Modifiable factors related to life-space mobility in community-dwelling older adults: results from the Canadian Longitudinal Study on Aging.

BACKGROUND: The most common methods for measuring mobility in older adulthood include performance-based tests, such as the Timed-Up-and-Go and gait speed. While these measures have strong predictive validity for adverse outcomes, they are limited to assessing what older adults do in standardized settings, rather than what they do in their daily life. Life-space mobility, which is the ability to move within environments that expand from one's home to the greater community, has been proposed as a more comprehensive measure of mobility. The aim of this study was to determine the association between modifiable factors and life-space mobility in older adults enrolled in the Canadian Longitudinal Study on Aging (CLSA). METHODS: Life-space mobility was measured using the Life Space Index (LSI). Explanatory factors included physical, psychosocial and cognitive determinants, as well as pain, fatigue, driving status, nutrition, body mass index, smoking status, and vision. To estimate the association between the LSI and explanatory variables, univariate and multivariable ordinary least squares regression analyses were performed. RESULTS: All adults 65 years and older (n = 12,646) were included in the analysis. Fifty percent were women and the mean age was 73.0 (SD5.7). The mean LSI score was 80.5, indicating that, on average, the sample was able to move outside of their neighborhood independently. All explanatory variables were significantly associated with the LSI except for balance and memory. The top 3 variables that explained the most variation in the LSI were driving, social support and walking speed. CONCLUSION: To our knowledge, this was the first study to examine the association between life-space mobility and a comprehensive set of modifiable factors that were selected based on a theoretical framework and existing research evidence. This study had two important messages. First, driving, social support and walking speed emerged as the most significant correlates of life-space mobility in older adults. Second, life-space mobility is multifactorial and interventions that are pragmatic in their design and testing are needed that consider the complexity involved. A multi-disciplinary approach to examining life-space mobility in older adults is needed to optimize opportunities for healthy aging and develop strategies that support mobility in older adulthood.

Compressed air massage hastens healing of the diabetic foot.

BACKGROUND: The management of diabetic foot ulcers remains a problem. A treatment modality that uses compressed air massage has been developed as a supplement to standard surgical and medical treatment. Compressed air massage is thought to improve local tissue oxygenation around ulcers. The aim of this study was to determine whether the addition of compressed air massage influences the rate of healing of diabetic ulcers. METHODS: Sixty consecutive patients with diabetes, admitted to one hospital for urgent surgical management of diabetic foot ulcers, were randomized into two groups. Both groups received standard medical and surgical management of their diabetes and ulcer. In addition, one group received 15-20 min of compressed air massage, at 1 bar pressure, daily, for 5 days a week, to the foot and the tissue around the ulcer. Healing time was calculated as the time from admission to the time of re-epithelialization. RESULTS: Fifty-seven patients completed the trial; 28 received compressed air massage. There was no difference in the mean age, Wagner score, ulcer size, pulse status, or peripheral sensation in the two groups. The time to healing in the compressed air massage group was significantly reduced: 58.1 +/- 22.3 days (95% confidence interval: 49.5-66.6) versus 82.7 +/- 30.7 days (95% confidence interval: 70.0-94.3) (P = 0.001). No adverse effects in response to compressed air massage were noted. CONCLUSIONS: The addition of compressed air massage to standard medical and surgical management of diabetic ulcers appears to enhance ulcer healing. Further studies with this new treatment modality are warranted.

c-Myc proteolysis by the ubiquitin-proteasome pathway: stabilization of c-Myc in Burkitt's lymphoma cells.

The c-Myc oncoprotein is a transcription factor which is a critical regulator of cellular proliferation. Deregulated expression of c-Myc is associated with many human cancers, including Burkitt's lymphoma. The c-Myc protein is normally degraded very rapidly with a half-life of 20 to 30 min. Here we demonstrate that proteolysis of c-Myc in vivo is mediated by the ubiquitin-proteasome pathway. Inhibition of proteasome activity blocks c-Myc degradation, and c-Myc is a substrate for ubiquitination in vivo. Furthermore, an increase in c-Myc stability occurs in mitotic cells and is associated with inhibited c-Myc ubiquitination. Deletion analysis was used to identify regions of the c-Myc protein which are required for rapid proteolysis. We found that a centrally located PEST sequence, amino acids 226 to 270, is necessary for rapid c-Myc degradation, but not for ubiquitination. Also, N-terminal sequences, located within the first 158 amino acids of c-Myc, are necessary for both efficient c-Myc ubiquitination and subsequent degradation. We found that c-Myc is significantly stabilized (two- to sixfold) in many Burkitt's lymphoma-derived cell lines, suggesting that aberrant c-Myc proteolysis may play a role in the pathogenesis of Burkitt's lymphoma. Finally, mutation of Thr-58, a major phosphorylation site in c-Myc and a mutational hot spot in Burkitt's lymphoma, increases c-Myc stability; however, mutation of c-Myc is not essential for stabilization in Burkitt's lymphoma cells.

Disruption of Myc-tubulin interaction by hyperphosphorylation of c-Myc during mitosis or by constitutive hyperphosphorylation of mutant c-Myc in Burkitt's lymphoma.

Somatic mutations at Thr-58 of c-Myc have been detected in Burkitt's lymphoma (BL) tumors and have been shown to affect the transforming potential of the Myc oncoprotein. In addition, the N-terminal domain of c-Myc has been shown to interact with microtubules in vivo, and the binding of c-Myc to alpha-tubulin was localized to amino acids 48 to 135 within the c-Myc protein. We demonstrate that c-Myc proteins harboring a naturally occurring mutation at Thr-58 from BL cell lines have increased stability and are constitutively hyperphosphorylated, which disrupts the in vivo interaction of c-Myc with alpha-tubulin. In addition, we show that wild-type c-Myc-alpha-tubulin interactions are also disrupted during a transient mitosis-specific hyperphosphorylation of c-Myc, which resembles the constitutive hyperphosphorylation pattern of Thr-58 in BL cells.

B-Myc is preferentially expressed in hormonally-controlled tissues and inhibits cellular proliferation.

The myc family of genes plays an important role in several cellular processes including proliferation, apoptosis, differentiation, and transformation. B-myc, a relatively new and largely unstudied member of the myc family, encodes a protein that is highly homologous to the N-terminal transcriptional regulatory domain of c-Myc. Here, we show that high level B-myc expression is restricted to specific mouse tissues, primarily hormonally-controlled tissues, with the highest level of expression in the epididymis. We also report the identification of the endogenous B-Myc protein from mouse tissues. Like other Myc family proteins, B-Myc is a short-lived nuclear protein which is phosphorylated on residues Ser-60 and Ser-68. Rapid proteolysis of B-Myc occurs via the ubiquitin-proteasome pathway. Finally, we found that overexpression of B-Myc significantly slows the growth of Rat la fibroblasts and COS cells suggesting B-Myc functions as an inhibitor of cellular proliferation.

Characterisation of normal human myocardium by means of morphometric analysis.

A morphometric analysis of ventricular myofibres, in specimens taken at necropsy from ten normal hearts, was performed to determine the distribution of fibre and nuclear diameters and their dependence on sampling position within the heart (group a). To assess the significance of the findings, two control groups of specimens were subjected to the same analysis: b) specimens from the hearts of four patients who had died of African cardiomyopathy; c) biopsies taken from the left ventricles of two hearts undergoing surgical repair of atrial septal defects (ASD), in which the myocardium is considered normal. Although mean values for the left ventricle were 13% greater on average than those for the right, a linear correlation, independent of sampling position, was found between nuclear and fibre diameter. Mean fibre and nuclear diameters for specimens from the normal and ASD control groups followed the same correlation as for individual normal fibres, whereas there was a significant deviation in the case of the cardiomyopathy specimens. The relationship between nuclear and fibre diameters was found to distinguish between normal and pathological specimens more clearly than the mean values of either dimension considered separately. It is suggested that this relationship is a more sensitive criterion of ventricular fibre normality or pathology than the parameters used in previous studies of this nature.

Preparation of the community-medical dietitian: a survey of graduates.

The 1984 Study Commission on Dietetics reports that dietetics education needs greater emphasis/depth on management, communications, and the scientific principles of nutrition, with a broader base in the behavioral sciences. This recommendation is supported by recent graduates and their employers. The skill area identified as deficient by the most employers was the ability to delegate or direct. At least 20% of these graduates felt a need to strengthen their role as interpreter of nutrition science and the curricular areas related to nutrient metabolism, educational methods, and behavior modification. Changes projected for the dietetics profession in the future include an increase in patient care outside the hospital; an increase in the need for nutrition services in independent medical practice associations, gerontology centers, and fitness centers; and an increase in opportunities in the business world. Educational programs must be sensitive to the new skills needed for practice in both clinical and community dietetics. They must continue to assess their effectiveness in providing these, because the dietitian best prepared with skills in both areas will be best prepared for the future.

Growth patterns, ultrastructure, and chromosomal constitution of normal kidney and nephroblastoma cells in short-term culture.

Nephrectomies were performed on four children with nephroblastomas (Wilms' tumor). Tumor tissue and normal kidney tissue were taken from each patient and were cultured. The in vitro characteristics of the cultured cells were then compared with their known in vivo characteristics. The normal kidney cells showed uniform cell morphology, had a relatively slow and orderly growth pattern and had the usual diploid chromosomal constitution. The tumor cells on the other hand were irregular in morphology and had a rapid and disorderly growth pattern. Electron microscopic examination confirmed the variation in the tumor cell morphology. In addition, microfilaments were seen to be abnormally abundant in many of the cells and some cells contained membrane-bound granules. Desmosomes were absent. Chromosome analyses showed cells from three of the nephroblastoma samples to maintain a constant hyperdiploid karyotype during the first few passages in vitro, whereas the normal kidney cells continued to have the normal diploid karyotype. Our study suggests that nephroblastoma and normal kidney cells are stable in culture, that is they retain most of their cellular characteristics in vitro and do not undergo rapid dedifferentitation in short-term culture.

Mongolian gerbil (Meriones unguiculatus) as a model of cerebral infarction for testing new therapeutic agents.

Stroke mortality represents the third leading cause of death worldwide, after coronary artery disease and cancer. It has been demonstrated that in Mongolian gerbils, a unilateral hemispheric cerebral infarction can be produced following unilateral occlusion of the carotid artery because of the absence of connecting arteries between the basilar and carotid systems in these animals. The objective of this study was to comprehensively characterize the model of cerebral infarction in gerbil, clinically, biochemically and especially morphologically for prospective use in testing new therapeutic agents. Cerebral infarction was produced by ligation of the left common carotid artery in experimental gerbils. The control animals were sham-operated. One hour after surgery, 0.5 ml of 1% trypan blue was administered intraperitoneally to all animals. Initial clinical evaluations were made 8 h after surgery and every day thereafter for 30 days. On each of days 10 and 30, 4 animals were sacrificed. The degree of cerebral infarction was evaluated on the basis of clinical response, electrolyte and enzyme changes, vascular permeability of blood-brain barrier and morphological alterations. The total post-infarction mortality rate was 50%. The clinical symptoms presented as ipsilateral hemiparesis, ptosis of the eyelid, circling behavior, decreased breathing rate, decreased blood pressure and increased heart rate. Such symptoms developed within 8 h of ligation and persisted to sacrifice at day 30. Creatine kinase increased significantly on the 10th day and remained high to day 30. Increased potassium from the damaged cells and breakdown of the blood-brain barrier were first detected 72 h post-infarction. The morphological data showed evidence of brain cell necrosis, autolysis and phagocytosis 10 and 30 days post-ligation in left hemispheres. Minor intercellular edema and some cell shrinkage was evident in the right brain. Areas of focal necrosis in the vicinity of blood vessels, especially in the left brain suggested a reperfusion injury as a consequence of minimal collateral reflow from the right brain into the left brain microvasculature. Experimental infarction in gerbil recreates the ischemic conditions causing stroke in humans. The animal model may be used for evaluating the efficacy of therapeutic agents that may ameliorate the condition in man.

Correlations between metal uptake in the soft tissue of Perna perna and gill filament pathology after exposure to mercury.

The accumulation of metal in soft tissues, filtration rate and gill filament morphology are correlated in the southern African rock mussel, Perna perna, during exposure to mercury (24 days) and recovery (24 days). The amount of Hg in soft tissues increased from 0.13 to 87.5 microg/g dry weight after 24 days exposure, and declined to 13 microg/g during recovery. Mean filtration rate fell from 3,979 to 1,818 ml/h/g dry weight by day 2, but recovered slightly through days 4 and 8 (3,037 ml/h/g), with a higher average rate (5,030 ml/h/g) being maintained over the 24-48 days recovery period. The initial decline in filtration coincided with epithelial cell deterioration presented as interstitial oedema, neural and epithelial cell degeneration and reduced ciliation. Between days 8 and 24, cilia regenerated and there was a general improvement in cell morphology. Gill filament morphology returned to near normal during the metal-free recovery period. The usefulness of P. perna as an indicator of pollution is discussed.

Does the duodenal cell ever return to normal? A comparison between treatment with cimetidine and denol.

After six weeks therapy with the bismuth-containing substance Denol, the ultrastructure of the duodenal cell is normal in most cases. Following therapy with the histamine-2 receptor antagonist (cimetidine), for the same period and even after one year continuous therapy, the denodenal cell remains abnormal in most instances. This may explain the frequent relapse of duodenal ulcers after cimetidine treatment.

Understanding equality in health care: a Christian free-market approach.

This paper examines the arguments presented by the Roman Catholic Bishops in their 1993 Pastoral Resolution, Comprehensive Health Care Reform: Protecting Human Life, Promoting Human Dignity, Pursuing the Common Good, concerning health care reform. Focusing on the meaning of equality in health care and traditional Roman Catholic doctrine, it is argued that the Bishops fail to grasp the force of the differences among persons, the value of the market, and traditional scholastic arguments concerning obligatory and extraordinary health care. To attempt to equalize the distribution of health care would be ruinous. A more traditional understanding of Christian thought reveals an acceptance of inequality in health care distribution and a bias against using the secular state to coerce a solution to such concerns for social justice.

Alterations in the morphology of skeletal myofibres after 90 minutes of ischaemia and 3 hours of reperfusion.

Morphometric, light and electron microscopic methods were employed to determine whether skeletal myofibres were damaged by 90 minutes of tourniquet-mediated ischaemia. Open biceps muscle biopsies were obtained before 90 minutes of upper limb tourniquet ischaemia in 5 Chacma baboons. Further biopsies were obtained just before tourniquet release in 2 animals and after 3 hours' reperfusion in the remaining 3 animals. Other than a slight reduction in myofibre diameter and the anaerobic depletion of intermyofibrillar glycogen, no pathological changes were noted in skeletal myofibres after ischaemia. However, after reperfusion there was myofibre enlargement, intermyofibrillar oedema, internalisation of nuclei, myofibrillar and mitochondrial disorganisation and dissolution, and Z-band streaming. These results show that reperfusion injury affects skeletal myofibres after 90 minutes of tourniquet-mediated ischaemia.

Plasma etomidate levels in mother and fetus.

The most commonly used induction agent in anaesthesia for Caesarean section is still thiopentone. The increasing incidence of Caesarean section for delivery of premature babies from a hostile environment may call in question the assumption that the dose of thiopentone received by the neonate will not cause depression in the hours following birth. Previous studies on thiopentone for Caesarean section have shown inconsistency in umbilical vein/maternal vein ratios. We have studied plasma etomidate levels in maternal and umbilical blood at the time of delivery to see whether equilibrium occurs with this agent. We were able to demonstrate an umbilical/maternal vein etomidate ratio of 0.5 (SD 0.18), with no relation to time in the range encountered. Also, the uterine artery/uterine vein etomidate ratio was 0.86 (SD 0.33), suggesting that etomidate uptake into the fetus is effectively complete. Further, in all cases the neonatal plasma etomidate levels were less than half those measured at recovery of consciousness in adults in other studies, despite a larger induction dose than is usually used.

A histometric analysis of skeletal myofibers following 90 min of tourniquet ischemia and reperfusion.

Routine tourniquet use causes sublethal hypoxic cellular injury and results in edema formation. Using a histochemical morphometric technique, edema caused by 90 min of tourniquet-induced ischemia and 3 hr of reperfusion is measured in the different muscle fibers of a primate model. The degree of cellular swelling is shown to be related to the fiber's metabolic dependence upon oxygen. After reperfusion, predominantly oxidative type 1 fibers show a 29% increase in diameter, P less than 0.0005, type 2a fibers which are both oxidative and glycolytic increase by 7%, P less than 0.005, and the glycolytic type 2b fibers increase by 5%, P less than 0.01. A 48% increase in interfiber distance occurs with reperfusion, P less than 0.01. By quantifying the different fibers' responses to ischemic injury, this method may be of use in investigating the pathophysiology and prevention of reperfusion injury and the post-tourniquet syndrome.

Compatibility of blood with solutions containing calcium.

Blood anticoagulated with citrate-phosphate-dextrose (CPD) was run through blood administration sets before and after Ringer-lactate solution (BP), Hidroliet, Maintelyte, Plasmalyte B and 0,9% saline. Clots, some of which were proven by electron microscopy to contain fibrin, formed distal to the filter when Ringer-lactate and Hidroliet were used, but not with other solutions. It is suggested that their formation was due to the calcium in Ringer-lactate and Hidroliet. As these two solutions are frequently used in combination with blood, especially in shocked patients, and as the clots would presumably be filtered out in the lung, it would seem wise to use either calcium-free Ringer-lactate solution or some other crystalloid solution such as 0,9% saline or Plasmalyte B.