tbuckley/cabot-search huggingface dataset:
Definition of Alcoholism
Authors: FRANK A. SEIXAS
Journal: Annals of Internal Medicine (1976)

Letters1 December 1976Definition of AlcoholismFRANK A. SEIXAS, M.D., CONVENOR, SHEILA BLUME, M.D., LUTHER A. CLOUD, M.D., CHARLES S. LIEBER, M.D., R. KEITH SIMPSON, D.O., D.P.H.FRANK A. SEIXAS, M.D., CONVENORSearch for more papers by this author, SHEILA BLUME, M.D.Search for more papers by this author, LUTHER A. CLOUD, M.D.Search for more papers by this author, CHARLES S. LIEBER, M.D.Search for more papers by this author, R. KEITH SIMPSON, D.O., D.P.H.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-85-6-764 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAlcoholism is a chronic, progressive, and potentially fatal disease. It is characterized by tolerance and physical dependency or pathologic organ changes, or both—all the direct or indirect consequences of the alcohol ingested.1. "Chronic and progressive" means that the physical, emotional, and social changes that develop are cumulative and progress as drinking continues.2. "Tolerance" means brain adaptation to the presence of high concentrations of alcohol.3. "Physical dependency" means that withdrawal symptoms occur from decreasing or ceasing consumption of alcohol.4. The person with alcoholism cannot consistently predict on any drinking occasion the duration of the episode or the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: NATIONAL COUNCIL ON ALCOHOLISM/AMERICAN MEDICAL SOCIETY ON ALCOHOLISM COMMITTEE ON DEFINITIONS PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAddiction Medicine and Addiction Psychiatry in America: Commonalities in the Medical Treatment of AddictionDEFINING DEPENDENCE: DESCRIBING SYMPTOM CLUSTERS VERSUS CENTRAL CONSTRUCTSAlcoholism/Addiction as a Chronic DiseaseEffect of Clarifying Students' Misperceptions Associated with Alcohol Consumption at a Connecticut Public UniversityThe case for liver transplantation in end-stage alcoholic liver diseaseAlcoholism and Liver Transplantation: Ethical and Nursing ImplicationsAlcohol Withdrawal SyndromesLiver Transplantation for Alcoholic Liver Disease: A Consideration of Reasons For and AgainstDefinition of AlcoholismThe Skin in AlcoholismAlcoholism in College: Early Case FindingAlcohol and Drug ProblemsNorm Qualities and AlcoholismNonproblem Drinking as a Goal in the Treatment of Problem DrinkersDelay in Seeking Help and Onset of Crisis among Al-Anon Wives 1 December 1976Volume 85, Issue 6Page: 764-764KeywordsAlcohol consumptionAlcoholismAlcoholsAttentionBrainEmotions ePublished: 1 December 2008 Issue Published: 1 December 1976 PDF downloadLoading ...
A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order
Authors: Adaikalavan Ramasamy, Ivan Curjuric, Lachlan J. Coin, Ashish Kumar, Wendy L. McArdle, Medea Imboden, Benedicte Leynaert, Manolis Kogevinas, Peter Schmid-Grendelmeier, Juha Pekkanen, Matthias Wjst, Andreas J. Bircher, Ulla Sovio, Thierry Rochat, Anna-Liisa Hartikainen, David J. Balding, Marjo-Riitta Jarvelin, Nicole Probst-Hensch, David P. Strachan, Deborah L. Jarvis
Journal: Journal of Allergy and Clinical Immunology (2011)
Chemokine Antagonists as Therapeutics: Focus on HIV-1
Authors: Athe M.N. Tsibris, Daniel R. Kuritzkes
Journal: Annual Review of Medicine (2006)

Human immunodeficiency virus type 1 (HIV-1) entry into target cells is a multistep process involving the interaction of viral envelope proteins with cell surface receptors. Binding to CD4 is followed by engagement of specific chemokine receptors (CCR5 or CXCR4), triggering molecular rearrangements in the envelope transmembrane subunit that result in membrane fusion. Chemokine receptor antagonists that block the interaction of the HIV-1 envelope with CCR5 or CXCR4 potently inhibit HIV-1 in vitro. Pilot studies of orally bioavailable small-molecule CCR5 inhibitors in HIV-1-infected subjects have provided proof of concept for this novel drug class; phase III safety and efficacy trials are under way.
Effects of Telmisartan on Glucose Levels in People at High Risk for Cardiovascular Disease but Free From Diabetes
Authors: Joshua I. Barzilay, Peggy Gao, Lars Rydén, Helmut Schumacher, Jeffrey Probstfield, Patrick Commerford, Antonio Dans, Rafael Ferreira, Mátyás Keltai, Ernesto Paolasso, Salim Yusuf, Koon Teo
Journal: Diabetes Care (2011)

OBJECTIVE Several large clinical trials suggest that ACE inhibitors may reduce the incidence of diabetes. Less is known about the effects of angiotensin receptor blockers (ARBs) on reducing incident diabetes or leading to regression of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) to normoglycemia. RESEARCH DESIGN AND METHODS Participants were 3,488 adults at high risk for cardiovascular disease but free from diabetes (mean age 67 years; 61% male) in the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) study. The participants were randomized to the ARB telmisartan 80 mg (n = 1,726) or placebo (n = 1,762) in addition to usual care. RESULTS During a median 56 months, 21.8% of participants treated with telmisartan and 22.4% of those on placebo developed diabetes (relative ratio 0.95 [95% CI 0.83–1.10]; P = 0.51). Participants originally diagnosed with IFG and/or IGT were equally likely to regress to normoglycemia (26.9 vs. 24.5%) or to progress to incident diabetes (20.1 vs. 21.1%; P = 0.59) on telmisartan or placebo. CONCLUSIONS There was no evidence that addition of the ARB telmisartan to usual care prevents incident diabetes or leads to regression of IFG or IGT in people at high risk for cardiovascular disease but free from diabetes.
1997 Winter Meeting of the British Thoracic Society
Authors: J A INNES
Journal: Thorax (1998)

The 1997 Winter Meeting of the British Thoracic Society attracted over 1300 delegates and 328 posters and presentations covering every aspect of respiratory disease. This article will highlight selected themes from the meeting.

The widespread adoption of inhaled steroids has transformed the management of asthma, yet the increasing recognition that high dose inhaled steroids carry significant risks of systemic adverse effects is stimulating increased interest in alternative ways of controlling airway inflammation. In a symposium on “New therapies for respiratory disease” Professor Tak Lee summarised the data supporting the use of 5-lipoxygenase inhibitors and leukotriene receptor blockers in asthma. These compounds, which are already on the market in the USA and in some European countries, appear to have significant asthma controlling activity that is complementary to β2 agonists and may prove useful as steroid sparing agents.

Dexa bone densitometry is highlighting the high incidence of osteopenia and osteoporosis secondary to prolonged or frequent steroid use in asthma1 and such scanning provides a tool for early detection and for monitoring response to treatment. Interpretation of scan results in patients with severe obstructive lung disease is complicated by the effects of immobility and nutritional state on bone density, and further controlled trials in this area are needed.

The origins of asthma in early life form the topic of an ambitious long term environmental intervention study2 3in which an attempt has been made to reduce the early domestic exposure to relevant antigens in a cohort of at-risk infants. Infants are prenatally randomised to allergen avoidance or control groups. These two presentations outlined the evidence to show that it is practicable to control significantly allergen exposure in the home, and the outcome of these interventions is awaited with interest.

The role of corticosteroids remains a focus of therapeutic interest in …
Point: Inpatient Glucose Management
Authors: Michael Bryer-Ash, Alan J. Garber
Journal: Diabetes Care (2005)

In January 2004, a panel convened by the American College of Endocrinology (ACE) and the American Association of Clinical Endocrinologists (AACE) issued a position statement on the management of glucose in hospitalized patients (1). This panel included representation by the American Diabetes Association (ADA), the Endocrine Society, the American Heart Association, the Society of Critical Care Medicine, the Society of Thoracic Surgeons, The American Association of Diabetes Educators, The American Society of Anesthesiologists, and The Society of Hospital Medicine, all of whom were cosignatories to the ensuing document. The position statement recommended that a preprandial target level of 110 mg/dl (6.0 mmol/l) be set for the plasma glucose level of all hospitalized patients, regardless of the presence or absence of a prior diagnosis of diabetes (1).

The impetus for establishment of a position on this issue largely arose from the publication of two major prospective controlled intervention trials that demonstrated significant reductions in serious morbidities and mortality in hospitalized patients in whom glycemia was tightly regulated (2,3). These trials were in turn undertaken to further address the findings of prior observational studies, which showed a strong correlation between hyperglycemia and poor clinical outcomes in a variety of inpatient settings (4–8). Until recently, it seemed intuitively obvious that hyperglycemia manifested under physiologically stressful situations was a consequence of the primary illness and a marker of its severity, rather than directly contributing additional morbidity to it. While the former may indeed be the case, it came as a surprise to many that prospective trials addressing the hyperglycemia alone, or to be more specific, addressing it by the administration of insulin, improved multiple immediate clinical outcomes, including reducing sepsis, renal failure, transfusion requirements, and polyneuropathy (3,9). Moreover, in one study, in-hospital mortality was reduced by >50% …
Interferon stimulates interleukin 1 receptor antagonist production in human articular chondrocytes and synovial fibroblasts
Authors: G Palmer
Journal: Annals of the Rheumatic Diseases (2003)

<b>Background:</b> Interferon (IFN) β displays anti-inflammatory and immunosuppressive activity and has been considered for the treatment of rheumatoid arthritis (RA). Information about the effects of this molecule on joint cells is scarce, however. <b>Objective:</b> To investigate the effects of IFNβ on the production of interleukin-1 receptor antagonist (IL1Ra) in human articular chondrocytes and synovial fibroblasts. <b>Methods:</b> Chondrocytes and synovial fibroblasts were stimulated with IFNβ alone or in combination with interleukin (IL) 1β. IL1Ra concentrations in culture supernatants and cell lysates were determined by ELISA. Expression of mRNA encoding the secreted sIL1Ra or the intracellular icIL1Ra1 isoforms was quantified by real time reverse transcriptase-polymerase chain reaction. <b>Results:</b> In chondrocytes, IFNβ alone had no effect, but dose dependently enhanced the secretion of IL1Ra induced by IL1β. Chondrocyte cell lysates contained undetectable or low levels of IL1Ra, even after stimulation with IL1β and IFNβ. Consistently, IL1β and IFNβ induced sIL1Ra mRNA expression in chondrocytes, while expression of icIL1Ra1 was not detectable. Human articular chondrocytes thus mainly produce secreted IL1Ra. In synovial fibroblasts, IFNβ alone dose dependently increased IL1Ra secretion. In addition, IFNβ enhanced the stimulatory effect of IL1β on IL1Ra production. In synovial cell lysates, IFNβ and IL1β also increased IL1Ra levels. Consistently, IFNβ and IL1β induced the expression of both sIL1Ra and icIL1Ra1 mRNA in synovial fibroblasts. <b>Conclusion:</b> IFNβ increases IL1Ra production in joint cells, which may be beneficial in cartilage damaging diseases such as RA or osteoarthritis.
High Stem Cell Frequency in Acute Myeloid Leukemia at Diagnosis Predicts High Minimal Residual Disease and Poor Survival
Authors: Anna van Rhenen, Nicole Feller, Angèle Kelder, August H. Westra, Elwin Rombouts, Sonja Zweegman, Marjolein A. van der Pol, Quinten Waisfisz, Gert J. Ossenkoppele, Gerrit Jan Schuurhuis
Journal: Clinical Cancer Research (2005)

Abstract Purpose: In CD34-positive acute myeloid leukemia (AML), the leukemia-initiating event originates from the CD34+CD38− stem cell compartment. Survival of these cells after chemotherapy may lead to minimal residual disease (MRD) and subsequently to relapse. Therefore, the prognostic impact of stem cell frequency in CD34-positive AML was investigated. Experimental Design: First, the leukemogenic potential of unpurified CD34+CD38− cells, present among other cells, was investigated in vivo using nonobese diabetic/severe combined immunodeficient mice transplantation experiments. Second, we analyzed whether the CD34+CD38− compartment at diagnosis correlates with MRD frequency after chemotherapy and clinical outcome in 92 AML patients. Results: In vivo data showed that engraftment of AML blasts in nonobese diabetic/severe combined immunodeficient mice directly correlated with stem cell frequency of the graft. In patients, a high percentage of CD34+CD38− stem cells at diagnosis significantly correlated with a high MRD frequency, especially after the third course of chemotherapy. Also, it directly correlated with poor survival. In contrast, total CD34+ percentage showed no such correlations. Conclusions: Both in vivo data, as well as the correlation studies, show that AML stem cell frequency at diagnosis offers a new prognostic factor. From our data, it is tempting to hypothesize that a large CD34+CD38− population at diagnosis reflects a higher percentage of chemotherapy-resistant cells that will lead to the outgrowth of MRD, thereby affecting clinical outcome. Ultimately, future therapies should be directed toward malignant stem cells.
Brainstem Aminergic Nuclei and Late-Life Depressive Symptoms
Authors: Robert S. Wilson, Sukriti Nag, Patricia A. Boyle, Loren P. Hizel, Lei Yu, Aron S. Buchman, Raj C. Shah, Julia A. Schneider, Steven E. Arnold, David A. Bennett
Journal: JAMA Psychiatry (2013)

The neurobiologic basis of late-life depressive symptoms is not well understood.To test the hypothesis that neurodegeneration and neuronal density in brainstem aminergic nuclei are related to late-life depressive symptoms. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE: Longitudinal clinicopathological cohort study at residences of participants in the Chicago, Illinois, metropolitan area. Participants included 124 older persons without dementia in the Rush Memory and Aging Project who had annual evaluations for a mean (SD) of 5.7 (2.8) years, died, and underwent a postmortem neuropathological examination that provided estimates of the densities of Lewy bodies, neurofibrillary tangles, and aminergic neurons in the locus ceruleus, dorsal raphe nucleus, substantia nigra, and ventral tegmental area.The number of depressive symptoms (mean [SD], 1.61 [1.48]; range, 0-6; skewness, 0.94) on the Center for Epidemiological Studies Depression Scale averaged across annual evaluations.Brainstem Lewy bodies were associated with depressive symptoms, and the association was attenuated in those taking antidepressant medication. Brainstem tangles were associated with more depressive symptoms in those without cognitive impairment but with fewer symptoms in those with mild cognitive impairment. Lower density of tyrosine hydroxylase-immunoreactive neurons in the ventral tegmental area was robustly associated with a higher level of depressive symptoms (mean [SE] estimate, -0.014 [0.003]; P < .001; 16.3% increase in adjusted R2). The association was not modified by medication use or cognitive impairment. Neither tyrosine hydroxlyase-immunoreactive neurons in the locus ceruleus nor tryptophan hydroxlyase-immunoreactive neurons in the dorsal raphe nucleus were related to depressive symptoms.The results suggest that the mesolimbic dopamine system, especially the ventral tegmental area, has an important role in late-life depressive symptoms.
PI3K integrates the action of insulin and leptin on hypothalamic neurons
Authors: Allison Wanting Xu, Christopher B. Kaelin, Kiyoshi Takeda, Shizuo Akira, Michael W. Schwartz, Gregory S. Barsh
Journal: Journal of Clinical Investigation (2005)

Central control of energy balance depends on the ability of proopiomelanocortin (POMC) or agouti-related protein (Agrp) hypothalamic neurons to sense and respond to changes in peripheral energy stores. Leptin and insulin have been implicated as circulating indicators of adiposity, but it is not clear how changes in their levels are perceived or integrated by individual neuronal subtypes. We developed mice in which a fluorescent reporter for PI3K activity is targeted to either Agrp or POMC neurons and used 2-photon microscopy to measure dynamic regulation of PI3K by insulin and leptin in brain slices. We show that leptin and insulin act in parallel to stimulate PI3K in POMC neurons but in opposite ways on Agrp neurons. These results suggest a new view of hypothalamic circuitry, in which the effects of leptin and insulin are integrated by anorexigenic but not by orexigenic neurons.
Clinical and Angiographic Risk Stratification and Differential Impact on Treatment Outcomes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial
Authors: Maria Mori Brooks, Bernard R. Chaitman, Richard W. Nesto, Regina M. Hardison, Frederick Feit, Bernard J. Gersh, Ronald J. Krone, Edward Y. Sako, William J. Rogers, Alan J. Garber, Spencer B. King, Charles J. Davidson, Fumiaki Ikeno, Robert L. Frye
Journal: Circulation (2012)

Background— The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial assigned patients with type 2 diabetes mellitus to prompt coronary revascularization plus intensive medical therapy versus intensive medical therapy alone and reported no significant difference in mortality. Among patients selected for coronary artery bypass graft surgery, prompt coronary revascularization was associated with a significant reduction in death/myocardial infarction/stroke compared with intensive medical therapy. We hypothesized that clinical and angiographic risk stratification would affect the effectiveness of the treatments overall and within revascularization strata. Methods and Results— An angiographic risk score was developed from variables assessed at randomization; independent prognostic factors were myocardial jeopardy index, total number of coronary lesions, prior coronary revascularization, and left ventricular ejection fraction. The Framingham Risk Score for patients with coronary disease was used to summarize clinical risk. Cardiovascular event rates were compared by assigned treatment within high-risk and low-risk subgroups. Overall, no outcome differences between the intensive medical therapy and prompt coronary revascularization groups were seen in any risk stratum. The 5-year risk of death/myocardial infarction/stroke was 36.8% for intensive medical therapy compared with 24.8% for prompt coronary revascularization among the 381 coronary artery bypass graft surgery–selected patients in the highest angiographic risk tertile ( P =0.005); this treatment effect was amplified in patients with both high angiographic and high Framingham risk (47.3% intensive medical therapy versus 27.1% prompt coronary revascularization; P =0.010; hazard ratio=2.10; P =0.009). Treatment group differences were not significant in other clinical-angiographic risk groups within the coronary artery bypass graft surgery stratum, or in any subgroups within the percutaneous coronary intervention stratum. Conclusion— Among patients with diabetes mellitus and stable ischemic heart disease, a strategy of prompt coronary artery bypass graft surgery significantly reduces the rate of death/myocardial infarction MI/stroke in those with extensive coronary artery disease or impaired left ventricular function. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00006305.
Personality correlates of physical activity: a review and meta-analysis: Table 1
Authors: R E Rhodes, N E I Smith
Journal: British Journal of Sports Medicine (2006)

This review aimed to combine the literature on major personality traits and physical activity alongside providing some meta-analytic summaries of the findings. Overall, 33 studies containing 35 independent samples, ranging from 1969 to 2006, met the inclusion criteria. Extraversion (r = 0.23), neuroticism (r = −0.11) and conscientiousness (r = 0.20) were identified as correlates of physical activity using random effects meta-analytic procedures correcting for sampling bias and attenuation of measurement error. The five-factor model traits of openness to experience/intellect and agreeableness, as well as Eysenck’s psychoticism trait, were not associated with physical activity. Potential moderators of personality and physical activity relationships such as sex, age, culture/country, design and instrumentation were inconclusive given the small number of studies. Still, the existing evidence was suggestive that personality and physical activity relationships are relatively invariant to these factors. Studies examining personality and different physical activity modes suggested differences by traits such as extraversion, but more research is needed to make any conclusions. Future research using multivariate analyses, personality-channelled physical activity interventions, longitudinal designs and objective physical activity measurement is recommended.
Therapeutic Synergism of Gemcitabine and CpG-Oligodeoxynucleotides in an Orthotopic Human Pancreatic Carcinoma Xenograft
Authors: Graziella Pratesi, Giovanna Petrangolini, Monica Tortoreto, Alessandro Addis, Sara Belluco, Anna Rossini, Silvia Selleri, Cristiano Rumio, Sylvie Menard, Andrea Balsari
Journal: Cancer Research (2005)

Abstract CpG-oligodeoxynucleotides (CpG-ODN) exhibit potent immunostimulatory activity by binding with Toll-like receptor 9 (TLR9). Based on the finding that TLR9 is highly expressed and functional in pancreatic tissue, we evaluated the antitumor effects of chemotherapy combined with CpG-ODNs in the orthotopic mouse model of a human pancreatic tumor xenograft. Chemotherapy consisted of the maximum tolerated dose of gemcitabine (i.v., 100 mg/kg, q3dx4). CpG-ODNs were delivered (i.p., 20 μg/mouse), weekly, after the end of chemotherapy. CpG-ODNs alone had little effect on tumor growth, whereas gemcitabine alone significantly delayed the median time of disease onset (palpable i.p. tumor) and of bulky disease development (extensive peritoneal tumor burden), but did not enhance survival time. When the gemcitabine regimen was followed by administration of the immunostimulator, development of bulky disease was delayed, survival time was significantly improved (median survival time, 106 days; P &amp;lt; 0.02 versus gemcitabine-treated mice). Autoptic examination showed that tumor spread in the peritoneal cavity was reduced to a greater extent than with gemcitabine alone. All treatment regimens were well-tolerated. The use of nude mice excluded a T cell–mediated immune response, whereas the high pancreatic expression of TLR9 might have contributed to the tumor response. The clear improvement of survival observed in an orthotopic murine model of human pancreatic cancer by the combined use of CpG-ODNs with chemotherapy suggests the promise of this therapeutic regimen in the clinical setting.