Polygenic risk score analyses of symptoms and treatment response in an antipsychotic-naive first episode of psychosis cohort.

In this study, we aimed to test if the schizophrenia (SCZ) polygenic risk score (PRS) was associated with clinical symptoms in (a) the first episode of psychosis pre-treatment (FEP), (b) at nine weeks after initiation of risperidone treatment (FEP-9W) and (c) with the response to risperidone. We performed a detailed clinical assessment of 60 FEP patients who were antipsychotic-naive and, again, after nine weeks of standardized treatment with risperidone. After blood collection and DNA isolation, the samples were genotyped using the Illumina PsychArrayChip and then imputed. To calculate PRS, we used the latest available GWAS summary statistics from the Psychiatric Genomics Consortium wave-2 SCZ group as a training set. We used Poisson regression to test association between PRS and clinical measurements correcting for the four principal components (genotyping). We considered a p-value < 0.0014 (Bonferroni correction) as significant. First, we verified that the schizophrenia PRS was also able to distinguish cases from controls in this south-eastern Brazilian sample, with a similar variance explained to that seen in Northern European populations. In addition, within-cases analyses, we found that PRS is significantly correlated with baseline (pre-treatment) symptoms, as measured by lower clinical global assessment of functioning (-GAF), higher depressive symptoms and higher scores on a derived excitement factor. After standardized treatment for nine weeks, the correlation with GAF and the excitement factor disappeared while depressive symptoms became negatively associated with PRS. We conclude that drug (and other treatments) may confound attempts to understand the aetiological influence on symptomatology of polygenic risk scores. These results highlight the importance of studying schizophrenia, and other disorders, pre-treatment to understand the relationship between polygenic risk and phenotypic features.

Accessing Gene Expression in Treatment-Resistant Schizophrenia.

Schizophrenia (SCZ) is a mental disorder arising from a complex interaction of genetic and environmental factors. It has been suggested that treatment-resistant schizophrenia (TRS) is a distinct, more severe, and homogenous subgroup of schizophrenia that could present specific biological markers. Our aim was to characterize expression of target genes in blood of TRS patients compared with non-TRS (NTRS) patients and healthy controls (HC). TRS has been defined using failure to respond to two previous antipsychotic trials. We hypothesized that genes involved in neurodevelopment, myelination, neuroplasticity, neurotransmission, and miRNA processing could be involved in treatment resistance; then, we investigated 13 genes related to those processes in 256 subjects, being 94 healthy controls and 162 schizophrenia patients treated with antipsychotics. Of those, 78 were TRS patients and 84 were NTRS patients. Peripheral blood samples were collected from all subjects and RNA was isolated. Gene expression analysis was performed using the TaqMan low-density array (TLDA) technology. To verify the influence of expression quantitative trait loci (eQTLs), we evaluated single-nucleotide polymorphism (SNP) of all genes using data from GTEx Project. SNP genotypes were obtained from HumanOmniExpress BeadChip. We did not detect gene expression differences between TRS and NTRS subjects, indicating candidate genes specific to treatment resistance. We detected an upregulation of CNR1 and UFD1L gene expression in patients (TRS and NTRS groups) when compared to controls, that may be associated with the release of neurotransmitters, which can influence neuronal plasticity, or with a stress response-activating protein degradation. DICER1 and AKT1 expression increased slightly across the groups and could differentiate only the extreme opposite groups, HC and TRS. Both genes act in heterogeneous pathways, such as cell signaling and miRNA processing, and seem to have an increased demand in the TRS group. We did not detect any eQTLs in our sample that could explain differences in mRNA levels, suggesting a possible regulation by other mechanism, not driven by genotypes. Our data strengthen the importance of several biological pathways involved in the schizophrenia refractoriness and severity, adding knowledge to develop more effective treatments in the future.

Leukocyte telomere length variation in different stages of schizophrenia.

Recent research has demonstrated that telomere maintenance might be a key integrating point for the cumulative effect of genetic and environmental factors in patients with first-episode psychosis (FEP) and schizophrenia (SCZ). Eighty-one participants with antipsychotic-naïve FEP, 173 with SCZ and 438 HC were enrolled in this study. Psychiatric diagnosis was assessed using the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I). The Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS) and Calgary Depression Scale for Schizophrenia (CDSS) were used to measure symptoms severity. Telomere length (TL) was determined using a multiplex qPCR assay. After adjustment for age, years of education, and smoking status, we found that patients with SCZ had longer TL (relative ratio (RR) = 1.08) than the HC group (RR = 1.00, Wald χ2 = 12.48, p = 0.002). Further, non-remitted SCZ patients presented longer TL (RR = 1.00) compared to remitted SCZ (RR = 0.88, Wald χ2 = 7.20, p = 0.007). TL in patients also correlated to psychopathology assessment in terms of total (p = 0.003) and positive PANSS scores (p = 0.001). No correlation with negative PANSS, YMRS, and CDSS or effects of medication was found on TL. Although the exact pathways underlying longer TL in SCZ patients remain unclear, these findings raise more questions than answers and suggest that TL may be of immense value on SCZ progression. Further studies are required to investigate the association of TL in FEP and SCZ.

The role of the CNR1 gene in schizophrenia: a systematic review including unpublished data

Objective: Schizophrenia is a multifactorial disorder. It is known that a combination of extensive multiple common alleles may be involved in its etiology, each contributing with a small to moderate effect, and, possibly, some rare alleles with a much larger effect size. We aimed to perform a systematic review of association studies between schizophrenia (and its subphenotypes) and polymorphisms in the CNR1 gene, which encodes cannabinoid receptors classically implicated in schizophrenia pathophysiology, as well as to present unpublished results of an association study in a Brazilian population. Methods: Two reviewers independently searched for eligible studies and extracted outcome data using a structured form. Papers were retrieved from PubMed and ISI Web of Knowledge using the search term schizophrenia in combination with CNR1 or CB1 or cannabinoid receptor. Twenty-four articles met our inclusion criteria. We additionally present data from a study of our own comparing 182 patients with schizophrenia and 244 healthy controls. Results: No consistent evidence is demonstrated. Conclusion: Some seemingly positive association studies stress the need for further investigations of the possible role of endocannabinoid genetics in schizophrenia.

The role of the CNR1 gene in schizophrenia: a systematic review including unpublished data.

OBJECTIVE:: Schizophrenia is a multifactorial disorder. It is known that a combination of extensive multiple common alleles may be involved in its etiology, each contributing with a small to moderate effect, and, possibly, some rare alleles with a much larger effect size. We aimed to perform a systematic review of association studies between schizophrenia (and its subphenotypes) and polymorphisms in the CNR1 gene, which encodes cannabinoid receptors classically implicated in schizophrenia pathophysiology, as well as to present unpublished results of an association study in a Brazilian population. METHODS:: Two reviewers independently searched for eligible studies and extracted outcome data using a structured form. Papers were retrieved from PubMed and ISI Web of Knowledge using the search term schizophrenia in combination with CNR1 or CB1 or cannabinoid receptor. Twenty-four articles met our inclusion criteria. We additionally present data from a study of our own comparing 182 patients with schizophrenia and 244 healthy controls. RESULTS:: No consistent evidence is demonstrated. CONCLUSION:: Some seemingly positive association studies stress the need for further investigations of the possible role of endocannabinoid genetics in schizophrenia.

Bipolar disorder course, impaired glucose metabolism and antioxidant enzymes activities: A preliminary report.

This study aimed to examine the role of oxidative stress in bipolar disorder (BD) by evaluating the relationship among antioxidant enzymes activities, impaired glucose metabolism (IGM) and illness course. We measured the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GPx) in individuals with BD (N = 55) and healthy controls (N = 28). Information related to current and past psychiatric/medical history, as well as prescription of any pharmacological treatments was captured. Impaired glucose metabolism was operationalized as pre-diabetes or type 2 diabetes mellitus. Our results showed that, after adjustment for age, gender, alcohol use, smoking and current medication, both BD (p < 0.001) and IGM (p = 0.019) were associated with increased GPx activity, whereas only BD was associated with decreased SOD activity (p = 0.008). We also observed an interaction between BD and IGM on SOD activity (p = 0.017), whereas the difference between BD and controls was only significant in individuals with IGM (p = 0.009). IGM, GPx and SOD activity were independently associated with variables of illness course. Moreover, IGM moderated the association between SOD activity and number of mood episodes (p < 0.001), as a positive correlation between SOD activity and mood episodes was observed only in participants with IGM. In conclusion, BD and IGM are associated with independent and synergistic effects on markers of oxidative stress. The foregoing observations suggest that the heterogeneity observed in previous studies evaluating antioxidant enzymes in BD may be a function of concurrent IGM; and that imbalances in the oxidative system may subserve the association between BD and IGM, as well as its relationship with illness course.

Depression, Cytokine, and Cytokine by Treatment Interactions Modulate Gene Expression in Antipsychotic Naïve First Episode Psychosis.

In schizophrenia, genetic and environmental factors affect neurodevelopment and neuroprogressive trajectory. Altered expression of neuro-immune genes and increased levels of cytokines are observed, especially in patients with comorbid depression. However, it remains unclear whether circulating levels of cytokines and expression of these genes are associated, and how antipsychotic treatments impact this association. Relationships between messenger RNA (mRNA) expression of 11 schizophrenia-related genes and circulating levels of cytokines (interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α) were analyzed in 174 antipsychotic naïve first episode psychosis (FEP) and in 77 healthy controls. A subgroup of 72 patients was reassessed after treatment with risperidone. FEP patients were divided into those with and without depression. FEP patients with depression showed increased COMT expression and decreased NDEL1 expression. Increased IL-6 was associated with lowered AKT1 and DROSHA expression, while increased IL-10 was associated with increased NDEL1, DISC1, and MBP expression. IL-6 levels significantly increased the risperidone-induced expression of AKT1, DICER1, DROSHA, and COMT mRNA. The differential mRNA gene expression in FEP is largely associated with increased cytokine levels. While increased IL-6 may downregulate AKT-mediated cellular functions and dysregulate genes involved in microRNA (miRNA) machinery, increased IL-10 has neuroprotective properties. Increased IL-6 levels may prime the expression of genes (AKT1, DICER1, DROSHA, and COMT) in response to risperidone, suggesting that cytokine × treatment × gene interactions may improve cell function profiles. FEP patients with depression show a different gene expression profile reinforcing the theory that depression in FEP is a different phenotype.

Increased expression of NDEL1 and MBP genes in the peripheral blood of antipsychotic-naïve patients with first-episode psychosis.

Schizophrenia is a multifactorial neurodevelopmental disorder with high heritability. First-episode psychosis (FEP) is a critical period for determining the disease prognosis and is especially helpful for identifying potential biomarkers associated with the onset and progression of the disorder. We investigated the mRNA expression of 12 schizophrenia-related genes in the blood of antipsychotic-naïve FEP patients (N=73) and healthy controls (N=73). To evaluate the influences of antipsychotic treatment and progression of the disorder, we compared the gene expression within patients before and after two months of treatment with risperidone (N=64). We observed a significantly increased myelin basic protein (MBP) and nuclear distribution protein nudE-like 1 (NDEL1) mRNA levels in FEP patients compared with controls. Comparing FEP before and after risperidone treatment, no significant differences were identified; however; a trend of relatively low NDEL1 expression was observed after risperidone treatment. Animals chronically treated with saline or risperidone exhibited no significant change in Ndel1 expression levels in the blood or the prefrontal cortex (PFC), suggesting that the trend of low NDEL1 expression observed in FEP patients after treatment is likely due to factors other than risperidone treatment (i.e., disease progression). In addition to the recognized association with schizophrenia, MBP and NDEL1 gene products also play an essential role in the functions that are deregulated in schizophrenia, such as neurodevelopment. Our data strengthen the importance of these biological processes in psychotic disorders, indicating that these changes can be detected peripherally and potentially represent putative novel blood biomarkers of susceptibility and disorder progression.

Effects of risperidone on cytokine profile in drug-naïve first-episode psychosis.

BACKGROUND: There is robust evidence that schizophrenia is characterized by immune-inflammatory abnormalities, including variations on cytokine levels. The results of previous studies, however, are heterogeneous due to several confounding factors, such as the effects of antipsychotic drugs. Therefore, research on drug-naïve first-episode psychosis (FEP) patients is essential to elucidate the role of immune processes in that disorder. METHODS: The aim of this study is to compare cytokine levels (IL-2, IL-10, IL-4, IL-6, IFN-γ, TNF-α, and IL-17) in drug-naïve FEP patients both before and after treatment with risperidone for 10 weeks, and to investigate possible associations between cytokine levels and clinical responses to treatment and presence of depressive symptoms. It this study, we included 55 drug-naïve FEP patients who had repeated measurements of cytokine levels and 57 healthy controls. RESULTS: We found that FEP patients had significantly higher IL-6, IL-10 and TNF-α levels than healthy controls. After risperidone treatment, these three cytokines and additionally IL-4 decreased significantly. No significant difference was found between the post-treatment cytokine levels in FEP patients and in healthy controls, suggesting that these alterations in cytokine profiles are a state marker of FEP. No significant association was found between risperidone-induced changes in cytokines and the clinical response to treatment or the presence of depression. There was a significant inverse association between the risperidone-induced changes in IL-10 and the negative symptoms. CONCLUSIONS: In conclusion, our results show a specific cytokine profile in FEP patients (monocytic and regulatory T-cell activation) and suggest immunoregulatory effects of risperidone treatment, characterized by suppressant effects on monocytic, Th2, and T-regulatory functions.

Changes in gene expression and methylation in the blood of patients with first-episode psychosis.

Schizophrenia is a severe mental health disorder with high heritability. The investigation of individuals during their first-episode psychosis (FEP), before the progression of psychotic disorders and especially before treatment with antipsychotic medications, is particularly helpful for understanding this complex disease and for the identification of potential biomarkers. In this study, we compared the expression of genes that are involved in neurotransmission and neurodevelopment of antipsychotic-naive FEP in the peripheral blood of patients (n=51) and healthy controls (n=51). In addition, we investigated the differentially expressed genes with respect to a) DNA methylation, b) the correlation between gene expression and clinical variables (PANSS), and c) gene expression changes after risperidone treatment. Expression levels of 11 genes were quantified with SYBR Green. For methylation analysis, bisulfite sequencing was performed. A significant decrease in GCH1 mRNA levels was observed in FEP patients relative to controls. Also, when we compare the FEP patients after risperidone treatment with controls, this difference remains significant, and no significant differences were observed in GCH1 mRNA levels when comparing patients before and after risperidone treatment. Additionally, although the differences were non-significant after Bonferroni correction, the expression of GCH1 seemed to be correlated with PANSS scores, and the GCH1 promoter region was more methylated in FEP than in controls, thus corroborating the results obtained at the mRNA level. Few studies have been conducted on GCH1, and future studies are needed to clarify its potential role in the progression of schizophrenia.

Análise da rejeição do transplante de aponeurose em coelhos / Analysis of transplant rejection in rabbits aponeurosis

OBJETIVO: Estudar a viabilidade de aponeurose heteróloga para fechar parede abdominal de coelhos, com ênfase no processo de rejeição. MÉTODOS: Este projeto foi aprovado pelo Comitê de Cuidados Animais da Faculdade de Ciências Médicas da Santa Casa de São Paulo e realizado na Unidade Técnica e Cirurgia Experimental. Quatro coelhas vermelhas trocaram aponeurose da parede abdominal com outros quatro animais machos brancos. Em dois coelhos, foi retirada e substituída a aponeurose como controle do processo cicatricial. Eles foram avaliados 1 vez por dia e sacrificados após 7 dias. Foi realizada a imunoistoquímica com CD20 e CD79. RESULTADOS: Os animais não tiveram celulite, abscesso, hematoma, deiscência da ferida ou hérnia. O local do enxerto mostrou hiperemia intensa. A análise histológica mostrou um processo inflamatório, com a presença de miofibroblastos em amadurecimento e colágeno, que variou de incipiente a moderado. O número de vasos estava reduzido e as células inflamatórias foram, em sua maioria, células plasmáticas e macrófagos. Não havia sinais morfológicos da rejeição aguda com a agressão do endotélio vascular. O músculo adjacente mostrou sinais de degeneração, com reação inflamatória dos núcleos e condensação do citoplasma. A análise imunoistoquímica (CD20 e CD79) mostrou que o processo inflamatório não foi mediado por linfócitos. O teste não paramétrico de Mann-Whitney mostrou que não se pode rejeitar a hipótese de igualdade (p>0,05). CONCLUSÃO: Não houve complicações pós-operatórias (fístulas, deiscência etc.) e a análise histológica revelou processo inflamatório inespecífico. A análise imunoistoquímica mostrou que o processo inflamatório não foi em razão de uma possível rejeição.

OBJECTIVE: To study the feasibility of heterologous aponeurosis to close the abdominal wall of rabbits emphasizing the rejection process. METHODS: This project was approved by the Animals Care Committee of the Faculdade de Ciências Médicas da Santa Casa de São Paulo, and it was carried out at the Experimental Surgery and Technical Unit. Four red female rabbits exchanged abdominal wall aponeurosis with other four white male animals. Two rabbits just had it removed and replaced to be the control group for the healing process. Animals were evaluated once a day, and after 7 days they were sacrificed. Immunohistochemical analysis with CD20 and CD79 was done. RESULTS: The animals did not have cellulitis, abscess, hematoma, wound dehiscence or herniation. The graft site showed intense hyperemia. The histological analysis showed an inflammatory process with maturing myofibroblasts and collagen ranging from incipient to moderate. The number of vessels was reduced and the inflammatory cells were most plasma cells and macrophages. There were no morphological signs of acute rejection with aggressive vascular endothelial damage. The adjacent muscle showed signs of degeneration with inflammatory centralization of nuclei and cytoplasmic condensation. The immunohistochemical analysis (CD20 and CD79) showed that the inflammatory process was not mediated by lymphocytes. Mann-Whitney nonparametric test showed that the hypothesis of equality (p>0.05) should not be discarded. CONCLUSION: There were no postoperative complications (fistulas, dehiscence etc.) and the histological analysis showed nonspecific inflammatory process. The immunohistochemical analysis showed that the inflammatory process was not due to a possible rejection.

Analysis of transplant rejection in rabbits aponeurosis.

OBJECTIVE: To study the feasibility of heterologous aponeurosis to close the abdominal wall of rabbits emphasizing the rejection process. METHODS: This project was approved by the Animals Care Committee of the Faculdade de Ciências Médicas da Santa Casa de São Paulo, and it was carried out at the Experimental Surgery and Technical Unit. Four red female rabbits exchanged abdominal wall aponeurosis with other four white male animals. Two rabbits just had it removed and replaced to be the control group for the healing process. Animals were evaluated once a day, and after 7 days they were sacrificed. Immunohistochemical analysis with CD20 and CD79 was done. RESULTS: The animals did not have cellulitis, abscess, hematoma, wound dehiscence or herniation. The graft site showed intense hyperemia. The histological analysis showed an inflammatory process with maturing myofibroblasts and collagen ranging from incipient to moderate. The number of vessels was reduced and the inflammatory cells were most plasma cells and macrophages. There were no morphological signs of acute rejection with aggressive vascular endothelial damage. The adjacent muscle showed signs of degeneration with inflammatory centralization of nuclei and cytoplasmic condensation. The immunohistochemical analysis (CD20 and CD79) showed that the inflammatory process was not mediated by lymphocytes. Mann-Whitney nonparametric test showed that the hypothesis of equality (p>0.05) should not be discarded. CONCLUSION: There were no postoperative complications (fistulas, dehiscence etc.) and the histological analysis showed nonspecific inflammatory process. The immunohistochemical analysis showed that the inflammatory process was not due to a possible rejection.

[Intestinal lengthening using a gastric graft: experimental study in pigs]. / Alongamento de intestino com tubo gástrico: estudo piloto em porcos.

OBJECTIVE: Novel experimental technique of intestinal lengthening with a gastric graft in swines is proposed. METHODS: Four male large white swines, weighing 15 to 20 kg and aging 50 to 60 days were underwent an intestinal lengthening using a gastric graft (Figure 1). Swines were re-operated to check the aspect of the lengthening surgery. At this time intestinal fragments of suture lines, respecting a 5 cm margin, were removed and sent to histological analysis. RESULTS: There wasn't any graft ischemia or necrosis, residual stomach was already dilated by the time of relaparotomies, regaining 50% of its original size. Only an intense atrophy of the gastric graft mucosa with no signs of necrosis at histological study (Figure 2). CONCLUSION: Lengthening using a gastric graft is technically feasible, with viability of the graft. Studies with swines with SBS in a larger cohort will be necessary to analyze stomach graft function. In the future, this technique can be a bridge to intestinal transplantation.

Alongamento de intestino com tubo gástrico: estudo piloto em porcos / Intestinal lengthening using a gastric graft: experimental study in pigs

OBJETIVO: Apresentar uma nova técnica de alongamento intestinal usando enxerto gástrico em suínos. MÉTODOS: Quatro porcos machos large white pesando de 15 a 20 kg. foram submetidos ao alongamento intestinal utilizando enxerto gástrico. Os porcos foram reoperados para observação do aspecto da operação, neste momento, fragmentos intestinais contendo as linhas de sutura, respeitando uma margem de 5 cm, foram removidos e enviados para análise histológica. RESULTADOS: O estômago residual estava dilatado no momento da necrópsia, recuperando aproximadamente 50 por cento do seu tamanho original aproximadamente 15 dias após a operação de alongamento. Somente atrofia intensa da mucosa gástrica foi observada no estudo histológico de todas as amostras, sem sinais de necrose. CONCLUSÃO: O alongamento com enxerto gástrico é tecnicamente viável, comprovado pela viabilidade do enxerto. Estudos com suínos com o SIC em uma maior cohort, serão necessários para analisar a função do enxerto gástrico. No futuro, essa técnica pode ser uma ponte para o transplante intestinal.

OBJECTIVE: Novel experimental technique of intestinal lengthening with a gastric graft in swines is proposed. METHODS: Four male large white swines, weighing 15 to 20 kg and aging 50 to 60 days were underwent an intestinal lengthening using a gastric graft (Figure 1). Swines were re-operated to check the aspect of the lengthening surgery. At this time intestinal fragments of suture lines, respecting a 5 cm margin, were removed and sent to histological analysis. RESULTS: There wasn't any graft ischemia or necrosis, residual stomach was already dilated by the time of relaparotomies, regaining 50 percent of its original size. Only an intense atrophy of the gastric graft mucosa with no signs of necrosis at histological study (Figure 2). CONCLUSION: Lengthening using a gastric graft is technically feasible, with viability of the graft. Studies with swines with SBS in a larger co-hort will be necessary to analyze stomach graft function. In the future, this technique can be a bridge to intestinal transplantation.

Comparative study between parietal peritoneum suture and nonsuture in midline laparotomies in rats / Estudo comparativo entre sutura e não sutura do peritônio parietal nas laparotomias medianas em ratos

PURPOSE: Compare the parietal peritoneum suture and nonsuture in midline laparotomies in rats, as for the formation of adhesions. METHODS: 40 adult albino Wistar rats (20 males and 20 females) underwent a surgery, weighing between 350 and 400 grams. After anesthesia, a midline laparotomy was performed, followed by cavity closure with and without peritoneum suture. After 40 days, the rats underwent a new surgery in order to verify the peritoneum and check if there were any adhesions, and the rats were then sacrificed. RESULTS: Statistical analysis showed there was no significant difference between the adhesions occurring or not with peritoneal suture or nonsuture, including in relation to the rats' gender. CONCLUSION: Closing the peritoneum or not does not interfere with the formation of adhesions after midline laparotomies in rats from both genders.

OBJETIVO: Comparar a sutura e não sutura do peritônio parietal nas laparotomias medianas em ratos, quanto à formação de aderências. MÉTODOS: Foram operados 40 ratos albinos Wistar (20 machos e 20 fêmeas), adultos, pesando entre 350 e 400 gramas. Após a anestesia, foi realizada laparotomia mediana seguida de fechamento da cavidade com sutura do peritônio e sem sutura do peritônio. Após 40 dias, os animais foram re-operados para a inspeção do peritônio e a constatação da presença ou não de aderências e, em seguida, sacrificados. RESULTADOS: A análise estatística demonstrou que não houve diferença significativa entre a ocorrência ou não de aderências com sutura e não sutura do peritônio, nem com relação ao sexo dos animais operados. CONCLUSÃO: O fechamento ou não do peritônio não interfere na formação de aderências após laparotomias medianas em ratos de ambos os sexos.

Comparative study between parietal peritoneum suture and nonsuture in midline laparotomies in rats.

PURPOSE: Compare the parietal peritoneum suture and nonsuture in midline laparotomies in rats, as for the formation of adhesions. METHODS: 40 adult albino Wistar rats (20 males and 20 females) underwent a surgery, weighing between 350 and 400 grams. After anesthesia, a midline laparotomy was performed, followed by cavity closure with and without peritoneum suture. After 40 days, the rats underwent a new surgery in order to verify the peritoneum and check if there were any adhesions, and the rats were then sacrificed. RESULTS: Statistical analysis showed there was no significant difference between the adhesions occurring or not with peritoneal suture or nonsuture, including in relation to the rats' gender. CONCLUSION: Closing the peritoneum or not does not interfere with the formation of adhesions after midline laparotomies in rats from both genders.

Eficácia da litotripsia extracorpórea por ondas de choque (LEOC) em cálculos de ureter inferior: a propósito de uma mudança na posiçäo do paciente / Efficacy of extracorporeal shock wave lithotripsy in distal ureteral stones: a modification in patient position

O presente trabalho compara os resultados da Litotripsia Extracorpórea por Ondas de Choque (LEOC) em cálculos de ureter inferior, levando em consideraçäo uma modificaçäo efetuada na posiçäo do paciente em relaçäo ao aparelho litotritor. Foram estudados 52 pacientes divididos em 2 grupos: 31 pacientes foram submetidos à LEOC em decúbito dorsal invertido e 21 em decúbito ventral, e a análise estatística dos resultados demonstrou melhora importante no índice de pacientes "livres de cálculo" no subgrupo de decúbito dorsal invertido (p<0,001). Estes resultados säo comparáveis aos resultados com o uso de uretero-renoscópio