Impact of the COVID-19 Pandemic on a Cancer Fast-Track Programme.

INTRODUCTION: The COVID-19 pandemic has disrupted many aspects of clinical practice in oncology, particularly regarding early cancer diagnosis, sparking public health concerns that possible delays could increase the proportion of patients diagnosed at advanced stages. In 2009, a cancer fast-track program (CFP) was implemented at the Clinico-Malvarrosa Health Department in Valencia, Spain with the aim of shortening waiting times between suspected cancer symptoms, diagnosis and therapy initiation. OBJECTIVES: The study aimed to explore the effects of the COVID-19 pandemic on our cancer diagnosis fast-track program. METHODS: The program workflow (patients included and time periods) was analysed from the beginning of the state of alarm on March 16th, 2020 until March 15th, 2021. Data was compared with data from the same period of time from the year before (2019). RESULTS: During the pandemic year, 975 suspected cancer cases were submitted to the CFP. The number of submissions only decreased during times of highest COVID-19 incidence and stricter lockdown, and overall, referrals were slightly higher than in the previous 2 years. Cancer diagnosis was confirmed in 197 (24.1%) cases, among which 33% were urological, 23% breast, 16% gastrointestinal and 9% lung cancer. The median time from referral to specialist appointment was 13 days and diagnosis was reached at a median of 18 days. In confirmed cancer cases, treatment was started at around 30 days from time of diagnosis. In total, 61% of cancer disease was detected at early stage, 20% at locally advanced stage, and 19% at advanced stage, displaying time frames and case proportions similar to pre-pandemic years. CONCLUSIONS: Our program has been able to maintain normal flow and efficacy despite the challenges of the current pandemic, and has proven a reliable tool to help primary care physicians referring suspected cancer patients.

The effectiveness of a psycho-educational group after early-stage breast cancer treatment: results of a randomized French study.

BACKGROUND: Many women with breast cancer need psychological help to cope more effectively after treatment. Cognitive and behavioural techniques are not yet well established in France. A multi-site randomized study was conducted to evaluate the effects of a psycho-educational group intervention in this population. METHODS: Two hundred and three patients, recruited after primary treatment, were randomly assigned either to a treatment group (psycho-educational intervention) or to a waiting-list control group. The 8-week programme of 2 h sessions comprised of thematic discussions, information and training in stress management techniques. Evaluation at baseline, after 8 sessions, and 1 month after programme completion, included evaluations using the STAI, POMS, MAC, EORTC QLQ-C30 and EORTC QLQ-BR23 breast module scales. RESULTS: We observed a significant reduction in anxiety (STAI, POMS) among group participants, a reduction in anger, depression and fatigue (POMS), a significant improvement in vigor and interpersonal relationships (POMS), in emotional and role functioning, in health status and fatigue level (EORTC QLQ-C30). In contrast, coping strategies (MAC) were not significantly different between groups. No group-related negative effects were observed and the global satisfaction levels were very high. CONCLUSION: This study demonstrates the feasibility and effectiveness of a psycho-educational intervention, which can accelerate the reduction of those negative affects which are present at the end of treatment. It represents an excellent complement or an alternative to individual psycho-oncologic therapeutic support, widely proposed in France, and should now be tested in groups with other types of cancer and at other disease phases.

[A case of Usher's syndrome associated with psychotic symptoms: diagnosis and follow-up in a psychiatric unit]. / A propos d'un cas de syndrome de Usher suivi en psychiatrie : intérêt du diagnostic somatique pour la prise en charge psychiatrique.

INTRODUCTION: Usher's syndrome is a heterogeneous autosomal recessive disorder characterised by dual sensory impairment: profound congenital hearing impairment and progressive visual loss due to retinitis pigmentosa, sometimes associated with vestibular dysfunction. Some patients develop a psychotic illness, the etiology of which is still debated. Diagnosis may be difficult, and there are only a few reports in the psychiatric literature. CASE REPORT: The present case reports a 57-year-old man, double diagnosed with sensory impairment and psychosis. The severity of his psychosis required several hospitalisations in a psychiatric in-unit, even under third party decision or compulsory hospitalisation, for acute states with disruptive behaviour, aggressiveness against his mother, persecutory delusion and auditory hallucinations, self-talking, major anxiety, and depressive affects, without dissociation. Deafness had been diagnosed when he was six years old; he was able to attend school and learn to read and speak, using hearing aids, and was able to hold a job for three months. Severe psychotic symptoms appeared when he was 18 years old and contributed in confirming the diagnosis. Progressive loss of vision until blindness began later, between the age of 40 to 50. No specific abnormal results were revealed during the neuroradiological check-up. Treatment consisted in antipsychotics, notably depot, first in a mental health care in-unit and subsequently in an out-patient unit: although he denied psychotic symptoms, he became compliant with medication and could go on with treatment, associated with multidisciplinary interventions at home, in order to improve his quality of life. DISCUSSION: Usher's syndrome is the most frequent cause of combined deafness and blindness in adults (three and five individuals per 100,000), but difficulties in communication need to increase clinical awareness of this disorder, especially for psychiatrists. Three subtypes are recognized by the International Usher Syndrome Consortium: Type 1 is characterised by profound congenital deafness, retinal degeneration beginning in childhood, and progressive vestibular dysfunction; Type 2 is characterised by moderate to severe hearing impairment, later onset of retinal degeneration, and normal vestibular function; Type 3 is characterised by progressive hearing loss and variable age of onset of retinal degeneration. Although nearly 23% may have psychotic symptoms, the aetiology remains unclear: sensory deprivation associated with environmental stress, organic changes such as cerebral abnormalities, genetic link (two genetic loci for both Usher's syndrome and psychotic illness are very close). Treatment of psychiatric symptoms is based on antipsychotics, well tolerated by the patients, who improve change of behaviour and communication abilities. Genetic counselling may be useful for parents. CONCLUSION: Access to mental health services is particularly difficult for deaf and deaf-blind people, and difficulties in communication are a challenge for patients and for caregivers too. Antipsychotic medications are helpful for associated psychotic symptoms. Potential link between Usher syndrome and psychosis is still unclear and needs further studies.

[Psychotropic drugs induced weight gain: a review of the literature concerning epidemiological data, mechanisms and management]. / Prise de poids pharmaco-induite par les psychotropes et sa prise en charge: revue des données de la littérature.

Weight gain is associated with the use of many psychotropic medications, including antidepressants, mood stabilizers, antipsychotic drugs, and may have serious long term consequences: it can increase health risks, specifically from overweight (BMI = 25-29.9 kg/m2) to obesity (BMI > or =30 kg/m2), according to Body Mass Index (BMI), and the morbidity associated therewith in a substantial part of patients (hypertension, coronary heart desease, ischemic stroke, impaired glucose tolerance, diabetes mellitus, dyslipidemia, respiratory problems, osteoarthritis, cancer); according to patients, psychosocial consequences such as a sense of demoralization, physical discomfort and being the target of substantial social stigma are so intolerable that they may discontinue the treatment even if it is effective. The paper reviews actual epidemiological data concerning drug induced weight gain and associated health problems in psychiatric patients : there is a high risk of overweight, obesity, impaired glucose tolerance, diabetes mellitus, premature death, in patients with schizophrenia or bipolar disorder; and the effects of specific drugs on body weight: Tricyclic Antidepressants (TCA) induced weight gain correlated positively with dosage and duration of treatment, more pronounced with amitriptyline ; Selective Serotonin Reuptake Inhibitors (SSRI) decrease transiently bodyweight during the first few weeks of treatment and may then increase bodyweight; weight gain appears to be most prominent with some mood stabilizers (lithium, valproate); atypical antipsychotics tend to cause more weight gain than conventional ones and weight gain, diabetes, dyslipidemia, seem to be most severe with clozapine and olanzapine. Conceming the underlying mechanisms of drug induced weight gain, medications might interfere with central nervous functions regulating energy balance; patients report about: increase of appetite for sweet and fatty foods or "food craving" (antidepressants, mood stabilizers, antipsychotic drugs) and weight gain despite reduced appetite which can be explained by an altered resting metabolic rate (TCA, SSRI, Monoaminoxidase Inhibitors MAO I). According to current concepts, appetite and feeding are regulated by a complex of neurotransmitters, neuromodulators, cytokines and hormones interacting with the hypothalamus, including the leptin and the tumor necrosis factor system. The pharmacologic mechanisms underlying weight gain are presently poorly understood: maybe the different activities at some receptor systems may induce it, but also genetic predisposition. Understanding of the metabolic consequences of psychotropic drugs (weight gain, diabetes, dyslipidemia) is essential: the insulin-like effect of lithium is known; treatment with antipsychotic medications increases the risk of impaired glucose tolerance and diabetes mellitus. Several management options of weight gain are available from choosing or switching to another drug, dietary advices, increasing physical activities, behavioural treatment, but the best approach seems to attempt to prevent the weight gain : patients beginning maintenance therapy should be informed of that risk, and nutritional assessment and counselling should be a routine part of treatment management, associated with monitoring of weight, BMI, blood pressure, biological parameters (baseline and three months monitoring of fasting glucose level, fasting cholesterol and triglyceride levels, glycosylated haemoglobin). Psychiatrics must pay attention to concomitant medications and individual factors underlying overweight and obesity. Weight gain has been described since the discovery and the use of the firstpsychotropic drugs, but seems to intensify with especially some of the second generation antipsychotic medications ; understanding of the side effects of psychotropic drugs, including their metabolic consequences (weight gain, diabetes, dyslipidemia) is essential for the psychiatrics to avoid on the one hand a risk of lack of compliance, a discontinuation of the pharmacological medication and also a risk of relapse and rehospitalization, and on the other hand to avoid acute life threatening events (diabetic ketoacidocetosis and non ketotic hyperosmolar coma, long term risk complications of diabetes and overweight).

Comparative study of the pharmacokinetics of zuclopenthixol decanoate and fluphenazine decanoate.

Seventeen outpatients were treated with depot neuroleptics, zuclopenthixol decanoate in Viscoleo or fluphenazine decanoate in sesame oil, with dosage intervals of 3 weeks. During the 4th, 6th, and 8th dosage interval blood samples were drawn in oxalated tubes. Plasma concentrations of the active neuroleptic drugs, zuclopenthixol and fluphenazine, were determined by high performance liquid chromatography. The concentrations indicated some interindividual as well as intraindividual variations. For zuclopenthixol the maximum concentration was most often seen at day 7 after injection, whereas the kinetics of the fluphenazine concentrations was more variable. There was an indication of more fluctuation in the 4th dosage interval than in the 8th dosage interval, possibly due to the fact that steady state has not yet been achieved at the 4th dosage interval.

Blood and plasma kinetics of cis(Z)-clopenthixol and fluphenazine in psychiatric patients after intramuscular injection of their decanoic esters.

Whole blood and plasma concentrations of active neuroleptic drugs were measured in eight schizophrenic outpatients who had received cis(Z)-clopenthixol decanoate in Viscoleo or fluphenazine decanoate in sesame oil by intramuscular injection. Whole blood and plasma concentrations were very similar, though there was a slight tendency for blood concentrations to be higher than plasma concentrations. Maximum concentrations appeared at 1 week after administration of cis(Z)-clopenthixol decanoate, whereas the highest concentrations after fluphenazine decanoate were seen at the end of the 3-week dosage interval. Some between-individual variation and a limited within-individual variation was seen.

Pharmacoclinical correlations in schizophrenic patients treated with haloperidol decanoate: clinical evaluations, concentrations of plasma and red blood cell haloperidol and its reduced metabolite, and plasma homovanillic acid.

1. The aim of this open study was to determine whether a more rational therapeutic approach could be devised for psychotic patients (n = 11) treated for long periods with long-acting (LA) haloperidol. The mean multiplication factor for the transition from the oral formulation to the long-acting one was 12.8 (10.4, standard deviation), lower than the theoretically recommended factor of 20. 2. The best dose (mg/kg)-concentration correlations were found for haloperidol (HAL) and reduced HAL (RHAL) in the red blood cells (RBC) (representative of the free drug fraction) rather than in the plasma of patients that had attained the steady state (at the third cycle and afterwards) 3. Pharmacokinetic analyses were conducted at the same time as clinical evaluations, grading using the BPRS and determinations of plasma levels of total, free and conjugated homovanillic acid (HVA), a marker of central dopaminergic activity. 4. A between groups comparison at the steady state (patients (n = 20) with oral administration and the above patients (n = 11) with long-acting form of HAL), showed that the plasma and RBC RHAL/HAL ratios of long-acting HAL decreased significantly (p < 0,005) in comparison with oral administration, at least by half. 5. Plasma HVA values complete the information provided by plasma and more especially RBC HAL and RHAL levels. All these results taken together, as substantiated by the clinical assessment scales (BPRS), assure a better pharmacoclinical surveillance and can be predictive of a patient's response.

Pharmacoclinical strategy in neuroleptic resistant schizophrenic patients treated by clozapine: clinical evolution, concentration of plasma and red blood cell clozapine and desmethylclozapine, whole blood serotonin and tryptophan.

1. The aim of the study was to determine if a more rational therapeutic approach could be devised for neuroleptic resistant psychotic patients treated for months and years with clozapine. Clozapine is an atypical antipsychotic medication, but its therapeutic benefit has been limited by a high incidence of agranulocytosis and seizures. 2. The study has been performed in an open setting and included 12 patients. Some of them developed a secondary depression and were treated with fluoxetine. 3. Pharmacokinetic analysis were conducted at the same time as clinical evaluations, grading using the BPRS, the PDS, and QLS, and determinations of plasma and red blood cell clozapine and desmethylclozapine, plasma and RBC fluoxetine and norfluoxetine, whole blood serotonin and tryptophan. 4. A positive linear correlation was found only between RBC concentration and the evolution of the QLS. 5. Clozapine is efficacious both on positive and negative symptoms but its mechanism of action remains unclear. Positive symptoms disappear more quickly, sometimes followed by a post psychotic depression. Negative symptoms improve more slowly but regularly. They seem to be correlated with serotoninergic mechanisms. For whole blood 5HT, an important increase was seen about 4 weeks after Cloza administration, and then a decrease. 6. Therapeutic drug monitoring (on the same sample drawn for haematological monitoring providing) could play a useful role in the management of patients treated by clozapine: compliance, lowest dose, possible toxicity, drug interaction, lack of efficacy, relapse predictivity.

Citalopram--a highly selective 5-HT uptake inhibitor--in the treatment of depressed patients.

In an open, clinical trial comprising a total of 21 depressed in-patients (6 men and 15 women) citalopram was administered in doses of 20-60 mg once daily for a period of at least 3 weeks. Fourteen of the patients were treated for 4 weeks, and 6 of these patients were treated for another 2 weeks. The CPRS subscale for depression (MADRS) and a global evaluation were used for assessment of the therapeutic effect. Twelve patients showed complete or partial response to treatment, and generally onset of therapeutic effect was seen within the first 2 weeks of treatment. Side-effects were generally few and mild, anxiety being the most frequent one. No pathological laboratory values were recorded, and apart from one case of slight and transient bradycardia no changes were observed in the cardiovascular parameters. Determination of plasma levels in 16 of the patients under presumed steady-state conditions showed an inter-individual variation between 28 and 616 nM/l for citalopram and between 32 and 338 nM/l for its monodemethylated metabolite for daily citalopram doses of 30-60 mg. The average ratio citalopram-desmethyl citalopram was 1.70. No correlation was found between clinical response and the plasma levels.

Quantitation and ultraviolet spectrum identification of buflomedil in whole blood and plasma by HPLC.

Buflomedil, a vasodilating agent, was determined in whole blood or plasma by HPLC with papaverine as internal standard after absorption of the alkaline sample on an Extrelut column and elution with diethylether-methylene chloride (70:30, v/v). The eluate was evaporated and the residue was dissolved in 100 microL of the mobile phase; 20 microL of this solution were injected into a mu Bondapak C18 column (10 microns) using acetonitrile-0.125M potassium dihydrogen phosphate (40:60, v/v) as mobile phase and UV detection at 280 nm, followed by UV spectrum identification (between 200 and 350 nm) with a photodiode array detector. The method is rapid (giving response within 20 min), reproducible, selective, and sensitive. It can be applied for pharmacokinetic studies and for both clinical pharmacology and forensic toxicology.

A rapid HPLC procedure for the simultaneous determination of chloroquine, monodesethylchloroquine, diazepam, and nordiazepam in blood.

Chloroquine, monodesethylchloroquine, diazepam, and nordiazepam levels are simultaneously determined in whole blood or plasma by HPLC. Papaverine is used as internal standard, and the analysis is performed after protein-binding hydrolysis, absorption on Extrelut, and elution with diethyl ether/methylene chloride (70:30 v/v). UV detection is used at 343 nm for 12 min, then changed to 242 nm. There are two mobile phases with two flow rates. The procedure requires 30 min, is reproducible, sensitive (8-10 ng/mL for chloroquine and its metabolite, 4 ng/mL for diazepam and nordiazepam), and selective, especially towards other antimalarial agents and drugs like adrenaline or barbiturates, which may be used in chloroquine poisoning therapy. It can be used for pharmacokinetic studies, therapeutic control, to establish the diagnosis and prognosis of a chloroquine poisoning, and to follow and optimize treatment.

Liquid chromatographic analysis of cocaine and benzoylecgonine in plasma of traditional coca chewers from Bolivia during exercise.

The purpose of the present study was to determine the amount of cocaine and benzoylecgonine in the plasma of Aymara Indians from the Bolivian Andes after traditional chewing of coca leaves during exercise performance. The determination was carried out by high performance liquid chromatography after solid-liquid extraction. The results showed that such use of coca leaves is well correlated with pharmacologically active concentration of cocaine in plasma.

Determination of chloroquine and monodesethylchloroquine in hair.

Using thin-layer and gas chromatography and mass spectrometry, chloroquine and its major metabolite (monodesethylchloroquine) were identified in hair samples of numerous patients who received this antimalarial drug for several months. In two patients the amounts of chloroquine were, respectively, 310 and 145 mg/kg hair and those of the monodesethylchloroquine 23 and 11 mg/kg. The respective proportions (93 and 7%) are the same in the two subjects. The chloroquine percentage was near those in the spleen or stomach wall after poisoning. Other metabolites in hair are being identified. Hair analysis may provide a good toxicologic and forensic science complement to the blood, urine, and tissues. It may be useful for the control of chloroquine therapy.

Respiratory symptoms and air pollution changes in children: the Gardanne Coal-Basin Study.

The influence of daily changes in sulfur dioxide (SO2) levels on the induction of respiratory symptoms was studied during the 1983-1984 winter in 450 children, aged 9 to 11 yr, living in the Gardanne coal-basin, France. In this area, SO2 originates mainly from a coal-fueled power plant. The mean SO2 level during the winter was 22 micrograms/m3 in low-pollution areas and 93 micrograms/m3 in polluted areas, with daily SO2 levels up to 356 micrograms/m3. Children completed a daily diary about respiratory symptoms. In the polluted communities only we demonstrated a significant association between daily SO2 levels (after controlling for temperature and respirable particle variations) and prevalence of upper and lower respiratory symptoms. However, in each polluted town, and for each respiratory symptom, there was no evidence for either a latency period or a delay in the effects of pollutants. Mean daily temperature was also closely correlated with upper and lower respiratory symptoms in most of the polluted and some low-pollution communities. In a second step, the prevalence of respiratory symptoms in each town was compared, during two 2-wk periods, with air pollution levels; higher prevalences were found during the pollution period. In conclusion, moderate daily changes in SO2 levels induce a significant but transient increase in the prevalence of respiratory symptoms in children.

[Pharmaco-clinical correlations during fluoxetine administration in patients with depressive schizophrenia treated with haloperidol decanoate]. / Corrélations pharmacocliniques lors de l'administration de fluoxétine chez des patients schizophrènes déprimés traités par halopéridol décanoate.

The study concerned 7 patients suffering from schizophrenic disorder according to the DSM III R criteria, treated with a stable dose of haloperidol decanoate (Haldol décanoas) added with fluoxetine (Prozac) from 20 mg to 40 mg/day because of major depression. Patients were assessed at baseline and weekly during the first cycle, and then once a month before each haloperidol decanoate injection, using the brief psychiatric rating scale (BPRS), the general clinical impression scale (CGI) and the Montgomery and Asberg depression rating scale (MADRS). Extrapyramidal and anticholinergic side-effects, blood pressure and pulse were noted. Determinations of plasma and red blood cells concentrations of haloperidol and reduced haloperidol, and of fluoxetine and norfluoxetine, were conducted at the same time than clinical evaluations. For all patients, we observed an improvement by the end of the first week, which became significant at the end of the second week, and continued in subsequent weeks (more than 30 per cent). Two weeks after the addition of fluoxetine, a very significant increase in haloperidol concentrations (more than 100 per cent) was noted; fluoxetine seems to have pharmacokinetic interactions with haloperidol, either by inhibiting its hepatic metabolism (inhibition of cytochrome P450 isoenzyme) or/and by displacing it from protein binding sites.

Neuroleptic-resistant schizophrenic patients treated by clozapine: clinical evolution, plasma and red blood cell clozapine and desmethylclozapine levels.

The aim of this open study was to determine a more rational therapeutic approach for psychotic patients treated with clozapine for several months, using measurement of plasma and red blood cell levels (P, RBC) of clozapine (cloza) and N-desmethylclozapine (descloza), the major metabolite of clozapine, which has been reported to be less active but more toxic (agranulocytosis) than clozapine itself. The RBC concentration may be considered as more representative of the free fraction drug. The study concerned 7 patients suffering from chronic paranoid schizophrenia according to the DSM-IV criteria. All of them were treatment-refractory schizophrenic inpatients (4 men, 3 women, mean age +/- SD: 38.2 +/- 8.4 years; mean duration of illness +/- SD: 14.4 +/- 5.1 years). They had received at least two different neuroleptics, for 6 weeks, before entering the study. Treatment started in our hospitalization unit with clozapine 25 mg up to a maximum of 900 mg/d (mean stabilized daily dose +/- SD: 507 +/- 211 mg and mean daily dose per kg: 6.91 +/- 3.08 mg). Clinical evaluations (Quality of Life Scale: QLS), regular blood monitoring and biological samples were conducted at the same time, weekly for 18 weeks and then monthly (duration of the study: 4 to 38 months; mean +/- SD: 12.9 +/- 11.5 months). Plasma and RBC (after lysis) levels were determined by reversed phase HPLC and UV detection after extraction with hexane. All the patients improved very quickly after the first week of treatment and six were able to leave the hospitalization unit and start outpatient care such as daily hospitalization, returning home or in sheltered accommodation. With the following plasma (P) and RBC levels: mean cloza +/- SD: (P = 294 +/- 146 ng/ml; RBC = 110 +/- 82 ng/ml) and mean descloza +/- SD: (P = 173 +/- 106 ng/ml; RBC = 76 +/- 54 ng/ml); none of the seven patients developed agranulocytosis. The blood levels, ensuring better surveillance, have a predictive value for clinical improvement. A linear pharmacoclinical correlation was only found between RBC cloza concentrations and the evolution of the QLS scores. Clozapine fulfils the criteria for therapeutic drug monitoring, and determination of plasma, and more particularly RBC, cloza and descloza levels may help to find the lowest effective dose with the fewest side effects.

[Pharmacokinetic profile of perphenazine enanthate]. / Sur le profil pharmacocinétique de l'énanthate de perphénazine

Publications on blood kinetics, biotransformations, excretion and tissular distribution of Perphenazine and its enanthic ester were analyzed. They allowed to make the pharmacokinetic profile of Perphenazine Enanthate, a long-acting neuroleptic, and to draw some information concerning its therapeutic use.

[Metabolism and blood levels study of antidepressants: a rationale of their therapeutical use (author's transl)]. / Etudu de métabolisme et des taux sanguins des antidépresseurs. Vers une rationalisation de leur emploi en thérapeutique.

The authors show with some examples the interest of pharmacokinetics for the optimization of the therapeutical use of antidepressive agents. They give some indications about bioavailabilty, metabolism and half-life of these compounds and note the importance of the individual variations. They also analyze the studies on the possible relations between the clinical response and the steady-state plasma levels of the unchanged drug and/or its active metabolite. The relation between these two parameters would be linear for imipramine, amitriptyline, clomipramine, doxepine, dibenzepine, and curvilinear for nortriptyline, desipramine, protriptyline, maprotiline and mianserine, especially in endogenous depression. From a previous pharmacokinetic study calculations allow to predict the steady-state plasma concentrations. The question of the side effects and drug interactions is considered.

[Plasma levels of metapramine and its 3 major metabolites in patients with depression. Results and preliminary interpretations]. / Concentrations plasmatiques de la métapramine et de ses trois principaux métabolites chez des patients déprimés. Résultats et interprétations préliminaires.

Metapramine (Timaxel) and his three major metabolites (19148 RP, 23669 RP, 19749 RP) have been determined in the plasma of 18 depressed inpatients treated by the antidepressant drug (12 women and 6 men; 7 are smokers and 11 non-smokers). In a steady state, interindividual variability is very important, especially for 23669 RP. No significant correlation exists between normalized doses (mg.kg-1) and normalized plasma concentrations (ng.ml-1/dose mg.kg-1) of metapramine or anyone of its metabolites. The plasma metabolic ratios reveal also important intraindividual and interindividual variability. Two populations of patients seem to exist: extensive metabolizers and relatively poor metabolizers, without apparent clinical consequence because 23669 RP shows an antidepressant activity. Women seem, with equal normalized doses, to exhibit higher plasma levels of unchanged metapramine than men, due to a lower protein-binding rather than to a more active metabolism. In patients who received a poly-medication smoking seems not to induce desmethylation of metapramine. The plasma metabolic ratios, compared by the analysis of variance and the Wilcoxon distribution-free test, are significatively influenced by sex and not by tobacco-smoking.

[Indoor air pollution and health: study of various problems]. / Pollution de l'air à l'intérieur des locaux et santé: étude de quelques problèmes.

Human beings are living between 70 and 90% inside of premises, where numerous air pollutants are existing: some of them have outdoor sources (industry, domestic burning, car traffic), some are produced indoors by human activities and equipment, by animals, or by various materials, products and furniture. According to their nature, they are listed as biological, physical or chemical pollutants. About health, serious poisonings and acute effects attributed to indoor air pollutants, and even short term effects (like sick building syndrome, infectious illness, pneumopathies,...), can be relatively easy to distinguish. Inversely the involvement of these pollutants in long term effects (like chronic bronchitis, asthma, cancers,...) is more difficult to establish. During the last 15 years we carried out several studies, which allowed us to separate the chemical air contaminants into two categories: those produced outdoors (sulphur dioxide, lead, chromium, nickel, nitrates), of whom we calculated the penetration coefficients, and those from both origin, outside and inside (nitrogen oxides, carbon monoxide, ammonia, aldehydes, particles, cadmium, vanadium, sulphates, ammonium salts). Aldehydes, which present important health risks, were especially investigated: in an office where several cigarettes were burning the measured concentrations were high in comparison with the threshold values existing in some foreign countries; in a cafeteria they were relatively low. To estimate the impregnation of non smokers by environmental tobacco smoke, we also determined, during same spaces of time, on the one hand nicotine in air, on the other hand nicotine and its metabolites excreted in the urine of exposed people. We thus observed that, in "real" situations, this impregnation is as a general rule extremely low.