The deleterious effects of bed rest among community-living older persons

BACKGROUND: Older persons often "take to bed" while they are ill or injured, but relatively little is known about the functional consequences of bed rest among community-living older persons. In this prospective cohort study, the association between episodes of bed rest and functional decline was evaluated during an 18-month period. METHODS: Participants included 680 nondisabled, community-living persons aged 70 years or older. They were separated into 2 groups according to the presence or absence of physical frailty, which was defined based on slow gait speed. Episodes of bed rest were ascertained each month in a telephone interview for a median of 18 months. The completion rate was 99.1%. Functional decline was defined as a worsening in scores between the baseline and 18-month follow-up assessments in 1 or more of the following measures: instrumental activities of daily living, mobility, physical activity, and social activity. RESULTS: Among the 404 (59.4%) participants who had at least 1 episode of bed rest, the mean number of months with bed rest was 2.8 (standard deviation, 2.4). After adjustments were made for several potential confounders, the number of months with bed rest was significantly associated with decline in each of the functional measures. Significant associations were also observed for each of the functional outcomes among participants who were not physically frail, but they were observed only for instrumental activities of daily living disability among participants who were physically frail. CONCLUSIONS: These findings indicate that episodes of bed rest among community-living older persons are associated with decline in several important indicators of function.     

Distribution of integrins on human peripheral blood mononuclear cells

The receptors for fibronectin (FN-R) and vitronectin (VN-R) belong to a family of integral membrane glycoproteins known to be involved in cell- extracellular matrix and cell-cell interactions named integrins (FN-R = beta 1 integrin and VN-R = beta 3 integrin). Adhesion studies using FN- coated plastic dishes and highly purified subpopulations of peripheral blood mononuclear cells (PBMCs) showed a strong binding of monocytes and T lymphocytes to FN but virtually no binding of B cells to FN. Binding of monocytes and T cells to FN could be partially inhibited by a hexapeptide (GRGDSP) containing the adhesive peptide sequence Arg-Gly- Asp (RGD) as well as by an anti-FN-R antibody. The distribution of beta 1 and beta 3 integrin complexes on PBMCs was characterized by immunoprecipitation of detergent extracts of 125I-labeled cells using polyclonal antibodies against these two receptors. Two surface polypeptides corresponding to the alpha and beta chains of FN-R and VN- R were found on all three cell types. To characterize these receptors further, monoclonal antibodies (MoAbs) against the very late antigens (VLAs) 1, 3, and 5 were used for immunoprecipitation studies. Monocytes and T cells reacted with VLA 5 that was previously identified as the human FN receptor, whereas no labeling with anti-VLA 5 could be shown for B cells. When cell populations were cultured in 10% human serum for 24 hours, an increase in beta 1-integrin+ monocytes and T cells was observed. The number of beta 3-integrin+ cells remained essentially unchanged. The presence of beta 1 and beta 3 integrins on monocytes as well as on T and B lymphocytes may be of significance in the ability of these cells to interact with each other and participate in hematopoiesis and certain immune reactions.     

Synergistic action of calcium ionophore A23187 and phorbol ester TPA on B-chronic lymphocytic leukemia cells

The peripheral blood mononuclear cells from 16 patients with B-chronic lymphocytic leukemia (B-CLL, n = 13), B-prolymphocytic leukemia (B-PLL, n = 2) or hairy cell leukemia (n = 1) were incubated in the presence of the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore A23187. A synergy between these inducers was found with respect to morphological changes and B cell proliferation and differentiation. A23187 used alone did not activate the cells. B-CLL cells treated with the double stimulus acquired a plasmacytoid morphology, showed significantly higher incorporation of 3H-thymidine and 3H-uridine, and produced significantly higher amounts of monoclonal immunoglobulin compared with the same cells exposed to either of the inducers alone. These results indicate that phorbol ester and calcium ionophore act synergistically on B-CLL cells to induce proliferation and differentiation. B-PLL cells responded more vigorously to the signals provided by TPA and A23187. Previous studies showed that TPA and A23187 can mimic the two physiological second messengers diacylglycerol and inositol trisphosphate in the transduction of signals leading to cell activation, proliferation, and differentiation in normal B cells. The present findings suggest that the capacity of B- CLL and B-PLL cells to differentiate in response to signals of the second messenger pathway is intact.     

Structural abnormalities and persistent complaints after an ankle sprain are not associated: an observational case control study in primary care

Background

Persistent complaints are very common after a lateral ankle sprain.

Aim

To investigate possible associations between structural abnormalities on radiography and MRI, and persistent complaints after a lateral ankle sprain.

Design and setting

Observational case control study on primary care patients in general practice.

Method

Patients were selected who had visited their GP with an ankle sprain 6–12 months before the study; all received a standardised questionnaire, underwent a physical examination, and radiography and MRI of the ankle. Patients with and without persistent complaints were compared regarding structural abnormalities found on radiography and MRI; analyses were adjusted for age, sex, and body mass index.

Results

Of the 206 included patients, 98 had persistent complaints and 108 did not. No significant differences were found in structural abnormalities between patients with and without persistent complaints. In both groups, however, many structural abnormalities were found on radiography in the talocrural joint (47.2% osteophytes and 45.1% osteoarthritis) and the talonavicular joint (36.5% sclerosis). On MRI, a high prevalence was found of bone oedema (33.8%) and osteophytes (39.5) in the talocrural joint; osteophytes (54.4%), sclerosis (47.2%), and osteoarthritis (55.4%, Kellgren and Lawrence grade >1) in the talonavicular joint, as well as ligament damage (16.4%) in the anterior talofibular ligament.

Conclusion

The prevalence of structural abnormalities is high on radiography and MRI in patients presenting in general practice with a previous ankle sprain. There is no difference in structural abnormalities, however, between patients with and without persistent complaints. Using imaging only will not lead to diagnosis of the explicit reason for the persistent complaint.     

Association between Women Veterans' Experiences with VA Outpatient Health Care and Designation as a Women's Health Provider in Primary Care Clinics

BackgroundWomen veterans comprise a small percentage of Department of Veterans Affairs (VA) health care users. Prior research on women veterans' experiences with primary care has focused on VA site differences and not individual provider characteristics. In 2010, the VA established policy requiring the provision of comprehensive women's health care by designated women's health providers (DWHPs). Little is known about the quality of health care delivered by DWHPs and women veterans' experience with care from these providers.MethodsSecondary data were obtained from the VA Survey of Healthcare Experience of Patients (SHEP) using the Consumer Assessment of Healthcare Providers and Systems (CAHPS) patient-centered medical home (PCMH) survey from March 2012 through February 2013, a survey designed to measure patient experience with care and the DWHPs Assessment of Workforce Capacity that discerns between DWHPs versus non-DWHPs.FindingsOf the 28,994 surveys mailed to women veterans, 24,789 were seen by primary care providers and 8,151 women responded to the survey (response rate, 32%). A total of 3,147 providers were evaluated by the SHEP-CAHPS-PCMH survey (40%; n = 1,267 were DWHPs). In a multivariable model, patients seen by DWHPs (relative risk, 1.02; 95% CI, 1.01–1.04) reported higher overall experiences with care compared with patients seen by non-DWHPs.ConclusionsThe main finding is that women veterans' overall experiences with outpatient health care are slightly better for those receiving care from DWHPs compared with those receiving care from non-DWHPs. Our findings have important policy implications for how to continue to improve women veterans' experiences. Our work provides support to increase access to DWHPs at VA primary care clinics.     

Bone marrow in children with acute lymphocytic leukemia: MR relaxation times

Magnetic resonance imaging of the lumbar spine was performed in 17 children with acute lymphocytic leukemia (ALL): eight with newly diagnosed ALL, four with ALL in relapse, and five with ALL in remission. Eleven age-matched children were also imaged as controls. The T1 and T2 relaxation times of the bone marrow in the lumbar spine were calculated for all the children. The T1 relaxation times of the bone marrow were as follows (mean +/- standard deviation): newly diagnosed ALL, 968 msec +/- 68; ALL in relapse, 765 msec +/- 19; ALL in remission, 404 msec +/- 135; and age-matched controls, 441 msec +/- 82. T1 relaxation time was statistically significant in differentiating children with newly diagnosed ALL from normal children and from children with ALL in remission. In addition, T1 may be useful in differentiating children with ALL in relapse from children with ALL in remission and from healthy children. T2 was not significantly different among the four groups.     

Dorsal onlay augmentation urethroplasty with small intestinal submucosa: Modified Barbagli technique for strictures of the bulbar urethra

AIM: To present the results from one clinic's experience of using small intestinal submucosa (SIS) in augmentation urethroplasty for management of strictures of the bulbar urethra. METHODS: Urethral surgery was performed in nine men with strictures 4-6 cm. All of the patients were evaluated by history, physical examination, retrograde urethrogram, and uroflowmetry. Four layers of SIS were soaked in saline or Ringer's solution for 15 minutes at 37 degrees C, and the inner surface of the patch was gently fenestrated with a thin scalpel. The patch was spread-fixed onto the tunica albuginea. The mucosa was sutured to the submucosal graft first at 2-3 mm inwards from the SIS margins, then the spongiosum tissue was attached to the margins with interrupted absorbable sutures. RESULTS: Of the nine patients who underwent augmentation urethroplasty using SIS, only one had re-stricture at 6 months due to urethral infection. At 18 months after the surgery the uroflowmetry of the other eight patients was 20-21 mL/s. In terms of complications, six patients reported having post-micturition dribbling, and seven patients reported lack of morning erections for 35-69 days after surgery. CONCLUSIONS: Using SIS is a safe procedure; however, long-term follow-up is needed to substantiate the good short-term results.     

Comparative evaluation of iohexol and inulin clearance for glomerular filtration rate determinations

We evaluated iohexol as a filtration marker in 150 children. The clearance of iohexol was compared with that of inulin or with a formula clearance. The single-sample clearance of iohexol showed a good correlation with the clearance of inulin ( r = 0.834). The clearance of iohexol correlated well ( r = 0.672) with the formula clearance. The optimal blood sampling time for iohexol clearance determinations appears to be between 120 and 180 min after injection, at least in patients with relatively normal filtration rates. We conclude that iohexol clearance is an accurate method of determining the glomerular filtration rate in clinical practice.     

In vitro activation of the human Harvey-ras proto-oncogene by aflatoxin B1

Activation of ras proto-oncogenes occurs frequently in vivo in chemically induced rodent tumours, including rat hepatomas induced by aflatoxin B1. This study examines the in vitro activation of a human ras gene by this mycotoxin. A plasmid containing the human Ha-ras proto- oncogene, together with a neomycin resistance gene (pECneo), was incubated in vitro with a microsomal system generating aflatoxin B1 8,9- epoxide. Subsequent transfection of the plasmid into mouse NIH 3T3 fibroblasts, followed by G418 selection and s.c. injection of surviving cells into immunodeficient mice demonstrated that the proto-oncogene had acquired transforming capacity. Although a single tumour resulted from similar treatment of incubated unconjugated plasmid, no tumours were produced by a secondary round of transfections using DNA from this tumour. Selective PCR amplification of the human Ha-ras gene in extracted tumour DNA followed by sequencing demonstrated the presence of G-->T transversions either at the first or middle base of codon 12 in tumours resulting from transfection with the aflatoxin-B1-modified pECneo plasmid, but this was not detected in the single tumour resulting from transfection with the unmodified plasmid. Thus, although a mutation in the Ha-ras gene has not been reported for human primary hepatomas occurring in aflatoxin-exposed populations, metabolically activated aflatoxin B1 is capable of mutating this proto-oncogene to its oncogenic form in vitro. No mutations were observed in codon 61. It appears that, in contrast to the frequently reported G-->T transversions in codon 249 of the p53 gene in primary hepatomas in aflatoxin-exposed humans, the failure to detect Ha-ras mutations in these tumours is not due to an inability of aflatoxin B1 to activate this proto-oncogene. The G-->T transversions observed in this study contrast with the most frequent aflatoxin B1 in vivo induced mutations, G-->A transitions in the rat Ki-ras gene. Possible mechanisms for these differences are discussed.