tbuckley/cabot-search huggingface dataset:
Atrio-Sinus Interaction Demonstrated by Blockade of the Rapid Delayed Rectifier Current
Authors: E. Etienne Verheijck, Ronald Wilders, Lennart N. Bouman
Journal: Circulation (2002)

Background — Proper pacemaking of the heart requires a specific organization of the sinoatrial (SA) node. The SA node drives the surrounding atrium but needs to be protected from its hyperpolarizing influence, which tends to suppress pacemaker activity. It has been suggested that the hyperpolarizing atrial influence is minimal at the site of the central nodal area. Methods and Results — Atrio-sinus interaction was assessed by specific depolarization of the SA node by blocking the HERG-encoded rapid delayed rectifier current (I K,r ) with the drug E-4031. In the SA node, E-4031 (1 μmol/L) changed action potential configuration drastically but never resulted in pacemaker arrest. In the atrium, E-4031 did not affect the membrane resting potential, thereby leaving the normal hyperpolarizing load on the SA node intact. When the SA node was sectioned into strips and subsequently separated from the atrium, spontaneous electrical activity of the strip containing the primary pacemaker ceased on I K,r blockade. When not separated from the atrium, I K,r blockade never resulted in pacemaker arrest. A similar effective atrio-sinus interaction was demonstrated in computer simulations. Conclusions — Our results demonstrate that the atrium provides an effective hyperpolarizing load on the central SA nodal area and is at least one of the controlling mechanisms for normal pacemaking function. The present study can be of help in understanding why patients with long-QT2 syndrome secondary to a mutation in HERG do not show sinus arrest.
Social Learning Intervention to Promote Metabolic Control in Type I Diabetes Mellitus: Pilot Experiment Results
Authors: Robert M Kaplan, Michele W Chadwick, Leslie E Schimmel
Journal: Diabetes Care (1985)

Patients with type I, or insulin-dependent, diabetes mellitus (IDDM) must comply with a complex behavioral regimen to control their diabetes. Compliance is often poor in teenage patients who are adversely influenced by peers. During a diabetes summer school, we randomly assigned 21 IDDM patients to one of two groups. One group participated in daily social-learning exercises designed to improve social skills and the ability to resist peer influence. The second group spent an equal amount of time learning medical facts about diabetes care. Four months after the intervention, hemoglobin A1 was significantly lower in the social skills intervention group. A variety of variables were significantly correlated with good metabolic control. These included self-reported compliance with a diabetes regimen and attitudes toward self-care. Unexpectedly, variables correlated with poor diabetes control included social problem-solving ability and satisfaction with social support.
Respiration: Physiologic Principles and Their Clinical Applications
Authors: C. I. Reed
Journal: JAMA (1961)

American translators, in collaboration with the Swiss authors, have expanded and edited this translation to produce an international review and compilation. It is pointed out that the German clinical studies have emphasized quantitative volumetric spirometry while Anglo-Americans have stressed alveolar air and blood chemical changes. An extensive bibliography is provided. The book is an analytic review, although much of the clinical experience of the translators has been incorporated. The high-tension mathematics involved takes this work out of the realm of everyday usage, but it should be a valuable reference for specialists in aerobiology, cardiopulmonary investigations, physiological fitness, pulmonary diffusion abnormalities, stress of metabolic origin, artificial respiration and oxygen therapy, high pressure submarine habitation, civil defense shelters, and gerontological adjustment. The subjects covered include ventilation function within physiological ranges, gaseous transfer between alveoli and blood, oxygen and carbon dioxide transport, respiratory regulation, tissue respiration, cyanosis, dyspnea, methods of clinical investigation, emphysema,
Parallel synthesis with fluorous reagents and reactants
Authors: Dennis P. Curran
Journal: Medicinal Research Reviews (1999)

Fluorous reagents and reactants provide emerging new options in parallel synthesis because they are easily prepared, reacted, and then separated from the desired reaction products. Some background information on fluorous reaction and separation techniques is provided, and the utility of fluorous reagents and reactants is illustrated with a number of case studies that feature both liquid-liquid and solid-solid separations.
In-Traffic Air Pollution Exposure and CC16, Blood Coagulation, and Inflammation Markers in Healthy Adults
Authors: Moniek Zuurbier, Gerard Hoek, Marieke Oldenwening, Kees Meliefste, Esmeralda Krop, Peter van den Hazel, Bert Brunekreef
Journal: Environmental Health Perspectives (2011)

Background: Exposure to traffic-related air pollution is a risk factor for cardiovascular events, probably involving mechanisms of inflammation and coagulation. Little is known about effects of the short exposures encountered while participating in traffic.Objectives: The objective of the study was to examine effects of exposure of commuters to air pollution on cardiovascular biomarkers.Methods: Thirty-four healthy adult volunteers commuted for 2 hr by bus, car, or bicycle during the morning rush hour. During the commute, exposure to particle number, particulate matter (PM) ≤ 2.5 µm in aerodynamic diameter (PM2.5), PM ≤ 10 µm in diameter (PM10), and soot was measured. We estimated inhaled doses based on heart rate monitoring. Shortly before exposure and 6 hr after exposure, blood samples were taken and analyzed for CC16 (Clara cell protein 16), blood cell count, coagulation markers, and inflammation markers. Between June 2007 and June 2008, 352 pre- and postexposure blood samples were collected on 47 test days. We used mixed models to analyze the associations between exposure and changes in health parameters.Results: We observed no consistent associations between the air pollution exposures and doses and the various biomarkers that we investigated.Conclusions: Air pollution exposure during commuting was not consistently associated with acute changes in inflammation markers, blood cell counts, or blood coagulation markers.
Which transplant technique will let cystic fibrosis patients breathe easier?
Authors: M. F. Goldsmith
Journal: JAMA (1990)

NEW LUNGS for old as a means of prolonging the lives of persons with cystic fibrosis is a prospect that has inspired researchers in the past few years. At two recent meetings, developments in this specialized area of organ transplantation were reported. In Toronto, Ontario, participants in the annual meeting of the American Association for Thoracic Surgery heard from Marc R. deLeval, MD, who is the group's 24th Evarts A. Graham Memorial Traveling Fellow. DeLeval has been working in the Lung Transplant Research Unit at Papworth Hospital, Cambridge, England. The program there receives worldwide recognition. He presented a report on heart-lung transplantation performed there during the past 4 years on 32 patients who were severely impaired—near death from advanced respiratory failure—because of cystic fibrosis. He then compared the results in this group with results in 61 patients without the disease who received heart-lung transplants at Papworth Hospital during the same
Recurrent ETNK1 mutations in atypical chronic myeloid leukemia
Authors: Carlo B. Gambacorti-Passerini, Carla Donadoni, Andrea Parmiani, Alessandra Pirola, Sara Redaelli, Giovanni Signore, Vincenzo Piazza, Luca Malcovati, Diletta Fontana, Roberta Spinelli, Vera Magistroni, Giuseppe Gaipa, Marco Peronaci, Alessandro Morotti, Cristina Panuzzo, Giuseppe Saglio, Emilio Usala, Dong-Wook Kim, Delphine Rea, Konstantinos Zervakis, Nora Viniou, Argiris Symeonidis, Heiko Becker, Jacqueline Boultwood, Leonardo Campiotti, Matteo Carrabba, Elena Elli, Graham R. Bignell, Elli Papaemmanuil, Peter J. Campbell, Mario Cazzola, Rocco Piazza
Journal: Blood (2014)
Abstract 4758: Inhibition of checkpoint kinase 1 (Chk1) as a potential therapeutic for pediatric neuroblastoma
Authors: Mike R. Russell, Kristina A. Cole, John M. Maris
Journal: Cancer Research (2011)

Abstract Neuroblastoma is a cancer derived from cells of the sympathetic nervous system that manifests with significant clinical heterogeneity. Although children diagnosed with low-risk neuroblastoma are very likely to be cured, high-risk patients are frequently resistant to even the most intensive of multi-modal regimens, and at least half of these children suffer relapse that is almost always fatal. To address the unmet need for novel therapeutic targets, our lab conducted an unbiased siRNA screen and determined that the loss of cell cycle checkpoint kinase 1 (Chk1) produced the most robust cytotoxic effect across multiple neuroblastoma cell lines. We subsequently confirmed that many neuroblastoma cell lines express constitutively phosphorylated Chk1 – a discovery that is supported by identical findings in tumors obtained from high-risk patients. Here we present evidence that the combination of a small molecule inhibitor of Chk1 with either irinotecan (SN-38) or cisplatin was synergistic or additive in vitro in cell lines sensitive to single agent Chk1 inhibition. Inhibition of Chk1 signaling as potential therapy in neuroblastoma is further supported by complimentary experiments in which we found that induction of shRNA specific for Chk1 results in marked cytotoxicity. To further understand the chemosensitizing aspect of Chk1 inhibition in neuroblastoma cells, we assayed the ATR/Chk1 pathway for potential biomarkers predictive of response. Candidate signaling partners in this pathway were isolated based upon either pharmacological inhibition or shRNA-induced silencing of Chk1, followed by hybridization to antibody microarrays. This technique has allowed for identification of Chk1-related signaling proteins involved in the DNA damage response pathway. Lastly, we have assessed the efficacy of Chk1 inhibition in an in vivo xenograft mouse model of pediatric neuroblastoma. We found that daily administration of a small molecule Chk1 inhibitor, currently undergoing Phase I clinical testing, was able to significantly impede the growth of NB1643 neuroblastoma xenografts (p=0.001). Efforts are currently underway in our laboratory to investigate a potentially synergistic effect in vivo through co-administration of this inhibitor with irinotecan or cisplatin. Taken together, these results provide a strong rationale for further studies to assess the use of Chk1 inhibition as either a single-agent or combinatorial therapy in pediatric neuroblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4758. doi:10.1158/1538-7445.AM2011-4758
The organization of Organization: Neuronal scaffold or cognitive straitjacket?
Authors: A. J. Amos, C. D. L. Wynne
Journal: Behavioral and Brain Sciences (2000)

We praise Arbib et al.'s Neural organization for its support of the integration of different levels of analysis, while noting that it does not always achieve what it advocates. We extend this approach into an area of neuropsychological activity in need of the structure offered by Organization at the intersection of the conflated fields of executive function and frontal lobe function.
Assessment of left atrial appendage function by biplane transesophageal echocardiography in patients with nonrheumatic atrial fibrillation: Identification of a subgroup of patients at increased embolic risk
Authors: Andreas Mügge, Henning Kühn, Peter Nikutta, Jochen Grote, J.Antonio G. Lopez, Werner G. Daniel
Journal: Journal of the American College of Cardiology (1994)
THE RESULTS OF NINETY-EIGHT CASES OF NERVE SUTURE
Authors: P. G. Dane
Journal: BMJ (1921)

RESULTS OF NERVE SUTURI.[TM Bao 885 and his knee was then found to be swollen and acutely tender.Pathological examination of the joint fluid showed that pus cells and streptococci were present.The patient was con- tinuallv asking for the leg to be amputated.On Januarv 12th it was decided to give the treatment above described a trial.This was carried out, and his condition rapidly improved, the temperature becoming normal on January 16th, and remaining so till his discharge.Several sequestra were subsequently removed from the site of the fracture.The Thomas splint was retained longer than usual owing to the condition of the fracture.He was discharged from hospital on February 24th.The patient now walks with a stick, and can flex his knee to a right angle. CASE III.A. R., a b3y aged 11 years, was admitted to the Royal Infirmary on January 29th, 1920, with a dirty wound over the left knee-joint, the result of a fall some days earlier.The wound did hot appear to communicate with the joint, and he was sent home on February 2nd.He was readmitted to hospital on February 16th.The knee was painful and s7wolleu, and his temperature was 103.60 F. X-ray examination showed no bony injuryv.The joint was aspirated on several occasions, and pus cells and staphylococci were found present.As the joint repeatedly filled up anid his temperature reached 104°F.the procedure describe(d was adopted.The temperature dropped slowly and his condition rapidly improved.He was discharged on March 24th, the wounds being healed.Thie knee-joint could be flexed about 45 degrees at that time.I have not seen the boy since that date.CASE IV.E. J., a boy aged 16 years, was admitted to the Royal Infirmarv on February 3rd, 1921, suffering from acute osteomyelitis of the right tibia.Operation was carried out for this condition the same day, when the medullary cavity of the tibia was freely opened.His progress continued satisfactorv till March 1st, when the righi knee-joint was found to be painful and swollen.Aspiration of the joint showed pus cells and streptococci to be presenit.The joint, was therefore opened, washed out, and bipp applied, the limb being placed in a Thomas splint.The right elbow- joint also became involved and was treated on similar lines, ateral incisions being made either side of the olecranon.A streptococcal vaccine was preparedl from the pus by Dr.G. E. Loveday, and injections given at regular intervals.This additional treatment contributed in no small degree to the successful result of the case.His subsequenlt progress was satisfactor, both joints quiickly cleared up, but the wound of the tibia continued discharging pus.He is still receiving hospital treatment for this condition, and massage to the affected joints, which are slowly improving.CONCLUSIONS.
Depression and Clinical Inertia in Patients With Uncontrolled Hypertension
Authors: Nathalie Moise, Karina W. Davidson, William Chaplin, Steven Shea, Ian Kronish
Journal: JAMA Internal Medicine (2014)

Depression is a known risk factor for poor prognosis among patients with cardiovascular disease1. Numerous biological and behavioral mechanisms have been proposed2. However, few studies have investigated the association between depression and ‘clinical inertia’, or lack of treatment intensification in individuals not at evidence-based goals for care3. To address this gap, we assessed whether a diagnosis of depression is associated with clinical inertia in patients with uncontrolled hypertension.
Evaluating Concordance to American Diabetes Association Standards of Care for Type 2 Diabetes Through Group Visits in an Uninsured or Inadequately Insured Patient Population
Authors: Dawn E. Clancy, Dennis W. Cope, Kathryn Marley Magruder, Peng Huang, Tamara E. Wolfman
Journal: Diabetes Care (2003)

OBJECTIVE—To evaluate the effectiveness of a managed care approach to health care delivery, group visits, in the management of uninsured or inadequately insured patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 120 patients with uncontrolled type 2 diabetes were randomly assigned to receive their care in group visits or usual care for 6 months. After 6 months, concordance with 10 process-of-care indicators recommended by the American Diabetes Association (ADA) standards of care was evaluated through chart abstraction. The 10 items evaluated were up-to-date HbA1c levels and lipid profiles, urine for microalbumin, appropriate use of ACE inhibitor or angiotensin receptor blockers, use of lipid-lowering agents where indicated, daily aspirin use, annual foot examinations, annual referrals for retinal examinations, and immunizations against streptococcal pneumonia and influenza. RESULTS—Patients who received care in group visits showed statistically significant improvement in concordance with these 10 process-of-care indicators (P &amp;lt; 0.001). Of the patients, 76% who received care in group visits had at least 9 of these 10 items up to date, as compared with 23% of control patients; 86% of patients in group visits had at least 8 of the 10 indicators compared with 47% of control patients. CONCLUSIONS—Group visits proved more effective in promoting concordance with ADA standards of care than usual care in the treatment of uninsured or inadequately insured patients with type 2 diabetes.
Report calls for collaboration on genome research
Authors: C. Court
Journal: BMJ (1994)

The British human genome mapping project has enormous potential for the improvement of health and wealth creation, according to a report from the Advisory Committee on Human Genome Research. “We predict that the increased knowledge of basic biology will eventually transform medical practice,” say the authors. The report was commissioned under the auspices of the Office of Science and Technology. The independent group of geneticists behind the report was chaired by Professor Kay Davies, who said: …
Regression of basal cell carcinoma by intralesional interferon-alpha treatment is mediated by CD95 (Apo-1/Fas)-CD95 ligand-induced suicide.
Authors: S A Buechner, M Wernli, T Harr, S Hahn, P Itin, P Erb
Journal: Journal of Clinical Investigation (1997)

Basal cell carcinoma (BCC) is the most common skin cancer in humans, and although metastasis rarely occurs, the tumor cells are nevertheless able to invade and destroy the surrounding tissue. Intralesional injection of IFN-alpha has been found to be highly effective in inducing BCC regression by an unknown mechanism. We show that in untreated patients, BCC cells express CD95 ligand, but not the receptor, which may allow tumor expansion by averting the attack of activated CD95 receptor-positive lymphoid effector cells. The CD95 ligand of BCC cells is functional as CD95-positive cells incubated on BCC cryosections become apoptotic and are lysed. In IFN-alpha-treated patients BCC cells express not only CD95 ligand but also CD95 receptor, whereas the peritumoral infiltrate that mainly consists of CD4+ T cells predominantly contains CD95 receptor and only few CD95 ligand-positive cells. Thus, in treated patients BCC most likely regresses by committing suicide through apoptosis induction via CD95 receptor-CD95 ligand interaction.
Effects of Different Modes of Exercise Training on Glucose Control and Risk Factors for Complications in Type 2 Diabetic Patients: a Meta-Analysis
Authors: Neil J. Snowling, Will G. Hopkins
Journal: Diabetes Care (2007)

According to the authors of the meta-analysis we cited for the effects of A1C on cardiovascular disease, the U.K. Prospective Diabetes Study “is largely considered negative by the medical community” (1). If we accept this assessment, it would seem reasonable to describe the benefits …
Wound Dressing Activity Mimicking Infection on Labeled Leukocyte Imaging
Authors: CHRISTOPHER J. PALESTRO, RANDELL COHEN, STANLEY J. GOLDSMITH
Journal: Clinical Nuclear Medicine (1992)

Although labeled leukocyte imaging is an extremely useful technique for the localization of infection, false-positive results in inflammatory conditions where no infection exists have been described. False-positive results secondary to bleeding have also been reported. The authors recently observed intense uptake of labeled cells in the wound dressings of two patients undergoing leukocyte imaging. Repeat imaging after the removal of these dressings confirmed that the activity seen was in the dressings and did not represent focal infection, as originally thought. Based on these observations, the authors think it prudent to remove such dressings before performing leukocyte imaging.
Development and validation of a disease-targeted quality of life instrument in chronic hepatitis B
Authors: Brennan M. R. Spiegel, Roger Bolus, Steven Han, Myron Tong, Eric Esrailian, Jennifer Talley, Tram Tran, Jason Smith, Hetal A. Karsan, Francisco Durazo, Bruce Bacon, Paul Martin, Zobair Younossi, Siew Hwa-Ong, Fasiha Kanwal
Journal: Hepatology (2007)

Despite the increasing realization that health-related quality of life (HRQOL) is an important outcome in chronic HBV infection, there are no validated, disease-targeted instruments currently available. We sought to develop and validate the first disease-targeted HRQOL instrument in noncirrhotic HBV: the Hepatitis B Quality of Life instrument, version 1.0 (HBQOL v1.0). We established content validity for the HBQOL v1.0 by conducting a systematic literature review, an expert focus group, and cognitive interviews with HBV patients. We administered the resultant questionnaire to 138 HBV patients. We used factor analysis to test hypotheses regarding HRQOL domains and measured construct validity by comparing HBQOL v1.0 scores across several anchors, including viral response to treatment, SF-36 scores, and global health. Finally, we measured test-retest and internal consistency reliability. Content validation revealed that HBV affects multiple aspects of psychological, social, and physical health. The resultant questionnaire summarized this HRQOL impact with 31 items across six subscales: psychological well-being, anticipation anxiety, vitality, disease stigma, vulnerability, and transmissibility. Internal consistency and test-retest reliability were excellent. The HBQOL v1.0 discriminated between viral responders versus nonresponders and correlated highly with SF-36 scores and global health.Patients with chronic HBV infection attribute a wide range of negative psychological, social, and physical symptoms to their condition, even in the absence of cirrhosis or cancer. The HBQOL v1.0 is a valid and reliable measure that captures this HRQOL decrement. This instrument may be useful in everyday clinical practice and in future clinical trials.
CLINICAL TRIAL WITH CYCLOPENTIMINE
Authors: L. SCHWARZ, T. BAN, R. SMITH
Journal: American Journal of Psychiatry (1961)

A clinical trial was conducted on 30 hospitalized female patients with cyclopentimine. Decreasing aggressiveness and euphoria were observed as beneficial effects in 8 patients. However, because of the uncontrollable side effects of severe nausea, vomiting, loss of weight and insomnia, as well as extrapyramidal symptoms, headache and allergic dermatitis, the trial had to be discontinued prematurely. It seems that these severe side effects at the present time overshadow the compound's potential therapeutic value.