tbuckley/cabot-search huggingface dataset:
Better efficacy of a 12-month interferon alfa-2b retreatment in patients with chronic hepatitis C relapsing after a 6-month treatment: A multicenter, controlled, randomized trial
Authors: Jean-Louis Payen, Jacques Izopet, Virginie Galindo-Migeot, Valérie Lauwers-Cances, Jean-Pierre Zarski, Jean-Marie Seigneurin, Elizabeth Dussaix, Jean-Jacques Voigt, Janick Selves, Karl Barange, Jacqueline Puel, Jean-Pierre Pascal
Journal: Hepatology (1998)

We studied the efficacy of three interferon alfa–2b (IFN–α2b) regimens for the retreatment of patients with chronic hepatitis C (CHC) with prior complete response followed by relapse. Consecutive patients with CHC who had a complete biochemical response but relapse after a first course of 6 months of IFN with 3 million units (MU) given subcutaneously three times per week were enrolled in the study. Six to 24 months after the end of the first treatment, the patients were randomly assigned to receive IFN with either the same regimen (group 1), a regimen of 12 months with 3 MU (group 2), or a regimen of 6 months with 10 MU (group 3). Sustained biochemical response was defined as normal serum alanine transaminase (ALT) values during the follow–up and sustained virological response as a clearance of hepatitis C virus (HCV) RNA from the serum at the end of follow–up (6 months' posttreatment). Histological improvement was defined as a decrease of 1 point in Metavir score between the first liver biopsy and a biopsy performed at 6 months' postretreatment. Two hundred forty–seven patients were randomized: 75 to group 1, 91 to group 2, and 81 to group 3. In an intent–to–treat analysis, 12%, 36.3%, and 18.5% of patients had a sustained biochemical response after retreatment in groups 1, 2, and 3, respectively ( P &lt; .001); 13.8%, 32.4%, and 17.2% of patients had a sustained virological response after retreatment in groups 1, 2, and 3, respectively ( P &lt; .05). A low viral load and patients in group 2 were independently associated with a sustained biochemical response. A low Knodell score index before treatment, patients with a high level of ALT before retreatment, genotype 3, low viral load, and patients in group 2 were independently associated with sustained virological response. Younger age, a high level of ALT, a low level of γ–glutamyl transferase before retreatment, low viral load, and patients in group 2 were independently associated with sustained biochemical and virological response. Among the 80 patients with repeated liver biopsies, 47.6% had improved histological activity scores; this improvement was associated with a sustained biochemical and virological response. In patients with CHC initially treated with 3 MU of IFN given subcutaneously three times per week over a 6–month period, and who subsequently developed a relapse after a biochemical response, retreatment with a regimen of 3 MU of IFN given three times per week for 12 months produced better biochemical and virological sustained response rates than regimens involving a higher dose or a shorter duration of retreatment. The biochemical and virological sustained response was associated with histological improvement.
Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis
Authors: Jorge Cortes, Philippe Rousselot, Dong-Wook Kim, Ellen Ritchie, Nelson Hamerschlak, Steven Coutre, Andreas Hochhaus, Francois Guilhot, Giuseppe Saglio, Jane Apperley, Oliver Ottmann, Neil Shah, Philipp Erben, Susan Branford, Prasheen Agarwal, Ashwin Gollerkeri, Michele Baccarani
Journal: Blood (2006)
Medical History of Contraception
Authors: NORMAN E. HIMES
Journal: New England Journal of Medicine (1934)

With an excellent foreward by Dr. Guttmacher indicating some of the recent developments, the publishers have issued a reprint edition of a book originally published in 1936 and now a rarity. An enormous amount of historical material is thus made readily available to gynecologists, sociologists, and all others interested in problems of contraception.
Prevention of Bronchoconstriction by an Orally Active Local Anesthetic
Authors: Robert H. Brown, Wendye Robbins, Peter Staats, Carol Hirshman
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Stimulation of airway irritant receptors produces reflex bronchoconstriction that can be prevented by pretreatment with anticholinergic drugs or local anesthetics delivered by aerosol or intravenously. We compared therapeutic doses of an orally administered local anesthetic, mexiletine hydrochloride, and intravenously administered lidocaine at blocking histamine-induced bronchoconstriction in five basenji-greyhound dogs, using high-resolution computed tomography (HRCT) to directly measure changes in airway size. In the dogs given placebo, a histamine infusion decreased airway area to 61 ± 2% (mean ± SEM) of control (p < 0.01). Mexiletine pretreatment completely prevented histamine-induced airway constriction, with an airway area that was 94 ± 4% of the control value during the histamine infusion (p = 0.07 compared with baseline). Mexiletine serum levels were therapeutic (1.7 ± 0.3 mg/L). Similarly, pretreatment with lidocaine significantly blunted the airway constriction provoked by intravenous histamine. In lidocaine-pretreated dogs, histamine decreased airway area to 79 ± 4% of baseline (p < 0.01). As in the case of mexiletine, lidocaine serum levels were also therapeutic (2.4 ± 0.3 mg/L). Mexiletine was more effective than lidocaine at preventing histamine-induced bronchoconstriction (p = 0.02). These data suggest that orally administered local anesthetics may be useful in preventing irritant-induced bronchoconstriction in humans.
Abstract 5561: Radiogenomic analysis indicates MR images are potentially predictive of EGFR mutation status in glioblastoma multiforme
Authors: Olivier Gevaert, Lex Mitchell, Jiajing Xu, Caroline Yu, Daniel Rubin, Greg Zaharchuk, Sandy Napel, Sylvia Plevritis
Journal: Cancer Research (2012)

Abstract Objective: To predict mutations of key genes in glioblastoma multiforme (GBM) from MR image features. Methods: We obtained mutational and MR image data from 35 patients in the Cancer Genome Atlas (TCGA) GBM database. T1-weighted axial images pre and post gadolinium contrast MRI were processed as follows: a board certified neuro-radiologist traced a region of interest (ROI) around the enhanced part of the largest lesion in the T1 post-contrast MRI and confirmed by comparing it with the T1 pre-contrast image. This ROI was then used to compute features that characterized the intensity of the enhanced lesion, the sharpness of lesion boundaries and the boundary shape. We used the resulting data set to build a linear regression model with regularization to predict the presence of a mutation in terms of image features. We focused on predicting mutations in EGFR because several drugs target it and because EGFR mutations are prevalent in the TCGA GBM data. We evaluated the performance of predicting EGFR mutations from MR imaging data using 5-fold cross validation (5F-CV) and the area under the ROC Curve (AUC). The optimal ROC operating point was defined as the point with the maximal sum of sensitivity and specificity when the cost of false positives and false negatives are considered equivalent. Results: We found that computationally-derived MR image features can predict the presence of EGFR mutations with an AUC of 0.80. The optimal operating point had a sensitivity and specificity of 83% and 93% respectively. The top ranked features in the image-based EGFR-predictor model suggest that EGFR-mutated tumors have blurrier edges than EGFR-wild-type tumors. Conclusion: Our preliminary radiogenomic analysis of GBM suggests MR images may be used to non-invasively determine the mutation status of EGFR, an important drug target in glioblastoma. The ability to determine important genomic aberrations based on image data suggests a increasingly important role for imaging in personalized medicine and warrants further investigation. 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 5561. doi:1538-7445.AM2012-5561
Therapeutic effect of the anti-Fas antibody on arthritis in HTLV-1 tax transgenic mice.
Authors: K Fujisawa, H Asahara, K Okamoto, H Aono, T Hasunuma, T Kobata, Y Iwakura, S Yonehara, T Sumida, K Nishioka
Journal: Journal of Clinical Investigation (1996)

We have recently demonstrated Fas-mediated apoptosis in the synovium, of patients with rheumatoid arthritis (RA) and suggested that it may be one factor responsible for the regression of RA. To examine whether the induction of apoptosis caused by anti-Fas mAb may play a potential role as a new therapeutic strategy for RA, we investigated the effect of anti-Fas mAb (RK-8) on synovitis in an animal model of RA, the human T cell leukemia virus type I (HTLV-1) tax transgenic mice. We report here that administration of anti-Fas mAb into mice intra-articularly improved the paw swelling and arthritis within 48 h. Immunohistochemical study and in vitro culture studies showed that 35% of synovial fibroblasts, 75% of mononuclear cells, and some of polymorphonuclear leukocytes infiltrating in synovium underwent apoptosis by anti-Fas mAb. In situ nick end labeling analysis and electron microscope analysis clearly showed that many cells in synovium were induced apoptosis by anti-Fas mAb administration. However, local administration of anti-Fas mAb did not produce systemic side effects. Results demonstrated that administration of anti-Fas mAb in arthritic joints of the HTLV-1 tax transgenic mice produced improvement of arthritis. These findings suggest that local administration of anti-Fas mAb may represent a useful therapeutic strategy for proliferative synovitis such as RA.
A David and Goliath story: tobacco advertising and self-regulation in Australia.
Authors: S Chapman
Journal: BMJ (1980)

A small group of health workers succeeded in getting the largest tobacco advertising campaign in Australia banned by testing a clause in the advertising industry9s voluntary code of self-regulation. The group complained about a series of cigarette advertisements that featured an Australian entertainer who was popular with the young. Though the tobacco company denied the entertainer9s major appeal to the young, the chairman of the Advertising Standards Council ruled that the campaign did breach the code. The delay before the complaint was adjudicated--18 months--contrasted with the speed with which a series of antismoking advertisements had been withdrawn after complaints by a tobacco company9s advertisers. MOP UP9s victory in this case contains several lessons for people interested in restricting the promotional activities of multinational tobacco companies.
Ga-67 Imaging of a Penile Abscess
Authors: LEO ACKERMAN, WENDELL Y. YAP, PARVEZ SHIRAZI, MARK VAN DRUNEN
Journal: Clinical Nuclear Medicine (1998)

Ga-67 scintigraphy was performed on a 48-year-old man to rule out osteomyelitis of the ischial bone. The patient had a history of spinal cord injury, neurogenic bladder, and multiple urinary tract infections, and presented with fever, penile swelling, and induration at the base of the penis. A Ga-67 scan failed to demonstrate osteomyelitis but revealed by serendipity abnormal uptake at the site of a penile abscess.
Renal Function in 29 Healthy Adults Before and After Nephrectomy
Authors: Arthur G. Krohn
Journal: JAMA (1966)

Twenty-nine healthy subjects, who served as renaltransplant donors, were studied to determine the effect of nephrectomy on blood urea nitrogen (BUN), serum creatinine level, and renal clearance in the early postoperative period (1 to 18 days). A mean increase in BUN and creatinine of 26% and 33%, respectively, occurred. Clearance levels of endogenous creatinine and of paraaminohippurate were 70.5% and 70.2%, respectively, of the preoperative mean, indicating a rapid 40% increase in the function of the remaining kidney. No variation in renal function in relation to age of patient or postoperative day could be demonstrated in the early postoperative period.
RDEA119/BAY 869766: A Potent, Selective, Allosteric Inhibitor of MEK1/2 for the Treatment of Cancer
Authors: Cory Iverson, Gary Larson, Chon Lai, Li-Tain Yeh, Claudia Dadson, Paul Weingarten, Todd Appleby, Todd Vo, Andreas Maderna, Jean-Michel Vernier, Robert Hamatake, Jeffrey N. Miner, Barry Quart
Journal: Cancer Research (2009)

The RAS-RAF-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway provides numerous opportunities for targeted oncology therapeutics. In particular, the MEK enzyme is attractive due to high selectivity for its target ERK and the central role that activated ERK plays in driving cell proliferation. The structural, pharmacologic, and pharmacokinetic properties of RDEA119/BAY 869766, an allosteric MEK inhibitor, are presented. RDEA119/BAY 869766 is selectively bound directly to an allosteric pocket in the MEK1/2 enzymes. This compound is highly efficacious at inhibiting cell proliferation in several tumor cell lines in vitro. In vivo, RDEA119/BAY 869766 exhibits potent activity in xenograft models of melanoma, colon, and epidermal carcinoma. RDEA119/BAY 869766 exhibits complete suppression of ERK phosphorylation at fully efficacious doses in mice. RDEA119/BAY 869766 shows a tissue selectivity that reduces its potential for central nervous system-related side effects. Using pharmacokinetic and pharmacodynamic data, we show that maintaining adequate MEK inhibition throughout the dosing interval is likely more important than achieving high peak levels because greater efficacy was achieved with more frequent but lower dosing. Based on its longer half-life in humans than in mice, RDEA119/BAY 869766 has the potential for use as a once- or twice-daily oral treatment for cancer. RDEA119/BAY 869766, an exquisitely selective, orally available MEK inhibitor, has been selected for clinical development because of its potency and favorable pharmacokinetic profile.
CANCER OF THE LUNG: ITS MODES OF BEHAVIOUR
Authors: F. G. Chandler
Journal: BMJ (1935)

BRITJSiL_ ~~T he education of the medical man and the worker in the recognition of these tumours and the dangers attend- ing their neglect has already resulted in the patients being referred for treatment at an earlier and more favourable stage than formerly.There remains much, however, to be done in teaching the early recognition of this form of cancer, which on account of its situation on the surface should be easily recognized before secondary deposits have formed.In shale workers the application to the skin of a pro- tective mixture of lanolin and olive oil, as advocated by Twort, is a useful means of prevention, but its success depends on the willing co-operation of the worker, and so its use is liable to be neglected.It gives me much pleasure to record my grateful thanks to the medical boards of the following hospitals: the Man- chester Skin Hospital, the Manchester Royal Infirmary, the Salford Royal Hospital, and the Holt Radium Institute-by whose permission I have had access to much clinical material and statistical information.I also wish to -acknowledge my debt to Dr. E. M
Comparing Cisplatin and Carboplatin
Authors: J. P. NEIJT, J. C. VAN HOUWELINGEN
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Comparing Cisplatin and Carboplatin Get access J. P. NEIJT, J. P. NEIJT Utrecht University HospitalP.O. Box 85500 3508 GA Utrecht The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar J. C. VAN HOUWELINGEN J. C. VAN HOUWELINGEN Utrecht University HospitalP.O. Box 85500 3508 GA Utrecht The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 5, 7 March 1990, Page 434, https://doi.org/10.1093/jnci/82.5.434 Published: 07 March 1990
Tuberculosis of the Pericardium
Authors: John H. Hageman, Nicholas D. D'Esopo, William W. L. Glenn
Journal: New England Journal of Medicine (1964)

NOTWITHSTANDING the great strides forward in the treatment of tuberculosis two questions concerning the treatment of the relatively rare tuberculous pericarditis remain to be answered: What is the effectiveness of chemotherapy on the course of the disease, and what are the criteria for supplementing the treatment with pericardiectomy?The purpose of this paper is to attempt to answer these questions through an analysis of 44 cases of treated tuberculous pericarditis culled from the records of the Veterans Administration.Seven to 10 per cent of all type's of pericarditis are caused by the tubercle bacillus, and another 10 per cent are . . .
Pediatric-inspired intensified therapy of adult T-ALL reveals the favorable outcome of NOTCH1/FBXW7 mutations, but not of low ERG/BAALC expression: a GRAALL study
Authors: Raouf Ben Abdelali, Vahid Asnafi, Thibaut Leguay, Nicolas Boissel, Agnès Buzyn, Patrice Chevallier, Xavier Thomas, Stephane Lepretre, Françoise Huguet, Norbert Vey, Martine Escoffre-Barbe, Emmanuelle Tavernier, Oumedaly Reman, Nathalie Fegueux, Pascal Turlure, Philippe Rousselot, Jean-Yves Cahn, Veronique Lheritier, Yves Chalandon, Marie-Christine Béné, Elizabeth Macintyre, Hervé Dombret, Norbert Ifrah
Journal: Blood (2011)
Sleep Disturbances in HIV-Seropositive Patients
Authors: Suzan E. Norman, Lionel Resnick, Martin A. Cohn, Ranjan Duara, Jay Herbst, Joseph R. Berger
Journal: JAMA (1988)

To the Editor.—  Human immunodeficiency virus (HIV) infects the central nervous system and is associated with neurological and psychiatric disease. 1,2 Neuropsychological disorders may appear as the primary or only manifestation of HIV infection. 3 Sleep/wake disturbances have been reported among HIV-seropositive individuals. To provide a better understanding of the etiology of sleep complaints, a pilot study that evaluated sleep variables was performed.  Study.—  Eight asymptomatic HIV-seropositive patients (enzyme-linked immunosorbent assay and Western blot) (group A) and four HIV-seronegative and culture-negative patients (group B) were included. Patients with neuropsychiatric diseases were excluded. All were homosexual and did not differ in life-styles. None were sleep-deprived shift workers and none were taking medications known to affect sleep. None abused intravenous drugs or alcohol and none used sedatives or narcotics.  An interview, written questionnaires, and a standardized polysomnogram (sleep study) were administered to provide objective measurements of sleep. A two-sample t test was
Beneficial IFN-α treatment of tumorous herpes simplex blepharoconjunctivitis in dedicator of cytokinesis 8 deficiency
Authors: Cihan Papan, Beate Hagl, Valerie Heinz, Michael H. Albert, Oliver Ehrt, Julie Sawalle-Belohradsky, Jens Neumann, Martin Ries, Philip Bufler, Andreas Wollenberg, Ellen D. Renner
Journal: Journal of Allergy and Clinical Immunology (2014)
Abstract P2-11-02: Mapping Mutations: Importance of Family Geographic Origin in Portuguese High-Risk Breast/Ovarian Cancer Families for BRCA Mutation Screening
Authors: S Fragoso, P Machado, S Santos, P Rodrigues, J Parreira, S Bento, A Luís, F. Vaz
Journal: Cancer Research (2010)

Abstract Background: Hereditary breast/ovarian cancer is mainly related with BRCA1/2 mutations. The complete screening of both genes is long and expensive due to their large number of exons and the inexistence of hotspots. Besides our most frequent BRCA mutation, c.156_157insAlu in BRCA2, the Portuguese population has many other mutations in these genes, described over the years. Aim: to evaluate the importance of screening specific mutations, found in BRCA positive families, in other probands with the same geographic origin. Patients and methods: 407 high risk breast/ovarian cancer patients were screened for c.156_157insAlu in BRCA2 (the Portuguese founder mutation), BRCA1/2 point mutations and large rearrangements. All probands were questioned about their family origin. Mutations detected in families were studied in new probands with the same geographic origin. Results: we were able to draw a map with the geographic origin of our 87 BRCA positive families. Most of our BRCA families have origin in the centre of Portugal. While searching probands with the same geographic origin as others previously detected, we found three additional mutations without screening the whole genes: 1 family from Madeira island; 1 family from the south (Algarve) and 1 non-affected individual, without previous family testing, that was positive for c.156_157insAlu in BRCA2 (her family had origin in an area of high prevalence of this mutation). Our maps also allowed the linking of several families with the same mutation and family origin, but apparently unrelated. Conclusion: Mapping geographic origin of BRCA1/2 mutations may help in the quick identification of new BRCA1/2 carriers and, in some cases, reduce the screening time. Most importantly it permits the linking of apparently unrelated families. This link permits a more accurate estimation of BRCA1/2 positive families and a better understanding of all at-risk family members. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-11-02.
Physostigmine Dose for Tricyclic Drug Overdose
Authors: ROBERT H. BRIER
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 October 1978Physostigmine Dose for Tricyclic Drug OverdoseROBERT H. BRIER, M.D.ROBERT H. BRIER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-89-4-579_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Doctor Hollister's excellent review, "Treatment of Depression with Drugs" (Ann Intern Med89:78-84, 1978), suggests that treatment of tricyclic overdosage with physostigmine is limited to an arbitrary total intravenous dose of 3 to 4 mg. Yet a number of authors have reported cases of successful treatment of tricyclic overdosage requiring up to 74 mg of physostigmine (1). I am aware of a 7-year-old child having been successfully treated for Tofranil® ingestion with a total dose of 260 mg of physostigmine during a 30-h period, including a continuous intravenous infusion of the drug at 16 mg/h at one...References1. MUNOZ R: Treatment of tricyclic intoxication. Am J Psychiatry 133:1085-1087, 1976 CrossrefMedlineGoogle Scholar2. RUMACK B: Anticholinergic poisoning: treatment with physostigmine. Pediatrics 52:449-451, 1973 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPhysostigminePhysostigmine 1 October 1978Volume 89, Issue 4Page: 579-579KeywordsAddictionDrugsIngestion Issue Published: 1 October 1978 PDF downloadLoading ...
Pigbel-like syndrome in a vegetarian in Oxford.
Authors: J M Farrant, Z Traill, C Conlon, B Warren, N Mortensen, F V Gleeson, D P Jewell
Journal: Gut (1996)

Enterocolitis necroticans or pigbel is a rare condition characteristically affecting chronically malnourished people who abruptly increase their intake of protein. The classic presentation of the disease as seen in the highlands of Papua New Guinea is that of a necrotising enterocolitis after the ritual ingestion of contaminated pork. In this context, the presentation of the same disease in a well nourished white vegetarian in Oxford was all the more intriguing.