tbuckley/cabot-search huggingface dataset:
Phase I dose escalation of 131I-metaiodobenzylguanidine with autologous bone marrow support in refractory neuroblastoma.
Authors: K K Matthay, K DeSantes, B Hasegawa, J Huberty, R S Hattner, A Ablin, C P Reynolds, R C Seeger, V K Weinberg, D Price
Journal: Journal of Clinical Oncology (1998)

PURPOSE The analogue 131I-metaiodobenzylguanidine (MIBG), which is specifically targeted to neuroblastoma cells, may provide more effective and less toxic treatment for neuroblastoma than conventional external-beam radiotherapy. We report a dose escalation study of 131I-MIBG to define dose-limiting toxicity without and with autologous bone marrow support. PATIENTS AND METHODS Thirty patients with relapsed neuroblastoma were treated in groups of six with escalating doses of 3 to 18 mCi/kg of 131I-MIBG. After rapid escalation in the first three patients treated at 3 to 6 mCi/kg, treatment was escalated in 3-mCi/kg increments from 9 to 18 mCi/kg. Autologous tumor-free bone marrow was cryopreserved in all patients receiving 12 mCi/kg and more. Toxicity and response were assessed. RESULTS Eighty percent of patients who received 12 mC/kg or more experienced grade 4 thrombocytopenia and/or neutropenia. Dose-limiting hematologic toxicity was reached at 15 mCi/kg, at which level two of five assessable patients required bone marrow reinfusion for absolute neutrophil count (ANC) of less than 200/microL for more than 2 weeks, and four of nine at the 18-mCi/kg level. Prolonged thrombocytopenia was common, with failure to become platelet-transfusion independent in nine patients. One patient with extensive prior treatment developed secondary leukemia and three became hypothyroid. Responses were seen in 37% of patients, with one complete response (CR), 10 partial response (PR), three mixed response, 10 stable disease, and six progressive disease. The minimum dose of 131I-MIBG for 10 of the 11 responders was 12 mCi/kg. CONCLUSION Treatment with 131I-MIBG has mainly hematologic toxicity, which can be abrogated with bone marrow rescue. The high response rate in refractory disease suggests that this agent may be useful in combination with myeloablative chemotherapy and autologous stem-cell rescue to improve outcome in advanced neuroblastoma.
Hyperplastic and Neoplastic Lesions of the Kidney in Buffalo Rats of Varying Ages Ingesting N-4-(4'-fluorobiphenyl)acetamide
Authors: Melvin D. Reuber
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Hyperplastic and Neoplastic Lesions of the Kidney in Buffalo Rats of Varying Ages Ingesting N-4-(4'-fluorobiphenyl)acetamide Get access Melvin D. Reuber, M.D. Melvin D. Reuber, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 54, Issue 2, February 1975, Pages 427–429, https://doi.org/10.1093/jnci/54.2.427 Published: 01 February 1975 Article history Received: 02 July 1974 Accepted: 24 September 1974 Published: 01 February 1975
Isotonic vs Hypotonic Intravenous Fluids for Hospitalized Children
Authors: Sarah McNab
Journal: JAMA (2015)

Is isotonic fluid associated with a lower incidence of hyponatremia when compared with hypotonic fluid for maintenance intravenous fluid therapy in children?Compared with hypotonic fluid, isotonic fluid is associated with a lower incidence of hyponatremia, without evidence of an increase in adverse outcomes.
Electrospun Collagen Fibers with Spatial Patterning of SDF1α for the Guidance of Neural Stem Cells
Authors: Xiaoran Li, Hui Liang, Jie Sun, Yan Zhuang, Bai Xu, Jianwu Dai
Journal: Advanced Healthcare Materials (2015)

Producing gradients of biological cues into nerve conduits is crucial for nerve guidance and regeneration. Herein, the fabrication of gradients of stromal cell-derived factor-1α (SDF1α) on electrospun collagen mats is reported using an electrohydrodynamic jet printing technique. The fabrication of various SDF1α gradated patterns on collagen fibrous mats is successfully demonstrated including shallow continuous gradient, steep continuous gradient, and step gradient by controlling the processing parameters. The SDF1α graded collagen scaffolds show a long-term stable gradient, as SDF1α is fused with a unique peptide of collagen binding domain (CBD), and CBD-SDF1α can specifically bind to the collagen mat. Such graded scaffolds exhibit sustained release of SDF1α. Further examination of neural stem cell (NSC) response to the CBD-SDF1α gradients with various patterns show that the NSCs can sense the CBD-SDF1α gradients, display a polarized morphology, and tend to migrate toward the region with a higher CBD-SDF1α content. The collagen mats with CBD-SDF1α gradients guide gradual distribution of NSCs, and NSC-differentiated neurons and astrocytes after seeding for 1 and 7 d. This new class of CBD-SDF1α gradient scaffolds can potentially be employed for guided nerve regeneration.
Association of a Novel<i>ACTA1</i>Mutation With a Dominant Progressive Scapuloperoneal Myopathy in an Extended Family
Authors: Kristen Zukosky, Katherine Meilleur, Bryan J. Traynor, Jahannaz Dastgir, Livija Medne, Marcella Devoto, James Collins, Jachinta Rooney, Yaqun Zou, Michele L. Yang, J. Raphael Gibbs, Markus Meier, Joerg Stetefeld, Richard S. Finkel, Joachim Schessl, Lauren Elman, Kevin Felice, Toby A. Ferguson, Ozge Ceyhan-Birsoy, Alan H. Beggs, Gihan Tennekoon, Janel O. Johnson, Carsten G. Bönnemann
Journal: JAMA Neurology (2015)

New genomic strategies can now be applied to identify a diagnosis in patients and families with previously undiagnosed rare genetic conditions. The large family evaluated in the present study was described in 1966 and now expands the phenotype of a known neuromuscular gene.To determine the genetic cause of a slowly progressive, autosomal dominant, scapuloperoneal neuromuscular disorder by using linkage and exome sequencing.Fourteen affected individuals in a 6-generation family with a progressive scapuloperoneal disorder were evaluated. Participants were examined at pediatric, neuromuscular, and research clinics from March 1, 2005, to May 31, 2014. Exome and linkage were performed in genetics laboratories of research institutions.Examination and evaluation by magnetic resonance imaging, ultrasonography, electrodiagnostic studies, and muscle biopsies (n = 3). Genetic analysis included linkage analysis (n = 17) with exome sequencing (n = 7).Clinical findings included progressive muscle weakness in an initially scapuloperoneal and distal distribution, including wrist extensor weakness, finger and foot drop, scapular winging, mild facial weakness, Achilles tendon contractures, and diminished or absent deep tendon reflexes. Both age at onset and progression of the disease showed clinical variability within the family. Muscle biopsy specimens demonstrated type I fiber atrophy and trabeculated fibers without nemaline rods. Analysis of exome sequences within the linkage region (4.8 megabases) revealed missense mutation c.591C>A p.Glu197Asp in a highly conserved residue in exon 4 of ACTA1. The mutation cosegregated with disease in all tested individuals and was not present in unaffected individuals.This family defines a new scapuloperoneal phenotype associated with an ACTA1 mutation. A highly conserved protein, ACTA1 is implicated in multiple muscle diseases, including nemaline myopathy, actin aggregate myopathy, fiber-type disproportion, and rod-core myopathy. To our knowledge, mutations in Glu197 have not been reported previously. This residue is highly conserved and located in an exposed position in the protein; the mutation affects the intermolecular and intramolecular electrostatic interactions as shown by structural modeling. The mutation in this residue does not appear to lead to rod formation or actin accumulation in vitro or in vivo, suggesting a different molecular mechanism from that of other ACTA1 diseases.
Expedition Health and Safety: A Risk Assessment
Authors: Sarah R Anderson, Chris J H Johnson
Journal: Journal of the Royal Society of Medicine (2000)

Little has been published on the risks of participating in an expedition. A questionnaire survey was conducted to quantify those risks and to determine how expedition organizers plan for medical mishaps. 246 expeditions, taking 2381 participants to more than one hundred countries, were studied retrospectively. 65 expeditions (26%) reported no medical incidents; the remaining 181 reported 835 in 130 000 man-days (6.4 per 1000 man-days). 59% of the medical incidents seen on expeditions were preventable, one-third of these being due to gastrointestinal upsets. 78% of medical incidents were classified as minor and only 5% (40) as serious. There was no excess of serious incidents in any particular organizational group or environment. The findings of this survey suggest that the health risks of participating in a well-planned expedition are similar to those encountered during normal active life.
Growth of lung and thorax dimensions during the pubertal growth spurt
Authors: EG DeGroodt, W van Pelt, GJ Borsboom, PH Quanjer, BC van Zomeren
Journal: European Respiratory Journal (1988)

In the follow-up study of adolescents residual volume (RV), vital capacity (VC), closing volume (CV), thorax height and thorax width were measured at six month intervals over a six year period; 149 girls and 477 boys, whose ages ranged between 11.5 and 18.5 yr during the follow-up, were investigated. In healthy subjects and in those with respiratory symptoms the rates of change of thoracic dimensions, as calculated by a robust linear regression technique, were moderately well correlated; the growth rates of RV and VC were only slightly correlated, and both were moderately well correlated with changes in thorax dimensions. Thorax height increased relative to thorax width in boys and girls during the follow-up. In boys, thorax height continued to grow, when standing height and thorax width had attained adult values in girls. Thus the thorax attains a more elongated shape. During the adolescent growth spurt the residual volume as a percentage of total lung capacity (RV%TLC) within subjects increased on average 0.6% per yr, and closing volume as a percentage of vital capacity (CV%VC) decreased on average 0.5% per yr. Both of these changes can be accounted for by decreased thorax compliance and increased outward chest recoil at low lung volumes.
Interleukin-10 Inhibits Activation of Coagulation and Fibrinolysis During Human Endotoxemia
Authors: Dasja Pajkrt, Tom van der Poll, Marcel Levi, David L. Cutler, Melton B. Affrime, Abraham van den Ende, Jan Wouter ten Cate, Sander J.H. van Deventer
Journal: Blood (1997)
Depression and panic attacks: the significance of overlap as reflected in follow-up and family study data
Authors: W Coryell, J Endicott, N C Andreasen, M B Keller, P J Clayton, R M Hirschfeld, W A Scheftner, G Winokur
Journal: American Journal of Psychiatry (1988)

Ninety-one patients with panic attacks limited historically to depressive episodes had more severe depressive symptoms and were less likely to recover during a 2-year follow-up than 417 depressed patients who did not have panic attacks. Family study data clearly distinguished another 15 patients with panic disorder and secondary depression; interviewed relatives of panic disorder patients were significantly less likely to have primary depression and significantly more likely to have various anxiety disorders. These data support the hierarchical system by which many of the contemporary diagnostic systems separate panic disorder and major depression.
Phase I and Pharmacokinetic Trial of Oral Irinotecan Administered Daily for 5 Days Every 3 Weeks in Patients With Solid Tumors
Authors: Ronald L. Drengler, John G. Kuhn, Larry J. Schaaf, Gladys I. Rodriguez, Miguel A. Villalona-Calero, Lisa A. Hammond, Joseph A. Stephenson, Jr., Stephanie Hodges, Maura A. Kraynak, Brian A. Staton, Gary L. Elfring, Paula K. Locker, Langdon L. Miller, Daniel D. Von Hoff, Mace L. Rothenberg
Journal: Journal of Clinical Oncology (1999)

PURPOSE: We conducted a phase I dose-escalation trial of orally administered irinotecan (CPT-11) to characterize the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetic profile, and antitumor effects in patients with refractory malignancies. PATIENTS AND METHODS: CPT-11 solution for intravenous (IV) use was mixed with CranGrape juice (Ocean Spray, Lakeville-Middleboro, MA) and administered orally once per day for 5 days every 3 weeks to 28 patients. Starting dosages ranged from 20 to 100 mg/m 2 /d. RESULTS: Grade 4 delayed diarrhea was the DLT at the 80 mg/m 2 /d dosage in patients younger than 65 years of age and at the 66 mg/m 2 /d dosage in patients 65 or older. The other most clinically significant toxicity of oral CPT-11 was neutropenia. A linear relationship was found between dose, peak plasma concentration, and area under the concentration-time curve (AUC) for both CPT-11 and SN-38 lactone, implying no saturation in the conversion of irinotecan to SN-38. The mean metabolic ratio ([AUC SN-38 total + AUC SN-38G total ]/AUC CPT-11 total ) was 0.7 to 0.8, which suggests that oral dosing results in presystemic conversion of CPT-11 to SN-38. An average of 72% of SN-38 was maintained in the lactone form during the first 24 hours after drug administration. One patient with previously treated colorectal cancer and liver metastases who received oral CPT-11 at the 80 mg/m 2 /d dosage achieved a confirmed partial response. CONCLUSION: The MTD and recommended phase II dosage for oral CPT-11 is 66 mg/m 2 /d in patients younger than 65 years of age and 50 mg/m 2 /d in patients 65 or older, administered daily for 5 days every 3 weeks. The DLT of diarrhea is similar to that observed with IV administration of CPT-11. The biologic activity and favorable pharmacokinetic characteristics make oral administration of CPT-11 an attractive option for further clinical development.
Prognostic Parameters For Remission Of and Survival In Acquired Hemophilia A: Results Of The GTH-AH 01/2010 Multicenter Study
Authors: Andreas Tiede, Jan-Malte Blumtritt, Robert Klamroth, Saskia Gottstein, Katharina Holstein, Jürgen Heinz, Rüdiger E. Scharf, Angela Huth-Kühne, Joachim F. Schenk, Richard Greil, Wolfgang A. Miesbach, Ralf Ulrich Trappe, Ute Scholz, Daniela Manner, Peter Neumeister, Charis von Auer-Wegener, Ulrich Kalus, Klaus Leimkühler, Paul Knoebl
Journal: Blood (2013)
Diffuse proliferative glomerulonephritis and acute renal failure associated with acute staphylococcal osteomyelitis.
Authors: M D Griffin, J Björnsson, S B Erickson
Journal: Journal of the American Society of Nephrology (1997)

A 72-year-old man developed acute renal failure after coronary bypass surgery that had been complicated by sternal osteomyelitis caused by the Staphylococcus aureus bacterium. Bacteremia and sepsis were not present. Renal biopsy demonstrated a florid, diffuse, proliferative glomerulonephritis with glomerular immune complex deposition. Management included hemodialysis, prolonged antibiotic therapy, and repeated surgical debridement. Spontaneous recovery of renal function occurred after eradication of infection and final surgical wound repair. The relationship between acute bacterial infections and glomerulonephritis and, in particular, the causal role of staphylococcal antigens in the pathogenesis of such lesions is discussed.
Letter from the authors of “Improved Growth in Young Children with Severe Chronic Renal Insufficiency Who Use Specified Nutritional Therapy,” which appeared on pages 2418–2426 of the November 2001 issue of JASN.
Authors: Rulan Parekh, William E. Smoyer, Joan L. Milne, David B. Kershaw, Aileen B. Sedman, Joseph T. Flynn, Timothy E. Bunchman
Journal: Journal of the American Society of Nephrology (2002)

Regarding the homemade sodium solutions that we provided in the appendix to our article (1), use of these solutions began at our institution over 10 y ago after a pharmacy error resulted in an adverse event in a young child. It is estimated that medication errors occur in 6 of 100 orders in a pediatric inpatient pharmacy, and errors in dosing are frequent by parents (2,3). Potential errors can occur by the physician, pharmacy, and patient. The controversy of homemade versus pharmacy-made solutions has also been under debate in the pediatric population with respect to the use of oral rehydration solutions. The error rate of homemade cereal-based rehydration solution was 3% when all ingredients were added and 1% in a premixed packet in a randomized clinical trial based in Boston (4). None of the mixing errors resulted in an adverse event. Nevertheless, it is important to have personal, written instruction to the family and regular review and education of medication dosing. We carefully screen families to make sure that they are capable of mixing both their child’s formula and the sodium solutions correctly. If not, we have a pharmacy make up the sodium chloride or bicarbonate solutions. Since minimizing the risk to the patient is of utmost importance, we would recommend that a pharmacy-based solution be used in an industrialized nation. We would also suggest that the solution be kept at a standard concentration of 1 mEq of sodium chloride/1 cc so that frequent adjustments by dietician and physician can be made without the risk of further errors. We previously made and tested our homemade salt solutions. However, in following these same instructions in 2001, we realize that the packaging of Arm and Hammer has changed, which would lead to errors in preparation of these home-based solutions if our original instructions were followed. Although our recent laboratory testing of the solution did not produce solutions of 1.7 mEq/cc sodium concentration as suggested, the inaccuracies with new packaging make it imperative that we revise our home-based solutions. In formulating a home-based regimen, local supplies, i.e., salt and bicarbonate sources and water constituents, all need to be considered. Our written outline is just an example and should not be used as a universal formula for a salt solution in any region or non-industrialized country. Sincerely, Rulan Parekh, William E. Smoyer, Joan L. Milne, David B. Kershaw, Aileen B. Sedman, Joseph T. Flynn, and Timothy E. Bunchman
FGF Receptors: Cancer Biology and Therapeutics
Authors: Masaru Katoh, Hitoshi Nakagama
Journal: Medicinal Research Reviews (2013)

Fibroblast growth factors (FGFs) are involved in a variety of cellular processes, such as stemness, proliferation, anti-apoptosis, drug resistance, and angiogenesis. Here, FGF signaling network, cancer genetics/genomics of FGF receptors (FGFRs), and FGFR-targeted therapeutics will be reviewed. FGF signaling to RAS-MAPK branch and canonical WNT signaling cascade mutually regulate transcription programming. FGF signaling to PI3K-AKT branch and Hedgehog, Notch, TGFβ, and noncanonical WNT signaling cascades regulate epithelial-to-mesenchymal transition (EMT) and invasion. Gene amplification of FGFR1 occurs in lung cancer and estrogen receptor (ER)-positive breast cancer, and that of FGFR2 in diffuse-type gastric cancer and triple-negative breast cancer. Chromosomal translocation of FGFR1 occurs in the 8p11 myeloproliferative syndrome and alveolar rhabdomyosarcoma, as with FGFR3 in multiple myeloma and peripheral T-cell lymphoma. FGFR1 and FGFR3 genes are fused to neighboring TACC1 and TACC3 genes, respectively, due to interstitial deletions in glioblastoma multiforme. Missense mutations of FGFR2 are found in endometrial uterine cancer and melanoma, and similar FGFR3 mutations in invasive bladder tumors, and FGFR4 mutations in rhabdomyosarcoma. Dovitinib, Ki23057, ponatinib, and AZD4547 are orally bioavailable FGFR inhibitors, which have demonstrated striking effects in preclinical model experiments. Dovitinib, ponatinib, and AZD4547 are currently in clinical trial as anticancer drugs. Because there are multiple mechanisms of actions for FGFR inhibitors to overcome drug resistance, FGFR-targeted therapy is a promising strategy for the treatment of refractory cancer. Whole exome/transcriptome sequencing will be introduced to the clinical laboratory as the companion diagnostic platform facilitating patient selection for FGFR-targeted therapeutics in the era of personalized medicine.
Abstract 6: Timing Of Major Adverse Cardiac Events During Endurance Races.
Authors: Victor Umans, Jasper Bennik, Jaap Ruiter, Hans de Swart, Jan H Cornel
Journal: Circulation (2007)

Background: Major adverse cardiac events (MACE) in endurance exercise are usually due to underlying and unsuspected heart disease. We present an analysis of the timing MACE that have occurred in en...
Subcutaneous Administration of Amifostine During Fractionated Radiotherapy: A Randomized Phase II Study
Authors: Michael I. Koukourakis, George Kyrias, Stelios Kakolyris, Charalambos Kouroussis, Chryssi Frangiadaki, Alexandra Giatromanolaki, George Retalis, Vassilios Georgoulias
Journal: Journal of Clinical Oncology (2000)

Amifostine (WR-2721) is an important cytoprotective agent. Although intravenous administration is the standard route, pharmacokinetic studies have shown acceptable plasma levels of the active metabolite of amifostine (WR-1605) after subcutaneous administration. The subcutaneous route, due to its simplicity, presents multiple advantages over the intravenous route when amifostine is used during fractionated radiotherapy.Sixty patients with thoracic, 40 with head and neck, and 40 with pelvic tumors who were undergoing radical radiotherapy were enrolled onto a randomized phase II trial to assess the feasibility, tolerance, and cytoprotective efficacy of amifostine administered subcutaneously. A flat dose of amifostine 500 mg, diluted in 2.5 mL of normal saline, was injected subcutaneously 20 minutes before each radiotherapy fraction.The subcutaneous amifostine regimen was well tolerated by 85% of patients. In approximately 5% of patients, amifostine therapy was interrupted due to cumulative asthenia, and in 10%, due to a fever/rash reaction. Hypotension was never noted, whereas nausea was frequent. A significant reduction of pharyngeal, esophageal, and rectal mucositis was noted in the amifostine arm (P <.04). The delays in radiotherapy because of grade 3 mucositis were significantly longer in the group of patients treated with radiotherapy alone (P <.04). Amifostine significantly reduced the incidence of acute perineal skin and bladder toxicity (P <.0006).Subcutaneous administration of amifostine is well tolerated, effectively reduces radiotherapy's early toxicity, and prevents delays in radiotherapy. The subcutaneous route is much simpler and saves time compared with the intravenous route of administration and can be safely and effectively applied in the daily, busy radiotherapy practice.
Dialysis plus ultrafiltration significantly improves the detection of cytokines in induced sputum
Authors: Costel Agache, Beate Rückert, Ioana Agache, Cristina Ciobanu, Cezmi Akdis
Journal: European Respiratory Journal (2013)

Background   Measurement of cytokines in induced sputum proves difficult due to sputum composition (mucus, proteases) and processing (DTT addition, filtration, dilution).   Research hypothesis   DTT eluting followed by sputum concentration will improve cytokine detection.   Methods   Study was approved by the Local Ethics Committee. Sputum induction and processing (ERS recommendations) was identical for two groups of adult asthmatics. Before cytokine detection (Bio-Plex Pro Human Cytokine 27-plex, Bio-Rad) the sputum was processed for group I by concentration with Centricon Ultracel YM-3 membrane (Millipore, 3000 NMWL) and for group II by dialysis (D-Tube Dialyzers Midi, MWCO 3.5 kDa, Novagen) followed by ultrafiltration (UF) - Amicon Ultra 3K, Millipore, 3000 NMWL. Data were analyzed with SPSS 21.   Results   Group I: 11 patients, mean age 52.73±12.87 years old, 36% females; group II: 24 patients, mean age 47.75±15.57 years old, 79% females.  Dialysis + UF lead to a significant better detection ratio (figure 1) and in higher concentrations (figure 2) of sputum cytokines.   Conclusion   Dialysis plus ultrafiltration proves a valuable method for measuring sputum cytokines.