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.

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.

Metal accumulation, filtration and O(2) uptake rates in the mussel Perna perna (Mollusca: Bivalvia) exposed to Hg(2+), Cu(2+) and Zn(2+).

Tissue metal concentrations, filtration and oxygen uptake rates were investigated for Perna perna (Bivalvia: Mollusca) during exposure to Hg(2+), Cu(2+) and Zn(2+) (50 microg/l for 24 days, and 24 days recovery with no metal). Hg and Cu tissue levels increased with exposure time, reaching maximum levels after 24 days (87.5 microg Hg/g dry mass and 45 microg Cu/g dry mass, respectively). Zn levels peaked after 4 days exposure (to 233 microg Zn/g dry mass) and stabilized thereafter. Accumulated metal was rapidly lost from tissues when mussels were returned to uncontaminated seawater, suggesting that tissue concentration data may be of limited use in biomonitoring situations where environmental metals fluctuate to low levels. Filtration rates fell below control rates during Hg(2+) exposure, and became elevated again during the recovery period. Cu(2+) and Zn(2+) exposure had little effect on filtration, but suppressed oxygen uptake. During recovery, oxygen uptake of Cu(2+) and Zn(2+) exposed mussels was elevated above the controls. Filtration and oxygen uptake rates were not correlated, but rather responded in different ways to metal pollution. While these physiological responses of P. perna may be of limited use in biomonitoring, they could indicate how populations may respond to marine pollution.

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.

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.

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.

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.

The complete genome sequence of the Streptomyces temperate phage straight phiC31: evolutionary relationships to other viruses.

The completed genome sequence of the temperate Streptomyces phage straight phiC31 is reported. straight phiC31 contains genes that are related by sequence similarities to several other dsDNA phages infecting many diverse bacterial hosts, including Escherichia, Arthrobacter, Mycobacterium, Rhodobacter, Staphylococcus, Bacillus, Streptococcus, Lactobacillus and Lactococcus. These observations provide further evidence that dsDNA phages from diverse bacterial hosts are related and have had access to a common genetic pool. Analysis of the late genes was particularly informative. The sequences of the head assembly proteins (portal, head protease and major capsid) were conserved between straight phiC31, coliphage HK97, staphylococcal phage straight phiPVL, two Rhodobacter capsulatus prophages and two Mycobacterium tuberculosis prophages. These phages and prophages (where non-defective) from evolutionarily diverse hosts are, therefore, likely to share a common head assembly mechanism i.e. that of HK97. The organisation of the tail genes in straight phiC31 is highly reminiscent of tail regions from other phage genomes. The unusual organisation of the putative lysis genes in straight phiC31 is discussed, and speculations are made as to the roles of some inessential early gene products. Similarities between certain phage gene products and eukaryotic dsDNA virus proteins were noted, in particular, the primase/helicases and the terminases (large subunits). Furthermore, the complete sequence clarifies the overall transcription map of the phage during lytic growth and the positions of elements involved in the maintenance of lysogeny.

The evolution of biofilms in venous access devices implanted in children with Wilms' tumour.

Biofilms form on all implanted foreign materials. In venous access ports (VAPs), the biofilm with entrapped organisms may be the source of recurring bacteraemia. At present, little is known of the development of biofilms in VAPs. In this study light, scanning, and transmission electron microscopy were used to investigate the evolution of biofilms in VAPs implanted in 15 African children with Wilms' tumour. The VAPs were removed either emergently because of infection (n = 6) or blockage (n = 3), or electively at the end of chemotherapy (n = 6). Intact biofilms were obtained from lengths of the catheter attached to ports that had been in place for 11 days to 3 years. Each was prepared for light and electron microscopy. In infected ports, shortly after implantation biofilms were thin and comprised of apparently healthy erythrocytes (RBCs) and occasional platelets, leucocytes (WBCs), and bacteria enmeshed in a network of fibrin. Three weeks after implantation, RBCs had autolysed and large numbers of WBCs and bacterial colonies were present within and on the luminal surface. In 1 instance, the lumen of a VAP had been occluded by a "plug" of WBCs. In non-infected patients, the biofilms in long-standing VAPs were of varying thickness and primarily composed of an amorphous granular material. In most cases, healthy and necrotic bacteria were present both within the core and on the surface of the biofilms. The results suggest that while bacteria, per se, are an important factor, the presence and degradation of blood components may be an equally important factor in the development of biofilms in VAP catheters.

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.

Morphological aspects of microarterial anastomoses: a comparison of nylon with polydioxanone.

The morphological appearance of longitudinally sectioned rat femoral arteries was determined in intact arteries and from 3 to 435 days after vessel division and anastomosis with either 9/0 gauge nylon or polydioxanone (PDS) in 26 animals. The purpose of the study was to establish the mechanisms and compare the quality of healing after microarterial anastomosis and to determine whether PDS was degraded before sufficient anastomotic healing had taken place. The results revealed that there was no difference in the process of healing or quality of anastomosis with either suture material. From 3 to 21 days post anastomosis, there was a progressive separation of the ends of vessels within the developing scar. Anastomotic patency was established and maintained at first by an adventitial overgrowth of fibroblasts and undifferentiated adventitial cells and later by the growth of a smooth myocyte scar that stretched between the cut ends of the vessel and over the intima in the form of elongated circumferential plaques. The vessel was morphologically healed by the 21st day. The sutures served little or no purpose in maintaining anastomotic integrity after the 5th day, being situated in the scar forming between the separating vessel ends. PDS was present within the vessel wall up to 120 days post anastomosis and was certainly intact at the time of morphological healing, suggesting that this material is safe as a microvascular suture.

The effects of hexane on rat myocardium: a morphometric and morphological study.

Specimens from the left ventricular myocardium of 10 rats that had been exposed to subcutaneously administered hexane for 30 days were morphometrically and morphologically examined. Other than the presence of occasional necrotic fibres in hexane-treated animals, there was little difference in the histological appearance of myofibres in control or experimental specimens. There was a slight reduction in the average diameter of cardiac myofibres after exposure to hexane. Pathological ultrastructural changes of the myofibres were noted in the experimental and not in the control groups. Mitochondrial oedema and necrosis and myofilament disorganization and dissolution were significant changes noted in the experimental group. These pathological changes suggest that hexane, a constituent of glue and benzine, is cardiotoxic.

Serial morphological changes in primate skeletal myofibres after 3 hours of ischaemia and 24 hours of reperfusion.

The sequential morphological changes occurring in skeletal myofibres after 3 hours' ischaemia and from 3 hours to 24 hours of reperfusion in vervet monkeys are described. Eight vervet monkeys were studied under general anaesthesia. A hind limb was exsanguinated and a tourniquet applied for 3 hours. Open muscle biopsy specimens were obtained from the tibialis anterior muscle before tourniquet application, just before tourniquet release and 3, 6, 12, 18 and 24 hours after tourniquet deflation. All specimens were prepared for transmission electron microscopy. After 3 hours of ischaemia and increasing periods of reperfusion, a small number of fibres showed progressive pathomorphological changes that eventually resulted in myofibre death. After initial glycogen loss and later intermyofibrillar oedema, the majority of myofibres returned to normal, while a group of fibres remained oedematous. The progressive morphological characteristics of reversibly injured myofibres undergoing repair and irreversible injured cells undergoing necrosis are described.

Alterations in the cytological composition of the juxta-scar villous mucosa after ulcer therapy with sucralfate or cimetidine.

A comparative light-microscopic morphometric analysis of non-metaplastic mucosa obtained from the pretreatment juxta-duodenal ulcer (DU) villous mucosa of 10 patients and from the first part of the duodenum of 5 normal volunteers revealed a significant increase (P less than 0.01) in the number of goblet cells (GCs) per 100 microns of villous mucosa (GC/100 microns). Such an increase was thought to represent a mucoprotective response by the mucosa to the corrosive lumenal factors that may cause or maintain ulceration. A similar morphometric analysis was performed on the endoscopically healed juxta-scar villous mucosa of 11 patients successfully treated for 6 weeks with sucralfate (5 patients) or cimetidine (6 patients). After treatment with cimetidine, GC/100 microns was reduced to near-normal levels, whereas after sucralfate therapy it was significantly raised (P less than 0.05). The difference in GC/100 microns after treatment with either sucralfate or cimetidine was significant at the P less than 0.02 level. The apparent drug-mediated difference in the cytological composition of the healed mucosa was thought to be a function of the pharmacodynamic mechanisms of action of the two drugs in promoting DU healing. It is proposed that the retention of GC hyperplasia after curative therapy with sucralfate may predisposed patients so treated to extended periods of remission.

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.

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.

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.

Disposition of propofol infusions for caesarean section.

The disposition of propofol was studied in women undergoing elective Caesarean section. Indices of maternal recovery and neonatal assessment were correlated with venous concentrations of propofol. After induction of anaesthesia with propofol 2.0 mg.kg-1, ten patients received propofol 6 mg.kg-1.hr-1 with nitrous oxide 50 per cent in oxygen (low group) and nine were given propofol 9 mg.kg-1.hr-1 with oxygen 100 per cent (high group). Pharmacokinetic variables were similar between the groups. The mean +/- SD Vss = 2.38 +/- 1.16 L.kg-1, Cl = 39.2 +/- 9.75 ml.min-1.kg-1 and t1/2 beta = 126 +/- 68.7 min. At the time of delivery (8-16 min), the concentration of propofol ranged from 1.91-3.82 micrograms.ml-1 in the maternal vein (MV), 1.00-2.00 micrograms.ml-1 in the umbilical vein (UV) and 0.53-1.66 micrograms.ml-1 in the umbilical artery (UA). Neonates with high UV concentrations of propofol at delivery had lower neurologic and adaptive capacity scores 15 minutes later. The concentrations of propofol were similar between groups during the infusion but they declined at a faster rate in the low group postoperatively. Maternal recovery times did not depend on the total dose of propofol but the concentration of propofol at the time of eye opening was greater in the high group than the low group (1.74 +/- 0.51 vs 1.24 +/- 0.32 micrograms.ml-1, P less than 0.01). The rapid placental transfer of propofol during Caesarean section requires propofol infusions to be given cautiously, especially when induction to delivery times are long.