tbuckley/cabot-search huggingface dataset:
Intestinal Obstruction in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Arin L. Madenci, Stacey Fisher, Lisa R. Diller, Robert E. Goldsby, Wendy M. Leisenring, Kevin C. Oeffinger, Leslie L. Robison, Charles A. Sklar, Marilyn Stovall, Rita E. Weathers, Gregory T. Armstrong, Yutaka Yasui, Christopher B. Weldon
Journal: Journal of Clinical Oncology (2015)

For adult survivors of childhood cancer, knowledge about the long-term risk of intestinal obstruction from surgery, chemotherapy, and radiotherapy is limited.Intestinal obstruction requiring surgery (IOS) occurring 5 or more years after cancer diagnosis was evaluated in 12,316 5-year survivors in the Childhood Cancer Survivor Study (2,002 with and 10,314 without abdominopelvic tumors) and 4,023 sibling participants. Cumulative incidence of IOS was calculated with second malignant neoplasm, late recurrence, and death as competing risks. Using piecewise exponential models, we assessed the associations of clinical and demographic factors with rate of IOS.Late IOS was reported by 165 survivors (median age at IOS, 19 years; range, 5 to 50 years; median time from diagnosis to IOS, 13 years) and 14 siblings. The cumulative incidence of late IOS at 35 years was 5.8% (95% CI, 4.4% to 7.3%) among survivors with abdominopelvic tumors, 1.0% (95% CI, 0.7% to 1.4%) among those without abdominopelvic tumors, and 0.3% (95% CI, 0.1% to 0.5%) among siblings. Among survivors, abdominopelvic tumor (adjusted rate ratio [ARR], 3.6; 95% CI, 1.9 to 6.8; P < .001) and abdominal/pelvic radiotherapy within 5 years of cancer diagnosis (ARR, 2.4; 95% CI, 1.6 to 3.7; P < .001) increased the rate of late IOS, adjusting for diagnosis year; sex; race/ethnicity; age at diagnosis; age during follow-up (as natural cubic spline); cancer type; and chemotherapy, radiotherapy, and surgery within 5 years of cancer diagnosis. Developing late IOS increased subsequent mortality among survivors (ARR, 1.8; 95% CI, 1.1 to 2.9; P = .016), adjusting for the same factors.The long-term risk of IOS and its association with subsequent mortality underscore the need to promote awareness of this complication among patients and providers.
Cardiovascular Magnetic Resonance in Cardiac Amyloidosis
Authors: Alicia Maria Maceira, Jayshree Joshi, Sanjay Kumar Prasad, James Charles Moon, Enrica Perugini, Idris Harding, Mary Noelle Sheppard, Philip Alexander Poole-Wilson, Philip Nigel Hawkins, Dudley John Pennell
Journal: Circulation (2005)

Background— Cardiac amyloidosis can be diagnostically challenging. Cardiovascular magnetic resonance (CMR) can assess abnormal myocardial interstitium. Methods and Results— Late gadolinium enhancement CMR was performed in 30 patients with cardiac amyloidosis. In 22 of these, myocardial gadolinium kinetics with T 1 mapping was compared with that in 16 hypertensive controls. One patient had CMR and autopsy only. Subendocardial T 1 in amyloid patients was shorter than in controls (at 4 minutes: 427±73 versus 579±75 ms; P &lt;0.01), was shorter than subepicardium T 1 for the first 8 minutes ( P ≤0.01), and was correlated with markers of increased myocardial amyloid load, as follows: left ventricular (LV) mass ( r =−0.51, P =0.013); wall thickness ( r =−0.54 to −0.63, P &lt;0.04); interatrial septal thickness ( r =−0.52, P =0.001); and diastolic function ( r =−0.42, P =0.025). Global subendocardial late gadolinium enhancement was found in 20 amyloid patients (69%); these patients had greater LV mass (126±30 versus 93±25 g/m 2 ; P =0.009) than unenhanced patients. Histological quantification showed substantial interstitial expansion with amyloid (30.5%) but only minor fibrosis (1.3%). Amyloid was dominantly subendocardial (42%) compared with midwall (29%) and subepicardium (18%). There was 97% concordance in diagnosis of cardiac amyloid by combining the presence of late gadolinium enhancement and an optimized T 1 threshold (191 ms at 4 minutes) between myocardium and blood. Conclusions— In cardiac amyloidosis, CMR shows a characteristic pattern of global subendocardial late enhancement coupled with abnormal myocardial and blood-pool gadolinium kinetics. The findings agree with the transmural histological distribution of amyloid protein and the cardiac amyloid load and may prove to have value in diagnosis and treatment follow-up.
Palladin Mutation Causes Familial Pancreatic Cancer and Suggests a New Cancer Mechanism
Authors: Kay L Pogue-Geile, Ru Chen, Mary P Bronner, Tatjana Crnogorac-Jurcevic, Kara White Moyes, Sally Dowen, Carol A Otey, David A Crispin, Ryan D George, David C Whitcomb, Teresa A Brentnall
Journal: PLoS Medicine (2006)

Background Pancreatic cancer is a deadly disease. Discovery of the mutated genes that cause the inherited form(s) of the disease may shed light on the mechanism(s) of oncogenesis. Previously we isolated a susceptibility locus for familial pancreatic cancer to chromosome location 4q32–34. In this study, our goal was to discover the identity of the familial pancreatic cancer gene on 4q32 and determine the function of that gene. Methods and Findings A customized microarray of the candidate chromosomal region affecting pancreatic cancer susceptibility revealed the greatest expression change in palladin (PALLD), a gene that encodes a component of the cytoskeleton that controls cell shape and motility. A mutation causing a proline (hydrophobic) to serine (hydrophilic) amino acid change (P239S) in a highly conserved region tracked with all affected family members and was absent in the non-affected members. The mutational change is not a known single nucleotide polymorphism. Palladin RNA, measured by quantitative RT-PCR, was overexpressed in the tissues from precancerous dysplasia and pancreatic adenocarcinoma in both familial and sporadic disease. Transfection of wild-type and P239S mutant palladin gene constructs into HeLa cells revealed a clear phenotypic effect: cells expressing P239S palladin exhibited cytoskeletal changes, abnormal actin bundle assembly, and an increased ability to migrate. Conclusions These observations suggest that the presence of an abnormal palladin gene in familial pancreatic cancer and the overexpression of palladin protein in sporadic pancreatic cancer cause cytoskeletal changes in pancreatic cancer and may be responsible for or contribute to the tumor's strong invasive and migratory abilities.
Imatinib-Induced Regression of AIDS-Related Kaposi's Sarcoma
Authors: Henry B. Koon, Glenn J. Bubley, Liron Pantanowitz, David Masiello, Brad Smith, Katherine Crosby, JoAnn Proper, Will Weeden, Thomas E. Miller, Pamela Chatis, Merrill J. Egorin, Steven R. Tahan, Bruce J. Dezube
Journal: Journal of Clinical Oncology (2004)

Purpose Activation of the platelet-derived growth factor (PDGF) and c-kit receptors has been proposed as important in mediating the growth of AIDS-related Kaposi's sarcoma (KS). We investigated the response of KS to the PDGF receptor (PDGFR)/c-kit inhibitor, imatinib mesylate, and investigated the effect of this therapy on critical signal transduction intermediates. Patients and Methods Ten male patients with AIDS-related cutaneous KS, which progressed despite chemotherapy and/or highly active antiretroviral therapy, received imatinib mesylate administered orally, 300 mg twice daily. Clinical response was determined by serial tumor measurements. To determine biologic and histologic response, skin lesion biopsies were obtained at baseline and following 4 weeks of therapy. Results Five of 10 participants had a partial response by tumor measurements. Biopsies after 4 weeks of therapy demonstrated histologic regression in four of six patients. Four patients' tumor biopsies were assessable for immunohistochemistry end points pre- and post-therapy. These demonstrated inhibition of PDGFR and its downstream effector, extracellular receptor kinase, which is a member of the mitogen-activated protein kinase family. The most common adverse event was diarrhea, which led to dose reduction in six patients. Conclusion Imatinib mesylate administered orally twice daily for AIDS-related KS results in clinical and histologic regression of cutaneous KS lesions within 4 weeks. These promising results demonstrate that inhibition of the c-kit and/or PDGF receptors may represent an effective strategy for treating KS.
Pathophysiology of Epidemic St. Louis Encephalitis: I. Inappropriate Secretion of Antidiuretic Hormone: II. Pituitary-Adrenal Function: III. Cerebral Blood Flow and Metabolism
Authors: M. G. White, N. W. Carter, F. C. Rector, Donald W Seldin, S. J. Drewry, J. P. Sanford, James P Luby, Roger H Unger, Norman M Kaplan, W. Shapiro, S. Eisenberg
Journal: Annals of Internal Medicine (1969)

Studies of pathophysiology in epidemic St. Louis encephalitis were undertaken during the 1966 Dallas epidemic. Eighteen of 52 patients were hyponatremic during their acute illness. Of this group, 13 patients appeared to have hyponatremia due to inappropriate secretion of antidiuretic hormone; the remaining patients were probably hyponatremic from salt depletion. Water loading in some of these patients showed that the defect (persistent elaboration of antidiuretic hormone) was only partial, allowing excretion of the water load with urine not maximally dilute. Severely ill patients tended to have 8 AM plasma 17-hydroxycorticoid (17-HOCS) values that were elevated or at the upper limit of normal. Normal diurnal variation in plasma 17-HOCS levels was absent. Plasma 17-HOCS rose after adrenocorticotrophic hormone (ACTH) administration but did not respond to dexamethasone suppression. An insulin-induced fall in blood sugar caused a rise in both plasma 17-HOCS and growth hormone. Patients had an increase in either urinary or plasma 11-deoxycorticoids (11-DOCS) after the administration of metyrapone. These findings probably represent the response to severe stress. The hypothalamic-pituitary-adrenal axis appeared to be functionally intact in these patients. Cerebral blood flow and metabolism were measured in five patients, one of whom was comatose when studied. In two of the conscious patients cerebral blood flow was normal despite normal arterial oxygen tension and systemic hypocapnia; inflammatory cerebral vasodilatation may have accounted for the findings. Inflammatory changes affecting the respiratory centers and an associated metabolic acidosis may have accounted, in part, for lowered carbon dioxide tensions found in at least two of the patients. In the comatose patient, although the cerebral blood flow was normal, the cerebral metabolic rate for oxygen was markedly depressed; this patient's findings represent what has been termed the "luxury-perfusion syndrome." Cerebral blood flow abnormalities per se were not responsible for the altered sensorium in these patients.
Paclitaxel-Eluting Stents versus Bare-Metal Stents in Acute Myocardial Infarction
Authors: Gregg W. Stone, Alexandra J. Lansky, Stuart J. Pocock, Bernard J. Gersh, George Dangas, S. Chiu Wong, Bernhard Witzenbichler, Giulio Guagliumi, Jan Z. Peruga, Bruce R. Brodie, Dariusz Dudek, Martin Möckel, Andrzej Ochala, Alison Kellock, Helen Parise, Roxana Mehran
Journal: New England Journal of Medicine (2009)

There is no consensus regarding the safety and efficacy of drug-eluting stents, as compared with bare-metal stents, in patients with ST-segment elevation myocardial infarction who are undergoing primary percutaneous coronary intervention (PCI).We randomly assigned, in a 3:1 ratio, 3006 patients presenting with ST-segment elevation myocardial infarction to receive paclitaxel-eluting stents (2257 patients) or otherwise identical bare-metal stents (749 patients). The two primary end points of the study were the 12-month rates of target-lesion revascularization for ischemia (analysis powered for superiority) and a composite safety outcome measure of death, reinfarction, stroke, or stent thrombosis (powered for noninferiority with a 3.0% margin). The major secondary end point was angiographic evidence of restenosis at 13 months.Patients who received paclitaxel-eluting stents, as compared with those who received bare-metal stents, had significantly lower 12-month rates of ischemia-driven target-lesion revascularization (4.5% vs. 7.5%; hazard ratio, 0.59; 95% confidence interval [CI], 0.43 to 0.83; P=0.002) and target-vessel revascularization (5.8% vs. 8.7%; hazard ratio, 0.65; 95% CI, 0.48 to 0.89; P=0.006), with noninferior rates of the composite safety end point (8.1% vs. 8.0%; hazard ratio, 1.02; 95% CI, 0.76 to 1.36; absolute difference, 0.1 percentage point; 95% CI, -2.1 to 2.4; P=0.01 for noninferiority; P=0.92 for superiority). Patients treated with paclitaxel-eluting stents and those treated with bare-metal stents had similar 12-month rates of death (3.5% and 3.5%, respectively; P=0.98) and stent thrombosis (3.2% and 3.4%, respectively; P=0.77). The 13-month rate of binary restenosis was significantly lower with paclitaxel-eluting stents than with bare-metal stents (10.0% vs. 22.9%; hazard ratio, 0.44; 95% CI, 0.33 to 0.57; P<0.001).In patients with ST-segment elevation myocardial infarction who were undergoing primary PCI, implantation of paclitaxel-eluting stents, as compared with bare-metal stents, significantly reduced angiographic evidence of restenosis and recurrent ischemia necessitating repeat revascularization procedures. No safety concerns were apparent at 1 year. (ClinicalTrials.gov number, NCT00433966.)
Surface staining and cytotoxic activity of heat-shock protein 60 antibody in stressed aortic endothelial cells.
Authors: Q Xu, G Schett, C S Seitz, Y Hu, R S Gupta, G Wick
Journal: Circulation Research (1994)

Heat-shock protein (hsp) expression can be induced by high temperature, exposure to cytokines or oxygen radicals, ischemia, hemodynamic overload, or viral infections. To determine whether surface expression of hsp60 occurs in aortic endothelial cells stressed by high temperature or cytokines, cells from rat aortas were cultivated and stained with several types of monoclonal antibodies against hsp60. Other antibodies, eg, those against intercellular adhesion molecule-1 (ICAM-1), or immune response-associated antigens were also used as controls. Positive staining of endothelial cells on the surface and in the cytoplasm was observed after pretreatment of the cells with cytokine-containing medium, tumor necrosis factor-alpha (TNF-alpha), or interleukin-1 alpha and labeling with a specific monoclonal antibody against hsp60 (II-13). Fluorescence-activated cell sorter analyses showed that over 80% of living endothelial cells stressed by cytokine-containing medium, by TNF-alpha, or at 42 degrees C, but not by interleukin-1 alpha, were positively surface stained with this antibody. Increased intensity of immunostaining with antibodies to ICAM-1 and immune response-associated antigen was also seen on the cytokine-stressed endothelial cells. Furthermore, when TNF-alpha stimulated endothelial cells labeled with 51Cr were incubated with antibody II-13 in the presence of complement, significant lysis occurred. In summary, endothelial cells stressed by high temperature or certain cytokines, eg, TNF-alpha, express hsp60 in the cytoplasm and on their surfaces, and these cells were susceptible to complement-dependent lysis by hsp60-specific antibody. These observations may be significant for elucidating the mechanisms of the involvement of immune reactions to hsp65/60 in initiating atherosclerosis.
The Time Is Ripe for a Randomized Trial of Metformin in Clinically Localized Prostate Cancer
Authors: Kathryn L. Penney, Meir J. Stampfer
Journal: Journal of Clinical Oncology (2013)

In a population study making excellent use of Ontario’s universal health plan electronic data, Margel et al 1 showed increasing duration of metformin use among diabetic men after a diagnosis of prostate cancer was associated with decreased prostate cancer–specific and all-cause mortality. Prostate cancer–specific mortality decreased by 24% for each additional 6 months of metformin use after diagnosis; use of other antidiabetic medications did not significantly decrease prostate cancer–specific mortality. The authors were thorough in their investigation, performing many sensitivity analyses to attempt to rule out possible biases. As the distribution of clinical characteristics specific to metformin users and nonusers was not provided, it is difficult to assess the possibility of residual confounding; however, the authors appropriately adjusted for many covariates. Also, the specificity of the results for metformin lends further support for causal relation. Interestingly, although postdiagnostic use of metformin was highly significant, the association of cumulative metformin use before prostate cancer diagnosis with prostate cancer death was null. As prostate cancer date of diagnosis is a rather arbitrary point in the progression of the disease, this discrepancy between the impact of pre- and postdiagnostic use is perplexing and warrants further study. Despite these concerns, the authors provide a convincing case for a causal interpretation and for initiating a randomized trial of metformin among men with localized prostate cancer at diagnosis. The potential benefits of metformin could exceed those of existing drug therapies, particularly given its safety profile. Margel et al 1 wisely chose to focus their analysis on prostate cancer mortality. Of course, this is clinically the most important out
Phase I trial of ixabepilone plus pegylated liposomal doxorubicin in patients with adenocarcinoma of breast or ovary
Authors: E. Chuang, N. Wiener, P. Christos, R. Kessler, M. Cobham, D. Donovan, G.L. Goldberg, T. Caputo, A. Doyle, L. Vahdat, J.A. Sparano
Journal: Annals of Oncology (2010)
Pemphigoid gestationis: early onset and blister formation are associated with adverse pregnancy outcomes
Authors: C-C. Chi, S-H. Wang, R. Charles-Holmes, C. Ambros-Rudolph, J. Powell, R. Jenkins, M. Black, F. Wojnarowska
Journal: British Journal of Dermatology (2009)

Journal Article Pemphigoid gestationis: early onset and blister formation are associated with adverse pregnancy outcomes Get access C‐C. Chi, C‐C. Chi Nuffield Department of Clinical Medicine, University of Oxford and Department of Dermatology, Churchill Hospital, Oxford OX3 7LJ, U.K.Department of Dermatology, Chang Gung Memorial Hospital Chiayi, Chang Gung University College of Medicine, Chiayi, Taiwan Search for other works by this author on: Oxford Academic Google Scholar S‐H. Wang, S‐H. Wang Nuffield Department of Clinical Medicine, University of Oxford and Department of Dermatology, Churchill Hospital, Oxford OX3 7LJ, U.K.Department of Dermatology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei and Department of Cosmetic Science, Chang Gung Institute of Technology, Taoyuan, Taiwan Correspondence: Shu‐Hui Wang. E‐mail: dermawang@hotmail.com;chingchi@cgmh.org.tw Search for other works by this author on: Oxford Academic Google Scholar R. Charles‐Holmes, R. Charles‐Holmes Department of Dermatology, Warwick Hospital, Warwick, U.K. Search for other works by this author on: Oxford Academic Google Scholar C. Ambros‐Rudolph, C. Ambros‐Rudolph Department of Dermatology, Medical University of Graz, Graz, Austria Search for other works by this author on: Oxford Academic Google Scholar J. Powell, J. Powell Department of Dermatology, North Hampshire Hospital, Basingstoke, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. Jenkins, R. Jenkins Department of Dermatology, West Suffolk Hospital, Bury St Edmunds, U.K.St John’s Institute of Dermatology, St Thomas’ Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar M. Black, M. Black St John’s Institute of Dermatology, St Thomas’ Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar F. Wojnarowska F. Wojnarowska Nuffield Department of Clinical Medicine, University of Oxford and Department of Dermatology, Churchill Hospital, Oxford OX3 7LJ, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 160, Issue 6, 1 June 2009, Pages 1222–1228, https://doi.org/10.1111/j.1365-2133.2009.09086.x Published: 01 June 2009
Comparison of Paroxetine and Nortriptyline in Depressed Patients With Ischemic Heart Disease
Authors: Steven P. Roose
Journal: JAMA (1998)

Context.—Depression and ischemic heart disease often are comorbid conditions and, in patients who have had a myocardial infarction, the presence of depression is associated with increased mortality. Patients with heart disease need a safe and effective treatment for depression.Objective.—To compare the efficacy, cardiovascular effects, and safety of a specific serotonin reuptake inhibitor, paroxetine, with a tricyclic antidepressant, nortriptyline hydrochloride, in depressed patients with ischemic heart disease.Design.—Two-week placebo lead-in followed by a double-blind randomized 6-week medication trial.Setting.—Research clinics in 4 university centers.Patients.—Eighty-one outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder and with documented ischemic heart disease.Interventions.—Treatment with either paroxetine, 20 to 30 mg/d, or nortriptyline targeted to a therapeutic plasma level, 190 to 570 nmol/L (50-150 ng/mL), for 6 weeks.Main Outcome Measures.—For effectiveness of treatment, a decline in the score of the Hamilton Rating Scale for Depression by 50% and final score of 8 or less; for cardiovascular safety, heart rate and rhythm, supine and standing systolic and diastolic blood pressures, electrocardiogram conduction intervals, indexes of heart rate variability, and rate of adverse events.Results.—By intent-to-treat analysis, 25 (61%) of 41 patients improved during treatment with paroxetine and 22 (55%) of 40 improved with nortriptyline. Neither drug significantly affected blood pressure or conduction intervals. Paroxetine had no sustained effects on heart rate or rhythm or indexes of heart rate variability, whereas patients treated with nortriptyline had a sustained 11% increase in heart rate from a mean of 75 to 83 beats per minute (P<.001) and a reduction in heart rate variability, as measured by the SD of all normal R-R intervals over a 24-hour period, from 112 to 96 (P<.01). Adverse cardiac events occurred in 1 (2%) of 41 patients treated with paroxetine and 7 (18%) of 40 patients treated with nortriptyline (P<.03).Conclusions.—Paroxetine and nortriptyline are effective treatments for depressed patients with ischemic heart disease. Nortriptyline treatment was associated with a significantly higher rate of serious adverse cardiac events compared with paroxetine.