tbuckley/cabot-search huggingface dataset:
Multinational evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative
Authors: P. Machado, I. Castrejon, W. Katchamart, R. Koevoets, B. Kuriya, M. Schoels, L. Silva-Fernandez, K. Thevissen, W. Vercoutere, E. Villeneuve, D. Aletaha, L. Carmona, R. Landewe, D. van der Heijde, J. W. J. Bijlsma, V. Bykerk, H. Canhao, A. I. Catrina, P. Durez, C. J. Edwards, M. D. Mjaavatten, B. F. Leeb, B. Losada, E. M. Martin-Mola, P. Martinez-Osuna, C. Montecucco, U. Muller-Ladner, M. Ostergaard, B. Sheane, R. M. Xavier, J. Zochling, C. Bombardier
Journal: Annals of the Rheumatic Diseases (2010)

To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA).697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed.A total of 39,756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA.Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.
Ad libitum adjustments to fluid intake during cool environmental conditions maintain hydration status during a 3-day mountain bike race
Authors: S Rose, E M Peters-Futre
Journal: British Journal of Sports Medicine (2008)

Objective In this study, the hydration status of amateur cyclists who voluntarily adjusted their fluid intake to environmental conditions during a 3-day, 248-km mountain bike (MTB) race was assessed. Design Prospective observational field study. Setting Sani2C MTB Race, KwaZulu-Natal, South Africa, 2006. Participants 18 randomly selected amateur, male MTB cyclists. Main outcome measures Reported usual fluid intake, environmental conditions, voluntary fluid intake, urine voided, changes in body mass, serum osmolality (SO), sodium concentration [Na + ] and urinary specific gravity (Usg) during each stage (S). Results Dry bulb temperature (adjusted for windchill) ranged from 6° to 21.4°C during S1, S2 and S3. While 77.8% (n = 14) of subjects reported a usual intake of &gt;750 ml h −1 in previous MTB events, mean (SE) fluid intake in this race ranged from 341 (32) ml h −1 during S1 to 551 (56) ml h −1 during S3. Changes in mean body mass ranged between −0.99% and −2.02% during the three stages. Mean SO and serum [Na + ] ranged between 292 (0.73) mOsm kg −1 and 298 mOsm kg −1 and 137 (0.35) mEq and 140 (0.42) mEq, respectively, during the 3-day period, while Usg remained ≤1.025. Conclusion Ad libitum fluid intake during the 2006 Sani2C MTB Race, which took place in unexpectedly cold environmental conditions, was substantially lower than the usual reported fluid intake of subjects. Changes in body mass, SO, serum [Na + ] and Usg were not clinically significant, indicating that an adequate hydration status was maintained during the multiday MTB cycle race.
Independent replication establishes the CD247 gene as a genetic systemic sclerosis susceptibility factor
Authors: P. Dieude, C. Boileau, M. Guedj, J. Avouac, B. Ruiz, E. Hachulla, E. Diot, J. L. Cracowski, K. Tiev, J. Sibilia, L. Mouthon, C. Frances, Z. Amoura, P. Carpentier, A. Cosnes, O. Meyer, A. Kahan, G. Chiocchia, Y. Allanore
Journal: Annals of the Rheumatic Diseases (2011)

The first large genome-wide association (GWA) study of systemic sclerosis (SSc) recently included 2296 SSc patients and 5014 healthy controls from four case–control series of Caucasian individuals and involved the analysis of about 280 000 single nucleotide polymorphisms (SNPs).1 Outside the HLA region, SNPs mapping to the known TNPO3 - IRF5 and STAT4 regions showed the strongest association but three other loci reached genome-wide significance (namely CD247 locus in 1q22–23, CDH7 in 18q22 and EXOC2 - IRF4 near 6p25) although only one ( CD247 ) could be replicated in the second set of samples. Given the major challenge of separating the many false-positive associations from the few true-positive associations with disease in GWA studies, resulting in a stratification bias, a critical strategy is replication of results in independent samples.2 Therefore, we herein provide an attempt of …
Residual Prostatitis after Chemotherapy of Acute Gonorrhoea
Authors: F. C. B. du Coudray
Journal: BMJ (1947)

The condition I am about to describe has not, so far as I am aware, been given any prominence in the current literature.As a result of careful personal observation in Mauritius, East Africa, and Cyprus (and so-,presumably throughout the Tropics and sub-tropics), covering a period of 41 years' continuous V.D. practice in the Army, I cani affirm that subacute and chronic residual prostatitis tfter chemotherapy in acute gonorrhoea is of very widespread occurrence, and gives rise to physical signs as long as it remains untreated.Under chemotherapy I include treat- ment by the sulphonamides, as I consider that, from a purely therapeutic point of view, penicillin has only one advantage over the sulphonamides in gonorrhoea-that there is no evidence of penicillin resistance or " fastness" so far as the gonococcus is concerned.Hence, when the sulphonamides act favourably, they are therapeutically as effective as pmnicillin.If the following are accepted as the criteria of cure in all cases of urethritis-(l) a persistently clear urine,,(2) a per- sistently " dry " urethra, (3) a prostate which feels normal on palpation per rectum, and (4) a prostatic fluid which is macroscopically clear, and which, when fixed and stainied, shows microscopically no pus cells, or at most only a few (not more than two or three in any field)-then I have found that after chemotherapy in every case of acute gonococcal urethritis return to normal is disappointingly infrequent.The departure from normality which occurs most often after treatment is the above-mentioned residual prostatitis, which fails to respond to further chemotherapy. Clinical FeaturesThe signs (there are no symptoms) of such a prosrtitis may be the following:
Comment. Is Incretin-Based Therapy Ready for the Care of Hospitalized Patients With Type 2 Diabetes?
Authors: Adam M. Deane, Michael Horowitz
Journal: Diabetes Care (2014)

We read with interest the narratives by Schwartz and DeFronzo (1) and Umpierrez and Korytkowski (2) relating to the use of incretin-based therapy in the care of hospitalized patients with hyperglycemia. We have performed a number of mechanistic studies to evaluate incretin-based therapies in the critically ill that were not referenced (3–5). In these articles, exogenous glucagon-like peptide 1 (GLP-1) was shown to attenuate the glycemic response to enteral nutrient in mechanically ventilated critically ill patients both with and without preexisting type 2 diabetes, and was associated with stimulation of serum insulin and suppression of plasma glucagon (3,5). Enteral nutrition can be administered directly into the …
Some Practical Applications of Genetics in Medicine and Surgery
Authors: J. A. F. Roberts
Journal: BMJ (1964)

Leonard Parsons was a man of transcendent ability and of transcendent personality.He was a pioneer in the study of child health and in the care of sick children.His memorial may be seen in the school of paediatrics which he founded in the University of Birmingham, and also in many other centres in this country and all over the world where his disciples have followed his example and practised what he taught.I could not hope to add to the tributes which have been paid to him, but I should like to mention one example of his insight and of his wisdom which comes close to the subject of these lectures.In 1933 he put forward the hypothesis that icterus gravis, hydrops foetalis, and haemolytic anaemia of the newborn were one and the same disease, due to a haemolytic process of then unknown nature.This conception prepared the way a few years later for the brilliant work of Levine.Levine showed that the haemolytic process was the result of maternal-foetal incompatibility.It is interesting to reflect that if the work on the rhesus monkey had been carried out a year or two later, or indeed if it had never been done at all, all we know now would probably have stemmed just as surely from Levine's observations, and without any help from our small relative.That was an example of Parsons's insight.About 12 years later he also showed his wisdom.In the early flush of enthusiasm it was proposed that haemolytic disease should be called rhesus disease.This Parsons opposed strongly, and thanks to him we now refer to haemolytic disease of the foetus and of the newborn.He was, of course, entirely right.To-day we know that although the commonest cause of haemolytic disease is maternal-foetal rhesus incompatibility there are many other causes as well, such as other blood-group antigens-for example, the original antigen of the Kell system. Change in Relative ImportanceIt was natural for the early paediatricians, and indeed even for those of Parsons's day, to concentrate on the environmental causes of diseases of children.The scope for prevention was still enormous; but as environmental causes were progressively elucidated and appropriate measures of prevention and treat- ment instituted a hard core of something resistant assumed an ever-growing relative importance.In the quinquennium 1901-5 the infant death rate was about 140 per thousand.By a smooth progression this has fallen to about 20 per thousand.Nearly all causes of death have shown a substantial or indeed striking decline, but there are two exceptions.One is deaths attributed to injury at birth, a subject outside the scope of these lectures.The other is deaths attributed to congenital malforma- * A shortened version of the Leonard Parsons Lectures delivered at the University of Birmingham on 13 and 14 May 1963.transmission is entirely different.Two outwardly normal carriers happen to marry and then there is one chance in four that any child will receive the abnormal gene from both parents and so be affected.The characteristic finding is a tendency
The influence of sex and histology on outcomes in non-small-cell lung cancer: a pooled analysis of five randomized trials
Authors: P. Wheatley-Price, F. Blackhall, S.-M. Lee, C. Ma, L. Ashcroft, M. Jitlal, W. Qian, A. Hackshaw, R. Rudd, R. Booton, S. Danson, P. Lorigan, N. Thatcher, F.A. Shepherd
Journal: Annals of Oncology (2010)
Antibodies to normal human melanocytes in vitiligo.
Authors: G K Naughton, M Eisinger, J C Bystryn
Journal: The Journal of Experimental Medicine (1983)

Most patients with active vitiligo (82% of 61) have antibodies to antigens of normal human melanocytes that can be detected by specific immunoprecipitation of radioiodinated, detergent-soluble, melanocyte macromolecules. Such antibodies were present in only 12% of patients with melanoma and in none of 35 patients with nonpigmentary skin diseases. The antibodies were directed to a common antigen(s) on melanocytes that was not present on normal fibroblasts or keratinocytes. These observations suggest that vitiligo is an autoimmune disease mediated by antibodies to melanocyte-associated antigen(s).
The distribution of functional impairment across the lateral border of acutely ischemic myocardium.
Authors: K P Gallagher, R A Gerren, M C Stirling, M Choy, R C Dysko, S P McManimon, W R Dunham
Journal: Circulation Research (1986)

To evaluate the degree and lateral extent of dysfunction in nonischemic myocardium adjacent to ischemic muscle, we measured systolic wall thickening with sonomicrometers during circumflex coronary occlusion in 12 anesthetized, open-chest dogs. The locations of the wall thickness measurements relative to the perfusion boundary were determined with myocardial blood flow (microspheres) maps constructed from multiple, small tissue samples. Five minutes after circumflex occlusion, systolic wall thickening in the central ischemic zone decreased from 3.00 +/- 0.61 (mean +/- SD) mm to -0.61 +/- 0.36 mm (P less than 0.01). In nonischemic myocardium greater than 10 mm from the perfusion boundary, systolic wall thickening increased from 2.56 +/- 0.57 to 3.24 +/- 0.72 mm (P less than 0.01). In nonischemic myocardium within 10 mm of the perfusion boundary, systolic wall thickening was slightly but significantly reduced compared with control (2.72 +/- 0.80 to 2.44 +/- 0.79 mm, P less than 0.05), supporting the concept of regional dysfunction in nonischemic myocardium at the lateral borders of an ischemic area. Sigmoid curves were fitted to the data to model changes in wall thickening as a continuous function of distance from the perfusion boundary. This allowed estimation of the extent of dysfunction into nonischemic myocardium which averaged less than 8 mm (approximately 30 degrees of endocardial circumference) at one border. The level of functional impairment in this zone was relatively modest, and systolic wall thickening in the immediate border area was reduced more than 50% from control only in tissue characterized by a blood supply of mixed ischemic and nonischemic origin. We conclude that a functional border zone exists lateral to an acutely ischemic area, but measurement of regional function produces relatively small exaggeration of the size of the acutely ischemic zone if severe reduction in mechanical performance is used to define the extent of the ischemic area.
Characterization of the <i>BMPR2</i> 5′-Untranslated Region and a Novel Mutation in Pulmonary Hypertension
Authors: Micheala A Aldred, Rajiv D Machado, Victoria James, Nicholas W Morrell, Richard C Trembath
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Familial pulmonary arterial hypertension results from heterozygous inactivating mutations of the BMPR2 gene. Traditional mutation analysis identifies pathogenic mutations in some 70% of linked families. We hypothesized that the apparent shortfall is due to mutations located in the promoter region of the gene, resulting in abnormal gene regulation.Objectives: To identify mutations in untranslated sequence regulating BMPR2 transcription.Methods: DNA upstream of the coding region was analyzed by direct sequencing in 16 families. Reverse transcription-polymerase chain reaction analysis and rapid amplification of cDNA ends of normal human lung RNA were used to investigate transcription of this region. Transcript levels were assessed by allele-specific expression analysis and inhibition of nonsense-mediated decay in lymphoblastoid cell lines.Measurements and Main Results: The wild-type transcriptional start site of BMPR2 was defined, 1,148 bp upstream of the ATG. Within this region, we identified a double-substitution mutation, predicted to form a cryptic translational start site, in one family. The mutant transcript contains a premature stop codon predicted to trigger nonsense-mediated decay. Expression analysis in the patient's cell line indeed showed reduced expression of the mutant transcript that could be restored to normal by inhibiting nonsense-mediated decay.Conclusions: Activation of a cryptic translation initiation site is a novel mutational mechanism in this disorder. These results demonstrate that the 5′-untranslated region of BMPR2 is considerably longer than previously thought, emphasizing the need to fully characterize the BMPR2 promoter and the importance of analyzing noncoding regions in patients with pulmonary arterial hypertension who are negative for mutations within the coding region and intron–exon junctions.
Active Smoking Depresses Prostaglandin Synthesis in Human Gastric Mucosa
Authors: G. FOREST QUIMBY
Journal: Annals of Internal Medicine (1986)

To determine the effect of smoking on gastroduodenal mucosal prostaglandin synthesis, endoscopies were done after an overnight fast on 10 nonsmokers, 12 active smokers who smoked four cigarettes in the hour before endoscopy, and then 11 of the smokers who refrained from smoking for 12 hours. Biopsy samples of fundic, antral, and duodenal mucosae were incubated, and the accumulation of prostaglandin E2 and 6-keto-prostaglandin F1α in the incubation medium was measured by radioimmunoassay. We assumed that accumulation of prostaglandins in the medium reflected mucosal synthesis. Comparison of active and inactive smoking showed that active smoking significantly depressed 6-keto-prostaglandin F1α synthesis in antral and fundic mucosa and prostaglandin E2 synthesis in antral mucosa. Comparison of nonsmokers and inactive smokers showed no difference in prostaglandin synthesis. Active smoking causes a transient decrease in prostaglandin synthesis in fundic and antral mucosae. This depression of prostaglandin synthesis may help explain slower ulcer healing and predisposition to ulcer recurrence in smokers.
Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial
Authors: Ben J Slotman, Harm van Tinteren, John O Praag, Joost L Knegjens, Sherif Y El Sharouni, Matthew Hatton, Astrid Keijser, Corinne Faivre-Finn, Suresh Senan
Journal: The Lancet (2014)

BackgroundMost patients with extensive stage small-cell lung cancer (ES-SCLC) who undergo chemotherapy, and prophylactic cranial irradiation, have persistent intrathoracic disease. We assessed thoracic radiotherapy for treatment of this patient group.MethodsWe did this phase 3 randomised controlled trial at 42 hospitals: 16 in Netherlands, 22 in the UK, three in Norway, and one in Belgium. We enrolled patients with WHO performance score 0–2 and confirmed ES-SCLC who responded to chemotherapy. They were randomly assigned (1:1) to receive either thoracic radiotherapy (30 Gy in ten fractions) or no thoracic radiotherapy. All underwent prophylactic cranial irradiation. The primary endpoint was overall survival at 1 year in the intention-to-treat population. Secondary endpoints included progression-free survival. This study is registered with the Nederlands Trial Register, number NTR1527.FindingsWe randomly assigned 498 patients between Feb 18, 2009, and Dec 21, 2012. Three withdrew informed consent, leaving 247 patients in the thoracic radiotherapy group and 248 in the control group. Mean interval between diagnosis and randomisation was 17 weeks. Median follow-up was 24 months. Overall survival at 1 year was not significantly different between groups: 33% (95% CI 27–39) for the thoracic radiotherapy group versus 28% (95% CI 22–34) for the control group (hazard ratio [HR] 0·84, 95% CI 0·69–1·01; p=0·066). However, in a secondary analysis, 2-year overall survival was 13% (95% CI 9–19) versus 3% (95% CI 2–8; p=0·004). Progression was less likely in the thoracic radiotherapy group than in the control group (HR 0·73, 95% CI 0·61–0·87; p=0·001). At 6 months, progression-free survival was 24% (95% CI 19–30) versus 7% (95% CI 4–11; p=0·001). We recorded no severe toxic effects. The most common grade 3 or higher toxic effects were fatigue (11 vs 9) and dyspnoea (three vs four).InterpretationThoracic radiotherapy in addition to prophylactic cranial irradiation should be considered for all patients with ES-SCLC who respond to chemotherapy.FundingDutch Cancer Society (CKTO), Dutch Lung Cancer Research Group, Cancer Research UK, Manchester Academic Health Science Centre Trials Coordination Unit, and the UK National Cancer Research Network.
Realizing the Potential of Plasma Genotyping in an Age of Genotype-Directed Therapies
Authors: J. J. Luke, G. R. Oxnard, C. P. Paweletz, D. R. Camidge, J. V. Heymach, D. B. Solit, B. E. Johnson
Journal: JNCI Journal of the National Cancer Institute (2014)

The identification of oncogenic driver mutations in cancer has led to the rapid rise of genotype-directed treatments such as EGFR and BRAF kinase inhibitors. Standard tumor biopsy remains a cumbersome and morbid procedure for patients, leading to a growing interest in noninvasive plasma genotyping approaches. Circulating tumor cells are of interest; however, the processing of specimens is complicated and time consuming. By comparison, cell-free DNA (cfDNA) genotyping has the potential to be convenient and relatively simple to process in a short time period. Several technologies are under development for cfDNA analysis, such as allele-specific polymerase chain reaction (PCR), coamplification at Lower Denaturation temperatures (COLD) PCR, emulsion PCR, and massively parallel sequencing. Broad clinical validity will need to be established for different assays, and clinical utility will need to be evaluated within prospective trials to determine which assays will best predict the efficacy of therapy and patient outcomes. In addition, assay standardization will be critical prior to widespread use in routine clinical practice. The Cell Free DNA Working Group, under the sponsorship of Transgenomic, was convened to evaluate the molecular assays in development and provide recommendations for application and interpretation of these tests in the context of future clinical research. The consensus commentary of the Cell Free DNA Working Group for the use of cfDNA plasma genotyping assays is presented here, including future steps in the development of these technologies.