Upon heat stress processing of ribosomal RNA precursors into mature rRNAs is compromised after cleavage at primary P site in Arabidopsis thaliana.

Transcription and processing of 45S rRNAs in the nucleolus are keystones of ribosome biogenesis. While these processes are severely impacted by stress conditions in multiple species, primarily upon heat exposure, we lack information about the molecular mechanisms allowing sessile organisms without a temperature-control system, like plants, to cope with such circumstances. We show that heat stress disturbs nucleolar structure, inhibits pre-rRNA processing and provokes imbalanced ribosome profiles in Arabidopsis thaliana plants. Notably, the accuracy of transcription initiation and cleavage at the primary P site in the 5'ETS (5' External Transcribed Spacer) are not affected but the levels of primary 45S and 35S transcripts are, respectively, increased and reduced. In contrast, precursors of 18S, 5.8S and 25S RNAs are rapidly undetectable upon heat stress. Remarkably, nucleolar structure, pre-rRNAs from major ITS1 processing pathway and ribosome profiles are restored after returning to optimal conditions, shedding light on the extreme plasticity of nucleolar functions in plant cells. Further genetic and molecular analysis to identify molecular clues implicated in these nucleolar responses indicate that cleavage rate at P site and nucleolin protein expression can act as a checkpoint control towards a productive pre-rRNA processing pathway.

APOBEC3A intratumoral DNA electroporation in mice.

Human APOBEC3A (A3A) cytidine deaminase shows pro-apoptotic properties resulting from hypermutation of genomic DNA, induction of double-stranded DNA breaks (DSBs) and G1 cell cycle arrest. Given this, we evaluated the antitumor efficacy of A3A by intratumoral electroporation of an A3A expression plasmid. DNA was repeatedly electroporated into B16OVA, B16Luc tumors of C57BL/6J mice as well as the aggressive fibrosarcoma Sarc2 tumor of HLA-A*0201/DRB1*0101 transgenic mice using noninvasive plate electrodes. Intratumoral electroporation of A3A plasmid DNA resulted in regression of ~50% of small B16OVA melanoma tumors that did not rebound in the following 2 months without treatment. Larger or more aggressive tumors escaped regression when so treated. As APOBEC3A was much less efficient in provoking hypermutation and DSBs in B16OVA cells compared with human or quail cells, it is likely that APOBEC3A would be more efficient in a human setting than in a mouse model.

Changes in Dendritic Spine Density and Inhibitory Perisomatic Connectivity onto Medium Spiny Neurons in L-Dopa-Induced Dyskinesia.

Using bacterial artificial chromosome-double transgenic mice expressing tdTomato in D1 receptor-medium spiny neurons (MSNs) and enhanced green fluorescent protein in D2 receptor-MSNs, we have studied changes in spine density and perisomatic GABAergic boutons density in MSNs of both the D1R and D2R pathways, in an experimental model of parkinsonism (mouse injected with 6-hydroxydopamine in the medial forebrain bundle), both in the parkinsonian and dyskinetic condition induced by L-DOPA treatment. To assess changes in perisomatic GABAergic connectivity onto MSNs, we measured the number of contacts originated from parvalbumin (PV)-containing striatal "fast-spiking" interneurons (FSIs), the major component of a feed-forward inhibition mechanism that regulates spike timing in MSNs, in both cell types as well as the number of vesicular GABA transporter (VGAT) contacts. Furthermore, we determined changes in PV-immunoreactive cell density by PV immunolabeling combined with Wisteria floribunda agglutinin (WFA) labeling to detect FSI in a PV-independent manner. We also explored the differential expression of striatal activity-regulated cytoskeleton-associated protein (Arc) and c-Fos in both types of MSNs as a measure of neuronal activation. Our results confirm previous findings of major structural changes in dendritic spine density after nigrostriatal denervation, which are further modified in the dyskinetic condition. Moreover, the finding of differential modifications in perisomatic GABAergic connectivity and neuronal activation in MSNs suggests an attempt by the system to regain homeostasis after denervation and an imbalance between excitation and inhibition leading to the development of dyskinesia after exposure to L-DOPA.

[Hypertensive emergencies]. / Les urgences hypertensives.

Hypertensive urgencies are common clinical occurrences in hypertensive patients. The definition of hypertensive urgencies (target blood pression) were not consistent, but involved often target end-organ damage in emergencies. Epidemiology and physiopathology are briefly described. Treatment practices of hypertensive crisis were difficult because of the lack of evidence supporting the use of one therapeutic agent over another and its posology.

[Application of guidelines concerning systolic hypertension in patients over 80 years of age: experience in a geriatric institute]. / Application des recommandations dans l'hypertension artérielle systolique après 80 ans: expérience en institution gériatrique.

Application of the guidelines concerning systolic hypertension in patients over 80 years of age: experience in a geriatric institute In order to compare the blood pressures of elderly hypertensive patients treated in accordance with recent guidelines, the authors measured the casual blood pressure of a population of long stay patients. Recent data from the FRAMINGHAM HEART STUDY shows that, in the general population, only 23% of women over 80 years of age attained the target values, a blood pressure less than 140/90 mmHg, and only 35% of those treated for hypertension. Eighty patients in the long stay unit of Allauch Hospital were studied in this transverse study performed from the 23rd to 25th of August 2005. The blood pressure (SBP, DBP and PP) and heart rate at consultation were measured by the same physician with the same sphygmomanometer (OMRON M4). The prescribed antihypertensive medication was noted; the presence of atrial fibrillation and the echocardiographic data including left atrial (LA) diameter in M-mode were also included. Forty-four of the 80 patients included were hypertensive (84% women, average age 88.7 years; 16% men, average age 86 years) and treated with the same objective of blood pressure (BP < 140/90 mmHg). The patients were treated by monotherapy in 6% of cases, bitherapy in 27% of cases, tritherapy in 6.8% of cases, and quadritherapy in 4.5% of cases. The distribution of antihypertensive agents in the patients over 80 years of age was almost identical to that of the ninety years of age group. The target blood pressure was attained in 67.5% of women and 71.5% of men. The incidence of atrial fibrillation in the hypertensive patients over 80 years of age was 32%, and 85.7% of them had dilated left atrium (>40 mm). The authors conclude that target blood pressures were more often attained (68% vs. 35%) in this Geriatric Institute than in the American general population probably because of environmental and motivational reasons, including those of the medical staff.

Increase in plasma concentration of plasminogen activator inhibitor, fibrinogen, von Willebrand factor, factor VIII:C and in erythrocyte sedimentation rate with age.

Elderly patients have previously been shown to have an increased plasma concentration of tissue plasminogen activator (t-PA) antigen (t-PA Ag). Since the concentration of t-PA Ag depends on both free t-PA and t-PA complexed with inhibitors, mainly plasminogen activator inhibitor (PA inhibitor), we have investigated the relationship between the plasma concentration of PA inhibitor and age in 20 elderly and 20 young individuals. Elderly individuals showed a slight increase in PA inhibitor, in parallel with increase on others, acute-phase proteins, fibrinogen, von Willebrand factor, factor VIII:C, and the erythrocyte sedimentation rate. The increase in PA inhibitor as well as other acute-phase proteins in the elderly may be significant in relation to the increased incidence of thrombotic disease.

Outbreak of Clostridium difficile-related diarrhoea in an adult oncology unit: risk factors and microbiological characteristics.

We describe the risk factors and microbiological findings of an outbreak of Clostridium difficile (CD)-related diarrhoea in the Medical Oncology Department of the Curie Institute. Screening for CD in stools was performed on 59 patients with diarrhoea and 146 patients without diarrhoea. Toxin secretion, serotyping (enzyme-linked immunosorbant assay) and genotyping (AP-polymerase chain reaction) were performed on 39 CD strains from 32 patients. The risk factors for toxigenic CD-positive diarrhoea were also investigated. Twenty-seven (46%) patients with diarrhoea and 12 (8%) patients without diarrhoea were CD-positive (P<0.001). Patients with diarrhoea were older (P=0.03). Chemotherapy was a risk factor for toxigenic CD-related diarrhoea (P=0.02) and antibiotic treatment was a risk factor only in those patients who were also receiving chemotherapy. Serotyping and genotyping showed that several strains were involved in this outbreak, with only two instances of patient-to-patient transmission, involving four and two patients.

Des-enkephalin-gamma-endorphin in the treatment of schizophrenia.

Ninety-three patients with an exacerbation of chronic schizophrenia were included in a 4 week trial comparing placebo with 1, 3 and 10 mg des-enkephalin-gamma-endorphin (DE gamma E; beta-lipotrophin 66-77; Org 5878) per day (i.m.). Maintenance antipsychotic and other medications were continued unchanged. Treatment effects were assessed by means of the Comprehensive Psychopathological Rating Scale--subscale schizophrenia (CPRS-S), Brief Psychiatric Rating Scale (BPRS) and Global Assessment Scale (GAS) rating scales at weekly intervals. Safety data, i.e. laboratory investigations, vital signs and ECG recordings, were assessed before and during the trial. Side-effects were evaluated by means of a Record of Symptoms Emerging. Sixty-eight patients completed the trial, the reason for drop-out mainly being inadequate treatment effects and refusal of medication administration. One patient violated the protocol. After 4 weeks of treatment the mean CPRS-S score of the group receiving 10 mg DE gamma E daily had decreased statistically significantly more than the corresponding score of the placebo group (p less than 0.01). The same trend was apparent with BPRS (p = 0.08) and GAS (p greater than 0.1) scores. Therefore, the study should be considered inconclusive. No clinically relevant side-effects attributable to DE gamma E were observed.

Primary meningococcal polyarthritis.

We report a case of primary meningococcal polyarthritis simulating bacteraemic gonococcal infection. The clinical similarity between extragenital gonococcal and meningococcal infections is well illustrated. If the clinical features of meningococcal and gonococcal infections are usually different, they may sometimes be indistinguishable. Both gonococcal pharyngitis and meningococcal urethritis have been recorded. The onset of acute polyarthritis, fever and skin lesions is typical of gonococcal infection but these clinical features may also indicate infection due to Neisseria meningitidis. In the case we report, the correct diagnosis of meningococcal arthritis was established only after N. meningitidis group C had been identified in synovial fluid from the knee.

[Standards, Options, and Recommendations for the management of brief neutropenias. Fedération Nationale des Centres de Lutte Contre le Cancer]. / Standards, Options et Recommandations pour la prise en charge des neutropénies courtes.

CONTEXT: The "Standards, Options and Recommendations" (SOR), initiated in 1993, is a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcomes for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary experts group, with feedback from specialists in cancer care delivery. OBJECTIVE: To develop a clinical practice guideline for the management of neutropenic cancer patients (excluding prolonged neutropenia). METHODS: Data have been identified by literature search using Medline and Current Contents (up to February 1997) and personal reference lists. The main end points considered were mortality, morbidity, risk factors, fever, source of infection, microbiological documentation, incidence and length of hospital stays, quality of life, efficacy of treatment, safety and costs. Once the guideline was defined, the document was submitted to 48 reviewers for peer review and to the medical committees of the 20 French Cancer Centres for review and agreement. RESULTS: The key recommendations are: 1) before receiving cytotoxic chemotherapy, patients must be informed of potential risks and precautions to observe; 2) non-febrile neutropenic patients can be followed at home (except specific context); antibiotic prophylaxis is not recommended; 3) initial empirical antibiotic therapy for febrile patients is mandatory, whether associated beta-lactam and aminoglycoside, or monotherapy with a broad-spectrum beta-lactam (except in case of septic shock or pneumopathy). A glycopeptide can be added in case of overt catheter-related or cutaneous infection, in case of microbiologically documented infection with a oxacillin-resistant Gram positive bacteria, or in case of persistent fever in a clinically deteriorating patient; 4) at the present time, there is insufficient evidence to recommend the management of febrile neutropenic patients at home. We recommend participation in studies to identify predicting factors of low-risk patients and to assess the feasibility and safety of early discharge and home therapy.

[Standards, Options and Recommendations (SOR) for the surveillance and the prevention of cross infections in oncology. Fédération Nationale des Centres de Lutte Contre le Cancer]. / Standards, Options et Recommandations (SOR) pour la surveillance et la prévention des infections nosocomiales en cancérologie.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the prevention and the surveillance of cross infection in oncology. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 106 independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: 1) Criteria of infection status and nosocomiality defined by the Centers for Infectious Diseases (CDC) and Prevention and the Superior Council of Public Hygiene (CSHPF) are not adapted and have to be redefined in oncology. 2) The epidemiology of nosocomial infections in oncology is not well known but their incidence seems to be higher. Numerous risk factors of cross infections coexist in cancer patients, among which the duration and depth of neutropenia. 3) Surveillance and prevention of cross infection are compulsory and were taken into account in the accreditation of hospitals. Obligation is expressed in terms of means and results. 4) The objectives of the cross infection surveillance are to detect major problems and critic situations, to guide probabilistic antibiotic therapy and to assess the effectiveness of the infections control. The surveillance means consist in prevalence and incidence survey, punctually and continuously conducted. 5) The three specific behaviors to be adopted to prevent cross infections are to control: all the patients, infected patients carrying multiresistant bacteria, immunodepressed patients. 6) Standards of care have to be applied to a/l patients with cancer. 7) It is necessary to add particular septic cares for the patients infected with micro-organisms indicated on reference lists or carrying multiresistant bacteria. 8) The only objective of the protective isolation of immunodepressed cancer patients is to reduce the cross infection. There is no standard behavior for the indications and the modalities of protective isolation. The prevention behaviors to be taken are defined by expert agreements.

[Antihypertensive effects of intravenous nicardipine in arterial hypertension in the elderly]. / Effets antihypertenseurs de la nicardipine intraveineuse dans l'hypertension artérielle du sujet âgé.

In order to evaluate the antihypertensive action of intravenous (i.v.) nicardipine, a calcium channel blocker, we included 28 patients (20 women and 8 men) aged from 71 to 93 years (mean age: 80.4 yrs) poorly controlled by their normal antihypertensive treatment, which had not consisted of a calcium channel blocker. These patients had past histories of a variety of cardiovascular disorders: valve disease (n = 4), disorders of cardiac rhythm (n = 3), paced or unpaced disorders of cardiac conduction (n = 8), and cerebrovascular accident (n = 12). On inclusion, their systolic blood pressure (SBP) was greater than or equal to 180 mmHg and/or their diastolic blood pressure (DBP) greater than or equal to 100 mmHg. Blood pressure recordings (SBP, DBP, MBP) and heart rate (HR) were simultaneously taken every 3 minutes for a period of 140 minutes by an automatic apparatus and a mercury manometer, before and after i.v. administration of nicardipine at 3 increasing dosages, respectively 1.25 mg (20 th min), 2.5 mg (32 th min) and 5 mg (44 th min), each injected over a period of 6 minutes. With a cumulative dose of 8.75 mg nicardipine i.v., the SBP decreased significantly from 192.6 to 138.8 mmHg (p less than 0.001); similarly, the DBP fell from 93.9 to 65.8 mmHg (p less than 0.001) and the MBP from 126.2 to 90.1 mmHg (Hg manometric measurement). In addition, after the final dose of nicardipine, the blood pressure progressively rose to reach levels, by the end of the trial, of 172.1 mmHg (SBP) and 91.1 mmHg (DBP).(ABSTRACT TRUNCATED AT 250 WORDS)

[Determination of the optimal dose of bromazepam in the elderly]. / Recherche d'une posologie optimale du bromazépam chez le sujet âgé.

The aim of our study was to determine in patients over 70 years, the optimal dose of Bromazepam. Seven patients were administered a unique dose of Bromazepam (3 mg), then repeated doses (1.5 mg) every 12 hours for 9 days. Cmax was 42.5 +/- 12 ng/ml in Tmax ranged from 2 to 12 hours after the first dose-concentrations of Bromazepam at steady-state were between 79 and 157 ng/ml. Half life was 30.5 +/- 14.7 hrs for the unique and the repeated doses. Sleeping was noted for concentrations over 40 ng/ml. The dose of 1.5 mg bid is recommended in old patients.

[Clinical and pharmacokinetic study of amikacin during repeated intramuscular administration in elderly patients]. / Etude pharmacocinétique et clinique de l'amikacine intramusculaire à posologie répétée chez le sujet âgé.

Pharmacokinetics of amikacin in elderly patients during repeated intramuscular administration. The aim of the study was to evaluate a standard dosage of Amikacin, 7.5 mg/kg every 12 hours, in elderly subjects whose renal function was reduced by half, in view of the narrow therapeutic interval of the aminoglycosides. Twelve subjects, aged from 72 to 96 years (mean age: 82 years; mean weight: 58.7 kg) and suffering from severe infections, were therefore treated with intramuscular Amikacin as monotherapy at the dosage of 7.5 mg/kg repeated every 12 hours for 5 days. Clinical, biological (creatinine clearance estimated by the method of Cockroft) and bacteriological data were recorded on D0 and D5. The pharmacokinetic study included plasma Amikacin assays at the following times: D0 (control), D1 (1h, 3h, 6h, 12h), D2 (24h, 25h, 27h, 36h), D3 (48h, 49h), D5 (96h, 97h, 99h, 102h, 105h, 108h), D6 (120h, 132h). Clinical success was observed in 9 out of the 12 cases, with no undesirable side effects. At this age and at this dosage, peak concentrations (Cmax) remain close to the required "therapeutic" levels, 25 to 30 mcg/ml; the residual concentrations (Cmin), highly-correlated with creatinine clearance values, are also close to the desired levels (4-10 mcg/ml). The absence of side effects, and in particular the lack of renal side effects, during this treatment trial suggest that the usual dosage of Amikacin IM, 7.5 mg/kg/12 h, need not be reduced in elderly subjects if creatinine clearance remains above 30 ml/mn and if the treatment is of short duration.

[Polysomnographic aspects of antidepressive therapy]. / Aspects polysomnographiques des thérapeutiques antidépressives.

Sleep disorders are very common in depression. They have been quantitatively and qualitatively described by polysomnographical recordings. It is of interest to know how treatments act on polysomnographical data. In this article, we propose to evaluate five treatment approaches proposed for depressive illness. Pharmacological treatment induces marked changes in sleep continuity, sleep architecture and REM sleep. However, no specific sleep profiles emerge neither for each treatment class nor for molecules within the same pharmacological class. But actually, sleep data cannot be viewed as markers of treatment response. Psychotherapeutic interventions have only few effects on sleep of depressed patients. Treatment efficiency does not seem to be correlated to abnormal sleep parameters. Sleep deprivation induces marked changes in nearly all sleep parameters and in temporal distribution of sleep stages during the night. Actually, the efficiency of sleep deprivation cannot longer be explained by suppression of REM sleep. Sleep deprivation has only a transient effect and treatment indications are therefore secondary. Sleep parameters do not distinguish responders from non-responders. Sleep deprivation shows that there is a depressogenic effect of sleep in the end of the night. Bright light therapy shows marked changes in sleep continuity parameters. Among all studies that examine the impact of treatment on sleep EEG, ECT has received little attention. The few studies available are either case studies or with poor effectifes++. For this reason and because of methodological bias, results are heterogeneous and no definite conclusions can be drawn. But all of them agree that ECT modifies sleep EEG. So, changes in polysomnographical data cannot predict response to any treatment. Prospective sleep studies are difficult to realise on a great number of patients explaining absence of treatment predictors.

[Sleep electroencephalography in depression and mental disorders with depressive comorbidity]. / La valeur de la polysomnographie dans la dépression et les pathologies mentales avec comorbidité dépressive.

Traditional scoring of sleep EEG in depressed patients shows abnormalities in sleep maintenance, sleep architecture, REM sleep, the distribution of slow wave and REM sleep during the night. Computerized analysis that comprises the period-amplitude analysis procedure and spectral analysis discloses changes in delta activity and distribution of delta activity. However, these methods of analysing EEG sleep are not able to distinguish the various concepts of depression: endogenous and non-endogenous depression, unipolar and bipolar depression, psychotic and non-psychotic depression. Polysomnographical data in patients with recurrent depression show alteration during remission suggesting trait-like abnormalities of sleep in depression illness. Shortened REM latency is not specific in depression. This sleep parameter is defined in many different ways explaining the heterogeneousness of study results and the failure of constituting a biological marker. Many sleep parameters are affected by several factors such as age, gender and severity. Several physiopathological hypotheses have been proposed to explain EEG sleep alterations. They refer either to circadian rhythms such as the two process model of Borbély, the phase advance hypothesis and the circadian amplitude hypothesis, or to neurotransmitter abnormalities such as the cholinergic hypothesis. None of them takes sufficient account of all the sleep abnormalities. Sleep abnormalities have also been described in other psychiatric disorders such as mania, panic and obsessional-compulsive disorders, generalized anxiety, phobias, post-traumatic stress disorder, eating disorders, borderline personality, schizophrenia and dementia. None of them have a particular sleep EEG profile which allows to differentiate between them. A concomitant episode of major depression cannot be uncovered by sleep recordings.

[Associations and interactions: tricyclic antidepressants and selective serotonin reuptake inhibitors]. / Associations et interactions: les antidépresseurs tricycliques et les inhibiteurs spécifiques de la recapture de la sérotonine.

Following the commercialization of the SSRIs clinicians described cases of drug interactions with tricyclic antidepressants among their patients. When combining tricyclic antidepressants and SSRIs clinical side effects and elevated plasma levels of tricyclics appeared. A better knowledge of the cytochrome P450 system allows to understand the mechanism of such drug interactions. The cytochrome P450 is composed of a group of isoenzymes, which are classified, into families and subfamilies on the basis of amino acid sequence homology. A number of the cytochrome genes have a genetic polymorphism responsible for poor and extensive metabolisers. The clinical importance of genetic polymorphism is highly dependent upon the therapeutic index. Thus, poor metabolisers, will experience side effects and rapid metabolisers prone to therapeutic failure. Concerning pharmacological issues SSRIs have a great affinity for at least one of the isoenzymes which accounts for drug interactions. Due to the inhibitory potential of the SSRIs drug interactions occur with tricyclics that have a narrow therapeutic index. The SSRIs do not exert the same inhibitory effect on the various isoenzymes. The inhibitory activity for an isoenzyme depends on the molecule of the SSRIs. In clinical practice, the associations between tricyclics and SSRIs should be practiced with caution. It is recommended to decrease the tricyclic dose before administering the SSRI, to start with low doses of the SSRI and to take into account the therapeutic index. Although the coadministration of tricyclics and SSRIs can produce adverse reactions it has also two main interests in clinical practice. First, the drug combination enhances clinical response to treatment. Secondly, it converts non-responders of pharmacological treatment to responders. Used with caution the association of tricyclics and SSRIs is well tolerated. However, it should be kept in mind that a single drug therapy should be tried first. These data show the complexity of drug interactions.

[Methodological obstacles encountered in the evaluation of psychotherapies of schizophrenic patients. A general review]. / Les obstacles méthodologiques rencontrés dans l'évaluation des psychothérapies de schizophrènes. Revue générale.

Through a critical review of literature, authors suggest a methodological reflexion about problems in evaluation of effects of psychotherapies of schizophrenics, taking into account not only individual techniques but also institutional ones with psychotherapeutic orientations. Among the main difficulties are: evaluation with too much unspecific and over simplified criteria, for example criterium of rehospitalisation; lack of real comparability between groups, or techniques, and lack of validity of randomisation, still considered as a pawn of methodological rigour; diversity of levels of experience, and education of therapists, too unmatched model of functional organisation of the different centers, and in the same time too unequal recruitment of patients and at length of proposed therapeutic programs. Moreover, and even before these methodological bias, a more basic obstacle must be considered. It is the non-opening of models to the falsification, denounced by Bignami as the impossible verification of the heuristic value of the proposed models, ie the impossible verification of the utility of the proposed programs for individual therapies of schizophrenics.

[Role of psychotherapy in the treatment of schizophrenia]. / Place des psychothérapies dans le traitement des schizophrénies.

Reality-adaptative, supportive psychotherapy, institutional cares, therapeutics with artistic mediations, family therapeutics are unanimously recognized as efficacious therapeutics for schizophrenic inpatients and outpatients. Conversely, the usefulness of psychoanalysis and exploratory, insight-oriented psychotherapy is questionnable. To clear up the question, we have studied controlled and non controlled studies comparing different psychotherapies, as well as the results of individual psychoanalysis. Among the controlled studies, Stanton's study stands out for its methological strictness. This study, in 164 schizophrenics, shows that insight-oriented psychotherapy is not more efficacious than supportive psychotherapy. In the continuation of this work, A. Frank and J. Gunderson show that the determinant factor of the psychotherapy's result is relational continuity and especially therapeutic alliance. Some works made in France show that 6 to 8 months are needed to appreciate the efficacy of institutional cares and psychotherapies can be observed. The psychoanalysis is not always efficacious. But these long acting experiences have provided irreplaceable knowledge towards the understanding of schizophrenic self and transference, effects of institutional cares, therapeutics with artistic mediations, supportive psychotherapy, theoretical reflection (Racamier, Rosenfeld, Searles, etc). Among the metapsychological knowledge, we must see: alterity's denial, struggle against thinking's activity, erotically paradoxical transference, receptacle's and depositary's function of therapists, inexistence of containing function. These knowledges explain that the two principal functions of the care given to schizophrenics are: help to self and presence.

[Delay of the antidepressant effect: clinical studies]. / Délai d'action des antidépresseurs: données cliniques.

The first controlled trials of antidepressants show up a delay of antidepressant effect to one or two weeks, with sedative or stimulant early effects. More recently, several controlled trials founded on more stringent criterions (DSM III, period of pre-therapeutic placebo of one minimal week, frequent quotations etc.) have showed up a delay of antidepressant effect assigned between the fourth and the sixth week, with all antidepressant drugs. Nevertheless, there are more early effects, either specific antidepressant but incomplete either non specific (sedative, stimulant). These early effects are more marked with the antidepressant drug than with the PBO, but they have not a predictive value of terminal response. Several factors have an influence on the delay of antidepressant effect. The clinical characteristics are not correlated with this delay. The intravenous administration does not reduce the length of this delay. The pulse loading doses with intravenous and oral antidepressant drug seem to reduce the length of this delay. The most important factor is the placebo effect (Quitkin et al.). Nevertheless, the differences of efficacy between antidepressant and PBO appear only towards the third week. There are some differences during the first two weeks. In fact the PBO effect is early and late longer than the antidepressant drug. With PBO, when the improvement is progressive and fasting, it is a spontaneous remission. These data have practical implications if we must know the delay of antidepressant drug.