tbuckley/cabot-search huggingface dataset:
Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London.
Authors: I T Gilmore, A Burroughs, I M Murray-Lyon, R Williams, D Jenkins, A Hopkins
Journal: Gut (1995)

The liver section of the British Society of Gastroenterology and the research unit of the Royal College of Physicians collaborated to set up a nationwide audit to investigate the practice of percutaneous liver biopsy in England and Wales. Each of 189 health districts in England and Wales was approached to provide a list of 10 consecutive percutaneous biopsies performed during 1991, and details of demographic data, indications, suspected diagnosis, investigations, biopsy technique, outcome, and influence on patient management were collected. Data were retrieved on 1500 (79%). The age distribution showed 6% of biopsies were done in those over 80 years of age and as many over 90 as under 10 years of age. Suspected malignancy and chronic liver disease each contributed one third of the indications. In 34% the procedure was carried out by radiologists under ultrasound image control. The remainder were done by general physicians and gastroenterologists, with the operator in the second group being more senior and experienced. The Trucut biopsy needle accounted for two thirds of biopsies, the remainder being the Menghini type. For both needles the samples were recorded as excellent or satisfactory in 83% and inadequate in only 5%. Bleeding complicated 26 procedures (1.7%), requiring transfusion in 11, and was commoner when clotting was impaired or serum bilirubin raised. There were two definite and three possible procedure related, given an overall mortality of 0.13-0.33%. The diagnosis made before biopsy was confirmed in 63% of patients, and the clinician found the biopsy helpful in treatment in 75%. Day case biopsy and techniques to reduce the risk of bleeding were surprisingly rare in this series, which has given a unique opportunity to examine everyday practice across a wide range of hospitals.
Role of Chemokines and Chemokine Receptors in Shaping the Effector Phase of the Antitumor Immune Response
Authors: Katarzyna Franciszkiewicz, Alexandre Boissonnas, Marie Boutet, Christophe Combadière, Fathia Mami-Chouaib
Journal: Cancer Research (2012)

Immune system-mediated eradication of neoplastic cells requires induction of a strong long-lasting antitumor T-cell response. However, generation of tumor-specific effector T cells does not necessarily result in tumor clearance. CTL must first be able to migrate to the tumor site, infiltrate the tumor tissue, and interact with the target to finally trigger effector functions indispensable for tumor destruction. Chemokines are involved in circulation, homing, retention, and activation of immunocompetent cells. Although some of them are known to contribute to tumor growth and metastasis, others are responsible for changes in the tumor microenvironment that lead to extensive infiltration of lymphocytes, resulting in tumor eradication. Given their chemoattractive and activating properties, a role for chemokines in the development of the effector phase of the antitumor immune response has been suggested. Here, we emphasize the role of the chemokine-chemokine receptor network at multiple levels of the T-cell-mediated antitumor immune response. The identification of chemokine-dependent molecular mechanisms implicated in tumor-specific CTL trafficking, retention, and regulation of their in situ effector functions may offer new perspectives for development of innovative immunotherapeutic approaches to cancer treatment.
An <i>In vivo</i> Platform for Translational Drug Development in Pancreatic Cancer
Authors: Belen Rubio-Viqueira, Antonio Jimeno, George Cusatis, Xianfeng Zhang, Christine Iacobuzio-Donahue, Collins Karikari, Chanjusn Shi, Kathleen Danenberg, Peter V. Danenberg, Hidekazu Kuramochi, Koji Tanaka, Sharat Singh, Hossein Salimi-Moosavi, Nadia Bouraoud, Maria L. Amador, Soner Altiok, Piotr Kulesza, Charles Yeo, Wells Messersmith, James Eshleman, Ralph H. Hruban, Anirban Maitra, Manuel Hidalgo
Journal: Clinical Cancer Research (2006)

Abstract Effective development of targeted anticancer agents includes the definition of the optimal biological dose and biomarkers of drug activity. Currently available preclinical models are not optimal to this end. We aimed at generating a model for translational drug development using pancreatic cancer as a prototype. Resected pancreatic cancers from 14 patients were xenografted and expanded in successive groups of nude mice to develop cohorts of tumor-bearing mice suitable for drug therapy in simulated early clinical trials. The xenografted tumors maintain their fundamental genotypic features despite serial passages and recapitulate the genetic heterogeneity of pancreatic cancer. The in vivo platform is useful for integrating drug screening with biomarker discovery. Passages of tumors in successive cohorts of mice do not change their susceptibility to anticancer agents and represent a perpetual live bank, facilitating the application of new technologies that will result in the creation of an integrated stable database of tumor-drug response data and biomarkers.
Creating health through physical activity
Authors: Sir Harry Burns, Andrew Duncan Murray
Journal: British Journal of Sports Medicine (2012)

In Scotland we aim to increase life expectancy by 5 years in the next 10 years and decrease health inequalities.

These ambitions are bold. If life expectancy trends continue, Scotland will fall further behind the rest of Western Europe. Although premature mortality continues to fall, the trajectory of our improvement is currently more modest than that being achieved by other countries. And despite all efforts, health inequalities continue to grow. The gap between the rich and the poor is widening, with the richest 20% now living 10 years longer than the poorest 20% in Scotland.

Albert Einstein defined insanity as ‘doing the same thing over and over again and expecting a different result.’

The excess mortality in Scotland requires something new to be done. It may partly stem from the social breakdown and loss of jobs when heavy industry (dominated by shipbuilding, coal mining and steel) declined, particularly in West Central Scotland in the latter half of the 20th century. Those affected were given housing and benefit, and remained predominantly in the region. Although the collapse of heavy industry happened in other countries in Europe, for example, Katowice in Poland, alternative suitable work was found and the sense of control, and community that goes with purpose and employment was preserved. The net result is that Scotland's excess mortality when compared with the rest of Europe can be partly attributed to causes such as violence, drug misuse, alcohol excess and suicide. Interestingly, similar patterns of excess mortality have been noticed in other population groups …
Pulmonary Vascular Changes with Chronic Unilateral Pulmonary Hypoxia
Authors: RICHARD L. NAEYE
Journal: Circulation Research (1965)

One main bronchus was ligated in each of twelve dogs and three calves. In eight of the animals, the bronchus reopened spontaneously with a 2 to 4 mm aperture permitting re-expansion of the associated lung. Both smooth muscle hyperplasia and hypertrophy developed in small arteries of the poorly ventilated dog lungs. In the calves, muscular hyperplasia and hypertrophy developed in small pulmonary veins of the hypoxic lungs. Since arterial pressures and pulmonary arterial oxygen saturation were presumably identical in hypoxic and control lungs, changes in vascular muscle are postulated to be the result of altered oxygen tension of the surrounding alveolar gas.
Time to Treatment in Primary Percutaneous Coronary Intervention
Authors: Brahmajee K. Nallamothu, Elizabeth H. Bradley, Harlan M. Krumholz
Journal: New England Journal of Medicine (2007)

Early administration of reperfusion therapy improves survival among patients with ST-elevation myocardial infarction. For primary percutaneous intervention, a goal of 90 minutes or less for door-to-balloon time is incorporated into many measures of quality performance, but delay remains common, with little improvement in this measure over recent years. This review examines the strategies for reducing door-to-balloon time and for selecting the appropriate reperfusion therapy, especially when a delay is unavoidable.
Percutaneous Recanalization of Chronically Occluded Coronary Arteries
Authors: Gregg W. Stone, Nicolaus J. Reifart, Issam Moussa, Angela Hoye, David A. Cox, Antonio Colombo, Donald S. Baim, Paul S. Teirstein, Bradley H. Strauss, Matthew Selmon, Gary S. Mintz, Osamu Katoh, Kazuaki Mitsudo, Takahiko Suzuki, Hideo Tamai, Eberhard Grube, Louis A. Cannon, David E. Kandzari, Mark Reisman, Robert S. Schwartz, Steven Bailey, George Dangas, Roxana Mehran, Alexander Abizaid, Jeffrey W. Moses, Martin B. Leon, Patrick W. Serruys
Journal: Circulation (2005)

I n Part I of this article, the definitions, prevalence, and clinical presentation of chronic total occlusions (CTOs) were reviewed, the histopathology of CTOs was examined, efforts to replicate human CTOs with experimental models were appraised, and the clinical relevance and rationale for CTO revascularization were evaluated. 1In Part II, we summarize the technical approach to and outcomes after percutaneous coronary intervention (PCI) of occluded coronary arteries, describe the novel devices and drugs approved and undergoing investigation for CTO recanalization, and conclude with practical perspectives on managing the patient with 1 or more chronic coronary occlusions.
Predictive Value of Foot Pressure Assessment as Part of a Population-Based Diabetes Disease Management Program
Authors: Lawrence A. Lavery, David G. Armstrong, Robert P. Wunderlich, Jeffrey Tredwell, Andrew J.M. Boulton
Journal: Diabetes Care (2003)

OBJECTIVE—To evaluate the effectiveness of dynamic plantar pressure assessment to determine patients at high risk for neuropathic ulceration. In choosing the cut point, we looked for an optimum combination of sensitivity and specificity of plantar pressure to screen for neuropathic ulceration. RESEARCH DESIGN AND METHODS—A total of 1,666 consecutive individuals with diabetes (50.3% male) presenting to a large urban managed care-based outpatient clinic were enrolled in this longitudinal 2-year outcome study. Patients received a standardized medical and musculoskeletal assessment at the time of enrollment, including evaluation in an onsite gait laboratory. RESULTS—Of the entire population, 263 patients (15.8%) either presented with or developed an ulcer during the 24-month follow-up period. As expected, baseline peak plantar pressure was significantly higher in the ulcerated group than in the group who did not ulcerate (95.5 ± 26.4 vs. 85.1 ± 27.3 N/cm2, P &amp;lt; 0.001). There was also a trend toward increased pressure with increasing numbers of foot deformities, as well as with increasing foot risk classification (P = 0.0001). Peak pressure was not a suitable diagnostic tool by itself to identify high-risk patients. After eliminating patients without loss of protective sensation, using receiver operating characteristic (ROC) analysis, the optimal cut point, as determined by a balance of sensitivity and specificity, was 87.5 N/cm2, yielding a sensitivity of 63.5% and a specificity of 46.3%. CONCLUSIONS—The data from this evaluation continue to support the notion that elevated foot pressure is an important risk factor for foot complications. However, the ROC analysis suggests that foot pressure is a poor tool by itself to predict foot ulcers.
Humanized Mouse Model of Thrombosis Is Predictive of the Clinical Efficacy of Antiplatelet Agents
Authors: Jorge Magallon, Jianchun Chen, Leroy Rabbani, George Dangas, Jing Yang, James Bussel, Thomas Diacovo
Journal: Circulation (2011)

In vivo testing of novel antiplatelet agents requires informative biomarkers. By genetically modifying mouse von Willebrand factor (VWF(R1326H)), we have developed a small animal model that supports human but not mouse platelet-mediated thrombosis. Here, we evaluate the use of this biological platform as a pharmacodynamic biomarker for antithrombotic therapies.The antithrombotic effects of several αIIbβ3 inhibitors were determined in VWF(R1326H) mutant mice infused with human platelets. Administration of abciximab, eptifibatide, or tirofiban at doses recommended for percutaneous coronary intervention (per 1 kg of body weight) significantly reduced human platelet-mediated thrombus formation in laser-injured arterioles by > 75% (P < 0.001). In contrast, clot size in wild-type control animals remained essentially unchanged (P > 0.05), results consistent with observed species differences in IC₅₀ values obtained by aggregometry. To further demonstrate that our biological platform is unique among standard mouse models, we evaluated the thrombogenic potential of platelets from healthy volunteers before and after clopidogrel therapy. Consistent with the antithrombotic effect of this agent, platelets postdrug administration formed smaller thrombi than cells before therapy and were less responsive to ADP-induced aggregation (P < 0.001).The ability of αIIbβ3 and P2Y₁₂ inhibitors to limit human platelet clot formation at doses recommended by the American College of Cardiology/American Heart Association suggests that VWF(R1326H) mutant mice can serve as both a pharmacodynamic and a functional response biomarker, attributes essential for not only expediting drug development but also designing clinical studies.
Autoantibodies to Ezrin are an early sign of pancreatic cancer in humans and in genetically engineered mouse models
Authors: Michela Capello, Paola Cappello, Federica Caterina Linty, Roberto Chiarle, Isabella Sperduti, Anna Novarino, Paola Salacone, Giorgia Mandili, Alessio Naccarati, Carlotta Sacerdote, Stefania Beghelli, Samantha Bersani, Stefano Barbi, Claudio Bassi, Aldo Scarpa, Paola Nisticò, Mirella Giovarelli, Paolo Vineis, Michele Milella, Francesco Novelli
Journal: Journal of Hematology & Oncology (2013)

Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive malignancy with only a 5% 5-year survival rate. Reliable biomarkers for early detection are still lacking. The goals of this study were (a) to identify early humoral responses in genetically engineered mice (GEM) spontaneously developing PDAC; and (b) to test their diagnostic/predictive value in newly diagnosed PDAC patients and in prediagnostic sera.The serum reactivity of GEM from inception to invasive cancer, and in resectable or advanced human PDAC was tested by two-dimensional electrophoresis Western blot against proteins from murine and human PDAC cell lines, respectively. A common mouse-to-human autoantibody signature, directed against six antigens identified by MALDI-TOF mass spectrometry, was determined. Of the six antigens, Ezrin displayed the highest frequency of autoantibodies in GEM with early disease and in PDAC patients with resectable disease. The diagnostic value of Ezrin-autoantibodies to discriminate PDAC from controls was further shown by ELISA and ROC analyses (P < 0.0001). This observation was confirmed in prediagnostic sera from the EPIC prospective study in patients who eventually developed PDAC (with a mean time lag of 61.2 months between blood drawing and PDAC diagnosis). A combination of Ezrin-autoantibodies with CA19.9 serum levels and phosphorylated α-Enolase autoantibodies showed an overall diagnostic accuracy of 0.96 ± 0.02.Autoantibodies against Ezrin are induced early in PDAC and their combination with other serological markers may provide a predictive and diagnostic signature.
Molecular determination of dermatophyte fungi using the arbitrarily primed polymerase chain reaction
Authors: D. LIU, S. COLOE, R. BAIRD, J. PEDERSEN
Journal: British Journal of Dermatology (1997)

Dermatophytes are keratinophilic fungi capable of causing dermatophytosis (commonly known as tinea or ringworm) in humans and animals. Previously, we reported the differentiation of the common dermatophytes Trichophyton rubrum, T. mentagrophytes and T. tonsurans using a random primer 5'-ACCCGACCTG-3' (OPAA11) in the arbitrarily primed polymerase chain reaction (AP-PCR). In the present study, by examining additional dermatophytes including eight Microsporum spp., 16 Trichophyton species/subspecies and Epidermophyton floccosum using both OPAA11 and a second random decamer 5'-GAGAGCCAAC-3' (OPD18) in AP-PCR, we show that except for T. rubrum and T. gourvilli, and three T. mentagrophytes varieties, most of the dermatophyte fungi investigated formed distinct DNA band patterns on gel electrophoresis. The amplification of specific DNA bands in AP-PCR appeared to be independent of culture variations shown by dermatophyte isolates. These results provide the basis for the rapid identification of dermatophytes at the genetic level, supplementing existing laboratory methods and improving the diagnosis of human dermatophytosis.
A Randomized Trial of Collaborative Depression Care in Obstetrics and Gynecology Clinics: Socioeconomic Disadvantage and Treatment Response
Authors: Wayne Katon, Joan Russo, Susan D. Reed, Carmen A. Croicu, Evette Ludman, Anna LaRocco, Jennifer L. Melville
Journal: American Journal of Psychiatry (2014)

Objective: The authors evaluated whether an obstetrics-gynecology clinic-based collaborative depression care intervention is differentially effective compared with usual care for socially disadvantaged women with either no health insurance or with public coverage compared with those with commercial insurance. Method: The study was a two-site randomized controlled trial with an 18-month follow-up. Women were recruited who screened positive (a score of at least 10 on the Patient Health Questionnaire–9) and met criteria for major depression or dysthymia. The authors tested whether insurance status had a differential effect on continuous depression outcomes between the intervention and usual care over 18 months. They also assessed differences between the intervention and usual care in quality of depression care and dichotomous clinical outcomes (a decrease of at least 50% in depressive symptom severity and patient-rated improvement on the Patient Global Improvement Scale). Results: The treatment effect was significantly associated with insurance status. Compared with patients with commercial insurance, those with no insurance or with public coverage had greater recovery from depression symptoms with collaborative care than with usual care over the 18-month follow-up period. At the 12-month follow-up, the effect size for depression improvement compared with usual care among women with no insurance or with public coverage was 0.81 (95% CI=0.41, 0.95), whereas it was 0.39 (95% CI=–0.08, 0.84) for women with commercial insurance. Conclusions: Collaborative depression care adapted to obstetrics-gynecology settings had a greater impact on depression outcomes for socially disadvantaged women with no insurance or with public coverage compared with women with commercial insurance.
Fever with Thrombocytopenia Associated with a Novel Bunyavirus in China
Authors: Xue-Jie Yu, Mi-Fang Liang, Shou-Yin Zhang, Yan Liu, Jian-Dong Li, Yu-Lan Sun, Lihong Zhang, Quan-Fu Zhang, Vsevolod L. Popov, Chuan Li, Jing Qu, Qun Li, Yan-Ping Zhang, Rong Hai, Wei Wu, Qin Wang, Fa-Xian Zhan, Xian-Jun Wang, Biao Kan, Shi-Wen Wang, Kang-Lin Wan, Huai-Qi Jing, Jin-Xin Lu, Wen-Wu Yin, Hang Zhou, Xu-Hua Guan, Jia-Fa Liu, Zhen-Qiang Bi, Guo-Hua Liu, Jun Ren, Hua Wang, Zhuo Zhao, Jing-Dong Song, Jin-Rong He, Tao Wan, Jing-Shan Zhang, Xiu-Ping Fu, Li-Na Sun, Xiao-Ping Dong, Zi-Jian Feng, Wei-Zhong Yang, Tao Hong, Yu Zhang, David H. Walker, Yu Wang, De-Xin Li
Journal: New England Journal of Medicine (2011)

Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an unknown cause. Infection with Anaplasma phagocytophilum has been suggested as a cause, but the pathogen has not been detected in most patients on laboratory testing.We obtained blood samples from patients with the case definition of SFTS in six provinces in China. The blood samples were used to isolate the causal pathogen by inoculation of cell culture and for detection of viral RNA on polymerase-chain-reaction assay. The pathogen was characterized on electron microscopy and nucleic acid sequencing. We used enzyme-linked immunosorbent assay, indirect immunofluorescence assay, and neutralization testing to analyze the level of virus-specific antibody in patients' serum samples.We isolated a novel virus, designated SFTS bunyavirus, from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction. RNA sequence analysis revealed that the virus was a newly identified member of the genus phlebovirus in the Bunyaviridae family. Electron-microscopical examination revealed virions with the morphologic characteristics of a bunyavirus. The presence of the virus was confirmed in 171 patients with SFTS from six provinces by detection of viral RNA, specific antibodies to the virus in blood, or both. Serologic assays showed a virus-specific immune response in all 35 pairs of serum samples collected from patients during the acute and convalescent phases of the illness.A novel phlebovirus was identified in patients with a life-threatening illness associated with fever and thrombocytopenia in China. (Funded by the China Mega-Project for Infectious Diseases and others.).
Small-Cell Carcinoma of the Prostate
Authors: Christopher J. Anker, Christopher Dechet, Jorge C. Isaac, Wallace Akerley, Dennis C. Shrieve
Journal: Journal of Clinical Oncology (2008)

Small-Cell Carcinoma of the ProstateA 72-year-old man with a 3-year history of obstructive urinary symptoms presented with painless hematuria.On examination, induration was noted along the right lobe of the prostate with a large, firm, irregular mass extending superiorly off the right base of the gland.His prostate-specific antigen (PSA) was 1.6 ng/mL, and a comprehensive metabolic panel and CBC were within normal limits.Transrectal ultrasound-guided biopsy revealed a mixed histology of adenocarcinoma, Gleason grade 4ϩ5, and small-cell carcinoma.A bone scan was normal and abdominopelvic computed tomography (CT) showed a large mass arising from the right base of the prostate and a right internal iliac node suspicious for cancer involvement.He was given a single 3-month injection of leuprolide and referred to the Huntsman Cancer Center at the University of Utah (Salt Lake City, UT), where the pathologic diagnosis was confirmed.Four of six core needle biopsies showed a homogeneous population of blue cells with round nuclei and a salt-and-pepper chromatin pattern consistent with small-cell carcinoma of the prostate (Fig 1A).Gleason 4ϩ5 adenocarcinoma