tbuckley/cabot-search huggingface dataset:
Association Between Valvular Surgery and Mortality Among Patients With Infective Endocarditis Complicated by Heart Failure
Authors: Todd Kiefer, Lawrence Park, Christophe Tribouilloy, Claudia Cortes, Roberta Casillo, Vivian Chu, Francois Delahaye, Emanuele Durante-Mangoni, Jameela Edathodu, Carlos Falces, Mateja Logar, José M. Miró, Christophe Naber, Marie Françoise Tripodi, David R. Murdoch, Philippe Moreillon, Riccardo Utili, Andrew Wang, for the ICE-PCS Investigators
Journal: JAMA (2011)

Heart failure (HF) is the most common complication of infective endocarditis. However, clinical characteristics of HF in patients with infective endocarditis, use of surgical therapy, and their associations with patient outcome are not well described.To determine the clinical, echocardiographic, and microbiological variables associated with HF in patients with definite infective endocarditis and to examine variables independently associated with in-hospital and 1-year mortality for patients with infective endocarditis and HF, including the use and association of surgery with outcome.The International Collaboration on Endocarditis-Prospective Cohort Study, a prospective, multicenter study enrolling 4166 patients with definite native- or prosthetic-valve infective endocarditis from 61 centers in 28 countries between June 2000 and December 2006.In-hospital and 1-year mortality.Of 4075 patients with infective endocarditis and known HF status enrolled, 1359 (33.4% [95% CI, 31.9%-34.8%]) had HF, and 906 (66.7% [95% CI, 64.2%-69.2%]) were classified as having New York Heart Association class III or IV symptom status. Within the subset with HF, 839 (61.7% [95% CI, 59.2%-64.3%]) underwent valvular surgery during the index hospitalization. In-hospital mortality was 29.7% (95% CI, 27.2%-32.1%) for the entire HF cohort, with lower mortality observed in patients undergoing valvular surgery compared with medical therapy alone (20.6% [95% CI, 17.9%-23.4%] vs 44.8% [95% CI, 40.4%-49.0%], respectively; P < .001). One-year mortality was 29.1% (95% CI, 26.0%-32.2%) in patients undergoing valvular surgery vs 58.4% (95% CI, 54.1%-62.6%) in those not undergoing surgery (P < .001). Cox proportional hazards modeling with propensity score adjustment for surgery showed that advanced age, diabetes mellitus, health care-associated infection, causative microorganism (Staphylococcus aureus or fungi), severe HF (New York Heart Association class III or IV), stroke, and paravalvular complications were independently associated with 1-year mortality, whereas valvular surgery during the initial hospitalization was associated with lower mortality.In this cohort of patients with infective endocarditis complicated by HF, severity of HF was strongly associated with surgical therapy and subsequent mortality, whereas valvular surgery was associated with lower in-hospital and 1-year mortality.
Expression of Epidermal Growth Factor and Epidermal Growth Factor Receptor Immunoreactivity in the Asthmatic Human Airway
Authors: MASARU AMISHIMA, MITSURU MUNAKATA, YASUYUKI NASUHARA, ATSUKO SATO, TORU TAKAHASHI, YUKIHIKO HOMMA, YOSHIKAZU KAWAKAMI
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Chronic airway inflammation, one of the pathophysiologic features of bronchial asthma, is suspected to be responsible for irreversible pathological changes of airways, called airway remodeling. To examine the mechanisms of airway remodeling in asthma, we investigated the expression of epidermal growth factor (EGF) and its receptor immunohistochemically in asthmatic human airways. Airway specimens from seven patients with asthma were obtained from autopsied and surgically resected lungs. Control specimens were obtained from lungs of eight subjects without asthma and other pulmonary complications at autopsy. We stained those specimens by the avidin–biotin–peroxidase complex (ABC) method with anti-human polyclonal EGF antibody and monoclonal EGF receptor antibodies. Three different portions of airways—large bronchi (about 1 cm in diameter), small bronchi (about 3 mm in diameter), and peripheral airways (less than 2 mm in diameter)—were examined. The thickness of the bronchial smooth muscle and basement membrane was significantly greater in the asthmatic airways than in controls. Clear immunoreactivities of EGF were widely observed on bronchial epithelium, glands, and smooth muscle in asthmatic airways. In the controls, the bronchial epithelium and the bronchial glands partially expressed faint EGF immunoreactivity. For the EGF receptor, clear immunoreactivities were also observed on bronchial epithelium, glands, smooth muscle, and basement membrane in asthmatic airways. In control airways, only part of the bronchial epithelium and smooth muscle weakly expressed EGF receptor immunoreactivity. These results suggest a possible contribution of EGF to the pathophysiology of bronchial asthma, including airway remodeling.
A new strategic phase for genomic medicine in UK health services
Authors: Hilary Burton, Caroline F Wright, Ron Zimmern
Journal: Genome Medicine (2009)

In June 2009, the Science and Technology Committee of the UK House of Lords published a report on genomic medicine, based on expert evidence collected over an 18-month period. Crucially, the report signaled that the use of genomic medicine was at a crossroads, due to the rapid development of new technologies, and opened up opportunities across the whole of medicine and healthcare. This commentary responds to the report's call for a new health service strategy, including a new genetics White Paper from the Government, and suggests some of the important elements that need further consideration.
Proteomic Analysis Reveals Hyperactivation of the Mammalian Target of Rapamycin Pathway in Neurofibromatosis 1–Associated Human and Mouse Brain Tumors
Authors: Biplab Dasgupta, Yijun Yi, David Y. Chen, Jason D. Weber, David H. Gutmann
Journal: Cancer Research (2005)

Abstract Individuals with the tumor predisposition syndrome, neurofibromatosis 1 (NF1), are prone to development of nervous system tumors, including neurofibromas and pilocytic astrocytomas. Based on the ability of the NF1 gene product (neurofibromin) to function as a GTPase activating protein for RAS, initial biologically based therapies for NF1-associated tumors focused on the use of RAS inhibitors, but with limited clinical success. In an effort to identify additional targets for therapeutic drug design in NF1, we used an unbiased proteomic approach to uncover unanticipated intracellular signaling pathways dysregulated in Nf1-deficient astrocytes. We found that the expression of proteins involved in promoting ribosome biogenesis was increased in the absence of neurofibromin. In addition, Nf1-deficient astrocytes exhibit high levels of mammalian target of rapamycin (mTOR) pathway activation, which was inhibited by blocking K-RAS or phosphatidylinositol 3-kinase activation. This mTOR pathway hyperactivation was reflected by high levels of ribosomal S6 activation in both Nf1 mutant mouse optic nerve gliomas and in human NF1-associated pilocytic astrocytoma tumors. Moreover, inhibition of mTOR signaling in Nf1−/− astrocytes abrogated their growth advantage in culture, restoring normal proliferative rates. These results suggest that mTOR pathway inhibition may represent a logical and tractable biologically based therapy for brain tumors in NF1.
Successful Treatment of Melanoma Brain Metastases with Adoptive Cell Therapy
Authors: Jenny J. Hong, Steven A. Rosenberg, Mark E. Dudley, James C. Yang, Donald E. White, John A. Butman, Richard M. Sherry
Journal: Clinical Cancer Research (2010)

To determine the objective response rate and response duration of melanoma brain metastases to adoptive cell therapy (ACT) with autologous antitumor lymphocytes plus interleukin-2 following a lymphodepleting preparative regimen.Between 2000 and 2009, 264 patients with metastatic melanoma received ACT, consisting of cyclophosphamide and fludarabine with or without total body irradiation, followed by the infusion of autologous tumor-infiltrating lymphocytes (TIL) or autologous peripheral blood lymphocytes retrovirally transduced to express a T-cell receptor (TCR) that recognized the melanocyte differentiation antigens gp-100 or MART-1. From this group, 26 patients were retrospectively identified to have had untreated brain metastases and extracranial disease before receiving ACT. The response rate and duration of melanoma brain metastases, as well as the overall response rate, response duration, and survival for these patients, are presented.Seventeen of these 26 patients received ACT with TIL. Seven of these patients (41%) achieved a complete response in the brain, and six patients achieved an overall partial response. In the nine patients that received TCR-transduced lymphocytes, two patients achieved a complete response in the brain (22%) and one of these two achieved an overall partial response. One patient developed a tumor-associated subarachnoid hemorrhage during the thrombocytopenic phase of therapy and had an uneventful metastatectomy.ACT with a nonmyeloablative preparative regimen using either TIL- or TCR gene-transduced cells and interleukin-2 can mediate complete and durable regression of melanoma brain metastases. This strategy can be used safely in selected patients with metastatic melanoma to the brain.
5-Hydroxytryptamine-3 Receptor Antagonist With or Without Short-Course Dexamethasone in the Prophylaxis of Radiation Induced Emesis: A Placebo-Controlled Randomized Trial of the National Cancer Institute of Canada Clinical Trials Group (SC19)
Authors: Rebecca K.S. Wong, Nancy Paul, Keyue Ding, Marlo Whitehead, Michael Brundage, Anthony Fyles, Derek Wilke, Abdenour Nabid, Andre Fortin, Don Wilson, Michael McKenzie, Ida Ackerman, Luis Souhami, Pierre Chabot, Joseph Pater
Journal: Journal of Clinical Oncology (2006)

To evaluate the effectiveness of prophylactic dexamethasone for the control of radiation induced emesis (RIE) when added to ondansetron during days 1 to 5 of fractionated radiotherapy. The study had two hypotheses: ondansetron and dexamethasone could provide superior control of RIE over ondansetron alone during the prophylactic period and; the combination could provide sustained control of RIE during subsequent fractions of radiotherapy.Between May 2001 to Jan 2004, 211 patients receiving radiotherapy (> or = 15 fractions) to the upper abdomen were randomly assigned to receive ondansetron 8 mg bid with either dexamethasone 4 mg daily or placebo during fractions 1 to 5. Rescue antiemetics were provided.During the prophylactic period there was a trend for improved complete control of nausea in the dexamethasone arm (50% v 38%; P = .06) while complete and partial control of emesis, average nausea score, and use of rescue medications were similar in the two groups. During the overall study period patients receiving dexamethasone had better complete control of emesis (23% v 12%; P = .02) and a lower average nausea score (0.28 v 0.39; P = .03); there was a trend towards less use of rescue medications with dexamethasone (70% v 80%; P = .09); other outcomes were similar on the two arms. Quality of life analysis showed a significant difference in appetite.The addition of dexamethasone to ondansetron as prophylaxis provides a modest improvement in protection against RIE during moderately emetogenic fractionated radiotherapy. It is a potentially useful addition to 5-hydroxytryptamine-3 receptor antagonists in this setting.
Points from Letters: Medical Eye Examinations
Authors: P. R. Day
Journal: BMJ (1970)

MEDIBCATOISNALin the Bristol centre" conceals some important facts.Rates marginally better than those described in the document were in- troduced here in September, and proved unacceptable to the deputies.This was mainly because these represented (as far as 90% of the sessions were concerned) only a 5 % increase on previous rates, even though
Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD)
Authors: Carsten Bergmann, Jan Senderek, Ellen Windelen, Fabian Küpper, Iris Middeldorf, Frank Schneider, Christian Dornia, Sabine Rudnik-Schöneborn, Martin Konrad, Claus P Schmitt, Tomas Seeman, Thomas J Neuhaus, Udo Vester, Jutta Kirfel, Reinhard Büttner, Klaus Zerres
Journal: Kidney International (2005)
Noninvasive Detection of Glutamate Predicts Survival in Pediatric Medulloblastoma
Authors: Martin Wilson, Simrandip K. Gill, Lesley MacPherson, Martin English, Theodoros N. Arvanitis, Andrew C. Peet
Journal: Clinical Cancer Research (2014)

Medulloblastoma is the most common malignant brain tumor occurring in childhood and is a significant cause of morbidity and mortality in pediatric oncology. More intense treatment strategies are recommended for patients displaying high-risk factors; however, considerable variation in outcome remains, indicating a need for improved predictive markers. In this study, 1H magnetic resonance spectroscopy (MRS) was used to investigate noninvasive molecular biomarkers of survival in medulloblastoma.MRS was performed on a series of 35 biopsy-confirmed medulloblastoma cases. One case was excluded because of poor quality MRS. The prognostic value of MRS detectable biomarkers was investigated using Cox regression, retrospectively (N=15). A subsequent validation analysis (N=19) was also performed to reduce the chance of type I errors. Where available, high-resolution ex vivo MRS of biopsy tissue was used to confirm biomarker assignments.The retrospective analysis revealed that creatine, glutamate, and glycine were markers of survival (P<0.01). The validation analysis showed that glutamate was a robust marker, with a hazard ration (HR) of 8.0 for the full dataset (P=0.0003, N=34). A good correlation between in vivo and ex vivo MRS glutamate/total-choline was found (P=0.001), validating the in vivo assignment. Ex vivo glutamate/total-choline was also associated with survival (P<0.01).The identification of glutamate as a predictive biomarker of survival in pediatric medulloblastoma provides a clinically viable risk factor and highlights the importance of more detailed studies into the metabolism of this disease. Noninvasive biomarker detection using MRS may offer improved disease monitoring and potential for widespread use following multicenter validation.
Pulmonary tumor thrombotic microangiopathy: A clinical analysis of 30 autopsy cases
Authors: Hironori Uruga, Takeshi Fujii, Atsuko Kurosaki, Yui Takahashi, Kazumasa Ogawa, Masayuki Ishibashi, Toshitaka Sato, Sayaka Mochiduki, Shigeo Hanada, Shinko Suzuki, Hisashi Takaya, Atsushi Miyamoto, Nasa Morokawa, Sakae Homma, Kazuma Kishi
Journal: European Respiratory Journal (2013)

Objective:  Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare, fatal form of pulmonary arterial tumor embolism. The aim of this study was to evaluate the clinical characteristics along the pathological and immunohistochemical findings of PTTM.   Methods:  Autopsy records in our hospital from 1983 to 2008 were reviewed, and those of patients who died from pulmonary tumor embolism resulting from malignant neoplasm were retrieved. The relevant tissue slides were reevaluated to confirm the diagnosis and examined immunohistochemically.   Results:  Among 2215 consecutive autopsy cases with carcinomas, 30 patients (1.4%) were diagnosed with definitive PTTM. The common symptom was progressive dyspnea. A hypercoagulative state was observed in all measured cases (n = 21). Chest computed tomography findings (n = 6) included consolidations, ground-glass opacities, small nodules, and tree-in-bud appearance. Perfusion scans was performed in 7 patients, 6 of whom demonstrated multiple small defects. The median survival time after initiation of oxygen supplementation was 9 days. The most frequent primary site was the stomach (n = 18; 60%), and the most frequent histological type was adenocarcinoma (28/30; 93.3%). Immunohistochemical findings for tumor cells located within the tumor emboli were positive for vascular endothelial growth factor (28/29; 96.6%) and tissue factor (29/29; 100%).   Conclusions:  We should suspect PTTM in cancer patients with acute worsening respiratory insufficiency accompanying elevated coagulation factors without embolism in major pulmonary arteries. The PTTM patients in our study had poor prognoses. Vascular endothelial growth factor and tissue factor may play important roles in PTTM.
Ion channel TRPV1-dependent activation of PTP1B suppresses EGFR-associated intestinal tumorigenesis
Authors: Petrus R. de Jong, Naoki Takahashi, Alexandra R. Harris, Jihyung Lee, Samuel Bertin, James Jeffries, Michael Jung, Jen Duong, Amy I. Triano, Jongdae Lee, Yaron Niv, David S. Herdman, Koji Taniguchi, Chang-Whan Kim, Hui Dong, Lars Eckmann, Stephanie M. Stanford, Nunzio Bottini, Maripat Corr, Eyal Raz
Journal: Journal of Clinical Investigation (2014)

The intestinal epithelium has a high rate of turnover, and dysregulation of pathways that regulate regeneration can lead to tumor development; however, the negative regulators of oncogenic events in the intestinal epithelium are not fully understood. Here we identified a feedback loop between the epidermal growth factor receptor (EGFR), a known mediator of proliferation, and the transient receptor potential cation channel, subfamily V, member 1 (TRPV1), in intestinal epithelial cells (IECs). We found that TRPV1 was expressed by IECs and was intrinsically activated upon EGFR stimulation. Subsequently, TRPV1 activation inhibited EGFR-induced epithelial cell proliferation via activation of Ca2+/calpain and resulting activation of protein tyrosine phosphatase 1B (PTP1B). In a murine model of multiple intestinal neoplasia (ApcMin/+ mice), TRPV1 deficiency increased adenoma formation, and treatment of these animals with an EGFR kinase inhibitor reversed protumorigenic phenotypes, supporting a functional association between TRPV1 and EGFR signaling in IECs. Administration of a TRPV1 agonist suppressed intestinal tumorigenesis in ApcMin/+ mice, similar to — as well as in conjunction with — a cyclooxygenase-2 (COX-2) inhibitor, which suggests that targeting both TRPV1 and COX-2 has potential as a therapeutic approach for tumor prevention. Our findings implicate TRPV1 as a regulator of growth factor signaling in the intestinal epithelium through activation of PTP1B and subsequent suppression of intestinal tumorigenesis.
The Challenge of Achieving National Cholesterol Goals in Patients With Diabetes
Authors: Amanda G. Kennedy, Charles D. MacLean, Benjamin Littenberg, Philip A. Ades, Richard G. Pinckney
Journal: Diabetes Care (2005)

OBJECTIVE—This study analyzed lipid results from a large community-based population of patients with diabetes to assess the feasibility of attaining the standard and new optional LDL-based lipid goals using currently available lipid-lowering medications. RESEARCH DESIGN AND METHODS—Ambulatory patients with diabetes who were interviewed as part of the Vermont Diabetes Information System trial with a reported LDL were analyzed. Patients were categorized into high-risk and very-high-risk cardiovascular status. For patients not at the LDL goal, the required changes in therapy to achieve the goal were assessed. RESULTS—Of the entire cohort, 49.4% (321 of 650) had LDL &amp;lt;100 mg/dl. According to the National Cholesterol Education Program, 29.4% (191 of 650) of patients were very high risk and have an optional LDL goal of &amp;lt;70 mg/dl. Only 15.7% (30 of 191) of very-high-risk patients had an LDL &amp;lt;70 mg/dl. Based on our analysis of high-risk patients, 17 of 459 (3.7%) would require more than two lipid-lowering drugs to achieve an LDL &amp;lt;100 mg/dl. In the very-high-risk group, we estimate that 26.2% (50 of 191) of patients will not reach LDL &amp;lt;70 mg/dl with two lipid-lowering medications. CONCLUSIONS—In many patients with diabetes and cardiovascular disease, it will be difficult to attain an LDL goal of &amp;lt;70 mg/dl. Approximately 25% of patients will require more than two lipid-lowering drugs at maximal doses to attain this goal, assuming 100% tolerance of lipid-lowering medications.
Lung inflammation, goblet cell hyperplasia, cytokine and chemokine production are reduced by a Chinese herbal formulation in a rat model of asthma
Authors: R.Y.T. Sung, Y.O. Wong, W.Y. Chan, K. Li, Y. Zhao, A.M. Li, T.F. Fok, K.P. Fung
Journal: Journal of Allergy and Clinical Immunology (2005)
Influence of age and Helicobacter pylori infection on serum pepsinogens in healthy blood transfusion donors.
Authors: R A Veenendaal, I Biemond, A S Pena, W van Duijn, J Kreuning, C B Lamers
Journal: Gut (1992)

In a healthy population pepsinogen A and pepsinogen C increase with advancing age. As pepsinogen A and C are raised in chronic superficial gastritis which is caused by H pylori infection, we investigated whether H pylori is responsible for the age related increase of pepsinogen A and C. In H pylori positive blood transfusion donors serum pepsinogen A (mean (SD) 73 (35) micrograms/ml v 52 (19) micrograms/ml, p much less than 0.01) and C (mean (SD) 24 (13) micrograms/ml v 10 (7) micrograms/ml, p much less than 0.01) concentrations were significantly higher than in H pylori negative blood transfusion donors, while the serum pepsinogen A:C ratio mean (SD) 3.5 (1.4) v 6.2 (3.4), p much less than 0.01) was significantly decreased because of a relative greater increase in serum pepsinogen C in H pylori positive blood transfusion donors. Analysis of variance showed that pepsinogen A and C concentrations differed significantly in the different age groups (p much less than 0.01) when we considered all blood transfusion donors and H pylori positive blood transfusion donors, the mean pepsinogen levels being highest in the older age categories. In H pylori negative blood transfusion donors no such age related difference in pepsinogen A and C could be shown. In H pylori positive blood transfusion donors a weak positive but significant correlation between pepsinogen A and C and age could be shown (r = 0.30; p = 0.01 and r = 0.31; p = 0.01 respectively). In H pylori negative blood transfusion donors no correlation between serum pepsinogens and age was found. We conclude that the age related increase in serum pepsinogen A and C described in healthy control populations is caused by an increasing prevalence of H pylori infection. Serum pepsinogen A and C concentrations in patients should therefore be related to the presence or absence of H pylori infection.
Intravenous sildenafil for postoperative pulmonary hypertension in children with congenital heart disease
Authors: Alain Fraisse, Ghazwan Butrous, Mary B. Taylor, Michael Oakes, Maria Dilleen, David L. Wessel
Journal: Intensive Care Medicine (2010)

To evaluate the efficacy and safety of intravenous sildenafil for immediate postoperative pulmonary hypertension (PH) in pediatric patients undergoing congenital heart surgery.A double-blind, multicenter, placebo-controlled, dose-ranging, parallel-group trial was conducted. Patients were randomized to one of three doses of intravenous sildenafil, or placebo, for a minimum of 24 h.The study was heavily underpowered. Whereas enrollment of 228 patients (57 per treatment arm) was required to achieve the sample size estimate to detect difference between arms, the sponsor terminated the study after 15 months owing to slow patient accrual. Seventeen patients (median age 5 months) experiencing postoperative PH were randomized and treated, five with placebo and four each with low-, medium-, and high-dose sildenafil. In the first 24 h, 40% of placebo and 17% of sildenafil patients required additional therapy (p = 0.330). Median time to extubation (3 versus 8 days, p = 0.023) and intensive care unit stay (6 versus 15 days, p = 0.008) were shorter for sildenafil patients. Mean ± standard deviation systolic pulmonary artery pressure was reduced with sildenafil (46 ± 11 to 35 ± 6 mmHg, p = 0.027 versus placebo). No adverse events or systemic hypotension were attributed to sildenafil.Intravenous sildenafil reduced pulmonary artery pressure and shortened time to extubation and intensive care unit stay in children with postoperative PH.