Cognitive effects of six months of treatment with quetiapine in antipsychotic-naïve first-episode schizophrenia

The aim of the study was to explore the relationships between subjective or objective symptoms and mortality in schizophrenia. 310 subjects meeting the ICD-10 criteria for schizophrenia were included in the study between 1998 and 2000. At the initial assessment the following variables were respectively assessed to evaluate subjective and objective symptoms: the Frankfurt Complaints Questionnaire (FCQ) and the Positive and Negative Syndrome Scale (PANSS). In May 2008, information about the subjects were collected in order to know if they are alive or not and if they are deceased to know the date and the causes of their death. Survival analysis was conducted using the Kaplan–Meier product-limit estimator and standardized mortality ratio (SMR) was calculated. A multivariate Cox regression was done to detect predictive factors associated with mortality. Absolute mortality rates were 10.01%, 4.46% and 5.42% for overall mortality, unnatural causes and natural causes, respectively. SMR for overall mortality was 4.73. Cox regression analyses showed that elevated scores of FCQ was significant predictor of deaths from unnatural causes. High levels of subjective symptoms, as rated by the FCQ were independent predictor of mortality by unnatural causes in schizophrenic subjects. There were several limitations: The causes of death were not determined by autopsy and secondly, the duration of the study could be insufficient to detect significant associations between clinical variables and mortality.     

Source localization of sensory gating: a combined EEG and fMRI study in healthy volunteers

Reduced sensory gating appears to be among the core features in schizophrenia. The sources of sensory gating however are largely unknown. The aim of the current study was to identify these sources, with concurrent EEG and fMRI methodology. Twenty healthy male volunteers were tested with identical P50 suppression paradigms in two separate sessions: an EEG setting, and an EEG concurrent with fMRI setting. The stimuli in the P50 paradigm consisted of weak electrical stimulation of the left median nerve. The stimuli were presented in pairs with either 500 ms or 1000 ms interstimulus intervals (ISI). No difference was found between the EEG setting and the concurrent EEG and fMRI setting. P50 suppression was, in both settings, found only in the 500 ms trials, not in the 1000 ms trials. EEG-dipole modeling resulted in 4 sources located in the medial frontal gyrus, the insula, the hippocampus, and primary somatosensory cortex. These sources corresponded to significant fMRI clusters located in the medial frontal gyrus, the insula, the claustrum, and the hippocampus. Activity in the hippocampus and the claustrum was higher in the trials with suppression, suggesting that these brain areas are involved in the inhibitory processes of P50 suppression. The opposite was found for activity in the medial frontal gyrus and the insula, suggesting that these brain areas are involved in the generation of the P50 amplitude. To our knowledge, this is the first study demonstrating that P50 suppression can be reliably assessed inside an MRI scanner.     

Muco-submucosal elongated polyps of the gastrointestinal tract:A case series and a review of the literature

We present three cases of gastrointestinal muco-submucosal elongated polyps,two located in the duodenum and one in the descending colon.All three cases had a characteristic,"worm-like" endoscopic appearance and were lined by unremarkable mucosa.The vascular component was located in the submucosa and was composed of a mixture of variably dilated blood vessels(capillaries and veins) and lymphatics.The duodenal polyps displayed lipomatous metaplasia of the submucosal stroma.The dual vascular phenotype of the vascular component was confirmed by immunohistochemistry with D2-40 and CD31.     

Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan

Mutations in OTOF , encoding otoferlin, cause non-syndromic recessive hearing loss. The goal of our study was to define the identities and frequencies of OTOF mutations in a model population. We screened a cohort of 557 large consanguineous Pakistani families segregating recessive, severe-to-profound, prelingual-onset deafness for linkage to DFNB9 . There were 13 families segregating deafness consistent with linkage to markers for DFNB9 . We analyzed the genomic nucleotide sequence of OTOF and detected probable pathogenic sequence variants among all 13 families. These include the previously reported nonsense mutation p.R708X and 10 novel variants: 3 nonsense mutations (p.R425X, p.W536X, and p.Y1603X), 1 frameshift (c.1103_1104delinsC), 1 single amino acid deletion (p.E766del) and 5 missense substitutions of conserved residues (p.L573R, p.A1090E, p.E1733K, p.R1856Q and p.R1939W). OTOF mutations thus account for deafness in 13 (2.3%) of 557 Pakistani families. This overall prevalence is similar, but the mutation spectrum is different from those for Western populations. In addition, we demonstrate the existence of an alternative splice isoform of OTOF expressed in the human cochlea. This isoform must be required for human hearing because it encodes a unique alternative C-terminus affected by some DFNB9 mutations.     

Serotonin2A receptor blockade and clinical effect in first-episode schizophrenia patients treated with quetiapine

Rationale

We have previously reported decreased frontal cortical serotonin2A receptor binding in 30 antipsychotic na?ve first-episode schizophrenic patients and a relationship between this binding and positive psychotic symptoms. Until now, no longitudinal studies of serotonin2A receptor in first-episode antipsychotic-na?ve schizophrenia patients have reported on the relationship between serotonin2A receptor occupancy and treatment effect after sustained treatment with a specific atypical antipsychotic compound.

Objectives

Here, we measured serotonin2A receptor occupancy with [¹⁸F]altanserin PET in 15 first-episode antipsychotic-na?ve schizophrenia patients before and after 6?months of quetiapine treatment. Moreover, we investigated possible relationships between clinical efficacy, oral dose, and plasma levels of quetiapine

Results

Significant nonlinear relationships were found between serotonin2A receptor occupancy, quetiapine dose, and plasma concentration. There was a modest effect on positive symptoms up until a serotonin2A receptor occupancy level of approximately 60%. A receptor occupancy level between 60% and 70% appeared to exert the optimal serotonin2A receptor related treatment effect on positive symptoms whereas no additional serotonin2A receptor associated treatment effect was obtained above a receptor occupancy of 70%.

Conclusions

Taken together, the data point to a therapeutic role of the serotonin2A receptor in the treatment of subgroups of patients with schizophrenia. Specifically, the study indicates a serotonin2A receptor associated therapeutic window on positive symptoms in responding patients in the range between 60% and 70% occupancy in antipsychotic-na?ve first-episode schizophrenia. We speculate that non-responding patients need higher dopamine D₂ receptor blockade. Future studies with concurrent measurement of interactions with the dopamine system are, however, warranted to clarify this.     

N,N′-亚烷基双(取代苯酚)氨基乙酸的合成及对放射性核素钍-234的促排效果

本文报道合成的16个N,N′-亚烷基双(取代苯酚)氨基乙酸除化合物3,4外对放射性钍-234的加速排出均有较好的效果。其中有二个化合物促排效果达到70%以上,根据动物实验结果初步探讨了构效关系。     

The clinical features of late onset acne compared with early onset acne in women

Background Little is known about the clinical characteristics of acne based on the age of onset. Objectives The aim of this study was to investigate the clinical characteristics of patients according to the age of onset of acne and evaluate whether the findings were related to regional differences in the density of Propionibacterium acnes or the levels of sebum secretion. Methods A total of 89 women were recruited. The acne lesions were assessed by counting the lesions using standard digital photographs. Digital fluorescent photography for the evaluation of the density of P. acnes were taken and quantitative measurements of facial sebum secretion were performed. Results In women with acne, the age of onset was negatively correlated with the number of comedones and the proportion of comedones. By comparing the number of comedones and the proportion of comedones, onset of acne after 21 years of age was defined as late onset acne. In the patients with late onset acne, the number of comedones, the total number of acne lesions and the proportions of comedones were significantly less than in the patients with early onset acne. However, there were no significant differences in the fluorescence density of P. acnes or the level of sebum secretion between the two groups. Conclusions The results of this study, using objective evaluation tools, suggest that late onset acne has different clinical characteristics. Other possible factors might explain the clinical differences in late onset acne.