A Longitudinal Study of Medicaid Coverage for Tobacco Dependence Treatments in Massachusetts and Associated Decreases in Hospitalizations for Cardiovascular Disease

Thomas Land and colleagues show that among Massachusetts Medicaid subscribers, use of a comprehensive tobacco cessation pharmacotherapy benefit was followed by a substantial decrease in claims for hospitalizations for acute myocardial infarction and acute coronary heart disease

Investigations on a clinically and functionally unusual and novel germline p53 mutation

This report describes an individual with a rare choroid plexus papilloma in adulthood (age 29) after earlier having an osteosarcoma (age 22). The results from this study, and others, suggest that it may be advisable to consider the possibility of a germline p53 mutation in adults presenting with choroid plexus tumours. In the current study automated DNA sequencing of genomic DNA detected a novel germline 7 base pair insertion in exon 5 of the p53 gene in this patient. The alteration in frame would produce amino acid substitutions beginning with alanine to glycine at position 161 and a stop codon at position 182 in the mutated protein. Surprisingly two assays of p53 function gave apparently wild-type results on peripheral blood lymphocytes from this individual. These results led us to carry out more detailed functional tests on the mutant protein. The mutant allele was expressed either at very low levels or not at all in phytohaemagglutinin stimulated lymphocytes. Further, the mutant protein was completely non-functional in terms of its ability to transactivate a series of p53-responsive genes (p21WAF1, bax, PIG3), to transrepress a target gene and to inhibit colony growth in transfected Saos-2 cells. However, surprisingly, data from irradiated peripheral blood lymphocytes and transfected Saos-2 cells, suggested that this truncated, mutant protein retains significant ability to induce apoptosis

Unbearability of suffering at the end of life: the development of a new measuring device, the SOS-V

AbstractBackgroundUnbearable suffering is an important issue in end-of-life decisions. However, there has been no systematic, prospective, patient-oriented research which has focused on unbearable suffering, nor is there a suitable measurement instrument. This article describes the methodological development of a quantitative instrument to measure the nature and intensity of unbearable suffering, practical aspects of its use in end-stage cancer patients in general practice, and studies content validity and psychometric properties.MethodsRecognizing the conceptual difference between unbearability of suffering and extent or intensity of suffering, we developed an instrument. The compilation of aspects considered to be of importance was based on a literature search. Psychometric properties were determined on results of the first interviews with 64 end-stage cancer patients that participated in a longitudinal study in the Netherlands.ResultsThe instrument measures five domains: medical signs and symptoms, loss of function, personal aspects, aspects of environment, and nature and prognosis of the disease. Sixty nine aspects were investigated, and an overall score was asked. In 64 end-stage cancer patients the instrument was used in total 153 times with an average interview time varying from 20-40 minutes. Cronbachs alpha's of the subscales were in majority above 0.7. The sum scores of (sub)scales were correlated strongly to overall measures on suffering.ConclusionThe SOS-V is an instrument for measuring the unbearability of suffering in end-stage cancer patients with good content validity and psychometric properties, which is feasible to be used in practice. This structured instrument makes it possible to identify and study unbearable suffering in a quantitative and patient-oriented way

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial

Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m−2, vinblastine 6 mg m−2 and cisplatin 50 mg m−2 (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III–IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial. © 1999 Cancer Research Campaig

Severe forms of partial androgen insensitivity syndrome due to p.L830F novel mutation in androgen receptor gene in a Brazilian family

<p>Abstract</p> <p>Background</p> <p>The androgen insensitivity syndrome may cause developmental failure of normal male external genitalia in individuals with 46,XY karyotype. It results from the diminished or absent biological action of androgens, which is mediated by the androgen receptor in both embryo and secondary sex development. Mutations in the androgen receptor gene, located on the X chromosome, are responsible for the disease. Almost 70% of 46,XY affected individuals inherited mutations from their carrier mothers.</p> <p>Findings</p> <p>Molecular abnormalities in the androgen receptor gene in individuals of a Brazilian family with clinical features of severe forms of partial androgen insensitivity syndrome were evaluated. Seven members (five 46,XY females and two healthy mothers) of the family were included in the investigation. The coding exons and exon-intron junctions of androgen receptor gene were sequenced. Five 46,XY members of the family have been found to be hemizygous for the c.3015C>T nucleotide change in exon 7 of the androgen receptor gene, whereas the two 46,XX mothers were heterozygote carriers. This nucleotide substitution leads to the p.L830F mutation in the androgen receptor.</p> <p>Conclusions</p> <p>The novel p.L830F mutation is responsible for grades 5 and 6 of partial androgen insensitivity syndrome in two generations of a Brazilian family.</p

High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event

Multiple genetic hits are detected in patients with acute myeloid leukemia (AML). To investigate this further, we developed a tetracycline-inducible mouse model of AML, in which the initial transforming event, overexpression of HOXA10, can be eliminated. Continuous overexpression of HOXA10 is required to generate AML in primary recipient mice, but is not essential for maintenance of the leukemia. Transplantation of AML to secondary recipients showed that in established leukemias, ∼80% of the leukemia-initiating cells (LICs) in bone marrow stopped proliferating upon withdrawal of HOXA10 overexpression. However, the population of LICs in primary recipients is heterogeneous, as ∼20% of the LICs induce leukemia in secondary recipients despite elimination of HOXA10-induced overexpression. Intrinsic genetic activation of several proto-oncogenes was observed in leukemic cells resistant to inactivation of the initial transformation event. Interestingly, high levels of the adhesion molecule CD44 on leukemic cells are essential to generate leukemia after removal of the primary event. This suggests that extrinsic niche-dependent factors are also involved in the host-dependent outgrowth of leukemias after withdrawal of HOXA10 overexpression event that initiates the leukemia

Promoting optimal parenting and children’s mental health : a preliminary evaluation of the How-to Parenting Program

Parenting quality is widely accepted as a primary predictor of children’s mental health. The present study examined the effectiveness of a parenting program in fostering optimal parenting and child mental health. The selected program was How to talk so kids will listen & listen so kids will talk (How-to Parenting Program). This program was selected because its content corresponds closely to what the parenting style literature suggests is optimal parenting (i.e., includes structure, affiliation and autonomy support). Eleven groups of six to twelve parents were conducted in 7 local grade schools. The program, offered by two trained leaders, consisted of eight weekly sessions and taught a total of 30 skills. A total of 82 parents completed questionnaires both prior to and after the program. Participants’ children between eight and 12 years old (N = 44) completed questionnaires at school, at both assessment points. Repeated measures ANOVAs using parent reports indicated that structure, affiliation and autonomy support were increased after the program, compared to baseline. The level of child internalizing and externalizing problems also decreased significantly. Importantly, children reports confirmed that parental autonomy support increased from pre to post-test and child-reported well-being improved as well. The preliminary evidence from this pre-test versus post-test repeated measures design suggests that the How-to Parenting Program is effective in improving parenting style and in promoting children’s mental health and that future evaluation research examining the potential of this program is warranted

Acute Effects of Sex Steroid Hormones on Susceptibility to Cardiac Arrhythmias: A Simulation Study

Acute effects of sex steroid hormones likely contribute to the observation that post-pubescent males have shorter QT intervals than females. However, the specific role for hormones in modulating cardiac electrophysiological parameters and arrhythmia vulnerability is unclear. Here we use a computational modeling approach to incorporate experimentally measured effects of physiological concentrations of testosterone, estrogen and progesterone on cardiac ion channel targets. We then study the hormone effects on ventricular cell and tissue dynamics comprised of Faber-Rudy computational models. The “female” model predicts changes in action potential duration (APD) at different stages of the menstrual cycle that are consistent with clinically observed QT interval fluctuations. The “male” model predicts shortening of APD and QT interval at physiological testosterone concentrations. The model suggests increased susceptibility to drug-induced arrhythmia when estradiol levels are high, while testosterone and progesterone are apparently protective. Simulations predict the effects of sex steroid hormones on clinically observed QT intervals and reveal mechanisms of estrogen-mediated susceptibility to prolongation of QT interval. The simulations also indicate that acute effects of estrogen are not alone sufficient to cause arrhythmia triggers and explain the increased risk of females to Torsades de Pointes. Our results suggest that acute effects of sex steroid hormones on cardiac ion channels are sufficient to account for some aspects of gender specific susceptibility to long-QT linked arrhythmias

On the Origin of S0 Galaxies

I will review the basic properties of S0 galaxies in the local Universe in relation to both elliptical and spiral galaxies, their neighbours on the Hubble sequence, and also in relation to dwarf spheroidal (dSph) galaxies. This will include colours, luminosities, spectral features, information about the age and metallicity composition of their stellar populations and globular clusters, about their ISM content, as well as kinematic signatures and their implications for central black hole masses and past interaction events, and the number ratios of S0s to other galaxy types in relation to environmental galaxy density. I will point out some caveats as to their morphological discrimination against other classes of galaxies, discuss the role of dust and the wavelength dependence of bulge/disk light ratios. These effects are of importance for investigations into the redshift evolution of S0 galaxies -- both as individual objects and as a population. The various formation and transformation scenarios for S0 and dSph galaxies will be presented and confronted with the available observations.Comment: Invited Review, 18 pages, ``BARS 2004'' Conference, South Africa, June 2004, eds.: K. C. Freeman, D. L. Block, I. Puerari, R. Groess, Kluwer, in pres