T Cells in Nonlymphoid Tissues Give Rise to Lymph-Node-Resident Memory T Cells

1. Download high-res image (357KB)
2. Download full-size image

     

Is it worth assessing progress as early as week 2 to adapt antidepressive treatment strategy? Results from a study on agomelatine and a global meta-analysis

ContextA delay of 4–8 weeks before modifying the prescribed antidepressant treatment is usually proposed when incomplete treatment response is observed. A number of studies nevertheless proposed that the lack of early improvement (usually 20% decrease of severity at week 2) is predictive of the absence of subsequent treatment response, potentially saving weeks of inadequate treatment, but with no information for non-interventional studies devoted to outpatients.MethodTwo thousand nine hundred and thirty-eight outpatients with major depressive disorder were included in a multicentre, non-interventional study, assessing at inclusion, week 2 and week 6, mood (QIDS-C, CGI, PGI and VAS) sleep (LSEQ) and functionality (SDS). All metrics at week 2 were tested for their capacity to predict response (and then remission) at week 6, all patients being treated by agomelatine. A meta-analysis of all studies (n = 12) assessing the predictive role of improvement at week 2 was also performed, assessing specific effect size of published studies and the weight of the different parameters they used.ResultsThe QIDS-C and the CGI-I were the only instruments with an area under the curve over 0.7, with different cut-offs for treatment response and remission. A decrease of more than five points at the QIDS-C had the highest positive predictive value for treatment response, and a CGI-I over three had the highest negative predictive value, which would favour relying on the clinicians for warning (too high CGI-I), and on instruments for confidence (favourable decrease of the QIDS-C). The meta-analysis of all studies also detected a large effect size of early improvement, stressing how rating week 2 severity could be beneficial in clinical practice.ConclusionsPrevious reports stressing the interest of an assessment at week 2 were reinforced by the present results, which also defined more accurately what could be the most appropriate cut-offs, and how combining these early results could be more effective.     

Apoptosis of cardiomyocytes in explanted and transplanted hearts. Comparison of results from in situ TUNEL, ISEL, and ISOL reactions

We assessed the efficiency of detecting myocyte apoptosis within human hearts using in situ enzymatic reactions in paraffin-embedded tissue samples: in situ end labeling (ISEL), terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL), and in situ oligoligation (ISOL). The reactions were carried out in explanted hearts (idiopathic dilatative cardiomyopathy, n = 6; ischemic heart disease, n = 3) and in endomyocardial biopsy specimens (EMBs; n = 32) obtained from transplanted human hearts. The results were verified by DNA laddering. The ISOL reaction led to a significantly (P = .027) smaller number of false-positive results (2/41 [5%]) compared with assessment by ISEL (9/41 [22%]) or TUNEL (9/41 [22%]). Only 1 ISEL+ apoptotic cardiomyocyte was found in specimens from explanted hearts. Among the EMBs, 1 specimens had TUNEL+ apoptotic cardiomyocytes and 1 specimen had ISEL+ apoptotic cardiomyocytes. This implies that verifying results by independent methods must be used for TUNEL and ISEL techniques. A smaller number of false-positive results makes interpretation of ISOL results easier, although the sensitivity of this reaction remains to be established.     

Systemic lupus erythematosus presenting with recurrent psychiatric disturbances

INTRODUCTION: There is a wide range of non-specific symptoms that can reveal neurolupus, sometimes making diagnosis difficult. OBSERVATION: A 29-year-old man presented, from 1996 to 2002, three episodes of mood disorders with hetero-aggression, preceded by seizures, which resolved completely. Repeated investigations were negative except for lymphopenia, an inflammatory cerebrospinal fluid and some rare non-specific areas of high intensity signals in the white matter on the brain MRI. After a six-year course, the patient was considered to have a severe mood disorder related to a schizoid personality. A new dot-blot search for antinuclear antibodies detected anti-Sm antibodies was positive, leading to the diagnosis of neuropsychiatric lupus since the patient's symptoms fulfilling four of the American Rheumatism Association criteria (neuropsychiatric events, lymphopenia, antinuclear and anti-Sm antibodies). The patient was given monthly pulses of cyclophosphamide and remained symptom free one year after the last flare up. CONCLUSIONS: Lupus can rarely be revealed by long-standing isolated psychiatric disorders. Search for auto-antibodies, using highly specialized techniques (western blot, dot blot) should be a routine practice since antibody titres fluctuate during the course of the disease; elevated titres may correlate with exacerbations. Considering the prominence and severity of these behavior disorders, systemic diseases may often be misdiagnosed.     

Value of a consultation center and crisis intervention in addressing psychiatric disorders in the perinatal period

The Psychiatry department of the University Hospital Centre of Lille has developed, over the last 10 years, a treatment network for psychiatric disorders during pregnancy or in the post-partum period. There are liaison consultations in the maternity department, screening and management of psychopathological disorders in the perinatal period, training of midwives, support of patients seeking genetic counselling, collaboration with teams providing "medically-assisted procreation", etc. For severe disorders of the post-partum period (severe depression, serious alteration of mother-child interaction, puerperal psychosis), the Psychiatry department has a specialized unit where 3 "mother-child" groups can be admitted. This unit is particularly effective if the patients and their family understand this healthcare system and stick to it to a certain extent. Even if improvements are always possible, cases in which situations occur as an emergency, are when dysfunctions are most frequently seen. On 7th December 1998, a Crisis Intervention Unit (CIU) was created with 15 short-term beds, for stays up to 72 hours. The CIU was opened in the Psychiatry department, close to the main Accident and Emergency department, with 2 aims: firstly to provide a setting and resources for a number of emergency psychiatric situations, and secondly to provide a place and time for crisis situations which we admit to the unit, with a view to facilitating interaction and to propose in certain cases a process of crisis intervention, which later continues on an outpatient basis. After being open for a year, the CIU has proved to be an improvement to all of the healthcare services which are available. It should be noted that the situations which need highly specialized resources in such a short time, are those which cause the most acute problems. This is at times when the emergency services network, with its internal logic, require another network based on a different logic, that the interface problems are at their most acute. The situations reported here, which require a fluid interface between the emergency services and the "mother-child" networks, are examples. We report 3 clinical situations, which illustrate 3 possibilities of action: the first, in which 2 successive stays in the CIU allowed an admission to the "mother-child" unit in satisfactory conditions, the second, in which overall management was based on hospitalization in the Obstetrics department and several visits to our Unit, and the last one, in which the whole medico-psycho-social approach was set up after a single stay of 3 days. Since the opening of Crisis Intervention Unit, around 1,000 patients have been treated there; 37 were women with difficulties with their pregnancy, 17 of whom required direct intervention by the "mother-child" team. The contexts were: 5 prenatal depressions, 4 post-partum depressions, 3 cases of hyperemesis gravidarum, 5 rejections of pregnancy and/or situations at risk of infanticide. The almost constant suicidal risk should be noted, or even attempted suicide, at the time of admission to the CIU. The other 20 women had psychopathological disorders linked to sterility, medically-assisted pregnancy, termination of pregnancy or pregnancy in women suffering from long-term somatic illnesses (insulin-dependent diabetes, lupus, etc.). When a psychopathological episode occurs during pregnancy, it is essential to preserve the developing relationship with the child in an intermediate place, in a healthcare perspective and to prevent any future impairment of the quality of the mother-child relationship by the psychiatric disorder. The Crisis Intervention Unit is not an emergency "mother-child" unit. Other French experiences have been reported, an example being mother-baby hospitalization in a crisis centre. The aim of our interventions is not the same, and our local context, together with the availability of a healthcare network on different floors, which is specific and close-by, allows this approach. Also, the contribution of Liaison Psychiatry in emergency situations should not be minimized. It is necessary to work in collaboration with the obstetricians. In fact, the chance to work with us was given by asking for a hospitalization in the Obstetric unit, during the prepartum period of pregnancies with a psychiatric risk. This way of proceeding allows somatic monitoring in hospital to be performed, whenever the risk run by the mother and/or the child requires it. This "analogue" procedure, however preventative it may be, does not always allow specific treatment of the psychiatric disorders to be given, despite liaison psychiatry interventions. Our interventions are not a specialized "mother-child" unit, or a substitute for Liaison Psychiatry, but they are specifically aimed at the context of the crisis. Obviously, it is precisely this dimension of the crisis which makes the other types of management temporarily unsuitable. This new working framework, with the simple possibility of admitting women and interacting with them in a crisis situation, with the aid of the competence of "mother-child" teams, most often seems to allow an alternative to hospitalization in the Psychiatry department, at the same time keeping up quality management of problems linked to the pregnancy or post-partum period. The specificity of the CIU, with its project of taking the special psychiatric vulnerability of pregnancy into account, makes sure that the psychopathological aspects of the crisis situation and the physiological aspects of adaptation reactions to the perinatal period are not neglected, but that are respected by this type of interaction/intervention.     

SPECT imaging,clinical features,and cognition before and after low doses of amisulpride in schizophrenic patients with the deficit syndrome

The aim of the study was to examine the action of low-dose amisulpride (100 mg/d), an atypical antipsychotic from the benzamide class with a high affinity for the D2 and D3 dopamine receptors, given for 4 weeks in 19 schizophrenic patients with the deficit syndrome, in terms of clinical response, modifications in their cognitive performance and changes in brain perfusion values. A secondary objective was to distinguish between primary and secondary deficit, according to Carpenter's definition. Both efficacy and a relatively low rate of side effects of low-dose amisulpride in the deficit forms of schizophrenia were found as expected from earlier placebo-controlled studies. Our study found significant changes in the cerebral blood flow, before and after treatment, more marked in the frontal area and particularly in the dorso-lateral frontal area. A significant improvement of cognitive function was found after treatment, without a link to any particular changes in a loco-regional perfusion value. Finally, a distinction between primary and secondary deficit showed a higher percentage of clinical improvement in the patients with a secondary deficit. The psychometric and cerebral perfusion changes were no different in the two groups.     

Regional cerebral blood flow in deficit/nondeficit types of schizophrenia according to SDS criteria

A relationship between "hypofrontality" and a negative form of schizophrenia is commonly found. The Schedule for the Deficit Syndrome (SDS) provides specific criteria for assessing the presence of negative symptoms, their duration and whether the symptoms are primary or secondary. The purpose of our study was to compare the regional cerebral blood flow (rCBF) at rest, in 62 deficit and nondeficit schizophrenic patients, according to the SDS criteria (French version). The deficit patients in our population were comparable to those described in the literature (stability of their negative symptoms with time, poor premorbid adjustment, duration of the illness, age at the first episode, etc.). No difference was found in the locoregional perfusion with respect to the DSM-III-R type of schizophrenia, the sex or the type of treatment received. The patients with a deficit form of schizophrenia showed a significant bilateral reduction in single photon emission computed tomography (SPECT) perfusion in the right frontodorsolateral cortex (P=.0105) and the left frontodorsolateral cortex (P=.0004) compared with the nondeficit schizophrenic patients. The contribution of SDS seems to be helpful in distinguishing between significant cerebral characteristics in deficit schizophrenics, as defined by Carpenter. These results suggest a decrease in prefrontal perfusion at rest, which corresponds with neuropsychological data.