tbuckley/cabot-search huggingface dataset:
Risk Factors Before Autologous Stem-Cell Transplantation for Lymphoma Predict for Secondary Myelodysplasia and Acute Myelogenous Leukemia
Authors: Matt Kalaycio, Lisa Rybicki, Brad Pohlman, Ronald Sobecks, Steven Andresen, Elizabeth Kuczkowski, Brian Bolwell
Journal: Journal of Clinical Oncology (2006)

The risk factors for treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (AML) after autologous stem-cell transplantation (ASCT) are similar to those that increase the risk of difficult stem-cell harvests. We reviewed our experience in 526 patients with lymphoma treated by ASCT to determine whether difficult stem-cell harvests predict for an increased risk of t-MDS/AML.Autologous peripheral stem cells were initially mobilized with granulocyte colony-stimulating factor (G-CSF; or granulocyte-macrophage colony-stimulating factor) alone (n = 334), etoposide and G-CSF (n = 166), or cyclophosphamide and G-CSF with or without etoposide (n = 26). Difficult harvests were those that required more than 5 days to collect enough stem cells and those that required additional attempts with etoposide and/or cyclophosphamide plus G-CSF (n = 52). All patients were then treated with high-dose chemotherapy alone and observed for outcome.With a median follow-up time for surviving patients of 69 months, 20 patients developed t-MDS/AML, for an actuarial incidence of 6.8% at 10 years. Pretransplantation characteristics, including age, diagnosis of non-Hodgkin's lymphoma or Hodgkin's disease, bone marrow involvement, prior radiation therapy, prior exposure to chemotherapy, lactate dehydrogenase at the time of ASCT, disease status, and method of stem-cell mobilization, were then analyzed with respect to the subsequent development of t-MDS/AML. By multivariable analysis, prior exposure to radiation therapy, four or more chemotherapy regimens, and more than 5 days of apheresis needed to harvest enough stem cells were identified as independent risk factors for t-MDS/AML. Bootstrap analysis confirmed these results.These results suggest that identifiable pretransplantation factors predict for t-MDS/AML after ASCT.
Management of Benign Prostatic Hyperplasia
Authors: Eric H. Kim, Jeffrey A. Larson, Gerald L. Andriole
Journal: Annual Review of Medicine (2015)

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) commonly affect older men. Age-related changes associated with metabolic disturbances, changes in hormone balance, and chronic inflammation may cause BPH development. The diagnosis of BPH hinges on a thorough medical history and focused physical examination, with attention to other conditions that may be causing LUTS. Digital rectal examination and urinalysis should be performed. Other testing may be considered depending on presentation of symptoms, including prostate-specific antigen, serum creatinine, urine cytology, imaging, cystourethroscopy, post-void residual, and pressure-flow studies. Many medical and surgical treatment options exist. Surgery should be reserved for patients who either have failed medical management or have complications from BPH, such as recurrent urinary tract infections, refractory urinary retention, bladder stones, or renal insufficiency as a result of obstructive uropathy.
Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection
Authors: L Bont
Journal: Thorax (2004)

<b>Background:</b> It is well known that respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with subsequent wheezing episodes, but the precise natural course of wheezing following RSV LRTI is not known. This study aimed to determine the continuous development of wheezing following RSV LRTI in children up to the age of 3 years. <b>Methods:</b> A prospective cohort study was performed in 140 hospitalised infants with RSV LRTI. Continuous follow up data were obtained with a unique log in which parents noted daily respiratory symptoms. <b>Results:</b> A marked decrease in wheezing was seen during the first year of follow up. The burden of wheezing following RSV LRTI was observed during the winter season. Signs of airflow limitation during RSV LRTI were strongly associated with wheezing during the follow up period. Total and specific serum immunoglobulin E levels, patient eczema, and parental history of atopy were not associated with wheezing. <b>Conclusions:</b> Airway morbidity following RSV LRTI has a seasonal pattern, which suggests that viral upper respiratory tract infections are the predominant trigger for wheezing following RSV LRTI. There is a significant decrease in airway symptoms during the first 12 months after admission to hospital. Simple clinical variables, but not allergic risk factors, can predict the development of wheezing following RSV LRTI.
Fibrin-based clot formation as an early and rapid biomarker for progression of postpartum hemorrhage: a prospective study
Authors: Peter W. Collins, Graeme Lilley, Daniel Bruynseels, David Burkett-St. Laurent, Rebecca Cannings-John, Elizabeth Precious, Vincent Hamlyn, Julia Sanders, Raza Alikhan, Rachel Rayment, Alexandra Rees, Abigail Kaye, Judith E. Hall, Shantini Paranjothy, Andrew Weeks, Rachel E. Collis
Journal: Blood (2014)
A Smartphone Application to Support Recovery From Alcoholism
Authors: David H. Gustafson, Fiona M. McTavish, Ming-Yuan Chih, Amy K. Atwood, Roberta A. Johnson, Michael G. Boyle, Michael S. Levy, Hilary Driscoll, Steven M. Chisholm, Lisa Dillenburg, Andrew Isham, Dhavan Shah
Journal: JAMA Psychiatry (2014)

<h3>Importance</h3> Patients leaving residential treatment for alcohol use disorders are not typically offered evidence-based continuing care, although research suggests that continuing care is associated with better outcomes. A smartphone-based application could provide effective continuing care. <h3>Objective</h3> To determine whether patients leaving residential treatment for alcohol use disorders with a smartphone application to support recovery have fewer risky drinking days than control patients. <h3>Design, Setting, and Participants</h3> An unmasked randomized clinical trial involving 3 residential programs operated by 1 nonprofit treatment organization in the Midwestern United States and 2 residential programs operated by 1 nonprofit organization in the Northeastern United States. In total, 349 patients who met the criteria for<i>DSM-IV</i>alcohol dependence when they entered residential treatment were randomized to treatment as usual (n = 179) or treatment as usual plus a smartphone (n = 170) with the Addiction–Comprehensive Health Enhancement Support System (A-CHESS), an application designed to improve continuing care for alcohol use disorders. <h3>Interventions</h3> Treatment as usual varied across programs; none offered patients coordinated continuing care after discharge. A-CHESS provides monitoring, information, communication, and support services to patients, including ways for patients and counselors to stay in contact. The intervention and follow-up period lasted 8 and 4 months, respectively. <h3>Main Outcomes and Measures</h3> Risky drinking days—the number of days during which a patient's drinking in a 2-hour period exceeded 4 standard drinks for men and 3 standard drinks for women, with<i>standard drink</i>defined as one that contains roughly 14 g of pure alcohol (12 oz of regular beer, 5 oz of wine, or 1.5 oz of distilled spirits). Patients were asked to report their risky drinking days in the previous 30 days on surveys taken 4, 8, and 12 months after discharge from residential treatment. <h3>Results</h3> For the 8 months of the intervention and 4 months of follow-up, patients in the A-CHESS group reported significantly fewer risky drinking days than did patients in the control group, with a mean of 1.39 vs 2.75 days (mean difference, 1.37; 95% CI, 0.46-2.27;<i>P</i> = .003). <h3>Conclusions and Relevance</h3> The findings suggest that a multifeatured smartphone application may have significant benefit to patients in continuing care for alcohol use disorders. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01003119
Drug Dosing for Renoprotection
Authors: Dick de Zeeuw, Hiddo Lambers-Heerspink
Journal: Journal of the American Society of Nephrology (2009)

The maximum recommended therapeutic dose (MRTD) of a drug is an important limit not only for the manufacturer but also for physicians and their patients.1 Limits are derived from a dose-response curve that represents the combination of optimal efficacy and highest safety. The MRTD is established during the developmental phase of a drug. An error in that process may be very costly for both the manufacturer and patients. For example, when looking at the development of drugs altering the renin-angiotensin-aldosterone system (RAAS), there are interesting examples of “mistakes.” Captopril was the first practical drug to target the RAAS in the angiotensin-converting enzyme inhibitor (ACEI) class. During initial testing, the drug was given at dosages of 450 mg/d. Although BP was very effectively lowered, these dosages produced adverse effects such as decreases in renal function, increases in albuminuria, and skin rashes.2 Too high a dosage was later determined as the reason for these unwanted effects. Ironically, subsequent ACEIs, including lower dosages of captopril, were used to reduce albuminuria and provide renoprotection.3 When the first drug in a second new class targeting RAAS, the angiotensin II receptor blockers (ARBs), was launched, the manufacturer and regulators did not want to make the same mistake twice, and care was taken in establishing the MRTD for losartan at 50 mg/d. The choice of this dosage may have been too …
A crucial role for interleukin (IL)-1 in the induction of IL-17–producing T cells that mediate autoimmune encephalomyelitis
Authors: Caroline Sutton, Corinna Brereton, Brian Keogh, Kingston H.G. Mills, Ed C. Lavelle
Journal: The Journal of Experimental Medicine (2006)

It was recently demonstrated that interleukin (IL)-23–driven IL-17–producing (ThIL-17) T cells mediate inflammatory pathology in certain autoimmune diseases. We show that the induction of antigen-specific ThIL-17 cells, but not T helper (Th)1 or Th2 cells, by immunization with antigens and adjuvants is abrogated in IL-1 receptor type I–deficient (IL-1RI−/−) mice. Furthermore, the incidence of experimental autoimmune encephalomyelitis (EAE) was significantly lower in IL-1RI−/− compared with wild-type mice, and this correlated with a failure to induce autoantigen-specific ThIL-17 cells, whereas induction of Th1 and Th2 responses was not substantially different. However, EAE was induced in IL-1RI−/− mice by adoptive transfer of autoantigen-specific cells from wild-type mice with EAE. IL-23 alone did not induce IL-17 production by T cells from IL-1RI−/− mice, and IL-23–induced IL-17 production was substantially enhanced by IL-1α or IL-1β, even in the absence of T cell receptor stimulation. We demonstrate essential roles for phosphatidylinositol 3-kinase, nuclear factor κB, and novel protein kinase C isoforms in IL-1– and IL-23–mediated IL-17 production. Tumor necrosis factor α also synergized with IL-23 to enhance IL-17 production, and this was IL-1 dependent. Our findings demonstrate that IL-1 functions upstream of IL-17 to promote pathogenic ThIL-17 cells in EAE.
Defining Death: The Role of Brain Function
Authors: Robert M. Veatch
Journal: JAMA (1979)

WhenThe Journalpublished the report of the Ad Hoc Committee of Harvard Medical School on the definition of irreversible coma,<sup>1</sup>now more than a decade ago, many thought that it would quickly lead to changes in clinical practices for pronouncing death—that at least change would come for those special cases where brain function has ceased irreversibly while respiratory and cardiac function continues. Of course, pronouncing death in such cases was contrary to legal tradition and remains so in some jurisdictions. Wise clinicians awaited a change in the law. In 1970 laws began to change. Although early proposals had serious problems,<sup>2</sup>model laws emerged that resolved the more obvious difficulties.<sup>3-4</sup> But the historical evolution has slowed. While approximately 20 states have adopted legal changes in the years after the Harvard report, the rate of change has recently decreased. Physicians are, or should be, bound by law. Where
Glomus vagale presenting as chronic cough
Authors: A. Fahim, S. Faruqi, N. D. Stafford, A. H. Morice
Journal: European Respiratory Journal (2010)

To the Editors: 

Chronic cough is one of the most common symptoms of medical importance with 12% of the population reporting significant symptoms on a daily or weekly basis. The differential diagnosis of chronic cough is extensive. Uncommon causes of chronic cough may be missed unless an adequate history is obtained, a detailed examination performed and appropriate investigations arranged. Herein, we present a case of chronic cough, the aetiology of which was previously unreported.

A 57-yr-old female presented with a history of chronic cough for 12 months. The cough had features of reflux 1 as it was precipitated by food and phonation, and associated with frequent clearing of the throat. Moreover, the cough was worse when she was lying flat and started upon rising in the morning. In addition, she described her cough to be precipitated by upward movement of her neck, for example looking at the top shelf in a supermarket. There was no history of decreased appetite or weight loss. She was known to have a hiatus hernia. Her past medical history was otherwise unremarkable. She was a life long nonsmoker and was not on any regular medications. In view of clinical history being highly suggestive of reflux cough, she was started on treatment with lansoprazole in combination with ranitidine; however, she …
Antigen-Specific CD4+ T Cells Regulate Function of Myeloid-Derived Suppressor Cells in Cancer via Retrograde MHC Class II Signaling
Authors: Srinivas Nagaraj, Allison Nelson, Je-in Youn, Pingyan Cheng, David Quiceno, Dmitry I. Gabrilovich
Journal: Cancer Research (2012)

Myeloid-derived suppressor cells (MDSC) play a major role in cancer-related immune suppression, yet the nature of this suppression remains controversial. In this study, we evaluated the ability of MDSCs to elicit CD4(+) T-cell tolerance in different mouse tumor models. In contrast to CD8(+) T-cell tolerance, which could be induced by MDSCs in all the tumor models tested, CD4(+) T-cell tolerance could be elicited in only one of the models (MC38) in which a substantial level of MHC class II was expressed on MDSCs compared with control myeloid cells. Mechanistic investigations revealed that MDSCs deficient in MHC class II could induce tolerance to CD8(+) T cells but not to CD4(+) T cells. Unexpectedly, antigen-specific CD4(+) T cells (but not CD8(+) T cells) could dramatically enhance the immune suppressive activity of MDSCs by converting them into powerful nonspecific suppressor cells. This striking effect was mediated by direct cell-cell contact through cross-linking of MHC class II on MDSCs. We also implicated an Ets-1 transcription factor-regulated increase in expression of Cox-2 and prostaglandin E2 in MDSCs in mediating this effect. Together, our findings suggest that activated CD4(+) T cells that are antigen specific may enhance the immune suppressive activity of MDSCs, a mechanism that might serve normally as a negative feedback loop to control immune responses that becomes dysregulated in cancer.
Synergistic induction of apoptosis by simultaneous disruption of the Bcl-2 and MEK/MAPK pathways in acute myelogenous leukemia
Authors: Michele Milella, Zeev Estrov, Steven M. Kornblau, Bing Z. Carter, Marina Konopleva, Ana Tari, Wendy D. Schober, David Harris, Clinton E. Leysath, Gabriel Lopez-Berestein, Ziwei Huang, Michael Andreeff
Journal: Blood (2002)
Combining Gemcitabine and Capecitabine in Patients With Advanced Biliary Cancer: A Phase II Trial
Authors: Jennifer J. Knox, David Hedley, Amit Oza, Ron Feld, Lillian L. Siu, Eric Chen, Mahsan Nematollahi, Gregory R. Pond, Jessica Zhang, Malcolm J. Moore
Journal: Journal of Clinical Oncology (2005)

Purpose Biliary cancer has a poor prognosis, and chemotherapy has had little impact. The objectives of this trial were to determine the response rate, time to disease progression, survival, and safety profile of the combination of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer. Patients and Methods Eligible patients had pathologically proven, locally advanced or metastatic adenocarcinoma arising from the intra- and extrahepatic bile ducts or gallbladder with no prior chemotherapy. Patients were treated on a 3-week cycle consisting of capecitabine at 650 mg/m 2 orally twice a day for 14 days and gemcitabine at a fixed dose of 1,000 mg/m 2 intravenously over 30 minutes on days 1 and 8. Results Forty-five patients were enrolled between July 2001 and January 2004. Fifty-three percent of patients had cholangiocarcinoma, 47% had gallbladder cancer, and 89% had metastatic disease. The overall objective response rate was 31%, with an additional 42% of patients with stable disease, for a disease control rate of 73%. The median overall survival time was 14 months (95% CI, 7.3 months to not available), and the median progression-free survival time was 7 months (95% CI, 4.6 to 11.8 months). This chemotherapy combination was generally well tolerated. Transient neutropenia, thrombocytopenia, fatigue, and hand-foot syndrome were commonly observed but were easily managed without discontinuing further treatment. Conclusion The significant antitumor activity combined with a mild toxicity profile seen in this study argue that GemCap chemotherapy may benefit patients with advanced biliary cancer. This regimen warrants further evaluation in a randomized study with survival and quality of life end points.
The effect of healing on bile reflux in gastric ulcer
Authors: R. B. Black, G. Roberts, J. Rhodes
Journal: Gut (1971)

Bile reflux has been studied by serial estimations of bile acid concentrations in the stomach before and after a liquid meal. Thirteen normal subjects and 38 patients with gastric ulcer were examined. Thirty-one in the ulcer group had the test repeated once or twice within two months of the initial test to observe any change in reflux associated with healing. Patients with gastric ulcer had significantly higher concentrations of bile acids than normal subjects, both before and after the meal, although there was an overlap between the groups. In patients with an ulcer which healed or showed some healing over two months, no consistent change in reflux was found.
Differential DNA methylation in discrete developmental stages of the parasitic nematode Trichinella spiralis
Authors: Fei Gao, Xiaolei Liu, Xiu-Ping Wu, Xue-Lin Wang, Desheng Gong, Hanlin Lu, Yudong Xia, Yanxia Song, Junwen Wang, Jing Du, Siyang Liu, Xu Han, Yizhi Tang, Huanming Yang, Qi Jin, Xiuqing Zhang, Mingyuan Liu
Journal: Genome biology (2012)

Abstract Background DNA methylation plays an essential role in regulating gene expression under a variety of conditions and it has therefore been hypothesized to underlie the transitions between life cycle stages in parasitic nematodes. So far, however, 5'-cytosine methylation has not been detected during any developmental stage of the nematode Caenorhabditis elegans . Given the new availability of high-resolution methylation detection methods, an investigation of life cycle methylation in a parasitic nematode can now be carried out. Results Here, using MethylC-seq, we present the first study to confirm the existence of DNA methylation in the parasitic nematode Trichinella spiralis , and we characterize the methylomes of the three life-cycle stages of this food-borne infectious human pathogen. We observe a drastic increase in DNA methylation during the transition from the new born to mature stage, and we further identify parasitism-related genes that show changes in DNA methylation status between life cycle stages. Conclusions Our data contribute to the understanding of the developmental changes that occur in an important human parasite, and raises the possibility that targeting DNA methylation processes may be a useful strategy in developing therapeutics to impede infection. In addition, our conclusion that DNA methylation is a mechanism for life cycle transition in T. spiralis prompts the question of whether this may also be the case in any other metazoans. Finally, our work constitutes the first report, to our knowledge, of DNA methylation in a nematode, prompting a re-evaluation of phyla in which this epigenetic mark was thought to be absent.
Acute Wounds Accelerate Tumorigenesis by a T Cell–Dependent Mechanism
Authors: Christina H. Stuelten, Adrian Barbul, Johanna I. Busch, Emily Sutton, Ryan Katz, Misako Sato, Lalage M. Wakefield, Anita B. Roberts, John E. Niederhuber
Journal: Cancer Research (2008)

Abstract We investigated the influence of acute wounding on tumor growth in a syngeneic mouse breast cancer model. Metastatic mouse breast cancer cells (4T1) were orthotopically injected into the mammary fat pads of BALB/c mice, and animals were wounded locally by full thickness dermal incisions above the mammary fat pads or remotely above the scapula 9 days later. Local, but not remote, wounding increased tumor size when compared with sham treatment. Injection of wound fluid close to the tumor site increased tumor growth, whereas in vitro wound fluid compared with serum increased the proliferation rate of 4T1 cells. Our results show that wound stroma can unfavorably influence growth of nearby tumors. This effect is T cell–dependent, as local wounding had no effect on tumor growth in nu/nu mice. The effect of wounding on tumor growth can be mimicked by acellular wound fluid, suggesting that T cells secrete or mediate secretion of cytokines or growth factors that then accelerate tumor growth. Here, we define an experimental model of wound-promoted tumor growth that will enable us to identify mechanisms and therapeutic targets to reduce the negative effect of tissue repair on residual tumors. [Cancer Res 2008;68(18):7278–82]
Surrogate end points for overall survival and local control in neoadjuvant rectal cancer trials: statistical evaluation based on the FFCD 9203 trial
Authors: N. Methy, L. Bedenne, T. Conroy, O. Bouché, O. Chapet, M. Ducreux, J.-P. Gérard, F. Bonnetain
Journal: Annals of Oncology (2009)

In resectable rectal cancer trials, pathological parameters are early preoperative treatment efficacy measures. Their validation as surrogate end points for long-term clinical outcomes would allow to reduce trial duration. The aim was to evaluate potential surrogates for overall survival (OS) and local control (LC) in preoperative T3/T4 rectal cancer trials. Candidate variables included ypT and ypN stages, T downstaging, tumor regression grade (TRG), and circumferential resection margin (CRM) status.In the Fédération Francophone de Cancérologie Digestive (FFCD) 9203 trial, 742 eligible patients were randomly assigned to receive preoperative radiotherapy with or without concurrent chemotherapy. Surrogacy was evaluated using Prentice criteria and the proportion of treatment effect (PTE) explained by each potential surrogate.None of the candidate surrogates fulfilled all Prentice criteria. Data analyses did not provide interpretable PTE measures for OS. Regarding LC, the highest PTE was reached by TRG, which explained 12% of the effect on local recurrence. This proportion may not exceed 41% [95% confidence interval (CI) -1% to 41%]. PTE explained by the CRM status was associated with a wide uncertainty (95% CI -81% to 105%), which does not exclude a potentially high degree of surrogacy.In the FFCD 9203 trial, pathological parameters were not surrogate for OS or LC.