tbuckley/cabot-search huggingface dataset:
Chemotherapy as an adjunct to radiation in the treatment of squamous cell carcinoma of the head and neck: results of the Yale Mitomycin Randomized Trials.
Authors: B G Haffty, Y H Son, R Papac, C T Sasaki, J B Weissberg, D Fischer, S Rockwell, A C Sartorelli, J J Fischer
Journal: Journal of Clinical Oncology (1997)

PURPOSE Two consecutive randomized trials were run at our institution using the bioreductive alkylating agent mitomycin as an adjunct to radiation therapy in an effort to improve outcome in patients with squamous cell carcinoma of the head and neck. METHODS Between 1980 and 1992, two consecutive randomized trials using mitomycin (trial 1) and mitomycin with dicumarol (trial 2) as an adjunct to radiation therapy in patients with squamous cell carcinoma of the head and neck were conducted at our institution. The patients were stratified by intent of therapy, extent of disease, and primary tumor site. Within each strata, patients were randomized to receive radiation therapy with or without mitomycin (trial 1) or mitomycin/dicumarol (trial 2). RESULTS A total of 203 patients were enrolled onto both trials, 195 of whom were eligible for analysis. Patients were equally balanced with respect to sex, age, extent of disease, primary site, radiation dose, and total duration of radiation treatment. Hematologic toxicities were more frequently noted in the drug-treated arms, but were acceptable with no drug-related treatment deaths. Nonhematologic toxicities were acceptable and not significantly different between the two arms. As of September 1995, with a median follow-up of 138 months, a statistically significant benefit occurred in the mitomycin arms with respect to cause-specific survival (0.74 +/- 0.05 v 0.51 +/- 0.05; P = .005), local recurrence-free survival (0.85 +/- 0.04 v 0.66 +/- 0.05; P = .002), and local regional recurrence-free survival (0.76 +/- 0.05 v 0.54 +/- 0.05; P = .003). No statistically significant difference in overall survival was obtained (0.48 +/- 0.05 mitomycin arms v 0.42 +/- 0.05 radiation alone). CONCLUSION The bioreductive alkylating agent mitomycin is a safe and effective adjunct to radiation therapy in the treatment of squamous cell carcinoma of the head and neck. The statistically and clinically significant improvement in local regional relapse and cause-specific survival obtained support the use of mitomycin as an adjunct to radiation therapy in the management of squamous cell carcinoma of the head and neck.
Abstract P048: Prediabetes Range Fasting Glucose and Hemoglobin A1C Levels and Their Associations with Subclinical Atherosclerosis: Observations from the Dallas Heart Study
Authors: Frank Xing, M. Odette Gore, Ian J Neeland, Colby R Ayers, Andre Paixao, Aslan T Turer, Darren K McGuire
Journal: Circulation (2013)

Background Over 1/3 of US adults have “prediabetes” defined by impaired fasting glucose (IFG) and/or “at risk” hemoglobin A1c (A1C) - criteria criticized by some for being too liberal. Their associations with subclinical atherosclerosis remain poorly defined. Methods/Results Prediabetes was determined (fasting plasma glucose (FPG) 100-125mg/dL and/or A1C 5.7-6.4%) and coronary artery calcium (CAC) was measured in 2,373 adults age 30-70 free from medically-treated diabetes or cardiovascular disease in the Dallas Heart Study 2, a population-based cohort with mean age 49 years, mean BMI 30.5 kg/m2; 60% women and 64% non-white. Those with vs. without prediabetes were older (52 vs. 48 yrs; p 10) was higher in those with vs. without prediabetes (31 vs. 21%; p<0.001), with no statistical difference in CAC prevalence between prediabetes sub-groups with IFG-only, A1C-...
Significant reduction of COPD hospitalizations after implementation of a public smoking ban in Graubünden, Switzerland
Authors: Frank Dusemund, Florent Baty, Martin Hugo Brutsche
Journal: European Respiratory Journal (2013)

Background  Only few studies have examined the effect of public smoking bans on respiratory conditions. These showed reduced admission rates for different respiratory diseases. Objective of the present study was to evaluate the effect of the public smoking ban implemented in Graubunden, Switzerland, on the incidence of acute hospital admissions for COPD, pneumonia, asthma and bronchitis.  Methods  We searched a database including all nation-wide hospitalizations in Switzerland for COPD, pneumonia, asthma and bronchitis and analysed incidence rate ratios (IRR) before and after introduction of the smoking ban using Poisson regression and incidence rate ratios.  Results  After introduction of the smoking ban we observed a significant 22.4%-decrease in the incidence of COPD hospitalizations in Graubunden (IRR = 0.78 (0.68-0.88), p  Conclusion  Our study supports the limited body of evidence demonstrating that a reduction of second hand smoke by legislated bans on smoking are associated with reduced rates of admission to hospital for respiratory conditions, hereby shown for COPD, in addition to the meanwhile well documented impact on cardiovascular disease.
GENETIC VARIANTS OF γG4 GLOBULIN
Authors: H. G. Kunkel, F. G. Joslin, G. M. Penn, J. B. Natvig
Journal: The Journal of Experimental Medicine (1970)

Two types of gammaG4 proteins, termed 4a and 4b, were characterized through antigenic studies of myeloma proteins. Both were recognized by specific antigens on the Fc fragment which were shared with other gammaG classes. The distinctive antigen of the common 4a type was shared with all gammaG1 and gammaG3 proteins but missing in those of the gammaG2 class; that for the rarer 4b type was selectively found in proteins of the gammaG2 class. Analyses on gammaG4 fractions isolated from normal sera showed that either the 4a or the 4b or a mixture of the two types was present in each serum. Evidence was obtained that these differences were on a genetic basis and that allelic genes linked to those of the Gm system were involved. Such a reciprocal occurrence in other classes of gammaG globulin of the antigenic markers distinguishing genetic variants has not been observed previously. A number of questions regarding the evolutionary development of the genes responsible are discussed. The possibility is raised that those for the gammaG4 class arose relatively early and preceded the development of those for the other gammaG classes.
Erratum. The Relationship Between Alcohol Consumption and Vascular Complications and Mortality in Individuals With Type 2 Diabetes. Diabetes Care 2014;37:1353–1359
Authors: Juuso I. Blomster, Sophia Zoungas, John Chalmers, Qiang Li, Clara K. Chow, Mark Woodward, Giuseppe Mancia, Neil Poulter, Bryan Williams, Stephen Harrap, Bruce Neal, Anushka Patel, Graham S. Hillis
Journal: Diabetes Care (2015)
Variability of Oestrogen and Progesterone Receptor Status between Primary Breast Cancer and Nodal Metastases: Preliminary Communication
Authors: Dolores Fernandez, Jamshid Alaghband-Zadeh, Paul Sauven, J Ian Burn
Journal: Journal of the Royal Society of Medicine (1982)

The synchronous relationship between oestrogen (ER) and progesterone (PgR) receptor status in primary tumours and their nodal metastases has been analysed in 26 patients. All patients with ER-negative primary tumours were found to have ER-negative axillary nodes but of those with ER-positive tumours only 65% had, correspondingly, all nodes ER-positive. The concentration of ER in the nodes was found to be significantly lower (P less than 0.001) than that in the primary tumour. PgR information was unobtainable in 3 patients. Of the remainder, 75% of those having PgR-negative tumours had all nodes PgR-negative but only 36% of those with PgR-positive tumours had all nodes PgR-positive. PgR levels were found to be generally lower in the axillary nodes but this did not reach statistical significance. The clinical relevance of these findings is discussed.
Atypical hyperlipidemia and nephropathy associated with apolipoprotein E homozygosity.
Authors: D Ellis, T J Orchard, S Lombardozzi, E J Yunis, J McCauley, R Agostini, J R Diamond
Journal: Journal of the American Society of Nephrology (1995)

Hyperlipidemia has been implicated in the pathogenesis of experimental progressive glomerulosclerosis, but its role in human renal injury is controversial. This report describes a 12-yr-old boy presenting with massive proteinuria, hepatomegaly, anemia, severe mixed hyperlipidemia, and progressive renal failure. The initial renal biopsy disclosed large numbers of foam cells that were shown to be monocytes. Evidence is presented suggesting that apoprotein-E2 homozygosity in our patient, together with an 88% reduction in plasma lipoprotein lipase activity associated with severe nephrotic syndrome, is responsible for the atypical clinical features, lipoprotein phenotype III with chylomicronemia, and renal lipidosis. A regimen of dietary lipid restriction, gemfibrozil, and niacin resulted in significant but partial improvement of the dyslipidemia and resolution of the hepatomegaly and ascites. This report stresses the importance of characterizing unique lipid disorders in patients with nephrotic syndrome in order to prescribe effective lipid-lowering strategies. Moreover, the striking resemblance of the clinical and nephrohistologic features of this patient to those occurring in experimental models of coexisting glomerular injury and hyperlipidemia led to the speculation that, in this setting, the hyperlipidemia may contribute to the development of progressive glomerulosclerosis.
Conditional Degradation of Plasmodium Calcineurin Reveals Functions in Parasite Colonization of both Host and Vector
Authors: Nisha Philip, Andrew P. Waters
Journal: Cell Host & Microbe (2015)

Functional analysis of essential genes in the malarial parasite, Plasmodium, is hindered by lack of efficient strategies for conditional protein regulation. We report the development of a rapid, specific, and inducible chemical-genetic tool in the rodent malaria parasite, P. berghei, in which endogenous proteins engineered to contain the auxin-inducible degron (AID) are selectively degraded upon adding auxin. Application of AID to the calcium-regulated protein phosphatase, calcineurin, revealed functions in host and vector stages of parasite development. Whereas depletion of calcineurin in late-stage schizonts demonstrated its critical role in erythrocyte attachment and invasion in vivo, stage-specific depletion uncovered roles in gamete development, fertilization, and ookinete-to-oocyst and sporozoite-to-liver stage transitions. Furthermore, AID technology facilitated concurrent generation and phenotyping of transgenic lines, allowing multiple lines to be assessed simultaneously with significant reductions in animal use. This study highlights the broad applicability of AID for functional analysis of proteins across the Plasmodium life cycle.
Consensus Standards for Acquisition, Measurement, and Reporting of Intravascular Optical Coherence Tomography Studies
Authors: Guillermo J. Tearney, Evelyn Regar, Takashi Akasaka, Tom Adriaenssens, Peter Barlis, Hiram G. Bezerra, Brett Bouma, Nico Bruining, Jin-man Cho, Saqib Chowdhary, Marco A. Costa, Ranil de Silva, Jouke Dijkstra, Carlo Di Mario, Darius Dudeck, Erlin Falk, Marc D. Feldman, Peter Fitzgerald, Hector Garcia, Nieves Gonzalo, Juan F. Granada, Giulio Guagliumi, Niels R. Holm, Yasuhiro Honda, Fumiaki Ikeno, Masanori Kawasaki, Janusz Kochman, Lukasz Koltowski, Takashi Kubo, Teruyoshi Kume, Hiroyuki Kyono, Cheung Chi Simon Lam, Guy Lamouche, David P. Lee, Martin B. Leon, Akiko Maehara, Olivia Manfrini, Gary S. Mintz, Kyiouchi Mizuno, Marie-angéle Morel, Seemantini Nadkarni, Hiroyuki Okura, Hiromasa Otake, Arkadiusz Pietrasik, Francesco Prati, Lorenz Räber, Maria D. Radu, Johannes Rieber, Maria Riga, Andrew Rollins, Mireille Rosenberg, Vasile Sirbu, Patrick W.J.C. Serruys, Kenei Shimada, Toshiro Shinke, Junya Shite, Eliot Siegel, Shinjo Sonada, Melissa Suter, Shigeho Takarada, Atsushi Tanaka, Mitsuyasu Terashima, Thim Troels, Shiro Uemura, Giovanni J. Ughi, Heleen M.M. van Beusekom, Antonius F.W. van der Steen, Gerrit-Ann van Es, Gijs van Soest, Renu Virmani, Sergio Waxman, Neil J. Weissman, Giora Weisz
Journal: Journal of the American College of Cardiology (2012)

The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ∼10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data.
Early prosthetic joint infection: outcomes with debridement and implant retention followed by antibiotic therapy
Authors: J. Cobo, L. Garcia San Miguel, G. Euba, D. Rodríguez, J.M. García-Lechuz, M. Riera, L. Falgueras, J. Palomino, N. Benito, M.D. del Toro, C. Pigrau, J. Ariza
Journal: Clinical Microbiology and Infection (2010)
Based on what parameters of clinical remission should inhaled corticosteroids be stopped in children with asthma
Authors: Iva Mihatov Stefanovic, Renata Vrsalovic, Biserka Cicak
Journal: European Respiratory Journal (2013)

Limited number of studies have assessed how long treatment with inhaled corticosteroids (ICS) should be continued after clinical remission. Many people have persistent bronchial hyperreactivity (BHR) after clinical remission.

Aims of this longitudinal study were to (1) determine if BHR was present one year after stopping ICS therapy , (2) compare FEV 1, PEF, type and duration of therapy in group of positive and negative methacholine test, (3) follow up patients for recurrence of asthma symptoms.

Based on clinical parameters, normal spirometry results, daily peak expiratory flow (PEF) and negative bronchodilator test, ICS therapy was stopped in group of 40 children. After 6 to 12 months of total asthma control was achieved, step down and withdrawal of ICS treatment was introduced. One year after stopping therapy, methacholine challenge test was performed in all patients. Clinical course and lung function were followed 12 months after stopping of ICS.

Positive methacholine test was noted in 20 patients (50%). There was no statistically significant difference between group of positive and negative methacholine test regarding age of starting and stopping ICS therapy, duration of ICS therapy, duration of stepping down period, FEV 1 and PEF at the time of withdrawal of ICS and one year later.

In two patients from positive methacholine group, ICS treatment had to be reintroduced because of recurrence of asthma symptoms.

Clinical parameters, normal spirometry, daily PEF values and negative bronchodilator test are good parameters to exclude ICS therapy in asthmatic children, even in group with persistent BHR. Children should be followed up since symptoms can recur.
An unusual case of a painful big toe
Authors: Tun Hing Lui, Kwok Fai Tam
Journal: BMJ (2015)

Digital health education develops an understanding of the pragmatic use of digital technologies, including health apps, artificial intelligence and wearables, in the National Health Service (NHS). Staff should feel confident accessing up-to-date, quality-assured digital health solutions. Digital health is a high priority in government, NHS organisations and Royal Colleges. However, there is a gap between what is expected and the education of staff or medical students to enable implementation. Digital health education needs to be up to date and universally included within training, continuing professional development activities and medical school curriculums. During COVID-19, more families across the UK became digitally enabled with school, council, charities and governments providing access to devices, WiFi and mobile data for those that needed it. Improved digital access brings equalities in access to health information and healthcare professionals. Health app use sharply rose during COVID-19, as patients self-managed and took control of their conditions, but most health apps do not reach NHS standards. Paediatricians are well positioned to advise on appropriate health app use and advocate for improved patient access to solutions. Many paediatricians adopted remote video consultations during the COVID-19 pandemic but could soon adopt more digital health strategies to remotely track, monitor and manage conditions remotely. Patient management now includes remote consultations and digital health solutions; therefore, medical histories should capture digital access, environments and literacy. This article explains the importance of digital health education, lists accessible resources and provides examples of health apps that can be recommended.
Molecular epidemiology of predominant clones and sporadic strains of methicillin resistant Staphylococcus aureus in Switzerland and comparison with European epidemic clones
Authors: D.S. Blanc, D. Pittet, C. Ruef, A.F. Widmer, K. Mühlemann, C. Petignat, S. Harbarth, R. Auckenthaler, J. Bille, R. Frei, R. Zbinden, P. Moreillon, P. Sudre, P. Francioli
Journal: Clinical Microbiology and Infection (2002)
Abstract 18219: Monitoring of Anti-Xa in Pregnant Patients with Mechanical Prosthetic Valves Receiving Low Molecular Weight Heparin: Peak or Trough Levels?
Authors: Fan John, Sorel Goland, Nudrat Khatri, Uri Elkayam
Journal: Circulation (2010)

Introduction: Low molecular weight heparin (LMWH) is often used for anticoagulation in pregnant women with mechanical prosthetic heart valves (PHV). Recent AHA/ACC guidelines recommend the measurem...
Nanotechnology: Future of Oncotherapy
Authors: Kshipra M. Gharpure, Sherry Y. Wu, Chun Li, Gabriel Lopez-Berestein, Anil K. Sood
Journal: Clinical Cancer Research (2015)

Abstract Recent advances in nanotechnology have established its importance in several areas including medicine. The myriad of applications in oncology range from detection and diagnosis to drug delivery and treatment. Although nanotechnology has attracted a lot of attention, the practical application of nanotechnology to clinical cancer care is still in its infancy. This review summarizes the role that nanotechnology has played in improving cancer therapy, its potential for affecting all aspects of cancer care, and the challenges that must be overcome to realize its full promise. Clin Cancer Res; 21(14); 3121–30. ©2015 AACR.
Body-Surface Area–Based Dosing Does Not Increase Accuracy of Predicting Cisplatin Exposure
Authors: Felix E. de Jongh, Jaap Verweij, Walter J. Loos, Ronald de Wit, Maja J.A. de Jonge, André S.T. Planting, Kees Nooter, Gerrit Stoter, Alex Sparreboom
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Most anticancer drugs are dosed based on body-surface area (BSA) to reduce interindividual variability of drug effects. We evaluated the relevance of this concept for cisplatin by analyzing cisplatin pharmacokinetics obtained in prospective studies in a large patient population. PATIENTS AND METHODS: Data were obtained from 268 adult patients (163 males/105 females; median age, 54 years [range, 21 to 74 years]) with advanced solid tumors treated in phase I/II trials with cisplatin monotherapy or combination chemotherapy with etoposide, irinotecan, topotecan, or docetaxel. Cisplatin was administered either weekly (n = 93) or once every 3 weeks (n = 175) at dose levels of 50 to 100 mg/m 2 (3-hour infusion). Analysis of 485 complete courses was based on measurement of total and non–protein-bound cisplatin in plasma by atomic absorption spectrometry. RESULTS: No pharmacokinetic interaction was found between cisplatin and the anticancer drugs used in combination therapies. A linear correlation was observed between area under the curves of unbound and total cisplatin (r = 0.63). The mean plasma clearance of unbound cisplatin (CL free ) was 57.1 ± 14.7 L/h (range, 31.0 to 116 L/h), with an interpatient variability of 25.6%. BSA varied between 1.43 and 2.40 m 2 (mean, 1.86 ± 0.19 m 2 ), with an interpatient variability of 10.4%. When CL free was corrected for BSA, interindividual variability remained in the same order (23.6 v 25.6%). Only a weak correlation was found between CL free and BSA (r = 0.42). Intrapatient variability in CL free , calculated from 90 patients was 12.1% ± 7.8% (range, 0.30% to 32.7%). CONCLUSION: In view of the high interpatient variability in CL free relative to variation in observed BSA, no rationale for continuing BSA-based dosing was found. We recommend fixed-dosing regimens for cisplatin.
The 5S ribosomal RNA gene in Pythium species: two different genomic locations.
Authors: A Belkhiri, J Buchko, G R Klassen
Journal: Molecular Biology and Evolution (1992)

The 5S ribosomal RNA (rRNA) genes in eukaryotes may occur either interspersed with the other rRNA genes in the ribosomal DNA (rDNA) repeat, or in separate tandem arrays, or dispersed throughout the genome. In Pythium species and in several related Oomycetes, polymerase chain reaction (PCR) amplification of the nontranscribed spacer (NTS) region with one primer specific for the 5S gene revealed, with several exceptions, that the 5S rRNA gene was present in the rDNA repeat of those species with filamentous sporangia and was absent from the rDNA repeat of those with globose or unknown sporangia. When present, the gene was located approximately 1 kb downstream of the large-subunit rRNA gene and on the strand opposite that on which the other rRNA genes were located. This was confirmed in P. torulosum by sequencing of the gene and its flanking regions. The 5S rRNA genes of P. ultimum were found in tandem arrays outside the rDNA repeat. Evidence of dispersed 5S rRNA sequences was also observed. For many of the species of Pythium having the 5S gene in the NTS, the region between the large-subunit rRNA gene and the 5S gene was found to have length heterogeneity. Oomycetes related to Pythium were also found to have the 5S gene in the NTS, although sometimes in the opposite orientation. This may mean that the presence of the gene in the NTS is ancestral for the Oomycetes and that the absence of the gene in the NTS in those Pythiums with globose sporangia is due to loss of the gene from the rDNA repeat in an ancestor of this group of species. These results favor the view that 5S rRNA gene linkage to the rRNA cistron existed prior to the unlinked arrangement seen in most plants and animals.
1.5-Year Posttreatment Follow-Up of Radium-223 Dichloride (Ra-223) Safety in Patients (Pts) with Castration-Resistant Prostate Cancer (Crpc) and Symptomatic Bone Metastases from Alsympca: Characterization of Hematologic Safety Profiles
Authors: C. Parker, N. Vogelzang, O. Sartor, D. Bottomley, R.E. Coleman, I. Skjorestad, A. Aksnes, M. Wahba, S. Nilsson
Journal: Annals of Oncology (2014)