Biomedical subjects

A R Robert

Publications and source records attributed to A R Robert.

15 recordsLinked to original sources

PubMed2001

Bone marrow micrometastasis might not be a short-term predictor of survival in early stages non-small cell lung carcinoma.

OBJECTIVE: To determine the presence of occult micrometastasis (OM) in a selected population of surgically resectable patients presenting with non-small cell lung carcinoma (NSCLC) and to evaluate its prognostic value on relapses and survival. METHODS: From February 1996 to December 1999, 99 patients undergoing surgical treatment for NSCLC were prospectively investigated for the presence of occult bone marrow micrometastasis. Tumor cells were detected with monoclonal primary antibodies directed against low molecular weight cytokeratins. RESULTS: Median follow-up time was 14.3 months (range 0.2-45.6 months). Overall prevalence of OM was 22.2% (22 out of 99). The presence of OM was not correlated to pathology, T status, or N status. In survival analysis, the only independent predictors of overall survival were N0 status and Stage I (P=0.016 and 0.004, respectively), while T1 was a predictor of disease-free survival (P=0.044). Metastasis and loco-regional recurrence were observed at follow-up in 18.2 (four out of 22) and 9% (two out of 22) of patients OM(+) and in 14.3 (11 out of 77) and 7.8% (six out of 77) of patients OM(-), respectively (P=not significant). OM was a predictor neither of overall survival nor of disease-free survival (P=0.52 and 0.97, respectively). In Stage I patients, 1-year overall survival and 1-year disease-free survival were 89 and 98% for OM(-) patients and 88 and 90% for OM(+) patients, respectively (P=0.57 and P=0.75). CONCLUSIONS: OM was present in >20% of surgically treated NSCLC patients and did not correlate to pathological variables. In contrast to previous published data, in this study the presence of OM had no influence on overall or disease-free survival.

Aged↗

PubMed2001

Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice.

PURPOSE: The purpose of this study was to evaluate in mice the anticonvulsant potential of N-palmitoylethanolamide, a putative endocannabinoid that accumulates in the body during inflammatory processes. METHODS: N-palmitoylethanolamide was injected intraperitoneally (i.p.) in mice and evaluated for anticonvulsant activity [in maximal electroshock seizure (MES) and chemical-induced convulsions] and for neurologic impairment (rotorod). It was compared with anandamide and with different palmitic acid analogues as well as with reference anticonvulsants (AEDs) injected under the same conditions. RESULTS: The MES test showed, after i.p. administration to mice, that N-palmitoy]ethanolamide had an median effective dose (ED50) value comparable to that of phenytoin (PHT; 8.9 and 9.2 mg/kg, respectively). In the subcutaneous pentylenetetrazol test and in the 3-mercaptropropionic acid test, it was effective only against tonic convulsions. N-palmitoylethanolamide was devoid of neurologic impairment < or = 250 mg/kg, yielding a high protective index. CONCLUSIONS: N-palmitoylethanolamide, an endogenous compound with antiinflammatory and analgesic activities, is a potent AED in mice. Its precise mechanism of action remains to be elucidated.

Amides↗

PubMed2001

Early short-term intensive cardiac rehabilitation induces positive results as long as one year after the acute coronary event: a prospective one-year controlled study.

AIMS: The one-year effects of early and short-term intensive cardiac rehabilitation programmes in patients after acute myocardial infarction or coronary artery bypass surgery (CABG) are not well established. METHODS AND RESULTS: One to four weeks after hospital discharge for acute myocardial infarction (n=55) or CABG (n=54), 109 patients were included in a multidisciplinary ambulatory cardiac rehabilitation programme, lasting 2 to 3 months and including a mean of 33 daily sessions. A complete cardiological assessment of the classical coronary risk factors was performed at entry into the study and again 12 months later, that is 9 to 10 months after the end of the rehabilitation programme. Major effects at one-year follow-up were a high rate of aspirin intake, a low rate of smoking (14% of the patients), a 15% increase in physical capacity, a 7 beats/min decrease in resting heart and a 4 mg/dl increase in the HDL-cholesterol. Body weight increased by 4.9 kg in the patients who stopped smoking; the modest increase in body weight in the other patients reflected a partial weight recovery in the CABG patients. Blood pressure levels also increased at the end of the study but our data in CABG patients and their extrapolation to the post MI patients strongly suggest a progressive return of blood pressure to the pre-acute event levels. In a control group matched for age, sex and type of coronary event, no significant modifications were observed after one year, except for an increase in body weight of 1.7 kg (P < 0.000). CONCLUSIONS: Cardiac rehabilitation which started early after an acute coronary event and regularly followed during 2 to 3 months induced beneficial effects which were still present 9 to 10 months later. Weight gain after smoking cessation was prevalent. The lack of changes in the control group reinforced the benefit of cardiac rehabilitation.

Adult↗

PubMed2001

Midazolam and cortisol metabolism before and after CYP3A induction in humans.

INTRODUCTION: CYP3A is responsible for the metabolism of numerous endogenous and exogenous compounds. Several substrates of CYP3A have been investigated to assess the CYP3A-metabolizing capacity of an individual in an attempt to predict the rate of metabolism of other CYP3A substrates. Two such tests of CYP3A activity are the midazolam plasma clearance after its intravenous administration and the 6beta-OH cortisol urinary ratio. Possible correlations between these 2 tests were investigated before and after treatment with rifampin in a group of healthy volunteers. METHODS: Pharmacokinetic parameters of midazolam and 6beta-OH cortisol urinary ratio were evaluated in 8 volunteers before and after 6 days treatment with rifampin, a potent inducer of CYP3A, and after cessation of rifampin treatment. RESULTS: Midazolam systemic clearance and the 6beta-OH cortisol urinary ratio were significantly higher at Days 7 and 10 than at Day 0. There was a strong positive correlation between these 2 parameters (r = 0.70, p < 0.001). In contrast, no correlation was observed between the ratio of the AUCs of 1'-OH midazolam vs. midazolam (AUC0-1(1'-OH)/AUC0-t(MDZ)) or the ratio of plasma concentration of 1'-OH midazolam vs. midazolam (C30 min(1'-OH)/C30 min(MDZ)) and the 6beta-OH cortisol urinary ratio (r = 0.05, p = 0.82; r = 0.04, p = 0.88, respectively). Considering only data obtained before or after treatment with rifampin, however, no correlation was observed between midazolam systemic clearance and the 6beta-OH cortisol urinary ratio. CONCLUSIONS: These data demonstrate that there is a strong positive correlation between systemic midazolam clearance and 6beta-OH cortisol urinary ratio before and after induction. This suggests that the 6beta-OH cortisol urinary ratio test is a non-invasive alternative to the use of systemic midazolam clearance for monitoring the time-course of CYP3A induction.

Adult↗

PubMed1999

Monoclonal antibodies to growth hormone (GH) prolong liver GH binding and GH-induced IGF-I/IGFBP-3 synthesis.

This time-course study further explored the mechanisms whereby monoclonal antibodies (MAbs) may enhance growth hormone (GH) effects. Hypophysectomized rats were killed 0, 1, 3, 6, 12, 24, and 48 h after a single injection of bovine (b) GH alone or complexed with an anti-bGH MAb. Serum insulin-like growth factor I (IGF-I) concentrations were increased more and for a longer period after MAb-GH complexes (peak at 24 h: 295 +/- 24 ng/ml) than after bGH alone (peak at 12 h: 219 +/- 37 ng/ml; P < 0.01), whereas liver IGF-I mRNA was similar at 12 h in both groups but remained higher at 24 h (by 65%, P < 0.001) and 48 h (by 64%, P < 0.001) in the presence of the MAb. Induction of serum insulin-like growth factor-binding protein (IGFBP)-3 and liver IGFBP-3 mRNA by bGH also was markedly amplified by the MAb (3.6- and 2-fold at 24 h, respectively; P < 0.01). GH receptors (GHR) remained occupied for a longer period after MAb-GH injection (36 +/- 16 and 35 +/- 8% at 6 and 12 h, respectively) compared with bGH alone (0 +/- 28 and -15 +/- 11%), whereas total liver GH-binding sites and GHR mRNA levels were not affected by the MAb. We conclude that MAbs against GH amplify and prolong the serum IGF-I response to GH, which may result from both a prolongation of liver IGF-I synthesis and an enhanced induction of IGFBP-3. These two effects may in turn be the consequences of sustained GH binding to its liver receptors in the presence of MAb.

Animals↗

PubMed1996

Computer-assisted study of ECG indices of the dispersion of ventricular repolarization.

A new computer-assisted method for the quantitative assessment of the dispersion of ventricular repolarization (DVR) has been developed. Through interactive editing of an averaged QRS-T cycle from a 15-lead electrocardiographic (ECG) record (12-lead ECG + XYZ leads), five ECG indices of DVR are automatically computed: they represent the maximal interlead difference of QT and the intervals from the J point to the T wave end, from the J point to the T wave apex, and from the T wave apex to the T wave end. The standard limits of these indices were then established in six clinical groups, including normal subjects and patients with left ventricular hypertrophy, with myocardial infarction, and with intraventricular conduction defect, all subjects being without ventricular arrhythmias and without interacting drugs. The mean values and percentile ranges of all DVR indices were lower in the normal group than in all pathologic groups. The 97.5th percentiles of the QT end dispersion and the JT end dispersion were, respectively, 65 and 76 ms in normal subjects, 84 and 86 ms in patients with inferior MI; 89 and 100 ms in those with anterior MI; 90 and 98 ms in those with left ventricular hypertrophy; and 94 and 99 ms in those with intraventricular conduction defects. This suggests that increased DVR is associated with the varieties of heart disease represented in this study, even in the absence of ventricular arrhythmias, and also that individual measurements of DVR used as predictors of future arrhythmic events should be referred to the standard range of their own clinical group.

Adult↗

PubMed1996

Prevalence of musculoskeletal disorders at the wrist as a function of angles, forces, repetitiveness and movement velocities.

OBJECTIVES: The purpose of this investigation was to study the relationship between the prevalence of musculoskeletal disorders at the wrists and the characteristics of the work conditions in terms of angles, forces, repetitiveness, and movement velocities. METHODS: Nine workplaces were selected and the prevalence of wrist disorders was determined by means of a questionnaire for both arms separately, along with characteristics of the 335 subjects (age, weight, height, seniority). A work analysis was performed on subjects selected at random from each workplace by recording, for both wrists during a representative number of work cycles, the angles both in radial and ulnar deviations and in flexion-extension and the surface electromyogram on the hand flexors of the forearm. Repetitiveness (defined as the number of transitions per minute) and movement velocities (in deviation and flexion-extension) were derived from the recordings of the angles. RESULTS: All the derived variables were highly correlated, greater angles and greater forces being associated with greater velocities and higher repetitiveness. A multivariate linear regression model for the prediction of the prevalence of musculoskeletal disorders of the wrist was constructed (R = 0.904). Height, weight, seniority, angles in radial-ulnar deviation, and forces were significant and independent predictors of the prevalence. CONCLUSIONS: The prevalence of wrist disorders is significantly linked to wrist angles in deviation and to forces exerted. Due to their high correlation with force, the repetitiveness indices and velocities, as defined, do not appear to play an additional role. Further research is needed to find alternative ways of characterizing repetitiveness.

Adult↗

PubMed1995

Noninvasive estimation of pulmonary arterial wedge pressure with Doppler transmitral flow velocity pattern in patients with known heart disease.

Pulmonary arterial wedge pressure (PAWP) is an important marker of cardiac function. Regrettably, it requires catheterization, which can occasionally result in serious complications. A noninvasive method of estimating PAWP would thus be helpful. Recent studies have indicated that the Doppler transmitral flow velocity pattern was strongly dependent on preload and could provide an estimate of PAWP. This study was therefore designed to evaluate the relation between doppler transmitral flow velocity indexes and measured PAWP in 91 patients (learning group: 73 men, mean age 57 +/- 13 years) with ischemic heart disease (n = 41), dilated (n = 29) or hypertrophic cardiomyopathy (n = 4), or aortic stenosis (n = 17). Multiple regression analysis was used to derive an equation for estimation of PAWP, which was subsequently tested in a separate group of 33 patients (testing group: 28 men, mean age 58 +/- 12 years) with similar cardiac conditions. PAWP ranged from 4 to 48 mm Hg in the learning group and from 7 to 40 mm Hg in the testing group. In the learning group, PAWP correlated with the E/A ratio (r = 0.95), atrial filling fraction (r = -0.80), peak E velocity (r = 0.79), isovolumic relaxation period (r = -0.75), and deceleration time (r = -0.61). In the learning group, PAWP was best predicted as PAWP = 18.4 + [17.1.In(E/A ratio)]. This equation allowed prediction of PAWP within 3 mm Hg of the measured value in 24 of 33 patients (73%) in the testing group. In 8 additional patients, the equation also accurately predicted the changes in PAWP induced by volume loading or intravenous nitrates (r = 0.98).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

Multicenter evaluation of a new commercial assay for detection of immunoglobulin M antibodies to Toxoplasma gondii. Multicenter Study Group.

A new commercial assay for detection of IgM-specific antibodies to Toxoplasma gondii (IMx Toxo IgM, Abbott, USA), based on microparticle enzyme immunoassay technology, was evaluated at 15 clinical sites in Europe and the USA. Performance characteristics were established by testing clinical specimens collected randomly from pregnant women, blood donors, individuals with suspected Toxoplasma gondii infection and individuals confirmed HIV positive. Reference testing was performed using Toxo-M EIA (Abbott). Specimens evaluated at European sites yielding discordant results between the new assay and the reference EIA were further tested with an immunosorbent agglutination assay; at sites in the USA, discordant results were resolved using Platelia Toxo IgM (Sanofi, France) and Vidas Toxo IgM (bioMérieux, France) assays. In addition, matched plasma and serum, heat-treated and non-heat-treated specimens, and fresh and frozen specimens were evaluated at the USA sites. At European sites the new commercial assay had a sensitivity of 95.6% (196/205), a specificity of 99.8% (3,137/3,143) and an agreement of 99.6% (3,333/3,348) following resolution of discordant results; sensitivity in the USA was 97.4% (184/189), specificity was 99.8% (1,204/1,207) and agreement was 99.4% (1,388/1,396) following resolution. The new IMx Toxo IgM is a sensitive and specific assay for measurement of IgM antibodies to Toxoplasma gondii in human serum and plasma.

Animals↗

PubMed1995

Delineation of myocardial viability with PET.

UNLABELLED: Relative flow and metabolic imaging (the "mismatch pattern") with PET have been proposed to identify the presence of viable myocardium in patients with ischemic left ventricular dysfunction. Yet, optimal criteria to identify dysfunctional but viable myocardium and predict significant functional improvement have not been fully defined. METHODS: Dynamic PET imaging with 13N-ammonia and 18F-deoxyglucose to assess absolute myocardial perfusion and glucose uptake was performed in 25 patients (20 men, 5 women; mean age 57 +/- 12 yr, range 30-72 yr) scheduled for coronary revascularization because of coronary artery disease, anterior wall dysfunction and mildly depressed left ventricular ejection fraction (49% +/- 11%). Global and regional left ventricular function was evaluated by contrast left ventriculography at baseline and after revascularization. RESULTS: As judged from the changes in end-systolic volume and resting anterior wall motion before and after revascularization, 17 patients with improved wall motion score and decreased end-systolic volume were considered to have viable myocardium, whereas 8 patients with either no change in regional wall motion or increased end-systolic volume were considered to have nonviable myocardium. Before revascularization, viable myocardium showed higher absolute myocardial blood flow (77 +/- 20 versus 51 +/- 9 ml (min.100 g)-1, p = 0.004) and absolute regional myocardial glucose uptake (36 +/- 14 versus 24 +/- 11 mumole (min.100 g)-1, p = 0.04) than nonviable myocardium. CONCLUSION: This study identified absolute myocardial blood flow and normalized glucose extraction as the most powerful predictors of the return of contractile function after coronary revascularization in patients with ischemic anterior wall dysfunction.

Adult↗

PubMed1991

Assay of anti-HBs antibodies using a recombinant antigen and latex particle counting: comparison with five commercial tests.

An assay of anti-HBs antibodies based on agglutination of latex particles coated with recombinant HBs-antigen was compared with Abbott radioimmunoassay (Abbott-RIA), which uses a human plasma-derived antigen. The population examined consisted of 76 Abbott-RIA anti-HBs-negative prevaccinated subjects and 1044 serum samples anti-HBs found positive by Abbott-RIA, including 283 samples of subjects vaccinated either with a human plasma-derived vaccine (group A; n = 180) or with a recombinant vaccine (group B; n = 103). Correlation coefficients between the two techniques were respectively r = 0.89 for the whole population (n = 1044), r = 0.98 in group A and r = 0.74 in group B. Anti-HBs titres were higher with latex than with RIA in group B as shown by the regression slopes: latex = 508 + 1.11 RIA in group A and latex = -1138 + 3.97 RIA in group B, suggesting that some vaccinated subjects from group B produced antibodies against epitopes proper to the recombinant antigen. In the prevaccinated population and in group A, the latex results were compared with those of radioimmunoassays (Abbott, Sorin) and enzyme immunoassays (Behring, Roche, Pasteur). Only the Roche-EIA detected anti-HBs in the prevaccinated subjects. The correlation between the various immunoassays was r greater than 0.96 only for values higher than 100 IU/l.

Agglutination Tests↗

PubMed1991

Prolonged exercise induces left ventricular dysfunction in healthy subjects.

To determine the effects of a moderately prolonged exercise on left ventricular systolic performance, 23 healthy male subjects, aged 18 to 51 yr (mean 37 yr) were studied. The subjects exercised first on a treadmill (brief exercise) and completed, on a separate day, a 20-km run. M-mode, two-dimensional, and Doppler echocardiography, as well as calibrated carotid pulse tracings, were obtained at rest and immediately on completion of both brief and prolonged exercise. Left ventricular systolic function was assessed by end-systolic stress-shortening relationships. Heart rate increased similarly after brief and prolonged exercise (+30%). Mean arterial pressure decreased from 99 +/- 7 to 92 +/- 8 mmHg (P less than 0.001) after prolonged exercise, but it remained unchanged after brief exercise. Left ventricular end-diastolic volume was decreased after prolonged exercise (130 +/- 23 vs. 147 +/- 18 ml at rest, P less than 0.01). Both ejection fraction and rate-adjusted mean velocity of fiber shortening decreased after prolonged exercise [from 67 +/- 5 to 60 +/- 6% (P less than 0.001) and from 1.12 +/- 0.2 to 0.91 +/- 0.2 cm/s (P less than 0.001), respectively] despite a lower circumferential end-systolic wall stress (133 +/- 23 vs. 152 +/- 20 g/cm2). The relationship between ejection fraction (or mean velocity of fiber shortening adjusted for heart rate) and end-systolic wall stress was displaced downward on race finish (P less than 0.05). These changes were independent of the changes in left ventricular end-diastolic volume and hence those in preload. The data suggest that moderately prolonged exercise may result in depressed left ventricular performance in healthy normal subjects.

Adult↗

PubMed1991

Logistic discriminant analysis improves diagnostic accuracy of exercise testing for coronary artery disease in women.

BACKGROUND: Diagnostic accuracy of the exercise electrocardiogram in women has been shown to be limited for the detection of coronary artery disease. New diagnostic methods based on computer analysis of the exercise electrocardiogram and multivariate analysis have improved the diagnostic value of exercise testing in male subjects. The aim of the present study was to assess whether the diagnostic value of exercise testing can be enhanced in women by using multivariate analysis of exercise data. METHODS AND RESULTS: Between 1978 and 1984, 135 infarct-free women underwent exercise testing and coronary angiography. Significant coronary artery disease was present in 41% of the patients. In this first group, maximal exercise variables were submitted to a stepwise logistic analysis. Work load, heart rate, and ST60X were selected to build a diagnostic model. The model was tested in a second group of 115 catheterized women (significant coronary artery disease in 47%) and of 76 volunteers. We compared the present model with conventional analysis of the exercise electrocardiogram, with ST changes adjusted for heart rate, and with a previously described analysis. In both groups, sensitivity was better with the present model (66% and 70%) than by conventional (68% and 59%) and by the previously described analysis (57% and 44%) without a loss of specificity (85% and 93%). Receiver-operator characteristic curves showed also a better diagnostic accuracy with the present model. CONCLUSIONS: In women, logistic analysis of exercise variables improves the diagnostic value of exercise testing. It yields a significantly better sensitivity without a loss of specificity.

Coronary Disease↗

PubMed1990

Left ventricular filling in dilated cardiomyopathy: relation to functional class and hemodynamics.

Left ventricular systolic function does not correlate well with functional class in patients with dilated cardiomyopathy. To determine whether the correlation is better with Doppler indexes of left ventricular diastolic function, 34 patients with dilated cardiomyopathy (M-mode echocardiographic end-diastolic dimension greater than 60 mm, fractional shortening less than 25%, increased E point-septal separation) were studied. Patients were classified into two groups according to functional class. Group 1 consisted of 16 patients in New York Heart Association functional class I or II; group 2 included 18 patients in functional class III or IV. Left ventricular dimensions, fractional shortening, left ventricular mass, meridional end-systolic wall stress, peak early and late transmitral filling velocities and their ratio, isovolumetric relaxation period and time to peak filling rate were computed from pulsed wave Doppler and M-mode echocardiograms and calibrated carotid pulse tracings. Right heart catheterization was performed in 20 of 34 patients. No differences were observed between groups with regard to age, gender distribution, heart rate, blood pressure and M-mode echocardiographic-derived indexes of systolic function. Peak early filling velocity (72 +/- 13 versus 40 +/- 10 cm/s, p less than 0.001) was higher and atrial filling fraction (27 +/- 4% versus 46 +/- 8%, p less than 0.001) was lower in group 2 than in group 1. The ratio of early to late transmitral filling velocities was higher in group 2 patients (2.3 +/- 0.5 versus 0.7 +/- 0.2, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Influence of age and sex on left ventricular volumes and ejection fraction during upright exercise in normal subjects.

To determine the effects of age and sex on exercise left ventricular volume indexes and ejection fraction, a cross-sectional study was performed in 18 young volunteers (nine men and nine women) and in 17 older volunteers (nine men and eight women) without evidence of coronary artery disease by exercise electrocardiographic and thallium-201 criteria. All subjects performed a multistage maximal upright exercise with measurements of maximal oxygen consumption and heart rate; left ventricular ejection fraction and absolute volume indexes were measured at rest and during submaximal and maximal exercise using equilibrium radionuclide ventriculography. At rest, no effect of age or sex on any parameter was observed. At peak exercise, an age-related increase in mean blood pressure, end-diastolic and end-systolic volume indexes, and decrease in ejection fraction, cardiac index, heart rate and oxygen consumption were noticed. Sex had a significant effect on maximal workload, maximal oxygen consumption and ejection fraction.

Adolescent↗