HLA associated genetic predisposition to autoimmune diseases: Genes involved and possible mechanisms

Autoimmune diseases are the result of an interplay between predisposing genes and triggering environmental factors, leading to loss of self-tolerance and an immune-mediated destruction of autologous cells and/or tissues. Genes in the HLA complex are among the strongest predisposing genetic factors. The HLA complex genes primarily involved are most often those encoding the peptide-presenting HLA class I or II molecules. A probable mechanism is preferential presentation by the disease-associated HLA molecules of peptides from autoantigens to T cells. Recent studies have shown, however, that other genes in the HLA complex also contribute. Taken together, available evidence suggests that the HLA complex harbour both disease predisposing genes which are quite specific for some autoimmune diseases (e.g. HLA-B27 for ankylosing spondylitis) and others which may be more common for several diseases. This will be briefly reviewed in the following.     

Determinants of smoking cessation among adolescents in South Africa

Data is required on the motivational determinants of smoking cessation among a multi-ethnic sample of adolescents in South Africa. The I-Change Model was used to explore the determinants of smoking cessation among a sample of 1267 Black African, Colored and White Grade 9-11 monthly smokers and former smokers in the Southern Cape-Karoo region. Across the ethnic groups, former smokers displayed a more positive attitude toward non-smoking, were surrounded by a social environment that was more supportive of non-smoking, displayed higher self-efficacy not to smoke in stressful, routine and social situations, and were more positive about their intention not to smoke in the next year. The I-Change Model can be used to address the cognitions of smoking in a multi-ethnic society like South Africa. However, some ethnic tailoring will be required. Black African students will benefit from a focus on attitudinal cognitions and cultural factors that motivate smoking. Colored students require the involvement of their social environment, while White students will benefit from the development of refusal skills in social situations.     

Impact of genetic versus environmental factors on the control of muscle glycogen synthase activation in twins

Storage of glucose as glycogen accounts for the largest proportion of muscle glucose metabolism during insulin infusion in normal and insulin-resistant subjects. Studies in first-degree relatives have indicated a genetic origin of the defective insulin activation of muscle glycogen synthase (GS) in type 2 diabetes. The aim of this study was to evaluate the relative impact of genetic versus nongenetic factors on muscle GS activation and regulation in young and elderly twins examined with a 2-h euglycemic-hyperinsulinemic (40 mU x m(-2) x min(-1)) clamp combined with indirect calorimetry and excision of muscle biopsies. The etiological components were determined using structural equation modeling. Fractional GS activity; GS phosphorylation at sites 2, 2 + 2a, and 3a + 3b corrected for total GS protein; and GS kinase 3 (GSK3) activity were similar in both age groups, whereas total GS activity and protein were lower in elderly compared with younger twins. GS fractional activity increased significantly during insulin stimulation in both young and elderly twins. Conversely, there was a significant decrease in GS phosphorylation at site 3a + 3b and GSK3 activity during insulin stimulation in both age groups, whereas GS phosphorylation at site 2 and 2 + 2a only decreased on insulin stimulation in the younger twins. The increment in whole-body glucose disposal (Rd) and nonoxidative glucose metabolism (insulin - basal) correlated significantly with the increment in GS fractional activity. Fractional GS activity had a major environmental component in both age groups. GSK3 activity exhibited a genetic component in young (basal: a2 = 0.42; insulin: a2 = 0.58) and elderly (insulin: a2 = 0.56) twins. Furthermore, GS phosphorylation at site 2 (insulin: a2 = 0.69) in the elderly and at site 3a + 3b (insulin: a2 = 0.50) in the young twins had a genetic component. In conclusion, GSK3 activity and GS phosphorylation, particularly at sites 2 and 3a + 3b, had major genetic components. Total and fractional GS activities per se were, on the other hand, predominantly controlled by environmental factors. Moreover, GS activity was intact with increasing age, despite a significant reduction in nonoxidative glucose metabolism.     

Skin flaps

Open wounds, particularly around the face, often require complicated techniques for optimal closure. The approach to the closure of the complicated wound depends largely on the nature of the wound, including the location and size of the defect, the functional outcome after closure, the medical comorbidities of the patient, neighboring structures, and whether the defect is secondary to a malignancy or trauma. The goals of wound management are optimal aesthetic outcome, preservation of function, and patient satisfaction. The authors briefly review basic skin closure options and discuss use of skin flaps, particularly of the head and neck region.     

Primary health care and hospital interactions: effects for hospital length of stay

AIMS: Norwegian healthcare services are divided between primary and secondary care providers. A growing problem is that every third patient of 75 years of age or more experiences an extended stay in a somatic hospital while waiting to be sent to primary healthcare services. The interaction between these two levels of healthcare services is analysed to examine the effect on a patient's length of stay in hospital. METHODS: Recent studies have asserted that research on length of stay in hospital should include influential factors such as system variation and system characteristics, in addition to standardizing for case-mix. New organizational routines are identified in 50 Norwegian somatic hospitals. A multivariate linear regression is used in both a static and a dynamic model to explain variations in hospital length of stay and in additional length of stay (5% of stays are defined as outliers). RESULTS: The study shows that newly specialized structures constructed to enhance the interaction between the two levels have had no effect. Length of stay is dependent on the capacity of the primary healthcare provider and on the share of elderly in the hospital catchment area, the type of patients, the procedure performed, and the characteristics of the hospital. CONCLUSION: Variation in length of stay between hospitals is primarily explained by the capacity of primary healthcare providers. However, some support is found in the dynamic model that introduces the proposition that a hospital-owned hotel would decrease the length of stay of patients in hospital.     

Temperature rise induced by some light emitting diode and quartz-tungsten-halogen curing units

Because of the risk of thermal damage to the pulp, the temperature rise induced by light-curing units should not be too high. LED (light emitting diode) curing units have the main part of their irradiation in the blue range and have been reported to generate less heat than QTH (quartz-tungsten-halogen) curing units. This study had two aims: first, to measure the temperature rise induced by ten LED and three QTH curing units; and, second, to relate the measured temperature rise to the power density of the curing units. The light-induced temperature rise was measured by means of a thermocouple embedded in a small cylinder of resin composite. The power density was measured by using a dental radiometer. For LED units, the temperature rise increased with increasing power density, in a statistically significant manner. Two of the three QTH curing units investigated resulted in a higher temperature rise than LED curing units of the same power density. Previous findings, that LED curing units induce less temperature rise than QTH units, does not hold true in general.     

Feeding, artificial sucking habits, and malocclusions in 3-year-old girls in different regions of the world

PURPOSE: The way babies and young children are reared is important to their health and development. Extensive breast-feeding has also been shown to reduce the development of artificial sucking habits like digit or pacifier-sucking. The aim of this study was to determine feeding methods, artificial sucking habits, and the presence of malocclusions in 3-year-old girls living in different regions of the world. METHODS: Children from the following countries were involved in the present study: (1) Brazil (Porto Alegre); (2) Japan (Niigata); (3) Mexico (Mexico City); (4) Norway (Oslo); (5) Sweden (Falk?ping); (6) Turkey (Istanbul); (7) and the United States (Iowa City, Iowa). During the interview and examination, the following variables were evaluated and registered: (1) breastfeeding and bottle-feeding; (2) duration and frequency; (3) sucking habits; (4) posterior and anterior crossbites; and (5) other malocclusions/normal occlusion. RESULTS: The prevalence of breast-feeding was very high in all groups, ranging between 78% and 98%. The prevalence of bottle-feeding in the different areas was also high. Except for Iowa City, the prevalence of digit-sucking was relatively low. Pacifier-sucking is fairly popular in most areas, with the exception of Niigata. The prevalence of normal occlusion in different cities ranged from 38% to 98%. CONCLUSIONS: There are considerable differences in feeding, as well as artificial sucking habits, in different areas of the world and at different periods.     

Comparison of the 6-minute walk test with established parameters for assessment of cardiopulmonary capacity in adults with complex congenital cardiac disease

BACKGROUND: Objective assessment of the cardiopulmonary capacity in patients with complex congenital cardiac disease often remains difficult in clinical practice. The cardiopulmonary exercise test and determination of the levels of brain natriuretic peptide in the plasma are established tests, but expensive. The 6-minute walk test is also validated, but has not often been used in patients with heart failure due to congenital heart disease, nor compared with other tests. We sought to compare its value with the results of cardiopulmonary exercise testing and measuring the levels of brain natriuretic peptide in the plasma. METHODS: We carried out a standardized 6-minute walk test in 31 patients with complex congenital cardiac disease on the same day that they underwent cardiopulmonary exercise testing and determination of levels of brain natriuretic peptide in the plasma. Of the patients, 7 had functionally univentricular hearts, 9 had transposition, 9 had tetralogy of Fallot, 3 had common arterial trunk, and 3 had pulmonary atresia with intact interventricular septum. Uptakes of oxygen at peak exercise, and at the anaerobic threshold, were determined using cardiopulmonary exercise testing, and classified as suggested by Weber. The 6-minute walk test was performed according to a standard protocol. RESULTS: There was a significant correlation between brain natriuretic peptide, oxygen uptakes at peak exercise and 6-minute walk. The correlation between the 6-minute walk test and oxygen uptakes at the anaerobic threshold, however, was not significant. CONCLUSIONS: The 6-minute walk test can be performed easily, is inexpensive, widely available, and correlates well with measurements of brain natriuretic peptide and cardiopulmonary exercise testing, even in patients with corrected or palliated congenital cardiac malformations. A cut-off value of 450 metres in the 6-minute walk test allows a semi-quantitative classification in analogy to the classification suggested by Weber for cardiopulmonary exercise testing, and to a level of brain natriuretic peptide in the plasma of less or more than 100 picograms per millilitre.