tbuckley/cabot-search huggingface dataset:
Magnetic Resonance Imaging–Detected Tumor Response for Locally Advanced Rectal Cancer Predicts Survival Outcomes: MERCURY Experience
Authors: Uday B. Patel, Fiona Taylor, Lennart Blomqvist, Christopher George, Hywel Evans, Paris Tekkis, Philip Quirke, David Sebag-Montefiore, Brendan Moran, Richard Heald, Ashley Guthrie, Nicola Bees, Ian Swift, Kjell Pennert, Gina Brown
Journal: Journal of Clinical Oncology (2011)

To assess magnetic resonance imaging (MRI) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter study.In a prospective cohort study, 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T, N and circumferential resection margin (CRM) status. Tumor regression grade (TRG) was also assessed by MRI. Overall survival (OS) was estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics.On multivariate analysis, the MRI-assessed TRG (mrTRG) hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI, 1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001), and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to 12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was 39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus 10% (P = .001). Pathology node status did not predict outcomes.MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome.
The Clinical Meaning of Walking Speed as Measured by the Timed 25-Foot Walk in Patients With Multiple Sclerosis
Authors: Jeffrey A. Cohen, Arun V. Krishnan, Andrew D. Goodman, James Potts, Ping Wang, Eva Havrdova, Chris Polman, Richard A. Rudick
Journal: JAMA Neurology (2014)

Walking impairment, a common clinical manifestation of multiple sclerosis (MS), is often measured in clinical practice and clinical trials using the Timed 25-Foot Walk (T25-FW).To evaluate the relationship between walking speed measured by the T25-FW and the Physical Component Summary (PCS) score of the 36-Item Short Form Health Survey (SF-36) to better understand the clinical meaning of T25-FW walking speed in MS.We retrospectively analyzed data from 3 clinical trials (Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis [AFFIRM], Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing-Remitting Multiple Sclerosis [SENTINEL], and International MS Secondary Progressive Avonex Controlled Trial [IMPACT]) that included T25-FW and SF-36 scores as outcomes in patients with MS. Patients had secondary-progressive MS and an Expanded Disability Status Scale score of 3.5 to 6.5 or relapsing-remitting MS and an Expanded Disability Status Scale score of 0 to 5.0.We used Spearman rank correlation and Pearson product moment correlation (r ) and descriptive statistics to evaluate retrospectively the relationship between the SF-36 PCS score and T25-FW walking speed at baseline and the 2-year changes from baseline.Among all 2549 patients from the 3 trials, walking speed and SF-36 PCS score at baseline were significantly correlated (n = 2333; r = 0.48; P < .001). In placebo-treated patients at 2 years, the percentage of change from baseline in walking speed was significantly correlated with the change from baseline in SF-36 PCS score (r = 0.35; P < .001). Significant correlations between the change in SF-36 PCS scores and the percentage of change in walking speed at 2 years also were observed in groups receiving active treatment (r, 0.13-0.28; P ≤ .005). Among placebo-treated patients, 27.5% had a clinically meaningful worsening (≥ 5-point decrease) in SF-36 PCS scores during the 2 years. Walking speed declined by 21.8% in these patients after 2 years, but only by 5.4% in those without worsening of SF-36 PCS scores.In patients with MS, walking speed measured using the T25-FW correlated with SF-36 PCS scores such that a decline in walking speed of 20% to 25% corresponded to a clinically meaningful worsening of SF-36 PCS scores. A 20% to 25% decline in walking speed may be a clinically meaningful threshold for defining worsening using the T25-FW in MS clinical trials and for monitoring patients in clinical settings.
Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: A meta-analysis of published randomised trials
Authors: E Mari, I Floriani, A Tinazzi, A Buda, M Belfiglio, M Valentini, S Cascinu, S Barni, R Labianca, V Torri
Journal: Annals of Oncology (2000)

Several studies have investigated the possible role of the adjuvant chemotherapy after curative resection for gastric cancer failing to show a clear indication; previous meta-analyses suggested small survival benefit of adjuvant chemotherapy, but the statistical methods used were open to criticisms.Randomised trials were identified by means of Medline and CancerLit and by selecting references from relevant articles. Systematic review of all randomised clinical trials of adjuvant chemotherapy for gastric cancer compared with surgery alone, published before January 2000, were considered. Pooling of data was performed using the fixed effect model. Death for any cause was the study endpoint. The hazard ratio and its 95% confidence intervals (95% CI), derived according to the method of Parmar, were the statistics chosen for summarising the relative benefit of chemotherapy versus control.Overall 20 articles (21 comparisons) were considered for analysis. Three studies used single agent chemotherapy, seven combination of 5-fluorouracil (5-FU) with anthracyclin, ten combination of 5-FU without anthracyclines. Information on 3658 patients, 2180 deaths, was collected. Chemotherapy reduced the risk of death by 18% (hazard ratio 0.82, 95% CI: 0.75-0.89, P < 0.001). Association of Anthracyclines to 5-FU did not show a statistically significant improvement when compared with the effect of the other regimens.Chemotherapy produces a small survival benefit in patients with curatively resected gastric cancer. However, taking into account the limitations of literature based meta-analyses, adjuvant chemotherapy is still to be considered as an investigational approach.
Hyaluronate degradation affects ventricular function of the early postlooped embryonic rat heart in situ.
Authors: H S Baldwin, T R Lloyd, M Solursh
Journal: Circulation Research (1994)

Hyaluronic acid is the major glycosaminoglycan of the early cardiac extracellular matrix or "cardiac jelly," yet little is known about its role in the ontogeny of early ventricular performance. To investigate the in situ effect of hyaluronate degradation on ventricular function, whole rat embryos were cultured in rat serum alone (control embryos) or rat serum plus 20 TRU/mL of Streptomyces hyaluronidase (treatment embryos) from gestational day 9.5 (before formation of the heart tube) through initial looping of the heart. Cardiac function was measured before looping (24 hours in culture) and immediately after looping (36 hours in culture) by video motion analysis of the external wall motion of the bulbus cordis and primitive ventricle. Degradation of hyaluronic acid in the treated embryos was confirmed by Alcian blue staining at pH 2.5. Significant increases in heart rate, circumferential shortening fraction, maximum velocity of circumferential contraction, and maximum velocity of circumferential relaxation were observed with looping in both control and treatment embryos. Although there was minimal difference in ventricular performance between control and treatment embryos before looping, there was a significant increase in all parameters of ventricular performance in the hyaluronidase-treated embryos immediately after looping of the heart. Endocardial cushions were absent in hyaluronidase-treated embryos, and an additional group of embryos cultured in the presence of Streptomyces hyaluronidase for 48 to 72 hours failed to develop endocardial cushions. These experiments are the first to (1) document a quantifiable increase in ventricular performance during early cardiac looping and (2) demonstrate that hyaluronate degradation results in abnormal endocardial cushion formation and altered ventricular performance of the postlooped heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Menopausal hormone therapy and risk of breast cancer: a meta-analysis of epidemiological studies and randomized controlled trials
Authors: Claudia M. Greiser, Eberhard M. Greiser, Martina Dören
Journal: Human Reproduction Update (2005)

We conducted meta-analyses to assess the impact of menopausal hormone therapy (MHT) on the risk of incident invasive breast cancer (BC) in cohort studies (CS), case–control studies (CCS) and randomized controlled trials (RCTs) published 1989–2004. We used published data providing information upon unopposed estrogen therapy (ET), estrogen–progestin therapy (EPT) or all MHT combined. Major outcomes were MHT-associated overall risk of BC and change of risk per year used. There is a linear increase of overall risk by midterm year of case ascertainment based upon data of all study types for MHT and to a larger extent for EPT, not for ET. Effects are larger in CS than in CCS. Meta-analyses stratified by <1992 versus $1992 as midterm year of case ascertainment indicate larger summary risks for the latter period for all MHT analysed, in particular for EPT. Annual increases in BC risk for EPT across study types are 0–9%, for ET 0–3%. In conclusion, there is evidence that relative risks for BC risks by MHT, in particular EPT, have been increasing in recent years. Given the widespread use of MHT, and often long duration, more detailed knowledge about differential BC risks of both estrogens and progestins are necessary to minimize BC risk in symptomatic women who consider MHT.
H1N1 influenza pneumonia and bacterial coinfection
Authors: E. Calbo, A. Robles, A. Sangil, S. Benet, M. E. Viladot, V. Pascual, B. Barreiro
Journal: Thorax (2011)

The model described by Bewick <i>et al</i> seems to be able to distinguish between H1N1 influenza-related pneumonia and non-H1N1 community acquired pneumonia (CAP) based on five criteria. However, bacterial infection in the influenza group has not been accurately excluded. Therefore, this model could misidentify these patients and lead to an inappropriate treatment. We conducted a prospective observational study to compare mixed pneumonia vs viral pneumonia. In the mixed pneumonia group patients were older, had higher levels of procalcitonine and higher scores of severity. In our cohort the model proposed by Bewick <i>et al</i> would not identify patients with coinfection.
Apoptosis Induction by Trastuzumab: Possible Role of the Core Biopsy Intervention
Authors: Sylvie Ménard, Serenella M. Pupa, Manuella Campiglio, Elda Taglibue, Andrea Balsari, Francesco Fagnoni, Alberto Costa
Journal: Journal of Clinical Oncology (2005)

Identification of the mechanism of action of trastuzumab is an important issue since it should provide the basis for optimization of one of the first biomolecular treatments in clinical oncology.
The Predictive Ability of Pre-Operative B-Type Natriuretic Peptide in Vascular Patients for Major Adverse Cardiac Events
Authors: Reitze N. Rodseth, Giovana A. Lurati Buse, Daniel Bolliger, Christoph S. Burkhart, Brian H. Cuthbertson, Simon C. Gibson, Elisabeth Mahla, David W. Leibowitz, Bruce M. Biccard
Journal: Journal of the American College of Cardiology (2011)
Development of Churg-Strauss syndrome with controlled asthma during omalizumab treatment
Authors: Anne-Marie Ruppert, Gerlinde Averous, Daniela Stanciu, Nicolas Deroide, Sophie Riehm, Vincent Poindron, Gabrielle Pauli, Christian Debry, Frédéric de Blay
Journal: Journal of Allergy and Clinical Immunology (2008)
Effect of hyper- and hypovolaemia on regional myocardial oxygen consumption
Authors: P M Scholz, J Kedem, S Sideman, R Beyar, H R Weiss
Journal: Cardiovascular Research (1990)

Study objective – The purpose of the investigation was to study the effect of preload on coronary blood flow and myocardial oxygen consumption in subendocardial and subepicardial regions of left ventricular free wall.
Analysis of restriction fragment length polymorphism for the HLA-DR gene in Japanese patients with sarcoidosis.
Authors: H Kunikane, S Abe, E Yamaguchi, J M Aparicio, A Wakisaka, T Yoshiki, Y Kawakami
Journal: Thorax (1994)

BACKGROUND--It is commonly assumed that some immunological disorder may play a part in the pathogenesis of sarcoidosis. Previous studies by several groups have shown a significant association with HLA-DR antigens in patients with sarcoidosis. In this study, restriction fragment length polymorphism (RFLP) analysis of the HLA-DR gene was designed to confirm the association at the gene level and to look for a gene rearrangement which may influence susceptibility to sarcoidosis. METHODS--Thirty two unrelated Japanese patients with sarcoidosis were tested for HLA antigens and subjected to RFLP analysis after digestion with Eco RI, Pst I, Bam HI, Pvu II, and Hind III by using an HLA-DR beta cDNA probe. A group of 47 unrelated healthy Japanese subjects served as controls. Frequencies of each restriction fragment were compared between the patients and the control subjects. Correlation between fragment frequencies and clinical features were also analysed. RESULTS--No restriction fragments of HLA-DR beta gene were found specific to the patients with sarcoidosis. The RFLP analysis could detect polymorphism of HLA-DR beta genes that was not distinguishable by conventional serological methods. Several restriction fragments of the DR beta gene were seen only in DRw52 positive individuals, and showed higher frequencies in the patients than in control subjects. The patients with these DNA fragments were likely to have limited stage disease with no ophthalmic involvement. CONCLUSIONS--An association between HLA and sarcoidosis was noted at the DNA level, although no restriction fragments were specific for this disease. RFLP analysis of the HLA gene is a more useful method than the usual HLA typing, and should be the first step in identifying the gene sequence which is connected with susceptibility to sarcoidosis.
Liver Toxicity After Treatment With Gefitinib and Anastrozole: Drug-Drug Interactions Through Cytochrome p450?
Authors: Paolo Carlini, Paola Papaldo, Alessandra Fabi, Alessandra Felici, Enzo Maria Ruggeri, Michele Milella, Mariangela Ciccarese, Carmen Nuzzo, Francesco Cognetti, Gianluigi Ferretti
Journal: Journal of Clinical Oncology (2006)
Angiogenesis and vascular endothelial growth factor in COPD
Authors: A J Knox
Journal: Thorax (2005)

A possible role for VEGF in the pathology of asthma and COPD

It has been recognised for several hundred years that the bronchial vasculature is an extensive one with early descriptions by Ruysch and possibly Da Vinci.1 However, its function and regulation in health and in disease remain poorly understood. Studies a number of years ago suggested an increased number of bronchial vessels in asthma where increased collagen IV staining, a marker of new vessels, was seen in bronchial biopsies of asthmatic airways compared with controls.2 Subsequent studies by the same group and by Salvato and colleagues have confirmed the presence of angiogenesis in the bronchial circulation in asthma.3,4 There are a number of candidate angiogenic factors for these changes, perhaps the most important of which are vascular endothelial growth factor (VEGF) and the angiopoietins which are distinct molecules that act together at different stages of angiogenic processes in several biological systems.5,6,7,8,9,10,11 Other molecules with angiogenic potential are fibroblast growth factor,9 angiogenin,9 and chemokines such as interleukin (IL)-812 and eotaxin.13 Interestingly, angiogenesis seems to be a feature of inflammatory diseases at a number of sites in the body including the joints14 and the gut.15

The study published in this issue of Thorax by Kranenburg and colleagues16 suggests that bronchial vascular changes may also occur in chronic obstructive …
Prognostic Implications of Multiple Lymphatic Basin Drainage in Patients With Truncal Melanoma
Authors: Ramon E. Jimenez, Katherine Panageas, Klaus J. Busam, Mary S. Brady
Journal: Journal of Clinical Oncology (2005)

Lymphatic drainage to multiple basins (MLBD) is frequently observed in patients with truncal melanoma undergoing sentinel lymph node (SLN) mapping. Recently published data suggest that patients with MLBD are at increased risk of nodal metastases compared with those with single lymphatic basin drainage (SLBD). We studied the impact of MLBD on SLN positivity and survival.We identified 266 patients with truncal melanoma undergoing SLN mapping and biopsy from 1995 to 2001. MLBD was defined as lymphoscintigraphic and intraoperative identification of an SLN in more than one nodal basin. Clinical and pathologic variables were recorded and analyzed for their impact on survival.MLBD occurred in 76 patients (29%), and SLBD occurred in 190 patients (71%). Clinical and pathologic variables were similar between the two groups, although there were more males in the MLBD group (78% v 64%; P = .034). Patients with MLBD did not have higher risk for positive SLNs compared with those with SLBD (22% v 21%, respectively). Five-year survival for patients with MLBD was less favorable than that of patients with SLBD (68% v 78%, respectively; log-rank P = .04). Multivariate analysis revealed that increasing Breslow thickness (P < .001), SLN metastasis (P < .001), and MLBD (P = .04) were independent predictors of poor overall and relapse-free survival. The negative prognostic implication of MLBD remained significant when only patients with negative SLNs were analyzed (relative risk, 2.7; P = .03).MLBD in patients with truncal melanoma undergoing SLN mapping is associated with a less favorable survival compared with patients with SLBD, independent of SLN status.
Potential implication of new torque teno mini viruses in parapneumonic empyema in children
Authors: Johanna Galmès, Yongjun Li, Alain Rajoharison, Lili Ren, Sandra Dollet, Nathalie Richard, Guy Vernet, Etienne Javouhey, Jianwei Wang, Jean-Noël Telles, Gláucia Paranhos-Baccalà
Journal: European Respiratory Journal (2012)

An unexplained increase in the incidence of parapneumonic empyema (PPE) in pneumonia cases has been reported in recent years. The present study investigated the genetic and biological specifications of new isolates of torque teno mini virus (TTMV) detected in pleural effusion samples from children hospitalised for severe pneumonia with PPE. A pathogen discovery protocol was applied in undiagnosed pleural effusion samples and led to the identification of three new isolates of TTMV (TTMV-LY). Isolated TTMV-LY genomes were transfected into A549 and human embryonic kidney 293T cells and viral replication was assessed by quantitative real-time PCR and full-length genome amplification. A549 cells were further infected with released TTMV-LY virions and the induced-innate immune response was measured by multiplex immunoassays. Genetic analyses of the three TTMV-LY genomes revealed a classic genomic organisation but a weak identity (&lt;64%) with known sequences. We demonstrated the in vitro replication of TTMV-LY in alveolar epithelial cells and the effective release of infectious viral particles. We also showed a selective production of inflammatory mediators in response to TTMV infection. This study reports the description of replicative TTMV-LY isolated from parapneumonic effusions of children hospitalised with PPE, suggesting a potential role of the virus in the pathogenesis of pneumonia.
Huntingtin and Huntingtin-Associated Protein 1 Influence Neuronal Calcium Signaling Mediated by Inositol-(1,4,5) Triphosphate Receptor Type 1
Authors: Tie-Shan Tang, Huiping Tu, Edmond Y.W Chan, Anton Maximov, Zhengnan Wang, Cheryl L Wellington, Michael R Hayden, Ilya Bezprozvanny
Journal: Neuron (2003)
Endothelin-1 potentiates cholinergic nerve-mediated contraction in human isolated bronchus
Authors: L.B. Fernandes, P.J. Henry, R.G. Goldie
Journal: European Respiratory Journal (1999)

<h3>Abstract</h3> <h3>Objective</h3> To explore the experiences of family physicians and pediatricians delivering immunizations, including perceived barriers and supports. <h3>Design</h3> Qualitative study using focus groups. <h3>Setting</h3> Ten cities throughout British Columbia. <h3>Participants</h3> A total of 46 family physicians or general practitioners, 10 pediatricians, and 2 residents. <h3>Methods</h3> A semistructured dialogue guide was used by a trained facilitator to explore participants’ experiences and views related to immunization delivery in British Columbia. Verbatim transcriptions were independently coded by 2 researchers. Key themes were analyzed and identified in an iterative manner using interpretive description. <h3>Main findings</h3> Physicians highly valued vaccine delivery. Factors facilitating physician-delivered immunizations included strong beliefs in the value of vaccines and having adequate information. Identified barriers included the large time commitment and insufficient communication about program changes, new vaccines, and the adult immunization program in general. Some physicians reported good relationships with local public health, while others reported the opposite experience, and this varied by geographic location. <h3>Conclusion</h3> These findings suggest that physicians are supportive of delivering vaccines. However, there are opportunities to improve the sustainability of physician-delivered immunizations. While compensation schemes remain under the purview of the provincial governments, local public health authorities can address the information needs of physicians.
An Address ON THE PREVENTION OF HEART DISEASE: Delivered before the Ulster Branch of the British Medical Association
Authors: W. Calwell
Journal: BMJ (1911)

PREVENTION OF HEART DISEkE.1 T[Mz B=J. " ably demonstrated recently, and which I trust this lecture will also emphtically reflect.Let me speak quite plainly.Any large, easily felt hydronephrosis is the evidence of failure; any large, easily-felt pyonephrosisis the evidence of culpable neglect both might have been avoided.Both will need mutilation, not surgery, for their cure, and if mutilation then curtailment of strength and life, in the place of that which early conservative surgery has in its power to confer.