tbuckley/cabot-search huggingface dataset:
Folate Deficiency, Hyperhomocysteinemia, Low Urinary Creatinine, and Hypomethylation of Leukocyte DNA Are Risk Factors for Arsenic-Induced Skin Lesions
Authors: J. Richard Pilsner, Xinhua Liu, Habibul Ahsan, Vesna Ilievski, Vesna Slavkovich, Diane Levy, Pam Factor-Litvak, Joseph H. Graziano, Mary V. Gamble
Journal: Environmental Health Perspectives (2008)

BackgroundArsenic methylation relies on folate-dependent one-carbon metabolism and facilitates urinary As elimination. Clinical manifestations of As toxicity vary considerably among individuals and populations, and poor methylation capacity is thought to confer greater susceptibility.ObjectiveAfter determining that folate deficiency, hyperhomocysteinemia, and low urinary creatinine are associated with reduced As methylation, and that As exposure is associated with increased genomic methylation of leukocyte DNA, we asked whether these factors are associated with As-induced skin lesion risk among Bangladeshi adults.MethodsWe conducted a nested case–control study of 274 cases who developed lesions 2 years after recruitment, and 274 controls matched to cases for sex, age, and water As.ResultsThe odds ratios and 95% confidence intervals (CIs) for development of skin lesions for participants who had low folate (< 9 nmol/L), hyperhomocysteinemia (men, > 11.4 μmol/L; women, > 10.4 μmol/L), or hypomethylated leukocyte DNA at recruitment (< median) were 1.8 (95% CI, 1.1–2.9), 1.7 (95% CI, 1.1–2.6), and 1.8 (95% CI, 1.2–2.8), respectively. Compared with the subjects in the first quartile, those in the third and fourth quartiles for urinary creatinine had a 0.4-fold decrease in the odds of skin lesions (p < 0.01).ConclusionsThese results suggest that folate deficiency, hyperhomocysteinemia, and low urinary creatinine, each associated with decreased As methylation, are risk factors for As-induced skin lesions. The increased DNA methylation associated with As exposure previously observed, and confirmed among controls in this study, may be an adaptive change because hypomethylation of leukocyte DNA is associated with increased risk for skin lesions.
Preclinical Evaluation of An Anti-HCV miRNA Cluster for Treatment of HCV Infection
Authors: Xiao Yang, Katherine Marcucci, Xavier Anguela, Linda B. Couto
Journal: Molecular Therapy (2013)

We developed a strategy to treat hepatitis C virus (HCV) infection by replacing five endogenous microRNA (miRNA) sequences of a natural miRNA cluster (miR-17–92) with sequences that are complementary to the HCV genome. This miRNA cluster (HCV-miR-Cluster 5) is delivered to cells using adeno-associated virus (AAV) vectors and the miRNAs are expressed in the liver, the site of HCV replication and assembly. AAV-HCV-miR-Cluster 5 inhibited bona fide HCV replication in vitro by up to 95% within 2 days, and the spread of HCV to uninfected cells was prevented by continuous expression of the anti-HCV miRNAs. Furthermore, the number of cells harboring HCV RNA replicons decreased dramatically by sustained expression of the anti-HCV miRNAs, suggesting that the vector is capable of curing cells of HCV. Delivery of AAV-HCV-miR-Cluster 5 to mice resulted in efficient transfer of the miRNA gene cluster and expression of all five miRNAs in liver tissue, at levels up to 1,300 copies/cell. These levels achieved up to 98% gene silencing of cognate HCV sequences, and no liver toxicity was observed, supporting the safety of this approach. Therefore, AAV-HCV-miR-Cluster 5 represents a different paradigm for the treatment of HCV infection. We developed a strategy to treat hepatitis C virus (HCV) infection by replacing five endogenous microRNA (miRNA) sequences of a natural miRNA cluster (miR-17–92) with sequences that are complementary to the HCV genome. This miRNA cluster (HCV-miR-Cluster 5) is delivered to cells using adeno-associated virus (AAV) vectors and the miRNAs are expressed in the liver, the site of HCV replication and assembly. AAV-HCV-miR-Cluster 5 inhibited bona fide HCV replication in vitro by up to 95% within 2 days, and the spread of HCV to uninfected cells was prevented by continuous expression of the anti-HCV miRNAs. Furthermore, the number of cells harboring HCV RNA replicons decreased dramatically by sustained expression of the anti-HCV miRNAs, suggesting that the vector is capable of curing cells of HCV. Delivery of AAV-HCV-miR-Cluster 5 to mice resulted in efficient transfer of the miRNA gene cluster and expression of all five miRNAs in liver tissue, at levels up to 1,300 copies/cell. These levels achieved up to 98% gene silencing of cognate HCV sequences, and no liver toxicity was observed, supporting the safety of this approach. Therefore, AAV-HCV-miR-Cluster 5 represents a different paradigm for the treatment of HCV infection.
Clonal Selection of Metastasis within the Life History of a Tumor
Authors: James E. Talmadge
Journal: Cancer Research (2007)

Tumor metastasis is a clonally selective process that occurs as part of tumor progression, a hypothesis supported by experimental and clinical research. Data supporting this hypothesis were first introduced by Fidler and Kripke in the late 1970s ( [1][1]), providing a powerful model to gain insight
Curing Chronic Hepatitis C — The Arc of a Medical Triumph
Authors: Raymond T. Chung, Thomas F. Baumert
Journal: New England Journal of Medicine (2014)

Interview with Dr. Raymond Chung on the science behind evolving treatments for hepatitis C and progress toward a cure. (16:14)Download The development of direct-acting antiviral agents has revolutionized the treatment of hepatitis C by offering genuine prospects for a comprehensive cure of a chronic viral infection. This success can be traced to important scientific, clinical, and regulatory developments.
Thomas McKeown and Archibald Cochrane: a journey through the diffusion of their ideas.
Authors: C Alvarez-Dardet, M T Ruiz
Journal: BMJ (1993)

In the 1970s Thomas McKeown and Archibald L Cochrane were two of the most influential voices in criticizing the dominance of medical thinking. A bibliometric study of the citations to McKeown9s The Role of Medicine: Dream, Mirage or Nemesis and Cochrane9s Effectiveness and Efficiency: Random Reflections on Health Services was performed from the publication of each book until 1988 to study how their ideas have been disseminated. During the study period 430 papers in the Science Citation Index or the Social Sciences Citation Index cited Cochrane9s book, 133 cited McKeown9s, and 166 cited both. The citations came mainly from original papers published in journals of internal medicine or public health and epidemiology (35%) and written by authors from the United States or the United Kingdom. Cochrane9s book was cited most frequently in medical journals, suggesting a higher degree of penetration of his ideas among medical scientists. Although the dominance of original papers among the citations suggests that these books have been important in stimulating new knowledge, the main problems that McKeown and Cochrane identified--namely, the relatively small impact of clinical medicine on health outcomes and the poor use of scientific methods in clinical practice--are still with us.
Oxygen, temperature and humidity of inspired gases and their influences on airway and lung tissue in near-term lambs
Authors: J. Jane Pillow, Noah H. Hillman, Graeme R. Polglase, Timothy J. M. Moss, Suhas G. Kallapur, Fook-Choe Cheah, Boris W. Kramer, Alan H. Jobe
Journal: Intensive Care Medicine (2009)
Lung function abnormalities in repaired oesophageal atresia and tracheo-oesophageal fistula.
Authors: P Chetcuti, P D Phelan, R Greenwood
Journal: Thorax (1992)

BACKGROUND: Respiratory complications are common after neonatal repair of oesophageal atresia and tracheo-oesophageal fistula. The prevalence of lung function abnormalities and the relation between gastrointestinal complications and lung function has not been studied in a large number of patients. METHODS: Lung volumes and flow-volume loops were measured in 155 patients without spinal curvature aged 6-37 years who had undergone surgery for oesophageal atresia and tracheo-oesophageal fistula. RESULTS: Sixty four of the 155 patients had evidence of mild lower airways disease, with values for FEV1 more than two standardised scores below the predicted value in 39 (25%) and above 2 standardised scores for the residual volume (RV)/total lung capacity (TLC) ratio in 64 (41%). Restrictive lung disease (TLC more than 2 standardised scores below predicted) was present in 28 (18%). Severe lung function abnormalities were present in under 10% of the 155. Half the subjects had some evidence of extra-thoracic tracheal obstruction, with a high ratio of expiratory to inspiratory flow for peak flow in 76 (50%) and at 50% of vital capacity in 59 (38%). Patients with radiological gastro-oesophageal reflux in early childhood had more airways obstruction and smaller lung volumes. Patients with current gastrointestinal symptoms were similar in their lung function to symptom free patients. CONCLUSIONS: Minor lung function abnormalities are common in patients after repair of oesophageal atresia. Early diagnosis and management of gastro-oesophageal reflux may help to minimise these lung function abnormalities.
Serum Vitamin C Levels in Type 2 Diabetic Nephropathy
Authors: Kenzo Iino, Takuko Fukui, Keizo Anzai, Masanori Iwase, Kazuhiko Kogawa, Masaro Ogimoto, Junko Ono, Takashi Asano, Mitsuo Iida, Kazuo Tamura
Journal: Diabetes Care (2005)

Serum vitamin C concentrations have been reported to be low in diabetic patients (1). Diabetic nephropathy is known to develop in diabetic individuals, and decreased renal function and hypertension could reportedly accelerate atherosclerosis in patients with type 2 diabetes (2). Observational epidemiologic studies showed an inverse relation between the dietary intake or serum levels of vitamin C and blood pressure (3). Although reduced concentrations of vitamin C were reported …
15-deoxy-D12, 14-PGJ2 regulates apoptosis induction and NF-κB activation via a PPARg-independent mechanism in hepatocellular carcinoma
Authors: H. Okano, K. Shiraki, H. Inoue, T. Kawakita, Y. Saitou, N. Enokimura, N. Yamamoto, M. Deguchi, K. Sugimoto, T. Sakai, K. Murata, T. Nakano
Journal: Journal of Hepatology (2003)
Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs
Authors: A.Gardulf Rn, L Hammarström, R Gustafson, T Nyström, C.I.Edvard Smith, R Gustafson, E Jonsson, A Gardulf, E Jonsson, G Möller, G Möller, J Björkander, D Ericson, V Andersen, B Søeberg, S Frøland, M.B Jacobsen
Journal: The Lancet (1995)
Isaac Godfry Watchman
Authors: A. Elliott
Journal: BMJ (2003)

Former general practitioner Liverpool (b 1921; q Queen's University, Belfast, 1943), died from stomach cancer on 10 August 2003.​2003.




Figure 1




Before going into general practice Godfry, as he liked to be called, did house jobs in Lurgan in Northern Ireland and in Merseyside. He was a member of a three man general practice in Anfield, Liverpool, from 1948 until his retirement in 1991. Godfry was a great family man devoted to his wife and daughter. Unfortunately he did not live to see his expected first grandchild. He was keen on bridge and golf, but his greatest hobby was taking motor cars to pieces and putting them back again, especially Morris Minors.
Anabolic Steroid Use in Adolescence
Authors: Wayne V. Moore
Journal: JAMA (1988)

The study of Buckley et al<sup>1</sup>in this issue ofTHE JOURNALis informative in describing the extent of usage of anabolic steroids (AS) in a segment of the population in which usage was suspected but data were lacking. Since many of the users among high school seniors might be described as habitual, the data may also be important in describing AS misuse in the adult population, the prevalence of which is not known and may be virtually impossible to ascertain. It may be reasonable to anticipate that adolescents will continue habitual use as adults; however, since the primary motivation among high school users was to increase strength among football athletes, the prevalence may decrease after high school, when participation in football declines. The current study achieved a reasonable response rate (approximately 50%). As with other surveys, the prevalence might be larger or smaller (this is a moot point)
Abnormal Reaction to Disulfiram
Authors: J. J. Cockburn
Journal: BMJ (1964)

MCBRTJISH so severe nor so frequent as those described by Drs.Garland and Sumner in adult patients.I have never seen ataxia, confusion, headache, dysarthria, or blurring of vision in my patients which I could attri- bute to sulthiame.Perhaps they are less suggestible than Dr. Garland's refractory adult epileptics.It is clearly time that control trials of sulthiame were carried out so that reliable indications of its uses and dangers may be established.I am sure that Drs.Garland and Sumner would agree.-Iam, etc.,
TCT-794 Intracoronary Infusion of Bone Marrow Mesenchymal Stem Cells in Acute Myocardial Infarction- A Critical Challenge for Dosage-Related Efficacy and Safety
Authors: lian R. Gao, Yu Chen, Qing A. Ding, Feng Guo, Tian C. Li, Hui L. Liu, Xue T. Pei, Zi C. Tong, Ning K. Zhang, Zhi M. Zhu
Journal: Journal of the American College of Cardiology (2013)
Exercise Treadmill Score for Predicting Prognosis in Coronary Artery Disease
Authors: DANIEL B. MARK
Journal: Annals of Internal Medicine (1987)

To determine the prognostic value of the treadmill exercise test, we evaluated 2842 consecutive patients with chest pain who had both treadmill testing cardiac catheterization. The population was randomly divided into two equal-sized groups and the Cox regression model was used in one to form a treadmill score that was then validated in the other group. The final treadmill score was calculated as follows: exercise time - (5 X ST deviation) - (4 X treadmill angina index). Using this treadmill score, 13% of the patients were found to be at high risk; 53%, at moderate risk; and 34%, at low risk. The treadmill score added independent prognostic information to that provided by clinical data, coronary anatomy, and left ventricular ejection fraction: patients with three-vessel disease with a score of -11 or less had a 5-year survival rate of 67%, and those with a score of +7 or more had a 5-year survival rate of 93%. The treadmill score was useful for stratifying prognosis in patients with suspected coronary artery disease who were referred to us for catheterization, and may provide a useful adjunct to clinical decision making in the larger population of patients being evaluated for chest pain.
Job share a consultant post.
Authors: G. Thornicroft, G. Strathdee
Journal: BMJ (1992)

Job sharing offers advantages to both employer and employee but it is still uncommon in medicine. Based on the experiences of two psychiatrists sharing a consultant post this article describes some of the problems in obtaining a job share. The most difficult part can be getting an interview, and once a post has been obtained the terms and conditions of service may have to be modified to suit job sharing. Getting on well with your job sharing partner and good communication will not only help overcome the obstacles but ensure that the sharing is successful.
Association between tumor necrosis factor inhibitor (TNFi) therapy and changes in C-reactive protein (CRP), blood pressure, and alanine aminotransferase (ALT) among patients with psoriasis, psoriatic arthritis, or rheumatoid arthritis
Authors: Jashin J. Wu, Christopher G. Rowan, Judith D. Bebchuk, Mary S. Anthony
Journal: Journal of the American Academy of Dermatology (2015)
Practice Imperfect — Treatment for Wheezing in Preschoolers
Authors: Andrew Bush
Journal: New England Journal of Medicine (2009)

Nearly one third of preschool children (4 years of age or younger) have intermittent wheezing, a condition that many of them outgrow. The most common early trigger is a respiratory virus infection, leading to a pattern of episodic wheezing, with no symptoms between viral infections. Some children, particularly those with atopy, have a different clinical phenotype known as "multitrigger" wheezing. This condition is characterized by wheezing after exposure to multiple triggers, such as exercise and exposure to smoke, allergens, or cold air, as well as viral infections.1 The distinctions among types of wheezing are not fixed. For example, an 18-month-old . . .
Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome
Authors: Paul J Coucke, Andy Willaert, Marja W Wessels, Bert Callewaert, Nicoletta Zoppi, Julie De Backer, Joyce E Fox, Grazia M S Mancini, Marios Kambouris, Rita Gardella, Fabio Facchetti, Patrick J Willems, Ramses Forsyth, Harry C Dietz, Sergio Barlati, Marina Colombi, Bart Loeys, Anne De Paepe
Journal: Nature Genetics (2006)
Differences in Treatment, Outcomes, and Quality of Life Among Patients With Heart Failure in Canada and the United States
Authors: Padma Kaul, Shelby D. Reed, Adrian F. Hernandez, Jonathan G. Howlett, Justin A. Ezekowitz, Yanhong Li, Yinggan Zheng, Jean L. Rouleau, Randall C. Starling, Christopher M. O'Connor, Robert M. Califf, Paul W. Armstrong
Journal: JACC Heart Failure (2013)
Physical Activity and Proliferative Retinopathy in People Diagnosed With Diabetes Before Age 30 Yr
Authors: Karen J Cruickshanks, Scot E Moss, Ronald Klein, Barbara E Klein
Journal: Diabetes Care (1992)

OBJECTIVE To examine the relationships of past and current physical activity to the prevalence of PDR. RESEARCH DESIGN AND METHODS Individuals diagnosed with diabetes &amp;lt; 30 yr of age (n = 818), who were participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy, were examined during 1984–1986. Stereoscopic fundus photographs were graded for presence of PDR. Physical activity was assessed by an interviewer-administered standardized questionnaire. RESULTS Women diagnosed with diabetes &amp;lt; 14 yr of age who reported a history of participation in team sports in high school or college were less likely to have PDR at examination (OR 0.46, 95% CI 0.23, 0.93). Those women who reported current strenuous activity levels were less likely to have PDR (OR 0.34, 95% CI 0.13, 0.87). There were no significant associations between past or current physical activity and PDR in men. Current levels of energy expenditure were not related to PDR in either sex. CONCLUSIONS Higher levels of physical activity may be associated with a reduced risk of having PDR in women. However, the lack of similar findings in men suggests that physical activity may be a relatively unimportant factor in the etiology of PDR.
Alanine and Terbutaline in the Prevention of Nocturnal Hypoglycemia in IDDM
Authors: Tarek Y Saleh, Philip E Cryer
Journal: Diabetes Care (1997)

OBJECTIVE To test the hypothesis that because of sustained glycemic actions, bedtime administration of the glucagon-releasing amino acid alanine or the epinephrine-simulating β2-adrenergic agonist terbutaline more effectively prevents nocturnal hypoglycemia than a conventional bedtime snack, we studied 15 patients with 1DDM. RESEARCH DESIGN AND METHODS On each of four occasions, the same individualized dose of NPH insulin (0.1–0.2 U/kg) was administered with either no treatment (control) or, in random sequence, oral treatment with a snack (240 ml of 2% milk plus one slice of toast, ∼200 kcal), alanine (40 g, plus 10 g of glucose, ∼200 kcal), or terbutaline (5.0 mg) at 2200. RESULTS During the first half of the night (2315–0300), mean plasma glucose concentrations were higher after the snack (P &amp;lt; 0.02), alanine plus glucose (P &amp;lt; 0.01), or terbutaline (P &amp;lt; 0.001), compared with no treatment. During the second half of the night, mean plasma glucose levels were no different from control values (73 ± 5 mg/dl, 4.1 ± 0.3 mmol/1) after the snack (73 ± 7 mg/dl, 4.1 ± 0.4 mmol/1), tended to be higher after alanine plus glucose (96 ± 16 mg/dl, 5.3 ± 0.9 mmol/1), and were significantly higher after terbutaline (124 ± 15 mg/dl, 6.9 ± 0.8 mmol/1, P &amp;lt; 0.01). Nocturnal plasma glucose levels of 40 mg/dl (2.2 mmol/1) or less(which were treated with intravenous glucose) occurred on 13 occasions in seven patients in the control arm and 10 occasions in six patients in the snack arm (not significantly different from the control arm), but on only 1 occasion in the alanine-plus-glucose.arm (P &amp;lt; 0.02) and the terbutaline arm (P &amp;lt; 0.02). CONCLUSIONS In patients with 1DDM given an evening dose of NPH insulin, a conventional bedtime snack exerts an inconsistent glycemic effect only during the first half of the night, and bedtime administration of the glucagon-releasing amino acid alanine or the epinephrine- simulating β2-adrenergic agonist terbutaline more effectively prevents nocturnal hypoglycemia than a conventional bedtime snack.
Passive smoking: Comment from the editor
Authors: R. Smith
Journal: BMJ (2003)

Editor—I can't respond to all the points raised in this debate, and I thought I would simply share some reflections.

Firstly, we've considered again whether we should we have a blanket policy of refusing to publish research funded by the tobacco industry. We've twice considered this question in the BMJ and twice decided against. The BMJ is passionately antitobacco, but we are also passionately prodebate and proscience. A ban would be antiscience.

Secondly, we are not in the “truth” business. Scientific truths are all provisional. Most of science falls away as new paradigms emerge. This doesn't mean that we are in the “lies” business, but we are in the “debate” business. We judged this paper1 to be a useful contribution to an important debate. We may be wrong, as we are with many papers. That's science.

Thirdly, with research papers we first ask if we are interested in the question. We must be interested in whether passive smoking kills, and the question has not been definitively answered. It's a hard question, and our methods are inadequate.

We then peer review the study, but we are well aware of the extreme deficiencies of peer review. Of course the study we published has flaws—all papers do—but it also has considerable strengths: long follow up, large sample size, and more complete follow up than many such studies. It's too easy to dismiss studies like this as “fatally flawed,” with the implication that the study means nothing.

Fourthly, I found it disturbing that so many people and organisations referred to the flaws in the study without specifying what they were. Indeed, this debate was much more remarkable for its passion than its precision.
Ethnic Differences in Survival Outcome in Patients with Advanced Stage Non-small Cell Lung Cancer: Results of a Meta-Analysis of Randomized Controlled Trials
Authors: Ross A. Soo, Marie Loh, Tony S. Mok, Sai-Hong I. Ou, Byoung-Chul Cho, Wee-Lee Yeo, Dan G. Tenen, Richie Soong
Journal: Journal of Thoracic Oncology (2011)
Telling the patient.
Authors: J R Burton-Brown
Journal: BMJ (1973)

be traced.Thus the work of Bernstein and others in Britain and America on the importance of early language stimulation, with which we are fully familiar, is not applicable to the present group of children.May we suggest that all of us who are genuinely concerned with language develop- ment in young children join together in tackling this important problem rather than widening divisions of opinion by criticizing large-scale screening procedures in a national survey which, though inevitably crude, did produce useful information hitherto unavail- able.-Weare, etc.