Severe visual loss by inhalation of methanol.

Purpose: To describe a clinical case of toxic optic neuropathy with severe visual loss caused by inhalation abuse of methanol products. Method: A 25-year-old male student was admitted to the emergency department with an acute bilateral visual loss and headaches, nausea, and cold sweats. A complete clinical and ophthalmologic examination was performed. Results: On ophthalmic examination, visual acuity (VA) was light perception in the right eye (RE) and no light perception in the left eye (LE). Pupillary examinations demonstrated dilated, non-reactive pupils. An arterial blood gas analysis showed systemic metabolic acidosis with a pH of 7.23 and Gap anion elevated. Consequently, these results were enough to provide a substantial suspicion of methanol toxicity and start the treatment. 72 hours after, he confessed that he had been inhaling methanol-based solvent for eight years. Conclusions: Methanol-induced toxicity can cause a non-reversible toxic optic neuropathy. Blood acidemia with Gap anion elevated and a suspicious fundus ophthalmic examination allows a fast diagnosis. A quick treatment based on dialysis, intravenous ethanol, sodium bicarbonate, vitamin B12, and intravenous methylprednisolone slows the secondary intoxication damages. We presented herein a procedure to identify and manage toxic optic neuropathy caused by methanol inhalation. Abbreviations: VA = Visual Acuity, RE = right eye, LE = left eye, OCT = Optical Coherence Tomography, RNFL = Retinal Nerve Fiber Layer, CT = computed tomography, MRI = magnetic resonance imaging, VEPs = visual evoked potentials.

Anatomical analysis of the pelvis to identify any predisposing anatomical factors for ischiofemoral space pathology: a retrospective study.

OBJECTIVE: Anatomical analysis of the hips and pelvis was performed using MRI to evaluate morphological characteristics and associations between them. We identified correlations between the ischiofemoral space (IFS), quadratus femoris space (QFS), femoral version angle (FVA) and cervicodiaphyseal angle (CDA). METHODS: This study involved a retrospective search of a database of consecutive reports of adult hip MRI examinations carried out between January and September 2016. Patients with a medical history likely to affect pelvic and hip morphometry were excluded. RESULTS: A total of 137 adult patients were enrolled in the study (45.3% males and 54.7% females), with a mean age of 50.16 ± 13.87 years. The mean IFS was 20.88 ± 5.96 mm, mean QFS was 15.2 ± 6.18 mm, mean FVA was 12.43 ± 6.98, and mean CDA was 121.27 ± 4.6°. The IFS measurements were significantly correlated with femoral measurements (p = 0.025). These visible differences showed a slight negative relationship (-0.191), and females had a smaller distance between these anatomical structures than males (p < 0.001). Females had a significantly smaller QFS than males (12.42 ± 5.94 vs 18.73 ± 4.48 mm, p = 0.000). There was a small but significant positive relationship between CDA and FVA (p = 0.022), with a correlation coefficient of 0.195. CONCLUSION: A higher FVA was correlated with a smaller IFS. Furthermore, an increase in the CDA appeared in tandem with an increase in the FVA. ADVANCES IN KNOWLEDGE: A single conventional MRI sequence can alert us to how anatomical factors could predispose individuals to a decrease in IFS.

Assessment of effectiveness and safety of repeat administration of proinflammatory primed allogeneic mesenchymal stem cells in an equine model of chemically induced osteoarthritis.

BACKGROUND: This study aimed at assessing the effectiveness and safety of repeated administrations of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) primed with tumor necrosis factor (TNF)-α and interferon-γ in an equine model of chemically-induced osteoarthritis. Arthritis was induced in both radio-carpal (RC)-joints by amphotericin-B in 18 ponies, divided into three groups depending on the treatment injected: MSC-naïve (n = 7), MSC-primed (n = 7) and control (n = 4). The study consisted of two phases and used one RC-joint of each animal in each phase, with four months time-lapse, in order to assess two end-points. Clinical, synovial, radiological and ultrasonographic follow-up was performed. At six months, animals were euthanized and both carpi were assessed by magnetic resonance imaging (MRI), gross anatomy, histopathology, histochemistry and gene expression. RESULTS: Clinical and synovial inflammatory signs were quicker reduced in MSC-treated groups and repeated allogeneic administration did not produce adverse reactions, but MSC-primed group showed slight and transient local inflammation after second injection. Radiology and MRI did not show significant differences between treated and control groups, whereas ultrasonography suggested reduced synovial effusion in MSC-treated groups. Both MSC-treated groups showed enhanced cartilage gross appearance at two compared to six months (MSC-naïve, p < 0.05). Cartilage histopathology did not reveal differences but histochemistry suggested delayed progression of proteoglycan loss in MSC-treated groups. Synovium histopathology indicated decreased inflammation (p < 0.01) in MSC-primed and MSC-naïve at two and six months, respectively. At two months, cartilage from MSC-primed group significantly (p < 0.05) upregulated collagen type II (COL2A1) and transforming growth factor (TGF)-ß1 and downregulated cyclooxygenase-2 and interleukin (IL)-1ß. At six months, MSC-treatments significantly downregulated TNFα (p < 0.05), plus MSC-primed upregulated (p < 0.05) COL2A1, aggrecan, cartilage oligomeric protein, tissue inhibitor of metalloproteinases-2 and TGF-ß1. In synovium, both MSC-treatments decreased (p < 0.01) matrix metalloproteinase-13 expression at two months and MSC-primed also downregulated TNFα (p < 0.05) and IL-1ß (p < 0.01). CONCLUSIONS: Both MSC-treatments provided beneficial effects, mostly observed at short-term. Despite no huge differences between MSC-treatments, the findings suggested enhanced anti-inflammatory and regulatory potential of MSC-primed. While further research is needed to better understand these effects and clarify immunogenicity implications, these findings contribute to enlarge the knowledge about MSC therapeutics and how they could be influenced.

The utility of magnetic resonance imaging for bone involvement in Gaucher disease. Assessing more than bone crises.

Bone effects are the most frequent cause of disability in Gaucher disease (GD). Magnetic resonance imaging (MRI) has improved the study of bone involvement making it possible to measure the extent of infiltration and to identify localized complications and other lesions. Here we describe the results of our analysis of all bone lesions registered in MRI studies performed in our GD Clinic. A retrospective study was undertaken for all patients with types 1 and 3 GD who underwent MRI evaluation and correlated with clinical, molecular, and other follow-up information obtained from the Spanish GD Registry. 350 MRI studies of 131 GD patients were reviewed (males 53.4%). Mean age: 37.5years (range 13-74yr), 94.6% (124) were GD1 patients. 113/131 (86.3%) of patients presented with at least one bone effect (bone infiltration, bone crisis, avascular necrosis) were 79.4%, while 28.8% showed another bone lesion such as neuronopathic-like arthropathy, hemangioma, other ischemic phenomena, infection-related lesions, secondary neoplasia and tissue infiltration. MRI is a routinely-used tool for the evaluation of GD lesions which improves the assessment of patients before and during therapy, identifies GD complications and finds other concomitant lesions. This work provides a new evaluation of MRI assessment in this complex rare disease.

Impaired Self-Monitoring of Inner Speech in Schizophrenia Patients with Verbal Hallucinations and in Non-clinical Individuals Prone to Hallucinations.

BACKGROUND: Previous research has shown that various memory errors reflecting failure in the self-monitoring of speech were associated with auditory/verbal hallucinations in schizophrenia patients and with proneness to hallucinations in non-clinical individuals. METHOD: We administered to 57 schizophrenia patients and 60 healthy participants a verbal memory task involving free recall and recognition of lists of words with different structures (high-frequency, low-frequency, and semantically organisable words). Extra-list intrusions in free recall were tallied, and the response bias reflecting tendency to make false recognitions of non-presented words was computed for each list. RESULTS: In the male patient subsample, extra-list intrusions were positively associated with verbal hallucinations and inversely associated with negative symptoms. In the healthy participants the extra-list intrusions were positively associated with proneness to hallucinations. A liberal response bias in the recognition of the high-frequency words was associated with verbal hallucinations in male patients and with proneness to hallucinations in healthy men. Meanwhile, a conservative response bias for these high-frequency words was associated with negative symptoms in male patients and with social anhedonia in healthy men. CONCLUSION: Misattribution of inner speech to an external source, reflected by false recollection of familiar material, seems to underlie both clinical and non-clinical hallucinations. Further, both clinical and non-clinical negative symptoms may exert on verbal memory errors an effect opposite to that of hallucinations.

How Hyperprolactinemia Affects Sexual Function in Patients Under Antipsychotic Treatment.

OBJECTIVE: We aimed to study the relationship between hyperprolactinemia (HPRL) and sexual dysfunction (SED) in a sample of patients being prescribed a dose-stable antipsychotic medication, and to evaluate sex differences in the prevalence of HPRL and SED and their relationship. METHOD: A cross-sectional study was carried out including patients between 18 and 55 years of age with a psychotic spectrum diagnosis who were attending community mental health services or hospitalized in medium and long stay units. Positive and Negative Syndrome scale, Calgary depression scale for schizophrenia, Personal and Social Performance scale, and Changes in Sexual Functioning questionnaire-short form were administered. Not later than 3 months, a determination of prolactin, follicle-stimulating hormone, luteinizing hormone, estrogen (only in women) and testosterone was performed. RESULTS: A final sample of 101 patients (30 women and 71 men) was recruited. Seventy-two patients (71.3%) showed HPRL. Sexual dysfunction was significantly higher in HPRL patients than in non-HPRL patients (79.17% vs 51.72%) (P = 0.006), and mean prolactin values were significantly higher in case of SED (P = 0.020). No sex differences were found in prevalence of HPRL or SED. Low Personal and Social Performance scale scores and HPRL were factors independently associated with SED, whereas alcohol use was an independent protector factor. CONCLUSIONS: In our study, SED was significantly related to HPRL without showing sex differences. Prevalence of HPRL and SED observed was higher than that in previous studies, which should be taken into consideration because these have been associated with higher morbimortality, and noncompliance and relapse, respectively.

Raloxifene as an Adjunctive Treatment for Postmenopausal Women With Schizophrenia: A 24-Week Double-Blind, Randomized, Parallel, Placebo-Controlled Trial.

UNLABELLED: The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator, appears to act similarly to estrogens on dopamine and serotonin brain systems. One previous trial by our team found that raloxifene was useful to improve negative, positive, and general psychopathological symptoms, without having the negative side effects of estrogens. In this study, we assess the utility of raloxifene in treating negative and other psychotic symptoms in postmenopausal women with schizophrenia exhibiting prominent negative symptoms. This was a 24-week, randomized, parallel, double-blind, placebo-controlled study. Patients were recruited from the inpatient and outpatient departments of Parc Sanitari Sant Joan de Déu, Hospital Universitari Institut Pere Mata, and Corporació Sanitària Parc Taulí. Seventy postmenopausal women with schizophrenia (DSM-IV) were randomized to either adjunctive raloxifene (38 women) or adjunctive placebo (32 women). Psychopathological symptoms were assessed at baseline and at weeks 4, 12, and 24 with the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). The addition of raloxifene (60 mg/d) to regular antipsychotic treatment significantly reduced negative (P = .027), general (P = .003), and total symptomatology (P = .005) measured with the PANSS during the 24-week trial, as compared to women receiving placebo. Also Alogia SANSS subscale improved more in the raloxifene (P = .048) than the placebo group. In conclusion, raloxifene improved negative and general psychopathological symptoms, compared with antipsychotic medication alone, in postmenopausal women with schizophrenia. These data replicate our previous results with a larger sample and a longer follow-up. TRIAL REGISTRATION: NCT01573637.

The influence of genetic variability and proinflammatory status on the development of bone disease in patients with Gaucher disease.

Gaucher disease, the most common lysosomal storage disorder, is caused by ß-glucocerebrosidase deficiency. Bone complications are the major cause of morbidity in patients with type 1 Gaucher disease (GD1). Genetic components strongly influence bone remodelling. In addition, chronic inflammation produced by Gaucher cells induces the production of several cytokines, which leads to direct changes in the bone remodelling process and can also affect the process indirectly through other immune cells. In this study, we analysed the association between bone mineral density (BMD), bone marrow burden score, and relevant genetic polymorphisms related to bone metabolism, as well as profiles of proinflammatory cytokines in a GD1 cohort. This study included 83 patients distributed according to bone status. BMD was measured with DXA and broadband ultrasound attenuation; bone marrow involvement was evaluated using MRI. We also analysed 26 SNPs located in 14 genes related to bone metabolism. To assess proinflammatory status, we analysed IL-4, IL-6, IL-7, IL-10, IL-13, MIP-1α, MIP-1ß, and TNFα in plasma samples from 71 control participants and GD1 patients. SNP genotype proportions and BMD differed significantly between ESRI c.453-397T>C and VDR c.1024+283G>A variants. We also observed significant associations between GD1 genotypes and bone affectation. When patients were stratified by spleen status, we observed significant correlations between non-/splenectomized groups and Spanish MRI (S-MRI) score. Across genotype proportions of non-/splenectomized patients and S-MRI, we observed significant differences in ESRI c.453-397T>C, VDR c.-83-25988G>A, and TNFRSF11B c.9C>G polymorphisms. We observed different significant proinflammatory profiles between control participants, treatment-naïve patients, and patients on enzyme replacement therapy (ERT); between non-/splenectomized patients (between untreated and ERT-treated patients) and among those with differing GBA genotypes. The data suggest that patients with GD1 have increased susceptibility to developing bone disease owing to the coexistence of genetic variants, and that genetic background in GD1 is fundamental to regulate the impact of proinflammatory status on the development of bone disease.

The effect of raloxifene on symptoms and cognitive functioning in a postmenopausal schizophrenia patient: a case report.

We report on a 61-year-old postmenopausal female with schizophrenia included in a raloxifene vs. placebo clinical trial and monitored during a 12-month period including a 3-month withdrawal period (6-9 months) without treatment. The patient was treated with raloxifene 60 mg/day adjuvant to antipsychotic medication for 6 months, medication was then withdrawn for 3 months and was reintroduced due to a worsening of symptoms. We assessed the patient with PANSS and other neuropsychological tests. The patient improved in psychopathology and cognitive level in some aspects related to executive functions. During 3 months without the drug, the patient's condition deteriorated. When the drug was reintroduced, improvements were again observed. Raloxifene may be useful as an adjuvant treatment for psychopathological symptoms and some cognitive aspects in women with chronic schizophrenia.

Visual encoding impairment in patients with schizophrenia: contribution of reduced working memory span, decreased processing speed, and affective symptoms.

OBJECTIVE: Previous research has revealed the contribution of decreased processing speed and reduced working memory span in verbal and visual memory impairment in patients with schizophrenia. The role of affective symptoms in verbal memory has also emerged in a few studies. The authors designed a picture recognition task to investigate the impact of these factors on visual encoding. METHOD: Two types of pictures (black and white vs. colored) were presented under 2 different conditions of context encoding (either displayed at a specific location or in association with another visual stimulus). It was assumed that the process of encoding associated pictures was more effortful than that of encoding pictures that were presented alone. Working memory span and processing speed were assessed. RESULTS: In the patient group, working memory span was significantly associated with the recognition of the associated pictures but not significantly with that of the other pictures. Controlling for processing speed eliminated the patients' deficit in the recognition of the colored pictures and greatly reduced their deficit in the recognition of the black-and-white pictures. The recognition of the black-and-white pictures was inversely related to anxiety in men and to depression in women. CONCLUSIONS: Working memory span constrains the effortful visual encoding processes in patients, whereas processing speed decrement accounts for most of their visual encoding deficit. Affective symptoms also have an impact on visual encoding, albeit differently in men and women.

Double-blind, placebo-controlled study of the efficacy of reboxetine and citalopram as adjuncts to atypical antipsychotics for negative symptoms of schizophrenia.

OBJECTIVE: In this study, we assessed the efficacy of 2 pharmacodynamically different antidepressants, citalopram (a selective serotonin reuptake inhibitor) and reboxetine (a norepinephrine reuptake inhibitor), as adjunctive therapy to risperidone and olanzapine for the treatment of negative symptoms in schizophrenia. METHOD: We performed a 6-month, multicenter, double-blind, randomized, placebo-controlled clinical trial. The recruitment period was from November 2008 to December 2011.The sample comprised 90 patients with a diagnosis of schizophrenia (DSM-IV criteria) who exhibited negative symptoms. The patients were recruited from 10 centers in different cities of the Spanish State. The primary efficacy measure was change in score on the negative subscale of the Positive and Negative Syndrome Scale (PANSS) between baseline and 6-month assessment. Other efficacy measures were changes in the PANSS subscales and total score, as well as the Scale for the Assessment of Negative Symptoms (SANS) subscales and total score. RESULTS: For statistical analysis, we employed mixed-effects models. We did not find statistically significant differences between the placebo group and the 2 treatment groups at 6-month assessments for the PANSS total (P=.6511), any PANSS subscale (negative [P=.5533], positive [P=.1723], or general psychopathology [P=.2083]), or the SANS (P= .5884). Cohen d measure showed a small effect size below the 0.5 threshold for all comparisons. CONCLUSIONS: In conclusion, our results do not support adjunctive use of citalopram or reboxetine with risperidone or olanzapine for the treatment of negative symptoms in schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01300364.

Effects of raloxifene on cognition in postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial.

Studies of estrogen therapy in postmenopausal women provide evidence of an effect of sex hormones on cognitive function. Estrogen has demonstrated some utility in the prevention of normal, age-related decline in cognitive functions, especially in memory. The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator (SERM), appears to act similarly to conjugated estrogens on dopamine and serotonin brain systems, and may be a better option since it lacks the possible negative effects of estrogen on breast and uterine tissue. We assessed the utility of raloxifene as an adjuvant treatment for cognitive symptoms in postmenopausal women with schizophrenia in a 12-week, double-blind, randomized, placebo-controlled study. Patients were recruited from both the inpatient and outpatient departments. Thirty-three postmenopausal women with schizophrenia (DSM-IV) were randomized to receive either adjuvant raloxifene (16 women) or adjuvant placebo (17 women) for three months. The main outcome measures were: Memory, attention and executive functions. Assessment was conducted at baseline and week 12. The total sample is homogenous with respect to: age, years of schooling, illness duration, baseline symptomatology and pharmacological treatment. The addition of raloxifene (60 mg) to regular antipsychotic treatment showed: we found significant differences in some aspects of memory and executive function in patients treated with raloxifene. This improvement does not correlate with clinical improvement. The use of raloxifene as an adjuvant treatment in postmenopausal women with schizophrenia seems to be useful in improving cognitive symptoms.

Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the "adenosine hypothesis".

Schizophrenia (SZ) is a major chronic neuropsychiatric disorder characterized by a hyperdopaminergic state. The hypoadenosinergic hypothesis proposes that reduced extracellular adenosine levels contribute to dopamine D2 receptor hyperactivity. ATP, through the action of ecto-nucleotidases, constitutes a main source of extracellular adenosine. In the present study, we examined the activity of ecto-nucleotidases (NTPDases, ecto-5'-nucleotidase, and alkaline phosphatase) in the postmortem putamen of SZ patients (n = 13) compared with aged-matched controls (n = 10). We firstly demonstrated, by means of artificial postmortem delay experiments, that ecto-nucleotidase activity in human brains was stable up to 24 h, indicating the reliability of this tissue for these enzyme determinations. Remarkably, NTPDase-attributable activity (both ATPase and ADPase) was found to be reduced in SZ patients, while ecto-5'-nucleotidase and alkaline phosphatase activity remained unchanged. In the present study, we also describe the localization of these ecto-enzymes in human putamen control samples, showing differential expression in blood vessels, neurons, and glial cells. In conclusion, reduced striatal NTPDase activity may contribute to the pathophysiology of SZ, and it represents a potential mechanism of adenosine signalling impairment in this illness.

Factors predicting hostility in outpatients with schizophrenia: 36-month results from the SOHO study.

This analysis explored the prevalence, incidence, and predictors of hostility in the European Schizophrenia Outpatient Health Outcomes (EU-SOHO) study. Data were collected at baseline and up to 36 months on the presence of hostility, clinical course and severity, medication compliance, side effects, substance/alcohol abuse, and being a crime survivor. Regression models were fitted to test the association between predictors and the presence of hostility. Hostility prevalence in the 6 months before baseline was 27.9%, and the incidence at 3 years was 14.0%. Variables related to hostility during follow-up were age, male sex, alcohol/substance abuse, tardive dyskinesia, extrapyramidal symptoms, cognitive impairment, noncompliance, and hospitalization. Being a crime survivor, being married, not living independently, and not being in paid employment were associated with hostility at baseline. Clinical and social variables are related to hostility in schizophrenia. Extrapyramidal symptoms and tardive dyskinesia, alcohol/substance abuse, cognitive impairment, medication noncompliance, and hospitalizations are predictors of future hostility.

Analysis of Sp transcription factors in the postmortem brain of chronic schizophrenia: a pilot study of relationship to negative symptoms.

Negative symptoms are the most resilient manifestations in schizophrenia. An imbalance in dopamine and glutamate pathways has been proposed for the emergence of these symptoms. SP1, SP3 and SP4 transcription factors regulate genes in these pathways, suggesting a possible involvement in negative symptoms. In this study, we characterized Sp factors in the brains of subjects with schizophrenia and explored a possible association with negative symptoms. We also included analysis of NR1, NR2A and DRD2 as Sp target genes. Postmortem cerebellum and prefrontal cortex from an antemortem clinically well-characterized and controlled collection of elderly subjects with chronic schizophrenia (n = 16) and control individuals (n = 14) were examined. We used the Positive and Negative Syndrome and the Clinical Global Impression Schizophrenia scales, quantitative PCR and immunoblot. SP1 protein and mRNA were reduced in the prefrontal cortex in schizophrenia whereas none of Sp factors were altered in the cerebellum. However, we found that SP1, SP3 and SP4 protein levels inversely correlated with negative symptoms in the cerebellum. Furthermore, NR2A and DRD2 mRNA levels correlated with negative symptoms in the cerebellum. In the prefrontal cortex, SP1 mRNA and NR1 and DRD2 inversely correlated with these symptoms while Sp protein levels did not. This pilot study not only reinforces the involvement of SP1 in schizophrenia, but also suggests that reduced levels or function of SP1, SP4 and SP3 may participate in negative symptoms, in part through the regulation of NMDA receptor subunits and/or Dopamine D2 receptor, providing novel information about the complex negative symptoms in this disorder.

Abnormal functioning of the semantic network in schizophrenia patients with thought disorganization. An exemplar production task.

Numerous studies have indicated that thought disorganization in schizophrenia is associated with an enhanced semantic priming effect. This suggests abnormal functioning of the semantic network in these patients, with disinhibited spreading of semantic activation. We investigated whether thought disorganization is also associated with atypical responses in the production of semantic category exemplars. An exemplar production task was administered to 43 patients with schizophrenia and 24 healthy controls. The names of 16 semantic categories were provided, and the participants were requested to produce an exemplar for each category. The typicality of the response was rated according to norms. Higher ratings of thought disorganization were associated with the production of more atypical exemplars. In addition, the patients with high thought disorganization scores were significantly more atypical in their responses than were the healthy controls. In contrast, the patients with low thought disorganization scores were equivalent to the healthy controls. Higher ratings of affective flattening were associated with the production of less atypical exemplars. The results corroborate, within a different paradigm than semantic priming, the theory that thought disorganization is associated with faster and more distant connections within the semantic network. This effect is counteracted by affective flattening.

Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator, appears to act similarly to conjugated estrogens on dopamine and serotonin brain systems and may be a better option since it lacks the possible negative effects of estrogen on breast and uterine tissue. In this study, we assess the utility of raloxifene as an adjunctive treatment for negative symptoms and other psychotic symptoms in postmenopausal women with schizophrenia. METHOD: This was a 12-week, double-blind, randomized, placebo-controlled study. Patients were recruited from both the inpatient and outpatient departments of Parc Sanitari Sant Joan de Déu, Barcelona, Spain, and Corporació Sanitària Parc Taulí, Sabadell, Spain. Thirty-three postmenopausal women with schizophrenia (DSM-IV criteria) who exhibited prominent negative symptoms were randomized to either adjunctive raloxifene (16 women; mean age = 60.14 years, SD = 6.41 years) or adjunctive placebo (17 women; mean age = 62.66 years, SD = 4.54 years) for 12 weeks. The period of recruitment lasted from January 2005 through June 2009. Psychopathological symptoms were assessed at baseline and weeks 4, 8, and 12 by means of the Positive and Negative Syndrome Scale. RESULTS: The addition of raloxifene (60 mg/d) to regular antipsychotic treatment significantly reduced negative (P = .044), positive (P = .031), and general psychopathological (P = .045) symptoms during the 12-week trial as compared with women receiving placebo. CONCLUSIONS: Raloxifene as an adjuvant treatment in postmenopausal women with schizophrenia who exhibit prominent negative symptoms appears to be useful in improving negative, positive, and general psychopathological symptoms. If more extensive and longer-term studies confirm and expand upon these positive results, the use of raloxifene could be recommended in postmenopausal patients with schizophrenia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01041092.

[Therapeutic targets in Gaucher's disease]. / Objetivos terapéuticos en la enfermedad de Gaucher.

Gaucher's disease (GD) occurs because of deficiency of the enzyme beta-glucocerebrosidase that results in accumulation of this glycolipid compound in the cells of the macrophage-monocyte system. There are 3 types: type 1 is non-neuronopathic with primarily visceral signs and symptoms which range tremendously in severity; infantile-onset type 2 and later-onset type 3 involve the central nervous system. More than 300 mutations have been described in the gene, partially explaining phenotypic heterogeneity. Commercialization in 1991 of the first enzyme replacement therapy, alglucerase, resulted in a revolution in the management of patients with symptomatic GD (i.e., by improving the hematological and visceral signs and symptoms). Within the first 5 years of alglucerase, its safety and efficacy in improving hemoglobin levels and platelet counts, and in reducing splenic and hepatic enlargement were confirmed albeit recognizing its inability to impact neurological symptoms and signs because of its large molecular size. Recombinant imiglucerase soon replaced alglucerase as the standard of care for GD. The therapeutic targets recently defined as treatment goals were: normalization of cell counts; reduction of liver and spleen volume; elimination of the infiltration in the bone marrow to prevent the complications, and improvement in surrogate biomarkers.

Antipsychotic treatment discontinuation in previously untreated patients with schizophrenia: 36-month results from the SOHO study.

Data from the 3-year, prospective, observational SOHO study were used to compare the effectiveness (in terms of treatment discontinuation) and the tolerability of olanzapine, risperidone, other atypicals and typical antipsychotics in 1009 previously untreated outpatients with schizophrenia who started monotherapy at baseline. Kaplan-Meier survival analysis estimated the time to treatment discontinuation by the treatment group, Cox proportional hazards regression models identified the variables associated with treatment discontinuation (adjusted for baseline differences between treatment groups), and logistic regression models compared the tolerability profiles of the different treatment groups. Of the 931 patients analyzed, 31.9% discontinued the medication initiated at baseline during the 3-year follow-up. Olanzapine had the lowest rate of discontinuation (28.9%), followed by other atypical (34.0%), risperidone (36.2%) and typical antipsychotics (44.5%). Compared to olanzapine, risk of treatment discontinuation was higher with typical antipsychotics (hazard ratio [HR] 1.75; 95% confidence interval [CI] 1.11, 2.78) or risperidone (HR 1.36; 95% CI 1.02, 1.82). A higher baseline Clinical Global Impression (CGI) positive score was associated with a higher risk of treatment discontinuation (HR 1.18; 95% CI 1.06, 1.30). Olanzapine was associated with a lower frequency of extrapyramidal symptoms than other antipsychotics, fewer prolactin-related adverse events than risperidone and other atypical antipsychotics, but greater weight gain than typicals and risperidone. For all analyses, comparison with the other atypical group is limited due to its small sample size (n=50). In conclusion, treatment effectiveness and tolerability varied among antipsychotic medications in previously untreated patients with schizophrenia. The results should be interpreted conservatively given the observational study design.