tbuckley/cabot-search huggingface dataset:
Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer.
Authors: T J Kinsella, J B Mitchell, A Russo, M Aiken, G Morstyn, S M Hsu, J Rowland, E Glatstein
Journal: Journal of Clinical Oncology (1984)

Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1,000 mg/m2/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients. Local toxicity (within the radiation field) was minimal, with the exception of one of four patients, who underwent abdominal irradiation. Pharmacology studies revealed a steady-state arterial plasma level of 6 X 10(-7) mol/L and 1 X 10(-6) mol/L during infusion of 650 and 1,000 mg/m2/d, respectively. In vivo BUdR uptake into normal bone marrow was evaluated in two patients by comparison of preinfusion and postinfusion in vitro radiation survival curves of marrow CFUc with enhancement ratios (D0-pre/D0-post) of 1.8 (with 650 mg/m2/d) and 2.5 (with 1,000 mg/m2/d). In vivo BUdR incorporation into normal skin and tumor cells using an anti-BUdR monoclonal antibody and immunohistochemistry was demonstrated in biopsies from three patients revealing substantially less cellular incorporation into normal skin (less than 10%) compared with tumor (up to 50% to 70%). We conclude that local and systemic toxicity of continuous infusion of BUdR at 1,000 mg/m2/d for approximately two weeks is tolerable. The observed normal tissue toxicity is comparable with our previous clinical experience with intermittent (12 hours every day for two weeks) infusions of BUdR. Theoretically, a constant infusion should allow for greater incorporation of BUdR into cycling tumor cells and thus, for further enhancement of radiosensitization.
Hepatoerythropoietic porphyria due to a novel mutation in the uroporphyrinogen decarboxylase gene
Authors: J. To-Figueras, J.D. Phillips, J.M. Gonzalez-López, C. Badenas, I. Madrigal, E.M. González-Romarís, C. Ramos, J.M. Aguirre, C. Herrero
Journal: British Journal of Dermatology (2011)

Hepatoerythropoietic porphyria (HEP) is a rare form of porphyria that results from a deficiency of uroporphyrinogen decarboxylase (UROD). The disease is caused by homoallelism or heteroallelism for mutations in the UROD gene.
Abstract 1679: Association Between Obesity, hsCRP≥2, and Subclinical Atherosclerosis -Implications for the JUPITER Trial: Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Michael J Blaha, Juan J Rivera, Matthew Budoff, Ron Blankstein, Arthur Agatston, Dan H O'Leary, Roger S Blumenthal, Khurram Nasir
Journal: Circulation (2009)

Background: The JUPITER trial has led to increasing interest in the use of high-sensitivity C-reactive protein (hsCRP) as a screening tool for initiating lipid-lowering therapy. hsCRP is an inflammatory marker that is markedly correlated with traditional cardiovascular risk factors, including anthropomorphic measures of obesity (ρ=0.40 – 0.55). To help elucidate the implications of hsCRP measurement, we conducted a stratified analysis of the relationship between obesity, hsCRP>=2, and subclinical atherosclerosis. Methods: MESA is a longitudinal, population-based study of 6,814 men and women aged 45– 84 without clinical cardiovascular disease at enrollment. 4,533 individuals had baseline LDL-C <130 mg/dL. Body mass index (BMI) and hsCRP were measured at baseline, and all participants underwent non-contrast cardiac CT to measure coronary artery calcium (CAC) as well as carotid ultrasound to determine carotid intima-media thickness (CIMT). Patients were divided into 4 groups: non-obese/hsCRP<2, non-obese/hsC...
Cholangiocarcinoma cells are selectively susceptible to rapamycin treatment
Authors: Young Sung Yun, Be Hak Hong, Sunmi Hong, Eui Ho Kim, Mi-Sook Lee, Dae-Ghon Kim, Kwan Yong Choi
Journal: Clinical Cancer Research (2007)

C36   Cholangiocarcinoma (CC) is a malignant tumor which originates from the bile epithelium. A lipophilic macrolide antibiotic, rapamycin, is known to inhibit raptor-mTOR protein complex which plays a key role in protein translation and cellular growth and it was suggested as one of the effective drug candidates to target some cancer types. However, the anticancer effect of rapamycin has recently been controversial since rapamycin treatment induces contrasting effects on tumor cells such as proliferation inhibition, no response, or what is more, an increase in cell growth and proliferation. To identify the efficacy of rapamycin on tumor cells and its underlying molecular mechanism, three adenomatous CC cells such as JCK, CHO-CK, and CHOI-CK, and one sarcomatous CC cell, SCK, were investigated on the susceptibility to rapamycin. Western blot data clearly showed that mTOR signaling pathway including upstream molecules of mTOR and effector molecules associated with mTOR was highly activated in SCK and JCK relative to the other two CC cells. However, MTS assay showed that the proliferation of all four cells was inhibited in both 10 % serum-supplemented and serum-free media. Among them, SCK which exhibits sarcomatous character was more susceptible to rapamycin treatment. Wound healing and transwell experiments exhibited that the migration and invasion of sarcomatous SCK can also be highly suppressed by rapamycin. These results indicate that rapamycin can effectively inhibit proliferation, migration, and invasion of CC cells by blocking downstream pathway of raptor-mTOR complex.
OC-002 Do steroids improve the long-term outcome of autoimmune pancreatitis
Authors: N S Sandanayake, M H Chapman, E Kalaitzakis, Z Amin, M Novelli, A Winstanley, M Rodriguez-Justo, A R Hatfield, S P Pereira, G J Webster
Journal: Gut (2010)

<h3>Introduction</h3> Improvement in jaundice and pancreatic enlargement with prednisolone is a reliable and characteristic feature of autoimmune pancreatitis (AIP). The aim of this study was to investigate whether immunosuppression results in long-term preservation of pancreatic structure and function, as this has not been well defined. <h3>Methods</h3> We report a single-centre cohort study of all patients diagnosed with AIP from 2004 to 2009. Diagnosis was based on the HISORt criteria, while assessment of pancreatic morphology was made pre and post-treatment, by CT and/or MRI, according to clinical need. Exocrine and endocrine function was measured by stool faecal elastase 1 (FE1) and plasma glucose/HbA1c. <h3>Results</h3> Forty-one patients (33M/F8; median age 62 years, range 29–83) were included. Median follow-up to date is 35 months (range 1–71). At diagnosis, a pancreatic mass/diffuse swelling was noted in 36/41 (88%), serum IgG4 was elevated (&gt;1.3 g/l) in 22/41 (54%), and 30/41 (73%) had an immunohistological diagnosis, with &gt;10 IgG4-positive plasma cells/high power field (n=15 pancreas, n=8 liver, n=8 ampulla, n=2 salivary gland, n=2 renal). 30/41 (73%) had IgG4-associated cholangitis, 14/41 (34%) had other organ involvement (n=7 renal, n=3 salivary gland, n=2 retroperitoneal fibrosis, n=2 neurological). Seven (17%) of 41 patients had previously undergone pancreatobiliary surgery for presumed pancreatic cancer (n=3 Whipple resection, n=4 biliary bypass). 38/41 (93%) patients were treated with a tapering oral prednisolone regimen, which was ceased at a median of 6 months (range 2.5–70.9 months). An initial clinical, radiological, and biochemical response was seen in all patients. Relapse following disease remission or failure to wean steroids occurred in 19/41 (46%), and of these patients 6/19 were treated with steroids, and 13/19 were treated with prednisolone 30 mg and azathioprine 2 mg/kg daily. Post-steroid pancreatic atrophy was seen in 23/41 (56%). Low FE1 (&lt;200 μg/g of stool) was noted in 23/41 (56%). 15/41 (37%) patients were diabetic, while 9/41 (22%) have reduced bone mineral density (n=5 osteopaenia, n=4 osteoporosis). Three patients have died during follow-up (n=1 liver failure, n=1 encephalitis, n=1 cholangiocarcinoma). <h3>Conclusion</h3> While a favourable initial response to steroids is predictable in patients with a definitive diagnosis of AIP, loss of pancreatic structure and function is common, and the disease is associated with long-term morbidity and mortality. It will be difficult to clearly define the impact of treatment on the outcome of pancreatic and extra-pancreatic disease without a placebo controlled trial.
Paclitaxel in combination chemotherapy with radiotherapy in patients with unresectable stage III non-small-cell lung cancer.
Authors: F A Greco, S L Stroup, J R Gray, J D Hainsworth
Journal: Journal of Clinical Oncology (1996)

PURPOSE The addition of combination chemotherapy to standard radiation therapy has improved treatment for locally unresectable non-small-cell lung cancer. In this phase II study, we evaluated the toxicity and efficacy of a novel chemotherapy regimen that included paclitaxel, cisplatin, and etoposide plus concurrent radiation therapy in this group of patients. PATIENTS AND METHODS Thirty-three patients with previously untreated, unresectable stage III non-small-cell lung cancer (stage IIIA, 11 patients; stage IIIB, 22 patients) initially received two courses of chemotherapy, which included paclitaxel 135 mg/m2 by 1-hour infusion on day 1, cisplatin 60 mg/m/ intravenously (i.v.) on day 2, and etoposide 100 mg/m2 i.v. on days 1, 2 and 3. On week 6, radiation therapy (60 Gy in 30 fractions) was initiated in conjunction with two additional courses of chemotherapy: paclitaxel 135 mg/m2 i.v. by 1-hour infusion on day 1, cisplatin 5 mg/m2 i.v. on days 2- to 10, and etoposide 25 mg/m2 on days 1 to 10. RESULTS This combined modality program was feasible and well tolerated by most patients. During the two courses of induction chemotherapy, grade 3 or 4 myelosuppression occurred in only six patients (18%). Esophagitis was common during combined modality therapy (grade 3, 10 patients; grade 4 five patients). Forty-two percent of patients had partial response after two courses of induction therapy, and 82% of patients had an objective response at completion of therapy. Twelve patients (36%) had a complete response. Nineteen patients remain progression-free at a median of 8 months; the median survival time has not been reached. CONCLUSION This paclitaxel-containing combined modality therapy is feasible and highly active in patients with inoperable stage III lung cancer. Esophagitis is the most common severe toxicity with this program. Further studies with paclitaxel-containing combination regimens in patients with stage III non-small-cell lung cancer are indicated.
Effects of long term home NIV on lung inflammation in stable COPD
Authors: Gregorino Paone, Vittoria Conti, Corrado Mollica, Patrizio Palermo, Ilio Cammarella, Giuseppe Brunetti, Gianluca Monaco, Gilda Giannunzio, Giovanni Puglisi, Giacomo Frati
Journal: European Respiratory Journal (2013)

Background.  COPD is the most frequent indication for home NIV. Despite this, while NIV role in COPD exacerbations is well established, its effectiveness in patients with stable disease is under debate. No studies have evaluated the lung inflammatory response during home NIV in stable COPD.   Aims and objectives.  We evaluated pulmonary inflammation during long-term home NIV in stable COPD. We also analyzed the hospitalization and mortality rate during a two years follow up period.   Methods.  A prospective observational study was conducted on a group of consecutive unselected patients treated with home NIV (n= 68) and on a control group of individuals undergoing long term oxygen-therapy (n=75). All participants underwent pulmonary function tests (PFTs), arterial blood gas analysis (ABG), and sputum samples collection for IL-6, TNF-α, IL-10 and Human Neutrophil Peptides (HNP) levels determination. Participants entered the follow up in which, at three months intervals, PFTs, ABG, hospital admission and survival rate were recorded.   Results.  Study and control group were similar in age, gender, PFTs and ABG parameters. Sputum levels of IL-6 (41.4±27 vs 36.3±17.6 pg/ml; p=0.4), TNF-α (68.4±50.9 vs 59.7±46.9 pg/ml; p=0.5), IL-10 (11.3±10 vs 14.3±10 pg/ml; p=0.3) and HNP (34.3±5.9 vs 34.3±3.7 µg/ml; p=0.9) did not show significant differences between the two subsets of individuals. A significant reduction was observed in hospital admission in patients undergoing home NIV during the follow up (3,42 ± 3 vs 1,3 ± 1,6; p=0,0001).   Conclusions.  Our study, confirms previous reports on the effect of NIV in reducing exacerbation numbers in COPD patients and shows that long-term home NIV may not affect lung inflammatory response.
Hepatitis C virus drug resistance–associated substitutions: State of the art summary
Authors: Erik Lontok, Patrick Harrington, Anita Howe, Tara Kieffer, Johan Lennerstrand, Oliver Lenz, Fiona McPhee, Hongmei Mo, Neil Parkin, Tami Pilot‐Matias, Veronica Miller
Journal: Hepatology (2015)

Hepatitis C virus (HCV) drug development has resulted in treatment regimens composed of interferon-free, all-oral combinations of direct-acting antivirals. While the new regimens are potent and highly efficacious, the full clinical impact of HCV drug resistance, its implications for retreatment, and the potential role of baseline resistance testing remain critical research and clinical questions. In this report, we discuss the viral proteins targeted by HCV direct-acting antivirals and summarize clinically relevant resistance data for compounds that have been approved or are currently in phase 3 clinical trials.This report provides a comprehensive, systematic review of all resistance information available from sponsors' trials as a tool to inform the HCV drug development field.
Prognostic Value of Initial Fasting Serum Gastrin Levels in Patients With Zollinger-Ellison Syndrome
Authors: Adam C. Berger, Fathia Gibril, David J. Venzon, John L. Doppman, Jeffrey A. Norton, David L. Bartlett, Steven K. Libutti, Robert T. Jensen, H. Richard Alexander
Journal: Journal of Clinical Oncology (2001)

To assess the value of the initial fasting serum gastrin (FSG) at presentation in patients with Zollinger-Ellison Syndrome (ZES) in predicting primary tumor characteristics and survival.A total of 239 patients were treated for ZES between December 1981 and September 1998, with a mean follow-up of 9.1 +/- 0.6 years. At initial evaluation, 86 patients (36%) had mild (0 to 499 pg/mL), 61 (25.5%) had moderate (500 to 1,000 pg/mL), and 92 (38.5%) had severe (> 1,000 pg/mL) elevations in FSG. Primary tumor location and size, presence of lymph node or hepatic metastases, and survival were analyzed based on the level of initial FSG.In patients with sporadic ZES, but not in those with multiple endocrine neoplasia type 1 (MEN-1) and ZES, there was a significant relationship between the level of initial FSG and tumor size and location of primary tumor, frequency of lymph node and liver metastases, and survival. The median 5- and 10-year survival decreased with increasing initial FSG (P <.001) in patients with sporadic ZES; MEN-1 patients lived longer than sporadic ZES patients (P =.012), and survival in this group was not associated with the level of initial FSG. Multivariate analysis showed that factors independently associated with death from disease in patients with sporadic ZES were liver metastases (P =.0001), a pancreatic site (P =.0027), and primary tumor size (P =.011) but not initial FSG (P >.30).The severity of FSG at presentation is associated with size and site of tumor and the presence of hepatic metastases, factors that are significant independent predictors of outcome. The level of FSG at presentation may be useful in planning the nature and extent of the initial evaluation and management in patients with sporadic ZES.
Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases
Authors: Yun R Li, Jin Li, Sihai D Zhao, Jonathan P Bradfield, Frank D Mentch, S Melkorka Maggadottir, Cuiping Hou, Debra J Abrams, Diana Chang, Feng Gao, Yiran Guo, Zhi Wei, John J Connolly, Christopher J Cardinale, Marina Bakay, Joseph T Glessner, Dong Li, Charlly Kao, Kelly A Thomas, Haijun Qiu, Rosetta M Chiavacci, Cecilia E Kim, Fengxiang Wang, James Snyder, Marylyn D Richie, Berit Flatø, Øystein Førre, Lee A Denson, Susan D Thompson, Mara L Becker, Stephen L Guthery, Anna Latiano, Elena Perez, Elena Resnick, Richard K Russell, David C Wilson, Mark S Silverberg, Vito Annese, Benedicte A Lie, Marilynn Punaro, Marla C Dubinsky, Dimitri S Monos, Caterina Strisciuglio, Annamaria Staiano, Erasmo Miele, Subra Kugathasan, Justine A Ellis, Jane E Munro, Kathleen E Sullivan, Carol A Wise, Helen Chapel, Charlotte Cunningham-Rundles, Struan F A Grant, Jordan S Orange, Patrick M A Sleiman, Edward M Behrens, Anne M Griffiths, Jack Satsangi, Terri H Finkel, Alon Keinan, Eline T Luning Prak, Constantin Polychronakos, Robert N Baldassano, Hongzhe Li, Brendan J Keating, Hakon Hakonarson
Journal: Nature Medicine (2015)
Prevalence of contralateral testicular intraepithelial neoplasia in patients with testicular germ cell neoplasms.
Authors: K P Dieckmann, V Loy
Journal: Journal of Clinical Oncology (1996)

PURPOSE Testicular intraepithelial neoplasia ([TIN], so-called carcinoma in situ of the testis) is hypothesized to be the precursor of testicular germ cell neoplasms. According to previous studies, it can be detected by testicular biopsy. Since patients with a unilateral testicular tumor are at high risk of a second testicular tumor, it seemed feasible to examine the prevalence of contralateral TIN in patients with testicular germ cell cancer and correlate it with the known prevalence of bilateral testicular tumors. The aim was to provide more evidence for the role of TIN as the preinvasive stage of testicular cancer. PATIENTS AND METHODS Nineteen hundred fifty-four consecutive patients with a unilateral testicular germ cell tumor underwent contralateral biopsy. All specimens were examined immunohistologically. RESULTS TIN was observed in 4.9% (95% confidence interval [CI], 3.95% to 5.91%). Testicular atrophy and a history of undescended testis were more frequently observed in patients with contralateral TIN, but only atrophy was shown to be independently associated by multivariate analysis. Patients with testicular atrophy have a 4.3-fold increased risk of having contralateral TIN. Sixty-four percent of TIN cases were found in normal testes. Patients with TIN were significantly younger than those without (P &lt; .0017). Three patients developed a second testicular tumor despite a negative biopsy for TIN. CONCLUSION The prevalence of contralateral TIN corresponds well to the known prevalence of bilateral testicular tumors. Testicular atrophy is a strong indicator for the presence of TIN, but approximately 60% of TIN cases occur without atrophy. The present data are in accordance with the theory that TIN is an early step in the histogenesis of testicular germ cell neoplasms.
Identification of patients with atrial fibrillation in general practice
Authors: E. Roderick, J. Cox, D A Fitzmaurice
Journal: BMJ (1999)

Laparoscopic versus open mesh repair of inguinal hernia For most patients hernias provoke minimal symptomsEditor-In Wellwood et al's trial of laparoscopic hernia repair versus open mesh repair only patients fit for general anaesthesia were preselected. 1 We do not know if the rejected patients were suitable for local anaesthesia, which is usually ideal for frail and elderly patients and those with high American Society of Anesthesiologists grades.The type of anaesthesia used greatly affects morbidity associated with elective hernia repair. 2 As the authors report, after laparoscopic repair with general anaesthesia, patients may have postoperative nausea, vomiting, and retention of urine.Disorientation and cognitive dysfunction may occur with elderly patients after general anaesthesia but are rare after local anaesthesia.In Wellwood et al's trial postoperative discomfort after laparoscopic repair was reduced slightly, but does it matter?Assessment of postoperative pain is difficult, but elderly patients commonly experience less pain and require less analgesia than young adults after open hernia repair.This might be attributed to the loss of neurones with ageing 3 combined with the decrease in muscle bulk.Although laparoscopic repair is more expensive, many people have suggested that there are economic benefits of early return to work.In reality this is not so: patients over 60 are unlikely to be engaged in the labour market, so there is minimal benefit.For elderly patients, who represent half of most series, whether laparoscopic repair offers any benefits at all remains to be proved.Even with rapid recovery most employees expect a traditional amount of time off, whereas self employed patients tend to return to work as soon as possible despite any slight discomfort.The ability and desire to return to work are subjective and greatly influenced by personal circumstances.Laparoscopic repair is a more complex invasive procedure, and catastrophic complications may occur 4 ; these are unheard of with open repair.In a statistical sense the non-occurrence of an adverse event in a surgical series, as reported in this trial, does not mean that it cannot happen.Major complications from the pneumoperitoneum, bowel and vascular perforation, and acute and delayed intestinal obstruction do occur.For most patients a hernia is a benign lump that provokes minimal symptoms.Why expose patients to the major risks of a laparoscopic approach when there are marginal differences in outcome compared with open mesh repair under local anaesthesia, especially when open mesh repair is technically simple, is easily learnt, has consistent results, and is safer and cost effective?
Bronchial thermoplasty in asthma: 2-year follow-up using optical coherence tomography
Authors: Miranda Kirby, Keishi Ohtani, Rosa Maria Lopez Lisbona, Anthony M.D. Lee, Wei Zhang, Pierre Lane, Nina Varfolomeva, Linda Hui, Diana Ionescu, Harvey O. Coxson, Calum MacAulay, J. Mark FitzGerald, Stephen Lam
Journal: European Respiratory Journal (2015)

Bronchial thermoplasty (BT) is a novel, nonpharmacological procedure for treatment of severe asthma. Recently, the Asthma Intervention Research 2 clinical trial demonstrated asthmatics had fewer hospitalisations following BT, which persisted 5 years after therapy [1]. However, it is well recognised that asthma is a heterogeneous disease with distinct asthma phenotypes and, not surprisingly, not all asthmatics in that trial benefited from BT [2]. Optical coherence tomography small airway imaging may be used for better patient phenotyping and selection for BT <http://ow.ly/O0Cm2> We thank Myles McKinnon, Jennifer Campbell and Chulho Hyun (British Columbia Cancer Agency, Vancouver, BC, Canada) for their assistance with the bronchoscopy procedures.