tbuckley/cabot-search huggingface dataset:
Melatonin Secretion and the Incidence of Type 2 Diabetes
Authors: Ciaran J. McMullan, Eva S. Schernhammer, Eric B. Rimm, Frank B. Hu, John P. Forman
Journal: JAMA (2013)

<h3>Importance</h3>Loss-of-function mutations in the melatonin receptor are associated with insulin resistance and type 2 diabetes. Additionally, in a cross-sectional analysis of persons without diabetes, lower nocturnal melatonin secretion was associated with increased insulin resistance.<h3>Objective</h3>To study the association between melatonin secretion and the risk of developing type 2 diabetes.<h3>Design, Setting, and Participants</h3>Case-control study nested within the Nurses' Health Study cohort. Among participants without diabetes who provided urine and blood samples at baseline in 2000, we identified 370 women who developed type 2 diabetes from 2000-2012 and matched 370 controls using risk-set sampling.<h3>Main Outcome Measures</h3>Associations between melatonin secretion at baseline and incidence of type 2 diabetes were evaluated with multivariable conditional logistic regression controlling for demographic characteristics, lifestyle habits, measures of sleep quality, and biomarkers of inflammation and endothelial dysfunction.<h3>Results</h3>The median urinary ratios of 6-sulfatoxymelatonin to creatinine were 28.2 ng/mg (5%-95% range, 5.5-84.2 ng/mg) among cases and 36.3 ng/mg (5%-95% range, 6.9-110.8 ng/mg) among controls. Women with lower ratios of 6-sulfatoxymelatonin to creatinine had increased risk of diabetes (multivariable odds ratio, 1.48 [95% CI, 1.11-1.98] per unit decrease in the estimated log ratio of 6-sulfatoxymelatonin to creatinine). Compared with women in the highest ratio category of 6-sulfatoxymelatonin to creatinine, those in the lowest category had a multivariable odds ratio of 2.17 (95% CI, 1.18-3.98) of developing type 2 diabetes. Women in the highest category of melatonin secretion had an estimated diabetes incidence rate of 4.27 cases/1000 person-years compared with 9.27 cases/1000 person-years in the lowest category.<h3>Conclusions and Relevance</h3>Lower melatonin secretion was independently associated with a higher risk of developing type 2 diabetes. Further research is warranted to assess if melatonin secretion is a modifiable risk factor for diabetes within the general population.
Multicentric Reticulohistiocytosis: Response to Alkylating Agents in Six Patients
Authors: William W. Ginsburg
Journal: Annals of Internal Medicine (1989)

To determine the efficacy of alkylating agents in multicentric reticulohistiocytosis.Open consecutive case series.Tertiary-care referral clinic.Six patients with skin-biopsy-proven multicentric reticulohistiocytosis. All had skin nodules and polyarthritis.Five patients received cyclophosphamide (dose range, 1.25 to 2.2 mg/kg body weight) and one patient received chlorambucil (0.1 mg/kg). Therapy was administered from 6 to 24 months.In five patients treated with cyclophosphamide a response was seen within 4 months. Four patients eventually had a complete remission and one had almost a complete remission. The four patients in complete remission had cyclophosphamide therapy discontinued after 6, 12, 16, and 18 months. Three of the four patients remained in complete remission off therapy at 6, 6, and 22 months, whereas one had a recurrence after 6 months. The one patient given chlorambucil went into a complete remission and stopped treatment after 12 months. He remained in complete remission 32 months after stopping medication.Our experience with patients with aggressive multicentric reticulohistiocytosis shows that alkylation therapy is warranted. We conclude that a response to an alkylating agent may be expected. Whether after treatment for 6 to 18 months most patients may be able to discontinue the drug and remain in remission has yet to be shown. The rarity of multicentric reticulohistiocytosis precludes the possibility of a double-blind study.
Misdeployment of Edwards Sapien Valve in Transfemoral Aortic Valve Implantation Due to Iatrogenic Endarterectomy
Authors: Rafael J. Ruiz-Salmerón, Omar Araji, Luis F. Valenzuela, Manuel Vizcaino, Antonio Fernández, Jose L. Villar, Jose M. Cruz, Jose M. Barquero, Daniela Martins-Romeo, Luis Cueto
Journal: Circulation (2010)
INSULIN-LIKE GROWTH FACTOR PREVENTS DIABETES INDUCED CARDIOMYOPATHY MEDIATED BY MICRORNA-1
Authors: Yangxin Li, Hanjing Wu, Mang Zhu, Harnath Shelat, Jiangbo Qu, Minjuan Zheng, Jiuhong Yuan, Guoqiang Yuan, Jiaming Xu, Hongwu Wang, Yong-jian Geng
Journal: Journal of the American College of Cardiology (2010)
Modification of Tamoxifen Response: What Have We Learned?
Authors: Timothy L. Lash, Thomas P. Ahern, Deirdre Cronin-Fenton, Jens Peter Garne, Stephen Hamilton-Dutoit, Marianne Ewertz Kvistgaard, Carol L. Rosenberg, Rebecca A. Silliman, Henrik Toft Sørensen
Journal: Journal of Clinical Oncology (2008)

TO THEEDITOR:InarecentJournalofClinicalOncologyeditorial, Desta and Flockhart 1 asked a yes-no question about the germline pharmacogeneticsoftamoxifenresponse:“Havewelearnedenough?” They ultimately answer by writing that recommendations regarding genetic testing for CYP2D6 variants must await further data, but the list of open questions preceding this answer did not include the question of whether there is a main effect. We therefore raise this question about the main effect: “Has it been established that tamoxifen is a less effectiveadjuvanttherapyforestrogenreceptor‐positivebreastcancer patients with functionally variant CYP2D6 allele(s) than for those without functionally variant alleles?” Figure 1 depicts the results of the five epidemiologic studies of thisquestion. 2-6 Toexaminethedepartureofthedistributionofthese results from the null (ie, relative risk of 1.0), we first ranked the five relative risks of recurrence from lowest to highest (citations 2 to 6 in ascending order). We then plotted each study’s relative risk and its 95%CIagainsttheinversenormalofitsrankpercentile. 7 Thestippled lineshowstheregressionofinverse-varianceweightedlog-relativerisk against the inverse normal of rank percentile. If the accumulated evidenceisarandomsamplefromalognormaldistributionofrelative risks centered on the null, then the relative risks should fall along this line and the line should intersect the x-axis at zero. The results of the accumulated studies fit just such a pattern. Indeed, the inversevariance weighted geometric mean of the relative risks equals 1.04 (95%CI,0.77,1.41).Eachstudyhascertainstrengthsandlimitations, some of which were pointed out by Desta and Flockhart, and consideration of them against one another is of value. Nonetheless, the simplest explanation for the results to date is that they are sampled from an underlying null association. The integer above each interval in Fig 1 shows the number of women in the study (as best we can determine) with a recurrence and with the variant allele(s). Because both recurrence and the variant allele are rare, this number is the primary determinant of the study’s precision. Summed over all of the studies, there are only approximately sixty women with both a recurrence and the variant allele(s), about half from studies reporting a protective association and half fromstudiesreportingacausalassociation.Inourview,sixtywomen, evenlydistributedaboutthenull,istoosmallanumbertoconsiderthe association between CYP2D6-variant alleles and tamoxifen effective
Biopsy of Colorectal Polyps Is Not Adequate for Grading of Neoplasia
Authors: G. Gondal, T. Grotmol, B. Hofstad, M. Bretthauer, T. Eide, G. Hoff
Journal: Endoscopy (2005)

Background and Study Aim: Valid tissue sampling of colorectal adenomas is crucial for their management in terms of treatment and follow-up. The aim of this study was to assess the validity of a cold biopsy sample as representative for the whole polypectomy specimen, with regard to histopathological features. Patients and Methods: As part of the Norwegian Colorectal Cancer Prevention trial, 442 participants (60 % men) who fulfilled the criterion of colonoscopic recovery of adenoma that had been biopsied at flexible sigmoidoscopy, had their adenomas subsequently removed by polypectomy (snare resection) at colonoscopy. Logistic regression analysis was used to determine which variables contributed to the histopathological discrepancy between cold biopsy and polypectomy specimens. Results: Among the 532 colorectal adenomas biopsied at flexible sigmoidoscopy and removed by colonoscopy, the assessment of intraepithelial neoplasia (dysplasia) status was changed in 51 adenomas (10 %), and 38 (7 %) of them had been underestimated at biopsy compared with polypectomy. Likewise, the assessment of villousness was changed in 45 adenomas (9 %), being upgraded in 26 (6 %) at polypectomy compared with biopsy. In a multivariate model, the diameter of neoplasia at polypectomy was positively associated with increased risk of the underestimation of intraepithelial neoplasia and/or villousness influencing a diagnosis of advanced colorectal neoplasia, when cold biopsy and polypectomy specimens were compared (P trend = 0.01). Among 56 cases of advanced neoplasia, 35 (63 %) showed only low-grade intraepithelial neoplasia on biopsy. Conclusions: Biopsy-based diagnosis underestimated histopathological diagnosis in about 10 % of colorectal adenomas detected by flexible sigmoidoscopy screening, but advanced neoplasia was underestimated in more than 60 %. Efforts must be made to obtain polypectomy specimens to secure precise diagnosis.
<i>SCCRO</i> (<i>DCUN1D1</i>) Induces Extracellular Matrix Invasion by Activating Matrix Metalloproteinase 2
Authors: Pornchai O-charoenrat, Inderpal Sarkaria, Simon G. Talbot, Pabbathi Reddy, Su Dao, Ivan Ngai, Ashok Shaha, Dennis Kraus, Jatin Shah, Valerie Rusch, Y. Ramanathan, Bhuvanesh Singh
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Ectopic expression of squamous cell carcinoma–related oncogene (SCCRO or DCUN1D1) in NIH-3T3 cells induces invasion in vitro and produces highly invasive xenografts in nude mice with a propensity for regional lymphatical metastasis. The aim of this study was to identify the molecular mechanism underlying SCCRO-induced invasion and metastasis. Experimental Design: The molecular mechanism of SCCRO-mediated effects on matrix metalloproteinase-2 (MMP2) levels and activity were assessed using a combination of cell biological and molecular methods, including real-time PCR, reporter assay, RNA interference, and chromatin immunoprecipitation assay. Tumor specimens from primary upper aerodigestive tract carcinomas (n = 89) were examined for levels of SCCRO, MMP2, MMP9, MT1-MMP, TIMP1, and TIMP2 mRNA by real-time PCR. Results: Overexpression of SCCRO increases MMP2 levels and activity, which is required for SCCRO-induced invasion. Modified McKay assays reveal that SCCRO does not bind to the MMP2 promoter, suggesting that its transcriptional effects are indirect. Deletion or mutation of the activator protein-2 (AP2) and p53 binding element within the MMP2 promoter abrogates SCCRO-driven activation. Ectopic expression of SCCRO increases AP2 levels and promotes the binding of p53 to the MMP2 promoter. Consistent with these findings, SCCRO and MMP2 are coexpressed (P &amp;lt; 0.0001; r2 = 0.58; 95% confidence interval, 0.46-0.69) in primary (upper aerodigestive tract) carcinomas (n = 89), and this coexpression is associated with an increased prevalence of regional nodal metastasis (P = 0.04; relative risk, 1.53). Conclusions: SCCRO-induced invasion involves activation of MMP2 transcription in an AP2- and p53-dependent manner. SCCRO is a potential marker for metastatic progression in affected cancers.
Hypertension in the elderly (developments in cardiovascular medicine, vol. 157): Edited by G. Leonetti, C. Cuspidi. 141 pp., 46 (hardback), Dordrecht: Kluwer Academic Publishers, 1994. ISBN 0-7923-2852-3
Authors: M. C. Sutter
Journal: Cardiovascular Research (1995)

Hypertension in the elderly (developments in cardiovascular medicine, vol. 157): Edited by G. Leonetti, C. Cuspidi. 141 pp., £46 (hardback), Dordrecht: Kluwer Academic Publishers, 1994. ISBN 0-7923-2852-3 Get access Morley C. Sutter Morley C. Sutter Vancouver, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 30, Issue 2, August 1995, Page 313, https://doi.org/10.1016/S0008-6363(95)90133-7 Published: 01 August 1995
Diagnosis and Management of Cancer
Authors: James C. Arseneau
Journal: JAMA (1983)

Dr Nixon has written this book "to help the practicing physician, house officer, and medical student understand the current concepts of diagnosis and treatment of adult cancers." The book is short (295 pages) and perhaps because of its size, almost cursory in its treatment of a large and complex subject. In fact, one is forced to wonder whether this book might not have been written originally as a chapter for a major textbook of medicine rather than as a work that would stand by itself. The orientation of the book is clearly toward medical oncology (eg, surgery and radiation therapy of breast cancer merit a total of four paragraphs of discussion), yet even the discussion of medical oncology is often remarkable for its brevity (adjuvant chemotherapy of breast cancer is discussed in two paragraphs). Brevity can sometimes be compensated by providing references to literature for further reading, yet the text
Adaptation to the stress of tachycardia in patients with coronary artery disease: insight into the mechanism of the warm-up phenomenon.
Authors: D O Williams, T A Bass, H Gewirtz, A S Most
Journal: Circulation (1985)

Adaptation to exercise or the "warm up phenomenon" has been observed in some patients with angina pectoris. To investigate adaptation, eleven patients with exertional angina pectoris and angiographic evidence of coronary artery disease underwent two identical bouts of sequential tachycardia stress separated by a brief recovery period. Manifestations of ischemia were less during the second stress, as evidenced by a reduction in the severity of angina pectoris, less ST segment depression, and improved lactate extraction. Peak coronary blood flow during the second stress (81 +/- 20 ml/min) was not significantly different from that during the first (95 +/- 32 ml/min). Regional myocardial oxygen consumption, however, was significantly (p = .03) lower during the second stress (8.8 +/- 2.4 ml O2/min) when compared with the first (11.4 +/- 3.0 ml O2/min). Thus, patients with coronary artery disease can develop anginal tolerance to the stress of tachycardia similar to that observed after repeated bouts of exercise. A relative reduction in myocardial oxygen consumption, rather than an increase in coronary blood flow, appears to account for this phenomenon.
Oily fish and omega 3 fat supplements
Authors: Eric Brunner
Journal: BMJ (2006)

Oily fish and omega 3 fat supplementsHealth recommendations conflict with concerns about dwindling supply S eventy five years ago, long chain omega 3 fatty acids were added to the list of essential nutrients.Later in the 20th century, the properties of marine polyunsaturated oils were linked with several health benefits, including protection from cardiovascular disease.However, a high quality systematic review published in this week's BMJ draws attention to uncertainties about some of the health benefits attributed to omega 3 fats. 1 The review shows that the evidence for a reduction in cardiovascular events and mortality is less conclusive than we believed.A previous meta-analysis indicates that mortality is reduced owing to fewer fatal coronary events among people ingesting omega 3 fatty acids, 2 but the current review found no strong evidence of a reduction in combined cardiovascular events.The claim that omega 3 fats reduce the risk of cancer is not supported here or by another recent systematic review. 3 For each health outcome there are too few trials with adequate allocation concealment, and too few cohort studies in which the intake of omega 3 fat rather than total fish intake was measured.Recent findings complicate our understanding of the cardioprotective effect of omega 3 fat.Until the publication of the DART-2 trial in 2003, 4 the evidence showed that omega 3 from oily fish or supplements reduced the risks of fatal myocardial infarction, sudden death, and overall mortality among people with existing disease. 2 DART-2 included 3114 men with stable angina and tested the hypothesis that the main benefit of omega 3 fat is derived from its antiarrhythmic action in the presence of chronic disease. 5Surprisingly, DART-2 did not confirm this, showing an excess of sudden and total cardiac deaths.The excess was clearest in participants taking fish oil capsules rather than eating oily fish.DART-2 is not the only study to show that omega 3 fat supplements have pro-arrhythmic as well as anti-arrhythmic actions.A two year trial randomised 200 participants with an implantable cardioverter defibrillator and a recent episode of ventricular tachycardia or ventricular fibrillation to 1.3 g/day of omega 3 fats or placebo.The supplements did not prevent recurrent arrhythmia and seemed to be proarrhythmic in patients with ventricular tachycardia. 6
Status of Eclectics, et al.
Authors: Q. C. Smith
Journal: JAMA (1894)

Austin, Texas, Oct. 4, 1894. <h3>To the Editor:</h3> —Yes, we are all proud of the<i>success</i>of theJournal! It has forged ahead, in spite of prejudice and local jealousies, and now is beyond the experimental stage of its life. See herewith a clipping from our daily paper, of — — Company, quoting. In various cities and towns of the United States there are both homeopathic, and eclectic physicians who would scorn to drag medicine in traffic-slime, as this company does. Now these said homeopathic and eclectic physicians thrust Dr. —'s advertising "rot" under my nose, and say, tauntingly: "How do you get on, Mr. Regular?" You, personally, are well and widely known as a large-hearted liberal man and representative physician of the common sense class. And I hope you will be brave enough (as well as discrete enough, to give us—the rank and file— some definite basis upon which
RELATION BETWEEN APPENDICITIS AND GALLSTONES.
Authors: JOHN G. SHELDON
Journal: JAMA (1906)

Previous to about three years ago I attributed to postoperative and preoperative adhesions the abdominal pains, distension and constipation that sometimes remained after I had removed gallstones from a patient. Since I have been removing the appendix during operations for bile-passage diseases, adhesions have given me little trouble. During the latter part of June, 1903, three patients from whom others had removed gallstones came to me complaining of pain in the abdomen, abdominal distension and constipation. Two of these patients gave definite histories of acute attacks of appendicitis occurring early in life; the third gave a history of longstanding "stomach trouble" before the biliary colics began; in all of them there was marked tenderness over the appendix areas. These three patients were operated on for appendicitis. Marked changes were found in the removed appendices and the abdominal symptoms disappeared. These cases suggested to me that perhaps I had made mistakes
Surface ultrastructure of silicone rubber aortic valve poppetts after long-term implantation. A scanning electron microscope study of four poppets.
Authors: S P Allwork, R Norton
Journal: Thorax (1976)

The surface ultrastructure, demonstrated by scanning electron microscopy, is described in four implanted Silastic aortic valve poppets. Ball variance was discovered at necropsy in two patients and clinically in one in whom the poppet was replaced. The fourth patient underwent reoperation, but ball variance was neither suspected nor found. All four poppets were densely coated with biological debris and microthrombi. The 9coat9 was soluble in a weak solution of sodium hydroxide. The true Silastic surface beneath the coat was little altered compared with unimplanted poppets, even after 10 years9 implantation.
Risk-benefit ratio favours treating all pulmonary emboli, no matter how small
Authors: S. J. Quantrill
Journal: BMJ (2013)

Wiener and colleagues state that computed tomography (CT) pulmonary angiography finds pulmonary emboli “that do not need to be found,”1 but great caution is needed when deciding not to treat emboli detected by this technique.

Anderson’s study,2 cited as providing the best evidence for overdiagnosis, was …
A Phase II Trial of Induction Epirubicin, Oxaliplatin, and Fluorouracil, Followed by Surgery and Postoperative Concurrent Cisplatin and Fluorouracil Chemoradiotherapy in Patients with Locoregionally Advanced Adenocarcinoma of the Esophagus and Gastroesophageal Junction
Authors: Michael J. McNamara, David J. Adelstein, Joanna W. Bodmann, John F. Greskovich, Denise I. Ives, David P. Mason, Sudish C. Murthy, Thomas W. Rice, Jerrold P. Saxton, Davendra Sohal, Kevin Stephans, Cristina P. Rodriguez, Gregory M.M. Videtic, Lisa A. Rybicki
Journal: Journal of Thoracic Oncology (2014)
Congenital Absence of Abdominal Musculature
Authors: Harry M. Spence, Terry Allen
Journal: JAMA (1964)

The developmental defect of absence of the abdominal musculature is part of a syndrome of multiple anomalies amongst which disorders of the urinary tract present the greatest threat to life. The condition is due to congenital dysplasia of the musculature of the abdominal wall and urinary tract. This leads to impaired emptying and upper tract dilation with kidney insufficiency. Some infants are doomed at birth by the severity of their renal damage. Others may be saved by urinary tract drainage. We suggest circumventing the highest point of obstruction first to preserve renal parenchyma, using "loop" or "double barrel" cutaneous ureterostomy as a preliminary measure. Later restoration of continuity can be established after correction of any impediment to bladder outflow. Longitudinal plication of attenuated abdominal wall structures has been successful in two cases. This reconstruction is important in regard to respiratory ventilation, bowel function, locomotion, and aiding voiding.
Abuse of Medical Students
Authors: Lydia Matkovich
Journal: JAMA (1990)

To the Editor. —  In response to the articles published on medical student abuse 1,2 : Why do resident and attending staff abuse medical students?  Because medical staff do not perceive their behavior as abusive. Why is this so?  First, there is a lack of professionalism. The personal growth and maturity that develop among other young adults during their 20s may fail to occur among students of medicine, who often do not complete their medical education until well into their 30s. Older students who have been outside this protected environment for a period of time are often more aware of mistreatment because they have a basis for comparison as well as additional maturity.  Second, medicine is somehow viewed by its members as exempt from the strictures of other professions. Unions have all but forbade more than 40 hours in the workweek as unhealthy and inhumane; medical residents often work more than
Points from Letters: Pensions and the Abatement Rule
Authors: A. S. Pearson
Journal: BMJ (1971)

gases, lactate metabolism, and acid-base balance during and after exercise, and some of the results are to be published shortly.Basically we found that none of these factors could explain the origin of exercise-induced asthma or the difference with different forms of exercise.Likewise, we have studied lung volumes and mechanical properties and found that they reflect rather than cause the asthma.Finally, we would like to repeat our earlier suggestion that the mechanism of exercise-induced asthma and the difference between the severe constriction due to running compared with the virtual absence during swimming may reflect neuro- muscular differences in the types of exercise.