tbuckley/cabot-search huggingface dataset:
Phase III Clinical Trials That Integrate Treatment and Biomarker Evaluation
Authors: Boris Freidlin, Zhuoxin Sun, Robert Gray, Edward L. Korn
Journal: Journal of Clinical Oncology (2013)

Article Tools STATISTICS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2012.48.3826 Journal of Clinical Oncology - published online before print April 8, 2013 PMID: 23569306 Phase III Clinical Trials That Integrate Treatment and Biomarker Evaluation Boris FreidlinxBoris FreidlinSearch for articles by this author , Zhuoxin SunxZhuoxin SunSearch for articles by this author , Robert GrayxRobert GraySearch for articles by this author , Edward L. KornxEdward L. KornSearch for articles by this author Show More Boris Freidlin and Edward L. Korn, National Cancer Institute, Bethesda, MD; and Zhuoxin Sun and Robert Gray, Eastern Cooperative Oncology Group, and Dana-Farber Cancer Institute, Boston, MA. https://doi.org/10.1200/JCO.2012.48.3826 First Page Full Text PDF Figures and Tables © 2013 by American Society of Clinical Oncology
Subacute Combined Degeneration Developing during Liver Therapy
Authors: J. F. Adams, G. C. Timbury
Journal: BMJ (1959)

Initial treatment of the disease is easy, it is over maintenance treatment that the patient comes to grief."Witts made this statement in 1934, when liver and liver extracts were the only forms of therapy available for the treatment of pernicious anaemia.Parenteral liver therapy is still in common use, and we report here the unfortunate consequences of the use of two such preparations, which were later found to contain only trivial quantities of vitamin B12'
Drink a Toast to Tap Water: Study Suggests Water Consumption Benefit Outweighs THM Hazard
Authors: John Tibbetts
Journal: Environmental Health Perspectives (2007)

About 15% of the U.S. population get their drinking and household water from a largely unmonitored source: private residential wells.About 400,000 new wells are drilled every year.A new USGS study suggests that the water in a small percentage of domestic wells could contain unsafe levels of volatile organic compounds (VOCs) [EHP 115:1539-1546; Rowe et al.].VOCs come from a wide variety of sources, including gasoline, plastics, paints, dyes, solvents, adhesives, insecticides, and spot removers, and have wide-ranging health effects.The chemical and physical properties of VOCs allow the compounds to move between the atmosphere, soil, surface water, and groundwater.Once in the environment, some VOCs degrade quickly whereas others persist for decades.The USGS collected data on 55 VOCs primarily between 1991 and 2002.The team analyzed water samples before homeowners treated or filtered the water, which could help reduce VOCs.Many-possibly half of all well users-don't filter their water.The wells ranged in depth from 6 to 1,500 feet, with a median depth of about 140 feet.Of the 2,401 wells studied, 65% had detectable levels of VOCs, and 1% had levels above the EPA maximum contaminant level for the compound(s) observed.The most common compounds found were chloroform, toluene, 1,2,4-trimethylbenzene, and perchloroethene.Factors associated with the presence of VOCs were dissolved oxygen content, precipitation, the presence of a hazardous waste site within 1 km of the well, aquifer type, and water temperature.The authors note that identifying factors associated with VOC occurrence may aid in understanding the sources, transport, and fate of these compounds in groundwater.-
State University and Higher Medical Education.
Authors: Parks Ritchie
Journal: JAMA (1900)

St. Paul, Minn., July 31, 1900. <h3>To the Editor:</h3> —In your editorial of July 21 you specifically mention Michigan, Minnesota and Iowa, and allege that by low fees and mediocre requirements for entrance and for graduation, university medical schools acquire larger classes than they can properly instruct, that their clinical material is insufficient, and inferentially they are obstructive to the advance of medical education. Michigan and Iowa will doubtless resent this attack and defend themselves. Minnesota's fees are $100 per annum. There are none higher to my knowledge, excepting a small number of schools in our largest cities. Our entrance requirements are equaled by few and<i>excelled by none excepting</i>Harvard and Johns Hopkins' Universities and possibly the College of Physicians and Surgeons, New York. Our entrance examination is now equivalent to that required for admission to the academic department of the University of Minnesota. In two years' time it
The U.S. Food and Drug Administration Risk Assessment on Lead in Women’s and Children’s Vitamins Is Based on Outdated Assumptions
Authors: Amir Miodovnik, Philip J. Landrigan
Journal: Environmental Health Perspectives (2009)

Following a recent report of lead in certain commercial vitamin products, the U.S. Food and Drug Administration (FDA) conducted a nationwide survey to determine the Pb content in 324 multivitamin/mineral products labeled for use by women and children. The FDA compared estimated Pb exposures from each product with safe/tolerable exposure levels, termed provisional total tolerable intake (PTTI) levels, previously developed for at-risk population groups in 1992.We investigated the FDA's conclusions that Pb concentrations in all vitamin products examined do not pose a hazard to health because they are below the PTTI levels for all groups considered.For their initial estimations of PTTI levels, the FDA used a blood lead level (BLL) of 10 microg/dL as the threshold for adverse effects in children and in pregnant or lactating women. Studies have repeatedly linked chronic exposure to BLLs < 10 microg/dL with impairments in cognitive function and behavior in young children despite the absence of overt signs of toxicity. The FDA analysis also omitted any consideration of nonfood sources of Pb exposure, which is inconsistent with our current understanding of how most children develop elevated BLLs.We feel that based on these oversights, the FDA's conclusions are unduly reassuring and that reconsideration of their current recommendations appears warranted.
Acute arterial occlusion and platelet deposition are markedly reduced by local delivery of a novel nitric oxide donor
Authors: Myung Ho Jeong, Whyte G. Owen, Amir Leman, David N. Fass, Jean Gregoire, Michael E. Staab, Sanjay S. Srivatsa, David R. Holmes, Robert S. Schwartz
Journal: Journal of the American College of Cardiology (1996)
Improved prospects for long-term survival in adults with acute myelogenous leukemia
Authors: Michael J. Keating, Kenneth B. McCredie, Gerald P. Bodey, Terry L. Smith, Edmund Gehan, Emil J Freireich
Journal: JAMA (1982)

An improved complete remission rate in acute myelogenous leukemia (AML) has been noted since cytarabine and anthracyclines were introduced into clinical practice. Forty-one (9%) of 457 patients with AML treated between 1965 and 1976 have survived more than five years. The proportion of five-year survivors for patients treated between 1973 and 1976, 1970 and 1972, and 1965 and 1969 were 11.8%, 8.8%, and 1.8%, respectively. The major factor influencing five-year survival was whether or not patients were treated with cytarabine alone or combined with an anthracycline. Thirty-six (17%) of the 207 complete responders remained in continuous complete remission for more than five years. Twenty-four of the 36 patients who are in remission for more than five years have not been receiving chemotherapy for more than five years and are considered potentially cured.
Systematic reviews and lifelong diseases
Authors: H. E Elphick
Journal: BMJ (2002)

Systematic reviews of randomised controlled trials provide an evidence base for treatment but too often fail to give adequate information on long term outcomes. Elphick and colleagues discuss the limitations of the systematic review of randomised controlled trials for patients with chronic or lifelong diseases and suggest that long term observational studies have a place in the evaluation of the benefits and risks of treatment

Synthesis of evidence from systematic reviews of randomised controlled trials is considered thegold standard when evaluating the effectiveness of treatments, yet systematic reviews do not always place as much emphasis on information about adverse effects or safety issues. 1 2 In people with chronic, or lifelong,diseases long term outcomes are particularly important but are much less likely to be evaluated inrandomised controlled trials. We discuss the results of a recent systematic review of randomised controlled trials of antibiotic therapy in cystic fibrosis, which provided preliminary information about antibiotic resistance but not about other adverse effects. Although the review suggested that this finding should be investigated by a further clinical trial, we discuss why this may be neither the most feasible nor the most efficient study design with which to evaluate long term outcomes in lifelong diseases.

### Summary points

A systematic review suggested that there was an increase in antibiotic resistance in patients treated with one compared with two antibiotics

Systematic reviews of randomised controlled trials are often unable to provide adequate information about long term outcomes, which are important for people with chronic diseases

A tension exists in randomised controlled trials between evaluating short term outcomes, which may indicate a need to change practice, and continuing the trial for sufficient time to evaluate long term outcomes

Databases specialising in a particular disease can play a part in capturing information on patients prospectively, provided the clinical questions are …
Critical Evaluation of Adult Treatment Panel III Criteria in Identifying Insulin Resistance With Dyslipidemia
Authors: Youlian Liao, Soonho Kwon, Sara Shaughnessy, Penny Wallace, Amy Hutto, Alicia J. Jenkins, Richard L. Klein, W. Timothy Garvey
Journal: Diabetes Care (2004)

OBJECTIVE—The goal of this study was to evaluate the efficacy of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) in identifying insulin resistance. RESEARCH DESIGN AND METHODS—This study included 74 nondiabetic Caucasians who were evaluated for insulin resistance and risk factors associated with the metabolic syndrome. Glucose disposal rate (GDR) was measured by hyperinsulinemic-euglycemic clamp and was used to quantify insulin resistance. Sensitivity and specificity of ATP III criteria in detecting insulin resistance were calculated for various cutoffs of GDR. RESULTS—Insulin resistance was associated with increased waist circumference, fasting glucose, blood pressure, triglycerides, and decreased levels of HDL cholesterol. Only 12.2% of study subjects met ATP III criteria for metabolic syndrome, and ATP III criteria exhibited low sensitivity for detecting insulin resistance. Although high in specificities (&amp;gt;90%), the sensitivities of ATP III criteria ranged only between 20 and 50% when insulin resistance was defined as various GDR cutoff values below 10 to 12 mg · kg−1 · min−1. The larger number of subjects who were insulin resistant but did not meet ATP III criteria were found to have an adverse cardiovascular disease risk profile, including higher BMI, waist circumference, fasting glucose, triglycerides, and an unfavorable lipoprotein subclass profile determined by nuclear magnetic resonance compared with insulin-sensitive individuals (i.e., increased large VLDL, increased small LDL, and decreased large HDL particle concentrations). CONCLUSIONS—ATP III criteria have low sensitivity for identifying insulin resistance with dyslipidemia in nondiabetic individuals who are at increased risk for cardiovascular disease and diabetes. More sensitive criteria should be developed for clinical assessment of metabolic and cardiovascular disease risk relevant to the metabolic syndrome.
Evaluation of intestinal pressure-controlled colon delivery capsule containing caffeine as a model drug in human volunteers
Authors: Motoki Muraoka, Zhaopeng Hu, Tatsuharu Shimokawa, Syu-ichi Sekino, Ri-e Kurogoshi, Yoshiko Kuboi, Yukako Yoshikawa, Kanji Takada
Journal: Journal of Controlled Release (1998)
Carbohydrate-deficient transferrin, a sensitive marker of chronic alcohol abuse, is highly influenced by body iron
Authors: Tullia Maria De Feo, Silvia Fargion, Lorena Duca, Michela Mattioli, Maria Domenica Cappellini, Maurizio Sampietro, Bruno Mario Cesana, Gemino Fiorelli
Journal: Hepatology (1999)

Carbohydrate–deficient transferrin(CDT) a microheterogeneous form of serum transferrin (Tf) has been proposed as the most reliable marker of chronic alcohol consumption, although unexplained false–positive and –negative results have been reported.We investigated whether body iron influenced CDT serum levels by studying alcohol abusers with or without iron overload and nonabusers with iron deficiency or iron overload caused by genetic hemochromatosis (GH).In alcohol abusers, CDT was significantly lower in the presence of iron overload than in the absence (24.6 ±16.5 U/L vs.33.3 ±11.7 U/L; P &lt;.01) with false–negative results almost exclusively in patients with iron overload. Similarly, in nonabusers with GH, CDT was lower than in normal controls (9.6±2.2 U/L vs.15.7 ± 3.3 U/L; P &lt;.0001) whereas, patients with iron deficiency anemia had significantly higher levels than controls (28.1±5.8 U/L vs.15.7±3.3 U/L; P &lt;.0001).In nonabusers, iron supplementation therapy significantly decreased CDT levels in patients with iron deficiency anemia (33.7±6.6 U/L vs.21.7± 5.2 U/L; P =.0007) while iron–depletion treatment significantly increased CDT levels in patients with GH (9.7 ± 2.0 U/L vs. 14.7 ± 4.0 U/L; P =.001).Alcohol abusers had a significant relationship between liver iron concentration (LIC)and the reciprocal of CDT ( r =.65; P &lt;.0001) while in nonabusers, there was a significant correlation between Tf and CDT ( r =.72; P &lt;.0001).In conclusion, CDT serum levels are markedly affected by the patient's iron status, with iron overload reducing its sensitivity in alcohol abusers and iron deficiency its specificity in nonabusers. CDT can be considered a reliable marker of alcohol abuse only when iron stores are normal.
Obesity–insulin targeted genes in the 3p26-25 region in human studies and LG/J and SM/J mice
Authors: Aldi T. Kraja, Heather A. Lawson, Donna K. Arnett, Ingrid B. Borecki, Ulrich Broeckel, Lisa de las Fuentes, Steven C. Hunt, Michael A. Province, James Cheverud, D.C. Rao
Journal: Metabolism (2012)
Psychological and Vocational Long-Term Outcomes of Cardiac Rehabilitation with Postinfarction Patients under the Age of Forty
Authors: W. Langosch, G. Brodner, H. Borcherding
Journal: Psychotherapy and Psychosomatics (1983)

70 male postinfarction patients, who were under 40 years of age at the time of transmural myocardial infarction, participated in an inpatient control examination 3.8 years following first hospitalization (mean age: 40 years, SD = 3.5 years). A multivessel disease occurred in 52% of the patients, in 80% a multilocular disease was diagnosed and in 25 % coronary angiography indicated a progression in coronary sclerosis. Coronary risk factors had been considerably reduced. 78% were capable of working. Job-related stress factors of at least moderate intensity were present in about 30% of the jobs now held by the patients. Progressive morphological change occurred in patients who are older, have a multilocular disease, are subjected to more frequent and more intensive job-related stress factors, show less concern for their health and tend to leave their old living habits unchanged. In patients with multivessel disease, time pressure elicited more psychophysiological activation; furthermore, doing too many tasks at the same time and a reduced control over vocational success, together with sufficient self-confidence and an exaggerated job devotion are found in these patients. Retired patients differ from those who went back to work in cardiological, psychological and psychophysiological aspects. The importance of psychological and psychophysiological findings for a successful vocational reintegration is emphasized by these results.
The Association Between HLA B7 Alleles and Human Atopic Dermatitis Complicated by Eczema Herpeticum
Authors: R.A. Mathias, N. Rafaels, C. Vergara, M. Boguniewicz, T. Hata, L. Schneider, J.M. Hanifin, R.L. Gallo, T.H. Beaty, L.A. Beck, K.C. Barnes, D.Y. Leung
Journal: Journal of Allergy and Clinical Immunology (2012)
THE EFFECT OF DIETARY PROTEIN ON THE COURSE OF NEPHROTOXIC NEPHRITIS IN RATS
Authors: Lee E. Farr, Joseph E. Smadel
Journal: The Journal of Experimental Medicine (1939)

Acute nephritis of medium severity, affecting both glomeruli and tubules, was produced in rats by injections of anti-rat-kidney serum, given on 3 consecutive days. The course of the nephritis was markedly influenced by the type of diet which was fed. Rats tended to recover promptly from the induced nephritis when a low protein-high carbohydrate diet was given. On the other hand, in nephritic rats maintained on a medium protein diet the nephritis almost invariably became chronic and half the animals died of renal insufficiency during the 10(1/2) months of observation. Finally none of the rats which received a high protein-low carbohydrate diet recovered from the acute renal injury; all developed chronic progressive nephritis and the majority died of renal failure after some months.
MICROALBUMINURIA IS AN INDEPENDENT PREDICTOR OF LEFT VENTRICULAR MASS INDEX IN SOUTH ASIANS
Authors: Mohan Thanikachalam, Vijayakumar Harivanzan, Wajih Syed, Jahnavi Sunderarajan, Natesa Pandian, Ragavendra Baliga, Sadagopan Thanikachalam
Journal: Journal of the American College of Cardiology (2014)
Cytokines IL-1 β , IL-6, and TNF- α Enhance<i>In Vitro</i> Growth of Bacteria
Authors: G. UMBERTO MEDURI, SIVA KANANGAT, JENNIFER STEFAN, ELIZABETH TOLLEY, DENNIS SCHABERG
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We have previously reported that in acute respiratory distress syndrome (ARDS), nonsurvivors have persistent elevation in pulmonary and circulating proinflammatory cytokine levels over time and a high rate of nosocomial infections antemortem. In these patients, none of the proven or suspected nosocomial infections caused a transient or sustained increase in plasma proinflammatory cytokine levels above preinfection values. We hypothesized that cytokines secreted by the host during ARDS may favor the growth of bacteria. We conducted an in vitro study of the growth of three bacteria clinically relevant in nosocomial infections, evaluating their in vitro response to various concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. We found that all three bacterial species showed concentration-dependent growth enhancement when incubated with one or more tested cytokines and that blockade by specific neutralizing cytokine MoAb significantly inhibited cytokine-induced growth. When compared with control, the 6-h growth response (cfu/ml) was maximal with IL-1beta at 1,000 pg for Staphylococcus aureus (36 +/- 16 versus 377 +/- 16; p = 0.0001) and Acinetobacter spp. (317 +/- 1,147 versus 1,124 +/- 147; p = 0.002) and with IL-6 at 1,000 pg for Pseudomonas aeruginosa (99 +/- 50 versus 509 +/- 50; p = 0.009). The effects of cytokines were seen only with fresh isolates and were lost with passage in vitro on bacteriologic medium without added cytokines. In this study we provide additional evidence for a newly described pathogenetic mechanism for bacterial proliferation in the presence of exaggerated and protracted inflammation.
Modulation of Atrioventricular Nodal Function by Metabolic and Allosteric Regulators of Endogenous Adenosine in Guinea Pig Heart
Authors: Donn M. Dennis, M.J. Pekka Raatikainen, Jeffrey R. Martens, Luiz Belardinelli
Journal: Circulation (1996)

Background There has been increasing interest in the development of agents that utilize endogenous adenosine to exert their actions. We tested the hypothesis that substances that either potentiate the activity (allosteric enhancers) or increase the interstitial concentration (inhibitors of metabolism) of endogenous adenosine may cause event (tachycardia)-specific depression of AV nodal conduction. Methods and Results The frequency-dependent effects of iodotubercidin (ITU, an inhibitor of adenosine kinase), erythro -9-(2-hydroxy-3-nonyl)adenine (EHNA, an inhibitor of adenosine deaminase), draflazine (a nucleoside transport blocker), and PD81,723 (an allosteric enhancer of the A 1 adenosine receptor binding) on the stimulus-to–His bundle (SH) interval, a measure of AV nodal conduction, were determined in guinea pig hearts and compared with those of adenosine and diltiazem. All drugs depressed AV nodal conduction in a frequency-dependent manner. The ratios of SH interval prolongations at fast to slow pacing rates for draflazine, ITU+EHNA, PD81,723, adenosine, and diltiazem were 17.5±3.4, 11.1±5.0, 3.5±0.9, 10.1±2.8, and 8.3±3.5, respectively. Coincident with the prolongation of the SH interval at rapid pacing rates, draflazine and ITU+EHNA increased the epicardial fluid adenosine concentrations by 2.2- and 2.6-fold, respectively. In contrast, epicardial transudate levels of adenosine do not change in the presence of PD81,723. The AV nodal effects of draflazine, ITU, EHNA, and PD81,723 were reversed by the A 1 adenosine receptor antagonist 8-cyclopentyltheophylline and adenosine deaminase, implicating endogenous adenosine acting at the A 1 adenosine receptor. Conclusions Adenosine-regulating agents that act in an event- and site-specific manner represent a novel drug design strategy that may potentially be valuable for the long-term treatment of supraventricular arrhythmias and control of ventricular rate during atrial fibrillation or flutter.
c-Jun N-terminal kinase activation failure is a new mechanism of anthracycline resistance in acute myeloid leukemia
Authors: E D Lagadinou, P G Ziros, O A Tsopra, K Dimas, D Kokkinou, E Thanopoulou, M Karakantza, P Pantazis, A Spyridonidis, N C Zoumbos
Journal: Leukemia (2008)
Bigger margins are not better in breast conserving surgery
Authors: J. M. Dixon, N. Houssami
Journal: BMJ (2012)

Jeevan and colleagues report that one in five women who have breast conserving surgery requires reoperation because of incomplete excision or inadequate clearance of margins.1 The first major review of surgical margins established that disease at the margins increased recurrence rates but concluded that wide margins compared with narrow margins did not reduce local …
Immunization of Six-Month-Old Infants with Different Doses of Edmonston–Zagreb and Schwarz Measles Vaccines
Authors: Lauri E. Markowitz, Jaime Sepulveda, Jose Luis Diaz-Ortega, Jose Luis Valdespino, Paul Albrecht, Elizabeth R. Zell, John Stewart, Maria Luisa Zarate, Roger H. Bernier
Journal: New England Journal of Medicine (1990)

Because measles causes an estimated 2 million deaths per year among children in developing countries, including a substantial proportion of infants less than nine months old — the age at which vaccination is recommended — there has been interest in using different strains of vaccine and higher doses to achieve immunization of younger infants.
Response to Brosch et al.
Authors: Jussi Pihlajamäki, Carles Lerin, Dorota Kaminska, Sari Venesmaa, Paula Itkonen, Tanner Boes, Thomas Floss, Joshua Schroeder, Farrell Dearie, Sarah Crunkhorn, Furkan Burak, Josep C. Jimenez-Chillaron, Tiina Kuulasmaa, Pekka Miettinen, Peter J. Park, Imad Nasser, Zhenwen Zhao, Zhaiyi Zhang, Yan Xu, Wolfgang Wurst, Hongmei Ren, Andrew J. Morris, Stefan Stamm, Allison B. Goldfine, Markku Laakso, Mary Elizabeth Patti
Journal: Cell Metabolism (2012)