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Psychosocial well-being of patients with inoperable non-small cell lung cancer. The importance of treatment- and disease-related factors.

Patients with inoperable non-small cell lung cancer, limited disease, were randomized to either chemotherapy (cisplatin and etoposide) or radiotherapy of the thorax. A set of questionnaires, covering 4 areas: psychosocial well-being, medical side effects, physical function, and everyday activity was filled out by 101 patients. The correlations between psychosocial well-being (dependent variable) on the one hand, and medical side effects, physical function, and everyday activity (independent variables) on the other were subjected to multiple regression analysis. No significant correlation was found between psychosocial well-being and chemotherapy- or radiotherapy-related subjective side effects. The disease-related symptoms correlated highly with psychosocial well-being during the observation period. Psychosocial well-being and the independent variables tended to be more strongly correlated during the follow-up period (14-52 weeks) than during the treatment period.

Adult↗

Effects of foods on the pharmacokinetics and clinical efficacy of quazepam.

The effects of foods on the pharmacokinetics and clinical efficacy of quazepam, a benzodiazepine derivative, in healthy persons were examined. Six healthy Japanese male subjects were randomly divided into three groups and each subject was treated with quazepam under the following three conditions by the crossover method. For the fasting state, subjects were administered 15 mg quazepam 11 hours after a meal. For the postprandial state, subjects were administered 15 mg or 30 mg quazepam 2 hours after a meal. Mean peak plasma concentration (Cmax) of quazepam was significantly higher [1.6-2.8 fold] with administration 2 hours after a meal than 11 hours after a meal. However, in regard to 15 mg of quazepam administration, the area under the curve (AUC) did not differ between administration 2 hours after a meal and 11 hours after a meal. In addition, differences were observed neither in other pharmacokinetic parameters or blood metabolite concentration under all of the study conditions, nor in clinical evaluation of subjective symptoms, complete blood count, or biochemical analyses between administrations 2 and 11 hrs after a meal. The present study showed that administration 2 hours after a meal did not affect subjective symptoms or physical functions so much; therefore it suggested favorable tolerance of this drug. However, it was also suggested that, in actual clinical use, it is important to evaluate the physical function including measurements of vital signs and hematological test results, carefully considering the effects of foods and daily life-style.

Adult↗

Significance of intima-media thickness in femoral artery in the determination of calcaneus osteo-sono index but not of lumbar spine bone mass in healthy Japanese people.

The aim of this cross-sectional study was to investigate whether physical activity and local arterial thickening may affect bone metabolism. To analyze the effects of physical activity and atherosclerosis on bone in healthy Japanese people, health-related quality of life (HRQL) and local arterial thickening were assessed by means of the Medical( )Outcomes Study 36-item Short Form (SF-36), and intimal-medial thickness (IMT) in common carotid artery (CA) and femoral artery (FA), respectively. Bone mineral density (BMD) in lumbar spine was measured by dual X-ray absorptiometry and the osteo-sono assessment index (OSI) of the calcaneus by ultrasound. Healthy subjects (106 male and 154 female) were recruited from those who participated in a local health check program at the Osaka City University Hospital. A significant correlation existed between lumbar spine BMD and calcaneus OSI (r=0.551, P<0.0001). Among various scores in SF-36, only physical functioning score correlated weakly but significantly in a positive manner with lumbar spine BMD (rho=0.156, P=0.0147) and calcaneus OSI (rho=0.190, P=0.0024). Lumbar spine BMD correlated negatively with FA IMT (rho=-0.191, P=0.0027) whereas calcaneus OSI with FA IMT (rho=-0.199, P=0.0014). Multiple regression analyses revealed a significant association between FA IMT and calcaneus OSI, whereas lumbar spine BMD did not correlate significantly with FA or CA IMT. When subjects were restricted to female, FA IMT, but not CA IMT, still showed tendency against independent factors negatively associated with calcaneus OSI. Furthermore, lumbar spine BMD, but not calcaneus OSI, was weakly but significantly associated with increased physical functioning score independently. In conclusion, it was suggested that physical activity may affect bone strength in lumbar spine and calcaneus and that FA IMT might be a significant determinant of bone strength in calcaneus, but not in lumbar spine, in healthy Japanese subjects.

Arteriosclerosis↗

Validation of the Western Ontario and Mcmaster University osteoarthritis index in Asians with osteoarthritis in Singapore.

OBJECTIVE: To assess the reliability and validity of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) as an outcome measure in Asian patients with knee or hip osteoarthritis (OA) in Singapore. DESIGN: The WOMAC was administered twice 7 days apart to 66 consecutive English-speaking Chinese, Malay or Indian inpatients and outpatients with knee or hip OA seen at a tertiary referral centre through a structured interview, which also assessed demographic and other characteristics. Internal consistency was assessed using Cronbach's alpha, reliability using Spearman's correlations, intraclass correlations and repeatability coefficients, and relationships between WOMAC domains and known determinants of function using Spearman's correlations and the Mann-Whitney U-test. RESULTS: The WOMAC showed good internal consistency (alpha=0.70 to 0.93) and good reliability, with intraclass correlations of 0.83 to 0.90 and mean test-retest score differences of 0.02 to 0.13 points (possible range 4 points). Results of Likert scoring assessment supported the validity of the WOMAC when interpreted in the context of the close association between pain and physical function. Eight of nine a priori hypotheses relating WOMAC Pain and Physical Function scores to known determinants of function were present, supporting construct validity of this scale. CONCLUSION: The WOMAC is a valid and reliable outcome measure in Asian patients with OA in Singapore.

Adult↗

Long-term consequences of upper extremity peripheral neuropathy in former Vietnam prisoners of war.

BACKGROUND: At the time of repatriation in 1973, a substantial number of Vietnam prisoners of war (POWs) were diagnosed with upper extremity peripheral neuropathy (UEPN). OBJECTIVE: To assess the long-term functional consequences of UEPN among former Vietnam POWs diagnosed with UEPN at repatriation. SUBJECTS: Former POWs with an International Classification of Diseases, Eighth Revision, code of peripheral neuropathy identified from a central database registry. METHODS: Cross-sectional survey. Standardized survey instruments and the SF-12 questionnaire were mailed to all subjects. A subsample of subjects completing the mailed survey was contacted by telephone to complete a semistructured questionnaire on current symptoms and physical limitations attributable to peripheral neuropathy. RESULTS: Seventy-nine percent of POWs diagnosed with peripheral neuropathy at repatriation currently experience some numbness or tingling more than 25 years after repatriation, and 63% currently experience pain in one or both hands. Although the average severity rating for numbness and pain was mild, 23% of the POWs still have moderate to severe pain. Ulnar neuropathy was present in more than 30% of the POWs. SF-12 physical composite scores were substantially lower among this group of POWs compared with an age-matched group from the Medical Outcomes Study. CONCLUSIONS: For those POWs diagnosed with UEPN at repatriation, nearly 80% continue to experience symptoms of numbness, tingling, and pain, with nearly 25% reporting a moderate or greater degree of symptoms. The low physical function scores of this cohort are particularly troubling. More research concerning physical symptoms and conditions among former POWs is needed, and this research should also investigate what causes are responsible for the significantly lower physical functional status.

Aged↗

Comprehensive rehabilitation of patients having chronic low back pain.

Seventy-two patients having chronic back pain, representative of high-risk demographic and personality populations, received a broad range of therapeutic modalities designed around the theme of self-regulation. The self-regulation principle was used in: (1) biofeedback training for teaching self-regulated muscle relaxation; (2) psychological counseling emphasizing self-control techniques for the management of stress and anxiety, including assertion training; (3) patient-regulated medication program; (4) patient involved case conferences; (5) physical therapy program emphasizing reconditoning; (6) comprehensive vocational rehabilitation services; (7) a series of educational lectures; (8) a therapeutic milieu designed for relaxation, recreation and socialization. Utilizing a success criteria of functional physical activity at discharge (average length of stay, 45 days) and levels of vocational restoration (employable, in training, or employed at 30 days postdischarge), 57 of the patients demonstrated unimpaired physical functioning levels and 59 of the patients were at success levels of vocational restoration.

Adult↗

The glucocorticoid receptor and STAT6 physically and functionally interact in T-lymphocytes.

In lymphocytes, glucocorticoids (GC)- and interleukin-4-signaling pathways are known to interact, as evidenced by inhibition of IL-4-mediated proliferation by dexamethasone or suppression of GC-induced apoptosis by IL-4. In this study, we characterized the molecular basis for this reciprocal interference. We report that, in murine CTLL-2 cells, IL-4 inhibits GC-induced MMTV (mouse mammary tumor virus) promoter transactivation, and that GC suppress IL-4-induced transactivation of a STAT6 (signal transducers and activators of transcription 6)-responsive promoter without affecting IL-4-stimulated STAT6 DNA-binding. Moreover, we evidenced a physical association between GC receptor and STAT6, which proved to be functionally relevant, since STAT6 overexpression increased the IL-4 inhibitory effect on GC-induced MMTV transactivation.

Animals↗

Community-based group exercise improves balance and reduces falls in at-risk older people: a randomised controlled trial.

BACKGROUND: recent studies have found that moderate intensity exercise is an effective intervention strategy for preventing falls in older people. However, research is required to determine whether supervised group exercise programmes, conducted in community settings with at-risk older people referred by their health care practitioner are also effective in improving physical functioning and preventing falls in this group. OBJECTIVES: to determine whether participation in a weekly group exercise programme with ancillary home exercises over one year improves balance, muscle strength, reaction time, physical functioning, health status and prevents falls in at-risk community-dwelling older people. METHODS: the sample comprised 163 people aged over 65 years identified as at risk of falling using a standardised assessment screen by their general practitioner or hospital-based physiotherapist, residing in South Western Sydney, Australia. Subjects were randomised into either an exercise intervention group or a control group. Physical performance and general health measures were assessed at baseline and repeated 6-months into the trial. Falls were measured over a 12-month follow-up period using monthly postal surveys. RESULTS: at baseline both groups were well matched in their physical performance, health and activity levels. The intervention subjects attended a median of 23 exercise classes over the year, and most undertook the home exercise sessions at least weekly. At retest, the exercise group performed significantly better than the controls in three of six balance measures; postural sway on the floor with eyes open and eyes closed and coordinated stability. The groups did not differ at retest in measures of strength, reaction time and walking speed or on Short-Form 36, Physical Activity Scale for the Elderly or fear of falling scales. Within the 12-month trial period, the rate of falls in the intervention group was 40% lower than that of the control group (IRR=0.60, 95% CI 0.36-0.99). CONCLUSIONS: these findings indicate that participation in a weekly group exercise programme with ancillary home exercises can improve balance and reduce the rate of falling in at-risk community dwelling older people.

Accidental Falls↗

Functional outcome and patient satisfaction in total knee patients over the age of 75.

Seventy-four patients, age 75 or older, who had undergone 98 primary total knee arthroplasties were evaluated in a retrospective cohort study, with validated questionnaires that assessed self-reported pain, physical function, mental health, and satisfaction. Average follow-up period was 34 months (range, 12-67 months). Overall, 90.8% reported improvement, 88.8% were satisfied with the results of surgery, and 91.8% felt they had made the right decision. Dissatisfaction with the results correlated with poorer mental health scores, decreased physical function, and increased bodily pain scores (P < .05). Satisfaction was correlated with better pain scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and SF-36 (P < .05) but not with Hospital for Special Surgery scores (P = .328). Poor surgical results leading to revision surgery (5%) were associated with preoperative deformity greater than 20 degrees. Based on this patient-assessed outcome analysis, total knee arthroplasty is a worthwhile and beneficial procedure in the elderly.

Age Factors↗

Does the menopausal transition affect health-related quality of life?

We address whether the menopausal transition affects health-related quality of life (HRQOL). To do this, we review how HRQOL is defined and measured, present HRQOL findings from the large, population-based studies of menopause, and identify key gaps in knowledge. HRQOL is defined as the value assigned to duration of life as modified by impairments, functional states, perceptions, and social opportunities that are influenced by disease, injury, treatment, or policy. The specific domains of HRQOL include resilience or the capacity to respond to stress, health perceptions, physical functioning, and symptoms. The majority of menopause studies have operationalized HRQOL as frequency and severity of symptoms. Taken together, the findings from 12 cross-sectional reports and 3 longitudinal studies suggest that the perimenopause is associated with higher levels of somatic symptoms. It is unclear whether the perimenopause is related to other domains of HRQOL. Only 1 longitudinal study reported an association between reduced physical functioning and perimenopause. Studies typically compare premenopausal women with women of other menopausal transition status separately, thereby not addressing the question of further change in HRQOL after the cessation of menses. There is a clear need for understanding the effects of the menopause beyond the domain of symptoms and to consider whether some domains of HRQOL may improve.

Female↗

Outcome measures in osteoarthritis: randomized controlled trials.

Accepted outcome measures in randomized controlled trials (RCTs) in osteoarthritis (OA) include patient-reported assessments of physical function and health-related quality of life (HRQOL). Available data can inform treatment decisions when statistically significant changes are viewed in terms of clinically important improvements. Patient-reported outcomes validated in OA include global assessments of pain, disease activity, and disease-specific and generic measures of physical function and HRQOL. Definitions of minimum clinically important differences (MCID) have been derived from RCTs with physical therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 selective agents. Definitions of MCID should serve only as guidelines based on mean changes in a treatment group, and do not necessarily reflect clinically meaningful improvements for an individual patient. They help to interpret data across treatments and patient populations. Definitions of MCID may differ for the type of intervention assessed; additional methodologic issues must be addressed when evaluating nonpharmacologic treatments. Based on RCTs in OA evaluating physical therapy, cyclooxygenase-2 agents, and NSAIDs, the Western Ontario and McMaster Osteoarthritis Index is valid, reliable, sensitive to change, and correlates closely with the generic Medical Outcomes Survey Short-Form 36 measure of HRQOL. When evaluating RCT data, understanding derivation and MCID values of outcome measures facilitates informed therapeutic decisions regarding therapeutic interventions.

Acupuncture↗

Physiotherapy in subtropic climate improves functional capacity and health-related quality of life in Swedish patients with rheumatoid arthritis and spondylarthropathies still after 6 months.

OBJECTIVE: The objective was to prospectively evaluate the short as well as the long-term effects of intensive physiotherapy in a stable, sunny and warm climate on physical function and health related quality of life in patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA). METHODS: Ninety-three Swedish patients with RA and SpA receiving physiotherapy for 4 weeks in Israel or Tenerife were followed for 6 months. Physical function was evaluated by the Swedish version of Stanford Health Assessment Questionnaire (HAQ) and quality of life by the Nottingham Health Profile (NHP) questionnaire. RESULTS: There were significant improvements in HAQ-scores and global NHP-scores as well as all subcategories of NHP immediately after the treatment abroad, effects that were still measurable after six months. At that time point nearly half of the patients had clinically meaningful reduction of HAQ-scores (> or = 0.25). CONCLUSION: Physiotherapy in a warm and stable climate, with many hours of daily sunshine, is a valuable treatment complement for Swedish patients with RA and SpA.

Arthritis, Rheumatoid↗

Do medical factors predict disability in older adults with persistent low back pain?

Persistent low back pain (LBP) is one of the most common and challenging persistent pain conditions in older adults. Medical comorbidity also is common in these individuals, but its impact on disability has not been examined. The purpose of this study was, using a cross-sectional design, to examine the functional impact of pain-related and general medical comorbidity on 100 community dwelling older adults (mean age 74.3) with persistent mechanical LBP. Subjects received a structured history and physical examination, lumbosacral spine X-rays, and standardized tests of physical function. Pain-related variables included intensity, duration, extent, and lumbar motion-induced pain. General medical variables included age, comorbidity, number of medications, depressive symptoms, back range of motion, body mass index, and severity of radiographic pathology. Function/disability measures included self-reported disability, gait speed, and mean number of static lifts and amount of work performed during a dynamic lifting task. Structural equation modeling was used to evaluate the influence of pain and medical variables on function/disability. The overall regression model indicated pain and medical variables were significantly associated with function/disability measures (R2=0.45, P<0.01). Individual regression coefficients, however, indicated that only pain duration (r=-0.36, P<0.05) and pain severity (r=0.37, P<0.001) were significantly associated with function/disability. Despite the prevalence of medical co-morbidities in older PLBP subjects, they appear to be of limited utility in understanding level of disability. These findings also underscore the need to optimize pain treatment in independent older adults to optimize physical function and delay the onset of dependent living status.

Aged↗

Physical and functional interactions between Lyn and p34cdc2 kinases in irradiated human B-cell precursors.

Exposure of human B-cell precursors (BCP) to ionizing radiation results in cell cycle arrest at the G2-M checkpoint as a result of inhibitory tyrosine phosphorylation of p34cdc2 . Here, we show that ionizing radiation promotes physical interactions between p34cdc2 and the Src family protein-tyrosine kinase Lyn in the cytoplasm of human BCP leading to tyrosine phosphorylation of p34cdc2. Lyn kinase immunoprecipitated from lysates of irradiated BCP as well as a full-length glutathione S-transferase (GST)-Lyn fusion protein-phosphorylated recombinant human p34cdc2 on tyrosine 15. Furthermore, Lyn kinase physically associated with and tyrosine-phosphorylated p34cdc2 kinase in vivo when co-expressed in COS-7 cells. Binding experiments with truncated GST-Lyn fusion proteins suggested a functional role for the SH3 rather than the SH2 domain of Lyn in Lyn-p34cdc2 interactions in BCP. The first 27 residues of the unique amino-terminal domain of Lyn were also essential for the ability of GST-Lyn fusion proteins to bind to p34cdc2 from BCP lysates. Ionizing radiation failed to cause tyrosine phosphorylation of p34cdc2 or G2 arrest in Lyn kinase-deficient BCP, supporting an important role of Lyn kinase in radiation-induced G2 phase-specific cell cycle arrest. Our findings implicate Lyn as an important cytoplasmic suppressor of p34cdc2 function.

Amino Acid Sequence↗

Quality-of-life assessment after ileoanal pull-through for ulcerative colitis and familial adenomatous polyposis.

BACKGROUND/PURPOSE: The ileoanal pull-through procedure (IAP) is gaining increasing favor and use in the surgical treatment of children with ulcerative colitis (UC) and familial adenomatous polyposis (FP). Although physiological studies have been performed to assess the outcome of these children, no long-term quality-of-life assessment after the procedure has been performed. METHODS: Forty-three patients were identified who had an IAP at our institution in the last 10 years and were at least 6 months postsurgery. Thirty-four were contacted, and 32 agreed to participate in the survey, which was approved by the Human Studies Committee. Participants completed the standardized Medical Outcome Study Short Form-36 (SF-36), which has well-established normative values. Several supplemental questions were prepared in a similar format dealing with issues specific to the ileoanal pull-through procedure. RESULTS: Of the 32 participants, 19 (59%) were girls and 26 (81%) had ulcerative colitis. Mean age at the time of survey was 18.1 years with 12 less than 18 years and 20 > or =18 years. Data from the latter group could be compared with national normative values for this age. The study group was not statistically different from age-appropriate US population normal values on all assessable scales of physical and mental health in the SF-36 survey including physical functioning, role limitations-physical, bodily pain, general health, vitality, social functioning, role limitations-emotional, and mental health (all P>.05 or mean difference SD units <0.8). The supplemental questionaire demonstrated little adverse effect of the surgery. There was limited consumption of medications to control bowel frequency and little restriction of activity because of the frequency of bowel movements or fear of incontinence. The surgical scar was the sole negative factor of significance. CONCLUSIONS: The ileoanal pull-through procedure is an excellent surgical option for children with ulcerative colitis or familial adenomatous polyposis, and it produced minimal, if any, adverse effects on their long-term quality of life.

Adenomatous Polyposis Coli↗

Risk factors for nonelective hospitalization in frail and older adult, inner-city outpatients.

PURPOSE: In our study, we sought to improve the accuracy of predicting the risk of hospitalization and to identify older, inner-city patients who could be targeted for preventive interventions. DESIGN AND METHODS: Participants (56% were African American) in a randomized trial were from a primary care practice and included 1,041 patients living in the inner city who were either > or = 75 years of age or were > or = 50 years of age with severe disease. As a secondary analysis, we assessed patient characteristics at baseline involving five domains of health, including utilization and satisfaction. We followed participants for 12 months and recorded the occurrence of nonelective hospitalization within the study period. We developed a multivariate model using logistic regression to predict this outcome. RESULTS: The following patient characteristics independently predicted an increased risk for nonelective hospitalization: having the diagnosis of congestive heart failure, diabetes mellitus, or anemia; and having more medications prescribed, having a lower body mass index, and having more emergency department visits during the previous year. Better physical functioning reduced the risk of hospitalization. IMPLICATIONS: Moderate accuracy of a prediction model (0.73) was observed. In addition to focusing on patients with chronic disease, helping them maintain physical functioning may help reduce nonelective hospitalization.

Black or African American↗

Nuclear factor Y and steroidogenic factor 1 physically and functionally interact to contribute to cell-specific expression of the mouse Follicle-stimulating hormone-beta gene.

FSH is a heterodimeric glycoprotein hormone secreted from the gonadotrope cell population of the anterior pituitary. Despite its crucial role in mammalian reproduction, very little is known about regulation of the FSH beta-subunit gene at the molecular level. In this report, we examine the basis for cell-specific expression of FSH beta using the mouse L beta T2 and alpha T3-1 gonadotrope-derived cell lines. Characterization of the hormonal content of L beta T2 and alpha T3-1 cells at the protein level classifies these cells as relatively mature and immature gonadotropes, respectively. We studied L beta T2 cell-specific expression of FSH beta using 398 bp of the mouse FSH beta regulatory region linked to a luciferase reporter gene in transient transfection assays. This mouse FSH beta promoter can direct reporter gene expression specifically to L beta T2 cells when compared with other pituitary- and non-pituitary-derived cell lines, including alpha T3-1 cells. Furthermore, it is induced by activin, and interruption of the autocrine activin loop in L beta T2 cells by the addition of follistatin reduces its expression. Truncation analysis indicates that several regions of the promoter are involved in this specificity and that these can be dissociated from activin regulation. We identify binding sites for the orphan nuclear receptor steroidogenic factor-1 and the heterotrimeric transcription factor nuclear factor Y and show that these elements functionally interact to regulate FSH beta gene expression in an L beta T2 cell-specific manner. Moreover, steroidogenic factor-1 and nuclear factor Y are shown to physically interact with each other. This study is the first to demonstrate the presence of basal FSH beta protein in L beta T2 cells and to identify specific elements within the FSH beta promoter that contribute to basal and cell-specific expression of the gene.

3T3 Cells↗

A comparative study of life-closing spirituality in home hospice patients.

This secondary analysis compared two groups of home hospice patients (expressed spirituality, N = 44, and nonexpressed spirituality, N = 53) on psychological well-being and adaptation, social support, physical function, pain, and demographic variables. Independent-samples t tests found no significant differences at p < .05 for age, psychological well-being and adaptation, social support, and physical function. Three components of the McGill-Melzack Pain Questionnaire were significantly higher for the nonexpressed spirituality group: Affective Dimension, Pain Rating Index, and Number of Words Chosen. A comparative analysis of two groups of home hospice patients supported higher pain reports as significant indicators of nonexpressed spirituality in a home hospice population.

Activities of Daily Living↗