Acute renal failure in critically ill patients : With special reference to prediction of outcome

Acute renal failure (ARF) is a clinical syndrome characterized by rapidly decreasing glomerular filtration rate, which results in disturbances in electrolyte- and acid-base homeostasis, derangement of extracellular fluid volume, and retention of nitrogenous waste products, and is often associated with decreased urine output. ARF affects about 5-25% of patients admitted to intensive care units (ICUs), and is linked to high mortality and morbidity rates. In this thesis outcome of critically ill patients with ARF and factors related to outcome were evaluated. A total of 1662 patients from two ICUs and one acute dialysis unit in Helsinki University Hospital were included. In study I the prevalence of ARF was calculated and classified according to two ARF-specific scoring methods, the RIFLE classification and the classification created by Bellomo et al. (2001). Study II evaluated monocyte human histocompatibility leukocyte antigen-DR (HLA-DR) expression and plasma levels of one proinflammatory (interleukin (IL) 6) and two anti-inflammatory (IL-8 and IL-10) cytokines in predicting survival of critically ill ARF patients. Study III investigated serum cystatin C as a marker of renal function in ARF and its power in predicting survival of critically ill ARF patients. Study IV evaluated the effect of intermittent hemodiafiltration (HDF) on myoglobin elimination from plasma in severe rhabdomyolysis. Study V assessed long-term survival and health-related quality of life (HRQoL) in ARF patients. Neither of the ARF-specific scoring methods presented good discriminative power regarding hospital mortality. The maximum RIFLE score for the first three days in the ICU was an independent predictor of hospital mortality. As a marker of renal dysfunction, serum cystatin C failed to show benefit compared with plasma creatinine in detecting ARF or predicting patient survival. Neither cystatin C nor plasma concentrations of IL-6, IL-8, and IL-10, nor monocyte HLA-DR expression were clinically useful in predicting mortality in ARF patients. HDF may be used to clear myoglobin from plasma in rhabdomyolysis, especially if the alkalization of diuresis does not succeed. The long-term survival of patients with ARF was found to be poor. The HRQoL of those who survive is lower than that of the age- and gender-matched general population.

Adipose tissue inflammation, liver fat and insulin resistance in humans

BACKGROUND: Obesity is closely associated with insulin resistance, which is a pathophysiologic condition contributing to the important co-morbidities of obesity, such as the metabolic syndrome and type 2 diabetes mellitus. In obese subjects, adipose tissue is characterized by inflammation (macrophage infiltration, increased expression insulin resistance genes and decreased expression of insulin sensitivity genes). Increased liver fat, without excessive alcohol consumption, is defined as non-alcoholic fatty liver disease (NAFLD) and also associated with obesity and insulin resistance. It is unknown whether and how insulin resistance is associated with altered expression of adipocytokines (adipose tissue-derived signaling molecules), and whether adipose tissue inflammation and NAFLD coexist independent of obesity. Genetic factors could explain variation in liver fat independent of obesity but the heritability of NAFLD is unknown. AIMS: To determine whether acute regulation of adipocytokine expression by insulin in adipose tissue is altered in obesity. To investigate the relationship between adipose tissue inflammation and liver fat content independent of obesity. To assess the heritability of serum alanine aminotransferase (ALT) activity, a surrogate marker of liver fat. METHODS: 55 healthy normal-weight and obese volunteers were recruited. Subcutaneous adipose tissue biopsies were obtained for measurement of gene expression before and during 6 hours of euglycemic hyperinsulinemia. Liver fat content was measured by proton magnetic resonance spectroscopy, and adipose tissue inflammation was assessed by gene expression, immunohistochemistry and lipidomics analysis. Genetic factors contributing to serum ALT activity were determined in 313 twins by statistical heritability modeling. RESULTS: During insulin infusion the expression of insulin sensitivity genes remains unchanged, while the expression of insulin resistance genes increases in obese/insulin-resistant subjects compared to insulin-sensitive subjects. Adipose tissue inflammation is associated with liver fat content independent of obesity. Adipose tissue of subjects with high liver fat content is characterized infiltrated macrophages and increased expression of inflammatory genes, as well as by increased concentrations of ceramides compared to equally obese subjects with normal liver fat. A significant heritability for serum ALT activity was verified. CONCLUSIONS: Effects of insulin infusion on adipose tissue gene expression in obese/insulin-resistant subjects are not only characterized by hyporesponse of insulin sensitivity genes but also by hyperresponse of insulin resistance and inflammatory genes. This suggests that in obesity, the impaired insulin action contributes or self-perpetuates alterations in adipocytokine expression in adipose tissue. Adipose tissue inflammation is increased in subjects with high liver fat compared to equally obese subjects with normal liver fat content. Concentrations of ceramides, the putative mediators of insulin resistance, are increased in adipose tissue in subjects with high liver fat. Genetic factors contribute significantly to variation in serum ALT activity, a surrogate marker of liver fat. These data imply that adipose tissue inflammation and increased liver fat content are closely interrelated, and determine insulin resistance even independent of obesity.

Mulibrey nanism : Clinical characteristics and pathophysiologic features of growth restriction, insulin resistance and tumour development

Background: Mulibrey nanism (MUL; Muscle-liver-brain-eye nanism; OMIM 253250) is an autosomal recessive growth disorder more prevalent in Finland than elsewhere in the world. Clinical characteristics include severe prenatal onset growth restriction, cardiopathy, multiple organ manifestations but no major neurological handicap. MUL is caused by mutations in the TRIM37 gene on chromosome 17q22-23, encoding a peroxisomal protein TRIM37 with ubiquitin E3-ligase activity. Nineteen different mutations have been detected, four of them present in the Finnish patients. Objective: This study aimed to characterize clinical and histopathological features of MUL in the national cohort of Finnish patients. Patients and methods: A total of 92 Finnish patients (age 0.7 to 77 years) participated in the clinical follow-up study. Patients hospital records and growth charts were reviewed. Physical, radiographic and laboratory examinations were performed according to a clinical protocol. Thirty patients (18 females) were treated with recombinant human GH for a median period of 5.7 years. Biopsies and autopsy samples were used for the histopathological and immunohistochemical analyses. Results: MUL patients were born small for gestational age (SGA) with immature craniofacial features after prenatal-onset growth restriction. They experienced a continuous deceleration in both height SDS and weight-for-height (WFH) postnatally. In infancy feeding difficulties and frequent pneumonias were common problems. At the time of diagnosis (median age 2.1 years) characteristic craniofacial, radiological and ocular features were the most constant findings. MUL patients showed a dramatic change in glucose metabolism with increasing age. While the children had low fasting glucose and insulin levels, 90% of the adults were insulin resistant, half had type 2 diabetes and an additional 42% showed impaired glucose tolerance (IGT). Seventy percent fulfilled the National Cholesterol Education Program (NCEP) Adult Treatment Panel III criteria for metabolic syndrome as adults. GH therapy improved pre-pubertal growth but had only minor impact on adult height (+5 cm). Interestingly, treated subjects were slimmer and had less frequent metabolic concerns as young adults. MUL patients displayed histologically a disturbed architecture with ectopic tissues and a high frequency of both benign and malignant tumours present in several internal organs. A total of 232 tumorous lesions were detected in our patient cohort. The majority of the tumours showed strong expression of endothelial cell marker CD34 as well as α-smooth muscle actin (α-SMA). Fifteen of the tumours were malignant and seven of them (five Wilms tumours) occurred in the kidney. Conclusions: MUL patients present a distinct postnatal growth pattern. Short-term response of GH treatment is substantial but the long-term impact remains modest. Although MUL patients form a distinct clinical and diagnostic entity, their clinical findings vary considerably from infancy to adulthood. While failure to thrive dominates early life, MUL adults develop metabolic syndrome and have a tendency for malignancies and vascular lesions in several organs. This speaks for a central role of TRIM37 in regulation of key cellular functions, such as proliferation, migration, angiogenesis and insulin signalling.

A Success Story or a Failure? : Representing the European Integration in the Curricula and Textbooks of Five Countries

The economic, political and social face of Europe has been changing rapidly in the past decades. These changes are unique in the history of Europe, but not without challenges for the nation states. The support for the European integration varies among the countries. In order to understand why certain developments or changes are perceived as threatening or as desired by different member countries, we must consider the social representations of the European integration on the national level: how the EU is represented to its citizens in media and in educational systems, particularly in the curricula and textbooks. The current study is concerned with the social representations of the European integration in the curricula and school textbooks in five European countries: France, Britain, Germany, Finland and Sweden. Besides that, the first volume of the common Franco-German history textbook was analyzed, since it has been seen as a model for a common European history textbook. As the collective representations, values and identities are dominantly mediated and imposed through media and educational systems, the national curricula and textbooks make an interesting starting point for the study of the European integration and of national and European identities. The social representations theory provides a comprehensive framework for the study of the European integration. By analyzing the curricula and history and civics textbooks of major educational publishers, the study aimed to demonstrate what is written on the European integration and how it is portrayed how the European integration is understood, made familiar and concretized in the educational context in the five European countries. To grasp the phenomenon of the European integration in the textbooks in its entirety, it was investigated from various perspectives. The two analysis methods of content analysis, the automatic analysis with ALCESTE and a more qualitative theory-driven content analysis, were carried out to give a more vivid and multifaceted picture of the object of the research. The analysis of the text was complemented with the analysis of visual material. Drawing on quantitative and qualitative methods, the contents, processes, visual images, transformations and structures of the social representations of European integration, as well as the communicative styles of the textbooks were examined. This study showed the divergent social representations of the European integration, anchored in the nation states, in the five member countries of the European Union. The social representations were constructed around different central core elements: French Europe in the French textbooks, Ambivalent Europe in the British textbooks, Influential and Unifying EU in the German textbooks, Enabling and Threatening EU in the Finnish textbooks, Sceptical EU in the Swedish textbooks and EU as a World Model in the Franco-German textbook. Some elements of the representations were shared by all countries such as peace and economic aspects of the European cooperation, whereas other elements of representations were found more frequently in some countries than in others, such as ideological, threatening or social components of the phenomenon European integration. The study also demonstrated the linkage between social representations of the EU and national and European identities. The findings of this study are applicable to the study of the European integration, to the study of education, as well as to the social representation theory.

Espoo shootings: A failure of restraint

Argues that focus on the immigrant status of the Espoo shooter deflects attention from the failure of the relevant authorities to effectively respond to a foreseeable threat to public safety. Response to public discussion of New Year's Day shootings in Espoo shopping mall.

Espoo shootings: A failure of restraint

Argues that focus on the immigrant status of the Espoo shooter deflects attention from the failure of the relevant authorities to effectively respond to a foreseeable threat to public safety. Response to public discussion of New Year's Day shootings in Espoo shopping mall.