tbuckley/cabot-search huggingface dataset:
NICE is likely to reject bevacizumab for bowel cancer
Authors: C. White
Journal: BMJ (2010)

The body that evaluates treatments for the NHS in England and Wales, the National Institute for Health and Clinical Excellence (NICE), is unlikely to recommend bevacizumab (Avastin) for patients with advanced bowel cancer, despite attempts by the manufacturer to make it cheaper for the NHS to use.

In an interim ruling NICE has indicated it is likely to reject bevacizumab, in combination with oxaliplatin and either 5-fluoracil or capecitabine, for the treatment of metastatic bowel cancer on the grounds that the costs of the drug outweighed its clinical benefits. It has already rejected the drug in the past.

An estimated 6500 people a year would be eligible for bevacizumab, which costs around £20 800 (€25 300; $32 200) for one year. However, if approved by NICE the drug would be free after the first …
Evolution of Language
Authors: Roger W. Pease
Journal: JAMA (1979)

To the Editor.—   editorial by Samuel Vaisrub, MD (241:830, 1979), concerning the word  overlooked two dictionaries in which the term is defined.  following definition appears in a Merriam-Webster publication 1 :   mul•ti•fac•to•ri•al* -fak′tōrē[unk]l, -′tȯr- or  mul•ti•fac•tor -¦fakt[unk](r) adj : having or involving a variety of elements  multifactorial study>  Entries in Merriam-Webster dictionaries are based on citational evidence. At present, the citation files contain more than 12 1/2 million examples of English word usage recorded on 3×5-in slips.  earliest record of the new sense of multifactorial in the files is dated 1965 from Dubois 2 : The concept of multifactorial causation is in reality but an extension of the doctrine of specificity that brings scientific understanding a little nearer to the complexities of the real world.   word is also defined in a recent supplement to the Oxford English Dictionary  1 under sense 1 of the combining form multi -, where
Hemodynamic role of extracellular fluid in hypertension.
Authors: R C Tarazi
Journal: Circulation Research (1976)

Plasma volume is usually lower in patients with essential hypertension than in normal subjects. Normal or expanded plasma volume in some hypertensive patients may respect either a specific hypervolemic subset of the disease or the upper end of a continuum of volume values. Difficulties in defining these groups stem from the small numbers of subjects studied, from the need for a reliable reference index for volume measurements, and from the multiple factors which may affect intravascular volume. Differences in plasma volume cap influence choice of antihypertensive therapy; patients with expanded volume tend also to have slightly exchangeable sodium and greater extracellular fluid (ECF) volume and to respond well to diuretic therapy. There is also some evidence that low plasma renin activity is more frequent among hypervolemic patients. Essential hypertensives as a group have low plasma to interstitial fluid volume ratio (PV/IF), indicating that ECF distribution between the intravascular and interstitial compartments is shifted toward the latter. This is probably related to altered capillary filtration pressure due to increased venous resistance. Hypovolemic essential hypertensives have significantly lower (P less than 0.01) PV/IF ratio than hypervolemic, but whether this is related to differences in neural venous tone is only speculative. Hemodynamic studies revealed no difference in cardiac output between hypertensive patients with contracted blood volume and those with hypervolemia; total peripheral resistance was even higher in the latter, suggesting that "vasoconstriction" is not different between the two groups. It is widely believed that the relationship between ECF expansion and hypertension depends on the development of hypervolemia, increased cardiac output, and subsequent rise in total peripheral resistance reducing volume expansion and normalizing systemic flow while maintaining a high blood pressure. This sequence of events has been demonstrated in some human and experimental forms of hypertension but not in all. Metyrapone-induced hypertension in dogs could be sustained for up to 6 weeks by increased output with no evidence of "autoregulation" developing, and similar observations were reported in some anephric patients. Complementing these findings are observations of elevated cardiac output in some patients with long-standing essential hypertension or primary aldosteronism. It is therefore suggested that the spectrum of hemodynamic changes associated with volume disturbances in hypertension is too wide to be forced under one hypothesis alone and that neurogenic and other factors may play an important role in that complex relationship.
The Oldest Alumnus.
Authors: G. P. Conn
Journal: JAMA (1896)

Concord, N. H. April, 13, 1896. <h3>To the Editor:</h3> —TheJounralof April 11, p. 748, says: "Death of the oldest Alumnus of Jefferson Medical College." Now while that is true, yet I would call your attention to the fact that theAmerican Medical Associationhas a member in Newport, N. H., who was 86 years old February 17, and therefore from February to September older than Dr. Gemmell, but as he did not graduate at the Jefferson Medical College until 1836, he has not the distinction of being the oldest alumnus. Dr. John L. Swett was born in Clairmont, N. H., February 17,1810. Graduated from Jefferson Medical College, in 1836, and located in Newport, N. H., the same year. He has done a good business and commands the universal respect of the profession and the public. Yours truly,
Air Leaks Localized With Lung Ventilation SPECT
Authors: Gaetane Ceulemans, Liesbeth De Meirleir, Marleen Keyaerts, Dirk Smets, Douwe Verdries, Walter Vincken, Hendrik Everaert
Journal: Clinical Nuclear Medicine (2012)

A 61-year-old man with severe chronic obstructive pulmonary disease presented to our hospital with recurrence of a right-sided spontaneous secondary pneumothorax. Thoracoscopic abrasion of the parietal pleura was performed, but an important air leak persisted. Presumed to originate from a bulla in the right upper lobe, bullectomy and pleural decortication were performed, but leakage remained. Lobectomy was considered, and quantitative ventilation/perfusion SPECT was performed to predict the functional outcome.Fused high-resolution CT/Tc Technegas images localized leakage not only to a bleb in the right upper lobe but also to the subcutaneous emphysema in the thoracic wall. The air leak resolved after conservative treatment.
POST-HOSPITAL DISCHARGE TREATMENT OF STATIN IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION: IS STATIN BENEFICIAL IN PATIENT WITH LDL-CHOLESTEROL LOWER THAN 70 MG/DL?
Authors: Hyun Kuk Kim, Myung Ho Jeong, Youngkeun Ahn, Jong Hyun Kim, Shung Chull Chae, Young Jo Kim, Seung Ho Hur, In Whan Seong, Taek Jong Hong, Dong Hoon Choi, Myeong Chan Cho, Chong Jin Kim, Ki Bae Seung, Wook Sung Chung, Yang Soo Jang, Seung Woon Rha, Jang Ho Bae, Jeong Gwan Cho, Seung Jung Park
Journal: Journal of the American College of Cardiology (2010)
Effect of Aerosolized Uridine-5 ′ -Triphosphate on Airway Clearance with Cough in Patients with Primary Ciliary Dyskinesia
Authors: PEADAR G. NOONE, WILLIAM D. BENNETT, JEFF A. REGNIS, KIRBY L. ZEMAN, JOHNNY L. CARSON, MALCOLM KING, RICHARD C. BOUCHER, MICHAEL R. KNOWLES
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormal ciliary structure and function and impaired mucociliary clearance. Because patients with PCD use cough clearance as an airway defense mechanism, we tested the hypothesis that aerosolized uridine-5 ′ -triphosphate (UTP) would improve clearance during cough by its actions to stimulate Cl− secretion and mucin release by goblet cells. We measured clearance during cough in 12 patients with PCD (ages 14 to 71 yr, FEV1 43% to 89% predicted) in a double blind, randomized, crossover study after aerosolization of a single dose of UTP (5 mg/ml, 3.5 ml) or vehicle (0.12% saline, 3.5 ml). Clearance during cough (whole lung) was quantified during and after a series of controlled coughs by measuring the clearance of [99mTc]Fe2O3 particles via gamma camera scanning over 120 min. Safety parameters were recorded during and after drug delivery. Aerosolized UTP improved whole-lung clearance during cough as compared with vehicle (from 0 to 60 min: 0.40 ± 0.07%/min [UTP] versus 0.26 ± 0.04%/min [vehicle] [mean ± SEM], p = 0.01), and from 0 to 120 min: 0.38 ± 0.05%/min [UTP] versus 0.25 ± 0.04%/ min [vehicle], p = 0.02). Aerosolized UTP is safe, with no serious adverse effects. Whole-lung clearance during cough in patients with defective ciliary function is enhanced after inhalation of UTP.
Evasion of Immune Responses to Introduced Human Acid α-Glucosidase by Liver-Restricted Expression in Glycogen Storage Disease Type II
Authors: Luis M. Franco, Baodong Sun, Xiaoyi Yang, Andrew Bird, Haoyue Zhang, Ayn Schneider, Talmage Brown, Sarah P. Young, Timothy M. Clay, Andrea Amalfitano, Y.T. Chen, Dwight D. Koeberl
Journal: Molecular Therapy (2005)

Glycogen storage disease type II (GSD-II; Pompe disease) is caused by a deficiency of acid α-glucosidase (GAA; acid maltase) and manifests as muscle weakness, hypertrophic cardiomyopathy, and respiratory failure. Adeno-associated virus vectors containing either a liver-specific promoter (LSP) (AAV-LSPhGAApA) or a hybrid CB promoter (AAV-CBhGAApA) to drive human GAA expression were pseudotyped as AAV8 and administered to immunocompetent GAA-knockout mice. Secreted hGAA was detectable in plasma between 1 day and 12 weeks postadministration with AAV-LSPhGAApA and only from 1 to 8 days postadministration for AAV-CBGAApA. No anti-GAA antibodies were detected in response to AAV-LSPhGAApA (<1:200), whereas AAV-CBhGAApA provoked an escalating antibody response starting 2 weeks postadministration. The LSP drove approximately 60-fold higher GAA expression than the CB promoter in the liver by 12 weeks following vector administration. Furthermore, the detected cellular immunity was provoked by AAV-CBhGAApA, as detected by ELISpot and CD4+/CD8+ lymphocyte immunodetection. GAA activity was increased to higher than normal and glycogen content was reduced to essentially normal levels in the heart and skeletal muscle following administration of AAV-LSPhGAApA. Therefore, liver-restricted GAA expression with an AAV vector evaded immunity and enhanced efficacy in GSD-II mice.
Prediction Rules Must Be Developed According to Methodological Guidelines
Authors: Wee-Shian Chan
Journal: Annals of Internal Medicine (2010)

Letters16 February 2010Prediction Rules Must Be Developed According to Methodological GuidelinesWee-Shian Chan, MD, MSc, Tim Ramsay, MSc, PhD, and Jeffrey S. Ginsberg, MDWee-Shian Chan, MD, MScFrom Women's College Hospital, Toronto, Ontario M5G 1B2, Canada; Ottawa Health Research Institute, Ottawa, Ontario K1Y 4E9, Canada; and McMaster University Medical Centre, Hamilton, Ontario L8N 3Z5, Canada.Search for more papers by this author, Tim Ramsay, MSc, PhDFrom Women's College Hospital, Toronto, Ontario M5G 1B2, Canada; Ottawa Health Research Institute, Ottawa, Ontario K1Y 4E9, Canada; and McMaster University Medical Centre, Hamilton, Ontario L8N 3Z5, Canada.Search for more papers by this author, and Jeffrey S. Ginsberg, MDFrom Women's College Hospital, Toronto, Ontario M5G 1B2, Canada; Ottawa Health Research Institute, Ottawa, Ontario K1Y 4E9, Canada; and McMaster University Medical Centre, Hamilton, Ontario L8N 3Z5, Canada.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-4-201002160-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate Dr. Janssen and colleagues' comments. They raise some important and valid concerns, which we address below.As Dr. Janssen and colleagues point out, prediction rules are important to guide clinical practice in many instances, because they provide absolute risks for individual patients that can be used to determine treatment choices or further diagnostic work-up. We agree that before any rule can be adopted, it must be properly validated (which we did not do in our initial study) and must be derived from solid methodology.It may be true that the c-statistic may not be the most ... Author, Article, and Disclosure InformationAffiliations: From Women's College Hospital, Toronto, Ontario M5G 1B2, Canada; Ottawa Health Research Institute, Ottawa, Ontario K1Y 4E9, Canada; and McMaster University Medical Centre, Hamilton, Ontario L8N 3Z5, Canada.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPredicting Deep Venous Thrombosis in Pregnancy: Out in “LEFt” Field? Wee-Shian Chan , Agnes Lee , Frederick A. Spencer , Mark Crowther , Marc Rodger , Tim Ramsay , and Jeffrey S. Ginsberg Prediction Rules Must Be Developed According to Methodological Guidelines Kristel J.M. Janssen , Karel G.M. Moons , and Frank E. Harrell Jr. Metrics 16 February 2010Volume 152, Issue 4Page: 263-264KeywordsConflicts of interestInflammationPregnancy ePublished: 16 February 2010 Issue Published: 16 February 2010 CopyrightCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Martin Avigdor Birnstingl
Authors: J. Lumley
Journal: BMJ (2011)

Martin Avigdor Birnstingl was one of the most respected surgeons of his generation, but few knew or shared his amazingly complex and multifaceted existence. He was a skilled surgeon, president of the Vascular Surgical Society, author, inspired teacher, and an enthusiastic sailor, walker, and skier. He was also multilingual and a talented musician with an immense knowledge of literature and passionate views on human rights, which frequently brought him into conflict with governments. But above all he was a deeply thoughtful and caring doctor and friend.

Martin was born of musical, Fabian orientated parents, his father being a master printer and his mother a painter. At school he acquired a lifelong interest in ornithology, which, over the course of many years, led to a vast knowledge of birds, worldwide. He loved biology and by extension medicine, going from Bedales to Barts to qualify as a doctor. He served as a captain of the Royal Army Medical Corps in East Africa and Mauritius (where he had a pet parrot).

He returned to the Barts surgical unit under Sir James Patterson Ross, and his interest in vascular surgery developed out of the surgical traditions of Barts at that time. In 1952 a visiting American fellow, Jack Connolly, …
Efficacy of a three day course of azithromycin in moderately severe community-acquired pneumonia
Authors: G Rizzato, L Montemurro, P Fraioli, G Montanari, D Fanti, R Pozzoli, E Magliano
Journal: European Respiratory Journal (1995)

This study was designed to evaluate the efficacy of a 3 day course of azithromycin in low to moderately severe community-acquired pneumonia. Forty patients with low to moderately severe community-acquired pneumonia (29 males, 11 females, mean age 46 +/- 17 yrs; 20 pretreated with betalactams for 2-10 days with no results before admission to hospital; 18 with evidence of co-morbidity) were enrolled in an open, randomized study with azithromycin, 500 mg q.d. oral therapy for 3 days, versus clarithromycin, 250 mg b.i.d. oral therapy for 10 +/- 2 days. The aetiology of pneumonia was identified in 18 patients by serology (nine Mycoplasma pneumoniae, four Chlamydia pneumoniae, five Legionella pneumophila; one patient with chlamydial infection also had Klebsiella pneumoniae bacteraemia). A presumptive aetiological diagnosis was obtained with sputum culture in three other patients (one Haemophilus influenzae, two Haemophilus parainfluenzae), all strains were sole isolates with 10(8) Colony forming units (CFU), and with Gram stain in one patient with Streptococcus pneumoniae. All patients in the azithromycin group (one after a second 3 day course), and all but two (of those available for evaluation) of the clarithromycin group were cured. Defervescence occurred after 2.6 +/- 1.6 days, and chest roentgenogram cleared after 8.9 +/- 3.3 days, with no difference between the two groups. Tolerance was good, and there were no withdrawals from therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
148 Impact of liver transplantation (LT) on survival of pugh B alcoholic cirrhotic patients: A multicenter randomized study
Authors: J.P. Miguet, C. Vanlemmens, V. Di Martino, C. Milan, M. Messner, A. Minello, C. Duvoux, J.M. Perarnau, P. Hillon, G. Mantion, S. Bresson-Hadni
Journal: Journal of Hepatology (2004)
The RAG-1/2 endonuclease causes genomic instability and controls CNS complications of lymphoblastic leukemia in p53/Prkdc-deficient mice
Authors: Rebecca A. Gladdy, Michael D. Taylor, Christine J. Williams, Ildiko Grandal, Jana Karaskova, Jeremy A. Squire, James T. Rutka, Cynthia J. Guidos, Jayne S. Danska
Journal: Cancer Cell (2003)
Lupus erythematosus panniculitis–induced facial atrophy: Effective treatment with poly-L-lactic acid and hyaluronic acid dermal fillers
Authors: A. Brooke Eastham, Christine A. Liang, Alisa N. Femia, Thomas C. Lee, Ruth Ann Vleugels, Joseph F. Merola
Journal: Journal of the American Academy of Dermatology (2013)
Abstract P5-10-02: Clinical Outcome of Two Sequences of Administering Paclitaxel (P) and Anthracyclines (A) as Primary Systemic Therapy (PST) and Adjuvant Chemotherapy (ACT) in Breast Cancer (BC) Patients: A Retrospective Analysis from the M. D. Anderson Cancer Center (MDACC)
Authors: RH Alvarez, G Bianchini, L Hsu, M Cristofanilli, FJ Esteva, L Pusztai, AU Buzdar, GN Hortobagyi, V. Valero
Journal: Cancer Research (2010)

Abstract Background: P-and A-based regimens are widely used as PST and ACT of early BC. It is unknown whether the efficacy of such combinations is affected by their sequence of administration. The purpose of this retrospective analysis was to assess the clinical outcome of two different sequences of P and A in pts receiving PST and ACT. Methods: We analyzed 3,010 pts (1,414 PST and 1,596 ACT) with stage I — III BC treated between 1994 -2009. These pts were identified through our prospective online MDACC breast cancer database. Pts treated with trastuzumab, docetaxel or adriamycin/cyclophosphamide-regimen were excluded. Pathological complete response (pCR) was defined as no residual invasive disease in breast and ipsilateral axillary lymph nodes. Results: PST cohort included 1.071 pts (75%) with clinical stage I-IIIA and 343 (24.2%) stage IIIB-IIIC BC; 1,188 pts (84%) received the sequence P→A and 226 pts (16%) A→P. In the PST cohort 958 pts (67.7%) and 161 (11.3%) had hormone-receptor (HR) positive (+) and HER-2 + BC, respectively. ACT cohort consisted of 1,503 pts (94%) with pathological stage I-IIIA and 93 (5.82%) stage IIIB-IIIC. 1,196 pts (75%) received the sequence P→A, and 400 pts (25%) A→P. In the ACT cohort 1,122 (70.3%) and 93 (3.9%) had HR+ and HER2+ BC, respectively. Both cohorts of pts were balanced by HR-status, clinical stage, and menopausal status. The combined p-values for ACT and PST cohorts were calculated and they were significant for both RFS (p=0.022) and OS (p=0.002). In univariate analysis the sequence A→P was associated with inferior outcome. In Cox multivariate analysis, after stratification for period at diagnosis and adjustment for age, clinical stage, HR status, grade, and LVI the A→P sequence administered as PST was associated with significantly higher risk of relapse (HR 1.49; CI 1. 10-2.03; p=0.01) but not death (HR 1.28; CI 0.90-1.84; p=0.17). In the ACT cohort, the Cox multivariate analysis, after stratification for age, HR status, HER2 the sequence A→P was significantly associated with higher risk of death (HR 2.02; CI 1.33-3.06; p=0.001) but not relapse (HR 1.21; CI 0.82-1.79; p=0.33). Conclusions: The P→A sequence compared to the A→P sequence is associated with lower risk of relapse and death in PST and ACT, respectively. This retrospective analysis is hypothesis-generating and should lead to a prospective randomized trial to compare the two sequences as PST or ACT in locally advanced or early BC, respectively. Primary Systemic Therapy (N=1,414) Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-02.
Studies of Glycolysis in Individual Intact Human Erythrocytes by a New Cytochemical Technique: The Mechanisms of Hemolytic Drug Action.
Authors: Virgil F. Fairbanks
Journal: Annals of Internal Medicine (1967)

s1 May 1967Studies of Glycolysis in Individual Intact Human Erythrocytes by a New Cytochemical Technique: The Mechanisms of Hemolytic Drug Action.Virgil F. Fairbanks, M.D., F.A.C.P.Virgil F. Fairbanks, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1042_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPrevious studies have shown that hemolytic drugs inhibit glucose-6-phosphate dehydrogenase in hemolysates, or oxidize glutathione in hemolysates, or alter the erythrocyte membrane.Development of a new cytochemical stain, specific for activity of the pentose-phosphate glycolytic pathway, has made it possible to study the effect of hemolytic drugs in individual, intact, metabolically active erythrocytes. These studies have shown that primaquine, sulfonamides, nitrofurantoin, and 1-acetylphenylhydrazine do not inhibit the pentose shunt when incubated in concentration as high as 10-2M with intact normal human erythrocytes. Of these substances, only 1-acetylphenylhydrazine can be clearly shown to gain access to the interior of the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, Minnesota PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySerum copper levels in rheumatoid arthritis: 1 May 1967Volume 66, Issue 5Page: 1042-1042KeywordsAttentionDehydrogenasesDrugsErythrocyte membraneGlutathionePrimaquineSulfonamide ePublished: 1 December 2008 Issue Published: 1 May 1967 PDF downloadLoading ...
Congenital Fixed Subvalvular Aortic Stenosis
Authors: ROBERT L. REIS, LYNN M. PETERSON, DEAN T. MASON, ALLAN L. SIMON, ANDREW G. MORROW
Journal: Circulation (1971)

Detailed assessments were carried out before and after operation in 33 consecutive patients with congenital fixed subvalvular aortic stenosis. Effective relief of obstruction to left ventricular outflow can be accomplished at minimal risk in patients with discrete subaortic stenosis, but a pressure gradient may persist after operation because of secondary hypertrophic obstruction which resolves with time. Tunnel subaortic stenosis is characterized by a diffusely narrowed left ventricular outflow tract. When an intraventricular pressure gradient was present in such patients, good but not complete relief of obstruction was achieved. In tunnel deformities with a gradient at the valve or annulus and in subaortic stenosis produced by mitral valve anomalies, operative intervention was ineffective.