Biomedical subjects
Publications and source records attributed to O Bouvet.
In this work we analyze the physiological state of cells after lethal-UV dose disinfection using independent metabolic markers. Through the detection of some metabolic activities we proved that cell lysis does not immediately follow death in UV-irradiated Escherichia coli K12 cells.
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Infectious excerbations of COPD are generally due to Streptococcus pneumoniae, Haemophilus species, and other Gram-negative bacteria. Ofloxacin has potent activity against Gram-negative species but is less effective against Gram-positive species including Streptococcus pneumoniae. It has also been shown that the administration of ambroxol increases the concentration of some antibiotics in pulmonary tissues. The aim of the study was to determine whether ambroxol increases the bronchial tissue concentrations of ofloxacin to a level exceeding the MIC90 of the bacterial species less susceptible to ofloxacin. 24 patients with COPD were randomized in two groups. Drug regimens of ofloxacin alone (200 mg twice daily) or ofloxacin (200 mg twice daily)+ambroxol (30 mg thrice daily) were administered over 10 d. A fibroscopy was performed on day 10 with bronchial biopsies and broncho-alveolar lavage. At steady state, concentrations of drug in plasma and bronchial samples were assayed by HPLC with fluorometric detection. There was no significant difference in the bronchial levels of ofloxacin between the two groups; however, in alveolar cells, ofloxacin concentration was three times higher in the group with ambroxol. Ambroxol does not increase ofloxacin concentrations in bronchial tissue because high concentrations are already present in the lung.
A high-performance liquid chromatographic method with fluorometric detection was developed for the analysis of ofloxacin in plasma and lung tissue. The detection was performed at 280 nm for excitation and 500 nm for emission. The procedure involves the addition of an internal standard followed by treatment of the samples with acetonitrile and dichloromethane. The proposed technique is reproducible, selective, reliable and sensitive. Linear detector response was observed for the calibration curve standards in the range of 0.1-5 micrograms ml-1 for plasma and 0.025-2.5 micrograms g-1 for lung tissue. The limit of quantitation is 5 ng ml-1 or 5 ng g-1. The accuracy of the method is good; that is, the relative error is < 10%. This method was applied to the pharmacokinetic study of ofloxacin in 24 chronic obstructive pulmonary disease patients.
Twenty-two patients suffering from intractable recurrent unipolar or bipolar mood disorders were enrolled in a maintenance-ECT protocol (ECT-M) for more than 18 months, with a treatment at approximately monthly intervals. Eleven have continued treatment for > 2 years. Whereas 44% of the year had been spent in the hospital with at least three episodes a year prior to ECT-M, only 7% of the year was spent in the hospital during ECT-M with only one relapse every 16 months requiring admission (p < 0.001). Forty-five percent of the patients were in full remission and 27% in partial remission according to DSM-III-R criteria. ECT-M responsiveness of rapid-cyclers and delusional depressed patients usually drug refractory has been very encouraging with full or partial remission for 100% of rapid-cyclers and 80% of delusional depressed patients.
The pharmacokinetic parameters of amikacin and ceftazidime were assessed in four patients undergoing hemofiltration for septic shock. The parameters were assessed during hemofiltration and in the interim period. The concentration-time profiles of these two drugs in plasma, urine, and ultrafiltrate were investigated after intravenous perfusion (30 min). In all cases a 1-g dose of ceftazidime was administered; for amikacin, the dosage regimen was adjusted according to the patient's amikacin levels (250 to 750 mg). Concentrations of drug in all samples were assayed by high-performance liquid chromatography with UV detection for ceftazidime and by enzyme multiplied immunoassay for amikacin. The elimination half-life (t1/2) and the total clearance of amikacin ranged from 31.1 to 138.2 h and from 5.4 to 8.9 ml/min, respectively, during the interhemofiltration period in anuric patients. Hemofiltration substantially decreased the t1/2 (3.5 +/- 0.49 h) and increased the total clearance (89.5 +/- 11.8 ml/min). The hemofiltration clearance of amikacin represented 71% of the total clearance, and the hemofiltration process removed, on average, 60% of the dose. During hemofiltration, the elimination t1/2 of ceftazidime (2.8 +/- 0.69 h) was greatly reduced and the total clearance increased (74.2 +/- 11.2 ml/min) compared with those in the interhemofiltration period (9 to 43.7 h and 7.4 to 16.8 ml/min, respectively). About 55% of the administered dose was recovered in the filtrate, and the hemofiltration clearance of ceftazidime was 46 +/- 14.3 ml/min. A redistribution phenomenon (rebound) in the amikacin and ceftazidime concentrations in plasma (35 and 28%, respectively) was reported after hemofiltration in two patients. The MICs for 90% of the most important pathogens were exceeded by the concentrations of the two drugs in plasma during the whole treatment of these patients.
Phenazone (antipyrine) 1g was given by short intravenous infusion to 62 study participants (10 healthy drug-free volunteers and 52 patients with chronic liver disease). A Bayesian approach was developed to determine the individual pharmacokinetic parameters of phenazone. Statistical characteristics of the population pharmacokinetic parameters were first evaluated for 30 patients. When combined with 1 plasma drug concentration from members of the second group, these led to a Bayesian estimation of individual pharmacokinetic parameters for the remaining 32 individuals. Total clearance computed by Bayesian estimation was compared with maximal likelihood estimation of this parameter, the classical procedure. No statistically significant differences were found. Performance of the developed methodology was evaluated by computing bias and precision. The mean error was 0.0477 L/h. The precision of the prediction of this parameter (0.155 L/h) remained lower than the interindividual standard deviation (0.765 L/h). This procedure enables the estimation of individual pharmacokinetic parameters for phenazone. In this study, numerous laboratory tests were performed. A highly significant correlation (p < 0.001) was found between phenazone clearance and the prothrombin time, albumin, gamma-globulin, factor V, antithrombin III, fibrinogen and total bilirubin. Discriminant analysis determined that protein, alkaline phosphatase, creatininaemia and gamma-globulin had more significant discriminating power and gave better prognostic results than those seen with the Child-Pugh test.
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In a prospective pharmacokinetic study, the plasma and tissue concentrations of pefloxacin were studied. Twelve patients were premedicated with pefloxacin 400 mg bd orally for three days followed by 400 mg iv preoperatively. Tissue samples during surgery were taken from the skin, peritoneum, ovary, myometrium and fallopian tubes. Pefloxacin concentrations were measured by high performance liquid chromatography with fluorescence detection. The mean elimination half-life of pefloxacin was 11.3 h, the mean residence time (MRT) was 15.8 h and the apparent volume of distribution 1.52 +/- 0.525 L/kg. Pefloxacin concentrations in myometrium, ovary and fallopian tubes exceeded four- to six-fold the corresponding plasma concentrations 3.5 h after the last drug intake. At the start of surgery, about 2.5 h after the last dose, the skin/plasma concentration ratio and the peritoneum/plasma concentration ratio were 2.65 and 1.18, respectively. At the end of surgery, these ratios were 4.65 and 1.5. The tissue concentrations exceeded the MIC90 for most common pathogens implicated in gynaecological infections.
Autoantibodies reacting with cell constituents other than antinuclear antibodies have seldom been reported in the literature on schizophrenia. Serum of 41 DSM-III-R schizophrenic patients was examined for the presence of various autoantibodies and compared with that of healthy volunteers (n = 10) and hospitalized controls. Titers of IgG, IgA and IgM autoantibodies directed against actin, tubulin, myosin, DNA, thyroglobulin, elastin, albumin, DNA and trinitrophenyl groups were determined using enzyme immunoassay. IgG and IgA titers were significantly decreased in schizophrenic patients. These results contrast with those obtained with various other autoimmune and nonautoimmune diseases in which titers are either unchanged or increased. A significant increase of various autoantibody levels was observed in the paranoid subgroup of schizophrenics compared with the disorganized subgroup. These autoantibodies possess characteristics similar to those of natural autoantibodies, which seem to play several biological roles.
The unipolar-bipolar distinction underlines the recurrence of the disorder (40 to 80% of unipolars and 95% of bipolars) and also the transition from one subtype to the other (10 to 15% of unipolars will become bipolars). Some semiological forms of depressive illness may give clues concerning the required management modalities. Depressions with psychotic features have a good response to ECT or to TCAs+neuroleptics. As other authors, Quitkin et al. find a good response of atypical depression to MAOIs. The comorbidity of mood disorders with personality disorders may be of poor prognosis. Akiskal suggested the presence of a depressive personality, Hudson and Pope suggest the notion of an affective disorders spectrum in which bulimia and OCD have a good response to serotoninergic antidepressants, whereas panic disorders have a good response to clomipramine, imipramine and MAOIs. Patient management should start with taking both the history of the disease and patient's previous treatment with a much precision as possible. Today the focus is on the particular progressive forms of resistant and chronic depressions, among which there are patients who have not received adequate treatment, and of rapid cyclers. The hypothesis of hypothyroïdism in rapid cyclers has been suggested recently. Carbamazepine and Valproate seem to be efficacious in several recent open studies and in controlled for carbamazepine. The initiation of chemotherapy to prevent the recurrences of depression takes into account the unipolar or bipolar aspect of the mood disorder. Lithium has emerged as the prophylactic agent of choice in bipolar disorders, especially if the index episode is manic. Early prophylaxis is justified when the first episode is manic or after two depressive episodes.(ABSTRACT TRUNCATED AT 250 WORDS)
Ten cases of psychotic patients requiring electroconvulsivotherapy (ECT) are reported during pregnancy and puerperium. The interest and the safety of ECT are confirmed. ECT is principally indicated in severe cases and in typical or atypical mood disorders.
BACKGROUND AND AIM OF THE STUDY: Overall, the efficacy of the newer antidepressants: serotonin selective reuptake inhibitors (SSRI), selective serotonin/norepinephrine reuptake inhibitor (SNRI), noradrenergic and specific serotonergic antidepressant (NaSSA) and tianeptine is similar to that of the tricyclics, and so their acceptability/safety becomes a selection criterion for the clinician. However, side-effect assessment comes up against several difficulties: distinguishing between somatic symptoms caused by the depression and those caused by the treatment -- which assessment tool to use (spontaneous notification, standardized scales that are not specific for the side effects caused by psychotropic drugs, standardised scales specific for the side effects caused by psychotropic drugs, meta-analysis, etc.) -- which data sources to consult (anecdotal reports, reviews, prospective studies), and which data set to use, etc. As a result, the question of the exhaustiveness and reliability of the data consulted by the clinician can arise. We therefore conducted a comparative study in patients treated with these newer antidepressants, of 2 antidepressants side-effect assessment tools: spontaneous notification (SN) versus the UKU scale, a standardised scale specific for the side effects of psychotropic drugs. METHODOLOGY: The depressed outpatients were selected from a psychiatric unit in a French psychiatric hospital and from a non-hospital consulting room. The main inclusion criteria were: male or female subjects, suffering from major depression without melancholia or psychotic features or suffering from mood disorders (according to DSM IV criteria), who had been treated for at least 4 weeks with one of the newer antidepressants. The main exclusion criteria were: any other psychiatric disorder, a serious physical disorder, treatment with neuroleptics, mood-changing drugs or other antidepressants, and patients who were not able to understand the questionnaire. The investigation was carried out by a clinical pharmacist. RESULTS: Fifty patients were included in the study. There were 18 men and 32 women. The mean age was 53.5 15.9 years [22 - 77], the mean period of treatment was 24 30.5 months [1 - 127] and 52% of the patients received concomitant medication with anxiolitic or hypnotic drug(s). The percentage of patients who reported at least one side effect was significantly higher for the UKU scale than for SN (84% vs 58%, p<0.01). The ratio between SN and UKU scale scores was 2/3. A similar pattern was found for the total number of side effects (n=177 vs n=47, p<0.001). The ratio between the total number of side effects for the SN and UKU scale was 1/4. The side effects were divided into five subgroups: psychiatric, neurovegetative, sexual, neurological and others. In all these subgroups, the number of side effects reported was significantly higher when the UKU scale was used than when SN was used. The values were as follows: psychiatric (n=44 vs n=15, p<0.001), neurovegetative (n=59 vs n=15, p<0.001), sexual (n=36 vs n=10, p<0.001), neurological (n=11 vs n=2, p<0.001) and other side effects (n=27 vs n=5, p<0.001). Nineteen side effects were only reported when SN was used (for example: dry eyes, incompatibility with alcohol, euphoria...). Twenty-four side effects were only reported when the UKU scale was used (for example: increased libido, loss of bodyweight...). The side effects had no impact on daily life in most of 80% of the patients; there was no significant difference between the patient's assessment of the discomfort caused by side effects and the clinician's assessment. In 90% of cases, the side effects did not lead to any change in the treatment. DISCUSSION: The findings of this study show that the collection of data regarding side effects depends on the assessment tool used: the number of side effects reported was significantly higher when the UKU scale was used than when SN was used. However, this finding must viewed with caution, because it has been showed that checklists can induce symptoms in suggestible patients. Neurovegetative troubles are the most commonly reported side effects, and neurological troubles the least often reported. This matches the tolerability profile of these antidepressants. The disorders that were least frequently spontaneously reported were the neurological, sexual and "other" side effects. These emerged only when the clinician asked the patient about them. The 19 side effects that were only reported when SN was used were side effects that were not included in the UKU scale or that had not been present during the three days before we started the investigation. The 34 side effects that were only reported when the UKU scale was used were either side effects with no apparent link with the treatment (for example: micturition troubles) or embarrassing effects (such as increased libido). CONCLUSION: Our findings show that the collection of data on side effects depends on the assessment tool used. These findings need to be confirmed by large-scale comparative studies, and the standardization of the assessment of side effects is a question that needs to be raised.
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