tbuckley/cabot-search huggingface dataset:
Failure to Engage Hospitalized Elderly Patients and Their Families in Advance Care Planning
Authors: Daren K. Heyland
Journal: JAMA Internal Medicine (2013)

Advance care planning can improve patient-centered care and potentially reduce intensification of care at the end of life.To inquire about patients' advance care planning activities before hospitalization and preferences for care from the perspectives of patients and family members, as well as to measure real-time concordance between expressed preferences for care and documentation of those preferences in the medical record.Prospective study.Twelve acute care hospitals in Canada.Elderly patients who were at high risk of dying in the next 6 months and their family members.Responses to an in-person administered questionnaire and concordance of expressed preferences and orders of care documented in the medical record.Of 513 patients and 366 family members approached, 278 patients (54.2%) and 225 family members (61.5%) consented to participate. The mean ages of patients and family members were 80.0 and 60.8 years, respectively. Before hospitalization, most patients (76.3%) had thought about end-of-life (EOL) care, and only 11.9% preferred life-prolonging care; 47.9% of patients had completed an advance care plan, and 73.3% had formally named a surrogate decision maker for health care. Of patients who had discussed their wishes, only 30.3% had done so with the family physician and 55.3% with any member of the health care team. Agreement between patients' expressed preferences for EOL care and documentation in the medical record was 30.2%. Family members' perspectives were similar to those of patients.Many elderly patients at high risk of dying and their family members have expressed preferences for medical treatments at the EOL. However, communication with health care professionals and documentation of these preferences remains inadequate. Efforts to reduce this significant medical error of omission are warranted.
THE COMPARTMENTALIZATION OF THE CEREBELLUM
Authors: Karl Herrup, Barbara Kuemerle
Journal: Annual Review of Neuroscience (1997)

▪ Abstract The concept of developmental compartments originated in studies of Drosophila embryogenesis. This review examines the hypothesis that the modular structure of the vertebrate cerebellum is strongly analogous to this earlier scheme. The pattern of cerebellar development, the adult circuitry, a variety of molecular markers expressed in specific subdivisions, and the phenotypes of several neurological mutations all provide abundant evidence that the vertebrate cerebellum is organized into modules. We present the case that, as a group, these markers reveal distinct boundaries that partition the cerebellum into true developmental compartments. Although this reductionist viewpoint advances our understanding of cerebellar organization, the relationship between these compartments and the functional behavior of the cerebellum remains a mystery.
Effects of cerebral oedema and arterial hypotension on cerebral blood flow in an animal model of hepatic failure
Authors: P. N. Trewby, M. A. Hanid, R. L. Mackenzie, P. J. Mellon, R. Williams
Journal: Gut (1978)

The effects of arterial hypotension and a raised intracranial pressure on cerebral blood flow (CBF) have been investigated in an animal model of hepatic failure. Arterial hypotension was associated with a fall in CBF in the animals with liver failure but not in the controls. Significant differences in mean CBF between the two groups of animals could be demonstrated when the systolic blood pressure was in the 30-60, 60-90, and 90-120 mmHg range, but not in the 120-150 mmHg range. A raised intracranial pressure also resulted in a fall in CBF in the animals with liver failure, and a significant difference could be demonstrated between the two groups when the intracranial pressure was in the 20-40 mmHg range but not in the 0-20 mmHg range. Furthermore, in the animals with liver failure the cerebral metabolic rate for oxygen (CMRO<sub>2</sub>) fell as the CBF fell, there being a highly significant correlation between these two parameters. In the controls no such relation existed. Treatment with neither charcoal haemoperfusion nor high dose corticosteroids affected the fall in cerebral blood flow that occurred during arterial hypotension in the animals with liver failure. Corticosteroids, however, did reduce the fall in cerebral blood flow associated with a high intracranial pressure. These results suggest a disruption of the cerebral circulatory responses in hepatic failure. They also raise the possibility that CMRO<sub>2</sub> and cerebral blood flow may be maintained at normal levels in hepatic encephalopathy if cerebral oedema and arterial hypotension can be prevented.
N-terminal-pro-brain natriuretic peptide as a haemodynamic marker in idiopathic pulmonary arterial hypertension
Authors: R. Souza, H. B. Bogossian, M. Humbert, C. Jardim, R. Rabelo, M. B. P. Amato, C. R. R. Carvalho
Journal: European Respiratory Journal (2005)

Patients with idiopathic pulmonary arterial hypertension usually undergo acute vasodilator tests with nitric oxide (NO) for haemodynamic evaluation and therapeutical planning. The aim of this study was to evaluate the link between the variation of N-terminal (NT)-pro-brain natriuretic peptide (BNP) levels and haemodynamic parameters during the acute vasodilator test. A total of 22 idiopathic pulmonary arterial hypertension patients who underwent acute vasodilator tests were studied. Blood samples were collected at baseline and after 30 and 60 min of NO inhalation. NT-pro-BNP levels were measured in each sample. A receiver-operating characteristic curve was used to evaluate the capability of the NT-pro-BNP level variation during NO inhalation in recognising nonresponders. To distinguish responders from nonresponders, the increase of the NT-pro-BNP (0% as cut-off value) determined a 50% specificity and 100% sensitivity (positive predictive value of 38% and a negative predictive value of 100%). These results suggest that N-terminal-pro-brain natriuretic peptide was able to distinguish nonresponder patients with the acute vasodilator test. N-terminal-pro-brain natriuretic peptide may be an interesting additional biological tool in the evaluation of idiopathic pulmonary arterial hypertension patients.
Surrogate Markers for Antiangiogenic Therapy and Dose-Limiting Toxicities for Bevacizumab With Radiation and Chemotherapy: Continued Experience of a Phase I Trial in Rectal Cancer Patients
Authors: Christopher G. Willett, Yves Boucher, Dan G. Duda, Emmanuelle di Tomaso, Lance L. Munn, Ricky T. Tong, Sergey V. Kozin, Lucine Petit, Rakesh K. Jain, Daniel C. Chung, Dushyant V. Sahani, Sanjeeva P. Kalva, Kenneth S. Cohen, David T. Scadden, Alan J. Fischman, Jeffrey W. Clark, David P. Ryan, Andrew X. Zhu, Lawrence S. Blaszkowsky, Paul C. Shellito, Mari Mino-Kenudson, Gregory Y. Lauwers
Journal: Journal of Clinical Oncology (2005)
Human reproductive failure II: Immunogenetic and interacting factors
Authors: Shormila Roy Choudhury, Leslie A. Knapp
Journal: Human Reproduction Update (2001)

Studies in humans suggest that reproductive failure may be influenced by immunological factors or by genes encoding immunological factors and regulatory mechanisms controlling immunological expression. Using molecular methods, immunological factors can be clearly studied in an immunogenetic context. One example, the major histocompatibility complex (MHC), known as the human leukocyte antigens (HLA) in humans and MHC in other mammals, affects many different stages of reproduction. Studies in some outbred, and in closely related, human populations indicate that HLA, or HLA-linked, genes and HLA regulatory factors affect gamete development, embryo cleavage, blastocyst and trophoblast formation, implantation, fetal development and survival. Studies in non-human mammals indicate that MHC, or MHC-linked, genes such as the grc complex, Ped/Qa-2, t haplotypes and MHC regulatory factors, have similar reproductive effects. Human reproductive failure may also be a consequence of disruption of interacting factors, including interactions between HLA antigens, cytokines and natural killer (NK) cells. In this review, we highlight the importance of immunogenetic and interacting factors in human reproductive failure. We argue that studies in closely related human populations and animal models may contribute to a better understanding of the ways in which immunogenetic and interacting factors are involved in human reproduction.
Dual Induction of Apoptosis and Senescence in Cancer Cells by Chk2 Activation: Checkpoint Activation as a Strategy against Cancer
Authors: Chang-Rung Chen, Wenxian Wang, Harry A. Rogoff, Xiaotong Li, William Mang, Chiang J. Li
Journal: Cancer Research (2005)

The human checkpoint kinase 2 (Chk2) plays a central role in regulation of the cellular response to DNA damage, resulting in cell cycle arrest, DNA repair, or apoptosis depending on severity of DNA damage and the cellular context. Chk2 inhibitors are being developed as sensitizers for chemotherapeutic agents. In contrast, here we report that direct activation of Chk2 alone (without chemotherapeutic agents) led to potent inhibition of cancer cell proliferation. In the absence of de novo DNA damage, checkpoint activation was achieved by increased Chk2 expression, as evidenced by its phosphorylation at Thr68, resulting in senescence and apoptosis of cancer cells (DLD1 and HeLa). The Chk2-induced apoptosis was p53 independent and was mediated by caspase activation triggered by loss of mitochondrial potential. The Chk2-induced senescence was also p53 independent and was associated with induction of p21. These results suggest that direct activation of checkpoint kinases may be a novel approach for cancer therapy.
Regulation of phosphorylase kinase in rat ventricular myocardium. Role of calmodulin.
Authors: D K Werth, D R Hathaway, A M Watanabe
Journal: Circulation Research (1982)

Conversion of phosphorylase b to a which is catalyzed by the enzyme phosphorylase kinase is known to require Ca++. Trifluoperazine, an inhibitor of calmodulin-dependent enzymes, was utilized in the present study to clarify the role in vivo of calcium-calmodulin regulation of phosphorylase kinase. Twenty-minute preperfusion of isolated rat ventricles with 10(-5) M trifluoperazine had no effect on basal levels of phosphorylase a but significantly attenuated phosphorylase activation induced by either calcium (3.75 mM) or isoproterenol (3 x 10(-9) M, 3 x 10(-8) M). The positive inotropic effect of both agents and cyclic adenosine 3',5'-monophosphate (cAMP) levels were not altered by trifluoperazine in the perfused hearts. In addition, no effects of 10(-5) M trifluoperazine were noted on beta-adrenergic receptor binding of [3H](+/-)carazolol or on adenylate cyclase activity. In vitro studies with partially purified rat cardiac phosphorylase kinase demonstrated 1.5- to 3-fold stimulation by exogenous calmodulin. The addition of 10(-5) M trifluoperazine prevented calmodulin stimulation but had little effect on activity in the absence of exogenous calmodulin. The present results suggest that reversible binding of calcium-calmodulin may represent a physiological means for regulating phosphorylase kinase activity in rat cardiac muscle.
Adenosine A1 receptor activation attenuates cardiac injury produced by hydrogen peroxide.
Authors: M Karmazyn, M A Cook
Journal: Circulation Research (1992)

Adenosine has been shown to protect the ischemic and reperfused myocardium. To examine whether the protective effect of the nucleoside is mediated by modulation of oxidative stress, isolated rat hearts were perfused for 30 minutes with 100 microM H2O2 or an exogenous free radical-generating system consisting of purine (3.06 mM) and xanthine oxidase (10 units/l) in the presence or absence of drugs acting on adenosine A1 or A2 receptors. H2O2 alone produced a greater than 90% loss in contractility concomitant with a threefold elevation in resting tension, although these effects occurred in the absence of ultrastructural damage. Two A1 receptor agonists N6-cyclopentyladenosine (CPA, 1 microM) and R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA, 1 microM) significantly attenuated the cardiodepressant effects of H2O2 and depressed the elevation in resting tension; however, only the effect of CPA was found to be significant with regard to the latter parameter. A similar concentration of S(+)-N6-(2-phenylisopropyl)adenosine (S-PIA), a markedly less potent A1 receptor agonist, was found to be without beneficial effect. However, a significant protective effect against both the reduction in contractility and the elevation in resting tension was seen with a 10-fold elevation in the concentration of S-PIA (10 microM). The protective effects on functional parameters were associated with preservation of high-energy phosphate and adenine nucleotide contents after 30 minutes of H2O2 treatment. The salutary effects of all drugs were reversed in the presence of the A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (0.5 microM). An A2 receptor agonist 2-[p-(carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosine, termed CGS 21680 (1 microM), failed to alter the cardiac response to H2O2 with regard to all parameters studied. Neither a 50% reduction in external CaCl2 concentration nor treatment with 10 microM DL-propranolol exerted salutary effects against H2O2-induced dysfunction. None of the A1 receptor agonists modulated the response to purine plus xanthine oxidase. Our results demonstrate a selective protective effect of adenosine A1 receptor activation against the cardiac toxicity of H2O2 and provide, at least in part, a basis for the cardioprotective actions of adenosine and its analogues.
Comparative frequency of patch test reactions to topical antibiotics
Authors: S.D. Morris, R.J.G. Rycroft, I.R. White, S.H. Wakelin, J.P. McFadden
Journal: British Journal of Dermatology (2002)

Journal Article Comparative frequency of patch test reactions to topical antibiotics Get access S.D. Morris, S.D. Morris St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K S.D.Morris. E‐mail: drsm@doctorsnet.co.uk Search for other works by this author on: Oxford Academic Google Scholar R.J.G. Rycroft, R.J.G. Rycroft St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K Search for other works by this author on: Oxford Academic Google Scholar I.R. White, I.R. White St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K Search for other works by this author on: Oxford Academic Google Scholar S.H. Wakelin, S.H. Wakelin St Mary's Hospital, Praed Street, London W2 1NY, U.K Search for other works by this author on: Oxford Academic Google Scholar J.P. McFadden J.P. McFadden St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 6, 1 June 2002, Pages 1047–1051, https://doi.org/10.1046/j.1365-2133.2002.04662.x Published: 01 June 2002 Article history Accepted: 25 October 2001 Published: 01 June 2002
Sjögren-Larsson syndrome in Brazil is caused by a common c.1108-1G→C splice-site mutation in the <i>ALDH3A2</i> gene
Authors: M.P. Auada, M.B. Puzzi, M.L. Cintra, C.E. Steiner, F. Alexandrino, E.L. Sartorato, T.S. Aguiar, R.D. Azulay, G. Carney, W.B. Rizzo
Journal: British Journal of Dermatology (2006)

Conflicts of interest: None declared. Sjögren–Larsson syndrome (SLS; OMIM 270200) is an autosomal recessive disorder characterized by the presence of pruritic ichthyosis, mental retardation, spastic diplegia or tetraplegia, retinal perimacular 'glistening white dots' and photophobia.1 SLS is caused by mutations in the ALDH3A2 gene, which codes for fatty aldehyde dehydrogenase (FALDH), a microsomal enzyme that catalyses the oxidation of medium‐ and long‐chain aliphatic aldehydes.2 More than 70 mutations have been identified in this disease.3 Most mutations are unique to each SLS family, but several common mutations have been reported among patients from Europe and the Middle East. In the first molecular genetic analysis of a cohort of patients with SLS from Brazil, we now report a common disease‐causing ALDH3A2 mutation, delineate its associated phenotypic spectrum and describe a diagnostic screening test using restriction enzyme digestion. Nine patients with SLS from three apparently unrelated Brazilian kindreds native to the south and southeastern part of the country were studied. Patients 1, 2 and 3 were previously reported4 and were born to consanguineous parents; patients 4, 5 and 6 are sisters and patients 7 and 8 are their cousins. Patient 9 was also born to first cousins. Blood specimens, skin biopsies and clinical data were collected after obtaining informed consent and with approval by the Institutional Review Board.
D-penicillamine for primary biliary cirrhosis.
Authors: O F James
Journal: Gut (1985)

<h3>Abstract</h3> Dysregulated microRNA (miRNA) expression is a well-established feature of human cancer. However, the role of specific miRNAs in determining cancer outcomes remains unclear. Using Level 3 expression data from the Cancer Genome Atlas (TCGA), we identified 61 miRNAs that are associated with overall survival in 469 ovarian cancers profiled by microarray (p&lt;0.01). We also identified 12 miRNAs that are associated with survival when miRNAs were profiled in the same specimens using Next Generation Sequencing (miRNA-Seq) (p&lt;0.01). Surprisingly, only 1 miRNA transcript is associated with ovarian cancer survival in both datasets. Our analyses indicate that this discrepancy is due to the fact that miRNA levels reported by the two platforms correlate poorly, even after correcting for potential issues inherent to signal detection algorithms. Further investigation is warranted.
Right Ventricular Structure Is Associated With the Risk of Heart Failure and Cardiovascular Death
Authors: Steven M. Kawut, R. Graham Barr, João A.C. Lima, Amy Praestgaard, W. Craig Johnson, Harjit Chahal, Kofo O. Ogunyankin, Michael R. Bristow, Jorge R. Kizer, Harikrishna Tandri, David A. Bluemke
Journal: Circulation (2012)

Changes in right ventricular (RV) morphology are associated with morbidity and mortality in heart and lung disease. We examined the association of abnormal RV structure and function with the risk of heart failure or cardiovascular death in a population-based multiethnic sample free of clinical cardiovascular disease at baseline. The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on 5098 participants between 2000 and 2002 with follow-up for incident heart failure and cardiovascular death ("death") until January 2008. RV volumes and mass were available for 4204 participants. The study sample (n=4144) was 61.4±10.1 years old and 47.6% male. The presence of RV hypertrophy (increased RV mass) was associated with more than twice the risk of heart failure or death after adjustment for demographics, body mass index, education, C-reactive protein level, hypertension, and smoking status (hazard ratio, 2.52; 95% confidence interval, 1.55-4.10; P<0.001) and a doubling (or more) of risk with left ventricular mass at the mean value or lower (P for interaction=0.05). RV hypertrophy was associated with the risk of heart failure or death in a multiethnic population free of clinical cardiovascular disease at baseline.
A New Perspective on the Biology of C-Reactive Protein
Authors: Edward T.H. Yeh
Journal: Circulation Research (2005)

reactive protein (CRP), composed of 5 23-kDa subunits, was traditionally viewed as one of the acute phase reactants. 1More recently, CRP has risen in statue to subsume the role of the "best" marker of inflammation useful in the prediction of future cardiovascular risks. 2 However, the clinical utility of CRP measurement in cardiovascular risk prediction is still not well defined.Furthermore, there is an intense debate on whether CRP is merely a marker of inflammation or a direct participant. 1The finding reported by Dr Janos Filep's group in this issue of Circulation Research provides additional insights into the current CRP debate. 3In this editorial, I will focus my discussion on 2 main issues.Where is CRP produced?And, is CRP biologically active?Where Is CRP Produced?CRP was traditionally thought to be produced by the liver in response to inflammatory cytokines.Several recent studies, however, clearly showed that CRP can be produced by nonhepatic tissues.Two studies have shown that both epithelial cells of the respiratory tract and renal epithelium can produce CRP under certain circumstances. 4,5Moreover, neuronal cells also seem to be capable of synthesizing acute phase reactants involved in the pathogenesis of neurodegenerative disease such as Alzheimer disease. 6These new sources of CRP production pointed to a more systemic generation of CRP in our body.However, these new sources provided only tenuous link to atherosclerosis.CRP has been shown to colocalize with the terminal complement complex in atherosclerotic plaques. 7urthermore, Yasojima et al reported that mRNAs for CRP and the classical complement components C1 to C9 could be detected in both normal artery and plaque tissue. 8We recently showed that human coronary artery smooth muscle cells, but not human umbilical vein endothelial cells, could synthesize CRP after stimulation by inflammatory cytokines. 9This locally produced CRP may directly participate in the pathogenesis of atherosclerosis.Moreover, we have also shown that human adipocytes could produce CRP after stimulation by inflammatory cytokines and by a specific adipokine, resistin. 10Production of CRP by adipocytes may partially explain why CRP levels are elevated in patients with metabolic syndrome (Figure).
Population-Based 20-Year Survival Among People Diagnosed With Thin Melanomas in Queensland, Australia
Authors: Adèle C. Green, Peter Baade, Michael Coory, Joanne F. Aitken, Mark Smithers
Journal: Journal of Clinical Oncology (2012)

The 20-year survival rates are unknown for the majority of melanoma patients-those with thin melanomas. We determined 20-year survival rates of patients diagnosed with thin melanomas (≤ 1.00 mm) in the general population and also determined the main prognostic factors.Available clinical and histologic data from the Queensland Cancer Registry were obtained for all patients diagnosed with a single thin invasive melanoma from 1982 to 2006 and matched against national death registration data. Melanoma-specific survival estimates to December 31, 2007, were assessed, and subgroup differences in prognosis were determined by fitting multivariate Cox proportional hazard models.Among 26,736 people in the state of Queensland diagnosed with thin melanomas, the 20-year survival was 96%. The most influential determinants of prognosis were tumor thickness ≥ 0.75 mm (adjusted hazard ratio [HR], 4.33; 95% CI, 2.8 to 6.8 compared with tumors < 0.25 mm) and patient age at diagnosis older than 65 years (HR, 2.8; 95% CI, 1.8 to 4.5) compared with age younger than 25 years. Acral lentiginous and nodular tumors, male sex, tumor site on the scalp or neck, or tumor invasion of the entire papillary dermis each independently increased the risk of dying from thin invasive melanoma.The outlook for patients with thin invasive melanoma is positive, although continued clinical vigilance is warranted for patients with nodular melanoma and those with the thickest tumors.
Pressure changes after balloon distension of the colon wall in diverticular disease.
Authors: A N Smith, J Shepherd, M A Eastwood
Journal: Gut (1981)

Balloon distension of the distal colon in diverticular disease does not produce the pressure change in response to increasing volumes that occurs in normal subjects. This phenomenon, though modified at first by resection, is not abolished by resection nor by myotomy or bran. This adaptive quality of the wall of the colon to balloon distension possibly reflects a structural change in its wall, as the phenomenon was present in the colon in diverticular disease in vitro as well as in vivo.