tbuckley/cabot-search huggingface dataset:
Plasma and urinary zinc in patients with malabsorption syndromes or hepatic cirrhosis
Authors: B. E. Walker, J. B. Dawson, J. Kelleher, M. S. Losowsky
Journal: Gut (1973)

Plasma and urinary zinc have been measured in 19 patients with malabsorption and 21 patients with hepatic cirrhosis. The results have been compared with those of 20 control subjects and 23 patients with a variety of other diseases. The diurnal variation in plasma zinc levels has been confirmed and is of such magnitude that this must be taken into account in comparing results in groups of subjects. Plasma zinc levels, both fasting and after a meal, are significantly lower in patients with cirrhosis (71 and 60 mug/100 ml) and malabsorption (76 and 64 mug/100 ml) than in controls (97 and 81 mug/100 ml). In the patients with cirrhosis or malabsorption similar correlations exist between plasma zinc and plasma albumin, suggesting that the low plasma zinc levels may be, at least in part, dependent on the plasma albumin level. Urinary zinc excretion is increased in cirrhosis, but not in malabsorption, indicating that increased urinary loss is unlikely to explain the low plasma levels.
Gene Expression Profiles Identify Epithelial-to-Mesenchymal Transition and Activation of Nuclear Factor-κB Signaling as Characteristics of a High-risk Head and Neck Squamous Cell Carcinoma
Authors: Christine H. Chung, Joel S. Parker, Kim Ely, Jesse Carter, Yajun Yi, Barbara A. Murphy, K. Kian Ang, Adel K. El-Naggar, Adam M. Zanation, Anthony J. Cmelak, Shawn Levy, Robbert J. Slebos, Wendell G. Yarbrough
Journal: Cancer Research (2006)

Abstract Gene expression signatures generated from DNA microarray analyses have shown promise as predictive biomarkers of clinical outcome. In this study, we determined a high-risk signature for disease recurrence using formalin-fixed head and neck squamous cell carcinoma (HNSCC) tumors and compared the results with an independent data set obtained from fresh frozen tumors. We also showed that genes involved in epithelial-to-mesenchymal transition (EMT) and nuclear factor-κB (NF-κB) signaling deregulation are the most prominent molecular characteristics of the high-risk tumors. Gene expression was determined in 40 samples, including 34 formalin-fixed tissues and 6 matched frozen tissues, from 29 HNSCC patients. A 75-gene list predictive of disease recurrence was determined by training on the formalin-fixed tumor data set and tested on data from the independent frozen tumor set from 60 HNSCC patients. The difference in recurrence-free survival (RFS) between the high-risk versus low-risk groups in the training and test sets was statistically significant (P = 0.002 and 0.03, respectively, log-rank test). In addition, the gene expression data was interrogated using Gene Set Enrichment Analysis to determine biological significance. The most significant sets of genes enriched in the high-risk tumors were genes involving EMT, NF-κB activation, and cell adhesion. In conclusion, global gene expression analysis is feasible using formalin-fixed tissue. The 75-gene list can be used as a prognostic biomarker of recurrence, and our data suggest that the molecular determinants of EMT and NF-κB activation can be targeted as the novel therapy in the identified high-risk patients. (Cancer Res 2006; 66(16): 8210-8)
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)
Authors: P J Mease, D D Gladman, G G Krueger
Journal: Annals of the Rheumatic Diseases (2005)

Psoriatic arthritis (PsA) is a condition characterised by inflammatory arthritis and enthesitis, which can occur in nearly a third of patients with psoriasis. These patients share unique genetic factors and immunopathogenic features in the joints, enthesium, and skin. The clinical characteristics of the joint disease associated with psoriasis have been more clearly elucidated over the past 30 years. Adding to this is an appreciation that standard systemic agents for psoriasis, such as methotrexate and ciclosporin, are also effective for PsA. However, it has been the recognition of the immunological features and the emergence of “biologicals” that target specific immune/inflammatory pathways of selected disease processes that have generated the current excitement and interest in autoimmune disease. These developments have given us new insights into pathogenesis while bringing new, more effective, and safer treatments for both the skin and joints. This supplement of the Annals of the Rheumatic Diseases is a compilation of articles summarising the state of the art in this field.

Several centres have contributed the majority of what we know about PsA due to longstanding research interest. Numerous inadequately explored questions remain about disease classification, disease pathophysiology, and the development of validated methodologies to assess disease outcomes, both in longitudinal cohorts and in clinical trials. There is an increasing international exchange of ideas among dermatologists and rheumatologists and between these two specialties about emerging findings in psoriasis and its related arthritis. This exchange has been broadened by advances in related fields in rheumatology, such as the other spondyloarthropathies and rheumatoid arthritis, and in dermatology, such as T cell mediated skin diseases. It has been supported by the biopharmaceutical industry, which sponsors both basic and applied research. Also participating …
Inflammation Markers and Metabolic Characteristics of Subjects With 1-h Plasma Glucose Levels
Authors: Gianluca Bardini, Ilaria Dicembrini, Barbara Cresci, Carlo Maria Rotella
Journal: Diabetes Care (2009)

OBJECTIVE To assess the association of 1-h plasma glucose (1hPG) and inflammation with normal glucose tolerance (NGT) and pre-diabetes. RESEARCH DESIGN AND METHODS A cohort of 1,062 subjects was enrolled. After oral glucose load (oral glucose tolerance test), we compared subjects with NGT and pre-diabetes above and below the 1hPG cut point (155 mg/dl). Fibrinogen and leukocytes count (white blood cells [WBCs]) for subclinical inflammation, lipid ratios, insulin sensitivity (Matsuda index) were determined. RESULTS Patients with NGT and pre-diabetes (1hPG &amp;gt;155 mg/dl) showed a significant increase of inflammatory markers and lipid ratios (for all, P &amp;lt; 0.05). In age-, sex-, and BMI-adjusted analysis, 1hPG was associated with a significantly higher WBC count and fibrinogen (P &amp;lt; 0.05). Patients with elevated 1hPG showed a highly significant lower insulin sensitivity than subjects &amp;lt;1hPG (P &amp;lt; 0.01). CONCLUSIONS Elevated 1hPG in subjects with NGT and pre-diabetes is associated with subclinical inflammation, high lipid ratios, and insulin resistance. Therefore, 1hPG &amp;gt;155 mg/dl could be considered a new “marker” for cardiovascular risk.
Transition from interleukin 1 beta (IL-1 beta) to IL-1 alpha production during maturation of inflammatory macrophages in vivo.
Authors: H U Beuscher, U P Rausch, I G Otterness, M Röllinghoff
Journal: The Journal of Experimental Medicine (1992)

In situ production of interleukin 1 alpha (IL-1 alpha) and IL-1 beta was investigated in Peyer's patches (PP) of mice undergoing an acute bacterial infection with Yersinia enterocolitica O8. Synthesis of IL-1 beta, as determined by immunohistochemistry, was found primarily in monocytes migrating into the inflamed PP. In comparison, synthesis of IL-1 alpha was temporarily delayed by at least 24 h and was only found in mature macrophages, which did not produce detectable levels of IL-1 beta. This indicates a transition from IL-1 beta to IL-1 alpha production during maturation of monocytes into inflammatory macrophages, and further emphasizes a dichotomy between IL-1 alpha and IL-1 beta.
Differentiation of malignant from normal and reactive mesothelial cells by the argyrophil technique for nucleolar organiser region associated proteins.
Authors: J G Ayres, J G Crocker, N Q Skilbeck
Journal: Thorax (1988)

Nucleolar organiser regions represent nucleolar activity in both normal and malignant cells. More numerous nucleolar organiser regions have been found in cells from many forms of malignancy than in normal cells. An argyrophilic method of staining these regions (the AgNOR technique) has been applied to specimens of pleura obtained by biopsy or at necropsy in an attempt to differentiate between normal, "reactive," and malignant pleural disease. The number of nucleolar organiser regions in samples taken from 10 patients with normal pleura (mean 1.04 (95% confidence interval 0.96-1.12] was less than the number seen in samples from 10 patients with "reactive" (inflammatory) pleural disease (1.75 (1.34-2.16); p less than 0.001). This is the first demonstration of increased numbers of nucleolar organiser regions in an inflammatory condition. In specimens from 25 patients with mesothelioma the corresponding numbers of nucleolar organiser regions were: tubulopapillary (n = 10) 5.43 (4.42-6.44); undifferentiated (n = 5) 5.00 (3.29-6.71); sarcomatous (n = 5) 7.52 (3.96-11.08); and mixed histological types (n = 5) 4.94 (3.2-6.68). All these values differ significantly from those for both normal and "reactive" tissue (p less than 0.001). It is concluded that the AgNOR technique separates "reactive" pleural disease from mesothelioma with a high degree of confidence and is an important advance in the diagnosis of malignant mesothelioma.
Glutathione peroxidase 7 protects against oxidative DNA damage in oesophageal cells
Authors: DunFa Peng, Abbes Belkhiri, TianLing Hu, Rupesh Chaturvedi, Mohammad Asim, Keith T Wilson, Alexander Zaika, Wael El-Rifai
Journal: Gut (2011)

Exposure of the oesophageal mucosa to gastric acid and bile acids leads to the accumulation of reactive oxygen species (ROS), a known risk factor for Barrett's oesophagus and progression to oesophageal adenocarcinoma (OAC). This study investigated the functions of glutathione peroxidase 7 (GPX7), frequently silenced in OAC, and its capacity in regulating ROS and its associated oxidative DNA damage.Using in-vitro cell models, experiments were performed that included glutathione peroxidase (GPX) activity, Amplex UltraRed, CM-H(2)DCFDA, Annexin V, 8-oxoguanine, phospho-H2A.X, quantitative real-time PCR and western blot assays.Enzymatic assays demonstrated limited GPX activity of the recombinant GPX7 protein. GPX7 exhibited a strong capacity to neutralise hydrogen peroxide (H(2)O(2)) independent of glutathione. Reconstitution of GPX7 expression in immortalised Barrett's oesophagus cells, BAR-T and CP-A led to resistance to H(2)O(2)-induced oxidative stress. Following exposure to acidic bile acids cocktail (pH4), these GPX7-expressing cells demonstrated lower levels of H(2)O(2), intracellular ROS, oxidative DNA damage and double-strand breaks, compared with controls (p<0.01). In addition, these cells demonstrated lower levels of ROS signalling, indicated by reduced phospho-JNK (Thr183/Tyr185) and phospho-p38 (Thr180/Tyr182), and demonstrated lower levels of apoptosis following the exposure to acidic bile acids or H(2)O(2)-induced oxidative stress. The knockdown of endogenous GPX7 in immortalised oesophageal squamous epithelial cells (HET1A) confirmed the protective functions of GPX7 against pH4 bile acids by showing an increase in the levels of H(2)O(2), intracellular ROS, oxidative DNA damage, double-strand breaks, apoptosis, and ROS-dependent signalling (p<0.01).The dysfunction of GPX7 in oesophageal cells increases the levels of ROS and oxidative DNA damage, which are common risk factors for Barrett's oesophagus and OAC.
Health Behaviors Influence Cancer Survival
Authors: Ellen R. Gritz, Wendy Demark-Wahnefried
Journal: Journal of Clinical Oncology (2009)

In this issue of Journal of Clinical Oncology, Duffy et al 1 have provided important evidence of the effect of pretreatment health behaviors on all-cause survival in a prospective cohort study of patients enrolled in the University of Michigan Head and Neck Cancer Specialized Program of Research Excellence (SPORE; Ann Arbor, MI).Analyses of data from 504 participants showed that smoking status (current or former) was the strongest predictor of survival in both univariate and multivariate analyses.In the univariate analysis only, problem drinking, low fruit intake and low level of physical activity negatively affected survival.Low vegetable intake and poor sleep behavior were not significant in either analysis.We comment on the importance of these findings and offer suggestions for additional research, concentrating primarily on smoking behavior, alcohol, diet, and physical activity.
Influence of tumor estrogen and progesterone receptor levels on the response to tamoxifen and chemotherapy in primary breast cancer.
Authors: B Fisher, C Redmond, A Brown, D L Wickerham, N Wolmark, J Allegra, G Escher, M Lippman, E Savlov, J Wittliff
Journal: Journal of Clinical Oncology (1983)

In 1977 the National Surgical Adjuvant Breast and Bowel Project initiated a prospectively randomized clinical trial for women with primary operable breast cancer and positive axillary nodes. In this study 1891 patients were randomized to receive L-phenylalanine mustard and 5-fluorouracil (PF) either with or without tamoxifen (T). In this interim report findings are presented concerning disease-free survival (DFS) and survival as related to age and to estrogen receptor (ER) and/or progesterone receptor (PR) content of the tumor. The median follow-up time is 3 yr. Patients 50 yr of age or older with either 1-3 or more than 3 positive axillary nodes had a markedly longer disease-free survival on PFT than did those receiving PF adjuvant therapy (p less than 0.001). The effectiveness of PFT was related to the levels of tumor receptors. Patients 50 yr old or more with both tumor ER and PR levels of 10 fmole or more ("high") displayed the greatest benefit in disease-free survival from PFT (p = 0.004). Analyses by age indicated that it is more appropriate to divide patients of 50 yr or older into two age groups, 50-59 and 60-70 yr old. In the former the survival results were poorer on PFT when tumor PR was low, whereas, regardless of receptor levels, those 60-70 yr old experienced an advantage on PFT. In women under 50 yr of age, there was no difference in disease-free survival (p = 0.64), but survival results favored the PF over the PFT treated (p = 0.06). Patients under 50 yr with tumor ER and PR levels under 10 fmole ("low") had a poorer survival when given PFT (p = 0.003). Those whose tumors demonstrated a high ER and a low PR also had a shorter survival on PFT (p = 0.01). The observation of no benefit in younger patients when both receptor levels were high, but a benefit in older patients with receptor-poor tumors, indicates that, at least according to the conditions of this study, the difference between the two age groups cannot be explained by the association of age with receptor content. Multivariate analyses considered the effects of the number of positive nodes, age, ER, and PR. They support the conclusion that, while nodes and ER exert strong prognostic influences in both PF- and PFT-treated patients, the PR content of tumors is a stronger predictor of the effectiveness of PFT therapy than is ER content.(ABSTRACT TRUNCATED AT 400 WORDS)
Extended-Release Niacin or Ezetimibe and Carotid Intima–Media Thickness
Authors: Allen J. Taylor, Todd C. Villines, Eric J. Stanek, Patrick J. Devine, Len Griffen, Michael Miller, Neil J. Weissman, Mark Turco
Journal: New England Journal of Medicine (2009)

Treatment added to statin monotherapy to further modify the lipid profile may include combination therapy to either raise the high-density lipoprotein (HDL) cholesterol level or further lower the low-density lipoprotein (LDL) cholesterol level.We enrolled patients who had coronary heart disease or a coronary heart disease risk equivalent, who were receiving long-term statin therapy, and in whom an LDL cholesterol level under 100 mg per deciliter (2.6 mmol per liter) and an HDL cholesterol level under 50 mg per deciliter for men or 55 mg per deciliter for women (1.3 or 1.4 mmol per liter, respectively) had been achieved. The patients were randomly assigned to receive extended-release niacin (target dose, 2000 mg per day) or ezetimibe (10 mg per day). The primary end point was the between-group difference in the change from baseline in the mean common carotid intima-media thickness after 14 months. The trial was terminated early, on the basis of efficacy, according to a prespecified analysis conducted after 208 patients had completed the trial.The mean HDL cholesterol level in the niacin group increased by 18.4% over the 14-month study period, to 50 mg per deciliter (P < 0.001), and the mean LDL cholesterol level in the ezetimibe group decreased by 19.2%, to 66 mg per deciliter (1.7 mmol per liter) (P < 0.001). Niacin therapy significantly reduced LDL cholesterol and triglyceride levels; ezetimibe reduced the HDL cholesterol and triglyceride levels. As compared with ezetimibe, niacin had greater efficacy regarding the change in mean carotid intima-media thickness over 14 months (P = 0.003), leading to significant reduction of both mean (P = 0.001) and maximal carotid intima-media thickness (P < or = 0.001 for all comparisons). Paradoxically, greater reductions in the LDL cholesterol level in association with ezetimibe were significantly associated with an increase in the carotid intima-media thickness (R = -0.31, P < 0.001). The incidence of major cardiovascular events was lower in the niacin group than in the ezetimibe group (1% vs. 5%, P = 0.04 by the chi-square test).This comparative-effectiveness trial shows that the use of extended-release niacin causes a significant regression of carotid intima-media thickness when combined with a statin and that niacin is superior to ezetimibe. (ClinicalTrials.gov number, NCT00397657.)
Alarm features and age for predicting upper gastrointestinal malignancy in Chinese patients with dyspepsia with high background prevalence of Helicobacter pylori infection and upper gastrointestinal malignancy: an endoscopic database review of 102 665 patients from 1996 to 2006
Authors: Y. Bai, Z. S. Li, D. W. Zou, R. P. Wu, Y. Z. Yao, Z. D. Jin, P. Ye, S. D. Li, W. J. Zhang, Y. Q. Du, X. B. Zhan, F. Liu, J. Gao, G. M. Xu
Journal: Gut (2010)

<h3>Objective</h3> Patients with dyspepsia with alarm features are suspected of having upper gastrointestinal (GI) malignancy; however, the true value of alarm features in predicting an underlying malignancy for patients with dyspepsia with high background prevalence of <i>Helicobacter pylori</i> infection and upper GI malignancy is uncertain. The aim of the present study was to determine the diagnostic accuracy of alarm features in predicting upper GI malignancy by reviewing an endoscopic database consisting of &gt;100 000 Chinese patients. <h3>Methods</h3> A retrospective analysis of prospectively collected data was conducted in a single tertiary medical centre. Consecutive patients who underwent oesophagogastroduodenoscopy (OGD) for dyspepsia in 1996–2006 were enrolled. The data including gender, age, symptoms, and endoscopic and pathological findings were analysed. The main outcome measure was the diagnostic accuracy of individual alarm feature. <h3>Results</h3> 102 665 patients were included in the final analysis. Among all the 4362 patients with malignancy, 52% (2258/4362) had alarm features. Among 15 235 patients who had alarm features, 2258 (14.8%) were found to have upper GI malignancy. The pooled sensitivity and specificity of the alarm features were 13.4% and 96.6%, respectively. Only the feature of dysphagia in patients between 36 and 74 years old had a positive likelihood ratio (PLR) &gt;10 for malignancy prediction, while all other alarm features in other age groups had a PLR &lt;10. <h3>Conclusions</h3> For uninvestigated Chinese patients with dyspepsia with high background prevalence of <i>H pylori</i> infection and upper GI malignancy, alarm features and age, except for dysphagia in patients between 36 and 74 years old, had limited predictive value for a potential malignancy; therefore, prompt endoscopy may be recommended for these patients. However, less invasive, inexpensive screening methods with high diagnostic yield are still needed to reduce unnecessary endoscopy workload.
A NOTE on a METHOD of OPERATING for ECTROPION of the LOWER EYELID
Authors: D. A. Robertson
Journal: BMJ (1898)

JUNE rl, u8g8W 4. The want of adaptability of the patient to his surround- ings.5. Overcrowding in ill-constructed and ill-planned houses.6. Second-rate food and wine.7. The want of reliable English doctors.These deficiencies it is the province of this Society to lessen and remove.Already your excellent Journal is di- seminating a large amount of useful knowledge, and I havp no doubt that the real wants of our expatriated invalids will be adequately provided if they should receive distinct utter ance at the hands of a powerful Society like this.
Early Functional Impairment of Sensory-Motor Connectivity in a Mouse Model of Spinal Muscular Atrophy
Authors: George Z. Mentis, Dvir Blivis, Wenfang Liu, Estelle Drobac, Melissa E. Crowder, Lingling Kong, Francisco J. Alvarez, Charlotte J. Sumner, Michael J. O'Donovan
Journal: Neuron (2011)
Clustering in asthma: why, how and for how long?
Authors: Arnaud Bourdin, Pascal Chanez
Journal: European Respiratory Journal (2013)

sthma and most chronic airway diseases are heterogeneous entities.Even severe asthma does not represent a single phenotype of asthma.This heterogeneity of phenotypes is the starting point of new approaches for characterisation, understanding and management of asthma in the near future.The ultimate approach will be to identify new phenotypes sharing coherent underlying biological mechanisms (i.e. the concept of endotypes [1]) to better predict future risks.Ultimately, new specific, targeted or personalised therapeutic avenues and management will be developed based on these new groupings of patients and used [2].
Expanding the Criteria for <i>BRCA</i> Mutation Testing in Breast Cancer Survivors
Authors: Janice S. Kwon, Angelica M. Gutierrez-Barrera, Diana Young, Charlotte C. Sun, Molly S. Daniels, Karen H. Lu, Banu Arun
Journal: Journal of Clinical Oncology (2010)

Every year approximately 25% of women diagnosed with breast cancer are younger than 50 years of age, and almost 10% of them have a BRCA mutation. Not all potential carriers are identified by existing criteria for BRCA testing. We estimated the costs and benefits of different BRCA testing criteria for women with breast cancer younger than 50 years.We developed a Markov Monte Carlo simulation to compare six criteria for BRCA mutation testing: (1) no testing (reference); (2) medullary breast cancer in patients younger than 50 years; (3) any breast cancer in patients younger than 40 years; (4) triple negative (TN) breast cancer in patients younger than 40 years; (5) TN breast cancer in patients younger than 50 years; (6) any breast cancer in patients younger than 50 years. Net health benefits were life expectancy and quality-adjusted life expectancy, and primary outcome was the incremental cost-effectiveness ratio (ICER). The model estimated the number of new breast and ovarian cancer cases.BRCA mutation testing for all women with breast cancer who were younger than 50 years could prevent the highest number of breast and ovarian cancer cases, but with unfavorable ICERs. Testing women with TN breast cancers who were younger than 50 years was cost-effective with an ICER of $8,027 per year of life gained ($9,084 per quality-adjusted life-year), and could reduce subsequent breast and ovarian cancer risks by 23% and 41%, respectively, compared with the reference strategy.Testing women with TN breast cancers who were younger than 50 years for BRCA mutations is a cost-effective strategy and should be adopted into current guidelines for genetic testing.