Alterations in the growth plate associated with growth modulation by sustained compression or distraction

Sustained mechanical load is known to modulate endochondral growth in the immature skeleton, but it is not known what causes this mechanical sensitivity. This study aimed to quantify alterations in parameters of growth plate performance associated with mechanically altered growth rate. Vertebral and proximal tibial growth plates of immature rats and cattle, and rabbit (proximal tibia only) were subjected to different magnitudes of sustained loading, which altered growth rates by up to 53%. The numbers of proliferative chondrocytes, their rate of proliferation, and the amount of chondrocytic enlargement occurring in the hypertrophic zone were quantified. It was found that reduced growth rate with compression and increased growth rate with distraction were associated with corresponding changes in the number of proliferative chondrocytes per unit width of growth plate, and in the final (maximum) chondrocytic height in the hypertrophic zone (overall correlation coefficients 0.38 and 0.56 respectively). According to multiple linear regression coefficients for these two variables (0.72 and 1.39 respectively), chondrocytic enlargement made a greater contribution to altered growth rates.     

Oxidative stress induces myeloperoxidase expression in endocardial endothelial cells from patients with chronic heart failure

Increased oxidative stress has been implicated in the pathogenesis of a number of cardiovascular diseases. Recent findings suggest that myeloperoxidase (MPO) may play a key role in the initiation and maintenance of chronic heart failure (CHF) by contributing to the depletion of the intracellular reservoir of nitric oxide (NO). NO consumption through MPO activity may lead to protein chlorination or nitration, leading to tissue damage. Primary cultures of human endocardial endothelial cells (EEC) obtained at heart transplantation of patients with CHF and human umbilical vein endothelial cells (HUVEC) were subjected to oxidative stress by incubation with hydrogen peroxide at non lethal (60 μM) dose for different exposure times (3 and 6 h). Treated and control cells were tested by immunohistochemistry and RT-PCR for MPO and 3-chlorotyrosine expression. Both endothelial cell types expressed myeloperoxidase following oxidative stress, with higher levels in EEC. Moreover, 3-chlorotyrosine accumulation in treated cells alone indicated the presence of MPO-derived hypochlorous acid. Immunohistochemistry on sections from post-infarcted heart confirmed in vivo the endothelial positivity to MPO, 3-chlorotyrosine and, to a minor extent, nitrotyrosine. Immunohistochemical observations were confirmed by detection of MPO mRNA in both stimulated EEC and HUVEC cells. This study demonstrates for the first time that EEC can express MPO after oxidative stress, both in vitro and in vivo, followed by accumulation of 3-chlorotyrosine, an end product of oxidative stress. Deregulation of endothelial functions may contribute to the development of a number of cardiovascular diseases, including CHF. The results also highlight the notion that endothelium is not only a target but also a key player in oxidative-driven cardiovascular stress. Electronic supplementary material  The online version of this article (doi: ) contains supplementary material, which is available to authorized users. G. La Rocca and A. Di Stefano contributed equally to the current work. Returned for 1. Revision: 7 January 2008 1. Revision received: 18 June 2008 Returned for 2. Revision: 17 July 2008 2. Revision received: 17 October 2008     

Disclosing Medical Errors to Patients: It’s Not What You Say, It’s What They Hear

BACKGROUND  There is consensus that patients should be told if they are injured by medical care. However, there is little information on how they react to different methods of disclosure. OBJECTIVE  To determine if volunteers’ reactions to videos of physicians disclosing adverse events are related to the physician apologizing and accepting responsibility. DESIGN  Survey of viewers randomized to watch videos of disclosures of three adverse events (missed mammogram, chemotherapy overdose, delay in surgical therapy) with designed variations in extent of apology (full, non-specific, none) and acceptance of responsibility (full, none). PARTICIPANTS  Adult volunteer sample from the general community in Baltimore. MEASUREMENTS  Viewer evaluations of physicians in the videos using standardized scales. RESULTS  Of 200 volunteers, 50% were <40 years, 25% were female, 80% were African American, and 50% had completed high school. For designed variations, scores were non-significantly higher for full apology/responsibility, and lower for no apology/no responsibility. Perceived apology or responsibility was related to significantly higher ratings (chi-square, 81% vs. 38% trusted; 56% vs. 27% would refer, p < 0.05), but inclination to sue was unchanged (43% vs. 47%). In logistic regression analyses adjusting for age, gender, race and education, perceived apology and perceived responsibility were independently related to higher ratings for all measures. Inclination to sue was reduced non-significantly. CONCLUSIONS  Patients will probably respond more favorably to physicians who apologize and accept responsibility for medical errors than those who do not apologize or give ambiguous responses. Patient perceptions of what is said may be more important than what is actually said. Desire to sue may not be affected despite a full apology and acceptance of responsibility. Presented in part at the 28th Annual Meeting of the Society for General Internal Medicine, New Orleans, LA, May 11–14, 2005     

A single nucleotide mutation results in loss of enzymatic activity in the hyaluronate lyase gene of Streptococcus pyogenes

Group A streptococci produce a variety of extracellular proteins, many of which are considered to be virulence factors. One of these is hyaluronate lyase (HylA), an enzyme capable of degrading the extracellular matrix of the host as well as the bacterial capsule. The current study examined three genotypes of hylA (full, truncated and deleted). Only isolates containing a full-length gene produced an enzymatically active hyaluronate lyase; however, truncation of the protein was not the reason for loss of activity. A single nucleotide substitution, resulting in an amino acid change at position 199 of the lyase was present in a highly-conserved region of the protein in isolates not producing active enzyme. In serotypes 4 and 22, those producing active enzymes, this residue was an aspartic acid, in serotypes not showing hyaluronate lyase activity, it was a valine. Site-directed mutagenesis indicated the loss of enzymatic activity of the hyaluronate lyase is in part determined by the mutation resulting in an amino acid residue change. This mutation results in an inactive form of the enzyme and is found in the more virulent serotypes of Streptococcus pyogenes, suggesting that hyaluronate lyase could interfere with the disease process, in essence being an anti-virulence factor.     

Levels of complexity in phonological disorders: evidence from Cantonese

Longitudinal data from ten phonologically disordered Cantonese-speaking boys were analysed for distinctive features (manner and place). The children labelled 95 pictures, attempting each initial Cantonese segment at least five times. The applicability of Dinnsen et al.'s implicational hierarchy to this data was examined. Categorization of each child's system according to an implicational hierarchy was successful for nine of the ten children when phonetic inventories were considered. In addition, a phonemic inventory based on Dinnsen et al.'s phonetic inventory captured the system of phonological contrasts used by eight of the ten children. The patterns of the children who did not match the hierarchy were considered deviant rather than delayed. The ability of the hierarchy to predict the route of development in this group of children was also examined. The hierarchies (both phonetic and phonemic) successfully predicted the route of change in these cases. Implications for the use of an implicational hierarchy in phonological assessment and treatment are discussed. Further research on feature-based phonological development, in both typically-developing and disordered phonological systems is required.     

Links Between Socio-Economic Circumstances and Changes in Smoking Behavior in the Mexican Population: 2002–2010

While deleterious consequences of smoking on health have been widely publicized, in many developing countries, smoking prevalence is high and increasing. Little is known about the dynamics underlying changes in smoking behavior. This paper examines socio-economic and demographic characteristics associated with smoking initiation and quitting in Mexico between 2002 and 2010. In addition to the influences of age, gender, education, household economic resources and location of residence, changes in marital status, living arrangements and health status are examined. Drawing data from the Mexican Family Life Survey, a rich population-based longitudinal study of individuals, smoking behavior of individuals in 2002 is compared with their behavior in 2010. Logistic models are used to examine socio-demographic and health factors that are associated with initiating and quitting smoking. There are three main findings. First, part of the relationship between education and smoking reflects the role of economic resources. Second, associations of smoking with education and economic resources differ for females and males. Third, there is considerable heterogeneity in the factors linked to smoking behavior in Mexico indicating that the smoking epidemic may be at different stages in different population subgroups. Mexico has recently implemented fiscal policies and public health campaigns aimed at reducing smoking prevalence and discouraging smoking initiation. These programs are likely to be more effective if they target particular socio-economic and demographic sub-groups.     

Nipple discharge and the efficacy of duct cytology in evaluating breast cancer risk

BackgroundNipple discharge accounts for up to 5% of referrals to breast surgical services. With the vast majority of breast carcinomas originating in the ductal system, symptomatic dysfunction of this system often raises disproportionate clinical concern. The aim of this study is firstly, to evaluate the clinical importance of nipple discharge as an indicator of underlying malignancy and secondly, to assess the diagnostic application of duct cytology in patients presenting with nipple discharge.Study designWe performed a retrospective analysis of all patients presenting with nipple discharge as their primary symptom to the symptomatic breast unit at a tertiary referral center over a 30-month period (n = 313). The Hospital Inpatient Enquiry (HIPE) System and BreastHealth database were used to identify our study cohort. Parameters evaluated included patient demographics, clinical presentation, clinical evaluation, radiological assessment and histological/cytological analysis.ResultsThree-hundred and thirteen patients presented with nipple discharge as their primary complaint. Invasive breast carcinoma was diagnosed by Triple Assessment in 5% of patients. 24% of patients presenting with nipple discharge underwent nipple aspiration and cytological analysis. Duct cytology was diagnostic of the underlying breast carcinoma in 50% of triple assessment diagnosed carcinoma. Four risk factors were identified as having a significant association with breast carcinoma, these included (a) age >50 years (p < 0.0001), (b) bloody nipple discharge (p < 0.008), (c) presence of a breast lump (p < 0.0001) and (d) single duct discharge (p < 0.006).ConclusionsNipple discharge is a poor indicator of an underlying malignancy. Use of nipple aspiration and duct cytology for the assessment of nipple discharge is of limited diagnostic benefit. However, by utilizing the systematic, gold standard approach of Triple Assessment (clinical, radiological and cytological evaluation), the risk of underlying carcinoma can be accurately defined.