Superior temporal metabolic changes related to auditory hallucinations: a 31P-MR spectroscopy study in antipsychotic-free schizophrenia patients

Structural deficits in the superior temporal cortex and transverse temporal gyri appear to be related to auditory hallucinations in schizophrenia, which are a key symptom of this disorder. However, the cellular and neurochemical underpinnings are poorly understood and hardly studied in vivo. We used ³¹P-MRS (magnetic resonance spectroscopy) with chemical shift imaging to assess the association between left superior temporal cortex metabolism and severity of auditory hallucinations in 29 schizophrenia patients off antipsychotics. Hallucinations scores derived from the Scale for the Assessment of Positive Symptoms showed significant positive correlations with both measures of phospholipids (phosphomonoesters and phosphodiesters), and energy (inorganic phosphate and phosphocreatine, but not adenosine tri-phosphate) metabolism in left superior temporal gyrus/Heschl gyrus voxels. There was no correlation of metabolites in these regions with formal thought disorder, a symptom also linked to superior temporal pathology, thus suggesting symptom specificity. Our findings provide a link between established structural deficits and neurochemical pathology related to membrane pathology and markers of general metabolic turnover.     

Intestinal Expression of Human Heat Shock Protein 90 in Patients with Crohn's Disease and Ulcerative Colitis

Heat shock proteins are induced by severalstress factors and are potential antigens in autoimmunedisorders. Expression of heat shock protein 90 (HSP 90)was investigated in patients with inflammatory bowel disease and normal controls. We combinedwestern blot analysis with laser densitometry forquantitation. Localization of HSP 90 was investigated byimmunohistochemistry. Western blots showed a significant mucosal expression of HSP 90, which wascomparable in patients and controls. There was also nodifference between normal and inflamed mucosa ininflammatory bowel disease. In immunohistochemicalstaining studies, HSP 90 was detected in epithelialcells, mononuclear cells, giant cells, nerve cells, andendothelial cells of small vessels. There was nodifference in the intensity of staining or localization in patients with inflammatory bowel diseasecompared to controls. These findings render a potentialprotective or immunogenic function of HSP 90 ininflammatory bowel disease unlikely.     

An elevated level of IL-10- and TGFβ-secreting T cells,B cells and macrophages in the synovial membrane of patients with reactive arthritis compared to rheumatoid arthritis

A relative high secretion level of IL-10 and a low secretion of TNF- has been described in the synovial fluid and peripheral blood of patients with reactive arthritis (ReA), possibly contributing to the persistence of bacteria. The role of TGF- is less clear. We investigated these cytokines in the synovial membrane of patients with ReA and rheumatoid arthritis (RA) and tried to identify their cellular source. We used sections from the synovial membrane of 4 ReA and 4 RA patients which were double stained with immunofluorescence antibodies against cell surface markers for T cells (CD3), macrophages (CD68) and B cells (CD20) in combination with antibodies against intracellular cytokines TNF-, IFN-, TGF-, IL-4 and IL-10, and quantified these using a fluorescence microscope. A lower number of TNF--secreting cells were found in ReA compared to RA: CD3+: 1.78±0.54% versus 5.02%±0.47% (p=0.034). CD68+: 2.86±0.52 versus 5.37±0.53% (p=0.034), CD20+ : 3.02±0.42% versus 3.58±0.48% (p>0.05). A higher number of IL-10 positive cells were found in ReA compared to RA: CD3+: 3.27±1.5% versus 1.13±0.50% (p=0.034), CD68+ 1.23±0.75% versus 0.83±0.35%(p>0.05), CD20+: 3.70±1.6% versus 1.6±1.1% (p>0.05). A difference between ReA and RA was also found for TGF-+ T cells: CD3+ 7.86+1.5% versus 1.78+0.35% (p= 0.032); CD20+: 7.91+2.1% versus 2.1+2.8% (p>0.05), CD68+: 7.81%+1.24% versus 2.12+0.28% (p= 0.032). In conclusion, we saw a different cytokine secretion pattern in the synovial membrane of ReA and RA. For T cells in ReA we found a cytokine secretion profile typical for T regulatory cells 1 (Tr1), with an elevated level of IL-10- and TGF--secreting cells. Whether this is due to a more general difference in TNF-, IL-10 or TGF- production which is genetically determined or regulated by T cells remains to be determined.Abbreviations AS Ankylosing spondylitis - RA Rheumatoid arthritis - ReA Reactive arthritis     

Guidelines for Best Practice in the Audiological Management of Adults with Severe and Profound Hearing Loss

Individuals with severe to profound hearing loss are likely to present with complex listening needs that require evidence-based solutions. This document is intended to inform the practice of hearing care professionals who are involved in the audiological management of adults with a severe to profound degree of hearing loss and will highlight the special considerations and practices required to optimize outcomes for these individuals.     

Regulation of mucosal structure and barrier function in rat colon exposed to tumor necrosis factor alpha and interferon gamma in vitro: A novel model for studying the pathomechanisms of inflammatory bowel disease cytokines

Objective. In Inflammatory bowel disease (IBD), elevated cytokines are responsible for disturbed intestinal transport and barrier function. The mechanisms of cytokine action have usually been studied in cell culture models only; therefore the aim of this study was to establish an in vitro model based on native intestine to analyze distinct cytokine effects on barrier function, mucosal structure, and inherent regulatory mechanisms. Material and methods. Rat colon was exposed to tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) in Ussing chambers. Transepithelial resistance (R^t) and ³H-mannitol fluxes were measured for characterization of the paracellular pathway. Transcellular transport was analyzed by horseradish peroxidase (HRP) flux measurements. Expression and distribution of tight junction proteins were characterized in immunoblots and by means of confocal laser-scanning microscopy (LSM). Results. Colonic viability could be preserved for 20 h in a specialized in vitro set-up. This was sufficient to alter mucosal architecture with crypt surface reduction. R^t was decreased (101±10 versus 189±10 Ω·cm²) with a parallel increase in mannitol permeability after cytokine exposure. Tight junction proteins claudin-1, -5, -7, and occludin decreased (45±10%, 16±7%, 42±8%, and 42±13% of controls, respectively), while claudin-2 increased to 208±32%. Occludin and claudin-1 translocated from the plasma membrane to the cytoplasm. HRP flux increased from 0.73±0.09 to 8.55±2.92 pmol·h^?1·cm^?2. Conclusions. A new experimental IBD model with native colon in vitro is presented. One-day exposure to TNFα and IFNγ alters mucosal morphology and impairs epithelial barrier function by up-regulation of the paracellular pore-former claudin-2 and down-regulation of the barrier-builders claudin-1, -5, and -7. These alterations resemble changes seen in IBD and thus underline their prominent role in IBD pathogenicity.     

The Effect of a Hypertension Self-Management Intervention on Diabetes and Cholesterol Control

Background

Most patient chronic disease self-management interventions target single-disease outcomes. We evaluated the effect of a tailored hypertension self-management intervention on the unintended targets of glycosylated hemoglobin (HbA_1c) and low-density lipoprotein cholesterol (LDL-C).

Methods

We evaluated patients from the Veterans Study to Improve the Control of Hypertension, a 2-year randomized controlled trial. Patients received either a hypertension self-management intervention delivered by a nurse over the telephone or usual care. Although the study focused on hypertension self-management, we compared changes in HbA_1c among a subgroup of 216 patients with diabetes and LDL-C among 528 patients with measurements during the study period. Changes in these laboratory values over time were compared between the 2 treatment groups using linear mixed-effects models.

Results

For the patients with diabetes, the hypertension self-management intervention resulted in a 0.46% reduction in HbA_1c over 2 years compared with usual care (95% confidence interval, 0.04%-0.89%; P = .03). For LDL-C, there was a minimal 0.9 mg/dL between-group difference that was not statistically significant (95% confidence interval, −7.3-5.6 mg/dL; P = .79).

Conclusions

There was a significant effect of the self-management intervention on the unintended target of HbA_1c,but not LDL-C. Chronic disease self-management interventions might have “spill-over” effects on patients' comorbid chronic conditions.