803 resultados para rigour and relevance


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Intestinal infections with Toxocara cati and Toxocara canis in their definitive host (felids and canids, respectively) are diagnosed by egg identification in faeces using coproscopical techniques. The Toxocara species is assumed to comply with the species from which the examined faeces were obtained, i.e. T. cati in cats and T. canis in dogs. We isolated and measured Toxocara eggs from faecal samples of 36 cats and 35 dogs from Switzerland and identified the Toxocara species by PCR. Amongst the isolates originating from dogs, 24 (68.5%) were determined as T. canis and 11 (31.5%) as T. cati. In all samples originating from cats, only T. cati was identified. Based on PCR identification, eggs of T. canis (n=241) and T. cati (n=442) were measured, revealing statistically significant different (p<0.001) mean sizes of 62.3 by 72.7 mum for T. cati and 74.8 by 86.0 mum for T. canis eggs. Considering that coprophagy is not unusual for dogs, a considerable percentage of Toxocara infections coproscopically diagnosed in dogs, as well as assumptions on anthelminthic resistance in regularly treated dogs, might in fact relate to intestinal passages of eggs following the uptake of other animals' faeces.

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Background: The current proposed model of colorectal tumorigenesis is based primarily on CpG island methylator phenotype (CIMP), microsatellite instability (MSI), KRAS, BRAF, and methylation status of 0-6-Methylguanine DNA Methyltransferase (MGMT) and classifies tumors into five subgroups. The aim of this study is to validate this molecular classification and test its prognostic relevance. Methods: Three hundred two patients were included in this study. Molecular analysis was performed for five CIMP-related promoters (CRABP1, MLH1, p16INK4a, CACNA1G, NEUROG1), MGMT, MSI, KRAS, and BRAF. Methylation in at least 4 promoters or in one to three promoters was considered CIMP-high and CIMP-low (CIMP-H/L), respectively. Results: CIMP-H, CIMP-L, and CIMP-negative were found in 7.1, 43, and 49.9% cases, respectively. One hundred twenty-three tumors (41%) could not be classified into any one of the proposed molecular subgroups, including 107 CIMP-L, 14 CIMP-H, and two CIMP-negative cases. The 10 year survival rate for CIMP-high patients [22.6% (95%CI: 7-43)] was significantly lower than for CIMP-L or CIMP-negative (p = 0.0295). Only the combined analysis of BRAF and CIMP (negative versus L/H) led to distinct prognostic subgroups. Conclusion: Although CIMP status has an effect on outcome, our results underline the need for standardized definitions of low- and high-level CIMP, which clearly hinders an effective prognostic and molecular classification of colorectal cancer.

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To evaluate the hard and the soft tissue parameters around implants supporting fixed prostheses over a period of 5 years and the possible association to the increase in periimplant bone density (IPBD).

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Aldosterone levels are markedly elevated during normal pregnancy but fall even though volume contracts when preeclampsia occurs. The level of aldosterone in either condition cannot be explained solely by the activity of the renin-angiotensin II system. In normal gestation, vascular endothelial growth factor (VEGF) is thought to maintain vascular health, but its role in adrenal hormone production is unknown. We hypothesized that the role of VEGF in the adrenal gland is to maintain vascular health and regulate aldosterone production. Here, we demonstrate that supernatant of endothelial cells grown in the presence of VEGF enhanced aldosterone synthase activity in human adrenocortical cells. VEGF either alone or combined with angiotensin II increased aldosterone production in adrenal cells. These data suggest that endothelial cell-dependent and independent activation of aldosterone is regulated by VEGF. In contrast to angiotensin II, VEGF did not upregulate the steroidogenic acute regulatory protein. Consistent with this observation, angiotensin II stimulated both aldosterone and cortisol synthesis from progesterone, whereas VEGF stimulated selectively aldosterone production. In rats, overexpression of soluble fms-like tyrosine kinase-1, an endogenous VEGF inhibitor, led to adrenocortical capillary rarefaction and fall in aldosterone concentrations that correlated inversely with soluble fms-like tyrosine kinase-1 levels. These findings may explain why aldosterone increases so markedly during normal gestation and why preeclampsia, a condition characterized by high soluble fms-like tyrosine kinase-1, is associated with inappropriately low aldosterone levels in spite of relatively lower plasma volumes.

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BACKGROUND: Eosinophilic esophagitis (EE) is often associated with concomitant atopic diseases. In children with EE in whom food allergens have been identified as causative factors, elemental and elimination diets result in an improvement or resolution of symptoms. Most adult EE patients are sensitized to aeroallergens, which cross-react with plant-derived food allergens, most commonly to grass pollen and cereals. AIMS OF THE STUDY: To investigate the clinical relevance of the sensitization to wheat and rye, and the efficacy of an allergen-specific elimination diet in adult EE patients. METHODS: Six patients (five men, one women) with permanently active EE sensitized to grass pollen and the cereals wheat and rye underwent a double-blind placebo-controlled food challenge and were kept on an elimination diet avoiding wheat and rye for 6 weeks. RESULTS: The challenge tests with wheat and rye did not provoke any EE symptoms in all patients. The elimination diet failed in reducing disease activity. Although one patient noticed an improvement of symptoms, endoscopic and histopathologic findings remained unchanged. CONCLUSIONS: In adult EE patients, sensitization to wheat and rye does not seem causative for EE. Elimination diet is not a reliable and efficient therapeutic measure in EE patients sensitized to wheat and rye. Low specific immunoglobulin-E levels to wheat and rye may be a consequence of the underlying grass pollen allergy.

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Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases that can occur spontaneously or can be caused by infection or mutations within the prion protein gene PRNP. Nonsynonymous DNA polymorphisms within the PRNP gene have been shown to influence susceptibility/resistance to infection in sheep and humans. Analysis of DNA polymorphisms within the core promoter region of the PRNP gene in four major German bovine breeds resulted in the identification of both SNPs and insertion/deletion (indel) polymorphisms. Comparative genotyping of both controls and animals that tested positive for bovine spongiform encephalopathy (BSE) revealed a significantly different distribution of two indel polymorphisms and two SNPs within Braunvieh animals, suggesting an association of these polymorphisms with BSE susceptibility. The functional relevance of these polymorphisms was analyzed using reporter gene constructs in neuronal cells. A specific haplotype near exon 1 was identified that exhibited a significantly lower expression level. Genotyping of nine polymorphisms within the promoter region and haplotype calculation revealed that the haplotype associated with the lowest expression level was underrepresented in the BSE group of all breeds compared to control animals, indicating a correlation of reduced PRNP expression and increased resistance to BSE.

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The role of platelets as inflammatory cells is demonstrated by the fact that they can release many growth factors and inflammatory mediators, including chemokines, when they are activated. The best known platelet chemokine family members are platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG), which are synthesized in megakaryocytes, stored as preformed proteins in alpha-granules and released from activated platelets. However, platelets also contain many other chemokines such as interleukin-8 (IL-8), growth-regulating oncogene-alpha(GRO-alpha), epithelial neutrophil-activating protein 78 (ENA-78), regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha), and monocyte chemotactic protein-3 (MCP-3). They also express chemokine receptors such as CCR4, CXCR4, CCR1 and CCR3. Platelet activation is a feature of many inflammatory diseases such as heparin-induced thrombocytopenia, acquired immunodeficiency syndrome, and congestive heart failure. Substantial amounts of PF4, beta-TG and RANTES are released from platelets on activation, which may occur during storage. Although very few data are available on the in vivo effects of transfused chemokines, it has been suggested that the high incidence of adverse reactions often observed after platelet transfusions may be attributed to the chemokines present in the plasma of stored platelet concentrates.

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REASONS FOR PERFORMING STUDY: Although endoscopic scoring of the tracheal septum thickness is used as a diagnostic tool for evaluation of lower airway disease, its clinical relevance and reliability have never been critically assessed in the horse. OBJECTIVES: To investigate if septum thickness scores (STS) are reliable and serve as a clinically useful indicator of lower airway disease status and/or inflammation. METHODS: The variance of STS attributable to the horse, observer and changes over time was determined. The distribution of STS in a population of clinically normal horses and correlations of STS with age, gender, as well as mucus accumulation and cell differentials of tracheobronchial secretions and bronchoalveolar lavage fluid were investigated. Effects of altered pulmonary ventilation, induced by different drugs, on STS were assessed. Finally, STS of horses affected with recurrent airway obstruction (RAO) were compared to those of clinically normal horses. RESULTS: Recorded STS showed excellent intra- and satisfactory interobserver agreement Established clinical, endoscopic and cytological measures of lower airway inflammation, i.e. mucus accumulation scores and airway neutrophilia, did not correlate with STS. In horses age > or = 10 years, septum scores were significantly higher (P = 0.022) than in younger horses. Septum thickness scores did not differ significantly between clinically normal and RAO-affected horses both in exacerbation and in remission. Horses with markedly increased breathing effort (i.e. with metacholine- or lobeline hydrochloride-challenge), often differed markedly (up to 1.9 scores), but the average of end-inspiratory and end-expiratory STS did not differ from baseline STS. CONCLUSIONS AND CLINICAL RELEVANCE: Endoscopic STS are a reproducible measure, but STS did not correlate with clinical, endoscopic and cytological findings indicative of RAO or inflammatory airway disease.

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Homicides with a survival of several days are not uncommon in forensic routine work. Reconstructions of these cases by autopsy alone are very difficult and may occasionally lead to unsatisfying results. For the medico-legal reconstruction of these cases, ante-mortem and post-mortem radiological imaging should always be included in the expertise. We report on a case of fatal penetrating stab wounds to the skull in which a case reconstruction was only possible by combining the radiological ante- and post-mortem data with the autopsy findings.

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We combined repetitive transcranial magnetic stimulation (rTMS) and functional magnetic resonance imaging (fMRI) to investigate the functional relevance of parietal cortex activation during the performance of visuospatial tasks. fMRI provides information about local transient changes in neuronal activation during behavioural or cognitive tasks. Information on the functional relevance of this activation was obtained by using rTMS to induce temporary regional deactivations. We thereby turned the physiological parameter of brain activity into an independent variable controlled and manipulated by the experimenter and investigated its effect on the performance of the cognitive tasks within a controlled experimental design. We investigated cognitive tasks that were performed on the same visual material but differed in the demand on visuospatial functions. For the visuospatial tasks we found a selective enhancement of fMRI signal in the superior parietal lobule (SPL) and a selective impairment of performance after rTMS to this region in comparison to a control group. We could thus show that the parietal cortex is functionally important for the execution of spatial judgements on visually presented material and that TMS as an experimental tool has the potential to interfere with higher cognitive functions such as visuospatial information processing.