tbuckley/cabot-search huggingface dataset:
CT or not CT? How should we look for distant metastases in invasive breast cancer in NHS highland?
Authors: Hollie Sapsford, Nick Abbott
Journal: International Journal of Surgery (2013)

Introduction   Invasive breast cancer can metastasize to distant organs. SIGN (1)  Guidelines (84) suggest that no staging is required for T1-2 N0-1 tumours in asymptomatic women .         Aims   To identify an effective strategy for staging investigations in NHS Highland.          M  et  hod  s  (including ethical approval)   Data from all patients with invasive breast cancer diagnosed over a 6 month period were retrieved from a prospectively maintained database. Investigations used as a staging strategy were recorded.      Ethical approval not required   Results    111 patients were diagnosed with invasive breast cancer.        98 patients went on to have surgery.        5 patients with asymptomatic metastatic disease were identified in the pre/peri-operative period.        3 of patients did not have surgery due to advanced disease.          Conclusions   CT chest/abdomen/pelvis is now used as the primary staging investigation for asymptomatic metastases in patients with:   Preoperative clinically bulky nodes   4 nodes positive on post-operative histology   Patients considered for reconstruction         References   (1) SIGN 84 Management of Breast Cancer in Women: A National Clinical Guideline December 2005
Multimodal pain stimulations in patients with grade B oesophagitis
Authors: A M Drewes
Journal: Gut (2005)

To obtain a better understanding of nociceptive processing in patients with oesophagitis.Eleven patients with grade B oesophagitis were compared with an age and sex matched group of 16 healthy subjects. A probe was positioned in the lower part of the oesophagus. After preconditioning of the tissue, painful mechanical stimuli were applied as distensions with a bag using an impedance planimetric method. Distensions were done before and after pharmacological impairment of distension induced smooth muscle contractions. Thermal stimulation was performed by recirculating water at 1 and 60 degrees C in the bag. The area under the temperature curve (AUC) represented caloric load. The referred pain area (being a proxy for the central pain mechanisms) to the mechanical stimuli was drawn at maximum pain intensities.Patients were hyposensitive to mechanical stimuli, as assessed by the distending volume (F=8.1, p=0.005). After relaxation of smooth muscle with butylscopolamine, the difference between the two groups was more evident (F=27.4, p<0.001). AUC for cold stimulation was 1048.6 (242.7) degrees Cxs in controls and 889.8 (202.6) degrees Cxs in patients (p=0.5). For heat stimuli, AUC values were 323.3 (104.1) and 81.3 (32.3) degrees Cxs in controls and patients, respectively (p=0.04). The referred pain area to the mechanical stimulations was larger and more widespread in patients (49.3 (6.2) cm2 compared with controls 23.9 (7) cm2; p=0.02).The data indicate that peripheral sensitisation of heat sensitive receptors and pathways combined with facilitation of central pain mechanisms may explain the symptoms in patients with oesophagitis.
Connective Tissue Growth Factor Acts as a Therapeutic Agent and Predictor for Peritoneal Carcinomatosis of Colorectal Cancer
Authors: Been-Ren Lin, Cheng-Chi Chang, Robert Jeen-Chen Chen, Yung-Ming Jeng, Jin-Tung Liang, Po-Huang Lee, King-Jen Chang, Min-Liang Kuo
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Here, we aimed to investigate the role of connective tissue growth factor (CTGF) in peritoneal carcinomatosis (PC) associated with colorectal cancer (CRC) and to characterize the underlying mechanism of CTGF mediating adhesion. Experimental Design: A cohort of 136 CRC patient specimens was analyzed in this study. CRC cell lines were used for in vitro adhesion assay and in vivo peritoneal dissemination experiment. Recombinant CTGF protein treatment, transfection of CTGF expression plasmids, and knockdown of CTGF expression in CRC cells were utilized to evaluate the integrin α5, which served as a target of CTGF in inhibiting peritoneal seeding. Results: The analysis of CRC tissues revealed an inverse correlation between CTGF expression and prevalence of PC. Lower CTGF level in CRC patients was associated with higher peritoneal recurrence rate after surgery. Inducing CTGF expression in cancer cells resulted in decreased incidence of PC and increased rate of mice survival. The mice received intraperitoneal injection of recombinant CTGF protein simultaneously with cancer cells or following tumor formation; in both cases, peritoneal tumor dissemination was found to be effectively inhibited in the mouse model. Functional assay revealed that CTGF significantly decreased the CRC cell adhesion ability, and integrin α5 was confirmed by reverse transcriptase PCR and functional blocking assay as a downstream effector in the CTGF-mediated inhibition of CRC cell adhesion. Conclusions: CTGF acts as a molecular predictor of PC and could be a potential therapeutic target for the chemoprevention and treatment of PC in CRC patients. Clin Cancer Res; 17(10); 3077–88. ©2011 AACR.
Molecular Control of Cell Fate in the Neural Crest: The Sympathoadrenal Lineage
Authors: D J Anderson
Journal: Annual Review of Neuroscience (1993)

Over the past five years, new insights have been gained into the biology of the SA lineage. These advances have been powered by the development of immunologic methods to isolate embryonic SA progenitors from fetal adrenal glands and sympathetic ganglia. Analysis of these embryonic progenitors has confirmed many of the ideas derived from earlier studies of postnatal cells, but has necessitated several revisions in our thinking, as well. First, embryonic SA progenitors appear to be distinct from mature SIF cells, a cell type initially postulated to be the central intermediate in the SA lineage. Second, FGF, not NGF, appears to be an important early influence on neuronal fate; NGF responsiveness appears relatively late in differentiation. Third, the development of both sympathetic neurons and adrenal chromaffin cells is not a one-step process, but rather involves a series of events, in which the cells change their responsiveness to growth factors and glucocorticoids. Fourth, emerging circumstantial evidence suggests that SA progenitors may have additional developmental potentials. Finally, new insights have been gained into the molecular mechanisms that underlie both the differentiation of SA progenitors and their determination from earlier multipotent neural crest cells. These advances have made the SA progenitor a well-defined system for studying the molecular control of cell fate in a vertebrate neurogenic precursor cell. The analysis of the SA lineage at the cell biological level has raised several interesting molecular questions for future investigation. In the neuronal branch of the SA lineage, how is the acquisition of NGF-responsiveness and NGF-dependence controlled, and what is the relationship of these events to the expression of p140trk and p75? In the chromaffin branch of the pathway, which molecules control the timing of PNMT expression? In the uncommitted SA progenitor, what is the molecular basis of the antagonism between the competing neuronal and chromaffin pathways of differentiation, and how does commitment to neuronal differentiation occur? Can SA progenitors differentiate to enteric neurons in vitro, and which differentiation and survival factors control this phenotype, as well as the other classical neurotransmitter and neuropeptide phenotypes expressed by SA derivatives? What are the roles of MASH1 and other regulatory genes in controlling early stages in neural crest cell determination, and how is the expression of these molecules in turn controlled? How much of the genetic regulatory network controlling neuronal differentiation in Drosophila has been conserved in vertebrates?(ABSTRACT TRUNCATED AT 400 WORDS)
Nonpegylated liposomal doxorubicin (Myocet™) combination (R-COMP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL): results from the phase II EUR018 trial
Authors: S. Luminari, A. Montanini, D. Caballero, S. Bologna, M. Notter, M.J.S. Dyer, A. Chiappella, J. Briones, M. Petrini, A. Barbato, L. Kayitalire, M. Federico
Journal: Annals of Oncology (2009)

BackgroundTo evaluate the activity and safety of nonpegylated liposomal doxorubicin (Myocet™) when substituted for doxorubicin in the R-CHOP regimen (R-COMP).Patients and methodsSeventy-five elderly patients with diffuse large B-cell lymphoma (DLBCL) were studied. Only patients with left ventricular ejection fraction (LVEF) ≥50% were allowed. R-COMP regimen was administered every 3 weeks for three cycles, followed by additional five cycles in case of complete response (CR) or partial response.ResultsFrom November 2002 to April 2005, 75 patients were registered, of which 72 were evaluated. Median age was 72 years (range 61–83); 56% of patients had high or high–intermediate International Prognostic Index score. Median LVEF at baseline was 61%. Thirty-eight patients had history of abnormal cardiovascular conditions. The overall response rate was 71%, with a CR rate of 57%. After a median follow-up of 33 months, the 3-year overall survival, failure-free survival, and progression-free survival rates were 72%, 39%, and 69%, respectively. Neutropenia (54%) was the most frequent grade 3–4 adverse event (AE); 21% of patients experienced cardiac AEs, graded as 3–4 in 4% of the cases.ConclusionR-COMP is an effective regimen for the treatment of DLBCL in elderly patients, with an acceptable tolerability profile.
Postprandial hypergastrinaemia in patients with colorectal cancer.
Authors: K Wong, K Beardshall, C M Waters, J Calam, G J Poston
Journal: Gut (1991)

Gastrin is trophic to colon cancers that possess gastrin receptors. Whether fasting serum gastrin concentrations are high in patients with colon cancer is controversial. We therefore studied the effect of food on serum gastrin concentrations in patients with colon cancer and control subjects. Fasting serum gastrin was greater, though not significantly so, in patients with colon cancer before surgery (mean (SD) 17.4 (3.6) pmol/l, n = 16) compared with control subjects (12.6 (1.9) pmol/l, n = 14). Postprandial increases in serum gastrin were significantly and persistently higher than normal in the cancer patients. These increases were due to a subset of six patients with serum gastrin concentrations greater than the control mean + 2 SD at 20 and 40 minutes (62 pmol/l-146 pmol/l). Four of the six patients had intra-abdominal metastases. The extent of the increase may well correlate with that of the disease. Surgical resection of the tumour resulted in a fall in serum gastrin values and probably reflects the cause of the hypergastrinaemia. Hypergastrinaemia may, therefore, be an important aetiological factor in colon carcinogenesis.
Inhibition of sympathetic vasoconstriction is a major principle of vasodilation by nitric oxide in vivo.
Authors: J Zanzinger, J Czachurski, H Seller
Journal: Circulation Research (1994)

The objective of this study was to determine whether vasodilator effects of nitric oxide (NO) can be explained by the inhibition of vasoconstriction caused by peripheral sympathetic nerve activity (SNA) in vivo. For this purpose, we studied the effects of systemic inhibition of NO synthesis during experimental variation of SNA in anesthetized cats. Intravenous infusion of NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) in baroreceptor-intact animals (n = 6) caused increases in mean arterial blood pressure (MAP) from 105.8 +/- 3.4 to 192.0 +/- 4.3 mm Hg that were associated with slight decreases in preganglionic SNA recorded from the white ramus of the third thoracic segment. Higher SNA appeared in completely baroreceptor-denervated cats (n = 10) than in the intact cats, but no changes in nerve activity occurred after the subsequent administration of L-NAME. In contrast, MAP increased from 123.3 +/- 4.0 to 245.8 +/- 5.1 mm Hg. In baroreceptor-denervated cats, reversible suppression of peripheral SNA produced by cooling of the ventral surface of the rostral ventrolateral medulla oblongata (RVLM) caused significant hypotension (61.1 +/- 2.6 mm Hg) and almost completely reversed the hypertension caused by L-NAME (76.0 +/- 3.7 mm Hg). Intravenous administration of the alpha 1-adrenergic receptor antagonist prazosin after L-NAME reduced MAP to a similar extent. In contrast, hypertension induced by angiotensin II could not be reversed by RVLM cooling. The pressor effects of intravenously administered noradrenaline during RVLM cooling were markedly potentiated by L-NAME and attenuated by the NO-donor compound S-nitroso-N-acetylpenicillamine (SNAP).(ABSTRACT TRUNCATED AT 250 WORDS)
Outcome of asthma: longitudinal changes in lung function
Authors: C.S. Ulrik
Journal: European Respiratory Journal (1999)

Current knowledge about factors determining outcome of asthma is limited, but observations over the last few decades suggest that active asthma has a negative impact on the longitudinal changes in lung function. This review aims to give an overview of the present knowledge concerning longitudinal changes in lung function, including clinical markers for distinctly poor outcome with regard to lung function, in children and adults suffering from asthma. The majority of patients with asthma have a good prognosis. However, some patients with asthma, especially those with more severe disease, are at risk of impaired growth of lung function during childhood, a lower maximally attained level of lung function and excessive decline in lung function in adulthood, which may lead to life-threatening lung function impairment. Clinical markers of poorly controlled airway inflammation appear to have a negative impact on the longitudinal changes in lung function, and disease progression to nonreversible airflow obstruction may be observed in a minority of patients with asthma. Early intervention with anti-inflammatory therapy may improve the short-term outcome of asthma, but long-term controlled studies are clearly needed in order to verify whether or not treatment, especially with inhaled corticosteroids, according to the current international guidelines alters the natural history of asthma, i.e. disease progression with regard to changes in lung function and possible development of nonreversible airflow obstruction.
A multicenter validation of an endoscopic classification with narrow band imaging for gastric precancerous and cancerous lesions
Authors: P. Pimentel-Nunes, M. Dinis-Ribeiro, J. Soares, R. Marcos-Pinto, C. Santos, C. Rolanda, R. Bastos, M. Areia, L. Afonso, J. Bergman, P. Sharma, T. Gotoda, R. Henrique, L. Moreira-Dias
Journal: Endoscopy (2012)

<b>Background and study aim: </b>The reliability and external validity of narrow band imaging (NBI) in the stomach have not been described consistently. The aim of the current study was to describe and estimate the accuracy and reliability of a simplified classification system for NBI in the diagnosis of gastric lesions. <b>Methods: </b>Consecutive patients undergoing NBI endoscopy at two reference centers (n = 85, 33 % with dysplasia) were included in two studies. In total, 224 different areas were biopsied and recorded onto video. In the derivation study, previously described NBI features were analyzed in order to develop a simplified classification. In the validation study the accuracy and reliability of this classification were estimated among three groups of endoscopists with different levels of expertise in NBI. <b>Results:</b> The reliability/accuracy results from the derivation study allowed the creation of a simplified NBI classification. In the validation study, “regular vessels with circular mucosa” (pattern A) was associated with normal histology (accuracy 83 %; 95 % confidence interval [CI] 75 % – 90 %); “tubulo-villous mucosa” (pattern B) was associated with intestinal metaplasia (accuracy 84 %; 95CI 77 % – 91 %; positive likelihood ratio [LR + ] = 4.75); and “irregular vessels and mucosa” (pattern C) was associated with dysplasia (accuracy 95 %; 95CI 90 % – 99 %; LR + = 44.33). The reproducibility of these patterns was high (k = 0.62). “Light-blue crest” was moderately reliable (k = 0.49) but specific (87 %) for intestinal metaplasia. A variable vascular density (additional pattern + ) was the best feature for <i>Helicobacter pylori</i> gastritis (accuracy 70 %; 95CI 59 % – 80 %) but showed only fair reliability (k = 0.38). Non-experienced endoscopists presented lower agreement (k = 0.6 vs. k = 0.75) and accuracy (74 % vs. 86 %) than international experts/experienced endoscopists. <b>Conclusion:</b> A simplified NBI classification is accurate and reliable for the diagnosis of intestinal metaplasia and dysplasia. The classification should be further assessed and validated on a per-patient assessment of NBI, and by comparing NBI with other imaging technologies.
Obliterative bronchiolitis with atypical features: CT scan and necropsy findings
Authors: MI Noble, B Fox, K Horsfield, I Gordon, R Heaton, WA Seed, A Guz
Journal: European Respiratory Journal (1993)

We describe the natural history of cryptogenic bronchiolitis obliterans in a patient followed for 24 yrs with serial pulmonary function tests and radiology. Severe, progressive airway obstruction developed, with overinflation but preservation of KCO. There was progressive hypoxaemia, which worsened on exertion; hypercapnoea was modest until late in the illness. Neither bronchodilators nor steroids were effective. The chest radiograph remained normal; CT showed irregular areas of low attenuation peripherally throughout the lungs, with Hounsfield numbers typical of emphysema, but no bullae. Postmortem studies included histology and quantitative studies of a corrosion cast of one lung. They showed marked airway narrowing at all levels, with pruning of peripheral branches, mucus plugging, and some emphysema. The case illustrates that cryptogenic bronchiolitis obliterans may be chronic and difficult to distinguish clinically or by investigation from other forms of chronic obstructive airways disease, particularly emphysema.
An Intersection of Atrial Fibrillation With Sudden Death
Authors: Kyndaron Reinier, Sumeet S. Chugh
Journal: JAMA Internal Medicine (2012)

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CD8+ T Cell–mediated Injury In Vivo Progresses in the Absence of Effector T Cells
Authors: Barbara A. Small, Sarah A. Dressel, Christopher W. Lawrence, Donald R. Drake, Mark H. Stoler, Richard I. Enelow, Thomas J. Braciale
Journal: The Journal of Experimental Medicine (2001)

Tissue injury is a common sequela of acute virus infection localized to a specific organ such as the lung. Tissue injury is an immediate consequence of infection with lytic viruses. It can also result from the direct destruction of infected cells by effector CD8+ T lymphocytes and indirectly through the action of the T cell–derived proinflammatory cytokines and recruited inflammatory cells on infected and uninfected tissue. We have examined CD8+ T cell–mediated pulmonary injury in a transgenic model in which adoptively transferred, virus-specific cytotoxic T lymphocytes (CTLs) produce lethal, progressive pulmonary injury in recipient mice expressing the viral target transgene exclusively in the lungs. We have found that over the 4–5 day course of the development of lethal pulmonary injury, the effector CTLs, while necessary for the induction of injury, are present only transiently (24–48 h) in the lung. We provide evidence that the target of the antiviral CD8+ T cells, the transgene expressing type II alveolar cells, are not immediately destroyed by the effector T cells. Rather, after T cell–target interaction, the type II alveolar cells are stimulated to produce the chemokine monocyte chemoattractant protein 1. These results reinforce the concept that, in vivo, the cellular targets of specific CTLs may participate directly in the development of progressive tissue injury by activating in response to interaction with the T cells and producing proinflammatory mediators without sustained in vivo activation of CD8+ T cell effectors.
Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population
Authors: David Dynnes Ørsted, Stig Egil Bojesen, Anne Tybjærg-Hansen, Børge Grønne Nordestgaard
Journal: The Journal of Experimental Medicine (2007)

p53 is an important tumor suppressor, normally preventing cancer development via apoptosis. A genomic Arg72Pro substitution in the p53 protein has important influence on cell death via apoptosis, which could be beneficial. We therefore tested the hypotheses that this polymorphism influences longevity, survival after a cancer diagnosis, and risk of cancer in the general population. We examined a cohort of 9,219 participants ages 20–95 from the Danish general population with 100% follow-up. The overall 12-yr survival was increased in p53 Arg/Pro heterozygotes with 3% (P = 0.003) and in Pro/Pro homozygotes with 6% (P = 0.002) versus Arg/Arg homozygotes, corresponding to an increase in median survival of 3 yr for Pro/Pro versus Arg/Arg homozygotes. We also demonstrated an increased survival after the development of cancer, or even after the development of other life-threatening diseases, for Pro/Pro versus Arg/Arg homozygotes. The Arg72Pro substitution did not associate with decreased risk of cancer. In conclusion, in this large cohort from the general population, we show that a well-known functional single nucleotide polymorphism in the tumor suppressor p53 protein leads to increased longevity, but not to decreased risk of cancer. The increased longevity may be due to increased survival after a diagnosis of cancer or other life-threatening diseases.