tbuckley/cabot-search huggingface dataset:
Cancer Risks of Medical Treatment
Authors: D. Schottenfeld
Journal: CA A Cancer Journal for Clinicians (1982)

The critical assessment for carcinogenicity of drugs presently in use must be balanced by demonstrable therapeutic benefits. Of approximately 20,000 generically different drug products currently available in the United States, those established as human oncogens are the cytotoxic alkylating agents. immunosuppressive agents, estrogens, oral contraceptives, androgenic anabolic steroids, methoxypsoralen, and phenacetin-containing analgesics. DES. and possibly phenytoin, are the only known examples of human transplacental carcinogens. The epidemiologic evidence of carcinogenicity for other suspect drugs such as metronidazole (Flagy®). isoniazid, and reserpine is at present either lacking or is conflicting. Of potential significance is the interaction of drugs that are tertiary amines (e.g., aminopyrine, chlorpromazine, methadone, and oxytetracycline) with nitrite in the acid solution of the stomach to form dialkylnitrosamines, which are potent carcinogens in animals. This process of nitrosation may be inhibited by antioxidants such as ascorbic acid or glutathione. The risk-benefit evaluation of a drug should take into account the likely outcome of the disease if untreated, and whether or not safer alternative therapeutic agents are available. For example, the risks incurred by the use of chlornaphazine or chlorambucil in the treatment of polycythemia vera are considered as excessive as compared with the benefits offered by alternative therapeutic measures. When agents are prescribed that are potentially carcinogenic, but whose continued use by society is viewed as cost-effective, then these should be formulated and prescribed at the lowest dose and for the shortest period of time required to achieve the desired result. Careful premarketing laboratory and clinical screening and postmarketing epidemiologic surveillance are essential for ensuring safety and efficacy. The clinician has a vital role in detecting previously unsuspected iatrogenic hazards, and in educating the public about the indications, contraindications, and side effects of each therapeutic agent.
Graphical aid for determining power of clinical trials involving two groups.
Authors: D. K. Miller, S. M. Homan
Journal: BMJ (1988)

Physicians need to evaluate clinical research critically, and determining the power of a study is an essential component of research evaluation. This report presents a graphical aid that permits rapid power determination for clinical trials with two groups. Power curves were developed for dichotomous outcomes by setting two tail alpha at 0.05 and varying the sample size, the control group response rate, and the clinically important difference between control and experimental groups as defined by the user. Use of the graphical aid was demonstrated to a group of 18 medical students, residents, fellows, and faculty in a 15 minute session. Evaluation of the trainees' application of the aid showed a small average bias of -0.0003 and an average variance of 0.006. Ninety percent of power estimates were within 0.05 of the true value determined by formula. This graphical aid is recommended as a rapid and accurate method for determining power in the critical appraisal of clinical research.
Patients should not be discouraged from entering trials
Authors: J. E Harrison
Journal: BMJ (1996)

EDITOR,—Charlotte Williamson's editorial highlights the benefits of involving patients in decisions about their treatment and of patients' participation in research.1 Two years ago I was diagnosed as having breast cancer. I had recently started a PhD investigating the application of randomised controlled trial methods to my specialty and had just returned from a course at which the ethics surrounding a randomised controlled trial in breast cancer were discussed.

I had decided, before I was told my diagnosis, that …
Long-term Nonprogressive Disease Among Individuals With Untreated HIV Infection
Authors: Geoffrey S. Gottlieb, Robert A. Smith, Papa Salif Sow
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Increased cyclic guanosine monophosphate production and overexpression of atrial natriuretic peptide A-receptor mRNA in spontaneously hypertensive rats.
Authors: J Tremblay, C Huot, R C Willenbrock, F Bayard, F Gossard, N Fujio, C Koch, O Kuchel, W Debinski, P Hamet
Journal: Journal of Clinical Investigation (1993)

Atrial natriuretic peptide (ANP) specifically stimulates particulate guanylate cyclase, and cyclic guanosine monophosphate (cGMP) has been recognized as its second messenger. Spontaneously hypertensive rats (SHR) have elevated plasma ANP levels, but manifest an exaggerated natriuretic and diuretic response to exogenous ANP when compared to normotensive strains. In isolated glomeruli, the maximal cGMP response to ANP corresponds to a 12- to 14-fold increase over basal levels in normotensive strains (Wistar 13 +/- 2; Wistar-Kyoto 12 +/- 2; Sprague-Dawley 14 +/- 2) while a maximal 33 +/- 3-fold elevation occurs in SHR (P < 0.001). This hyperresponsiveness of cGMP is reproducible in intact glomeruli from SHR from various commercial sources. Furthermore, this abnormality develops early in life, even before hypertension is clearly established, and persists despite pharmacological modulation of blood pressure, indicating that it is a primary event in hypertension. In vitro studies have revealed a higher particulate guanylate cyclase activity in membranes from glomeruli and other tissues from SHR. This increase is not accounted for by different patterns of ANP binding to its receptor subtypes between normotensive and hypertensive strains, as assessed by competitive displacement with C-ANP102-121, an analog which selectively binds to one ANP receptor subtype. The hyperactivity of particulate guanylate cyclase in SHR and its behavior under basal, ligand (ANP), and detergent-enhanced conditions could be attributed either to increased expression or augmented sensitivity of the enzyme. Radiation-inactivation analysis does not evoke a disturbance in the size of regulatory elements normally repressing enzymatic activity, while the expression of particulate guanylate cyclase gene using mutated standard of A- and B-receptors partial cDNAs, quantified by polymerase chain reaction (PCR) transcript titration assay, manifests a selective increase of one guanylate cyclase subtype. Our data suggest that in hypertension, genetic overexpression of the ANP A-receptor subtype is related to the exaggerated biological response to ANP in this disease.
Deoxythymidine and deoxycytidine incorporation into DNA in B leukemic cells
Authors: F. Vertongen, A.‐M. Lebacq, P. Fondu, I. M. Mandelbaum
Journal: American Journal of Hematology (1986)

Abstract Measurements of radioactive DNA after incubation of normal and B leukemic peripheral mononuclear cells, from c‐ALL and CLL with labeled deoxythymidine (dTh) and deoxycytidine (dCt) showed that for dTh, incorporation into DNA was similar for normal and c‐ALL cells but lower in B‐CLL cells and that for dCt, incorporation was highest in c‐ALL and lowest in CLL cells. These results contrast with those of dTh and dCt kinase activities; the former has been previously found elevated in c‐ALL cells, and the latter is found, in the present study, similar in the three groups tested.
Polyps of the Colon
Authors: Michael A. Appel
Journal: JAMA (1976)

<h3>To the Editor.—</h3> It is out of my great respect for Dr Richard Marshak as a diagnostic radiologist that I reply to the recent article in the "Topics in Radiology" section (235:2856, 1976) in which Dr Marshak and his co-authors describe their concept of a rational approach to the management of adenomatous polyps of the colon. I am writing to emphasize the principle of colonoscopic polypectomy for all polyps identified by the radiologists. First, it has been well documented now that presumably adequate radiology is not as complete in its demonstration of all the polyps in an individual's colon as is equally competent endoscopy. The meticulous preparation of the bowel for barium enema described by Dr Marshak is not easily come by for most radiologists, and I can only commend his tenacity if all of his patients have such meticulous preparation that 4-mm polyps can always be demonstrated. On the
Esophageal Varices without Hemorrhage in Cirrhosis
Authors: Eddy D. Palmer, Irving B. Brick, Edward J. Jahnke
Journal: New England Journal of Medicine (1954)

AMONG the first 50 surgical portal decompressions carried out for the treatment of esophageal varices at three university-affiliated hospitals in Washington, 18 patients were operated on in the absence of a history of hemorrhage. From the start of a local program to attack varices by definitive surgical shunt procedures, the attitude was adopted that the mere presence of esophageal varices constitutes such a dangerous threat that they should not be permitted to hemorrhage once to fill the requirements for active therapy. The indication for operation in this group was the presence of varices, not a history of hemorrhage.Considerable opposition . . .
Debulking Nephrectomy in Metastatic Renal Cancer
Authors: Robert C. Flanigan
Journal: Clinical Cancer Research (2004)

Abstract Up to one third of patients with renal cell carcinoma will present with metastatic disease, and 20 to 40% of those with clinically localized disease will eventually be found to have metastatic involvement. Prognosis continues to be guarded for this population, with a 2-year survival of only 10 to 30%. Although advances are being made in the medical management of renal cell carcinoma, the role of surgery in the treatment algorithm is also being additionally refined. Palliative surgery either via nephrectomy or metastasectomy has a role in certain well-selected patients. There are also data to support total metastasectomy at the time of either nephrectomy or recurrence in a small subset of patients with minimal, resectable metastases. More controversial is the idea of cytoreductive nephrectomy as an adjunct to immunotherapy. Recent phase III trials indicate that nephrectomy may play an important role in management of metastatic renal cell carcinoma in conjunction with cytokine-based immunotherapy. Nephrectomy is also an essential component of tumor-based vaccine and adoptive immunotherapy protocols and may play a role in other novel therapies.
Safe dental anaesthesia
Authors: D. Simpson
Journal: BMJ (1982)

<h3>Background</h3> The time–benefit relationship of endovascular thrombectomy (EVT) according to the size of the core infarct has been incompletely explored in prior studies. We investigated whether established infarct core size on baseline imaging modifies the relationship between onset-to-reperfusion time (OTR) and functional outcomes in patients with acute ischemic stroke treated with EVT. <h3>Methods</h3> We analyzed a database containing individual patient data pooled from three prospective Solitaire stent retriever studies. The inclusion criteria were treatment with a Solitaire device and achievement of substantial reperfusion (modified Thrombolysis in Cerebral Infarction 2b–3). Main analyses were performed in patients with baseline Alberta Stroke Program Early CT Scores (ASPECTSs) of 7–10. <h3>Results</h3> Among the 305 patients (mean age 67±13 years, 58% women), the proportions of patients in different categories of pretreatment infarct extent were: small (ASPECTS 9–10) 52.0%, moderate (ASPECTS 7–8) 37.1%, and large (ASPECTS 0–6) 7.6%. The mean OTR was 297±95 min. At 3 months, 60.1% of the patients achieved a good outcome. For OTRs of 2–8 hours, the rates of good outcomes at all time points were higher with higher baseline ASPECTS but declined with similar steepness. Both baseline ASPECTS (OR 1.23 (95% CI 1.04 to 1.45)) and OTR (every 30 min delay, OR 0.80 (95% CI 0.73 to 0.88)) were independently associated with a good 3-month outcome. No interaction between OTR and baseline ASPECTS was observed. <h3>Conclusions</h3> Although patients with higher baseline ASPECTS are more likely to have good clinical outcomes at all OTR intervals after 2 hours, this benefit consistently declines with time, even in patients with a small infarct core, reinforcing the need to treat all patients as quickly as possible.
The impact on general practitioners of the changing balance of care for elderly people living in institutions
Authors: S. Kavanagh, M. Knapp
Journal: BMJ (1998)

<b>Objectives</b>: To describe utilisation of general practitioners by elderly people resident in communal establishments;to examine variations in general practitioner utilisation and estimate the likely impact of the "downsizing" of long stay provision in NHS hospitals. <b>Design</b>: Secondary analyses of the survey of disability among adults in communal establishments conducted by the Office of Population Censuses and Surveys in 1986,&nbsp;and projection to present day. <b>Setting</b>: Nationally representative sample of communal establishments in Great Britain. <b>Subjects</b>: Disabled residents aged 65&nbsp;or more without mental handicap. <b>Results</b>: Residents with higher levels of disability, disorders of the digestive system, resident in smaller local authority homes or larger voluntary residential homes were more likely to consult a general practitioner. For those who consulted, higher levels of disability and morbidity and residence in a private nursing home or a larger private residential home were all associated with greater general practitioner utilisation. Overall, when residents9 characteristics and size of home was controlled for, residents in nursing homes had greater predicted utilisation than those in residential care homes. People who would previously have been cared for in NHS hospitals and are now cared for in nursing homes have high predicted utilisation due to their greater morbidity and disability. <b>Conclusion</b>: The "downsizing" of NHS provision for elderly people has increased demand on general practitioners by 160 whole time equivalents per year in Britain.
Benzo(a)pyrene metabolism, DNA-binding and UV-induced repair of DNA damage in cultured skin fibroblasts from a patient with unilateral multiple basal cell carcinoma
Authors: P.S.C. DON, H. MUKHTAR, M. DAS, N.A. BERGER, D.R. BICKERS
Journal: British Journal of Dermatology (2006)

Journal Article Benzo(a)pyrene metabolism, DNA‐binding and UV‐induced repair of DNA damage in cultured skin fibroblasts from a patient with unilateral multiple basal cell carcinoma Get access P.S.C. DON, P.S.C. DON Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University and Veterans Administration Medical Center, Cleveland, Ohio, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar H. MUKHTAR, H. MUKHTAR Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University and Veterans Administration Medical Center, Cleveland, Ohio, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar M. DAS, M. DAS Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University and Veterans Administration Medical Center, Cleveland, Ohio, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar N.A. BERGER, N.A. BERGER Department of Medicine, Hematology/Oncology Division, R.Livingstone Ireland Cancer Center, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar D.R. BICKERS D.R. BICKERS Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University and Veterans Administration Medical Center, Cleveland, Ohio, U.S.A. David R. Bickers, M.D., Department of Dermatology, University Hospitals of Cleveland, 2074 Abington Road, Cleveland, Ohio 44106, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 120, Issue 2, 1 February 1989, Pages 161–171, https://doi.org/10.1111/j.1365-2133.1989.tb07780.x Published: 01 February 1989
Effect of diltiazem upon episodes of silent myocardial ischemia during daily life
Authors: Pierra Théroux, Michael Baird, Martin Juneau, Wayne Warnica, Peter Klinke, William Kostuk, Peter Pflugfelder, Eric Lavallée, Christine Chin, Ellen Dempsey, Michael Grace, David Waters
Journal: Journal of the American College of Cardiology (1990)
A Functional Haplotype in the 3′Untranslated Region of<i>TNFRSF1B</i>Is Associated with Tuberculosis in Two African Populations
Authors: Marlo Möller, Friederike Flachsbart, Andreas Till, Thorsten Thye, Rolf D. Horstmann, Christian G. Meyer, Ivy Osei, Paul D. van Helden, Eileen G. Hoal, Stefan Schreiber, Almut Nebel, Andre Franke
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Susceptibility to tuberculosis is not only determined by Mycobacterium tuberculosis infection, but also by the genetic component of the host. The pleiotropic cytokine tumor necrosis factor-α is essential to control tuberculosis infection, and various tumor necrosis factor family members and their respective receptors may contribute to tuberculosis risk.Objectives: To investigate four functionally relevant polymorphisms in the tumor necrosis factor receptor 2–encoding gene, tumor necrosis factor receptor superfamily member 1B, for association with tuberculosis susceptibility.Methods: Genotyping of four polymorphisms was performed in independent populations from South Africa (429 cases and 482 control subjects) and Ghana (640 cases and 1,158 control subjects), and the association of the variants with tuberculosis was tested using two case-control association studies.Measurements and Main Results: Single-point and haplotype analysis in South Africans revealed an association in the 3′untranslated region of the investigated gene. The T allele of rs3397 alone and/or the 3′ untranslated region haplotype GTT may confer protection against tuberculosis insofar as both allele and haplotype frequencies were significantly lower in case subjects than in controls. The GTT genotype had previously been shown to increase the decay of tumor necrosis factor receptor 2 messenger ribonucleic acid, and messenger ribonucleic acid destabilization may represent a key molecular mechanism for disease susceptibility. Interestingly, the association signal appeared to be restricted to women. The genetic finding was validated in female participants from Ghana. The combined P value in the haplotype analysis was P = 0.00011.Conclusions: Our finding emphasizes the importance of tumor necrosis factor/tumor necrosis factor receptor–mediated immune responses in the pathogenesis of tuberculosis.
Comparative Study of Glucose Homeostasis, Lipids and Lipoproteins, HDL Functionality, and Cardiometabolic Parameters in Modestly Severely Obese African Americans and White Americans With Prediabetes: Implications for the Metabolic Paradoxes
Authors: Sara J. Healy, Kwame Osei, Trudy Gaillard
Journal: Diabetes Care (2014)

OBJECTIVE To determine whether modestly severe obesity modifies glucose homeostasis, levels of cardiometabolic markers, and HDL function in African Americans (AAs) and white Americans (WAs) with prediabetes. RESEARCH DESIGN AND METHODS We studied 145 subjects with prediabetes (N = 61 WAs, N = 84 AAs, mean age 46.5 ± 11.2 years, mean BMI 37.8 ± 6.3 kg/m2). We measured fasting levels of lipids, lipoproteins, and an inflammatory marker (C-reactive protein [CRP]); HDL functionality (i.e., levels of paraoxonase 1 [PON1]); and levels of oxidized LDL, adiponectin, and interleukin-6 (IL-6). We measured serum levels of glucose, insulin, and C-peptide during an oral glucose tolerance test. Values for insulin sensitivity index (Si), glucose effectiveness index (Sg), glucose effectiveness at zero insulin (GEZI), and acute insulin response to glucose (AIRg) were derived using a frequently sampled intravenous glucose tolerance test (using MINMOD software). RESULTS Mean levels of fasting and incremental serum glucose, insulin, and C-peptide tended to be higher in WAs versus AAs. The mean Si was not different in WAs versus AAs (2.6 ± 2.3 vs. 2.9 ± 3.0 × 10−4 × min−1 [μU/mL]−1). Mean values for AIRg and disposition index as well as Sg and GEZI were lower in WAs than AAs. WAs had higher serum triglyceride levels than AAs (116.1 ± 55.5 vs. 82.7 ± 44.2 mg/dL, P = 0.0002). Mean levels of apolipoprotein (apo) A1, HDL cholesterol, PON1, oxidized LDL, CRP, adiponectin, and IL-6 were not significantly different in obese AAs versus WAs with prediabetes. CONCLUSIONS Modestly severe obesity attenuated the ethnic differences in Si, but not in Sg and triglyceride levels in WAs and AAs with prediabetes. Despite the lower Si and PON1 values, AAs preserved paradoxical relationships between the Si and HDL/apoA1/triglyceride ratios. We conclude that modestly severe obesity has differential effects on the pathogenic mechanisms underlying glucose homeostasis and atherogenesis in obese AAs and WAs with prediabetes.
Challenges Facing the US Patient-Centered Outcomes Research Institute
Authors: Alexander K. Ommaya
Journal: JAMA (2011)

REALIZING THE PROMISE OF COMPARATIVE EFFECTIVEness research and achieving health care practice change require not only identifying research priorities, but also determining how to conduct the studies and implement the results. The new PatientCentered Outcomes Research Institute (PCORI) is a nonprofit entity charged with prioritizing and supporting studies and improvement in the methods of comparative effectiveness research. By 2014, the PCORI budget may increase to more than $500 million. It is funded by Medicare, private health insurers, and self-insured plans.
Science, medicine, and the future: Lung cancer
Authors: T. Sethi
Journal: BMJ (1997)

Lung cancer, the most prevalent cancer in the Western world, is mainly caused by smoking. Nevertheless, only 20% of smokers develop lung cancer and while prevention is important, environmental factors are expected to contribute to the predicted rise in the incidence of lung cancer in the next 25 years. Survival of lung cancer is still poor, and new treatments are urgently needed. This review examines potential new therapeutic developments which have arisen from a greater understanding of the molecular and cellular biology of lung cancers.