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61.
62.
Zafer Tandogdu Justin Collins Greg Shaw Jennifer Rohn Bela Koves Ashwin Sachdeva Ahmed Ghazi Alexander Haese Alex Mottrie Anup Kumar Ananthakrishnan Sivaraman Ashutosh Tewari Benjamin Challacombe Bernardo Rocco Camilo Giedelman Christian Wagner Craig G. Rogers Declan G. Murphy Dmitry Pushkar Gabriel Ogaya-Pinies James Porter Kulthe Ramesh Seetharam Markus Graefen Marcelo A. Orvieto Marcio Covas Moschovas Oscar Schatloff Peter Wiklund Rafael Coelho Rair Valero Theo M. de Reijke Thomas Ahlering Travis Rogers Henk G. van der Poel Vipul Patel Walter Artibani Florian Wagenlehner Kris Maes Koon H. Rha Senthil Nathan Truls Erik Bjerklund Johansen Peter Hawkey John Kelly 《BJU international》2021,127(6):729-741
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Objective: To assess whether site of prenatal care influences the content of prenatal care for low-income women. Design: Bivariate and logistic analyses of prenatal care content for low-income women provided at five different types of care sites (private offices, HMOs, publicly funded clinics, hospital clinics, and other sites of care), controlling for sociodemographic, behavioral, and maternal health characteristics. Participants: A sample of 3405 low-income women selected from a nationally representative sample of 9953 women surveyed by the National Maternal and Infant Health Survey, who had singleton live births in 1988, had some prenatal care (PNC), Medicaid participation, or a family income less than $12,000/year. Outcome Measures: Maternal report of seven initial PNC procedures (individually and combined), six areas of PNC advice (individually and combined), and participation in the Women Infant Children (WIC) nutrition program. Results: The content of PNC provided for low-income women does not meet the recommendations of the U.S. Public Health Service, and varies by site of delivery. Low-income women in publicly funded clinics (health departments and community health centers) report receiving more total initial PNC procedures and total PNC advice and have greater participation in the WIC program than similar women receiving PNC in private offices. Conclusions: Publicly funded sites of care appear to provide more comprehensive prenatal care services than private office settings. Health care systems reforms which assume equality of care across all sites, or which limit services to restricted sites, may foster unequal access to comprehensive PNC. 相似文献
65.
William C Stanley Bin Li Douglas W Bonhaus Lowell G Johnson Keiho Lee Seth Porter Keith Walker Greg Martinez Richard M Eglen Roger L Whiting Sharath S Hegde 《British journal of pharmacology》1997,121(8):1803-1809
- Inhibitory modulation of sympathetic nerve function may have a favourable impact on the progression of congestive heart failure. Nepicastat is a novel inhibitor of dopamine-β-hydroxylase, the enzyme which catalyses the conversion of dopamine to noradrenaline in sympathetic nerves. The in vitro pharmacology and in vivo catecholamine modulatory effects of nepicastat were investigated in the present study.
- Nepicastat produced concentration-dependent inhibition of bovine (IC50=8.5±0.8 nM) and human (IC50=9.0±0.8 nM)dopamine-β-hydroxylase. The corresponding R-enantiomer (RS-25560-198) was approximately 2–3 fold less potent than nepicastat. Nepicastat had negligible affinity (>10 μM) for twelve other enzymes and thirteen neurotransmitter receptors.
- Administration of nepicastat to spontaneously hypertensive rats (SHRs) (three consecutive doses of either 3, 10, 30 or 100 mg kg−1, p.o.; 12 h apart) or beagle dogs (0.05, 0.5, 1.5 or 5 mg kg−1, p.o.; b.i.d., for 5 days) produced dose-dependent decreases in noradrenaline content, increases in dopamine content and increases in dopamine/noradrenaline ratio in the artery (mesenteric or renal), left ventricle and cerebral cortex. At the highest dose studied, the decreases in tissue noradrenaline were 47%, 35% and 42% (in SHRs) and 88%, 91% and 96% (in dogs) in the artery, left ventricle and cerebral cortex, respectively. When tested at 30 mg kg−1, p.o., in SHRs, nepicastat produced significantly greater changes in noradrenaline and dopamine content, as compared to the R-enantiomer (RS-25560-198), in the mesenteric artery and left ventricle.
- Administration of nepicastat (2 mg kg−1, b.i.d, p.o.) to beagle dogs for 15 days produced significant decreases in plasma concentrations of noradrenaline and increases in plasma concentrations of dopamine and dopamine/noradrenaline ratio. The peak reduction (52%) in plasma concentration of noradrenaline and the peak increase (646%) in plasma concentration of dopamine were observed on day-6 and day-7 of dosing, respectively.
- The findings of this study suggest that nepicastat is a potent, selective and orally active inhibitor of dopamine-β-hydroxylase which produces gradual modulation of the sympathetic nervous system by inhibiting the biosynthesis of noradrenaline. This drug may, therefore, be of value in the treatment of cardiovascular disorders associated with over-activation of the sympathetic nervous system, such as congestive heart failure.
66.
Boddy Alexander W. Snikeris Fred C. Kringle Robert O. Wei Greg C. G. Oppermann James A. Midha K. K. 《Pharmaceutical research》1995,12(12):1865-1868
Purpose. Highly variable drugs pose a problem in bioequivalence assessment because they often fail to meet current regulatory acceptance criteria for average bioequivalence (80–125%). This paper examines alternative approaches to establishing bioequivalence.
Methods. Suggested solutions have included alternate study designs, e.g., replicate and multiple dose studies, reducing the level of the confidence interval, and widening the acceptance limits. We focus on the latter approach.
Results. A rationale is presented for defining wider acceptance limits for highly variable drugs. Two previously described methods are evaluated, and a new method having more desirable properties is proposed.
Conclusions. We challenge the one size fits all current definition of bioequivalence acceptance limits for highly variable drugs, proposing alternative limits or goal posts which vary in accordance with the intrasubject variability of the reference product. 相似文献
67.
Kieffer EC Mor JM Alexander GR 《Asian American and Pacific Islander journal of health》1996,4(4):343-351
PURPOSE OF THE PAPER: This study provides baseline information on the characteristics of Native Hawaiian mothers and the health status of their infants, comparing residents of Hawaii with those of the continental U.S. The impact of Hawaii residence on low birth weight and infant mortality among Native Hawaiians is assessed. SUMMARY OF METHODS UTILIZED: Data from the National Center for Health Statistics 19831987 Linked U.S. Live Birth and Infant Death file were used to examine parental characteristics, prenatal care use and infant outcomes using chisquare and logistic regression procedures. PRINCIPAL FINDINGS: Despite a higher sociodemographic risk profile among Hawaii resident mothers, preterm birth, low and very low birth weight percentages were similar. Continental infants had significantly highter percentages of very preterm birth and macrosomia. Mortality rates in both the neonatal and postneonatal periods, and for SIDS and perinatal causes were elevated among continental infants. Hawaii residence had a borderline protective effect on infant mortality, wehn sociodemographic and prenatal care differences were controlled. CONCLUSIONS: This study suggests a possibly protective effect of Hawaii residence on the health of Native Hawaiian infants during the period of following employermandated health insurance coverage but before the initiation of "gapgroup" coverage and the Native Hawaiian Health Care Systems in Hawaii. RELEVANCE TO ASIAN PACIFIC ISLANDER AMERICAN POPULATIONS. This is the first report documenting the sociodemographic and health status of the growing number of Native Hawaiian mothers and their infants residing outside of Hawaii. Expanded health insurance coverage and culturally appropriate and accessible health care may contribute to improved infant health status in Hawaii. Their absence, along with possible barriers of sociocultural isolation, may account for the poorer than expected outcomes of continental infants and predict a widening gap between them and their counterparts in Hawaii. A followup study of the health status of Native Hawaiian mothers and infants, and their access to appropriate care in Hawaii and thei continental U.S. is recommended. 相似文献
68.
Joseph G Rajendran David A Mankoff Finbarr O'Sullivan Lanell M Peterson David L Schwartz Ernest U Conrad Alexander M Spence Mark Muzi D Greg Farwell Kenneth A Krohn 《Clinical cancer research》2004,10(7):2245-2252
PURPOSE: The aim of this study is to compare glucose metabolism and hypoxia in four different tumor types using positron emission tomography (PET). (18)F-labeled fluorodeoxyglucose (FDG) evaluates energy metabolism, whereas the uptake of (18)F-labeled fluoromisonidazole (FMISO) is proportional to tissue hypoxia. Although acute hypoxia results in accelerated glycolysis, cellular metabolism is slowed in chronic hypoxia, prompting us to look for discordance between FMISO and FDG uptake. EXPERIMENTAL DESIGN: Forty-nine patients (26 with head and neck cancer, 11 with soft tissue sarcoma, 7 with breast cancer, and 5 with glioblastoma multiforme) who had both FMISO and FDG PET scans as part of research protocols through February 2003 were included in this study. The maximum standardized uptake value was used to depict FDG uptake, and hypoxic volume and maximum tissue:blood ratio were used to quantify hypoxia. Pixel-by-pixel correlation of radiotracer uptake was performed on coregistered images for each corresponding tumor plane. RESULTS: Hypoxia was detected in all four patient groups. The mean correlation coefficients between FMISO and FDG uptake were 0.62 for head and neck cancer, 0.47 for breast cancer, 0.38 for glioblastoma multiforme, and 0.32 for soft tissue sarcoma. The correlation between the overall tumor maximum standardized uptake value for FDG and hypoxic volume was small (Spearman r = 0.24), with highly significant differences among the different tumor types (P < 0.005). CONCLUSIONS: Hypoxia is a general factor affecting glucose metabolism; however, some hypoxic tumors can have modest glucose metabolism, whereas some highly metabolic tumors are not hypoxic, showing discordance in tracer uptake that can be tumor type specific. 相似文献
69.
Cell-free 59 kDa immunoreactive integrin-linked kinase: a novel marker for ovarian carcinoma. 总被引:9,自引:0,他引:9
PURPOSE: We reported that the expression of integrin-linked kinase (ILK) is up-regulated in ovarian carcinomas and that ovarian cancer cells have high expression of ILK. In this study, we have examined the expression of cell-free 59 kDa immunoreactive (ir)ILK in the serum and peritoneal fluid (PTF) of patients with ovarian cancer and evaluated its potential as a serum biomarker for early-stage screening and for monitoring clinical status of patients after chemotherapy treatment. EXPERIMENTAL DESIGN: Thirty-six serum specimens, including normal (n = 6), benign (n = 6), borderline (n = 4), grade 1 (n = 5), grade 2 (n = 5), and grade 3 (n = 10), were evaluated for the expression of irILK by Western blotting. The expression of irILK was evaluated in PTF (n = 10) and peritoneal washings from women with benign ovarian cysts (n = 4). In addition, tissue-conditioned medium obtained from the cultures of primary ovarian tumors (n = 9) was examined for the presence of irILK. Finally, the potential of serum irILK as a biomarker for ovarian cancer screening was evaluated by comparison with cancer antigen 125 (CA 125) concentrations in cancer patients before and after chemotherapy. RESULTS: irILK expression was present in normal serum and in serum of patients with benign ovarian tumors. irILK expression was 6-9-fold higher in the serum of patients with grade 1, grade 2, and grade 3 ovarian cancer than in the serum of healthy volunteers and patients with benign ovarian tumors (P < 0.01). Enhanced expression of irILK in the serum of ovarian cancer patients correlated with the concentration of CA 125. High expression of irILK was present in all 10 PTF tested. Tissue-conditioned medium prepared from malignant ovarian tumors had 4-fold more irILK expression than conditioned medium obtained from borderline and benign tumors (P < 0.01). irILK expression in serum of cancer patients was reduced to basal normal levels after six cycles of Taxol/carboplatin and was consistent with the change of CA 125 levels before and after chemotherapy. CONCLUSIONS: These data suggest that irILK is an ovarian tumor-associated antigen and implicates its potential not only as a biomarker for early-stage screening but also as a marker for monitoring the clinical condition of patients after treatment. 相似文献
70.
A treatment portal or simulator image has traditionally been used to demonstrate the lung and heart coverage of the breast tangential portal. In many cases, these images were acquired as a planning session on the linear accelerator. The patients were also CT scanned to assess the lung/heart volume and to determine the surgical site depth for the electron‐boost energy. A study using 50 consecutive patients was performed comparing the digitally reconstructed radiograph (DRR) from the virtual simulation with treatment portal images. Modification to the patient's arm position is required when performing the planning CT scans due to the aperture size of the CT scanner. Virtual simulation was used to assess the potential variation of lung and heart measurements. The average difference in lung volume between the DRR and portal image was less than 2 mm, with a range of 0?5 mm. Arm position did not have a significant impact on field deviation; however, great care was taken to minimize any changes in arm position. The modification of the arm position for CT scanning did not lead to significant variations between the DRRs and portal images. The Advantage Sim software has proven capable of producing good quality DRR images, providing a realistic representation of the lung and heart volume included in the treatment portal. 相似文献