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1.
Osteoporos Int ; 33(1): 293-298, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34341833

ABSTRACT

Fracture prevention in cognitively impaired individuals is lacking. This work highlights the benefits of zoledronic acid on bone health in cognitively impaired older adults. Demonstrating benefits of therapy may increase treatment uptake and reduce fracture risk in this group. INTRODUCTION: Osteoporosis has detrimental consequences for frail older adults. The effects on those with both osteoporosis and cognitive impairment are compounded due to increased risk of falls and changes in mobility, both of which can lead to fracture. However, there are limited data on treatment benefits for osteoporotic individuals with cognitive impairment. METHODS: This post hoc, secondary analysis of data from a randomized, double-blind, placebo-controlled clinical trial of single-dose zoledronic acid included 179 women age ≥ 65 years residing in assisted living facilities or nursing homes, 43 of whom had mild to severe cognitive impairment. We assessed bone mineral density (BMD) of the total hip, femoral neck, and lumbar spine by dual-energy x-ray absorptiometry and serum bone turnover markers (C-terminal telopeptide of type I collagen and procollagen type I N propeptide) at 6 and 12 months. RESULTS: In participants with cognitive impairment, those who received zoledronic acid had 4.3% greater BMD at the total hip (p=.005) and 5.3% greater BMD at the femoral neck (p<.001) after 12 months compared to those in the placebo group. Bone turnover markers demonstrated significant decreases at 6 months in those with cognitive impairment who received active treatment compared to the placebo group. Improvements in bone health measures with zoledronic acid were similar to those seen in participants without cognitive impairment. CONCLUSION: Zoledronic acid improves bone health in frail older women with cognitive impairment similar to those without impairment. Further studies are warranted to assess the benefit for fracture reduction in this undertreated population.


Subject(s)
Bone Density Conservation Agents , Cognitive Dysfunction , Aged , Bone Density , Bone Density Conservation Agents/therapeutic use , Bone Remodeling , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Collagen Type I , Diphosphonates/therapeutic use , Double-Blind Method , Female , Femur Neck , Humans , Imidazoles/therapeutic use , Zoledronic Acid
2.
Osteoporos Int ; 28(4): 1347-1353, 2017 04.
Article in English | MEDLINE | ID: mdl-27975302

ABSTRACT

We examined the impact of daily supplementation on vitamin D deficiency, function, and falls in female long-term care residents. Initial vitamin D deficiency was associated with greater functional decline and increased fall risk despite guideline-recommended supplementation, highlighting the importance of preventing vitamin D deficiency in frail elderly. INTRODUCTION: Institute of Medicine (IOM) guidelines recommend 800 IU vitamin D daily for older adults and maintaining serum 25-hydroxyvitamin D [25(OH) D] above 20 ng/ml for optimal skeletal health. The adequacy of IOM guidelines for sustaining function and reducing falls in frail elderly is unknown. METHODS: Female long-term care residents aged ≥65 enrolled in an osteoporosis clinical trial were included in this analysis (n = 137). Participants were classified based on baseline 25(OH) D levels as deficient (<20 ng/ml, n = 26), insufficient (20-30 ng/ml, n = 40), or sufficient (>30 ng/ml, n = 71). Deficient women were provided initial vitamin D repletion (50,000 IU D3 weekly for 8 weeks). All were supplemented with 800 IU vitamin D3 daily for 24 months. Annual functional assessments included Activities of Daily Living (ADLs), Instrumental ADL (IADL), physical performance test (PPT), gait speed, cognition (SPMSQ), and mental health (PHQ-9). We used linear mixed models for analysis of functional measures and logistic regression for falls. RESULTS: Daily supplementation maintained 25(OH) D levels above 20 ng/ml in 95% of participants. All groups demonstrated functional decline. Women initially deficient had a greater decline in physical function at 12 (IADL -2.0 ± 0.4, PPT -3.1 ± 0.7, both p < 0.01) and 24 months (IADL -2.5 ± 0.6, ADL -2.5 ± 0.6, both p < 0.01), a larger increase in cognitive deficits at 12 months (1.7 ± 0.4: p = 0.01) and more fallers (88.5%, p = 0.04) compared to those sufficient at baseline, despite supplementation to sufficient levels. CONCLUSIONS: IOM guidelines may not be adequate for frail elderly. Further study of optimal 25(OH) D levels for maintaining function and preventing falls is needed.


Subject(s)
Accidental Falls , Cholecalciferol/therapeutic use , Dietary Supplements , Vitamin D Deficiency/physiopathology , Accidental Falls/prevention & control , Activities of Daily Living , Aged , Aged, 80 and over , Cholecalciferol/administration & dosage , Drug Administration Schedule , Female , Frail Elderly , Gait , Homes for the Aged , Humans , Parathyroid Hormone/blood , Practice Guidelines as Topic , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/drug therapy
3.
J Urol ; 167(2 Pt 1): 578-84; discussion 584-5, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11792922

ABSTRACT

PURPOSE: Urge incontinence, which is the predominant type of geriatric incontinence, is generally attributed to detrusor overactivity. However, detrusor overactivity is present in up to half of continent elderly individuals. We postulated that detrusor overactivity associated with urge incontinence would be more severe but there are no established criteria for judging severity. Using urge incontinence frequency as a yardstick and controlling for nonurodynamic contributing factors we sought intrinsic lower urinary tract parameters that reflect detrusor overactivity severity. We postulated that parameters in 1 or more of 5 domains would be important, namely characteristics of uninhibited contraction, bladder capacity, bladder proprioception, detrusor contractility and sphincter adequacy. MATERIALS AND METHODS: We analyzed data on 79 community dwelling incontinent individuals older than 60 years old. All subjects had urge incontinence on a 4-day voiding record and underwent multichannel videourodynamics. We examined the associations of urge incontinence frequency with the postulated key factors. RESULTS: Multivariable analysis revealed that 24-hour urine output and functional bladder capacity consistently predicted urge incontinence frequency. Bladder proprioception was significant in some models. Uninhibited contraction pressure was another predictor. Surprisingly higher uninhibited contraction pressure was associated with lower urge incontinence frequency. This negative correlation was more pronounced in a subgroup with a less adequate sphincter but absent in those with good sphincter function, implying that low uninhibited contraction pressure does not necessarily indicate less severe detrusor overactivity but rather reflects sphincter inadequacy in many patients. Age was not independently associated with urge incontinence frequency. CONCLUSIONS: We identified functional bladder capacity as a measure of detrusor overactivity severity. The measure commonly used, namely uninhibited contraction pressure, is inappropriate because it is severely confounded by sphincter function, especially in older individuals. Furthermore, we confirmed that urine output, and possibly bladder sensation and sphincter strength modify the clinical manifestation of detrusor overactivity.


Subject(s)
Muscle Contraction/physiology , Muscle, Smooth/physiopathology , Urinary Bladder/physiopathology , Urinary Incontinence/physiopathology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Multivariate Analysis , Prospective Studies , Urodynamics
4.
J Urol ; 166(3): 1136-41, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11490312

ABSTRACT

PURPOSE: Although detrusor hyperactivity with impaired contractility is a common urodynamic finding in elderly subjects, to our knowledge its pathogenesis remains unknown. Biopsy studies indicate that subjects with detrusor hyperactivity and impaired contractility have ultrastructural evidence of dysjunction and degeneration patterns in isolated detrusor hyperactivity and impaired contractility, respectively. Based on the known cellular effects of estrogen we postulated that declines in ovarian hormone production may contribute to the pathogenesis of detrusor hyperactivity with impaired contractility. MATERIALS AND METHODS: Mature 13 to 14-month-old female Fisher 344 rats were studied 4 months after bilateral ovariectomy or sham surgery. Detrusor structure was evaluated by electron microscopy and contractility was evaluated by muscle strip studies. RESULTS: After bilateral ovariectomy detrusor smooth muscle decreased by 25% with a 12% decrease in the number of nucleated muscle profiles and degenerative changes in many axons. Muscle strips from bilaterally ovariectomized animals generated 40% to 50% less tension per strip in response to carbachol than strips of equal size from sham operated animals with no apparent change in muscarinic receptor affinity. CONCLUSIONS: Bilateral ovariectomy resulted in many changes of the degeneration ultrastructural pattern but in none of the characteristic features of the dysjunction pattern. Our results indicate that the mature rodent detrusor and its innervation are sensitive to prolonged ovarian hormonal deficiency, contributing to impaired contractility in rodents. Future studies are required to establish whether estrogen has a role in the degeneration ultrastructural pattern or impaired contractility in humans.


Subject(s)
Estrogens/physiology , Muscle Contraction , Muscle, Smooth/physiopathology , Ovariectomy , Urinary Bladder/physiopathology , Animals , Axons/pathology , Carbachol/pharmacology , Cholinergic Agonists/pharmacology , Female , Muscle, Smooth/drug effects , Muscle, Smooth/pathology , Rats , Rats, Inbred F344
5.
J Am Geriatr Soc ; 49(5): 516-22, 2001 May.
Article in English | MEDLINE | ID: mdl-11380742

ABSTRACT

OBJECTIVES: Delirium (or acute confusional state) affects 35% to 65% of patients after hip-fracture repair, and has been independently associated with poor functional recovery. We performed a randomized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture. DESIGN: Prospective, randomized, blinded. SETTING: Inpatient academic tertiary medical center. PARTICIPANTS: 126 consenting patients 65 and older (mean age 79 +/- 8 years, 79% women) admitted emergently for surgical repair of hip fracture. MEASUREMENTS: Detailed assessment through interviews with patients and designated proxies and review of medical records was performed at enrollment to ascertain prefracture status. Subjects were then randomized to proactive geriatrics consultation, which began preoperatively or within 24 hours of surgery, or "usual care." A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol. To ascertain study outcomes, all subjects underwent daily, blinded interviews for the duration of their hospitalization, including the Mini-Mental State Examination (MMSE), the Delirium Symptom Interview (DSI), and the Memorial Delirium Assessment Scale (MDAS). Delirium was diagnosed using the Confusion Assessment Method (CAM) algorithm. RESULTS: The 62 patients randomized to geriatrics consultation were not significantly different (P>.1) from the 64 usual-care patients in terms of age, gender, prefracture dementia, comorbidity, type of hip fracture, or type of surgical repair. Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively. A mean of 10 recommendations were made throughout the duration of the hospitalization, with 77% adherence by the orthopedics team. Delirium occurred in 20 /62 (32%) intervention patients, versus 32 / 64 (50%) usual-care patients (P =.04), representing a relative risk of 0.64 (95% confidence interval (CI) = 0.37-0.98) for the consultation group. One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group. There was an even greater reduction in cases of severe delirium, occurring in 7/ 60 (12%) of intervention patients and 18 / 62 (29%) of usual-care patients, with a relative risk of 0.40 (95% CI = 0.18-0.89). Despite this reduction in delirium, length of stay did not significantly differ between intervention and usual-care groups (median +/- interquartile range = 5 +/- 2 days in both groups), likely because protocols and pathways predetermined length of stay. In subgroup analyses, geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living (ADL) functional impairment. CONCLUSIONS: Proactive geriatrics consultation was successfully implemented with good adherence after hip-fracture repair. Geriatrics consultation reduced delirium by over one-third, and reduced severe delirium by over one-half. Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients.


Subject(s)
Delirium/etiology , Delirium/prevention & control , Geriatric Assessment , Geriatrics/methods , Hip Fractures/surgery , Postoperative Care/methods , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Preoperative Care/methods , Referral and Consultation , Activities of Daily Living , Aged , Aged, 80 and over , Algorithms , Delirium/classification , Delirium/diagnosis , Female , Humans , Incidence , Length of Stay/statistics & numerical data , Male , Mental Status Schedule , Postoperative Complications/classification , Postoperative Complications/diagnosis , Prospective Studies , Severity of Illness Index , Single-Blind Method , Surveys and Questionnaires
6.
J Womens Health Gend Based Med ; 10(2): 109-16, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11268296

ABSTRACT

Hormone replacement therapy (HRT) has been proposed for the prevention and treatment of many chronic conditions, ranging from osteoporosis, heart disease, urinary incontinence, and Alzheimer's disease. With the exception of osteoporosis, however, many of the suggested benefits remain controversial. Part of the controversy stems from the relative absence of randomized controlled trials, particularly those enrolling sufficient numbers of elderly women. We propose that another factor may also contribute, one that has been overlooked - failure to consider the variable endogenous estrogen status of elderly women. Highly variable levels of estrogens are present in nearly all postmenopausal women, even at advanced ages. Similar to other endocrine systems, estrogen deficiency and the need for its replacement are, therefore, likely to be relative rather than absolute. Recent studies indicate that elderly women who are less able to compensate for declining ovarian 17beta-estradiol production by adipose synthesis of estrone (E1) may be at greater risk for certain chronic conditions associated with relative estrogen deficiency. Because many markers of estrogen deficiency exhibit overlap between risk groups, their clinical usefulness as predictors of frailty, disability, and response to HRT has been limited. Future studies will need to focus not only on the use of highly variable circulating serum estrogen levels but also on markers of overall estrogenic effects at the level of individual target tissues (i.e., markers of bone turnover, karyopyknotic index on a vaginal wall smear). We propose that a clinical approach that takes into consideration the remarkable heterogeneity (physiological as well as psychological) of elderly women will enable us to approach the decision about HRT in a more individualized and possibly better targeted fashion.


Subject(s)
Decision Making , Estrogen Replacement Therapy , Estrogens/blood , Estrogens/deficiency , Patient Selection , Postmenopause/blood , Aged , Alzheimer Disease/etiology , Alzheimer Disease/prevention & control , Biomarkers/blood , Chronic Disease , Estrogen Replacement Therapy/adverse effects , Estrogen Replacement Therapy/methods , Estrogen Replacement Therapy/standards , Female , Forecasting , Humans , Life Expectancy , Osteoporosis, Postmenopausal/etiology , Osteoporosis, Postmenopausal/prevention & control , Predictive Value of Tests , Reproducibility of Results , Risk Factors , Urinary Incontinence/etiology , Urinary Incontinence/prevention & control
7.
J Public Health Policy ; 22(4): 415-28, 2001.
Article in English | MEDLINE | ID: mdl-11787307

ABSTRACT

Massachusetts tobacco control activists participated in focus groups to explore their knowledge, beliefs, and attitudes regarding international tobacco control. Initially, each of three focus groups ranked this issue at or near the bottom of important tobacco control issues. Participants ranked ten message concepts for their ability to motivate politically active Americans to contact a government representative about international tobacco issues. The top four message concepts dealt with deliberate marketing of cigarettes to children, dramatic increases in global mortality due to smoking, American hypocrisy in being the world's largest tobacco exporter, and use of overseas profits to finance youth-oriented marketing in the U.S. The rankings revealed little initial concern about U.S. diplomatic pressure to force foreign nations to open up their markets to American tobacco products. Yet during the subsequent discussion this was among the message concepts the generated the most outrage. This suggests that international tobacco control issues would resonate among U.S. opinion leaders once the facts were presented to them through a media advocacy campaign.


Subject(s)
Attitude to Health , Tobacco Industry/legislation & jurisprudence , Commerce/standards , Focus Groups , Government , Humans , International Cooperation , Mass Media , Massachusetts , Social Control Policies , Surveys and Questionnaires , United States
8.
J Urol ; 164(3 Pt 1): 698-701, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10953128

ABSTRACT

PURPOSE: We assessed the test-retest reliability of a 24, 48 and 72-hour micturition diary and pad test in patients referred for the evaluation of urinary incontinence and lower urinary tract symptoms. MATERIALS AND METHODS: We prospectively enrolled 109 patients referred for the evaluation of lower urinary tract symptoms in our multicenter study. Patients were requested to complete a 72-hour micturition diary and pad test, and repeat each test during a 1-week interval. The test-retest reliability of various parameters of the 72-hour micturition diary and pad test was analyzed and compared. Further analysis was done to compare the test-retest reliability of 24, 48 and 72-hour studies performed on the same days after a 1-week interval. Reliability was assessed by Lin's concordance correlation coefficient (CCC) with a cutoff value of 0.7 indicating test-retest reliability. RESULTS: Of the 109 patients 106 (97%) with a median age of 64 years completed the study. The number of pads and total weight gain appeared to be reliable measures of the 24, 48 and 72-hour pad tests. For the 24-hour diary the total number of incontinence episodes was a reliable measure, while the total number of voiding episodes was marginally reliable (mean CCC 0.785 and 0. 689, respectively). For the 48-hour diary the number of incontinence episodes and total number of voiding episodes were reliable measures (mean CCC 0.78 and 0.83, respectively), while for the 72-hour diary each parameter was highly reliable (CCC 0.86 and 0.826, respectively). However, an increased test period was associated with decreased patient compliance. CONCLUSIONS: The 24-hour pad test and micturition diary are reliable instruments for assessing the degree of urinary loss and number of incontinent episodes, respectively. Increasing test duration to 48 and 72 hours increases reliability but is associated with decreased patient compliance.


Subject(s)
Incontinence Pads , Medical Records , Urinary Incontinence/classification , Urination Disorders/classification , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Patient Compliance , Prospective Studies , Reproducibility of Results , Time Factors , Urination
9.
J Am Geriatr Soc ; 48(6): 618-24, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10855596

ABSTRACT

OBJECTIVE: To evaluate the role of delirium in the natural history of functional recovery after hip fracture surgery, independent of prefracture status. DESIGN: Prospective cohort study. SETTING: Orthopedic surgery service at a large academic tertiary hospital, with follow-up extending into rehabilitation hospitals, nursing homes, and the community. PARTICIPANTS: One hundred twenty-six consenting subjects older than 65 years (mean age 79 +/- 8 years, 79% women) admitted emergently for surgical repair of hip fracture. MEASUREMENTS: Detailed assessment at enrollment to ascertain prefracture status through interviews with the patient and designated proxy and review of the medical record. Interviews included administration of standardized instruments (Activities of Daily Living (ADL) Scale, Blessed Dementia Rating Scale, Delirium Symptom Interview) and assessment of ambulation, and prefracture living situation. Medical comorbidity, the nature of the hip fracture, and the surgical repair were obtained from the medical record. All subjects underwent daily interviews for the duration of the hospitalization, including the Mini-Mental State Examination and Delirium Symptom Interview, and delirium was diagnosed using the Confusion Assessment Methods algorithm. Patients and proxies were recontacted 1 and 6 months after fracture, and underwent interviews similar to those at enrollment to determine death, persistent delirium, decline in ADL function, decline in ambulation, or new nursing home placement. RESULTS: Delirium occurred in 52/126 (41%) of patients, and persisted in 20/52 (39%) at hospital discharge, 15/52 (32%) at 1 month, and 3/52 (6%) at 6 months. Patients aged 80 years or older, and those with prefracture cognitive impairment, ADL functional impairment, and high medical comorbidity were more likely to develop delirium. However, after adjusting for these factors, delirium was still significantly associated with outcomes indicative of poor functional recovery 1 month after hip fracture: ADL decline (odds ratio (OR) = 2.6; 95% confidence interval (95% CI), 1.1- 6.1), decline in ambulation (OR = 2.6; 95% CI, 1.03-6.5), and death or new nursing home placement (OR = 3.0; 95% CI, 1.1-8.4). Patients whose delirium persisted at 1 month had worse outcomes than those whose delirium had resolved. CONCLUSIONS: Delirium is common, persistent, and independently associated with poor functional recovery 1 month after hip fracture even after adjusting for prefracture frailty. Further research is necessary to identify the mechanisms by which delirium contributes to poor functional recovery, and to determine whether interventions designed to prevent or reduce delirium can improve recovery after hip fracture.


Subject(s)
Activities of Daily Living , Delirium/etiology , Hip Fractures/rehabilitation , Aged , Aged, 80 and over , Cognition Disorders/complications , Female , Hip Fractures/complications , Hip Fractures/diagnosis , Hip Fractures/mortality , Humans , Length of Stay , Male , Prognosis , Prospective Studies , Risk Factors , United States/epidemiology , Walking
10.
Curr Opin Lipidol ; 11(2): 167-77, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10787179

ABSTRACT

Major advances in our understanding of how endothelial cells sense and respond to haemodynamic forces and, more specifically, to fluid shear stress have been achieved during the past 3 years. These include definition of potential shear stress receptors and multiple signalling pathways that mediate shear stress regulation of gene expression. A few studies have also pointed to the unique effects of complex shear stress on endothelial activation, thus leading to better understanding of the mechanisms that lead to the development of atherosclerosis.


Subject(s)
Arteriosclerosis/metabolism , Endothelium, Vascular/metabolism , Signal Transduction , Stress, Mechanical , Arteriosclerosis/genetics , Humans , Models, Biological , Transcription Factors/metabolism , Transcription, Genetic
11.
J Urol ; 163(4): 1216-8, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10737500

ABSTRACT

PURPOSE: We report voiding cystourethrography findings associated with urge incontinence in elderly women. MATERIALS AND METHODS: Two observers jointly reviewed voiding cystourethrograms of 50 cognitively intact and mobile elderly female participants in a drug trial for urge incontinence and 19 continent volunteers. Multichannel urodynamic testing was performed in all subjects. Bladder wall trabeculation and diverticula, cystocele and vesicoureteral reflux were noted. Maximal bladder capacity, post-void residual, and history of bladder suspension and hysterectomy were obtained from clinical records. RESULTS: Of the incontinent women 35 (70%) had trabeculation, which was mild in 30 (60%) and moderate in 5 (10%), and 41 (82%) had cystocele, which was mild in 23 (46%), moderate in 15 (30%) and severe in 3 (6%). Maximal bladder capacity ranged from less than 100 to more than 900 cc, and was greater than 500 in 37 incontinent women (74%). Of the continent women 16 (84%) had smooth bladders, 2 had mild (11%) and 1 had moderate (5%) trabeculation, and 11 (58%) had cystocele, which was mild in 8 (42%) and moderate in 3 (16%). In 7 continent women maximal bladder capacity was greater than 500 cc (37%). Differences between the 2 groups in regard to bladder wall trabeculation, maximal bladder capacity and presence of cystocele were significant at p<0.05. CONCLUSIONS: Large bladder capacity, bladder wall trabeculation and small to moderate cystocele on voiding cystourethrography are associated with urge incontinence in the elderly female population.


Subject(s)
Urinary Incontinence/diagnostic imaging , Age Factors , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Radiography , Retrospective Studies , Urethra/diagnostic imaging , Urinary Bladder/diagnostic imaging , Urinary Incontinence/physiopathology , Urination
12.
Mol Diagn ; 4(3): 219-32, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10553022

ABSTRACT

BACKGROUND: The polymorphic cell adhesion molecule CD44 exists as a family of proteins generated by extensive alternative splicing of the CD44 pre-messenger RNA and marked posttranslational modification. The differential expression of CD44 isoforms in a variety of human cancers has been proposed to influence tumorigenesis and metastasis. In this study, CD44 gene expression was analyzed in primary and metastatic tumors and in cell lines derived from tumors that affect the central nervous system (CNS), including tumors metastatic to the spine. MATERIALS AND METHODS: Fifty-four samples were subjected to semiquantitative reverse-transcriptase polymerase chain reaction with CD44-specific primers and hybridized individually with probes specific for the CD44 variant (CD44v) exons v3 to v10. RESULTS: Compared with CD44v-positive breast cancer cell lines and CD44v-negative normal brain tissue, CD44v expression was weak in primary brain tumors and cell lines derived from normal brain and tumor tissue. However, high levels of isoforms encoding multiple-variant exons were shown in all metastatic brain tumors. In contrast, tumors metastatic to the spine were virtually negative for CD44v expression. Several rare CD44 isoforms composed of single-variant exons v3, v4, v6, or v9 were identified in primary brain tumors and may reflect their invasive potential or culturability in vitro. CONCLUSION: These data suggest differential expression of CD44v may substantially influence the end-organ site of metastasis for tumor cells destined for the CNS.


Subject(s)
Antigens, Neoplasm/genetics , Central Nervous System Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Hyaluronan Receptors/genetics , Protein Isoforms/genetics , RNA Splicing , Antigens, Neoplasm/biosynthesis , Astrocytoma/genetics , Astrocytoma/metabolism , Astrocytoma/pathology , Biomarkers, Tumor , Blotting, Southern , Breast Neoplasms/immunology , Carcinoma/genetics , Carcinoma/metabolism , Carcinoma/secondary , Cell Adhesion , Central Nervous System Neoplasms/metabolism , Central Nervous System Neoplasms/pathology , Central Nervous System Neoplasms/secondary , Chondrosarcoma/genetics , Chondrosarcoma/metabolism , Chondrosarcoma/pathology , DNA, Complementary/genetics , Ependymoma/genetics , Ependymoma/metabolism , Ependymoma/pathology , Exons/genetics , Female , Glioblastoma/genetics , Glioblastoma/metabolism , Glioblastoma/pathology , Humans , Hyaluronan Receptors/biosynthesis , Male , Melanoma/genetics , Melanoma/metabolism , Meningeal Neoplasms/genetics , Meningeal Neoplasms/metabolism , Meningeal Neoplasms/pathology , Meningioma/genetics , Meningioma/metabolism , Meningioma/pathology , Neoplasm Metastasis , Organ Specificity , Protein Isoforms/biosynthesis , RNA Precursors/metabolism , RNA, Neoplasm/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured
13.
J Am Geriatr Soc ; 47(8): 989-94, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10443861

ABSTRACT

OBJECTIVE: To develop a condition-specific measure for assessing the impact of urge urinary incontinence (UI) on the quality of life (QoL) of older persons. DESIGN: A 32-item Urge Impact Scale (URIS) was drafted using content area data from focus groups composed of urge incontinent older persons. Pilot testing in 21 urge incontinent persons (mean age 67.7 years) resulted in the elimination of eight items by internal consistency, skew, and patient response criteria. The resulting scale (URIS-24) was tested for reliability (internal consistency and test-retest correlation) and construct validity (correlation with UI severity from voiding records) in a separate group of 27 urge incontinent persons (89% women, mean age 72 years). Factor analysis of URIS-24 data from the combined 48 persons was used to explore the conceptual structure underlying urge UI-related QoL. SETTING: University-affiliated community-based practice and tertiary hospital. PARTICIPANTS: Community-dwelling women and men, older than age 60 and with urge incontinence at least twice weekly, recruited from newspaper, newsletter, and radio advertisements. RESULTS: Cronbach's alpha for URIS-32 was 0.84, and for URIS-24 it was 0.94. When administered (mean +/- standard deviation) 9.2 +/- 5.1 days apart, URIS-24 had good test-retest reliability for total scores (interclass coefficient = .88, concordance coefficient = .88), and individual item scores at time 2 were within 1 point (on a 5-category Likert scale) of time 1 answers for 89% of responses. URIS-24 scores had modest but nearly significant correlation with the number of UI episodes (r = -0.39, P = .05). Factor analysis revealed a three component structure corresponding to psychological burden, perception of personal control, and self concept. CONCLUSIONS: The URIS-24 is an internally-consistent, highly reproducible tool for the assessment of the QoL impact of urge UI on older persons. It can be used to evaluate QoL impact by specific items as well as by overall score. Compared with other UI-specific QoL measures, the URIS-24 had similar or superior internal consistency, test-retest reliability, and validity, but it is the first measure designed and tested specifically for older persons with urge UI. These results also highlight the multifactorial structure of urge UI-related QoL and the importance of its psychological dimensions.


Subject(s)
Quality of Life , Urinary Incontinence/psychology , Aged , Confidence Intervals , Cost of Illness , Factor Analysis, Statistical , Female , Focus Groups , Humans , Internal-External Control , Male , Middle Aged , Pilot Projects , Psychometrics , Reproducibility of Results , Self Concept , Sickness Impact Profile , Urinary Incontinence/physiopathology
14.
Arterioscler Thromb Vasc Biol ; 19(8): 1825-34, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10446060

ABSTRACT

The vascular endothelium is exposed to a spectrum of fluid mechanical forces generated by blood flow; some of these, such as fluid shear stress, can directly modulate endothelial gene expression. Previous work by others and in our laboratory, using an in vitro uniform laminar shear stress model, has identified various shear stress response elements (SSREs) within the promoters of certain endothelial genes that regulate their expression by interacting with various transcription factors, including nuclear factor-kappaB (NF-kappaB), early growth response-1 (Egr-1), and activator protein-1 (AP-1, composed of c-Jun/c-Jun and c-Jun/c-Fos protein dimers). In the current study, we have examined the topographical patterns of NF-kappaB, Egr-1, c-Jun, and c-Fos activation in a specially designed in vitro disturbed laminar shear stress model, which incorporates regions of significant spatial shear stress gradients similar to those found in atherosclerosis-prone arterial geometries in vivo (eg, arterial bifurcations, curvatures, ostial openings). Using newly developed quantitative image analysis techniques, we demonstrate that endothelial cells subjected to disturbed laminar shear stress exhibit increased levels of nuclear localized NF-kappaB, Egr-1, c-Jun, and c-Fos, compared with cells exposed to uniform laminar shear stress or maintained under static conditions. In addition, individual cells display a heterogeneity in responsiveness to disturbed flow, as measured by the amount of NF-kappaB, Egr-1, c-Jun, and c-Fos in their nuclei. This differential regulation of transcription factor expression by disturbed versus uniform laminar shear stress indicates that regional differences in blood flow patterns in vivo-in particular, the occurrence of spatial shear stress gradients-may represent important local modulators of endothelial gene expression at anatomic sites predisposed for atherosclerotic development.


Subject(s)
Endothelium, Vascular/cytology , Immediate-Early Proteins , Transcription Factors/metabolism , DNA-Binding Proteins/metabolism , Early Growth Response Protein 1 , Endothelium, Vascular/chemistry , Fetal Blood , Hemorheology , Humans , Image Interpretation, Computer-Assisted , NF-kappa B/metabolism , Nuclear Proteins/blood , Proto-Oncogene Proteins c-fos/metabolism , Proto-Oncogene Proteins c-jun/metabolism , Stress, Mechanical , Umbilical Veins
15.
J Vasc Surg ; 29(6): 1104-51, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10359945

ABSTRACT

The following extended abstracts were presented at the Research Initiatives in Vascular Disease Conference, Movers and Shakers in the Vascular Tree-Hemodynamic and Biomechanical Factors in Blood Vessel Pathology, sponsored by The Lifeline Foundation and the Cardiovascular & Interventional Radiology Research and Educational Foundation; jointly sponsored by the International Society for Cardiovascular Surgery, North American Chapter, The Society for Vascular Surgery, and The Society of Cardiovascular and Interventional Radiology; in cooperation with the National Institutes of Health-National Heart, Lung &Blood Institute on Mar 11-12, 1999, in Bethesda, Md.

17.
J Gen Intern Med ; 13(9): 621-3, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9754518

ABSTRACT

To determine whether delirium can be diagnosed by telephone, we interviewed 41 subjects aged 65 years or older 1 month after repair of hip fracture, first by telephone and then face-to-face. Interviews included the modified telephone Mini-Mental State Examination and the Delirium Symptom Interview. Delirium was diagnosed using the Confusion Assessment Method diagnostic algorithm, and the telephone results were compared with the face-to-face results (the "gold standard"). Of 41 subjects, 6 were delirious by face-to-face assessment; all 6 were delirious by telephone (sensitivity 1.00). Of 35 patients not delirious by face-to-face assessment, 33 patients were not delirious by telephone (specificity = 0.94). We conclude that telephone interviews can effectively rule out delirium, but the positive diagnosis should be confirmed by a face-to-face assessment, especially in populations with a low prevalence of delirium.


Subject(s)
Delirium/diagnosis , Telephone , Aged , Aged, 80 and over , Diagnostic Errors , Female , Frail Elderly , Humans , Interviews as Topic , Male , Massachusetts , Remote Consultation , Sensitivity and Specificity
18.
J Am Geriatr Soc ; 46(9): 1118-24, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9736105

ABSTRACT

OBJECTIVES: Many older men with voiding symptoms do not have bladder outlet obstruction (BOO) but have conditions amenable to medical treatment. If primary care providers could reliably exclude men who have BOO, then they could initiate appropriate evaluation and treatment in a substantial proportion of the remainder. Urine flow rate, although widely used, is insufficiently sensitive to exclude BOO reliably. We investigated whether the decline in flow rate with age could be utilized to improve the utility of flow rate for excluding BOO in symptomatic men, especially when combined with knowledge of the patient's postvoiding residual volume (PVR). DESIGN: Prospective study using two patient cohorts. SETTINGS: A Veterans Affairs urology clinic serving community-dwelling and institutionalized healthy older men. PARTICIPANTS: 111 men with voiding symptoms (mean age 72.4 +/- 9.2 years). MEASUREMENTS: Maximum urine flow rate, measured with standard flowmeter, and PVR, measured by catheterization. BOO was determined by multichannel videourodynamic testing. RESULTS: The sensitivity of flowrate for BOO increased significantly with age (P = .0001) and did not appear to be confounded by comorbid conditions. An algorithm incorporating age, flow rate, and PVR had a sensitivity of 90%, specificity of 43%, and accuracy of 74% in screening for BOO. The algorithm's sensitivity was better than that of flow rate alone (55%); its sensitivity was also similar to a "refer all" strategy (100%) but had improved specificity (41% vs 0%). CONCLUSIONS: Flow rate alone is insufficiently sensitive as a screening test to exclude BOO, but a simple diagnostic algorithm using age, flowrate, and PVR was more sensitive and accurate. This algorithm allows primary care evaluation and initial management of men with voiding symptoms while potentially reducing unnecessary referrals and costs.


Subject(s)
Urinary Bladder Neck Obstruction/diagnosis , Urination Disorders/etiology , Urodynamics , Aged , Aging/physiology , Algorithms , Comorbidity , Humans , Male , Middle Aged , Prevalence , Prospective Studies , Sensitivity and Specificity , Urination Disorders/epidemiology , Urination Disorders/therapy , Urine
19.
Am J Med ; 104(6): 539-45, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9674716

ABSTRACT

PURPOSE: To determine the importance of fall characteristics, body habitus, function, and hip bone mineral density as independent risk factors for hip fracture in frail nursing home residents. SUBJECTS AND METHODS: In this prospective, case-control study of a single, long-term care facility, we enrolled 132 ambulatory residents (95 women and 37 men) aged 65 and older, including 32 cases (fallers with hip fracture) and 100 controls (fallers with no hip fracture). Principal risk factors included fall characteristics, body habitus, measures of functional assessment, and hip bone mineral density by dual-energy X-ray absorptiometry. RESULTS: In multivariate analysis, including only those with knowledge of the fall direction (n=100), those who fell and suffered a hip fracture were more likely to have fallen sideways (odds ratio 5.7, 95% confidence interval [CI] 1.7 to 18, P= 0.004) and have a low hip bone mineral density (odds ratio 1.9, 95% CI 0.97 to 3.7, P=0.06) than those who fell and did not fracture. When all participants were included (n=132) and subjects who did not know fall direction were coded as not having fallen to the side, a fall to the side (odds ratio 3.9, 95% CI 1.3 to 11, P=0.01), low hip bone density (odds ratio 1.8, 95% CI 1.03 to 3, P=0.04), and impaired mobility (odds ratios 6.4, 95% CI 1.9 to 21, P=0.002) were independently associated with hip fracture. Sixty-seven percent of subjects (87% with and 62% without hip fracture) had a total hip bone mineral density greater than 2.5 SD below adult peak bone mass and were therefore classified as having osteoporosis using World Health Organization criteria. CONCLUSIONS: Among frail elderly nursing home fallers, the preponderance of whom are osteoporotic, a fall to the side, a low hip bone density, and impairment in mobility are all important and independent risk factors for hip fracture. These data suggest that, among the frailest elderly, measures to reduce the severity of a sideways fall and improve mobility touch on new domains of risk, independent of bone mineral density, that need to be targeted for hip fracture prevention in this high-risk group.


Subject(s)
Accidental Falls , Bone Density , Frail Elderly , Hip Fractures/etiology , Psychomotor Performance , Aged , Case-Control Studies , Female , Homes for the Aged , Humans , Logistic Models , Male , Nursing Homes , Odds Ratio , Prospective Studies , Risk Factors
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