tbuckley/cabot-search huggingface dataset:
How to diagnose axial spondyloarthritis early
Authors: M Rudwaleit
Journal: Annals of the Rheumatic Diseases (2004)

Chronic low back pain (LBP), the leading symptom of ankylosing spondylitis (AS) and undifferentiated axial spondyloarthritis (SpA), precedes the development of radiographic sacroiliitis, sometimes by many years.To assign disease probabilities and to develop an algorithm to help in the early diagnosis of axial SpA.Axial SpA comprises AS and undifferentiated SpA with predominant axial involvement. Clinical features include inflammatory back pain (IBP), alternating buttock pain, enthesitis, arthritis, dactylitis, acute anterior uveitis, a positive family history, psoriasis, inflammatory bowel disease, and good response to NSAIDs. Associated laboratory findings include raised acute phase reactions, HLA-B27 association, and abnormalities on skeletal imaging. Sensitivities, specificities, and likelihood ratios (LRs) of these parameters were determined from published studies. A 5% prevalence of axial SpA among patients with chronic LBP was used. The probability of the presence of axial SpA, depending on the presence or absence of the above clinical features of SpA, was determined. A probability of > or = 90% was used to make a diagnosis of axial SpA.The presence of inflammatory back pain features increased the probability of axial SpA from the background 5% prevalence to 14%. The presence of 2-3 SpA features was necessary to increase the probability of axial SpA to 90%. The highest LRs were obtained for HLA-B27 and MRI. Diagnostic algorithms to be used in daily practice were suggested.This approach can help clinicians to diagnose with a high degree of confidence axial SpA at an early stage in patients with IBP who lack radiographic sacroiliitis.
Prognostic and Predictive Factors for Breast Cancer: Translating Technology to Oncology
Authors: Daniel F. Hayes
Journal: Journal of Clinical Oncology (2005)

In medical school, we were taught that clinical decision making requires a consideration of the balance of benefits and risks to provide optimal care for the patient. As we train and then practice medicine, understanding and conveying the risks and benefits of a given treatment are constantly refined by personal experience, interactions with patients, our colleagues and experts in the field, and availability of evidence derived from well-designed and -analyzed clinical trials. Managementofpatientswithbreastcancerisagreatillustration of this complex and iterative process. In the preventive, primary care, and adjuvant settings, decisions are made for individuals based on our hope that, in general, we help more patients than we harm. For women with relatively low risk of developing metastatic disease, such as those with high-risk but benign breast findings or women withsmall,hormone-dependent,node-negativebreastcancers,weneveractuallyknowifwehavehelpedanindividual patient. Indeed, a majority of such patients will not recur despite our care, not because of it. On the other hand, treatment of patients with metastatic disease, although ultimately almost always associated with a tragic outcome, canbeextraordinarilyrewarding.Inthissetting,wecanobserve a highly symptomatic patient regain her quality of life as a clear-cut consequence of judiciously applied local and systemic therapies, including endocrine and chemotherapiesand,morerecently,noveltherapysuchastrastuzumab. Arguably, prognostic and predictive factors have been of value to help individualize therapy of breast cancer more than for any other solid tumors. The substantial benefits of adjuvant systemic therapy have been well documented for over 30 years. 1,2 Furthermore, it is a disease for which disparate therapies are beneficial in different subgroups. For example, it appears that adjuvant chemotherapy reduces the annual odds of recurrence by approximately 25% to 30% for all patients. 2 In those with an initially poor prog
Frequency of Driver Mutations in Lung Adenocarcinoma from Female Never-Smokers Varies with Histologic Subtypes and Age at Diagnosis
Authors: Yang Zhang, Yihua Sun, Yunjian Pan, Chenguang Li, Lei Shen, Yuan Li, Xiaoyang Luo, Ting Ye, Rui Wang, Haichuan Hu, Hang Li, Lei Wang, William Pao, Haiquan Chen
Journal: Clinical Cancer Research (2012)

Our previous study revealed that 90% [47 of 52; 95% confidence interval (CI), 0.79-0.96] of Chinese never-smokers with lung adenocarcinoma harbor known oncogenic driver mutations in just four genes EGFR, ALK, HER2, and KRAS. Here, we examined the status of known driver mutations specifically in female never-smokers with lung adenocarcinoma.Tumors were genotyped for mutations in EGFR, KRAS, ALK, HER2, and BRAF. Data on age, stage, tumor differentiation, histologic subtypes, and molecular alterations were recorded from 349 resected lung adenocarcinomas from female never-smokers. We further compared the clinicopathologic parameters according to mutational status of these genes.Two hundred and sixty-six (76.2%) tumors harbored EGFR mutations, 16 (4.6%) HER2 mutations, 15 (4.3%) EML4-ALK fusions, seven (2.0%) KRAS mutations, and two (0.6%) BRAF mutations. In univariate analysis, patients harboring EGFR mutations were significantly older (P < 0.001), whereas patients harboring HER2 mutations were significantly younger (P = 0.036). Higher prevalence of KRAS (P = 0.028) and HER2 (P = 0.021) mutations was found in invasive mucinous adenocarcinoma (IMA). The frequency of EGFR mutations was positively correlated with acinar predominant tumors (P = 0.002). Multivariate analysis revealed that older age at diagnosis (P = 0.013) and acinar predominant subtype (P = 0.005) were independent predictors of EGFR mutations. Independent predictors of HER2 mutations included younger age (P = 0.030) and IMA (P = 0.017). IMA (P = 0.006) and poor differentiation (P = 0.028) were independently associated with KRAS mutations.The frequency of driver mutations in never-smoking female lung adenocarcinoma varies with histologic subtypes and age at diagnosis. These data have implications for both clinical trial design and therapeutic strategies.
Effect of β2-adrenergic receptor polymorphism on response to longacting β2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial
Authors: Michael E Wechsler, Susan J Kunselman, Vernon M Chinchilli, Eugene Bleecker, Homer A Boushey, William J Calhoun, Bill T Ameredes, Mario Castro, Timothy J Craig, Loren Denlinger, John V Fahy, Nizar Jarjour, Shamsah Kazani, Sophia Kim, Monica Kraft, Stephen C Lazarus, Robert F Lemanske, Amy Markezich, Richard J Martin, Perdita Permaul, Stephen P Peters, Joe Ramsdell, Christine A Sorkness, E Rand Sutherland, Stanley J Szefler, Michael J Walter, Stephen I Wasserman, Elliot Israel
Journal: The Lancet (2009)
Serum granulocyte colony‐stimulating factor in patients with repeated infections
Authors: Mutsumi Kawakami, Hisashi Tsutsumi, Toshiro Kumakawa, Makiko Hirai, Shinichiro Kurosawa, Mayumi Mori, Masafumi Fukushima
Journal: American Journal of Hematology (1992)

Abstract We have already reported significant elevation of serum granulocyte colony‐stimulating factor (G‐CSF) in the acute phase of infection. In this study, we compared the responses to infection between patients with frequently repeated infection (repeaters) and others (non‐repeaters). We examined the clinical data and serum G‐CSF levels in 48 patients with acute infections. Serum G‐CSF levels were significantly lower in repeaters than in non‐repeaters (197.7 ± 370.0 vs. 1014.1 ± 924.4 pg/ml. P &lt; 0.001). There were no significant differences in age, serum total protein, or cholinesterase between the groups, but serum albumin was significantly lower in repeaters than in non‐repeaters (2.87 ± 0.5 vs. 3.31 ± 0.4 g/dl. P &lt; 0.005). It is suggested that administration of recombinant G‐CSF may be useful for patients with repeated infections. © 1992 Wiley‐Liss, Inc.
Bedside Monitoring to Adjust Antiplatelet Therapy for Coronary Stenting
Authors: Jean-Philippe Collet, Thomas Cuisset, Grégoire Rangé, Guillaume Cayla, Simon Elhadad, Christophe Pouillot, Patrick Henry, Pascal Motreff, Didier Carrié, Ziad Boueri, Loic Belle, Eric Van Belle, Hélène Rousseau, Pierre Aubry, Jacques Monségu, Pierre Sabouret, Stephen A. O'Connor, Jérémie Abtan, Mathieu Kerneis, Christophe Saint-Etienne, Olivier Barthélémy, Farzin Beygui, Johanne Silvain, Eric Vicaut, Gilles Montalescot
Journal: New England Journal of Medicine (2012)

Patients' responses to oral antiplatelet therapy are subject to variation. Bedside monitoring offers the opportunity to improve outcomes after coronary stenting by individualizing therapy.
Stage IV sarcoidosis: comparison of survival with the general population and causes of death
Authors: A. Nardi, P-Y. Brillet, P. Letoumelin, F. Girard, M. Brauner, Y. Uzunhan, J-M. Naccache, D. Valeyre, H. Nunes
Journal: European Respiratory Journal (2011)

The objectives of this study were to compare the survival of sarcoid patients with pulmonary fibrosis with that of the general population and to determine the causes of death and the incidence of evolutive complications. This retrospective cohort included 142 sarcoid patients in radiographic stage IV (74 males; mean ± SD age 48.1 ± 12 yrs). Their survival was compared with that of the general French population, matched for the year and age at diagnosis of stage IV disease, sex and length of follow-up. Expected survival probabilities were calculated year-by-year on the basis of probabilities provided by official demographic data for France. Survival curves were based on the Kaplan-Meier method and compared using the log-rank test. During the follow-up period (7.1 ± 4.8 yrs), pulmonary hypertension (PH) was observed in 29.7% of cases and aspergilloma in 11.3%. Long-term oxygen therapy was required in 12%. Survival was 84.1% at 10 yrs, which was worse than for the general population (p = 0.013). 16 (11.3%) patients died from the following causes: refractory PH (n = 5), chronic respiratory insufficiency (n = 4), acute respiratory insufficiency (n = 2), haemoptysis due to aspergilloma (n = 1), heart sarcoidosis (n = 1), nocardiosis (n = 1) and unknown causes (n = 2). Survival is significantly decreased in stage IV patients. 75% of fatalities are directly attributable to respiratory causes.
Early cellular events in a systemic graft-vs.-host reaction. II. Autoradiographic estimates of the frequency of donor lymphocytes which respond to each Ag-B-determined antigenic complex.
Authors: W L Ford, S J Simmonds, R C Atkins
Journal: The Journal of Experimental Medicine (1975)

A graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain (AO) lymphocytes into irradiated (AO times HO)F1 or (AO times DA)F1 hybrids. The proportion of donor T cells which had responded to the F1 hybrid antigens within 24 h was estimated by two methods. (a) Donor lymphocytes were labeled with [3H]uridine in vitro before injection. The proportion of labeled cells which had morphologically transformed in the recipient's spleen was 17-19%. In both series of experiments syngeneic transfers were performed in which case the proportion of transformed cells was 1-2.4%. A similar low proportion was found after parental to F1 transfer in a non-Ag-B strain combination. These figures were used to calculate the frequency of responding cells in the injected population given three additional pieces of information: (a) the extent of selection in the spleen which transformed the estimate to 4.5%-6.0% responders; (b) division of donor cells was shown to be negligible under the conditions of the experiment; and (c) the nonspecific recruitment of lymphocytes was shown to be negligible. A speculative model of antigen recognition by T cells which accounts for the high proportion of responders is outlined.
Serum hepatocyte growth factor as an index of extensive catabolism of patients awaiting liver transplantation
Authors: C Miki, A D Mayer, J A C Buckels, K Iriyama, H Suzuki, P McMaster
Journal: Gut (1999)

Whole body catabolism as the result of intrahepatic metabolic derangement is common in liver transplant candidates. However, individual nutritional assessment parameters lack sensitivity and specificity in determining energy status of these patients. Recently, serum hepatocyte growth factor (HGF) has been shown to reflect the recovery of hepatic energy metabolism after liver transplantation.The relation between preoperative levels of serum HGF and metabolic variables was investigated to clarify the clinical value of measuring HGF in evaluations of the catabolism.Blood samples were obtained from 30 liver transplant recipients, and biopsy specimens were taken from each recipient's rectus muscle and the explanted liver. Preoperative serum concentration of HGF was determined. Whole body energy metabolism was assessed by measuring glycogen contents of biopsy specimens and plasma or serum levels of glucose, insulin, total ketone bodies, total carnitine, and amino acids.Serum HGF concentration was elevated in 22 of 30 patients and correlated with the Child-Pugh score. It showed a negative association with muscle glycogen content, and a positive correlation with serum levels of glucose, total carnitine, and total ketone bodies. Patients with elevated serum HGF concentrations had higher preoperative plasma levels of aromatic amino acids and branched chain amino acids, associated with lower branched chain to aromatic amino acid ratios.The elevated serum concentration of HGF in liver transplant candidates reflected inhibition of peripheral glucose storage, enhanced lipid oxidation, and increased peripheral release of branched chain amino acids, and thus extensive energy catabolism.
Fatty acid bile acid conjugates (FABACs)---New molecules for the prevention of cholesterol crystallisation in bile
Authors: T Gilat, G J Somjen, Y Mazur, A Leikin-Frenkel, R Rosenberg, Z Halpern, FM Konikoff
Journal: Gut (2001)

Cholesterol gall stones are a frequent disease for which at present surgery is the usual therapy. Despite the importance of bile acids it has become evident that phospholipids are the main cholesterol solubilisers in bile. Even phospholipid components, such as fatty acids, have anticrystallising activity.To synthesise fatty acid bile acid conjugates (FABACs) and study their effects on cholesterol crystallisation in bile in vitro and in vivo.FABACs were prepared by conjugation of cholic acid at position 3 with saturated fatty acids of variable chain length using an amide bond. Cholesterol crystallisation and its kinetics (crystal observation time, crystal mass) were studied in model bile, pooled enriched human bile, and fresh human bile using FABACs with saturated fatty acids of varying chain length (C-6 to C-22). Absorption of FABACs into blood and bile was tested in hamsters. Prevention of biliary cholesterol crystallisation in vivo was tested in hamsters and inbred mice.FABACs strongly inhibited cholesterol crystallisation in model as well as native bile. The FABACs with longer acyl chains (C-16 to C-22) were more effective. At a concentration of 5 mM, FABACs almost completely inhibited cholesterol crystallisation in fresh human bile for 21 days. FABACs were absorbed and found in both portal and heart blood of hamsters. Levels in bile were 2-3 times higher than in blood, indicating active secretion. Appreciable levels were found in the systemic circulation 24-48 hours after a single administration. Ingested FABACs completely prevented the formation of cholesterol crystals in the gall bladders of hamsters and mice fed a lithogenic diet.FABACs are potent inhibitors of cholesterol crystallisation in bile. They are absorbed and secreted into bile and prevent the earliest step of cholesterol gall stone formation in animals. These compounds may be of potential use in cholesterol gall stone disease in humans.
At risk or not at risk? A meta‐analysis of the prognostic accuracy of psychometric interviews for psychosis prediction
Authors: Paolo Fusar‐Poli, Marco Cappucciati, Grazia Rutigliano, Frauke Schultze‐Lutter, Ilaria Bonoldi, Stefan Borgwardt, Anita Riecher‐Rössler, Jean Addington, Diana Perkins, Scott W. Woods, Thomas H. McGlashan, Jimmy Lee, Joachim Klosterkötter, Alison R. Yung, Philip McGuire
Journal: World Psychiatry (2015)

An accurate detection of individuals at clinical high risk (CHR) for psychosis is a prerequisite for effective preventive interventions. Several psychometric interviews are available, but their prognostic accuracy is unknown. We conducted a prognostic accuracy meta‐analysis of psychometric interviews used to examine referrals to high risk services. The index test was an established CHR psychometric instrument used to identify subjects with and without CHR (CHR+ and CHR−). The reference index was psychosis onset over time in both CHR+ and CHR− subjects. Data were analyzed with MIDAS (STATA13). Area under the curve (AUC), summary receiver operating characteristic curves, quality assessment, likelihood ratios, Fagan's nomogram and probability modified plots were computed. Eleven independent studies were included, with a total of 2,519 help‐seeking, predominately adult subjects (CHR+: N=1,359; CHR−: N=1,160) referred to high risk services. The mean follow‐up duration was 38 months. The AUC was excellent (0.90; 95% CI: 0.87‐0.93), and comparable to other tests in preventive medicine, suggesting clinical utility in subjects referred to high risk services. Meta‐regression analyses revealed an effect for exposure to antipsychotics and no effects for type of instrument, age, gender, follow‐up time, sample size, quality assessment, proportion of CHR+ subjects in the total sample. Fagan's nomogram indicated a low positive predictive value (5.74%) in the general non‐help‐seeking population. Albeit the clear need to further improve prediction of psychosis, these findings support the use of psychometric prognostic interviews for CHR as clinical tools for an indicated prevention in subjects seeking help at high risk services worldwide.
Induction and differential regulation of bee venom phospholipase A2–specific human IgE and IgG4 antibodies in vitro requires allergen-specific and nonspecific activation of T and B cells☆, ☆☆, ★, ★★
Authors: C AKDIS, T BLESKEN, M AKDIS, S ALKAN, B WUTHRICH, C HEUSSER, K BLASER
Journal: Journal of Allergy and Clinical Immunology (1997)
A pilot study to determine the effect of trunk and hip focused neuromuscular training on hip and knee isokinetic strength
Authors: Gregory Myer, Jensen Brent, Kevin Ford, Timothy Hewett
Journal: British Journal of Sports Medicine (2008)

Objectives: The objective was to determine the effect of trunk focused neuromuscular training (TNMT) on hip and knee strength. The hypothesis was that TNMT would increase standing isokinetic hip abduction, but not knee flexion/extension, strength. Methods: Twenty-one (TMNT n=14: 15.4 ± 1.4 yrs, 170.5 ± 5.0 cm, 64.1 ± 8.5 kg; CTRL n =7: 16.0 ± 1.7 yrs, 173.4 ± 10.0 cm, 63.9 ± 5.3 kg; p&gt;0.05) high school female volleyball players were recruited to participate in this study. Fourteen participated in TNMT protocol (2 X/wk) over a ten week period in addition to their standard off-season strength training (1X/wk). Standing isokinetic hip abduction strength and seated knee flexion/extension strength were measured prior to and after TNMT. Results: A significant interaction of group and time was observed. The TNMT group increased isokinetic hip abduction strength approximately 15% (13.5% dominant leg: 46.6 ± 10.1 to 52.9 ± 11.4 ft-lbs and 17.1% in the non-dominant leg: 46.1 ± 10.4 to 54.0 ± 10.7 ft-lbs; p = 0.01). There was no difference in the control group in pre- versus post-test measures. Post-test results also indicated no effect of TNMT on isokinetic knee extension (p=0.57) or knee flexion (p=0.57) strength. Conclusions: Ten weeks of TNMT increased standing hip abduction strength in female athletes. Increased hip abduction strength and recruitment may improve the ability of female athletes to increase control of lower extremity alignment and decrease loads resulting from increased trunk displacement during sports activities.
The effects of iron deficiency on the respiratory function and cytochrome content of rat heart mitochondria.
Authors: L Blayney, R Bailey-Wood, A Jacobs, A Henderson, J Muir
Journal: Circulation Research (1976)

We have examined the effects of total body iron deficiency on the function of mitochondria isolated from rat hearts. Male Wistar rats were weaned at 21 days and divided into an experimental iron-deficient group and a control group. Both groups received identical diet but an iron supplement (180 mg of ferrous sulfate per kg of diet) was added for the control group. Rats were studied at 7 and 14 weeks. Iron-deficient rats weighed less than controls but showed significantly increased ventricle to body weight ratio at both 7 and 14 weeks, indicating relative cardiac hypertrophy. Isolated mitochondrial fractions from iron-deficient and control rats contained similar proportions of whole homogenate protein and succinic cytochrome c reductase activity, indicating that the fractions isolated from the experimental and control rats were comparable. In iron-deficient rats NADH cytochrome c reductase, succinic cytochrome c reductase, succinic dehydrogenase, and NADH ferricyanide oxidoreductase activities were all significantly reduced at 7 and 14 weeks. Cytochrome c oxidase activity was significantly reduced only at 14 weeks as were the concentrations of cytochromes a3, c1, and b. The rate of oxygen uptake by mitochondria was significantly lower at both 7 and 14 weeks but the P/O ratio was unaltered. We conclude that iron deficiency is associated with impairment of myocardial mitochondrial electron transport.
A Randomized Phase III Multicenter Trial of Customized Chemotherapy Versus Standard of Care for 1St Line Treatment of Elderly Patients with Advanced Non-Small-Cell Lung Cancer (Nsclc): the Elderly Patient Individualized Chemotherapy (Epic) Trial
Authors: T. Vavala, S. Novello, F. Grossi, A. Misino, D. Cortinovis, G. Valmadre, G. Meoni, O. Caffo, A. Follador, A. Bearz, P. Trenta, V. Gregorc, C. Defferrari, L. Cordero, I. Colantonio, V. Torri, V. Monica, M. Papotti, G. Scagliotti
Journal: Annals of Oncology (2014)