tbuckley/cabot-search huggingface dataset:
OC-134 Intra-abdominal metastatic neuroendocrine tumours: how feasible is the laparoscopic approach to liver resections?
Authors: L M Edwards, M J White, S O Cawich, M Abu Hilal, C Frola, N W Pearce
Journal: Gut (2012)

<h3>Introduction</h3> Approach to liver metastases in neuroendocrine tumours (NETs) significantly impacts on 5-year survival. A symptom based approach yields 5-year survival of 30% compared to &gt;60% with multi-modal cytoreduction.<sup>1</sup> At our NET tertiary referral centre patients are managed in line with the European Neuroendocrine Tumour Society guidelines,<sup>2</sup> but with greater emphasis on multimodal cytoreduction for patients with unfavourable patterns of metastatic disease. We currently perform 60% of liver resections laparoscopically: over 300 procedures from 2003 to 2011. No existing study describes laparoscopic liver resections in patients with NETs. This study evaluates the feasibility and efficacy of the laparoscopic approach to liver resections in NETs in our tertiary referral unit. <h3>Methods</h3> All patients assessed for intra-abdominal NETs from April 2005 to January 2012 were prospectively registered on a database. Patients undergoing laparoscopic liver resection were identified. Demographic, peri-operative and survival data were analysed using SPSS V.12.0. Severity of operative and post-operative morbidity was graded using the Clavien system. <h3>Results</h3> The NET MDT assessed 239 patients. 99 patients had liver metastases; 58 underwent liver resection. 29 laparoscopic liver resections were performed on 27 patients (12F:15M), median age 63 (41–78). 11 major; eight minor and 10 multiple resections were performed. Intent of resection was curative (n=4), cytoreductive (n=19) or diagnostic/staging (n=6). Peri-operative mortality was 0% with no cases of carcinoid crisis, bile leak or port site metastases. Metastatic resections with no primary resection (n=27) had a complication rate of 11% (n=3) with no complication greater than grade IIIa. Median post-operative stay was 4 days (0–12). 24 patients are alive after median 32 months (9–64) follow-up post diagnosis and median 21 months (7–62) follow-up post surgery. 3 patients died of recurrence after median 25 months (20–30) follow-up post diagnosis and 20 months (16–25) follow-up post surgery. <h3>Conclusion</h3> This is the first series to demonstrate laparoscopic liver resection for metastatic NETs can be performed with low morbidity and mortality by experienced surgeons in a tertiary referral unit. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Saxena A</b>, Chua T, Sarkar A, <i>et al.</i> Progression and survival results after radial hepatic metastectomy of indolent advanced neuroendocrine neoplasms (NENs) supports and aggressive surgical approach. <i>Surgery</i> 2011;<b>149</b>:209–20. 2. <b>Steinmuller T</b>, Kianmanes R, Falconi M, <i>et al.</i> Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: foregut, midgut, hindgut and unknown primary. <i>Neuro-endocrinology</i> 2008;<b>87</b>:47–62.
A Female Way to Protect the Heart
Authors: Fabio Di Lisa
Journal: Circulation Research (2006)

oth clinical and experimental observations support the concept that female hearts are less susceptible to myocardial injury caused by ischemia and reperfusion. 1,2A large body of evidence indicates that estrogen is involved in gender-related mechanisms of protection.The protective effect of 17-␤-estradiol (E2) administration was described as a reduced extent of necrosis in rabbit hearts undergoing coronary occlusion followed by reperfusion. 3his initial observation, as well as the reduced myocardial injury in female hearts, has been confirmed in different animal species using various experimental protocols. 4 -11 Myocardial protection was shown to be associated with activation of estrogen receptors (ER), 5 and specifically of ER␣. 6 Besides the well-established cytosolic/nuclear localization, 12,13 ER, or at least proteins recognized by anti-ER antibodies, have also been detected at the level of plasma membrane and mitochondria. 14 -17 However, the lack of a typical transmembrane domain in cytosolic ER casts doubts about these additional membrane receptors. 15The activated estrogen-receptor complex triggers the synthesis of specific mRNAs and the production of a number of proteins that are responsible for the various effects elicited in the different cell types.Along with these "genomic" effects, additional processes termed "nongenomic" or alternative occur rapidly and independently of protein synthesis. 18mong the many pathways that can modify the susceptibility to ischemic injury in female hearts, the relevance of nitric oxide (NO) signaling was addressed by Sun et al in this issue of Circulation Research.
Changes in Serum Lipids in Relation to Emotional Stress during Rigid Control of Diet and Exercise
Authors: STEWART WOLF, WILLIAM R. MCCABE, JOE YAMAMOTO, C. A. ADSETT, W. W. SCHOTTSTAEDT
Journal: Circulation (1962)

IN AN earlier study of ambulatory human subjects, significant increases in the serum concentration of lipids and cholesterol were observed to correlate with emotionally stressful events in the life situation.'Other workers have also observed such changes.?The changes seemed to occur independently of diet and exercise, but since it was not possible in ambulatory subjects to rule out such influences, the present study was undertaken while subjects were hospitalized, and with careful attention to maintaining diet and exercise constant. MethodsFour subjects, three men and one woman, were admitted to the metabolic ward of the Oklahoma Medical Research Foundation and were maintained on balanced regimens for periods varying from 4 weeks to 5 months.Exercise was carefully regulated and maintained as uniform as possible.Three of the subjects had had a well-documented myo- cardial infaretion.Two were hypertensive.The fourth had mild hypertension and hyperlipemia, which was presumed to be familial.As soon as each patient was admitted to the hospital a stand- ard diet approximating his usual eating habits was begun.All four of the diets selected happened to be of the "average American" type, with ap- proximately 40 per cent of calories coming from fat, mainly aninmal fat.Calories were adjusted to the eating habits and size of the individual.The diet of one of the subjects is illustrated in table 1. Periodic blood samples were drawn at the same time of day.Cholesterol was determined in some instances by the method of Zak and in others by the technic of Schoenheimer and Sperry, and in others by the auto-analyzer.Frequent checks were
Tumor Rejection by Modulation of Tumor Stromal Fibroblasts
Authors: Thomas Schüler, Sandra Körnig, Thomas Blankenstein
Journal: The Journal of Experimental Medicine (2003)

Interleukin (IL)-4–secreting tumors are rejected in mice, an effect that is thought to be immune mediated. However, solid tumors are embedded in a stroma that often contains tumor-promoting fibroblasts, a cell population whose function is also affected by IL-4. Here we show that IL-4–secreting tumors grew undiminished in IL-4 receptor (R)–deficient (IL-4R−/−) mice. In IL-4R+/+ mice they were long-term suppressed in the absence of T cells but complete rejection required T cells, compatible with the assumption that hematopoietic cells needed to respond to IL-4. Surprisingly, bone marrow (BM) chimeric mice revealed that IL-4R expression exclusively on non-BM–derived cells was sufficient for tumor rejection. Fibroblasts in the tumor stroma were identified as a target cell type for IL-4 because they accumulated in IL-4–secreting tumors and displayed an activated phenotype. Additionally, coinjection of IL-4R+/+ but not IL-4R−/− fibroblasts was sufficient for the rejection of IL-4–secreting tumors in IL-4R−/− mice. Our data demonstrate a novel mechanism by which IL-4 contributes to tumor rejection and show that the targeted modulation of tumor-associated fibroblasts can be sufficient for tumor rejection.
Adherent-invasive E. coli in Crohn disease: bacterial “agent provocateur”
Authors: Warren Strober
Journal: Journal of Clinical Investigation (2011)

The role of adherent-invasive E. coli (AIEC) in Crohn disease (CD) has been in debate for decades. AIEC bacteria are found in the small intestine of patients with chronic CD, but it has remained unclear whether this infection is causal or secondary to underlying immune deficiencies in CD patients. In this issue of the JCI, Chassaing and colleagues demonstrate that AIEC bacteria express an adherence factor called long polar fimbriae (LPF) that aids in the binding of these bacteria to M cells overlying Peyer's patches and subsequent entry into lymphoid tissue. These findings provide a mechanism of AIEC penetration but do not prove that AIEC is causing a primary infection in the Peyer's patches that is necessary for the initiation or persistence of CD inflammation.
Risk-factors for gastrointestinal colonisation with resistant Enterobacteriaceae among hospitalised patients: a prospective study
Authors: D. Lepelletier, N. Caroff, D. Riochet, P. Bizouarn, A. Bourdeau, F. Le Gallou, E. Espaze, A. Reynaud, H. Richet
Journal: Clinical Microbiology and Infection (2006)
Step-up treatment for children with uncontrolled asthma
Authors: C. Chambers
Journal: Thorax (2010)

Uncontrolled asthma can occur in children receiving low dose inhaled corticosteroids, but evidence to guide step-up treatment is currently lacking. In this study, 182 children (6–17 years of age) with uncontrolled asthma on 100 μg of fluticasone twice daily were randomly assigned to receive each of three blinded step-up treatments in a random order for …
Human complement in the arachidonic acid transformation pathway in platelets.
Authors: M J Polley, R L Nachman, B B Weksler
Journal: The Journal of Experimental Medicine (1981)

Arachidonate-mediated release of 14C serotonin and thromboxane B2 (TXB2) is significantly enhanced in the presence of complement. Only purified complement components C5, C6, C7, C8, and C9 are required for this reactivity. No known activating mechanism of the classical or alternative pathway is required, nor is C3. In the absence of exogenously added complement, platelet membrane-bound complement components play an essential role in modulating arachidonate-mediated serotonin release. Incubation of platelet membranes with arachidonate and C5--C9 led to the production of dimers of the membrane attack complex (C5b--9) on the platelet surface. These macromolecular complexes were eluted from the platelet membrane and were identified physicochemically and morphologically. The possibility arises that C3 in association with C5--C9 is required for mobilization of the arachidonic acid from the phospholipid of the platelet membrane. Once the arachidonic acid is mobilized, C3 is no longer required, C5--C9 being sufficient to modulate this pathway leading to enhanced production of TXB2.
Noninvasive quantification of regional myocardial perfusion with rubidium-82 and positron emission tomography. Exploration of a mathematical model.
Authors: P Herrero, J Markham, M E Shelton, C J Weinheimer, S R Bergmann
Journal: Circulation (1990)

Positron emission tomography (PET) centers without cyclotrons use generator-produced rubidium-82 (82Rb) for assessment of myocardial perfusion. The aim of the present study was to determine whether myocardial blood flow could be assessed quantitatively with 82Rb and PET. Because the myocardial extraction fraction of 82Rb varies inversely and nonlinearly with flow and cannot be measured conveniently with PET, we used an experimentally derived mathematical function defining the relation between single-pass extraction fraction of 82Rb and flow to obviate the necessity of measuring the extraction fraction directly. Myocardial blood flow in absolute terms (ml/g/min) was estimated from dynamic PET scans after intravenous administration of 82Rb in intact dogs and compared with flows measured with radiolabeled microspheres. In 36 comparisons in 13 dogs studied at rest, or after coronary occlusion, reperfusion, or after coronary hyperemia induced with intravenous dipyridamole, over the flow range from 0.2 to 2.0 ml/g/min, estimates of perfusion with rubidium correlated well with flows measured concomitantly with microspheres, although there was a slight underestimation of flow with rubidium (flow by 82Rb = 0.92 x flow by microspheres-0.021, r = 0.83). In general, estimates of flow in ischemic regions were less reliable than estimates for regions with normal flow. Thus, although the relation between myocardial extraction and retention of 82Rb and flow can vary under a variety of physiological and pathophysiological conditions, this study demonstrates the ability to obtain quantitative estimates of myocardial blood flow with 82Rb and PET under carefully defined conditions without measuring the extraction fraction directly.
The role of 5-lipoxygenase products in preclinical models of asthma
Authors: Craig D. Wegner, Robert H. Gundel, William M. Abraham, Edward S. Schulman, Mark J. Kontny, Edward S. Lazer, Carol A. Homon, Anne G. Graham, Carol A. Torcellini, Cosmos C. Clarke, Paul Jager, Walter W. Wolyniec, L.Gordon Letts, Peter R. Farina
Journal: Journal of Allergy and Clinical Immunology (1993)
Properties of a potassium channel in cultured human gastric cells (HGT-1) possessing specific omeprazole binding sites.
Authors: G I Sandle, G Fraser, K Fogg, G Warhurst
Journal: Gut (1993)

The HGT-1 human gastric cell line is similar to acid secreting parietal cells in that it possesses H2 receptors, histamine sensitive adenyl cyclase, and Cl- channels, which are activated by histamine by a cyclic adenosine monophosphate (cAMP) dependent mechanism. To discover if HGT-1 cells have additional properties found in parietal cells, [3H]omeprazole and patch clamp recording techniques were used to evaluate specific omeprazole binding sites and K+ channels in the plasma membrane. HGT-1 cells exhibited [3H]omeprazole binding in the non-stimulated state, which increased 100% in the presence of 1 mM histamine. High conductance (about 155 pS) K+ channels were active spontaneously in 17% of cell attached or excised inside out patches in non-stimulated subconfluent HGT-1 cells. In inside out patches, channel activity increased fivefold during depolarisation, ion substitution experiments confirmed that the channels were highly selective for K+, and channel activity was almost abolished by removal of Ca2+ or addition of 5 mM Ba2+. In quiescent cell attached patches, 0.1 mM dibutyryl cAMP failed to activate K+ channels. In contrast, 6.7 microM A23187 (a Ca2+ ionophore) increased intracellular Ca2+ concentration from mean (SEM) 14 (3) nM to 248 (30) nM and activated K+ channels in 21% of patches. It is concluded that the plasma membrane of HGT-1 cells possesses (a) specific 3H-omeprazole binding sites, which may reflect the omeprazole sensitive H+,K(+)-ATPase present in gastric parietal cells; and (b) Ca(2+)-activated K+ channels, which may be located in the basolateral membrane of human gastric parietal cells and play a part in acid secretion triggered by Ca(2+)-mediated secretory agonists.
Tumor-Specific Expression of Vascular Endothelial Growth Factor Receptor 2 but Not Vascular Endothelial Growth Factor or Human Epidermal Growth Factor Receptor 2 Is Associated With Impaired Response to Adjuvant Tamoxifen in Premenopausal Breast Cancer
Authors: Lisa Rydén, Karin Jirström, Pär-Ola Bendahl, Mårten Fernö, Bo Nordenskjöld, Olle Stål, Sten Thorstenson, Per-Ebbe Jönsson, Göran Landberg
Journal: Journal of Clinical Oncology (2005)

Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) are often coexpressed in breast cancer, and potentially affect cellular pathways and key proteins such as the estrogen receptor (ER) targeted by endocrine treatment. We therefore explored the association between adjuvant tamoxifen treatment in breast cancer and expression of VEGF-A and VEGFR2, as well as human epidermal growth factor receptor 2 (HER2), which represents a candidate gene product involved in tamoxifen resistance.Immunohistochemical expression of tumor-specific VEGF-A, VEGFR2, and HER2 was evaluated in tumor specimens from premenopausal breast cancer patients randomly assigned to 2 years of tamoxifen or no treatment (n = 564), with 14 years of follow-up. Hormone receptor status was determined in 96% of the tumors.VEGF-A, VEGFR2, and HER2 were assessable in 460, 472, and 428 of the tumors, respectively. In patients with ER-positive and VEGFR2-low tumors, adjuvant tamoxifen significantly increased recurrence-free survival (RFS; [HR] hazard ratio for RFS, 0.53; P = .001). In contrast, tamoxifen treatment had no effect in patients with VEGFR2-high tumors (HR for RFS, 2.44; P = .2). When multivariate interaction analyses were used, this difference in treatment efficacy relative to VEGFR2 expression status was statistically significant for both ER-positive (P = .04) plus ER-positive and progesterone receptor-positive tumors. We found no significant difference in tamoxifen treatment effects in relation to VEGF-A or HER2 status.Tumor-specific expression of VEGFR2 was associated with an impaired tamoxifen effect in hormone receptor-positive premenopausal breast cancer. Tamoxifen in combination with VEGFR2 inhibitors might be a novel treatment approach for VEGFR2-expressing breast cancer, and such a treatment might restore the tamoxifen response.
Prostacyclin produced by the pregnant uterus in the dog may act as a circulating vasodepressor substance.
Authors: J G Gerber, N A Payne, R C Murphy, A S Nies
Journal: Journal of Clinical Investigation (1981)

Uterine production of PGI2 (prostacyclin) was quantitated in late pregnant dogs to evaluate if PGI2 could act as circulating vasodepressor substance in pregnancy. In five anesthetized, laparotomized dogs, the uterine venous plasma concentration of 6-keto PGF1 alpha (the in vitro hydrolysis product of PGI2) was 6.7 +/- 1.9 ng/ml and the arterial plasma concentration was 2.6 +/0 0.8 ng/ml. In four nonpregnant female dogs the arterial plasma concentration of 6-keto PGF1 alpha was consistently below 0.2 ng/ml. In eight pregnant dogs we also evaluated the ability of the pregnant uterus to inactivate PGI2 by comparing the hypotensive response to increasing doses of PGI2 infused into the uterine artery to the hypotensive response to increasing doses of PGI2 infused into the inferior vena cava. In addition, the effect of PGI2 infused into the uterine artery on uterine blood flow and intraamniotic fluid pressure was evaluated. The dose-response curves of intrauterine and intravenous PGI2 in causing systemic hypotension were identical suggesting that the pregnant uterus does not inactivate infused PGI2. Intrauterine PGI2 had no consistent effect on uterine hemodynamics although it did increase intraamniotic fluid pressure significantly. These data demonstrate that the pregnant uterus has the capacity to produce large quantities of PGI2 which is not inactivated in the uterus and therefore can appear in the arterial blood to exert a systemic vasodepressor effect.
Immune response gene function correlates with the expression of an Ia antigen. I. Preferential association of certain Ae and E alpha chains results in a quantitative deficiency in expression of an Ae:E alpha complex.
Authors: J M McNicholas, D B Murphy, L A Matis, R H Schwartz, E A Lerner, C A Janeway, P P Jones
Journal: The Journal of Experimental Medicine (1982)

These studies were stimulated by the observation, reported in the accompanying paper (19), that IEu failed to interact with I-Ak or I-As in F1 mice to allow a response to the antigen, pigeon cytochrome c, unlike I-E subregions derived from other Ia.7+ haplotypes. Serological and biochemical analyses were performed to determine whether or not cells from these F1 mice express the Ak,se:E alpha complexes that should function as restriction elements for T cell recognition of pigeon cytochrome c on antigen-presenting cells. Using the Y-17 monoclonal antibody, which recognizes the combinatorial or conformational determinant Ia.m44 on certain Ae:E alpha complexes, we were able to distinguish between Aue:Eu alpha and Ab,k,se:Eu alpha complexes on cell surfaces. Although complement-dependent microcytotoxicity with Y-17 failed to detect Ab,k,se:Eu alpha complexes on cells from appropriate F1 mice, these molecules were detected by both quantitative absorption and quantitative immunofluorescence studies. However, Ab,k,se:Eu alpha complexes were found to be present at levels only one-seventh to one-eighth the levels expressed by homozygous I-Ab, I-Ek; I-Ak, I-Ek; and I-As, I-Ek cells. The results of two-dimensional polyacrylamide gel electrophoresis analyses suggest that the low levels of expression of Ab,k,se:Eu alpha complexes are a consequence of the preferential association of Aue and Eu alpha chains with each other in the F1 cells. As will be shown in the following paper (19), the quantitative deficiency in the expression of Ake:Eu alpha and Ase:Eu alpha complexes results in a corresponding defect in antigen-presenting cell function, thus providing strong evidence that Ia antigens represent products of Ir genes.
Quantitative Determinants of the Outcome of Asymptomatic Mitral Regurgitation
Authors: Maurice Enriquez-Sarano, Jean-François Avierinos, David Messika-Zeitoun, Delphine Detaint, Maryann Capps, Vuyisile Nkomo, Christopher Scott, Hartzell V. Schaff, A. Jamil Tajik
Journal: New England Journal of Medicine (2005)

The clinical outcome of asymptomatic mitral regurgitation is poorly defined, and the treatment is uncertain. We studied the effect on the outcome of quantifying mitral regurgitation according to recent guidelines.We prospectively enrolled 456 patients (mean [+/-SD] age, 63+/-14 years; 63 percent men; ejection fraction, 70+/-8 percent) with asymptomatic organic mitral regurgitation, quantified according to current recommendations (regurgitant volume, 66+/-40 ml per beat; effective regurgitant orifice, 40+/-27 mm2).The estimated five-year rates (+/-SE) of death from any cause, death from cardiac causes, and cardiac events (death from cardiac causes, heart failure, or new atrial fibrillation) with medical management were 22+/-3 percent, 14+/-3 percent, and 33+/-3 percent, respectively. Independent determinants of survival were increasing age, the presence of diabetes, and increasing effective regurgitant orifice (adjusted risk ratio per 10-mm2 increment, 1.18; 95 percent confidence interval, 1.06 to 1.30; P<0.01), the predictive power of which superseded all other qualitative and quantitative measures of regurgitation. Patients with an effective regurgitant orifice of at least 40 mm2 had a five-year survival rate that was lower than expected on the basis of U.S. Census data (58+/-9 percent vs. 78 percent, P=0.03). As compared with patients with a regurgitant orifice of less than 20 mm2, those with an orifice of at least 40 mm2 had an increased risk of death from any cause (adjusted risk ratio, 2.90; 95 percent confidence interval, 1.33 to 6.32; P<0.01), death from cardiac causes (adjusted risk ratio, 5.21; 95 percent confidence interval, 1.98 to 14.40; P<0.01), and cardiac events (adjusted risk ratio, 5.66; 95 percent confidence interval, 3.07 to 10.56; P<0.01). Cardiac surgery was ultimately performed in 232 patients and was independently associated with improved survival (adjusted risk ratio, 0.28; 95 percent confidence interval, 0.14 to 0.55; P<0.01).Quantitative grading of mitral regurgitation is a powerful predictor of the clinical outcome of asymptomatic mitral regurgitation. Patients with an effective regurgitant orifice of at least 40 mm2 should promptly be considered for cardiac surgery.
Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia
Authors: Tatsuya Suzuki, Hitoshi Kiyoi, Kazutaka Ozeki, Akihiro Tomita, Satomi Yamaji, Ritsuro Suzuki, Yoshihisa Kodera, Shuichi Miyawaki, Norio Asou, Kazutaka Kuriyama, Fumiharu Yagasaki, Chihiro Shimazaki, Hideki Akiyama, Miki Nishimura, Toshiko Motoji, Katsuji Shinagawa, Akihiro Takeshita, Ryuzo Ueda, Tomohiro Kinoshita, Nobuhiko Emi, Tomoki Naoe
Journal: Blood (2005)