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Biomedical subjects

S Leslie

Publications and source records attributed to S Leslie.

At least 19 recordsLinked to original sources
PubMed2002

High doses of atorvastatin do not affect activity of prothrombinase in patients with acute coronary syndromes.

Membrane-dependent coagulation processes play a key role in acute coronary syndromes (ACS), where the generation of thrombin depends on the complex of activated factors X and V (prothrombinase complex) assembled on activated platelets. The aim of the present study was to evaluate prothrombinase activity in patients with ACS and to examine the effect of treatment with 80 mg/day atorvastatin on prothrombinase activity. Blood samples were obtained at admission from 22 patients with ACS, and then again at 2 weeks and at 16 weeks after double-blind randomization to either placebo or atorvastatin. Prothrombinase activity was evaluated by measuring the generation of thrombin by in vitro reconstructed thrombi, and also by measuring plasma levels of prothrombin fragment F1 + 2. Twenty age-matched subjects with stable angina and 11 without coronary disease were used as controls. At admission, prothrombinase activity and F1 + 2 were significantly higher in ACS patients than in controls. Prothrombinase activity was still high at 2 weeks while it returned to normal levels at 16 weeks. F1 + 2 remained high both at 2 and at 16 weeks. Our data indicate that prothrombinase activity is high in patients with ACS, and that it is not affected by high-dose atorvastatin.

Acute Disease↗
PubMed2001

Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.

CONTEXT: Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome, but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events. OBJECTIVE: To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic events. DESIGN AND SETTING: A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia. PATIENTS: A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction. INTERVENTIONS: Patients were stratified by center and randomly assigned to receive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission. MAIN OUTCOME MEASURES: Primary end point event defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. RESULTS: A primary end point event occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P =.048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =.02). Likewise, there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12 vs 24 events; P =.045). In the atorvastatin group, mean low-density lipoprotein cholesterol level declined from 124 mg/dL (3.2 mmol/L) to 72 mg/dL (1.9 mmol/L). Abnormal liver transaminases (>3 times upper limit of normal) were more common in the atorvastatin group than in the placebo group (2.5% vs 0.6%; P<.001). CONCLUSION: For patients with acute coronary syndrome, lipid-lowering therapy with atorvastatin, 80 mg/d, reduces recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalization.

Aged↗
PubMed2001

Rethinking the role of urinary magnesium in calcium urolithiasis.

BACKGROUND AND PURPOSE: The role of magnesium in urinary stone formation remains undefined. In vivo, magnesium inhibits stone formation in hyperoxaluric rats, and small clinical studies suggest a protective effect of magnesium supplementation in calcium oxalate stone formers. We performed a retrospective review of more than 7,000 stone patients to see if there is a relation between urinary magnesium and other stone risk variable constituents. MATERIALS AND METHODS: A national database of stone formers categorized by residential ZIP code was queried, and, using strict inclusion criteria, 2,147 patients having pure calcium oxalate stones were identified. There were 1,912 (89%) eumagnesuric (43-246 mg/24 hours) and 235 (11%) hypomagnesuric (<43 mg/24 hours) patients. RESULTS: Patients with decreased urinary magnesium excretion had significantly less daily urine excretion of citrate, calcium, oxalate, uric acid, and sodium than the eumagnesuric group (p < 0.0001). Stone recurrence was slightly more common in the hypomagnesuric group, although the difference was not statistically significant. The percentage of patients voiding <1 L of urine per day was significantly higher in the hypomagnesuric group. In the eumagnesuric group, males outnumbered females 2:1, whereas hypomagnesuric patients showed a female predominance of 1.4:1. CONCLUSION: The beneficial effects of urinary magnesium on stone formation may be less than previously reported. The role of oral magnesium supplementation and the subsequent increase in urinary magnesium in calcium urinary stone formation remains unknown. Our data suggest that its effect on or interaction with citrate may be influential on urinary citrate concentrations. If magnesium has a protective effect, it may work through pathways that enhance citrate excretion.

Calcium Oxalate↗
PubMed2001

Online consulting. The experience of a commercial service.

Doctor Global Ltd began online consulting in April 1999. It was one of the first online medical consulting services in the world. Doctor Global does not derive a significant portion of its income from providing or supervising online consultations via its Website, although experience with enabling them has been important for the development of its core product, a consumer-oriented Web-based electronic medical record.

Attitude of Health Personnel↗
PubMed2001

Why use soap?

Explore the source record for details and available documents.

Dermatitis↗
PubMed2000

Reversible cross-linking and CO treatment as an approach in red cell stabilization.

We explored the use of the reversible cross-linking reagent dimethyl 3,3-dithiobispropionimidate (DTBP) in combination with CO treatment as an approach to stabilizing erythrocyte structure and function. Erythrocytes were cross-linked with different concentrations of DTBP for different times. DTBP increased erythrocyte osmotic stability, blocked lysolecithin-induced echinocytosis, and decreased erythrocyte deformability in a concentration- and time-dependent manner. Reversal of the cross-linking with the reducing agent dithioerythritol (DTE) restored osmotic fragility and response to lysolecithin as well as deformability. Complete reversal, however, is a function of the DTBP concentration and the time of cross-linking. The effects of cross-linking with 5 mM DTBP for 1 h were completely reversible after treatment with 10 mM DTE for 20 min. Longer incubation times or higher concentrations of DTBP resulted in partial reversal by DTE of the effects produced by DTBP. Cross-linking and reversal only slightly reduced the ATP content. The hemoglobin contained in the cross-linked and reversed cells could still undergo reversible oxygenation and deoxygenation. Erythrocytes were pretreated with CO, cross-linked with 5 mM DTBP for 1 or 3 h, loaded with a solution containing 500 mM glucose for 24 h, and freeze-dried in a medium containing 15% (w/v) albumin. Rehydration followed in distilled water. Complete recovery, measured as the percentage of free hemoglobin, was achieved for cells cross-linked with 5 mM DTBP for 3 h and freeze-dried to a final water content of 10-15%. Non-cross-linked cells lysed 100% on rehydration in distilled water. No methemoglobin (MetHb) formation as a result of freeze-drying was detected in CO-treated cells. In non-CO-treated cells 20% of the Hb was converted to MetHb.

Adenosine Triphosphate↗
PubMed2000

The effect of progestins on vascular endothelial growth factor, oestrogen receptor and progesterone receptor immunoreactivity and endothelial cell density in human endometrium.

One common side-effect of contraceptive use is that it often leads to disrupted endometrial bleeding patterns. This may be due to changes in endothelial density and vessel integrity. To investigate whether the level of endometrial immunoreactive vascular endothelial growth factor (VEGF), oestrogen receptor or progesterone receptor (PR) have any role in this, women were treated with either Mircette, a monophasic oral contraceptive, or Implanon, a long-acting gestagen, and immunohistochemistry performed. In addition a small number of endometria were studied from women treated with levonorgestrel released from an intrauterine coil. During the untreated normal cycle, there was a significant increase in glandular VEGF immunoreactivity and a significant decrease in PR immunoreactivity in the midand late secretory phases compared to the proliferative phase. There was a significant positive correlation between stromal VEGF immunoreactivity and endothelial cell density. This correlation was also apparent during treatment with Implanon, but not with Mircette. Disrupted bleeding patterns were associated with Implanon and to a lesser extent with Mircette. Both contraceptives significantly reduced glandular VEGF immunoreactivity but the intrauterine treatment with levonorgestrel resulted in strong glandular epithelial staining and intense staining of decidualized stromal cells. Implanon significantly increased glandular PR staining, but Mircette significantly reduced stromal PR staining when compared to secretory phase before-treatment biopsies. There were no changes in endothelial cell density or glandular or stromal ER during the normal cycle, or with use of either contraceptive. There was no association of the parameters measured with bleeding patterns or histological category.

Cell Count↗
PubMed1999

The effect of etonogestrel on VEGF, oestrogen and progesterone receptor immunoreactivity and endothelial cell number in human endometrium.

Contraceptive use often leads to disrupted endometrial bleeding patterns in women. In this study, two different contraceptive regimes (Mircette, a monophasic oral contraceptive and Implanon, a long-acting gestagen) were used and their effects on the immunoreactivity of vascular endothelial growth factor (VEGF), oestrogen receptor (ER), progesterone receptor (PR) and endothelial cell number were determined. During the untreated normal cycle, there was a significant increase (P = 0.005) in glandular VEGF immunoreactivity and a significant decrease (P < 0.05) in PR immunoreactivity in the mid- and late secretory phases compared with the proliferative phase. There was a significant positive correlation (gamma = 0.38, P = 0.046) between stromal VEGF immunoreactivity and endothelial cell number. This correlation was also apparent during treatment with Implanon, but not with Mircette. Disrupted bleeding patterns were associated with Implanon and, to a lesser extent, with Mircette. Both contraceptives significantly reduced glandular VEGF immunoreactivity. Implanon significantly increased (P = 0.016) glandular PR staining, but Mircette significantly reduced (P = 0.027) stromal PR staining when compared with secretory before-treatment biopsies. There were no changes in endothelial cell number or glandular or stromal ER during the normal cycle, or with use of either contraceptive. There was no association between the parameters measured with bleeding patterns and histological category.

Adolescent↗
PubMed1998

Prolonged prothrombin time and activated partial thromboplastin time due to underfilled specimen tubes with 109 mmol/L (3.2%) citrate anticoagulant.

Underfilling of specimen tubes containing 129 mmol/L (3.8%) buffered citrate prolongs prothrombin time (PT) and activated partial thromboplastin time (APTT) values. We studied this phenomenon by using 109 mmol/L (3.2%) buffered citrate as the anticoagulant, anticipating some increase in tolerance to underfilling. Venous blood drawn from 12 healthy subjects and 30 patients receiving long-term oral warfarin therapy was mixed with 109 mmol/L buffered citrate solution in proportions equivalent to filling the collection tubes from 52% to 100% of capacity. Accurate PT values were obtained from normal specimens if the tubes were filled to 65% or more of capacity. Accurate PT results in the therapeutic range were obtained only with filling to 80% or more of capacity (using a "moderately sensitive" thromboplastin reagent, International Sensitivity Index [ISI] = 2.06) or 90% or more of capacity (using a "highly sensitive" thromboplastin reagent, ISI = 1.01). In contrast, APTT was much less tolerant to underfilling, with prolonged values observed in most specimens filled to less than 90% of capacity. No false low values were observed. Specimen tubes should be filled to at least 90% of capacity to avoid falsely elevated PT or APTT results, but values within the reference range may be acceptable even from underfilled tubes.

Adult↗
PubMed1998

Isokinetic strength testing does not predict hamstring injury in Australian Rules footballers.

OBJECTIVE: To determine the relation of hamstring and quadriceps muscle strength and imbalance to hamstring injury using a prospective observational cohort study METHOD: A total of 102 senior male Australian Rules footballers aged 22.2 (3.6) years were tested at the start of a football season. Maximum voluntary concentric and eccentric torque of the hamstring and quadriceps muscles of both legs was assessed using a Kin-Com isokinetic dynamometer at angular velocities of 60 and 180 degrees/second. Twelve (11.8%) players sustained clinically diagnosed hamstring strains which caused them to miss one or more matches over the ensuing season. RESULTS: There were no significant differences for any of the isokinetic variables comparing the injured and non-injured legs in players with unilateral hamstring strains (n=9). Neither the injured nor the non-injured leg of injured players differed from the mean of left and right legs in non-injured players for any isokinetic variable. The hamstring to opposite hamstring ratios also did not differ between injured and non-injured players. A hamstring to opposite hamstring ratio of less than 0.90 and a hamstring to quadriceps ratio of less than 0.60 were not associated with an increased risk of hamstring injury. A significantly greater percentage of players who sustained a hamstring strain reported a history of hamstring strain compared with non-injured players (p=0.02). However, this was not related to muscle weakness or imbalance. CONCLUSIONS: Isokinetic muscle strength testing was not able to directly discriminate Australian Rules football players at risk for a hamstring injury.

Adult↗
PubMed1996

Isolation and identification of a protein with capsaicin-inhibited NADH oxidase activity from culture media conditioned by growth of HeLa cells.

A ca. 33.5-kDa protein has been identified as a soluble NADH oxidase activity of culture media conditioned by growth of HeLa cells. The protein appears to be derived from a 34-kDa protein of the HeLa plasma membrane. Both proteins are characterized by an ability to oxidize NADH in the absence of exogenous electron acceptors. The activity is inhibited by 8-methyl-N-vanillyl-6-noneamide (capsaicin). The soluble and the plasma membrane forms of the activity exhibit a similar EC50 of about 5 nM for inhibition of the activity by capsaicin. The activity was purified from culture media conditioned by growth of HeLa cells using DEAE ion exchange chromatography, G-200 size exclusion chromatography, and preparative SDS-PAGE. Purification was monitored on the basis of the capsaicin-inhibited oxidation of NADH, including the final electrophoretic purification. Activity was restored following SDS-PAGE by reduction with dithiothreitol or reduced glutathione in the presence of NADH followed by the addition of 0.03% hydrogen peroxide and preincubation in the presence of NADH for 5-15 min. For affinity purification, the vanillylamine portion of capsaicin was linked to agarose. The agarose-linked vanillylamine bound a ca. 33.5-kDa protein band with capsaicin-inhibited NADH activity from total defined culture media conditioned by growth of HeLa cells. The NADH oxidase activity of both the soluble and the plasma membrane-associated form of the activity was inhibited by antisera corresponding to the 33.5-kDa protein. The antisera also immunoprecipitated and reacted on Western blots with both the soluble (33.5 kDa) and plasma membrane (34 kDa)-associated forms of the capsaicin-inhibited activity. The results identify the capsaicin-inhibited NADH oxidase of the conditioned media of HeLa cells as being a ca. 33.5-kDa shed form of the previously reported capsaicin-inhibited NADH oxidase of the HeLa cell plasma membrane.

Capsaicin↗
PubMed1996

Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation.

PURPOSE: To determine whether the expression of epidermal growth factor receptor (EGFR) protein was predictive of patient survival independently of other prognostic factors in astrocytic tumors. METHODS AND MATERIALS: Epidermal growth factor receptor protein expression was investigated immunohistochemically in formalin-fixed, paraffin-embedded surgical specimens of 55 glioblastoma multiforme, 14 anaplastic astrocytoma, and 2 astrocytomas given definitive irradiation. We evaluated the relationship of EGFR protein expression and tumor grade, histologic features, age at diagnosis, sex, patient survival, and recurrence-free survival. RESULTS: The percentage of tumor cells which were EGFR positive related to reduced survival by Cox regression analysis in both univariate (p = 0.0424) and multivariate analysis (p = 0.0016). Epidermal growth factor receptor positivity was the only 1 of 11 clinical and histological variables associated with decreased recurrence-free survival by either univariate (p = 0.0353) or multivariate (p=0.0182) analysis. Epidermal growth factor receptor protein expression was not related to patient age, sex, or histologic features. CONCLUSION: Epidermal growth factor receptor positivity was a significant and independent prognostic indicator for overall survival and recurrence-free survival for irradiated patients with astrocytic gliomas.

Astrocytoma↗
PubMed1996

Detection of air emboli in radiographic contrast media by microwave radiometry.

To evaluate the efficacy of a microwave radiometry system in detecting in-line air emboli in radiographic contrast media, air emboli ranging in volume from 0.1 to 0.005 ml were introduced into ionic (ioxaglate) and nonionic (iohexol) contrast media at 22 or 37 degrees pumped at flow rates of 16.7, 180 or 300 ml/min through polyvinlychloride tubing with an inner diameter of 0.100 inches (2.54 mm) over which was fitted a radiometer antenna connected to a Microwave Medical System F+ radiometer and a computerized data acquisition system. A total of 400 determinations were run, with 10 replicate determinations for each unique set of experimental conditions. The success of air emboli detection was not significantly related to contrast media (p = 0.73) or contrast temperature (p = 0.68). Embolus volume (p < 0.0001) and pump speed (p < 0.0001) were significant factors affecting system performance. The system could reliably detect small (0.005 ml) emboli in both ionic and nonionic low-osmolar contrast media.

Air↗
PubMed1996

Tobacco control in a traditional Fijian village: indigenous methods of smoking cessation and relapse prevention.

This case study outlines the unique process by which a village in Fiji (N = 238) developed and implemented an extremely successful community-based smoking cessation program. Both Western smoking cessation methods and native traditional rituals were used. Specific strategies included a group pledge, village rapid inhalation ceremony, social contracting through notices and media, and a tabu formalized through a kava ceremony. Whereas the more conventional, external, health professional oriented approaches were largely unsuccessful, longer term collaborative and village empowerment methods proved most successful. Eventually all persons in the village who smoked were able to give up smoking, with specific exceptions (elders, visitors, etc.) and became nationally known as the village that gave up smoking. Follow up evaluation at 9 and 21 months indicated sustained success. Cases of relapse are described involving supernatural consequences remedied by group and ceremonial methods. The socio-cultural context and larger relationship issues are discussed in order to more fully understand the effectiveness of the program.

Adolescent↗
PubMed1989

Cathepsin B, D and H activities in muscles of chicks of fast and slow growing strains: effect of age and diet.

1. Activities of cathepsins B, D and H were measured in leg and breast muscles of fast growing (broiler) and slow growing (layer) chicks at eight time intervals between 1 and 29 days of age. 2. These enzyme activities were also measured in muscles from fast and slow growing chicks given a low protein (125 g/kg crude protein) diet between the ages of 17 and 24 days. 3. Activities of none of these cathepsins differed greatly between muscle type or strain of chick. However in both strains of chick cathepsin D and H in muscles significantly decreased with increasing age (muscle size) of the chick. Cathepsin D activity also increased when muscle proteolytic rates were increased by feeding a low protein diet. This latter effect was significant only in the muscles of fast growing chicks. 4. The results suggest that lysosomal proteases are not responsible for the differences in muscle protein degradation and growth between fast and slow growing strains of chicks, or between muscle types in the chick.

Aging↗
PubMed1988

Muscle growth and protein degradation during early development in chicks of fast and slow growing strains.

1. Growth of breast and leg muscles and excretion of N tau methyl histidine in layer (slow growing) and broiler (fast growing) chicks were measured at five time intervals between 2 and 33 days of age. 2. The results indicate that muscles of the broiler chick grow faster than in layer chicks and that breast muscles of both strains grow faster than leg muscles in the first 2 weeks after hatching. 3. N tau methyl histidine excretion by layer chicks is higher than that by broilers relative to body weight, musculature and relative maturity at all ages examined. 4. The results suggest that faster growth of muscles is accompanied by a lower rate of protein degradation although at ages of less than 2 weeks differences in protein synthesis rates may also contribute to muscle growth.

Aging↗