bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthy Elderly People Lack Neutrophil‐Mediated Functional Activity to Type V Group B Streptococcus
Authors: Amaya Rene A. , Baker Carol J. , Keitel Wendy A. , Edwards Morven S.
Published: December 2003

Objectives: To determine the function of capsular polysaccharide (CPS)‐specific immunoglobulin‐G (IgG) and neutrophils from older adults in increasing ingestion and killing of type V group B Streptococcus (GBS).

Design: Cross‐sectional study.

Setting: Outpatient clinic at Baylor College of Medicine.

Participants: The subjects were 40 healthy, community‐dwelling adults aged 65 and older from Houston, Texas.

Measurements: The serum level of type V GBS CPS‐specific IgG was measured using an enzyme‐linked immunosorbent assay. Functional activity was evaluated using an opsonophagocytosis assay.

Results: Sera from four subjects promoted efficient neutrophil‐mediated phagocytosis and killing of type V GBS (mean log10 reduction±standard deviation in colony‐forming units (cfu)=1.51±0.39). Each had serum CPS‐specific IgG concentrations exceeding 1 μg/mL. Sera from 36 subjects did not promote neutrophil‐mediated functional activity (mean log10 reduction in cfu=−0.09±0.06; P=.025). Only one of these 36 had a CPS‐specific IgG concentration exceeding 1 μg/mL. When pooled sera from young adults given type V GBS conjugate vaccine was added at CPS‐specific IgG concentrations of 4 μg/mL or 0.4 μg/mL, sera from all subjects promoted neutrophil‐mediated killing of type V GBS. No impairment was evident in the neutrophil function of elderly subjects when it was compared with that of young adults.

Conclusion:  CPS‐specific IgG and neutrophils from healthy older adults function to ingest and kill type V GBS, but these antibodies are not present in sufficient amounts in most individuals. Further studies should determine whether a type V GBS vaccine induces functionally active antibodies in older people.
Effect of Do‐Not‐Resuscitate Orders on Hospitalization of Nursing Home Residents Evaluated for Lower Respiratory Infections
Authors: Zweig Steven C. , Kruse Robin L. , Binder Ellen F. , Szafara Kristina L. , Mehr David R.
Published: December 2003

(See editorial comments by Dr. Joan Teno on pp 159–160)

Objectives: To determine resident and facility characteristics associated with do‐not‐resuscitate (DNR) orders and to test the effect of DNR orders on hospitalization of acutely ill nursing home (NH) residents with lower respiratory tract infections (LRIs).

Design: Prospective cohort.

Setting: Thirty‐six NHs (almost 4,000 residents) in central and eastern Missouri in the Missouri Lower Respiratory Infection study.

Participants: NH residents with a LRI (n=1031).

Measurements: Data were obtained from new Minimum Data Set evaluations, resident examination, and chart review. Associations between resident, physician, and facility characteristics and the presence of a DNR order and hospitalization within 30 days from evaluation for an LRI were analyzed.

Results: Sixty percent of subjects had a DNR order, and 2% had a do‐not‐hospitalize order. Resident characteristics associated with a DNR order included older age, white race, having a surrogate decision‐maker, NH residence for longer than 3 years, and more‐impaired cognition. Residents with DNR orders were more likely to live in facilities with more licensed beds, a lower proportion of Medicaid recipients, and a higher prevalence of influenza vaccination. After controlling for potential confounders, residents with a DNR order before the acute illness episode were significantly less likely to be hospitalized (adjusted odds ratio=0.69, 95% confidence interval=0.49–0.97).

Conclusion: DNR orders independently reduce the risk of hospitalization for LRI and may function as a marker for undocumented care limitations or as a mandate to limit care (unrelated to resuscitation) in NH residents with LRI.
Nutrition Risk Factors for Survival in the Elderly Living in Canadian Long‐Term Care Facilities
Authors: Allard Johane P. , Aghdassi Elaheh , Mcarthur Margaret , Mcgeer Allison , Simor Andrew , Abdolell Mohamed , Stephens Derek , Liu Barbara
Published: December 2003

Objectives: To determine the role of nutritional parameters in influencing the risk of mortality in institutionalized elderly.

Design: A prospective cohort study in which subjects had several nutritional parameters measured at baseline and were followed for 19 months. Time to death and mortality were recorded starting immediately after enrollment.

Setting: Fourteen long‐term care facilities (LTCFs).

Participants: Four hundred eight elderly long‐term care residents aged 60 and older who resided in the facility for more than 6 weeks.

Measurements: At baseline, knee height, weight, mid‐arm circumference (MAC), skin‐fold thickness, and fat‐free mass using bioelectric impedance analysis were measured. Covariates included demographic factors, length of stay in the facility, functional status, and medical diagnoses. Cox proportional hazards regression analysis was used to identify independent predictors of mortality. Results are reported as mean±standard error of the mean (SEM).

Results: Overall, mortality rate was 28.4%. Univariate predictors included male sex, body mass index, MAC, and triceps skin fold. In multivariate analysis, male sex (hazard ratio (HR)=1.7, 95% confidence interval (CI)=1.2–2.7, P=.0096) and MAC less than 26 cm were significantly associated with increased risk of mortality (HR=4.8, 95% CI: 2.8–8.3, P<.0001).

Conclusion: Among this elderly population living in LTCFs, MAC is the best nutritional predictor of mortality.
Metabolic Markers of Cobalamin Deficiency and Cognitive Function in Normal Older Adults
Authors: Garcia Angeles A. , Haron Yafa , Evans Lisa R. , Smith Matthew G. , Freedman Morris , Roman Gustavo C.
Published: December 2003

Objectives: To investigate the relationship between metabolic markers of cobalamin deficiency and cognitive function in normal older adults.

Design: Cross‐sectional study.

Setting: Queen's University and St. Mary's of the Lake Hospital, Kingston, Ontario, Canada.

Participants: Two hundred eighty‐one cognitively normal, community‐dwelling participants aged 65 and older.

Measurements: Serum cobalamin, red blood cell folate, methylcitric acid, homocysteine, and methylmalonic acid were determined. Cognitive instruments included the California Verbal Learning Test, Mattis Dementia Rating Scale, and the Stroop Neuropsychological Screening Inventory (Stroop).

Results: Serum levels of methylcitric acid had a significant negative correlation with recall, learning, and discriminability (factor 1) of the California Verbal Learning Test after adjusting for age and sex (β=−0.138, P=.019). Subjects with elevated methylcitric acid had significantly lower scores (factor 1) than subjects with normal methylcitric acid (P<.01). Bivariate analysis showed significant correlations between levels of homocysteine and the Stroop score and between cobalamin, methylmalonic acid, and homocysteine and some scores of the California Verbal Learning Test, but these relationships did not remain significant after multivariate analysis. Subjects with high homocysteine (tHcy) had lower Stroop scores than subjects with normal tHcy (P<.05). No biochemical parameters were associated with the Mattis Dementia Rating Scale scores.

Conclusion: This study indicates that, in normal elderly subjects, some cognitive scores are related to serum methylcitric acid and possibly homocysteine.
The Healthcare Costs of Sarcopenia in the United States
Authors: Janssen Ian , Shepard Donald S. , Katzmarzyk Peter T. , Roubenoff Ronenn
Published: December 2003

Objectives: To estimate the healthcare costs of sarcopenia in the United States and to examine the effect that a reduced sarcopenia prevalence would have on healthcare expenditures.

Design: Cross‐sectional surveys.

Setting: Nationally representative surveys using data from the U.S. Census, Third National Health and Nutrition Examination Survey, and National Medical Care and Utilization Expenditure Survey.

Participants: Representative samples of U.S. adults aged 60 and older.

Measurements: The healthcare costs of sarcopenia were estimated based on the effect of sarcopenia on increasing physical disability risk in older persons. In the first step, the healthcare cost of disability in older Americans was estimated from national surveys. In the second step, the proportion of the disability cost due to sarcopenia (population‐attributable risk) was calculated to determine the healthcare costs of sarcopenia. These calculations relied upon previously published relative risk values for disability in sarcopenic individuals and sarcopenia prevalence rates in the older population.

Results: The estimated direct healthcare cost attributable to sarcopenia in the United States in 2000 was $18.5 billion ($10.8 billion in men, $7.7 billion in women), which represented about 1.5% of total healthcare expenditures for that year. A sensitivity analysis indicated that the costs could be as low as $11.8 billion and as high as $26.2 billion. The excess healthcare expenditures were $860 for every sarcopenic man and $933 for every sarcopenic woman. A 10% reduction in sarcopenia prevalence would result in savings of $1.1 billion (dollars adjusted to 2000 rate) per year in U.S. healthcare costs.

Conclusion: Sarcopenia imposes a significant but modifiable economic burden on government‐reimbursed healthcare services in the United States. Because the number of older Americans is increasing, the economic costs of sarcopenia will escalate unless effective public health campaigns aimed at reducing the occurrence of sarcopenia are implemented.
Achieving Goals in Geriatric Assessment: Role of Caregiver Agreement and Adherence to Recommendations
Authors: Bogardus Sidney T. , Bradley Elizabeth H. , Williams Christianna S. , Maciejewski Paul K. , Gallo William T. , Inouye Sharon K.
Published: December 2003

Objectives: To determine predictors of recommendation adherence and goal attainment of family caregivers of patients at a geriatric assessment center.

Design: One‐year prospective cohort study.

Setting: Outpatient geriatric assessment center in Connecticut.

Participants: Two hundred consecutive new patients and their family caregivers.

Measurements: Family caregivers were interviewed after geriatric assessment to ascertain their treatment goals for the patient. Medical records were reviewed to identify treatment recommendations. Family caregivers were interviewed 1 year later to assess adherence to recommendations and attainment of goals.

Results: Follow‐up interviews were completed with 176 (88%) family caregivers. Common recommendations pertained to physician referral (71%), medications (46%), counseling/education (31%), diagnostic tests (30%), residential planning (26%), healthcare planning (21%), and community services (21%). Goal attainment was reported in 44% to 67% of the patient cases, depending on goal category. Caregiver agreement with recommendations predicted adherence to recommendations (adjusted relative risk (ARR)=1.99, 95% confidence interval (CI)=1.04–5.92) after adjusting for available clinical and demographic factors. In addition, adherence to recommendations predicted goal attainment in adjusted analyses (ARR=1.70, 95% CI=1.09–2.64).

Conclusion: This study revealed a broad range of treatment recommendations in geriatric assessment and suggests that agreeing with recommendations can promote adherence and that adherence can promote goal attainment. Taken together, the results imply that articulating shared treatment recommendations may improve the quality of health care.
Effect of Depression on Diagnosis, Treatment, and Survival of Older Women with Breast Cancer
Authors: Goodwin James S. , Zhang Dong D. , Ostir Glenn V.
Published: December 2003

Objectives: To assess the effect of a prior diagnosis of depression on the diagnosis, treatment, and survival of older women with breast cancer.

Design: Retrospective analysis of records from Surveillance, Epidemiology and End Results (SEER) and Medicare claims.

Setting: Registries from seven major cities and five states.

Participants: A total of 24,696 women aged 67 to 90 diagnosed with breast cancer between 1993 and 1996 and included in the SEER Medicare linked database were studied.

Measurements: Information on patient demographics, tumor characteristics, treatment received, and survival were obtained from SEER, and the Medicare inpatient and professional charges for the 2 years before diagnosis were searched for a diagnosis of depression.

Results: A total of 1,841 of the 24,696 women (7.5%) had been given a diagnosis of depression sometime in the 2 years before the diagnosis of breast cancer. There was no difference in tumor size or stage at diagnosis between depressed and nondepressed women. Women diagnosed with depression were less likely to receive treatment generally considered definitive (59.7% vs 66.2%, P< .0001), and this difference remained after controlling for age, ethnicity, comorbidity, and SEER site. Also, women with a prior diagnosis of depression had a higher risk of death (hazard ratio=1.42; 95% confidence interval= 1.13–1.79) after controlling for other factors that might affect survival. The higher risk of death associated with a prior diagnosis of depression was also seen in analyses restricted to women who received definitive treatment.

Conclusion: Women with a recent diagnosis of depression are at greater risk for receiving nondefinitive treatment and experience worse survival after a diagnosis of breast cancer, but differences in treatment do not explain the worse survival.
Effect of a Comprehensive, Multidisciplinary, Educational Program on the Use of Antibiotics in a Geriatric University Hospital
Authors: Lutters Monika , Harbarth Stephan , Janssens Jean‐Paul , Freudiger Hans , Herrmann François , Michel Jean‐Pierre , Vogt Nicole
Published: December 2003

Objectives: To assess the effect of a comprehensive, educational antibiotic management program designed to improve antibiotic use and reduce treatment costs in elderly patients with suspected urinary or respiratory tract infection.

Design: Interventional cohort study with 12 cross‐sectional drug utilization reviews of antibiotic use before, during, and after the multifaceted intervention.

Setting: A 304‐bed university hospital for geriatric patients.

Participants: A total of 3,383 elderly patients.

Interventions: An educational program including distribution of guidelines on the diagnosis and treatment of urinary and respiratory tract infections; lectures on geriatric infectious diseases; weekly ward rounds for patients with suspected infection; and targeted, individual counseling on diagnosis and antibiotic treatment of infections.

Measurements: Antibiotic utilization data were collected from the patients' records. Antimicrobial costs were calculated using 1998 hospital wholesale prices.

Results: Of 3,383 screened patients, 680 (20%) received at least one antibiotic. During the study period, the mean number of prescribed drugs per patient increased from 5.9 to 7.6 (29%; P<.001). In contrast, a reduction of 15% was observed in the proportion of patients exposed to antibiotic agents (P=.08) and a drop of 26% in the number of antibiotics administered (P<.001). This resulted in a 54% decrease in cumulative daily antibiotic costs. In 83 (75%) of 110 surveyed patients, the guidelines were correctly implemented. The intervention had no measurable negative clinical effect.

Conclusion: A comprehensive, multifaceted educational program for treating urinary and respiratory tract infections in the elderly was a safe and practical method to change physicians' antibiotic prescribing practice and significantly reduce the consumption and costs of antibiotics in a geriatric hospital.
Agreement Between Self‐Report of Disease Diagnoses and Medical Record Validation in Disabled Older Women: Factors That Modify Agreement
Authors: Simpson Crystal F. , Boyd Cynthia M. , Carlson Michelle C. , Griswold Michael E. , Guralnik Jack M. , Fried Linda P.
Published: December 2003

Objectives: To determine the agreement between self‐report of chronic disease and validated evidence of disease using multiple ascertainment methods and to assess effects of cognition, education, age, and comorbidity.

Design: Cross‐sectional analysis.

Setting: Community Baltimore, Maryland.

Participants: One thousand two community‐dwelling disabled women aged 65 and older.

Measurements: Kappa statistics were calculated to determine the relationship between self‐report of 14 diseases and standardized algorithms. Analyses were stratified using Mini‐Mental State Examination score, education, number of chronic diseases, and age.

Results: Kappa was excellent for hip fracture (HF), Parkinson's disease (PD), diabetes mellitus (DM), cancer, stroke, and disc disease (DD); fair to good for angina pectoris, congestive heart failure, and myocardial infarction; and poor for peripheral arterial disease, spinal stenosis, osteoporosis, arthritis, and lung disease. Overall, kappa decreased with decreasing cognition and education, increasing age, and four or more diseases.

Conclusion: In disabled older women, self‐report of physician diagnosis of HF, PD, DM, cancer, stroke, and DD appears valid. In general, increasing comorbidity and age and decreasing cognition and education do not reduce validity for diseases where agreement was excellent overall.
Reproducibility of the Jumping Mechanography As a Test of Mechanical Power Output in Physically Competent Adult and Elderly Subjects
Authors: Rittweger Jörn , Schiessl Hans , Felsenberg Dieter , Runge Martin
Published: December 2003

Objectives: To compare the reproducibility of the newly developed jumping mechanography with other physical tests.

Design: Study 1: Repeated testing with an interval of 2 weeks to assess the short‐term repetition error. Study 2: Testing on 5 successive days to assess learning effects.

Setting: Geriatric clinic, Esslingen, Germany.

Participants: Study 1 had 36 subjects aged 24 to 88; Study 2 had 22 subjects aged 19 to 86. Locomotor competence in all subjects was assessed using the ability to walk unaided and to perform a tandem stand and tandem walk.

Measurements: The test battery consisted of timed up and go, freely chosen gait speed, maximum gait speed, chair‐rising test, and maximum power in jumping mechanography.

Results: All subjects performed the jumping mechanography without major problems. Study 1: Of all tests, maximum power in jumping mechanography depicted the smallest intrasubject short‐term error (3.6%), the largest intersubject coefficient of variation (45.4%), and the greatest test‐retest correlation coefficient (r=0.99). Study 2: The only tests for which the learning effects were confined to the 1% range were the maximum gait speed test and the maximum power in jumping mechanography.

Conclusion: Assessment of maximum power in jumping mechanography appears to have good test‐retest reliability with negligible learning effects. Moreover, it results in a comparatively large intersubject variability, which makes it an interesting method in the assessment of aging effects in middle‐aged to older subjects and patients.
Curricular Framework: Core Competencies in Multicultural Geriatric Care
Authors: Xakellis George , Brangman Sharon A. , Ladson Hinton W. , Jones Vida Y. , Masterman Donna , Pan Cynthia X. , Rivero Jorge , Wallhagen Margaret , Yeo Gwen
Published: December 2003

Strategies to reduce the documented disparities in health and health care for the rapidly growing numbers of older patients from diverse ethnic populations include increased cultural competence of providers. To assist geriatric faculty in medical and other health professional schools develop cultural competence training for their ethnogeriatric programs, the University of California Academic Geriatric Resource Program partnered with the Ethnogeriatric Committee of the American Geriatrics Society to develop a curricular framework.

The framework includes core competencies based on the format of the Core Competencies for the Care of Older Patients developed by the Education Committee of the American Geriatrics Society. Competencies in attitudes, knowledge, and skills for medical providers caring for elders from diverse populations are specified. Also included are recommended teaching strategies and resources for faculty to pursue the development of full curricula.
Older Driver Safety: A Report from the Older Drivers Project
Authors: Wang Claire C. , Carr David B. ,   for the Older Drivers Project
Published: December 2003

Older driver safety is a growing public health concern for which interventions are currently being sought. Statistics show that older drivers suffer a disproportionately high rate of motor vehicle fatalities compared with other adult drivers. This disproportion is due to two factors: an increased crash rate per vehicle mile driven and an increased risk of fatality in the event of a crash.

Traditionally, traffic safety efforts for the older population have focused on methods to identify unsafe drivers to enforce driving cessation, but driving cessation deprives the majority of older Americans of their primary form of transportation and has been associated with an increase in depressive symptoms. In response to these concerns, the Older Drivers Project, created by the American Medical Association in partnership with the National Highway Traffic Safety Administration, describes and advocates a more acceptable approach to traffic safety.

The primary objective of this approach involves helping older drivers stay on the road safely to preserve their mobility and independence. This can be accomplished through three methods: (1) optimizing the driver, (2) optimizing the driving environment, and (3) optimizing the vehicle. In this approach, driving cessation is recommended only after the safety of the driver cannot be secured through any other means.
The Northern California Chronic Care Network for Dementia
Authors: Coon David W. , Williams Marilyn P. , Moore Richard J. , Edgerly Elizabeth S. , Steinbach Catherine M. , Roth Susan P. , Phillips Cheryl L. , Nguyen Hanh , Dowling Glenna A. , Dunning Erika A. , Feigenbaum Lawrence Z.
Published: December 2003

The Northern California Chronic Care Network for Dementia brings together Northern California's major providers of managed care, community‐based care, consumer education, and advocacy in new partnerships to improve the care of persons with dementia enrolled in managed care plans and their family caregivers. These partnerships are part of a national initiative entitled the Chronic Care Network for Alzheimer's Disease (CCN/AD) sponsored by the National Chronic Care Consortium and the Alzheimer's Association. This initiative selected eight promising provider‐consumer partnerships across the country to implement and evaluate a new model of coordinated care for people with dementia and their families. This paper describes the Northern California network's partnerships and its intervention and challenges. The intervention is grounded in the key components of the CCN/AD model: “identification of patients with possible dementia, diagnostic assessment, care management and family caregiver information and support.” These components, in turn, are translated into protocols and pathways designed to create timely, comprehensive, appropriate, and effective systems of care services that address the unique needs of dementia patients and their caregivers over the course of the disease.
Interest‐Based Negotiations in a Transformed Labor–Management Setting
Authors: Fonstad Nils O. , McKersie Robert B. , Eaton Susan C.
Published: December 2003

The authors introduce a group of essays that evolved from a March 2003 symposium on the path‐breaking new partnership and use of interest‐based negotiation (IBN) at Kaiser Permanente (KP), one of the largest integrated health care programs in the United States. They briefly trace the history of the IBN approach (both success stories and failures); the growth of this phenomenon; and its use in collective bargaining settings. The KP case, the focus of the symposium (which was jointly sponsored by MIT's Institute for Work and Employment Relations and Harvard's Program on Negotiation), is by far the largest instance of the use of IBN in U.S. labor relations history.
Kaiser Permanente: Using Interest‐Based Negotiations to Craft a New Collective Bargaining Agreement
Authors: McKersie Robert B. , Eaton Susan C. , Kochan Thomas A.
Published: December 2003

Building on a new labor–management partnership, Kaiser Permanente and its nearly seventy thousand union employees negotiated a five‐year contract agreement in 2000 based on the principles of “interest‐based negotiations.” The people who made this remarkable achievement happen as well as the historic background of the case are described and analyzed. A key element to the success of this initiative was the back‐and‐forth work of many different groups, including joint labor–management committee, coalitions of unions, bargaining task groups focused on particular subject areas, and local and national leaders of the company and its unions. Using illustrative comments from actual participants in this complex, nearly year‐long negotiation process, the authors explore how the parties crafted their agreement.
Taking Stock of the Kaiser Permanente Partnership Story
Authors: Eaton Susan C. , McKersie Robert B. , Fonstad Nils O.
Published: December 2003

The success of the 2000 interest‐based contract negotiation at Kaiser Permanente (KP) does not mean that future challenges to this approach to negotiation have evaporated. Among the factors that contributed to the success thus far were: establishing buy‐in to what was a new approach for many people; effective coordination in a complex environment; deadline pressure; managing internal negotiations; effective leadership; an investment in training; facilitation; creative brainstorming; and establishing ground rules. In addition to reviewing the KP experience, the authors focus on lessons learned and guidelines for future negotiations, as well as the role of interest‐based processes in an organization's daily routine.
Culture and Negotiation Strategy
Authors: Adair Wendi , Brett Jeanne , Lempereur Alain , Okumura Tetsushi , Shikhirev Peter , Tinsley Catherine , Lytle Anne
Published: December 2003

In this article the authors investigate the relationship between culture and joint gains by examining the role of information sharing and power strategies in intracultural negotiations. Previously, the authors found that the relationship between cultural values or norms and joint gains was uncertain in six cultures: France, Russia, Japan, Hong Kong, Brazil, and the United States. Of the five values and norms measured, only norms for information sharing in negotiation were directly related to joint gains. This article explores and extends prior findings by investigating the strategies used by negotiators in the same six cultures. Cultures that maximized joint gains used direct information‐sharing strategies or a combination of indirect and direct strategies. Power strategies may help or hurt joint gains, depending on a culture's values and norms for power and whether or not power‐based influence is used in conjunction with sufficient information exchange. The findings suggest that understanding the other party's cultural characteristics and strategies can help negotiators plan how to focus on information exchange and deal with unusual power strategies that they may encounter.
Rocks and Hard Places: Managing Two Tensions in Negotiation
Authors: Nelson Dana , Wheeler Michael
Published: December 2003

Theorists posit two fundamental tensions in negotiation. One is strategic: the tug‐and‐pull between creating value and claiming one's share of it. The other is interpersonal: the tension between asserting one's own interests and, at the same time, empathizing with the feelings and needs of other parties.1 This research report analyzes how negotiators experience these tensions in practice. Specifically, their self‐perceptions about their relative competence in several key areas allow us to see how strength along one dimension (like getting the maximum) is correlated with other important skills. Some of the authors’ findings confirm familiar models. For example, people implicitly feel that being successful at asserting their own interests imposes a cost with respect to understanding others. There were some surprises, however: most notably, people who rated themselves as strong value claimers also saw themselves as good value creators. The authors explore some of the implications of their findings for both practice and teaching, and foreshadow a follow‐up report they plan. They also note how other researchers can access their data for their own studies.
Gender‐dependent attenuation of cardiac potassium currents in type 2 diabetic db/db mice
Authors: Shimoni Yakhin , Chuang Mariette , Abel E. Dale , Severson David. L.
Published: December 2003

Single ventricular myocytes were prepared from control db/+ and insulin‐resistant diabetic db/db male mice at 6 and 12 weeks of age. Peak and sustained outward potassium currents were measured using whole‐cell voltage clamp methods. At 6 weeks currents were fully developed in control and diabetic mice, with no differences in the density of either current. By 12 weeks both currents were significantly attenuated in the diabetic mice, but could be augmented by in vitro incubation with the angiotensin‐converting enzyme (ACE) inhibitor quinapril (1 μm, 5–9 h). In cells from female db/db mice (12 weeks of age), K+ currents were not attenuated and no effects of quinapril were observed. To investigate whether lack of insulin action accounts for these gender differences, cells were also isolated from cardiomyocte‐specific insulin receptor knockout (CIRKO) mice. Both K+ currents were significantly attenuated in cells from male and female CIRKO mice, and action potentials were significantly prolonged. Incubation with quinapril did not augment K+ currents. Our results demonstrate that type 2 diabetes is associated with gender‐selective attenuation of K+ currents in cardiomyocytes, which may underlie gender differences in the development of some cardiac arrhythmias. The mechanism for attenuation of K+ currents in cells from male mice is due, at least in part, to an autocrine effect resulting from activation of a cardiac renin–angiotensin system. Insulin is not involved in these gender differences, since the absence of insulin action in CIRKO mice diminishes K+ currents in cells from both males and females.
Rab3A negatively regulates activity‐dependent modulation of exocytosis in bovine adrenal chromaffin cells
Authors: Thiagarajan Ramachandran , Tewolde Teclemichael , Li Yingjie , Becker Peter L. , Rich Mark M. , Engisch Kathrin L.
Published: December 2003

Members of the Rab family of monomeric GTPases have been implicated in vesicle trafficking, and Rab3A, located on synaptic vesicles in neurones and secretory vesicles in neuroendocrine cells, is likely to be involved in vesicle fusion leading to neurotransmitter release. A hydrolysis‐deficient mutant of Rab3A, Rab3AQ81L, has been shown to potently inhibit hormone release. Here we show that the inhibition of hormone release by Rab3AQ81L is activity‐dependent. Bovine adrenal chromaffin cells were induced to express Rab3AQ81L and green fluorescent protein by adenoviral gene transfer of a bicistronic construct. Fluorescent cells were stimulated with single depolarizations and trains of depolarizing pulses in whole cell perforated patch clamp recordings, and exocytosis was detected with cell capacitance measurements and carbon fibre amperometry. When single depolarizations were used to evoke exocytosis, cells expressing Rab3AQ81L showed a 50% reduction in response amplitude. When trains of brief depolarizations (10 or 40 ms) were used to evoke exocytosis, responses rapidly declined to zero in cells expressing Rab3AQ81L. Wild‐type Rab3A had effects similar to Rab3AQ81L, causing significant inhibition of exocytosis only during repetitive stimulation. Expression of Rab5A did not alter exocytosis evoked by single depolarizations or repetitive stimulation. Applying a long duration depolarization in the middle of a stimulus train revealed that exocytotic efficacy (capacitance increase per amount of calcium influx) was not decreased in Rab3AQ81L‐expressing cells. Instead, the activity‐dependent increase in exocytotic efficacy observed in control cells did not occur in Rab3AQ81L‐expressing cells. Our results suggest that Rab3A in the GTP bound conformation prevents activity‐dependent facilitation.
Early Supplier Involvement in New Product Development With WeBid: A Case Study on Video Conferencing System
Authors: Huang G. Q. , Zhao J. B. , Mak K. L.
Published: December 2003

WeBid is a prototype web-based framework developed for supporting and facilitating early supplier involvement in new product development on the Internet. It provides a suite of rigorous and yet pragmatic constructs for establishing and managing the customer-supplier relationships in new product development process. This paper reports on some insights and experience gained from a real-life case study using WeBid system and approach in the tendering process of developing a Video Conferencing System (VCS).
Indexing and Retrieval in Metal Stamping Die Design Using Case-based Reasoning
Authors: Tor S. B. , Britton , and G. A. , Zhang W. Y.
Published: December 2003

This paper presents a case-based reasoning (CBR) methodology for metal stamping die design, that in particular addresses the indexing and retrieval of die design cases. A feature relation graph representation of stamped metal parts are used to create a high level of geometric abstraction, which is used to index design cases quickly and accurately. Though the potential search space for case retrieval is huge, by employing a novel dual-step similarity analysis between a new stamped part and existing parts in the case library, the proposed retrieval strategy can narrow down the search space efficiently and retrieve the most similar case in a reasonable period of time. An illustrative example is included to demonstrate the operation of the proposed approach and show its effectiveness in speeding up stamping die design.
Surface and Volume Discretization of Functionally Based Heterogeneous Objects
Authors: Kartasheva Elena , Adzhiev Valery , Pasko Alexander , Fryazinov Oleg , Gasilov Vladimir
Published: December 2003

The presented approach to discretization of functionally defined heterogeneous objects is oriented towards applications associated with numerical simulation procedures, for example, finite element analysis (FEA). Such applications impose specific constraints upon the resulting surface and volume meshes in terms of their topology and metric characteristics, exactness of the geometry approximation, and conformity with initial attributes. The function representation of the initial object is converted into the resulting cellular representation described by a simplicial complex. We consider in detail all phases of the discretization algorithm from initial surface polygonization to final tetrahedral mesh generation and its adaptation to special FEA needs. The initial object attributes are used at all steps both for controlling geometry and topology of the resulting object and for calculating new attributes for the resulting cellular representation.
Dynamic Remeshing and Applications
Authors: Vorsatz , J. , Ro¨ssl , and Ch. , Seidel H.-P.
Published: December 2003

Triangle meshes are a flexible and generally accepted boundary representation for complex geometric shapes. In addition to their geometric qualities or topological simplicity, intrinsic qualities such as the shape of the triangles, their distribution on the surface and the connectivity are essential for many algorithms working on them. In this paper we present a flexible and efficient remeshing framework that improves these intrinsic properties while keeping the mesh geometrically close to the original surface. We use a particle system approach and combine it with an incremental connectivity optimization process to trim the mesh towards the requirements imposed by the user. The particle system uniformly distributes the vertices on the mesh, whereas the connectivity optimization is done by means of Dynamic Connectivity Meshes, a combination of local topological operators that lead to a fairly regular connectivity. A dynamic skeleton ensures that our approach is able to preserve surface features, which are particularly important for the visual quality of the mesh. None of the algorithms requires a global parameterization or patch layouting in a preprocessing step but uses local parameterizations only. In particular we will sketch several application scenarios of our general framework and we will show how the users can adapt the involved algorithms in a way that the resulting remesh meets their personal requirements.
Generalization of the Mid-Element Based Dimensional Reduction
Authors: Suresh Krishnan
Published: December 2003

Boundary value problems posed over thin solids are often amenable to a dimensional reduction in that one or more spatial dimensions may be eliminated from the governing equation. One of the popular methods of achieving dimensional reduction is the Kantorovich method, where based on certain a priori assumptions, a lower-dimensional problem over a ‘mid-element’ is obtained. Unfortunately, the mid-element geometry is often disjoint, and sometimes ill defined, resulting in both numerical and automation problems. A natural generalization of the mid-element representation is a skeletal representation. We propose here a generalization of the mid-element based Kantorovich method that exploits the unique topologic and geometric properties of the skeletal representation. The proposed method rests on a quasi-disjoint Voronoi decomposition of a domain induced by its skeletal representation. The generality and limitations of the proposed method are discussed using the Poisson’s equation as a vehicle.
Shape Intrinsic Properties for Free-Form Object Matching
Authors: Ko K. H. , Maekawa T. , Patrikalakis N. M. , Masuda H. , Wolter F.-E.
Published: December 2003

Despite extensive research and rapid increase of computing power, free-form object matching still remains a challenging problem in CAD/CAM areas. In this paper, various object features are discussed, and matching methods which use these features are introduced along with robust computational algorithms for umbilical points and intrinsic wireframes. The similarity of matched objects is assessed with three proposed tests. Each algorithm is demonstrated with examples.
Tight Cocone: A Water-tight Surface Reconstructor
Authors: Dey Tamal K. , Goswami Samrat
Published: December 2003

Surface reconstruction from unorganized sample points is an important problem in computer graphics, computer aided design, medical imaging and solid modeling. Recently a few algorithms have been developed that have theoretical guarantee of computing a topologically correct and geometrically close surface under certain condition on sampling density. Unfortunately, this sampling condition is not always met in practice due to noise, non-smoothness or simply due to inadequate sampling. This leads to undesired holes and other artifacts in the output surface. Certain CAD applications such as creating a prototype from a model boundary require a water-tight surface, i.e., no hole should be allowed in the surface. In this paper we describe a simple algorithm called Tight Cocone that works on an initial mesh generated by a popular surface reconstruction algorithm and fills up all holes to output a water-tight surface. In doing so, it does not introduce any extra points and produces a triangulated surface interpolating the input sample points. In support of our method we present experimental results with a number of difficult data sets.
Sensitive Enzyme Immunoassay for Measuring Plasma and Intracellular Nevirapine Levels in Human Immunodeficiency Virus-Infected Patients
Authors: Azoulay Stéphane , Nevers Marie-Claire , Créminon Christophe , Heripret Laurence , Durant Jacques , Dellamonica Pierre , Grassi Jacques , Guedj Roger , Duval Danièle
Published: December 2003

We have developed an enzyme immunoassay to measure nevirapine (NVP) in plasma and peripheral blood mononuclear cells. Anti-NVP polyclonal antibodies were raised in rabbits by using a synthetic NVP derivative coupled to keyhole limpet hemocyanin as the immunogen, and the enzyme tracer was prepared by chemically coupling the NVP derivative with acetylcholinesterase. These reagents were used to develop a sensitive competitive enzyme immunoassay performed in microtitration plates with a 100-pg ml
−1
limit of detection and thus ∼100 times more sensitive than previously published techniques. The plasma assay was performed directly without extraction (in this case, a 500-pg ml
−1
limit of detection was observed) on a minimum of 30 μl of plasma. This assay shows good precision and efficiency, since recovery from human plasma and cell extracts spiked with NVP ranged between 87 and 104%, with coefficients of variation of <10%. A pharmacokinetic analysis of plasma NVP was performed for seven patients infected with human immunodeficiency virus (HIV), and it gave results similar to published findings. Intracellular concentrations of NVP were measured in cultured human T-lymphoblastoid cells and peripheral blood mononuclear cells from HIV-infected patients. The results indicated a very low intracellular/extracellular concentration ratio (0.134), thus demonstrating the absence of intracellular drug accumulation. This is the first intracellular assay of a nonnucleoside reverse-transcriptase inhibitor, and this method could be useful in monitoring plasma and intracellular NVP levels in HIV-infected patients.
Human Salivary Histatin 5 Fungicidal Action Does Not Induce Programmed Cell Death Pathways in
Candida albicans
Authors: Wunder David , Dong Jin , Baev Didi , Edgerton Mira
Published: December 2003

Salivary histatins (Hsts) are potent candidacidal proteins that induce a nonlytic form of cell death in
Candida albicans
accompanied by loss of mean cell volume, cell cycle arrest, and elevation of intracellular levels of reactive oxygen species (ROS). Since these phenotypes are often markers of programmed cell death and apoptosis, we investigated whether other classical markers of apoptosis, including generation of intracellular ROS and protein carbonyl groups, chromosomal fragmentation (laddering), and cytochrome
c
release, are found in Hst 5-mediated cell death. Increased intracellular levels of ROS in
C. albicans
were detected in cells both following exogenous application of Hst 5 and following intracellular expression of Hst 5. However, Western blot analysis failed to detect specifically increased protein carbonylation in Hst 5-treated cells. There was no evidence of chromosomal laddering and no cytochrome
c
release was observed following treatment of
C. albicans
mitochondria with Hst 5. Superoxide dismutase enzymes of
C. albicans
and
Saccharomyces cerevisiae
provide essential protection against oxidative stress; therefore, we tested whether
SOD
mutants have increased susceptibility to Hst 5, as expected if ROS mediate fungicidal effects. Cell survival of
S. cerevisiae SOD1/SOD2
mutants and
C. albicans SOD1
mutants following Hst 5 treatment (31 μM) was indistinguishable from the survival of wild-type cells treated with Hst 5. We conclude that ROS may not play a direct role in fungicidal activity and that Hst 5 does not initiate apoptosis or programmed cell death pathways.
Six-Week Randomized Controlled Trial To Compare the Tolerabilities, Pharmacokinetics, and Antiviral Activities of GW433908 and Amprenavir in Human Immunodeficiency Virus Type 1-Infected Patients
Authors: Wood Robin , Arasteh Keikawus , Stellbrink Hans-Jürgen , Teofilo Eugenio , Raffi François , Pollard Richard B. , Eron Joseph , Yeo Jane , Millard Judith , Wire Mary Beth , Naderer Odin J.
Published: December 2003

This study compared the plasma amprenavir pharmacokinetics of the human immunodeficiency virus (HIV) protease inhibitors amprenavir (Agenerase) 1,200 mg twice daily (BID) and the amprenavir prodrug GW433908, a formulation that substantially reduces the number of tablets per dose compared with amprenavir, at doses of 1,395 mg and 1,860 mg BID, in combination with abacavir 300 mg BID and lamivudine 150 mg BID in patients with HIV infection. Overall, 78 patients received study treatment. Compared with amprenavir 1,200 mg BID, both GW433908 1,395 mg BID and GW433908 1,860 mg BID delivered equivalent steady-state (ss) values for area under the plasma amprenavir concentration-time curve (AUC) at the end of a dosing interval (τ), lower maximum plasma amprenavir concentrations (30% lower), and higher plasma amprenavir concentrations at the end of a dosing interval (28% higher for GW433908 1,395 mg BID and 46% higher for GW433908 1,860 mg BID). Time-variant plasma amprenavir pharmacokinetics were observed with reductions in plasma amprenavir exposure over the first 4 weeks of dosing; the decrease in plasma amprenavir AUC
τ,ss
versus the AUC from 0 h to ∞ was 27% for GW43308 1,395 mg, 45% for GW433908 1,860 mg, and 23% for amprenavir 1,200 mg. All three regimens reduced plasma HIV-1 RNA (∼2 log
10
copies/ml) and increased CD4
+
cell counts (∼100 cells/mm
3
) over the initial 28 days. Adverse event profiles were consistent with those previously reported for amprenavir. Although not statistically tested, the GW433908 groups appeared to have fewer gastrointestinal symptoms. In conclusion, the protease inhibitor GW433908 delivered comparable plasma amprenavir concentrations to those delivered by amprenavir 1,200 mg BID. GW433908, in combination with abacavir and lamivudine, demonstrated potent antiviral activity and was generally well tolerated over a 4-week period.
Single-Dose and Steady-State Pharmacokinetics of Tenofovir Disoproxil Fumarate in Human Immunodeficiency Virus-Infected Children
Authors: Hazra Rohan , Balis Frank M. , Tullio Antonella N. , DeCarlo Ellen , Worrell Carol J. , Steinberg Seth M. , Flaherty John F. , Yale Kitty , Poblenz Marianne , Kearney Brian P. , Zhong Lijie , Coakley Dion F. , Blanche Stephane , Bresson Jean Louis , Zuckerman Judith A. , Zeichner Steven L.
Published: December 2003

Tenofovir disoproxil fumarate (DF) is a potent nucleotide analog reverse transcriptase inhibitor approved for the treatment of human immunodeficiency virus (HIV)-infected adults. The single-dose and steady-state pharmacokinetics of tenofovir were evaluated following administration of tenofovir DF in treatment-experienced HIV-infected children requiring a change in antiretroviral therapy. Using increments of tenofovir DF 75-mg tablets, the target dose was 175 mg/m
2
; the median administered dose was 208 mg/m
2
. Single-dose pharmacokinetics were evaluated in 18 subjects, and the geometric mean area under the concentration-time curve from 0 h to ∞ (AUC
0-∞
) was 2,150 ng · h/ml and the geometric mean maximum concentration (
C
max
) was 266 ng/ml. Subsequently, other antiretrovirals were added to each patient's regimen based upon treatment history and baseline viral resistance results. Steady-state pharmacokinetics were evaluated in 16 subjects at week 4. The steady-state, geometric mean AUC for the 24-h dosing interval was 2,920 ng · h/ml and was significantly higher than the AUC
0-∞
after the first dose (
P
= 0.0004). The geometric mean
C
max
at steady state was 302 ng/ml. Tenofovir DF was generally very well tolerated. Steady-state tenofovir exposures in children receiving tenofovir DF-containing combination antiretroviral therapy approached values seen in HIV-infected adults (AUC, ∼3,000 ng · h/ml;
C
max
, ∼300 ng/ml) treated with tenofovir DF at 300 mg.