tbuckley/cabot-search huggingface dataset:
Conflicts of Interest at Medical Journals: The Influence of Industry-Supported Randomised Trials on Journal Impact Factors and Revenue – Cohort Study
Authors: Andreas Lundh, Marija Barbateskovic, Asbjørn Hróbjartsson, Peter C. Gøtzsche
Journal: PLoS Medicine (2010)

Background Transparency in reporting of conflict of interest is an increasingly important aspect of publication in medical journals. Publication of large industry-supported trials may generate many citations and journal income through reprint sales and thereby be a source of conflicts of interest for journals. We investigated industry-supported trials' influence on journal impact factors and revenue. Methods and Findings We sampled six major medical journals (Annals of Internal Medicine, Archives of Internal Medicine, BMJ, JAMA, The Lancet, and New England Journal of Medicine [NEJM]). For each journal, we identified randomised trials published in 1996–1997 and 2005–2006 using PubMed, and categorized the type of financial support. Using Web of Science, we investigated citations of industry-supported trials and the influence on journal impact factors over a ten-year period. We contacted journal editors and retrieved tax information on income from industry sources. The proportion of trials with sole industry support varied between journals, from 7% in BMJ to 32% in NEJM in 2005–2006. Industry-supported trials were more frequently cited than trials with other types of support, and omitting them from the impact factor calculation decreased journal impact factors. The decrease varied considerably between journals, with 1% for BMJ to 15% for NEJM in 2007. For the two journals disclosing data, income from the sales of reprints contributed to 3% and 41% of the total income for BMJ and The Lancet in 2005–2006. Conclusions Publication of industry-supported trials was associated with an increase in journal impact factors. Sales of reprints may provide a substantial income. We suggest that journals disclose financial information in the same way that they require them from their authors, so that readers can assess the potential effect of different types of papers on journals' revenue and impact. Please see later in the article for the Editors' Summary
The role of the natriuretic peptides in the cardiovascular system
Authors: T Suzuki
Journal: Cardiovascular Research (2001)

The discovery of the natriuretic peptide family was a breakthrough in modern cardiovascular physiology as it provided a direct link between the heart and the kidneys in the regulation of natriuresis. Along with vasopressin and the renin–angiotensin–aldosterone system, the natriuretic peptides comprise the key peptides on which our present understanding of neuroendocrine regulation of the cardiovascular system is based. Three natriuretic peptides have been identified; the A-type, B-type and C-type natriuretic peptides. The former two, the A- and B-type natriuretic peptides, function mainly in the cardiovascular system and comprise the cardiac natriuretic peptides. Together with our increased understanding of the neurohormonal regulation of the cardiovascular system in recent years, the discovery of the natriuretic peptide family was important in the establishment of the new field of cardiovascular endocrinology.
Combination Chemotherapy in the Treatment of Advanced Hodgkin's Disease
Authors: VINCENT T. DEVITA
Journal: Annals of Internal Medicine (1970)

Forty-three patients with advanced, primarily untreated Hodgkin's disease were treated with a combination of vincristine sulfate, nitrogen mustard (or cyclophosphamide), procarbazine hydrochloride, and prednisone, given in cyclical fashion for 6 months. The limiting toxicity was primarily bone marrow suppression and, although occasionally severe, was generally tolerable. Other toxicity such as alopecia and neurotoxicity were troublesome but reversible. The response rate was superior to that previously reported with the use of single drugs with 35 of 43, or 81% of the patients achieving a complete remission, defined as the complete disappearance of all tumor and return to normal performance status. The duration of these responses after all therapy was discontinued was gratifyingly long, with a median of not less than 29 and not more than 42 months. Seventeen of 35 patients continue free of their disease, and 28 of these 35 are still alive. The median survival of the responding group is greater than 42 months, and life table analysis of the results indicates that of those complete responders at risk for 4 years, 77% remain alive and 47% are continuously free of their disease. The surviving fraction of the entire group at risk 4 years is 63%. It appears that combinations of effective drugs that act by different mechanisms and manifest different toxicities can be used effectively to increase the response rate and probably the survival of patients with sensitive tumors such as Hodgkin's disease.
THE AGING HEART IS SUSCEPTIBLE TO CARDIOMYOCYTE APOPTOSIS AND RESISTANT TO ANTI-APOPTOTIC THERAPIES
Authors: Joy I. Hwang, Henry H. Shih, Brian Lee, Yan Zhang, Jianqin Ye, Richard E. Sievers, Eddie Rame, William Grossman, Randall J. Lee, Yerem Yeghiazarians, Andrew J. Boyle
Journal: Journal of the American College of Cardiology (2010)
Mechanism of acid-induced release of secretin in rats. Presence of a secretin-releasing peptide.
Authors: P Li, K Y Lee, T M Chang, W Y Chey
Journal: Journal of Clinical Investigation (1990)

In fasting rats, intraduodenal infusion of dilute hydrochloric acid results in significant increases in both pancreatic exocrine secretion and plasma concentration of secretin. To test the hypothesis that acid-induced release of secretin is mediated by a secretin-releasing factor (S-RF), anesthetized rats were prepared with pyloric ligation, duodenal and jejunal cannulas, and pancreatic duct cannulas. Donor rats were infused intraduodenally with 0.01 N HCl, 0.15 M NaCl, or a combination of 0.01 N HCl and 0.05 N NaHCO3 at 0.3 ml/min for 1.5 h, and the perfusates were collected via jejunal cannulas. The perfusates with pH adjusted to 6.0 were concentrated threefold and infused into the duodena of recipient rats. The concentrate of acid perfusate (CAP) significantly increased both pancreatic volume flow and bicarbonate output and plasma concentration of secretin, whereas concentrates of the saline perfusate (CSP) or the perfusate of a combination of 0.01 N HCl and 0.05 N NaHCO3 (CABP) did not influence pancreatic secretion or plasma concentration of secretin. The increased pancreatic secretion by CAP was attributed to increased circulating secretin because when secretin was immunoneutralized by a rabbit antisecretin serum, CAP-stimulated pancreatic secretion was abolished. The bioactivity of CAP was trypsin-sensitive and heat stable. The active substance in CAP had a molecular weight of less than 5,000 and greater than 1,000, as determined by ultrafiltration and bioassay. In conclusion, dilute HCl releases an S-RF into the upper small intestinal lumen to stimulate release of secretin. This substance, with molecular weight of less than 5,000, is heat stable and trypsin sensitive. Thus, the acid-stimulated release of secretin is mediated by a secretin-releasing peptide in the upper small intestinal lumen.
Direct demonstration of iron in a term placenta in two cases of β‐thalassemia
Authors: M. Artico, G. Ballati, S. Bosco, D. Cantarelli, G. Nagar, A. Grosso, F.M. Tranquilli Leali, C. Cavallotti
Journal: American Journal of Hematology (2004)

Abstract The aim of this study was to quantify iron in the placentas at the end of pregnancy in two patients suffering from β‐thalassemia and compare the data to that recorded from the placentas of healthy women. Iron was quantified in placental specimens taken after the delivery. The specimens were subjected to chemical treatments in order to remove extracellular iron and leave the intracellular iron intact. After coloration, each specimen was subjected to quantitative analysis of images in order to identify and quantify iron. Our results demonstrated that in β‐thalassemia there is an accumulation of iron in the outer basal cytoplasm of the epithelial cells of placental cotyledons. Am. J. Hematol. 75:241–242, 2004. © 2004 Wiley‐Liss, Inc.
Comparative Study of Two Different TRUS&amp;ndash;Guided Sextant Biopsy Techniques in Detecting Prostate Cancer in One Biopsy Session
Authors: Clemens Br&ouml;ssner, Stefan Madersbacher, Guenther Bayer, Armin Pycha, H. Christoph Klingler, Ulrich Maier
Journal: European Urology (2000)
Abstract 3510: Evaluation of PI3K Inhibitor chemosensitivity in human tumor explants using the Mosaic Blue assay and relationship to biomarkers by immunohistochemistry.
Authors: Lisa Dauffenbach, Patricia A. Cash, Gela C. Sia, Sherif K. Girees, Ryan S. Lim, Jianping Zheng, Eric P. Olsen, Christopher A. Kerfoot
Journal: Cancer Research (2013)

Abstract The AKT protein family plays an important role in cellular survival by inhibiting apoptotic processes and is one of the major downstream targets of the phosphatidylinositol 3-kinase (PI3K) pathway. Mammalian target of rapamycin (mTOR) is a key kinase acting downstream of the activation of PI3K. Several chemotherapeutic agents target this pathway and are in clinical trials to treat patients with solid tumors. The use of chemosensitivity testing using human cancer explants is very useful in identifying biomarkers that relate to the intrinsic sensitivity of the tumor to a chemotherapetuic agent. The Mosaic Blue assay is a soft agar, ex vivo tumor response assay that utilized non-expanded patient cancer cells. Human tumors with matched fresh tissue and formalin-fixed, paraffin embedded (FFPE) tissue were used for this study. Fresh tissues were disaggregated into single cells and exposed to various inhibitors of the PI3K pathway. Samples were classified as resistant or sensitive. The corresponding FFPE tissue block was stained by immunohistochemistry for several phosphorylated proteins, which included AKT, PRAS40, 4EBP1, S6 kinase, S6 ribosomal protein, and PTEN in accordance with validated protocols. Additional fresh cells were also treated with inhibitors, harvested, and phophorylated proteins were evaluated in the pre and post-dose tumor cells. Results were compared the chemosensitivity results and 2 relationships were identified. First, biomarker status of the archival tissue was evaluated in order to understand the intrinsic chemosensitivity. Second, biomarker status upon treatment was evaluated to understand modulation of proteins due to therapy. In summary, use of soft agar ex vivo tumor response assays such as the Mosaic Blue assay is a useful tool to predict relative sensitivity across tumor types and allow investigation of potential biomarkers. Citation Format: Lisa Dauffenbach, Patricia A. Cash, Gela C. Sia, Sherif K. Girees, Ryan S. Lim, Jianping Zheng, Eric P. Olsen, Christopher A. Kerfoot. Evaluation of PI3K Inhibitor chemosensitivity in human tumor explants using the Mosaic Blue assay and relationship to biomarkers by immunohistochemistry. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3510. doi:10.1158/1538-7445.AM2013-3510
Book Review Pediatric Retina: Medical and Surgical Approaches Edited by Mary Elizabeth Hartnett, Michael Trese, Antonio Capone, Jr., Bronya J.B. Keats, and Scott M. Steidl. 559 pp., illustrated. Philadelphia, Lippincott Williams &amp; Wilkins, 2005. $249. 0-7817-4782-1
Authors: Arlene Drack
Journal: New England Journal of Medicine (2005)
Clinical and autoantibody correlations in Orientals with systemic lupus erythematosus.
Authors: M.L Boey, C.L Peebles, G Tsay, P.H Feng, E.M Tan
Journal: Annals of the Rheumatic Diseases (1988)

Serum samples from 94 patients with systemic lupus erythematosus (SLE) from a medical unit in Singapore were analysed for autoantibodies of 10 different specificities. The prevalence of antibodies to the following antigens was as follows: double stranded (ds) DNA (43%), histone (81%), Sm (26%), nuclear ribonuclear protein (nRNP) (32%), SS-A(Ro) (63%), SS-B(La) (12%), SL/Ki (9%), ribosomal RNP (rRNP) (16%), p70/p80 (5%), proliferating cell nuclear antigen (PCNA) (3%). Except for a higher prevalence of anti-SS-A(Ro), other autoantibodies were within the range reported from Western countries, indicating a high uniformity of autoantibody profiles in SLE in different countries. Patients with neuropsychiatric manifestations showed a higher plurality of antibodies per patient than patients without neuropsychiatric symptoms, 4.22 v 2.77. Patients with anti-Sm were more likely to have active lupus disease. There was no increased prevalence or specific type of autoantibody in those with renal manifestations.
Recertification in the United States
Authors: J. J Norcini
Journal: BMJ (1999)

Editorial by Buckley 

From the creation of the first board (in ophthalmology) in 1917 to the late 1960s, the specialty boards in the United States focused exclusively on initial certification. With its inception in 1969, however, the American Board of Family Practice limited the validity of its certificates to seven years, and since then other boards have followed suit, some after attempting voluntary processes that ultimately failed. Of the 24 boards that are members of the American Board of Medical Specialties all have limited, or plan to limit, the duration of validity of their certificates to seven to 10 years.1

According to Benson, the goals of recertification are to improve the care of patients, to set standards for the practice of medicine, to encourage continued learning, and to reassure patients and the public that doctors remain competent throughout their careers.2 To meet these goals, an ideal programme for recertification should have three components for evaluation.3–5 Firstly, to ensure that doctors are providing good care in practice an assessment of patient outcomes is needed. Secondly, to ensure that doctors are aware of recent advances in medicine and have the potential to treat the broad range of less frequent but medically important problems an evaluation of medical knowledge and judgment is needed. Thirdly, to ensure that doctors exhibit professionalism a review of credentials (for example, a valid licence and attestation of competence from the hospital or other local authorities) and the judgments of peers and patients are needed.

The assessment of patient outcomes is the most important component of a recertification programme. It directly reassures the public that doctors are performing well, and it is tailored to practice so it offers evaluation of what doctors actually do, rather than what they do in an artificial testing situation. …
Improved Recurrence-Free Survival with ARCON for Anemic Patients with Laryngeal Cancer
Authors: Geert O. Janssens, Saskia E. Rademakers, Chris H. Terhaard, Patricia A. Doornaert, Hendrik P. Bijl, Piet van den Ende, Alim Chin, Robert P. Takes, Remco de Bree, Ilse J. Hoogsteen, Johan Bussink, Paul N. Span, Johannes H. Kaanders
Journal: Clinical Cancer Research (2014)

Anemia is associated with poor tumor control. It was previously observed that accelerated radiotherapy combined with carbogen breathing and nicotinamide (ARCON) can correct this adverse outcome in patients with head and neck cancer. The purpose of this study was to validate this observation based on data from a randomized trial.Of 345 patients with cT2-4 laryngeal cancer, 174 were randomly assigned to accelerated radiotherapy and 171 to ARCON. Hemoglobin levels, measured before treatment, were defined as low when <7.5 mmol/L for women and <8.5 mmol/L for men. The hypoxia marker pimonidazole was used to assess the oxygenation status in tumor biopsies. Data were analyzed 2 years after inclusion of the last patient.Pretreatment hemoglobin levels were available and below normal in 27 of 173 (16%) accelerated radiotherapy and 27 of 167 (16%) ARCON patients. In patients with normal pretreatment, hemoglobin levels treatment with ARCON had no significant effect on 5-year loco-regional control (LRC, 79% versus 75%; P = 0.44) and disease-free survival (DFS, 75% vs. 70%; P = 0.46) compared with accelerated radiotherapy. However, in patients with low pretreatment, hemoglobin levels ARCON significantly improved 5-year LRC (79% vs. 53%; P = 0.03) and DFS (68% vs. 45%; P = 0.04). In multivariate analysis including other prognostic factors, pretreatment hemoglobin remained prognostic for LRC and DFS in the accelerated radiotherapy treatment arm. No correlation between pretreatment hemoglobin levels and pimonidazole uptake was observed.Results from the randomized phase III trial support previous observations that ARCON has the potential to correct the poor outcome of cancer patients with anemia (ClinicalTrials.gov number, NCT00147732).
Comment
Authors: Philip Rubin
Journal: JAMA (1968)

Death of children with Wilms tumor is invariably due to lung metastases. Characteristically, the lungs are the first sites involved in the process of dissemination, and often the only site, although liver, brain, and rarely, bony deposits are seen. Dactinomycin is the end of a long odyssey in search of a means to prevent metastases and to achieve better survival. The credit for advancing and introducing surgical, radiotherapeutic, and chemotherapeutic approaches in controlling this disease and curing the patient belongs to the group at Boston Children's Hospital. It is an important "success story" with which to be familiar since the management of Wilms' tumor forms one of the cornerstones on which the philosophy and principles of caring for childhood cancers in general have been erected. The primary concern in Wilms' tumor is preventing its dissemination. As soon as the child with a suspected Wilms' tumor has been admitted to the
Phalangeal metastases from bronchogenic carcinoma
Authors: I. Karten
Journal: JAMA (1978)

To the Editor.—  The recent report Phalangeal Metastases From Bronchogenic Carcinoma (239:226, 1978) verifies the uncommon occurrence of metastatic implants in digits giving the appearance of osteomyelitis or gout. The authors emphasize the presentation of their cases with involvement of a single toe or finger, but actually bone scans and roentgenograms showed polyarticular disease.  We reported a similar case (179:162, 1962) in which five fingers showed metastases from bronchogenic carcinoma. Our initial diagnosis was rheumatoid arthritis because of the symmetrical fusiform swellings present in our patient. The physician, therefore, should be alert to the fact that swellings in three or more digits resembling rheumatoid arthritis, and not just monarticular disease, may occasionally be from metastases from carcinoma of the lung.
Effect of dry cleaning on mite allergen levels in blankets
Authors: T. Vandenhove, M. Soler, J. Birnbaum, D. Charpin, D. Vervloet
Journal: Allergy (1993)

Since one of the greatest reservoirs of allergens is the blanket, we assessed mite allergen levels in dust collected from five blankets by vacuuming before and after dry cleaning with perchlorethylene and compared the results with five control blankets. Assays with monoclonal antibodies showed that group I ( Der p I and Der f I) mite allergen levels per g dust were 78%, lower after dry cleaning. Group 1 allergen levels per m 2 of dry‐cleaned blankets were 98% lower. RAST inhibition showed that total allergen levels decreased 70% after dry cleaning. Mite allergens were not denatured by perchlorethylene. The effect of dry cleaning resulted from physical washing out of dust and allergens.
Epinephrine Secretion, Hypoglycemia Unawareness, and Diabetic Autonomic Neuropathy
Authors: Robert D. Hoeldtke
Journal: Annals of Internal Medicine (1994)

The pathophysiology of iatrogenic hypoglycemia in patients with insulin-dependent diabetes mellitus has been studied extensively during the past decade. It is now widely recognized that some patients with long-standing diabetes lose their ability to secrete the major counterregulatory hormones, glucagon and epinephrine, and fail to have hypoglycemia-related autonomic warning symptoms. Many investigators focused initially on the role of autonomic neuropathy, assuming that the latter might explain the diminished epinephrine response to hypoglycemia and the blunted adrenergic warning signs. Although these studies confirmed that patients with advanced diabetic autonomic neuropathy have attenuated counterregulatory hormonal responses to hypoglycemia, many patients with inadequate counterregulatory hormone secretion lack the typical signs, symptoms, or cardiovascular reflex abnormalities typical of diabetic autonomic neuropathy. These patients may have a new variant of diabetic autonomic failure that selectively affects the central and peripheral autonomic mechanisms, which initiate epinephrine secretion and the defense against hypoglycemia. A potentially reversible cause for the failure of the counterregulatory hormone response to hypoglycemia has also been recently described.In this instance, the central nervous system fails to recognize hypoglycemia. The brain does not activate counterregulation, and the patient develops no symptoms of hypoglycemia. Decreased central recognition of hypoglycemia results from either strict antecedent control or from a recent hypoglycemic event.
The promoter of the long variant of collagen XVIII, the precursor of endostatin, contains liver-specific regulatory elements
Authors: Jocelyne Liétard, Nathalie Théret, Marko Rehn, Orlando Musso, Delphine Dargère, Taina Pihlajaniemi, Bruno Clément
Journal: Hepatology (2000)

The endostatin precursor collagen XVIII is expressed at high levels in human livers, the main source being hepatocytes. We have studied the regulatory elements in the promoter 2 of the Col18a1 gene that directs the transcription of the NC1-517 variant of collagen alpha1(XVIII), which is the main form expressed in the liver. The 5'-flanking region of Col18a1 gene was cloned, and a series of 5'-deletions from -3286 bp to +285 bp were linked to the luciferase reporter gene. Transfection experiments in HepG2 cells allowed to identify a silencer-like element containing putative HNF1 and HNF3 sites and activator elements containing stretches of GC-rich sequences. Another putative HNF3 site in close apposition to a NF1/CTF site was localized upstream of the silencer-like element. Cotransfection experiments showed that the Col18a1 promoter 2 was transactivated by Sp1 and HNF3alpha. Gel-shift analyses showed that HNF3, NF1/CTF, and Sp1-like sites specifically recognized nuclear factors. Super-shift experiments indicated that HNF3beta was the major form of HNF3 interacting with the HNF3/NF1 site. The well-differentiated hepatoma cell line mhATFS315 transfected with a truncated form of HNF3beta, which competitively blocks HNF3 transactivating activity, expressed the Col18a1gene at a very low level. Taken together, these data strongly suggest that Col18a1 is a liver-specific gene. Furthermore, gel-shift analyses performed with nuclear factors prepared from well-differentiated hepatocellular carcinomas showed increased HNF3/NF1 binding activity compared with normal livers. Consequently, the precursor of endostatin might be differently expressed according to the differentiated and/or transformed state of hepatocytes.