tbuckley/cabot-search huggingface dataset:
Phase I trial of esorubicin (4'deoxydoxorubicin).
Authors: H S Garewal, A Robertone, S E Salmon, S E Jones, D S Alberts, R Brooks
Journal: Journal of Clinical Oncology (1984)

A phase I study of 4'deoxydoxorubicin (esorubicin) was performed on an every-21-day bolus intravenous (IV) schedule in 36 patients with advanced cancer. Thirty-four patients were evaluable for toxicity analysis. Toxicity included mild nausea, occasional local skin reactions, and mild to moderate alopecia. Myelo-suppression was dose limiting. Clinically evident congestive heart failure was not observed. However, two patients developed premature ventricular contractions. Overall, esorubicin was better tolerated than doxorubicin at equally potent doses. Although response analysis was not the primary objective of this phase I study, minor responses were observed in melanoma, breast cancer, lymphoma, and gastric cancer. On the basis of this study, a starting dose of 30 mg/m2 IV every 21 days is recommended for good-risk patients with escalation to 32.5 mg/m2 depending on bone marrow tolerance. For patients with poor bone marrow reserve, a starting dose of 25 mg/m2 every 21 days is recommended. Phase II trials with esorubicin in this dosage schedule are clearly warranted in a wide variety of metastatic neoplasms including a substantial population of patients who have not received prior chemotherapy.
Repetitive cycles of cyclophosphamide, thiotepa, and carboplatin intensification with peripheral-blood progenitor cells and filgrastim in advanced breast cancer patients.
Authors: C L Shapiro, L Ayash, I J Webb, R Gelman, J Keating, L Williams, G Demetri, P Clark, A Elias, D Duggan, D Hayes, D Hurd, I C Henderson
Journal: Journal of Clinical Oncology (1997)

PURPOSE As an alternative to single-cycle cyclophosphamide, thiotepa, and carboplatin (CTCb) intensification, we evaluated the feasibility of administering one-quarter dose CTCb for four cycles with peripheral-blood progenitor-cell (PBPC) and filgrastim (granulocyte colony-stimulating factor [G-CSF]) in advanced-stage breast cancer patients. PATIENTS AND METHODS From June 1992 to August 1993, 20 stage IIIB (n = 7) and IV (n = 13) breast cancer patients received 78 cycles of induction with doxorubicin 90 mg/m2 by intravenous (IV) bolus with G-CSF 5 microg/kg/d by subcutaneous injection (SC) repeated every 14 to 21 days for four cycles. PBPC were collected by 2-hour single-blood volume leukapheresis on 2 consecutive days at the time of hematologic recovery from each cycle of doxorubicin. Eighteen patients received 61 cycles of intensification with cyclophosphamide 1,500 mg/m2, thiotepa 125 mg/m2, and carboplatin 200 mg/m2 by IV continuous infusion with G-CSF 10 microg/kg/d SC and PBPC support repeated every 21 to 42 days for four cycles. RESULTS Twelve of 20 patients (60%) completed all four planned cycles of doxorubicin induction followed by four cycles of one-quarter dose CTCb intensification. Statistically significantly decreases in the yield of mononuclear cells (MNC) (median slope per day, -0.032; P = .03), granulocyte-macrophage colony-forming unit (CFU-GM) (median slope per day, -0.57; P = .0008), and burst-forming unit-erythroid (BFU-E) (median slope per day, -1.18; P = .006) were observed over the course of the eight leukaphereses. Of 18 patients who began CTCb, 12 (67%) completed four cycles. Six patients were removed from study during intensification: two for progressive disease (PD), one refused further treatment, and three for dose-limiting hematologic toxicity. A fourth patient fulfilled the criteria for dose-limiting hematologic toxicity after cycle 4. The toxicity of the multiple cycle CTCb intensification regimen consisted of grade IV leukopenia, grade IV thrombocytopenia, and febrile neutropenia in 100%, 100%, and 26% of cycles, respectively. The median duration of each CTCb cycle was 24 days (range, 18 to 63), and the median duration of an absolute neutrophil count (ANC) &lt; or = 500/microL and platelet count &lt; or = 20,000/microL during each cycle was 6 days (range, 2 to 15) and 4 days (range, 0 to 38), respectively. CONCLUSION It is feasible to administer repetitive cycles of one-quarter dose CTCb intensification with PBPC and G-CSF. Additional studies are required to determine whether multiple cycles of CTCb intensification might offer a therapeutic advantage over a single high-dose cycle.
Specificity of JAK-kinase inhibition determines impact on human and murine T-cell function
Authors: F Perner, T M Schnöder, S Ranjan, D Wolleschak, C Ebert, M C Pils, S Frey, A Polanetzki, C Fahldieck, U Schönborn, B Schraven, B Isermann, T Fischer, F H Heidel
Journal: Leukemia (2015)
Anzup 1302 P3Bep Companion Translational Study: Prospective Collection of Whole Blood, Serum, Plasma and Tumour Tissue in a Randomized Trial of Chemotherapy for Metastatic Germ Cell Tumours (Gct)
Authors: P. Grimison, M.R. Stockler, S. Yip, G. Toner, L. Horvath
Journal: Annals of Oncology (2014)
Cystic fibrosis epithelial cells are primed for apoptosis as a result of increased Fas
Authors: Sinéad Weldon, Qiwei Chen, Irene Oglesby, Christine Wohlford-Lenane, Jennifer Bartlett, Gerry McElvaney, Stuart Elborn, Paul McCray, Catherine Greene, Clifford Taggart
Journal: European Respiratory Journal (2012)

Apoptosis is a physiological process essential for homeostasis of epithelial organisation and function. Cystic fibrosis (CF) lung disease is characterised by chronic infection and inflammation and previous work suggests that apoptosis is dysfunctional in the CF airways with conflicting results. In addition, controversy exists regarding how CFTR misfolding contributes to apoptosis. In this study, we evaluated the relationship between CFTR mutation and apoptosis in CF airway epithelial cells. Basal activity of the executioner caspase, caspase-3, was significantly increased in CF tracheal and bronchial epithelial cell lines and primary bronchial epithelial cells compared to non-CF controls. In addition, activity of the upstream initiator caspase, caspase-8, was significantly increased in CF epithelial cells compared to controls, suggesting involvement of extrinsic apoptosis signalling, which is mediated by the activation of death receptors, such as Fas (CD95). Increased levels of Fas were observed in CF epithelial cells and bronchial brushings, reciprocal decreases in a selection of microRNAs predicted to target Fas were evident in the brushing samples, and neutralization of Fas significantly inhibited caspase-3 activity in CF epithelial cells compared to untreated cells. Furthermore, activation of Fas significantly increased caspase-3 activity and apoptosis in CF epithelial cells compared to control cells. Overall, these results suggest that CF airway epithelial cells are more sensitive to apoptosis via increased levels of Fas and subsequent activation of the Fas death receptor pathway. Further work will delineate the mechanism underlying increased Fas expression in CF epithelial cells.
Treatment Patterns and Outcomes in Patients With Hepatocellular Carcinoma Stratified by Stage-Guided Treatment Categories
Authors: Kuan-Ling Kuo, David Stenehjem, Frederick Albright, Saurabh Ray, Diana Brixner
Journal: Journal of the National Comprehensive Cancer Network (2015)

Purpose: The purpose of this study was to assess the survival and treatment patterns of hepatocellular carcinoma (HCC) stratified by the NCCN stage–guided treatment categories in the absence of a universally accepted staging system for HCC. Methods: Patients with HCC were identified using ICD-9 codes and inclusion in the Huntsman Cancer Institute tumor registry. Patients were stratified by the NCCN groupings around the time of diagnosis as potentially resectable or operable (RESECT), potentially transplantable (TRANSP), unresectable (UNRESECT), inoperable due to performance status (INOPER), or having metastatic (METAST) disease. Survival and treatment patterns were assessed by NCCN stage–guided treatment categories. Results: A total of 221 patients (72.9% men) with HCC were identified. At the time of diagnosis, patients were categorized as RESECT (n=28, 12.7%), TRANSP (n=33, 14.9%), UNRESECT (n=77, 34.8%), INOPER (n=40, 18.1%), and METAST (n=38, 17.2%). Staging information was not specified for 5 patients (2.3%) even after chart review. Kaplan-Meier analysis demonstrated significant differences in survival between RESECT and UNRESECT categories, and between UNRESECT and METAST categories. The median survivals in RESECT, TRANSP, UNRESECT, INOPER, and METAST categories were 594, 562, 247, 167, and 44 days, respectively. Patients considered RESECT most frequently underwent resection (61%, n=17) and patients considered TRANSP had the highest use of liver transplants (33.3%, n=11). Use of any treatment was low in the METAST (31.6%, n=12) and INOPER (60.0%, n=24) groups. Conclusions: Treatment patterns in the NCCN groupings correlated with recommended treatment strategies. Overall, the NCCN groupings have a linear relationship in overall survival.
Questions remain over alfacalcidol's efficacy in preventing secondary hyperparathyroidism
Authors: A Fournier, R Oprisiu, N E L Esper, P Moriniere, A Marie
Journal: BMJ (1995)

Use non-invasive dark adaptometry to screen children and adolescents ED1TOR,-N J Watson and colleagues remind readers of the possibility of vitamin A deficiency in patients with gastrointestinal or liver disease.'I am surprised, however, that they do not also mention its possibility in cystic fibrosis.23They suggest measurement of serum vitamin A concentrations and cytological examination of conjunctival specimens, presumably as a screening technique in people at risk.I suggest that dark adaptometry, which is non-invasive, might be more appropriate, particularly in children and adolescents.
Effect of fluticasone and formoterol combination therapy on airway remodeling
Authors: Michael Roth, Jun Zhong, Chong S'ng, Michael Tamm
Journal: European Respiratory Journal (2011)

Background:  Mucosal inflammation, thickening of the basement membrane and increased mass of airway smooth muscle influence asthma airway remodeling. Different cell types contribute to extracellular matrix deposition. Airway smooth muscle cells (ASMC) not only contract and relax but also proliferate, respond to inflammatory stimuli and produce extracellular matrix. As shown previously, glucocorticoids increase the deposition of extracellular matrix by human ASMC under inflammatory conditions.   Methods:  To analyse the effect of the β2-agonist formoterol on glucocorticoid-induced extracellular matrix deposition, primary ASMC cultures were set up from asthmatics and non-asthmatic controls. Confluent cells were stimulated with 5% serum with or without a single drug or a combination for a further 72 hr with [3H] proline (0.5microCi). Total extracellular matrix and collagen deposition were monitored by scintillation counts, described earlier.   Results:  Compared to non-stimulated cells 5% serum increased matrix and collagen deposition by +42% which was further increased in the presence of 10-8 M glucocorticoids (dexamethasone: +86%, budesonide: +66%, beclomethasone: +59%, fluticasone: +55%). However, 10-8 M formoterol reduced serum-induced matrix and collagen deposition by 36%. In combination, formoterol abolished the stimulating effect of glucocorticoids on matrix and collagen deposition and reduced matrix deposition. This was dose-dependent.   Conclusions:  Our data show that β2-agonists combined with glucocorticoids reduce the excessive matrix deposition induced by glucocorticoids alone. Thus, combination therapy may exhibit benefits for asthmatic patients beyond bronchodilating and anti-inflammatory effects.
Epiphrenic diverticulum of the esophagus after peroral endoscopic myotomy
Authors: Hiroki Sato, Kazuya Takahashi, Manabu Takeuchi, Yuichi Sato, Satoru Hashimoto, Kenichi Mizuno, Shuji Terai
Journal: Endoscopy (2015)

A 34-year-old man was referred to our hospital because of chest pain and dysphagia that had lasted for 5 years. Endoscopy showed a tight esophagogastric junction ([Fig. 1]). On high resolution manometry (Star Medical, Tokyo, Japan), the mean lower esophageal sphincter (LES) pressure and integrated relaxation pressure were 44.3 and 43.3 mmHg, respectively ([Fig. 2]). Type II achalasia was diagnosed according to the Chicago classification criteria [1].
Chelsea team doctor acted with “integrity and professionalism,” says medical body
Authors: Nigel Hawkes
Journal: BMJ (2015)

The body that represents doctors and health professionals in football has sprung to the defence of Eva Carneiro, team doctor for the Chelsea football club, after she became the butt of criticism from the club’s manager, Jose Mourinho, for going on to the field to treat an injured player.

In the final minutes of a match against Swansea on 8 August, the Chelsea player Eden Hazard was tripped, and Carneiro, together with the physiotherapist Jon Fearn, went onto the field to attend to him after the referee had waved them on. Chelsea were already down to 10 men after a player was sent off, and Mourinho feared that with only nine men they might lose the match, which was eventually drawn 2-2.

Mourinho said that the medical staff had been “impulsive and naive” and that they did not understand the game, but other medical professionals argued that they had no alternative. Eamonn Salmon, chief executive of the Football Medical Association, a UK body formed in 2010 to represent the interests of health professionals involved in professional football, said that …
Association between traffic-related air pollution exposure and risk of obstruction
Authors: Artur Badyda, Piotr Dabrowiecki, Wojciech Lubinski
Journal: European Respiratory Journal (2011)

Background:  Air pollution is associated with a number of respiratory diseases, but there is still a relatively small evidence between traffic-related (T-R) air pollutants concentration and a risk of obstruction among people living close to busy roads in East-Central Europe.   Material:  In 2 studies taken in 2005-2006 (Warsaw, Poland) and 2008-2009 (Gliwice, Poland) there were analyzed 1506 and 2000 persons respectively (inhabitants of urban and rural areas). Pulmonary function tests were completed (using Easy One spirometer) and occurrence of common respiratory system diseases symptoms, allergies, smoking habit, etc. were proved. Simultaneously traffic density and air pollutants concentration were measured. Association between place of living and air pollutants exposure and lung obstruction was explored by logistic regression analysis.   Results:  In both studies T-R air pollutants concentrations were statistically significant higher (p   Conclusion:  Presumably high T-R air pollutants concentration in the proximity of main roads is one of the significant reason of airways flow limitation. Therefore the risk of obstruction highly depends on place of living, particularly among non-smoking people.
A Bar Code of Selected Gene Copy Number Alterations is Associated with Disease-Free Survival in Stage Ii-Iii Microsatellite Stable (Mss) Colon Cancer
Authors: F. Di Fiore, L. Armengol-Debeir, F. Blanchard, C. Chapusot, B. Tournier, R. Sesboué, D. Sefrioui, P. Basile, A. Gangloff, M. Hebbar, M. Copin, C. Vasseur, J. Tuech, T. Vermeulin, E. Houivet, T. Frebourg, J. Sabourin, C. Lepage, P. Michel
Journal: Annals of Oncology (2014)
Age-Dependent Tumor-Host Barrier and Effect of Carcinogen-Induced Immunodepression on Rejection of Isografted Methylcholanthrene-Induced Sarcoma Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Jan Stjernswärd
Journal: JNCI Journal of the National Cancer Institute (1966)
The significance of residual mediastinal abnormality on the chest radiograph following treatment for Hodgkin's disease.
Authors: J A Radford, R A Cowan, M Flanagan, G Dunn, D Crowther, R J Johnson, B Eddleston
Journal: Journal of Clinical Oncology (1988)

The chest radiographs (CXRs) of 110 patients with mediastinal Hodgkin's disease (HD) were reviewed to determine the incidence, degree, and significance of mediastinal abnormalities following treatment. Residual mediastinal abnormalities were defined as either minimal or measurable, and occurred in 64% of all patients at the completion of treatment, but were more common in those with bulky mediastinal disease at presentation (40 of 48, 83%). Fifty-one patients with a mediastinal abnormality at the end of treatment had follow-up films available. Partial or complete regression of the abnormality occurred by 1 year in 30 of these patients (59%). Over a median follow-up of 80.5 months, there were more relapses (13 of 70, 19%) in patients with residual abnormalities following treatment than in those where the mediastinum was considered normal (four of 40, 10%). Measurable abnormality was associated with a higher relapse rate (six of 25, 24%) than minimal abnormality (seven of 45, 16%), but none of these differences were statistically significant. the subsequent relapse rate for patients with persisting abnormality at 1 year was 14%, compared with 17% for patients in whom regression had occurred and 14% in whom the mediastinum had always been considered normal. Considering the whole group, the presence of a mediastinal abnormality following treatment did not predict for relapse, but for the 34 patients treated by chemotherapy (CTR) alone, a residual abnormality was associated with a significantly higher relapse rate (P = .029). We conclude that following mediastinal radiotherapy (XRT) administered either alone or combined with CTR, residual mediastinal abnormalities do not indicate the need for further treatment. However, following CTR alone, such abnormalities may signify persisting disease and we recommend that XRT be considered for these patients.
Leadership by example: saying no to health industry board membership
Authors: David Rothman
Journal: BMJ (2015)

Prohibition is the best way to safeguard scientific and clinical integrity

Although medicine came late to managing conflict of interest and promoting transparency, well after law, finance, and government, it now confronts many of the critical issues. Part of the impetus to change was externally driven, with state and federal legislation playing a key role in the United States. For example, US senator Charles Grassley led the initiative to compel drug and device companies to disclose all payments over $10 (£6.47; €8.95) to physicians and teaching hospitals, with the data accessible, name by name, on a public website.1 But part of the impetus also came from within medicine. Several medical school deans believed that cozy ties between industry and faculty violated professional standards.2 At the same time, medical researchers documented the extent and impact of these relations. In a linked paper (doi:10.1136/bmj.h4826) a study of this problem by Anderson and colleagues is an excellent case in point.3

The research into physician-industry ties helped alter attitudes and practices. Dozens of well designed articles refuted …
Repeatability of MR imaging in chronic obstructive pulmonary disease (COPD)
Authors: Sebastian Ley, Angela Anjorin, Julia Ley-Zaporozhan, Annette Opgenorth, Oliver Sedlaczek, Claus-Peter Heussel, Hans-Ulrich Kauczor
Journal: European Respiratory Journal (2011)

Purpose:  COPD is a broad disease entity defined by PFT, however providing only a global measure of the disease. With the increasing number of therapeutic options, particularly when it is advanced, there is a high demand for a non-invasive imaging test to identify different phenotypes providing regional information on structural and functional changes in order to target therapies accordingly. Recent developments have opened the way for introduction of proton MRI of the lung into the clinical arena. This technique allows for radiation free assessment of the above mentioned issues. So far, no data regarding the repeatability of this technique is available.   Materials/Methods:  A comprehensive MR protocol (1.5T) was developed to investigate different aspects of the disease. The protocol consisted of morphological, pulmonary perfusion, cardiac function and respiratory dynamics sequences. Overall, 9 patients (COPD stages III&IV) were investigated twice in a 24h interval.   Results:  The mean examination time was 64min and all patients tolerated the examination well. Visual evaluation of morphological and perfusion sequences demonstrated a good repeatability of the visualization of the parenchymal loss and perfusion defects. Quantitative evaluation of flow measurements revealed considerable variations (interexamination difference for the PA flow: 7-64ml). Evaluation of the respiratory dynamics showed a broad variation allowing for no meaningful interpretation.   Conclusions:  Overall, the proposed imaging protocol is feasible and applicable even in significantly ill COPD patients. The protocol is easy to use and shows a high repeatability in the key aspects for assessment of morphological and functional disease components.
Re-irradiation using high precision radiotherapy and concomitant temozolomide in patients with recurrent glioma: Re- challenge with radio-chemotherapy
Authors: S. E. Combs, D. Schulz-Ertner, T. Welzel, M. Bischof, J. Debus
Journal: Journal of Clinical Oncology (2007)

12517 Background: This study was aimed to assess the toxicity and efficacy of radiochemotherapy (RCHT) with temozolomide performed as re-irradiation in patients with recurrent glioma. Patients and Methods: We treated 17 patients with RCHT for recurrent glioma between July 2005 and December 2006. Nine patients were female, eight were male. Pathology evaluation revealed WHO grade II astrocytoma in 5, anaplastic astrocytoma in 4 and glioblastoma multiforme (GBM) in 7 patients. One patient suffered from gliosarcoma. Median age at primary diagnosis was 33 years (range, 6–60 years). In 4 patients surgery had been performed as total resection, subtotal resection in 9 and as a biopsy in 4 patients. Median doses of radiotherapy (RT) of 60 Gy had been applied. Prior treatment with temozolomide either as RCHT or as chemotherapy alone for tumor progression had been performed in 8 patients. The median time interval between primary RT and re-irradiation was 29.5 months (range 5–180 months). Re-irradiation was performed as high precision radiotherapy using fractionated stereotactic radiotherapy (FSRT) in 16 patients with a median total dose of 36 Gy (range, 28–36 Gy); in one patients stereotactic radiosurgery (SRS) was applied for a very small lesion with a single dose of 18Gy/80% isodose. The target volume was defined as the area of contrast enhancement on T1-weighed MRI-scans including a safety margin of 0.5 to 1 cm. Chemotherapy was applied concomitantly in a median dose of 50 mg/m 2 per day (median of 100mg TMZ qd); in 14 patients RCHT was followed by adjuvant cycles of temozolomide. Results: Treatment could be completed in all patients without interruptions due to side effects; no severe acute or long-term toxicities were observed. One patient with recurrent GBM showed tumor progression during therapy and treatment was stopped at 32 Gy out of 36 Gy. Progression-free survival was 56% at 6 months after FSRT; survival after FSRT was 75% at 6 months. Median overall survival was 39 months, with 92% at 1 and 2 years. Conclusions: High-precision RT and concomitant temozolomide is safe and effective when performed as re-irradiation in recurrent glioma. The data demonstrate that re-challenge with temozolomide justifies further evaluation. No significant financial relationships to disclose.
Validation of an ELISA for the diagnosis of recent Campylobacter infections in Guillain–Barré and reactive arthritis patients
Authors: C.W. Ang, K. Krogfelt, P. Herbrink, J. Keijser, W. van Pelt, T. Dalby, M. Kuijf, B.C. Jacobs, M.P. Bergman, P. Schiellerup, C.E. Visser
Journal: Clinical Microbiology and Infection (2007)
Identification of Obesity and Cardiovascular Risk in Ethnically and Racially Diverse Populations
Authors: Goutham Rao, Tiffany M. Powell-Wiley, Irma Ancheta, Kristen Hairston, Katherine Kirley, Scott A. Lear, Kari E. North, Latha Palaniappan, Milagros C. Rosal
Journal: Circulation (2015)