Quality of life is associated with chronic inflammation in schizophrenia: a cross-sectional study

International audienceInflammation may play a crucial role in the pathogenesis of schizophrenia. However, the association between chronic inflammation and health outcomes in schizophrenia remains unclear, particularly for patient-reported outcomes. The aim of this study was to investigate the relationship between quality of life (QoL) and chronic inflammation assessed using C -Reactive Protein (CRP) in patients with schizophrenia. Two hundred and fifty six patients with schizophrenia were enrolled in this study. After adjusting for key socio-demographic and clinical confounding factors, patients with high levels of CRP (>3.0 mg/l) had a lower QoL than patients with normal CRP levels (OR = 0.97, 95% CI = 0.94-0.99). An investigation of the dimensions of QoL revealed that psychological well-being, physical well-being and sentimental life were the most salient features of QoL associated with CRP. Significant associations were found between lower educational level (OR = 4.15, 95% CI = 1.55-11.07), higher body mass index (OR = 1.16, 95% CI = 1.06-1.28), higher Fagerstrom score (OR = 1.22, 95% CI = 1.01-1.47) and high levels of CRP. After replications with longitudinal approaches, the association between QoL and chronic inflammation may offer interesting interventional prospects to act both on inflammation and QoL in patients with schizophrenia

Predictive value of dorso-lateral prefrontal connectivity for rTMS response in treatment-resistant depression: A brain perfusion SPECT study

Background: Previous clinical trials have suggested that repetitive transcranial magnetic stimulation (rTMS) has a significant antidepressant effect in patients with treatment resistant depression (TRD). However, results remain heterogeneous with many patients without effective response. / Objective: The aim of this SPECT study was to determine before treatment the predictive value of the connectivity of the stimulated area on further rTMS response in patients with TRD. / Methods: Fifty-eight TRD patients performed a brain perfusion SPECT before high frequency rTMS of the left dorsolateral prefrontal cortex (DLPFC). A voxel based-analysis was achieved to compare connectivity of the left DLPFC in responders and non-responders using inter-regional correlations (p < 0.005, corrected for cluster volume). A multiple logistic regression model was thereafter used with the goal of establishing a predictive score. / Results: Before rTMS, responders exhibited increased SPECT connectivity between the left DLPFC and the right cerebellum in comparison to non-responders, independently of age, gender, severity of depression, and severity of treatment resistance. The area under the curve for the combination of these two SPECT clusters to predict rTMS response was 0.756 (p < 0.005). / Conclusions: SPECT connectivity of the left DLPFC predicts rTMS response before treatment

Acro-cardio-facial syndrome

Acro-cardio-facial syndrome (ACFS) is a rare genetic disorder characterized by split-hand/split-foot malformation (SHFM), facial anomalies, cleft lip/palate, congenital heart defect (CHD), genital anomalies, and mental retardation. Up to now, 9 patients have been described, and most of the reported cases were not surviving the first days or months of age. The spectrum of defects occurring in ACFS is wide, and both interindividual variability and clinical differences among sibs have been reported. The diagnosis is based on clinical criteria, since the genetic mechanism underlying ACFS is still unknown. The differential diagnosis includes other disorders with ectrodactyly, and clefting conditions associated with genital anomalies and heart defects. An autosomal recessive pattern of inheritance has been suggested, based on parental consanguinity and disease's recurrence in sibs in some families. The more appropriate recurrence risk of transmitting the disease for the parents of an affected child seems to be up to one in four. Management of affected patients includes treatment of cardiac, respiratory, and feeding problems by neonatal pediatricians and other specialists. Prognosis of ACFS is poor

Insight et qualité de vie subjective chez les personnes souffrant de schizophrénie

International audienceL'évaluation de la qualité de vie subjective constitue l'un des indicateurs des états de santé des patients souffrant de schizophrénie. Les relations entre l'insight et la qualité de vie sont contradictoires dans la littérature. Ces différences peuvent s'expliquer par plusieurs facteurs : populations d'étude différentes, instruments de mesure de l'insight et/ou de la qualité de vie très divers et souvent peu valides, facteurs de confusion. Parmi les facteurs de confusion pouvant être impliqués dans les relations entre insight et qualité de vie, il semble que les troubles des fonctions cognitives jouent un rôle central, comme le montrent certaines études. Il reste toutefois difficile de savoir comment ces différents facteurs interagissent entre eux

Birth defects in newborns and stillborns: an example of the Brazilian reality

<p>Abstract</p> <p>Background</p> <p>This study constitutes a clinical and genetic study of all newborn and stillborn infants with birth defects seen in a period of one year in a medical school hospital located in Brazil. The aims of this study were to estimate the incidence, causes and consequences of the defects.</p> <p>Methods</p> <p>For all infants we carried out physical assessment, photographic records, analysis of medical records and collection of additional information with the family, besides the karyotypic analysis or molecular tests in indicated cases.</p> <p>Result</p> <p>The incidence of birth defects was 2.8%. Among them, the etiology was identified in 73.6% (ci95%: 64.4-81.6%). Etiology involving the participation of genetic factors single or associated with environmental factors) was more frequent 94.5%, ci95%: 88.5-98.0%) than those caused exclusively by environmental factors (alcohol in and gestational diabetes mellitus). The conclusive or presumed diagnosis was possible in 85% of the cases. Among them, the isolated congenital heart disease (9.5%) and Down syndrome (9.5%) were the most common, followed by gastroschisis (8.4%), neural tube defects (7.4%) and clubfoot (5.3%). Maternal age, parental consanguinity, exposure to teratogenic agents and family susceptibility were some of the identified risk factors. The most common observed consequences were prolonged hospital stays and death.</p> <p>Conclusions</p> <p>The current incidence of birth defects among newborns and stillbirths of in our population is similar to those obtained by other studies performed in Brazil and in other underdeveloped countries. Birth defects are one of the major causes leading to lost years of potential life. The study of birth defects in underdeveloped countries should continue. The identification of incidence, risk factors and consequences are essential for planning preventive measures and effective treatments.</p

Fibrinolysis in a lipid environment: modulation through release of free fatty acids

Background: Thrombolysis is conventionally regarded as dissolution of the fibrin matrix of thrombi by plasmin, but the structure of clots in vivo includes additional constituents (proteins, phospholipids) that modulate their solubilization. Objective: We examined the presence of free fatty acids in thrombi and their effects on distinct stages of fibrinolysis (plasminogen activation, plasmin activity). Methods and Results: Using the fluorescent probe acrylodated intestinal fatty acid-binding protein, variable quantities (up to millimolar concentrations) of free fatty acids were demonstrated in surgically removed human thrombi. Oleic acid at relevant concentrations reversibly inhibits more than 90% of the amidolytic activity of plasmin on a synthetic substrate (Spectrozyme PL), but only partially inhibits its fibrinolytic activity measured using turbidimetry. Chromogenic assays detecting the generated plasmin activity show that plasminogen activation by tissue-type plasminogen activator (t-PA) is completely blocked by oleic acid in the fluid phase, but is accelerated on a fibrin matrix. A recombinant derivative of t-PA (reteplase) develops higher fibrin specificity in the presence of oleic acid, because both the inhibition of plasminogen activation in free solution and its enhancement on fibrin template are stronger than with wild-type t-PA. Conclusion: Through the stimulation of plasminogen activation on a fibrin template and the inhibition of plasminogen activators and plasmin in the fluid phase, free fatty acids confine the action of fibrinolytic proteases to the site of clotting, where they partially oppose the thrombolytic barrier function of phospholipids

Waardenburg Syndrome: Clinical Differentiation Between Types I and II

Here we present the results of a study performed on 59 patients affected by Waardenburg syndrome (WS), 30 with the I variant, 21 having the type II, and 8 of them being isolated cases without telecanthus. These patients belong to 37 families; the main contributions and conclusions are based on the detailed study of 25 of these families, examined using standard procedures. All patients were examined as to the presence of eight cardinal signs important for the diagnosis of the condition; from each patient, from many of his/her normal relatives, and from a control sample of 300 normal individuals stratified by age and sex, 23 different craniofacial measurements were obtained. We also estimated, using our own data as well those collected from the literature, the frequencies of the cardinal signs, based on a total sample of 461 affected individuals with WSI and 121 with WSII. In order to originate discriminant functions to separate individuals affected by one of the two variants, both metric (from craniofacial measurements) as well as categoric data (based on the frequencies of the cardinal signs or symptoms) were used. Discriminant analysis based on the frequency of the eight cardinal signs can improve the separation of WSI patients without telecanthus from those presenting the variant II. We present also a Table with the conditional probabilities favoring the diagnosis of WSI for suspect subjects without telecanthus and any combination of the other seven signs/symptoms. The discriminant function based on the four ocular measurements (inner and outer intercanthal, interpupillary, and inferior lacrymal distances), on the other side, perfectly classifies patients affected by one of the variants of WS, the same taking place when the average values of the W index of all affected individuals per family are used. The discriminant function based solely in the individual W index values of patients correctly classifies 93% of WSII subjects, but only 60% of the patients with the I variant of WS. ß 2003 Wiley-Liss, Inc. KEY WORDS: Waardenburg syndrome; genetic heterogeneity; discriminant analysis INTRODUCTION The Waardenburg syndrome (WS), first comprehensively described in 1951, is a genetically heterogeneous condition, each of its forms having a wide clinical spectrum with a very high degree of phenotypic expressivity. In the present paper, we will consider only the two most frequent variants (WSI and WSII) out of the four described so far. These two forms, together accounting for a prevalence of 2 to 3 affected individuals/100,000 in the general population, are determined by non-allelic autosomal dominant mutant genes with a high penetrance. WS is characterized clinically by the association of craniofacial dysmorphim, pigmentation defects, and severe sensorineural congenital hearing impairment. The craniofacial dysmorphisms most commonly seen in affected individuals include telecanthus (in WSI only), broad and high nasal root, hypoplasia of the alae nasi, lower lacrimal dystopia, and synophrys. Telecanthus (dystopia canthorum lateroversa) is classically described as an increase of inner ocular intercantal distance (IID) with preservation of both interpupillary (IPD) and outer intercantal (OID) distances. WS patients with this sign, however, commonly present larger values of the other two measurements, so that they exhibit a certain degree of hypertelorism. Patients frequently display conspicuous pigmentary defects of the irides (totally or partially heterochromic and bright hypochromic blue irides), hypopigmented skin spots, and partial hair albinism (white forelock or early graying). The first variant (WSI), with telecanthus, is caused by mutations at the PAX3 gene located in 2q35, while the second (WSII) is determined by other non-allelic autosomal dominant mutations located in the region 3p12.3 ! 3p14.1 of the MITF gene. Many of these are point mutations involving single-base substitutions and the number of different mutations described so far for both loci is so large that the molecular screening for them in WS can not be routinely performed in most laboratories. Because of all this, the differential diagnosis between variants I and II still relies largely on classic clinical methods. Clinical signs and symptoms are similar in both conditions, but telecanthus is known to occur only in WSI; the other characteristics have contrasting frequencies in both forms, especially iris and hair pigmentary disturbances and deafness. The penetrance of the last trait is higher in the second variant of WS, which has therefore a poorer clinical prognosis. Telecanthus (sometimes hypertelorism) is the most important sign for the differentiation between both forms, because it is present in the vast majority (95-99%) of WSI patients and virtually absent in those with the WSII variant. The presence of conspicuous craniofacial dysmorphisms in WS explains why the condition has been widely studied anthropometrically. The first of these studies was performed on Waardenburg&apos;s original data by Since the penetrance of the telecanthus trait and consequently the efficiency of the W index-although generally high-are both incomplete In this paper, we describe 59 individuals affected by the Waardenburg syndromes WSI and WSII, belonging to 25 Brazilian families. A detailed craniofacial phenotypic description of all affected individuals is presented, as well as the values of several measurements taken in these patients. The relative frequencies of cardinal signs and the values of craniofacial measurements are used to compare, through discriminant analysis, WSI and WSII affected individuals. MATERIALS AND METHODS Out of the 25 families studied personally, 18 were ascertained in the Laboratory of Human Genetics (LGH, Departamento de Biologia, IB USP, São Paulo) and seven were examined at the Hospital de Reabilitação de Anomalias Cranio-Faciais (HRAC, Faculdade de Odontologia, USP, Bauru). For this, we used a standardized routine for physical examination that included the investigation, in all affected individuals (with the exception of a few instances in which one measurement could not be recorded and the corresponding feature could not be evaluated objectively), of the following eight cardinal signs and symptoms of WS: telecanthus, synophrys, iris pigmentation disturbances, localized albinism on hair (white forelock and early graying), hearing impairment, nasal root hyperplasia, hypopigmented skin spots, and lower lacrimal dystopia. We selected also, through review of the international literature, 44 different papers published from 1951 to 1995 with complete clinical presentation of cases of WS Waardenburg Syndrome 225 non-mentioned characteristic was absent, the estimate for its frequency is given by under the hypothesis (b) that the non-mentioned sign/ symptom was not investigated, its frequency estimate is given by x 00 ¼ X/(X þ Y) ¼ X/(N À Z), with expected binomial variance var(x 00 ) ¼ x 00 (1 À x 00 )/(N À Z). Obviously, the true estimate of the frequency is given by an unknown quantity within an interval with lower und upper limits given by x 0 and x 00 . If there is no additional information enabling us to choose one out of the two hypotheses above, an estimate of the true frequency x can be obtained by weighing the estimates x 0 and x 00 by the reciprocal of their expected binomial variances. This estimate will be used throughout this work to contrast the frequencies of the cardinal signs in a sample of WSI and WSII patients combining our data with those from the literature. We also determined-in random samples of Caucasian individuals stratified by sex and age (total of 300 individuals) and in affected individuals and in their relatives belonging to ten of our 25 families-23 different craniofacial measurements of interest in the diagnosis of WS. Some of these measurements were used for comparing controls and patients as well as types I and II of WS. 226 Pardono et al. We have classified as WSI all the patients, familial or isolated, that presented conspicuous telecanthus. In order to classify as WSI a case of WS without telecanthus, this affected individual should always belong to a family with at least one typical case of WSI (with telecanthus). Therefore, all cases of WSI without telecanthus presented here are familial, whereas all isolated cases of WS classified as WSI present with the sign. Inversely, all cases of WS classified as WSII are necessarily familial, that is, they belong strictly to families with at least one more affected individual, none of them presenting telecanthus. In the cases selected from literature, we applied the same classification criteria, systematically disregarding the classification of isolated cases of WS without telecanthus as being WSII. In the presentation of our cases in the Results and Discussion section, all isolated WS patients without telecanthus were grouped in a group labelled as WSII?, but their data were not used in the statistical analyses described below. For the study of cardinal characteristics, the application of the above-mentioned stringent criteria to the cases from literature enabled us to consider a total of 461 WSI patients (29 of them not presenting telecanthus) and 121 carriers of the WSII variant. With the addition of our own data to those from the literature, the discriminant analysis performed with categorical data was based, therefore, on totals of 491 WSI and 142 WSII patients, respectively. The techniques of statistical analysis used throughout this paper are detailed in standard textbooks (e.g., Zar [1999]). Those on linear and non-linear discriminant analysis in particular are detailed in Smith [1947, 1969], Penrose [1947], and Karn and Penrose [1951]. RESULTS AND DISCUSSION Description of Cases Using a modification of the genealogy symbols proposed by Discriminant Analysis Using the Frequencies of Cardinal Signs and Symptoms The estimated frequencies of the eight cardinal characteristics of WS were calculated from reliable case descriptions in the literature and are shown in Waardenburg Syndrome 227 Comparing the observed frequencies of each sign in the groups of WSI and WSII patients through chisquared tests in 2 Â 2 contingency tables, we obtained in all cases test figures that were significant at least at the 1% level. The elements necessary for performing a simplified categoric discriminant analysis, together with an application example, are summarized in Since there are only seven other possible signs besides telecanthus, all the possible combinations of these seven signs/symptoms (presence or absence) reduce to 2 7 ¼ 128. 38 out of these 128 combinations generate probability figures larger than 95% or less than 5% favoring the diagnosis of WSI and are shown in We could obtain, combining our data with those from the literature, complete individual phenotypic descriptions of 111 patients affected by WSII out of the 142 used for deriving the probabilities shown in Discriminant Analysis Based on Craniofacial Measurements First we compared the craniofacial measurements between WSI and WSII patients, and between WS patients and controls through t tests with allowance for variance heterogeneity. Using as selection criterion all variables that were statistically different between any of the two comparison groups at least at the 0.001 significance level, we chose the following variables to be used on discriminant analysis: inner intercanthal distance (IID); outer intercanthal distance (OID); interpupillary distance (IPD); lower interlacrimal distance (LID); nose interalar distance (IAD); mean length of ear (EML), obtained by averaging the longitudinal length of both auricles; and the W index (WI), a composite measure used in the literature for separating WSI and WSII patients and described in the introduction section. We decided to also include the variables facial length or morphological face height (MFH) and the mean width of ear (EMW), a measurement obtained by averaging the transversal length of both auricles. These two measurements, in spite of not showing statistical significance at the 0.001 level, exhibited differences at a critical level much less than 0.01. The statistical parameters of these nine measurements, estimated in the groups of WSI and WSII patients and controls, are shown i