The effect of cognitive behavioral treatment on the positive symptoms of schizophrenia spectrum disorders: a meta-analysis

(from the journal abstract) Background: Despite the effectiveness of anti-psychotic pharmacotherapy, residual hallucinations and delusions do not completely resolve in some medicated patients. Additional cognitive behavioral therapy (CBT) seems to improve the management of positive symptoms. Despite promising results, the efficacy of CBT is still unclear. The present study addresses this issue taking into account a number of newly published controlled studies. Method: Fourteen studies including 1484 patients, published between 1990 and 2004 were identified and a meta-analysis of their results performed. Results: Compared to other adjunctive measures, CBT showed significant reduction in positive symptoms and there was a higher benefit of CBT for patients suffering an acute psychotic episode versus the chronic condition (effect size of 0.57 vs. 0.27). Discussion: CBT is a promising adjunctive treatment for positive symptoms in schizophrenia spectrum disorders. However, a number of potentially modifying variables have not yet been examined, such as therapeutic alliance and neuropsychological deficits. (PsycINFO Database Record (c) 2005 APA, all rights reserved)

Spectrum of congenital anomalies in pregnancies with pregestational diabetes.

BACKGROUND: Maternal pregestational diabetes is a well-known risk factor for congenital anomalies. This study analyses the spectrum of congenital anomalies associated with maternal diabetes using data from a large European database for the population-based surveillance of congenital anomalies. METHODS: Data from 18 population-based EUROCAT registries of congenital anomalies in 1990-2005. All malformed cases occurring to mothers with pregestational diabetes (diabetes cases) were compared to all malformed cases in the same registry areas to mothers without diabetes (non-diabetes cases). RESULTS: There were 669 diabetes cases and 92,976 non diabetes cases. Odds ratios in diabetes pregnancies relative to non-diabetes pregnancies comparing each EUROCAT subgroup to all other non-chromosomal anomalies combined showed significantly increased odds ratios for neural tube defects (anencephaly and encephalocele, but not spina bifida) and several subgroups of congenital heart defects. Other subgroups with significantly increased odds ratios were anotia, omphalocele and bilateral renal agenesis. Frequency of hip dislocation was significantly lower among diabetes (odds ratio 0.15, 95% CI 0.05-0.39) than non-diabetes cases. Multiple congenital anomalies were present in 13.6 % of diabetes cases and 6.1 % of non-diabetes cases. The odds ratio for caudal regression sequence was very high (26.40,95% CI 8.98-77.64), but only 17% of all caudal regression cases resulted from a pregnancy with pregestational diabetes. CONCLUSIONS: The increased risk of congenital anomalies in pregnancies with pregestational diabetes is related to specific non-chromosomal congenital anomalies and multiple congenital anomalies and not a general increased risk.

A multi-center study: intra-scan and inter-scan variability of diffusion spectrum imaging.

The objective of this study was to investigate whether it is possible to pool together diffusion spectrum imaging data from four different scanners, located at three different sites. Two of the scanners had identical configuration whereas two did not. To measure the variability, we extracted three scalar maps (ADC, FA and GFA) from the DSI and utilized a region and a tract-based analysis. Additionally, a phantom study was performed to rule out some potential factors arising from the scanner performance in case some systematic bias occurred in the subject study. This work was split into three experiments: intra-scanner reproducibility, reproducibility with twin-scanner settings and reproducibility with other configurations. Overall for the intra-scanner and twin-scanner experiments, the region-based analysis coefficient of variation (CV) was in a range of 1%-4.2% and below 3% for almost every bundle for the tract-based analysis. The uncinate fasciculus showed the worst reproducibility, especially for FA and GFA values (CV 3.7-6%). For the GFA and FA maps, an ICC value of 0.7 and above is observed in almost all the regions/tracts. Looking at the last experiment, it was found that there is a very high similarity of the outcomes from the two scanners with identical setting. However, this was not the case for the two other imagers. Given the fact that the overall variation in our study is low for the imagers with identical settings, our findings support the feasibility of cross-site pooling of DSI data from identical scanners.

Reactivity spectrum of 30 monoclonal antimelanoma antibodies to a panel of 28 melanoma and control cell lines.

Thirty monoclonal antibodies from eight laboratories exchanged after the First Workshop on Monoclonal Antibodies to Human Melanoma held in March 1981 at NIH were tested in an antibody-binding radioimmunoassay using a panel of 28 different cell lines. This panel included 12 melanomas, three neuroblastomas, four gliomas, one retinoblastoma, four colon carcinomas, one lung carcinoma, one cervical carcinoma, one endometrial carcinoma, and one breast carcinoma. The reactivity pattern of the 30 monoclonal antibodies tested showed that none of them were directed against antigens strictly restricted to melanoma, but that several of them recognize antigenic structures preferentially expressed on melanoma cells. A large number of antibodies were found to crossreact with gliomas and neuroblastomas. Thus, they seem to recognize neuroectoderm associated differentiation antigens. Four monoclonal antibodies produced in our laboratory were further studied for the immunohistological localization of melanoma associated antigens on fresh tumor material. In a three-layer biotin-avidin-peroxidase system each antibody showed a different staining pattern with the tumor cells, suggesting that they were directed against different antigens.

The spectrum of opportunistic diseases complicating sarcoidosis.

Sarcoidosis is an inflammatory disease marked by a paradoxical immune status. The anergic state, which results from various immune defects, contrasts with the inflammatory formation of granulomas. Sarcoidosis patients may be at risk for opportunistic infections (OIs) and a substantial number of cases have been reported, even in untreated sarcoidosis. It is not clear how OIs in patients with sarcoidosis are different from other groups at risk. In this review, we discuss the most common OIs: mycobacterial infection (including tuberculosis), cryptococcosis, progressive multifocal leukoencephalopathy, and aspergillosis. Unlike peripheral lymphocytopenia, corticosteroids are a major risk factor for OIs but the occurrence of Ols in untreated patients suggests more complex predisposing mechanisms. Opportunistic infections presenting with extrapulmonary features are often misdiagnosed as new localizations of sarcoidosis. Aspergillomas mostly develop on fibrocystic lungs. Overall, physicians should be aware of the possible occurrence of OIs during sarcoidosis, even in untreated patients.

Rapid cohort generation and analysis of disease spectrum of large animal model of cone dystrophy.

Large animal models are an important resource for the understanding of human disease and for evaluating the applicability of new therapies to human patients. For many diseases, such as cone dystrophy, research effort is hampered by the lack of such models. Lentiviral transgenesis is a methodology broadly applicable to animals from many different species. When conjugated to the expression of a dominant mutant protein, this technology offers an attractive approach to generate new large animal models in a heterogeneous background. We adopted this strategy to mimic the phenotype diversity encounter in humans and generate a cohort of pigs for cone dystrophy by expressing a dominant mutant allele of the guanylate cyclase 2D (GUCY2D) gene. Sixty percent of the piglets were transgenic, with mutant GUCY2D mRNA detected in the retina of all animals tested. Functional impairment of vision was observed among the transgenic pigs at 3 months of age, with a follow-up at 1 year indicating a subsequent slower progression of phenotype. Abnormal retina morphology, notably among the cone photoreceptor cell population, was observed exclusively amongst the transgenic animals. Of particular note, these transgenic animals were characterized by a range in the severity of the phenotype, reflecting the human clinical situation. We demonstrate that a transgenic approach using lentiviral vectors offers a powerful tool for large animal model development. Not only is the efficiency of transgenesis higher than conventional transgenic methodology but this technique also produces a heterogeneous cohort of transgenic animals that mimics the genetic variation encountered in human patients.

Diffusion Spectrum Imaging after stroke shows structural changes in the contra-lateral motor network correlating with functional recovery

There is growing interest in understanding the role of the non-injured contra-lateral hemisphere in stroke recovery. In the experimental field, histological evidence has been reported that structural changes occur in the contra-lateral connectivity and circuits during stroke recovery. In humans, some recent imaging studies indicated that contra-lateral sub-cortical pathways and functional and structural cortical networks are remodeling, after stroke. Structural changes in the contra-lateral networks, however, have never been correlated to clinical recovery in patients. To determine the importance of the contra-lateral structural changes in post-stroke recovery, we selected a population of patients with motor deficits after stroke affecting the motor cortex and/or sub-cortical motor white matter. We explored i) the presence of Generalized Fractional Anisotropy (GFA) changes indicating structural alterations in the motor network of patientsâeuro? contra-lateral hemisphere as well as their longitudinal evolution ii) the correlation of GFA changes with patientsâeuro? clinical scores, stroke size and demographics data iii) and a predictive model.

A new method for the determination of plutonium and americium using high pressure microwave digestion and alpha-spectrometry or ICP-SMS

Plutonium and americium are radionuclides particularly difficult to measure in environmental samples because they are alpha-emitters and therefore necessitate a careful separation before any measurement, either using radiometric methods or ICP-SMS. Recent developments in extraction chromatography resins such as Eichrom (R) TRU and TEVA have resolved many of the analytical problems but drawbacks such as low recovery and spectral interferences still occasionally occur. Here, we report on the use of the new Eichrom (R) DGA resin in association with TEVA resin and high pressure microwave acid leaching for the sequential determination of plutonium and americium in environmental samples. The method results in average recoveries of 83 +/- 15% for plutonium and 73 +/- 22% for americium (n = 60), and a less than 10% deviation from reference values of four IAEA reference materials and three samples from intercomparisons exercises. The method is also suitable for measuring Pu-239 in water samples at the mu Bq/l level, if ICP-SMS is used for the measurement.

Activities of fosfomycin, tigecycline, colistin, and gentamicin against extended-spectrum-β-lactamase-producing Escherichia coli in a foreign-body infection model.

Limited antimicrobial agents are available for the treatment of implant-associated infections caused by fluoroquinolone-resistant Gram-negative bacilli. We compared the activities of fosfomycin, tigecycline, colistin, and gentamicin (alone and in combination) against a CTX-M15-producing strain of Escherichia coli (Bj HDE-1) in vitro and in a foreign-body infection model. The MIC and the minimal bactericidal concentration in logarithmic phase (MBC(log)) and stationary phase (MBC(stat)) were 0.12, 0.12, and 8 μg/ml for fosfomycin, 0.25, 32, and 32 μg/ml for tigecycline, 0.25, 0.5, and 2 μg/ml for colistin, and 2, 8, and 16 μg/ml for gentamicin, respectively. In time-kill studies, colistin showed concentration-dependent activity, but regrowth occurred after 24 h. Fosfomycin demonstrated rapid bactericidal activity at the MIC, and no regrowth occurred. Synergistic activity between fosfomycin and colistin in vitro was observed, with no detectable bacterial counts after 6 h. In animal studies, fosfomycin reduced planktonic counts by 4 log(10) CFU/ml, whereas in combination with colistin, tigecycline, or gentamicin, it reduced counts by >6 log(10) CFU/ml. Fosfomycin was the only single agent which was able to eradicate E. coli biofilms (cure rate, 17% of implanted, infected cages). In combination, colistin plus tigecycline (50%) and fosfomycin plus gentamicin (42%) cured significantly more infected cages than colistin plus gentamicin (33%) or fosfomycin plus tigecycline (25%) (P < 0.05). The combination of fosfomycin plus colistin showed the highest cure rate (67%), which was significantly better than that of fosfomycin alone (P < 0.05). In conclusion, the combination of fosfomycin plus colistin is a promising treatment option for implant-associated infections caused by fluoroquinolone-resistant Gram-negative bacilli.

Changes in the use of broad-spectrum antibiotics after cefepime shortage: a time series analysis.

The original cefepime product was withdrawn from the Swiss market in January 2007, and replaced by a generic 10 months later. The goals of the study were to assess the impact of this cefepime shortage on the use and costs of alternative broad-spectrum antibiotics, on antibiotic policy, and on resistance of Pseudomonas aeruginosa towards carbapenems, ceftazidime and piperacillin-tazobactam. A generalized regression-based interrupted time series model assessed how much the shortage changed the monthly use and costs of cefepime and of selected alternative broad-spectrum antibiotics (ceftazidime, imipenem-cilastatin, meropenem, piperacillin-tazobactam) in 15 Swiss acute care hospitals from January 2005 to December 2008. Resistance of P. aeruginosa was compared before and after the cefepime shortage. There was a statistically significant increase in the consumption of piperacillin-tazobactam in hospitals with definitive interruption of cefepime supply, and of meropenem in hospitals with transient interruption of cefepime supply. Consumption of each alternative antibiotic tended to increase during the cefepime shortage and to decrease when the cefepime generic was released. These shifts were associated with significantly higher overall costs. There was no significant change in hospitals with uninterrupted cefepime supply. The alternative antibiotics for which an increase in consumption showed the strongest association with a progression of resistance were the carbapenems. The use of alternative antibiotics after cefepime withdrawal was associated with a significant increase in piperacillin-tazobactam and meropenem use and in overall costs, and with a decrease in susceptibility of P. aeruginosa in hospitals. This warrants caution with regard to shortages and withdrawals of antibiotics.

Mutations in the human UBR1 gene and the associated phenotypic spectrum.

Johanson-Blizzard syndrome (JBS) is a rare, autosomal recessive disorder characterized by exocrine pancreatic insufficiency, typical facial features, dental anomalies, hypothyroidism, sensorineural hearing loss, scalp defects, urogenital and anorectal anomalies, short stature, and cognitive impairment of variable degree. This syndrome is caused by a defect of the E3 ubiquitin ligase UBR1, which is part of the proteolytic N-end rule pathway. Herein, we review previously reported (n = 29) and a total of 31 novel UBR1 mutations in relation to the associated phenotype in patients from 50 unrelated families. Mutation types include nonsense, frameshift, splice site, missense, and small in-frame deletions consistent with the hypothesis that loss of UBR1 protein function is the molecular basis of JBS. There is an association of missense mutations and small in-frame deletions with milder physical abnormalities and a normal intellectual capacity, thus suggesting that at least some of these may represent hypomorphic UBR1 alleles. The review of clinical data of a large number of molecularly confirmed JBS cases allows us to define minimal clinical criteria for the diagnosis of JBS. For all previously reported and novel UBR1 mutations together with their clinical data, a mutation database has been established at LOVD.

Characterizing the connectome in schizophrenia with diffusion spectrum imaging.

Schizophrenia is a complex psychiatric disorder characterized by disabling symptoms and cognitive deficit. Recent neuroimaging findings suggest that large parts of the brain are affected by the disease, and that the capacity of functional integration between brain areas is decreased. In this study we questioned (i) which brain areas underlie the loss of network integration properties observed in the pathology, (ii) what is the topological role of the affected regions within the overall brain network and how this topological status might be altered in patients, and (iii) how white matter properties of tracts connecting affected regions may be disrupted. We acquired diffusion spectrum imaging (a technique sensitive to fiber crossing and slow diffusion compartment) data from 16 schizophrenia patients and 15 healthy controls, and investigated their weighted brain networks. The global connectivity analysis confirmed that patients present disrupted integration and segregation properties. The nodal analysis allowed identifying a distributed set of brain nodes affected in the pathology, including hubs and peripheral areas. To characterize the topological role of this affected core, we investigated the brain network shortest paths layout, and quantified the network damage after targeted attack toward the affected core. The centrality of the affected core was compromised in patients. Moreover the connectivity strength within the affected core, quantified with generalized fractional anisotropy and apparent diffusion coefficient, was altered in patients. Taken together, these findings suggest that the structural alterations and topological decentralization of the affected core might be major mechanisms underlying the schizophrenia dysconnectivity disorder. Hum Brain Mapp, 36:354-366, 2015. © 2014 Wiley Periodicals, Inc.

Nouveau spectre des troubles cognitifs liés à l'infection par le VIH à l'ère des trithérapies [New spectrum of HIV-associated cognitive disorders in the HAART era]

Highly active anti-retroviral therapy (HAART) has almost abolished HIV-related mortality and serious opportunistic diseases; among them, AIDS-related dementia. However, minor forms of cognitive dysfunction, have not disappeared, and even increased in frequency. Ageing of HIV+ patients, insufficient penetration of anti-viral drugs into the brain with continuous low-grade viral production and inflammation may play a role. Minor cognitive dysfunction in HIV infection shares some clinical and pathophysiological features with neuro-degenerative diseases, in particular Alzheimers disease. It can thus be postulated that, such in Alzheimer disease, anti-cholinesterase drugs might also be efficacious in AIDS-related minor cognitive dysfunction. This hypothesis has not been tested yet however A clinical trial using ravistigmine is starting this spring in patients with HIV-associated cognitive dysfunction in Geneva and Lausanne.

3D noise power spectrum applied on clinical mdct scanners: effects of reconstruction algorithms and reconstruction filters

The noise power spectrum (NPS) is the reference metric for understanding the noise content in computed tomography (CT) images. To evaluate the noise properties of clinical multidetector (MDCT) scanners, local 2D and 3D NPSs were computed for different acquisition reconstruction parameters.A 64- and a 128-MDCT scanners were employed. Measurements were performed on a water phantom in axial and helical acquisition modes. CT dose index was identical for both installations. Influence of parameters such as the pitch, the reconstruction filter (soft, standard and bone) and the reconstruction algorithm (filtered-back projection (FBP), adaptive statistical iterative reconstruction (ASIR)) were investigated. Images were also reconstructed in the coronal plane using a reformat process. Then 2D and 3D NPS methods were computed.In axial acquisition mode, the 2D axial NPS showed an important magnitude variation as a function of the z-direction when measured at the phantom center. In helical mode, a directional dependency with lobular shape was observed while the magnitude of the NPS was kept constant. Important effects of the reconstruction filter, pitch and reconstruction algorithm were observed on 3D NPS results for both MDCTs. With ASIR, a reduction of the NPS magnitude and a shift of the NPS peak to the low frequency range were visible. 2D coronal NPS obtained from the reformat images was impacted by the interpolation when compared to 2D coronal NPS obtained from 3D measurements.The noise properties of volume measured in last generation MDCTs was studied using local 3D NPS metric. However, impact of the non-stationarity noise effect may need further investigations.