tbuckley/cabot-search huggingface dataset:
Asthma and epididymitis: the calm before the storm
Authors: G. H M George, J. S Axford
Journal: Annals of the Rheumatic Diseases (1999)

Case reportA 17 year old Asian college student presented with a two month history of arthralgia, arthritis of his ankles and wrists, numbness of his feet and weight loss.He had a history, for the previous month, of epididymo-orchitis treated at another hospital.He had been investigated for abdominal pain and weight loss by plain abdominal radiography, abdominal ultrasound scan and rectal biopsy.Results were all normal.The symptoms were associated with a poor appetite but no history of nausea, vomiting or diarrhoea.No definite diagnosis was reached.He had a painful left ankle with associated numbness of the lateral aspect of his left foot.He felt generally weak and lethargic.He subsequently developed right ankle discomfort and swelling and bilateral wrist swelling and pain.Past medical history included allergic rhinitis and asthma, since childhood, for which he was treated regularly with beclomethasone and salbutamol inhalers.Clinical examination on presentation revealed a thin, unwell, feverish patient.He was 160 cm tall and weighed 43 kg.His fever persisted during the early stages of his admission to hospital.Hand examination revealed splinter haemorrhages, macular pigmented lesions on the palmar surface of his hands, and subcutaneous nodules at both elbows.He had a tachycardia with a soft ejection systolic murmur and his blood pressure was normal.His chest was clear and abdomen soft and non-tender with no palpable organs or masses.Central nervous system examination was normal.Peripheral nervous system examination revealed an asymmetrical subjective light touch sensory diminution in the lower limbs below the knees and absent ankle jerk reflexes bilaterally.Plantar reflexes were both flexor.There was grade 3/5 weakness of dorsiflexion at both ankles.Urine analysis was negative for blood and protein. InvestigationsLaboratory investigations showed: haemoglobin 15.0 g/dl, leucocyte count 21.5 × 10 9 /1, platelets 461 × 10 9 /1, erythocyte sedimentation rate (ESR) 146 mm 1st h, and C reactive protein (CRP) 37 mg/l.Serum urea, creatinine, electrolytes, liver function tests, bone biochemistry, creatine kinase and angiotensin convert-
Novel Role for STAT-5B in the Regulation of Hsp27–FGF-2 Axis Facilitating Thrombin-Induced Vascular Smooth Muscle Cell Growth and Motility
Authors: Huiqing Cao, Nagadhara Dronadula, Farhan Rizvi, Quanyi Li, Kalyan Srivastava, William T. Gerthoffer, Gadiparthi N. Rao
Journal: Circulation Research (2006)

Previously, we have demonstrated that STAT-3 plays a role in thrombin-induced VSMC motility. To learn more about the role of STATs in the mitogenic and chemotactic signaling events of thrombin, here we have studied the role of STAT-5. Thrombin activated STAT-5 as measured by its tyrosine phosphorylation, DNA binding, and reporter gene activity. Inhibition of STAT-5B, but not STAT-5A, by adenovirus-mediated expression of its respective dominant-negative mutants suppressed thrombin-induced VSMC growth and motility. Thrombin induced the expression of Hsp27 and FGF-2 in a time- and STAT-5B-dependent manner in VSMC. In addition, small interfering RNA-directed depletion of Hsp27 levels or adenovirus-mediated expression of its dominant-negative mutant attenuated thrombin-induced FGF-2 expression, growth, and motility of VSMC. An increased association of STAT-5B with STAT-3 occurred in response to thrombin and adenovirus-mediated expression of dnSTAT-3 suppressed thrombin-induced Hsp27 and FGF-2 induction, DNA synthesis and motility in VSMC. Together, these results indicate that thrombin-induced VSMC growth and motility require STAT-5B/STAT-3–dependent expression of Hsp27 and FGF-2. These observations also suggest that STAT-5B/STAT-3/Hsp27/FGF-2 signaling via its involvement in the regulation of VSMC growth and motility may play an important role in the pathogenesis of vascular diseases such as restenosis after angioplasty.
Career prospects in medical gastroenterology in the UK: a follow up survey 1980-2.
Authors: J E Lennard-Jones
Journal: Gut (1983)

In 1980 there were 279 physicians with a special interest in gastroenterology distributed through the United Kingdom and 102 trainees of senior registrar status who aspired to a consultant post in general medicine with this special interest. A survey has been undertaken in September 1982 to record changes over the subsequent two year period.
P97 Diverging Trends In Prevalences Of Asthma, Eczema And Hayfever In Children Aged 9-12 Years
Authors: M. Barnish, N. Tagiyeva, L. Aucott, G. Devereux, S. Turner
Journal: Thorax (2014)

<h3>Introduction</h3> The prevalences of childhood asthma, eczema and hayfever have been recorded in our local population since 1964. The prevalence of a lifetime history of asthma rose from 4% in 1964 to a peak of 28% in 2004 before falling back to 22% in 2009. Wheeze in the past 12 months fell from 19% in 2004 to 16% in 2009. Lifetime prevalences of eczema and hay fever were approximately 5% in 1964 and had risen to 30% and 25% in 2004 and 2009. Here we present the results of our 2014 survey where we tested the hypothesis that eczema and hayfever prevalence will have followed the earlier trend for asthma and fallen since 2009. <h3>Methods</h3> Children aged 9 to 12 years attending local primary schools were eligible. The questionnaire used in previous surveys was distributed to children by teaching staff, completed by parents at home and returned directly to the researchers. <h3>Results</h3> Forty-seven schools were invited to participate of whom 41 took part. There were 4175 questionnaires distributed and 1378 returned (33%). The mean (SD) age was 10.9 (1.1) and 50% were boys. A lifetime history of asthma was reported in 17%. Lifetime prevalences of eczema and hay fever were 31% and 30% respectively. Wheeze in the past 12 months was reported in 13%. <h3>Conclusions</h3> The proportion of children with a history of ever having had asthma and of recent wheeze continues to fall in our population at a time when the prevalences of eczema and hayfever remained static (see Figure). There was a low response rate in this survey and the results should be interpreted with some caution but the findings suggest different underlying mechanisms for asthma and other “allergic” conditions.
Anti-tumour necrosis factor treatment in a patient with anorexia nervosa and juvenile idiopathic arthritis
Authors: J Barber, T Sheeran, D Mulherin
Journal: Annals of the Rheumatic Diseases (2003)

Tumour necrosis factor α (TNFα) is believed to have a pivotal role in the pathogenesis of many forms of inflammatory arthritis, and anti-TNFα therapies are now licensed and recommended for the treatment of refractory rheumatoid arthritis and juvenile idiopathic arthritis (JIA).1,2 An important role for TNFα in the pathophysiology of anorexia nervosa has also been postulated, although authors differ on the precise mechanisms underlying its role.3 Some authors have suggested that TNFα may be mediating a stress response, whereas others have proposed that raised levels of TNFα in these patients may be secondary to anorexia rather than a cause.4,5 Although the role of anti-TNFα therapies in the management of inflammatory arthritis is well recognised, we are not aware of experience with the use of anti-TNFα treatment in the management of anorexia nervosa. We describe the effect of such treatment prescribed to a woman with refractory JIA and anorexia nervosa.

A …
Development of CD4+CD8+ thymocytes in RAG-deficient mice through a T cell receptor β chain-independent pathway.
Authors: C J Guidos, C J Williams, G E Wu, C J Paige, J S Danska
Journal: The Journal of Experimental Medicine (1995)

Antigen-binding diversity is generated by site-specific V(D)J recombination of the T cell receptor (TCR) and immunoglobulin loci in lymphocyte precursors. Coordinate expression of two structurally distinct recombinase activating genes, RAG-1 and RAG-2, is necessary for activation of site-specific V(D)J recombination. In mice bearing targeted disruptions of either the RAG-1 or RAG-2 genes, T and B lymphocyte development is arrested at the CD4-8- double negative (DN) thymocyte or B220+/CD43+ pro-B cell stage. Development of CD4+CD8+ double positive (DP) thymocytes is restored by expression of a functionally rearranged TCR beta transgene, suggesting that TCR beta expression is critical for this developmental transition. We have found that treatment of adult or newborn RAG-deficient mice with a single sublethal dose of gamma-irradiation rescues the DN to DP transition in early thymocytes, and this is accompanied by a dramatic increase in thymus cellularity. In contrast to the observed induction of thymocyte maturation, there was no phenotypic or functional evidence of coincident B lymphocyte development in irradiated RAG-deficient mice. Interestingly, maturation of DP thymocytes occurred without expression of TCR beta protein in the cytoplasm or on the cell surface. These results suggest an in vivo pathway for DP thymocyte development which is TCR beta chain independent.
The Use of Ornithine Salts of Branched-Chain Ketoacids in Portal-Systemic Encephalopathy
Authors: H. FRANKLIN HERLONG
Journal: Annals of Internal Medicine (1980)

In eight patients with chronic portal-systemic encephalopathy who were symptomatic despite protein restriction and lactulose, a double-blind crossover comparison was conducted of branched-chain amino acids (68 mmol/d) versus ornithine salts of branched-chain ketoacids (34 mmol/d), both mixtures being administered orally for 7 to 10 days, after control periods, during a single hospitalization. Ornithine salts of branched-chain ketoacids markedly improved electroencephalographic abnormalities and clinical grade of encephalopathy; branched-chain amino acids had significantly lesser effects, which were of borderline statistical significance. To ascertain whether ornithine or branched-chain ketoacids were responsible for the improvement observed, we administered to six patients calcium salts of branched-chain ketoacids (34 mmol/d) after control periods; only slight improvement was seen. Four patients received a daily dose of ornithine alphaketoglutarate containing the same quantity of ornithine; one did not change and three deteriorated rapidly. We conclude that the combination of ornithine and branched-chain ketoacids improves chronic portal-systemic encephalopathy more than its components given separately and more than branched-chain amino acids at twice the molar dose.
Evidence-based sports medicine
Authors: P. McCrory
Journal: British Journal of Sports Medicine (2001)

We have the curse of living in exciting times. Sports medicine, for so long an art, is slowly but surely turning into a science. One of the important factors in this is the increased number of clinicians turning to this area as a vocation. In parallel, the development of academic sports medicine departments and the recognition by (some) insurers of the specialist value of sports physicians fosters this process.

How do we progress further? Research, research, research. If sports medicine is to be seen as a viable and valid speciality then there must be an evidence base behind it. This is no different to where, for example, cardiology was 40 years ago or neurology 20 years ago. How do we foster the development of a culture that embraces EBM and recognises the need for research publication? Firstly, those individuals mentoring or supervising other clinicians have a duty to include research into individual performance goals. I am continually told in every county I visit that each person has a pile of cases “ready to write …
Inpatient Diabetes Education Is Associated With Less Frequent Hospital Readmission Among Patients With Poor Glycemic Control
Authors: Sara J. Healy, Dawn Black, Cara Harris, Andrew Lorenz, Kathleen M. Dungan
Journal: Diabetes Care (2013)

To explore the relationship between inpatient diabetes education (IDE) and hospital readmissions in patients with poorly controlled diabetes.Patients with a discharge diagnosis of diabetes (ICD-9 code 250.x) and HbA1c>9% who were hospitalized between 2008 and 2010 were retrospectively identified. All-cause first readmissions were determined within 30 days and 180 days after discharge. IDE was conducted by a certified diabetes educator or trainee. Relationships between IDE and hospital readmission were analyzed with stepwise backward logistic regression models.In all, 2,265 patients were included in the 30-day analysis and 2,069 patients were included in the 180-day analysis. Patients who received IDE had a lower frequency of readmission within 30 days than did those who did not (11 vs. 16%; P=0.0001). This relationship persisted after adjustment for sociodemographic and illness-related factors (odds ratio 0.66 [95% CI 0.51-0.85]; P=0.001). Medicaid insurance and longer stay were also independent predictors in this model. IDE was also associated with reduced readmissions within 180 days, although the relationship was attenuated. In the final 180-day model, no IDE, African American race, Medicaid or Medicare insurance, longer stay, and lower HbA1c were independently associated with increased hospital readmission. Further analysis determined that higher HbA1c was associated with lower frequency of readmission only among patients who received a diabetes education consult.Formal IDE was independently associated with a lower frequency of all-cause hospital readmission within 30 days; this relationship was attenuated by 180 days. Prospective studies are needed to confirm this association.
Combined Survival Analysis of Prospective Clinical Trials of Gefitinib for Non–Small Cell Lung Cancer with <i>EGFR</i> Mutations
Authors: Satoshi Morita, Isamu Okamoto, Kunihiko Kobayashi, Koichi Yamazaki, Hajime Asahina, Akira Inoue, Koichi Hagiwara, Noriaki Sunaga, Noriko Yanagitani, Toyoaki Hida, Kimihide Yoshida, Tomonori Hirashima, Kosei Yasumoto, Kenji Sugio, Tetsuya Mitsudomi, Masahiro Fukuoka, Toshihiro Nukiwa
Journal: Clinical Cancer Research (2009)

Somatic mutations of the epidermal growth factor receptor (EGFR) gene are associated with an increased response to gefitinib in patients with non-small cell lung cancer. We have examined the impact of gefitinib on progression-free survival and overall survival in patients with EGFR mutation-positive non-small cell lung cancer.We searched for all clinical trials that prospectively evaluated the efficacy of gefitinib for advanced non-small cell lung cancer with EGFR mutations in Japan. We did a combined analysis based on individual patient data from the identified trials.Seven eligible trials were identified for a total of 148 non-small cell lung cancer patients with EGFR mutations. The overall response rate to gefitinib was 76.4% [95% confidence interval (95% CI), 69.5-83.2]. The median progression-free survival and overall survival were 9.7 months (95% CI, 8.2-11.1) and 24.3 months (95% CI, 19.8-28.2), respectively. Good performance status and chemotherapy-naïve status were significantly associated with a longer progression-free survival or overall survival. Of the 148 patients, 87 received gefitinib as a first-line therapy, whereas 61 received systemic chemotherapy before gefitinib treatment. The median progression-free survival after the start of first-line therapy was significantly longer in the gefitinib-first group than in the chemotherapy-first group (10.7 versus 6.0 months; P < 0.001), whereas no significant difference in median overall survival was apparent between the two groups (27.7 versus 25.7 months; P = 0.782).Gefitinib monotherapy confers substantial clinical benefit in terms of progression-free survival and overall survival in non-small cell lung cancer patients with EGFR mutations. Randomized trials comparing chemotherapy with gefitinib as a first-line treatment are warranted in such patients.
β <sub>2</sub> -Adrenergic and Several Other G Protein–Coupled Receptors in Human Atrial Membranes Activate Both G <sub>s</sub> and G <sub>i</sub>
Authors: Jason D. Kilts, Mark A. Gerhardt, Mark D. Richardson, Gautam Sreeram, G. Burkhard Mackensen, Hilary P. Grocott, William D. White, R. Duane Davis, Mark F. Newman, Joseph G. Reves, Debra A. Schwinn, Madan M. Kwatra
Journal: Circulation Research (2000)

Abstract —Cardiac G protein–coupled receptors that couple to Gα s and stimulate cAMP formation (eg, β-adrenergic, histamine, serotonin, and glucagon receptors) play a key role in cardiac inotropy. Recent studies in rodent cardiac myocytes and transfected cells have revealed that one of these receptors, the β 2 -adrenergic receptor (AR), also couples to the inhibitory G protein Gα i (activation of which inhibits cAMP formation). If β 2 ARs could be shown to couple to Gα i in the human heart, it would have important ramifications, because levels of Gα i increase with age and in failing human heart. Therefore, we investigated whether β 2 ARs in the human heart activate Gα i . By photoaffinity labeling human atrial membranes with [ 32 P]azidoanilido-GTP, followed by immunoprecipitation with antibodies specific for Gα i , we found that Gα i is activated by stimulation of β 2 ARs but not of β 1 ARs. In addition, we found that other Gα s -coupled receptors also couple to Gα i , including histamine, serotonin, and glucagon. When coupling of these receptors to Gα i is disrupted by pertussis toxin, their ability to stimulate adenylyl cyclase is enhanced. These data provide the first evidence that β 2 AR and many other Gα s -coupled receptors in human atrium also couple to Gα i and that abolishing the coupling of these receptors to Gα i increases the receptor-mediated adenylyl cyclase activity.
Sleep Duration, Lifestyle Intervention, and Incidence of Type 2 Diabetes in Impaired Glucose Tolerance
Authors: Henri Tuomilehto, Markku Peltonen, Markku Partinen, Gilles Lavigne, Johan G. Eriksson, Christian Herder, Sirkka Aunola, Sirkka Keinänen-Kiukaanniemi, Pirjo Ilanne-Parikka, Matti Uusitupa, Jaakko Tuomilehto, Jaana Lindström
Journal: Diabetes Care (2009)

OBJECTIVE Both short and long sleep duration have frequently been found to be associated with an increased risk for diabetes. The aim of the present exploratory analysis was to examine the association between sleep duration and type 2 diabetes after lifestyle intervention in overweight individuals with impaired glucose tolerance in a 7-year prospective follow-up. RESEARCH DESIGN AND METHODS A total of 522 individuals (aged 40–64 years) were randomly allocated either to an intensive diet-exercise counseling group or to a control group. Diabetes incidence during follow-up was calculated according to sleep duration at baseline. Sleep duration was obtained for a 24-h period. Physical activity, dietary intakes, body weight, and immune mediators (C-reactive protein and interleukin-6) were measured. RESULTS Interaction between sleep duration and treatment group was statistically significant (P = 0.003). In the control group, the adjusted hazard ratios (HRs) (95% CI) for diabetes were 2.29 (1.38–3.80) and 2.74 (1.67–4.50) in the sleep duration groups 9–9.5 h and ≥10 h, respectively, compared with for that of the 7–8.5 h group. In contrast, sleep duration did not influence the incidence of diabetes in the intervention group; for sleep duration groups 9–9.5 h and ≥10 h, the adjusted HRs (95% CI) were 1.10 (0.60–2.01) and 0.73 (0.34–1.56), respectively, compared with that in the reference group (7–8.5 h sleep). Lifestyle intervention resulted in similar improvement in body weight, insulin sensitivity, and immune mediator levels regardless of sleep duration. CONCLUSIONS Long sleep duration is associated with increased type 2 diabetes risk. Lifestyle intervention with the aim of weight reduction, healthy diet, and increased physical activity may ameliorate some of this excess risk.
Adverse Reactions to Allogeneic Whole Blood Donation by 16- and 17-Year-Olds
Authors: Anne F. Eder
Journal: JAMA (2008)

Context Donations by minors (16-and 17-year-olds) now account for approximately 8% of the whole blood collected by the American Red Cross, but young age and first-time donation status are known to be independent risk factors for donationrelated complications.Objective To evaluate adverse reactions to allogeneic whole blood donation by 16and 17-year-olds compared with older donors in American Red Cross blood centers.Design, Setting, and Participants Prospective documentation of adverse events among 16-and 17-year-old donors using standardized collection protocols, definitions, and reporting methods in 2006.Data were from 9 American Red Cross blood centers that routinely collect from 16-and 17-year-olds, a population that provides 80% of its donations at high school blood drives.Main Outcome Measures Rate of systemic (syncopal-type) and phlebotomyrelated donor complications per 10 000 collections. ResultsIn 2006, 9 American Red Cross regions collected 145 678 whole blood donations from 16-and 17-year-olds, 113 307 from 18-and 19-year-olds, and 1 517 460 from donors aged 20 years or older.Complications were recorded in 15 632 (10.7%), 9359 (8.3%), and 42 987 (2.8%) donations in each corresponding age group.In a multivariate logistic regression model, young age had the strongest association with complications (odds ratio [OR], 3.05; 95% confidence interval [CI], 2.52-3.69;PϽ.001), followed by first-time donation status (OR, 2.63; 95% CI, 2.24-3.09;PϽ.001) and female sex (OR, 1.87; 95% CI, 1.62-2.16;P Ͻ .001).Infrequent but medically relevant complications, in particular physical injury from syncope-related falls, were significantly more likely in 16-and 17-year-old donors (86 events; 5.9/10 000 collections) compared with 18-and 19-year-old donors (27 events; 2.4/10 000 collections; OR, 2.48; 95% CI, 1.61-3.82)or adults aged 20 years or older (62 events; 0.4/ 10 000 collections; OR, 14.46; 95% CI, 10.43 -20.04).Sixteen-year-old donors who experienced even a minor complication were less likely to return to donate within 12 months than 16-year-olds who experienced uncomplicated donations (52% vs 73% return rate; OR, 0.40; 95% CI, 0.36-0.44).Conclusions A higher incidence of donation-related complications and injury occurs among 16-and 17-year-old blood donors compared with older donors.The increasing dependence on recruiting and retaining young blood donors requires a committed approach to donor safety, especially at high school blood drives.
Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial
Authors: Gwenaelle Gravis, Karim Fizazi, Florence Joly, Stéphane Oudard, Franck Priou, Benjamin Esterni, Igor Latorzeff, Remy Delva, Ivan Krakowski, Brigitte Laguerre, Fréderic Rolland, Christine Théodore, Gael Deplanque, Jean Marc Ferrero, Damien Pouessel, Loïc Mourey, Philippe Beuzeboc, Sylvie Zanetta, Muriel Habibian, Jean François Berdah, Jerome Dauba, Marjorie Baciuchka, Christian Platini, Claude Linassier, Jean Luc Labourey, Jean Pascal Machiels, Claude El Kouri, Alain Ravaud, Etienne Suc, Jean Christophe Eymard, Ali Hasbini, Guilhem Bousquet, Michel Soulie
Journal: The Lancet Oncology (2013)