tbuckley/cabot-search huggingface dataset:
Comparison between women and men with recent onset rheumatoid arthritis of disease activity and functional ability over two years (the TIRA project)
Authors: E Hallert
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To describe the course of recent onset rheumatoid arthritis (RA) and to compare consequences of the disease in men and women. <b>Methods:</b> 284 patients with recent onset RA were followed up prospectively for two years from the time of diagnosis. Measures of disease activity (for example, 28 joint disease activity score (DAS28), C reactive protein, morning stiffness, physician's global assessment) and function outcome (for example, range of movement, hand function, walking time) were determined. The patients' self reported assessment of functional capacity (Health Assessment Questionnaire (HAQ)) and grading of wellbeing and pain (visual analogue scale) were registered. Changes over time and differences between men and women were evaluated. <b>Results:</b> Improvements were seen for all variables within the first three months. Disease activity then remained unchanged. Function variables followed the same pattern during the first year, but then tended to worsen. HAQ scores were similar at baseline, but significantly worse in women than in men at the one and two year follow ups. <b>Conclusions:</b> Disease activity was well managed and had improved substantially after two years, whereas function seemed slowly to deteriorate. Although disease variables were similar for men and women, functional ability (HAQ) had a less favourable course in women.
In situ real-time investigation of cancer cell photothermolysis mediated by excited gold nanorod surface plasmons
Authors: Cheng-Lung Chen, Ling-Ru Kuo, Ching-Lin Chang, Yeu-Kuang Hwu, Cheng-Kuang Huang, Shin-Yu Lee, Kowa Chen, Su-Jien Lin, Jing-Duan Huang, Yang-Yuan Chen
Journal: Biomaterials (2010)
Immunohistochemical Expression of Estrogen and Progesterone Receptors Identifies a Subset of NSCLCs and Correlates with <i>EGFR</i> Mutation
Authors: Maria G. Raso, Carmen Behrens, Matthew H. Herynk, Suyu Liu, Ludmila Prudkin, Natalie C. Ozburn, Denise M. Woods, Ximing Tang, Reza J. Mehran, Cesar Moran, J. Jack Lee, Ignacio I. Wistuba
Journal: Clinical Cancer Research (2009)

To determine the frequency of estrogen receptor alpha and beta and progesterone receptor protein immunohistochemical expression in a large set of non-small cell lung carcinoma (NSCLC) specimens and to compare our results with those for some of the same antibodies that have provided inconsistent results in previously published reports.Using multiple antibodies, we investigated the immunohistochemical expression of estrogen receptors alpha and beta and progesterone receptor in 317 NSCLCs placed in tissue microarrays and correlated their expression with patients' clinicopathologic characteristics and in adenocarcinomas with EGFR mutation status.Estrogen receptors alpha and beta were detected in the nucleus and cytoplasm of NSCLC cells; however, the frequency of expression (nucleus, 5-36% for alpha and 42-56% for beta; cytoplasm: <1-42% for alpha and 20-98% for beta) varied among the different antibodies tested. Progesterone receptor was expressed in the nuclei of malignant cells in 63% of the tumors. Estrogen receptor alpha nuclear expression significantly correlated with adenocarcinoma histology, female gender, and history of never smoking (P = 0.0048 to <0.0001). In NSCLC, higher cytoplasmic estrogen receptor alpha expression significantly correlated with worse recurrence-free survival (hazard ratio, 1.77; 95% confidence interval, 1.12, 2.82; P = 0.015) in multivariate analysis. In adenocarcinomas, estrogen receptor alpha expression correlated with EGFR mutation (P = 0.0029 to <0.0001). Estrogen receptor beta and progesterone receptor but not estrogen receptor alpha expressed in the normal epithelium adjacent to lung adenocarcinomas.Estrogen receptor alpha and beta expression distinguishes a subset of NSCLC that has defined clinicopathologic and genetic features. In lung adenocarcinoma, estrogen receptor alpha expression correlates with EGFR mutations.
Update on tuberculosis and other opportunistic infections associated with drugs blocking tumour necrosis factor 
Authors: K L Winthrop
Journal: Annals of the Rheumatic Diseases (2005)

The World Health Organization estimates that a third of the world’s population is infected with tuberculosis (TB). In approximately 90% of people, the infection remains latent. In others, TB disease develops, often in the first two years after infection. Individuals whose immune systems are compromised by disease or drugs are at increased risk for developing TB disease.

The pathogenesis of TB is complex. In pulmonary TB, inhaled TB bacilli are first engulfed by alveolar macrophages. Next, they replicate and briefly disseminate haematogenously throughout the body. The host attempts to limit bacilli spread with granuloma formation, a process mediated by tumour necrosis factor (TNF) α.1,2 This proinflammatory cytokine is released by activated immune cells. It mediates systemic inflammatory responses and tissue destruction, and is important in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease.

Recently, TNFα blocking drugs (infliximab, etanercept, and adalimumab) have been shown to be highly successful in the treatment of the above mentioned autoimmune diseases and other conditions. However, infectious complications have been reported with all three drugs including the reactivation of latent TB infection, which …
Role of gonadotropin-releasing hormone analogues in metastatic male breast cancer: results from a pooled analysis
Authors: Luigi Di Lauro, Laura Pizzuti, Maddalena Barba, Domenico Sergi, Isabella Sperduti, Marcella Mottolese, Carla Azzurra Amoreo, Franca Belli, Patrizia Vici, Valerie Speirs, Daniele Santini, Ruggero De Maria, Marcello Maugeri-Saccà
Journal: Journal of Hematology & Oncology (2015)

Male breast cancer is a rare malignancy. Despite the lack of prospectively generated data from trials in either the adjuvant or metastatic setting, patients are commonly treated with hormone therapies. Much controversy exists over the use of gonadotropin-releasing hormone analogues in metastatic male breast cancer patients. We conducted this study to provide more concrete ground on the use of gonadotropin-releasing hormone analogues in this setting.We herein present results from a pooled analysis including 60 metastatic male breast cancer patients treated with either an aromatase inhibitor or cyproterone acetate as a monotherapy (23 patients) or combined with a gonadotropin-releasing hormone analogue (37 patients).Overall response rate was 43.5% in patients treated with monotherapy and 51.3% with combination therapy (p = 0.6). Survival outcomes favored combination therapy in terms of median progression-free survival (11.6 months versus 6 months; p = 0.05), 1-year progression-free survival rate (43.2% versus 21.7%; p = 0.05), median overall survival (29.7 months versus 22 months; p = 0.05), and 2-year survival rate (64.9% versus 43.5%; p = 0.05).In metastatic male breast cancer patients, the combined use of gonadotropin-releasing hormone analogues and aromatase inhibitors or antiandrogens seems to be associated with greater efficacy, particularly in terms of survival outcomes, compared with monotherapy. Collectively, these results encourage considering these agents in the metastatic setting.
Living related liver transplantation: a Japanese experience and development of a checklist for donors' informed consent
Authors: A Akabayashi
Journal: Gut (2002)

In the February 2002 issue of Gut , Broelsch et al argued for a controversial therapy of living related liver transplantation ( Gut 2002; 50 :143). The Japanese experience is somewhat different from those of other countries, as indicated in the article. Japan has long been the subject of sociocultural studies because of its delay in using the organs of brain dead persons for transplantation purposes. Since the Organ Transplant Law was enacted in 1997,1 only 16 liver transplant operations using brain dead donors have taken place. In contrast, more than 700 cases of liver transplants (with both children and adults as …
A prospective study of circulating mutant KRAS2 in the serum of patients with colorectal neoplasia: strong prognostic indicator in postoperative follow up
Authors: B M Ryan
Journal: Gut (2002)

Background and aims: Mutant tumour derived DNA has been detected in the sera of colorectal cancer patients. We investigated if mutant serum KRAS2 was detectable preoperatively in a large group of patients with colorectal neoplasia. A prospective study of 94 patients who underwent putative curative resection for colorectal carcinoma (CRC) was performed to ascertain if serum mutant KRAS2 could be used postoperatively as a disease marker. Methods: Preoperative sera from 78 patients were analysed (group A). Sera from 94 patients were obtained three monthly for up to three years during the postoperative period (group B). Codon 12 and 13 KRAS2 mutations were analysed in matched tumour and serum samples. Results: In the preoperative group (group A), KRAS2 mutation was found in 41/78 (53%) tumours and in 32/78 (41%) preoperative sera. Of 41 tumour KRAS2 mutation positive cases, 31/41 (76%) had an identical serum mutation detectable. In group B, the postoperative follow up group, 60/94 cases were primary tumour KRAS2 mutation positive. Of these 60, 16/60 (27%) became persistently serum mutant KRAS2 positive postoperatively. Ten of 16 (63%) of these developed a recurrence compared with only 1/44 (2%) patients who remained serum mutant negative (odds ratio 71.7 (95% confidence interval 7.7–663.9; p=0.0000). None of 34 tumour mutation negative cases became serum mutant KRAS2 positive postoperatively, despite recurrence in 9/34 patients. The relative hazard of disease recurrence in postoperative serum mutant KRAS2 positive patients was 6.37 (2.26–18.0; p=0.000). Conclusions: Serum mutant KRAS2 can be detected preoperatively in all stages of colorectal neoplasia. Postoperatively, serum mutant KRAS2 is a strong predictor of disease recurrence, stronger even than Dukes' stage of disease, and thus shows potential for use in clinical practice as a marker of preclinical disease recurrence.
Vitamin D effects in atopic dermatitis
Authors: Zbigniew Samochocki, Jaroslaw Bogaczewicz, Renata Jeziorkowska, Anna Sysa-Jędrzejowska, Olga Glińska, Elizabeth Karczmarewicz, Daniel P. McCauliffe, Anna Woźniacka
Journal: Journal of the American Academy of Dermatology (2013)
A Review of the Recent Evidence (2006–2008) for 532-nm Photoselective Laser Vaporisation and Holmium Laser Enucleation of the Prostate
Authors: Richard Naspro, Alexander Bachmann, Peter Gilling, Rainer Kuntz, Stephan Madersbacher, Francesco Montorsi, Oliver Reich, Christian Stief, Ivano Vavassori
Journal: European Urology (2009)
Gastric emptying: a contributory factor in gastro-oesophageal reflux activity?
Authors: G Stacher
Journal: Gut (2000)

To evaluate the impact of total and proximal stomach emptying on 24 hour and postprandial reflux as well as the number of reflux episodes per hour in relation to the impact of lower oesophageal sphincter (LOS) pressure, and oesophageal contractile and clearance function.Seventy one outpatients (37 female, 34 male; age 23-82 years) with symptoms suggestive of both delayed gastric emptying and reflux referred for further investigations participated in the study. Gastric emptying of a semisolid 1168 kJ meal and oesophageal clearance of a water bolus (supine) were recorded scintigraphically, reflux by 24 hour pH monitoring, and oesophageal motility manometrically.Slow proximal but not slow distal or total stomach emptying correlated with increased 24 hour and postprandial acid exposure and increased number of reflux episodes/hour. No relationship was found between total or proximal emptying and LOS resting pressure, oesophageal contraction amplitude, percentage of failed contractions, or clearance. Multiple linear regression analyses showed that slow proximal emptying and low LOS pressure contributed significantly to both 24 hour (p=0.0007 and p=0. 0001) and two hour postprandial acid exposure (p=0.007 and p=0.0001). In contrast, the rate of total emptying contributed to neither 24 hour nor postprandial acid exposure.Our data suggest that in contrast with total stomach emptying, the rate of proximal stomach emptying contributes to the extent of 24 hour as well as postprandial acid exposure and the number of reflux episodes/hour.
Genotype analysis for ΔF508, G551D and R553X mutations in children and young adults with cystic fibrosis with and without chronic liver disease
Authors: Ann Duthie, Derek G. Doherty, Carolyn Williams, Robert Scott-Jupp, J. O. Warner, Stuart M. Tanner, Robert Williamson, Alex P. Mowat
Journal: Hepatology (1992)

Genetic factors have been implicated in the pathogenesis of liver disease in cystic fibrosis. To investigate whether liver disease is associated with particular mutations of the defective gene in cystic fibrosis, we have determined the frequencies of three mutations - ΔF508, G551D and R553X - in 111 children and young adults with cystic fibrosis by analysis of genomic DNA segments amplified by the polymerase chain reaction. Twenty–nine patients had severe liver disease with portal hypertension, 19 had clinical and/or biochemical evidence of liver disease but no associated portal hypertension and 63 had no evidence of liver disease. No significant differences in the frequencies of the ΔF508, G551D or R553X mutations in the three clinical subgroups were found, and we conclude that the development of liver disease in cystic fibrosis is unlikely to be associated with a specific mutation in the gene. However, because 27% of cystic fibrosis chromosomes do not have a defined mutation, this possibility cannot be ruled out. A familial concordance for clinical liver disease of 20% in this study, compared with a reported prevalence of 4.7%, suggests that genes outside the cystic fibrosis locus and/or environmental factors are involved in the pathogenesis of liver disease in cystic fibrosis. (Hepatology 1992;15:660-664).
HDAC4 controls histone methylation in response to elevated cardiac load
Authors: Mathias Hohl, Michael Wagner, Jan-Christian Reil, Sarah-Anne Müller, Marcus Tauchnitz, Angela M. Zimmer, Lorenz H. Lehmann, Gerald Thiel, Michael Böhm, Johannes Backs, Christoph Maack
Journal: Journal of Clinical Investigation (2013)

In patients with heart failure, reactivation of a fetal gene program, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), is a hallmark for maladaptive remodeling of the LV. The mechanisms that regulate this reactivation are incompletely understood. Histone acetylation and methylation affect the conformation of chromatin, which in turn governs the accessibility of DNA for transcription factors. Using human LV myocardium, we found that, despite nuclear export of histone deacetylase 4 (HDAC4), upregulation of ANP and BNP in failing hearts did not require increased histone acetylation in the promoter regions of these genes. In contrast, di- and trimethylation of lysine 9 of histone 3 (H3K9) and binding of heterochromatin protein 1 (HP1) in the promoter regions of these genes were substantially reduced. In isolated working murine hearts, an acute increase of cardiac preload induced HDAC4 nuclear export, H3K9 demethylation, HP1 dissociation from the promoter region, and activation of the ANP gene. These processes were reversed in hearts with myocyte-specific deletion of Hdac4. We conclude that HDAC4 plays a central role for rapid modifications of histone methylation in response to variations in cardiac load and may represent a target for pharmacological interventions to prevent maladaptive remodeling in patients with heart failure.
Increased risk of vascular disease associated with gout: a retrospective, matched cohort study in the UK Clinical Practice Research Datalink
Authors: Lorna E Clarson, Samantha L Hider, John Belcher, Carl Heneghan, Edward Roddy, Christian D Mallen
Journal: Annals of the Rheumatic Diseases (2014)

To determine whether gout increases risk of incident coronary heart disease (CHD), cerebrovascular (CVD) and peripheral vascular disease (PVD) in a large cohort of primary care patients with gout, since there have been no such large studies in primary care.A retrospective cohort study was performed using data from the Clinical Practice Research Datalink (CPRD). Risk of incident CHD, CVD and PVD was compared in 8386 patients with an incident diagnosis of gout, and 39 766 age, sex and registered general practice-matched controls, all aged over 50 years and with no prior vascular history, in the 10 years following incidence of gout, or matched index date (baseline). Multivariable Cox Regression was used to estimate HRs and covariates included sex and baseline measures of age, Body Mass Index, smoking, alcohol consumption, Charlson comorbidity index, history of hypertension, hyperlipidaemia, chronic kidney disease, statin use and aspirin use.Multivariable analysis showed men were at increased risk of any vascular event (HRs (95% CIs)) HR 1.06 (1.01 to 1.12), any CHD HR 1.08 (1.01 to 1.15) and PVD HR 1.18 (1.01 to 1.38), while women were at increased risk of any vascular event, HR 1.25 (1.15 to 1.35), any CHD HR 1.25 (1.12 to 1.39), and PVD 1.89 (1.50 to 2.38)) but not any CVD.In this cohort of over 50s with gout, female patients with gout were at greatest risk of incident vascular events, even after adjustment for vascular risk factors, despite a higher prevalence of both gout and vascular disease in men. Further research is required to establish the reason for this sex difference.
Relationship between plasma glucose and insulin concentration, glucose production, and glucose disposal in normal subjects and patients with non-insulin-dependent diabetes.
Authors: Y D Chen, C Y Jeng, C B Hollenbeck, M S Wu, G M Reaven
Journal: Journal of Clinical Investigation (1988)

The changes in hepatic glucose production (Ra), tissue glucose disposal (Rd), and plasma glucose and insulin concentration that took place over a 16-h period from 10 to 2 p.m. were documented in 14 individuals; 8 with non-insulin-dependent diabetes mellitus (NIDDM) and 6 with normal glucose tolerance. Values for Ra were higher than normal in patients with NIDDM at 10 p.m. (4.73 +/- 0.41 vs. 3.51 +/- 0.36 mg/kg per min, P less than 0.001), but fell at a much faster rate throughout the night than that seen in normal subjects. As a consequence, the difference between Ra in normal individuals and patients with NIDDM progressively narrowed, and by 2 p.m., had ceased to exist (1.75 +/- 0.61 vs. 1.67 +/- 0.47 mg/kg per min, P = NS). Plasma glucose concentration also declined in patients with NIDDM over the same period of time, but they remained quite hyperglycemic, and the value of 245 +/- 27 mg/dl at 2 p.m. was about three times greater than in normal individuals. Plasma insulin concentrations also fell progressively from 10 to 2 p.m., and were similar in both groups throughout most of the 16-h study period. Thus, the progressive decline in Ra in patients with NIDDM occurred despite concomitant falls in both plasma glucose and insulin concentration. Glucose disposal rates also fell progressively in both groups, but the magnitude of the fall was greater in patients with NIDDM. Consequently, Rd in patients with NIDDM was higher at 10 p.m. (3.97 +/- 0.48 vs. 3.25 +/- 0.13 mg/kg per min, P less than 0.001) and lower the following day at 2 p.m. (1.64 +/- 0.21 vs. 1.97 +/- 0.35 mg/kg per min, P less than 0.01). These results indicate that a greatly expanded pool size can exist in patients with NIDDM at a time when values for Ra are identical to those in normal subjects studied under comparable conditions, which suggests that fasting hyperglycemia in NIDDM is not simply a function of an increase in Ra.
THE INACTIVATION OF ENTEROVIRUS INFECTIVITY BY THE SULFHYDRYL REAGENT <i>p</i>-CHLOROMERCURIBENZOATE
Authors: Purnell W. Choppin, Lennart Philipson
Journal: The Journal of Experimental Medicine (1961)

The infectivity of several enteroviruses was inactivated by the sulfhydryl reagent p-chloromercuribenzoate (PCMB). The rate of inactivation was dependent on the ionic environment in which the reaction was carried out. Inactivation of infectivity was reversed by the thiol compound, reduced glutathione. Under certain conditions, PCMB prevented the adsorption of some enteroviruses to monolayer cultures of monkey kidney cells. The results suggest that enterovirus sulfhydryl groups are involved in the establishment of infection, and that they play a role in the adsorption of virus to host cells.
Women doctors and their careers: what now?
Authors: Brian H McKinstry, Iain Colthart, Katy Elliot, Colin Hunter
Journal: BMJ (2005)

EDITOR—Allen is rightly optimistic about women's current and future contribution to medicine.1 She also rightly emphasises the combined impact of the feminisation of general practice and part time working, which has implications not only for the delivery of services but also for the development of the specialty.

The problem is probably worse than she portrays because the common definition of full time (> 26 h/week) is usually derived from government figures based on previous contract status. We conducted an anonymous survey …
Adhesion to fibronectin prolongs eosinophil survival.
Authors: A R Anwar, R Moqbel, G M Walsh, A B Kay, A J Wardlaw
Journal: The Journal of Experimental Medicine (1993)

We have investigated the effect of adhesion to fibronectin (Fn) on the survival of eosinophils in culture. Peripheral blood eosinophils from normal human donors were separated by immunomagnetic selection and cultured in RPMI on Fn- (100 micrograms/ml) coated microtiter plates for up to 96 h. Survival was measured by trypan blue exclusion. There was a significant enhancement of eosinophil survival with Fn as compared with both bovine serum albumin-coated and uncoated wells (p &amp;lt; 0.05-0.01). Fn-induced eosinophil survival was comparable to that obtained with exogenous interleukin 3 (IL-3) or granulocyte/macrophage colony-stimulating factor (GM-CSF) and was inhibitable by antibodies against Fn, very late antigen 4 (VLA-4), IL-3, and GM-CSF. Supernatants from Fn-, but not BSA-coated wells contained picogram amounts of IL-3 and GM-CSF, and eosinophils cultured on Fn for 24 h expressed mRNA for GM-CSF as determined by in situ hybridization. Therefore, Fn prolongs eosinophil survival in culture by triggering autocrine generation of cytokines by eosinophils. Since neutrophils lack VLA-4, this could provide a partial explanation for the preferential accumulation of eosinophils at sites of allergic inflammation, as well as the predominant tissue localization of eosinophils in healthy individuals.