tbuckley/cabot-search huggingface dataset:
A prospective randomized trial comparing somatostatin and sclerotherapy in the treatment of acute variceal bleeding
Authors: Ramon Planas, Juan Carlos Quer, Jaume Boix, Jaume Canet, Manel Armengol, Eduard Cabre, Teresa Pintanel, Pere Humbert, Benjamin Oller, Marc Antoni Broggi, Miquel Angel Gassull
Journal: Hepatology (1994)

Somatostatin and endoscopic sclerotherapy are widely used in the treatment of acute variceal bleeding. Although objective evidence does exist about the advantages of either treatment, data comparing both procedures are scarce. In order to compare the effectiveness and safety of somatostatin and sclerotherapy in the treatment of acute variceal bleeding, 70 consecutive cirrhotic patients suffering from esophageal variceal hemorrhage and meeting the inclusion criteria were randomly assigned to treatment with somatostatin (35 patients) or sclerotherapy (35 patients). No differences in age, sex, alcohol intake, etiology of cirrhosis and severity of liver failure were found between groups. Failure of treatment (defined as persistence of bleeding despite therapy or subsequent rebleeding within the 48-hr trial period) occurred in seven patients (20%) in the somatostatin group and in six (17.1%) in the sclerotherapy group (NS). Early rebleeding occurred in seven of 28 patients (25%) in the somatostatin group and in five of 29 (17.2%) in the sclerotherapy group (NS). Mortality within the first 6 wk was no different between both groups: 10 (28.5%) and eight (22.8%) in the somatostatin and sclerotherapy groups, respectively. Sclerotherapy, but not somatostatin, was associated with major complications in five cases (14.2%) (p = 0.026), two of which resulted in patient's death. These results suggest that somatostatin is safer, and as effective as sclerotherapy, in controlling acute variceal bleeding until an elective treatment can be established.
Expression of p16 and Retinoblastoma Determines Response to CDK4/6 Inhibition in Ovarian Cancer
Authors: Gottfried E. Konecny, Boris Winterhoff, Teodora Kolarova, Jingwei Qi, Kanthinh Manivong, Judy Dering, Guorong Yang, Meenal Chalukya, He-Jing Wang, Lee Anderson, Kimberly R. Kalli, Richard S. Finn, Charles Ginther, Siân Jones, Victor E. Velculescu, Darren Riehle, William A. Cliby, Sophia Randolph, Maria Koehler, Lynn C. Hartmann, Dennis J. Slamon
Journal: Clinical Cancer Research (2011)

Abstract Purpose: PD-0332991 is a selective inhibitor of the CDK4/6 kinases with the ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. Here we investigate the role of CDK4/6 inhibition in human ovarian cancer. Experimental Design: We examined the effects of PD-0332991 on proliferation, cell-cycle, apoptosis, and Rb phosphorylation using a panel of 40 established human ovarian cancer cell lines. Molecular markers for response prediction, including p16 and Rb, were studied using gene expression profiling, Western blot, and array CGH. Multiple drug effect analysis was used to study interactions with chemotherapeutic drugs. Expression of p16 and Rb was studied using immunohistochemistry in a large clinical cohort of ovarian cancer patients. Results: Concentration-dependent antiproliferative effects of PD-0332991 were seen in all ovarian cancer cell lines, but varied significantly between individual lines. Rb-proficient cell lines with low p16 expression were most responsive to CDK4/6 inhibition. Copy number variations of CDKN2A, RB, CCNE1, and CCND1 were associated with response to PD-0332991. CDK4/6 inhibition induced G0/G1 cell cycle arrest, blocked Rb phosphorylation in a concentration-and time-dependent manner, and enhanced the effects of chemotherapy. Rb-proficiency with low p16 expression was seen in 97/262 (37%) of ovarian cancer patients and was independently associated with poor progression-free survival (adjusted relative risk 1.49, 95% CI 1.00–2.24, P = 0.052). Conclusions: PD-0332991 shows promising biologic activity in ovarian cancer cell lines. Assessment of Rb and p16 expression may help select patients most likely to benefit from CDK4/6 inhibition in ovarian cancer. Clin Cancer Res; 17(6); 1591–602. ©2011 AACR.
Impact of climate change on skin cancer
Authors: Ak Bharath, Rj Turner
Journal: Journal of the Royal Society of Medicine (2009)

Climate change refers to the global shift in weather patterns occurring over long periods of time. These changes encompass temperature, rainfall, wind speeds and cloud cover. Climate change has accelerated rapidly in the past half century and while international focus has concentrated on the environmental and economic consequences, the effects on human diseases such as skin cancer have been relatively under-represented. The association between ultraviolet (UV) exposure from the sun and the development of malignant skin disease has long been recognized but is still not completely understood. The relationship between climate change and UV exposure will be explored in an attempt to qualify the impact of climate change on skin cancer.
Antiangiogenic Therapy for Glioblastoma: Current Status and Future Prospects
Authors: Tracy T. Batchelor, David A. Reardon, John F. de Groot, Wolfgang Wick, Michael Weller
Journal: Clinical Cancer Research (2014)

Abstract Glioblastoma is characterized by high expression levels of proangiogenic cytokines and microvascular proliferation, highlighting the potential value of treatments targeting angiogenesis. Antiangiogenic treatment likely achieves a beneficial impact through multiple mechanisms of action. Ultimately, however, alternative proangiogenic signal transduction pathways are activated, leading to the development of resistance, even in tumors that initially respond. The identification of biomarkers or imaging parameters to predict response and to herald resistance is of high priority. Despite promising phase II clinical trial results and patient benefit in terms of clinical improvement and longer progression-free survival, an overall survival benefit has not been demonstrated in four randomized phase III trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin in recurrent glioblastoma. However, future studies are warranted. Predictive markers may allow appropriate patient enrichment, combination with chemotherapy may ultimately prove successful in improving overall survival, and novel agents targeting multiple proangiogenic pathways may prove effective. See all articles in this CCR Focus section, “Discoveries, Challenges, and Progress in Primary Brain Tumors.” Clin Cancer Res; 20(22); 5612–9. ©2014 AACR.
Targeting the Intracellular WT1 Oncogene Product with a Therapeutic Human Antibody
Authors: Tao Dao, Su Yan, Nicholas Veomett, Dmitry Pankov, Liang Zhou, Tatyana Korontsvit, Andrew Scott, Joseph Whitten, Peter Maslak, Emily Casey, Taochao Tan, Hong Liu, Victoria Zakhaleva, Michael Curcio, Ekaterina Doubrovina, Richard J. O’Reilly, Cheng Liu, David A. Scheinberg
Journal: Science Translational Medicine (2013)

A therapeutic monoclonal antibody specific for the intracellular oncoprotein Wilms tumor 1 treats human leukemias in mice.
Treatment of hepatocellular carcinoma in compensated cirrhosis with radio-frequency thermal ablation (RFTA): a prospective study
Authors: C CAMMA, V DIMARCO, A ORLANDO, L SANDONATO, A CASARIL, P PARISI, S ALIZZI, E SCIARRINO, R VIRDONE, S PARDO
Journal: Journal of Hepatology (2005)
Tracheal size is a determinant of the bronchoconstrictive response to inhaled methacholine
Authors: J Bourbeau, R Delfino, P Ernst
Journal: European Respiratory Journal (1993)

We hypothesized that the size of the large airways is a determinant of bronchial responsiveness to inhaled methacholine. This was investigated by measuring the relationship of tracheal size and branching angle to the bronchoconstrictive response to methacholine, in 169 male construction insulators, aged 20-50 yrs, as part of a workforce-based, cross-sectional survey of respiratory health. Bronchial responsiveness was expressed as the concentration of methacholine, inhaled for 2 min of tidal breathing, which provoked a 15% fall in forced expiratory volume in one second (FEV1). Tracheal size was assessed from tracings of standard posteroanterior chest radiographs, at full inspiration. After accounting for the effect of airway calibre (FEV1/forced vital capacity (FVC)), age, height, and pack-years of cigarette smoking, on airways responsiveness, there was a significant association (p < 0.05) between tracheal length, diameter, or surface area and the degree of bronchoconstriction obtained by inhaling methacholine. The increase in airway responsiveness with decreasing tracheal size may reflect increased deposition of methacholine, secondary to smaller cross-sectional area and greater linear velocity of air in the trachea and main bronchi.
Influence of matrix metalloproteinase genotype on cardiovascular disease susceptibility and outcome
Authors: S YE
Journal: Cardiovascular Research (2005)

Data have been accumulating that indicate that matrix metalloproteinase (MMP) gene polymorphisms contribute to inter-individual differences in susceptibility to and outcome of cardiovascular disease. This is currently best exemplified by the MMP3 gene 5A/6A polymorphism which has an effect on MMP3 expression and has been shown to be associated with coronary stenosis, myocardial infarction, coronary artery calcification, post-angioplasty coronary restenosis, carotid atherosclerosis, stroke, arterial stiffness, and blood pressure. Functional polymorphisms in the MMP1, MMP2, MMP7, MMP9, MMP12, and MMP13 genes have also been related to coronary artery disease, arterial stiffness, and/or abdominal aortic aneurysm. These genetic findings support the notion that MMPs play important roles in the pathogenesis of these conditions. There is also some evidence suggesting that MMP genotyping could aid in identifying patients who are likely to have unfavourable prognosis and/or adverse response to treatment.
Cloth destruction and haemolysis with totally cloth-covered Starr-Edwards prostheses
Authors: M. Schottenfeld, J. D. Wisheart, J. K. Ross, J. C. R. Lincoln, D. N. Ross
Journal: Thorax (1971)

Four cases are described in which totally cloth-covered Starr-Edwards valves (model 2300) had to be removed. All were causing significant haemolysis, two in the absence of a peripheral leak. The principal operative finding was destruction of the Dacron covering the struts. Following replacement of these prostheses there was complete resolution of signs and symptoms. The possible causes of haemolysis and consequences of cloth destruction are discussed.
No associations of the mineralocorticoid and glucocorticoid receptor genes with asthma: Table 1–
Authors: N.M. Vink, D.S. Postma, M.A.E. Nieuwenhuis, G.H. Koppelman, J.G.M. Rosmalen, H.M. Boezen
Journal: European Respiratory Journal (2012)

To the Editors:

Asthma is a multifactorial disease. Although a number of host and environmental risk factors have been identified in the past decades, these cannot fully explain the prevalence of asthma. Previous studies have shown that psychosocial stress confers a risk for the development of asthma [1].

Stress activates the hypothalamus–pituitary–adrenal (HPA) axis, which leads to secretion of cortisol. Cortisol in turn influences the activity of many systems in the human body and shifts, among others, the T-helper type (Th1/Th2) balance of the peripheral blood mononuclear cells towards a predominantly type 2 response. Cortisol binds to the high affinity mineralocorticoid receptor ( NR3C2 ) and the low affinity glucocorticoid receptor ( NR3C1 ). Single nucleotide polymorphisms (SNPs) in these receptors have been associated with basal cortisol and cortisol responses to stress [2]. So far, two studies have found an association between SNPs in NR3C1 ( i.e. rs6195, rs41423247) and asthma development [3, 4]. However, these results have not been replicated in other populations so far. Additionally, it is unknown whether other functional or tagging SNPs in the NR3C1 are associated with asthma development. In addition, SNPs …
Tumour necrosis factor receptor gene expression and shedding in human whole lung tissue and pulmonary epithelium
Authors: H Nakamura, T Hino, S Kato, Y Shibata, H Takahashi, H Tomoike
Journal: European Respiratory Journal (1996)

This study aimed to investigate the expression of tumour necrosis factor receptor (TNF-R) at the gene and surface level, and its shedding in human lung tissue and a pulmonary epithelial cell line, A549. Levels of gene expression of TNF-R were evaluated by Northern blot analysis. Human lung tissue expressed both type I and type II TNF-R gene, while A549 cells expressed only type I TNF-R gene. Phorbol ester upregulated and TNF-alpha down-regulated the TNF-R gene expression in A549 cells. Consistent with these modulations of TNF-R gene expression, 125I-TNF binding capacities were increased with phorbol ester stimulation and decreased with TNF stimulation after 24 h in A549 cells. The shedding of TNF-R from A549 cells was investigated using enzyme-linked immunosorbent assay (ELISA) for soluble type I TNF-R. Not only lung tissues but also A549 cells spontaneously released soluble type I TNF-R into the culture medium. Both phorbol ester and TNF stimulation accelerated the shedding of soluble TNF-R from A549 cells. These results suggest that type I TNF-R gene expression and shedding of soluble TNF-R are differentially regulated in A549 cells. We conclude that tumour necrosis factor receptor surface expression is regulated, at least in part, at the gene expression level and shedding of soluble tumour necrosis factor receptor is modulated by inflammatory mediators, such as tumour necrosis factor in A549 cells.
Genetics of Food Intake and Eating Behavior Phenotypes in Humans
Authors: Tuomo Rankinen, Claude Bouchard
Journal: Annual Review of Nutrition (2006)

▪ Abstract This review summarizes the research advances of the past decade regarding the role of human genetic differences in energy and nutrient intake as well as in eating behavior phenotypes and selected eating disorders. The evidence for familial aggregation and heritability based on twin and nuclear family study designs is summarized. Genome-wide linkage scans and quantitative trait loci identified to date are discussed. DNA sequence variants in candidate genes are reviewed. Single genes associated with classical eating disorders are also incorporated. Epigenetic events will need to be incorporated in future studies designed to investigate the effects of DNA variants on dietary phenotypes. Understanding the relative contribution of global genetic variation and of DNA sequence variants in specific genes is important in the effort to influence dietary habits in a healthier direction.
The effect of tea on iron absorption.
Authors: P B Disler, S R Lynch, R W Charlton, J D Torrance, T H Bothwell, R B Walker, F Mayet
Journal: Gut (1975)

The effect of tea on iron absorption was studied in human volunteers. Absorption from solutions of FeCl3 and FeSO4, bread, a meal of rice with potato and onion soup, and uncooked haemoglobin was inhibited whether ascorbic acid was present or not. No inhibition was noted if the haemoglobin was cooked. The effect on the absorption of non-haem iron was ascribed to the formation of insoluble iron tannate complexes. Drinking tannin-containing beverages such as tea with meals may contribute to the pathogenesis of iron deficiency if the diet consists largely of vegetable foodstuffs.
Knowledge transfer principles as applied to sport concussion education
Authors: C F Provvidenza, K M Johnston
Journal: British Journal of Sports Medicine (2009)

Objective: To (a) examine knowledge transfer literature and optimal learning needs as applied to healthcare professionals, coaches and student athletes; (b) apply the practice of knowledge transfer to sport concussion education resources; and (c) identify needs and make recommendations for optimising concussion education. Design: Qualitative literature review of knowledge transfer and concussion education literature. Intervention: Pubmed, Medline, Psych Info and Sport Discus databases were reviewed. 52 journal articles, 20 websites and 2 books were reviewed. Results: The methods in which individuals experience optimal learning varies and should be considered when developing effective concussion education strategies. Physician knowledge and performance are impacted by education outreach, interaction and reminder messages. Educational strategies associated with optimal learning for physio and athletic therapists include problem and evidence-based practice, socialisation and peer-assisted learning. From a coaching perspective, research supports the reflective process as a learning modality. Student athletes have strengths and weaknesses in different areas and so perform differently on activities requiring distinct strategies. Knowing the impact of sport concussion resources on knowledge enhancement and modifying attitudes and behaviours toward concussion requires evaluation strategies. Review of concussion resources using the perspective of knowledge transfer and methods for improvement is discussed. Conclusions: Knowledge transfer is a relatively new concept in sports medicine and its influence on enhancing concussion education is not well known. The needs and optimal learning styles of target audiences coupled with evaluation need to be a piece of the overall concussion education puzzle to effectively impact knowledge of and attitudes and behaviours towards sport concussion.
Triple-Negative Breast Cancer: Distinguishing between Basal and Nonbasal Subtypes
Authors: Emad A. Rakha, Somaia E. Elsheikh, Muhammed A. Aleskandarany, Hany O. Habashi, Andrew R. Green, Desmond G. Powe, Maysa E. El-Sayed, Ahmed Benhasouna, Jean-Sébastien Brunet, Lars A. Akslen, Andy J. Evans, Roger Blamey, Jorge S. Reis-Filho, William D. Foulkes, Ian O. Ellis
Journal: Clinical Cancer Research (2009)

Triple-negative (TN; estrogen receptor, progesterone receptor, and HER-2 negative) cancer and basal-like breast cancer (BLBC) are associated with poor outcome and lack the benefit of targeted therapy. It is widely perceived that BLBC and TN tumors are synonymous and BLBC can be defined using a TN definition without the need for the expression of basal markers.We have used two well-defined cohorts of breast cancers with a large panel of biomarkers, BRCA1 mutation status, and follow-up data to compare the clinicopathologic and immunohistochemical features of TN tumors expressing one or more of the specific basal markers (CK5/6, CK17, CK14, and epidermal growth factor receptor; BLBC) with those TN tumors that express none of these markers (TN3BKE-).Here, we show that although the morphologic features of BLBC are not significantly different from that of TN3BKE- tumors, BLBC showed distinct clinical and immunophenotypic differences. BLBC showed a statistically significant association with the expression of the hypoxia-associated factor (CA9), neuroendocrine markers, and other markers of poor prognosis such as p53. A difference in the expression of cell cycle-associated proteins and biomarkers involved in the immunologic portrait of tumors was seen. Compared with TN3BKE- tumors, BLBC was positively associated with BRCA1 mutation status and showed a unique pattern of distant metastasis, better response to chemotherapy, and shorter survival.TN breast cancers encompass a remarkably heterogeneous group of tumors. Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors, justifying the use of basal markers (in TN tumors) to define BLBC.
HAS THE CHANGE TO BETA-AGONISTS COMBINED WITH ORAL THEOPHYLLINE INCREASED CASES OF FATAL ASTHMA?
Authors: IanW.B. Grant, G. Koeter, H.J. Sluiter, J. De Monchy, K. De Vries, J.A. Henry, D.J. Berry, JohnG. Prior, G.M. Cochrane, J.R. Whittington, R. Beaglehole, E.A. Harris, H.H. Rea
Journal: The Lancet (1981)
Growth Hormone Therapy in Adults
Authors: David E. Cummings, George R. Merriam
Journal: Annual Review of Medicine (2003)

Growth hormone (GH) is classically linked with linear growth in childhood but continues to have important metabolic actions throughout life. GH deficiency in adulthood causes a distinct syndrome with significant morbidities. These include increased total and visceral fat, decreased muscle mass and aerobic capacity, affective disturbances, abnormal lipids, and increased vascular mortality, all of which are ameliorated with GH replacement. The possibility of adult GH deficiency (AGHD) should always be considered in individuals with a history of childhood GH deficiency or significant hypothalamic-pituitary damage, and the diagnosis should then be confirmed by biochemical testing. Adult GH dosing is much lower than that in pediatric practice, as appropriate for physiologic reconstitution. Hormonal side effects are minimized by stepwise dose titration. Lingering concerns remain regarding the possibility of increased cancer risk with long-term treatment, but this hazard has not been unequivocally demonstrated. Compared with AGHD, there is much less information about GH replacement in other diseases or in normal aging, or about the use of supraphysiologic GH doses to treat catabolic states. In critical illness, high-dose GH therapy has proven clearly harmful, and the balance of risks and benefits of GH administration in most adult contexts other than AGHD has not been defined.
Suppression of HPA axis in adults taking inhaled corticosteroids
Authors: J R Greenfield
Journal: Thorax (2006)

Fluticasone propionate, a frequently prescribed potent inhaled corticosteroid, is an effective and generally safe treatment for chronic asthma. However, rare cases of dose related systemic absorption of inhaled corticosteroids leading to suppression of the hypothalamic-pituitary-adrenal (HPA) axis have been reported, particularly in children.1,2 Using the insulin tolerance test (ITT), we report two cases of symptomatic adrenocortical suppression in asthmatic adults taking inhaled fluticasone. The two patients reported here were selected from a review of 59 patients undergoing ITTs for investigation of suspected HPA dysfunction.3

Patient 1, a 38 year old woman (weight 49.9 kg) with a history of chronic asthma and allergic rhinitis, was referred for investigation of a 2 year history of fatigue, presyncope, and reduced libido. She denied symptoms of neuroglycopenia, thyroid dysfunction, headaches, arthralgia, myalgia, weight change, constipation, and diarrhoea. Past history included depression (in remission, on no current treatment) and bulimia nervosa. Menses were regular. There was no history of postpartum haemorrhage. Medications included fluticasone propionate/salmeterol xinafoate (Seretide) 250/25 µg one inhalation twice daily and mometasone …