tbuckley/cabot-search huggingface dataset:
Intensity-Modulated Radiotherapy in the Standard Management of Head and Neck Cancer: Promises and Pitfalls
Authors: William M. Mendenhall, Robert J. Amdur, Jatinder R. Palta
Journal: Journal of Clinical Oncology (2006)

The purpose of this article is to review the role of intensity-modulated radiotherapy (IMRT) in the standard management of patients with head and neck cancer through a critical review of the pertinent literature. IMRT may result in a dose distribution that is more conformal than that achieved with three-dimensional conformal radiotherapy (3D CRT), allowing dose reduction to normal structures and thus decreasing toxicity and possibly enhancing locoregional control through dose escalation. Disadvantages associated with IMRT include increased risk of a marginal miss, decreased dose homogeneity, increased total body dose, and increased labor and expense. Outcomes data after IMRT are limited, and follow-up is relatively short. Locoregional control rates appear to be comparable to those achieved with 3D CRT and, depending on the location and extent of the tumor, late toxicity may be lower. Despite limited data on clinical outcomes, IMRT has been widely adopted as a standard technique in routine practice and clinical trials. The use of IMRT involves a learning curve for the practitioner and will continue to evolve, requiring continuing education and monitoring of outcomes from routine practice. Additional standards pertaining to a variety of issues, including target definitions and dose specification, need to be developed. Phase III trials will better define the role of IMRT in coming years.
Medicinal Cannabis in Oncology Practice: Still a Bridge Too Far?
Authors: Floris A. de Jong, Frederike K. Engels, Ron H.J. Mathijssen, Lia van Zuylen, Jaap Verweij, Remco P.H. Peters, Alex Sparreboom
Journal: Journal of Clinical Oncology (2005)

Floris A. de Jong, Frederike K. Engels, Ron H.J. Mathijssen, Lia van Zuylen, and Jaap Verweij, Department of Medical Oncology, Erasmus MC University Medical Center Rotterdam—Daniel den Hoed Cancer Center, Rotterdam Remco P.H. Peters, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands Alex Sparreboom, Erasmus MC University Medical Center Rotterdam—Daniel den Hoed Cancer Center, Rotterdam and Clinical Pharmacology Research Core, National Cancer Institute, Bethesda, MD
Conventional Cardiovascular Risk Factors and Metabolic Syndrome in Predicting Carotid Intima-Media Thickness Progression in Young Adults
Authors: Juha Koskinen, Mika Kähönen, Jorma S.A. Viikari, Leena Taittonen, Tomi Laitinen, Tapani Rönnemaa, Terho Lehtimäki, Nina Hutri-Kähönen, Matti Pietikäinen, Eero Jokinen, Hans Helenius, Noora Mattsson, Olli T. Raitakari, Markus Juonala
Journal: Circulation (2009)

Conventional risk factors and metabolic syndrome (MetS) are cross-sectionally associated with subclinical atherosclerosis in young adults. We evaluated the relations of conventional risk factors and MetS to the 6-year progression of carotid intima-media thickness (IMT) in a population of young adults.The study included 1809 subjects (aged 32+/-5 years) who had IMT measured in 2001 and 2007. Risk factor measurements included low-density lipoprotein cholesterol, body mass index, C-reactive protein, smoking, and family history of coronary disease in addition to MetS components. We used European Group for the Study of Insulin Resistance, revised National Cholesterol Education Program, and International Diabetes Federation definitions to diagnose MetS in 2001. Waist circumference (P<0.0001), low-density lipoprotein cholesterol (P=0.01), and insulin (P=0.003) were directly associated with IMT progression in a multivariable model adjusted for age, sex, and baseline IMT (model R(2)=24%). When the MetS/European Group for the Study of Insulin Resistance definition was included in the model, it was directly associated with IMT progression (P=0.03), but its inclusion did not improve the model's predictive value. IMT increased 79+/-7 mum (mean+/-SEM) in subjects with MetS according to the MetS/European Group for the Study of Insulin Resistance definition and 42+/-2 mum in subjects without MetS (P<0.0001). In addition, the number of MetS components was linearly associated with IMT progression (P<0.0001). Similar results were seen with MetS/revised National Cholesterol Education Program and MetS/International Diabetes Federation definitions.Obesity, high low-density lipoprotein cholesterol, and high insulin level predicted IMT progression in young adults. All MetS definitions identified young adults with accelerated IMT progression, but we found no evidence that MetS would predict IMT progression more than expected from the sum of its risk components.
675 STIMULATION OF HEPATOBILIARY DETOXIFICATION AND TRANSPORT SYSTEMS IN HUMAN LIVER BY COMBINED TREATMENT WITH RIFAMPICIN AND URSODEOXYCHOLIC ACID
Authors: H.-U. Marschall, M. Wagner, G. Zollner, P. Fickert, T. Lundåsen, U. Gustafsson, S. Sahlin, M. Trauner
Journal: Journal of Hepatology (2009)
Tardive Dyskinesia in Patients Treated with Major Neuroleptics: A Review of the Literature
Authors: GEORGE E. CRANE
Journal: American Journal of Psychiatry (1968)

Since 1959 a growing number of reports have described a new type of neurological disorder in mental patients. This disorder, known as tardive dyskinesia, has been observed in approximately 500 cases but, judging from the accurate observations made by three separate groups of investigators, the syndrome is likely to be more frequent than one may suspect. Although manifestations of tardive dyskinesia occur in a number of diseases of the central nervous system, there is considerable evidence that the largescale use of phenothiazines or similar drugs in recent years is responsible for the great number of patients in mental hospitals exhibiting myoclonia and choreo-athetoid symptoms.
Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene
Authors: Joshua W. Knowles, Weijia Xie, Zhongyang Zhang, Indumathi Chennemsetty, Themistocles L. Assimes, Jussi Paananen, Ola Hansson, James Pankow, Mark O. Goodarzi, Ivan Carcamo-Orive, Andrew P. Morris, Yii-Der I. Chen, Ville-Petteri Mäkinen, Andrea Ganna, Anubha Mahajan, Xiuqing Guo, Fahim Abbasi, Danielle M. Greenawalt, Pek Lum, Cliona Molony, Lars Lind, Cecilia Lindgren, Leslie J. Raffel, Philip S. Tsao, Eric E. Schadt, Jerome I. Rotter, Alan Sinaiko, Gerald Reaven, Xia Yang, Chao A. Hsiung, Leif Groop, Heather J. Cordell, Markku Laakso, Ke Hao, Erik Ingelsson, Timothy M. Frayling, Michael N. Weedon, Mark Walker, Thomas Quertermous
Journal: Journal of Clinical Investigation (2015)

Decreased insulin sensitivity, also referred to as insulin resistance (IR), is a fundamental abnormality in patients with type 2 diabetes and a risk factor for cardiovascular disease. While IR predisposition is heritable, the genetic basis remains largely unknown. The GENEticS of Insulin Sensitivity consortium conducted a genome-wide association study (GWAS) for direct measures of insulin sensitivity, such as euglycemic clamp or insulin suppression test, in 2,764 European individuals, with replication in an additional 2,860 individuals. The presence of a nonsynonymous variant of N-acetyltransferase 2 (NAT2) [rs1208 (803A>G, K268R)] was strongly associated with decreased insulin sensitivity that was independent of BMI. The rs1208 "A" allele was nominally associated with IR-related traits, including increased fasting glucose, hemoglobin A1C, total and LDL cholesterol, triglycerides, and coronary artery disease. NAT2 acetylates arylamine and hydrazine drugs and carcinogens, but predicted acetylator NAT2 phenotypes were not associated with insulin sensitivity. In a murine adipocyte cell line, silencing of NAT2 ortholog Nat1 decreased insulin-mediated glucose uptake, increased basal and isoproterenol-stimulated lipolysis, and decreased adipocyte differentiation, while Nat1 overexpression produced opposite effects. Nat1-deficient mice had elevations in fasting blood glucose, insulin, and triglycerides and decreased insulin sensitivity, as measured by glucose and insulin tolerance tests, with intermediate effects in Nat1 heterozygote mice. Our results support a role for NAT2 in insulin sensitivity.
Randomized Trial Comparing Two Fractionation Schedules for Patients With Localized Prostate Cancer
Authors: Himu Lukka, Charles Hayter, Jim A. Julian, Padraig Warde, W. James Morris, Mary Gospodarowicz, Mark Levine, Jinka Sathya, Richard Choo, Hugh Prichard, Michael Brundage, Winkle Kwan
Journal: Journal of Clinical Oncology (2005)

The optimal radiation dose fractionation schedule for localized prostate cancer is unclear. This study was designed to compare two dose fractionation schemes (a shorter 4-week radiation schedule v a longer 6.5-week schedule).Patients with early-stage (T1 or T2) prostate cancer were randomly assigned to 66 Gy in 33 fractions over 45 days (long arm) or 52.5 Gy in 20 fractions over 28 days (short arm). The study was designed as a noninferiority investigation with a predefined tolerance of -7.5%. The primary outcome was a composite of biochemical or clinical failure (BCF). Secondary outcomes included presence of tumor on prostate biopsy at 2 years, survival, and toxicity.From March 1995 to December 1998, 936 men were randomly assigned to treatment; 470 were assigned to the long arm, and 466 were assigned to the short arm. The median follow-up time was 5.7 years. At 5 years, the BCF probability was 52.95% in the long arm and 59.95% in the short arm (difference = -7.0%; 90% CI, -12.6% to -1.4%), favoring the long arm. No difference in 2-year postradiotherapy biopsy or in overall survival was detected between the arms. Acute toxicity was found to be slightly higher in the short arm (11.4%) compared with the long arm (7%; difference = -4.4%; 95% CI, -8.1% to -0.6%); however, late toxicity was similarly low in both arms (3.2%).Given the results, we cannot exclude the possibility that the chosen hypofractionated radiation regimen may be inferior to the standard regimen. Further evaluation involving higher dose hypofractionated radiation regimens in contemporary radiation settings is necessary.
The biological basis of non-invasive strategies for selection of human oocytes and embryos
Authors: L. Scott
Journal: Human Reproduction Update (2003)

There is a need for more accurate embryo selection in human assisted reproduction, if the goal of reducing the number of embryos used in embryo transfer is to be realized. Furthermore, any selection strategy should be non‐invasive if the embryos are to be used in embryo transfer. Currently, the strategy is selection by one to three parameters in the cleaving‐ and blastocyst‐stage embryo, sometimes with additional pronuclear selection. It is clear that no one system is ideal, as the vast majority of transferred embryos do not implant. As the health of the embryo is largely dictated by the originating gametes, the very early events in oocyte development should be considered. This review will point to the early biological events in the unfertilized and fertilized oocyte that can be scored non‐invasively and which can have a profound effect on the later developmental stages. Using a sequential scoring system, with emphasis on the oocyte, a system for selecting the most viable single embryo for transfer may hopefully be achieved.
Nasal Continuous Positive Airway Pressure Reduces Sleep-induced Blood Pressure Increments In Preeclampsia
Authors: N. EDWARDS, D. M. BLYTON, T. KIRJAVAINEN, G. J. KESBY, C. E. SULLIVAN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Preeclampsia is the predominant cause of admissions to neonatal intensive care. The diurnal blood pressure pattern is flattened or reversed in preeclampsia. We hypothesized that snoring and partial upper airway obstruction contribute to nocturnal rises in blood pressure. We tested this hypothesis by controlling sleep- induced upper airway flow limitation and snoring with nasal positive pressure. Eleven women with preeclampsia underwent two consecutive polygraphic sleep studies with simultaneous beat-to-beat blood pressure monitoring. Average blood pressure for the night overall and in each sleep stage was calculated. Sleep architecture was similar on the two study nights. Sleep-induced partial upper airway flow limitation occurred in all patients in the initial study. Autosetting nasal continuous positive airway pressure (CPAP) applied at a mean maximal pressure of 6 ± 1 cm H2O eliminated flow limitation throughout sleep on the treatment night. Blood pressure was markedly reduced on the treatment night [(128 ± 3)/(73 ± 3)] when compared with the initial nontreatment study night [(146 ± 6)/(92 ± 4)], p = (0.007)/(0.002). We conclude that partial upper airway obstruction during sleep in women with preeclampsia is associated with increments in blood pressure, which can be eliminated with the use of nasal CPAP.
Early responder myeloma: kinetic studies identify a patient subgroup characterized by very poor prognosis.
Authors: M Boccadoro, F Marmont, M Tribalto, G Fossati, V Redoglia, S Battaglio, M Massaia, A Gallamini, B Comotti, T Barbui
Journal: Journal of Clinical Oncology (1989)

In order to assess the prognostic value of rapid tumor mass reduction in responding multiple myeloma (MM) patients, 100 consecutive patients were analyzed, and bone marrow plasma cell kinetic characteristics were evaluated at diagnosis. Forty-two patients obtained a tumor mass reduction greater than or equal to 50% with three cycles of chemotherapy and within 3 months (early responder myeloma [ERM]), and 23 in greater than 3 months (slow responder myeloma [SRM]). Survival rates in these two groups were not statistically different (P = .07). The labeling index (LI) of bone marrow plasma cells was significantly higher in ERM patients than in SRM patients (1.8 +/- 2.0 v 0.8 +/- 0.7, P = .006). The LI was used to separate the ERM patients into two well-defined subgroups. ERM patients with a LI greater than or equal to 2% showed a median survival of 16.4 months, whereas ERM patients with a LI less than 2% did not reach the median survival at 46.9 months (P less than .0044). Remission duration was also significantly different: 12.2 months in the high LI subgroup and 26.3 months in the low LI subgroup (P less than .0025). Early response itself does not correspond to shorter remission duration and shorter survival, but it is a poor prognostic factor if associated with a high plasma cell proliferative activity.
Severe heterogeneous emphysema treated unilaterally with endobronchial coils in patients with bilaterally incomplete fissures. Aiming for long lasting endoscopic lung volume reduction (ELVR); is effectiveness sustained at one year follow-up?
Authors: Konstantina Kontogianni, Vasiliki Gerovasili, Daniela Gompelmann, Maren Schuhmann, Philine Kaukel, Claus Peter Heussel, Felix J.F. Herth, Ralf Eberhardt
Journal: European Respiratory Journal (2014)

ELVR with coils has so far been shown to be effective on short term observations.  In this retrospective analysis 17 patients with chronic obstructive pulmonary disease ([male]/[female]:10/7, age: 66±7 years), heterogeneous emphysema and incomplete fissures were included. 10 Coils were implanted unilaterally. Patients were followed up at 90 and 365 days after treatment and changes in pulmonary function tests (PFT), 6-Minute-Walk-Test (6MWT) and modified Medical Research Council (mMRC) dyspnea scale were recorded.   Results : PFT significantly improved at 90 days but improvement was not sustained at the 365 day follow up; Forced expiratory volume in the 1 st  second improved at 90 days (0.71±0.14L vs 0.84±0.22L, p:0.02) but at 365 days benefit was lost (0.71±0.14L vs 0.71±0.15L). Similar changes were noted for vital capacity at 90 days (2.2±0.54L vs 2.48±0.81L, p:0.05) and after 365 days (2.2±0.54L vs 2.2±0.71L) and also for residual volume and total lung capacity. 6MWT also improved at 90 days (199±114m vs 251±88m, p:0.003), dropping back at baseline levels after one year (208±108m vs 232±89m) as did mMRC at 90 days (3±1 vs 2±1, p:0.05) losing benefit after one year though(3±1 vs 2±1, p:0.95).   Conclusions : Our study shows that unilateral treatment with coils, initially helps improve PFT, exercise capacity and perception of dyspnea up to 90 days post intervention; these benefits are not sustained after one year though. Further large scale studies are needed to assess the long term effects of LVRC and possible benefits of a bilateral treatment.
IPF or NSIP? That is the question
Authors: C. Vogelmeier
Journal: European Respiratory Journal (2003)

Bronchoalveolar lavage (BAL) has been crucial in elucidating the immune effector cells involved in the inflammatory processes in idiopathic interstitial pneumonias 1. Despite its value as a research tool, the diagnostic usefulness of BAL in idiopathic interstitial pneumonias is limited. An increase in neutrophils and/or eosinophils and/or lymphocytes may be seen. The idiopathic interstitial pneumonia with the worst prognosis is idiopathic pulmonary fibrosis (IPF) showing a histological pattern of usual interstitial pneumonia (UIP) 2. In IPF, historical data suggests that certain changes in BAL cell differentials may have prognostic importance; in some studies, patients with increased percentages of neutrophils or eosinophils (or both) had a worse prognosis, whereas BAL lymphocytosis has been associated with a greater responsiveness to corticosteroid therapy 3–6.

The most detailed data in that context have been published by Watters et al. 4. In their cohort, pretreatment BAL lymphocytosis was associated with significant subsequent clinical improvement. They also reported on the histology of their patients, evaluating 11 separate histological features. They found that BAL lymphcytosis was associated with moderate-to-severe alveolar septal inflammation and with a relative lack of histological honeycombing. These data suggested that BAL fluid lymphocytosis identifies a subset of patients with IPF who are more “cellular” in biopsy and likely to improve in response to corticosteroid therapy.

Katzenstein and Myers 7 already emphasised the limitations of this study. Only 19 patients were available for follow-up at 1 yr. Of these, five of …
Association of DNA With Melanin Granules
Authors: Walter C. Schneider, Emma Shelton, Edward L. Kuff
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Association of DNA With Melanin Granules Get access Walter C. Schneider, Walter C. Schneider Search for other works by this author on: Oxford Academic PubMed Google Scholar Emma Shelton, Emma Shelton Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward L. Kuff Edward L. Kuff Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 55, Issue 3, September 1975, Pages 665–670, https://doi.org/10.1093/jnci/55.3.665 Published: 01 September 1975 Article history Received: 07 March 1975 Accepted: 16 May 1975 Published: 01 September 1975
Complexity of FGFR signalling in metastatic urothelial cancer
Authors: Alejo Rodriguez-Vida, Matilde Saggese, Simon Hughes, Sarah Rudman, Simon Chowdhury, Neil R. Smith, Peter Lawrence, Claire Rooney, Brian Dougherty, Donal Landers, Elaine Kilgour, Hendrik-Tobias Arkenau
Journal: Journal of Hematology & Oncology (2015)

Urothelial cancers (UC) are the fourth most common tumours worldwide after prostate (or breast), lung and colorectal cancer. Despite recent improvements in their management, UC remain an aggressive disease associated with a poor outcome. Following disease progression on first-line platinum-based chemotherapy, very few effective treatment options are available and none of them have shown significant improvement in overall survival. Alterations of the fibroblast growth factor receptor (FGFR) pathway including amplification, mutations and overexpression are common in UC. Pre-clinical data suggest that the presence of such dysregulations may confer sensitivity to FGFR inhibitors. We present here the case of a patient with a metastatic UC of the renal pelvis with lymph node metastases treated with the selective FGFR inhibitor AZD4547. To date, the patient has been on a study drug for 32 months with acceptable tolerance and maintained radiological partial response as per RECIST 1.1 criteria. Exploratory biomarker analysis showed FGFR3, FGFR1, FGF-ligand and fibroblast growth factor receptor substrate 2 (FRS2) expression in the patient's tumour, together with the presence of a germ-line mutation in the FGFR3 extracellular binding domain. This is not a known hotspot mutation, and the functional significance remains unclear. The FGFR inhibitor AZD4547 exhibits antitumour activity in a metastatic urothelial cancer displaying FGFR1, FGFR3, FGF-ligand and FRS2 expression. This lends support to the further exploration of FGFR inhibitors in urothelial cancer. Further studies are required to determinate the most effective way to select those patients most likely to respond.
The Speed of Ventricular Activation Measured in the Spatial Vectorcardiograms
Authors: ERNST SIMONSON, OTTO H. SCHMITT, HENRY W. BLACKBURN, RAPHAEL B. LEVINE
Journal: Circulation Research (1955)

The total QRS interval or R wave crest time in single leads is not accurate for measuring the total ventricular activation time, and is inadequate for an estimate of the ventricular activation rate, as related to the directional time rate of excitation of the total contributing muscle mass. For a more detailed and precise analysis of the ventricular activation, the angular speed in the central segment of the spatial QRS loop was determined in 103 normal men and 26 patients, and significant differences independent of the total QRS duration were obtained.
The EuroPrevall‐INCO surveys on the prevalence of food allergies in children from China, India and Russia: the study methodology
Authors: G. W. K. Wong, P. A. Mahesh, L. Ogorodova, T. F. Leung, O. Fedorova, A. D. Holla, M. Fernandez‐Rivas, E. N. Clare Mills, I. Kummeling, R. Van Ree, M. Yazdanbakhsh, P. Burney
Journal: Allergy (2009)

Very little is known regarding the global variations in the prevalence of food allergies. The EuroPrevall-INCO project has been developed to evaluate the prevalence of food allergies in China, India and Russia using the standardized methodology of the EuroPrevall protocol used for studies in the European Union. The epidemiological surveys of the project were designed to estimate variations in the prevalence of food allergy and exposure to known or suspected risk factors for food allergy and to compare the data with different European countries.Random samples of primary schoolchildren were recruited from urban and rural regions of China, Russia and India for screening to ascertain possible adverse reactions to foods. Cases and controls were then selected to answer a detailed questionnaire designed to evaluate the possible risk factors of food allergies. Objective evidence of sensitisation including skin-prick test and serum specific IgE measurement was also collected.More than 37 000 children from the three participating countries have been screened. The response rates for the screening phase ranged from 83% to 95%. More than 3000 cases and controls were studied in the second phase of the study. Further confirmation of food allergies by double blind food challenge was conducted.This will be the first comparative study of the epidemiology of food allergies in China, India, and Russia using the same standardized methodology. The findings of these surveys will complement the data obtained from Europe and provide insights into the development of food allergy.