A note on the action of glutamine on cortical spreading depression

Application of a solution of 1-glutamine, 75 mM, to the pia-arachnoid surface of the dorsolateral neocortex of rabbits under dial-urethane anaesthesia was found to reversibly render the tissue insusceptible to spreading depression. It is suggested that this amide may play a part in the opposition normally offered by the tissue to undergo spreading depression. Some evidence is adduced which seems to support this suggestion.     

An economic assessment of quetiapine and haloperidol in patients with schizophrenia only partially responsive to conventional antipsychotics

BACKGROUND: Many patients with schizophrenia exhibit only a partial response to conventional antipsychotic agents, making them difficult to treat adequately. OBJECTIVE: This analysis models the cost-effectiveness of quetiapine compared with haloperidol in partial responders with schizophrenia. METHODS: Outcome data from the Partial Responders International schiZophrenia Evaluation (PRIZE) clinical trial comparing quetiapine and haloperidol in partial responders with schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were combined with data from the literature to construct a Markov model. The model was used to calculate treatment outcomes and total direct treatment costs from the perspective of the United Kingdom National Health Service over 5 years. RESULTS: The PRIZE study showed that quetiapine treatment resulted in a higher response rate and better tolerability than haloperidol treatment. These benefits have the potential to improve compliance and reduce relapse rates. The model showed that the higher acquisition cost of quetiapine was offset by lower costs for other medications, hospitalization, and other medical services. The total treatment cost over 5 years was 38,106 pounds for quetiapine and 38,350 pounds for haloperidol, a cost saving of 244 pounds in favor of quetiapine. Quetiapine-treated patients also spent longer in response states and experienced fewer relapses. Sensitivity analysis showed these results to be robust across a range of conditions. CONCLUSIONS: Quetiapine has the potential to improve outcomes compared with haloperidol in partial responders with schizophrenia, at a slightly lower total cost. The higher acquisition cost of quetiapine was offset by savings in other medical costs. Quetiapine could significantly improve the management of this patient group, without increasing the economic burden on the health service.     

Integrin-targeted nanocomplexes for tumour specific delivery and therapy by systemic administration

Nanoparticle formulations offer opportunities for tumour delivery of therapeutic reagents. The Receptor-Targeted Nanocomplex (RTN) formulation consists of a PEGylated, endosomally-cleavable lipid and an RGD integrin-targeting, endosomally-cleavable peptide. Nancomplexes self-assemble on mixing with plasmid DNA to produce nanoparticles of about 100 nm. The environmentally-sensitive linkers promote intracellular disassembly and release of the DNA. RTNs carrying luciferase genes were administered intravenously to mice carrying subcutaneous neuroblastoma tumours. Luciferase expression was much higher in tumours than in liver, spleen and lungs while plasmid biodistribution studies supported the expression data. Transfection in tumours was enhanced two-fold by integrin-targeting peptides compared to non-targeted nanocomplexes. RTNs containing the interleukin-2 (IL-2) and IL-12 genes were administered intravenously with seven doses at 48 h intervals and tumour growth monitored. Tumours from treated animals were approximately 75% smaller on day 11 compared with RTNs containing control plasmids with one third of treated mice surviving long-term. Extensive leukocyte infiltration, decreased vascularization and increased necrotic areas were observed in the tumours from IL2/IL12 treated animals. Splenocytes from re-challenged mice displayed enhanced IL-2 production following Neuro-2A co-culture, which, combined with infiltration studies, suggested a cytotoxic T cell-mediated9 tumour-rejection process. The integrin-targeted RTN formulation may have broader applications in the further development of cancer therapeutics.     

Predictors of response to group cognitive-behavioral therapy in the treatment of obsessive-compulsive disorder

PurposeTo identify the presence of factors associated with treatment outcome in patients under group cognitive-behavioral therapy (GCBT) for obsessive-compulsive disorder (OCD).Subjects and methodsThis study evaluated 181 patients with OCD that attended a 12-session weekly GCBT program. Response criteria were: ≥35% reduction in Y-BOCS scores and global improvement score of the Clinical Global Impression (CGI) ≤ 2 at post-treatment evaluation. Sociodemographic data, OCD characteristics, and treatment data were studied.ResultsIn the bivariate analysis, the following variables showed statistical significance (p < 0.20) to enter the regression model: being woman (p = 0.074), greater insight (p = 0.017) and better quality of life (QOL) in all domains before treatment (p = 0.053), overall severity of disease according to the CGI (p = 0.007), number of associated comorbidities (p = 0.063), social phobia (p = 0.044), and dysthymia (p = 0.072). In the final regression model, these variables were associated with response to GCBT: female gender (p = 0.021); WHOQOL-BREF psychological domain (p = 0.011); insight (p = 0.042); and global improvement score of the CGI severity-scale before therapy (p = 0.045).ConclusionSpecial attention should be paid to patients with poor insight, increasing the cognitive aspects of the therapy in an attempt to modify the rigidity and fixity of their beliefs. In addition, male patients should be more observed, since they showed lower chance of response to GCBT when compared to women. Patients with more severe global symptoms (CGI) are poorer responders to GCBT, which indicates that not only obsessive-compulsive symptoms (OCS) should be evaluated, since other symptoms, such as depression and anxiety, may affect the treatment; therefore, an attempt to reduce these symptoms, prior to the treatment of OCD, should be considered as an option in some cases.     

Fascia lata allograft bridging of a rotator cuff tear in a rabbit animal model

Purpose:

Despite advances in surgical treatment options, large rotator cuff (r-c) tears still represent a challenge for orthopedic surgeons. The purpose of this study was to evaluate the temporary and spatial histological incorporation of fascia lata allografts, used for bridging artificially created defects of the r-c.

Materials and Methods:

Seventy-two rabbits were divided into two groups and a supraspinatus tendinous defect was created. Half of the rabbit population underwent repair only, while in the other half, the defect was bridged utilizing fascia lata allograft. The animals were euthanized at 2, 4, and 6 weeks postoperative. Half of the specimens were evaluated histologically and the other half underwent mechanical testing.

Results:

There was an increased remodeling activity, fibroblastic in growth and strong presence of collagen fibers observed at 6 weeks on both groups. A gradually increasing mechanical strength was noticed by week 6 and increased toughness was also found at the same time period. There was no significant difference observed between the two groups regarding their histological and mechanical properties.

Conclusions:

In the difficult scenario of a large irreparable tear where the simple suture of the remaining r-c is impossible, allograft bridging, could be used with satisfactory results.

Clinical Relevance:

Treatment Study, Level 1.