Atopic dermatitis in adults: evaluation of peripheral blood mononuclear cells proliferation response to Staphylococcus aureus enterotoxins A and B and analysis of interleukin-18 secretion

Atopic dermatitis (AD) is a chronic, inflammatory skin disease with a high prevalence and complex pathogenesis. The skin of AD patients is usually colonized by Staphylococcus aureus (S. aureus); its exotoxins may trigger or enhance the cutaneous inflammation. Several mediators are related to the AD immune imbalance and interleukin-18 (IL-18), an inflammatory cytokine, may play a role in the atopic skin inflammation. To evaluate peripheral blood mononuclear cells (PBMC) proliferation response to staphylococcal enterotoxins A (SEA) and B (SEB) and the levels of IL-18 in adults with AD. Thirty-eight adult patients with AD and 33 healthy controls were analysed. PBMC were stimulated with SEA and SEB, phytohemaglutinin (PHA), pokeweed (PWM), tetanus toxoid (TT) and Candida albicans (CMA). IL-18 secretion from PBMC culture supernatants and sera were measured by ELISA. A significant inhibition of the PBMC proliferation response to SEA, PHA, TT and CMA of AD patients was detected (P <= 0.05). Furthermore, increased levels of IL-18 were detected both in sera and non-stimulated PBMC culture supernatants from AD patients (P <= 0.05). A decreased PBMC proliferation response to distinct antigens and mitogens (TT, CMA, SEA and PHA) in adults with AD suggest a compromised immune profile. IL-18 secretion from AD upon stimulation was similar from controls, which may indicate a diverse mechanism of skin inflammation maintained by Staphylococcus aureus. On the other hand, augmented IL-18 secretion from AD sera and non-stimulated cell culture may enhance the immune dysfunction observed in AD, leading to constant skin inflammation.

The impact of gender, age and hearing loss on tinnitus severity

Tinnitus is a symptom present in approximately 15% of the world population. Most patients are between 40 and 80 years of age; the prevalence above 60 reaches 33%. About 20% have moderate to severe impact in the quality of life but the factors associated with the tinnitus annoyance are not completely known. Aim: The objective of this study is to evaluate the relationship between age, gender and hearing loss on tinnitus annoyance. Materials and methods: 68 patients were evaluated at the tinnitus center at our hospital, from March 2007 to march 2008, with a detailed interview, complete otolaryngological examination, the Portuguese version of the Tinnitus Handicap Inventory and pure tone audiometry. Results: Age varied from 24 to 83 (mean=59); the mean THI value was 39 (females: 36; males: 44). THI grades were: slight: 32.3%; mild: 19.1%; moderate: 20.6%; severe: 13.2% and catastrophic: 14.7%. No significant correlation was found between gender (p=0.30), age (p=0.77) hearing loss (p>0.05 for all averages analyzed) and tinnitus severity. Conclusion: Gender, age and hearing loss do not influence tinnitus annoyance, using the THI.

Platelet GSK3B activity in patients with late-life depression: Marker of depressive episode severity and cognitive impairment?

Objective. Increased GSK3B activity has been reported as a state marker of major affective episodes in patients with depression and bipolar disorder. No study so far has addressed GSK3B activity in late-life depression. The aims of the present study were to determine GSK3B activity in platelets of elderly patients with major depression, and the association between GSK3B activity and the severity of depressive symptoms and cognitive impairment. Methods. Forty drug-free elderly patients with major depressive episode were compared to healthy older adults (n == 13). Severity of the depressive episode and current cognitive state were determined by the Hamilton Depression Scale (HAM-D) and the Cambridge Cognitive Test (CAMCOG), respectively. Total- and ser-9-phosphorylated GSK3B (tGSK3B and pGSK3B) were determined in platelets by enzyme immunometric assays (EIA). GSK3B activity was indirectly inferred by the GSK3B ratio (i.e. pGSK3B/tGSK3B). Results. Elderly depressed patients had significantly lower pGSK3B levels (P == 0.03) and GSK3B ratio (P == 0.03), indicating higher GSK3B activity. Higher GSK3B activity were observed in patients with severe depressive episode (HAM-D scores > 22, P == 0.03) and with cognitive impairment (CAMCOG scores < 86, P == 0.01). Conclusion. The present findings provide additional evidence of the involvement of GSK3B in the pathophysiology of late-life major depression. Higher GSK3B activity may be more relevant in those patients with more severe depressive symptoms and cognitive impairment.

The role of alcoholic beverage preference in the severity of alcohol dependence and adherence to the treatment

The severity of dependence on alcohol and the efficacy of diverse types of treatments for alcoholism have been the subject of various researches. This study focused on the types of beverages preferentially consumed by alcohol-dependent outpatients and their effects on the severity of dependence and therapeutic outcomes. Our sample comprised 153 patients, 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence, who were randomly divided into three different groups to receive topiramate (up to 300 mg/day), naltrexone (50 mg/day), or placebo during 12 weeks of follow-up. Spirits and beer were the main beverages consumed. At the start of this research, the group of spirits drinkers showed higher severity of alcohol dependence, higher craving for alcohol, more frequent history of treatments for alcoholism, and lower income than the group of beer preference drinkers. During the study, beer preference drinkers demonstrated higher adherence to the treatment, independently of the types of medications prescribed (P = .02, odds ratio, 2.46, 95% confidence interval, 1.17-5.19). This study suggests that the severity of dependence and the adherence to the treatment can be factors that set apart beer drinkers from spirits drinkers. As the compliance with the treatment for alcoholism was lower among spirits preference drinkers, a more intensive model of treatment would be necessary. (C) 2009 Elsevier Inc. All rights reserved.

Association between symptom severity and internal capsule volume in obsessive-compulsive disorder

Neurobiological models support an involvement of white matter tracts in the pathophysiology of obsessive-compulsive disorder (OCD), but there has been little systematic evaluation of white matter volumes in OCD using magnetic resonance imaging (MRI). We investigated potential differences in the volume of the cingulum bundle (CB) and anterior limb of internal capsule (ALIC) in OCD patients (n = 19) relative to asymptomatic control subjects (n = 15). White matter volumes were assessed using a 1.5T MRI scanner. Between-group comparisons were carried out after spatial normalization and image segmentation using optimized voxel-based morphometry. Correlations between regional white matter volumes in OCD subjects and symptom severity ratings were also investigated. We found significant global white matter reductions in OCD patients compared to control subjects. The voxel-based search for regional abnormalities (with covariance for total white matter volumes) showed no specific white matter volume deficits in brain portions predicted a priori to be affected in OCD (CB and ALIC). However, large clusters of significant positive correlation with OCD severity scores were found bilaterally on the ALIC. These findings provide evidence of OCD-related ALIC abnormalities and suggest a connectivity dysfunction within frontal-striatal-thalamic-cortical circuits. Further studies are warranted to better define the role of such white matter alterations in the pathophysiology of OCD, and may provide clues for a more effectively targeting of neurosurgical treatments for OCD. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Does the degree of smoking effect the severity of tardive dyskinesia? A longitudinal clinical trial

Background. - Tardive dyskinesia (TD) is a movement disorder observed after chronic neuroleptic treatment. Smoking is presumed to increase the prevalence of TD. The question of a cause-effect-relationship between smoking and TD, however, remains to be answered. Purpose of this study was to examine the correlation between the degree of smoking and the severity of TD with respect to differences caused by medication. Method. - We examined 60 patients suffering from schizophrenia and TD, We compared a clozapine-treated group With a group treated with typical neuroleptics. Movement disorders were assessed using the Abnormal-Involuntary-Movement-Scale and the technical device digital image processing, providing rater independent information on perioral movements. Results. - We found a strong correlation (.80 < r < .90, always p < .0001) between the degree of smoking and severity of TD. Repeated measurements revealed a positive correlation between changes in cigarette consumption and changes of the severity of TD (p < .0001). Analyses of covariance indicated a significant group-effect with a lower severity of TD in the clozapine-group compared to the typical-neuroleptics-group (p = .010). Interaction-analyses indicated a higher impact of smoking oil the severity of TD in the typical-neuroleptics-group compared to the clozapine-group (p = .033). Conclusion. - Concerning a possible cause-effect-relationship between smoking and TD, smoking is more of a general health hazard than neuroleptic exposure in terms of TD. (C) 2008 Elsevier Masson SAS. All rights reserved.

Airway smooth muscle thickness in asthma is related to severity but not duration of asthma

Asthma is characterised by an increased airway smooth muscle (ASM) area (ASMarea) within the airway wall. The present study examined the relationship of factors including severity and duration of asthma to ASMarea. The perimeter of the basement membrane (PBM) and ASMarea were measured on transverse sections of large and small airways from post mortem cases of fatal (n=107) and nonfatal asthma (n=37) and from control subjects (n=69). The thickness of ASM (ASMarea/PBM) was compared between asthma groups using multivariate linear regression. When all airways were considered together, ASMarea/PBM (in millimetres) was increased in nonfatal (median 0.04; interquartile range 0.013-0.051; p=0.034) and fatal cases of asthma (0.048; 0.025-0.078; p<0.001) compared with controls (0.036; 0.024-0.042). Compared with cases of nonfatal asthma, ASMarea/PBM was greater in cases of fatal asthma in large (p<0.001) and medium (p<0.001), but not small, airways. ASMarea/PBM was not related to duration of asthma, age of onset of asthma, sex or smoking. No effect due to study centre, other than that due to sampling strategy, was found. The thickness of the ASM layer is increased in asthma and is related to the severity of asthma but not its duration.

Melatonin reduces the severity of experimental amoebiasis

Background: Melatonin has immunomodulatory effects but very little is known about its influence in protozoan infections, such as Entamoeba histolytica, which causes amoebiasis, a disease with significant morbidity and mortality. In this study, we evaluated the effects of exogenous melatonin interference in experimental amoebiasis and on interactions between human blood cells and E. histolytica trophozoites. Methods: The effect of melatonin was investigated in models of experimental amoebiasis in hamsters and rats by evaluating the area of necrosis induced by E. histolytica. The activity of melatonin on the interactions between leukocytes and amoebae was determined by examining leukophagocytosis. For in vitro tests, polymorphonuclear and mononuclear human blood leucocytes were incubated with E. histolytica trophozoites. Results: The areas of amoebic necrosis were significantly reduced in animals treated with melatonin. Melatonin treatment increased leukophagocytosis but was associated with a greater number of dead amoebae. Conclusions: These results suggest that melatonin may play a beneficial role in the control of amoebic lesions, raising the possibility that this drug may be used as an adjuvant in anti-amoebic therapy.

Effect of Disease Severity and Optic Disc Size on Diagnostic Accuracy of RTVue Spectral Domain Optical Coherence Tomograph in Glaucoma

PURPOSE. To evaluate the effect of disease severity and optic disc size on the diagnostic accuracies of optic nerve head (ONH), retinal nerve fiber layer (RNFL), and macular parameters with RTVue (Optovue, Fremont, CA) spectral domain optical coherence tomography (SDOCT) in glaucoma. METHODS. 110 eyes of 62 normal subjects and 193 eyes of 136 glaucoma patients from the Diagnostic Innovations in Glaucoma Study underwent ONH, RNFL, and macular imaging with RTVue. Severity of glaucoma was based on visual field index (VFI) values from standard automated perimetry. Optic disc size was based on disc area measurement using the Heidelberg Retina Tomograph II (Heidelberg Engineering, Dossenheim, Germany). Influence of disease severity and disc size on the diagnostic accuracy of RTVue was evaluated by receiver operating characteristic (ROC) and logistic regression models. RESULTS. Areas under ROC curve (AUC) of all scanning areas increased (P < 0.05) as disease severity increased. For a VFI value of 99%, indicating early damage, AUCs for rim area, average RNLI thickness, and ganglion cell complex-root mean square were 0.693, 0.799, and 0.779, respectively. For a VFI of 70%, indicating severe damage, corresponding AUCs were 0.828, 0.985, and 0.992, respectively. Optic disc size did not influence the AUCs of any of the SDOCT scanning protocols of RTVue (P > 0.05). Sensitivity of the rim area increased and specificity decreased in large optic discs. CONCLUSIONS. Diagnostic accuracies of RTVue scanning protocols for glaucoma were significantly influenced by disease severity. Sensitivity of the rim area increased in large optic discs at the expense of specificity. (Invest Ophthalmol Vis Sci. 2011;92:1290-1296) DOI:10.1167/iovs.10-5516

Effect of Disease Severity on the Performance of Cirrus Spectral-Domain OCT for Glaucoma Diagnosis

PURPOSE. To evaluate the effect of disease severity on the diagnostic accuracy of the Cirrus Optical Coherence Tomograph (Cirrus HD-OCT; Carl Zeiss Meditec, Inc., Dublin, CA) for glaucoma detection. METHODS. One hundred thirty-five glaucomatous eyes of 99 patients and 79 normal eyes of 47 control subjects were recruited from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS). The severity of the disease was graded based on the visual field index (VFI) from standard automated perimetry. Imaging of the retinal nerve fiber layer (RNFL) was obtained using the optic disc cube protocol available on the Cirrus HD-OCT. Pooled receiver operating characteristic (ROC) curves were initially obtained for each parameter of the Cirrus HD-OCT. The effect of disease severity on diagnostic performance was evaluated by fitting an ROC regression model, with VFI used as a covariate, and calculating the area under the ROC curve (AUCs) for different levels of disease severity. RESULTS. The largest pooled AUCs were for average thickness (0.892), inferior quadrant thickness (0.881), and superior quadrant thickness (0.874). Disease severity had a significant influence on the detection of glaucoma. For the average RNFL thickness parameter, AUCs were 0.962, 0.932, 0.886, and 0.822 for VFIs of 70%, 80%, 90%, and 100%, respectively. CONCLUSIONS. Disease severity had a significant effect on the diagnostic performance of the Cirrus HD-OCT and thus should be considered when interpreting results from this device and when considering the potential applications of this instrument for diagnosing glaucoma in the various clinical settings. (Invest Ophthalmol Vis Sci. 2010;51:4104-4109) DOI:10.1167/iovs.094716

Impaired interhemispheric interactions in patients with major depression

Previous studies have shown that patients with major depression have an interhemispheric imbalance between right and left prefrontal and motor cortex. We aimed to investigate the interhemispheric interactions in patients with major depression using repetitive transcranial magnetic stimulation (rTMS). Thirteen patients with major depression and 14 age-matched healthy subjects participated in this study. Corticospinal excitability before and after 1 Hz rTMS (applied to the left primary motor cortex) was assessed in the left and right motor cortex and these results were compared with those in healthy subjects. There was a significant difference in the interhemispheric effects between patients with depression and healthy subjects. In healthy subjects, 1 Hz rTMS significantly decreased corticospinal excitability in the stimulated, left hemisphere and increased it in the contralateral, right hemisphere. In depressed subjects, 1 Hz rTMS also decreased corticospinal excitability in the left hemisphere; however, it induced no significant changes in corticospinal excitability in the contralateral, right hemisphere. In addition, there was a significant correlation between the degree of interhemispheric modulation and the severity of the depression as indexed by the Beck Depression Inventory scores. Our findings showing a decreased interhemispheric modulation in patients with major depression are consistent with the notion that mood disorders are associated with slow interhemispheric switching mechanisms.

Vestibular rehabilitation with biofeedback in patients with central imbalance

Central Nervous System disorders may cause important functional unbalance in the maintenance of balance and posture. There is no effective rehabilitation for these symptoms until now. Objective: The aim of this paper is to evaluate the use of tongue electrotactile stimulation on patients with central imbalance using BrainPort. Materials and Methods: This is a prospective case series study. We evaluated 8 patients with central imbalance, 6 men and 2 women, with mean age of 67.75 years. The patients were submitted to Computed Dynamic Posturography (CDP) and then received 18 sessions of electrotactile stimulation by BrainPort (R) device for 20 minutes, twice a day. Then they were submitted to a new CDP test and to a self-perception scale to assess symptom remission, partial improvement and no improvement at all. Results: 75% of the patients reported being more stable. There was no improvement in the balance control of the mass center in these patients. Conclusion: The patients were able to use the electrotactile stimulus to improve their balance control.

Toxoplasma gondii: The severity of toxoplasmic encephalitis in C57BL/6 mice is associated with increased ALCAM and VCAM-1 expression in the central nervous system and higher blood-brain barrier permeability

In order to investigate the differential ALCAM, ICAM-1 and VCAM-1 adhesion molecules mRNA expression and the blood-brain barrier (BBB) permeability in C57BL/6 and BALB/c mice in Toxoplasma gondii infection, animals were infected with ME-49 strain. It was observed higher ALCAM on day 9 and VCAM-1 expression on days 9 and 14 of infection in the central nervous system (CNS) of C57BL/6 compared to BALB/c mice. The expression of ICAM-1 was high and similar in the CNS of both lineages of infected mice. In addition, C57BL/6 presented higher BBB permeability and higher IFN-gamma and iNOS expression in the CNS compared to BALB/c mice. The CNS of C578L/6 mice presented elevated tissue pathology and parasitism. In conclusion, our data suggest that the higher adhesion molecules expression and higher BBB permeability contributed to the major inflammatory cell infiltration into the CNS of C57BL/6 mice that was not efficient to control the parasite. (C) 2010 Elsevier Inc. All rights reserved.

Human leukocyte antigen (HLA) and single nucleotide polymorphisms (SNPs) tumor necrosis factor (TNF)-alpha-238 and-308 as genetic markers of susceptibility to psoriasis and severity of the disease in a long-term follow-up Brazilian study

Background The strongest genetic marker for psoriasis is Cw*06. Polymorphisms in the tumor necrosis factor (TNF)-alpha promoter region, especially replacement of guanine with adenine in positions -238 and -308 are related to higher TNF-alpha production and higher risk for psoriasis in Caucasoid populations, not found in Asians. We performed a case-control study of 69 patients with psoriasis type I and 70 controls, characterized clinical progression along 10-years of follow-up in mild or severe disease and determined HLA class I, II, and TNF single nucleotide polymorphisms (SNPs) -238 and -308 polymorphisms to demonstrate whether these polymorphisms may be genetic risk for susceptibility to psoriasis or severity of the disease in Brazilians. Methods Polymorphisms were identified using PCR/SSP. Alleles, genotypes, and haplotypes frequencies were compared using Fisher`s test. Results More severe disease was found in male patients. It may be suggested that alleles B*37, Cw*06, Cw*12, and DRB1*07 were associated with severe disease course, while B*57 with mild disease. No statistical difference was found between the patients and controls regarding polymorphisms frequencies in TNF SNPs. This study pointed to a higher TNF-238 G/G genotype frequency (OR: 3.21; CI: 1.06-9.71; P = 0.04) in the group with severe disease. Conclusions Polymorphisms in the TNF-alpha SNPs do not seem to be a more important genetic risk factor for psoriasis than the already known Cw*06 in Brazilian patients, but these markers may be related to clinical manifestations.

Severity dependent increases in circulating cardiac troponin I and MMP-9 concentrations after experimental acute pulmonary thromboembolism

Background: Making the diagnosis of acute pulmonary thromboembolism (APT) and assessing its severity is very challenging, While cardiac troponin I (cTnI) concentrations are promising in risk stratification, no previous study has examined whether there is a linear relation between cTnI concentrations and the severity of APT. Moreover, matrix metalloprotemases (MMPs) are involved in the pathophysiology of APT. However, it is unknown whether the increases in MMP concentrations after APT reflect the severity of this condition. We examined whether the circulating concentrations of these biomarkers increase in proportion to the severity of experimental APT induced in anesthetized dogs. Methods: APT was induced with autologous blood clots (saline, 1, 3, or 5 ml/kg) injected into the right atrium. Hemodynamic evaluations were carried out for 120 min. Gelatin zymography of MMP-2 and MMP-9 from plasma samples were performed and serum cTnI concentrations were determined at baseline and 120 min after APT. Results: While no significant increases in pro-MMP-2 concentrations were found after APT, pro-MMP-9 concentrations increased by 80% only after 5 ml/kg of clot embolization. Serum cTnI and plasma pro-MMP-9 concentrations correlated positively with pulmonary vascular resistance (P=0.007 and rs=0.833 for troponin 1, and P=0.034 and rs=0.684 for pro-MMP-9) and with pulmonary artery pressure (P=0.005 and rs=0.610 for troponin 1, and P=0.022 and rs=0.720 for pro-MMP-9). Conclusions: Circulating cTnI and pro-MMP-9 increase in proportion to the severity of APT, although the increases in plasma pro-MMP-9 are less clear with less severe APT. These findings may be relevant for clinical APT. (C) 2007 Elsevier B.V. All rights reserved.