Obsessive-compulsive symptoms and disorder in patients with schizophrenia treated with clozapine or haloperidol

We conducted a cross-sectional study to compare the prevalence and severity of obsessive-compulsive symptoms (OCSs) and obsessive-compulsive disorder (OCD) in patients with schizophrenia treated with clozapine or haloperidol. Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I disorders-patient edition was used to diagnose schizophrenia and OCD. Sixty subjects, 40 of them using clozapine and 20 using haloperidol, completed the Yale-Brown Obsessive-Compulsive Scale, the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression. The prevalence of OCD in patients taking clozapine was 20%, whereas the prevalence of patients taking haloperidol was 10%, although this difference was not statistically significant (P = .540). However, patients using clozapine showed higher severity of OCSs than patients using haloperidol (P = .027) did. When schizophrenia patients were divided according to the presence or absence of OCD or OCSs, patients with schizophrenia and OCD or OCSs showed higher severity of schizophrenia symptoms when compared to those with schizophrenia without OCD and OCSs (P = .002). A PANSS total score higher than 70 and the use of antidepressants were predictors of the presence of OCSs or OCD. Schizophrenia patients taking clozapine had higher severity scores both in obsessive-compulsive and schizophrenia rating scales. These results may support an association between the exacerbation of obsessive-compulsive phenomena and the use of clozapine. (C) 2009 Elsevier Inc. All rights reserved.

State-dependent microstructural white matter changes in bipolar I depression

Abnormalities in fronto-limbic-striatal white matter (WM) have been reported in bipolar disorder (BD), but results have been inconsistent across studies. Furthermore, there have been no detailed investigations as to whether acute mood states contribute to microstructural changes in WM tracts. In order to compare fiber density and structural integrity within WM tracts between BD depression and remission, whole-brain fractional anisotropy (FA) and mean diffusivity (MD) were assessed in 37 bipolar I disorder (BD-I) patients (16 depressed and 21 remitted), and 26 healthy individuals with diffusion tensor imaging. Significantly decreased FA and increased MD in bilateral prefronto-limbic-striatal white matter and right inferior fronto-occipital, superior and inferior longitudinal fasciculi were shown in all BD-I patients versus controls, as well as in depressed BD-I patients compared to both controls and remitted BD-I patients. Depressed BD-I patients also exhibited increased FA in the ventromedial prefrontal cortex. Remitted BD-I patients did not differ from controls in FA or MD. These findings suggest that BD-I depression may be associated with acute microstructural WM changes.

Schizophrenia Modifying the Expression of Gender Identity Disorder

According to the Brazilian Federal Medical Association, transsexualism is recognized as a gender identity disorder if a long-term diagnostic therapeutic process has demonstrated that the transposition of gender roles is irreversible, and if only hormonal and surgical procedures are appropriate to relieve the stress associated with the gender identity. Although such treatment will only be initiated with caution and after a long phase of intense diagnostic screening, the differentiation between pure identity disorders and transsexual feelings secondary to an ongoing psychopathologic process, such as schizophrenia, can be arduous for many health professionals. To report a case of a female patient with schizophrenia and transsexualism and the risks of a potential diagnostic confusion. A 19-year-old black woman, with an 8-year history of undifferentiated schizophrenia and intense gender dysphoria, was referred for sex reassignment surgery evaluation in the Ambulatory for the Treatment of Sexual Disorders of the ABC Medical School. After a more adequate antipsychotic treatment, her masculine behavior has persisted, but her desire to change her own genital organs has decreased. A better acceptance of the multiplicity of possible genders should neither contribute to inadequate interpretations of the signs and symptoms of our patients nor facilitate dangerous clinical or surgical recommendations. Baltieri DA, and De Andrade AG. Schizophrenia Modifying the expression of gender identity disorder. J Sex Med **;**:**-**.

Aripiprazole for Patients with Schizophrenia and Schizoaffective Disorder: An Open-Label, Randomized, Study Versus Haloperidol

Introduction: Aripiprazole, a dopamine D(2) receptor partial agonist, has also partial agonist activity at serotonin (5-HT)(1A) receptors and antagonist activity at 5-HT(2A) receptors. Methods: In this 8-week, multicenter, randomized, parallel-group, open-label, flexible-dose study, patients diagnosed with schizophrenia or schizoaffective disorder were randomized to aripiprazole 15-30 mg/day or haloperidol 10-15 mg/day. Results: Patients treated with both aripiprazole and haloperidol improved from baseline in Positive and Negative Syndrome Scale total, positive, and negative scores as well as in Clinical Global Impressions scores (all P<.001). At the end of the study, the percentage of patients classified as responders-according to >= 40% reduction in the Positive and Negative Syndrome Scale negative subscale score-was significantly higher in the aripiprazole group (20%) than in the haloperidol group (0%) (P<.05). Additionally, a higher number of patients receiving haloperidol required more anticholinergic medications (P<.001) than aripiprazole-treated patients, whereas more aripiprazole (45.5%) than haloperidol-treated patients (12.9%) required benzodiazepines (P=.002). At endpoint, rates of preference of medication were higher in the aripiprazole group (63.2%) than in the haloperidol group (21.7%), as expressed by patients and caregivers (P=.001). Conclusion: Aripiprazole and haloperidol had similar efficacy in terms of reduction of overall psychopathology. Although aripiprazole has been demonstrated to be superior concerning negative symptoms and in terms of tolerability (extrapyramidal symptoms) and preferred by patients and caregivers than haloperidol, significantly more aripiprazole-treated patients required benzodiazepines.

Differential expression of presynaptic genes in a rat model of postnatal hypoxia: relevance to schizophrenia

Obstetric complications play a role in the pathophysiology of schizophrenia. However, the biological consequences during neurodevelopment until adulthood are unknown. Microarrays have been used for expression profiling in four brain regions of a rat model of neonatal hypoxia as a common factor of obstetric complications. Animals were repeatedly exposed to chronic hypoxia from postnatal (PD) day 4 through day 8 and killed at the age of 150 days. Additional groups of rats were treated with clozapine from PD 120-150. Self-spotted chips containing 340 cDNAs related to the glutamate system (""glutamate chips"") were used. The data show differential (up and down) regulations of numerous genes in frontal (FR), temporal (TE) and parietal cortex (PAR), and in caudate putamen (CPU), but evidently many more genes are upregulated in frontal and temporal cortex, whereas in parietal cortex the majority of genes are downregulated. Because of their primary presynaptic occurrence, five differentially expressed genes (CPX1, NPY, NRXN1, SNAP-25, and STX1A) have been selected for comparisons with clozapine-treated animals by qRT-PCR. Complexin 1 is upregulated in FR and TE cortex but unchanged in PAR by hypoxic treatment. Clozapine downregulates it in FR but upregulates it in PAR cortex. Similarly, syntaxin 1A was upregulated in FR, but downregulated in TE and unchanged in PAR cortex, whereas clozapine downregulated it in FR but upregulated it in PAR cortex. Hence, hypoxia alters gene expression regionally specific, which is in agreement with reports on differentially expressed presynaptic genes in schizophrenia. Chronic clozapine treatment may contribute to normalize synaptic connectivity.

Chronic polyarthritis as the first manifestation of juvenile systemic lupus erythematosus patients

Objective: To evaluate the prevalence of chronic polyarthritis in juvenile systemic lupus erythematosus (JSLE) and to describe the manifestations, treatments, and outcomes in these patients. Methods: From January 1983 to July 2010, 5419 patients were followed up at the Pediatric Rheumatology Unit of the University Hospital and 271 (5%) of them had JSLE (American College of Rheumatology [ACR] criteria). `Rhupus` was classified as the overlap of juvenile idiopathic arthritis (International League of Associations for Rheumatology [ILAR] criteria) and JSLE. We evaluated demographic data, polyarthritis and other clinical manifestations, disease activity and damage, laboratory exams, radiographic findings, treatments, and outcomes. Results: The prevalence of chronic polyarthritis in this JSLE population was 2.6% (7/271). This articular involvement was the initial manifestation in all seven JSLE patients. The median duration of chronic polyarthritis was 11 months (range 2-15 months). Interestingly, rhupus with chronic polyarthritis and limitation of movement, presence of rheumatoid factor, autoantibodies, and/or radiographic abnormalities (juxtaarticular osteopenia, joint-space narrowing, or erosions) was evidenced in three patients. No patient had deformities of hands and feet associated with Jaccoud`s arthropathy or osteonecrosis. All patients were treated with nonsteroidal anti-inflammatory drugs (NSAIDs, naproxen 10-15 mg/kg/day) when polyarthritis diagnosis was established. Prednisone and antimalarials were administered at JSLE diagnosis. The three non-responsive rhupus patients were treated in conjunction with immunosuppressive drugs (methotrexate, azathioprine, and/or cyclosporine). Conclusions: Chronic polyarthritis was a rare lupus manifestation in active pediatric patients. The interesting overlap between chronic arthritis and lupus, called rhupus suggests a new entity with a different clinical profile and a poor response to treatment with NSAIDs alone. In addition, the occurrence of this association in JSLE patients could be classified as a clinical sub-group of JSLE with possible specific genetic determinants. Lupus (2011) 20, 960-964.

Cost Effectiveness of Positron Emission Tomography in Patients With Hodgkin`s Lymphoma in Unconfirmed Complete Remission or Partial Remission After First-Line Therapy

Purpose To assess the cost effectiveness of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with Hodgkin`s lymphoma (HL) with unconfirmed complete remission (CRu) or partial remission (PR) after first-line treatment. Patients and Methods One hundred thirty patients with HL were prospectively studied. After treatment, all patients with CRu/PR were evaluated with FDG-PET. In addition, PET-negative patients were evaluated with standard follow-up, and PET-positive patients were evaluated with biopsies of the positive lesions. Local unit costs of procedures and tests were evaluated. Cost effectiveness was determined by evaluating projected annual economic impact of strategies without and with FDG-PET on HL management. Results After treatment, CRu/PR was observed in 50 (40.0%) of the 127 patients; the sensitivity, specificity, and positive and negative predictive values of FDG-PET were 100%, 92.0%, 92.3%, and 100%, respectively (accuracy of 95.9%). Local restaging costs without PET were $350,050 compared with $283,262 with PET, a 19% decrease. The incremental cost-effectiveness ratio is -$3,268 to detect one true case. PET costs represented 1% of total costs of HL treatment. Simulated costs in the 974 patients registered in the 2008 Brazilian public health care database showed that the strategy including restaging PET would have a total program cost of $56,498,314, which is $516,942 less than without restaging PET, resulting in a 1% cost saving. Conclusion FDG-PET demonstrated 95.9% accuracy in restaging for patients with HL with CRu/PR after first-line therapy. Given the observed probabilities, FDG-PET is highly cost effective and would reduce costs for the public health care program in Brazil.

Impact of Cytomegalovirus Infection in Lung Transplant Patients Under Universal Prophylaxis: Single-Center Experience in Brazil

Introduction. Cytomegalovirus (CMV) infection, a common complication in lung transplant (LT) patients, is associated with worse outcomes. Therefore, prophylaxis and surveillance with preemptive treatment is recommended. Objectives. Describe the epidemiology and impact on mortality of CMV infection in LT patients receiving CMV prophylaxis. Methods. Single-center retrospective cohort of LT recipients from August 2003 to March 2008. We excluded patients with survival or follow-up shorter than 30 days. We reviewed medical charts and all CMV pp65 antigen results. Results. Forty-seven patients met the inclusion criteria and 19 (40%) developed a CMV event: eight CMV infections, seven CMV syndromes, and 15 CMV diseases. The mean number of CMV events for each patient was 1.68 +/- 0.88. Twelve patients developed CMV events during prophylaxis (5/12 had CMV serology D+/R-). Forty-six of the 47 patients had at least one episode of acute rejection (mean 2.23 +/- 1.1). Median follow-up was 22 months (range = 3-50). There were seven deaths. Upon univariate analysis, CMV events were related to greater mortality (P = .04), especially if the patient experienced more than two events (P = .013) and if the first event occurred during the first 3 months after LT (P = .003). Nevertheless, a marginally significant relationship between CMV event during the first 3 months after LT and mortality was observed in the multivariate analysis (hazards ratio: 7.46; 95% confidence interval: 0.98-56.63; P = .052). Patients with CMV events more than 3 months post-LT showed the same survival as those who remained CMV-free. Conclusion. Prophylaxis and preemptive treatment are safe and effective; however, the patients who develop CMV events during prophylaxis experience a worse prognosis.

Physiological Responses to Brain Stimulation During Limbic Surgery: Further Evidence of Anterior Cingulate Modulation of Autonomic Arousal

Background: In view of conflicting neuroimaging results regarding autonomic-specific activity within the anterior cingulate cortex (ACC), we investigated autonomic responses to direct brain stimulation during sterecitactic limbic surgery. Methods: Skin conductance activity and accelerative heart rate responses to multi-voltage stimulation of the ACC (n = 7) and paralimbic subcauclate (n = 5) regions were recorded during bilateral anterior cingulotomy and bilateral subcauclate tractotomy (in patients that had previously received an adequate lesion in the ACC), respectively. Results: Stimulations in both groups were accompanied by increased autonomic arousal. Skin conductance activity was significantly increased during ACC stimulations compared with paralimbic targets at 2 V (2.34 +/- .68 [score in microSiemens +/- SE] vs. .34 +/- .09, p = .013) and 3 V (3.52 +/- .86 vs. 1.12 +/- .37, p = .036), exhibiting a strong ""voltage-response"" relationship between stimulus magnitude and response amplitude (difference from 1 to 3 V = 1.15 +/- .90 vs. 3.52 +/- .86, p = .041). Heart rate response was less indicative of between-group differences. Conclusions: This is the first study of its kind aiming at seeking novel insights into the mechanisms responsible for central autonomic modulation. It supports a concept that interregional interactions account for the coordination of autonomic arousal.

Early fetal cystoscopy for first-trimester severe megacystis

Objectives To report the feasibility of early fetal cystoscopy for the prenatal diagnosis and therapy of severe first-trimester megacystis. Methods Between January 2008 and February 2010, early fetal cystoscopy at 16 weeks of gestation was offered to 15 patients whose fetuses presented with severe first-trimester megacystis. All infants were followed up for 6-12 months after birth. Autopsy was always performed whenever fetal or neonatal deaths occurred. Results Seven patients decided to undergo fetal therapy, and eight elected to continue with expectant observation. One fetus died before early fetal cystoscopy was performed. Therefore, six fetuses underwent early fetal cystoscopy. Urethral atresia was diagnosed in three fetuses during fetal cystoscopy and confirmed at autopsy following termination of pregnancy at 19-20 weeks in all cases. Posterior urethral valves were diagnosed and successfully fulgurated by laser during early cystoscopy in three fetuses, two of which survived with normal renal and bladder function after birth; the remaining fetus had a postnatal diagnosis of megacystis-microcolon intestinal hypoperistalsis syndrome and died neonatally. In the expectantly managed group, no survivals were observed, even among cases with `isolated` posterior urethral valves. Conclusions Percutaneous early fetal cystoscopy is feasible for prenatal diagnosis and therapy of severe megacystis. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.

The renin-angiotensin system is upregulated in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis

Purpose: As reported by several authors, angiotensin II (AngII) is a proinflammatory molecule that stimulates the release of inflammatory cytokines and activates nuclear factor kappa B (NF kappa B), being also associated with the increase of cellular oxidative stress. Its production depends on the activity of the angiotensin converting enzyme (ACE) that hydrolyzes the inactive precursor angiotensin I (AngI) into AngII. It has been suggested that AngII underlies the physiopathological mechanisms of several brain disorders such as stroke, bipolar disorder, schizophrenia, and disease. The aim of the present work was to localize and quantify AngII AT1 and AT2 receptors in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis (MTS) submitted to corticoamygdalohippocampectomy for seizure control. Method: Immunohistochemistry, Western blot, and real-time PCR techniques were employed to analyze the expression of these receptors. Results: The results showed an upregulation of AngII AT1 receptor as well as its messenger ribonucleic acid (mRNA) expression in the cortex and hippocampus of patients with MTS. In addition, an increased immunoexpression of AngII AT2 receptors was found only in the hippocampus of these patients with no changes in its mRNA levels. Discussion: These data show, for the first time, changes in components of renin-angiotensin system (RAS) that could be implicated in the physiopathology of MTS.

Chronic autoimmune urticaria as the first manifestation of juvenile systemic lupus erythematosus

Chronic urticaria (daily or almost daily symptoms lasting for more than six weeks) is characterized by wheals and erythema, with or without itching. A few case reports have shown chronic autoimmune urticaria at the beginning of systemic lupus erythematosus (SLE), particularly in adults. However, the prevalence of this manifestation in a lupus paediatric population was not studied. During 27 consecutive years, 5419 patients were followed up at our University Hospital and 271 (5%) had juvenile SLE (American College of Rheumatology criteria). Two of them (0.7%) had chronic and painless autoimmune urticaria as the first manifestation of juvenile SLE, and were reported herein. One case was a five-year old female with continuous widespread urticaria (duration 120 days), antinuclear antibodies (ANA) 1:640 (dense fine speckled pattern) and elevated complement levels. The juvenile SLE diagnosis was established after one year. The other case was a 13-year old female who had chronic widespread urticaria (lasting 45 days), ANA 1:160 (fine speckled pattern) and normal complement levels. The juvenile SLE diagnosis was established after three years. In conclusion, chronic autoimmune urticaria is very rare and may be the first lupus manifestation, particularly associated with the presence of autoantibodies. This study reinforces the importance of a rigorous follow-up in children and adolescents suffering from autoimmune urticaria due to the possibility of connective tissue disorders, such as paediatric lupus. Lupus (2011) 20, 763-766.

Experimental Model of Isolated Lung Perfusion in Rats: First Brazilian Experience Using the IL-2 Isolated Perfused Rat or Guinea Pig Lung System

Introduction. Lung transplantation has become the mainstay therapy for patients with end-stage lung disease refractory to medical management. However, the number of patients listed for lung transplantation largely exceeds available donors. The study of lung preservation requires accurate, cost-effective small animal models. We have described a model of ex vivo rat lung perfusion using a commercially available system. Methods. Male Wistar rats weighing 250 g-300 g were anesthetized with intraperitoneal sodium thiopental (50 mg/kg body weight). The surgical technique included heart-lung block extraction, assembly, and preparation for perfusion and data collection. We used an IL-2 Isolated Perfused Rat or Guinea Pig Lung System (Harvard Apparatus, Holliston, Mass, United States; Hugo Sachs Elektronik, Alemanha). Results. Preliminary results included hemodynamic and pulmonary mechanics data gathered in the experiments. Conclusion. The isolated rat lung perfusion system is a reliable method to assess lung preservation.

Liver transplantation at a University Hospital, Faculty of the Medicine of Ribeirao Preto, University of Sao Paulo: Results for the first 60 recipients

The purpose of the present article was to present the series operated by a Liver Transplant Group of the interior of the State of Sao Paulo, Brazil. Sixty patients were transplanted from May 2001 to May 2007. Thirty percent of the patients had alcoholic cirrhosis. 18.3% had C virus-induced cirrhosis, 10% had C virus- and alcohol-induced cirrhosis, 6% had B virus-induced cirrhosis, 13.3% had cryptogenic cirrhosis, 8.3% autoimmune cirrhosis, 13.3% had familial amyloidotic polyneuropathy (FAP), and 13.3% had hepatocellular carcinomas. The series was divided by a chronological criterion into two periods: A (n = 42) and B (n = 18) with the latter group operated based upon the Model for End-stage Liver Disease (MELD) criterion. Sixty-nine percent were men. Age ranged from 14 to 66 years. Period A included 12% Child A: 59.2%, Child B; 24%, Child C; and 4.8%, FAR Period B comprises 22.2% Child A: 11.1%, Child B: 33.3%, Child C: and 33.3%, FAP. MELD scores ranged from 8 to 35 for period A and from 14 to 31 for period B. Intraoperative mortality was 2/42 patients for period A and 0/18 for period B, overall postoperative mortality was 40% including for period A, 35% among Child B and C patients, and 5 % among FAP and Child A patients (P <.05) and 16.6% for period B among 11. 1 % Child B patients and 5.5 % FAP patients; 3.3 % of patients required retransplantation due to hepatic artery thrombosis. Real postoperative survival was 60% during period A and 83.3% during period B, with an overall survival rate of 67% for the two periods. The present results show levels of postoperative mortality, (especially during period B), and survival rates similar to those reported by several other centers in Brazil.

Monoclonal B-cell lymphocytosis in first-degree relatives of patients with sporadic (non-familial) chronic lymphocytic leukaemia

Although biological similarities have been described among monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukaemia (CLL), the relationships between these two conditions are not fully understood, and new epidemiological studies in different populations and different countries continue to be reported. Here, we investigated 167 first-degree relatives from 42 families of patients with non-familial (sporadic) CLL, using four-colour flow cytometry. MBL was found in seven of 167 subjects (4.1%). Monoclonality was detected in all cases either by light-chain restriction or by polymerase chain reaction. Fluourescence in situ hybridization did not show any chromosomal abnormality. The prevalence of MBL according to age was 0 (0/54) in individuals aged less than 40 years, 2.5% (2/81) between 40 and 60 years, and 15.6% (5/32) in individuals over 60 years. The prevalence of MBL cases in individuals over 60 years was similar to that found in familial CLL relatives at the same age group. This suggests that in older first-degree relatives of patients with sporadic CLL, the risk of MBL detection is as high as in older first-degree relatives from CLL families, which could render these individuals belonging to `sporadic CLL families` as susceptible as individuals from `familial CLL` to the development of clinical CLL.