tbuckley/cabot-search huggingface dataset:
Effect of superoxide dismutase on myocardial infarct size in the canine heart after 6 hours of regional ischemia and reperfusion: a demonstration of myocardial salvage.
Authors: L G Chi, Y Tamura, P T Hoff, M Macha, K P Gallagher, M A Schork, B R Lucchesi
Journal: Circulation Research (1989)

Available data demonstrate that oxygen free radicals and derived reactive species of oxygen are produced during myocardial ischemia as well as upon reperfusion of the ischemic tissue. The present study was designed to determine if polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), with its extended plasma half-life in excess of 30 hours in contrast to the native form of the enzyme (Native-SOD), could provide protection to the ischemic myocardium subjected to a 6-hour regional ischemia followed by reperfusion for 24 hours. We hypothesized that myocardial injury due to an ischemic interval is a dynamic process involving the sustained production of cytotoxic oxygen radicals that may continue beyond the ischemic interval. The ability to demonstrate a protective effect of the free radical scavenger enzyme superoxide dismutase would require the continued presence of the antioxidant during the ischemic interval and especially during reperfusion. To test this hypothesis, 22 anesthetized, open-chest dogs underwent 6 hours of circumflex coronary artery occlusion followed by reperfusion for 24 hours. Rapid administration of either Native-SOD (1,000 U/kg), PEG-SOD (1,000 U/kg), PEG-albumin (PEG-ALB), or 0.9% sodium chloride solution for injection (saline) was administered via the left atrium 15 minutes before occlusion of the vessel. A continuous infusion of an additional 1,000 U/kg of the respective enzyme interventions or an equivalent volume of PEG-ALB or saline was given during the 6-hour coronary artery occlusion and terminated 15 minutes after reperfusion. The animals were euthanized 24 hours after reperfusion, and the myocardial region at risk and the infarct region were quantitated by the tetrazolium method. The area of myocardium at risk of infarction, expressed as a percent of the left ventricle, did not differ among the groups: Native-SOD (n = 8), 46.2 +/- 1.8%; PEG-SOD (n = 6), 45.7 +/- 2.1%; PEG-ALB, 38.4 +/- 2.3% (n = 4); and saline 46.0 +/- 2.1% (n = 4). Hemodynamic parameters, the calculated rate-pressure-product, as well as regional myocardial blood flow (radiolabeled microsphere method) in the endocardial, midmyocardial, and epicardial segments of the risk and the nonrisk regions were comparable for all groups. Mean infarct size, determined 24 hours after reperfusion, in the group treated with PEG-SOD was 47.1 +/- 2.9% of the area at risk (n = 6), significantly smaller than that observed in each of the other treatment groups: Native-SOD, 63.5 +/- 2.2% (n = 8); PEG-ALB, 64.6 +/- 2.4% (n = 4); saline, 70.8 +/- 2.2% (n = 4).(ABSTRACT TRUNCATED AT 400 WORDS)
Noninvasive assessment of respiratory resistance in severe chronic respiratory patients with nasal CPAP
Authors: R. Farré, E Gavela, M. Rotger, M Ferrer, J Roca, D. Navajas
Journal: European Respiratory Journal (2000)

Noninvasive measurement of respiratory resistance during nasal ventilatory support could be useful to assess the mechanical status of the patient and to optimize the ventilator settings. The aim was to investigate whether the forced oscillation technique (FOT) applied through a nasal mask allows reliable noninvasive estimation of respiratory resistance (Rrs) in patients with severe chronic respiratory disease. FOT Rrs (5 Hz) and lung resistance (R(L)) measured simultaneously from spontaneous breathing signals by an oesophageal balloon were compared in eight patients with chronic obstructive pulmonary disease and in six patients with a restrictive ventilatory defect due to chest wall disease. Measurements were performed in sitting and supine postures during application of nasal continuous positive airway pressure (CPAP): 4, 8 and 12 cmH2O in obstructive patients and 4 cmH2O in restrictive patients. In the restrictive patients Rrs and R(L) (in cmH2O x s x L(-1)) were virtually coincident: mean+/-SD, 12.6+/-6.1 and 11.6+/-6.6 (r=0.96) in sitting and 9.7+/-3.1 and 10.2+/-3.3 (r=0.92) in supine posture, respectively. In the obstructive patients (CPAP = 4 cmH2O), Rrs slightly underestimated R(L): mean+/-SD, 11.5+/-5.9 and 14.4+/-16.8 (r=0.92) in sitting and 15.0+/-9.8 and 21.1+/-12.6 (r=0.96) in supine posture, respectively. Similar results were found at CPAP = 8 and 12 cmH2O. The results obtained in patients with resistance values in the range typically found in nasal ventilatory support suggest that forced oscillation technique could be valuable to noninvasively estimate a patient9s respiratory mechanical resistance.
The JAK-STAT Pathway: Impact on Human Disease and Therapeutic Intervention
Authors: John J. O'Shea, Daniella M. Schwartz, Alejandro V. Villarino, Massimo Gadina, Iain B. McInnes, Arian Laurence
Journal: Annual Review of Medicine (2015)

The Janus kinase (JAK)–signal transducer of activators of transcription (STAT) pathway is now recognized as an evolutionarily conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules. This pathway provides an elegant and remarkably straightforward mechanism whereby extracellular factors control gene expression. It thus serves as a fundamental paradigm for how cells sense environmental cues and interpret these signals to regulate cell growth and differentiation. Genetic mutations and polymorphisms are functionally relevant to a variety of human diseases, especially cancer and immune-related conditions. The clinical relevance of the pathway has been confirmed by the emergence of a new class of therapeutics that targets JAKs.
A method for establishing allocation equity among patients with and without hepatocellular carcinoma on a common liver transplant waiting list
Authors: Alessandro Vitale, Michael L. Volk, Tullia Maria De Feo, Patrizia Burra, Anna Chiara Frigo, Rafael Ramirez Morales, Luciano De Carlis, Luca Belli, Michele Colledan, Stefano Fagiuoli, Giorgio Rossi, Enzo Andorno, Umberto Baccarani, Enrico Regalia, Marco Vivarelli, Matteo Donataccio, Umberto Cillo
Journal: Journal of Hepatology (2013)
Ingenol Mebutate Gel for Actinic Keratosis
Authors: Mark Lebwohl, Neil Swanson, Lawrence L. Anderson, Anita Melgaard, Zhenyi Xu, Brian Berman
Journal: New England Journal of Medicine (2012)

Actinic keratosis is a common precursor to sun-related squamous-cell carcinoma. Treating actinic keratoses and the surrounding skin area (i.e., field therapy) can eradicate clinical and subclinical actinic keratoses. Topical field therapy currently requires weeks or months of treatment. We investigated the efficacy and safety of a new topical field therapy for actinic keratosis, ingenol mebutate gel (0.015% for face and scalp and 0.05% for trunk and extremities).In four multicenter, randomized, double-blind studies, we randomly assigned patients with actinic keratoses on the face or scalp or on the trunk or extremities to receive ingenol mebutate or placebo (vehicle), self-applied to a 25-cm(2) contiguous field once daily for 3 consecutive days for lesions on the face or scalp or for 2 consecutive days for the trunk or extremities. Complete clearance (primary outcome) was assessed at 57 days, and local reactions were quantitatively measured.In a pooled analysis of the two trials involving the face and scalp, the rate of complete clearance was higher with ingenol mebutate than with placebo (42.2% vs. 3.7%, P<0.001). Local reactions peaked at day 4, with a mean maximum composite score of 9.1 on the local-skin-response scale (which ranges from 0 to 4 for six types of reaction, yielding a composite score of 0 to 24, with higher numbers indicating more severe reactions), rapidly decreased by day 8, and continued to decrease, approaching baseline scores by day 29. In a pooled analysis of the two trials involving the trunk and extremities, the rate of complete clearance was also higher with ingenol mebutate than with placebo (34.1% vs. 4.7%, P<0.001). Local skin reactions peaked between days 3 and 8 and declined rapidly, approaching baseline by day 29, with a mean maximum score of 6.8. Adverse events were generally mild to moderate in intensity and resolved without sequelae.Ingenol mebutate gel applied topically for 2 to 3 days is effective for field treatment of actinic keratoses. (Funded by LEO Pharma; ClinicalTrials.gov numbers, NCT00742391, NCT00916006, NCT00915551, and NCT00942604.).
Guanine ribonucleotide depletion inhibits T cell activation. Mechanism of action of the immunosuppressive drug mizoribine.
Authors: L A Turka, J Dayton, G Sinclair, C B Thompson, B S Mitchell
Journal: Journal of Clinical Investigation (1991)

The immunosuppressive drug, mizoribine, has been used to prevent rejection of organ allografts in humans and in animal models. Based on studies in cell lines, mizoribine has been postulated to be an inhibitor of inosine monophosphate (IMP) dehydrogenase (EC1.2.1.14), a pivotal enzyme in the formation of guanine ribonucleotides from IMP. To further characterize the mechanism of action of this drug, we studied the effect of mizoribine on human peripheral blood T cells stimulated with alloantigen, anti-CD3 MAb, or pharmacologic mitogens. Mizoribine (1-50 micrograms/ml) was able to inhibit T cell proliferation by 10-100% in a dose-dependent fashion to all stimuli tested. Measurements of purine ribonucleotide pools by HPLC showed that mizoribine led to a decrease in intracellular GTP levels, and that repletion of GTP reversed its antiproliferative effects. We also examined sequential events occurring after T cell stimulation. Early events in T cell activation, as assessed by steady-state mRNA levels of c-myc, IL-2, c-myb, histone, and cdc2 kinase, as well as surface IL-2 receptor expression, were unaffected. However, cell cycle analysis revealed decreased numbers of cells in S, G2, and M phases, and showed that the G1/S block was reversed with GTP repletion. These data indicate that mizoribine has an effect on T cell proliferation by a mechanism distinct from that of cyclosporine or corticosteroids, and therefore may be useful in combination immunosuppressive regimens.
Effect of Montelukast on Experimentally-Induced RV16 Infection in Volunteers with Mild Allergic Asthma
Authors: K.M. Kloepfer, J.P. Denmore, J.A. Bork, F. Vang, M.J. Wolff, M.D. Evans, C.A. Swenson, J.E. Gern
Journal: Journal of Allergy and Clinical Immunology (2010)
Events leading to anterior cruciate ligament injury in World Cup Alpine Skiing: a systematic video analysis of 20 cases
Authors: Tone Bere, Tonje Wåle Flørenes, Tron Krosshaug, Lars Nordsletten, Roald Bahr
Journal: British Journal of Sports Medicine (2011)

Background The authors have recently identified three main mechanisms for anterior cruciate ligament (ACL) injuries among World Cup (WC) alpine skiers, termed as “the slip-catch”, “the landing back-weighted” and “the dynamic snowplow”. However, for a more complete understanding of how these injuries occur, a description of the events leading to the injury situations is also needed. Objective To describe the skiing situation leading to ACL injuries in WC alpine skiing. Methods Twenty cases of ACL injuries reported through the International Ski Federation Injury Surveillance System (FIS ISS)for three consecutive WC seasons (2006–2009) were obtained on video. Ten experts (9 WC coaches, 1 former WC athlete) performed visual analyses of each case to describe in their own words, factors they thought may have contributed to the injury situation related to different predefined categories: (1) skier technique, (2) skier strategy, (3) equipment, (4) speed and course setting, (5) visibility, snow and piste conditions and (6) any other factors. Results Factors related to the three categories, namely skier technique, skier strategy, and visibility, snow and piste conditions, were assumed to be the main contributors to the injury situations. Skier errors, technical mistakes and inappropriate tactical choices, were the dominant factors. In addition, bumpy conditions, aggressive snow, reduced visibility and course difficulties were assumed to contribute. Conclusion Based on this systematic video analysis of 20 injury situations, factors related to skier technique, skier strategy and specific race conditions were identified as the main contributors leading to injury situations.
A Neutralizing Anti–Fibroblast Growth Factor 8 Monoclonal Antibody Shows Potent Antitumor Activity against Androgen-Dependent Mouse Mammary Tumors <i>In vivo</i>
Authors: Naoki Shimada, Toshihiko Ishii, Teruyoshi Imada, Katsumi Takaba, Yuka Sasaki, Kumiko Maruyama-Takahashi, Yoshimi Maekawa-Tokuda, Hideaki Kusaka, Shiro Akinaga, Akira Tanaka, Kenya Shitara
Journal: Clinical Cancer Research (2005)

Fibroblast growth factor 8b (FGF8b) has been implicated in oncogenesis of sex hormone-related malignancies. A murine monoclonal anti-FGF8 antibody, KM1334, has been raised against a FGF8b-derived peptide and shown to neutralize FGF8b activity in an androgen-dependent mouse mammary cell line (SC-3) in vitro growth. The purpose of this study was to evaluate KM1334 as a therapeutic agent for FGF8-dependent cancer.Specificity and neutralizing activity of KM1334 were examined in vitro. In vivo therapeutic studies were done in nude mice bearing SC-3 tumors s.c.KM1334 recognized FGF8b and FGF8f specifically out of four human FGF8 isoforms and showed little binding to other members of FGF family. Neutralizing activity of KM1334 was confirmed by both blocking of FGF8b binding to its three receptors (FGFR2IIIc, FGFR3IIIc, and FGFR4) and FGF8b-induced phosphorylation of FGFR substrate 2alpha and extracellular signal-regulated kinase 1/2 in SC-3 cells. The in vitro inhibitory effect could be extended to in vivo tumor models, where KM1334 caused rapid regression of established SC-3 tumors in nude mice. This rapid regression of tumors after KM1334 treatment was explained by two independent mechanisms: (a) decreased DNA synthesis, as evidenced by a decrease in uptake of 5-bromo-2'-deoxyuridine, and (b) induction of apoptosis as shown by the terminal deoxynucleotidyl transferase-mediated nick end labeling assay.KM1334 possesses strong blocking activity in vitro and antitumor activity in vivo and therefore may be an effective therapeutic candidate for the treatment of cancers that are dependent on FGF8b signaling for growth and survival.
Advanced Glycation End Products and Antioxidant Status in Type 2 Diabetic Patients With and Without Peripheral Artery Disease
Authors: Annunziata Lapolla, Francesco Piarulli, Giovanni Sartore, Antonio Ceriello, Eugenio Ragazzi, Rachele Reitano, Lorenzo Baccarin, Barbara Laverda, Domenico Fedele
Journal: Diabetes Care (2007)

OBJECTIVE—Advanced glycation end products (AGEs), pentosidine and malondialdehyde (MDA), are elevated in type 2 diabetic subjects with coronary and carotid angiopathy. We investigated the relationship of AGEs, MDA, total reactive antioxidant potentials (TRAPs), and vitamin E in type 2 diabetic patients with and without peripheral artery disease (PAD). RESEARCH DESIGN AND METHODS—AGEs, pentosidine, MDA, TRAP, vitamin E, and ankle-brachial index (ABI) were measured in 99 consecutive type 2 diabetic subjects and 20 control subjects. RESULTS—AGEs, pentosidine, and MDA were higher and vitamin E and TRAP were lower in patients with PAD (ABI &amp;lt;0.9) than in patients without PAD (ABI &amp;gt;0.9) (P &amp;lt; 0.001). After multiple regression analysis, a correlation between AGEs and pentosidine, as independent variables, and ABI, as the dependent variable, was found in both patients with and without PAD (r = 0.9198, P &amp;lt; 0.001 and r = 0.5764, P &amp;lt; 0.001, respectively) but not in control subjects. When individual regression coefficients were evaluated, only that due to pentosidine was confirmed as significant. For patients with PAD, considering TRAP, vitamin E, and MDA as independent variables and ABI as the dependent variable produced an overall significant regression (r = 0.6913, P &amp;lt; 0.001). The regression coefficients for TRAP and vitamin E were not significant, indicating that the model is best explained by a single linear regression between MDA and ABI. These findings were also confirmed by principal component analysis. CONCLUSIONS—Results show that pentosidine and MDA are strongly associated with PAD in type 2 diabetic patients.
Directing Surgical Quality Improvement Initiatives: Comparison of Perioperative Mortality and Long-Term Survival for Cancer Surgery
Authors: Karl Y. Bilimoria, David J. Bentrem, Joseph M. Feinglass, Andrew K. Stewart, David P. Winchester, Mark S. Talamonti, Clifford Y. Ko
Journal: Journal of Clinical Oncology (2008)

Purpose Quality-improvement initiatives are being developed to decrease volume-based variability in surgical outcomes. Resources for national and hospital quality-improvement initiatives are limited. It is unclear whether quality initiatives in surgical oncology should focus on factors affecting perioperative mortality or long-term survival. Our objective was to determine whether differences in hospital surgical volume have a larger effect on perioperative mortality or long-term survival using two methods. Patients and Methods From the National Cancer Data Base, 243,103 patients who underwent surgery for nonmetastatic colon, esophageal, gastric, liver, lung, pancreatic, or rectal cancer were identified. Multivariable modeling was used to evaluate 60-day mortality and 5-year conditional survival (excluding perioperative deaths) across hospital volume strata. The number of potentially avoidable perioperative and long-term deaths were calculated if outcomes at low-volume hospitals were improved to those of the highest-volume hospitals. Results Risk-adjusted perioperative mortality and long-term conditional survival worsened as hospital surgical volume decreased for all cancer sites, except for liver resections where there was no difference in survival. When comparing low- with high-volume hospitals, the hazard ratios for perioperative mortality were substantially larger than for long-term survival. However, the number of potentially avoidable deaths each year in the United States, if outcomes at low-volume hospitals were improved to the level of highest-volume centers, was significantly larger for long-term survival. Conclusion Although the magnitude of the hazard ratios implies that quality-improvement efforts should focus on perioperative mortality, a larger number of deaths could be avoided by focusing quality initiatives on factors associated with long-term survival.
Intravascular papillary endothelial hyperplasia of superior vena cava: a rare cause of the superior vena cava syndrome.
Authors: J Y Park, M Chung-Park, M Snow
Journal: Thorax (1991)

The superior vena cava syndrome associated with an intraluminal vascular proliferative lesion is extremely rare. A case of intravascular papillary endothelial hyperplasia of the superior vena cava causing obstructive symptoms is reported that was successfully managed by surgical excision.
Responses to music: Emotional signaling, and learning
Authors: Martin F. Gardiner
Journal: Behavioral and Brain Sciences (2008)

Abstract In the target article, Juslin &amp; Västfjäll (J&amp;V) contend that neural mechanisms not unique to music are critical to its capability to convey emotion. The work reviewed here provides a broader context for this proposal. Human abilities to signal emotion through sound could have been essential to human evolution, and may have contributed vital foundations for music. Future learning experiments are needed to further clarify engagement underlying musical and broader emotional signaling.
Graduate Medical Education: A Vital Renewal for Internal Medicine
Authors: LAWRENCE SCHERR
Journal: Annals of Internal Medicine (1987)

Editorials1 November 1987Graduate Medical Education: A Vital Renewal for Internal MedicineLAWRENCE SCHERR, M.D.LAWRENCE SCHERR, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-107-5-769 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn this issue, the Federated Council for Internal Medicine (FCIM) states its position on methods to enhance excellence in internal medicine through graduate training programs and the methods and principles by which they operate (1). With this goal of assuring quality care and preserving the professionalism of internal medicine, FCIM has appropriately chosen graduate medical education as its effector pathway. Recognizing the influence of its five member organizations, it proposes a major revision of the content, structure, and function of residencies in internal medicine and its subspecialties. The revision would directly relate to the work of the Residency Review Committee...References1. . Enhancing standards of excellence in Internal Medicine training. Ann Intern Med. 1987;107:775-8. LinkGoogle Scholar2. SCHERR L. Decline in internal medicine careers: a foreboding trend. ACP Observer. 1987;7(5):2. Google Scholar3. MCCARTY D. Why are today's medical students choosing high-technology specialties over internal medicine? N Engl J Med. 1987;317:567-9. CrossrefMedlineGoogle Scholar4. KARPFLEVEY MG. Training internists for the changing medical scene. Ann Intern Med. 1986;104:567-8. LinkGoogle Scholar5. SCHROEDERSHOWSTACKGERBERT SJB. Residency training in internal medicine: time for a change? Ann Intern Med. 1986;104:554-61. LinkGoogle Scholar6. NORCINIGROSSOSHEAWEBSTER JLJG. The relationship between features of residency training and ABIM certifying examination performance. J Gen Intern Med. 1987;2:330-6. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: American College of Physicians Philadelphia, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byIntensive one-week orientation for foreign medical graduates entering an internal medicine residency program 1 November 1987Volume 107, Issue 5Page: 769-771KeywordsGraduate medical educationHealth care qualityResidencySub-specialty care Issue Published: 1 November 1987 PDF downloadLoading ...
Familial isolated hypoparathyroidism caused by a mutation in the gene for the transcription factor GCMB
Authors: Changlin Ding, Bruce Buckingham, Michael A. Levine
Journal: Journal of Clinical Investigation (2001)

Hypoparathyroidism is characterized by hypocalcemia, hyperphosphatemia, and absent or markedly reduced circulating concentrations of parathyroid hormone. The transcription factor GCMB is predominantly, if not exclusively, expressed in parathyroid cells and is critical for development of the parathyroid glands in mice. Thus, in the present study we examined the GCMB gene, mapped to 6p23–24, as a candidate for isolated hypoparathyroidism. We defined the boundaries of the five exons of the human GCMB gene and then identified a large intragenic mutation in the GCMB genes of the proband of an extensive kindred with isolated hypoparathyroidism. Her parents and several other unaffected relatives were heterozygous for the mutation. Despite an absence of any history of consanguinity, microsatellite analysis showed shared genotypes that flanked the GCMB gene over a span of 5 cM, suggesting that both of the proband’s GCMB alleles had been derived from a single common ancestor. Analysis of additional, unrelated cases did not disclose the same mutation. We conclude that homozygous loss of function of the GCMB gene impairs normal parathyroid gland embryology and is responsible for isolated hypoparathyroidism in a subset of patients with this disease.