tbuckley/cabot-search huggingface dataset:
Favism and Thalassemia Minor in a Pregnant Woman
Authors: Kevin M. Cahill
Journal: JAMA (1962)

In the past few years, favism and hemolytic anemia induced by a variety of drugs have been shown to be associated with a specific defect in glucose-6-phosphate dehydrogenase (G-6-PD) activity of the erythrocytes of susceptible individuals. This defect, like thalassemia, occurs particularly among individuals of Mediterranean racial background. In the case reported here, a 35-year-old woman of Greek extraction who was in her sixth month of pregnancy had an acute hemolytic episode after ingestion of an inordinate quantity of fava beans. Investigation showed that, while she had inherited thalassemia through her paternal lineage, she had inherited a glucose-6-phosphate dehydrogenase deficiency from her mother. Recognition of such susceptible individuals is important, not only in differential diagnosis of hemolytic syndromes but also in the prevention of hemolytic episodes induced by a variety of commonly used drugs.
Soluble CD163, a macrophage activation marker, is independently associated with fibrosis in patients with chronic viral hepatitis B and C
Authors: Konstantin Kazankov, Francisco Barrera, Holger Jon Mφller, Bo Martin Bibby, Hendrik Vilstrup, Jacob George, Henning Grφnbæk
Journal: Hepatology (2014)

Macrophages are involved in inflammation and liver fibrosis and soluble (s)CD163 is a specific marker of activated macrophages. We investigated associations between sCD163 and biochemical and histological parameters of inflammatory activity and fibrosis in 551 patients with chronic hepatitis C virus (HCV) and 203 patients with chronic hepatitis B virus (HBV) before antiviral treatment. Scheuer histological scores of activity and fibrosis were obtained. Clinical, biochemical, and metabolic parameters were recorded. We measured sCD163 by enzyme-linked immunosorbent assay (ELISA). Soluble CD163 was higher in patients with HCV compared to HBV (3.6 [interquartile range (IQR) 2.5-5.4] versus 2.4 [IQR 1.8-3.6] mg/L, P &lt; 0.001). sCD163 was associated with fibrosis stages for both HCV (odds ratio [OR] 1.49, 95% confidence interval [CI]: 1.38-1.61) and HBV (OR 1.32, 95% CI: 1.17-1.49) patients, with highest levels in patients with advanced fibrosis and cirrhosis. sCD163 was a marker of fibrosis independent of other biochemical parameters and known risk factors. We created two novel sCD163-based fibrosis scores, CD163-HCV-FS and CD163-HBV-FS, which showed areas under the receiver operating characteristics curve (AUROC) of 0.79 (95% CI: 0.74-0.83) and 0.71 (95% CI: 0.62-0.79), respectively, for significant fibrosis. Compared to existing fibrosis scores, CD163-HCV-FS was significantly superior to the aspartate aminotransferase (AST) to platelet ratio index (APRI) for all fibrosis stages and to FIB-4 for significant fibrosis, but CD163-HBV-FS was not. Conclusion : sCD163 levels are increased in patients with chronic viral hepatitis, reflecting macrophage activation. Increased sCD163 is associated with the severity of disease and predicts fibrosis. A sCD163-based fibrosis score, CD163-HCV-FS, is superior to APRI and FIB-4 for the diagnosis of significant fibrosis in patients with HCV infection. (Hepatology 2014;60:521–530)
Tumor Necrosis Factor Receptor Signaling in Keratinocytes Triggers Interleukin-24-Dependent Psoriasis-like Skin Inflammation in Mice
Authors: Snehlata Kumari, Marion C. Bonnet, Maria H. Ulvmar, Kerstin Wolk, Niki Karagianni, Ellen Witte, Claudia Uthoff-Hachenberg, Jean-Christophe Renauld, George Kollias, Rune Toftgard, Robert Sabat, Manolis Pasparakis, Ingo Haase
Journal: Immunity (2013)
Recurrent vascular thrombosis in an adolescent transplant recipient.
Authors: S Balachandra, A Tejani
Journal: Journal of the American Society of Nephrology (1997)

Vascular thrombosis is one of the more difficult problems of pediatric renal transplantation; its etiology in multifactorial and, in most cases, it is irreversible. Vascular thrombosis accounts for 12.9% of graft failures in primary transplants in children and for 20% of graft failures in repeat transplants. Although it is seen most often in very young recipients and in recipients of kidneys from young donors, it can manifest in older children and adolescents as well. The peak incidence is seen in the first 48 h after transplantation; however, the event may be delayed until after the first week. When thrombosis occurs in an adolescent patients late in the course of transplantation, the pathogenesis is undetermined and immunosuppressive therapy is frequently implicated. This article describes a 19-yr-old patient with a three-antigen-matched cadaveric kidney who received cyclosporine and anti-thymocyte globulin for induction. Vascular thrombosis occurred after 7 d of initial good function. Eventually the graft was removed after attempts to re-establish vascularization failed. The patient received a second graft and despite an optimal six-antigen-match and different immunosuppression with tacrolimus, thrombosis recurred by the fifth postoperative day. The discussion that follows reviews the incidence and the factors implicated in the pathogenesis of this entity.
Inhibition of the Phosphatidylinositol 3′-Kinase Pathway Promotes Autocrine Fas-Induced Death of Phosphatase and Tensin Homologue–Deficient Prostate Cancer Cells
Authors: Jerod Bertram, James W. Peacock, Clara Tan, Alice L-F. Mui, Stephen W. Chung, Martin E. Gleave, Shoukat Dedhar, Michael E. Cox, Christopher J. Ong
Journal: Cancer Research (2006)

Abstract Rationally designed therapeutics that target the phosphatidylinositol 3′-kinase (PI3K) cell survival pathway are currently in preclinical and clinical development for cancer therapy. Drugs targeting the PI3K pathway aim to inhibit proliferation, promote apoptosis, and enhance chemosensitivity and radiosensitivity of cancer cells. The phosphatase and tensin homologue (PTEN) phosphatidylinositol 3′-phosphatase is a key negative regulator of the PI3K pathway. Inactivation of the PTEN tumor suppressor results in constitutive activation of the PI3K pathway and is found in ∼50% of advanced prostate cancers, which correlates with a high Gleason score and poor prognosis. Inhibition of the PI3K pathway leads to apoptosis of prostate cancer cells; however, the precise mechanism by which this occurs is unknown. Here we report that apoptotic cell death of PTEN-deficient LNCaP and PC3 prostate cancer cells induced by the PI3K inhibitor LY294002 can be abrogated by disrupting Fas/Fas ligand (FasL) interactions with recombinant Fas:Fc fusion protein or FasL neutralizing antibody (Nok-1), or by expressing dominant-negative Fas-associated death domain. Furthermore, we find that apoptosis induced by expression of wild-type PTEN, driven by a tetracycline-inducible expression system in LNCaP cells, can be inhibited by blocking Fas/FasL interaction using Fas:Fc or Nok-1. These data show that apoptosis induced by blockade of the PI3K pathway in prostate tumor cells is mediated by an autocrine Fas/FasL apoptotic mechanism and the Fas apoptotic pathway is both necessary and sufficient to mediate apoptosis by PI3K inhibition. (Cancer Res 2006; 66(9): 4781-8)
Complement Component C3 and Risk of Age-Related Macular Degeneration
Authors: Dominiek D.G. Despriet, Cornelia M. van Duijn, Ben A. Oostra, Andre G. Uitterlinden, Albert Hofman, Alan F. Wright, Jacoline B. ten Brink, Arne Bakker, Paulus T.V.M. de Jong, Johannes R. Vingerling, Arthur A.B. Bergen, Caroline C.W. Klaver
Journal: Ophthalmology (2009)
A Coding Single-Nucleotide Polymorphism in Lysine Demethylase <i>KDM4A</i> Associates with Increased Sensitivity to mTOR Inhibitors
Authors: Capucine Van Rechem, Joshua C. Black, Patricia Greninger, Yang Zhao, Carlos Donado, Paul d. Burrowes, Brendon Ladd, David C. Christiani, Cyril H. Benes, Johnathan R. Whetstine
Journal: Cancer Discovery (2015)

SNPs occur within chromatin-modulating factors; however, little is known about how these variants within the coding sequence affect cancer progression or treatment. Therefore, there is a need to establish their biochemical and/or molecular contribution, their use in subclassifying patients, and their impact on therapeutic response. In this report, we demonstrate that coding SNP-A482 within the lysine tridemethylase gene KDM4A/JMJD2A has different allelic frequencies across ethnic populations, associates with differential outcome in patients with non-small cell lung cancer (NSCLC), and promotes KDM4A protein turnover. Using an unbiased drug screen against 87 preclinical and clinical compounds, we demonstrate that homozygous SNP-A482 cells have increased mTOR inhibitor sensitivity. mTOR inhibitors significantly reduce SNP-A482 protein levels, which parallels the increased drug sensitivity observed with KDM4A depletion. Our data emphasize the importance of using variant status as candidate biomarkers and highlight the importance of studying SNPs in chromatin modifiers to achieve better targeted therapy.This report documents the first coding SNP within a lysine demethylase that associates with worse outcome in patients with NSCLC. We demonstrate that this coding SNP alters the protein turnover and associates with increased mTOR inhibitor sensitivity, which identifies a candidate biomarker for mTOR inhibitor therapy and a therapeutic target for combination therapy.
Clinical and physiological evaluation of mucolytic agents nebulized with isoproterenol: 10% N-acetylcysteine versus 10% 2-mercaptoethane sulphonate
Authors: S. R. Hirsch, P. F. Viernes, R. C. Kory
Journal: Thorax (1970)

In a controlled five-week cross-over study in 12 patients with chronic bronchitis, the effects of nebulized 10% N-acetylcysteine plus isoproterenol were compared with a new drug, sodium 2-mercaptoethane sulphonate, in 10% concentration also nebulized with isoproterenol. Both combinations were compared with a control aerosol of saline and a second control aerosol of saline plus isoproterenol. Both 10% 2-mercaptoethane sulphonate and 10% N-acetylcysteine were highly effective in thinning mucoid, mucopurulent or purulent sputum. Subjective improvement in these patients, however, was related to the isoproterenol rather than to the mucolytic agents. When nebulized with isoproterenol, neither mucolytic agent was associated with bronchospasm in any patient. Physical findings, spirometric values, and sputum volume were unaffected by these mucolytic agents.
Scale of protection and the various types of sports mouthguard
Authors: D G Patrick, R van Noort, M S Found
Journal: British Journal of Sports Medicine (2005)

Objectives: To present a grading system of the protection offered by various types of mouthguard, together with an indication of associated risks, in order to make athletes aware of the consequences of improper or no mouth protection. Methods: A review of the literature on mouthguards, mouthguard materials, and novel laminates for mouthguards was carried out as it was apparent that information on mouthguards was lacking. Studies on stock (or unfitted) mouthguards, mouth formed (boil and bite) mouthguards, and custom mouthguards are reviewed. Results: A scale of protection offered by various mouthguards and novel laminates has been produced, where 0 indicates no mouthguard and 10 indicates a custom made mouthguard offering excellent protection. Conclusions: From work carried out on laminates and the manufacturing processes of mouthguards, it became apparent that information was lacking to enable athletes make informed decisions about the best oral protection for their chosen sport.
Sputum Mediators in Children with Mild Persistent Asthma Indicate Immune Dysregulation and Correlate with Lower Lung Function
Authors: N. Patel, A.M. Schiltz, R. Harbeck, R.A. Covar, S.M. Wood, S.J. DeMichele, E.W. Gelfand, S.J. Szefler, A.H. Liu
Journal: Journal of Allergy and Clinical Immunology (2007)
Relationship between parental lung function and their children's lung function early in life
Authors: N. van Putte-Katier, M. Koopmans, C. S. P. M. Uiterwaal, B. M. de Jong, J. L. L. Kimpen, T. J. M. Verheij, M. E. Numans, C. K. van der Ent
Journal: European Respiratory Journal (2011)

This study investigated the relationship between parental lung function and their children’s lung function measured early in life. Infants were participants in the Wheezing Illnesses Study Leidsche Rijn (WHISTLER). Lung function was measured before the age of 2 months using the single occlusion technique. Parental data on lung function (spirometry), medical history and environmental factors were obtained from the linked database of the Utrecht Health Project. Parental data on pulmonary function and covariates were available in 546 infants. Univariate linear regression analysis demonstrated a significant positive relationship between the infant9s respiratory compliance and parental forced expiratory flow at 25–75% of forced vital capacity (FEF<sub>25–75%</sub>)<sub>,</sub> forced expiratory volume in 1 s (FEV<sub>1</sub>) and forced vital capacity. A significant negative relationship was found between the infant9s respiratory resistance and parental FEF<sub>25–75%</sub>and FEV<sub>1</sub>. No significant relationship was found between the infant9s respiratory time constant and parental lung function. Adjusting for body size partially reduced the significance of the observed relationship; adjusting for shared environmental factors did not change the observed results. Parental lung function levels are predictors of the respiratory mechanics of their newborn infants, which can only partially be explained by familial aggregation of body size. This suggests genetic mechanisms in familial aggregation of lung function, which are already detectable early in life.
Point: Are Insulin Pumps Underutilized in Type 1 Diabetes? Yes
Authors: John C. Pickup
Journal: Diabetes Care (2006)

Continuous subcutaneous insulin infusion (CSII), popularly called insulin pump therapy, has evolved from its invention in the 1970s as an experimental treatment designed to test the relationship between glycemic control and diabetic tissue complications (1) to its present status as a routine therapy for selected type 1 diabetic patients (2). However, the use of insulin pump therapy varies markedly throughout the world; there are some notable high-use countries, e.g., the U.S. and Israel, where it is estimated that ∼20% of type 1 diabetic patients use CSII (manufacturers’ estimates), whereas in other countries, such as the U.K. and Denmark, ∼1% use pump therapy (3).

The reasons for this variation include the availability of financial resources and health care professionals to supervise CSII and a lack of knowledge on the effectiveness of CSII (3), but there is also disagreement on which diabetic subjects should be treated with CSII, as evidenced by both the different intercountry usage and the large number of reasons for starting insulin pump therapy (4–6).

As noted by Schade and Valentine (7), “the challenge for the health care provider is to select the diabetic patients who will really benefit from pump usage.” What proportion and what types of type 1 diabetic patients should then be offered a trial of CSII on clinical grounds alone, leaving aside the legitimate issues of supply on the basis of patient preference and restrictions due to availability of funding and staffing? I shall argue that the target proportion best treated by CSII, or offered a trial of CSII, can be derived from an estimate of the effectiveness of this therapy compared with the best insulin injection treatment for particular clinical problems in type 1 diabetes.

Most current guidelines (4,6) or reviews of the evidence base on CSII (2 …
Serotype-specific pneumococcal disease may be influenced by mannose-binding lectin deficiency
Authors: X. Vallès, A. Roca, F. Lozano, L. Morais, B. Suárez, F. Casals, I. Mandomando, B. Sigaúque, D. Nhalungo, C. Esquinas, L. Quintó, P.L. Alonso, A. Torres
Journal: European Respiratory Journal (2010)

Previous studies of the association between the mannose-binding lectin pathway deficiencies and invasive pneumococcal disease are inconclusive. Invasiveness of Streptococcus pneumoniae is dependent on serotype. We aimed to determine the association between invasive pneumococcal disease and MBL2 and MASP2 genetic variants, regarding serotype distribution. A hospital-based case–control study was conducted in children admitted to hospital in rural Mozambique in June 2002–November 2003. The study included children admitted to hospital with invasive pneumococcal disease, in whom S. pneumoniae was isolated from blood and subsequently serotyped. Sequence-based typing analysis of amplicons covering the polymorphic regions of MASP2 (exon 3) and MBL2 (promoter and exon 1) was performed. An overall high frequency of MBL2 genotypes associated with low serum levels of MBL (43%) was found. Carriers of MBL-deficient genotypes were associated with invasive pneumococcal disease produced by low-invasive serotypes (OR 5.55, 95% CI 1.4–21.9; p = 0.01). Our data suggest that susceptibility to pneumococcal disease among MBL-deficient patients may be influenced by serotype invasiveness. Type-specific capsular serotype of S. pneumoniae would need to be taken into account in further genetic association studies of invasive pneumococcal disease.
Inaccuracy of routine susceptibility tests for detection of erythromycin resistance of Campylobacter jejuni and Campylobacter coli
Authors: M.T. van der Beek, E.C.J. Claas, D.J. Mevius, W. van Pelt, J.A. Wagenaar, E.J. Kuijper
Journal: Clinical Microbiology and Infection (2009)
No evidence of WT1 involvement in a Burkitt’s lymphoma in a patient with Denys–Drash syndrome
Authors: D. Perotti, P. Mondini, R. Giardini, A. Ferrari, M. Massimino, F. Gambirasio, M.A. Pierotti, F. Fossati-Bellani, P. Radice
Journal: Annals of Oncology (1998)
Volumetric computed tomography screening for lung cancer: three rounds of the NELSON trial
Authors: Nanda Horeweg, Carlijn M. van der Aalst, Rozemarijn Vliegenthart, Yingru Zhao, Xueqian Xie, Ernst Th. Scholten, Willem Mali, Erik Thunnissen, Carla Weenink, Harry J.M. Groen, Jan-Willem J. Lammers, Kristiaan Nackaerts, Joost van Rosmalen, Matthijs Oudkerk, Harry J. de Koning
Journal: European Respiratory Journal (2013)

Several medical associations recommended lung cancer screening by low-dose computed tomography scanning for high-risk groups. Counselling of the candidates on the potential harms and benefits and their lung cancer risk is a prerequisite for screening. In the NELSON trial, screenings are considered positive for (part) solid lung nodules with a volume >500 mm3 and for (part) solid or nonsolid nodules with a volume-doubling time <400 days. For this study, the performance of the NELSON strategy in three screening rounds was evaluated and risk calculations were made for a follow-up period of 5.5 years. 458 (6%) of the 7582 participants screened had a positive screen result and 200 (2.6%) were diagnosed with lung cancer. The positive screenings had a predictive value of 40.6% and only 1.2% of all scan results were false-positive. In a period of 5.5 years, the risk of screen-detected lung cancer strongly depends on the result of the first scan: 1.0% after a negative baseline result, 5.7% after an indeterminate baseline and 48.3% after a positive baseline. The screening strategy yielded few positive and false-positive scans with a reasonable positive predictive value. The 5.5-year lung cancer risk calculations aid clinicians in counselling candidates for lung cancer screening with low-dose computed tomography.
Prevention of Bacterial Endocarditis
Authors: Adnan S. Dajani, Kathryn A. Taubert, Walter Wilson, Ann F. Bolger, Arnold Bayer, Patricia Ferrieri, Michael H. Gewitz, Stanford T. Shulman, Soraya Nouri, Jane W. Newburger, Cecilia Hutto, Thomas J. Pallasch, Tommy W. Gage, Matthew E. Levison, Georges Peter, Gregory Zuccaro
Journal: Circulation (1997)

Objective To update recommendations issued by the American Heart Association last published in 1990 for the prevention of bacterial endocarditis in individuals at risk for this disease. Participants An ad hoc writing group appointed by the American Heart Association for their expertise in endocarditis and treatment with liaison members representing the American Dental Association, the Infectious Diseases Society of America, the American Academy of Pediatrics, and the American Society for Gastrointestinal Endoscopy. Evidence The recommendations in this article reflect analyses of relevant literature regarding procedure-related endocarditis, in vitro susceptibility data of pathogens causing endocarditis, results of prophylactic studies in animal models of endocarditis, and retrospective analyses of human endocarditis cases in terms of antibiotic prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database searches from 1936 through 1996 were done using the root words endocarditis, bacteremia, and antibiotic prophylaxis. Recommendations in this document fall into evidence level III of the US Preventive Services Task Force categories of evidence. Consensus Process The recommendations were formulated by the writing group after specific therapeutic regimens were discussed. The consensus statement was subsequently reviewed by outside experts not affiliated with the writing group and by the Science Advisory and Coordinating Committee of the American Heart Association. These guidelines are meant to aid practitioners but are not intended as the standard of care or as a substitute for clinical judgment. Conclusions Major changes in the updated recommendations include the following: (1) emphasis that most cases of endocarditis are not attributable to an invasive procedure; (2) cardiac conditions are stratified into high-, moderate-, and negligible-risk categories based on potential outcome if endocarditis develops; (3) procedures that may cause bacteremia and for which prophylaxis is recommended are more clearly specified; (4) an algorithm was developed to more clearly define when prophylaxis is recommended for patients with mitral valve prolapse; (5) for oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic individuals, but clindamycin and other alternatives are offered; and (6) for gastrointestinal or genitourinary procedures, the prophylactic regimens have been simplified. These changes were instituted to more clearly define when prophylaxis is or is not recommended, improve practitioner and patient compliance, reduce cost and potential gastrointestinal adverse effects, and approach more uniform worldwide recommendations.
Cross-Sector Partnerships and Public Health: Challenges and Opportunities for Addressing Obesity and Noncommunicable Diseases Through Engagement with the Private Sector
Authors: Lee M. Johnston, Diane T. Finegood
Journal: Annual Review of Public Health (2015)

Over the past few decades, cross-sector partnerships with the private sector have become an increasingly accepted practice in public health, particularly in efforts to address infectious diseases in low- and middle-income countries. Now these partnerships are becoming a popular tool in efforts to reduce and prevent obesity and the epidemic of noncommunicable diseases. Partnering with businesses presents a means to acquire resources, as well as opportunities to influence the private sector toward more healthful practices. Yet even though collaboration is a core principle of public health practice, public-private or nonprofit-private partnerships present risks and challenges that warrant specific consideration. In this article, we review the role of public health partnerships with the private sector, with a focus on efforts to address obesity and noncommunicable diseases in high-income settings. We identify key challenges-including goal alignment and conflict of interest-and consider how changes to partnership practice might address these.