tbuckley/cabot-search huggingface dataset:
Treatment of Myelodysplasia in a Patient with Active Rheumatoid Arthritis
Authors: Alan J. Birnbaum, Patrick Gentile
Journal: Annals of Internal Medicine (2000)

Letters7 November 2000Treatment of Myelodysplasia in a Patient with Active Rheumatoid ArthritisAlan J. Birnbaum, MD and Patrick Gentile, MDAlan J. Birnbaum, MDSouth Bend Clinic; South Bend, IN 46617 (Birnbaum, Gentile)Search for more papers by this author and Patrick Gentile, MDSouth Bend Clinic; South Bend, IN 46617 (Birnbaum, Gentile)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-133-9-200011070-00037 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We describe a patient with the myelodysplastic syndrome in whom anemia resolved and bone marrow structure returned to normal after etanercept treatment.The patient is a 54-year-old woman with an 11-year history of rheumatoid arthritis. Previous treatment with prednisone (≤ 7.5 mg/d) and hydroxychloroquine controlled her arthritis. Her baseline complete blood count had shown mild anemia of chronic disease, with a hemoglobin level of 100 to 110 g/L.In August 1998, the patient reported shortness of breath, and her hemoglobin level was 61 g/L. Leukocyte and platelet counts were normal. Two independent bone marrow samples revealed myelodysplasia ...References1. Selleri C, Sato T, Anderson S, Young NS, Maciejewski JP. Interferon-γ and tumor necrosis factor-α suppress both early and late stages of hematopoiesis and induce programmed cell death. J Cell Physiol. 1995;165:538-46. CrossrefMedlineGoogle Scholar2. Udupa KB, Sharma BG. Possible role of tumor necrosis factor-α in erythropoietic suppression by endotoxin and granulocyte/macrophage colony-stimulating factor. Am J Hematol. 1996;52:178-83. CrossrefMedlineGoogle Scholar3. Shetty V, Mundle S, Alvi S, Showel M, Broady-Robinson L, Dar S, et al . Measurement of apoptosis, proliferation and three cytokines in 46 patients with myelodysplastic syndromes. Leuk Res. 1996;20:891-900. CrossrefMedlineGoogle Scholar4. Winter SS, Hanissian GA, Harville TO, Ware RE. Tumor necrosis factor-α suppresses hematopoiesis in children with myelodysplasia. Med Pediatr Oncol. 1997;28:69-74. CrossrefMedlineGoogle Scholar5. Heaney ML, Golde DW. Myelodysplasia. N Engl J Med. 1999;340:1649-60. CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Alan J. Birnbaum, MD; Patrick Gentile, MDAffiliations: South Bend Clinic; South Bend, IN 46617 (Birnbaum, Gentile) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 November 2000Volume 133, Issue 9Page: 753-754KeywordsAnemiaArthritisBone marrowHematopoiesisHemoglobinMyelodysplastic syndromesPlateletsRheumatoid arthritisSplenomegalyTumor necrosis factor ePublished: 7 November 2000 Issue Published: 7 November 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
INTERNAL SECRETIONS OF THE GASTROINTESTINAL TRACT
Authors: ANDREW C. IVY
Journal: JAMA (1941)

<h3>GASTRIC SECRETION—GASTRIN</h3> The secretory response of the gastric glands to a meal is due in part at least to a humoral mechanism. This has been amply demonstrated by means of transplanted pouches of the stomach.<sup>1</sup>Just what proportion of the total secretory response is mediated humorally is difficult to determine. There is still no direct evidence to indicate what area or areas of the gastrointestinal tract are the site of action for the stimuli which give rise to the humoral phase. It has recently been shown,<sup>2</sup>contrary to earlier views, that the fundus is sensitive to chemical stimuli, although less so than the pyloric region. Whether a humoral mechanism is elicited from either area is not known. The weak point in the gastrin theory has been the difficulty in demonstrating that the humoral secretion is due to a hormone rather than to the absorption of secretagogues or to
Pandemic influenza A(H1N1) 2009 and respiratory syncytial virus associated hospitalizations
Authors: Fernando Lovato-Salas, Lorena Matienzo-Serment, César Monjarás-Ávila, Elizabeth E. Godoy-Lozano, Andreu Comas-García, Marcela Aguilera-Barragán, Adriana Durham-González, Soledad Contreras-Vidales, Uciel Ochoa-Pérez, Alejandro Gómez-Gómez, Christian A. García-Sepúlveda, Daniel E. Noyola
Journal: Journal of Infection (2010)
ELECTRIC MOUTH BATTERY.
Authors: L. L. Funk
Journal: JAMA (1895)

The object of this invention is to obtain an electric battery which can be worn in the mouth of a person for its therapeutic effects, and also to give strength to the plate when false teeth are worn. This battery consists of a non-conducting plate arranged to fit in the mouth, metal plates of opposite electric polarity imbedded in the non-conducting plate, conductors connecting the metal plates, such conductors imbedded in the non-conducting plate, and such metal plates so disposed as to be exposed to the action of an electric excitation by the saliva or other fluids in the mouth, and the organs of the mouth, to form elements completing the circuit of the battery. We believe this to be the most rational form of electric treatment for cases which are indicated, inasmuch as we have a mild and uninterrupted current which may be made stronger or weaker to suit
Abstract B47: Identification of a novel ALK inhibitor active against Crizotinib-allele resistant mutants
Authors: Jean-Paul Nicolas, Loreley Calvet, Fabrice Vergne, Vincent Leroy, Carlos Garcia-Echeverria, Iris Valtingojer, Laurent Dassencourt, Francoise Herve, Emerson Serres, Laure Delarbre, Meredith Wolfrom, Amanda Lennon, Dietmar Hoffmann, Stephanie Deprets
Journal: Clinical Cancer Research (2012)

Abstract Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase belonging to the insulin receptor superfamily. Activating mutations in ALK are oncogenic and cause 10% to 15% of neuroblastoma cases. Similarly, activating ALK fusions have been detected in several cancers, including ALCL (NPM-ALK in 70% of patients) and NSCLC (EML4-ALK in 3% to 7% of patients). Several ALK inhibitors are currently undergoing clinical development, among which crizotinib has recently received marketing approval from the U.S. FDA under the name Xalkori. This nonselective ALK inhibitor has provided clinical benefit to lung cancer patients, but its sustained efficacy seems to be impaired by acquired drug resistance and several publications have already described ALK secondary mutations identified in patients who progressed while on crizotinib therapy. In this study, we have: Identified EML4-ALK mutations able to confer resistance to crizotinib. A screen using the Ba/F3 system found 24 residues in the ALK kinase domain where mutations can cause crizotinib resistance. Some of these mutations (L1152R, C1156Y, F1174L, G1202R, S1206F) have been identified in lung cancer patients progressing under crizotinib treatment Evaluated the activity of novel in-house and reference ALK kinase inhibitors against Ba/F3 cell lines stably expressing wild-type EML4-ALK and selected crizotinib-allele resistant mutantsPerformed in vivo head to head studies with a representative in-house ALK inhibitor and crizotinib to compare their pharmacodynamic properties This work resulted in the identification of an ALK kinase inhibitor with similar potency against wild-type EML4-ALK and crizotinib-allele resistant mutants and displaying significant target coverage in in vivo settings.
Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials
Authors: M. Shun-Shin, M. Thompson, C. Heneghan, R. Perera, A. Harnden, D. Mant
Journal: BMJ (2009)

<b>Objective</b> To assess the effects of the neuraminidase inhibitors oseltamivir and zanamivir in treatment of children with seasonal influenza and prevention of transmission to children in households. <b>Design</b> Systematic review and meta-analysis of data from published and unpublished randomised controlled trials. <b>Data sources</b> Medline and Embase to June 2009, trial registries, and manufacturers and authors of relevant studies. <b>Review methods</b> Eligible studies were randomised controlled trials of neuraminidase inhibitors in children aged ≤12 in the community (that is, not admitted to hospital) with confirmed or clinically suspected influenza. Primary outcome measures were time to resolution of illness and incidence of influenza in children living in households with index cases of influenza. <b>Results</b> We identified four randomised trials of treatment of influenza (two with oseltamivir, two with zanamivir) involving 1766 children (1243 with confirmed influenza, of whom 55-69% had influenza A), and three randomised trials for postexposure prophylaxis (one with oseltamivir, two with zanamivir) involving 863 children; none of these trials tested efficacy with the current pandemic strain. Treatment trials showed reductions in median time to resolution of symptoms or return to normal activities, or both, of 0.5-1.5 days, which were significant in only two trials. A 10 day course of postexposure prophylaxis with zanamivir or oseltamivir resulted in an 8% (95% confidence interval 5% to 12%) decrease in the incidence of symptomatic influenza. Based on only one trial, oseltamivir did not reduce asthma exacerbations or improve peak flow in children with asthma. Treatment was not associated with reduction in overall use of antibiotics (risk difference −0.30, −0.13 to 0.01). Zanamivir was well tolerated, but oseltamivir was associated with an increased risk of vomiting (0.05, 0.02 to 0.09, number needed to harm=20). <b>Conclusions</b> Neuraminidase inhibitors provide a small benefit by shortening the duration of illness in children with seasonal influenza and reducing household transmission. They have little effect on asthma exacerbations or the use of antibiotics. Their effects on the incidence of serious complications, and on the current A/H1N1 influenza strain remain to be determined.
The Malignant Uterus Yesterday, Today, and Tomorrow
Authors: John Stallworthy
Journal: JAMA (1966)

One hundred years is not a long time in the history of mankind. If by "yesterday" we mean the beginning of the century, the malignant uterus was then almost invariably fatal. The way of death was painful, miserably offensive, and often prolonged, but hope had dawned for the future. If by "tomorrow" we mean the end of the century, 35 years from now, it is safe to prophesy that carcinoma of the cervix will have taken its place with smallpox and poliomyelitis as a generally recognized preventable disease. It is not improbable that the same will apply to carcinoma of the corpus. There will be a great and progressive reduction in the incidence of cervical cancer and a corresponding relative increase in carcinoma in situ and microinvasive lesions. Stage 1 cancer will be diagnosed in the early phase of invasion and the cure rate will be nearly 100%. One result
Long-term prognosis after recovery from myocardial infarction: a nine year follow-up of the Perth Coronary Register.
Authors: C A Martin, P L Thompson, B K Armstrong, M S Hobbs, N de Klerk
Journal: Circulation (1983)

Patients registered by the 1971 Perth Coronary Register as having suffered a myocardial infarction were followed up for 9 years. The Register was a community-based study that used standard methods and criteria as part of a World Health Organization collaborative investigation. Of the 1078 patients studied, 77% survived the first 24 hr and 62% the first 28 days; 0.3% were lost to follow-up. For the 666 patients alive at 28 days, the crude 1, 5, and 9 year survival rates were 88%, 67%, and 52%, respectively. The relationship between 54 variables and the survival of patients alive 28 days after myocardial infarction was examined by life-table methods and the log rank test, and then by fitting a proportional hazards model to the data. The important prognostic factors were age, sex, past history of myocardial infarction, stroke, diabetes and hypertension, tachycardia at presentation, hypotension at presentation, and the occurrence of arrhythmias as short-term complications. The most appropriate mathematical description of the joint effects of the prognostic factors was a multiplicative model with no interaction.
The Impact of Underreported Veterans Affairs Data on National Cancer Statistics: Analysis Using Population-Based SEER Registries
Authors: N. Howlader, L. A. Ries, D. G. Stinchcomb, B. K. Edwards
Journal: JNCI Journal of the National Cancer Institute (2009)

Reduced cancer reporting by the US Department of Veterans Affairs (VA) hospitals in 2007 (for patients diagnosed through 2005) impacted the most recent US cancer surveillance data. To quantify the impact of the reduced VA reporting on cancer incidence and trends produced by the Surveillance, Epidemiology, and End Results Program, we estimated numbers of missing VA patients in 2005 by sex, age, race, selected cancer sites, and registry and calculated adjustment factors to correct for the 2005 incidence rates and trends. Based on our adjustment factors, we estimated that as a result of the underreporting, the overall cancer burden was underestimated by 1.6% for males and 0.05% for females. For males, the percentage of patients missing ranged from 2.5% for liver cancer to 0.4% for melanoma of the skin. For age-adjusted male overall cancer incidence rates, the adjustment factors were 1.015, 1.012, and 1.035 for all races, white males, and black males, respectively. Modest changes in long-term incidence trends were observed, particularly in black males.
From skin cells to hepatocytes: advances in application of iPS cell technology
Authors: Linda E. Greenbaum
Journal: Journal of Clinical Investigation (2010)

The discovery several years ago that fibroblasts and other somatic cells from mice and humans can be reprogrammed to become inducible pluripotent stem (iPS) cells has created enthusiasm for their potential applications in regenerative medicine and for modeling human diseases. Two independent studies in this issue of the JCI provide evidence that iPS cells represent a promising source of hepatocytes for a wide range of applications, including cell transplantation, drug toxicity testing, patient-specific disease modeling, and even ex vivo gene therapy. But how far have we come?
Cellular Mechanisms for Low-Dose Ionizing Radiation–Induced Perturbation of the Breast Tissue Microenvironment
Authors: Kelvin K.C. Tsai, Eric Yao-Yu Chuang, John B. Little, Zhi-Min Yuan
Journal: Cancer Research (2005)

Abstract Radiation exposure is an important form of environmental carcinogen and has been associated with increased risk of breast cancer. Epigenetic events, especially those involving alterations in the breast stromal microenvironment, may play an important role in radiation-induced carcinogenesis but remain not well understood. We here show that human mammary stromal fibroblasts respond to protracted low-dose ionizing radiation exposures by displaying a senescence-like phenotype. Using a three-dimensional coculture system to model the interactions of different mammary cell types with their neighbors and with their environment, we provide a direct experimental proof that ionizing radiation–induced senescence-like fibroblasts significantly perturb the mammary stromal microenvironment, which is highlighted by impaired formation of pseudopodia networks due to marked cytoskeletal alterations in senescence-like fibroblasts and increased extracellular matrix degradation because of the up-regulation of multiple secreted matrix metalloproteinases. Within such a perturbed environment, mammary ductal morphogenesis is completely disrupted and epithelial cells instead grow into enlarged cystic structures, which further develop and become disorganized cell masses on inactivation of cellular death pathways. Breast carcinoma cells growing in such an environment are enabled to fully express their malignant potential as evidenced by the α6β4 integrin/phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway–dependent invasive growth. Our results suggest that ionizing radiation, in addition to causing gene mutations in epithelial cells, can contribute to breast carcinogenesis by perturbing the tissue microenvironment that leads to dysregulated cell-cell and cell-matrix interactions.
Optimising prostate biopsy
Authors: B. Djavan, B. Rocco
Journal: BMJ (2011)

Lack of standardised procedures means that large variations in cancer detection remain

In the linked study (doi:10.1136/bmj.d7894), Rosario and colleagues assess the effects of transrectal ultrasound guided prostate biopsy in primary and secondary healthcare on patient reported outcomes.1

Transrectal ultrasound guided prostate biopsy is the core means but also the core problem of diagnosing prostate cancer. New and old serum markers, such as prostate specific antigen and its isoforms p2PSA and benign prostatic hyperplasia associated PSA,2 and improved imaging techniques based on fusion of images guided by transrectal ultrasound and magnetic resonance imaging, will certainly optimise patient selection, thus improving specificity (by reducing the number of men undergoing unnecessary biopsy procedures). However, the entire process is handicapped by an ailing biopsy procedure, which has changed little since the introduction of Stamey’s sextant biopsy technique.

Most of today’s research aims to identify new and better serum markers for prostate cancer.3 The main concern is that most of these studies rely on the biopsy procedure and its outcome to judge the statistical performance of the test. The biopsy procedure itself is not standardised across the study participants. The number of …
A Philological Problem from Philadelphia.
Authors: D. W. Neal
Journal: JAMA (1895)

Philadelphia, Pa., Aug. 15, 1895. <h3>To the Editor:</h3> —In one of the latest numbers of theJournalis an extract from the<i>Deutsche Medicinische Wochenschrift</i>on " The New Anatomic Nomenclature," and the number also contains an editorial commendation of the idea. In reading the extract I note that, " it was resolved that the terms should be in one language, that is, Latin designations only.... The names shall be Latin, and etymologically correct." That promises well, but when I look at the examples given by theJournal, I find the first one given to be " osteologia," a pure Greek word, with nothing Latin about it! Liddell and Scott define Oστεoλoγια as " the science which treats of bones." " Splanchnologia" and " angiologia" are also Greek, from Σπλαγχoν viscera, and `Aγγε[unk]oν a blood vessel, respectively, and these are not the only examples. I do not wish to be considered a captious critic, but isn't
Hepatic adducts, circulating antibodies, and cytokine polymorphisms in patients with diclofenac hepatotoxicity
Authors: Guruprasad P. Aithal, Lesley Ramsay, Ann K. Daly, Nhareet Sonchit, Julian B. S. Leathart, Graeme Alexander, Gerald J. Kenna, John Caldwell, Christopher P. Day
Journal: Hepatology (2004)

Diclofenac is a nonsteroidal anti-inflammatory drug that causes rare but serious hepatotoxicity, the mechanism of which is unclear. The purpose of the present study was to explore the potential role played by the immune processes. Antibodies to diclofenac metabolite-modified liver protein adducts were detected in the sera of seven out of seven patients with diclofenac-induced hepatotoxicity, 12 of 20 subjects on diclofenac without hepatotoxicity, and none of four healthy controls. The antibodies recognized adducts expressed in livers from rats treated with multiple doses of diclofenac, but not in those given single doses. In addition, several potential diclofenac adducts were identified in the liver of a patient with diclofenac-induced hepatic failure, but not from a normal human donor liver, by immunoblotting with an adduct-selective rabbit antiserum. To determine whether or not polymorphisms in genes encoding cytokine-related proteins influence susceptibility to hepatotoxicity, genotyping for the polymorphisms -627 in the interleukin (IL)-10 gene, -590 in the IL-4 gene, and codon 551 in the IL-4 receptor (IL-4R) were performed on DNA from 24 patients on diclofenac with hepatotoxicity, 48 subjects on diclofenac without hepatotoxicity, and healthy controls. The frequencies of the variant alleles for IL-10 and IL-4 were higher in patients (OR [odds ratio]: 2.8 for IL-10; 2.6 for IL-4; 5.3 for IL-10 + IL-4) compared with healthy controls and subjects on diclofenac without hepatotoxicity (OR: 2.8 for IL-10; 1.2 for IL-4; 5.0 for IL-10 + IL-4). In conclusion, the observed polymorphisms, resulting in low IL-10 and high IL-4 gene transcription, could favor a T helper (Th)-2 mediated antibody response to neoantigenic stimulation associated with disease susceptibility. Hepatology 2004;39:1430-1440.)
Comment: An Occupational Disease
Authors: Philip Rubin
Journal: JAMA (1968)

Cancer is most often thought of as a spontaneous process in which no known inciting agent has been identified. This does not mean that known causes do not exist. There is an extensive literature dealing with carcinogenic agents, and Dr. McDonald has succinctly defined those related to chronic industrial exposures in bladder tumorigenesis. Despite the known relationship between certain chemical carcinogens and bladder cancer, the translation of scientific facts into effective legislation is slow and virtually nonexistent in the United States. It should be emphasized that despite the facts that cancer of the bladder has been produced in workers in chemical, rubber, cable, and a number of other industries, and that its incidence is on the increase, to date—with the exception of the Commonwealth of Pennsylvania— no federal or state legislation exists in the United States for the regulation of the manufacture, use, or importation of these chemicals. The lack
Elevated Intrasynaptic Dopamine Release in Tourette’s Syndrome Measured by PET
Authors: Harvey S. Singer, Sally Szymanski, Joseph Giuliano, Fuji Yokoi, A. Semih Dogan, James R. Brasic, Yun Zhou, Anthony A. Grace, Dean F. Wong
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Dopaminergic abnormalities in frontal-subcortical circuits have been hypothesized as the underlying pathophysiologic mechanism in Tourette's syndrome. The objective of this study was to test the hypothesis that presynaptic dopamine release from the striatum is abnormal in adults with Tourette's syndrome. METHOD: Seven adults with Tourette's syndrome and five age-matched comparison subjects each received two positron emission tomography (PET) scans with high specific activity [11C]raclopride. The first scan followed an intravenous injection of saline; the second followed an intravenous injection of amphetamine. The relative dopamine release was estimated as the percentage difference in binding potential between the postsaline and postamphetamine scans. RESULTS: Binding potential determined after the initial [11C]raclopride scan did not significantly differ between Tourette's syndrome and comparison subjects. After amphetamine challenge, the mean value of intrasynaptic dopamine in the putamen (as determined by true equilibrium bolus estimation) increased by 21% in the subjects with Tourette's syndrome and did not change in the comparison subjects; the mean values increased by 16.9% and decreased by 1.8%, respectively, when measured by the constrained method. Dopamine release in the caudate region was not significantly different in the Tourette's syndrome and comparison subjects. CONCLUSIONS: Greater putamen dopamine release was seen in adults with Tourette's syndrome than in comparison subjects after a pharmacologic challenge with amphetamine. These results suggest that the underlying pathobiology in Tourette's syndrome is a phasic dysfunction of dopamine transmission.