8 results on '"Hilliard DA"'
Search Results
2. Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study
- Author
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Elovitz Michal A, Gomez Ricardo, Kusanovic Juan P, Srinivas Sindhu, York Timothy P, Hilliard DaShaunda D, Hill Lori D, Romero Roberto, and Strauss Jerome F
- Subjects
Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. This complex disorder is characterized by alterations in the immune and vascular systems and involves multiple organs. There is strong evidence for a genetic contribution to preeclampsia. Two different single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene were recently reported to be associated with increased risk for preeclampsia in two different populations. ERAP2 is expressed in placental tissue and it is involved in immune responses, inflammation, and blood pressure regulation; making it is an attractive preeclampsia candidate gene. Furthermore, ERAP2 expression is altered in first trimester placentas of women destined to develop preeclampsia. Methods A case-control design was used to test for associations between two SNPs in ERAP2, rs2549782 and rs17408150, and preeclampsia status in 1103 Chilean maternal-fetal dyads and 1637 unpaired African American samples (836 maternal, 837 fetal). Results We found that the fetal minor allele (G) of rs2549782 was associated with an increased risk for preeclampsia in the African American population (P = 0.009), but not in the Chilean population. We found no association between rs17408150 and risk for preeclampsia in the Chilean population. Association between rs17408150 and risk for preeclampsia was not tested in the African American population due to the absence of the minor allele in this population. Conclusions We report an association between fetal ERAP2 and preeclampsia in an African American population. In conjunction with previous studies, which have found maternal associations with this gene in an Australian/New Zealand population and a Norwegian population, ERAP2 has now been associated with preeclampsia in three populations. This provides strong evidence that ERAP2 plays a role in the development of preeclampsia.
- Published
- 2011
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3. Comparative inhibitory activity of etoricoxib, celecoxib, and diclofenac on COX-2 versus COX-1 in healthy subjects.
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Schwartz JI, Dallob AL, Larson PJ, Laterza OF, Miller J, Royalty J, Snyder KM, Chappell DL, Hilliard DA, Flynn ME, Cavanaugh PF Jr, and Wagner JA
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- Adult, Aged, Celecoxib, Cross-Over Studies, Cyclooxygenase 1 metabolism, Cyclooxygenase 2 metabolism, Diclofenac pharmacology, Dinoprostone metabolism, Double-Blind Method, Etoricoxib, Female, Humans, Male, Middle Aged, Pyrazoles pharmacology, Pyridines pharmacology, Sulfonamides pharmacology, Sulfones pharmacology, Thromboxane B2 metabolism, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Cyclooxygenase 1 drug effects, Cyclooxygenase 2 drug effects, Cyclooxygenase Inhibitors pharmacology
- Abstract
We determined cyclo-oxygenase-1 and cyclo-oxygenase-2 inhibition in healthy middle-aged subjects (41-65 years) randomly assigned to four 7-day treatment sequences of etoricoxib 90 mg every day, celecoxib 200 mg twice a day, diclofenac 75 mg twice a day, or placebo in a double-blind, randomized, 4-period crossover study. Maximum inhibition of thromboxane B(2) (cyclo-oxygenase-1 activity) in clotting whole blood on day 7 (0-24 hours postdose) was the primary endpoint. Inhibition of lipopolysaccharide-induced prostaglandin E(2) in whole blood (cyclo-oxygenase-2 activity) was assessed on day 7 (0-24 hours postdose) as a secondary endpoint. Diclofenac had significantly greater maximum inhibition of thromboxane B(2) versus each comparator (P < .001); placebo 2.4% (95% confidence interval: -8.7% to 12.3%), diclofenac 92.2% (91.4% to 92.9%), etoricoxib 15.5% (6.6% to 23.5%), and celecoxib 20.2% (11.5% to 28.1%). Prostaglandin E(2) synthesis was inhibited with a rank order of potency of diclofenac > etoricoxib > celecoxib. In summary, at doses commonly used in rheumatoid arthritis, diclofenac significantly inhibits both cyclo-oxygenase-1 and cyclo-oxygenase-2, whereas etoricoxib and celecoxib significantly inhibit cyclo-oxygenase-2 and do not substantially inhibit cyclo-oxygenase-1.
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- 2008
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4. Effects of etoricoxib and comparator nonsteroidal anti-inflammatory drugs on urinary sodium excretion, blood pressure, and other renal function indicators in elderly subjects consuming a controlled sodium diet.
- Author
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Schwartz JI, Thach C, Lasseter KC, Miller J, Hreniuk D, Hilliard DA, Snyder KM, Gertz BJ, and Gottesdiener KM
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- 6-Ketoprostaglandin F1 alpha analogs & derivatives, 6-Ketoprostaglandin F1 alpha urine, Administration, Oral, Aged, Aged, 80 and over, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Body Weight drug effects, Celecoxib, Constipation chemically induced, Creatinine blood, Creatinine urine, Diarrhea chemically induced, Dose-Response Relationship, Drug, Double-Blind Method, Electrolytes blood, Etoricoxib, Female, Headache chemically induced, Humans, Male, Middle Aged, Naproxen administration & dosage, Naproxen adverse effects, Naproxen pharmacology, Potassium urine, Prostaglandins urine, Pyrazoles administration & dosage, Pyrazoles adverse effects, Pyrazoles pharmacology, Pyridines administration & dosage, Pyridines adverse effects, Sulfonamides administration & dosage, Sulfonamides adverse effects, Sulfonamides pharmacology, Sulfones administration & dosage, Sulfones adverse effects, Thromboxane B2 analogs & derivatives, Thromboxane B2 urine, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Blood Pressure drug effects, Pyridines pharmacology, Sodium urine, Sulfones pharmacology
- Abstract
This multicenter, double-blind, randomized, placebo-controlled, parallel-group study assessed renal function during dosing with etoricoxib 90 mg daily, celecoxib 200 mg twice daily, and naproxen 500 mg twice daily. Male and female subjects 60 to 81 years old (n = 85), in sodium balance on a controlled, normal sodium diet, were treated for 15 days. There were no clinically meaningful between-treatment differences in urinary sodium excretion, creatinine clearance, body weight, or serum electrolytes during the 2 weeks of treatment. Etoricoxib and celecoxib had no effect on the urinary thromboxane metabolite, 11-dehydrothromboxane B(2), while significantly decreasing the urinary prostacyclin metabolite, 2,3-dinor-6-keto PGF(1alpha). Decreases were greater for both metabolites following naproxen. Ambulatory systolic blood pressures were significantly higher than placebo for all treatments, with moderately greater increases for etoricoxib relative to other active treatments on day 14. Ambulatory diastolic blood pressures were significantly higher than placebo for etoricoxib and naproxen but not for celecoxib.
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- 2007
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5. A high-precision fluorogenic cholesteryl ester transfer protein assay compatible with animal serum and 3456-well assay technology.
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Eveland SS, Milot DP, Guo Q, Chen Y, Hyland SA, Peterson LB, Jezequel-Sur S, O'Donnell GT, Zuck PD, Ferrer M, Strulovici B, Wagner JA, Tanaka WK, Hilliard DA, Laterza O, Wright SD, Sparrow CP, and Anderson MS
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- Animals, CHO Cells, Cholesterol Ester Transfer Proteins metabolism, Cholesterol Esters metabolism, Cricetinae, Cricetulus, Fluorescence Resonance Energy Transfer, Humans, Models, Biological, Time Factors, Transfection, Biological Assay methods, Cholesterol Ester Transfer Proteins blood, Fluorescent Dyes chemistry, Spectrometry, Fluorescence methods
- Abstract
Cholesteryl ester transfer protein (CETP) is a serum component responsible for both cholesteryl ester and triglyceride trafficking between high-density lipoprotein (HDL) and the apolipoprotein B (apoB)-containing very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL). Several fluorescence-based assays that monitor these transfers have been reported, but to date such assays have suffered from a low signal/background (S/B) ratio and have been described for use only in relatively purified in vitro systems. We have modified the more advanced of these assays to incorporate a noninterfering, nondiffusable fluorescence quencher into previously described cosonicate particles, often referred to as microemulsions. This simple improvement resulted in particles that had an average threefold enhanced S/B window over particles without quenchers but that continued to show the essential properties of a catalytic assay, including catalysis to a single endpoint, excellent linearity with protein and particle concentration, and an appropriate sensitivity to inhibition. This reduced assay noise allowed the subsequent development of protocols for the direct measure of cholesteryl ester (CE) transfer activity resident in human and animal serum as well as the development of 384- and 3456-well screening protocols with good precision and accuracy. Thus, by expanding the dynamic response window of the assay, we have created an assay generalizable to many settings.
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- 2007
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6. Tamoxifen response following no response to orchiectomy in metastatic male breast cancer: a case report.
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Hilliard DA, Wilbur DW, and Camacho ES
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- Breast Neoplasms drug therapy, Carcinoma, Intraductal, Noninfiltrating drug therapy, Carcinoma, Intraductal, Noninfiltrating secondary, Carcinoma, Intraductal, Noninfiltrating therapy, Humans, Male, Middle Aged, Neoplasms, Hormone-Dependent drug therapy, Breast Neoplasms therapy, Castration, Tamoxifen therapeutic use
- Abstract
A male patient with advanced breast cancer had no response to orchiectomy but subsequently enjoyed a 17-month partial response to tamoxifen 10 mg B.I.D. His tumor estrogen receptor (ER) protein was 555 fmol protein/ml cytosol. The potential role of ER determinations in the selection of therapy for advanced male breast cancer is discussed.
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- 1984
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7. Randomized trial of the addition of cis-platin (DDP) and/or BCG to cyclophosphamide (CTX) chemotherapy for ovarian carcinoma.
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Wilbur DW, Rentschler RE, Wagner RJ, Keeney ED, King A, and Hilliard DA
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- Antineoplastic Combined Chemotherapy Protocols adverse effects, BCG Vaccine administration & dosage, Cisplatin administration & dosage, Clinical Trials as Topic, Cyclophosphamide administration & dosage, Drug Administration Schedule, Female, Humans, Laparotomy, Middle Aged, Ovarian Neoplasms pathology, Ovarian Neoplasms therapy, Prognosis, Prospective Studies, Random Allocation, Statistics as Topic, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Ovarian Neoplasms drug therapy
- Abstract
A prospective randomized trial has compared cyclophosphamide (CTX) with CTX plus cis-diamminodichloroplatinum (DDP) as the initial chemotherapy for advanced ovarian carcinoma. A secondary randomization compared the addition of BCG treatment to either chemotherapy. The addition of DDP had no measurable impact on survival, but a small survival trend favoring BCG-treated patients was noted (P less than 0.08). Toxicity from BCG treatment was insignificant, but the addition of DDP increased both early nausea and vomiting and later hematologic toxicity. There were three long-term complete remission patients, and these all came from the group of six patients with pretreatment residual disease less than 2 cm. A univariate analysis of pretreatment prognostic factors indicated significantly better prognosis (P less than 0.02) for patients with no palpable tumor, platelet count less than 400,000/mm3, residual tumor less than 2 cm, resting pulse less than 91/min. and LDH less than 250 U/L. The authors conclude that for patients with large (greater than 2 cm) residual disease, there is no compelling evidence that initial combination therapy is superior to aggressive single alkylating agent treatment.
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- 1987
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8. Adjuvant methotrexate escalated to toxicity for resectable stage III and IV squamous head and neck carcinomas--a prospective, randomized study.
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Rentschler RE, Wilbur DW, Petti GH, Chonkich GD, Hilliard DA, Camacho ES, and Thorpe RB
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- Adult, Aged, Carcinoma, Squamous Cell mortality, Combined Modality Therapy, Head and Neck Neoplasms mortality, Humans, Methotrexate toxicity, Middle Aged, Postoperative Care, Prospective Studies, Random Allocation, Carcinoma, Squamous Cell drug therapy, Head and Neck Neoplasms drug therapy, Methotrexate therapeutic use
- Abstract
To determine if adjuvant methotrexate (MTX), escalated weekly to toxicity, could improve disease-free survival (DFS) and overall survival by preventing recurrent disease, 60 patients with potentially resectable stage III or IV squamous head and neck carcinomas were stratified by primary site, stage, and nutritional status, then randomized by pairs to receive or not receive adjuvant MTX. All received standard surgery and postoperative radiation therapy. Five patients were taken off study because of unresectability at the time of surgery, leaving 55 evaluable patients. There were no statistically significant imbalances in known prognostic factors between the two treatment arms. MTX was begun at 40 mg/m2 and escalated 10 mg/m2 weekly (four doses preoperatively; four doses postoperatively, preradiation therapy; eight doses postradiation therapy) to mucosal or hematologic toxicity. The median peak MTX dose achieved was 80 mg/m2. Although three patients were hospitalized with MTX toxicity, none died of MTX toxicity. No patient receiving MTX had disease progression during treatment, and there was no increase in postoperative complications. Thirty-two patients died (median survival, 19 months); 23 patients are alive with median follow-up of 43 months. There was no statistically significant difference in actuarial DFS (P = 1.0) or overall survival (P = .61). Although patients on the MTX arm appeared to have less local and regional recurrences at first recurrence (thus more distant metastases), this did not reach statistical significance (P = .06). There was no significant difference between the sites of recurrence at death or last follow-up (P = .38).
- Published
- 1987
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