tbuckley/cabot-search huggingface dataset:
Effect of statins on atrial fibrillation: collaborative meta-analysis of published and unpublished evidence from randomised controlled trials
Authors: K. Rahimi, J. Emberson, P. McGale, W. Majoni, A. Merhi, F. W. Asselbergs, V. Krane, P. W. Macfarlane
Journal: BMJ (2011)

<b>Objective</b> To examine whether statins can reduce the risk of atrial fibrillation. <b>Design</b> Meta-analysis of published and unpublished results from larger scale statin trials, with comparison of the findings against the published results from smaller scale or shorter duration studies. <b>Data sources</b> Medline, Embase, and Cochrane's CENTRAL up to October 2010. Unpublished data from longer term trials were obtained through contact with investigators. <b>Study selection</b> Randomised controlled trials comparing statin with no statin or comparing high dose versus standard dose statin; all longer term trials had at least 100 participants and at least six months' follow-up. <b>Results</b> In published data from 13 short term trials (4414 randomised patients, 659 events), statin treatment seemed to reduce the odds of an episode of atrial fibrillation by 39% (odds ratio 0.61, 95% confidence interval 0.51 to 0.74; P&lt;0.001), but there was significant heterogeneity (P&lt;0.001) between the trials. In contrast, among 22 longer term and mostly larger trials of statin versus control (105 791 randomised patients, 2535 events), statin treatment was not associated with a significant reduction in atrial fibrillation (0.95, 0.88 to 1.03; P=0.24) (P&lt;0.001 for test of difference between the two sets of trials). Seven longer term trials of more intensive versus standard statin regimens (28 964 randomised patients and 1419 events) also showed no evidence of a reduction in the risk of atrial fibrillation (1.00, 0.90 to 1.12; P=0.99). <b>Conclusions</b> The suggested beneficial effect of statins on atrial fibrillation from published shorter term studies is not supported by a comprehensive review of published and unpublished evidence from larger scale trials.
Knee injury in a 12 year old girl
Authors: Satish Babu, Bilal Al-Obaidi, Hani B Abdul-Jabar, Nawfal Al-Hadithy, Chinmay Gupte
Journal: BMJ (2015)

A 12 year old girl presented to the emergency department with sudden onset of knee pain. Her parents reported that she had twisted her left knee while her foot was fixed on the ground during a game of tennis. She reported hearing a “popping” sound followed by immediate pain and swelling in her left knee. She was initially unable to weight bear. She was otherwise fit and well. She was born at full term and her growth had been normal to date. On examination, her knee was swollen but there was no joint line tenderness or bony deformity. She would not cooperate with range of motion assessment because of the pain. She was distally neurovascularly intact.



### 1. What is the most likely diagnosis and what are the differential diagnoses?

#### Answer

The most likely diagnosis is acute anterior cruciate ligament (ACL) injury. Differential diagnoses include meniscal tear, osteochondral injury, tibial spine injury, patella dislocation, and collateral ligament injury.

#### Discussion

The most likely diagnosis is an acute ACL tear. The ACL is one of a pair of intra-articular ligaments (anterior and posterior cruciate) within the knee joint that provide the knee with sagittal (anteroposterior) stability. The tibial attachment of the ACL is just anterior and medial to the interspinous area of the tibial plateau. It runs posterolaterally to its attachment on the medial aspect of the lateral femoral condyle. In younger children, the ACL fibres form a strong connection between the ligament, perichondrium, and epiphyseal cartilage.1 Fibres are stronger than the cancellous bone of the unossified tibial eminence. With age, weaker Sharpey’s fibres link the ligament to …
Smallpox Immunization in the United States
Authors: C. Henry Kempe
Journal: JAMA (1965)

The current international campaign to eradicate smallpox proposes to eliminate the threat of this dread disease to the health of man. In this massive worldwide effort, undertaken with the professional and technical aid of the World Health Organization, primary emphasis is placed on the eradication of the disease from endemic foci. Until the time that smallpox is no longer a medical problem of significance, questions will naturally continue to be raised about the proper role to be taken by physicians in the United States, where there have been no cases of variola major since 1949. The freedom from variola major enjoyed by the United States is widely but erroneously believed to be evidence of a high level of immunity. Actually, the United States is no better protected than Sweden, Poland, Great Britain, or the rest of Western Europe, where in 1963 the importation of 4 cases resulted in 141 secondary
Rotation and Restricted Use of Antibiotics in a Medical Intensive Care Unit
Authors: DIDIER GRUSON, GILLES HILBERT, FREDERIC VARGAS, RUDDY VALENTINO, CECILE BEBEAR, ANNIE ALLERY, CHRISTIANE BEBEAR, GEORGES GBIKPI-BENISSAN, JEAN-PIERRE CARDINAUD
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

To test the hypothesis that a new program of antibiotic strategy control can minimize the incidence of ventilator-associated pneumonia (VAP) caused by potentially antibiotic-resistant microorganisms, we performed a prospective before-after study in 3, 455 patients admitted to a single intensive care unit over a 4-yr period. Regarding the bacterial ecology and the increasing antimicrobial resistance in our medical intensive care unit (MICU), we decided to vary our choice of empiric and therapeutic antibiotic treatment, with a supervised rotation, and a restricted use of ceftazidime and ciprofloxacin, which were widely prescribed before this scheduled change. For all patients, VAP was diagnosed based on the results of quantitative culture of bronchoalveolar lavage specimens (>/= 10(4) cfu/ml). We studied 1,044 and 1,022 patients requiring more than 48 h of mechanical ventilation (MV), respectively, in the before-period (2 yr: 1995-1996) and the after-period (2 yr: 1997-1998). We observed a decrease from 231 consecutive episodes of VAP in the before-period to 161 episodes of VAP in the after-period (p < 0.01), particularly for VAP occurring before 7 d of MV. The total number of potentially antibiotic-resistant gram-negative bacilli responsible for VAP such as Pseudomonas aeruginosa, Burkholderia cepacia, Steno-trophomonas maltophilia, and Acinetobacter baumanii decreased from 140 to 79 isolated bacilli. The susceptibilities of these bacteria to the antibiotics regimen increased significantly, especially for P. aeruginosa and B. cepacia. The percentage of methicillin-sensitive Staphylococcus aureus increased significantly from 40% to 60% of S. aureus responsible for VAP. These results suggest that a new strategy of antibiotics use could be an efficient means to reduce the incidence of VAP caused by antibiotic-resistant bacteria. Nevertheless, further studies are needed to validate these data.
Immunophenotyping of lymphocytes in liver tissue of patients with chronic liver diseases by flow cytometry
Authors: Xiuming Li, Lennox J. Jeffers, Rajender K. Reddy, Maria de Medina, Marcelo Silva, Steven Villanueva, Nancy G. Klimas, Violet Esquenazi, Eugene R. Schiff
Journal: Hepatology (1991)

Immunological factors are important in the pathogenesis of a spectrum of hepatobiliary diseases. To characterize the nature of specific immunological responses in liver disease, we determined lymphocyte changes in liver tissue and in blood using flow cytometry. A total of 113 liver biopsy specimens was collected from patients with the following diseases: 19 chronic hepatitis B; 39 chronic non-A, non-B hepatitis; 27 alcoholic liver disease; 10 hepatic malignancy; 8 autoimmune hepatitis; 6 fatty liver and 4 primary biliary cirrhosis. The lymphocytes were isolated from the liver biopsy specimens by mechanical and enzymatic methods. The lymphocyte yield was 7,901 +/- 575 cells/mg of liver tissue. The viability of lymphocytes was 97.7% +/- 0.3%. Lymphocytes were stained with four pairs of two-color mixed fluorescein-conjugated monoclonal antibodies, including T4-T8 (CD4/CD8), T11-B1 (CD2-CD20), NKH1-T8 (CD56-CD8), IL-2R1-T11 (CD25-CD2), and the ratios were determined by an Epics Profile flow cytometer. Immunophenotyping of lymphocytes in whole blood samples was simultaneously analyzed. Variability in lymphocyte yield and different patterns of lymphocyte subsets were found in the liver biopsy specimens. The yields of lymphocytes from patients with chronic non-A, non-B and autoimmune hepatitis were highest, and the lowest yield was from patients with fatty liver. Patients with primary biliary cirrhosis, fatty liver and hepatic malignancy had relatively high ratios of CD4/CD8, CD56/CD8 and CD25/CD2; whereas patients with chronic hepatitis B, autoimmune hepatitis and non-A, non-B hepatitis had lower ratios of CD4/CD8, CD56/CD8 and CD25/CD2. No difference in lymphocyte ratios between the patients with cirrhotic and noncirrhotic alcoholic liver disease was found.(ABSTRACT TRUNCATED AT 250 WORDS)
SP0090 Fibrotic Disease Models
Authors: J. H. Distler
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Vasculopathy, immune activation, and fibrosis are hallmarks in the pathogenesis of systemic sclerosis (SSc). So far, the complex interplay of vasculopathy, the cellular immune system, and fibrosis in SSc remains enigmatic. A better understanding of the pathogenesis, however, may help to develop effective targeted therapies for the treatment of SSc. Several mouse models are available to study different aspects of the disease. Because none of these models can encompass all features of human SSc, a critical selection of animal models is the basis for successful in vivo studies. Herein, we will present the most important animal models of SSc. The characteristics, advantages, and limitations of each model will be discussed and compared. The talk aims to guide the selection of suitable animal models of SSc for different research purposes. <h3>Disclosure of Interest</h3> J. Distler Shareholder of: 4D Science, Consultant for: Actelion, Pfizer, Ergonex, BMS, Celgene, Bayer Pharma, Boehringer Ingelheim, JB Therapeutics, Sanofi-Aventis, Novartis, Array Biopharma and Active Biotech, Roche, Speakers bureau: BMS, Celgene, Bayer Pharma, Boehringer Ingelheim
Differential Radiosensitization in DNA Mismatch Repair-Proficient and -Deficient Human Colon Cancer Xenografts with 5-Iodo-2-pyrimidinone-2′-deoxyribose
Authors: Yuji Seo, Tao Yan, Jane E. Schupp, Valdir Colussi, Kerri L. Taylor, Timothy J. Kinsella
Journal: Clinical Cancer Research (2004)

Abstract Purpose: 5-Iodo-2-pyrimidinone-2′-deoxyribose (IPdR) is a pyrimidinone nucleoside prodrug of 5-iododeoxyuridine (IUdR) under investigation as an orally administered radiosensitizer. We previously reported that the mismatch repair (MMR) proteins (both hMSH2 and hMLH1) impact on the extent (percentage) of IUdR-DNA incorporation and subsequent in vitro IUdR-mediated radiosensitization in human tumor cell lines. In this study, we used oral IPdR to assess in vivo radiosensitization in MMR-proficient (MMR+) and -deficient (MMR−) human colon cancer xenografts. Experimental Design: We tested whether oral IPdR treatment (1 g/kg/d for 14 days) can result in differential IUdR incorporation in tumor cell DNA and subsequent radiosensitization after a short course (every day for 4 days) of fractionated radiation therapy, by using athymic nude mice with an isogenic pair of human colon cancer xenografts, HCT116 (MMR−, hMLH1−) and HCT116/3-6 (MMR+, hMLH1+). A tumor regrowth assay was used to assess radiosensitization. Systemic toxicity was assessed by daily body weights and by percentage of IUdR-DNA incorporation in normal bone marrow and intestine. Results: After a 14-day once-daily IPdR treatment by gastric gavage, significantly higher IUdR-DNA incorporation was found in HCT116 (MMR−) tumor xenografts compared with HCT116/3-6 (MMR+) tumor xenografts. Using a tumor regrowth assay after the 14-day drug treatment and a 4-day radiation therapy course (days 11–14 of IPdR), we found substantial radiosensitization in both HCT116 and HCT116/3-6 tumor xenografts. However, the sensitizer enhancement ratio (SER) was substantially higher in HCT116 (MMR−) tumor xenografts (1.48 at 2 Gy per fraction, 1.41 at 4 Gy per fraction), compared with HCT116/3-6 (MMR+) tumor xenografts (1.21 at 2 Gy per fraction, 1.20 at 4 Gy per fraction). No substantial systemic toxicity was found in the treatment groups. Conclusions: These results suggest that IPdR-mediated radiosensitization can be an effective in vivo approach to treat “drug-resistant” MMR-deficient tumors as well as MMR-proficient tumors.
Low Plasma Apelin in Newly Diagnosed Type 2 Diabetes in Chinese People
Authors: Yu Zhang, Chunfang Shen, Xuesong Li, Guoguang Ren, Xiaofang Fan, Fengdong Ren, Ning Zhang, Jue Sun, Jialin Yang
Journal: Diabetes Care (2009)

It has been unclear whether there is a pathway that regulates plasma glucose through the action of peripheral tissue of apelin with the secretory function of insulin, which exerts a control in adipocytes in addition to the direct regulation of plasma glucose. Our study was designed to identify the changes in plasma apelin levels in newly diagnosed type 2 diabetes in Chinese people. We also tried to investigate the possible association of apelin, the status of hyperglycemia, and insulin secretion.

The study population consisted of 75 patients with newly diagnosed and untreated type 2 diabetes and 36 healthy control subjects matched for …
Trace metals in hematopoiesis
Authors: Charles J. Deur, Marvin J. Stone, Eugene P. Frenkel
Journal: American Journal of Hematology (1981)

Abstract The trace metals represent an extremely small part of the total mass of the organism. In spite of this, these elements appear to play major roles in metabolism. At the level of the hematopoietic system, specific roles can be identified for iron, copper, zinc, and cobalt. Other trace metals appear to play less clearly defined roles in hematopoiesis but clearly are involved by virtue of a number of interactions at the level of absorption, intermediary metabolism, or modulation of toxicity. Still other trace metals, such as lithium, appear to have a therapeutic role in altering production of granulocytes, by an as yet unidentified mechanism.
Evolutionary History of Chimpanzees Inferred from Complete Mitochondrial Genomes
Authors: A. Bjork, W. Liu, J. O. Wertheim, B. H. Hahn, M. Worobey
Journal: Molecular Biology and Evolution (2010)

Investigations into the evolutionary history of the common chimpanzee, Pan troglodytes, have produced inconsistent results due to differences in the types of molecular data considered, the model assumptions employed, and the quantity and geographical range of samples used. We amplified and sequenced 24 complete P. troglodytes mitochondrial genomes from fecal samples collected at multiple study sites throughout sub-Saharan Africa. Using a "relaxed molecular clock," fossil calibrations, and 12 additional complete primate mitochondrial genomes, we analyzed the pattern and timing of primate diversification in a Bayesian framework. Our results support the recognition of four chimpanzee subspecies. Within P. troglodytes, we report a mean (95% highest posterior density [HPD]) time since most recent common ancestor (tMRCA) of 1.026 (0.811–1.263) Ma for the four proposed subspecies, with two major lineages. One of these lineages (tMRCA = 0.510 [0.387–0.650] Ma) contains P. t. verus (tMRCA = 0.155 [0.101–0.213] Ma) and P. t. ellioti (formerly P. t. vellerosus; tMRCA = 0.157 [0.102–0.215] Ma), both of which are monophyletic. The other major lineage contains P. t. schweinfurthii (tMRCA = 0.111 [0.077–0.146] Ma), a monophyletic clade nested within the P. t. troglodytes lineage (tMRCA = 0.380 [0.296–0.476] Ma). We utilized two analysis techniques that may be of widespread interest. First, we implemented a Yule speciation prior across the entire primate tree with separate coalescent priors on each of the chimpanzee subspecies. The validity of this approach was confirmed by estimates based on more traditional techniques. We also suggest that accurate tMRCA estimates from large computationally difficult sequence alignments may be obtained by implementing our novel method of bootstrapping smaller randomly subsampled alignments.
Localised pulmonary arteritis in rheumatoid disease.
Authors: J G Armstrong, R H Steele
Journal: Thorax (1982)

Patients with rheumatoid disease may develop thoracic complications, including pleural effusion, solitary or multiple necrobiotic nodules, pulmonary fibrosis, and Caplan's syndrome.1-3Although vasculitis occurs in rheumatoid disease in a number of sites, pulmonary vasculitis has received little attention in the literature.We describe a case of acute, localised, necrotising pulmonary arteritis in a patient with rheumatoid disease. Case reportA 58-year-old housewife was diagnosed as having rheumatoid arthritis in 1967.She subsequently developed painful joint deformities and in June 1980 her left hip was replaced with a Muller prosthesis.The patient was admitted to hospital on 30 September 1980, complaining of right-sided pleuritic chest pain and mild dyspnoea for one week.Physical examination revealed that she was afebrile, blood pressure was 110/60,
Pediatric and Adolescent Extracranial Germ Cell Tumors: The Road to Collaboration
Authors: Thomas A. Olson, Matthew J. Murray, Carlos Rodriguez-Galindo, James C. Nicholson, Deborah F. Billmire, Mark D. Krailo, Ha M. Dang, James F. Amatruda, Claire M. Thornton, G. Suren Arul, Sara J. Stoneham, Farzana Pashankar, Daniel Stark, Furqan Shaikh, David M. Gershenson, Allan Covens, Jean Hurteau, Sally P. Stenning, Darren R. Feldman, Peter S. Grimison, Robert A. Huddart, Christopher Sweeney, Thomas Powles, Luiz Fernando Lopes, Simone dos Santos Agular, Girish Chinnaswamy, Sahar Khaleel, Sherif Abouelnaga, Juliet P. Hale, A. Lindsay Frazier
Journal: Journal of Clinical Oncology (2015)

During the past 35 years, survival rates for children with extracranial malignant germ cell tumors (GCTs) have increased significantly. Success has been achieved primarily through the application of platinum-based chemotherapy regimens; however, clinical challenges in GCTs remain. Excellent outcomes are not distributed uniformly across the heterogeneous distribution of age, histologic features, and primary tumor site. Despite good outcomes overall, the likelihood of a cure for certain sites and histologic conditions is less than 50%. In addition, there are considerable long-term treatment-related effects for survivors. Even modest cisplatin dosing can cause significant long-term morbidities. A particular challenge in designing new therapies for GCT is that a variety of specialists use different risk stratifications, staging systems, and treatment approaches for three distinct age groups (childhood, adolescence, and young adulthood). Traditionally, pediatric cancer patients younger than 15 years have been treated by pediatric oncologists in collaboration with their surgical specialty colleagues. Adolescents and young adults with GCTs often are treated by medical oncologists, urologists, or gynecologic oncologists. The therapeutic dilemma for all is how to best define disease risk so that therapy and toxicity can be appropriately reduced for some patients and intensified for others. Further clinical and biologic insights can only be achieved through collaborations that do not set limitations by age, sex, and primary tumor site. Therefore, international collaborations, spanning different cooperative groups and disciplines, have been developed to address these challenges.
<i>SF3B1</i>and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia
Authors: Lili Wang, Michael S. Lawrence, Youzhong Wan, Petar Stojanov, Carrie Sougnez, Kristen Stevenson, Lillian Werner, Andrey Sivachenko, David S. DeLuca, Li Zhang, Wandi Zhang, Alexander R. Vartanov, Stacey M. Fernandes, Natalie R. Goldstein, Eric G. Folco, Kristian Cibulskis, Bethany Tesar, Quinlan L. Sievers, Erica Shefler, Stacey Gabriel, Nir Hacohen, Robin Reed, Matthew Meyerson, Todd R. Golub, Eric S. Lander, Donna Neuberg, Jennifer R. Brown, Gad Getz, Catherine J. Wu
Journal: New England Journal of Medicine (2011)

The somatic genetic basis of chronic lymphocytic leukemia, a common and clinically heterogeneous leukemia occurring in adults, remains poorly understood.
Nearly identical allelic distributions of xanthine dehydrogenase in two populations of Drosophila pseudoobscura.
Authors: T P Keith, L D Brooks, R C Lewontin, J C Martinez-Cruzado, D L Rigby
Journal: Molecular Biology and Evolution (1985)

In a previous study, Keith (1983) showed by sequential gel electrophoresis of the esterase-5 protein in Drosophila pseudoobscura that a highly polymorphic locus with many alleles can have very similar frequency distributions in populations separated by 500 km. The present work studies another highly polymorphic locus, xanthine dehydrogenase, in the same California population samples, using the same technique to distinguish allelic classes. Twelve electromorphs were found in one population and 15 in the other. Both populations shared a single very frequent (approximately 60%) allele, as well as five other alleles in low but similar frequencies. In addition, each population had an array of unique alleles present only once in one population sample but absent in the other. A statistical test against the stationary distribution for neutral alleles shows that, if the populations are at equilibrium, then purifying selection is operating on xanthine dehydrogenase. The extremely close similarity in frequency distributions of the alleles between populations for both the xanthine dehydrogenase and esterase-5 loci, despite differences in allele frequency distribution between loci, strongly emphasizes the importance of migration in influencing genic diversity in these populations.
Effect of ACTH and Sodium Salicylate on the Urinary Uric Acid: Creatinine Ratio, and Circulating Eosinophils in Man
Authors: F. G. W. Marson
Journal: Annals of the Rheumatic Diseases (1953)

<h3>Objectives</h3> This article summarizes the modern development of navel therapy, analyses future trends and puts forward suggestions for future development. <h3>Methods</h3> This paper provides a history of the development of navel therapy, describes the theory of traditional Chinese medicine and reports the clinical application of umbilical therapy in detail. <h3>Results</h3> The author describes some problems in modern navel therapy development, for instance there is no unified national standard and proprietary Chinese medicine products are not listed or promoted. <h3>Conclusions</h3> Navel therapy is a unique TCM treatment. Doctors apply the particular drug externally to the navel or to the appropriate external stimulus on the navel in order to treat disease. This method is also called ‘green therapy’. In future research, we will apply modern science and technology to explore the mechanisms of navel therapy, establish an optimization scheme for navel therapy and develop a unified national standard to promote this traditional Chinese treatment worldwide. <h3>Acknowledgments</h3> This research was financially supported by the Henan Province Outstanding Scientific and Technological Innovation Team (Grant No. TCJ2014-391), Natural Science Foundation of Henan Province (Grant No. 132300410019) and Zhengzhou Science and Technology Innovation Team (Grant No. 131PCXTD612).