Correlated optical and electrical analyses of inhomogeneous core/shell InGaN/GaN nanowire light emitting diodes.

The performance of core-shell InGaN/GaN nanowire (NW) light emitting diodes (LEDs) can be limited by wire-to-wire electrical inhomogeneities. Here we investigate an array of core-shell InGaN/GaN NWs which are morphologically identical, but present electrical dissimilarities in order to understand how the nanoscale phenomena observed in individual NWs affect the working performance of the whole array. The LED shows a low number of NWs (∼20%) producing electroluminescence under operating conditions. This is related to a presence of a potential barrier at the interface between the NW core and the radially grown n-doped layer, which differently affects the electrical properties of the NWs although they are morphologically identical. The impact of the potential barrier on the performance of the NW array is investigated by correlating multi-scanning techniques, namely electron beam induced current microscopy, electroluminescence mapping and cathodoluminescence analysis. It is found that the main cause of inhomogeneity in the array is related to a non-optimized charge injection into the active region, which can be overcome by changing the contact architecture so that the electrons become injected directly in the n-doped underlayer. The LED with so-called 'front-n-contacting' is developed leading to an increase of the yield of emitting NWs from 20% to 65%.

[Do initial experience with an enhanced recovery program after surgery (ERAS) improve postoperative outcomes after cystectomy?] / L'application d'un programme de réhabilitation précoce (ERAS) améliore-t-elle les résultats périopératoires après cystectomie ?

OBJECTIVE: To estimate the feasibility and the impact of an ERAS program after radical cystectomy for bladder cancer. MATERIALS AND METHODS: This was a retrospective study comparing a historical pre ERAS group, including all the patients undergoing cystectomy for bladder cancer from January 2013 to December 2015 with a classic procedure, and an interventional ERAS group after introducing an enhanced recovery protocol before, during and after surgery, from February 2016. The principal outcome was the postoperative length of stay. Secondary outcomes mesures were impact on perioperative complication rate (Clavien classification≥3B), readmission rate, reanimation length of stay, ileus rate and adherence to the ERAS protocol. RESULTS: There were no differences between the 2 groups as far as demographics characteristics are concerned. In total, 97 patients were included, 56 in the control group, and 41 in the ERAS group. The adherence to the protocol was about 65.8%. The ERAS group had statistically significantly shorter median length of stay (D19 versus D14; P: 0.021). The major complications rate (Clavien≥3B) were about 23.2% for the control group and 12.1% for the ERAS group (P: NS). The reinsertion of nasogastric tube were higher in the control group (39.3% vs 21.9%; P: NS) and the readmission rate was about 7.1% in the control group versus 14.6% in the ERAS group (P: NS). CONCLUSION: In conclusion, introduction and application of an enhanced recovery protocol (ERAS) after cystectomy for bladder cancer allowed for better management of postoperative outcomes. It is clearly feasible in cystectomy, and improve significantly the median postoperative length of stay. Moreover, it may be effective in terms of faster return of bowel function and reduction of majors complications. LEVEL OF EVIDENCE: 4.

[ADH/D and impulsiveness: Prevalence of impulse control disorders and other comorbidities, in 81 adults with attention deficit/hyperactivity disorder (ADH/D)]. / L'impulsivité dans le TDAH: prévalence des troubles du contrôle des impulsions et autres comorbidités, chez 81 adultes présentant un trouble déficit de l'attention/hyperactivité (TDA/H).

UNLABELLED: Attention deficit hyperactivity disorder (ADH/D) is a neuropsychological developmental disorder characterized by pervasive and impairing symptoms of inattention, hyperactivity, and impulsivity. Whereas it is well known in children, there is still little information about ADH/D in adults, including prevalence. Indeed, there are actually no epidemiological studies in France, despite the considerable impact of this disorder in a patient's professional and affective life. Moreover, ADH/D rarely stays isolated, and many comorbidities often complicate the diagnostic investigation. It is well known that the so-called ADH/D is composed of two main categories of symptoms (Attentional Disorder/Hyperactiviy Disorder), but Impulsiveness also remains a major symptom. OBJECTIVE: The aim of this study was to evaluate not only the prevalence of Impulse Control Disorders (ICD) but also psychological and addictive comorbidities among adult patients with ADH/D. A total of 100 patients from specialized consultations of adult ADH/D were evaluated in this study, but only 81 were included after presenting all the clinical criteria of ADH/D. METHOD: We used the DSM IV-T-R for ADH/D, the Minnesota Impulsive Disorders Interview a semi-structured clinical interview assessing impulse control disorders (ICD) (compulsive buying, trichotillomania, compulsive sexual behaviour, kleptomania, pyromania and intermittent explosive disorder), and the Mini International Neuropsychiatric Interview in order to evaluate psychiatric and addictive comorbidities. RESULTS: More than 90 % of the patients met the early apparition criteria of ADH/D (before 7years). More than half of the patients presented a mixed type of ADH/D (both inattentive and hyperactive-impulsive forms): 55.6 % vs 44.4 % for the inattentive type. The vast majority of patients showed a complete form (with a total of 6 or more symptoms out of 9, of inattentive and/or impulsive-hyperactivity category): 93.8 % and only 6.2 % presented a sub-syndromic form of ADH/D (with 3 symptoms at least of one and/or the other category). Regarding the ICDs, we found a proportion of 66 % of patients manifesting at least one, the most frequent ICD being the Intermittent Explosive Disorder (IED): 29.6 %, followed by Compulsive Buying (CB): 23.4 %, Pathological Gambling (PG): 7.4 %, Kleptomania and Compulsive Sexual Behaviour: 2.4 %, and Trichotillomania: 1.2 %. Among the psychiatric comorbidities evaluated, generalized anxiety disorder: 61.7 %, followed by dysthymia: 44.4 %, major depressive episode: 28.3 %, Agoraphobia: 22.2 %, panic disorder: 17.2 %, hypomanic episode: 16 %, social phobia: 11.1 %, bulimia nervosa: 8.6 %, and antisocial personality disorder and obsessive-compulsive disorder: 3.7 %. Regarding the addictive comorbidities, we found a prevalence of 14.8 % of substance abuse (non-alcohol), followed by 7.4 % of alcohol abuse, 6.1 % of substance dependence (non-alcohol), and 3.7 % of alcohol dependence. CONCLUSION: ADH/D in adults continues to be unrecognized in France. The aim of this study was to evaluate the prevalence of impulse control disorders, psychiatric and addictive comorbidities in adults with ADH/D. The results enable us to appreciate quantitative and qualitative data for 81 French adults with ADH/D. This disorder rarely remains isolated and is often associated with many others, especially anxiety and mood disorders. We also observed that impulsivity stays at the heart of the ADH/D, either through impulsive behaviours or addictive disorders. Considering the lack of studies with ADH/D adults, it is difficult to compare our data. The diagnosis of ADH/D is complex and stays controversial, moreover the strong prevalence of comorbidities points out the importance of differential diagnosis.

Daclizumab Versus Rabbit Antithymocyte Globulin in High-Risk Renal Transplants: Five-Year Follow-up of a Randomized Study.

We previously reported a randomized controlled trial in which 227 de novo deceased-donor kidney transplant recipients were randomized to rabbit antithymocyte (rATG, Thymoglobulin) or daclizumab if they were considered to be at high immunological risk, defined as high panel reactive antibodies (PRA), loss of a first kidney graft through rejection within 2 years of transplantation, or third or fourth transplantation. Patients treated with rATG had lower incidences of biopsy-proven acute rejection (BPAR) and steroid-resistant rejection at 1 year. Patients were followed to 5 years posttransplant in an observational study; findings are described here. Treatment with rATG was associated with a lower rate of BPAR at 5 years (14.2% vs. 26.0% with daclizumab; p = 0.035). Only one rATG-treated patient (0.9%) and one daclizumab-treated patient (1.0%) developed BPAR after 1 year. Five-year graft and patient survival rates, and renal function, were similar between the two groups. Overall graft survival at 5 years was significantly higher in patients without BPAR (81.0% vs. 54.8%; p < 0.001). In conclusion, rATG is superior to daclizumab for the prevention of BPAR among high-immunological-risk renal transplant recipients. Overall graft survival at 5 years was approximately 70% with either induction therapy, which compares favorably to low-risk cohorts.

Experimental and theoretical analysis of transport properties of core-shell wire light emitting diodes probed by electron beam induced current microscopy.

We report a systematic experimental and theoretical investigation of core-shell InGaN/GaN single wire light-emitting diodes (LEDs) using electron beam induced current (EBIC) microscopy. The wires were grown by catalyst-free MOVPE and processed into single wire LEDs using electron beam lithography on dispersed wires. The influence of the acceleration voltage and of the applied bias on the EBIC maps was investigated. We show that the EBIC maps provide information both on the minority carrier effects (i.e. on the local p-n junction collection efficiency) and on the majority carrier effects (i.e. the transport efficiency from the excited region toward the contacts). Because of a finite core and shell resistance a non-negligible current redistribution into the p-n junction takes place during the majority carrier transport. A theoretical model for transport in a core-shell wire is developed, allowing to explain the dependence of the EBIC profiles on the experimental parameters (the electron beam acceleration voltage and the bias applied on the device) and on the structural parameters of the wire (core and shell resistance, shunt resistance, etc). Comparison between simulated and experimental profiles provides valuable information concerning the structure inhomogeneities and gives insight into the wire electrical parameters.

[Evaluation of functional remission in schizophrenic disorder. The FROGS Scale]. / Évaluation de la rémission fonctionnelle dans le trouble schizophrénique: l'échelle FROGS.

INTRODUCTION: Functional remission is an important treatment goal in schizophrenia, as independent living and reintegration of patients into the community is the ultimate goal of any treatment. Nevertheless, assessing functional remission in schizophrenia is problematic, as it is a multifactorial entity reflecting various aspects such as symptoms severity, personal skills and sociocultural expectancies. METHOD: The purpose of this study was to create and validate a novel scale for the evaluation of functional remission in schizophrenia. Unlike previous scales, this one was built on the basis of patients with few schizophrenia symptoms. The "Functional Remission of General Schizophrenia" (FROGS) scale was developed using the expert consensus method following a MEDLINE and standard database search. Out of the 61 initially proposed, 19 items were selected as gathering the core aspects of functional remission in schizophrenia detected in the literature. The FROGS was then evaluated in 432 patients with DSM-IV criteria of schizophrenia, all of them meeting Andreasen's symptomatic remission criteria. Such an instrument should have a stable structure over time but also be able to detect improvement in functioning with time. So we have further analysed the validity of the FROGS scale, specifically assessing time stability. We re-evaluated the initial patient sample around 1.5 years after the first evaluation (mean=17.1 months ± 1.9), restricting the analyses to patients who were still being followed-up and in clinical remission (n=140). RESULTS: Total score was highly reliable. Exploratory factor analysis after oblique rotation revealed that a three-factor solution was the most meaningful. On the basis of item content these three factors were labelled 'Social Functioning', 'Daily Life' and 'Treatment'. The FROGS total score can be used to measure a general construct for the evaluation of functional remission in schizophrenia. The mean FROGS total score was 75.8 (sd=10.8) at the second evaluation showing a significant improvement with time (3.8; P<0.0001 versus the first evaluation). The internal consistency/reliability of the FROGS scale was still very high (Cronbach's α=0.919). Significant improvement between the first and second evaluation were also apparent for all the individual items in the FROGS scale (P<0.01) as well as for the subscores for three extracted factors (P<0.0001). Statistically significant correlations were observed between the FROGS scale and other indices, including the Global Assessment of functioning (r=0.58; P<0.0001). These results provide further evidence of the solid psychometric properties of the FROGS scale. DISCUSSION/CONCLUSION: The results of these two validation studies provide further evidence of the scale's utility and its solid psychometric properties. Furthermore, it is sensitive to the duration of clinical remission. Our scale may be a step towards developing a consensual definition of functional remission in schizophrenia.

[Pharmacological management of anxiety in patients suffering from schizophrenia]. / Prise en charge médicamenteuse de l'anxiété chez le patient souffrant de schizophrénie.

INTRODUCTION: Anxiety is a major and frequent symptom of schizophrenia, which is associated with an increased risk of relapse, impaired functioning, lower quality of life and increased incidence of suicide attempts. Despite its clinical relevance, anxiety in schizophrenia remains poorly understood. In the prodromic phase, anxiety indicates a progression towards psychotic decompensation. After a first episode, it is an indicator of relapse. LITERATURE FINDINGS: Two approaches have been used to investigate anxiety in schizophrenia: (i) categorical approach (comorbidity of schizophrenia and anxiety disorders) and (ii) dimensional approach (anxiety as a major symptom of the "dysphoric" dimension). Clinical categorical studies reported an increased frequency of comorbidity between schizophrenia and obsessive-compulsive disorder, panic disorder, social phobia, post-traumatic stress disorder, generalized anxiety disorder, agoraphobia, and specific phobia. The dimensional approach proposes that five different factors contribute to the structure of the Positive and Negative Syndrome Scale (PANSS), with anxiety as a major symptom of the "dysphoria" dimension. Concerning diagnosis, it is unclear whether psychotic and neurotic anxiety differs in nature or intensity. Nevertheless, both are frequently opposed. DISCUSSION: Psychotic anxiety is intense, profound and hermetic. In contrast to neurotic anxiety, it is associated with psychomotor disturbances, such as agitation and sideration. There is no specific tool to evaluate anxiety in schizophrenia. The dimensional approach usually runs an evaluation using items or factors extracted from the most widely-used scales, i.e. PANSS or Brief Psychiatric Rating Scale (BPRS) or from anxiety scales developed in non-schizophrenic populations, such as the Hamilton Anxiety Scale (HAMA). Recently, we developed a specific scale for hetero-evaluation (Échelle Anxiété Schizophrénie [EAS scale]). The EAS scale was recently validated and the study of its sensitivity is ongoing. THERAPEUTICAL ISSUES: Several studies have examined the effects of antipsychotics on the anxious/depressive cluster extracted from the PANSS, and some other studies have specifically evaluated the effect of antipsychotics on depressive symptoms using the Montgomery and Asberg Depression Rating Scale (MADRS) and Calgary Depression Scale for Schizophrenia (CDSS), but to our knowledge, no study has reported the effect of antipsychotics or other treatment on anxiety when using a schizophrenia-specific scale. There are no specific guideline treatments for anxiety in schizophrenia. Among phenothiazines, cyamemazine is frequently prescribed in France, because of its potent anxiolytic activity and good neurological tolerance. Some authors have suggested a specific treatment with benzodiazepines. However, benzodiazepines should be used with caution, due to undesirable actions such as dependence, rebound and potentiation of certain lateral effects.

Evidence for humoral rejection of a pancreatic islet graft and rescue with rituximab and IV immunoglobulin therapy.

We describe the decline in islet function, in relation to HLA sensitization, in an islet transplant recipient and the recovery of this function after treatment with anti-CD20 monoclonal antibody and IV immunoglobulins. A 51-year-old woman with type 1 diabetes received one intraportal islet infusion. Following this transplantation, she became insulin independent. A search for HLA antibodies by using an ELISA technique remained consistently negative for HLA class I and II. It was only 2 years after the islet transplantation that this search became positive against class II antigens, reaching a peak of reactivity concomitantly with the appearance of a deterioration of glucose control requiring low-dose insulin therapy. Luminex screening and single-antigen assays then revealed the presence of both nondonor-specific and donor-specific antibodies against HLA class II molecules. This immunization, already present in the pretransplant serum, had increased during the 6 months preceding the clinical deterioration. Since these data nevertheless pointed to antibody-mediated rejection of the islet allograft, treatment with anti-CD20 monoclonal antibody and IV immunoglobulins was initiated. One month later, the search by ELISA for antibodies against HLA class II antigens became negative, the Luminex tests normalizing more gradually. As the result of an improvement in glucose control, the patient was again insulin-free.

Quality of life after islet transplantation: data from the GRAGIL 1 and 2 trials.

BACKGROUND: Rigorous assessment of health-related quality of life (HRQL) is mandatory to establish the benefits of islet transplantation. METHODS: The 36-Item Short Form Health Survey (SF-36) and the Diabetes Quality of Life (DQOL) scales were completed by patients included in an Islet Transplantation Alone (ITA) trial (n = 10) and an Islet After Kidney (IAK) trial (n = 10). RESULTS: The two populations differed by HRQL scores at baseline, with poorer scores in ITA patients. SF-36 scores for physical limitations, bodily pain, general health perception, social functioning, and health transition improved significantly in ITA patients 6 and 12 months post transplantation. The DQOL global score was significantly improved at 6 months and remained so at 12 months, because of a significant improvement in the dimensions of satisfaction and impact of diabetes. No improvement was observed in the IAK patients. CONCLUSION: HRQL assessment may help in the selection of candidates with brittle diabetes for islet transplantation.

Evaluation of intrarenal oxygenation by blood oxygen level-dependent magnetic resonance imaging in living kidney donors and their recipients: preliminary results.

OBJECTIVE: Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) is a noninvasive tool to measure modifications in tissue oxygen content. Lower deoxyhemoglobin concentrations due to increased tissue oxygenation induce a longer transverse relaxation time (T2*), thus a stronger MRI signal. We have studied the changes in the kidney oxygenation profiles of living donors and their recipients by BOLD-MRI associated with transplantation and nephrectomy. MATERIALS AND METHODS: Two donor/recipient couples were selected for this preliminary study. BOLD-MRI was performed on the donor on the day prior to surgery, on day 4, and 1 month thereafter, and on the recipient on day 4 and 1 month postsurgery. Mean T2* values were measured in specific target regions in the cortical and medullary regions of each kidney using the T2StarMappingTool (Philips, Eindhoven, Netherlands). Modifications of tissue oxygen profiles were then compared considering the proportionality between T2* values and tissue oxygen content. RESULTS: The clinical courses posttransplantation were uneventful throughout the study; kidney function resumed rapidly. All MRI examinations showed a significantly higher T2* level in the cortex than in the medulla, confirming the notion that the medulla is hypoxic compared to the cortex. Nephrectomy and transplantation induced a significant rise in cortical T2* values in the remnant and transplanted kidney at day 4 and 1 month. Medullary T2* level only increased in the transplanted kidney. CONCLUSIONS: Profound modifications in renal oxygenation intervene following transplantation and nephrectomy. BOLD-MRI may be a useful tool to explore these modifications and possibly identify pathological patterns.

Proposed diagnostic criteria for apathy in Alzheimer's disease and other neuropsychiatric disorders.

There is wide acknowledgement that apathy is an important behavioural syndrome in Alzheimer's disease and in various neuropsychiatric disorders. In light of recent research and the renewed interest in the correlates and impacts of apathy, and in its treatments, it is important to develop criteria for apathy that will be widely accepted, have clear operational steps, and that will be easily applied in practice and research settings. Meeting these needs is the focus of the task force work reported here. The task force includes members of the Association Française de Psychiatrie Biologique, the European Psychiatric Association, the European Alzheimer's Disease Consortium and experts from Europe, Australia and North America. An advanced draft was discussed at the consensus meeting (during the EPA conference in April 7th 2008) and a final agreement reached concerning operational definitions and hierarchy of the criteria. Apathy is defined as a disorder of motivation that persists over time and should meet the following requirements. Firstly, the core feature of apathy, diminished motivation, must be present for at least four weeks; secondly two of the three dimensions of apathy (reduced goal-directed behaviour, goal-directed cognitive activity, and emotions) must also be present; thirdly there should be identifiable functional impairments attributable to the apathy. Finally, exclusion criteria are specified to exclude symptoms and states that mimic apathy.

[Psychiatric assessment]. / Evaluation psychiatrique.

Psychiatric disorders and behavioral disturbances may complicate the postsurgical outcome in patients and de novo psychiatric symptoms have been reported. In numerous, but not all epilepsy surgical centers, a psychiatric assessment is included as part of the presurgical evaluation of potential candidates for surgery. Affective disorders and psychosis are the most frequently reported postsurgical psychiatric disorders. There are no absolute psychiatric contraindications to surgery. Specific preexisting psychiatric conditions may need cautious consideration because there may be a risk of postsurgical psychiatric complications. Routine pre- and postsurgical psychiatric evaluations in patients undergoing epilepsy surgery are urgently needed. Clinicians involved in the care of surgical candidates should be aware of the possible psychiatric complications following surgery.

Validation of a four items version of the Functional Remission of General Schizophrenia scale (the mini-FROGS) to capture the functional benefits of clinical remission.

OBJECTIVES: We previously developed the Functional Remission Of General Schizophrenia (FROGS) scale demonstrating first, reliable assessment in a cross-sectional study and second, good time-stability. The purpose of the present analysis was to propose a shorter version (mini-FROGS), more compatible with the limited time available in a psychiatric visit, focusing on the functional domains that have higher likelihood of being improved with higher and/or longer symptomatic remission in different cultural backgrounds. METHODS: We used multiple regressions to find the most informative items explaining increased length of symptomatic remission, using prospective data from a national observational multicenter survey. Then, the mini-FROGS was used in different European countries to test its between-center reliability, compared to other scales. RESULTS: Four domains were retained as capturing the maximum of symptomatic remission, namely (1) travel and communication, (2) management of illness and treatment, (3) self-esteem and sense of independence and (4) respect of biological rhythms. First, the mini-FROG was evaluated in 443 French patients with clinical remission and 22 without, and 12/18 months later in 140 patients still in clinical remission and 23 in relapse. In Europe, 295 schizophrenia patients were assessed with the mini-FROGS and other scales devoted to functional remission, allowing comparisons. The mini-FROGS showed good correlations with other scales in different countries and demonstrated good psychometric properties. CONCLUSION: These results give evidence that a 4 items-only version of the FROGS scale may be useful to assess important aspects of functional remission, tightly linked to the length of clinical remission.

[Intermittent explosive disorder: current status]. / Trouble explosif intermittent: situation actuelle.

BACKGROUND: Intermittent Explosive Disorder (IED) is a recently reported mental disorder. It was introduced in the edition of the Diagnostic and Statistical Manual of mental disorders. Since then, the clinical criteria have developed, but some ambiguity has remained. LITERATURE FINDINGS: In fact, the utility of excluding this diagnosis in the presence of some personality disorders (antisocial and borderline personalities) is being discussed. On the one hand, the recurrence of violent behaviour is not always found among these personalities and, on the other, to accept both diagnoses of personality disorder and IED would permit one to distinguish a subgroup of patients to whom it would be possible to offer appropriate treatment. However, some criteria could be introduced among those needed for the diagnosis. These criteria include signs of tension, immediately preceding the assaults, as well as signs of release, or even pleasure, after performing the act. These symptoms are frequently reported by IED patients and they are still found in the diagnosis criteria of other impulse control disorders. IED starts during adolescence and it is more frequent among boys. Due to the criteria restrictions, its prevalence is considered as low. However, violent behaviour and impulsivity among psychiatric patients are frequent. The comorbidity of IED has been studied without taking these restrictions into account. A high level of comorbidity is noted with mood disorder. Some reports agree with the hypothesis of a disorder included in the spectrum of a mood disorder. The other psychiatric disorders, frequently associated with IED, are cluster B personality disorders and anxious disorders. There are few studies on the etiopathogeny of IED. However, some results warrant more attention. They concern the deregulation of the serotoninergic system and mild brain injuries. The etiopathogenic hypotheses have influenced the choice of the drugs offered to IED patients, which are mainly selective serotonin reuptake inhibitors, mood stabilisers, and beta-blockers. The efficacy of these treatments was determined essentially by case reports. Some controlled trials are needed to confirm the utility of these molecules in this disorder. In spite of the frequency and the seriousness of violent impulsive behaviour, it is still studied much less than mood or anxious symptoms. CONCLUSION: We believe that IED diagnosis permits the categorization of such violent behaviour in many psychiatric pathologies. The evolution of IED diagnostic criteria should permit psychiatrists to recognise and handle recognition and management of violent behaviour better.

Tolerability of enteric-coated mycophenolate sodium to 1 year in combination with cyclosporine and corticosteroids in renal transplant recipients.

Enteric-coated mycophenolate sodium (EC-MPS) is therapeutically equivalent to mycophenolate mofetil, but delays release of mycophenolic acid until it reaches the small intestine. De novo renal transplant patients taking part in a 12-month, multicenter, randomized study received cyclosporine microemulsion (CsA-ME, early or delayed to day 6), EC-MPS, steroids, and interleukin-2 antagonist induction. Tolerability data relating to EC-MPS are reported. Ninety-seven patients were randomized to early CsA-ME and 100 patients to delayed CsA-ME. Median daily dose of EC-MPS was 1440 mg at all time points throughout the 12-month period. The most frequently reported adverse events were constipation, anemia, urinary tract infection, abdominal pain, leukopenia, and cytomegalovirus infection; there were four malignancies. Fifty patients (24.6%) discontinued EC-MPS prematurely by 12 months, including 42 patients (84%) who discontinued owing to adverse events. No patient discontinued treatment because of gastrointestinal adverse events. Two-thirds of patients (137 [67.5%]) maintained full EC-MPS dose throughout the 12-month study and did not require any dose reduction or dose interruption. EC-MPS is well tolerated in de novo renal transplant recipients when administered in combination with CsA-ME and steroids, with low rates of dose reductions or interruptions. Gastrointestinal adverse events were responsible for dose reduction or interruption in only 5% of patients.

[Benzodiazepines and schizophrenia, a review of the literature]. / Benzodiazépines et schizophrénie, revue de la littérature.

AIn this work, the authors have analysed the principal studies on the interest in the use of benzodiazepines in schizophrenia. The first double-controlled study concerning this question was conducted in 1961. The results of the first studies are criticisable due to the variability of the diagnostic and clinical assessment criteria, as well as to the divergences between the different conclusions. Through this review of literature, the authors wish to clarify the questions and hypothesis raised specify certain therapeutic strategies. MECHANISM OF GABA-ERGIC TREATMENTS: The analysis of the principle works on this question provides evidence on the use of benzodiazepines in schizophrenia. By fixing on their receptors, benzodiazepines facilitate GABA-ergic transmission. GABA is an inhibitor neurotransmitter. The GABA stimulation induced by benzodiazepines may be at the origin of a reduction of the pre-synaptic release of dopamine in the mesolimbic region. The GABA stimulation may also delay the post-synaptic adaptation of the dopaminergic neurons to neuroleptics. This phenomenon may enhance the activity of neuroleptics in resistant schizophrenia. Benzodiazepines would also have an effect on the mesoprefrontocortical regions where neuroleptics may be less efficient. It is interesting to note that this cerebral region is particularly sensitive to stress. This effect of benzodiazepines on the mesoprefrontocortical region might explain a preferentially beneficial effect in patients who have radiographic signs consistent with prefroncortical atrophy, although this observation remains preliminary. BENZODIAZEPINES IN MONOTHERAPY: In monotherapy their action on productive and deficient psychotic symptoms is greatly discussed and not very convincing. The main studies in the use of benzodiazepines alone ) are heterogeneous for their diagnosis criteria, their methodology and their results. The conclusions of the publications are not totally clear, and different points are to be criticized: heterogeneity of assessment criteria, heterogeneity and variability of methodology, use of non standardized scales, most of the studies are open studies, variability of benzodiazepines dose. BENZODIAZEPINES IN ASSOCIATION WITH NEUROLEPTICS: In few controlled studies, most authors have underlined ) the advantage of the association of benzodiazepines with neuroleptics. This association may act either on positive symptoms (hallucinations, delusions) or on negative symptoms. The latent period and the length of the effect of benzodiazepines in the treatment of psychotic patients remain unclear. According to certain studies, the therapeutic effect may appear in a short time, and then disappear within the fourth week. The association of benzodiazepines with neuroleptics is particularly helpful for patients with great anxiety, whether they have neuroleptic intolerance or not. There is no robust convergence about the type of benzodiazepines and their optimal dose in the treatment of schizophrenia. Their use may permit a reduction in the neuroleptic dose. They could increase the plasma concentration of neuroleptics and they might act on the mesoprefrontocortical regions where there are fewer dopaminergic auto receptors. BENZODIAZEPINES AND ANXIETY IN SCHIZOPHRENIA: States of anxiety, and in particular panic disorders that would participate in the exacerbation of psychotic symptoms, would benefit from the use of benzodiazepines. Anxiety can be considered as a major symptom of schizophrenia: insecure feelings and impressions of threatening events are frequent during schizophrenia. Interpretations or brutal hallucinations can lead to the feeling of imminent catastrophe or anxiety. Nevertheless, anxious phenomenons are under-estimated for many reasons: on the one hand, positive symptoms may hide anxiety, and on the other, the symptoms that are observed in patients treated with neuroleptics are often attributed to the neuroleptic side effects rather than linked to anxiety. Benzodiazepines and catatonia - Lorazepam has demonstrated its efficacy on catatonia. This effect seems to be specific of small doses of lorazepam (<5 mg/day). It should be compared to the effect of zolpidem in the same conditions. This prescription should be limited to acute catatonia, with no effect on chronic catatonia. Benzodiazepines and neuroleptic side effects - The use of benzodiazepines to treat some side effects of neuroleptics such as akathesia is reported by certain authors but remains little explained. They may have no effect or only small effects on tardive dyskinesia, but could reduce their incidence with the use of the smallest doses of neuroleptics in association with benzodiazepines. Safety of use - The safety of use of benzodiazepines in schizophrenia, particularly in association with neuroleptics is admitted, however recommended precautions with clozapine are to be noted. Benzodiazepine combined with clozapine clearly increases the frequency of cardiovascular and respiratory accidents. Some studies point out the risk of behavioural desinhibition and dysphoria. Their use should also be limited to patients with good compliancy, in order to avoid exacerbation of symptoms in the case of brutal interruption of the treatment. Dependency, which is an important issue in the use of benzodiazepines, seems much lesser in schizophrenia than in personality disorders and anxiety. Conversely, some studies point out the benefits of benzodiazepine use in schizophrenia, with their efficacy in the treatment and prevention of drug abuse. Finally, benzodiazepines contribute to the establishment of a good patient-doctor relationship, and may guarantee enhanced treatment compliancy.

A positron emission tomography (PET) study of cerebral dopamine D2 and serotonine 5-HT2A receptor occupancy in patients treated with cyamemazine (Tercian).

RATIONALE: Cyamemazine (Tercian) is an antipsychotic drug with anxiolytic properties. Recently, an in vitro study showed that cyamemazine possesses high affinity for serotonin 5-HT(2A) receptors, which was fourfold higher than its affinity for dopamine D(2) receptors (Hameg et al. 2003). OBJECTIVES: The aim of this study is to confirm these previous data in vivo in patients treated with clinically relevant doses of Tercian. METHODS: Eight patients received 37.5, 75, 150 or 300 mg/day of Tercian depending on their symptomatology. Dopamine D(2) and serotonin 5-HT(2A) receptor occupancies (RO) were assessed at steady-state plasma levels of cyamemazine with positron emission tomography (PET), using [(11)C]raclopride and [(11)C]N-methyl-spiperone, respectively. The effective plasma level of the drug leading to 50% of receptor occupancy was estimated by fitting RO with plasma levels of cyamemazine at the time of the PET scan. RESULTS: Cyamemazine induced near saturation of 5-HT(2A) receptors (RO=62.1-98.2%) in the frontal cortex even at low plasma levels of the drug. On the contrary, occupancy of striatal D(2) receptors increased with plasma levels, and no saturation was obtained even at high plasma levels (RO=25.2-74.9%). The effective plasma level of cyamemazine leading to 50% of D(2) receptor occupancy was fourfold higher than that for 5-HT(2A) receptors. Accordingly, individual 5-HT(2A)/D(2) RO ratios ranged from 1.26 to 2.68. No patients presented relevant increased prolactin levels, and only mild extrapyramidal side effects were noticed on Simpson and Angus Scale. CONCLUSION: This in vivo binding study conducted in patients confirms previous in vitro findings indicating that cyamemazine has a higher affinity for serotonin 5-HT(2A) receptors compared to dopamine D(2) receptors. In the dose range 37.5-300 mg, levels of dopamine D(2) occupancy remained below the level for motor side effects observed with typical antipsychotics and is likely to explain the low propensity of the drug to induce extrapyramidal side effects.

Profiles and prognostic values of LDH isoenzymes in patients with non-Hodgkin's lymphoma.

Serum lactic dehydrogenase (LDH) is an important prognostic factor in patients with non-Hodgkin's lymphoma (NHL). We have examined the LDH isoenzyme content in serum and CSF of patients with NHL, at diagnosis and at relapse. In patients with increased serum LDH at diagnosis, the percentage of isoenzyme 2 was increased in 52% of patients and the absolute value of isoenzyme 3 was increased in 64% of patients. In relapsing patients these values were respectively 69% and 65%. Conversely in patients with increased serum LDH due to myeloid regeneration after chemotherapy, isoenzymes 4 and 5, but not isoenzymes 2 or 3, were increased. High absolute values of isoenzyme 3 were correlated with an altered performance status, advanced tumor stage, and aggressive histology whereas high isoenzyme 2 percentages were correlated with altered performance status only. Among patients with high total serum LDH, a high content of isoenzyme 2 and a high absolute value of isoenzyme 3 were correlated with high serum levels of TNFalpha and TNF receptor p75. Analysis of total LDH and LDH isoenzyme profiles in CSF did not reveal any correlation with meningeal involvement by lymphoma. High isoenzyme 2 percentages and high absolute values of isoenzyme 3 in serum were both significantly associated with a shorter freedom-from-progression and overall survival. Isoenzyme 3 remained a prognostic factor for survival even when considering only patients with high total serum LDH at diagnosis. We conclude that there are some characteristic serum LDH isoenzyme profiles in patients with NHL and that some of these specific alterations may help refine the prognostic value of total serum LDH.

[Acute schizophrenia concept and definition: investigation of a French psychiatrist population]. / Définition de l'etat aigu dans la schizophrénie: enquête réalisée auprès des psychiatres français.

For schizophrenic disorders, the clinical conception of "acute state" is widely used in clinical settings to assess the effectiveness of therapeutic programs as well as epidemiological studies. Schizophrenic-specific symptomatology modification, need for hospitalization, significant change in care, disturbances in social behavior or suicide attempts were all used to define acute schizophrenic state. The decision to hospitalize is frequently used to define acute state but refers to multiple factors such as mood disorder, suicide attempts, drug abuse or social and environmental problems. Indeed, several and distinct definitions in a criteria basis form are available but no one has reached consensus. Because recognition of acute schizophrenic state remains based on the subjective clinician's advice, epidemiological and therapeutic studies fail in validity and reliability. The aim of the study was to evaluate how a population of French psychiatrists define criteria and therapeutic targets of acute schizophrenic state in their clinical practice. Psychiatrists filled out a self administered interview. At the time the interview was given, clinicians were notified that they were participating in a clinical consensus survey about schizophrenia. Six major indicators for acute state definition based on the literature data were proposed: general schizophrenic symptomatology modification (depression, anxiety, agitation, impulsivity/aggressiveness), specific schizophrenic symptomatology modification (positive symptoms, negative symptoms, disorganization), need for hospitalization, significant change in care, disturbance in social behavior and lastly, suicidal behavior. Minimal duration (1.2 or 4 weeks) of general and specific schizophrenic symptomatology modification required to define acute state were evaluated. The booklet included the 30 PANSS symptoms listed with their definitions. Among this symptom list, clinicians were instructed to select the ten criteria which they estimated best defined the acute state, followed by the ten most important target symptoms to be treated. Out of 2,369 questionnaires, 1,584 were collected on time (66.9%). Among the six majors indicators proposed to define acute state 75% of psychiatrists considered 1 to 3 criteria. Three were more frequently rated, including core schizophrenic symptomatology disturbance (68.4%), general schizophrenic symptomatology disturbance (68.0%) and suicidal behavior (64.9%). The other criteria were rated as follows: need for hospitalization (26.8%), significant change in care (18.3%), and disturbance in social behavior (29.1%). For 53.2% of psychiatrists the definition of acute state requires the presence of specific schizophrenic symptomatology for a minimal duration of one week. Two weeks with general symptomatology was required for 45.5% of psychiatrists to define acute state. Symptoms more often rated within the four first choices for acute state definition included delusions, conceptual disorganization, hallucinatory behavior and excitement. Except for grandiosity, all the PANSS positive subscale items were chosen to be included in the definition (delusions, conceptual disorganization, hallucinatory behavior, excitement, suspiciousness/persecution and hostility). Four items, including anxiety, depression, uncontrolled hostility, inner tension from the general psychopathology subscale were chosen as part of the ten most important criteria to define acute state. On the PANSS negative subscale (blunted affect, emotional withdrawal, poor relationships, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity/flow of conversation and stereotyped thinking), no item was rated to be included in the acute state definition. The highest rated symptoms among the four first choices for treatment included delusions, hallucinatory behavior, excitement and anxiety. The ten most important criteria for treatment were the same as for acute state definition with differences in frequency. Excited state, depression and suspiciousness/persecution were more rated for treatment than definition whereas delusion, hostility and conceptual disorganization were less rated as treatment target than definition criteria. In clinical practice, recognition of acute schizophrenic state is underscored by the association of specific schizophrenic symptomatology (positive symptoms, negative symptoms, disorganization) and general symptomatology (impulsivity/aggressiveness, anxiety, depression, agitation) of schizophrenia. For most clinicians, acute state definition requires specific symptom for a minimum of one week and other non-specific indicators such as suicidal behaviour have to be taken into account. With regard to PANSS criteria, most positive schizophrenic symptoms and some general schizophrenic symptoms are necessary for definition and designated as treatment priorities. Negative symptoms were not taken into account. Hallucinatory behavior is the first symptom rated in definition and is considered by psychiatrists as the absolute therapeutic priority. This survey could be a first step in the construction of an operational and consensual definition. This definition is strongly needed as a valid measurement in therapeutic and epidemiological outcome studies, which remain at least partly based on clinician subjective judgment.

An increase in joy after two weeks is more specific of later antidepressant response than a decrease in sadness.

BACKGROUND: Early improvement in positive emotions-more than decreases in negative emotions-was highly predictive of treatment response in an ecologically valid prospective manner. This result needs replication with simpler assessments to determine whether it can be translated into clinical practice. METHODS: 2049 adult depressed outpatients receiving agomelatine were assessed at inclusion, week 2, and week 6 using the clinician-rated Quick Inventory of Depressive Symptomatology, Sheehan Disability Scale, Clinical Global Impression scale, and Multidimensional Assessment of Thymic States (MATHYS), an auto-questionnaire rating the frequency of emotions, including sadness and joy, over the previous week. RESULTS: Joy and sadness had a relatively low correlation coefficient at baseline (r=-0.277), joy (r=-0.160) being less correlated with clinical severity than sadness (r=0.317). An increase in joy at week 2 had higher specificity (85.04%) and positive predictive value (70.55%) for treatment response than decreased sadness (57.92% and 66.04%, respectively), and the global capacity of the former to predict remission, either clinical (Yule Q coefficient, 39.96%) or functional (44.35%), was even better compared to the prediction of clinical response (37.38%). LIMITATIONS: MATHYS retrospectively assesses emotions, with five possible ratings only, relying on self-rated frequencies. With only a 6-week follow-up, conclusions are limited to short-term aspects of clinical and functional remission. CONCLUSIONS: Early improvement in joy during the first 2 weeks of treatment is strongly specific for treatment response and remission. The frequency of joy captures the predictivity and may deserve further study regarding inclusion in depressive rating scales.