe measurements significantly differed between the treatment group and control group on Day 7.Conclusions
[18F]FDG PET and acidoCEST MRI studies can be performed simultaneously. The synergistic combination of assessing glucose uptake and tumor acidosis can improve differentiation of a drug-treated group from a control group during drug treatment of a tumor model.73.
High and long‐term von Willebrand factor expression after Sleeping Beauty transposon‐mediated gene therapy in a mouse model of severe von Willebrand disease 下载免费PDF全文
I. Portier K. Vanhoorelbeke S. Verhenne I. Pareyn N. Vandeputte H. Deckmyn D. S. Goldenberg H. B. Samal M. Singh Z. Ivics Z. Izsvák S. F. De Meyer 《Journal of thrombosis and haemostasis》2018,16(3):592-604
Essentials
- von Willebrand disease (VWD) is the most common inherited bleeding disorder.
- Gene therapy for VWD offers long‐term therapy for VWD patients.
- Transposons efficiently integrate the large von Willebrand factor (VWF) cDNA in mice.
- Liver‐directed transposons support sustained VWF expression with suboptimal multimerization.
Summary
Background
Type 3 von Willebrand disease (VWD) is characterized by complete absence of von Willebrand factor (VWF). Current therapy is limited to treatment with exogenous VWF/FVIII products, which only provide a short‐term solution. Gene therapy offers the potential for a long‐term treatment for VWD.Objectives
To develop an integrative Sleeping Beauty (SB) transposon‐mediated VWF gene transfer approach in a preclinical mouse model of severe VWD.Methods
We established a robust platform for sustained transgene murine VWF (mVWF) expression in the liver of Vwf?/? mice by combining a liver‐specific promoter with a sandwich transposon design and the SB100X transposase via hydrodynamic gene delivery.Results
The sandwich SB transposon was suitable to deliver the full‐length mVWF cDNA (8.4 kb) and supported supra‐physiological expression that remained stable for up to 1.5 years after gene transfer. The sandwich vector stayed episomal (~60 weeks) or integrated in the host genome, respectively, in the absence or presence of the transposase. Transgene integration was confirmed using carbon tetrachloride‐induced liver regeneration. Analysis of integration sites by high‐throughput analysis revealed random integration of the sandwich vector. Although the SB vector supported long‐term expression of supra‐physiological VWF levels, the bleeding phenotype was not corrected in all mice. Long‐term expression of VWF by hepatocytes resulted in relatively reduced amounts of high‐molecular‐weight multimers, potentially limiting its hemostatic efficacy.Conclusions
Although this integrative platform for VWF gene transfer is an important milestone of VWD gene therapy, cell type‐specific targeting is yet to be achieved.74.
75.
Kwok Benjamin Brosnahan Shari B. Amoroso Nancy E. Goldenberg Ronald M. Heyman Brooke Horowitz James M. Jamin Catherine Sista Akhilesh K. Smith Deane E. Yuriditsky Eugene Maldonado Thomas S. 《Journal of thrombosis and thrombolysis》2021,51(2):330-338
Journal of Thrombosis and Thrombolysis - Coronavirus disease 2019 (COVID-19) is associated with increased rates of deep vein thrombosis (DVT) and pulmonary embolism (PE). Pulmonary Embolism... 相似文献
76.
77.
Ilan Goldenberg Arthur J Moss Scott McNitt Wojciech Zareba W Jackson Hall Mark L Andrews David J Wilber Helmut U Klein 《Journal of the American College of Cardiology》2006,47(9):1811-1817
OBJECTIVES: The study was designed to assess the effect of elapsed time from coronary revascularization (CR) on the benefit of the implantable cardioverter-defibrillator (ICD) and the risk of sudden cardiac death (SCD) in patients with ischemic left ventricular dysfunction. BACKGROUND: The ICD improves survival in appropriately selected high-risk cardiac patients by 30% to 54%. However, in the Coronary Artery Bypass Graft (CABG)-Patch trial no evidence of improved survival was shown among a similar population of patients in whom an ICD was implanted prophylactically at the time of elective CABG. METHODS: The outcome by time from CR was analyzed in 951 patients in whom a revascularization procedure was performed before enrollment in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. RESULTS: The adjusted hazard ratio (HR) of ICD versus conventional therapy was 0.64 (p = 0.01) among patients enrolled more than six months after CR, whereas no survival benefit with ICD therapy was shown among patients enrolled six months or earlier after CR (HR = 1.19; p = 0.76). In the conventional therapy group, the risk of cardiac death increased significantly with increasing time from CR (p for trend = 0.009), corresponding mainly to a six-fold increase in the risk of SCD among patients enrolled more than six months after CR. CONCLUSIONS: In patients with ischemic left ventricular dysfunction, the efficacy of ICD therapy after CR is time dependent, with a significant life-saving benefit in patients receiving device implantation more than six months after CR. The lack of ICD benefit when implanted early after CR may be related to a relatively low risk of SCD during this time period. 相似文献
78.
Lindquist R Dupuis G Terrin ML Hoogwerf B Czajkowski S Herd JA Barton FB Tracy MF Hunninghake DB Treat-Jacobson D Shumaker S Zyzanski S Goldenberg I Knatterud GL;POST CABG Biobehavioral Study Investigators 《American heart journal》2003,146(6):1038-1044
Background
Women undergoing coronary artery bypass graft (CABG) surgery have a worse medical condition and fewer social and financial resources than men. Some studies have found that women recover less well than men after CABG, whereas others have found women's outcomes comparable to those of men. Past studies of health-related quality of life after CABG have too few women for adequate comparison with men and have not included patients whose data are not available at baseline (eg, emergency CABG), limiting generalizability.Methods
A longitudinal study of symptoms and health-related quality of life was conducted among patients from four clinical centers enrolling both men (n = 405) and women (n = 269) in the Post CABG Biobehavioral Study in the United States and Canada.Results
After 6 weeks from CABG (average 81 days), both men and women had less anxiety and symptoms related to depression than before surgery (P < .001). After 6 months (average 294 days), both men and women improved in physical and social functioning (P < .001). Although changes in scale scores were similar for men and women at each time point, women scored lower than men on these domains (P < .001, adjusted for baseline medical and sociodemographic differences) and had more symptoms related to depression through 1 year after CABG (P = .003).Conclusions
Both male and female patients improve in physical, social, and emotional functioning after CABG, and recovery over time is similar in men and women. However, women's health-related quality-of-life scale scores remained less favorable than men's through 1 year after surgery. 相似文献79.
80.
Pregnancy loss, polycystic ovary syndrome, thrombophilia, hypofibrinolysis, enoxaparin, metformin. 总被引:3,自引:0,他引:3
Charles J Glueck Ping Wang Naila Goldenberg Luann Sieve 《Clinical and applied thrombosis/hemostasis》2004,10(4):323-334
Thrombophilia, hypofibrinolysis, and polycystic ovary syndrome (PCOS) are associated with recurrent pregnancy loss (RPL) and spontaneous abortion (SAB) alone and concurrently. The efficacy and safety of combined enoxaparin-metformin was prospectively assessed in women with PCOS with one or more previous SAB, thrombophilia, and/or hypofibrinolysis. Twenty-four white women with PCOS were studied; 23 with previous pregnancies, seven with RPL of unknown etiology (>/=three consecutive pregnancy losses <20 weeks' gestation), two with two consecutive SABs, 13 with one SAB, and one with one live birth (HELLP syndrome). Prospectively, metformin (1.5 to 2.55 g/day) was administered before and throughout gestation, with concurrent enoxaparin (60 mg/day) throughout gestation. The 24 cases differed from 93 normal white female controls for the factor V Leiden mutation, 17% vs. 2%, Fisher's p [p(f)] = .016, and for the 4G4G mutation of the plasminogen activator inhibitor-1 (PAI-1) gene (46% vs. 24%, Chi-square 4.63, p =. 031). The patients also differed from 44 normal white female controls for high levels (> 21.1 U/mL) of the PAI-1 gene product, plasminogen activator inhibitor activity (PAI-Fx) (33% vs. 8%, p(f) =. 018), and for high factor VIII (>150%) (22% vs. 0%, p(f) = .037). Of the 24 women, 23 had 65 previous pregnancies without metformin or enoxaparin, with 18 live births, 46 SAB (71%), and one elective abortion. On metforminenoxaparin, the same 23 women had 26 current pregnancies (28 fetuses), with 20 live births, two normal pregnancies 13 weeks or longer, and six SAB (21%), 3.4-fold lower than previous gestations (McNemar's S = 33.6, p <. 0001). There were no adverse maternal or fetal therapy effects. Enoxaparin-metformin reduces pregnancy loss in women with PCOS with one or more previous SAB, who also have thrombophilia and/or hypofibrinolysis. 相似文献