tbuckley/cabot-search huggingface dataset:
Alcohol Consumption and Risk of Postmenopausal Breast Cancer by Subtype: The Women's Health Initiative Observational Study
Authors: C. I. Li, R. T. Chlebowski, M. Freiberg, K. C. Johnson, L. Kuller, D. Lane, L. Lessin, M. J. O'Sullivan, J. Wactawski-Wende, S. Yasmeen, R. Prentice
Journal: JNCI Journal of the National Cancer Institute (2010)

Alcohol consumption is a well-established risk factor for breast cancer. This association is thought to be largely hormonally driven, so alcohol use may be more strongly associated with hormonally sensitive breast cancers. Few studies have evaluated how alcohol-related risk varies by breast cancer subtype.We assessed the relationship between self-reported alcohol consumption and postmenopausal breast cancer risk among 87 724 women in the Women's Health Initiative Observational Study prospective cohort from 1993 through 1998. Multivariable adjusted Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.A total of 2944 invasive breast cancer patients were diagnosed during follow-up through September 15, 2005. In multivariable adjusted analyses, alcohol consumption was positively related to risk of invasive breast cancer overall, invasive lobular carcinoma, and hormone receptor-positive tumors (all P(trend) ≤ .022). However, alcohol consumption was more strongly related to risk of certain types of invasive breast cancer compared with others. Compared with never drinkers, women who consumed seven or more alcoholic beverages per week had an almost twofold increased risk of hormone receptor-positive invasive lobular carcinoma (HR = 1.82; 95% CI = 1.18 to 2.81) but not a statistically significant increased risk of hormone receptor-positive invasive ductal carcinoma (HR = 1.14; 95% CI = 0.87 to 1.50; difference in HRs per drink per day among current drinkers = 1.15; 95% CI = 1.01 to 1.32, P = .042). The absolute rates of hormone receptor-positive lobular cancer among never drinkers and current drinkers were, 5.2 and 8.5 per 10 000 person-years, respectively, whereas for hormne receptor-positive ductal cancer they were 15.2 and 17.9 per 10 000 person-years, respectively.Alcohol use may be more strongly associated with risk of hormone-sensitive breast cancers than hormone-insensitive subtypes, suggesting distinct etiologic pathways for these two breast cancer subtypes.
Medicine in the Modern Navy
Authors: V Adm R. B. Brown
Journal: JAMA (1966)

The painting reproduced on the cover of this issue symbolizes medicine in the modern Navy and the progress accomplished in the medical support of our naval force. In John Paul Jones's day a Navy doctor signed on for the length of the cruise; he had available a most rudimentary medicine chest; he was paid by a share of the booty; his assistant, the loblolly boy, spread sand upon the deck to render blood from the wounded less slippery. Today's Navy doctor has available the latest in clinical and research equipment and is assisted by well-qualified allied specialists. He is a full-fledged member of the Navy officer corps. Medicine in the Navy can be divided into three broad categories: training and practice in clinical medicine, military medical specialties, and research. <h3>Clinical Medicine</h3> Clinical training is excellent. The intern or resident reporting to a naval hospital will find an abundance of clinical
Effects of Stress Management Training and Dietary Changes in Treating Ischemic Heart Disease
Authors: D. Ornish, L. W. Scherwitz, R. S. Doody, D. Kesten, S. M. McLanahan, S. E. Brown, E. DePuey, R. Sonnemaker, C. Haynes, J. Lester, G. K. McAllister, R. J. Hall, J. A. Burdine, Antonio Gotto
Journal: JAMA (1983)

To evaluate the short-term effects of an intervention that consists of stress management training and dietary changes in patients with ischemic heart disease (IHD), we compared the cardiovascular status of 23 patients who received this intervention with a randomized control group of 23 patients who did not. After 24 days, patients in the experimental group demonstrated a 44% mean increase in duration of exercise, a 55% mean increase in total work performed, somewhat improved left ventricular regional wall motion during peak exercise, and a net change in the left ventricular ejection fraction from rest to maximum exercise of +6.4%. Also, we measured a 20.5% mean decrease in plasma cholesterol levels and a 91.0% mean reduction in frequency of anginal episodes. In this selected sample, short-term improvements in cardiovascular status seem to result from these adjuncts to conventional treatments of IHD. (<i>JAMA</i>1983;249:54-59)
Immune system activation and ischemic heart disease: Relation of interleukin‐2 soluble receptor serum levels and left ventricular dysfunction
Authors: A. D'Ambrosio, G. Patti, A. Abbate, A. Manzoli, G. Dicuonzo, G. Guarnieri, A. Dobrina, G. Di Sciascio
Journal: European Journal of Heart Failure (2000)
Proposed Classification of Childhood Depression
Authors: LEON CYTRYN, DONALD H. McKNEW
Journal: American Journal of Psychiatry (1972)

Neurotic depressive reactions of mid-childhood may be classified into three distinct categories. Masked depression is the most frequent, appearing in children whose personality and family display severe psychopathology. Children suffering acute depression are fairly well adjusted prior to the traumatic event that precipitates the depression; there may be mild psychopathology in the family. Chronically depressed children have a history of marginal premorbid social adjustment, depression, and repeated separations from important adults; in addition, at least one parent has a history of recurrent depression.
An Academic Center's Delivery of Care After the Haitian Earthquake
Authors: Amir K. Jaffer
Journal: Annals of Internal Medicine (2010)

The Miller School of Medicine of the University of Miami and Project Medishare, an affiliated not-for-profit organization, provided a large-scale relief effort in Haiti after the earthquake of 12 January 2010. Their experience demonstrates that academic medical centers in proximity to natural disasters can help deliver effective medical care through a coordinated process involving mobilization of their own resources, establishment of focused management teams at home and on the ground with formal organizational oversight, and partnership with governmental and nongovernmental relief agencies. Proximity to the disaster area allows for prompt arrival of medical personnel and equipment. The recruitment and organized deployment of large numbers of local and national volunteers are indispensable parts of this effort. Multidisciplinary teams on short rotations can form the core of the medical response.
Meta-Analysis of Postoperative Adjuvant Chemotherapy With Tegafur-Uracil in Non–Small-Cell Lung Cancer
Authors: Chikuma Hamada, Fumihiro Tanaka, Mitsuo Ohta, Shigefumi Fujimura, Ken Kodama, Munehisa Imaizumi, Hiromi Wada
Journal: Journal of Clinical Oncology (2005)

Recent clinical trials have shown the efficacy of platinum-based adjuvant chemotherapy for completely resected non-small-cell lung cancer (NSCLC). In Japan, many clinical trials of adjuvant chemotherapy with tegafur-uracil (UFT) have been conducted, and some trials showed positive results while others showed negative results. Thus, we performed a meta-analysis to assess the efficacy of postoperative adjuvant chemotherapy with UFT in NSCLC.Among nine trials of postoperative adjuvant UFT-containing chemotherapy, six trials comparing surgery alone with surgery plus UFT were identified. Of six trials, two were three-arm trials including cisplatin-based chemotherapy followed by UFT, and data from that arm were not included in the meta-analysis.Of 2,003 eligible patients, most (98.8%) had squamous cell carcinoma or adenocarcinoma, and most had stage I disease; the tumor classification was T1 in 1,308 (65.3%), T2 in 674 (33.6%), and the nodal status was N0 in 1,923 (96.0%). The two treatment groups did not differ significantly in major prognostic factors. The median duration of follow-up was 6.44 years. The survival rates at 5 and 7 years were significantly higher in the surgery plus UFT group (81.5% and 76.5%, respectively) than in the surgery alone group (77.2% and 69.5%, respectively; P = .011 and .001, respectively). The overall pooled hazard ratio was 0.74, and its 95% CI was 0.61 to 0.88 (P = .001).This meta-analysis showed that postoperative adjuvant chemotherapy with UFT was associated with improved 5- and 7-year survival in a Japanese patient population composed primarily of stage I adenocarcinoma patients.
Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD
Authors: A. H. Remels, P. Schrauwen, R. Broekhuizen, J. Willems, S. Kersten, H. R. Gosker, A. M. Schols
Journal: European Respiratory Journal (2007)

Chronic obstructive pulmonary disease (COPD) is a multiorgan systemic disease. The systemic features are skeletal muscle weakness and cachexia, the latter being associated with systemic inflammation. The exact mechanisms underlying skeletal muscle dysfunction in COPD remain obscure. Recent evidence suggests involvement of the peroxisome proliferator-activated receptors (PPARs) and PPAR-γ coactivator (PGC)-1α in regulation of skeletal muscle morphology and metabolism, and mitochondrial transcription factor A (TFAM) has been implicated in the process of mitochondrial biogenesis. The aim of the present exploratory study was, therefore, to compare these factors in the skeletal muscle of nine healthy control subjects and 14 COPD patients stratified by cachexia. PPAR-γ, PPAR-δ and TFAM were measured at the mRNA and protein level by real-time quantitative PCR and Western blotting, respectively. PPAR-α and PGC-1α were meansured at the mRNA level. PPAR-δ and TFAM protein content, as well as PGC-1α mRNA levels, were decreased in the skeletal muscle of COPD patients compared with healthy controls. The cachectic COPD subgroup was further characterised by decreased PPAR-α mRNA expression and decreased TFAM protein and mRNA levels compared with noncachectic COPD patients. In addition, PPAR-α mRNA levels in skeletal muscle correlated negatively with inflammatory markers in plasma. Therefore, a disturbed expression of these regulatory factors may well underlie the disturbed skeletal muscle functioning in chronic obstructive pulmonary disease.
Determinants of disability in osteoarthritis of the knee.
Authors: T E McAlindon, C Cooper, J R Kirwan, P A Dieppe
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES: To evaluate the influences of radiographic severity, quadriceps strength, knee pain, age, and gender on functional ability in patients with osteoarthritis of the knee. METHODS: Equal numbers of knee pain positive and negative respondents to a survey of registrants aged more than 55 years at a general practice were invited to attend for knee radiographs and quadriceps femoris isometric strength estimations. Disability was measured using the Stanford Health Assessment Questionnaire. RESULTS: Complete data were available on 70 men (mean age 72.7 years) and 89 women (mean age 68.1 years); 44% reported knee pain, 48% had radiographic features of osteoarthritis, and 32% reported some degree of disability. Significant correlations were observed between disability and radiographic score, quadriceps strength, and knee pain. Logistic regression analysis, however, showed significant independent contributions from quadriceps strength (odds ratio 0.84 kgF), knee pain (odds ratio 1.67), and age (odds ratio 1.06 per year) only; the radiographic score had no influence on the model. These results were not influenced by confining the analysis to the group with radiographic features of osteoarthritis. CONCLUSIONS: Quadriceps strength, knee pain, and age are more important determinants of functional impairment in elderly subjects than the severity of knee osteoarthritis as assessed radiographically. Strategies designed to optimise muscle strength may have the potential to reduce a vast burden of disability, dependency, and cost.
Role of Radiotherapy in Supratentorial Primitive Neuroectodermal Tumor in Young Children: Results of the German HIT-SKK87 and HIT-SKK92 Trials
Authors: Beate Timmermann, Rolf-Dieter Kortmann, Joachim Kühl, Stefan Rutkowski, Christof Meisner, Torsten Pietsch, Frank Deinlein, Christian Urban, Monika Warmuth-Metz, Michael Bamberg
Journal: Journal of Clinical Oncology (2006)

To assess the outcome of young children with supratentorial primitive neuroectodermal tumor (stPNET) treated by intensive postoperative chemotherapy alone compared with treatment with chemotherapy and delayed radiotherapy (RT).From 1987 to 1992, children younger than 3 years of age with stPNET were enrolled in the HIT-SKK87 trial in Germany and Austria. After surgery, low-risk patients received maintenance chemotherapy before RT. In high-risk patients, intensive induction chemotherapy was followed by maintenance chemotherapy until delayed RT was initiated. In the following trial, HIT-SKK92 methotrexate-based chemotherapy was applied. In children with complete remission after three cycles, therapy was finished without irradiation. Otherwise, radiotherapy or salvage chemotherapy was administered.Twenty-nine children were eligible (age, 3.0 to 37.0 months). All children received chemotherapy. In 15 children, no RT was administered. Four children had tumor progression during chemotherapy and underwent irradiation. In 10 patients, RT was given after chemotherapy. Overall survival (OS) and progression-free survival (PFS) rates after 3 years were 17.2% and 14.9%, respectively. Twenty-four children relapsed (13 at the tumor site only, three at distant site, and eight at both local and distant sites). Positive impact on survival was observed in children with complete resection but without statistical significance. Administration of RT was the only significant predictive factor for OS and PFS. Only one child not having RT survived.Outcome of infants and babies with stPNET is unsatisfactory. Omission of RT jeopardizes survival, even if intensive chemotherapy is applied. We suggest to limit any delay of RT to a maximum of 6 months even in young children.
Impact of Dietary and Exercise Interventions on Weight Change and Metabolic Outcomes in Obese Children and Adolescents
Authors: Mandy Ho, Sarah P. Garnett, Louise A. Baur, Tracy Burrows, Laura Stewart, Melinda Neve, Clare Collins
Journal: JAMA Pediatrics (2013)

Diet and exercise represent the mainstays of obesity treatment. No systematic review has been conducted comparing the effect of dietary and exercise intervention in reducing metabolic risks in overweight children.To compare the effects of diet-only intervention with those of diet plus exercise or exercise only on weight loss and metabolic risk reduction in overweight children.English-language articles from 1975 to 2010 available from 7 databases were reviewed. One person searched the databases. Two independent reviewers assessed abstracts and articles against the following eligibility criteria: randomized controlled trials conducted in overweight and obese children aged 18 years or younger, comparing dietary intervention with a diet plus exercise program or an exercise-only program. Study quality was critically appraised by 2 reviewers using established criteria. The main outcome measures were body mass index, body fat percentage, lean body mass, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting glucose, and fasting insulin.Fifteen studies were identified and included. Based on the small number of short-term trials currently available, both diet-only and diet plus exercise interventions resulted in weight loss and metabolic profile improvement. However, the addition of exercise to dietary intervention led to greater improvements in levels of high-density lipoprotein cholesterol (3.86 mg/dL [to convert to millimoles per liter, multiply by 0.0259]; 95% CI, 2.70 to 4.63), fasting glucose (-2.16 mg/dL [to convert to millimoles per liter, multiply by 0.0555]; 95% CI, -3.78 to -0.72), and fasting insulin (-2.75 μIU/mL [to convert to picomoles per liter, multiply by 6.945]; 95% CI, -4.50 to -1.00) over 6 months. The diet-only intervention caused greater reductions in levels of triglycerides (at the end of active intervention) and low-density lipoprotein cholesterol (at subsequent follow-up).This review provides insights into the impact of dietary and exercise interventions on metabolic risk reduction in the pediatric population. However, further studies are required to confirm the evidence with rigorous design, appropriate sample size, longer duration of follow-up, and better strategies to improve compliance and achieve long-term sustainability.
Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study
Authors: Hedy L Kindler, Tatsuya Ioka, Dirk J Richel, Jaafar Bennouna, Richard Létourneau, Takuji Okusaka, Akihiro Funakoshi, Junji Furuse, Young Suk Park, Shinichi Ohkawa, Gregory M Springett, Harpreet S Wasan, Peter C Trask, Paul Bycott, Alejandro D Ricart, Sinil Kim, Eric Van Cutsem
Journal: The Lancet Oncology (2011)
Inhaled Rho Kinase Inhibitors Are Potent and Selective Vasodilators in Rat Pulmonary Hypertension
Authors: Tetsutaro Nagaoka, Karen A. Fagan, Sarah A. Gebb, Kenneth G. Morris, Tsutomu Suzuki, Hiroaki Shimokawa, Ivan F. McMurtry, Masahiko Oka
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

We have found in chronically hypoxic rats that acute intravenous administration of the Rho kinase inhibitor Y-27632 nearly normalizes the pulmonary hypertension (PH) but has no pulmonary vascular selectivity. In this study, we tested if oral or inhaled Y-27632 would be an effective and selective pulmonary vasodilator in hypoxic PH. Although acute oral Y-27632 caused a marked and sustained decrease in mean pulmonary arterial pressure (MPAP), it also decreased mean systemic arterial pressure (MSAP). In contrast, 5 minutes of inhaled Y-27632 decreased MPAP without reducing MSAP. The hypotensive effect of inhaled Y-27632 on hypoxic PH was greater than that of inhaled nitric oxide, and the effect lasted for at least 5 hours. Inhaled fasudil, another Rho kinase inhibitor, caused selective MPAP reductions in monocrotaline-induced PH and in spontaneous PH in fawn-hooded rats, as well as in chronically hypoxic rats. These results suggested that inhaled Y-27632 was more effective than inhaled nitric oxide as a selective pulmonary vasodilator in hypoxic PH, and that Rho kinase–mediated vasoconstriction was also involved in the other models of PH. Inhaled Rho kinase inhibitors might be useful for acute vasodilator testing in patients with PH, and future work should evaluate their efficacy in the long-term treatment of PH.
Phenotypic and genotypic variation in Giardia lamblia isolates during chronic infection.
Authors: P D Butcher, A M Cevallos, S Carnaby, E M Alstead, E T Swarbrick, M J Farthing
Journal: Gut (1994)

Two Giardia isolates were axenised in vitro after recovery by duodenal aspiration from a man with hypo-gamma globulinaemia and chronic giardiasis, before and after three unsuccessful courses of metronidazole. In vitro drug sensitivity assays showed that the pretreatment isolate was sensitive to metronidazole with minimum inhibitory concentration (MIC) and dose that inhibited growth by 50% (ED50) values of 0.1 and 0.03 mumol/l, respectively. The post-treatment isolate was 20-fold more resistant (MIC and ED50 4.3 and 0.58 mumol/l, respectively). Differences between these isolates were also found in the surface protein profiles after radioiodination, metabolic labelling patterns with 35S-methionine, malic enzyme isoenzyme patterns, and by DNA fingerprinting with a M-13 bacteriophage probe. The phenotypic and genotypic differences between the pretreatment and post-treatment isolates suggest that we have isolated two different strains from the same patient and that treatment with metronidazole resulted in selection of the more resistant strain.
Behavioral and transcriptome alterations in male and female mice with postnatal deletion of TrkB in dorsal striatal medium spiny neurons
Authors: Ellen M Unterwald, Michelle E Page, Timothy B Brown, Jonathan S Miller, Marta Ruiz, Karen A Pescatore, Baoji Xu, Louis French Reichardt, Joel Beverley, Bin Tang, Heinz Steiner, Elizabeth A Thomas, Michelle E Ehrlich
Journal: Molecular Neurodegeneration (2013)

The high affinity tyrosine kinase receptor, TrkB, is the primary receptor for brain derived neurotrophic factor (BDNF) and plays an important role in development, maintenance and plasticity of the striatal output medium size spiny neuron. The striatal BDNF/TrkB system is thereby implicated in many physiologic and pathophysiologic processes, the latter including mood disorders, addiction, and Huntington’s disease. We crossed a mouse harboring a transgene directing cre-recombinase expression primarily to postnatal, dorsal striatal medium spiny neurons, to a mouse containing a floxed TrkB allele (fB) mouse designed for deletion of TrkB to determine its role in the adult striatum. We found that there were sexually dimorphic alterations in behaviors in response to stressful situations and drugs of abuse. Significant sex and/or genotype differences were found in the forced swim test of depression-like behaviors, anxiety-like behaviors on the elevated plus maze, and cocaine conditioned reward. Microarray analysis of dorsal striatum revealed significant dysregulation in individual and groups of genes that may contribute to the observed behavioral responses and in some cases, represent previously unidentified downstream targets of TrkB. The data point to a set of behaviors and changes in gene expression following postnatal deletion of TrkB in the dorsal striatum distinct from those in other brain regions.
Elovl6 promotes nonalcoholic steatohepatitis
Authors: Takashi Matsuzaka, Ayaka Atsumi, Rie Matsumori, Tang Nie, Haruna Shinozaki, Noriko Suzuki-Kemuriyama, Motoko Kuba, Yoshimi Nakagawa, Kiyoaki Ishii, Masako Shimada, Kazuto Kobayashi, Shigeru Yatoh, Akimitsu Takahashi, Kazuhiro Takekoshi, Hirohito Sone, Naoya Yahagi, Hiroaki Suzuki, Soichiro Murata, Makoto Nakamuta, Nobuhiro Yamada, Hitoshi Shimano
Journal: Hepatology (2012)

Nonalcoholic steatohepatitis (NASH) is associated with obesity and type 2 diabetes, and an increased risk for liver cirrhosis and cancer. ELOVL family member 6, elongation of very long chain fatty acids (Elovl6), is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids (FAs). We have shown previously that Elovl6 is a major target for sterol regulatory element binding proteins in the liver and that it plays a critical role in the development of obesity-induced insulin resistance by modifying FA composition. To further investigate the role of Elovl6 in the development of NASH and its underlying mechanism, we used three independent mouse models with loss or gain of function of Elovl6, and human liver samples isolated from patients with NASH. Our results demonstrate that (1) Elovl6 is a critical modulator for atherogenic high-fat diet-induced inflammation, oxidative stress, and fibrosis in the liver; (2) Elovl6 expression is positively correlated with severity of hepatosteatosis and liver injury in NASH patients; and (3) deletion of Elovl6 reduces palmitate-induced activation of the NLR family pyrin domain-containing 3 inflammasome; this could be at least one of the underlying mechanisms by which Elovl6 modulates the progress of NASH.Hepatic long-chain fatty acid composition is a novel determinant in NASH development, and Elovl6 could be a potential therapeutic target for the prevention and treatment of NASH.