Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia of the parathyroid glands, the endocrine pancreas, and the anterior pituitary gland. In addition, families with isolated endocrine neoplasia, notably familial isolated hyperparathyroidism (FIHP) and familial acromegaly, have also been reported. However, whether these families constitute MEN 1 variants or separate entities remains speculative as the genetic bases for these diseases are unclear. The gene for MEN 1 has recently been cloned and characterized. Using single strand conformation analysis (SSCA) and sequencing, we performed mutation analysis in: a) a total of 55 MEN 1 families from 7 countries, b) 13 isolated MEN 1 cases without family history of the disease, c) 8 acromegaly families, and d) 4 FIHP families. Mutations were identified in 27 MEN 1 families and 9 isolated cases. The 22 different mutations spread across most of the 9 translated exons and included frameshift (11), nonsense (6), splice (2), missense mutations (2), and in-frame deletions (1). Among the 19 Finnish MEN 1 probands, a 1466del12 mutation was identified in 6 families with identical 11q13 haplotypes and in 2 isolated cases indicating a common founder. One frameshift mutation caused by 359del4 (GTCT) was found in 1 isolated case and 4 kindreds of different origin and haplotypes; this mutation therefore represents a common "warm" spot in the MEN1 gene. By analyzing the DNA of the parents of an isolated case one mutation was confirmed to be de novo. No mutation was found in any of the acromegaly and small FIHP families, suggesting that genetic defects other than the MEN1 gene might be involved and that additional such families need to be analyzed.     

Effect of skin hydration on the dynamics of fingertip gripping contact

The dynamics of fingertip contact manifest themselves in the complex skin movements observed during the transition from a stuck state to a fully developed slip. While investigating this transition, we found that it depended on skin hydration. To quantify this dependency, we asked subjects to slide their index fingertip on a glass surface while keeping the normal component of the interaction force constant with the help of visual feedback. Skin deformation inside the contact region was imaged with an optical apparatus that allowed us to quantify the relative sizes of the slipping and sticking regions. The ratio of the stuck skin area to the total contact area decreased linearly from 1 to 0 when the tangential force component increased from 0 to a maximum. The slope of this relationship was inversely correlated to the normal force component. The skin hydration level dramatically affected the dynamics of the contact encapsulated in the course of evolution from sticking to slipping. The specific effect was to reduce the tendency of a contact to slip, regardless of the variations of the coefficient of friction. Since grips were more unstable under dry skin conditions, our results suggest that the nervous system responds to dry skin by exaggerated grip forces that cannot be simply explained by a change in the coefficient of friction.     

Extended treatment with bupropion SR for cigarette smoking cessation.

The authors present results of a randomized clinical trial of the efficacy of extended treatment with bupropion SR in producing longer term cigarette smoking cessation. Adult smokers (N = 362) received open-label treatment (11 weeks) that combined relapse prevention training, bupropion SR, and nicotine patch followed by extended treatment (14 weeks) with bupropion SR or matching placebo. Abstinence percentages were relatively high (week 11: 52%; week 25: bupropion, 42%; placebo, 38%; week 52: bupropion, 33%; placebo, 34%), but bupropion SR did not surpass placebo. Gender and baseline craving level were identified as significant, independent moderators of treatment response. Men were more likely to abstain than women (week 11: 59% vs. 43%, p = .001; week 25: 48% vs. 31%, p = .001; week 52: 39% vs. 27%, p = .01). Because most smokers suffer relapse with any current cessation treatment, the comparatively high abstinence percentages achieved in this trial are of interest. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Domestic and personal accidents. Prevention in the absence of professional supervision

This paper provides a review of a selection of recent papers, most of which derive from presentations given at the 4th World Conference on Injury Prevention and Control or the 6th International Conference on Product Safety Research, both of which took place in Amsterdam in May 1998. What all the accidents studied in these papers have in common is the absence of professional supervision. Everyone immediately involved in the incident--whether as injured party, unintended cause or informal supervisor is an 'amateur'. It is proposed that the term 'domestic and personal accidents' should be used to describe this group of accidents, the study of which has been neglected in comparison to transport and occupational injuries. It is argued that domestic and personal activities are more heterogeneous than ones with an element of professional supervision and are therefore more difficult to prevent. Nevertheless examples are given of where 'horizontal' approaches to analysis and prevention of these accidents have proved possible.     

Heat inactivation of hepatitis A virus in dairy foods

Experiments were performed to determine the thermal resistance of hepatitis A virus (HAV) in three types of dairy products containing increased amounts of fat content (skim milk, homogenized milk; 3.5% MFG, and table cream; 18% MFG). HAV-inoculated dairy products were introduced into custom-made U-shaped microcapillary tubes that in turn were simultaneously immersed in a waterbath, using custom-made floating boats and a carrying platform. Following exposure to the desired time and temperature combinations, the contents of each of the tubes was retrieved and was tested by plaque assay to determine the reduction in virus titer. Our data indicated that < 0.5 min at 85 degrees C was sufficient to cause a 5-log reduction in HAV titer in all three dairy products, whereas at 80 degrees C, < or = 0.68 min (for skim and homogenized milk), and 1.24 min (for cream) were needed to cause a similar log reduction. Using a nonlinear two-phase negative exponential model (two-compartment model) to analyze the data, it was found that at temperatures of 65, 67, 69, 71, and 75 degrees C, significantly (P < 0.05) higher exposure times were needed to achieve a 1-log reduction in virus titer in cream, as compared to skim and homogenized milk. For example, at 71 degrees C, a significantly (P < 0.05) higher exposure time of 0.52 min (for cream) was needed as compared to < or = 0.18 min (for skim and homogenized milk) to achieve a 1-log reduction in virus titer. A similar trend of inactivation was observed at 73 and 75 degrees C where significantly (P < 0.05) higher exposure times of 0.29 to 0.36 min for cream were needed to cause a 1-log reduction in HAV in cream, as compared to < or = 0.17 min for skim and homogenized milk. This study has provided information on the heat resistance of HAV in skim milk, homogenized milk, and table cream and demonstrated that an increase in fat content appears to play a protective role and contributes to the heat stability of HAV.     

In situ, High-Resolution Measurement of Dissolved Sulfide Using Diffusive Gradients in Thin Films with Computer-Imaging Densitometry

The technique of diffusive gradients in thin films (DGT) has been developed for the measurement of dissolved sulfide. Sulfide species from the sampled waters diffuse through a polyacrylamide hydrogel and then react with pale yellow AgI((s)), incorporated at the surface of a second gel, to form black Ag(2)S((s)). The accumulated sulfide can be measured with a conventional purge-and-trap method followed by colorimetry (methylene blue). This enables the dissolved-sulfide concentration to be calculated under suitable conditions. Alternatively, the color change in the accumulating gel can be used to measure sulfide. A conventional flat-bed scanner, allied to imaging software, provided a densitometric measurement that was quantitatively related to the amount of sulfide accumulated. DGT measurements on synthetic solutions accurately determined the sulfide concentration (95% recovery), thereby confirming the unobstructed diffusion of HS(-) through the gel. The accumulated mass was inversely proportional to the diffusion-layer thickness as theoretically predicted. With the selected geometry, the limit of detection of the densitometric procedure for a 24-h deployment was 0.13 μmol L(-)(1), and the maximum concentration measurable was 60 μmol L(-)(1). When used in anoxic lacustrine waters, DGT provided sensible concentrations. It was also used to measure depth profiles at submillimeter resolution in estuarine surface sediments.     

Functional performance in people with chronic obstructive pulmonary disease

The extent to which individuals with a chronic physical illness perform their day-to-day activities and maintain the independence and autonomy they desire is both an indicator of adaptation and an important clinical outcome criterion. Yet the concept of functional performance is not well understood. Studies of people with chronic obstructive pulmonary disease (COPD) have attempted to identify physiologic and psychosocial factors that contribute to functioning in this population. These studies have used a melange of terms, including functional status, functional ability, quality of life, and health status interchangeably. They have also employed a variety of instruments to operationalize functional performance and an assortment of predictors to understand the phenomena. Perhaps as a result of this disarray, no attempt has been made to synthesize the literature for nursing research and practice. The purpose of this paper is to summarize the research on functional performance in people with COPD, indicate areas of understanding and quandary, suggest possible flaws, and propose several new directions for practice and research.