PubMed Health⌕ Search

Biomedical subjects

M K James

Publications and source records attributed to M K James.

At least 19 recordsLinked to original sources
PubMed1999

Functional status, assistance, and the risk of a community-based move.

This study examined the effects of declining functional status and the availability of assistance on community-based residential mobility. Wolinsky and colleagues (1993), using data from the 1984, 1986, and 1988 waves of the Longitudinal Study on Aging, reported other transitions that result from increased health demand, namely those of nursing home placement and death. Using their functional health scales and recently available statistical techniques, we performed a two-stage analysis within a health behavior conceptual framework. We conclude that older adults who report several cognitive limitations in the absence of assistance in the home are more likely to make residential changes. Additionally, we determined that the independent effects of cognitive and lower body deterioration trigger, in this case, community-based moves even when adjusting for the effect of baseline levels of functional health and other factors in the model. Our analysis extends the earlier findings of Wolinsky and colleagues to encompass residential change as an ecological outcome of health decline in old age.

Activities of Daily Living↗
PubMed1998

The Kidney Outcomes Prediction and Evaluation (KOPE) study: a prospective cohort investigation of patients undergoing hemodialysis. Study design and baseline characteristics.

PURPOSE: The purpose of the Kidney Outcomes Prediction and Evaluation (KOPE) study, was to more fully characterize the end-stage renal disease (ESRD) population with respect to social, psychological, and clinical characteristics, and to prospectively study the biomedical, social, and psychological factors that influence a range of ESRD outcomes in a large observational study of black and white patients on hemodialysis. This paper focuses on the KOPE study design as well as characteristics of patients at baseline. METHODS: KOPE was a prospective cohort investigation of patients treated at four dialysis centers in Forsyth County, North Carolina. Participants were interviewed at the dialysis centers, semi-annually over a 3 1/2 year period. Prevalent cases who were being treated with hemodialysis at the initiation of the study were enrolled into KOPE. Incident cases were subsequently enrolled as they presented to the participating units for hemodialysis. A total of 304 prevalent and 162 incident cases were enrolled into the study. The baseline health and sociodemographic characteristics of KOPE participants reported in this paper were obtained from medical records and Southeast Kidney Council data. Laboratory values taken within a 30-day interval around the baseline interview are also reported. RESULTS: KOPE participants differ from national statistics on race, age, and gender. Differences between KOPE participants and patients living in the region, but who did not participate in the study, can be explained by our recruitment criteria. CONCLUSIONS: KOPE will enable the characterization of the ESRD population, identification of factors related to poor outcomes, and identification of opportunities for interventions to prevent death and morbidity.

Adult↗
PubMed1998

The timing of change: patterns in transitions in functional status among elderly persons.

Data from the Longitudinal Study on Aging (LSOA) were analyzed to describe the heterogeneity of functional status transitions over 2-years (single-state model), and to explore whether changes in status in the previous two to four year period enhance the prediction of a subsequent transition (two-state model). Multivariate logistic regression with a robust estimate of variance was used to analyze a 7-category nominal response of: functional status (4 levels), institutionalization, death, and missing. Weighted percentages for functional status transitions and stability (unchanged status) showed that unchanged or improved functioning were at least as common as death or worsened functional status. Initial disability level, morbidities, and self-rated health were the strongest predictors of disability status after 2-years. The two-state model revealed that a previous transition (positive or negative) increases the risk for a subsequent transition, independent of initial disability level. The predictive and explanatory quality of the two-state model is substantially improved over single-state models, particularly from its ability to identify subgroups of individuals with marked functional status instability.

Activities of Daily Living↗
PubMed1997

Can we measure prior postmenopausal estrogen/progestin use? The Postmenopausal Estrogen/Progestin Interventions Trial. The PEPI Investigators.

The objective of this study was to assess: 1) the accuracy of a single self-report question about postmenopausal estrogen use; and 2) the performance and repeated measures agreement of a standardized hormone use interview. Women (n = 863) in the Postmenopausal Estrogen/Progestin Interventions Trial (PEPI) completed a self-report baseline questionnaire (BQ) at enrollment and a History of Hormone Use interview (HHU) at the 3-month follow-up visit (HHU3mos). A subsample of 101 women completed a second HHU interview 3 years later (HHU3yrs). As determined by the HHU3mos, 479 (56%) of women had ever used postmenopausal estrogen and 261 (30%) had ever used postmenopausal progestin. The mean number of years since last estrogen or progestin use was 2.2 and 1.3 years, respectively. Overall, there was 95% agreement between self-reported estrogen use on the BQ and the HHU3mos (kappa = 0.91). Using the HHU3mos as the criterion standard, the BQ misclassified 2.3% of women as false positives and 6.3% as false negatives. The average duration of estrogen use in the false-negative classifications was 1.9 years (range: 1-9 years). On the HHU3mos, 39.7% of participants could not recall at least one of the specific details of estrogen use (preparation, dose, route, or starting or stopping year); similar patterns of recall were found for progestin use. Factors associated with discordant reporting of ever-use of ERT (BQ vs. HHU3mos) or incomplete reporting of estrogen/progestin use on the HHU3mos were: route of administration, recency of hormone use, duration of hormone use, and race. Age, years since menopause, education, income, and hysterectomy status were not related to discordant and/or incomplete reporting. Agreement between the HHU3mos and HHU3yrs for ever-use of estrogen was 85.2% (kappa = 0.71). In sum, a single self-report question was adequate to ascertain ever-use of postmenopausal estrogen. When a structured interview form was used, details of postmenopausal estrogen and progestin use were not well remembered. Some features of hormone use and participant characteristics were associated with completeness of recalled hormone use, which suggests the potential for differential misclassification.

Age Factors↗
PubMed1997

Optimization of 3-(1H-indazol-3-ylmethyl)-1,5-benzodiazepines as potent, orally active CCK-A agonists.

We previously described a series of 3-(1H-indazol-3-ylmethyl)-1,5-benzodiazepine CCK-A agonists exemplified by compound 1 (GW 5823), which is the first reported binding selective CCK-A full agonist demonstrating oral efficacy in a rat feeding model. In this report we describe analogs of compound 1 designed to explore changes to the C3 and N1 pharmacophores and their effect on agonist activity and receptor selectivity. Agonist efficacy in this series was affected by stereoelectronic factors within the C3 moiety. Binding affinity for the CCK-A vs CCK-B receptor showed little dependence on the structure of the C3 moiety but was affected by the nature of the second substituent at C3. Structure-activity relationships at the N1-anilidoacetamide "trigger" moiety within the C3 indazole series were also investigated. Both agonist efficacy and binding affinity within this series were modulated by variation of substituents on the N1-anilidoacetamide moiety. Evaluation of several analogs in an vivo mouse gallbladder emptying assay revealed compound 1 to be the most potent and efficacious of all the analogs tested. The pharmacokinetic and pharmacodynamic profile of 1 in rats is also discussed.

Administration, Oral↗
PubMed1997

Benefits of linkage to the National Death Index in the Longitudinal Study of Aging.

To reduce the potential bias resulting from differential loss to follow-up in the Longitudinal Study of Aging (LSOA), information obtained from household contact methods was supplemented with information from the National Death Index (NDI). This article examines the degree of agreement in the vital status data from two sources (reinterview contacts and the NDI system) and evaluates the potential gains of using the NDI data as a supplement to define participants' vital status. Results reveal that NDI information, used to supplement reinterview information, can substantially reduce bias due to the differential loss of participants to follow-up. Reliance on reinterview information alone was less likely to capture those deaths occurring in study participants who at the initial contact lived alone, were below the poverty index, were interviewed without use of a proxy, did not supply a phone number, and did not own a home.

Aging↗
PubMed1997

Effect of postmenopausal hormone therapy on body weight and waist and hip girths. Postmenopausal Estrogen-Progestin Interventions Study Investigators.

Reports from cross-sectional comparisons, nonrandomized prospective studies, and relatively small clinical trials indicate that postmenopausal hormone therapy may slightly decrease the amount of weight typically gained by women during the decade following menopause. Despite this, widespread belief remains that hormone therapy may cause weight gain. We use data from the Postmenopausal Estrogen/Progestin Interventions trial to characterize the impact of postmenopausal hormone therapy on weight and fat distribution and to examine the consistency of this impact among subgroups of women defined by lifestyle, clinical, and demographic factors. The Postmenopausal Estrogen/Progestin Interventions trial was a 3-yr, placebo-controlled, randomized clinical trial of 875 women assessing the effects on cardiovascular risk factors of four hormone regimens: oral conjugated equine estrogen (CEE) therapy (0.625 mg daily alone), CEE in combination with medroxyprogesterone acetate (2.5 mg daily), CEE in combination with medroxyprogesterone acetate (10 mg daily on days 1-12), and CEE in combination with micronized progesterone (200 mg daily on days 1-12). Women randomly assigned to CEE with or without a progestational agent averaged 1.0 kg less weight gain at the end of 3 yr (P = 0.006) than those assigned to placebo. Assignment to CEE was also associated with averages of 1.2 cm less increase in waist girth (P = 0.01) and 0.3 cm less increase in hip (P = 0.07) girth. In regression models that included weight change as a covariate, none of these differences reached statistical significance. There were no significant differences in weight or girth changes among any of the four active hormone regimens. After accounting for the effects of assignment to active hormone therapy and baseline weight, older age (P 0.008) and higher physical activity level at baseline (P = 0.002) were also independently predictive of less weight gain. The impact of hormone therapy on weight gain was similar among subgroups, except for those defined by baseline smoking status (P = 0.04) and physical activity level at home (P = 0.02). Factors that were independently associated with smaller increases in girths were: for waist, greater overall activity (P = 0.005) and Hispanic ethnicity (P = 0.02); and for hip, work activity (P = 0.003) and greater alcohol consumption (P = 0.03). None of these factors significantly affected the observed overall relationships between estrogen and changes in girth.

Animals↗
PubMed1997

Comparative pharmacokinetics and pharmacodynamics of remifentanil, its principle metabolite (GR90291) and alfentanil in dogs.

Remifentanil is an esterase-metabolized opioid developed for use in anesthesia. The principal metabolite of remifentanil, GR90291, is considered to be less potent. This study determined the relative potency of GR90291 and alfentanil, compared with remifentanil, in anesthetized dogs. Male dogs received thiamylal sodium, and anesthesia was maintained using isoflurane and N2O in oxygen. Each dog received a 5-min infusion of 0.5 microg/kg/min remifentanil, 500 microg/kg/min GR90291 and 1.6 mg/kg/min alfentanil in random order, separated by 1 week. Serial blood samples were collected during and after the infusion. The electroencephalogram was evaluated using aperiodic analysis. The pharmacokinetics and pharmacodynamics of remifentanil, GR90291 and alfentanil were determined using nonlinear least-squares regression analysis. Remifentanil was rapidly eliminated, with a terminal half-life of 6 min, compared with 19 min for GR90291 and alfentanil. Using the estimated concentration that elicits 50% of the maximum response (EC50) for delta EEG activity and spectral edge95, remifentanil was 4213 to 4637 times more potent than GR90291 and 7.7 to 8.5 times more potent than alfentanil. The blood-brain equilibration half-life was 2.3 to 5.2 min for remifentanil, 0.39 to 0.41 min for GR90291 and 3.1 to 3.7 min for alfentanil.

Alfentanil↗
PubMed1997

Unique preclinical characteristics of GG745, a potent dual inhibitor of 5AR.

Selective inhibition of type 2 5alpha-reductase has been shown to be efficacious in the treatment of benign prostatic hyperplasia. Pharmacokinetic and pharmacodynamic results are reported of treatment with a potent inhibitor of both 5alpha-reductase isozymes, GG745, in rats, dogs and men. In the rat, GG745 has a similar effect on DHT-driven prostatic growth as finasteride, another dual 5alpha-reductase inhibitor in this species. However, GG745 appears to be more potent in the rat, a result that likely reflects the greater inherent potency and terminal half-life of GG745 (14 hr) compared with that of finasteride (1 hr). These pharmacokinetic differences are also maintained in the dog (65 and 4 hr for GG745 and finasteride, respectively). From these results, the literature, and in vitro studies, we estimated doses of GG745 likely to prove efficacious in reducing DHT levels in man. These estimated values were predictive of single-dose effects of GG745 in man. Results from single-dose evaluations in man indicate that GG745 has a terminal half-life of approximately 240 hr, and single doses of >10 mg decreased DHT levels significantly more than did single 5-mg doses of finasteride. These data support the hypothesis that a molecule (GG745) that effectively inhibits both 5alpha-reductases will lower serum DHT levels significantly more than a molecule that inhibits only a single 5alpha-reductase isozyme (e.g., finasteride, a selective inhibitor of the type 2 enzyme in man).

Animals↗
PubMed1996

Discovery of 1,5-benzodiazepines with peripheral cholecystokinin (CCK-A) receptor agonist activity (II): Optimization of the C3 amino substituent.

Analogs of the previously reported 1,5-benzodiazepine peripheral cholecystokinin (CCK-A) receptor agonist 1 were prepared which explore substitution and/or replacement of the C-3 phenyl urea moiety. Agonist efficacy on the isolated guinea pig gallbladder (GPGB) was retained with a variety of substituted ureas and amide analogs. Three compounds were identified which were orally active in the mouse gallbladder emptying assay (MGBE). The 2-indolamide (52) and N-(carboxymethyl)-2-indolamide (54) derivatives had improved affinity for the human CCK-A receptor but reduced agonist efficacy on the GPGB. Neither indolamide was orally active in a rat feeding assay. In contrast, the (3-carboxyphenyl)urea derivative (29, GW7854) had moderately increased affinity for the human CCK-B receptor but was a potent full agonist on the GPGB and was orally active in both the MGBE and rat feeding assays. GW7854 was a full agonist (EC50 = 60 nM) for calcium mobilization on CHO K1 cells expressing hCCK-A receptors and a potent antagonist of CCK-8 (pA2 = 9.1) on CHO K1 cells expressing hCCK-B receptors. GW7854 is a potent mixed CCK-A agonist/CCK-B antagonist which is orally active in two in vivo models of CCK-A-mediated agonist activity.

Animals↗
PubMed1996

3-[2-(N-phenylacetamide)]-1,5-benzodiazepines: orally active, binding selective CCK-A agonists.

A series of modifications were made to the C-3 substituent of the 1,5-benzodiazepine CCK-A agonist 1. Replacement of the inner urea NH and addition of a methyl group to generate a C-3 quaternary carbon resulted in acetamide 6, which showed CCK-A receptor binding selectivity and sub-micromolar agonist activity in vitro. Benzodiazepine 6 was active in an in vivo mouse gallbladder emptying assay and represents a novel orally active, binding selective CCK-A agonist.

Acetanilides↗
PubMed1996

Some techniques for the analysis of work sampling data.

Work sampling is an observational technique that produces counts representing the number of times that an individual has been observed performing each of several tasks. These data are collected using either systematic or random times of observation, and typically exhibit correlation between repeated observations on the same individual, with the degree of correlation being a function of the amount of time elapsed between measurements. Using several recently developed statistical techniques, we illustrate how it is possible to carry out analyses of these nominal outcomes that account for the correlation between repeated outcomes. We use description of a work sampling study to motivate the techniques and we compare empirically results from analyses based on several different underlying assumptions.

Adult↗
PubMed1996

Discovery of 1,5-benzodiazepines with peripheral cholecystokinin (CCK-A) receptor agonist activity. 1. Optimization of the agonist "trigger".

Directed screening of compounds selected from the Glaxo registry file for contractile activity on the isolated guinea pig gallbladder (GPGB) identified a series of 1,5-benzodiazepines with peripheral cholecystokinin (CCK) receptor agonist activity. Agonist efficacy within this series was modulated by variation of substituents on the N1-anilinoacetamide moiety. Remarkably, a single methyl group confers agonist activity, with an N-isopropyl substituent providing optimal efficacy. Hydrophilic substituents on the anilino nitrogen abolish agonist activity or produce antagonists of CCK. In contrast, hydrophilic electron-donating groups at the para-position of the anilino ring enhance or maintain in vitro and in vivo agonist activity. Despite decreased affinity for the human CCK-A receptor, relative to CCK-8, some of these compounds are equipotent to CCK as anorectic agents in rats following intraperitoneal administration.

Amino Acid Sequence↗
PubMed1995

Modification of receptor selectivity and functional activity in cholecystokinin peptoid ligands.

Hybrid analogs of the cholecystokinin A (CCK-A) receptor selective tetrapeptide agonist Boc-Trp-Lys(Tac)-Asp-MePhe-NH2 (1,A-71623) and the CCK-B receptor selective antagonists PD-135118 (2) and CI-988 (3) were prepared. Incorporation of the Lys(Tac) side chain into 2 produced a moderately potent antagonist of CCK-8 in the isolated guinea pig gallbladder (GPGB). Incorporation of the Lys(Tac) side chain into 3 produced the novel agonist analog 7 (EC50 = 28 nM in the GPGB) with excellent affinity for both human CCK-A (IC50 = 12 nM) and CCK-B (IC50 = 17 nM) receptors. Analog 7 was a full agonist (EC50 = 3.5 nM) for calcium mobilization on CHO-K1 cells expressing hCCK-A receptors but a partial agonist on CHO-K1 cells expressing hCCK-B receptors, eliciting a weak agonist response (EC50 = 2800 nM) and antagonizing CCK-8-induced calcium mobilization (KB = 20 nM). Despite this unusual in vitro profile, analog 7 was a potent anorectic agent in rats (ED50 = 30 nmol/kg) following intraperitoneal administration.

Adamantane↗
PubMed1995

Predicting inpatient costs with admitting clinical data.

Hospital cost-containment programs should themselves be cost-effective, targeting high-cost physicians (which requires adjusting for case mix) and patients (which requires early identification). In this study, clinical data available within 24 hours of admission from an electronic medical record system were used to develop statistical models to predict hospital costs. In this retrospective analysis of clinical data and diagnosis-related groups (DRGs), study subjects were 2,355 patients admitted for at least 1 day to the medicine service at an urban teaching hospital with sophisticated electronic medical records. Of these 2,355 patients, 1,663 (71%) had one of the 41 most common DRGs. Predictive models were derived on a random subset of two thirds of the patients and were validated on the remaining third. The following patient data were obtained: admission and prior diagnostic test results, diagnoses, vital signs; demographic data; prior inpatient and outpatient visits; tests and treatments ordered within 24 hours of admission (discretionary data); DRGs; and total inpatient costs (estimated from charges). Diagnosis-related groups explained 24% of the variance in total costs in the derivation patient set and 16% in the validation set. When only nondiscretionary data were used, the models retained only clinical laboratory results and prior diagnoses, explaining 20% of the derivation set variance in total costs and 16% in the validation set. Adding DRGs increased the variance explained in the derivation set to 34%, but decreased to 24% in the validation set. Adding discretionary data substantially increased the explained variance in the derivation and validation patient sets. The models' median predicted costs underestimated true costs by 10% to 13%, with the lowest error in the models using all types of variables. Clinical data gathered during routine clinical care can be used to adjust for case mix and identify high-cost patients early in their hospital stays, when they could be targeted by cost-containment interventions.

Cost Control↗
PubMed1995

Etiology of iliotibial band friction syndrome in distance runners.

The objectives of our study were: 1) to examine differences between a noninjured cohort of runners (N = 70) and runners afflicted with iliotibial band friction syndrome (ITBFS) (N = 56) according to selected anthropometric, biomechanical, muscular strength, and training measures; 2) to explore multivariate relationships among these measures in both the well and injured groups; and 3) to develop specific hypotheses concerning risk factors for injury that will later be tested in a prospective observational study. High speed videography (200 fps), a force platform (500 Hz), and a Cybex II+ isokinetic dynamometer were used to assess rearfoot motion, ground reaction forces, and knee muscular strength and endurance, respectively. A linear discriminant function analysis of the training data revealed weekly mileage, training pace, number of months using current training protocol, % time spent swimming, and % time spent running on a track to be significant (P < 0.10). Height was a significant anthropometric discriminator, while seven isokinetic strength and endurance measures were found to discriminate significantly between the groups. Calcaneal to vertical touchdown angle, and maximum supination velocity were significant rearfoot movement discriminators. Maximum braking force was the only significant kinetic discriminator. A combined discriminant analysis using those variables found to be significant in the previous analyses revealed weekly mileage, and maximum normalized braking force to be the best discriminators (model P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗