P50 inhibitory gating deficit is correlated with the negative symptomatology of schizophrenia

Abnormal sensory gating in schizophrenia has frequently been reported. The strength of central inhibitory pathways was measured using the P50 component of the auditory evoked potential in a conditioning-testing paradigm. The relationships between a relative decrease in P50 amplitude to repeated auditory stimuli and clinical symptoms remain controversial. Using the Positive and Negative Syndrome Scale, we studied the P50 auditory conditioning-testing paradigm in 81 schizophrenic subjects, categorized into subgroups with and without prominent negative symptoms, in comparison with 88 control subjects. We found increased ratios of testing stimuli to conditioning stimuli in both schizophrenic subgroups relative to findings in the control group. In addition, we found significantly increased mean latencies of the P50 responses to conditioning (C) and testing (T) stimuli and significantly increased T/C ratios in the subgroup with negative symptoms compared with the subgroup with non-negative symptoms.     

Epidemiology and treatment of juvenile sexual offending

The juvenile sex offender is defined as a youth who commits any sexual act with a person of any age against the victim's will, or in an aggressive, exploitative, or threatening manner. The term 'child molester' refers to those who choose only, or primarily, child victims. In this article, we mostly focus on adolescents aged between 13 and 18 years. To reduce sex crimes and the risk of adolescent sexual re-offending, effective treatment strategies have to be implemented for adolescent sexual offenders. Supervision and treatment recommendations for juvenile sex offenders initially emerged from the literature on adult sex offenders. Treatment must include behavioral therapy, family therapy, and psychosocial interventions. Pharmacotherapy is not always a first-line treatment. Antidepressants (especially selective serotonin reuptake inhibitors) offer promise in the treatment of adolescent sexual offending but further controlled studies are needed. In some rare situations, however, especially when severe paraphilic behaviors (such as pedophilia) are present, an hormonal intervention such as cyproterone acetate treatment may be needed.     

Relationship between elevated levels of the alpha 1 acid glycoprotein in chronic myelogenous leukemia in blast crisis and pharmacological resistance to imatinib (Gleevec) in vitro and in vivo

The Abl tyrosine kinase inhibitor imatinb is becoming a standard for the treatment of chronic myelogenous leukemia (CML). However, Bcr-Abl gene mutations have been reported mainly in relapsing or resistant patients. In primary resistant patients, only few mutations have been documented so far, suggesting alternative mechanisms. We aimed to investigate if alpha 1 acid glycoprotein (AGP), an acute phase drug binding protein, could be a biological marker for pharmacological resistance to imatinib in nine patients in acute phase CML. All patients (3/3) with high AGP dosages (2.31+/-0.17 mg/mL; normal values, 0.5-1.3mg/mL) were primary resistant to imatinib whereas an early clinical response was observed for the six patients with normal AGP levels (1.13+/-0.2mg/mL). No mutation in the adenosine triphosphate domain of Abl were detected before the initiation of imatinib therapy. By using in vitro tests combining various imatinib concentrations (1-10 microM) with purified human AGP (1 and 3 mg/mL), we demonstrate that imatinib-induced apoptosis of K562 or fresh leukemic CML cells is abrogated or reduced. The same effect was observed using sera from donors with high AGP levels (1.9-3.28 mg/mL). In patients with CML in blastic phase, AGP levels could reflect pharmacological resistance to imatinib, suggesting that increased dosage of imatinib or the use of a competitor to drug binding should be recommended to optimize the therapeutic effect of the drug.     

No evidence for linkage between COMT and schizophrenia in a French population

Catechol-O-methyltransferase is a candidate in the predisposition to schizophrenia both because of its function and the position of its gene. A multipoint non-parametric linkage analysis and a transmission disequilibrium test were performed on 42 multiplex families genotyped for Pml I and Bcl I polymorphisms using two definitions of the affected phenotype. Neither linkage nor preferential transmission of any allele or haplotype was detected, failing to replicate previous positive findings.     

Saccadic and smooth-pursuit eye movements in deficit and non-deficit schizophrenia

We have analyzed eye movement performances in schizophrenics showing primary negative or deficit symptoms (n=16) and non-deficit schizophrenics (n=55), and compared them with those of controls (n=34) in order to study the relationships between negative symptoms and eye movement abnormalities. Patients were subtyped into deficit and non-deficit subgroups using the Schedule for the Deficit Syndrome. Three oculomotor paradigms were used: smooth pursuit, a reflexive saccade paradigm and an antisaccadic task.The smooth pursuit gain was significantly decreased (and the rate of catch-up saccades increased) in schizophrenics as compared with controls, but no difference was observed between patient groups. In the reflexive saccade paradigm, no difference was found between controls and patients, except for latency in deficit patients. In the antisaccade paradigm, the number of errors and the latency of successful antisaccades were significantly increased in schizophrenics as compared with controls. The latency of successful antisaccades in both directions was significantly increased in deficit patients as compared with non-deficit patients. The latency of rightward successful antisaccades was significantly increased as compared with the latency of leftward antisaccades in deficit patients only. However, when patients were classified into negative and non-negative groups using the PANSS, no difference was found in the antisaccade paradigm.Smooth pursuit impairment does not seem to depend on the primary enduring negative symptoms.In deficit schizophrenics, the abnormalities observed in the antisaccadic task are consistent with prefrontal dysfunction, and may suggest parietal lobe dysfunction as well.     

A simulation method for studying scintillation camera collimators

This paper presents a computer simulation of photon interaction with collimator septa, which allows the point spread function of scintillation camera collimators to be calculated. The method simulates photon attenuation along their propagation direction in a determinist way. Using this simulation, the spatial resolution, geometric efficiency and penetration index of collimators may be easily assessed. Results obtained with this method are presented and compared with those obtained from standard formulae. We show the usefulness of the simulation which precisely accounts for effects of septum penetration. Measurements performed on two collimators with 131I and 99Tcm point sources provide results consistent with those obtained from the simulation method. In conclusion we show that this method is an accurate tool to assist conception of collimators for nuclear medicine.     

Receptor-interacting protein kinase-1 ablation in liver parenchymal cells promotes liver fibrosis in murine NASH without affecting other symptoms

Journal of Molecular Medicine - Non-alcoholic steatohepatitis (NASH), a chronic liver disease that emerged in industrialized countries, can further progress into liver fibrosis, cirrhosis, and...