tbuckley/cabot-search huggingface dataset:
Efficacy of Oxaliplatin Plus Capecitabine or Infusional Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer: A Pooled Analysis of Randomized Trials
Authors: Hendrik-Tobias Arkenau, Dirk Arnold, Jim Cassidy, Eduardo Diaz-Rubio, Jean-Yves Douillard, Howard Hochster, Andrea Martoni, Axel Grothey, Axel Hinke, Wolff Schmiegel, Hans-Joachim Schmoll, Rainer Porschen
Journal: Journal of Clinical Oncology (2008)

Six randomized phase II and III trials have investigated the role of oxaliplatin (OX) in combination with capecitabine (CAP) or infusional fluorouracil (FU) in metastatic colorectal cancer. This meta-analysis compared the efficacy of CAP/OX compared with infusional FU/OX.This analysis compared all published CAP/OX versus infusional FU/OX regimens. A total of 3,494 patients (FU, n = 1,737; CAP, n = 1,757) were analyzed for response rate (RR), progression-free (PFS), overall survival (OS), and toxicity.The fixed-effect pooled estimate for RR showed higher RR for FU-based regimens (Odds ratio [OR] = 0.85; 95% CI, 0.74 to 0.97; P = .02) whereas the analysis of chemotherapy-only trials, excluding the bevacizumab containing NO16966 and TREE 2 trials, led to an OR of 0.74 (95% CI, 0.60 to 0.92; P = .007). However, for PFS (hazard ratio [HR] = 1.04; 95% CI, 0.96 to 1.12; P = .17) and OS (HR = 1.04; 95% CI, 0.95 to 1.12; P = .41) all models suggested similar outcome within the range of noninferiority. Grade 3/4 toxicities (thrombocytopenia-HR = 2.07, 95% CI, 1.42 to 3.03; P < .0002; diarrhea-HR = 1.34; 95% CI, 1.08 to 1.66; P < .0009; and grade 2/3 hand-foot-syndrome [HFS]-HR = 3.54; 95% CI, 2.07 to 6.05; P < .00001) were less prominent with FU-based regimens whereas neutropenia (HR = 0.15; 95% CI, 0.11 to 0.19; P < .00001) was lower in the CAP regimens.The combination of CAP and OX resulted in lower RR, but this did not affect PFS and OS, which were similar in both treatment arms. The toxicity analysis showed the characteristic toxicity of each of the different FU schedules, with thrombocytopenia and HFS consistently more prominent in the CAP regimens.
Non-Invasive Respiratory Support: A K Simonds. Edward Arnold, 2001, pound29.99, pp 304. ISBN 0 340 76259 4
Authors: L Turner
Journal: Thorax (2002)

The second edition of Dr Simonds' book gives a comprehensive up to date review of the rapidly expanding field of non-invasive respiratory support. The material covers acute and chronic applications of non-invasive ventilation (NIV), giving an overview of NIV in these settings followed by discussions on specific …
A critical role for the autophagy gene Atg5 in T cell survival and proliferation
Authors: Heather H. Pua, Ivan Dzhagalov, Mariana Chuck, Noboru Mizushima, You-Wen He
Journal: The Journal of Experimental Medicine (2006)

Macroautophagy (hereafter referred to as autophagy) is a well-conserved intracellular degradation process. Recent studies examining cells lacking the autophagy genes Atg5 and Atg7 have demonstrated that autophagy plays essential roles in cell survival during starvation, in innate cell clearance of microbial pathogens, and in neural cell maintenance. However, the role of autophagy in T lymphocyte development and survival is not known. Here, we demonstrate that autophagosomes form in primary mouse T lymphocytes. By generating Atg5−/− chimeric mice, we found that Atg5-deficient T lymphocytes underwent full maturation. However, the numbers of total thymocytes and peripheral T and B lymphocytes were reduced in Atg5 chimeras. In the periphery, Atg5−/− CD8+ T lymphocytes displayed dramatically increased cell death. Furthermore, Atg5−/− CD4+ and CD8+ T cells failed to undergo efficient proliferation after TCR stimulation. These results demonstrate a critical role for Atg5 in multiple aspects of lymphocyte development and function and suggest that autophagy may be essential for both T lymphocyte survival and proliferation.
Purified Rat Liver Fat-Storing Cells in Culture Divide and Contain Collagen
Authors: A. De Margreet Leeuw, Séan P. Mccarthy, Albert Geerts, Dick L. Knook
Journal: Hepatology (1984)

Primary cultures and cell lines were established from suspensions of purified fat-storing cells isolated from the rat liver. When seeded at a suitable density, fat-storing cells in primary culture reached confluency in 3 to 4 days and could be transferred and established as cell lines for at least two passages. The typical morphological characteristics of fat-storing cells in vivo were retained in the cells during primary culture. Vitamin A fluorescence was still associated with lipid droplets of cells in culture up to and including the second passage. Investigation of the cytoskeletal structure by indirect immunofluorescence showed the presence of vimentin, actin and tubulin in the cells; no alpha-prekeratin was present. The presence of vimentin suggested a fibroblastic or possible myogenic origin for fat-storing cells. The presence of connective tissue components in fat-storing cells in culture was demonstrated by indirect immunofluorescence. Collagen Types I and IV and laminin were present intracellularly in small granules in fat-storing cells in primary culture and in the first passage. Cells in the fourth passage contained only collagen Type 1. Fibronectin was only aligned extracellularly along the cell membrane, which did not exclude an extracellular source. Rat liver fat-storing cells in culture show a high proliferating capacity. Cell multiplication during prolonged culture was associated with phenotypic transition to a more fibroblastic appearance and gradual disappearance of vitamin A. These results indicate that fat-storing cells may be among the cell types involved in pathological changes observed during development of liver fibrosis.
Aluminium potroom asthma: the Norwegian experience
Authors: J Kongerud, J Boe, V Soyseth, A Naalsund, P Magnus
Journal: European Respiratory Journal (1994)

Work-related asthma in aluminium potroom workers, is reviewed and discussed, mainly on the basis of own investigations. The occurrence of work-related asthma has been shown to be associated with the duration of potroom employment, although the prevalence of asthmatic symptoms is not significantly different from that of the general population. Typical manifestations of occupational asthma are described in potroom workers, and a close relationship between the levels of fluoride exposure and work-related asthmatic symptoms has been observed. The existence of occupational asthma in aluminium potroom workers has been confirmed by characteristic patterns of repeated peak flow measurements, supported by changes in methacholine responsiveness in workers with suspected work-related asthma. However, no immunological test is available to establish the diagnosis. Methacholine challenge appears to be inappropriate for screening aluminium potroom workers in order to detect work-related asthma. Current smoking, but not self-reported allergy, is a risk factor for potroom asthma. A family history of asthma and previous occupational exposure may have some effect on the risk of developing symptoms. The prognosis of potroom asthma seems to depend on early replacement to unexposed work. The pathogenetic mechanisms are unknown, although some studies indirectly imply a hypersensitivity reaction. Future studies involving specific bronchial challenge appear to be necessary to find the causal agent(s) of aluminium potroom asthma.
Effect of fibreoptic bronchoscopy on pulmonary function.
Authors: A J Peacock, R Benson-Mitchell, R Godfrey
Journal: Thorax (1990)

Several studies have shown that after fibreoptic bronchoscopy there may be a deterioration in lung function but it is not known whether this is due to the premedication, the topical anaesthetic, or the obstruction produced by the bronchoscope. The effects of each part of the procedure on spirometric measurements were studied in patients with lung disease and in normal non-smokers. Measurements were made after premedication (papaveretum and atropine) in seven patients and after topical anaesthesia of the bronchial tree (340 mg lignocaine) with and without the bronchoscope in the trachea in 21 patients and 10 control subjects. Premedication had no effect. In the normal subjects lignocaine produced significant falls in FEV1, forced vital capacity (FVC), peak expiratory flow (PEF), and peak inspiratory flow (PIF), and insertion of the bronchoscope caused further falls that were also significant. In the patients, however, although anaesthesia produced significant falls in FEV1, FVC, PEF, and PIF of similar magnitude to those found in the normal subjects, there was no further important decrease when the bronchoscope was inserted. It is concluded that the major effect of bronchoscopy on lung function is due to topical lignocaine in the airways, and in patients with lung disease (excluding asthma or a central obstructing carcinoma) the insertion of the bronchoscope causes little additional obstruction.
Circulating Lysophosphatidylcholines Are Markers of a Metabolically Benign Nonalcoholic Fatty Liver
Authors: Rainer Lehmann, Holger Franken, Sascha Dammeier, Lars Rosenbaum, Konstantinos Kantartzis, Andreas Peter, Andreas Zell, Patrick Adam, Jia Li, Guowang Xu, Alfred Königsrainer, Jürgen Machann, Fritz Schick, Martin Hrabé de Angelis, Matthias Schwab, Harald Staiger, Erwin Schleicher, Amalia Gastaldelli, Andreas Fritsche, Hans-Ulrich Häring, Norbert Stefan
Journal: Diabetes Care (2013)

Nonalcoholic fatty liver (NAFL) is thought to contribute to insulin resistance and its metabolic complications. However, some individuals with NAFL remain insulin sensitive. Mechanisms involved in the susceptibility to develop insulin resistance in humans with NAFL are largely unknown. We investigated circulating markers and mechanisms of a metabolically benign and malignant NAFL by applying a metabolomic approach.A total of 265 metabolites were analyzed before and after a 9-month lifestyle intervention in plasma from 20 insulin-sensitive and 20 insulin-resistant subjects with NAFL. The relevant plasma metabolites were then tested for relationships with insulin sensitivity in 17 subjects without NAFL and in plasma from 29 subjects with liver tissue samples.The best separation of the insulin-sensitive from the insulin-resistant NAFL group was achieved by a metabolite pattern including the branched-chain amino acids leucine and isoleucine, ornithine, the acylcarnitines C3:0-, C16:0-, and C18:0-carnitine, and lysophosphatidylcholine (lyso-PC) C16:0 (area under the ROC curve, 0.77 [P = 0.00023] at baseline and 0.80 [P = 0.000019] at follow-up). Among the individual metabolites, predominantly higher levels of lyso-PC C16:0, both at baseline (P = 0.0039) and at follow-up (P = 0.001), were found in the insulin-sensitive compared with the insulin-resistant subjects. In the non-NAFL groups, no differences in lyso-PC C16:0 levels were found between the insulin-sensitive and insulin-resistant subjects, and these relationships were replicated in plasma from subjects with liver tissue samples.From a plasma metabolomic pattern, particularly lyso-PCs are able to separate metabolically benign from malignant NAFL in humans and may highlight important pathways in the pathogenesis of fatty liver-induced insulin resistance.
Extralobar pulmonary sequestration
Authors: A. O. Williams, F. I. Enumah
Journal: Thorax (1968)

Extralobar sequestration of pulmonary tissues is relatively rare and seldom produces symptoms. An incidental finding is described of extralobar sequestration of the lung in a Nigerian child, presenting as an anterior mediastinal polycystic mass. The mass was attached to the right pulmonary artery by a fibrovascular pedicle which contained a small elastic artery, veins, and nerve bundles. Sequestrated lobes are usually situated in the posterior basal lobes of the lungs and may be associated with other congenital abnormalities, but the case reported here differs in these respects. Death was due to enterocolitis unrelated to the congenital abnormality.
Esophageal Cancer: A Critical Evaluation of Systemic Second-Line Therapy
Authors: Christiane Maria Rosina Thallinger, Markus Raderer, Michael Hejna
Journal: Journal of Clinical Oncology (2011)

The objective of this article was to review clinical trials that used antineoplastic second-line chemotherapy and/or targeted therapies in patients with esophageal cancer after first-line therapy. Computerized (MEDLINE) and manual searches were performed to identify articles published on this topic between 1996 and 2011. Twenty-five published trials and four abstracts presented at scientific meetings were identified. A total of 10 trials included only patients with squamous cell carcinomas (SCCs), four focused exclusively on adenocarcinoma (AC), the remaining 15 studies included both SCC and AC. The majority of trials (17 of 29) used docetaxel in combination with platinum analogs, eight used single-agent cytotoxic chemotherapy, and six evaluated targeted therapies. The numbers of patients were relatively small, ranging from eight to 55 patients. The response rates were generally low (between 0% and 39%), with only two small studies reporting objective responses of 50% and 63%, respectively. Time to progression ranged from 1.4 to 6.2 months, and the overall survival was disappointing at 4.0 to 11.4 months. Approximately 40% of patients who experience progressive disease after first-line chemotherapy are able to undergo second-line treatment. On the basis of data published so far, no standard second-line therapy has emerged. Future research will need to focus on individual therapy strategies such as genetic receptor mutations to increase the therapeutic outcome.
The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface
Authors: Silvia Cappello, Alessio Attardo, Xunwei Wu, Takuji Iwasato, Shigeyoshi Itohara, Michaela Wilsch-Bräuninger, Hanna M Eilken, Michael A Rieger, Timm T Schroeder, Wieland B Huttner, Cord Brakebusch, Magdalena Götz
Journal: Nature Neuroscience (2006)
Transvenous Pacing Leads and Systemic Thromboemboli in Patients With Intracardiac Shunts
Authors: Paul Khairy, Michael J. Landzberg, Michael A. Gatzoulis, Lise-Andrée Mercier, Susan M. Fernandes, Jean-Marc Côté, Jean-Pierre Lavoie, Anne Fournier, Peter G. Guerra, Alexandra Frogoudaki, Edward P. Walsh, Annie Dore
Journal: Circulation (2006)

The risk of systemic thromboemboli associated with transvenous leads in the presence of an intracardiac shunt is currently unknown.To define this risk, we conducted a multicenter, retrospective cohort study of 202 patients with intracardiac shunts: Sixty-four had transvenous leads (group 1), 56 had epicardial leads (group 2), and 82 had right-to-left shunts but no pacemaker or implantable cardioverter defibrillator leads (group 3). Patient-years were accrued until the occurrence of systemic thromboemboli or study termination. Censoring occurred in the event of complete shunt closure, death, or loss to follow-up. Mean ages for groups 1, 2, and 3 were 33.9+/-18.0, 22.2+/-12.6, and 22.9+/-15.0 years, respectively. Respective oxygen saturations were 91.2+/-9.1%, 88.1+/-8.1%, and 79.7+/-6.7%. During respective median follow-ups of 7.3, 9.3, and 17.0 years, 24 patients had at least 1 systemic thromboembolus: 10 (15.6%), 5 (8.9%), and 9 (11.0%) in groups 1, 2, and 3, respectively. Univariate risk factors were older age (hazard ratio [HR], 1.05; P=0.0001), ongoing phlebotomy (HR, 3.1; P=0.0415), and an transvenous lead (HR, 2.4; P=0.0421). In multivariate, stepwise regression analyses, transvenous leads remained an independent predictor of systemic thromboemboli (HR, 2.6; P=0.0265). In patients with transvenous leads, independent risk factors were older age (HR, 1.05; P=0.0080), atrial fibrillation or flutter (HR, 6.7; P=0.0214), and ongoing phlebotomy (HR, 14.4; P=0.0349). Having had aspirin or warfarin prescribed was not protective. Epicardial leads were, however, associated with higher atrial (P=0.0407) and ventricular (P=0.0270) thresholds and shorter generator longevity (HR, 1.9; P=0.0176).Transvenous leads incur a >2-fold increased risk of systemic thromboemboli in patients with intracardiac shunts.
Transcription Factor Fos-Related Antigen-2 Induces Progressive Peripheral Vasculopathy in Mice Closely Resembling Human Systemic Sclerosis
Authors: Britta Maurer, Nicole Busch, Astrid Jüngel, Margarita Pileckyte, Renate E. Gay, Beat A. Michel, Georg Schett, Steffen Gay, Jörg Distler, Oliver Distler
Journal: Circulation (2009)

Microvascular damage is one of the first pathological changes in systemic sclerosis. In this study, we investigated the role of Fos-related antigen-2 (Fra-2), a transcription factor of the activator protein-1 family, in the peripheral vasculopathy of systemic sclerosis and examined the underlying mechanisms.Expression of Fra-2 protein was significantly increased in skin biopsies of systemic sclerosis patients compared with healthy controls, especially in endothelial and vascular smooth muscle cells. Fra-2 transgenic mice developed a severe loss of small blood vessels in the skin that was paralleled by progressive skin fibrosis at 12 weeks of age. The reduction in capillary density was preceded by a significant increase in apoptosis in endothelial cells at week 9 as detected by immunohistochemistry. Similarly, suppression of Fra-2 by small interfering RNA prevented human microvascular endothelial cells from staurosporine-induced apoptosis and improved both the number of tubes and the cumulative tube lengths in the tube formation assay. In addition, cell migration in the scratch assay and vascular endothelial growth factor-dependent chemotaxis in a modified Boyden chamber assay were increased after transfection of human microvascular endothelial cells with Fra-2 small interfering RNA, whereas proliferation was not affected.Fra-2 is present in human systemic sclerosis and may contribute to the development of microvasculopathy by inducing endothelial cell apoptosis and by reducing endothelial cell migration and chemotaxis. Fra-2 transgenic mice are a promising preclinical model to study the mechanisms and therapeutic approaches of the peripheral vasculopathy in systemic sclerosis.
HCV-core protein accelerates recovery from the insensitivity of liver cells to Fas-mediated apoptosis induced by an injection of anti-Fas antibody in mice
Authors: Arata Honda, Masahiko Hatano, Michinori Kohara, Yutaka Arai, Tety Hartatik, Takashi Moriyama, Michio Imawari, Katsuro Koike, Osamu Yokosuka, Kunitada Shimotohno, Takeshi Tokuhisa
Journal: Journal of Hepatology (2000)
Caeco-colic Intussusception Following Appendicectomy
Authors: C. D. Levis
Journal: BMJ (1958)

Direct anti-globulin tests on the red cells from fresh clotted blood from 100 cases of malignant disease gave negative results.Positive results were obtained if the specimens were stored overnight at 40 C.Indirect anti-globulin tests on the sera from some of these cases gave positive results against fresh group 0 rhesus-positive cells at 40 C. only, but this was abolished by previous absorption of the serum with secretor saliva.It was considered that the antibody involved was the incomplete cold auto-antibody described by Dacie (1950).Possible reasons for the discrepancy with other workers are discussed.
Letter by Wexler and Feldman Regarding Article, “Ethnic and Gender Differences in Ambulatory Blood Pressure Trajectories: Results From a 15-Year Longitudinal Study in Youth and Adults”
Authors: Randy Wexler, David Feldman
Journal: Circulation (2007)

The research presented by Wang et al 1 is an important contribution toward understanding and reducing disparities in health care in general and hypertension in particular.Although we agree with their conclusion that "further work will be needed to determine specific risk factors, both genetic and environmental," we hope we will not forget that the explanation of a problem does not always equal a solution.As pointed out in the editorial by Jones and Hall, 2 "the challenges to understanding the science of racial differences and disparities in cardiovascular disease are substantial," and the "study by Wang et al makes an important contribution to our understanding of racial differences in blood pressure."Such information is vitally important, but it will provide very minimal benefit to African American patients unless we can address some of the cultural differences that also exist.Many African Americans continue to be wary of the healthcare system, and with good reason.The research conducted at Tuskegee still resonates within the African American community.As such, any interventions developed on the basis of genetic or environmental risk must also address the cultural gap that exists in some African American communities between perceptions of hypertension and the healthcare system.This includes the beliefs that (1) foods such as pork cause hypertension, 3 (2) pharmaceutical companies use patients to test medications, 4 (3) physicians use authoritarian and ethnically inappropriate communication patterns, 5 and (4) African Americans expect to be active participants in their care even though they may not be treated as such by physicians. 6nless we work to overcome the cultural differences (both real and imagined) that also exist within health care, any treatment(s) for hypertension developed from a better understanding of genetic and environmental influences will not yield the hoped-for results.
Adipocytes Cause Leukemia Cell Resistance to <scp>L</scp>-Asparaginase via Release of Glutamine
Authors: Ehsan A. Ehsanipour, Xia Sheng, James W. Behan, Xingchao Wang, Anna Butturini, Vassilios I. Avramis, Steven D. Mittelman
Journal: Cancer Research (2013)

Obesity is a significant risk factor for cancer. A link between obesity and a childhood cancer has been identified: obese children diagnosed with high-risk acute lymphoblastic leukemia (ALL) had a 50% greater risk of relapse than their lean counterparts. l-asparaginase (ASNase) is a first-line therapy for ALL that breaks down asparagine and glutamine, exploiting the fact that ALL cells are more dependent on these amino acids than other cells. In the present study, we investigated whether adipocytes, which produce significant quantities of glutamine, may counteract the effects of ASNase. In children being treated for high-risk ALL, obesity was not associated with altered plasma levels of asparagine or glutamine. However, glutamine synthetase was markedly increased in bone marrow adipocytes after induction chemotherapy. Obesity substantially impaired ASNase efficacy in mice transplanted with syngeneic ALL cells and, like in humans, without affecting plasma asparagine or glutamine levels. In coculture, adipocytes inhibited leukemic cell cytotoxicity induced by ASNase, and this protection was dependent on glutamine secretion. These findings suggest that adipocytes work in conjunction with other cells of the leukemia microenvironment to protect leukemia cells during ASNase treatment.
Fixed and Reproducible Orthostatic Proteinuria: Results of a 20-Year Follow-up Study
Authors: PETER D. SPRINGBERG
Journal: Annals of Internal Medicine (1982)

A 20-year follow-up evaluation of young men with fixed and reproducible orthostatic proteinuria showed no evidence of progressive renal disease. Follow-up information was obtained on 43 of the original 64 patients and detailed information was secured on 36. All had normal renal function and only six patients continued to show qualitative proteinuria. The prevalence of hypertension found was similar to that of a comparably aged group of the general population. The 20-year prognosis of patients with fixed and reproducible orthostatic proteinuria is excellent.