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Biomedical subjects

S Currie

Publications and source records attributed to S Currie.

At least 19 recordsLinked to original sources
PubMed2001

Impact of HIV infection on mortality in a cohort of injection drug users.

The prevalence of HIV has been rising among injection drug users (IDUs) and AIDS is now an important cause of death among that population. We tracked mortality and recorded detailed causes of death in the Vancouver Injection Drug Users Study (VIDUS). This is an open cohort of over 1,400 active IDUs that began in May 1996. At enrollment and at semiannual follow-up visits, a trained interviewer administers a detailed semistructured questionnaire. Mortality was recorded during follow-up and detailed causes of death were collected from coroner's reports, hospital records, and the provincial (British Columbia) registry. Causes of death were obtained on 125 participants. Overall, the leading cause of death was overdose accounting for 25% of deaths among HIV-positive participants and 42% among HIV-negative participants. Of the 65 deaths among HIV-positive individuals, 22 (34%) were HIV related. Mortality was associated with older age (adjusted hazards ratio [AHR], 1.03 per year), HIV positivity (AHR, 2.67), injection cocaine use (AHR, 2.23) and methadone treatment (AHR, 0.47). The high rate of HIV in this population has added significantly to the burden of illness and death in this marginalized population.

Adolescent↗
PubMed2001

Increased contractility and calcium sensitivity in cardiac myocytes isolated from endurance trained rats.

OBJECTIVE: Regular exercise enhances cardiac function and modulates myocyte growth in healthy individuals. The purpose of the present study was to assess contractile function and expression of selected genes associated with intracellular Ca2+ regulation after intensity controlled aerobic endurance training in the rat. METHODS: Female Sprague-Dawley rats were randomly assigned to sedentary control (SED) or treadmill running (TR) 2 h per day, 5 days per week for 2, 4 or 13 weeks. Rats ran 8-min intervals at 85-90% of VO2max separated by 2 min at 50-60%. Myocyte length, intracellular Ca2+ (Fura-2), and intracellular pH (BCECF) were measured in dissociated cells in response to electrical stimulation at a range of stimulation rates. RESULTS: The increase in VO2max plateaued after 6-8 weeks, 60% above SED. After 13 weeks, left and right ventricular weights were 39 and 36% higher than in SED. Left ventricular myocytes were 13% longer, whereas width remained unchanged. After 4 weeks training, myocyte contractility was approximately 20% higher in TR. Peak systolic intracellular Ca2+ and time for the decay from systole were 20-35 and 12-17% lower, respectively. These results suggest that increased myofilament Ca2+ sensitivity is the dominant effect responsible for enhanced myocyte contractility in TR. Intracellular pH progressively decreased as stimulation frequency was increased in the SED group. This decrease was markedly attenuated in TR and the intracellular pH was significantly higher in the TR group at a stimulation rate of 5-10 Hz. This effect may contribute to the increased contractility observed at the higher stimulation frequencies in TR. A higher intrinsic myofilament Ca2+ sensitivity was observed in permeabilised myocytes from the TR group under conditions of constant pH and [Ca2+]. Western blot analysis indicated 21 and 46% higher myocardial SERCA-2 and phospholamban, but unaltered Na+/Ca(2+)-exchanger levels. Competitive RT-PCR revealed that TR significantly increased Na+/H(+)-exchanger mRNA. CONCLUSION: Intensity controlled interval training increases cardiomyocyte contractility. Higher myofilament Ca(2+)-sensitivity, and enhanced Ca(2+)-handling and pH-regulation are putative mechanisms. Our results suggest that physical exercise induces adaptive hypertrophy in cardiac myocytes with improved contractile function.

Animals↗
PubMed1999

Calcium/calmodulin-dependent protein kinase II activity is increased in sarcoplasmic reticulum from coronary artery ligated rabbit hearts.

A protein kinase activity intrinsic to the sarcoplasmic reticulum was studied in normal and hypertrophied rabbit hearts. The relationship between this kinase activity and phospholamban phosphorylation was examined. Calmodulin-dependent kinase II activity was found to be increased in sarcoplasmic reticulum preparations from hypertrophied hearts compared with normal. This was evident by measuring the phosphotransferase activity of the kinase and also by examining phospholamban phosphorylation by electrophoretic band shift analysis. Increased phospholamban phosphorylation by Calmodulin-dependent protein kinase II was dependent on prior phosphorylation by cAMP-dependent protein kinase, indicating potential crosstalk. Specific immunoblot analysis of the rabbit sarcoplasmic reticulum identified the presence of the delta form of calmodulin dependent protein kinase II and showed it to be up-regulated in hypertrophied hearts.

Animals↗
PubMed1999

Do needle exchange programmes increase the spread of HIV among injection drug users?: an investigation of the Vancouver outbreak.

OBJECTIVE: An association between needle exchange attendance and higher HIV prevalence rates among injecting drug users (IDU) in Vancouver has been interpreted by some to suggest that needle exchange programmes (NEP) may exacerbate HIV spread. We investigated this observed association to determine whether needle exchange was causally associated with the spread of HIV. DESIGN AND METHOD: Prospective cohort study of 694 IDU recruited in the downtown eastside of Vancouver. Subjects were HIV-negative at the time of recruitment and had injected illicit drugs within the previous month. RESULTS: Of 694 subjects, the 15-month cumulative HIV incidence was significantly elevated in frequent NEP attendees (11.8+/-1.7 versus 6.2+/-1.5%; log-rank P = 0.012). Frequent attendees (one or more visits per week) were younger and were more likely to report: unstable housing and hotel living, the downtown eastside as their primary injecting site, frequent cocaine injection, sex trade involvement, injecting in 'shooting galleries', and incarceration within the previous 6 months. The Cox regression model predicted 48 seroconversions among frequent attendees; 47 were observed. Although significant proportions of subjects reported obtaining needles, swabs, water and bleach from the NEP, only five (0.7%) reported meeting new friends or people there. When asked where subjects had met their new sharing partners, only one out of 498 respondents cited the needle exchange. Paired analysis of risk variables at baseline and the first follow-up visit did not reveal any increase in risk behaviours among frequent attendees, regardless of whether they had initiated drug injection after establishment of the NEP. CONCLUSIONS: We found no evidence that this NEP is causally associated with HIV transmission. The observed association should not be cited as evidence that NEP may promote the spread of HIV. By attracting higher risk users, NEP may furnish a valuable opportunity to provide additional preventive/support services to these difficult-to-reach individuals.

Adult↗
PubMed1999

Enhanced phosphorylation of phospholamban and downregulation of sarco/endoplasmic reticulum Ca2+ ATPase type 2 (SERCA 2) in cardiac sarcoplasmic reticulum from rabbits with heart failure.

OBJECTIVES: To assess the phosphorylation of myocardial phospholamban (PLB) and quantify protein levels of PLB and sarco/endoplasmic reticulum Ca2+ ATPase type 2 (SERCA 2) in a rabbit model of heart failure. Furthermore, to correlate these parameters with the rate of Ca2+ uptake into sarcoplasmic reticulum (SR) vesicles. METHODS: Heart failure in the rabbit was indicated by the pronounced ventricular contractile dysfunction accompanied by post-mortem evidence of lung and liver congestion 8 weeks after a coronary artery ligation procedure. Phosphorylation of PLB was measured by reduced mobility of the phosphorylated forms on Tris-glycine gels. Phosphoserine and phosphothreonine-specific antibodies against PLB were used to determine the phosphorylated residues. Immunoblotting combined with densitometry was used to assess PLB and SERCA 2 levels. Finally, oxalate-supported Ca2+ uptake into SR vesicles was studied using the fluorescent indicator Fura-2. RESULTS: The phosphorylation state of PLB was significantly higher in myocardium isolated from left ventricles of heart failure rabbits (8.3 +/- 0.42 P-PLB) when compared with sham-operated animals (4.0 +/- 1.7 P-PLB). The kinase activity associated with SR vesicles isolated from animals with heart failure was a factor of 1.58 +/- 0.21-times higher than sham hearts, as assessed by the initial rate of phosphorylation of PLB. This higher kinase activity observed in heart failure was not completely abolished by inhibitors of either A-kinase, C-kinase or Ca2+/calmodulin-dependent protein kinase (CaM-kinase). Abundance of SERCA in heart failure myocardial homogenates was significantly less than sham values (0.68 +/- 0.11 vs. 1.74 +/- 0.27) as was PLB (0.41 +/- 0.08 vs. 0.69 +/- 0.13), similar reductions were seen in vesicle preparations. The rate constant of Ca2+ uptake into the isolated SR vesicles was lower in preparations from heart failure myocardium than from sham myocardium (2.50 +/- 0.23 ms vs. 4.43 +/- 0.3 ms). CONCLUSIONS: The higher level of phosphorylation of PLB observed in the left ventricle of rabbits with heart failure is associated with a higher intrinsic kinase activity of the SR. However, the abundance of both of SERCA 2 and PLB proteins are lower in heart failure. The net effect of these changes appears to be a reduced rate of Ca2+ uptake by the SR in heart failure.

Animals↗
PubMed1999

Correlation between early, measurable improvement in quality of life and speed of visual rehabilitation after phacoemulsification.

PURPOSE: To assess whether improvements in measurable health-related quality-of-life (HR-QoL) functions parallel the rapid visual recovery after phacoemulsification. SETTING: The Cataract Treatment Center, Sunderland Eye Infirmary, Sunderland, England. METHODS: This study comprised 144 patients having first-eye phacoemulsification cataract extraction. They were assessed using a standard EuroQoL generic (non-disease specific) multidimensional HR-QoL instrument to evaluate preoperative and 1 month postoperative health profile measures in social, psychological, and general health aspects. RESULTS: Within 1 month of phacoemulsification, change in vision was accompanied by significant changes in HR-QoL functions such as home activities, social activities, self-care, mobility, and psychological well-being. CONCLUSION: The speed of visual rehabilitation after phacoemulsification was paralleled by improvement across HR-QoL functions, resulting in the rapid recovery of functional independence and health status.

Adult↗
PubMed1999

Influence of bioenergetic stress on heat shock protein gene expression in nucleated red blood cells of fish.

The physiological and biochemical signals that induce stress protein (HSP) synthesis remain conjectural. In this study, we used the nucleated red blood cells from rainbow trout, Oncorhynchus mykiss, to address the interaction between energy status and HSP gene expression. Heat shock (25 degrees C) did not significantly affect ATP levels but resulted in an increase in HSP70 mRNA. Hypoxia alone did not induce HSP transcription in these cells despite a significant depression in ATP. Inhibition of oxidative phosphorylation with azide, in the absence of thermal stress, decreased ATP by 56% and increased lactate production by 62% but did not induce HSP gene transcription. Inhibition of oxidative phosphorylation and glycolysis with azide and iodoacetic acid respectively, decreased ATP by 79% and prevented lactate production, but did not induce either HSP70 or HSP30 gene transcription in these cells. This study demonstrates that a reduction in the cellular energy status will not induce stress protein gene transcription in rainbow trout red blood cells and may, in fact, limit induction during extreme metabolic inhibition.

Animals↗
PubMed1998

Different red blood cell characteristics in a primitive agnathan (M. glutinosa) and a more recent teleost (O. mykiss) influence their strategies for blood CO2 transport.

This study examines how the different red blood cell (rbc) characteristics in two lower vertebrates, the phylogenetically primitive hagfish and a more recent teleost, the rainbow trout, influence their strategies for blood CO2 transport. Deoxygenation of the blood resulted in a significant increase in rbc CO2 content in hagfish, but there were no significant changes in the CO2 content of plasma or whole blood under these conditions. In contrast, deoxygenation increased the CO2 content of the rbc, plasma and whole blood in the trout. These results demonstrate that the Haldane effect is much less important for CO2 transport in the hagfish as compared to the trout. The relative importance of the rbc and plasma in blood CO2 transport were roughly similar in hagfish and trout and were very different from that previously documented in another primitive vertebrate, the lamprey. In trout, however, the role of the rbc in CO2 carriage was increased upon the addition of the beta-adrenergic agonist isoproterenol (10(-5) M) to the blood. Taken together, these results and those recently collected for lampreys demonstrate that changes in rbc characteristics during vertebrate evolution have probably resulted in several important transitions in the strategy for blood CO2 transport.

Adrenergic beta-Agonists↗
PubMed1997

Synthesis of stress protein 70 (Hsp70) in rainbow trout (Oncorhynchus mykiss) red blood cells

Unlike enucleated mammalian red blood cells (rbcs), the nucleated rbcs of lower vertebrates are capable of protein synthesis and may, therefore, serve as a valuable model to investigate the adaptive significance of stress protein synthesis in cells. This study examined the synthesis of stress protein 70 (Hsp70) in rbcs of the temperature-sensitive rainbow trout Oncorhynchus mykiss in response to heat shock and anoxia. Through western blot analysis, we have demonstrated that rainbow trout rbcs synthesize Hsp70 both constitutively and in response to an increase in temperature. Radioisotopic labelling experiments indicated that the temperature at which Hsp70 synthesis was induced in fish acclimated to 10 °C was between 20 and 25 °C. Actinomycin D blocked de novo Hsp70 synthesis, implying that synthesis of Hsp70 is regulated at the level of transcription in rainbow trout rbcs. Since trout rbcs rely heavily on aerobic metabolism, but may also experience very low oxygen levels within the circulation, we also examined the relative importance of (1) anoxia as a stimulus for Hsp70 synthesis and (2) oxygen as a requirement for protein synthesis under control and heat-shock conditions. We found that trout rbcs were capable of protein synthesis during 2 h of anoxia, but did not increase Hsp70 synthesis. Moreover, rbcs subjected to combined anoxia and heat shock exhibited increases in Hsp70 synthesis that were similar in magnitude to those in cells exposed to heat shock alone. The latter results suggest that rainbow trout rbcs are (1) able to synthesize non-stress proteins during anoxia, (2) capable of tolerating periods of reduced oxygen availability without increased synthesis of stress proteins and (3) able to maintain the integrity of their heat-shock response even during periods of anoxia.

Journal Article↗
PubMed1996

Socioeconomic circumstances and the risk of bowel cancer in Northern Ireland.

OBJECTIVE: To describe the variation in the incidence of colorectal cancer across Northern Ireland and relate it to factors associated with community deprivation. DESIGN: This was a cross sectional descriptive study. SETTING: Incidence data were obtained from a population based register for the period 1990-91. Small areas were characterised by their "affluence", or lack of it, by deriving a Townsend deprivation score for each electoral ward, using information from the 1991 census. PARTICIPANTS, MAIN OUTCOME MEASURES, AND STATISTICAL METHODS: The age standardised incidence was calculated for all colorectal cancer cases diagnosed histologically in 1990-91. Electoral wards were grouped into quintiles of the population after ranking of their Townsend scores and the association with incidence was studied using Poisson regression. RESULTS: The age standardised colorectal cancer incidence ranged from 22.5 (for quintile 1) to 29.9/100,000 (quintile 5) for men but the trend for women was less regular and rates were 18.4, 23.8, 27.3, 26.5, and 23.9/100,000 for quintiles 1-5 respectively (that is, from the most "affluent" to the most "deprived" fifths of the population). After adjusting for age and sex in Poisson regression, there was a significant association between the total colorectal cancer incidence and levels of community deprivation. The rate ratio for the most deprived quintile of the population (compared with the least) was 1.28 (95% CI 1.06,1.53). The effect was stronger for rectal cancer than for colonic cancer. There was no association between community deprivation and the cancer stage at diagnosis. CONCLUSIONS: In this population, the colorectal cancer incidence is associated with the level of material deprivation. The disease stages at the time of diagnosis in patients from more deprived areas seem to be comparable with those of patients from affluent areas. As others have shown, associations such as these are not explicable entirely on the basis of the distribution of known risk factors. Further research is needed to determine plausible mechanisms for the association.

Adolescent↗
PubMed1996

Relative effects of carbonic anhydrase infusion or inhibition on carbon dioxide transport and acid-base status in the sea lamprey Petromyzon marinus following exercise

In vivo experiments were carried out to determine the relative effects of carbonic anhydrase (CA) infusion or inhibition on carbon dioxide (CO2) transport and acid-base status in the arterial and venous blood of sea lampreys recovering from exhaustive exercise. Infusion of CA into the extracellular fluid did not significantly affect CO2 transport or acid-base status in exercised lampreys. In contrast, infusion of the CA inhibitor acetazolamide resulted in a respiratory acidosis in the blood of recovering lampreys. In acetazolamide-treated lampreys, the post-exercise extracellular pH (pHe) of arterial blood was significantly lower than that in the saline-infused (control) lampreys. The calculated arterial and venous partial pressure of carbon dioxide (PCO2) and the total CO2 concentration in whole blood (CCO2wb) and red blood cells (CCO2rbc) during recovery in the acetazolamide-infused lampreys were also significantly greater than those values in the saline-infused control lampreys. These results suggest that the CO2 reactions in the extracellular compartment of lampreys may already be in equilibrium and that the access of plasma bicarbonate to CA is probably not the sole factor limiting CO2 transport in these animals. Furthermore, endogenous red blood cell CA clearly has an important role in CO2 transport in exercising lampreys.

Journal Article↗
PubMed1995

The effects of blood CO2 reaction rates on CO2 removal from muscle in exercised trout.

The purpose of this study was to examine the relative importance of some of the factors potentially limiting carbon dioxide (CO2) removal from the white muscle in the rainbow trout following exhaustive exercise. Inhibition of red blood cell carbonic anhydrase (CA) activity by acetazolamide (Az) infusion following exercise caused a large increase in both arterial and muscle PCO2 indicating retention of CO2 in the animal. Despite the increase in muscle PCO2, there was no significant decrease in muscle pH in Az-treated fish, probably due to the relatively high buffer capacity of white muscle. The presence of CA in the plasma had a transient, significant effect on blood PCO2 and pH, but no significant effect on muscle PCO2 or pH. Thus, CA treatment transiently enhances CO2 removal from the animal following exercise, but the extracellular catalysis of the CO2 reactions in the plasma does not appear to have a large impact on CO2 removal from the tissues.

Acetazolamide↗
PubMed1994

Phosphorylation and activation of Ca(2+)-sensitive cytosolic phospholipase A2 in MCII mast cells mediated by high-affinity Fc receptor for IgE.

In the present study we examined the activation of Ca(2+)-sensitive cytosolic phospholipase A2 (cPLA2) after aggregation of cell-surface high-affinity Fc receptors for IgE (Fc epsilon RI) on mast cells. MCII mast cells (a factor-dependent bone-marrow-derived murine mast cell line) produce significant amounts of leukotriene C4 (LTC4) (70 ng/10(6) cells) on cross-linking of Fc epsilon RI. Using enzymic and immunochemical analysis we found that cPLA2 is the predominant form of this enzyme in MCII mast cells (0.2 micrograms/mg of total protein) and other forms (i.e. secretory PLA2 or Ca2+ independent cytosolic PLA2) could not be detected. Therefore MCII mast cells represent an excellent cellular model for the study of the biochemical mechanism(s) responsible for Fc epsilon RI-induced activation of cPLA2 and the involvement of cPLA2 in Fc epsilon RI-mediated production of LTC4. After activation of Fc epsilon RI by cross-linking, cPLA2 in MCII mast cells exhibited a decreased electrophoretic mobility and its enzyme activity was increased 3-fold. Treatment with phosphatase reversed both the altered electrophoretic mobility and the enhanced enzyme activity demonstrating that they were the result of Fc epsilon RI-induced phosphorylation. On cross-linking of Fc epsilon RI, cPLA2 was phosphorylated within 30 s and appeared to be an early substrate for Fc epsilon RI-activated protein kinases in MCII mast cells. Tyrosine phosphorylation may be a critical component in this process, as genistein, an inhibitor of protein tyrosine kinases, blocked the activation of cPLA2. Using anti-phosphotyrosine antibodies we observed that the activating phosphorylation was not on tyrosine residues of cPLA2, indicating that tyrosine kinases participate upstream in the signalling cascade that couples Fc epsilon RI to cPLA2. We conclude that in MCII mast cells cPLA2 is activated by kinase-dependent mechanisms and may be responsible for Fc epsilon RI-induced mobilization of arachidonic acid for the generation of LTC4.

Animals↗
PubMed1994

EFFECTS OF ENVIRONMENTAL TEMPERATURE ON THE METABOLIC AND ACID-BASE RESPONSES OF RAINBOW TROUT TO EXHAUSTIVE EXERCISE

In vivo experiments were conducted to determine how the physiological response to exhaustive exercise in rainbow trout (Oncorhynchus mykiss) is affected by environmental temperature. The white muscle acid­base status (e.g. pH, PCO2, HCO3- and deltaH+m) and metabolite (e.g. lactate, phosphocreatine, ATP and glycogen) content, and the acid­base status and lactate concentrations in the blood, were measured at rest and during recovery from burst exercise in rainbow trout acclimated to either 5 or 18 °C. Trout acclimated to the warmer temperature had higher resting levels of white muscle phosphocreatine (PCr) and also utilized a greater proportion of their muscle ATP and glycogen stores during burst activity compared with trout acclimated to the colder temperature. Recovery of muscle PCr and glycogen levels was independent of acclimation temperature, but muscle ATP levels recovered faster at 18 °C. Exhaustive exercise resulted in a similar lactacidosis in the muscle of trout acclimated to either temperature. In contrast, temperature had a marked influence on the lactacidosis in the blood. Blood lactate and metabolic proton concentrations following exercise were about twofold greater in fish acclimated to 18 °C than in fish acclimated to 5 °C. Despite the more severe acidosis and the greater lactate accumulation in the plasma of fish acclimated to warmer temperatures, the time required for recovery of these variables was similar to that at 5 °C. Taken together, these results suggest that acclimation temperature does not significantly affect anaerobic capacity in rainbow trout, but may account for much of the documented variability in the dynamics of the lactacidosis in blood following exhaustive exercise in fish.

Journal Article↗
PubMed1993

Access to coronary catheterisation: fair shares for all?

OBJECTIVE: To determine the effects of patient's sex and area's material deprivation on utilisation rates of coronary catheterisation and angiography in the investigation of ischaemic heart disease. DESIGN: Retrospective analysis of routinely collected hospital statistics. SETTING: Acute hospitals throughout Northern Ireland. SUBJECTS: 24,179 episodes of patients discharged from hospital with a primary diagnosis of ischaemic heart disease and 1270 episodes relating to patients with an underlying diagnosis of ischaemic heart disease who had either coronary catheterisation or angiography. MAIN OUTCOME MEASURES: Age standardised admission rates for heart disease and age standardised utilisation rates for catheterisation or angiography, or both, for 566 electoral wards ranked by Townsend "deprivation" scores. RESULTS: Catheterisation-angiography rates in men were over fivefold those of women, ranging from 85.5/100,000 v 16/100,000 in patients from "well off" areas to 123/100,000 v 22/100,000 for patients from deprived areas. After admission rates for heart disease were controlled for, the overall rate ratio for women was 0.48 (95% confidence interval 0.38 to 0.60). After differential admission rates for heart disease and other potential clinical confounders were controlled for, the investigation rates of patients from the least and most "deprived" areas were not significantly different (rate ratio 1.04 (0.87 to 1.25)). CONCLUSION: Although investigation rates were significantly lower in women than in men, further clinical data would be required before labelling this underutilisation as evidence of bias. There was no significant difference in invasive investigation rates for heart disease in areas of varying deprivation or affluence.

Adult↗
PubMed1993

Useless hand of Oppenheim--magnetic resonance imaging findings.

A patient with multiple sclerosis developed a useless, deafferented left hand, as described previously by Oppenheim. Magnetic resonance imaging demonstrates that this is caused by an ipsilateral plaque of demyelination in the posterior columns of the cervical cord.

Adult↗