tbuckley/cabot-search huggingface dataset:
Abstract 764: Multiple testing in a phase II trial design for the detection of tumor subtypes
Authors: John D. Roberts, Viswanathan Ramakrishnan
Journal: Cancer Research (2012)

Abstract Tumor subtypes may be especially responsive to a particular treatment. Phase II designs that incorporate tumor subtypes typically require prospective tumor subtyping and stratified patient enrollment. These features are cumbersome, discourage patient and investigator participation, and select for patients with relatively indolent disease who can wait for subtyping results. Previously we described a two stage phase II design that permits tumor subtyping at the end of stage 1 and that does not require stratified enrollment (Clin Cancer Res 2011;17:5538). In this design results from stage 1 are used to select an appropriate stage 2 objective. The stage 2 objective may be either to estimate the response rate of either the tumor or a subtype or a formal test of the hypothesis that the response rate for a subtype is greater than the overall response rate. Previously, although our design accommodated multiple subtypes in stage 1, it allowed further testing of only a single subtype in stage 2. Here we expand upon the previous design by describing a method to evaluate multiple tumor subtypes in stage 2 with appropriate adjustments for multiple testing. As there are practical limits on sample size, these adjustments tend to reduce power. We identify strategies to limit loss of power by taking advantage of tumor biology. For example, when tumor subtypes are mutually exclusive or nested, some comparisons can be made without further “alpha spending”. We explore the promise of our approach for the efficient identification of clinically significant tumor subtypes more responsive to a specific targeted therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 764. doi:1538-7445.AM2012-764
Early cellular rejection after orthotopic liver transplantation correlates with low concentrations of FK506 in hepatic tissue
Authors: William J. Sandborn, George M. Lawson, Timothy J. Cody, Michael K. Porayko, Eileen J. Hay, Gregory J. Gores, Jeffery L. Steers, Ruud A. F. Krom, Russell H. Wiesner
Journal: Hepatology (1995)

We have previously reported that low hepatic tissue cyclosporine levels correlate with early cellular rejection after liver transplantation. The aim of this study is to determine whether there is a similar relationship in patients treated with FK506. Twenty-five liver biopsies were performed in 10 patients immunosuppressed with FK506 without cellular rejection: day 7 = 10; day 14 = 3; day 21 = 9; day 28 = 1; day 35 = 1; and day 42 = 1. These 10 patients without cellular rejection were compared with 7 patients immunosuppressed with FK506 with cellular rejection who underwent a total of 23 liver biopsies, including 9 biopsies that showed rejection: day 7 = 4; day 14 = 2; day 21 = 1; day 28 = 1; and day 49 = 1. There was no significant difference between the nonrejection and current rejection groups in the median plasma concentration of FK506, 0.9 ng/mL versus 0.9 ng/mL (P = .50). In contrast, the median hepatic tissue concentration of FK506 was significantly higher in the nonrejection group than it was in the current rejection group, 144 ng/g versus 48 ng/g (P = .02). In the current rejection group, 7 of 9 hepatic tissue concentrations of FK506 were < 100 ng/g, and in the nonrejection group, 18 of 25 hepatic tissue concentrations were > 100 ng/g. Low hepatic tissue concentrations of FK506 correlate with the occurrence of early cellular rejection after liver transplantation, in contrast to plasma concentrations of FK506. A hepatic tissue concentration of FK506 < 100 ng/g is 78% sensitive and 72% specific for cellular rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
Therapeutic Deep Brain Stimulation in Parkinsonian Rats Directly Influences Motor Cortex
Authors: Qian Li, Ya Ke, Danny C.W. Chan, Zhong-Ming Qian, Ken K.L. Yung, Ho Ko, Gordon W. Arbuthnott, Wing-Ho Yung
Journal: Neuron (2012)

Much recent discussion about the origin of Parkinsonian symptoms has centered around the idea that they arise with the increase of beta frequency waves in the EEG. This activity may be closely related to an oscillation between subthalamic nucleus (STN) and globus pallidus. Since STN is the target of deep brain stimulation, it had been assumed that its action is on the nucleus itself. By means of simultaneous recordings of the firing activities from populations of neurons and the local field potentials in the motor cortex of freely moving Parkinsonian rats, this study casts doubt on this assumption. Instead, we found evidence that the corrective action is upon the cortex, where stochastic antidromic spikes originating from the STN directly modify the firing probability of the corticofugal projection neurons, destroy the dominance of beta rhythm, and thus restore motor control to the subjects, be they patients or rodents.
Randomized Comparison of Sevoflurane Versus Propofol to Reduce Perioperative Myocardial Ischemia in Patients Undergoing Noncardiac Surgery
Authors: Giovanna A.L. Lurati Buse, Philippe Schumacher, Esther Seeberger, Wolfgang Studer, Regina M. Schuman, Jens Fassl, Jorge Kasper, Miodrag Filipovic, Daniel Bolliger, Manfred D. Seeberger
Journal: Circulation (2012)

Background— Volatile anesthetics provide myocardial preconditioning in coronary surgery patients. We hypothesized that sevoflurane compared with propofol reduces the incidence of myocardial ischemia in patients undergoing major noncardiac surgery. Methods and Results— We enrolled 385 patients at cardiovascular risk in 3 centers. Patients were randomized to maintenance of anesthesia with sevoflurane or propofol. We recorded continuous ECG for 48 hours perioperatively, measured troponin T and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) on postoperative days 1 and 2, and evaluated postoperative delirium by the Confusion Assessment Method. At 6 and 12 months, we contacted patients by telephone to assess major adverse cardiac events. The primary end point was a composite of myocardial ischemia detected by continuous ECG and/or troponin elevation. Additional end points were postoperative NT-proBNP concentrations, major adverse cardiac events, and delirium. Patients and outcome assessors were blinded. We tested dichotomous end points by χ 2 test and NT-proBNP by Mann–Whitney test on an intention-to-treat basis. Myocardial ischemia occurred in 75 patients (40.8%) in the sevoflurane and 81 (40.3%) in the propofol group (relative risk, 1.01; 95% confidence interval, 0.78–1.30). NT-proBNP release did not differ across allocation on postoperative day 1 or 2. Within 12 months, 14 patients (7.6%) suffered a major adverse cardiac event after sevoflurane and 17 (8.5%) after propofol (relative risk, 0.90; 95% confidence interval, 0.44–1.83). The incidence of delirium did not differ (11.4% versus 14.4%; P =0.379). Conclusions— Compared with propofol, sevoflurane did not reduce the incidence of myocardial ischemia in high-risk patients undergoing major noncardiac surgery. The sevoflurane and propofol groups did not differ in postoperative NT-proBNP release, major adverse cardiac events at 1 year, or delirium. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00286585.
My pelvis and I
Authors: James Owen Drife
Journal: BMJ (2005)

Medical student assessments (or “exams” as we used to call them) are like military exercises nowadays. “Examiners must rendezvous at 0800 hours sharp in the Sports Hall.” This was the only academic building large enough to house objective structured clinical examinations for all 194 candidates in a single morning in July.

The problem for me, unfamiliar with sports halls, was finding the door. The command team had foreseen this and a snatch squad rescued me from …
Clinical Value of Lung Scintigraphy with Tc-99m Gluconate in Distinguishing Benign from Malignant Lung Diseases
Authors: CANMAO XIE, YIXUAN LI, CILING ZHANG, SHIQUAN ZENG
Journal: Clinical Nuclear Medicine (1992)

One hundred patients were studied with three-phase lung scintigraphy with Tc-99m gluconate. The results showed that there were statistically significant differences between benign and malignant lung lesions in the intensity of accumulation, the blood supply index ratio, and the radioactive uptake ratio. However, no difference was observed between the benign lung lesions and the healthy lungs. Analysis of false negatives and false positives revealed that false negatives had something to do with the cell types of the malignancies, in addition to the relatively small size of the lesions; the false positives were mostly caused by acute inflammation, for which obstructive pneumonitis might be responsible in part. It is concluded that Tc-99m gluconate is tumor-avid and can be used as an agent for positive imaging of lung cancer, because quantitative parameters, blood supply index ratio, and radioactive uptake ratio are more objective in distinguishing malignant lung lesions from benign ones, and are of relatively higher sensitivity and specificity. Thus, lung scintigraphy with Tc-99m gluconate provides an efficient supplementary measure for differentiating between malignant and benign lung lesions.
Wavebreak Formation During Ventricular Fibrillation in the Isolated, Regionally Ischemic Pig Heart
Authors: Alexey V. Zaitsev, Prabal K. Guha, Farzad Sarmast, Arun Kolli, Omer Berenfeld, Arkady M. Pertsov, Joris R. de Groot, Ruben Coronel, José Jalife
Journal: Circulation Research (2003)

Both fixed and dynamic heterogeneities were implicated in the mechanism of wavebreak (WB) generation during ventricular fibrillation (VF). However, their relative roles remain unclear. We hypothesized that during ischemic VF, the WBs are produced primarily because of a fixed heterogeneity; namely, the gradient of refractoriness across the ischemic border zone (BZ). Ischemia was induced in 15 isolated blood-perfused hearts by occluding the left anterior descending coronary artery. Simultaneous video imaging (approximately 32x32 mm2) of Di-4-ANEPPS fluorescence in the ischemic zone (IZ), the BZ, and the nonischemic zone (NIZ) was performed. Dominant-frequency maps were constructed to assess gradients of refractoriness during VF. We used singularity points analysis to quantify the incidence of WBs per square centimeter per second. During preischemic VF, the distribution of WBs was relatively uniform. Ischemia caused an increase of WBs in the BZ (from 6.2+/-2.8 to 10.8+/-4.0) and a decrease of WBs in the IZ (from 5.8+/-2.8 to 2.8+/-1.4), without a significant change in NIZ (from 6.4+/-2.3 to 4.1+/-1.7). This finding is fully consistent with the dominant-frequency distribution during ischemic VF: the average dominant frequency was significantly slower in IZ than in NIZ (7.8+/-0.7 versus 10.1+/-1.0 Hz), suggesting a large gradient in refractory periods across the BZ. We concluded that acute regional ischemia plays a dual role in the maintenance of VF, decreasing the incidence of WB in the IZ while increasing it in the BZ. This suggests a predominant role of fixed heterogeneities in the formation of WB during VF in acute regional ischemia.
Interleukin 6 receptor antibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice.
Authors: T Tsujinaka, J Fujita, C Ebisui, M Yano, E Kominami, K Suzuki, K Tanaka, A Katsume, Y Ohsugi, H Shiozaki, M Monden
Journal: Journal of Clinical Investigation (1996)

The muscles of IL-6 transgenic mice suffer from atrophy. Experiments were carried out on these transgenic mice to elucidate activation of proteolytic systems in the gastrocnemius muscles and blockage of this activation by treatment with the anti-mouse IL-6 receptor (mIL-6R) antibody. Muscle atrophy observed in 16-wk-old transgenic mice was completely blocked by treatment with the mIL-6R antibody. In association with muscle atrophy, enzymatic activities and mRNA levels of cathepsins (B and L) and mRNA levels of ubiquitins (poly- and mono-ubiquitins) increased, whereas the mRNA level of muscle-specific calpain (calpain 3) decreased. All these changes were completely eliminated by treatment with the mIL-6R antibody. This IL-6 receptor antibody could, therefore, be effective against muscle wasting in sepsis and cancer cachexia, where IL-6 plays an important role.
DRY CUPPING IN LABOUR
Authors: A. J. Manson
Journal: BMJ (1854)

L OKKUNICATIONS.big.Tha the aow cel is not quite le ing el my be admitted; but so are some r e cells unlikeanything normally found in the adult body.-As an accdental aecompaniment of cancerous deposit, I am lastly bound to mention inflammation or hypermmia.As in varous processes plastic effusion may be or not ac- companied by this condition, so may or may not cancer.'The following case may be an illustration.CASE.M. B.,aged 40; soft cancer of skin of chest superven- ingon mole;
Derivation of hazard ratios
Authors: P. Sedgwick
Journal: BMJ (2011)

Researchers investigated the extent to which referral from primary care for defined symptoms of hip pain varied by age, sex, and social deprivation in the United Kingdom. A cohort study design was used. Data for individual patients registered at 326 general practices between 2001 and 2007 were extracted from the health improvement network database in primary care. In total, 23 121 patients presented with defined symptoms of hip pain, of whom 4019 (17.4%) were referred to specialist secondary care.1

The primary outcome was length of time from date of first presentation in primary care until referral to specialist secondary care. The table⇓ shows the unadjusted and adjusted hazard ratios for sex, categorised age, social deprivation, and comorbidity as indicated by number of drugs prescribed. It was reported that women, patients aged older than 85 years, and patients with greater social deprivation …
Renal SPECT With Tc-99m DMSA in Children With Upper Urinary Tract Infections Using a Triple-Headed Gamma Camera
Authors: BRUNO BAGNI, PIERGIUSEPPE ORSOLON, ANDREA FATTORI, UGO PAOLO GUERRA
Journal: Clinical Nuclear Medicine (1997)

Renal cortical scintigraphy with Tc-99m DMSA provides an excellent imaging modality for the assessment of cortical damage secondary to upper urinary tract infection(UTI). Methods The authors evaluated 48 children with UTI, 12 of whom had a history of vescico-ureteral reflux (from first to fourth degree), by planar scintigraphy and SPECT using a triple-headed gamma camera equipped with parallel-hole, high-resolution collimators. Results SPECT images yielded positive findings in 36 kidneys, whereas planar scans yielded positive findings in 18 kidneys. The total number of lesions detected by SPECT was 51, whereas the number found with the planar technique was 23. Conclusion This study demonstrates the superiority of SPECT scanning in detecting kidney lesions in children with UTI.
Regurgitant flow in cardiac valve prostheses: Diagnostic value of gradient echo nuclear magnetic resonance imaging in reference to transesophageal two-dimensional color Doppler echocardiography
Authors: Hans J. Deutsch, Rainald Bachmann, Udo Sechtem, Julius M. Curtius, Markus Jungehülsing, Harald Schicha, Hans H. Hilger
Journal: Journal of the American College of Cardiology (1992)
Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease.
Authors: B Volc-Platzer, O Majdic, W Knapp, K Wolff, W Hinterberger, K Lechner, G Stingl
Journal: The Journal of Experimental Medicine (1984)

As opposed to normal human skin where HLA-DR expression is restricted to the Langerhans cell (LC) population, HLA-DR, but not HLA-DS antigens can be readily detected on keratinocytes (KC) in certain disease states, i.e., cutaneous T cell lymphoma (CTCL), graft-vs-host disease (GVHD), and lichen planus (LP). To clarify the cellular origin of KC-bound HLA-DR antigens, we used a monoclonal antibody directed against determinants solely expressed on the cytoplasmic HLA-DR gamma chain (VIC-Y1) and observed that, by immunofluorescence, KC displaying HLA-DR alpha/beta complexes on their surface uniformly displayed cytoplasmic VIC-Y1 reactivity. In view of the crucial role of the gamma chain for HLA-DR biosynthesis, we conclude that HLA-DR antigens on KC are actively synthesized by these cells.
The Abuse of Erythropoietin to Enhance Athletic Performance
Authors: William C. Scott
Journal: JAMA (1990)

To the Editor.—  Epoetin is a recombinant DNA-derived preparation of the human hematopoietic hormone erythropoietin, which stimulates production of red  cells from bone marrow progenitors. 1 Epoetin is indicated for treating the anemia of chronic renal failure. It is also under investigation as therapy for other anemias. The Council on Scientific Affairs has been asked to respond to recent accounts that describe the misuse of epoetin by endurance athletes who seek to increase the oxygen-carrying capacity of the  and thus to enhance performance ( Business Week . December 1989:123). 2,3 The American Medical Association opposes the use of drugs to enhance athletic performance or to sustain athletic achievement, 4 which clearly includes the abuse of epoetin as an alternative to erythrocyte reinfusion, or blood doping.  In patients given epoetin for anemia, hematocrit and  pressure must be monitored frequently to adjust dosage and frequency and thus avoid toxic reactions. Hematocrits above
Atrophia maculosa varioliformis cutis
Authors: V.J. MARKS, O.F. MILLER
Journal: British Journal of Dermatology (1986)

Journal Article Atrophia maculosa varioliformis cutis Get access V.J. MARKS, V.J. MARKS Geisinger Clinic, Danville, Pennsylvania 17822, U.S.A. Dr V.J.Marks. Search for other works by this author on: Oxford Academic Google Scholar O.F. MILLER O.F. MILLER Geisinger Clinic, Danville, Pennsylvania 17822, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue 1, 1 July 1986, Pages 105–109, https://doi.org/10.1111/j.1365-2133.1986.tb06227.x Published: 01 July 1986 Article history Accepted: 17 December 1985 Published: 01 July 1986
Characterisation of CD8+ T cell subsets in the synovial fluid and peripheral blood of rheumatoid arthritis patients
Authors: H. Carvalheiro, D. Antunes, C. Duarte, S. Silva-Cardoso, T. Rodrigues-Sousa, J. da Silva, M. Souto-Carneiro
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Detailed information on CD8<sup>+</sup> T cells in rheumatoid arthritis (RA) is still reduced. However, studies on animal models of arthritis from the authors9 team and others suggest a major potential role of CD8<sup>+</sup> T cells in the pathogenesis of chronic polyarthritis. In the present study the authors characterised the phenotype and cytokine-production profile of CD8<sup>+</sup> T cells from peripheral blood (PB) and synovial fluid (SF) of RA patients. <h3>Materials and methods</h3> Unstimulated CD8<sup>+</sup> T cells from the PB and SF of 40 patients with established RA were analysed by flow-cytometry for cell surface markers expression and intracellular cytokine production, and compared to the ones present in the PB of 15 healthy donors. <h3>Results</h3> 40% of the total T cells infiltrating the SF were CD8<sup>+</sup>. The SF was characterised by a significant (p&lt;0.05) accumulation of mature CD45Ro+CD8+ T cells when compared to the RA and control PB. The majority of these CD8<sup>+</sup> T cells infiltrating the SF presented an effector phenotype (CD62L<sup>−</sup>CD27<sup>−</sup> short-term effector, or CD62L<sup>−</sup>CD27<sup>+</sup> central effector), and the presence of the activation markers CD69 and CD25 were significantly (p&lt;0.05) higher in the SF than in the PB of RA patients or controls. The expression of the pro-inflammatory homing chemokine receptors CCR7 and CXCR4 were significantly (p&lt;0.05) increased in the short-term effector CD62L<sup>−</sup>CD27<sup>−</sup>CD8<sup>+</sup> T cells and in the SF central memory CD62L<sup>+</sup>CD27<sup>+</sup>CD8<sup>+</sup> T cells when compared to RA PB. The intracellular expression of the pro-inflammatory cytokines IFN-γ, interleukin-6, interleukin-17 and tumour necrosis factor-α in central memory CD62L<sup>+</sup>CD8<sup>+</sup> T cells were significantly (p&lt;0.05) higher in the SF when compared to RA PB, and absent in controls. <h3>Conclusions</h3> The present study presents strong evidence for a marked role of CD8<sup>+</sup> T cells in RA pathogenesis. The authors propose that activated effector CD8<sup>+</sup> T cells, home into the SF, where they might contribute to articular destruction and maintenance of a chronic pro-inflammatory environment through the production of cytokines and cytotoxic agents.
Genetic Analysis of a Quantitative Trait in a Mouse Model of Polycystic Kidney Disease
Authors: OLGA A. IAKOUBOVA, HOLLY DUSHKIN, DAVID R. BEIER
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

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