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Biomedical subjects

Elizabeth Sullivan

Publications and source records attributed to Elizabeth Sullivan.

11 recordsLinked to original sources

Hypertension produced by reductions in uterine perfusion in the pregnant rat: role of interleukin 6.

The purpose of this study was to determine the role of interleukin (IL) 6 in mediating the increase in arterial pressure (AP) in response to chronic reductions in uterine perfusion pressure (RUPP) in pregnant rats. AP was higher in RUPP rats (138+/-1 mm Hg) than in normal pregnant (NP) rats (104+/-1 mm Hg). Serum IL-6 levels in the RUPP rats were 104.5+/-28.6 pg/mL as compared with 36.6+/-7.4 pg/mL in NP rats. To determine the long-term effects of a 2- to 3-fold elevation in plasma IL-6 on renal function and AP in pregnant rats, we infused IL-6 for 5 days (2.5 ng/day) in NP rats starting at day 14 of gestation. Five days later, serum IL-6 levels were 55.5+/-6.5 pg/mL in the control NP rats and 157.0+/-36.1 pg/mL in the IL-6-treated NP rats. AP was higher in the IL-6-treated NP rats (115+/-3 mm Hg) as compared with NP controls (101+/-1 mm Hg) at day 19 of gestation. Renal plasma flow and GFR were lower in the IL-6-treated NP rats than in the NP group. IL-6 increased plasma renin activity but did not affect endothelin in IL-6-treated NP rats. In contrast to the NP rats, IL-6 had no effect on AP or renal hemodynamics in virgin rats. In summary, these data indicate that plasma IL-6 is elevated in response to chronic reductions in uterine perfusion in pregnant rats and that a comparable elevation in plasma IL-6 increases AP and reduces renal function in pregnant rats.

Animals↗

The ICMART glossary on ART terminology.

The International Committee Monitoring Assisted Reproductive Technologies (ICMART) is an independent, international non-profit organization that has taken a leading role in the development, collection and dissemination of worldwide data on ART. Information on availability, efficacy and safety is provided to health professionals, health authorities and the public. The glossary facilitates dissemination of ART data through a set of agreed definitions as seen in the most recent World Report on ART. It provides a conceptual framework for further international terminology and data development of ART.

Journal Article↗

The International Committee Monitoring Assisted Reproductive Technologies (ICMART) glossary on ART terminology.

The International Committee Monitoring Assisted Reproductive Technologies (ICMART) is an independent international nonprofit organization that has taken a leading role in the development, collection, and dissemination of worldwide data on assisted reproductive technology (ART). Information on availability, efficacy, and safety is provided to health professionals, health authorities, and the public. The glossary facilitates dissemination of ART data through a set of agreed-upon definitions, as seen in the most recent World Report on ART. It provides a conceptual framework for further international terminology and data development of ART.

Databases, Factual↗

Chemokine receptor CXCR3 desensitization by IL-16/CD4 signaling is dependent on CCR5 and intact membrane cholesterol.

Previous work has shown that IL-16/CD4 induces desensitization of both CCR5- and CXCR4-induced migration, with no apparent effect on CCR2b or CCR3. To investigate the functional relationship between CD4 and other chemokine receptors, we determined the effects of IL-16 interaction with CD4 on CXCR3-induced migration. In this study we demonstrate that IL-16/CD4 induced receptor desensitization of CXCR3 on primary human T cells. IL-16/CD4 stimulation does not result in surface modulation of CXCR3 or changes in CXCL10 binding affinity. This effect does require p56(lck) enzymatic activity and the presence of CCR5, because desensitization is not transmitted in the absence of CCR5. Treatment of human T cells with methyl-beta-cyclodextrin, a cholesterol chelator, prevented the desensitization of CXCR3 via IL-16/CD4, which was restored after reloading of cholesterol, indicating a requirement for intact cholesterol. These studies demonstrate an intimate functional relationship among CD4, CCR5, and CXCR3, in which CCR5 can act as an adaptor molecule for CD4 signaling. This process of regulating Th1 cell chemoattraction may represent a mechanism for orchestrating cell recruitment in Th1-mediated diseases.

Animals↗

World collaborative report on in vitro fertilization, 2000.

The International Committee for Monitoring Assisted Reproductive Technology's 7th World Report for the year 2000 analyzes wide variations in live and multiple birth rates from 49 countries and six regions by type of assisted reproductive technology, age, number of embryos transferred, and multiple births. More than 460,157 procedures resulted in delivery rate per aspiration for conventional in vitro fertilization (IVF) of 18.6%; for intracytoplasmic sperm injection (ICSI), 20.4%; for egg donation, 32.3% per transfer; and for frozen ET, 12.0% per transfer. Conventional IVF and ICSI twin rates were 26.9% and 26.2%, respectively, and triplet rates were 2.8% and 2.9%, respectively, for an estimated total of approximately 197,000 to 220,000 babies worldwide.

Adult↗

An evaluation of a patient-reported outcomes found computerized adaptive testing was efficient in assessing osteoarthritis impact.

BACKGROUND AND OBJECTIVES: Evaluate a patient-reported outcomes questionnaire that uses computerized adaptive testing (CAT) to measure the impact of osteoarthritis (OA) on functioning and well-being. MATERIALS AND METHODS: OA patients completed 37 questions about the impact of OA on physical, social and role functioning, emotional well-being, and vitality. Questionnaire responses were calibrated and scored using item response theory, and two scores were estimated: a Total-OA score based on patients' responses to all 37 questions, and a simulated CAT-OA score where the computer selected and scored the five most informative questions for each patient. Agreement between Total-OA and CAT-OA scores was assessed using correlations. Discriminant validity of Total-OA and CAT-OA scores was assessed with analysis of variance. Criterion measures included OA pain and severity, patient global assessment, and missed work days. RESULTS: Simulated CAT-OA and Total-OA scores correlated highly (r = 0.96). Both Total-OA and simulated CAT-OA scores discriminated significantly between patients differing on the criterion measures. F-statistics across criterion measures ranged from 39.0 (P < .001) to 225.1 (P < .001) for the Total-OA score, and from 40.5 (P < .001) to 221.5 (P < .001) for the simulated CAT-OA score. CONCLUSIONS: CAT methods produce valid and precise estimates of the impact of OA on functioning and well-being with significant reduction in response burden.

Adaptation, Psychological↗

Does size matter? A population-based study of birth in lower volume maternity hospitals for low risk women.

OBJECTIVE: To study the association between volume of hospital births per annum and birth outcome for low risk women. DESIGN: Population-based study using the National Perinatal Data Collection (NPDC). SETTING: Australia. PARTICIPANTS: Of 750,491 women who gave birth during 1999-2001, there were 331,147 (47.14%) medically 'low risk' including 132,696 (40.07%) primiparae and 198,451 (59.93%) multiparae. METHODS: The frequency of each birth and infant outcome was described according to the size of the hospital where birth took place. We investigated whether unit size (defined by volume) was an independent risk factor for each outcome factor using public hospitals with greater than 2000 births per annum as a reference point. MAIN OUTCOME MEASURES: Rates of intervention at birth and neonatal mortality for low risk women in relation to hospitals with <100, 100-500, 501-1000, 1001-2000 and >2001 births per annum. RESULTS: Neonatal death was less likely in hospitals with less than 2000 births per annum regardless of parity. For multiparous low risk women in hospitals of 100 and 500 births per annum compared with hospitals of >2000 births per annum the adjusted odds of neonatal mortality [adjusted odds ratio (AOR) 0.36; 99% confidence interval (CI) 0.14-0.93]. For low risk primiparous women in hospitals with less than 100 births per annum, there were lower rates of induction of labour (AOR 0.62; 99% CI 0.54-0.73); intrathecal analgesia/anaesthesia (AOR 0.34; 99% CI 0.28-0.42); instrumental birth (AOR 0.80; 99% CI 0.69-0.93); caesarean section after labour (AOR 0.59; 99% CI 0.49-0.72) and admission to a neonatal unit (AOR 0.15; 99% CI 0.10-0.22) and for low risk multiparous women in hospitals with less than 100 births per annum: induction (AOR 0.69; 99% CI 0.62-0.76); intrathecal analgesia/anaesthesia (AOR 0.32; 99% CI 0.29-0.36); instrumental birth (AOR 0.52; 99% CI 0.41-0.67); caesarean section after labour (AOR 0.41; 99% CI 0.33-0.52); and admission to a neonatal unit (AOR 0.09; 99% CI 0.07-0.12). CONCLUSIONS: In Australia, lower hospital volume is not associated with adverse outcomes for low risk women.

Adult↗

Role of endothelin in mediating tumor necrosis factor-induced hypertension in pregnant rats.

Hypertension during preeclampsia is associated with an increase in plasma levels of tumor necrosis factor (TNF)-alpha, a cytokine known to contribute to endothelial dysfunction. Recently, our laboratory reported that a 2-fold increase in plasma TNF-alpha produces hypertension in pregnant rats. Endothelin is also elevated in preeclampsia and endothelin synthesis is enhanced by TNF-alpha. The purpose of this study was to determine the role of endothlelin in mediating TNF-alpha-induced hypertension in pregnant rats. To achieve this goal, TNF-alpha (50 ng/d for 5 days) was infused into control pregnant rats and pregnant rats treated with an endothelin receptor A antagonist, ABT 627 (5 mg/kg per day for 5 days). At day 19 of gestation, arterial pressure was measured and aorta, kidneys, and placentas were harvested. Infusion of TNF-alpha into pregnant rats increased plasma concentration of TNF-alpha (13.5+/-0.8 to 28.0+/-3.7 pg/mL) and arterial pressure (101+/-2 to 122+/-1 mm Hg). The increase in arterial pressure was associated with an increase in preproendothelin mRNA expression in placenta, aorta, and kidneys measured by real-time polymerase chain reaction (PCR). Pretreatment with the endothelin receptor A antagonist completely abolished the blood pressure response to TNF-alpha in pregnant rats (105+/-1 versus 97+/-2 mm Hg). In sharp contrast, the ETA receptor antagonist had no effect on arterial pressure in normal pregnant rats (97+/-2 versus 101+/-2 mm Hg). Moreover, chronic infusion of TNF-alpha had no significant effect on arterial pressure or renal preproendothelin levels in virgin rats. These results suggest an important role for endothelin in mediating TNF-alpha-induced hypertension in pregnant rats.

Animals↗

Caspofungin versus amphotericin B for candidemia: a pharmacoeconomic analysis.

BACKGROUND: In a randomized, comparative, clinical trial, caspofungin was found to be as effective as amphotericin B deoxycholate (ampho B) for treating candidemia (favorable outcomes in 71.7% and 62.8% of patients, respectively) and exhibited a generally better safety profile, particularly with respect to impaired renal function (IRF) (P = 0.02). OBJECTIVE: The goal of this study was to examine whether cost savings generated from the reduced rates of IRF observed in the clinical trial would be enough to offset the higher acquisition cost of caspofungin relative to ampho B. METHODS: We developed an economic model in which 100 hypothetical patients with candidemia were treated with caspofungin or ampho B. Rates of IRF and duration of drug therapy were taken from the clinical trial. Information on the cost of treating IRF was obtained through a search of MEDLINE using the terms amphotericin and cost, amphotericin and resource, amphotericin and hospital, and amphotericin and toxicity; and the medical subject headings kidney failure, acute/drug therapy; kidney failure, acute/epidemiology; kidney failure, acute/etiology; kidney/drug effects; cost of illness; costs and cost analysis; kidney failure, acute, and economics; and kidney failure, acute/economics. In addition, the Web site was searched for relevant references, and the Merck publication alert system was used. Antifungal drug costs were estimated using data from IMS Health. Costs were reported in year-2003 US dollars. RESULTS: In the base case, the model projected that using caspofungin instead of ampho B would result in substantially lower treatment costs for IRF, which would more than offset the higher drug acquisition cost (cost-offset percentage, 122%), leading to a net mean savings of 758.60 US dollars per patient. These results were not very sensitive to the difference in daily drug cost, but were sensitive to the mean cost attributable to treating IRF. As that varied, the cost-offset percentage varied from 61% (substantial cost offset) to 183% (cost savings). CONCLUSIONS: The results of this economic model suggest that, based only on differences in drug acquisition cost and renal toxicity, the use of caspofungin instead of ampho B in patients with candidemia may be a cost-saving strategy from the perspective of a hospital.

Amphotericin B↗

Does initial choice of antimicrobial therapy affect length of stay for patients with complicated intra-abdominal infections?

Outcomes for complicated intra-abdominal infection are influenced by operation for source control, patient-related factors, and medical management, including antibiotic treatment. We analyzed length of stay (LOS) at 33 hospitals for 2,150 patients discharged between February 2002 and June 2003, who were > 18 years, had intra-abdominal infection, and received one of 6 first-line antimicrobials. A regression tree analysis selected important variables, their interactions, and their order of significance in explaining LOS. A linear mixed model evaluated the difference in LOS between treatment groups. Adjusted LOS was calculated by the least squares means from the model and was used to assess treatment differences. Mean LOS analyzed by initial antimicrobial therapy and stratified by diagnosis showed LOS for ampicillin/sulbactam and ertapenem to be significantly shorter from levofloxacin, ceftriaxone, and piperacillin/tazobactam (all P < 0.05). Adjusting for all other factors, the variables associated with severity (e.g., diagnosis, ICU stay, and comorbidities) had the greatest impact on adjusted LOS (all P < 0.001). Our findings indicate ampicillin/sulbactam and ertapenem were associated with shorter hospital stays, which may be explained by unaccounted for underlying severity of infection and/or by surgeons stratifying antimicrobial selection according to severity of illness.

Abdominal Cavity↗

Matrix metalloproteinases in the aneurysm wall of patients treated with low-dose doxycycline.

The purpose of this study was to determine the effect of low-dose doxycycline on matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP)-1 expression in the wall of abdominal aortic aneurysms. A double-blind, randomized study was conducted of patients treated with doxycycline (100 mg/d orally) or placebo for 1 month prior to surgery. MMP-2, -3, and -9 (zymogen and activity); MMP-1, -2, -3, -7, -9, -11, -12, and -14; and TIMP-1 (messenger ribonucleic acid [mRNA]) were measured in the aneurysm wall. No differences were found between the treatment and placebo groups in zymogen levels of MMP-2, -3, or -9 or in the free or total activities of MMP-2 and -9. Treatment with doxycycline also had no effect on the concentration of any mRNA measured. No relationship was found between the number of tablets taken and MMP or TIMP protein, mRNA, or activity levels in the aneurysm wall. Low-dose doxycycline treatment does not alter the expression or activity of metalloproteinases or their inhibitor, TIMP-1, in the aneurysm wall.

Administration, Oral↗