Increased Heparanase Levels in Urine during Acute Puumala Orthohantavirus Infection Are Associated with Disease Severity

Old–world orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS), characterized by acute kidney injury (AKI) with transient proteinuria. It seems plausible that proteinuria during acute HFRS is mediated by the disruption of the glomerular filtration barrier (GFB) due to vascular leakage, a hallmark of orthohantavirus–caused diseases. However, direct infection of endothelial cells by orthohantaviruses does not result in increased endothelial permeability, and alternative explanations for vascular leakage and diminished GFB function are necessary. Vascular integrity is partly dependent on an intact endothelial glycocalyx, which is susceptible to cleavage by heparanase (HPSE). To understand the role of glycocalyx degradation in HFRS–associated proteinuria, we investigated the levels of HPSE in urine and plasma during acute, convalescent and recovery stages of HFRS caused by Puumala orthohantavirus. HPSE levels in urine during acute HFRS were significantly increased and strongly associated with the severity of AKI and other markers of disease severity. Furthermore, increased expression of HPSE was detected in vitro in orthohantavirus–infected podocytes, which line the outer surfaces of glomerular capillaries. Taken together, these findings suggest the local activation of HPSE in the kidneys of orthohantavirus–infected patients with the potential to disrupt the endothelial glycocalyx, leading to increased protein leakage through the GFB, resulting in high amounts of proteinuria.     

Alumina‐reinforced zirconia implants: survival rate and fracture strength in a masticatory simulation trial

Background: Alumina‐toughened zirconia (ATZ) is a possible alternative material to titanium for oral implants. No data are available on the fracture strength of ATZ oral implants. Purpose: The purpose of this study was to examine one‐piece implants made of ATZ ceramic under artificial loading conditions and to compare the fracture strength of these implants with implants fabricated from tetragonal zirconium dioxide poylcrystal (TZP)‐A. Materials and methods: A total of 72 implants, 48 ATZ implants (groups A and B) and 24 TZP‐A implants (group C), were investigated. A chamfer preparation at the implant heads was performed on all implants of groups B and C. Eight implants of each group underwent 1.2 or five million thermomechanical loading cycles in the chewing simulator (load value: 98 N). Further eight implants of each group were not cyclic loaded. Finally, the fracture strength of all implants was determined using a universal testing machine. Results: No implant fractured during loading in the chewing simulator. All implants were placed in the universal testing machine to evaluate fracture strength. The mean fracture strength values±standard deviations for the implants without artificial loading were 1734±165 N (ATZ, no preparation), 1220±85 N (ATZ, with preparation), and 578±49 N (TZP‐A, with preparation); 1489±190 N (ATZ, no preparation), 1064±121 N (ATZ, with preparation), and 607±57 N (TZP‐A, with preparation) with 1.2 million loading cycles; and 1358±187 N (ATZ, no preparation), 1098±97 N (ATZ, with preparation), and 516±45 N (TZP‐A, with preparation) with five million cycles. The ATZ implants showed significantly higher mean fracture strengths compared with the TZP‐A implants. Modification of the implant head using diamond burs and increased loading time also led to a significant decrease in fracture strength. Conclusions: The ATZ implants showed an increased mechanical stability compared with the TZP‐A. Modification of the implant head resulted in a decrease in fracture strength. However, within the limits of this in vitro investigation it can be concluded that ATZ implants will withstand functional loading over an estimated period of 20 years. To cite this article:
Kohal R‐J, Wolkewitz M, Mueller C. Alumina‐reinforced zirconia implants: survival rate and fracture strength in a masticatory simulation trial.
Clin. Oral Impl. Res. 21 , 2010; 1345–1352.
doi: 10.1111/j.1600‐0501.2010.01954.x     

Predictors of treatment outcomes after removal of amalgam fillings: associations between subjective symptoms,psychometric variables and mercury levels

Weidenhammer W, Bornschein S, Zilker T, Eyer F, Melchart D, Hausteiner C. Predictors of treatment outcomes after removal of amalgam fillings: associations between subjective symptoms, psychometric variables and mercury levels. Community Dent Oral Epidemiol 2010. © 2010 John Wiley & Sons A/S Abstract – Objective: This analysis aimed to study predictors of different treatment outcomes and associations between subjective symptoms, psychometric variables and mercury levels in patients who subjectively attributed their health problems to dental amalgam. Material and methods: A secondary and retrospective analysis of data of a recently published randomized clinical trial was performed. Seventy‐eight patients [44% female, mean (SD) age 35 (6) years, randomly assigned to either amalgam removal or a health promotion program] were included into statistical analysis. Prior to intervention and 12 months later, questionnaires for assessing symptoms, psychological distress and health status were presented, and mercury levels in blood and urine were determined. Results: The patients’ personality profile at study onset was characterized by slightly reduced extraversion and slightly elevated emotional instability. Overall, subjective symptoms decreased slightly and there were no statistically significant differences in the decrease of symptoms after intervention between both groups. Decrease of mercury levels after intervention was closely associated with removal of amalgam fillings (r_mult = 0.64 in regression analysis). Statistically significant correlations could be found between mercury levels and subjective symptoms with respect to baseline (r = 0.29–0.39) and to changes after intervention (r = 0.24–0.42), but not for psychological distress (r = 0.05–0.25) and health related quality of life (r = ?0.03–0.18). Prediction of symptom improvement after intervention was poor (r_mult = 0.44). Conclusions: Results contribute some new aspects to the inconsistent findings in the literature with respect to associations between symptoms and subtoxic mercury levels. More emphasis should be placed on exploring individual vulnerability for amalgam sensitivity.     

The antihistamine fexofenadine does not affect I(Kr) currents in a case report of drug-induced cardiac arrhythmia

1. The human HERG gene encodes the cardiac repolarizing K(+) current I(Kr) and is genetically inactivated in inherited long QT syndrome 2 (LQTS2). The antihistamine terfenadine blocks HERG channels, and can cause QT prolongation and torsades de pointes, whereas its carboxylate fexofenadine lacks HERG blocking activity. 2. In the present study the ability of fexofenadine to block the K897T HERG channel variant was investigated. The underlying single nucleotide polymorphism (SNP) A2960C was identified in a patient reported to develop fexofenadine-associated LQTS. 3. K897T HERG channels produced wild-type-like currents in Xenopus oocytes. Even at a concentration of 100 micro M, fexofenadine did not inhibit wild-type or K897T HERG channels. Coexpression of wild-type and K897T HERG with the ss-subunit MiRP1, slightly changed current kinetics but did not change sensitivity to terfenadine and fexofenadine. 4. Western blot analysis and immunostaining of transiently transfected COS-7 cells demonstrated that overall expression level, glycosylation pattern and subcellular localization of K897T HERG is indistinguishable from wild-type HERG protein, and not altered in the presence of 1 micro M fexofenadine. 5. We provide the first functional characterization of the K897T HERG variant. We demonstrated that K897T HERG is similar to wild-type HERG, and is insensitive to fexofenadine. Although the polymorphism changes PKA and PKC phosphorylation sites, regulation of K897T HERG by these kinases is not altered. 6. Our results strongly indicate that QT lengthening and cardiac arrhythmia in the reported case of drug-induced LQT are not due to the K897T exchange or to an inhibitory effect of fexofenadine on cardiac I(Kr) currents. British Journal of     

Psychiatric morbidity and low self-attentiveness in patients with environmental illness

Controversy surrounds the origin of symptoms attributed to environmental pollutants or widely used chemicals, and the authors believed that a psychiatric evaluation could advance understanding of this contentious condition. They assessed psychiatric morbidity, somatization, and self-attentiveness in patients seen in their Environmental Clinic. Two hundred ninety-five consecutive patients underwent SCID-I and -II interviews and were investigated with self-rating scales for self-attentiveness and somatization. The authors found a high prevalence of mental disorders (66% had a current SCID diagnosis, and 75% had a lifetime SCID diagnosis) and a low level of self-attentiveness, which was not necessarily associated with psychiatric disease. Among patients visiting an Environmental Clinic, mental disorders were common and needed to be diagnosed and treated by standard interventions. Patients who did not meet diagnostic criteria for a psychiatric disorder had relatively low somatization scores and low private self-attentiveness. These "externalizers" could benefit from an intervention that teaches them to focus on their internal and emotional lives. In these patients, the authors consider low self-attentiveness a major feature that may act as a pathogenic factor for environmental illness.     

Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia

OBJECTIVE: Abnormalities in the immune system in schizophrenia have been described. However, important findings such as high levels of activating cytokines in the CSF and signs of CNS inflammation have been controversial. The authors conducted a trial of the new selective cyclooxygenase-2 inhibitor celecoxib, an immunomodulatory drug, in schizophrenic patients to evaluate its therapeutic effects. METHOD: In a prospective, double-blind evaluation, 50 patients with an acute exacerbation of schizophrenia were randomly assigned to either risperidone plus celecoxib or risperidone plus placebo. After a washout period, 25 patients received 2-6 mg/day of risperidone plus placebo and 25 received risperidone plus 400 mg/day of celecoxib for 5 weeks. The treatment effect was calculated by analysis of covariance. There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or risperidone dose or plasma level. RESULTS: Over 5 weeks, both groups of patients showed significant improvement in scores on the Positive and Negative Syndrome Scale and on all subscales. However, the celecoxib group showed significantly greater improvement in the total score. CONCLUSIONS: Additional treatment with celecoxib has significant positive effects on the therapeutic action of risperidone with regard to total schizophrenia psychopathology. Moreover, the fact that treatment with an immunomodulatory drug showed beneficial effects on schizophrenia symptoms indicates that immune dysfunction in schizophrenia is not just an epiphenomenon but is related to the pathomechanism of the disorder. However, a nonimmunological therapeutic effect of celecoxib mediated by the N-methyl-D-aspartic acid receptor has to be taken into account.     

Differences in hand hygiene behavior related to the contamination risk of healthcare activities in different groups of healthcare workers.

BACKGROUND: The Fulkerson scale lists 15 typical clinical activities ranked according to their risk of hand contamination. OBJECTIVE: To investigate how often healthcare workers (HCWs) apply antiseptic handrubs after each of the specified activities ranked in the Fulkerson scale. DESIGN: Observational study. SETTING: University Hospital of Heidelberg, a 1,600-bed teaching hospital. METHODS: Using a structured protocol, 41 observers recorded whether HCWs rubbed their hands in 1 of 15 given situations. RESULTS: Handrubs were used in 1,115 (52.2%) of 2,138 observations. Comparatively high rates of handrub use were observed after contact with sterile materials (39.6%) and after contact with excretions (90% to 97%). Nurses used handrubs significantly more frequently than did physicians after contact with the inanimate environment, but physicians applied handrubs significantly more frequently after contact with body secretions. CONCLUSIONS: This study showed better compliance with hand hygiene than that reported by many previous studies, but compliance was still inadequate and varied significantly by type of HCW, type of activity, and location in the hospital.     

Recurrent perivascular inflammation induced by lipopolysaccharide (endotoxin) results in the formation of atheromatous lesions in vivo

Bacteria and viruses are suspected to induce arteriosclerosis; however, most investigators have focused on coincidences rather than causal relationships. The aim of this work was to establish a rabbit model in which the vessel reaction to local perivascular injection of defined bacterial products can be analyzed. A total of 23 rabbits were randomized to four groups. Groups A and B were fed a normal diet, groups C and D were fed a cholesterol-enriched diet. Groups A and C were treated with a single perivascular injection of bacterial lipopolysaccharide (LPS, endotoxin) placed next to auricular, carotid and femoral arteries, and sodium chloride placed next to the contralateral arteries (control). Group B and D animals were treated with repeated perivascular injections over 90 days. Vascular tissues (n=116 treated segments of 23 rabbits) were analyzed using morphometry at histology, and using immunohistochemistry to detect macrophages, lymphocytes and vascular smooth muscle cells. LPS treatment resulted in transient focal intima thickening. After single LPS application, no increase in atheromatous lesion formation was observed in comparison with controls (group C, lesion area index 0.031+/-0.012 vs 0.015+/-0.006, P=1.0). Repeated LPS application resulted in significant atheromatous lesion formation compared with saline control (group D, lesion area index 0.148+/-0.049 vs 0.008+/-0.006, P=0.003) in hypercholesterolemic rabbits. Repeated LPS inflammation in normocholesterolemic did not lead to atheromatous lesion formation (intima media ratio 0.04+/-0.01 vs 0.04+/-0.007, P=1.0). Single perivascular administration of low-dose bacterial LPS resulted in transient focal intimal thickening, while significant increase in lesion formation occurred after repeated LPS application in cholesterol-fed animals. In conclusion, this animal model will allow the assessment of the impact of defined dosages of different bacterial pathogens onto the vascular wall in the context of atherogenesis. The atheromatous lesion-promoting effect of repeated perivascular administration of LPS supports the hypothesis that bacterial pathogens may be involved in atherogenesis.     

Relationship between cytokine concentrations (FGF, sICAM-1 and SCF) in serum, follicular fluid and ICSI outcome

OBJECTIVE: The aim of this study was (i) to investigate the existence of fibroblast growth factor (FGF), soluble intracellular adhesion molecule-1 (sICAM-1), and stem cell factor (SCF) in serum and human follicular fluid (FF) of intracytoplasmic sperm injection (ICSI) patients, and (ii) to determine the relationship between these parameters and ICSI outcome. MATERIAL AND METHOD: Seventy-five patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropin (hMG) after down-regulation with GnRHa were included in this study. The concentrations of FGF, SCF, and sICAM-1 were measured by using commercially available enzyme-linked immunosorbent assay test kits. RESULTS: The FGF, sICAM-1, and SCF concentrations in the serum of women who become pregnant (group I) were 8.5 +/- 1.5 pg/mL, 235.8 +/- 81.1 ng/mL, and 597.7 +/- 139.9 pg/mL, and the corresponding concentrations of women who did not (group II) were 6.4 +/- 3.6 pg/mL, 230.6 +/- 66.5 ng/mL, and 569.6 +/- 91.4 pg/mL respectively. No significant difference was observed between the two investigated groups with regard to the number of hMG ampoules administered for controlled ovarian hyperstimulation, estradiol concentration on the day of human chorionic gonadotropin (hCG) injection, number of retrieved oocytes and fertilization rate. CONCLUSION: The concentration of FGF, sICAM-1, and SCF did not differ significantly between the two groups in serum or in FF. Besides, the ICSI outcome was not related to their concentrations in serum or FF. Therefore, these parameters could not be used as a prognostic factor in ICSI program.     

Snoring and progression of coronary artery disease: The Stockholm Female Coronary Angiography Study

STUDY OBJECTIVES: Snoring is associated with a significant increased risk for acute myocardial infarction and stroke. However, our knowledge of mechanisms is still incomplete. The aim of the study was to investigate the influence of snoring in combination with feelings of tiredness on the 3-year progression of atherosclerosis in women with cardiovascular disease. DESIGN: Repeated quantitative coronary angiograms were carried out with an average time interval of 3.25 years. SETTING: Department of Thoracic Radiology at Karolinska Hospital, Stockholm, Sweden. PARTICIPANTS: The study sample comprised 103 women cardiac patients with repeated, valid, and comparable measurement of quantitative coronary angiograms. MEASUREMENTS AND RESULTS: Absolute luminal diameter (in mm) was measured in 10 predefined coronary segments. Mean segment diameter was calculated as the mean of all diameters measured along a given segment. The change over time was calculated by subtracting the first from the second measurement. Snoring and feelings of tiredness were measured by a short version of the Karolinska Sleep Questionnaire. We found that snoring women, after adjusting for age, waist-hip ratio, smoking, event at hospitalization, education, hypertension and alcohol intake, had a statistically significantly larger progression of atherosclerosis than did nonsnoring women (0.18 mm vs 0.07 mm change; P = .0006). CONCLUSION: Snoring contributes to the atherosclerotic process and should be taken into consideration when treating patients with cardiac disease.