tbuckley/cabot-search huggingface dataset:
International Myeloma Working Group recommendations for global myeloma care
Authors: H Ludwig, J S Miguel, M A Dimopoulos, A Palumbo, R Garcia Sanz, R Powles, S Lentzsch, W Ming Chen, J Hou, A Jurczyszyn, K Romeril, R Hajek, E Terpos, K Shimizu, D Joshua, V Hungria, A Rodriguez Morales, D Ben-Yehuda, P Sondergeld, E Zamagni, B Durie
Journal: Leukemia (2013)
A dominant suppressive MHC class II haplotype interacting with autosomal genes controls autoantibody production and chronicity of arthritis
Authors: K. S. Nandakumar, A.-K. B. Lindqvist, R. Holmdahl
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To investigate the genetic control of chronic arthritis and collagen epitope specific antibody responses in an experimental model for rheumatoid arthritis. <h3>Methods</h3> The chronic collagen induced arthritis (CCIA) model was used, induced with collagen type II (CII) in mineral oil lacking mycobacterium in BALB/c (n=24), B10.Q (n=44), (BALB/c × B10.Q) F1 (n=85) and B10.Q × (BALB/c × B10.Q) N2 (n=684) mice. Genome-wide genotyping for 190 N2 mice was performed with extreme phenotypes: chronic arthritis that persisted for 4 months or non-affected. Statistical and linkage analysis were performed with R/qtl software using arthritis and serum subphenotypes. <h3>Results</h3> (BALB/c × B10.Q) F1 mice were highly prone to develop a chronic relapsing arthritis (66%), whereas both parental strains were relatively resistant: BALB/c (H-2<sup>d</sup>; 0%) and B10.Q (H-2<sup>q</sup>; 4.5%). CCIA experiments were performed on 684 mice backcrossed to B10.Q; 38% of the mice developed arthritis and more than half of them developed chronic arthritis phenotype. Genome-wide genotyping revealed mainly the major histocompatibility complex (MHC) locus that had an independent and dominant influence on the chronicity. Interestingly, the H2<sup>d</sup> allele had a dominant suppressive effect. This effect overrode the role of other loci as interaction analysis, after conditioning MHC, revealed additional loci, controlling arthritis and autoantibody phenotypes. <h3>Conclusions</h3> A dominant negative influence of specific MHC haplotype (H2<sup>d</sup>) on CCIA was identified. Further, loci controlling the autoantibody response to different CII epitopes were also identified, and it has been shown that these are dependent on MHC and non-MHC genes.
Measuring the Quality of Physician Practice by Using Clinical Vignettes: A Prospective Validation Study
Authors: John W. Peabody, Jeff Luck, Peter Glassman, Sharad Jain, Joyce Hansen, Maureen Spell, Martin Lee
Journal: Annals of Internal Medicine (2004)

Background: Worldwide efforts are under way to improve the quality of clinical practice. Most quality measurements, however, are poorly validated, expensive, and difficult to compare among sites. Objective: To validate whether vignettes accurately measure the quality of clinical practice by using a comparison with standardized patients (the gold standard method), and to determine whether vignettes are a more or less accurate method than medical record abstraction. Design: Prospective, multisite study. Setting: Outpatient primary care clinics in 2 Veterans Affairs medical centers and 2 large, private medical centers. Participants: 144 of 163 eligible physicians agreed to participate, and, of these, 116 were randomly selected to see standardized patients, to complete vignettes, or both. Measurements: Scores, expressed as the percentage of explicit quality criteria correctly completed, were obtained by using 3 methods. Results: Among all physicians, the quality of clinical practice as measured by the standardized patients was 73% correct (95% CI, 72.1% to 73.4%). By using exactly the same criteria, physicians scored 68% (CI, 67.9% to 68.9%) when measured by the vignettes but only 63% (CI, 62.7% to 64.0%) when assessed by medical record abstraction. These findings were consistent across all diseases and were independent of case complexity or physician training level. Vignettes also accurately measured unnecessary care. Finally, vignettes seem to capture the range in the quality of clinical practice among physicians within a site. Limitations: Despite finding variation in the quality of clinical practice, we did not determine whether poorer quality translated into worse health status for patients. In addition, the quality scores are based on measurements from 1 patient–provider interaction. As with all other scoring criteria, vignette criteria must be regularly updated. Conclusions: Vignettes are a valid tool for measuring the quality of clinical practice. They can be used for diverse clinical settings, diseases, physician types, and situations in which case-mix variation is a concern. They are inexpensive and easy to use. Vignettes are particularly useful for comparing quality among and within sites and may be useful for longitudinal evaluations of interventions intended to change clinical practice.
Combined Lifestyle Factors and Cardiovascular Disease Mortality in Chinese Men and Women
Authors: Andrew O. Odegaard, Woon-Puay Koh, Myron D. Gross, Jian-Min Yuan, Mark A. Pereira
Journal: Circulation (2011)

Lifestyle factors directly influence cardiovascular disease (CVD) risk, yet little research has examined the association of combined lifestyle factors with CVD mortality, especially in Asian populations.We examined the association of 6 combined lifestyle factors (dietary pattern, physical activity, alcohol intake, usual sleep, smoking status, and body mass index) with CVD mortality in 50 466 (44 056 without a history of diabetes mellitus, CVD, or cancer and 6410 with diabetes mellitus or history of clinical CVD) Chinese men and women in Singapore who were 45 to 74 years of age during enrollment in the Singapore Chinese Health Study in 1993 to 1998 and followed up through 2009. Each lifestyle factor was independently associated with CVD mortality. When combined, there was a strong, monotonic decrease in age- and sex-standardized CVD mortality rates with an increasing number of protective lifestyle factors. Relative to participants with no protective lifestyle factors, the hazard ratios of CVD mortality for 1, 2, 3, 4, and 5 to 6 protective lifestyle factors were 0.60 (95% confidence interval, 0.45-0.84), 0.50 (95% confidence interval, 0.38-0.67), 0.40 (95% confidence interval, 0.30-0.53), 0.32 (95% confidence interval, 0.24-0.43), and 0.24 (95% confidence interval, 0.17-0.34), respectively, among those without a history of diabetes mellitus, CVD, or cancer (P for trend <0.0001). A parallel graded inverse association was observed in participants with a history of CVD or diabetes mellitus at baseline. Results were consistent for coronary heart disease and cerebrovascular disease mortality.An increasing number of protective lifestyle factors is associated with a marked decreased risk of coronary heart disease, cerebrovascular disease, and overall CVD mortality in Chinese men and women.
Induction of Centrosome Amplification during Arsenite-Induced Mitotic Arrest in CGL-2 Cells
Authors: Ling-Huei Yih, Yun-Yu Tseng, Yi-Chen Wu, Te-Chang Lee
Journal: Cancer Research (2006)

Abstract Arsenite-induced mitotic abnormalities result in mitotic death in several cancer cell lines. However, how arsenite induces these effects is not known. We have previously shown that arsenite induces mitotic arrest, mitotic abnormalities, and mitotic death in CGL-2 cells. To further delineate the mechanism of action of arsenite, we examined its effect on centrosome duplication and the possible link between centrosome dysregulation and arsenite-induced mitotic death. Immunofluorescence staining of γ-tubulin revealed that centrosome amplification was induced in arsenite-arrested mitotic cells but not in nocodazole-arrested cells. When S phase–enriched cells were treated with arsenite, they progressed into and arrested at mitosis and then formed supernumerary centrosomes. A further increase in arsenite-induced centrosome amplification was seen during the prolonged mitotic arrest. The arsenite-induced supernumerary centrosomes might result from uneven fragmentation of centrosome, overexpression of pericentriolar materials, and inhibition of centrosomal coalescence during mitosis. Furthermore, termination of mitotic arrest by treatment of arsenite-arrested mitotic cells with cyclin-dependent kinase 1 inhibitors or by suppression of spindle checkpoint function by small interfering RNA–mediated silencing of BubR1 or Mad2 markedly reduced the induction of centrosome amplification and mitotic death in arsenite-treated cells. These results indicate that centrosome amplification is induced in arsenite-arrested mitotic CGL-2 cells in a spindle checkpoint-dependent manner and is involved in the induction of arsenite-induced mitotic death. (Cancer Res 2006; 66(4): 2098-106)
Author response: oral contraceptives and Crohn’s disease
Authors: Hamed Khalili, Andrew T Chan
Journal: Gut (2014)

<b>Background:</b> Moscow city has one of the lowest levels of TB mortality rate in the Russia (2.9 per 100K, 2014) which is decreasing annually. To further decrease of TB mortality, the Moscow TB program includes activities targeted to the various components of indicator, depend on mortality among TB patients with: 1) different status of inhabitancy before death, including permanent residents (PR), homeless (HL), arrived from other Russian regions (RF) and migrants (MG), and 2) different status of TB death registration, relatively to time of TB notification: postmortem detected TB (PM), died before 1 month (D1M) or later 1 month after TB notification. <b>Method:</b> Retrospective study of TB mortality components, defined by statuses of inhabitancy and TB registration, was conducted, based on data about 1928 and 1156 cases of death from TB, registered in Moscow in two comparable periods: A - 2007-2009 and B - 2012-2014, which characterized the time before and after certain management reforms in TB control in the city. <b>Results:</b> The B period, in comparison with A, were mainly characterized by: - increasing of proportion not-PR among TB death cases: RF - from 6.9% (95% CI 5.8-8.1) to 13.6% (11.7-15.7), MG - 2.7% (2.1-3.6) to 6.3% (5.0-7.9), p&lt;0.01, and HL - from 22.7% to 23%, p&gt;0.05; - increasing of PM and D1M among PR from 26.3% (23.9-28.9) to 34.8% (31.2-38.6), p&lt;0.05; - decreasing of the proportion of TB deaths under 45 years both between PR and not PR cases: from 31.1% to 26.7% and from 56.8% to 50.4%, accordingly, p&lt;0.05. <b>Conclusions:</b> Activities for decrease of TB mortality have to be specified according to particularities of TB mortality components, and taking into account of possibilities of them control.
Catecholaminergic Modulation of Corticotropin-Releasing Factor and Adrenocorticotropin Secretion
Authors: PAUL M. PLOTSKY, EMMETT T. CUNNINGHAM, ERIC P. WIDMAIER
Journal: Endocrine Reviews (1989)

THE STABILITY of the "milieu interieur" was first recognized by Claude Bernard (1), and this concept was extended by Walter Cannon (2), who coined the term homeostasis to denote the condition of relative constancy of the internal environment. The hypothalamic-pituitary-adrenal axis (HPA) and the autonomic nervous system are recognized as primary effector systems which serve to minimize excursions from the homeostatic state and to restore a relative equilibrium in response to disturbances (3, 4). Many of the physiological adjustments accompanying sympathetic activation complement those brought about by glucocorticoid secretion. Indeed, the responsiveness and physiological consequences of activation of these two systems are so inter-twined as to have generated the hypothesis that activation of the HPA is evoked by sympathoadrenomedullary activation (5, 6). Thus an organism's response to an actual or perceived challenge (stressor) usually involves activation of both the HPA and the sympathetic-adrenomedullary system (7–9). Interest in the central neurochemical regulation of the HPA and autonomic nervous system focused upon the catecholamines with the demonstration that norepinephrine (NE) was present within neurons of the brain (10). The possibility that central catecholamines might modulate HPA function (11–15) received morphological support after the mapping of central catecholaminergic projections (16–21).
Book: Matrons, Medics and Maladies: Edinburgh Royal Infirmary in the 1840s The Edinburgh City Hospital
Authors: P D. Kumar
Journal: BMJ (2000)

Bill Yule Tuckwell Press, £12.99, pp 248 ISBN: 1 86232 091 8 Rating: ![Graphic][1]</img>![Graphic][2]</img> James A Gray Tuckwell Press, £20, pp 488 ISBN 1 86232 096 9 Rating: ![Graphic][3]</img>![Graphic][4]</img> These two books tell the story of medicine in the city of Edinburgh, spanning about 160 years. Bill Yule's Matrons, Medics and Maladies is pleasantly formatted with boxed case histories and hand drawn caricatures of the late 19th century lifestyle. The notes of the house officers in the 1850s show … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Lactobacillus pneumonia in a patient with oesophageal carcinoma
Authors: JM Querol, F Manresa, J Izquierdo, M Cisnal
Journal: European Respiratory Journal (1989)

We report a case of necrotizing pneumonia caused by Lactobacillus secondary to a tracheo-oesophageal fistula created by an oesophageal carcinoma. We emphasize the presence of resistance of Lactobacillus to clindamycin and cotrimoxazole, previously reported to be effective.
Chronic AT1 receptor blockade and angiotensin-converting enzyme (ACE) inhibition in (CHF 146) cardiomyopathic hamsters: effects on cardiac hypertrophy and survival
Authors: N Bastien
Journal: Cardiovascular Research (1999)

Objective: We have reported that angiotensin II AT1 receptors are upregulated and that there are no AT2 receptors in the ventricles of cardiomyopathic hamsters. Since the upregulation was present even when no histological lesions were detectable, these results suggested that angiotensin II plays a role in the genesis/maintenance of this pathology. A survival study was conducted to compare the effects of an angiotensin II AT1 receptor antagonist, losartan (L), to those of a placebo (P). Since the angiotensin-converting enzyme (ACE) inhibitor quinapril (Q) has been shown to have beneficial effects in this animal model, a Q group was included. Methods: Male Syrian cardiomyopathic hamsters (CHF 146, n=360) were orally administered P, low- (30 mg/kg/day) or high-dose (100 mg/kg/day) L, or Q (100 mg/kg/day), starting at day 50 of life. Inbred control hamsters (CHF 148, n=180) were treated with P or L (100 mg/kg/day) as controls. Animals were sacrificed at intervals to evaluate cardiac hypertrophy. Kaplan–Meier analysis was performed to assess differences in survival. Results: High-dose L had no effects on the survival of control hamsters. There was an unexpected dose-dependent decrease in the survival of cardiomyopathics treated with L (low-dose, P=0.14; high-dose, P=0.0015) compared to an increase with Q (P=0.0003). Cardiac hypertrophy compared to P was increased with L but significantly decreased with Q in cardiomyopathics. Conclusions: In this model, losartan did not improve survival compared to placebo and quinapril and, if anything, increased mortality. Our results suggest that AT1 receptor antagonists and ACE inhibitors are not necessarily equivalent or interchangeable in terms of their effects on cardiac hypertrophy and survival in selected progressive heart failure models.
Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain
Authors: A Akbar, Y Yiangou, P Facer, J R F Walters, P Anand, S Ghosh
Journal: Gut (2008)

<h3>Objective:</h3> The capsaicin receptor TRPV1 (transient receptor potential vanilloid type-1) may play an important role in visceral pain and hypersensitivity states. In irritable bowel syndrome (IBS), abdominal pain is a common and distressing symptom where the pathophysiology is still not clearly defined. TRPV1-immunoreactive nerve fibres were investigated in colonic biopsies from patients with IBS, and this was related to abdominal pain. <h3>Methods:</h3> Rectosigmoid biopsies were collected from 23 IBS patients fulfilling Rome II criteria, and from 22 controls. Abdominal pain scores were recorded using a validated questionnaire. TRPV1-, substance P- and neuronal marker protein gene product (PGP) 9.5-expressing nerve fibres, mast cells (c-kit) and lymphocytes (CD3 and CD4) were quantified, following immunohistochemistry with specific antibodies. The biopsy findings were related to the abdominal pain scores. <h3>Results:</h3> A significant 3.5-fold increase in median numbers of TRPV1-immunoreactive fibres was found in biopsies from IBS patients compared with controls (p&lt;0.0001). Substance P-immunoreactive fibres (p = 0.01), total nerve fibres (PGP9.5) (p = 0.002), mast cells (c-kit) (p = 0.02) and lymphocytes (CD3) (p = 0.03) were also significantly increased in the IBS group. In multivariate regression analysis, only TRPV1-immuno-reactive fibres (p = 0.005) and mast cells (p = 0.008) were significantly related to the abdominal pain score. <h3>Conclusions:</h3> Increased TRPV1 nerve fibres are observed in IBS, together with a low-grade inflammatory response. The increased TRPV1 nerve fibres may contribute to visceral hypersensitivity and pain in IBS, and provide a novel therapeutic target.
Serum ferritin concentration and transferrin saturation before liver transplantation predict decreased long-term recipient survival
Authors: Tobias J. Weismüller, Gabriele I. Kirchner, Marcus N. Scherer, Ahmed A. Negm, Andreas A. Schnitzbauer, Frank Lehner, Jürgen Klempnauer, Hans J. Schlitt, Michael P. Manns, Christian P. Strassburg
Journal: Hepatology (2010)

Abstract Serum ferritin (SF) concentration is a widely available parameter used to assess iron homeostasis. It has been described as a marker to identify high-risk patients awaiting liver transplantation (LT) but is also elevated in systemic immune-mediated diseases, metabolic syndrome, and in hemodialysis where it is associated with an inferior prognosis. This study analyzed whether SF is not only a predictor of liver-related mortality prior to LT but also an independent marker of survival following LT. In a dual-center, retrospective study, a cohort of 328 consecutive first-LT patients from Hannover Medical School, Germany (2003-2008, follow-up 1260 days), and 82 consecutive LT patients from Regensburg University Hospital, Germany (2003-2007, follow-up 1355 days) as validation cohort were analyzed. In patients exhibiting SF ≥365 μg/L versus &lt;365 μg/L prior to LT, 1-, 3-, and 5-year post-LT survival was 73.3% versus 81.1%, 64.4% versus 77.3%, and 61.1% versus 74.4%, respectively (overall survival P = 0.0097), which was confirmed in the validation cohort (overall survival of 55% versus 83.3%, P = 0.005). Multivariate analyses identified SF ≥365 μg/L combined with transferrin saturation (TFS) &lt;55%, hepatocellular carcinoma, and the survival after LT (SALT) score as independent risk factors for death. In patients with SF concentrations ≥365 μg/L and TFS &lt;55%, overall survival was 54% versus 74.8% in the remaining group ( P = 0.003). In the validation cohort, it was 28.6% versus 72% ( P = 0.017), respectively. Conclusion: SF concentration ≥365 μg/L in combination with TFS &lt;55% before LT is an independent risk factor for mortality following LT. Lower TFS combined with elevated SF concentrations indicate that acute phase mechanisms beyond iron overload may play a prognostic role. SF concentration therefore not only predicts pre-LT mortality but also death following LT. (Hepatology 2011;)
High Thioredoxin Expression Is Associated with Resistance to Docetaxel in Primary Breast Cancer
Authors: Seung Jin Kim, Yasuo Miyoshi, Tetsuya Taguchi, Yasuhiro Tamaki, Hajime Nakamura, Junji Yodoi, Kikuya Kato, Shinzaburo Noguchi
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Thioredoxin overexpression is suggested to be associated with resistance to several chemotherapeutic agents in vitro. In the present study, it has been studied whether or not high thioredoxin expression is associated with resistance to docetaxel therapy in breast cancer patients. Patients and Methods: Sixty-three primary breast cancer patients were treated with docetaxel (60 mg/m2, q3w) for four cycles in the neoadjuvant setting. Expression of thioredoxin, estrogen receptor (ER), p53, BRCA-1, and Bcl-2 in tumor tissues obtained before docetaxel therapy was studied by immunohistochemistry (thioredoxin, p53, BRCA-1, and Bcl-2) and enzyme immunoassay (ER), and relationship of expression of these biomarkers with a pathologic response was investigated. Results: There was no significant correlation between the expression of p53, BRCA-1, or Bcl-2 and a response to docetaxel. However, tumors with high thioredoxin expression showed a significantly lower response rate (0%) than those with low thioredoxin expression (30.6%; P = 0.018) and ER-negative tumors showed a significantly higher response rate (32.4%) than ER-positive tumors (10.7%; P = 0.043). Thioredoxin expression significantly increased after docetaxel therapy (mean, 56.1%) as compared with that before docetaxel therapy (mean, 28.6%; P &amp;lt; 0.0001) but there was no significant association between the extent of increase in thioredoxin expression and response. Conclusion: High thioredoxin expression in prechemotherapy tumor samples, but not the increase in thioredoxin expression induced by docetaxel, is associated with resistance to docetaxel in breast cancer. Thioredoxin and ER might be clinically useful in the prediction of a response to docetaxel.
STUDIES ON A PROTEOLYTIC ENZYME IN HUMAN PLASMA
Authors: Oscar D. Ratnoff
Journal: The Journal of Experimental Medicine (1952)

Calcium ions accelerated the activation of the proteolytic enzyme of plasma from its precursor in the globulin fraction. Calcium did not appear to potentiate fibrinolysis by active bovine or human plasma proteolytic enzyme, nor did it accelerate the activation of the precursor of this enzyme by chloroform or by streptokinase. Experiments with partially purified plasma proteolytic enzyme suggested that the acceleratory effect of calcium was mediated indirectly. Since the concentration of calcium which was effective was comparable to that present in plasma, it is possible that the phenomena reported are of biological significance.