tbuckley/cabot-search huggingface dataset:
A Combined Morphological and Electrophysiological Study of the Atrioventricular Node of the Rabbit Heart
Authors: ROBERT H. ANDERSON, Dirk Durrer, MICHIEL J. JANSE, FRANS J. L. VAN CAPELLE, JACQUES BILLETE, ANTON E. BECKER, DIRK DURRER
Journal: Circulation Research (1974)

Thirteen rabbit atrioventricular nodes were studied both morphologically and electrophysiologically. Two of these nodes were subsequently reconstructed in three-dimensional fashion. From the morphological standpoint, it was shown that the atrioventricular node was divided into a smaller enclosed portion and a larger open portion by a fibrous collar derived from the central fibrous body. Three distinct nodal cell types were identified within these nodal segments. The open node was mostly occupied by transitional cells which merged proximally with the atrial myocardium. As they entered the enclosed node, some of these transitional cells merged into a knot of midnodal cells. Others passed circumferentially round this knot and together with the midnodal cells, joined with a tract of lower nodal cells. The latter cells were continuous with the His bundle anteriorly, but they also extended into the open node posteriorly. It was possible to correlate the activation sequence of the node accurately with the disposition of these cells. Using both reconstructions and techniques to mark cells from which action potentials had been recorded, it was shown that the transitional cells correlated with the AN zone of the node. Cells with N potentials were located in the environs of the midnodal cell knot. The anterior portion of the lower nodal cells correlated with the NH nodal zone. The posterior extension of the lower nodal cells and the overlay fibers of the anterior transitional cells both functioned as dead-end pathways. Histologically distinct tracts were not identified within the internodal atrial myocardium.
Diethylstilbestrol-Induced Jaundice in the Chinese and Armenian Hamster
Authors: John E. Coe, Kamal G. Ishak, Mary J. Ross
Journal: Hepatology (1983)

An unusual and impressive hyperbilirubinemia was induced in Chinese hamsters by administration of diethylstilbestrol (DES). This icterus was dose-dependent and affected females more severely than males. However, a similar mortality was detected in both sexes. Another hamster, the Armenian hamster, was even more susceptible to the icteric and lethal effects of DES. The hamster model of DES-induced icterus showed many clinical dissimilarities when compared to the human estrogen-induced jaundice, simple cholestatic jaundice. Furthermore, hepatic pathology was distinctly different as canalicular cholestasis was absent although other degenerative and regenerative hepatocellular changes were present. Livers of Armenian hamsters were more severely affected than were livers from Chinese hamsters and contained Mallory bodies even within 1 week after DES treatment. A modest, nonlethal jaundice also was detected in European hamsters after DES injection, whereas Syrian hamsters were not affected even after larger doses. This unique sensitivity to DES, and the spectrum of sensitivity within these related hamsters (Armenian ± Chinese ± European vs. resistant Syrian) provide an interesting model for study of DES effect on hepatic function.
Facial Disfigurement in Automobile Accidents
Authors: John Marquis Converse
Journal: JAMA (1963)

A review of the methods of treating victims of automobile accidents emphasizes the need for expert care to insure prevention of facial disfigurement and to improve the rehabilitation of individuals with such disfigurement which constitutes a serious physical, psychological, and vocational handicap. Among the disfigurements are cutaneous scars; frontal, nasal, and naso-orbital deformities; fractures involving the bones of the orbit; fractures of the jaw; and loss of contour of the bony framework of the face. The medical profession is faced with the rehabilitation of a steadily increasing number of such patients. The injured patient should be placed as soon as possible in a treatment center in which a specialist in plastic surgery is available. Knowledge concerning techniques of surgery should be disseminated in order that a larger number of surgical practitioners will be trained to render adequate early treatment.
Abstract 2897: Profiling lipoxygenase metabolism in specific steps of colorectal tumorigenesis
Authors: Imad Shureiqi, Dongning Chen, R. Sue Day, Xiangsheng Zuo, William Ross, Ofir Moy, Jeffrey Scott Morris, Lianchun Xiao, Robert A. Newman, Peiying Yang, Scott M. Lippman
Journal: Cancer Research (2010)

Abstract Lipoxygenases (LOXs) are key enzymes for the oxidative metabolism of polyunsaturated fatty acids into products that influence cell signaling, structure, and metabolism. Previous data on comparative levels of various LOX products in human tumorigenesis are limited primarily to retrospectively collected surgical samples from cancer patients. Therefore, we examined LOX product profiles by liquid chromatography/tandem mass spectrometry in the major steps of colorectal tumorigenesis (normal, polyp, and cancer) in a clinical study of 125 subjects (49 with a normal colon, 36 with colorectal polyps, and 40 with colorectal cancer) who underwent prospective colorectal biopsies to control for various potential confounding factors (e.g. diet, medications). Mean 13-hydroxyoctadecadienoic acid (13-HODE) levels were significantly higher in normal colons (mean = 36.11 ng/mg protein, 95% confidence interval [CI]: 31.56-40.67) than in paired colorectal cancer mucosa (mean = 27.01 ng/mg protein, 95% CI: 22.00-32.02; P = 0.0002) and in normal colons (mean = 37.15 ng/mg protein, 95% CI: 31.95-42.34) than in paired colorectal polyp mucosa (mean = 28.07 ng/mg protein, 95% CI: 23.66-32.48; P &amp;lt; 0.001). Mean 13-HODE levels, however, were similar between the left (mean = 37.15 ng/mg protein, 95% CI: 31.95-42.35) and right normal colons (mean = 32.46 ng/mg protein, 95% CI: 27.95-36.98; P = 0.09). No significant differences with regard to 12-hydroxyeicosatetraenoic acid (12-HETE), 15-HETE, or leukotriene B4 (LTB4) levels were detected between normal, polyp and cancer mucosa. Downregulation of 15-LOX-1 expression, the rate limiting enzyme for 13-HODE production, in human colorectal neoplastic mucosa was confirmed by quantitative real time PCR in a subset colorectal cancer patients for whom samples with adequate RNA quality were available. This study establishes that reduced 13-HODE levels are a specific alteration in the LOX product profile associated with human colorectal tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2897.
Not playing with a full DEC: why development and evaluation committee methods for appraising new drugs may be inadequate
Authors: N. Freemantle, J. Mason
Journal: BMJ (1999)

The consultation document A First Class Service: Quality in the New NHS 1 heralded the introduction of the National Institute for Clinical Excellence (NICE). A key task of the institute is to provide rapid appraisal of new drugs in the period before licensing. New products may be accepted or refused NHS reimbursement, or they may be allocated “continuing research status.”

The review process described in A First Class Service and developed in a subsequent discussion paper2 mirrors that used for regionally funded development and evaluation committee (DEC) reports. Development and evaluation committee reports are produced by an independent arbitration committee comprising senior clinicians and others, who review the quality of available evidence, give explicit consideration to cost utility estimates, and make recommendations about interventions. Reports are published by NHS Research and Development (www.epi.bris.ac.uk/rd). Are the methods used by the development and evaluation committee up to the task?

#### Summary points

The National Institute for Clinical Excellence will appraise 30-50 drugs and technologies each year to inform decisions on whether these should be accepted or refused NHS reimbursement

The appraisal process will mirror that of regional development and evaluation committees, but this may lead to poor decision making since the methods used are inappropriate

The cost utility method of ranking treatments is based on strong assumptions and selective use of available evidence

New drugs should be appraised in terms of physical outcomes that mean something to doctors and patients

Because of limited resources and medical cost inflation, new drugs can place a considerable strain on prescribing budgets.3 New and expensive drugs can benefit patients, but only if worthwhile advances can be differentiated from costly ways of achieving equivocal results. However, new drugs present particular difficulties; they have usually been evaluated in relatively few clinical trials in which measures of effectiveness are narrow—and …
Effect of substratum and retinoids upon the mucosecretory differentiation of airway epithelial cells in vitro.
Authors: J I Rearick, A M Jetten
Journal: Environmental Health Perspectives (1989)

The lining of the trachea consists of a pseudostratified, mucociliary epithelium that under a variety of conditions, such as vitamin A deficiency, toxic and mechanical injury, becomes a stratified squamous epithelium. Several in vitro cell culture models have been established to study the regulation of the mucosecretory phenotype. Such studies have indicated that the mucosecretory phenotype in tracheal epithelial cells can be modulated by substratum and the presence of retinoids. Cells grown on a collagen type I gel matrix in the absence of retinoids undergo stratification and squamous cell differentiation. Cells grown on a collagen gel matrix in the presence of retinoids express a mucosecretory phenotype. As in the normal tracheal epithelium, these cultures contain columnar, polarized cells that exhibit apical tight junctions and secretory granules. Biochemical analysis of radiolabeled glycoconjugates released into the medium indicate the synthesis of mucinlike glycoproteins. Retinoids appear to determine whether tracheal epithelial cells become committed to a pathway of squamous differentiation or to a mucosecretory pathway of differentiation. The collagen gel matrix appears not to determine the commitment of the pathway of differentiation but allows the expression of the secretory phenotype in retinoic acid-treated cultures. The mechanisms by which retinoids and substratum modulate differentiation in tracheal epithelial cells is still poorly understood. It is clear that differentiation into squamous or mucous cells requires the activation and suppression of different genes. In the case of retinoids, the alterations in gene activity may be mediated by the nuclear retinoic acid receptor. In summary, in tracheal epithelial cells the substratum and extracellular matrix in conjunction with hormonal factors such as retinoids determine the ultimate function of these cells.
Characteristics of T-lymphocytes infiltrating human B-cell lymphomas.
Authors: P Marquardt, H K Müller-Hermelink
Journal: Environmental Health Perspectives (1990)

Using a recently described technique for direct expansion of human T-lymphocytes isolated from small intestine biopsies, we have investigated the local cellular immune response in six patients with B-cell lymphomas of various subtypes. T-cell lines (TCL) were established by seeding tumor-infiltrating T-lymphocytes (T1TL) at limiting dilution in the presence of irradiated feeder cells in culture medium containing rIl-2 and phytohemagglutinin (PHA). About 1/50 T-cells gave rise to a TCL; they all were CD3+. The CD4/CD8 ratio was 3.8:1 before and after cloning. Of 45 TCLs analysed so far from one patient with B-cell lymphoma of the lung, 4 were cytotoxic as shown by their ability to exert lectin-dependent cytotoxicity against allogeneic target cells. Of these, 3 demonstrated specificity for the autologous malignant B-cells. Five TCLs lysed the NK-sensitive K562 cell line in a HLA-unrestricted manner. When tested for antigen-specific proliferative activity, 4 TCLS only responded to the autologous lymphoma cells, but 5 TCLs reacted to the autoantigenic ganglioside GM1. Southern Blot analyses did not show a clonal pattern of T-cell receptor gene rearrangement within all TITL populations. The peripheral T-lymphocytes of the lymphoma patients showed a drastically reduced response to the mitogens PHA. Concanavalin A, and pokeweed mitogen. The present report demonstrates that it is possible to analyze TITL at clonal level. This technique may be the only means of investigating the specificity of the TITL and may help us to identify the relevant tumor-associated autoantigens if tumor-induced autoimmunization is indeed one of the mechanisms that control the growth of tumors and metastases.
Australian drug industry seeks to improve its image
Authors: Bob Burton
Journal: BMJ (2008)

Australia’s leading drug industry lobby group, Medicines Australia, is canvassing options on how to counter what it describes as “challenges” to its “credibility and trust.” The move comes after new rules were introduced making it mandatory for drug companies to publicly disclose details of their involvement in meetings and conferences for doctors ( BMJ 2008;336:742; doi: 10.1136/bmj.39535.488299.DB).

The lobby group’s annual one day “members only” conference included presentations from an ethicist on “ethical conduct,” a public relations adviser on “shaping a new image,” and a market researcher on “moral responsibility and corporate reputation.”

In the conference programme the group’s chief executive, Ian Chalmers, …
Searching for the Right Search — Reaching the Medical Literature
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (2006)

Web-based search engines are transforming our use of the medical literature. Although we continue to read the print issues of journals and to browse current issues online, we are now using links from Google — the flagship search engine of the Mountain View, California, company of the same name — and other search engines, as well as citation links in other articles, to gain direct access to the articles we want. For example, by quickly searching by the title of an article, an author, or a specific topic, we can often link to a bibliographic citation, the abstract, or the . . .
Absence of Both Cytochrome <i>P</i>450 3A and P-glycoprotein Dramatically Increases Docetaxel Oral Bioavailability and Risk of Intestinal Toxicity
Authors: Robert A.B. van Waterschoot, Jurjen S. Lagas, Els Wagenaar, Cornelia M.M. van der Kruijssen, Antonius E. van Herwaarden, Ji-Ying Song, Rogier W. Rooswinkel, Olaf van Tellingen, Hilde Rosing, Jos H. Beijnen, Alfred H. Schinkel
Journal: Cancer Research (2009)

Docetaxel is one of the most widely used anticancer drugs. A major problem with docetaxel treatment, however, is the considerable interpatient variability in docetaxel exposure. Another disadvantage of the drug is that it has a very low oral bioavailability and can therefore only be administered i.v. The drug-metabolizing enzyme cytochrome P450 3A (CYP3A) and the drug transporter P-glycoprotein (P-gp; MDR1) are considered to be major determinants of docetaxel pharmacokinetics. It has been hypothesized that CYP3A and P-gp work synergistically in limiting the systemic exposure to many orally ingested drugs. However, it has been difficult to examine this interplay in vivo. We therefore generated mice lacking all CYP3A and P-gp genes. Although missing two primary detoxification systems, Cyp3a/Mdr1a/1b(-/-) mice are viable, fertile, and without spontaneous abnormalities. When orally challenged with docetaxel, a disproportionate (>70-fold) increase in systemic exposure was observed compared with the increases in single Cyp3a(-/-) (12-fold) or Mdr1a/1b(-/-) (3-fold) mice. Unexpectedly, although CYP3A and P-gp collaborated extremely efficiently in lowering docetaxel exposure, their individual efficacy was not dependent on activity of the other protein. On reflection, this absence of functional synergism makes biological sense, as synergism would conflict with a robust detoxification defense. Importantly, the disproportionate increase in docetaxel exposure in Cyp3a/Mdr1a/1b(-/-) mice resulted in dramatically altered and lethal toxicity, with severe intestinal lesions as a major cause of death. Simultaneous inhibition of CYP3A/P-gp might thus be a highly effective strategy to improve oral drug bioavailability but with serious risks when applied to drugs with narrow therapeutic windows.
Serum, Atrial, and Urinary Digoxin Levels During Cardiopulmonary Bypass in Children
Authors: RICHARD W. KRASULA, ALOIS R. HASTREITER, SIDNEY LEVITSKY, RUTH YANAGI, LESTER F. SOYKA
Journal: Circulation (1974)

Serum, urine, and tissue samples were collected from 42 children undergoing open-heart surgery and analyzed for digoxin by radioimmunoassay. Of these, 24 had been digitalized prophylactically (RECENT) and 18 had been receiving maintenance therapy (MAINT) for one month or longer. Twenty-five percent of the RECENT patients exhibited arrhythmias during the postoperative period as compared to none in the MAINT group. Serum digoxin levels were equivalent in the two groups throughout the study. Although no change in tissue digoxin concentrations occurred during bypass, right atrial appendage concentrations were significantly higher in the RECENT group (109 vs 62 ng/g; P &lt; 0.001). This high atrial digoxin concentration presumably resulted from the large doses used for initial digitalization, and concomitant with postoperative hypokalemia and myocardial metabolic changes secondary to perfusion, may have been responsible for the high incidence of arrhythmias in the RECENT group. Both digoxin and creatinine excretion were depressed following bypass. The amount of biotransformation of digoxin was 2-59.
Shin Splints
Authors: Hans Balink
Journal: Clinical Nuclear Medicine (2009)

A 26-year-old woman presented with pain in both lower legs, mainly in the medial side of both tibiae, and more on the left side than the right side. Her history revealed osteogenesis imperfecta. In 1999, a Harrington spondylodesis was placed. Because of the high frequency of bone fractures, she became depressed and was bed-ridden for a few years. After treatment with intravenous bisphosphonates in a bi-monthly frequency, she became more self-confident and started to mobilize again. Based on bone scintigraphy, the diagnosis of “shin splints” was made, although they are mainly seen in athletes.
Reporting of precision of estimates for diagnostic accuracy: a review
Authors: R. Harper, B. Reeves
Journal: BMJ (1999)

Diagnostic accuracy is usually characterised by the sensitivity and specificity of a test, and these indices are most commonly presented when evaluations of diagnostic tests are reported. It is important to emphasise that, as in other empirical studies, specific values of diagnostic accuracy are merely estimates. Therefore, when evaluations of diagnostic accuracy are reported the precision of the sensitivity and specificity estimates or likelihood ratios should be stated.1–3 If sensitivity and specificity estimates are reported without a measure of precision, clinicians cannot know the range within which the true values of the indices are likely to lie.

Confidence intervals are widely used in medical literature, and journals usually require confidence intervals to be specified for other descriptive estimates and for epidemiological or experimental analytical comparisons. Journals seem less vigilant, however, for evaluations of diagnostic accuracy. For example, a recent review of compliance with methodological standards in diagnostic test research …
Sex Differences in Mortality After Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis
Authors: Karin H. Humphries, Stefan Toggweiler, Josep Rodés-Cabau, Luis Nombela-Franco, Eric Dumont, David A. Wood, Alexander B. Willson, Ronald K. Binder, Melanie Freeman, May K. Lee, Min Gao, Mona Izadnegahdar, Jian Ye, Anson Cheung, John G. Webb
Journal: Journal of the American College of Cardiology (2012)
Lung Development, Lung Function, and Retinoids
Authors: Donald Massaro, Gloria DeCarlo Massaro
Journal: New England Journal of Medicine (2010)

In this issue of the Journal, Checkley et al. report that, in a region with endemic vitamin A (retinol) deficiency, children whose mothers had received vitamin A supplementation before, during, and for 6 months after pregnancy had better lung function when they were tested at 9 to 11 years of age than children whose mothers had received beta carotene supplementation or placebo.1 The extent of the increased lung function was linearly related to the mother's postpartum serum retinol concentration. Because of a local ordinance, all children received supplemental vitamin A beginning at 6 months of age.1 Thus, the period during . . .
Late hepatitis B virus reactivation after lamivudine prophylaxis interruption in an anti-HBs-positive and anti-HBc-negative patient treated with rituximab-containing therapy
Authors: Laura Ceccarelli, Romina Salpini, Loredana Sarmati, Valentina Svicher, Ada Bertoli, Pasquale Sordillo, Alessandra Ricciardi, Carlo Federico Perno, Massimo Andreoni, Cesare Sarrecchia
Journal: Journal of Infection (2011)
Chemoradiotherapy for Localized Non-Hodgkin's Lymphoma
Authors: J.M. Cosset
Journal: New England Journal of Medicine (1998)

The search for the optimal treatment for localized intermediate- and high-grade non-Hodgkin's lymphoma has progressed through several phases in recent decades. In the 1960s and early 1970s, irradiation had a prominent, if not exclusive, role. However, radiation oncologists soon had to admit that the results achieved by irradiation alone were not satisfactory.1 In the early 1980s, a number of oncologists, carrying matters to the other extreme, advocated chemotherapy alone for localized lymphomas with unfavorable histologic features.2 Since then, the issue of how to treat localized intermediate- and high-grade non-Hodgkin's lymphoma has divided the world of lymphoma specialists into three parts. . . .
Coronary Artery Calcium Score and Cardiovascular Event Prediction
Authors: John W. McEvoy
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