A new Screening Tool for Detecting Early Atheroslerosis

In a study published in the current issue of the Journal of Geriatric Cardiology, Ang and co-investigators used the highresolution 64-slice CT coronary angiography to detect coronary lesions in a group of patients with atypical angina.1 The clinical data of these patients were also used to calculate their risk according the Framingham and PROCAM scoring system.2,3 As the cohort is composed with a majority of low risk patients with atypical angina, only a small minority of the patients were classified as having medium and high risk. The results showed that MDCT uncovered 18% either significant lesions (＞50% stenosis) or calcifications (＞400Agatston units)in the low risk patients and 33% in the medium and high risk subgroups.……     

A southern analysis of Rh blood group genes: association between restriction fragment length polymorphism patterns and Rh serotypes

Polymorphisms within the Rh blood group system have been defined by serologic agglutination methods, but have not yet been defined at the DNA level. Two closely related genes associated with the Rh D antigen and with the Rh C/c and E/e antigens have been cloned. We used a Southern analysis incorporating probes to the 5' and 3' regions of the Rh C, E gene and D gene to identify polymorphisms associated with Rh C/c and E/e antigens, respectively. The D gene dosage could be determined by comparing the relative intensities of the D bands with bands from the 5' and 3' region of the Rh C, E gene. The concordance between restriction fragment length polymorphism (RFLP) patterns and serologic phenotypes for 102 randomly selected blood donors was 100% for C, e, and D, 94.8% for c, and 94.3% for E. The data are consistent with the sequences encoding the C/c epitopes residing on the 5' side of those for the E/e epitopes. All samples discordant for the 3' probe and E had the cE (r") serotype. These data show that the gene coding for the cE serotype is different in Rh-positive and -negative individuals. The study demonstrates that Rh DNA typing, including D gene dosage measurements and Rh gene haplotyping, may supplement traditional serotyping methods in transfusion medicine.     

Identification Of Two New Pmp22 Mouse Mutants Using Large-Scale Mutagenesis And A Novel Rapid Mapping Strategy

In some alcohol-related pathologies of chronic alcoholism women are more vulnerable than men. A consecutive sample of 62 chronic alcoholics was studied, 18 females and 44 males, aged between 28 and 69 years to assess the incidence and distribution of peripheral neuropathy with regard to gender. All patients underwent clinical and neurological observations, laboratory tests, and electroneurography. Total lifetime dose of ethanol (TLDE) and other risk factors for neuropathy (disease duration, age, nutritional status) were calculated and correlated to sural nerve sensory-evoked potential (SEP) amplitude. In 42 patients (67.7%), we observed the presence of clinical and/or infraclinical neuropathy, mostly axonal, in 29 males (65.9%) and 13 females (72.2%). In women, compared to men, TLDE and disease duration were significantly inversely correlated to sural nerve SEP amplitude, i.e in women, SEP amplitude is significantly reduced in relation to TLDE and disease duration increase. These data indicate a higher sensitivity of females towards the toxic effects of ethanol, other than malnutrition, on peripheral nerve fibres.     

Changing treatment patterns among patients with HIV: Royal Free Hospital 1987–97

Objective Following the publication of results of large-scale clinical trials, antiretroviral treatment for HIV has changed dramatically. The aim of this study was to describe changes in antiretroviral treatment and the way treatments were combined among 1806 patients with HIV seen at a single centre at the Royal Free Hospital, London, UK.
Design and method Each calendar year was divided into quarters, and the number of patients receiving treatment and participating in clinical trials was determined.
Results The proportion of patients on no therapy decreased from over 90% at the beginning of 1988 to under 15% at the end of 1997. Monotherapy was the only form of treatment available before 1992 but its use dropped to 2% by the end of 1997. The standard of care at the end of 1997 was triple combination therapy, used in over 40% of patients. There were dramatic changes in the use of individual agents; use of zidovudine decreased from 50% during 1989 to 25% during 1997, while use of lamivudine and stavudine saw an exponential rise in 1997. The protease inhibitors were used in equal proportions in this clinic population; the use of dual protease therapy began in 1997 and was rising rapidly by the end of the year.
Conclusions There have been major changes in the use of antiretroviral therapy at this centre, particularly during 1996 and 1997. The long-term cost implications and side-effects of intensive treatment regimens remain to be addressed.     

Emerging roles of endoglin/CD105 and angiogenic cytokines for disease development and progression in multiple myeloma patients

Angiogenesis is an essential process for the expansion of multiple myeloma (MM), in which many angiogenic factors participate. Endoglin (CD105) is a transforming growth factor‐β co‐receptor, being mainly expressed in angiogenic endothelial cells and has been used as a marker of tumor angiogenesis, having prognostic potential. The aim of the study was to evaluate serum levels of soluble CD105 (sCD105) in MM patients, both during diagnosis and after effective conventional chemotherapy, in the plateau phase, and to correlate them with the clinical stage of the disease, as well as with the known angiogenic factors vascular endothelial growth factor, angiogenin and interleukin‐18 (IL‐18). Serum levels of the aforementioned factors were measured, by enzyme‐linked immunosorbent assay, in 56 newly diagnosed MM patients, in 35 of them who entered plateau phase and in 24 healthy controls. Bone marrow aspirations were also performed in all patients to determine plasma cell infiltration. All measured cytokines were higher in MM patients compared with controls and with advancing disease stage (p < 0.001 for all cases). Furthermore, the values of all factors decreased significantly in the plateau phase (p < 0.001 for all cases). Serum levels of sCD105 correlated with the other angiogenic cytokines, whereas only serum levels of angiogenin had prognostic value for the survival. In conclusion, CD105 and the angiogenic cytokines vascular endothelial growth factor, angiogenin and IL‐18, seem to have emerging roles both in angiogenesis and tumor growth in MM. Copyright © 2013 John Wiley & Sons, Ltd.     

The ethics of executive compensation in the Canadian public health system

The method of executive compensation in the Canadian public health system presently contains complex ethical issues related to transparency and fairness, not only within single organizations, but across provinces, and in comparison with other wage earners. The increasing interest of the public, elected officials, and health decision makers in public sector compensation will bring heightened scrutiny and intervention in the future. This article explores some of the current ethical issues of executive compensation and their implications and points to reform initiatives for the future.     

The role of germline AIP,MEN1, PRKAR1A,CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children,adolescents, and patients with genetic syndromes

Stratakis CA, Tichomirowa MA, Boikos S, Azevedo MF, Lodish M, Martari M, Verma S, Daly AF, Raygada M, Keil MF, Papademetriou J, Drori‐Herishanu L, Horvath A, Tsang KM, Nesterova M, Franklin S, Vanbellinghen J‐F, Bours V, Salvatori R, Beckers A. The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes. The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among pediatric patients with pituitary adenomas (PA). In this study, we screened children with PA for mutations in these genes; somatic GNAS mutations were also studied in a limited number of growth hormone (GH) or prolactin (PRL)‐secreting PA. We studied 74 and 6 patients with either isolated Cushing disease (CD) or GH‐ or PRL‐secreting PA, respectively. We also screened four pediatric patients with CD, and four with GH/PRL‐secreting tumors who had some syndromic features. There was one AIP mutation (p.Lys103Arg) among 74 CD patients. Two MEN1 mutations that occurred in patients with recurrent or difficult‐to‐treat disease were found among patients with CD. There was one MEN1 and three AIP mutations (p.Gln307ProfsX104, p.Pro114fsX, p.Lys241X) among pediatric patients with isolated GH‐ or PRL‐secreting PA and one additional MEN1 mutation in a patient with positive family history. There were no mutations in the PRKAR1A, CDKN1B, CDKN2C or GNAS genes. Thus, germline AIP or MEN1 gene mutations are frequent among pediatric patients with GH‐ or PRL‐secreting PA but are significantly rarer in pediatric CD; PRKAR1A mutations are not present in PA outside of Carney complex.