tbuckley/cabot-search huggingface dataset:
554. Improved Efficiency of Gene Expression Using the Stiletto™ Endocardial Direct Injection Catheter
Authors: Samuel J. Epstein, Wendy Naimark, Maria Palasis, KianK. Poh, Tengiz Tkebuchava, Corinne Luedemann, Douglas Losordo
Journal: Molecular Therapy (2006)

Background: Percutaneous intramyocardial delivery approaches are currently being used in gene therapy clinical trials for the treatment of ischemic heart disease. To further understand drug delivery using a percutaneous direct endocardial injection approach, we examined the effect of varying plasmid DNA concentration and volume on localized intramyocardial gene expression. Methods: The Stiletto™ system (Boston Scientific) was used to inject 0.2 mg of pCMV- luciferase or vehicle into 12 Yorkshire swine (30-40kg). The animals were divided into 3 groups (4 animals/group) with each animal receiving 4 injections in the lateral wall of the left ventricle as follows: (i) Low volume/High concentration group: 0.5 mg/mL, 0.1 mL/injection; (ii) High volume/Low concentration group: 0.05 mg/mL, 1.0 mL/injection and (iii) Controls: Vehicle only (Dulbecco's solution) 0.1 mL/injection (n=2) and 1.0 mL/injection (n=2). The animals were sacrificed at 3 days and the lateral wall tissue of each animal was assayed for luciferase protein. Results and Conclusions: Although the same total dose (0.2 mg of plasmid) was delivered in each plasmid group, the Low volume/High concentration group showed a statistically significant increase in luciferase protein as a function of total tissue protein compared to the High volume/Low concentration group (p<0.01, ANOVA). The Low volume/High concentration group also exhibited less intra-group variation compared with the High volume /Low concentration (21% error v. 113% error). This data suggests that greater efficiency of gene delivery and protein expression may be achieved by delivering higher concentrations of plasmids at lower injection volumes using the direct endocardial injection approach. Employee.
Evaluation of Lung Function
Authors: DANIEL H. SIMMONS
Journal: Annals of Internal Medicine (1969)

Evaluation of lung function requires evaluation of the function of the entire respiratory apparatus of which the lung is ordinarily the most critical part. It is of diagnostic value in determining the presence, type, and extent of disease. It is of therapeutic value in following the course of disease and its response to management. And, finally, it is of value in making relatively objective determinations of the degree of disability due to respiratory disease. Ideally, lung function tests should independently evaluate the function of the airways, lung circulation, and lung parenchyma where gas exchange occurs. In addition, interactions between these three parts of the system are often very important. Usually, the functions are evaluated by techniques that give only indirect evidence concerning their status and their contribution to disability. Techniques discussed include spirometry, measurement of blood gases, and lung scans.
Outpatient Care Patterns and Organizational Accountability in Medicare
Authors: J. Michael McWilliams, Michael E. Chernew, Jesse B. Dalton, Bruce E. Landon
Journal: JAMA Internal Medicine (2014)

Fostering accountability in the Medicare Accountable Care Organization (ACO) programs may be challenging because traditional Medicare beneficiaries have unrestricted choice of health care providers, are attributed to ACOs based on utilization, and often receive fragmented care.To measure 3 related constructs relevant to ACO incentives and their capacity to manage care: stability of patient assignment, leakage of outpatient care, and contract penetration.Using 2010-2011 Medicare claims and rosters of physicians in organizations participating in ACO programs, we examined these constructs among 524,246 beneficiaries hypothetically assigned to 145 ACOs prior to the start of the Medicare ACO programs. We compared estimates by patient complexity, ACO size, and the primary care orientation of ACO specialty mix.Three related construct measurements: stability of assignment, defined as the proportion of patients whose assignment to an ACO in 2010 was unchanged in 2011; leakage of outpatient care, defined as the proportion of office visits for an assigned population that occurred outside of the contracting organization; and contract penetration, defined as the proportion of Medicare outpatient spending billed by an ACO that was devoted to assigned patients.Of beneficiaries assigned to an ACO in 2010, 80.4% were assigned to the same ACO in 2011. Of those assigned to an ACO in 2010 or 2011, 66.0% were consistently assigned in both years. Unstable assignment was more common among beneficiaries with fewer conditions and office visits but also among those in several high-cost categories, including the highest decile of per-beneficiary spending. Among ACO-assigned beneficiaries, 8.7% of office visits with primary care physicians were provided outside of the assigned ACO, and 66.7% of office visits with specialists were provided outside of the assigned ACO. Leakage of outpatient specialty care was greater for higher-cost beneficiaries and substantial even among specialty-oriented ACOs (54.6% for lowest quartile of primary care orientation). Of Medicare spending on outpatient care billed by ACO physicians, 37.9% was devoted to assigned beneficiaries. This proportion was higher for ACOs with greater primary care orientation (60.0% for highest quartile vs 33.6% for lowest).Care patterns among beneficiaries served by ACOs suggest distinct challenges in achieving organizational accountability in Medicare. Continued monitoring of these patterns may be important to determine the regulatory need for enhancing ACOs' incentives and their ability to improve care efficiency.
Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial
Authors: C B Reeder, D E Reece, V Kukreti, C Chen, S Trudel, J Hentz, B Noble, N A Pirooz, J E Spong, J G Piza, V H J Zepeda, J R Mikhael, J F Leis, P L Bergsagel, R Fonseca, A K Stewart
Journal: Leukemia (2009)
Abstract 4452: p90RSK mediates resistance to PI3K-pathway inhibitors in breast cancer.
Authors: Violeta Serra, Pieter JA Eichhorn, Celina García-García, Yasir Ibrahim, Ludmila Prudkin, Olga Rodríguez, Sara Marlow, Aleix Prat, William C. Hahn, José Baselga
Journal: Cancer Research (2013)

Abstract The PI3K signaling pathway regulates diverse cellular processes including proliferation, survival and metabolism and is aberrantly activated in human cancer. As such, numerous compounds targeting the PI3K pathway are currently being clinically evaluated for the treatment of cancer and they have shown some early indications of efficacy in breast cancer. However, resistance against these agents, both de novo and acquired, may ultimately limit the efficacy of these compounds. Here, we have taken a systematic functional approach to uncover potential mechanisms of resistance to PI3K inhibitors and have identified several genes whose expression promotes survival under conditions of PI3K/mTOR blockade, including the ribosomal S6 kinases RPS6KA2 (RSK3) and RPS6KA6 (RSK4). We demonstrate that overexpression of RSK3 or RSK4 supports proliferation upon PI3K inhibition both in vitro and in vivo, in part through the attenuation of an apoptotic response and upregulation of protein translation. The addition of MEK- or RSK-specific inhibitors can extinguish these resistance phenotypes, both in cells engineered to overexpress RSK and in breast cancer cells that have elevated levels of RSK activity. These observations provide a strong rationale for the combined use of RSK and PI3K pathway inhibitors to elicit favorable responses in breast cancer patients with activated RSK. Citation Format: Violeta Serra, Pieter JA Eichhorn, Celina García-García, Yasir Ibrahim, Ludmila Prudkin, Olga Rodríguez, Sara Marlow, Aleix Prat, William C. Hahn, José Baselga. p90RSK mediates resistance to PI3K-pathway inhibitors in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4452. doi:10.1158/1538-7445.AM2013-4452
The Effectiveness of Hypertonic Glucose in Resuscitation of the Hypothermic Heart Following Potassium Chloride Arrest
Authors: GEORGE E. MAVOR, RICHARD K. MCEVOY, EARLE B. MAHONEY, R. Allan Harder
Journal: Circulation Research (1956)

Cardiac arrest was produced by coronary perfusion of potassium chloride in hypothermic dogs during sinus rhythm and during ventricular fibrillation. Resuscitation of rhythmic beats was facilitated by injection of hypertonic glucose when the ventricles responded to a light tap (responsive phase).
A novel genetic leukocyte adhesion deficiency in subsecond triggering of integrin avidity by endothelial chemokines results in impaired leukocyte arrest on vascular endothelium under shear flow
Authors: Ronen Alon, Memet Aker, Sara Feigelson, Maya Sokolovsky-Eisenberg, Donald E. Staunton, Guy Cinamon, Valentin Grabovsky, Revital Shamri, Amos Etzioni
Journal: Blood (2003)
The Next Generation of Obesity Research
Authors: Griffin P. Rodgers, Francis S. Collins
Journal: JAMA (2012)

THE OBESITY EPIDEMIC IS NOT THE FIRST MAJOR health crisis that the United States has faced. In recent decades, progress has been made against such daunting challenges as tobacco use, infant mortality, and HIV/AIDS. However, obesity may pose the most significant challenge yet because it involves changing approaches to 2 fundamental aspects of daily life: food consumption and physical activity. To have any chance of release from obesity’s ever-tightening grip, the nation will require broad-based efforts in every corner of society: homes, schools, community organizations, all levels of government, urban design, transportation, agriculture, the food industry, the media, medical practice, and, without question, biomedical research.
Adjuvant interferon for hepatocellular carcinoma
Authors: Shuichi Okada, Toshiya Sato, Seiichiro Yamamoto
Journal: Hepatology (2001)

We read with interest the recent article by Ikeda et al. 1 and the accompanying editorial 2 on the use of interferon beta (IFN-␤) to prevent recurrent hepatocellular carcinoma (HCC) after treatment of the primary tumor.We offer comments from an oncologic perspective.The investigators repeatedly note that the data were part of an ongoing trial but provided no details of that trial.It is important to know the full study design, particularly for evaluating marked differences in a small-scale trial.How long was the period of patient recruitment?How many patients were scheduled to be recruited, and what was the basis of the sample size calculation?How were patients randomized?What type of formal interim analysis was used?Who reviewed the interim data and recommended early termination?This information is necessary to assess the quality of the interim result.The post-treatment recurrence rates among patients with no adjuvant therapy were much higher (62.5% at 1 year and 100% at 2 years) than those reported by others, suggesting an unrecognized bias in the randomization process. 2,3Recurrence detected shortly after treatment has been presumed to represent intrahepatic metastasis.Therefore, if IFN-␤ played a truly significant role as an adjuvant to local treatment, this agent should have shown antitumor activity against intrahepatic metastasis unrecognized at the initial treatment.However, an antitumor effect of IFN-␤ for HCC has not been evaluated preclinically and was never established in a clinical setting.Thus, the rationale for IFN-␤ as adjuvant therapy for HCC, remains unclear, even though IFN may prevent the development of second primary HCC in patients with hepatitis C virus-related HCC. 4,5revention of recurrence after local treatment is of paramount importance to improve the long-term results for patients with HCC.Acyclic retinoid (polyprenoic acid) and iodine-131-labeled lipiodol have been evaluated in a prospective randomized manner and show promise as adjuvants to local treatment. 6,7The current preliminary data, while promising, are not yet definitive.Prospective randomized trials, with patients stratified according to expected recurrence and survival, are mandatory to define the real role of IFN-␤ as an adjuvant to local treatment for HCC.
Expression of endothelial and inducible nitric oxide synthase in human glomerulonephritis
Authors: Akira Furusu, Masanobu Miyazaki, Katsushige Abe, Shoko Tsukasaki, Kei Shioshita, Osamu Sasaki, Kenichi Miyazaki, Yoshiyuki Ozono, Takehiko Koji, Takashi Harada, Hideto Sakai, Shigeru Kohno
Journal: Kidney International (1998)
Occlusion of a Renal Artery as a Cause of Hypertension
Authors: EUGENE F. POUTASSE
Journal: Circulation (1956)

This paper presents three cases and the summary of a fourth case, in which occlusion of a renal artery was the cause of hypertension. Three patients were relieved of hypertension by nephrectomy. The literature on nonembolic renal artery occlusion with hypertension is reviewed, including 21 autopsy reports and 16 cases in which the patients were relieved of hypertension by nephrectomy or thromboendarterectomy. When a patient is found to have renal hypertension, the possibility of renal artery occlusion should be considered. Translumbar aortography currently is the best means of demonstrating renal artery occlusion.
Successful administration of cytarabine after a previous anaphylactic reaction
Authors: M. Blanca, M. J. Torres, M. Girón, J. L. Corzo, A. Martínez‐Valverde
Journal: Allergy (1997)

Cytarabine (Cyt) is an antimetabolite used primarily in the treatment of leukemia, and both immediate and delayed hypersensitity reactions have been reported. We studied a 9‐year‐old girl with lymphoblastic leukemia, who developed three anaphylactoid reactions during Cyt treatment courses over a 1‐year period. Three years later, Cyt was required again. Although a skin test was negative to Cyt at the concentration of 4 μg/ml, we decided on placebo‐controlled administration of the drug. The Cyt was well tolerated, and urine values of N‐methylhistamine showed no important variations throughout this period compared to those during the placebo administration. Skin tests carried out 14 days after the study were positive at the concentration of 4 μg/ml. The history of different episodes of allergic reactions to Cyt, the last one being the most severe, indicated the possible participation of an immediate hypersensitivity phenomenon, but because no studies had been carried out initially, we could not establish the presence of IgE antibodies. These results indicate that good tolerance existed after the control administration procedure. The long interval, 3 years, between the allergic episode and our protocol and the appearance of a positive skin test 14 clays after the protocol indicated that the subject had lost sensitivity and become resensitized after the controlled administration procedure.
Superficial Cortical Atrophy Simulating Bilateral Subdural Hematomas
Authors: CHARLES D. TEATES, DONALD M. ALLEN
Journal: Clinical Nuclear Medicine (1976)

It is well recognized that there are many conditions which may simulate a subdural hematoma on static brain scintiphotographs. A case is presented where brain atrophy simulated bilateral subdural hematomas on scintiangiograms, static scintiphotographs and cerebral angiography. This study demonstrates that there are pitfalls in the evaluation of scintiangiograms and illustrates another cause of crescentric activity.
Points from Letters: Significant Differences and Medical Ones
Authors: A. C. Carr
Journal: BMJ (1971)

Analyzer.The conditions remained identical apart from increased concentration of indicator enzymes.3Normal ranges were determined for each system on blood drawn from healthy volunteers.The results are given in the Table .The range for asparate amino- transferase was much narrower with the LKB instrument, the upper limit of normal falling by 8 units.This was due to the standard deviation being virtually halved, since the mean was similar to the previous value.Instrument No.
CONTINUOUS AXIAL FLOW LEFT VENTRICULAR ASSIST DEVICES IMPROVE PULMONARY HEMODYNAMICS IN PATIENTS WITH SEVERE CONGESTIVE HEART FAILURE.
Authors: Ravi Rasalingam, Kyle R. Bilhorn, Stephanie N. Johnson, Carl B. Kapadia, Majesh Makan, Nader Moazami, Julio E. Perez
Journal: Journal of the American College of Cardiology (2010)
SPECT in Neurosyphilis
Authors: NEIL J. ORTEGO, BRUCE L. MILLER, ISMAEL MENA, BARTON W. PALMER
Journal: Clinical Nuclear Medicine (1995)

A 41-year-old woman had a mild confuslonal state after an assault. She reported a history of sexual promiscuity, and subsequent testing revealed a serum rapid plasma reagin titer of 1:64, a cerebral spinal fluid venereal disease research laboratory titer of 1:8, and fluorescent treponemal antibody absorption reactive in both serum and CSF. Neurobehavioral testing revealed only subtle deficits in attention. MRI (T1 and T2 weighted of the brain), and EEG were normal. SPECT showed areas of hypoperfusion in a patchy distribution involving the parietal lobes bilaterally. This pattern is suggestive of meningovasculitis.
A CONTRIBUTION TO THE RELATIONS OF OVULATION AND MENSTRUATION.
Authors: A. REEVES JACKSON
Journal: JAMA (1884)

Read in the Section on Obstetrics and Diseases of Women, May, 1884. Mr. Chairman and Gentlemen. —The aim of all investigation should be the attainment of truth. And, in order that the discussion of any scientific question should be profitable, it is essential that the arguments advanced be based upon known facts. Any process of reasoning without such foundation is presumptuous, if not impertinent. In deference to this plain and just principle I shall abstain from making any assertion, or educing any inference not fairly warranted by the observations of trustworthy investigators. In the year 1673, De Graaf, a Dutch anatomist, described, in connection with the anatomy of the ovaries the bodies which have since borne his name. They were thought to be the ova of mammalia, and this belief obtained for many years. Sir Edward Home noticed the ruptured follicle during menstruation, but attached no importance to the coincidence.
More Magazines Forgo Tobacco Ads, Some by Choice, Many by Chance
Authors: Marsha F. Goldsmith
Journal: JAMA (1994)

UPDATING the<i>JAMA</i>list of magazines that carry no advertisements for cigarettes or other tobacco products is a daunting task. Hundreds of new periodicals debut each year even as hundreds of others disappear. Yet the Medical News &amp; Perspectives staff perseveres, trying to make it easier for physicians to fill their reception rooms with reading material whose commercial content is not hazardous to their patients' health. Thanks also to the contributions of a number ofThe Journal's readers, particularly the members of DOC (Doctors Ought to Care), a group of physicians dedicated to educating the public about the causes of preventable illness, this list contains many new tobacco-free titles along with the no-smoking standbys. A word of warning is in order, however. According to Alan Blum, MD, associate professor of family medicine at Baylor College of Medicine, Houston, Tex, chair of DOC, and former<i>JAMA</i>Fishbein Fellow in Medical
Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care
Authors: L M Mynors-Wallis, D H Gath, A R Lloyd-Thomas, D Tomlinson
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To determine whether, in the treatment of major depression in primary care, a brief psychological treatment (problem solving) was (a) as effective as antidepressant drugs and more effective than placebo; (b) feasible in practice; and (c) acceptable to patients. <b>Design</b>: Randomised controlled trial of problem solving treatment, amitriptyline plus standard clinical management, and drug placebo plus standard clinical management. Each treatment was delivered in six sessions over 12 weeks. <b>Setting</b>: Primary care in Oxfordshire. <b>Subjects</b>: 91 patients in primary care who had major depression. <b>Main outcome measures</b>: Observer and self reported measures of severity of depression, self reported measure of social outcome, and observer measure of psychological symptoms at six and 12 weeks; self reported measure of patient satisfaction at 12 weeks. Numbers of patients recovered at six and 12 weeks. <b>Results</b>: At six and 12 weeks the difference in score on the Hamilton rating scale for depression between problem solving and placebo treatments was significant (5.3 (95% confidence interval 1.6 to 9.0) and 4.7 (0.4 to 9.0) respectively), but the difference between problem solving and amitriptyline was not significant (1.8 (−1.8 to 5.5) and 0.9 (−3.3 to 5.2) respectively). At 12 weeks 60% (18/30) of patients given problem solving treatment had recovered on the Hamilton scale compared with 52% (16/31) given amitriptyline and 27% (8/30) given placebo. Patients were satisfied with problem solving treatment; all patients who completed treatment (28/30) rated the treatment as helpful or very helpful. The six sessions of problem solving treatment totalled a mean therapy time of 3 1/2 hours. <b>Conclusions</b>: As a treatment for major depression in primary care, problem solving treatment is effective, feasible, and acceptable to patients. <h3>Key messages</h3> Key messages Patient compliance with antidepressant treatment is often poor, so there is a need for a psychological treatment This study found that problem solving is an effective psychological treatment for major depression in primary care—as effective as amitriptyline and more effective than placebo Problem solving is a feasible treatment in primary care, being effective when given over six sessions by a general practitioner Problem solving treatment is acceptable to patients
Iceland's database is ethically questionable
Authors: B. Andersen, E. Arnason
Journal: BMJ (1999)

Last December the Icelandic parliament, Althingi, passed an act on a health sector database. The legislation was instigated by a Delaware corporation, deCODE, a biotechnology company operating in Iceland (2 January, 11).

The company will receive an exclusive licence to construct a database containing the entire country's health records and permission to combine and analyse them with genetic and genealogical data.

“Some issues … should be left out of politicians' hands” 

The Icelandic government and deCODE maintain that the project will uphold patients' rights and conform to international obligations and will serve as a model for similar databases elsewhere (20March, p 806).

Few geneticists dispute the usefulness of databases. Rather, the debate focuses on how deCODE, through the act, has been permitted to break fundamental principles of scientific conduct: the requirement that research plans should be evaluated and approved by independent ethics committees before recruiting patients for studies. Without submitting a …
Differential Excretion of a Transplanted Kidney with Dual Vascular Supply
Authors: JEFFREY NEMEROFF, SAID ZU??BI, GEORGE LIPKOWITZ
Journal: Clinical Nuclear Medicine (1993)

A case is reported of a 14-year-old girl with a history of congenital vesicoureteral reflux, recurrent urinary tract infections, hypertension, and chronic renal failure. She has had a ureteric reimplantation. The patient presented to our institution for a donor renal transplant from a living relative. Preoperative arteriography of the donor kidney revealed two right renal arteries, each supplying half of the kidney. Renal transplant scintigraphy with Tc-99m MAG3 on the first day after the operation demonstrated normal uptake, but markedly reduced excretion of tracer from the lower half of the kidney. This would suggest acute tubular necrosis of the region supplied by one of the two renal arteries.