tbuckley/cabot-search huggingface dataset:
Topics in cancer risk assessment.
Authors: S S Olin, D A Neumann, J A Foran, G J Scarano
Journal: Environmental Health Perspectives (1997)

The estimation of carcinogenic risks from exposure to chemicals has become an integral part of the regulatory process in the United States within the past decade. With it have come considerable controversy and debate over the scientific merits and shortcomings of the methods and their impact on risk management decisions. In this paper we highlight selected topics of current interest in the debate. As an indication of the level of public concern, we note the major recent reports on risk assessment from the National Academy of Sciences and the U.S Environmental Protection Agency's proposed substantial revisions to its Guidelines for Carcinogen Risk Assessment. We identify and briefly frame several key scientific issues in cancer risk assessment, including the growing recognition of the importance of understanding the mode of action of carcinogenesis in experimental animals and in humans, the methodologies and challenges in quantitative extrapolation of cancer risks, and the question of how to assess and account for human variability in susceptibility to carcinogens. In addition, we discuss initiatives in progress that may fundamentally alter the carcinogenesis testing paradigm.
Surfactant Palmitoylmyristoylphosphatidylcholine Is a Marker for Alveolar Size during Disease
Authors: Ross Ridsdale, Matthias Roth-Kleiner, Frank D'Ovidio, Sharon Unger, Man Yi, Shaf Keshavjee, A. Keith Tanswell, Martin Post
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Two common lung-related complications in the neonate are respiratory distress syndrome, which is associated with a failure to generate low surface tension at the air-liquid interface because of pulmonary surfactant insufficiency, and bronchopulmonary dysplasia (BPD), a chronic lung injury with reduced alveolarization. Surfactant phosphatidylcholine (PC) molecular species composition during alveolarization has not been examined. Mass spectrometry analysis of bronchoalveolar lavage fluid of rodents and humans revealed significant changes in surfactant PC during alveolar development and BPD. In rats, total PC content rose during alveolarization, which was caused by an increase in palmitoylmyristoyl-PC (16:0/14:0PC) concentration. Furthermore, two animal models of BPD exhibited a specific reduction in 16:0/14:0PC content. In humans, 16:0/14:0PC content was specifically decreased in patients with BPD and emphysema compared with patients without alveolar pathology. Palmitoylmyristoyl-PC content increased with increasing intrinsic surfactant curvature, suggesting that it affects surfactant function in the septating lung. The changes in acyl composition of PC were attributed to type II cells producing an altered surfactant during alveolar development. These data are compatible with extracellular surfactant 16:0/14:0PC content being an indicator of alveolar architecture of the lung.
Thromboembolism after Cardioversion for Atrial Fibrillation
Authors: Marilyn J. Weigner
Journal: Annals of Internal Medicine (1997)

Letters1 December 1997Thromboembolism after Cardioversion for Atrial FibrillationMarilyn J. Weigner, MD, David I. Silverman, MD, and Warren J. Manning, MDMarilyn J. Weigner, MDBeth Israel Deaconess Medical Center; Boston, MA 02215Search for more papers by this author, David I. Silverman, MDBeth Israel Deaconess Medical Center; Boston, MA 02215Search for more papers by this author, and Warren J. Manning, MDBeth Israel Deaconess Medical Center; Boston, MA 02215Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-11-199712010-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We agree with Dr. Cheng that our data did not show that intravenous heparin had a significant benefit for hospitalized patients with atrial fibrillation that had lasted less than 48 hours. Our study, however, was underpowered to detect such a difference, with an estimated sample size in excess of 2500 patients (α level, 0.05; power, 8%) needed to show statistical significance given the low incidence of clinical thromboembolism in this group. Our recommendation that heparin anticoagulation be administered on admission is based on our concern that delaying anticoagulation may inadvertently allow many patients to go “unprotected” for an ...References1. Manning WJ, Silverman DI, Keighley CS, Oettgen P, Douglas PS. Transesophageal echocardiographically facilitated early cardioversion from atrial fibrillation using short-term anticoagulation: final results of a prospective 4.5 year study. J Am Coll Cardiol. 1995; 25:1354-61. Google Scholar2. Klein AL, Grimm RA, Black IW, Leung DY, Chung MK, Vaughn SE, et al. Cardioversion guided by transesophageal echocardiography: the ACUTE pilot study. A randomized, controlled trial. Ann Intern Med. 1997; 126:200-9. Google Scholar3. Falk RH, Knowlton AA, Bernard SA, Gotlieb NE, Battinelli NJ. Digoxin for converting recent-onset atrial fibrillation to sinus rhythm. A randomized, double-blinded trial. Ann Intern Med. 1987; 106:503-6. Google Scholar4. Galve E, Ruis T, Ballester R, Artaza MA, Arnau JM, Garcia-Dorado D, et al. Intravenous amiodarone in treatment of recent-onset atrial fibrillation: results of a randomized, controlled study. J Am Coll Cardiol. 1996; 27:1079-82. Google Scholar5. Danias PG, Caulfield TA, Weigner MJ, Silverman DI, Manning WJ. Predictors of spontaneous conversion of new onset atrial fibrillation to sinus rhythm [Abstract]. Circulation. 1996; 94:I-572. Google Scholar Author, Article, and Disclosure InformationAffiliations: Beth Israel Deaconess Medical Center; Boston, MA 02215 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1997Volume 127, Issue 11Page: 1039-1040KeywordsAtrial fibrillationHeparinThromboembolism Issue Published: 1 December 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Enterotoxins from Clostridium difficile; diarrhoeogenic potency and morphological effects in the rat intestine.
Authors: J Torres, E Jennische, S Lange, I Lonnroth
Journal: Gut (1990)

The action of toxins A, B, and C from Clostridium difficile was studied in the small intestine and colon of rats. All three caused fluid accumulation in the small intestine, maximal secretion being induced by 1 micrograms of toxin A, 20 micrograms of B, and 15 micrograms of C. Both toxins A and C caused shedding of epithelial cells from the villi without visible damage to crypt cells; toxin A caused further extensive necrosis and bleeding. Toxin B caused secretion without visible damage to the epithelial cells, though this activity was unstable and decreased significantly after one week of storage. In the colon, toxin A caused secretion and shedding of surface epithelial cells without damage to crypt cells, toxin C caused only a weak secretion, and toxin B had no effect at all. In terms of immunohistochemistry, it was found that toxin A bound to the enterocytes at the tips of the villi but not to goblet and crypt cells. The complex expression or interaction of the toxins produced by Cl difficile may explain the broad spectrum of disease (diarrhoea, colitis, and pseudomembranous colitis) associated with this micro-organism.
Stabilization of Carotid Atheroma Assessed by Quantitative Ultrasound Analysis in Nonhypercholesterolemic Patients With Coronary Artery Disease
Authors: Keisuke Watanabe, Seigo Sugiyama, Kiyotaka Kugiyama, Osamu Honda, Hironobu Fukushima, Hidenobu Koga, Yoko Horibata, Toshinori Hirai, Tomohiro Sakamoto, Michihiro Yoshimura, Yasuyuki Yamashita, Hisao Ogawa
Journal: Journal of the American College of Cardiology (2005)
Case of "dysfunctional" Dutch doctor exposes "culture of silence surrounding mistakes"
Authors: T. Sheldon
Journal: BMJ (2009)

A report into how a Dutch teaching hospital allowed a “dysfunctional” consultant neurologist to continue working unchecked for more than a decade has raised serious questions about the supervision of hospital consultants in the Netherlands.

The report, And Where was the Patient . . . ? followed an external investigation into neurologist Ernst Jansen Steur, who worked at the Medisch Spectrum Twente in Enschede between 1992 and 2003.

Investigators led by Wolter Lemstra, former chairman of the Dutch Hospitals Association, concluded that Dr Jansen harmed patients through misdiagnoses and incorrect prescribing.

Although alerted to errors by other hospital staff in 1998, the hospital’s management board failed to act. The report concludes, “The …
Anemia With Erythropoietin Deficiency Occurs Early in Diabetic Nephropathy
Authors: Deborah R. Bosman, Andrea S. Winkler, Joanne T. Marsden, Iain C. Macdougall, Peter J. Watkins
Journal: Diabetes Care (2001)

OBJECTIVE—The normochromic normocytic anemia of erythropoietin (EPO) deficiency is recognized in advanced renal failure but not in early renal disease. The aim of this study was to determine whether anemia with EPO deficiency is found in type 1 diabetic patients with diabetic nephropathy in the absence of advanced renal failure and to compare them with patients with nondiabetic renal disease of similar severity. RESEARCH DESIGN AND METHODS—A total of 27 type 1 diabetic patients with diabetic nephropathy (DN), defined as having persistent proteinuria (mean 1,086 mg/day [CI 120–5,190]), a serum creatinine ≤180 μmol/l, and retinopathy, were compared with 26 nondiabetic patients with glomerulonephritis (GN) and persistent proteinuria (1,874 mg/day [349–5,005]). The Hb concentration, red cell indexes, and serum EPO levels were measured, and other causes for the anemia were excluded. The EPO values were compared with a normal reference range obtained from nondiabetic patients with a microcytic anemia. The DN patients were tested for signs of diabetic peripheral and autonomic neuropathy. RESULTS—We found that 13 of the 27 DN patients were anemic (Hb 10.6 ± 0.9 g/dl) in marked contrast to none of the GN patients (Hb 13.7 ± 1.4 g/dl, P &amp;lt; 0.005). In the DN group, serum EPO concentrations failed to increase in response to anemia compared with the response seen in patients with microcytic anemia. Thus, the anemia of the DN group was associated with EPO deficiency. The anemic DN patients showed evidence of more severe proteinuria and diabetic neuropathy than the nonanemic DN patients. CONCLUSIONS—Anemia associated with EPO deficiency can occur early in DN before the onset of advanced renal failure, but does not normally occur in nondiabetic renal disease of similar severity. The pathogenesis requires elucidation.
An Evaluation of Serum Pesticide Residue Levels and Liver Function in Persons Exposed to Dairy Products Contaminated With Heptachlor
Authors: Paul A. Stehr-Green
Journal: JAMA (1988)

We studied a group of 45 dairy farm family members who had consumed undiluted raw milk products known to be contaminated with residues of the pesticide heptachlor at concentrations as high as 89.2 ppm (fat basis). We compared results of serum pesticide assays for these exposed persons with results for an unexposed group of 94 persons from the same geographic area and the results from the Second National Health and Nutrition Examination Survey. The exposed group had significantly higher mean levels of primary heptachlor metabolites--ie, heptachlor epoxide (0.84 +/- 1.0 vs 0.50 +/- 0.9 parts per billion) and oxychlordane (0.71 +/- 0.8 vs 0.49 +/- 1.1 parts per billion)--than the unexposed group. In the exposed group, 21.2% had elevated serum concentrations of these same metabolites; this rate was significantly greater than the rates in both the unexposed farm family members (heptachlor epoxide, 3.8%; oxychlordane, 6.3%) and the Second National Health and Nutrition Examination Survey sample (2.5% for both metabolites). However, we found no evidence of related acute and/or subacute hepatic effects in these exposed persons regardless of their serum concentrations of pesticide residues.
Predicting the Outcome of Unsuccessful Prehospital Advanced Cardiac Life Support
Authors: Arthur L. Kellermann
Journal: JAMA (1993)

To determine if failure to achieve return of spontaneous circulation following prehospital advanced cardiac life support (ACLS) warrants termination of efforts at the scene.Retrospective case series.Memphis, Tenn, a city of 610337 people that is served by a fire department-based emergency medical service system. All city ambulances provide ACLS.Adult victims of out-of-hospital cardiac arrest due to heart disease.All patients received prehospital ACLS according to the 1986 American Heart Association guidelines. Following prehospital ACLS, all patients were transported to the nearest hospital emergency department whether or not a pulse was restored in the field.Survival to hospital admission, survival to hospital discharge, and neurological status at discharge.Over the 39-month study interval, the Memphis Fire Department treated 1068 victims of out-of-hospital cardiac arrest. Three hundred ten of these (29%) had return of spontaneous circulation prior to transport for some period. The remaining 758 patients (71%) never regained a pulse and were transported with ongoing cardiopulmonary resuscitation. Patients who had return of spontaneous circulation prior to transport were more likely to be admitted (69% vs 7.0%) and far more likely to be discharged alive (26.5% vs 0.4%) than patients who failed to respond to prehospital ACLS. Three patients who survived to hospital discharge despite failure to achieve return of spontaneous circulation prior to emergency medical service transport sustained their cardiac arrest after paramedic arrival. All three were discharged with moderate to severe cerebral disability.Rapid transport of adults who fail to respond to an adequate trial of prehospital ACLS does not result in meaningful rates of survival. In such cases, on-line emergency medical service physicians should authorize paramedics to cease efforts in the field.
Computerised updating of clinical summaries: new opportunities for clinical practice and research?
Authors: D. E. Llewelyn, D. L. Ewins, J. Horn, T. G. Evans, A. M. McGregor
Journal: BMJ (1988)

A new type of clinical summary, produced by copying standard descriptions of diseases on to a computer screen and editing them to match a patient9s findings and diagnoses, was updated and reprinted as the patient9s condition changed in the ward or as an outpatient. When this method was used to produce typed medical discharge summaries over a three month period, 73 out of 91 (80%) were sent out within a week after discharge compared with five out of 56 (9%) conventionally typed summaries received in a single general practice. Even completely new computerised summaries are quicker for the secretary to produce than conventional summaries, and the computerised summaries are designed to be scanned rapidly for relevant information. They can also be used to collect data automatically for research, clinical audit, and resource management.
Prescription Change: Methyldopa for Levodopa
Authors: Harry B. Weinberg
Journal: JAMA (1972)

<h3>To the Editor.—</h3> In his letter (222:210, 1972), Dr. Engelman describes instances where the use of generic names had led to errors in filling prescriptions, and he suggests that the use of a brand name might be advantageous. There is another safeguard that can be very helpful in preventing errors. I refer to including the intended purpose of the drug in the labeled instructions. Had the directions read: "tab 1 qid for blood pressure," the pharmacist would certainly have recognized that methyldopa was intended, not levodopa. This is an added advantage of the procedure, the primary purpose being to better identify the drug to the patient. The system is equally applicable in prescribing brand name drugs, which are also often confusingly similar.
IMPACT OF NT-PROBNP LEVELS IN PATIENTS WITH ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION WHO HAVE NORMAL LEFT VENTRICULAR SYSTOLIC FUNCTION WITHOUT REGIONAL WALL MOTION ABNORMALITY
Authors: Youngkeun Ahn, Seo Na Hong, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang
Journal: Journal of the American College of Cardiology (2011)
Replacing the first epidermal growth factor-like domain of factor IX with that of factor VII enhances activity in vitro and in canine hemophilia B.
Authors: J Y Chang, D M Monroe, D W Stafford, K M Brinkhous, H R Roberts
Journal: Journal of Clinical Investigation (1997)

Using the techniques of molecular biology, we made a chimeric Factor IX by replacing the first epidermal growth factor-like domain with that of Factor VII. The resulting recombinant chimeric molecule, Factor IXVIIEGF1, had at least a twofold increase in functional activity in the one-stage clotting assay when compared to recombinant wild-type Factor IX. The increased activity was not due to contamination with activated Factor IX, nor was it due to an increased rate of activation by Factor VIIa-tissue factor or by Factor XIa. Rather, the increased activity was due to a higher affinity of Factor IXVIIEGF1 for Factor VIIIa with a Kd for Factor VIIIa about one order of magnitude lower than that of recombinant wild-type Factor IXa. In addition, results from animal studies show that this chimeric Factor IX, when infused into a dog with hemophilia B, exhibits a greater than threefold increase in clotting activity, and has a biological half-life equivalent to recombinant wild-type Factor IX.
Ways for Surgeons to Increase the Efficiency of Their Use of Hospitals
Authors: Richard H. Egdahl
Journal: New England Journal of Medicine (1983)

Pressure from the federal government and industry to improve the efficiency of medical-care delivery will continue to increase. There is considerable evidence that various kinds of overuse are common, but traditional medical education, conflicting reimbursement incentives, a laissez faire approach to the economic consequences of medical practice, and aggressive marketing programs have provided an environment resistant to change. Today, physicians are being compelled, both by regulatory initiatives and competition from health-maintenance organizations and other alternative delivery systems, to reexamine traditional practice routines, with the goal of achieving cost savings from decreased hospitalization and less use of diagnostic and treatment procedures. . . .
Notice of Duplicate Publication-Reply
Authors: Matthew Menken
Journal: JAMA (1985)

<h3>In Reply.—</h3> I am sorry that the editors have obtained the impression that the article was a duplicate publication of an earlier article in the<i>New England</i><i>Journal of Medicine</i>. I am surprised by this editorial decision, because my coauthor and I believe that both in purpose and content the two articles are significantly different from each other. The material in the recent<i>JAMA</i>article was first prepared for presentation by one of us at a meeting of the Fourth International Congress of the World Federation of Public Health Associations, whose theme was "Lessons Learned in Primary Care." A review of the literature led us to conclude that the effects of a glut of specialists on primary care, and the organization of care, had received insufficient attention, and we decided to develop a more detailed discussion of these issues. To be sure, these manuscripts contain some common material, in terms
Evaluation of clinical efficacy and safety of adapalene 0·1% gel versus tretinoin 0·025% gel in the treatment of acne vulgaris, with particular reference to the onset of action and impact on quality of life
Authors: None Grosshans, None Marks, None Mascaro, None Torras, None Meynadier, None Alirezai, None Finlay, None Soto, None Poncet, None Verschoore, None Clucas
Journal: British Journal of Dermatology (1998)

A randomized, multicentre, investigator-masked study was conducted in 105 patients with mild to moderate acne vulgaris to compare the efficacy and safety of adapalene 0·1% gel with tretinoin 0·025% gel after three months of treatment, with particular emphasis on reduction in inflammatory lesion counts after one week of treatment and impact on quality of life. In terms of efficacy, adapalene gel was found to be superior to tretinoin gel after one week of treatment, with respect to reduction in inflammatory lesion counts (32% vs. 17%, respectively; P = 0·001), total lesion counts (28% vs. 22%, respectively; P = 0·042) and global severity grade (28% vs. 16%, respectively; P = 0·001). No significant difference between the two treatments was found after 12 weeks of treatment for any of these variables. Evaluation of facial skin tolerance parameters showed significant differences between the two treatments in favour of adapalene for dryness, erythema, immediate and persistent burning and pruritus for at least one time point. One patient in the adapalene group and three patients in the tretinoin group experienced medical events which lead to discontinuation of treatment (skin irritation; NS). Quality of life scores improved more rapidly in the adapalene group than in the tretinoin group, with significant differences (P < 0·05) appearing at week 1 for questions related to problems with partners, close friends or relatives and to skin symptoms. There was also a significantly greater improvement in social and leisure activity in the adapalene group at week 12. Adapalene 0·1% gel reduced inflammatory and total lesion counts more rapidly than tretinoin 0·025% gel, and was also better tolerated. These differences appear to result in an earlier and greater quality of life improvement for the patients receiving adapalene.
Immunosuppression in Liver Transplantation
Authors: Roy Y. Calne
Journal: New England Journal of Medicine (1994)

The introduction of cyclosporine as an immunosuppressive agent improved the results of all types of organ transplantations1 and allowed liver transplantation to become the treatment of choice for many patients with end-stage liver disease.2 The rejection seen after liver transplantation tends to be less severe than that occurring after heart or kidney transplantation. Although acute rejection of the liver is common, it can usually be reversed with high doses of corticosteroids. Chronic rejection that is resistant to treatment with corticosteroids and antilymphocyte antibodies occurs in approximately 10 percent of cases. The liver is the main site of metabolism of cyclosporine. . . .