Biomedical subjects

B Gillespie

Publications and source records attributed to B Gillespie.

At least 19 recordsLinked to original sources

PubMed2006

Effect of renal function on the pharmacokinetics of palifermin.

Palifermin (deltaN23KGF) decreases the incidence, severity, and duration of oral mucositis. The objectives of this open-label study were to evaluate the pharmacokinetics of single-dose palifermin in subjects with varying degrees of renal function. A single 90-mcg/kg intravenous dose of palifermin was administered to 31 subjects with varying levels of renal function (normal to requiring hemodialysis). Pharmacokinetic analyses were conducted using serum palifermin concentrations. There was considerable overlap in mean palifermin serum clearance among the groups, ranging from 318 to 495 mL/h/kg, indicating that the level of renal function did not affect clearance in humans; thus, no dose adjustment of palifermin is indicated for patients with renal dysfunction.

Adult↗

PubMed2001

Urinary tract infection among women aged 40 to 65: behavioral and sexual risk factors.

We conducted a case-control study to explore the role of health behavior and sexual and medical history on urinary tract infection (UTI) risk among otherwise healthy women aged 40-65. Cases and controls were recruited from nine practices and clinics in Michigan and a single clinic in Israel. In both countries, several factors were reported significantly more frequently among UTI cases than controls: a previous UTI within 12 months, incontinence symptoms, a recent episode of 30-plus minutes of cold hands, feet, back or buttocks, and recent antibiotic use. Cases were less likely than controls to report recent estrogen use, but the results were only statistically significant in Michigan. Sexual activity during the previous 2 weeks and having ceased menses were modestly, but not statistically significantly, protective at both study sites. Risk factors for UTI among women 40-65 differ from those for younger women and these differences cannot be attributed solely to changes in menopausal status.

Adult↗

PubMed2001

Oxygen desaturation on the six-minute walk test and mortality in untreated primary pulmonary hypertension.

There are no reliable predictors of mortality in primary pulmonary hypertension (PPH). This study assessed whether exercise oxygen desaturation and distance achieved during a six-minute walk are associated with mortality in moderately symptomatic patients with PPH. Thirty-four patients with PPH underwent a pretreatment six-minute walk test, and an invasive haemodynamic assessment of pulmonary vasodilator reserve, to select the best treatment option (epoprostenol in 27 and nifedipine in 7). Median follow-up was 26 months (12 months for the nonsurvivors was 26%), and median survival, >46 months by Kaplan-Maier estimate. The mean+/-SD distance walked was 275+/-155 m and reduction in arterial oxygen saturation (Sa,O2) at maximal distance (deltaSa,O2) was 8.4+/-4.5%). A distance < or =300 m increased mortality risk by 2.4, and a deltaSa,O2 of > or = 10% increased mortality risk by 2.9. Only Sa,O2 at peak distance, deltaSa,O2 and pulmonary vascular resistance (PVR) were related to mortality. After adjusting for PVR, there remained a 27% increase in risk of death for each per cent decrease in Sa,O2. The six-minute walk distance and exercise oxygen saturation may be helpful in selecting patients with primary pulmonary hypertension for whom transplant listing is appropriate.

Adult↗

PubMed2000

Nonglassy kinetics in the folding of a simple single-domain protein.

Theory suggests that the otherwise rapid folding of simple heteropolymer models becomes "glassy"-dominated by multiple kinetically trapped misfolded states-at low temperatures or when the overall bias toward the native state is reduced relative to the depth of local minima. Experimental observations of nonsingle-exponential protein-folding kinetics have been taken as evidence that the protein-folding free energy landscape is similarly rough. No equivalent analysis, however, has been reported for a simple single-domain protein lacking prolines, disulfide bonds, prosthetic groups, or other gross structural features that might complicate folding. In an effort to characterize the glassiness of a folding free energy landscape in the absence of these potentially complicating factors, we have monitored the folding of a kinetically simple protein, peptostreptococcal protein L (protein L). We observe no statistically significant deviation from homogeneous single-exponential relaxation kinetics across temperatures ranging from near the protein's melting temperature to as low as -15 degrees C. On the basis of these observations, we estimate that, if there is a glass transition in the folding of protein L, it occurs at least 45 degrees C and possibly more than 145 degrees C below the freezing point of water. Apparently the folding free energy landscape of protein L is extremely smooth, which may be indicative of a rate-limiting step in folding that is, effectively, a nonglassy process.

Circular Dichroism↗

PubMed2000

Risk factors for second urinary tract infection among college women.

To better understand the etiology of recurrent urinary tract infection (UTI), the authors followed a cohort of 285 female college students with first UTI for 6 months or until second UTI. A first UTI due to Escherichia coli was followed by a second UTI three times more often than was a non-E. coli first UTI (24 vs. 8%; p = 0.02). In a logistic regression analysis limited to the 224 women from the University of Michigan Health Service and the University of Texas at Austin Health Service from September 1992 to December 1994, with a first UTI due to E. coli, vaginal intercourse increased the risk of a second UTI with both a different (odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.19, 2.15) and the same (OR = 1.37, 95% CI: 0.91, 2.07) uropathogen, as did using a diaphragm, cervical cap, and/or spermicide (same uropathogen: OR = 1.53, 95% CI: 0.95, 2.47; different uropathogen: OR = 1.77, 95% CI: 1.22, 2.58). Condom use decreased the risk of a second UTI caused by a different uropathogen (OR = 0.68, 95% CI: 0.48, 0.99) but had no effect on a second UTI caused by the same E. coli (OR = 0.99; 95% CI: 0.66, 1.50). Type or duration of treatment was not associated with a second UTI. Although the risk of second UTI is strongly influenced by sexual behavior, women with a first UTI caused by E. coli are more likely than are those with a non-E. coli first UTI to have a second UTI within 6 months.

Adolescent↗

PubMed2000

Urinary tract infection: self-reported incidence and associated costs.

PURPOSE: To estimate the annual incidence, cumulative probability of presumed urinary tract infection (UTI) by age, and the social costs. METHODS: Analysis of a random digit dialing survey of 2000 women in the United States. RESULTS: 10.8 percent (95% CI: 9.4, 12.1%) of women aged 18 and older reported at least one presumed UTI during the past 12 months, with the majority of the cases occurring among women with a history of two or more UTI episodes in their life. We estimate that by age 24, one-third of women will have at least one physician-diagnosed UTI that was treated with prescription medication. Overall, an estimated 11.3 million women in the United States had at least one presumed UTI treated with antibiotics in 1995. We estimate the annual cost of UTI cases with prescriptions to be $1.6 billion in 1995. If the costs occurring after 1995 are discounted at 5% annually, the total cost over 20 years has a present value of $25.5 billion. CONCLUSION: If a vaccine were developed that would prevent either initial or recurrent UTI the net benefits to society would be substantial, even at a developmental cost of one billion dollars.

Adolescent↗

PubMed2000

Diagnostic value of resting tricuspid regurgitation velocity and right ventricular ejection flow parameters for the detection of exercise induced pulmonary arterial hypertension.

UNLABELLED: Our objectives were to evaluate resting tricuspid regurgitation velocity (TRV) and right ventricular outflow tract velocity curve (RVOTvc) profiles as markers for development of exercise induced pulmonary arterial hypertension (ExPHT). ExPHT is an elusive cause of dyspnea and fatigue. When present, Doppler echocardiography can detect and quantify elevated pulmonary pressure. However, the characteristics and diagnostic value of resting TRV and RVOTvc indices in patients with ExPHT have not been fully addressed. The study population consisted of 52 subjects (mean age 40.5 +/- 10.9, range 22-68 years) and was divided into three subsets as follows: 1. Patients (n = 22) with overt pulmonary hypertension (PHT), 2. Patients (n = 8) with ExPHT, 3. Healthy, asymptomatic volunteers (n = 22). RVOTvc indices included: Mean and peak velocity, systolic velocity time integral (VTI); velocity time integral at peak velocity (VTImax), acceleration time; ejection time. TRV was used as an index of pulmonary artery systolic pressure. There were significant differences between normals and ExPHT for TRV, acceleration time, VTI(Vmax). TRV and VTImax were predictive of EXPHT in a logistic regression model. CONCLUSION: (1) Patients with ExPHT have distinct Doppler velocity patterns suggesting the presence of a compromised pulmonary vascular bed even with normal pulmonary pressure at rest. (2) TRV and RVOTvc indices have potential diagnostic value in the early detection of ExPHT.

Adult↗

PubMed2000

Birth weight references for twins.

OBJECTIVE: We sought to formulate fetal and birth weight references for twins from longitudinal data. STUDY DESIGN: This historic cohort study was based on 1831 pregnancies of twins born alive at >/=28 weeks' gestation from Baltimore, Maryland; Miami, Florida; Charleston, South Carolina; and Ann Arbor, Michigan. RESULTS: When we compared singletons and twins, the percentiles of twins fell substantially below the 10th percentile of singletons by 28 weeks' gestation, below the 50th percentile by 30 weeks' gestation, and below the 90th percentile by 34 weeks' gestation. The difference at the 50th percentile was 147 g (10%) at 30 weeks' gestation, 242 g (14%) at 32 weeks' gestation, 347 g (17%) at 34 weeks' gestation, 450 g (19%) at 36 weeks' gestation, 579 g (22%) at 38 weeks' gestation, and 772 g (27%) at 40 weeks' gestation. CONCLUSION: This new reference demonstrates that, although the overall pattern of fetal growth is slower for twins versus singletons from about 30 weeks' gestation, well-grown twins and singletons do not differ as much as previously believed.

Adult↗

PubMed2000

Candida vaginitis: self-reported incidence and associated costs.

BACKGROUND AND OBJECTIVES: Incidence of Candida vaginitis by age and racial or ethnic group is poorly described. GOAL: Estimate incidence, cumulative probability of presumed C vaginitis by age, racial or ethnic group, and associated costs. STUDY DESIGN: Random digit-dialing survey of 2000 US women. RESULTS: A total of 6.5 percent (95% CI, 5.4-7.5%) of women older than 18 years reported a least one episode of presumed C vaginitis during the previous 2 months. Women reporting a 1-year period with four or more episodes comprised 8.0% of the sample but accounted for 37.2% of women reporting episodes. Black women reported approximately three times more yeast infections in the previous 2 months (17.4%; 95% CI, 11.2-23.5%) than white women (5.8%; 95% CI, 4.7-6.9%). CONCLUSION: The high incidence and the propensity for recurrence underscore the need for a better understanding of the epidemiology and pathogenesis, and stress the need for the development of more accurate, rapid diagnostics and effective treatments.

Adolescent↗

PubMed2000

Improved sealant retention with bonding agents: a clinical study of two-bottle and single-bottle systems.

Recent in vitro work and a short clinical study suggest that adding a bonding agent layer between sealant and saliva-contaminated enamel allows for adequate bond strength and retention of resin sealants and may improve success of all sealant applications. This five-year clinical study scored 617 occlusal and 441 buccal/lingual molar sealants, with use of a split-mouth design, with half receiving sealant alone and half bonding agent plus sealant. Treatment effects and potential risk factors for sealant failure were tested by means of a Cox regression model. Three bonding agent groups were analyzed for treatment effect: Tenure primer, Scotchbond Multi-Purpose, and 3 single-bottle dentin bonding agents as a third group. The single-bottle group was successful in reducing risk of sealant failure, with a hazard ratio (HR) of 0.53 (p = 0.014) for occlusal and 0.35 (p = 0.006) for buccal/lingual sealants. Scotchbond was detrimental to occlusal sealant success, with a HR of 2.96 (p = 0.0003). Tenure primer was neutral, showing HRs close to 1.0. Variables that affected success differed between occlusal and buccal/lingual sealants, suggesting that failures on these two surfaces may be dependent upon differing factors. Early eruption stage was a significant risk factor for both surfaces (HR = 2.91, p = 0.00001, occlusal; and HR = 1.52, p = 0.015, buccal/lingual). Behavior (HR = 1.96, p = 0.0007), salivary problems (HR = 1.73, p = 0.002), and visually apparent variations in enamel (HR = 1.51, p = 0.018) were significant risk factors for occlusal sealants only. In addition to completing detailed analyses of risk factors for sealant survival, this study shows that single-bottle bonding agents protect sealant survival, yielding half the usual risk of failure for occlusal sealants and one-third the risk of failure for buccal/lingual sealants.

Child↗

PubMed2000

Respiratory symptoms in mothers of young children.

OBJECTIVES: Children receiving child care outside the home are at greater risk of upper respiratory infection, but whether parents of those children are also at increased risk is undocumented. We describe the incidence of 2 or more respiratory symptoms in the previous 2 weeks among 185 mothers of children 3 years of age or younger by child care use. METHODS: Mothers in Michigan and Nebraska were interviewed by phone regarding respiratory symptoms, use of outside child care (for an index child), sleeping habits, and demographic information. RESULTS: Nearly one half (46.5%) reported 2 or more symptoms during the past 2 weeks; 15.1% had contacted a health care provider and 13.0% spent 1 or more days in bed because of their symptoms, which lasted an average of 5.5 days. Prevalence of symptoms was invariant to sociodemographic characteristics. Mothers using outside child care (74.6%) were twice as likely as those without outside care to have been ill in the past 2 weeks (odds ratio: 2.26; 95% confidence interval [CI]: 1.12,4.54). Most mothers (69.2%) reported having their sleep interrupted by their children at least once in the last 2 weeks or sharing a bed with a child part or all of the night (61.1%); 25.4% slept 6 hours or less nightly. Women reporting that they rarely or never felt rested (26. 5%) were 2.65 times more likely to be ill (95% CI: 1.26,5.55), compared with those reporting that they frequently or always felt rested (46.5%), after adjusting for any outside child care. CONCLUSIONS: Future studies should focus on risk factors that can be modified to reduce illness among both children and their parents.

Adult↗

PubMed1999

The energetics of T4 lysozyme reveal a hierarchy of conformations.

We have used native state exchange to examine the energy landscape of the well-characterized protein T4 lysozyme. Although the protein exhibits two-state behavior by traditional probes, the energy landscape determined here is much more complex. The average stability of the C-terminal subdomain is significantly higher than that for the N-terminus suggesting at least two regions of unfolding. At a more detailed level, there appears to be a broad continuum of stabilities throughout each region. The overall subdomain hierarchy of energies does not mirror data on the folding pathway for this protein, challenging the relationship between energy landscapes and folding trajectories.

Bacteriophage T4↗

PubMed1999

FDA evaluations using in vitro metabolism to predict and interpret in vivo metabolic drug-drug interactions: impact on labeling.

Recent advances in in vitro metabolism methods have led to an improved ability to predict clinically relevant metabolic drug-drug interactions. To address the relationships of in vitro metabolism data and in vivo metabolism outcomes, the Office of Clinical Pharmacology and Biopharmaceutics in the Center for Drug Evaluation and Research, Food and Drug Administration, evaluated a number of recently approved new drug applications. The goal of these evaluations was to determine the contribution of in vitro metabolism data in (1) predicting in vivo drug-drug interactions, (2) determining the need to conduct an in vivo drug-drug interaction study, and (3) incorporating findings into drug product labeling. Ten cases are presented in this article. They fall into two major groups: (1) in vitro data were predictive of in vivo results, and (2) in vitro data were not predictive of in vivo results. Discussion of these cases highlights factors limiting predictability of in vivo metabolic interactions from in vitro metabolism data. The integration of these findings into drug product labeling is also discussed.

Data Collection↗

PubMed1998

Regulation of phosphatase activity in bacterial chemotaxis.

Bacterial chemotaxis is the most studied model system for signaling by the widely spread family of two-component regulatory systems. It is controlled by changes in the phosphorylation level of the chemotactic response regulator, CheY, mediated by a histidine kinase (CheA) and a specific phosphatase (CheZ). While it is known that CheA activity is regulated, via the receptors, by chemotactic stimuli, the input that may regulate CheY dephosphorylation by CheZ has not been found. We measured, by using stopped-flow fluorometry, the kinetics of CheZ-mediated dephosphorylation of CheY. The onset of dephosphorylation was delayed by approximately 50 ms after mixing phosphorylated CheY (CheY approximately P) with CheZ, and a distinct overshoot was observed in the approach to the new steady state of CheY approximately P. The delay and overshoot were not observed in a hyperactive mutant CheZ protein (CheZ54RC) that does not support chemotaxis in vivo and appears to be constitutively active. CheZ activity was cooperative with respect to CheY approximately P, with a Hill-coefficient of 2.5. The observed delayed modulation of CheZ activity and its cooperativity suggest that the phosphatase activity is regulated at the level of CheY approximately P-CheZ interaction. This novel kind of interplay between a response regulator and its phosphatase may be involved in signal tuning and in adaptation to chemotactic signals.

Bacterial Proteins↗

PubMed1998

The importance of early weight gain in the intrauterine growth and birth weight of twins.

OBJECTIVE: It was our objective to evaluate the association between early maternal weight gain (before 20 weeks), midpregnancy weight gain (20-28 weeks), and late pregnancy weight gain (28 weeks to birth) with fetal growth and birth weight in twins. STUDY DESIGN: This historic cohort study was based on 1564 births of live twins >/=28 weeks' gestation from Baltimore, Maryland, Miami, Florida, Charleston, South Carolina, and Ann Arbor, Michigan. RESULTS: Early fetal growth was affected only by smoking and chorionicity. Factors in models of both mid and late fetal growth included maternal age, pregravid weight, parity, rates of early pregnancy and midpregnancy maternal weight gain, smoking, and pre-eclampsia. Increased midpregnancy fetal growth was associated with early maternal weight gain (10.91 g/wk per pound per week) and midpregnancy maternal weight gain (15.89 g/wk per pound per week). Increased late fetal growth was associated with early maternal weight gain (16.86 g/wk per pound per week) and midpregnancy maternal weight gain (23.88 g/wk per pound per week). Increased birth weight was associated with early (283.02 g per pound per week), mid (163.58 g per pound per week), and late (69.76 g per pound per week) maternal weight gains. CONCLUSIONS: These findings confirm the importance of early maternal weight gain in twin fetal growth and birth weight.

Adult↗

PubMed1998

Frequency and response to vaginal symptoms among white and African American women: results of a random digit dialing survey.

The prevalence of vaginal symptoms and response to those symptoms in a nonclinic setting has not been previously described. Two thousand women living throughout the United States identified by random digit dialing completed a computer-assisted telephone interview about history of vaginal symptoms and use of healthcare services in response to these symptoms. The analysis was limited to 1698 white (WA) and 144 African American (AA) women (n = 1842). An episode of vaginal symptoms of any severity during 1995 was reported by 7.5% of WA women and 18.1% of AA women. Fifty-five percent of WA women and 83% of AA women with symptoms consulted a healthcare professional about their most recent episode. The racial difference in prevalence and consultation was not explained by marital status, education, employment, or lifetime number of sex partners. Most women purchased an over-the-counter antifungal preparation to treat their symptoms, whether or not a physician was consulted. The racial differences in prevalence and use of health services in response to vaginal symptoms observed here should be confirmed, and the potential causes should be explored.

Black or African American↗

PubMed1998

A model for the number of cores per prostate biopsy based on patient age and prostate gland volume.

PURPOSE: The systematic sextant biopsy is currently the gold standard for the tissue diagnosis of prostate cancer. However, it is unknown whether this 6 core approach provides optimal sampling of all prostate glands in men of all ages. The goal of the current study was to determine the appropriate number of cores per prostate biopsy based on patient age and prostate gland volume. MATERIALS AND METHODS: Patient age and tumor volume doubling time were used to calculate life threatening, clinically significant tumor volumes at diagnosis for 5-year intervals of patient age. A mathematical model was created to determine the minimum number of cores necessary to identify these life threatening tumor volumes in prostate glands 10 to 80 cm.3 without detecting clinically insignificant cancers. RESULTS: Younger men and men with larger prostate glands require more than 6 cores to ensure the diagnosis of life threatening prostate cancer. These prostates are currently under sampled by sextant biopsy. In a select group of older men who require fewer than 6 cores sextant biopsy may over sample these prostates and lead to over treatment. CONCLUSIONS: The standard sextant biopsy provides optimal sampling of only a minority of prostate glands. An approach to prostate biopsy based on patient age and prostate gland volume maximizes the detection of clinically significant prostate cancer.

Age Factors↗

PubMed1997

Critical periods of maternal weight gain: effect on twin birth weight.

OBJECTIVE: Our purpose was to evaluate the association between maternal weight gain and twin birth weight. STUDY DESIGN: This historic cohort study was based on 646 live-born twin births of > or = 28 weeks from Baltimore, Maryland, Miami, Florida, and Ann Arbor, Michigan. The sum of twin-pair birth weight was modeled as a function of either net maternal weight at delivery or rates of maternal weight gain with use of multiple regression. RESULTS: Birth weight was significantly associated with weight gain before 20 weeks in underweight women, before 20 weeks and after 28 weeks in overweight women, and during all three gestational periods in normal-weight women. Weight gain before 20 weeks had the largest effect on infants of underweight women, less of an effect on infants of normal-weight women, and half as much effect on infants of overweight women. Weight gain after 28 weeks significantly affected the infant birth weights of normal-weight and overweight women, but the effect was half as great among infants of the latter group. CONCLUSIONS: These findings suggest that weight gain during critical periods of gestation significantly influences twin birth weight; these critical periods vary by maternal pregravid weight status.

Adult↗