tbuckley/cabot-search huggingface dataset:
Clara cell protein (CC-16) induces a phospholipase A2-mediated inhibition of fibroblast migration in vitro.
Authors: O Lesur, A Bernard, K Arsalane, R Lauwerys, R Bégin, A Cantin, D Lane
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Clara cell protein (CC-16, also designated CC-10) is synthesized by the bronchiolar epithelium and has been suggested as an inhibitor of phospholipase A2 (PLA2) activity. Therefore, CC-16 is a candidate for controlling inflammatory events in the lung. Because CC-16 amounts and function may be altered in fibrosing lung diseases in which bronchiolar injury has been reported, it was measured in alveolar fluids and sera. Secretory PLA2 activity in alveolar fluids and the influence of CC-16 on platelet-derived growth factor-induced human fibroblast chemotaxis and cytosolic PLA2 activity were also explored. CC-16 content was decreased in alveolar fluids from idiopathic pulmonary fibrosis (IPF: 1.3 +/- 0.1 mg/L) and bleomycin lung (1.1 +/- 0.2 versus 2.1 +/- 0.2 mg/L in controls, p < 0.05), whereas there was a three- to ninefold increase in secretory PLA2 activity (p < 0.05 versus controls). CC-16 inhibited fibroblast chemotaxis in a dose-dependent manner (90% inhibition at 30 micrograms/ml CC-16). This inhibition was reversed by reducing CC-16. CC-16 was also able to lower fibroblastic cytosolic PLA2 activity by 50% in vitro. In summary, CC-16 is able to inhibit fibroblast chemotaxis in vitro by mechanisms that may be related to a blockage of cytosolic PLA2 activity. It can be postulated that CC-16 deficiency may contribute to fibroblast burden activity in fibrosing lung diseases.
The Effect of Short Periods of Caloric Restriction on Weight Loss and Glycemic Control in Type 2 Diabetes
Authors: Katherine V Williams, Monica L Mullen, David E Kelley, Rena R Wing
Journal: Diabetes Care (1998)

OBJECTIVE To determine whether an intermittent very-low-calorie diet (VLCD) improves weight loss and glycemic control more than moderate caloric restriction alone. RESEARCH DESIGN AND METHODS Individuals with type 2 diabetes (n = 54) who were ≥ 20% over ideal body weight participated in a 20-week behavioral weight control program. Subjects were randomized to either a standard behavioral therapy (SBT) group or to one of two VLCD groups. SBT subjects received a 1,500−1,800 kcal/day diet throughout. Both VLCD groups followed a VLCD for 5 consecutive days during week 2, followed by either intermittent VLCD therapy for 1 day/week for 15 weeks (1-day) or for 5 consecutive days every 5 weeks (5-day), with a 1,500−1,800 kcal/day diet at other times. RESULTS Both VLCD groups lost more weight than the SBT group over the 20 weeks (P = 0.04). Although the groups did not differ in fasting plasma glucose (FPG) changes at 20 weeks, more subjects in the 5-day group attained a normal HbA1c when compared with the SBT group (P = 0.04). This benefit was independent of the effects of weight loss. The best predictor of overall change in FPG and HbA1c was the FPG response during the first 3 weeks of the program. CONCLUSIONS Periodic VLCDs improved weight loss in diabetic subjects. A regimen with intermittent 5-day VLCD therapy seemed particularly promising, because more subjects in this group attained a normal HbA1c. Moreover, the glucose response to a 3-week period of diet therapy predicted glycemic response at 20 weeks, and it was a better predictor of the 20-week response than initial or overall weight loss.
<i>EGFR</i>Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib
Authors: Susumu Kobayashi, Titus J. Boggon, Tajhal Dayaram, Pasi A. Jänne, Olivier Kocher, Matthew Meyerson, Bruce E. Johnson, Michael J. Eck, Daniel G. Tenen, Balázs Halmos
Journal: New England Journal of Medicine (2005)

Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in specimens from patients with non-small-cell lung cancer who have a response to anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to such inhibitors, most patients ultimately have a relapse. The mechanism of the drug resistance is unknown. Here we report the case of a patient with EGFR-mutant, gefitinib-responsive, advanced non-small-cell lung cancer who had a relapse after two years of complete remission during treatment with gefitinib. The DNA sequence of the EGFR gene in his tumor biopsy specimen at relapse revealed the presence of a second point mutation, resulting in threonine-to-methionine amino acid change at position 790 of EGFR. Structural modeling and biochemical studies showed that this second mutation led to gefitinib resistance.
Fusion or Apposition? A Case of a Broken Horseshoe Kidney
Authors: JOSEPH C.H. WONG, SUSAN E.M. CLARKE, JOHN B. BINGHAM
Journal: Clinical Nuclear Medicine (1997)

A Tc-99m DMSA renal study in a child showed a horseshoe pattern of uptake with upper pole “fusion.” T2-weighted MRI images showed a parenchymal bridge joining the upper poles. However, a repeat MRI study performed 2 months later with T1-weighting showed fatty tissue separation of the upper poles. This unusual case shows apposition of the upper poles, but it does not represent a true horseshoe kidney because of the absence of a parenchymal or fibrous bridge. The occurrence of fusion of the upper poles is exceptionally rare; it occurs in only 5% of horseshoe kidneys, which have an overall prevalence of about 1:600.
Comment on: Wheeler et al. Macronutrients, Food Groups, and Eating Patterns in the Management of Diabetes: A Systematic Review of the Literature, 2010. Diabetes Care 2012;35:434–445
Authors: Katherine Esposito, Dario Giugliano
Journal: Diabetes Care (2012)

In their attempt to answer the question of how eating patterns affect glycemic control of diabetes, Wheeler et al. (1) concluded that “there appears to be no advantage in using the Mediterranean-style eating pattern compared with other eating patterns for glycemic control.” We strongly disagree with this summary statement because it is based on wrong reporting of published data and multiple publications from the same study, and is also missing reporting of published studies. According to the search strategy detailed on the systematic review procedure (1), randomized controlled trials (RCTs), prospective, cross-sectional, or case-control studies published through October 2010 could be included, with multiple publications from the same study limited to …
Normal-Pressure Hydrocephalus and Arthritis
Authors: Robert A. Fishman
Journal: New England Journal of Medicine (1985)

Just 20 years ago, normal-pressure hydrocephalus was established as a clinical entity by Adams and colleagues in a landmark article in the Journal. 1 The clinical features include the triad of dementia, gait disorder, and urinary incontinence associated with ventricular dilatation in the absence of evidence of increased intracranial pressure.Although the delayed onset of hydrocephalus after subarachnoid hemorrhage and meningitis had been well established earlier, normal-pressure hydrocephalus attracted special interest because it was often idiopathic and occult and particularly because it entered into the differential diagnosis of the treatable dementias. The fact that the syndrome was reversed in some patients . . .
Bilateral Orchiectomy with or without Flutamide for Metastatic Prostate Cancer
Authors: Mario A. Eisenberger, Brent A. Blumenstein, E. David Crawford, Gary Miller, David G. McLeod, Patrick J. Loehrer, George Wilding, Kathy Sears, Daniel J. Culkin, Ian M. Thompson, Anton J. Bueschen, Bruce A. Lowe
Journal: New England Journal of Medicine (1998)

Combined androgen blockade for the treatment of metastatic prostate cancer consists of an antiandrogen drug plus castration. In a previous trial, we found that adding the antiandrogen flutamide to leuprolide acetate (a synthetic gonadotropin-releasing hormone that results in medical ablation of testicular function) significantly improved survival as compared with that achieved with placebo plus leuprolide acetate. In the current trial, we compared flutamide plus bilateral orchiectomy with placebo plus orchiectomy.
Abstract 3698: ODSH, a heparin derivative, enhances the efficacy of gemcitabine in a refractory human pancreatic tumor xenograft model
Authors: Stephen G. Marcus, Pedro M. Quintana-Diez, Stephen Gately, Paul Gonzales, Bernardo Chavira, Daniel D. Von Hoff
Journal: Cancer Research (2012)

Abstract ODSH, a new chemical entity, is 2-0, 3-0 desulfated heparin, a desulfated heparin analog that has been shown to bind to the receptor for advanced glycation endproducts (RAGE). This interaction prevents RAGE from binding to a principal ligand, HMGB1, as well as to other ligands including S-100 calgranulin, which attenuates the activation of RAGE. RAGE activation is known to induce resistance to chemotherapy and promote pancreatic tumor cell survival. We have shown, in vivo, an increase in response with gemcitabine when combined with ODSH. ODSH was tested alone and in combination with standard of care agent, gemcitabine, against BxPC-3 human pancreatic tumor xenograft model. Single agent ODSH and gemcitabine treatment showed an 18.8% and 16.8% decrease in tumor weight, respectively. The combination regimen of ODSH and gemcitabine increased tumor growth inhibition to 37.9%. This decrease was statistically significant (P&amp;lt;0.05) compared to ODSH and gemcitabine treatments alone according to Student's t-test. We believe this is a novel approach to treat metastatic pancreatic cancer. ODSH has already shown a favorable safety profile in Phase I and II studies. A clinical trial with ODSH treatment in combination with gemcitabine+nab-paclitaxel in newly diagnosed patients with metastatic pancreatic cancer is underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3698. doi:1538-7445.AM2012-3698
Hysterectomy, HMOs, and Appropriateness
Authors: R. P. (Jack) Davidson
Journal: JAMA (1993)

<h3>To the Editor.</h3> —Several aspects of the study by Bernstein et al<sup>1</sup>deserve further discussion. In the absence of longitudinal, outcomes-based studies defining which patients benefit from a given intervention, efforts to determine appropriateness of care must rely on the use of expert opinion. Attempts to model the decision-making process of experts and incorporate expert opinion into a series of portable algorithms represent a major advancement in the development of appropriateness criteria. However, it is important to bear in mind the limitations inherent in this approach. Depending on the quality and quantity of scientific information available to them, experts frequently disagree, and even when they agree, experts can be wrong. Despite obvious weaknesses, the current criterion standard for appropriateness determinations is individual case review by experts in the same field. The design of the study by Bernstein et al assumes that the RAND protocols alone, without subsequent peer review
Trends in Study Methods Used in Undergraduate Medical Education Research, 1969-2007
Authors: Amy Baernstein, Hillary K. Liss, Patricia A. Carney, Joann G. Elmore
Journal: JAMA (2007)

Evidence-based medical education requires rigorous studies appraising educational efficacy.To assess trends over time in methods used to evaluate undergraduate medical education interventions and to identify whether participation of medical education departments or centers is associated with more rigorous methods.The PubMed, Cochrane Controlled Trials Registry, Campbell Collaboration, and ERIC databases (January 1966-March 2007) were searched using terms equivalent to students, medical and education, medical crossed with all relevant study designs.We selected publications in all languages from every fifth year, plus the most recent 12 months, that evaluated an educational intervention for undergraduate medical students. Four hundred seventy-two publications met criteria for review.Data were abstracted on number of participants; types of comparison groups; whether outcomes assessed were objective, subjective, and/or validated; timing of outcome assessments; funding; and participation of medical education departments and centers. Ten percent of publications were independently abstracted by 2 authors to assess validity of the data abstraction.The annual number of publications increased over time from 1 (1969-1970) to 147 (2006-2007). In the most recent year, there was a mean of 145 medical student participants; 9 (6%) recruited participants from multiple institutions; 80 (54%) used comparison groups; 37 (25%) used randomized control groups; 91 (62%) had objective outcomes; 23 (16%) had validated outcomes; 35 (24%) assessed an outcome more than 1 month later; 21 (14%) estimated statistical power; and 66 (45%) reported funding. In 2006-2007, medical education department or center participation, reported in 46 (31%) of the recent publications, was associated only with enrolling more medical student participants (P = .04); for all studies from 1969 to 2007, it was associated only with measuring an objective outcome (P = .048). Between 1969 and 2007, the percentage of publications reporting statistical power and funding increased; percentages did not change for other study features.The annual number of published studies of undergraduate medical education interventions demonstrating methodological rigor has been increasing. However, considerable opportunities for improvement remain.
Intrapleural Tetracycline for Recurrent Pneumothorax-Reply
Authors: Richard W. Light
Journal: JAMA (1991)

In Reply.—  Dr Corboy disagrees with our recommendation that patients who are hospitalized and are treated with tube thoracostomy should receive intrapleural tetracycline. Rather, he maintains that patients with their first spontaneous pneumothorax should be treated with tube thoracostomy; then, if there is a recurrent pneumothorax, the patient with primary spontaneous pneumothorax should be treated surgically while the patient with secondary spontaneous pneumothorax should be treated with intrapleural tetracycline.  We still maintain that patients with spontaneous pneumothorax who are treated with tube thoracostomy should receive intrapleural tetracycline. The intrapleural administration of tetracycline will decrease the likelihood of recurrence by approximately 40%. Then, if the patient has a recurrent pneumothorax after the tetracycline pleurodesis, we would agree with Dr Corboy that the patient should be subjected to thoracotomy. We would perform a thoracotomy in this situation whether the patient had a primary or a secondary spontaneous pneumothorax. Essentially the intrapleural instillation
Plasma chitotriosidase activity in patients with β‐thalassemia
Authors: G. Altarescu, B. Rudensky, A. Abrahamov, A. Goldfarb, D. Rund, A. Zimran, D. Elstein
Journal: American Journal of Hematology (2002)

Abstract Variable increases in chitotriosidase levels have been reported in Italian patients with β‐thalassemia major and intermedia. We measured plasma chitotriosidase levels in Israeli patients with β‐thalassemia to ascertain its use as a universal marker of disease and/or response to therapy. Chitotriosidase levels in 39 adults (16–53 years; 30 with β‐thalassemia major, 9 with intermedia), and in 14 children (0.7–15 years; 12 with β‐thalassemia major, 2 with intermedia) were compared with other measures of disease, such as ferritin, hemoglobin, liver function tests, and genotype. Plasma chitotriosidase levels were normal (0.37 ± 0.04 mU/mL) in all children. Twelve adults (31%) had elevated levels (&gt;1.33 mU/mL): 11 patients (37%) with thalassemia major and 1 patient (11%) with thalassemia intermedia. A significant correlation was only found between plasma chitotriosidase levels and ferritin levels, and with mean number of transfusions per year. The patient with the highest chitotriosidase (1,440 nmol/mL/hr) had the highest ferritin (5,175 μg/L), required the most transfusions per year (40), and had abnormal liver tests. Normal chitotriosidase levels in the pediatric cohort and increased levels in only some adults may reflect status of iron overload in macrophages; thus there may be a role for monitoring chitotriosidase in patients with β‐thalassemia. Our results confirm results of the Italian cohort; however, in the latter, a more universal correlation was noted and chitotriosidase levels were much higher. Am. J. Hematol. 71:7–10, 2002. © 2002 Wiley‐Liss, Inc.
Ligation of a Bleeding Colonic Varix using an Upper Gastrointestinal Endoscope
Authors: S. Misra, M. Dwivedi
Journal: Endoscopy (2006)

Although anorectal and colonic varices are not uncommon, bleeding from these varices is extremely rare [1] [2] [3]. However, when they do bleed, the bleeding may be massive and occasionally fatal [4]. Endoscopic variceal ligation (EVL) is a well-established procedure for emergency as well as elective ligation of esophageal varices. Although there have been a few reports of variceal ligation to arrest rectal variceal bleeding [5], there have been no reports of its use in bleeding colonic varices, so far as we are aware.
Coronary Arteriographic and Ventriculography Correlations with the ECG Diagnosis of Diaphragmatic Myocardial Infarction (DMI).
Authors: Jacob I. Haft
Journal: Annals of Internal Medicine (1969)

s1 May 1969Coronary Arteriographic and Ventriculography Correlations with the ECG Diagnosis of Diaphragmatic Myocardial Infarction (DMI).Jacob I. Haft, M.D., Michael V. Herman, M.D., Richard Gorlin, M.D., F.A.C.P.Jacob I. Haft, M.D.Search for more papers by this author, Michael V. Herman, M.D.Search for more papers by this author, Richard Gorlin, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1077_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo more accurately determine the value of the electrocardiogram (ECG) in diagnosing coronary artery disease, 48 patients with a history of chest pain and ECG evidence of diaphragmatic myocardial infarction (Q ≥ 0.02 sec in 2 of the leads II, III, or aVF), and complete cardiac catheterization studies including coronary arteriography and left ventricular angiograms were studied. All patients who showed evidence of anterior myocardial infarction (12) or true posterior myocardial infarction (4) in addition to diaphragmatic myocardial infarction were found to have significant disease of all three main coronary arteries. Fifteen patients with Q ≥ 0.04 sec in 2... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Mass. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1077-1077KeywordsAngiographyCatheterizationCoronary arteriesElectrocardiographyHeart diseasesIschemiaMyocardial infarctionStable coronary artery disease Issue Published: 1 May 1969 PDF DownloadLoading ...
Abstract 3339: HSP90 inhibitor 17-allylamino-geldanamycin enhances sensitivity to double-strand DNA break-inducing agents (platinum and PARP inhibitors) in epithelial ovarian cancer.
Authors: Chiara Battelli, Alexander Morse, Hai Hu, Elena Levantini, Gerburg Wulf, Panagiotis A. Konstantinopoulos
Journal: Cancer Research (2013)

Abstract Double-strand DNA break (DSB)-inducing agents such as platinum analogues and poly (ADP-ribose) polymerase inhibitors (PARPis) exhibit significant antitumor activity in epithelial ovarian cancer (EOC). Approximately 50% of patients with EOC harbor genetic or epigenetic alterations of the homologous recombination (HR) DNA repair pathway and are highly responsive to these agents. However, resistance to DSB-inducing agents develops in the majority of patients and represents a major limitation for successful treatment of EOC. We recently defined a gene expression profile of “BRCAness” that correlates with responsiveness to double-strand DNA break-inducing agents (platinum and PARPis) in EOC. We applied this profile to the Connectivity Map to identify candidate compounds that might be able to enhance sensitivity to these agents. This analysis showed that the top-performing compound was the heat shock protein 90 (HSP90) inhibitor 17-allylamino-geldanamycin (17-AAG) with very high connectivity scores (&amp;gt;0.8) across several cell lines and concentrations (permutation p value &amp;lt; 0.00001). We then evaluated the ability of 17-AAG to enhance sensitivity to double-strand DNA break-inducing agents in a panel of ovarian cancer cell lines. Exposure to increasing concentrations of 17-AAG (0.02-0.1uM) was associated with increased sensitivity of 36M2 and OVCAR5 cells to carboplatin in a dose response manner. Similarly, exposure to increasing concentrations of 17-AAG (0.02-0.1uM) was associated with increased sensitivity of 36M2 and OVCAR5 cells to PARPi olaparib in a dose response manner. Exposure of these cell lines to combination of 17-AAG with carboplatin induced increased phosphorylation of H2AX (gamma H2AX) - a surrogate of DNA double-strand breaks - compared to carboplatin alone, as assessed by Western blotting. In conclusion, the HSP90 inhibitor 17-AAG enhances sensitivity of ovarian cancer cell lines to carboplatin and olaparib. The mechanism of this previously unknown, off-target effect, seems to be due to increasing DNA double strand breaks. Citation Format: Chiara Battelli, Alexander Morse, Hai Hu, Elena Levantini, Gerburg Wulf, Panagiotis A. Konstantinopoulos. HSP90 inhibitor 17-allylamino-geldanamycin enhances sensitivity to double-strand DNA break-inducing agents (platinum and PARP inhibitors) in epithelial ovarian cancer. [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 3339. doi:10.1158/1538-7445.AM2013-3339
Tuberculosis in children
Authors: Edwin L. Kendig
Journal: JAMA (1963)

In his foreword, Dr. Arvid Walgren states, "If any American physician is able to write a textbook on tuberculosis in children, it is Edith Lincoln." Almost all physicians who have been interested in tuberculosis in children share that feeling, and this long-awaited book will not disappoint them. It contains everything one needs to know about childhood tuberculosis, and will prove useful to the specialist in tuberculosis and the practitioner who treats children. This book surveys a follow-up study of 1,000 children with early tuberculous infections and 2,500 with various tuberculous diseases. All of these patients have been seen by Dr. Lincoln during her 30 years of practice and teaching. She has seen the disease when there was no specific treatment and has pioneered in the use of antimicrobial therapy. There are 21 chapters, including those on epidemiology, diagnostic procedures, and treatment, and one devoted to consideration of each of the