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Biomedical subjects

C Lucas

Publications and source records attributed to C Lucas.

At least 55 records · Page 3Linked to original sources
PubMed2001

Effect of orlistat-assisted weight loss in decreasing coronary heart disease risk in patients with syndrome X.

This study describes the changes in risk factors for coronary heart disease in obese persons with syndrome X after orlistat-assisted weight loss. Data were available for 1,700 patients who completed 52 weeks of weight loss; 128 were defined as having syndrome X by being in the quintile with the highest plasma triglyceride levels (>2.2 mM/L) and the lowest high-density lipoprotein cholesterol (HDL, <1.0 mM/L) concentrations. Initial characteristics of those with syndrome X were similar to the 119 subjects (non-syndrome X) in the lowest quintile of plasma triglyceride (<0.975 mM/L) and highest quintile of HDL cholesterol (>1.5 mM/L). Subjects were placed on a calorie-restricted diet, and randomized to receive orlistat or placebo. Initial values were higher in those with syndrome X for diastolic blood pressure (p = 0.03), plasma insulin (p = 0.0001), triglyceride (p = 0.0001) concentrations, and ratio of low-density lipoprotein cholesterol to HDL cholesterol (p = 0.0001), and were lower for HDL cholesterol (p = 0.001) concentrations. Weight loss was greater in both groups of orlistat-treated patients (p = 0.026); in those with syndrome X, it was associated with a significant reduction in plasma insulin (p = 0.019) and triglyceride (p = 0.0001) concentrations, an increase in HDL cholesterol concentration, and a decrease in low-density lipoprotein/HDL cholesterol ratio (p = 0.0001). There were no significant changes in plasma insulin, triglycerides, or HDL cholesterol concentration in the non-syndrome X group. In conclusion, weight loss attenuates coronary heart disease risk factors in obese persons with syndrome X, and the risk factor reduction is enhanced with administration of orlistat.

Adult↗
PubMed2001

[Migraine. Immediate and long-term treatment].

ACUTE EPISODES: Patients who experience acute episodes of migraine headache can be treated with non-specific antalgics, non-steroidal antiinflammatory drugs, or specific agents, ergot derivatives, triptans. The rationale for specific treatment results from recent advances in our understanding of the pathophysiology of migraine. Triptans are serotoninergic agonists. CURRENT RECOMMENDATIONS: It is recommended to start with a non-specific agent. This approach is a purely economical attitude based on direct costs (excluding indirect costs). Specific treatment should be initiated immediately in case of failure to avoid self-medication or fatalism. The absence of adapted management can lead to a chronic condition called "transformed migraine" (more than 15 episodes daily) and subsequent abusive use of antalgics. An estimated 1 to 2 million people in France suffer from transformed migraine. LONG-TERM TREATMENT: A large number of long-term strategies are known but should be proposed for selected patients with frequent, invalidating episodes which have an important impact on the patient's quality of life and respond poorly to acute treatment. Classically, a long-term treatment should be proposed for patients with more than 2 or 3 severe acute episodes per month. This attitude has been revisited since the advent of specific treatments because a patient who gets rapid relief from specific treatment may not desire a long-term daily regimen. When effective, long-term regimens should be tapered off after about 12 months due to the fluctuating nature of the migraine headache. No valid algorithm predictive of therapeutic response to long-term treatment has been developed. The choice of the appropriate agent depends on potential side effects and comorbidities.

Acute Disease↗
PubMed2001

Fotemustine combined with procarbazine in recurrent malignant gliomas: a phase I study with evaluation of lymphocyte 06-alkylguanine-DNA alkyltransferase activity.

The aims of this phase I study in patients with recurrent malignant gliomas were to determine the maximum tolerated dose (MTD) and toxicity profile of fotemustine when combined with a fixed dose of procarbazine (PCZ), and to evaluate the extent of O6-alkylguanine-DNA alkyltransferase (ATase) depletion in circulating lymphocytes during treatment. Sixteen patients received an induction cycle consisting of 100 mg/day oral PCZ for 12 consecutive days and a 1-h intravenous infusion of fotemustine given 4 h after PCZ on days 5 and 12 at escalated doses (50, 75, 100 and 125 mg/m2/day). After a 6-week rest period, a maximum of 4 maintenance cycles (PCZ 300 mg/day, 4 days; fotemustine, day 4) was given every 4 weeks. ATase activity was measured on days 1, 5 and 12 over 4 h after PCZ intake. Fifteen patients had previously received at least one nitrosourea-based chemotherapy, associated with PCZ in 12 cases. The MTD of fotemustine was 125 mg/m2 (days 5 and 12) with myelosuppression as the dose limiting toxicity (DLT). At this dose level, half of patients experienced grade 3 anemia, neutropenia or thrombopenia. No extra-hematological DLT was observed. No significant depletion of ATase activity by PCZ was evidenced. One partial response and 7 stable diseases were obtained leading to a disease control rate of 50%. The median times to progression and survival were 2.6 and 9.7 months, respectively. This combined regimen of PCZ and fotemustine was well tolerated with a good disease control rate in heavily pretreated glioma patients and merits further investigation in phase II studies.

Adult↗
PubMed2001

A multicentre evaluation of a new filtration protocol for leucocyte depletion of high-haematocrit red blood cells collected by an automated blood collection system.

BACKGROUND AND OBJECTIVES: A multicentre trial was set up to evaluate the performance of a new leucodepletion protocol. MATERIALS AND METHODS: Filtration at high haematocrit was started during collection of red blood cell (RBC) products by apheresis with Trima. SAG-M was added after filtration through the filter. Haematocrits and haemoglobin of the filtered RBCs were measured. Residual leucocytes were determined by Nageotte counting. RESULTS: One-hundred and forty seven procedures were carried out. The haematocrit and haemoglobin contents were 57.3 +/- 3.0% and 55.1 +/- 4.3 g/unit, respectively. All products showed low residual leucocyte levels (< or = 0.75 x 106/unit; 99.31% < 1 x 106). CONCLUSION: Immediate, on-line, high-haematocrit filtration of red cells collected on Trima resulted in leucoreduced RBCs, which met the AABB and Council of Europe criteria.

Blood Cell Count↗
PubMed2001

Acute myelopathies: Clinical, laboratory and outcome profiles in 79 cases.

The main aetiologies of acute myelopathy (AM) are: multiple sclerosis, systemic disease (SD), spinal cord infarct (SCI), parainfectious myelopathy (PIM) and delayed radiation myelopathy (DRM). Although a large amount of data have been published for each individual aetiology, comparison studies are scarce. The aim of this study was to assess the various aetiological and outcome profiles of AM. We studied 79 cases: 34 (43%) in multiple sclerosis; 13 (16.5%) in SD; 11 (14%) in SCI; five (6%) in PIM; and three (4%) in DRM. Myelopathies were of unknown origin in 13 (16.5%) patients. We evaluated clinical, spinal cord and brain MRI, CSF and evoked potentials data at admission, MRI outcome at 6 months and clinical outcome at 12 months. A statistical comparison of clinical, laboratory and outcome data was only performed between multiple sclerosis, SD and SCI patients due to the small number of cases in the other groups. A motor deficit was more frequent in SD and SCI than in multiple sclerosis where initial symptoms were predominantly sensory (P < 0.001). Spinal cord MRI showed lateral or posterior lesions of less than two vertebral levels in multiple sclerosis, in contrast to SD and SCI, where lesions involved more vertebral levels and were centromedullar (P < 0.001). Brain MRI was most frequently abnormal in multiple sclerosis (68%), but was also abnormal in 31% of SD patients (P < 0.05). Oligoclonal bands in CSF were more frequent in multiple sclerosis than in SD (P < 0.001) and were never found in SCI. Clinical outcome at 12 months was good in 88% of multiple sclerosis cases, and poor or fair in 91% of SCI and 77% of SD. Aetiologies of AM may be differentiated on the basis of clinical, spinal cord and brain MRI, CSF and outcome data, and allow a probable diagnosis to be made in previously undetermined cases. These findings may have therapeutic implications for cases with a questionable diagnosis.

Acute Disease↗
PubMed2001

Importance of accurate geometry in the study of the total cavopulmonary connection: computational simulations and in vitro experiments.

Previous in vitro studies have shown that total cavopulmonary connection (TCPC) models incorporating offset between the vena cavae are energetically more efficient than those without offsets. In this study, the impact of reducing simplifying assumptions, thereby producing more physiologic models, was investigated by computational fluid dynamics (CFD) and particle flow visualization experiments. Two models were constructed based on angiography measurements. The first model retained planar arrangement of all vessels involved in the TCPC but incorporated physiologic vessel diameters. The second model consisted of constant-diameter vessels with non-planar vascular features. CFD and in vitro experiments were used to study flow patterns and energy losses within each model. Energy losses were determined using three methods: theoretical control volume, simplified control volume, and velocity gradient based dissipation. Results were compared to a simplified model control. Energy loss in the model with physiologically more accurate vessel diameters was 150% greater than the simplified model. The model with nonplanar features produced an asymmetric flow field with energy losses approximately 10% higher than simplified model losses. With the velocity gradient based dissipation technique, the map of energy dissipation was plotted revealing that most of the energy was dissipated near the pulmonary artery walls.

Algorithms↗
PubMed2001

Noninvasive fluid dynamic power loss assessments for total cavopulmonary connections using the viscous dissipation function: a feasibility study.

The total cavopulmonary connection (TCPC) has shown great promise as an effective palliation for single-ventricle congenital heart defects. However, because the procedure results in complete bypass of the right-heart, fluid dynamic power losses may play a vital role in postoperative patient success. Past research has focused on determining power losses using control volume methods. Such methods are not directly applicable clinically without highly invasive pressure measurements. This work proposes the use of the viscous dissipation function as a tool for velocity gradient based estimation of fluid dynamic power loss. To validate this technique, numerical simulations were conducted in a model of the TCPC incorporating a 13.34 mm (one caval diameter) caval offset and a steady cardiac output of 2 L x min(-1). Inlet flow through the superior vena cava was 40 percent of the cardiac output, while outflow through the right pulmonary artery (RPA) was varied between 30 and 70 percent, simulating different blood flow distributions to the lungs. Power losses were determined using control volume and dissipation function techniques applied to the numerical data. Differences between losses computed using these techniques ranged between 3.2 and 9.9 percent over the range of RPA outflows studied. These losses were also compared with experimental measurements front a previous study. Computed power losses slightly exceeded experimental results due to different inlet flow conditions. Although additional experimental study is necessary to establish the clinical applicability of the dissipation function, it is believed that this method, in conjunction with velocity gradient information derived from imaging modalities such as magnetic resonance imaging, can provide a noninvasive means of assessing power losses within the TCPC in vivo.

Biomechanical Phenomena↗
PubMed2001

The olivacine S16020 enhances the antitumor effect of ionizing radiation without increasing radio-induced mucositis.

The combination of a novel topoisomerase II inhibitor, S16020, and ionizing radiation (IR) was investigated with the aim of assessing normal tissue tolerance using a mouse mucosal lip model and antitumor activity in a human carcinoma (HEP2) cell line. No increase of acute mucosal reactions was seen when combining S16020 with IR as compared with IR alone. Using clonogenic cell survival assay, a marked enhancement of HEP2 cell killing was found when S16020 was combined with irradiation. Additional in vivo combination of S16020-IR was able to increase markedly the antitumor efficacy as compared with S16020 or irradiation alone. Interestingly, the radiosensitization effect in vivo was observed at relatively low and nontoxic concentrations of S16020, and no dose-effect relationship was found beyond 30 mg/kg. In conclusion, the combination of IR and S16020 seems promising to enhance antitumor activity without increasing deleterious effect in normal tissues and to provide the basis for a new radio-chemotherapy combination.

Animals↗
PubMed2000

Protection of Aotus monkeys by Plasmodium falciparum EBA-175 region II DNA prime-protein boost immunization regimen.

Aotus monkeys received 4 doses of Plasmodium falciparum EBA-175 region II vaccine as plasmid DNA (Dv-Dv) or recombinant protein in adjuvant (Pv-Pv) or as 3 doses of DNA and 1 dose of protein (Dv-Pv). After 3 doses, antibody titers were approximately 10(4) in DNA-immunized monkeys and 10(6) in protein-immunized monkeys. A fourth dose did not significantly boost antibody responses in the Dv-Dv only or Pv-Pv only groups, but titers were boosted to approximately 10(6) in monkeys in the Dv-Pv group. Four weeks after the last immunization, the animals were challenged with 10(4) P. falciparum-parasitized erythrocytes. Peak levels of parasitemia were lower in the 16 monkeys that received region II-containing plasmids or proteins than in the 16 controls (geometric mean: 194,178 and 410,110 parasites/microL, respectively; P=.013, Student's t test). Three of 4 monkeys in the Dv-Pv group did not require treatment. These data demonstrate that immunization with EBA-175 region II induces a significant antiparasite effect in vivo.

Adjuvants, Immunologic↗
PubMed2000

Common carotid artery intima-media thickness and brain infarction : the Etude du Profil Génétique de l'Infarctus Cérébral (GENIC) case-control study. The GENIC Investigators.

BACKGROUND-The use of intima-media thickness (IMT) as an outcome measure in observational studies and intervention trials relies on the view that it reflects early stages of atherosclerosis and cardiovascular risk. There is little knowledge concerning the relation between IMT and brain infarction (BI). METHODS AND RESULTS-We investigated the relation of IMT with BI and its subtypes in 470 cases and 463 controls. Cases with BI proven by MRI were consecutively recruited and classified into subtypes by cause of BI. Controls were recruited among individuals hospitalized at the same institutions and matched for age, sex, and center. IMT was measured at the far wall of both common carotid arteries (CCA) using an automatic detection system. Adventitia-to-adventitia diameters and CCA-IMT were measured on transverse views; lumen diameter was computed using these measures. Mean (+/-SEM) CCA-IMT was higher in cases (0.797+/-0.006 mm) than in controls (0.735+/-0.006 mm; P<0. 0001). This difference remained after adjustment for lumen diameter and when analyses were restricted to subjects free of previous cardiovascular or cerebrovascular history. The difference in CCA-IMT between cases and controls was significant in the main subtypes. The risk of BI increased continuously with increasing CCA-IMT. The odds ratio per SD increase (0.150 mm) was 1.82 (95% confidence interval, 1.54 to 2.15); adjustment for cardiovascular risk factors slightly attenuated this relation (odds ratio, 1.73; 95% confidence interval, 1.45 to 2.07). CONCLUSIONS-An increased CCA-IMT was associated with BI, both overall and in the main subtypes. An increased IMT may help select patients at high risk for BI.

Adult↗
PubMed2000

Orlistat in the long-term treatment of obesity in primary care settings.

OBJECTIVE: To evaluate the long-term efficacy and tolerability within primary care settings of orlistat, a gastrointestinal lipase inhibitor, for the treatment of obesity. DESIGN: Randomized, double-blind, placebo-controlled, multicenter study. PARTICIPANTS: A group of 796 obese patients (body mass index, 30-44 kg/m2), treated with placebo 3 times a day (TID), 60 mg of orlistat TID, or 120 mg of orlistat TID, in conjunction with a reduced-energy diet for the first year and a weight-maintenance diet during the second year. SETTING: Seventeen primary care centers in the United States. MAIN OUTCOME MEASURES: Changes in body weight and obesity-related disease risk factors. RESULTS: Patients treated with orlistat lost significantly more weight (7.08 +/- 0.54 and 7.94 +/- 0.57 kg for the 60-mg and 120-mg orlistat groups, respectively) than those treated with placebo (4.14 +/- 0.56 kg) in year 1 (P<.001) and sustained more of this weight loss during year 2 (P<.001). More patients treated with orlistat lost 5% or more of their initial weight in year 1 (48.8% and 50.5% of patients in the 60-mg and 120-mg groups, respectively) compared with placebo (30.7%; P<.001), and approximately 34% of patients in the orlistat groups sustained weight loss of 5% or greater over 2 years compared with 24% in the placebo group (P<.001). Orlistat produced greater improvements than placebo in serum lipid levels and blood pressure and was well tolerated, although treatment resulted in a higher incidence of gastrointestinal events. CONCLUSIONS: This long-term study indicates that orlistat is an effective adjunct to dietary intervention in the treatment of obesity in primary care settings.

Adult↗
PubMed2000

Leuprorelin depot 3.75 mg versus lynestrenol in the preoperative treatment of symptomatic uterine myomas: a multicentre randomised trial.

OBJECTIVES: To compare the effect of the gonadotrophin-releasing hormone agonist leuprorelin and progestin lynestrenol, given prior to surgical treatment of symptomatic uterine myomas, on the pre-operative symptoms, tolerance, and operative blood loss. STUDY DESIGN: Fifty-six women were randomly selected to receive, during 16 weeks, either monthly subcutaneous injections of leuprorelin 3.75 mg sustained release (n=33) or lynestrenol 5 mg two tabs per day (5th to the 25th menstrual cycle) (n=23). RESULTS: Intent-to-treat analysis of the main efficacy criterion, namely ultrasonographic reduction of myoma(s) diameter, showed a significant difference in favour of leuprorelin (P=0.02) with a mean decrease of 26.5+/-4.5% (n=29) as opposed to 7.3+/-5% in the lynestrenol group (n=17). Clinical improvement was satisfactory in both groups. Hematocrit decrease between the preoperative value and the value measured 48 h postoperatively was significantly lower in the leuprorelin group than in the lynestrenol one (P=0.02) (for hemoglobin: P=0.07). CONCLUSION: Leuprorelin was more effective than lynestrenol because of its more intense antigonadotropic activity. The tolerance was good, reflecting each drug mechanism of action.

Adult↗
PubMed2000

GUP1 and its close homologue GUP2, encoding multimembrane-spanning proteins involved in active glycerol uptake in Saccharomyces cerevisiae.

Many yeast species can utilize glycerol, both as a sole carbon source and as an osmolyte. In Saccharomyces cerevisiae, physiological studies have previously shown the presence of an active uptake system driven by electrogenic proton symport. We have used transposon mutagenesis to isolate mutants affected in the transport of glycerol into the cell. Here we present the identification of YGL084c, encoding a multimembrane-spanning protein, as being essential for proton symport of glycerol into S. cerevisiae. The gene is named GUP1 (glycerol uptake) and, for growth on glycerol, is important as a carbon and energy source. In addition, in strains deficient in glycerol production it also provides osmotic protection by the addition of glycerol. Another open reading frame (ORF), YPL189w, presenting a high degree of homology to YGL084c, similarly appears to be involved in active glycerol uptake in salt-containing glucose-based media in strains deficient in glycerol production. Analogously, this gene is named GUP2. To our knowledge, this is the first report on a gene product involved in active transport of glycerol in yeasts. Mutations with the same phenotypes occurred in two other ORFs of previously unknown function, YDL074c and YPL180w.

Amino Acid Sequence↗
PubMed2000

Long-term evaluation of autonomic tone in patients below 50 years of age with unexplained cerebral infarction: relation to atrial vulnerability.

UNLABELLED: Preliminary studies have described, in young patients with unexplained cerebral infarction, electrophysiological abnormalities similar to those observed in paroxysmal atrial fibrillation. Moreover, in young adults with 'normal' hearts, increased susceptibility to paroxysmal atrial fibrillation with autonomic abnormalities as assessed by heart rate variability analysis have been reported. METHODS: The long-term time and frequency domain measures of heart rate variability were analysed prospectively from 24-h Holter ECG recordings in 25 patients (39 +/- 8 years) with unexplained cerebral infarction, and in 25 age-, sex- and cigarette-smoking-matched healthy control subjects. The day following the Holter ECG recordings, 9 +/- 4 months (mean) after the stroke, stroke patients underwent an electrophysiological study in order to analyse the electrical characteristics of their right atria and also to determine their vulnerability to atrial fibrillation. The correlations between autonomic tone parameters and electrophysiological findings were therefore assessed with linear regression analyses. RESULTS: All the measured components of heart rate variability either in time (SDNN, pNN50, SDANN/5, rMSSD) or frequency domains (total power, low-frequency, high-frequency power, low-frequency/high-frequency power ratio) were similar between stroke patients and controls. During electrophysiological study, atrial fibrillation was induced in 80% of stroke patients. Among these patients, atrial refractory periods were significantly shorter, local electrograms were longer, and latent atrial vulnerability index was markedly decreased when compared with patients having no inducible atrial fibrillation. Concerning heart rate variability analysis, no difference was found between patients with induced atrial fibrillation when compared with a matched subgroup of healthy control subjects. Furthermore, there was no statistically linear correlation between any of the measured autonomic tone parameters and any of the discovered atrial vulnerability markers. CONCLUSIONS: The long-term autonomic tone parameters of young patients presenting with a history of unexplained cerebral infarction are similar to those of healthy control subjects and are not correlated with atrial vulnerability parameters or atrial fibrillation inducibility.

Adult↗
PubMed2000

An outbreak of Serratia marcescens in two neonatal intensive care units.

Outbreaks of infection in neonatal intensive care units (NICUs) due to Serratia marcescens are well recognized. In some outbreaks no point source has been found, whereas in others cross-infection has been associated with contaminated ventilator equipment, disinfectants, hands and breast pumps. We report an outbreak due to S. marcescens that involved two geographically distinct NICUs. The outbreak occurred over a six week period; 17 babies were colonized, 12 at Glasgow Royal Maternity Hospital (GRMH) and five at the Queen Mothers Hospital (QMH). At GRMH three babies developed septicaemia, of whom two died. The outbreak isolates were of the same serotype and phage type and were indistinguishable on the basis of restriction fragment length polymorphism analysis. During the outbreak, two babies shown consistently to be negative on screening, were transferred between the two units. In addition, two members of medical staff attended both units. In QMH no means of cross infection was identified. However, in GRMH the outbreak strain of S. marcescens was isolated from a laryngoscope blade and a sample of expressed breast milk.

Breast Feeding↗