A genome-wide linkage scan reveals CD53 as an important regulator of innate TNF-α levels

Cytokines are major immune system regulators. Previously, innate cytokine profiles determined by lipopolysaccharide stimulation were shown to be highly heritable. To identify regulating genes in innate immunity, we analyzed data from a genome-wide linkage scan using microsatellites in osteoarthritis (OA) patients (The GARP study) and their innate cytokine data on interleukin (IL)-1β, IL-1Ra, IL-10 and tumor necrosis factor (TNF)α. A confirmation cohort consisted of the Leiden 85-Plus study. In this study, a linkage analysis was followed by manual selection of candidate genes in linkage regions showing LOD scores over 2.5. An single-nucleotide polymorphism (SNP) gene tagging method was applied to select SNPs on the basis of the highest level of gene tagging and possible functional effects. QTDT was used to identify the SNPs associated with innate cytokine production. Initial association signals were modeled by a linear mixed model. Through these analyses, we identified 10 putative genes involved in the regulation of TNFα. SNP rs6679497 in gene CD53 showed significant association with TNFα levels (P=0.001). No association of this SNP was observed with OA. A novel gene involved in the innate immune response of TNFα is identified. Genetic variation in this gene may have a role in diseases and disorders in which TNFα is closely involved.     

Hyperglycaemia in critically ill patients: marker or mediator of mortality?

Acute hyperglycaemia has been associated with complications, prolonged intensive care unit and hospital stay, and increased mortality. We made an inventory of the prevalence and prognostic value of hyperglycaemia, and of the effects of glucose control in different groups of critically ill patients. The prevalence of hyperglycaemia in critically ill patients, using stringent criteria, approaches 100%. An unambiguous negative correlation between hyperglycaemia and mortality has been described in various groups of critically ill patients. Although the available evidence remains inconsistent, there appears to be a favourable effect of glucose regulation. This effect on morbidity and mortality depends on patient characteristics. To be able to compare results of future studies involving glucose regulation, better definitions of hyperglycaemia (and consequently of normoglycaemia) and patient populations are needed.     

Age determines the prognostic role of the cancer stem cell marker aldehyde dehydrogenase-1 in breast cancer

Background  

The purpose of this study was to compare the expression and the prognostic effect of the breast cancer stem cell marker aldehyde dehydrogenase-1 (ALDH1) in young and elderly breast cancer patients.     

Prostatic evaluation by transrectal sonography: criteria for diagnosis of early carcinoma

Over a 7-month period, from a total of 417 transrectal ultrasound (US) studies, 45 transperineal biopsies of the prostate were performed in the radiology department. Transrectal US guidance and local anesthesia were used. Twenty-two of 32 hypoechoic lesions, located within the peripheral zone tissue of the gland, were proved by histologic study to be cancerous. Hyperechoic lesions were all histologically benign hyperplasias. The patients experienced no major complications necessitating hospitalization or increased length of hospital stay as a result of the procedure.     

Complications of intravenous DSA performed for carotid artery disease: a prospective study

One hundred and two patients, who were being evaluated for carotid artery disease, were prospectively studied for complications occurring as a result of intravenous digital subtraction angiography (DSA). We recorded the type, number, and outcome of complications and reviewed the amount of contrast material used, along with the patient's age and medical history for possible correlation with increased complications. There were 55 total complications or side effects involving 37 patients. Central nervous system (CNS) complications included six major-transient and one major-permanent complication. Systemic complications included 20 major-transient and two major-permanent events. The patient's age and the amount of contrast material used did not appear to be significant risk factors. Complications in our series were significantly higher than previous DSA reports and published data on conventional angiography studies. Many of our patients were in a relatively high risk group, including 74 patients who had multisystem disease and 30 who had histories of angina.     

Colonization pressure: a critical parameter in the epidemiology of antibiotic-resistant bacteria

ABSTRACT: The recognition of colonization pressure as an important risk factor for acquisition of antibiotic-resistant bacteria in the ICU, including Acinetobacter species, has major consequences for our understanding of risk factor analyses. Moreover, the importance of colonization pressure underpins the role of cross-transmission in the dynamics of antibiotic-resistant bacteria in the ICU, which has major consequences for the evaluation of the effectiveness of infection control measures.