Current Treatment Modalities for Symptomatic Gallstones

Gallstone disease is an important clinical problem: approximately 10% of all adults in the western population have gallstones. Most gallstones, however, remain asymptomatic, and from various disciplines there is consensus that only symptomatic gallstones require therapy. Since the first gallbladder extirpation in 1882, cholecystectomy has been considered the gold standard. Nowadays, this operation is performed laparoscopically in most hospitals. Despite relatively low morbidity and mortality rates, a number of alternative therapies have been developed in the past few years. These alternative treatment modalities are especially indicated in high risk patients and in patients rejecting surgery. In this review article, the currently available treatment modalities are discussed.     

Efficacy of smoking prevention program 'Smoke-free Kids': study protocol of a randomized controlled trial

Background  

A strong increase in smoking is noted especially among adolescents. In the Netherlands, about 5% of all 10-year olds, 25% of all 13-year olds and 62% of all 17-year olds report ever smoking. In the U.S., an intervention program called 'Smoke-free Kids' was developed to prevent children from smoking. The present study aims to assess the effects of this home-based smoking prevention program in the Netherlands.     

The effect of crystal imperfections on particle fracture behaviour

Micronisation of active pharmaceutical ingredients is a process which is sometimes difficult to control. The main purpose of this study was to assess the effect of the pre-existing flaws in the material to be milled. The rate of breakage of four samples of a model compound (sodium chloride), originating from different sources, was determined in a jet mill. It appeared that each type of sodium chloride has a distinct particle rate of breakage and breakage pattern. The numbers of flaws in the different types of sodium chloride have been determined by immersing the sodium chloride particles in a liquid with the same refractive index. This makes the cracks better visible. Microphotographs were made and flaws were counted manually. The study shows that the flaw density has an impact on the fracture behaviour of particles. The degree of fracture tends to increase with increasing flaw density. The paper shows however that the mechanical properties of the material as well as the starting particle size dominate the significance of the impact of flaws on fracture behaviour.     

Absence of renal lesions in C57BL/KaLwRij mice with advanced myeloma due to 5T2MM cells

Renal failure is one of the main complications in multiple myeloma (MM) and histopathological lesions are due to light chains accumulation in the kidney. The 5T2MM mouse model closely mimics osteolytic lesions observed in clinics. We studied the occurrence of pathological changes in the kidney of mice inoculated with 5T2MM myeloma cells. No renal lesions due to light chain deposition were observed after histological, immunological staining and dosage of creatinine in serum and urine. PTH levels decreased in 5T2MM mice, confirming the absence of secondary hyperparathyroidism. Osteolytic lesions appear to be the unique consequence of 5T2MM cells inoculation.     

The elimination of trans fats from spreads: how science helped to turn an industry around

Mensink and Katan showed in 1990 that trans fats reduce high- and increase low-density lipoprotein cholesterol. Unilever aided this study because the company considered knowledge on trans fats incomplete in spite of their long history of safe use. The decision in 1994 to remove trans fats from Unilever's retail spreads was triggered by media events, but it was built on a solid understanding of the nutritional and technological aspects of trans fats. Over the next 14 years, manufacturers worldwide followed suit. This experience illustrates that food companies need to know about the health effects of their products and how to apply that knowledge.     

Maximum Lyapunov exponents as predictors of global gait stability: a modelling approach

To examine the stability of human walking, methods such as local dynamic stability have been adopted from dynamical systems theory. Local dynamic stability is calculated by estimating maximal finite time Lyapunov exponents (λ(S) and λ(L)), which quantify how a system responds continuously to very small (i.e. "local") perturbations. However, it is unknown if, and to what extent, these measures are correlated to global stability, defined operationally as the probability of falling. We studied whether changes in probability of falling of a simple model of human walking (a so-called dynamic walker) could be predicted from maximum finite time Lyapunov exponents. We used an extended version of the simplest walking model with arced feet and a hip spring. This allowed us to change the probability of falling of the model by changing either the foot radius, the slope at which the model walks, the stiffness of the hip spring, or a combination of these factors. Results showed that λ(S) correlated fairly well with global stability, although this relationship was dependent upon differences in the distance between initial nearest neighbours on the divergence curve. A measure independent of such changes (the log(distance between initially nearest neighbours after 50 samples)) correlated better with global stability, and, more importantly, showed a more consistent relationship across conditions. In contrast, λ(L) showed either weak correlations, or correlations opposite to expected, thus casting doubt on the use of this measure as a predictor of global gait stability. Our findings support the use of λ(S), but not of λ(L), as measure of human gait stability.     

A common polymorphism in the mineralocorticoid receptor modulates stress responsiveness

CONTEXT: Mineralocorticoid receptors (MR) mediate the action of aldosterone on sodium resorption in kidney tubular cells, but in brain they respond to the glucocorticoid cortisol in stress regulation and cognitive processes. OBJECTIVE: The objective of the study was to investigate the role of the MR gene variant I180V in the neuroendocrine response to a psychosocial stressor and in electrolyte regulation. DESIGN: Associations between the MRI180V and outcome variables in a healthy cohort subjected to psychosocial challenge (Trier Social Stress Test) and in a mild hypertensive cohort exposed to acute salt loading (Weinberger's test) were investigated. In vitro transactivational assays were applied to compare the effects of cortisol and aldosterone on the MRI180V. RESULTS: Carriers of the MR180V allele showed higher saliva (P < 0.01), plasma cortisol (P < 0.01), and heart rate responses (P < 0.05) to the Trier Social Stress Test than noncarriers (MR180I). After 3 d of a normal salt diet and the Weinberger's test, no association was found with urinary sodium excretion, plasma aldosterone, and plasma renin activity or with changes in blood pressure, aldosterone, and renin responses. In vitro testing of the MR180V allele revealed a mild loss of function using cortisol as a ligand, compared with the MR180I allele. Significantly higher doses of cortisol were needed for half-maximal induction on the TAT-1 (P < 0.002), TAT-3 (P < 0.03), or mouse mammary tumor virus (P < 0.02) promoters, whereas maximal induction was not different. These differences were not observed using aldosterone as a ligand. CONCLUSION: The findings reveal that cortisol and heart rate responses to a psychosocial stressor are enhanced in carriers of the MR180V variant.