bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional characterization of nonsynonymous single nucleotide polymorphisms in the human organic anion transporter 4 (hOAT4)
Authors: Zhou Fanfan , Zhu Ling , Cui Pei H. , Church W. Bret , Murray Michael 
Published: December 2009

Background and purpose: The human organic anion transporter (hOAT) family of transmembrane carrier proteins mediate the cellular flux of anionic substances, including certain hormones and anti‐cancer drugs. hOAT4 is highly expressed at the apical membrane of the renal tubular cell and facilitates drug re‐absorption in the kidney. In the present study, the impact of 10 nonsynonymous single nucleotide polymorphisms (SNPs) of hOAT4 on transport function in COS‐7 cells was characterized.Experimental approach: Transport uptake assay was used to assess the function of the variant transporters. Cell surface biotinylation and western blot analysis were used to investigate the expression characteristics of the transporter proteins. Comparative modelling was used to interpret the influence of nonsynonymous changes in terms of hOAT4 structure.Key results: Four naturally occurring hOAT4 variants (L29P, R48Y, V155G and T392I) exhibited a significant loss of function. Substitution of leucine‐29, which is a conserved residue in OATs, with a proline residue, impaired the synthesis or the apparent stability of the transporter and membrane insertion was disrupted in the R48Y variant. In the case of the V155G and T392I variants, impaired function was due to decreased affinity of the transporter for oestrone sulphate and impaired transporter‐substrate turnover respectively. The T392I variant was inhibited more extensively than the wild‐type transporter by the cationic substrate tetraethyl ammonium.Conclusions and implications: Several naturally occurring SNPs encode variant hOAT4s that may impair the renal tubular re‐absorption of important drug substrates.
Haloperidol Prophylaxis for Elderly Hip‐Surgery Patients at Risk for Delirium: A Randomized Placebo‐Controlled Study
Authors: Kalisvaart Kees J. , De Jonghe Jos F. M. , Bogaards Marja J. , Vreeswijk Ralph , Egberts Toine C. G. , Burger Bart J. , Eikelenboom Piet , Van Gool Willem A. 
Published: December 2009

Objectives:To study the effectiveness of haloperidol prophylaxis on incidence, severity, and duration of postoperative delirium in elderly hip‐surgery patients at risk for delirium.Design:Randomized, double‐blind, placebo‐controlled trial.Setting:Large medical school–affiliated general hospital in Alkmaar, the Netherlands.Participants:A total of 430 hip‐surgery patients aged 70 and older at risk for postoperative delirium.Intervention:Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively. Proactive geriatric consultation was provided for all randomized patients.Measurements:The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). Secondary outcomes were the severity of delirium (Delirium Rating Scale, revised version‐98 (DRS‐R‐98)), the duration of delirium, and the length of hospital stay.Results:The overall incidence of postoperative delirium was 15.8%. The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1% and 16.5%, respectively (relative risk=0.91, 95% confidence interval (CI)=0.6–1.3); the mean highest DRS‐R‐98 score±standard deviation was 14.4±3.4 and 18.4±4.3, respectively (mean difference 4.0, 95% CI=2.0–5.8;P<.001); delirium duration was 5.4 versus 11.8 days, respectively (mean difference 6.4 days, 95% CI=4.0–8.0;P<.001); and the mean number of days in the hospital was 17.1±11.1 and 22.6±16.7, respectively (mean difference 5.5 days, 95% CI=1.4–2.3;P<.001). No haloperidol‐related side effects were noted.Conclusion:Low‐dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium. It did have a positive effect on the severity and duration of delirium. Moreover, haloperidol reduced the number of days patients stayed in the hospital, and the therapy was well tolerated.
Relationship Between Serum Insulin‐Like Growth Factor‐1 Levels and Alzheimer's Disease and Vascular Dementia
Authors: Watanabe Takuya , Miyazaki Akira , Katagiri Takashi , Yamamoto Hideki , Idei Tsunenori , Iguchi Takashi 
Published: December 2009

Objectives: To determine whether decreased serum insulin‐like growth factor‐1 (IGF‐1) levels could be a risk factor for dementia in older people.Design: Case control study.Setting: Showa University Karasuyama Hospital, Tokyo, Japan.Participants: A total of 436 Japanese elderly subjects: 106 patients with Alzheimer's disease (AD), 103 patients with vascular dementia (VaD), and 227 age‐matched controls without dementia.Mesurements: Serum concentrations of IGF‐1 and atherogenic lipoproteins, carotid artery intima‐media thickness (IMT), and plaques were determined.Results: Mini‐Mental State Examination (MMSE) scores were positively correlated with serum IGF‐1 concentrations as well as mean blood pressure or body mass index and were negatively correlated with age, serum low‐density lipoprotein cholesterol and lipoprotein(a) concentrations, and carotid IMT. Serum IGF‐1 concentrations had a significant inverse correlation with carotid IMT. Analysis across the IGF‐1 quartiles revealed a threshold effect of low IGF‐1 on MMSE score in subjects with the IGF‐1 levels of 140 ng/mL or less (50% percentile) versus those with IGF‐1 levels greater than 140 ng/mL. Multiple logistic regression concerning AD and VaD retained serum IGF‐1 concentrations of 140 ng/mL or less and carotid IMT of 0.9 mm or more. Patients with AD and VaD had significantly lower IGF‐1 concentrations and greater mean IMT than nondemented controls.Conclusion: These results suggest that decreased serum IGF‐1 level and the progression of carotid atherosclerosis could play a role as independent risk factors for dementia.
Intraindividual Variability and the Effect of Acute Illness on Immune Senescence Markers
Authors: High Kevin P. , Trader Melissa , Pahor Marco , Loeb Mark 
Published: December 2009

Objectives: To determine the intraindividual variability and effect of acute illness on two markers of immune senescence.Design: Cohort study with repeated measures.Setting: Clinical research center and emergency department at two academic medical centers.Participants: Seventy‐three subjects aged 65 and older enrolled in three groups: chronic underlying conditions but no acute illness, acutely ill with infection (community‐acquired pneumonia), and acutely ill without infection.Measurements: CD16 density on polymorphonuclear neutrophils (PMNs) and the proportion of CD8+ T cells that express CD28 determined twice in the nonacutely ill group and three times (Days 0, 30, and 60) in the acute illness groups.Results: In the nonacutely ill group, PMN CD16 density demonstrated wide intraindividual variation, but there was a strong correlation for repeated measures of the percentage of CD8+ T cells expressing CD28 (correlation coefficient (r)=0.77, P<.001). Acute illness markedly affected both measures, regardless of whether the illness was due to infection; there was no correlation between measures obtained on Day 0 versus Day 30 for either immune marker. In contrast, a strong correlation existed between Day 30 and Day 60 values, particularly for CD8+/CD28+ percentage (r=0.58–0.86; P=.006 to <.001).Conclusion: The percentage of CD8+ T cells that express CD28 is a highly reproducible marker of immune senescence. Although acute illness affects this marker, 30 to 60 days of convalescence appears adequate for it to return to baseline.
Identification of Dementia Cases in the Community: A Brazilian Experience
Authors: Ramos‐Cerqueira Ana Teresa A. , Torres Albina R. , Crepaldi André L. , Oliveira Nair I. L. , Scazufca Márcia , Menezes Paulo R. , Prince Martin 
Published: December 2009

Objectives: To describe the application in Brazil of a simple, low‐cost procedure, developed in India by the 10/66 Dementia Research Group, for the identification of dementia cases in the community.Design: Community‐based dementia case‐finding method.Setting: Piraju, São Paulo, Brazil.Participants: Twenty‐five community health workers were trained to identify dementia cases in 2,222 people aged 65 and older in Piraju, a Brazilian town with 27,871 inhabitants.Measurements: After the training, the health workers prepared a list of possible cases that afterward an experienced psychiatrist clinically evaluated, according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV), criteria and the Clinical Dementia Rating.Results: Of the 72 cases that were clinically assessed, 45 met the DSM‐IV diagnostic criteria for dementia. Therefore, the positive predictive value of this case finding method was 62.5%; the estimated frequency of dementia was 2%. Most of the confirmed cases met clinical criteria for Alzheimer's disease and vascular dementia.Conclusion: This simple method was appropriate to identify cases of dementia in the general population and can possibly be extended to other developing countries with limited resources to be applied in health programs.
Indwelling Device Use and Antibiotic Resistance in Nursing Homes: Identifying a High‐Risk Group
Authors: Mody Lona , Maheshwari Shweta , Galecki Andrzej , Kauffman Carol A. , Bradley Suzanne F. 
Published: December 2009

OBJECTIVES: To quantify the relationship between indwelling devices (urinary catheters, feeding tubes, and peripherally inserted central catheters) and carriage of antimicrobial‐resistant pathogens in nursing home residents.DESIGN: Cross‐sectional.SETTING: Community nursing home in Southeast Michigan.PARTICIPANTS: Residents with indwelling devices (n=100) and randomly selected control residents (n=100) in 14 nursing homes.MEASUREMENTS: Data on age, functional status, and Charlson comorbidity score were collected. Samples were obtained from nares, oropharynx, groin, wounds, perianal area, and enteral feeding tube site. Standard microbiological methods were used to identify methicillin‐resistant Staphylococcus aureus (MRSA), vancomycin‐resistant enterococci (VRE), and ceftazidime‐resistant (CTZ‐R) gram‐negative bacteria (GNB).RESULTS: Use of indwelling devices was associated with colonization with MRSA at any site (odds ratio (OR)=2.0, P=.04), groin (OR=4.8, P=.006), and perianal area (OR=3.6, P=.01) and CTZ‐R GNB at any site (OR=5.6, P=.003). Use of enteral feeding tubes was associated with MRSA colonization in the oropharynx (OR=3.3, P=.02).CONCLUSION: Use of indwelling devices is associated with greater colonization with antimicrobial‐resistant pathogens. This study serves as an initial step in defining a high‐risk group that merits intensive infection control efforts.
The Effect of Age on Outcomes of Sling Surgery for Urinary Incontinence
Authors: Anger Jennifer T. , Litwin Mark S. , Wang Qin , Pashos Chris L. , Rodríguez Larissa V. 
Published: December 2009

OBJECTIVES: To measure the effect of patient age on outcomes of sling surgery for stress urinary incontinence.DESIGN: Analysis of Medicare claims data.SETTING: Analysis of the 1999 to 2001 Medicare Public Use Files provided by the Centers for Medicare and Medicaid Services on a 5% national random sample of beneficiaries.PARTICIPANTS: Women who underwent sling procedures between July 1, 1999, and December 31, 2000, were identified according to Common Procedural Terminology, Fourth Edition, code 57288 (sling operation for stress incontinence). Subjects were tracked for 6 months before surgery to identify preoperative comorbidities and for 12 months after surgery to assess short‐term complications. Subjects were stratified for analysis at age 75.MEASUREMENTS: Bivariate analyses were conducted with patients stratified at age 75, and multivariate analyses were also conducted to identify the independent effects of patient age and comorbidities on outcomes.RESULTS: A total of 1,356 procedures were performed during the 18‐month index period. This extrapolates to 27,120 procedures in all Medicare beneficiaries. At 1 year after surgery, overall outcomes in younger women (aged 65–74) were significantly better than in older women with respect to postoperative urge incontinence (20.0% vs 12.6%), treatment failure (10.5% vs 7.2%), and outlet obstruction (10.5% vs 6.6%). Older age and greater comorbidity were associated with greater risk of nonurological events (e.g., pulmonary embolism and cardiac events).CONCLUSION: Women aged 75 and older are more likely to experience postoperative urge incontinence, treatment failure, and outlet obstruction after sling surgery. Older age and comorbidities were associated with higher rates of nonurological complications.
Discussion of Depression in Follow‐Up Medical Visits with Older Patients
Authors: Adelman Ronald D. , Greene Michele G. , Friedmann Erika , Cook Mary Ann 
Published: December 2009

OBJECTIVES: To determine the frequency of discussion about depression in follow‐up medical visits of older patients, who initiates these discussions, the quality of responsiveness of physicians and patients in these discussions, and patient and physician characteristics that influence these discussions.DESIGN: Convenience sample of 482 audiotaped follow‐up visits.SETTING: Three community‐based practice sites.PARTICIPANTS: Three hundred seventy‐six community‐dwelling older patients without dementia and 43 primary care physicians.MEASUREMENTS: Audiotapes were analyzed using the Multi‐Dimensional Interaction Analysis system to determine the content and process of medical conversations; patients completed Medical Outcomes Study 36‐item Short Form Survey questionnaires immediately after the visit.RESULTS: Depression was discussed in 7.3% of medical visits; physicians raised this topic in 41% of visits, patients raised it in 48% of visits, and accompanying persons raised it in 10% of visits. Visits were longer when the topic of depression was discussed. Depression was raised almost exclusively in the first 2.5 years of the patient–physician relationship. Physicians with some geriatric training were more likely to discuss depression, and these visits were shorter than visits to physicians without geriatric training.CONCLUSION: Depression was raised infrequently in follow‐up visits. The high prevalence of depression in older people and the associated mortality merit discussion of depression early and later in the patient–physician relationship. Although visits were longer when depression was discussed, physicians with some geriatric training were more likely to raise depression, and more time‐efficient when they did so, than physicians without geriatric training.
Sleep‐Disordered Breathing and Cognition in Older Women
Authors: Spira Adam P. , Blackwell Terri , Stone Katie L. , Redline Susan , Cauley Jane A. , Ancoli‐Israel Sonia , Yaffe Kristine 
Published: December 2009

OBJECTIVES: To investigate the association between objectively measured sleep‐disordered breathing (SDB) and cognitive impairment in community‐dwelling older women and to determine whether the apolipoprotein E (APOE) ɛ4 allele modifies this association.DESIGN: Cross‐sectional.SETTING: Participants' homes and two sites of the Study of Osteoporotic Fractures (SOF).PARTICIPANTS: Four hundred forty‐eight women with a mean age±standard deviation (SD) of 82.8±3.4.MEASUREMENTS: Participants completed the Mini‐Mental State Examination (MMSE), Trail Making Test Part B (Trails B), and polysomnography (PSG). SDB indices were the apnea–hypopnea index (AHI), the central apnea index (CAI), and oxygen saturation (SaO2) nadir less than 80%. APOE ɛ4 was determined for a subset of 242 women. Cognitive impairment was defined as 1.5 SDs or more from the sample mean on either cognitive test (MMSE or Trails B).RESULTS: All SDB indices were associated with cognitive impairment according to the MMSE (AHI (per SD, odds ratio (OR)=1.4, 95% confidence interval (CI)=1.03–1.9), AHI of ≥30 (OR=3.4, 95% CI=1.4–8.1), SaO2 nadir <80% (OR=2.7, 95% CI=1.1–6.6), and CAI (per SD, OR=1.4, 95% CI=1.1–1.7)). Weaker, nonsignificant associations emerged between SDB and Trails B. In women who completed genotyping, each SD increase in AHI was associated with 70% greater odds of cognitive impairment according to the MMSE (OR=1.7, 95% CI=1.2–2.6). Women with the ɛ4 allele had a nearly five times greater odds of impairment (per SD, OR=4.6, 95% CI‐1.0–20.7); the association was smaller and nonsignificant in women without the ɛ4 allele (per SD, OR=1.5, 95% CI‐0.9–2.4; P for interaction=.08).CONCLUSION: SDB is an important risk factor for cognitive impairment in older women, especially those with the APOE ɛ4 allele. Mechanisms linking these disorders need to be identified.
Transitioning Residents from Nursing Facilities to Community Living: Who Wants to Leave?
Authors: Nishita Christy M. , Wilber Kathleen H. , Matsumoto Saki , Schnelle John F. 
Published: December 2009

OBJECTIVES: To examine nursing facility residents' or their legal proxies' perspectives on transitioning out of nursing facilities by assessing residents' perceptions of their ability to live more independently, their preferences regarding leaving the facility, and the feasibility of transitioning with community support.DESIGN: Analysis of survey findings from the California Nursing Facility Transition Screen (CNFTS).SETTING: Eight nursing facilities in southern California.PARTICIPANTS: All chronic maintenance, long‐stay residents receiving Medi‐Cal (California's Medicaid program) were eligible for the study (n=218). Of these, 121 (56%) self‐consenting residents or legal proxies were interviewed. No presumptions were made as to which residents were appropriate candidates for transition based on health or functional capacity.MEASUREMENTS: CNFTS contains 27 open‐ and closed‐ended questions on preference, ability, and feasibility of transitioning.RESULTS: Twenty‐three percent of residents and proxies believed that the resident had the ability to transition; 46% indicated a preference to transition; and after discussing potential living arrangements and services, 33% thought that transitioning would be feasible. Of those who consented to allow access to their Minimum Data Set 2.0 (MDS) information (n=41; 34% of the sample), agreement in the assessment of preference was found in 39% of cases.CONCLUSION: Transition decisions are complex and include preference, as well as perceptions of the resident's ability to live in a more independent setting and the feasibility of transitioning. Compared with the MDS, the screen identified a higher proportion of residents who want to transition, suggesting that a systematic approach to assessing the complex decision to transition is needed.
Fecal Incontinence in Elderly Koreans
Authors: Joh Hee‐Kyung , Seong Moo‐Kyung , Oh Seung‐Won 
Published: December 2009

OBJECTIVES: To estimate the prevalence and correlates of fecal incontinence (FI) and its effect on quality of life in ambulatory elderly people in Korea.DESIGN: Cross‐sectional, convenience sample–based survey.SETTING: Twenty‐seven senior citizen centers and two health clinics in two cities of Korea.PARTICIPANTS: Nine hundred eighty‐one relatively healthy and ambulatory community‐dwelling people aged 60 and older.MEASUREMENTS: Data were collected through in‐person interviews with a structured questionnaire. Multivariate logistic regression analysis was used to determine independent risk factors for FI.RESULTS: The prevalence of FI was 15.5%. FI was significantly associated with lower quality of life (Medical Outcomes Study 36‐item Short‐Form Survey) for physical and mental health. In men, FI was significantly associated with urinary incontinence (odds ratio (OR)=4.89, 95% confidence interval (CI)=2.45–9.77), hemorrhoids (OR=4.66, 95% CI=1.67–12.97), and poor self‐perceived health status (P for trend=.02). In women, FI was associated with urinary incontinence (OR=2.91, 95% CI=1.76–4.81), diabetes mellitus (OR=2.04, 95% CI=1.24–3.37), hemorrhoids (OR=2.99, 95% CI=1.31–6.83), and infrequent dietary fiber intake (P for trend=.02).CONCLUSION: FI is prevalent in elderly Koreans and has a profound effect on quality of life. Physicians should closely screen for FI in elderly patients with certain risk factors and evaluate to control these potentially preventable or modifiable factors.
Efficient generation of clinical‐grade genetically modified dendritic cells for presentation of multiple tumor‐associated proteins
Authors: Garritsen Henk S.P. , Macke Lars , Meyring Wilhelm , Hannig Horst , Pägelow Ute , Wörmann Bernhard , Geffers Robert , Dittmar Kurt E.J. , Lindenmaier Werner 
Published: December 2009

BACKGROUND: Dendritic cells (DCs) play a central role in the initiation and regulation of immune responses. DCs for clinical applications can be generated with high yield from leukapheresis products. Using adenoviral transduction we genetically modified human DCs to produce and present melanoma‐associated antigens. Coexpression of green fluorescent protein and epitope tags were used to monitor genetic modification. Generation, genetic modification, and cryoconservation of gene modified human DCs on a clinical scale in a closed system is feasible.STUDY DESIGN AND METHODS: CD14‐positive monomuclear cells were isolated from leukapheresis products of HLA‐A* 0201 positive voluntary blood donors using immunomagnetic beads. Selected cells were cultivated for 7 days. Adenovirus transduction was optimal on Day 4. Maturation was induced on Day 5. Mature DC were aliquoted and cryoconserved on Day 7. Quality control was performed using flow cytometry, expression profiling, and functional assays (ELISPOT, CBA).RESULTS: We were able to generate sufficient genetically modified mature DCs in serum‐free cultures that could be stored by cryopreservation. The use of a closed system facilitated development of methods for standardized production of clinically applicable genetically modified DCs. The adenoviral transduction system allowed simultaneous and flexible expression of tumor‐associated antigens for prolonged presentation of multiple epitopes.CONCLUSION: The feasibility of a closed‐bag system for the cultivation of genetically modified human DCs is shown. The immature DCs were genetically modified by recombinant replication‐deficient adenoviruses to express multiple epitopes of tumor‐associated proteins and then differentiated to mature antigen‐presenting DCs.