tbuckley/cabot-search huggingface dataset:
Autologous and Allogeneic Stem-Cell Transplantation for Transformed Follicular Lymphoma: A Report of the Canadian Blood and Marrow Transplant Group
Authors: Diego Villa, Michael Crump, Tony Panzarella, Kerry J. Savage, Cynthia L. Toze, Douglas A. Stewart, David A. MacDonald, Rena Buckstein, Christina Lee, Mohsen Alzahrani, Morel Rubinger, Ronan Foley, Anargyros Xenocostas, Mitchell Sabloff, Alexandra Muccilli, Neil Chua, Felix Couture, Jean-François Larouche, Sandra Cohen, Joseph M. Connors, Kimberley Ambler, Abdulwahab Al-Tourah, Khaled M. Ramadan, John Kuruvilla
Journal: Journal of Clinical Oncology (2013)

To determine whether autologous (auto) or allogeneic (allo) stem-cell transplantation (SCT) improves outcome in patients with transformed follicular lymphoma compared with rituximab-containing chemotherapy alone.This was a multicenter cohort study of patients with follicular lymphoma and subsequent biopsy-proven aggressive histology transformation. Patient, treatment, and outcome data were collected from each transplantation center and combined for analysis. A separate control group was composed of patients with transformation treated with rituximab-containing chemotherapy but not SCT. The primary end point was overall survival (OS) after transformation.One hundred seventy-two patients were identified: 22 (13%) treated with alloSCT, 97 (56%) with autoSCT, and 53 (31%) with rituximab-containing chemotherapy. Five-year OS after transformation was 46% for patients treated with alloSCT, 65% with autoSCT, and 61% with rituximab-containing chemotherapy (P = .24). Five-year progression-free survival (PFS) after transformation was 46% for those treated with alloSCT, 55% with autoSCT, and 40% with rituximab-containing chemotherapy (P = .12). In multivariate analysis, patients treated with autoSCT had improved OS compared with those who received rituximab-containing chemotherapy (hazard ratio [HR], 0.13; 95% CI, 0.05 to 0.34; P < .001). On the other hand, there was no OS difference between those treated with alloSCT and rituximab-containing chemotherapy (HR, 0.44; 95% CI, 0.16 to 1.24; P = .12). OS and PFS after SCT were similar between those treated with autoSCT and alloSCT. Five-year transplantation-related mortality was 23% for those treated with alloSCT and 5% for autoSCT.Patients undergoing autoSCT had better outcomes than those treated with rituximab-containing chemotherapy alone. AlloSCT did not improve outcome compared with rituximab-containing chemotherapy and was associated with clinically significant toxicity.
Oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular carcinoma
Authors: A.B. Benson, E. Mitchell, N. Abramson, B. Klencke, P. Ritch, J.P. Burnham, C. McGuirt, T. Bonny, J. Levin, J. Hohneker
Journal: Annals of Oncology (2002)
The Department of Health's research governance framework remains an impediment to multi-centre studies: findings from a national descriptive study
Authors: T. Kielmann, A. Tierney, R. Porteous, G. Huby, A. Sheikh, H. Pinnock
Journal: Journal of the Royal Society of Medicine (2007)

We describe our experience of using the standard application form, designed to streamline applications for multi-centre research, to seek approval from all primary care organizations (PCOs) in England and Wales to undertake a single telephone interview with a health service manager.We sent applications (n=316), by email to each PCO, or consortium of PCOs, attaching a completed standard application form, the 15 required documents, and the approval we had been granted by the lead NHS organization. We maintained detailed records of the responses to our application, subsequent correspondence, additional paperwork requested, and time spent on the approval process.The UK Research Governance Framework, which regulates all research conducted in health and social care settings.All PCOs in England and Wales.None.Time taken to obtain approval to undertake a telephone interview with a health service manager.We were unable to establish contact with 13 (4%) PCOs. Six months after submitting our application we had received approval from 259/316 (82%) PCOs and were still awaiting a verdict from 41 (13%). The median time to approval was 56 days (IQR 42-72). Overall, an estimated 318 staff-hours were spent completing supplementary forms, providing additional information and chasing up dormant applications.Recent initiatives to 'streamline' research governance approval have failed to address the problems that face researchers undertaking multi-centre studies. There is an urgent need to develop a simpler process that allows low risk research to take place without threatening staff morale and endangering the quality of the research outputs. In the meantime, we advise researchers to allow far greater time than might reasonably be envisioned to obtain research governance approval.
Increased incidence of nonfatal cardiovascular events in stroke patients with sleep apnoea: effect of CPAP treatment
Authors: M-A. Martínez-García, F. Campos-Rodríguez, J-J. Soler-Cataluña, P. Catalán-Serra, P. Román-Sánchez, J-M. Montserrat
Journal: European Respiratory Journal (2011)

Obstructive sleep apnoea (OSA) is a risk factor for stroke, but little is known about the effect of OSA and continuous positive airway pressure (CPAP) on the incidence of long-term, nonfatal cardiovascular events (CVE) in stroke patients. A prospective observational study was made in 223 patients consecutively admitted for stroke. A sleep study was performed on 166 of them. 31 had an apnoea/hypopnoea index (AHI) &lt;10 events·h −1 ; 39 had an AHI between 10 and 19 events·h −1 and 96 had an AHI ≥20 events·h −1 . CPAP treatment was offered when AHI was ≥20 events·h −1 . Patients were followed up for 7 yrs and incident CVE data were recorded. The mean± sd age of the subjects was 73.3±11 yrs; mean AHI was 26±16.7 events·h −1 . Patients with moderate-to-severe OSA who could not tolerate CPAP (AHI ≥20 events·h −1 ; n=68) showed an increased adjusted incidence of nonfatal CVE, especially new ischaemic strokes (hazard ratio 2.87, 95% CI 1.11–7.71; p=0.03), compared with patients with moderate-to-severe OSA who tolerated CPAP (n=28), patients with mild disease (AHI 10–19 events·h −1 ; n=36) and patients without OSA (AHI &lt;10 events·h −1 ; n=31). Our results suggest that the presence of moderate-to-severe OSA is associated with an increased long-term incidence of nonfatal CVE in stroke patients and that CPAP reduces the excess of incidence seen in these patients.
Role of Cyclooxygenase-2 in the Generation of Vasoactive Prostanoids in the Rat Pulmonary and Systemic Vascular Beds
Authors: Syed R. Baber, Hunter C. Champion, Trinity J. Bivalacqua, Albert L. Hyman, Philip J. Kadowitz
Journal: Circulation (2003)

Background— Prostanoid synthesis by the cyclooxygenase (COX)-2 pathway plays an important role in inflammation, and recent studies have shown the presence of COX-2 in the normal rat lung. However, the role of COX-2 in the generation of vasoactive prostanoids in the rat is uncertain. In the present study, the hypothesis that synthesis of vasoactive prostanoids via the COX-2 pathway can alter pulmonary and systemic vascular resistance was investigated, and the effects of selective COX-2 inhibitors on pulmonary and systemic responses to the prostanoid precursor arachidonic acid were examined in the anesthetized rat with a recently developed right-heart catheterization technique. Methods and Results— Injections of arachidonic acid caused dose-related increases in pulmonary vascular resistance and decreases in systemic vascular resistance. These responses were attenuated by selective COX-2 inhibitors and a selective COX-1 inhibitor, whereas responses to exogenous prostanoids were not altered. Nimesulide or NS-398 did not alter arachidonic acid–induced platelet aggregation in rat platelet-rich plasma. Western blot analysis and immunostaining showed the expression of both COX isoforms in the rat lung. Conclusions— The results of these experiments suggest that arachidonic acid is converted into vasoactive prostanoids by the COX-2 and COX-1 pathway in the pulmonary and peripheral vascular beds in the rat and that TXA 2 is a major prostanoid formed in the normal rat lung.
Frequency of Morning Ketosis After Overnight Insulin Suspension Using an Automated Nocturnal Predictive Low Glucose Suspend System
Authors: Roy W. Beck, Dan Raghinaru, R. Paul Wadwa, H. Peter Chase, David M. Maahs, Bruce A. Buckingham
Journal: Diabetes Care (2014)

To assess the effect of overnight insulin pump suspension in an automated predictive low glucose suspend system on morning blood glucose and ketone levels in an attempt to determine whether routine measurement of ketone levels is useful when a closed-loop system that suspends insulin delivery overnight is being used.Data from an in-home randomized trial of 45 individuals with type 1 diabetes (age range 15-45 years) were analyzed, evaluating an automated predictive low glucose pump suspension system in which blood glucose, blood ketone, and urine ketone levels were measured on 1,954 mornings.One or more pump suspensions occurred during 744 of the 977 intervention nights (76%). The morning blood ketone level was ≥0.6 mmol/L after 11 of the 744 nights (1.5%) during which a pump suspension occurred and 2 of the 233 nights (0.9%) during which there was no suspension compared with 11 of 977 control nights (1.1%). The morning blood ketone level was ≥0.6 mmol/L after only 2 of 159 nights (1.3%) with a pump suspension exceeding 2 h. Morning fasting blood glucose level was not a good predictor of the presence of blood ketones.Routine measurement of blood or urine ketones during use of an automated pump suspension system using continuous glucose monitoring, whether threshold based or predictive, is not necessary. Recommendations for checking ketone levels should be no different when a patient is using a system with automated insulin suspension than it is for conventional diabetes self-management.
Comparative Genomics of the Pine Pathogens and Beetle Symbionts in the Genus Grosmannia
Authors: Sepideh Massoumi Alamouti, Sajeet Haridas, Nicolas Feau, Gordon Robertson, Jörg Bohlmann, Colette Breuil
Journal: Molecular Biology and Evolution (2014)

Studies on beetle/tree fungal symbionts typically characterize the ecological and geographic distributions of the fungal populations. There is limited understanding of the genome-wide evolutionary processes that act within and between species as such fungi adapt to different environments, leading to physiological differences and reproductive isolation. Here, we assess genomic evidence for such evolutionary processes by extending our recent work on Grosmannia clavigera, which is vectored by the mountain pine beetle and jeffrey pine beetle. We report the genome sequences of an additional 11 G. clavigera (Gc) sensu lato strains from the two known sibling species, Grosmannia sp. (Gs) and Gc. The 12 fungal genomes are structurally similar, showing large-scale synteny within and between species. We identified 103,430 single-nucleotide variations that separated the Grosmannia strains into divergent Gs and Gc clades, and further divided each of these clades into two subclades, one of which may represent an additional species. Comparing variable genes between these lineages, we identified truncated genes and potential pseudogenes, as well as seven genes that show evidence of positive selection. As these variable genes are involved in secondary metabolism and in detoxifying or utilizing host-tree defense chemicals (e.g., polyketide synthases, oxidoreductases, and mono-oxygenases), their variants may reflect adaptation to the specific chemistries of the host trees Pinus contorta, P. ponderosa, and P. jeffreyi. This work provides a comprehensive resource for developing informative markers for landscape population genomics of these ecologically and economically important fungi, and an approach that could be extended to other beetle–tree-associated fungi.
Identifying Psychosocial Risk Indicative of Subsequent Resource Use in Families of Newly Diagnosed Pediatric Oncology Patients
Authors: Anne E. Kazak, M. Catherine Cant, Merritt M. Jensen, Mary McSherry, Mary T. Rourke, Wei-Ting Hwang, Melissa A. Alderfer, David Beele, Steven Simms, Beverly J. Lange
Journal: Journal of Clinical Oncology (2003)

The primary purpose of this prospective study was to identify the level of risk for psychosocial distress in families of children newly diagnosed with cancer. Additional study aims were to examine concordance among family and staff reports of psychosocial risk, changes in risk status over time, and to predict the use of psychosocial resources during the first months of treatment.Caregivers of 125 children newly diagnosed with cancer completed the Psychosocial Assessment Tool (PAT) at diagnosis (t1) and 3 to 6 months later (t2). Primary oncologists and nurses completed an analogous measure of perceived family psychosocial risk at t1 and t2. At t2, oncology social workers reported types and intensity of psychosocial interventions provided.The PAT identified three subsets of families who presented with increasing levels of psychosocial risk at diagnosis. In general, there was moderate concordance among family, oncologist, and nurse reports of psychosocial risk. PAT scores at t1 predicted t2 PAT scores and psychosocial resource use at t2 beyond demographic or disease factors.A brief screening tool (PAT) is valuable in identifying psychosocial risk factors at diagnosis and is predictive of later use of psychosocial resources. As a next step in this research, the development of psychosocial interventions to match family risk level may be an effective and cost-efficient approach to working with families to address their concerns and promote short- and long-term adjustment.
The effect of aminophylline on function and intracellular pH of the rat diaphragm
Authors: CD Shee, AM Wright, IR Cameron
Journal: European Respiratory Journal (1990)

We studied the effect of aminophylline on twitch tension (TT) and intracellular pH (pHi) in isolated rat diaphragm strips that were fatigued, hypercapnic, or hypoxic. Superfused muscles were directly stimulated at 0.5 Hz. The pHi was measured from distribution volumes of dimethyl-oxazolidinedione. Fatigue was induced by intermittent tetanic stimulation. Hypercapnia and hypoxia were produced by altering superfusate carbon dioxide tension (PCO2) or oxygen tension (PO2). Aminophylline (1.0 mmol.l-1) reversed the twitch decay seen during fatigue or hypercapnic acidosis, and caused partial recovery of twitch depression during hypoxia. Muscle fatigue was not due to an intracellular acidosis. Both hypercapnia and hypoxia lowered pHi. Aminophylline did not alter pHi in unstimulated muscles, but caused a significant fall in pHi in stimulated muscles that were fatigued or hypoxic. High dose aminophylline improved twitch tension in diaphragm strips that were fatigued, acidotic, or hypoxic. Twitch potentiation was not due to an intracellular alkalosis. Aminophylline lowered pHi in stimulated muscle, and thus, theoretically, could sometimes be harmful in the treatment of muscle fatigue.
Inflammation in Nocturnal Asthma?
Authors: D. S. Postma, Y. Oosterhoff, W. M. C. Van Aalderen, H. F. Kauffman, J. B. Wempe, G. H. Koëter
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

At present there is some indirect evidence for increased nocturnal inflammation in patients suffering from nocturnal asthma: 1. Circulating eosinophil numbers and activation, as reflected by increased levels of ECP and EDN and low-density eosinophils, are increased at night. 2. Circulating histamine levels are increased at night. 3. Hyperresponsiveness to AMP at night is increased compared with hyperresponsiveness to methacholine. However, most results of various studies point to nocturnal asthma's being an expression of more severe asthma: 1. Both AMP and propranolol responsiveness, indirect measures of airway hyperresponsiveness, are lower both at 4:00 A.M. and 4:00 P.M. in asthmatics with nocturnal asthma than those without nocturnal asthma. 2. Patients with nocturnal asthma have higher circulating numbers of eosinophils at both 4:00 A.M. and 4:00 P.M. than those without nocturnal asthma, and eosinophil survival is not different at these times. 3. Patients with nocturnal asthma have higher PGD2 levels in BAL both at 4:00 A.M. and 4:00 P.M. than those without nocturnal asthma, but show no significant difference between levels at these two times. 4. Two studies have shown no difference in BAL eosinophil numbers and activation parameters at night in nocturnal asthma. 5. Histamine levels in BAL fluid are comparable day and night in patients with and without nocturnal asthma. 6. Inflammatory mediators in BAL are higher in asthmatic patients than in normal subjects, but are not different between patients with and without nocturnal asthma. Thus, patients with nocturnal asthmatic symptoms show an overall increased burden of mediators released from mast cells and other inflammatory cells. In conclusion, we feel that the term "nocturnal asthma" is misleading, in that it does not describe a unique entity in certain patients with asthma. We prefer, in view of the previous arguments, to consider nocturnal asthma a mere expression of more severe asthma. Thus we suggest the term "nocturnal asthma" be changed to "asthma with nocturnal symptoms."
Timing Is Everything: Preclinical Evidence Supporting Simultaneous Rather Than Sequential Chemohormonal Therapy for Prostate Cancer
Authors: Bernhard J.C. Eigl, Scott E. Eggener, Jenny Baybik, Susan Ettinger, Kim N. Chi, Colleen Nelson, Zhou Wang, Martin E. Gleave
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Androgen ablation is the mainstay of systemic therapy for prostate cancer, with cytotoxic therapies reserved for hormone-refractory disease. It is not clear, however, that this is the most appropriate sequence of interventions for this disease. This study addresses the ideal timing of systemic treatments in the Shionogi and LNCaP xenograft models. We explored the hypothesis that stress-induced gene expression changes after chemotherapy can induce a hormone-independent phenotype. Experimental Design: Three groups of mice bearing either Shionogi or LNCaP xenografts were treated with (a) initial castration and delayed paclitaxel, (b) initial paclitaxel and delayed castration, or (c) simultaneous castration plus paclitaxel. End points were time to tumor progression and time to sacrifice. Microarray and reverse transcription-PCR analyses were carried out to assess changes in gene expression induced by paclitaxel. Results: Mice receiving simultaneous therapy showed a significant improvement in median time to progression (TTP: Shionogi, 65 versus 38 days, P = 0.004; LNCaP, 105 versus 70 days, P = 0.032) and time to sacrifice (Shionogi, 83 versus 66 days, P &amp;lt; 0.014) versus best sequential therapy. A marked lack of response to castration was observed after initial paclitaxel therapy. Gene expression and reverse transcription-PCR studies confirmed that several genes known to play a role in androgen independence were up-regulated in response to paclitaxel exposure. Conclusions: In laboratory models of prostate cancer, simultaneous androgen deprivation plus paclitaxel is more effective than sequential treatments. These findings provide preclinical proof-of-principle for ongoing clinical trials addressing the role and timing of systemic therapies in prostate cancer.
The effects of stenting on shear stress: relevance to endothelial injury and repair
Authors: Kim Van der Heiden, Frank J. H. Gijsen, Andrew Narracott, Sarah Hsiao, Ian Halliday, Julian Gunn, Jolanda J. Wentzel, Paul C. Evans
Journal: Cardiovascular Research (2013)

Stent deployment following balloon angioplasty is used routinely to treat coronary artery disease. These interventions cause damage and loss of endothelial cells (EC), and thus promote in-stent thrombosis and restenosis. Injured arteries are repaired (intrinsically) by locally derived EC and by circulating endothelial progenitor cells which migrate and proliferate to re-populate denuded regions. However, re-endothelialization is not always complete and often dysfunctional. Moreover, the molecular and biomechanical mechanisms that control EC repair and function in stented segments are poorly understood. Here, we propose that stents modify endothelial repair processes, in part, by altering fluid shear stress, a mechanical force that influences EC migration and proliferation. A more detailed understanding of the biomechanical processes that control endothelial healing would provide a platform for the development of novel therapeutic approaches to minimize damage and promote vascular repair in stented arteries.
Bortezomib-Mediated Up-Regulation of TRAIL-R1 and TRAIL-R2 Is Not Necessary for but Contributes to Sensitization of Primary Human Glioma Cells to TRAIL
Authors: Ronald Koschny, Jaromir Sykora, Henning Walczak, Tom M. Ganten, Tobias L. Haas, Martin R. Sprick, Heidrum Holland, Peter Ahnert, Wolfgang Krupp, Jürgen Meixensberger, Manfred Bauer
Journal: Clinical Cancer Research (2007)

In Response: In their Letter, Kyritsis et al. discussed the interesting question of the contribution of up-regulation of the apoptosis-inducing tumor necrosis factor–related apoptosis inducing ligand (TRAIL) receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5), to the sensitization of tumor cells to TRAIL
Fetal Programming of Diabetes: Still So Much to Learn!
Authors: Chittaranjan Sakerlal Yajnik
Journal: Diabetes Care (2010)

In the preinsulin era, pregnancy in a diabetic mother had a bleak outcome for both the mother and the baby. Availability of insulin and modern methods of treatment improved the survival of these babies, but they appear to be at increased risk of obesity and diabetes (1–3). Spread of the diabetes pandemic to the young means there is now a growing epidemic of gestational diabetes mellitus (GDM). This label encompasses all varieties of diabetes that happen to be diagnosed during pregnancy, but the majority of GDM cases have type 2 pathology and metabolic syndrome–like features. There is a tacit assumption that glucose intolerance may have arisen de novo, but this is unlikely. The majority of women have risk factors dating back before pregnancy, sometimes traceable to early life growth and development (4,5), and many continue to be diabetic after delivery or develop diabetes soon after (6). The degree of glucose intolerance qualifying for the diagnosis of GDM is still being debated, and there is little consideration of other metabolic parameters, such as lipids, in the diagnosis. There is a growing realization that even a mild change in the intrauterine environment influences the baby's prospects not only in the perinatal period but over the entire length of its life (7). These ideas are at the core of the emerging specialty of Developmental Origins of Health and Disease (DOHaD) (8). The process influencing long-term fetal outcomes is called fetal programming (9).

The conceptus begins its life as a bag of genes that directs the development of a new individual. The new and important realization is that the intrauterine environment dictates how these genes function. A small change in this environment has the potential to permanentl y alter the working of genes and therefore the structure and function …