Complex Polysaccharide-Based Nanocomposites for Oral Insulin Delivery.

Polyelectrolyte nanocomposites rarely reach a stable state and aggregation often occurs. Here, we report the synthesis of nanocomposites for the oral delivery of insulin composed of alginate, dextran sulfate, poly-(ethylene glycol) 4000, poloxamer 188, chitosan, and bovine serum albumin. The nanocomposites were obtained by Ca2+-induced gelation of alginate followed by an electrostatic-interaction process among the polyelectrolytes. Chitosan seemed to be essential for the final size of the nanocomposites and there was an optimal content that led to the synthesis of nanocomposites of 400-600 nm hydrodynamic size. The enhanced stability of the synthesized nanocomposites was assessed with LUMiSizer after synthesis. Nanocomposite stability over time and under variations of ionic strength and pH were assessed with dynamic light scattering. The rounded shapes of nanocomposites were confirmed by scanning electron microscopy. After loading with insulin, analysis by HPLC revealed complete drug release under physiologically simulated conditions.

Rapid spread of the novel respiratory syncytial virus A ON1 genotype, central Italy, 2011 to 2013.

Respiratory infections positive for human respiratory syncytial virus (RSV) subtype A were characterised in children admitted to hospitals in Rome and Ancona (Italy) over the last three epidemic seasons. Different strains of the novel RSV-A genotype ON1, first identified in Ontario (Canada) in December 2010, were detected for the first time in Italy in the following 2011/12 epidemic season. They bear an insertion of 24 amino acids in the G glycoprotein as well as amino acid changes likely to change antigenicity. By early 2013, ON1 strains had spread so efficiently that they had nearly replaced other RSV-A strains. Notably, the RSV peak in the 2012/13 epidemic season occurred earlier and, compared with the previous two seasons, influenza-like illnesses diagnoses were more frequent in younger children; bronchiolitis cases had a less severe clinical course. Nonetheless, the ON1-associated intensive care unit admission rate was similar, if not greater, than that attributable to other RSV-A strains. Improving RSV surveillance would allow timely understanding of the epidemiological and clinicopathological features of the novel RSV-A genotype.

Clinical and genetic findings in a series of Italian children with pure hereditary spastic paraplegia.

BACKGROUND: hereditary spastic paraplegias (HSP) are a group of neurodegenerative disorders characterized by progressive lower extremity spastic weakness. SPG7, SPG4 and SPG3A are some of the autosomal genes recently found as mutated in recessive or dominant forms of HSP in childhood. SPG31 is more often associated with a pure spastic paraplegia phenotype, but genotype-phenotype correlation is still unclear. The aims of the current study was: (i) to verify the mutational frequency of SPG4, SPG3A, SPG31 and SPG7 genes in our very-well-selected childhood sample, and (ii) to improve our knowledge about the clinical and electrophysiological HSP phenotypes and their possible correlation with a specific mutation. METHODS: a sample of 14 Italian children affected by pure HSP (mean age at diagnosis 5.9 years) was extensively investigated with electrophysiological, neuroradiological and genetic tests. RESULTS: three SPG4 mutations were identified in three patients: two novel missense mutations, both sporadic, and one multiexonic deletion already reported. A novel large deletion in SPG31 gene involving exons 2-5 was also detected in one young patient. No mutations in the SPG7 and in the SPG3A genes were found. CONCLUSIONS: our data confirm that HSP represent a heterogeneous group of genetic neurodegenerative disorders, also in sporadic or autosomal recessive early onset forms. Multiplex Ligation-dependent Probe Amplification-based mutation screening for SPG4 and SPG31 genes would be added to sequencing-based screening of SPG4, SPG31 and SPG3A genes in the routine diagnosis of HSP children.

Interferon-induced gene expression in cervical mucosa during human papillomavirus infection.

The aim of this study is to monitor type I interferon (IFN) activation in the cervical mucosa of Human Papillomavirus (HPV)-infected and uninfected women attending a routine gynaecologic clinic. The expression of three IFN-induced genes (MxA coding for human Mixovirus resistance protein A, ISG15 Interferon Stimulated Gene coding for a 15 kDa ubiquitin-like protein and UBP43 coding for the ISG15 isopeptidase) was determined as the mRNA copy number in cervical cells, normalized to the mRNA ones of the beta-glucuronidase gene. Type-specific HPV-DNA load was concurrently determined in the HPV-positive samples. Out of 127 samples tested, 54 were sufficient for both DNA and RNA extraction. The type-specific HPV-DNA copy numbers in the 34 HPV-positive samples varied widely. No significant association was found between copy numbers of MxA, ISG15, UBP43 and HPV status or viral load. However, despite a marked inter-individual variability, ISG15 expression was significantly higher when low-risk HPV infections were compared with HPV-negative samples, while high-risk HPV infections had very low ISG15 levels. The lack of ISG15 activation in high-risk HPV-infected cervical cells could be due to the lack of p53-mediated induction or to HPV-directed specific inhibition of type I IFN pathways. This study approach might be of value in clarifying the role of type I IFN activation in determining the clearance or persistence of HPV infections.

Measurement of the sensitivity of different commercial assays in the diagnosis of CMV infection in pregnancy.

To evaluate the performance of different commercial assays for the detection of recent cytomegalovirus (CMV) in pregnancy, the sensitivity and specificity of assays for CMV-specific IgM antibodies were compared. Routine specimens from pregnant women were screened for CMV IgM using the Abbott AxSYM assay. Sera that were reactive according to AxSYM were further tested for IgM by other commercial assays. In selected IgM positive samples a CMV IgG avidity assay (Radim) and virus isolation from urine (shell vial) were also performed. The positivity rate for IgM anti-CMV by AxSYM was relatively high (140 out of 492, combining reactive and grayzone results). Only 26 of the 140 samples were positive for IgM according to Radim. The IgG avidity was low in 16 of the 43 samples tested, and the Radim and DiaSorin IgM assays were negative in 5 of them; 2 of the latter cases were also positive for viral isolation according to a shell vial method. There are differences in the sensitivity of the commercially available tests for CMV antibodies. CMV screening in pregnancy is performed as a first step by immunoassays and the choice of highly sensitive IgM test associated with further serological and virological methods could help to identify early primary infections.

Tolerance to the sedative and anxiolytic effects of diazepam is associated with different alterations of GABAA receptors in rat cerebral cortex.

The clinical use of benzodiazepines is limited by the development of tolerance to their pharmacological effects. Tolerance to each of the pharmacological actions of benzodiazepines develops at different rates. The aim of this work was to investigate the mechanism of tolerance by performing behavioral tests in combination with biochemical studies. To this end, we administered prolonged treatments of diazepam to rats for 7 or 14 days. Tolerance to the sedative effects of diazepam was detected by means of the open field test after the 7- and 14-day treatments, whereas tolerance to the anxiolytic actions of benzodiazepine manifested following only the 14-day treatment in the elevated plus maze. The cerebral cortical concentrations of diazepam did not decline after the diazepam treatments, indicating that tolerance was not due to alterations in pharmacokinetic factors. The uncoupling of GABA/benzodiazepine site interactions and an increase in the degree of phosphorylation of the GABAA receptor γ2 subunit at serine 327 in the cerebral cortex were produced by day 7 of diazepam treatment and persisted after 14 days of exposure to benzodiazepine. Thus, these alterations could be part of the mechanism of tolerance to the sedative effects of diazepam. An increase in the percentage of α1-containing GABAA receptors in the cerebral cortex was observed following the 14-day treatment with diazepam but not the 7-day treatment, suggesting that tolerance to the anxiolytic effects is associated with a change in receptor subunit composition. The understanding of the molecular bases of tolerance could be important for the development of new drugs that maintain their efficacies over long-term treatments.

Initial monoamine oxidase-A inhibition by moclobemide does not predict the therapeutic response in patients with major depression. A double blind, randomized study.

It is generally accepted that the clinical efficacy of monoamine oxidase inhibitors (MAOI) is related to inhibition of this enzyme. In order to evaluate the predictive ability of monoamine oxidase-A inhibition for therapeutic efficacy, the start of treatment effects of moclobemide, a selective, reversible monoamine oxidase-A inhibitor, on plasma concentrations of monoamines and monoamine metabolites were determined. The plasma levels of 3,4-dihydroxyphenylglycol (DHPG, deaminated metabolite of noradrenaline), 5-hydroxyindoleacetic acid (5-HIAA, deaminated metabolite of serotonin), 3,4-dihydroxyphenylacetic acid and homovanillic acid (DOPAC and HVA, deaminated metabolites of dopamine), L-dihydroxyphenylalanine (L-dopa) and noradrenaline were investigated and related to treatment outcome. This was a randomized double blind parallel group study in 47 patients with criteria of major depression according to DSM III R. Moclobemide 300 mg/day, 450 mg/day or 600 mg/day was administered continuously for 6 weeks. Plasma concentrations of monoamine metabolites and monoamines were determined just before treatment by moclobemide, 4 h after the first dose, 24 h after the first dose, before the first dose on day 7, and 4 h after the first dose, on day 7. Each moclobemide dose improved depression as measured by MADRS (Montgomery-Asberg Depression Rating scale) but there was no difference between the three doses. Moclobemide dose-dependently reduced plasma concentration of DHPG, L-dopa and HVA. No dose-dependent treatment effect was observed for plasma 5-HIAA, noradrenaline and DOPAC. The clinical outcome as defined by the final MADRS score was not related to any start of treatment changes in plasma monoamine metabolites reflecting inhibition of MAO-A. It is concluded that monoamine oxidase-A inhibition at the beginning of the treatment does not predict clinical outcome.

Fluoxetine versus amineptine in the treatment of outpatients with major depressive disorders.

Fluoxetine, a selective serotonin reuptake inhibitor, was compared to amineptine, a tricyclic antidepressant agent, in the treatment of 63 outpatients with major depressive disorders of mild or moderate severity. Patients were randomly assigned to 6 weeks of treatment with either fluoxetine or amineptine. Fluoxetine was found to have a more marked therapeutic effect than that of amineptine: better efficacy, fewer side-effects, and quicker and better improvement on the self evaluation scales.

Efficacy of amineptine in the prevention of relapse in unipolar depression.

The clinical properties of amineptine, a mainly dopaminergic antidepressant, were assessed in a double-blind controlled study involving patients fulfilling Diagnostic and Statistical Manual of Mental Disorders (DSM-III) criteria for unipolar depression. The aim was to determine how relapses could be prevented in this frequently recessing disorder. The study was a two-phase, 12-month, multicentre trial of patients suffering from major depression or dysthymia, diagnosed using DSM-III criteria and evaluated on the Montgomery-Asberg Depression Rating Scale and the Mood, Anxiety, Retardation, Danger scale. Phase I was an open-label 3-month period, with the patients being given 200 mg amineptine per day. The second, 9-month period was a placebo-controlled prophylactic phase. A total of 458 patients were initially included in the study. Of the 376 who completed phase I, 303 (66%) were responders; 284 entered the prophylactic study, randomly assigned to two groups. Of the 134 patients in the placebo group who completed phase II, 25 (18.7%) suffered a relapse, compared with nine out of the 136 (6.6%) in the amineptine group. After resolution of an acute episode of major depression or dysthymia, long-term antidepressant therapy with amineptine significantly reduced the relapse rate.

Fava's Anger Attacks Questionnaire: evaluation of the French version in depressed patients.

The prevalence, symptomatology and correlates of anger attacks were studied in 103 depressed French patients, using a French version of the Anger Attacks Questionnaire. The prevalence of anger attacks during the previous month was 46.7%, and the most frequently reported symptoms were feeling of panic (85.1%), tachycardia (83.7%), and feeling out of control (81.3%). The occurrence of anger attacks was significantly associated with intensity of loss of control, and history of panic attacks. There was no significant association with age, gender, severity of depression or anxiety, history of suicidal attempts or mood disorder. Three weeks of treatment with serotoninergic antidepressants induced a significant decrease in anger attack prevalence.

[Ultrasensitive TSH and thyroliberin test in patients hospitalized for depression]. / Etude des valeurs de la TSH ultrasensible et due test à la thyrolibérine chez les sujets hospitalisés pour dépression.

In this prospective study of 35 patients hospitalized for depression, TSH levels were measured before and after stimulation by TRH. The type of depression was determined and its intensity was evaluated by means of the HARD scale. Subjects with systemic disease or receiving treatments known as being likely to influence TSH levels had been excluded. In none of these 35 patients was the TSH level below the lower limit of normal values, nor was there any blunting of response to TRH. These results suggest that depression is not a cause of TSH fall and that a low TSH level with normal hormonaemia must call for scintiscanning, even in depressed subjects.

[Classification and psychiatric practice]. / Classifications et pratique psychiatrique.

The DSM IV/CIM 10 classifications constitute an important effort to organize some aspects of psychiatric field. It represents a specific model--categorical, descriptive, discontinuous--aiming at identifying and classifying the mental disorders. The needs of daily psychiatric practice imply that the clinician should use new frames and models in which the dynamical, interactive, continuous component prevails.

[Neurotic inhibition and transnosographic approach. Apropos of a multicenter study of carpipramine]. / Inhibition névrotique et approche transnosographique. A propos d'une étude multicentrique de la carpipramine.

We have performed a national multicentric atrial in psychiatry, collecting 546 patients with neurotic inhibition. The efficacy of carpipramine was evaluated in this disease. A transnosographic and epidemiologic analysis of this syndrome was realized on this group of out patients. The statistical study by a factorial analysis of correspondences shows the epidemiological and symptomatic characteristics of inhibition. The endpoints were DSM-III criteria of chronic anxiety, adaptation disorders and functional sexual disorders on the first axis and different types of personality on the second axis.

[Sulpiride: study of 669 patient presenting with pain of psychological origin]. / Sulpiride: étude chez 669 patients présentant un trouble douloureux d'origine psychologique.

Among somatoform disorders, pain disorder (DSM IV) appears to be relatively common in general practice and to cause social, psychological, and functional impairment. A previous study conducted by Lemoine (1997) has shown that sulpiride is more effective than placebo in reducing intensity and frequency of pain in this disorder. The aim of our study was to assess safety and efficacy of sulpiride in a large sample of patients under natural conditions of use, in general practice. In a multicenter, open clinical trial, 669 patients (mean age: 47 years +/- 12; male: 245, female: 424) fulfilling the DSM IV criteria for pain disorder (of gastrointestinal localization), were included by 321 general practitioners (GP) and treated for 6 weeks with sulpiride 150 mg/d. Investigators' evaluations were planned at D14 and D42. Furthermore a diary was given to each patient for self evaluation and intercurrent events reporting. The pain was of psychological type in 93% of cases and caused social or working disabilities in 78% of patients. At inclusion the mean score of the Hamilton Anxiety Rating Scale was 18 +/- 8, and the mean score of the depression scale HARD (Humeur, Angoisse, Ralentissement, Danger) was 14.8 +/- 6.4. During the study 7.9% of the patients had at least one adverse event, and 3% of patients were withdrawn for adverse event. Safety assessed with a specific variable (grouping together adverse events' reporting and results of CGI item 3) was good for 88% of patients. The principal criterion of efficacy was the clinician's evaluation of the intensity and frequency of abdominal pain on a four-point scale from 0 (asymptomatic) to 3 (important/continuous) from D0 to D End a decrease in pain intensity (91% of patients) and in pain frequency (89%) was observed as well as in frequency and intensity of related gastroenterological symptoms such as disturbances of bowel movements (79% and 78%), bloated symptoms (88% and 83%), nausea/vomiting (90% and 90%). A similar improvement (p < 0.001) was observed from D0 to End point on the self evaluation parameters (Visual Analogic Scales), assessing pain (mean score D0-D End: 17.1 +/- 15.9), quality of sleep (mean score D0-D End: 27.1 +/- 17.8), activity (mean score D0-D End: 24.4 +/- 18.8), and appetite (mean score D0-D End: 22.6 +/- 16.6). In conclusion these results confirm the usefulness of sulpiride in the treatment of pain disorders a symptomatology known to cause difficulties to GP's in their practice.

[Residual symptoms after a treated major depressive disorder: in practice ambulatory observatory carried out of city]. / Symptômes résiduels après traitement antidépresseur d'un épisode dépressif majeur: observatoire réalisé en pratique ambulatoire de ville.

INTRODUCTION: The main therapeutic objective for depression is remission (absence of clinical signs of the disorder and low scores on assessment scales), yet partial remission rates remain high (insufficient criteria for diagnosing the disorder while clinically and psychometrically assessable symptoms continue to linger. The presence of residual symptoms is associated with a higher relapse rate of depression, occurring up to 5 times earlier, an increased suicide rate, significant use of healthcare services and a marked social impairment. The most frequently reported symptoms are specific to depression, i.e. anxiety and irritability, depressed mood, feelings of guilt and loss of interest in activities, asthenia and difficulty falling asleep at night. Residual symptoms constitute a valid and reliable clinical marker of prognosis (especially for relapse and chronicity) and must be treated with specific therapeutic strategies. Studies on depression with residual symptoms are few and mainly focus on populations of hospitalized patients or those with a severe form of depression. Since little work has been done with regard to patients monitored on an outpatient basis, we felt it was appropriate to select a population of depressed patients from private psychiatric practice. Our main objective was to analyze the frequency of residual symptoms after 8 to 12 weeks of antidepressant treatment and to study the clinical and socio-demographic characteristics of these subjects. DESIGN: 1 790 patients who had presented with one major depressive episode per DSM IV criteria and who had been receiving antidepressant treatment for 8 to 12 weeks were included and evaluated. 463 private psychiatrists practicing in metropolitan France were randomly selected and stratified by region and sex ratio (30% female and 70% male) to obtain a sample as representative as possible of the French psychiatrist population. The following were measured and assessed: anthropometric and socio-demographic characteristics, the history of depression, a description of the last major depressive episode, a description of its management, current clinical variables, the Hamilton Depression Rating Scale (HDRS) score, the physician's assessment of residual symptoms, and a description of the patient's management on the day of the appointment. RESULTS: Following acute treatment, evaluation of depressive symptoms on the Hamilton scale showed that 549 (32%) of subjects had a score below 8; 792 patients (46.7%) had a score between 8 and 18; and 354 (20%) had a score above 18. Patients in the first group (HDRS<8) who were considered to be in remission started treatment early (chi2=18.28, DOF=4, p<0.01) for a first episode (51.3%) with a low number of initial symptoms (chi2=27.03, DOF=6, p<0.01). The evaluators found persistent depressogenic factors (chi2=15.9, DOF=2, p<0.01) and significant psychiatric co-morbidity (chi2=18.28, DOF=4, p<0.01) in subjects in partial remission (HDRS between 8 and 18). The non-responders (HDRS>18) presented a history of more depressive episodes (chi2=17.04, DOF=4, p<0.01) and a delay of more than 30 days before treatment was initiated (chi2=18.2, DOF=4, p<0.01). With regard to the nature of residual symptoms, at least 50% of subjects in partial remission were very symptomatic for depressive mood (65.4%), psychic anxiety (56.6%), and loss of interest and time away from work (49.4%). Indicators of severe depression (early morning insomnia, psychomotor retardation, agitation, hypochondriasis, weight loss and lack of awareness of the disorder) were reported less frequently, and usually not at all. Conclusion - These results illustrate three important points. First, a significant percentage (46.7%) of patients who responded to treatment subsequent to the acute period presented with residual symptoms. Second, these symptoms are included in the areas of depressed mood - psychic anxiety . Third, a delay in initiating treatment seems to have an effect on response. These results confirm the need to develop strategies to screen for these residual forms for these residual forms of depression, as well as specific methods to treat them.

[Residual symptoms after a treated major depressive disorder: a survey among private psychiatrists]. / Symptômes résiduels après traitement antidépresseur d'un épisode dépressif majeur: enquête d'opinion réalisée auprès de psychiatres à activité libérale.

UNLABELLED: Recent studies suggest that depression with residual symptoms is a frequent progressive form of this disease. It is associated with a poor prognosis that translates into an earlier and higher relapse rate, and has a significant medical and social impact. Several literature reviews emphasize that residual symptoms are under-evaluated and that their treatment should follow an incisive strategy with the goal of complete eradication of symptoms. Specific patterns have not been detected either, and the evaluation of residual symptoms remains subject to numerous biases due to the lack of a validated definition. The purpose of this study was to analyze the opinions and attitudes of psychiatrists about residual symptoms following major depressive episodes treated with antidepressants as part of their daily private practice. DESIGN: 867 psychiatrists were selected from across France to form a representative sample of the medical specialization. They were questioned with a closed-choice questionnaire on the scope of the residual depressive symptoms concept (definition, professional consensus), determining factors in their onset (factors associated with the patient, with the initial episode, with management) and their practical and therapeutic attitude towards these symptoms. RESULTS: The estimated prevalence of residual symptoms in their depressed patients was 25%. Fifty-seven percent of the physicians queried felt the concept was appropriate, but 70.3% thought that it did not have a strong professional consensus. The definitions deemed most appropriate were those involving the persistence of clinical signs (asthenia or minor cognitive impairment), whereas the use of psychometric criteria was mentioned less often. There is a clear absence of consensus concerning the diagnostic delay of residual symptoms, as 30% diagnosed them after 6 months. Responses about factors that may be predictive or affect the onset of residual symptoms (associated with the patient, the nature of the initial episode and the management) did not reflect a unified position, nor did they necessarily correspond to the data in the literature. However, while the therapeutic attitude seemed adequate (verifying treatment compliance, clinical re-evaluation, therapeutic re-adjustment), 64% of the physicians considered residual symptoms to be a therapeutic challenge. CONCLUSION: Through the wide disparity of responses, this observational study demonstrates the absence of consensus with regard to the concept of residual symptoms. While it does appear that practitioners often adopt an approach that is pragmatic yet still close to that recommended by the ANAES [Agence National d'Accréditation et d'Evaluation en Santé, French National Health Accreditation and Evaluation Agency], such an approach does not seem to be optimized for the specific treatment of these symptoms. This clinical concept remains little studied, and lacking a specific definition, appears to be under-evaluated and under-treated by conventional treatment strategies. Further research on residual symptoms is necessary in order to establish true and valid definitions that will.

[Value of hydroxyzine in generalized anxiety disorder: controlled double-blind study versus placebo]. / Intérêt de l'hydroxyzine dans le trouble anxiété généralisée: étude contrôlée en double aveugle versus placebo.

A multi-centre study was designed to evaluate the efficacy of hydroxyzine in the treatment of patients presenting a generalized anxiety disorder (GAD). One hundred and thirty three patients, suffering from a GAD (according to DSM III-R criteria with 6 months duration criteria), were enrolled in a randomised, double-blind, hydroxyzine (50 mg/day) versus placebo, over a 4-week trial period. By the end of the first week, the decrease of anxiety scores was significant for the hydroxyzine group, as compared to placebo (in respect of all rating criteria of anxiety). The statistical superiority for hydroxyzine continued to the end of the 4-weeks study period, and persisted at a further evaluation a week after abrupt discontinuation of active treatment. The tolerance evaluation showed that side effects were reported in 52% of hydroxyzine group versus 35% of placebo group. The most commun side effects were sleepiness (28% vs 14% with placebo), weight gain (12% vs 10%), dry mouth (14% vs 5%), loss of concentration (9% vs 8%) and insomnia (9% vs 6%). Sleepiness in the hydroxyzine group appeared during the first week and progressively disappeared later during treatment. We concluded that hydroxyzine at 50 mg/day produces a statistically and clinically significant anxiolytic effect, commencing during the first week of treatment and maintained throughout the 4-week period and after abrupt discontinuation without rebound of anxiety or withdrawal symptoms. The most commun side effect with hydroxyzine is transient sleepiness.

[Factorial validation of the HARD scale in 2 groups of depressive patients]. / Validation factorielle de l'échelle HARD dans deux groupes de déprimés.

A factor analysis performed in two groups of depressed patients first pointed out the validity of the total score of the scale, then pointed out four factors which are very similar to those used in the HARD diagram and clinically constructed by the authors.

[Catatonia de novo, report on a case: immediate vital prognosis and psychiatric prognosis in longer term]. / Catatonie de novo, à propos d'un cas: pronostic vital immédiat et pronostic psychiatrique à plus long terme.

We report on the case of a 20 year old woman with no previous psychiatric history, who displayed a first episode of catatonia with acute onset. Symptoms started plainly with sudden general impairment, intense asthenia, headache, abdominal pain and confusion. After 48 hours, the patient was first admitted to an emergency unit and transferred to an internal medicine ward afterwards. She kept confused. Her behaviour was bizarre with permanent swinging of pelvis, mannerism, answers off the point and increasingly poor. The general clinical examination was normal, except for the presence of a regular tachycardia (120 bpm). The paraclinical investigations also showed normal: biology, EEG, CT Scan, lumbar puncture. Confusion persisted. The patient remained stuporous, with fixed gazing and listening-like attitudes. She managed to eat and move with the help of nurses but remained bedridden. The neurological examination showed hypokinaesia, extended hypotonia, sweating, urinary incontinence, bilateral sharp reflexes with no Babinski's sign and an inexhaustible nasoorbicular reflex. The patient was mute and contrary, actively closed her eyes, but responded occasionally to simple instructions. For short moments, she suddenly engaged in inappropriate behaviors (wandering around) while connecting back to her environment answering the telephone and talking to her parents. The patient's temperature rose twice in the first days but with no specific etiology found. During the first 8 days of hospitalization, an antipsychotic treatment was administered: haloperidol 10 mg per os daily and cyamemazine 37.5 mg i.m. daily. Despite these medications, the patient worsened and was transferred to our psychiatric unit in order to manage this catatonic picture with rapid onset for which no organic etiology was found. On admission, the patient was stuporous, immobile, unresponsive to any instruction, with catalepsy, maintenance of postures, severe negativism and refusal to eat. A first treatment by benzodiazepine (clorazepate 20 mg i.v.) did not lead to any improvement. The organic investigations were completed with cerebral MRI and the ruling out of a Wilson's disease. Convulsive therapy was then decided. It proved dramatically effective from the first attempt; 4 shocks were carried out before the patient's relatives ask for her discharge from hospital. The patient revealed she had experienced low delirium during her catatonic state. The clinical picture that followed showed retardation with anxiety. She was scared with fear both for the other patients and the nursing team. She kept distant and expressed few affects. The treatment at the time of discharge was olanzapine 10 mg per os. She was discharged with a diagnosis of catatonia but with no specific psychiatric etiological diagnosis associated. She discontinued her follow-up a few weeks later. After one year, we had no information about her. Catatonia has now become rare but remains a problem for clinicians. We reviewed data concerning short term vital prognosis and psychiatric long term prognosis in catatonia. Lethal catatonia is associated with acute onset, both marked psychomotor and neurovegetative symptoms. In the light of literature, there is no proband clinical criterion during the episode that is of relevant diagnostic value to ascertain the psychiatric etiology.

[Validation of HARD (Hamilton depression rating scale) a diagram of the evaluation of depression by MADRS (Montgomery-Asberg depression rating scale) Multicentric study of mianserin]. / Validation du HARD, diagramme d'évaluation de la dépression par la MADRS. A propos d'une étude multicentrique de la miansérine.

A national multicentric trial has included 402 depressed patients (DSM III Criteria) and has validated diagram HARD by MADRS. A constant and similar decrease in the total of the two rating scales has been shown at several times of assessment, Day 0, 10, 20, 60, and 90. High coefficents of correlation are found between HARD and MADRS. The sensitivity to change under treatment (mianserin 60 mg) is equal for the two rating scales.