tbuckley/cabot-search huggingface dataset:
Ion-Exchange Resins for the Treatment of Hyperkalemia
Authors: Richard H. Sterns, Maria Rojas, Paul Bernstein, Sreedevi Chennupati
Journal: Journal of the American Society of Nephrology (2010)

Sodium polystyrene sulfonate (SPS), an ion-exchange resin designed to bind potassium in the colon, was approved in 1958 as a treatment for hyperkalemia by the US Food and Drug Administration, 4 years before drug manufacturers were required to prove the effectiveness and safety of their drugs. In September 2009, citing reports of colonic necrosis, the Food and Drug Administration issued a warning advising against concomitant administration of sorbitol, an osmotic cathartic used to prevent SPS-induced fecal impaction and to speed delivery of resin to the colon, with the powdered resin; however, a premixed suspension of SPS in sorbitol, the only preparation stocked by many hospital pharmacies, is prescribed routinely for treatment of hyperkalemia. We can find no convincing evidence that SPS increases fecal potassium losses in experimental animals or humans and no evidence that adding sorbitol to the resin increases its effectiveness as a treatment for hyperkalemia. There is growing concern, however, that suspensions of SPS in sorbitol can be harmful. It would be wise to exhaust other alternatives for managing hyperkalemia before turning to these largely unproven and potentially harmful therapies.
Phase II Study of SMILE Chemotherapy for Newly Diagnosed Stage IV, Relapsed, or Refractory Extranodal Natural Killer (NK)/T-Cell Lymphoma, Nasal Type: The NK-Cell Tumor Study Group Study
Authors: Motoko Yamaguchi, Yok-Lam Kwong, Won Seog Kim, Yoshinobu Maeda, Chizuko Hashimoto, Cheolwon Suh, Koji Izutsu, Fumihiro Ishida, Yasushi Isobe, Eisaburo Sueoka, Junji Suzumiya, Takao Kodama, Hiroshi Kimura, Rie Hyo, Shigeo Nakamura, Kazuo Oshimi, Ritsuro Suzuki
Journal: Journal of Clinical Oncology (2011)

To explore a more effective treatment for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKL), we conducted a phase II study of the steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) regimen.Patients with newly diagnosed stage IV, relapsed, or refractory disease and a performance status of 0 to 2 were eligible. Two cycles of SMILE chemotherapy were administered as the protocol treatment. The primary end point was the overall response rate (ORR) after the protocol treatment.A total of 38 eligible patients were enrolled. The median age was 47 years (range, 16 to 67 years), and the male:female ratio was 21:17. The disease status was newly diagnosed stage IV in 20 patients, first relapse in 14 patients, and primary refractory in four patients. The eligibility was revised to include lymphocyte counts of 500/μL or more because the first two patients died from infections. No treatment-related deaths were observed after the revision. The ORR and complete response rate after two cycles of SMILE chemotherapy were 79% (90% CI, 65% to 89%) and 45%, respectively. In the 28 patients who completed the protocol treatment, 19 underwent hematopoietic stem-cell transplantation. The 1-year overall survival rate was 55% (95% CI, 38% to 69%). Grade 4 neutropenia was observed in 92% of the patients. The most common grade 3 or 4 nonhematologic complication was infection (61%).SMILE chemotherapy is an effective treatment for newly diagnosed stage IV, relapsed or refractory ENKL. Myelosuppression and infection during the treatment should be carefully managed.
Risk factors for the development of retroperitoneal hematoma after percutaneous coronary intervention in the era of glycoprotein IIb/IIIa inhibitors and vascular closure devices
Authors: H.M. Omar Farouque, Jennifer A. Tremmel, Farshad Raissi Shabari, Meenakshi Aggarwal, William F. Fearon, Martin K.C. Ng, Mehrdad Rezaee, Alan C. Yeung, David P. Lee
Journal: Journal of the American College of Cardiology (2005)
ANAPHYLAXIS IN CHOPPED GUINEA PIG LUNG
Authors: K. F. Austen, W. E. Brocklehurst
Journal: The Journal of Experimental Medicine (1961)

The anaphylactic release of histamine from perfused, chopped guinea pig lung is very sensitive to changes in the NaCl concentration of the containing medium, and it is ionic strength rather than particle concentration which is critical. Consequently, in studies with inhibitors care must be taken to avoid inadvertently increasing ionic strength and thereby misinterpreting the cause of the inhibition. Since immune hemolysis exhibits a similar sensitivity to changes in the NaCl concentration of the suspending medium, salicylaldoxime and phlorizin, which prevent the participation of the third component of complement in immune hemolysis, were investigated for their effect on the anaphylactic reaction. Salicylaldoxime is a potent inhibitor of in vitro anaphylaxis in guinea pig lung, but phlorizin is only a weak inhibitor. Potassium cyanide, 1 mM, inhibits the anaphylactic release of histamine most effectively if the duration of contact between the tissue and the cyanide prior to antigen addition is minimal; preincubation of the tissue with cyanide prior to antigen addition results in progressive diminution of inhibition even when there is only minimal loss of cyanide from the containing medium. The anaphylactic release of histamine from perfused whole lungs or suspensions of blood-free chopped lung is not prevented by the cytochrome oxidase inhibitor, carbon monoxide. In addition, 2-heptyl 4 hydroxyquinoline N oxide and malonic acid, which inhibit aerobic metabolism at different sites, do not prevent the reaction. These studies and those with cyanide indicate that the anaphylactic release of histamine in guinea pig lung is not dependent on cytochrome-mediated aerobic metabolism.
Health Issues of Air Travel
Authors: Roy L. DeHart
Journal: Annual Review of Public Health (2003)

▪ Abstract Every day in the United States the airline industry boards over 1.7 million passengers for a total of 600 million passengers per year. As these passengers enter the cabin of their aircraft few are aware of the artificial environment that will protect them from the hazards of flight. Passengers are exposed to reduced atmospheric pressure, reduced available oxygen, noise, vibration, and are subject to below zero temperatures that are only a quarter inch away—the thickness of the aircraft's skin. Over the past decade there have been both technical and lay articles written on the perception of poor cabin air quality. Studies have, in part, supported some of those concerns, but, in general, the air quality exceeds that found in most enclosed spaces on terra firma. Since the events of September 11th, passengers have not only been exposed to the physical stress of flight, but also to social and emotional stress preceding departure. There has been a significant increase in air rage on board aircraft, which poses a threat to flight safety and a fear of harm to passengers and crew. The phrase “economy class syndrome” has received popular press attention and refers to the possibility of deep vein thrombosis (DVT) in the tight confines of an aircraft cabin. Studies have been conducted that demonstrate DVT can occur in flight just as it occurs in other modes of transportation or with prolonged sitting. In part, because of the stress related to commercial flight it is not a mode of transportation for everyone. Certain cardiovascular, pulmonary, and neuropsychiatric conditions are best left on the ground. Although medical problems and death are rare in flight, they do occur, and one major airline reported 1.52 medical diversions per billion revenue passenger miles flown. To provide medical support at 36,000 ft (11,000 m) most airlines now carry on-board medical kits as well as automatic external defibrillators. A recent survey conducted by a major airline revealed that there was at least one physician on 85% of all its flights. Both passenger and cargo aircraft have proven to be vectors of disease in that they transport humans, mosquitoes, and other insects and animals who, in turn, transmit disease. Transmission to other passengers has occurred with tuberculosis and influenza. Vectors for yellow fever, malaria, and dengue have been identified on aircraft. Although there are numerous health issues associated with air travel they pale in comparison to the enormous benefits to the traveler, to commerce, to international affairs, and to the public's health.
S64 Circulating polymers are found in alpha-1-antitrypsin deficiency and are associated with lung disease
Authors: JA Dickens, L Tan, DL DeMeo, E Miranda, J Perez, ST Rashid, J Day, A Ordonez, SJ Marciniak, I Haq, AF Barker, EJ Campbell, E Eden, NG McElvaney, SI Rennard, RA Sandhaus, JM Stocks, JK Stoller, C Strange, G Turino, FN Rouhani, M Brantly, DA Lomas
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> The severe Z deficiency allele of alpha-1-antitrypsin (Glu<sup>342</sup>Lys) results in the formation of polymers that are retained within hepatocytes, leading to hepatitis, cirrhosis and hepatocellular carcinoma. The concomitant lack of circulating protein predisposes to early onset emphysema. Polymers are also found in the lung, skin and kidney and are known to be proinflammatory, but it is unknown whether those polymers are produced locally or are deposited from a circulating source. We wished to establish whether polymers are present in the plasma of individuals with alpha-1-antitrypsin deficiency, from where they originate and whether they are associated with any clinical phenotype. <h3>Methods</h3> We used a novel anti-alpha-1-antitrypsin polymer monoclonal antibody (2C1) in an ELISA assay to evaluate whether polymers are present in a cohort of 513 individuals with ZZ alpha-1-antitrypsin deficiency. Serial samples from an individual with ZZ alpha-1-antitrypsin deficiency undergoing liver transplantation were used to investigate the source of circulating polymers. We then used a 2<sup>nd</sup> cohort of 293 individuals with mixed alpha-1-antitrypsin phenotypes to determine whether circulating polymers could be used as a screening test for the presence of a polymerogenic allele. Disease associations were sought using clinical data from the ZZ alpha-1-antitrypsin deficient cohort. <h3>Results</h3> In the cohort of 513 individuals with PiZZ alpha-1-antitrypsin deficiency, we found 512 had quantifiable polymers present within serum, the 513<sup>th</sup> having previously had a liver transplant. Circulating polymer levels were higher in men and individuals with COPD and a there was a correlation with older age and lower lung function. The presence of circulating polymers was 100% sensitive and 89% specific in identifying 20 PiZZ alpha-1-antitrypsin homozygotes in a mix of 293 alpha-1-antitrypsin genotypes. Serial blood samples from a PiZZ individual undergoing liver transplantation showed that circulating polymers originate from the liver, clearing with a half-life of approximately 30 hours and becoming undetectable 5 days after transplantation. <h3>Conclusions</h3> We have shown that circulating polymers are present in PiZZ alpha-1-antitrypsin individuals and originate from the liver. Polymer levels are associated with COPD, suggesting they may play a role in disease pathogenesis.
A Randomized Trial of Letrozole in Postmenopausal Women after Five Years of Tamoxifen Therapy for Early-Stage Breast Cancer
Authors: Paul E. Goss, James N. Ingle, Silvana Martino, Nicholas J. Robert, Hyman B. Muss, Martine J. Piccart, Monica Castiglione, Dongsheng Tu, Lois E. Shepherd, Kathleen I. Pritchard, Robert B. Livingston, Nancy E. Davidson, Larry Norton, Edith A. Perez, Jeffrey S. Abrams, Patrick Therasse, Michael J. Palmer, Joseph L. Pater
Journal: New England Journal of Medicine (2003)

In hormone-dependent breast cancer, five years of postoperative tamoxifen therapy--but not tamoxifen therapy of longer duration--prolongs disease-free and overall survival. The aromatase inhibitor letrozole, by suppressing estrogen production, might improve the outcome after the discontinuation of tamoxifen therapy.We conducted a double-blind, placebo-controlled trial to test the effectiveness of five years of letrozole therapy in postmenopausal women with breast cancer who have completed five years of tamoxifen therapy. The primary end point was disease-free survival.A total of 5187 women were enrolled (median follow-up, 2.4 years). At the first interim analysis, there were 207 local or metastatic recurrences of breast cancer or new primary cancers in the contralateral breast--75 in the letrozole group and 132 in the placebo group--with estimated four-year disease-free survival rates of 93 percent and 87 percent, respectively, in the two groups (P< or =0.001 for the comparison of disease-free survival). A total of 42 women in the placebo group and 31 women in the letrozole group died (P=0.25 for the comparison of overall survival). Low-grade hot flashes, arthritis, arthralgia, and myalgia were more frequent in the letrozole group, but vaginal bleeding was less frequent. There were new diagnoses of osteoporosis in 5.8 percent of the women in the letrozole group and 4.5 percent of the women in the placebo group (P=0.07); the rates of fracture were similar. After the first interim analysis, the independent data and safety monitoring committee recommended termination of the trial and prompt communication of the results to the participants.As compared with placebo, letrozole therapy after the completion of standard tamoxifen treatment significantly improves disease-free survival.
Etomoxir, a carnitine palmitoyltransferase I inhibitor, protects hearts from fatty acid-induced ischemic injury independent of changes in long chain acylcarnitine.
Authors: G D Lopaschuk, S R Wall, P M Olley, N J Davies
Journal: Circulation Research (1988)

Fatty acids are known to increase the severity of injury during acute myocardial ischemia. In this study, we determined the effects of a carnitine palmitoyltransferase I inhibitor, ethyl 2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate (Etomoxir) on reperfusion recovery of fatty acid perfused hearts. Following a 25-minute period of global ischemia, isolated working hearts reperfused with 1.2 mM palmitate, 11 mM glucose exhibited depressed function compared to hearts perfused with 11 mM glucose alone. A low dose of Etomoxir (10(-9) M) decreased long chain acylcarnitine and long chain acyl-coenzyme A (CoA) levels but did not prevent depressed function. In contrast, a high dose of Etomoxir (10(-6) M) prevented the palmitate-induced depression of function but did not decrease myocardial long chain acylcarnitine or long chain acyl-CoA levels. At this high dose of Etomoxir, oxygen consumption per unit work was decreased during reperfusion recovery, and ATP and creatine-phosphate levels were significantly higher after reperfusion. In aerobic hearts not subjected to ischemia, Etomoxir (10(-6) M) increased glucose oxidation both in the presence and absence of palmitate, while 10(-9) M Etomoxir had no effect. In these aerobic hearts, only the low dose of Etomoxir decreased long chain acylcarnitine and long chain acyl-CoA levels. These data demonstrate that Etomoxir (10(-6) M) increases functional recovery of fatty acid perfused ischemic hearts. This protection is unrelated to changes in levels of long chain acylcarnitines but may be due to increased glucose use by the reperfused heart, resulting in decreased oxygen consumption per unit work.
1060-102 Risk scores derived from clinical trials do not generalize to real world acute coronary syndrome patients: Insights from the Canadian acute coronary syndromes registry
Authors: Andrew T Yan, Philip Jong, Raymond T Yan, Mary Tan, Robin A Kuritzky, Laura Drozdiak, Chi-Ming Chow, David H Fitchett, Anatoly Langer, Shaun G Goodman
Journal: Journal of the American College of Cardiology (2004)
Bronchoprotection by salmeterol: cell stabilization or functional antagonism? Comparative effects on histamine- and AMP-induced bronchoconstriction
Authors: M Soler, L Joos, CT Bolliger, S Elsasser, AP Perruchoud
Journal: European Respiratory Journal (1994)

Salmeterol provides bronchoprotection against a number of constrictor stimuli for more than 12 h after a single dose. This effect could be due either to functional antagonism at the level of airway smooth muscle or to cell-stabilizing effects of the compound. In this study, we attempted to clarify this mechanism by comparing the effects of salmeterol (50 micrograms), salbutamol (200 micrograms) and placebo on the airway responsiveness to histamine (to assess functional antagonism), and to adenosine 5'-monophosphate (AMP) (to assess additional cell-stabilizing effects), 14 h after drug treatment. Thirteen patients with mild allergic asthma were studied in a double-blind, randomized protocol on 6 days, at least 48 h apart. Forced expiratory volume in one second (FEV1) was measured before and 15 min after inhalation of the study medication. Then, 14 h later (8 a.m. the following morning), a bronchoprovocation test with histamine or AMP was performed. We found that 14 h after inhalation, salmeterol still had a significant effect on FEV1 in comparison to placebo and salbutamol. The provocative dose producing a 20% fall in FEV1 (PD20histamine) was significantly increased after salmeterol, whilst the increase in PD20AMP did not reach significance. The shift in PD20 (in doubling dose steps) induced by salmeterol pretreatment was not different between histamine and AMP. We conclude that the prolonged protective effect of salmeterol occurs via an extended bronchodilating and functional antagonistic action and not via a cell-stabilizing effect.
Regulation of B Lymphocyte Responses to Foreign and Self-Antigens by the CD19/CD21 Complex
Authors: Douglas T. Fearon, Michael C. Carroll, Michael C. Carroll
Journal: Annual Review of Immunology (2000)

The membrane protein complex CD19/CD21 couples the innate immune recognition of microbial antigens by the complement system to the activation of B cells. CD21 binds the C3d fragment of activated C3 that becomes covalently attached to targets of complement activation, and CD19 co-stimulates signaling through the antigen receptor, membrane immunoglobulin. CD21 is also expressed by follicular dendritic cells and mediates the long-term retention of antigen that is required for the maintenance of memory B cells. Understanding of the biology of this receptor complex has been enriched by analyses of genetically modified mice; these analyses have uncovered roles not only in positive responses to foreign antigens, but also in the development of tolerance to self-antigens. Studies of signal transduction have begun to determine the basis for the coreceptor activities of CD19. The integration of innate and adaptive immune recognition at this molecular site on the B cell guides the appropriate selection of antigen by adaptive immunity and emphasizes the importance of this coreceptor complex.
Description of Conditions Found in the Head and Neck Two Years and A-Quarter after Ligature of All the Carotid Arteries, Jugular Veins, Etc., of the Left Side
Authors: W. T. Thomas
Journal: BMJ (1897)

JOURNAL of December 7th, I895, I recorded a case of cut throat, and the treatment of the case was summarised thus: October 5th, I894.Ligature of the common carotid artery in two places, of the internal jugular vein in two places, of the external and anterior jugular veins * perfusion of 20 ounces saline fluid.October 27th.SeconAary huemorrhage; attempted ligature of common carotid, which was rotten, so that tie ex-ternal and internal carotid arteries were tied, along with other ligatures on the internal jugular vein and a branch, by my colleague Mr. R. A. Bickersteth, who was fortunately at hand when the hoemorrhage occurred.November 5th.Hremorrhage from internal carotid artery arrested by
The inflammatory reflex and risk for rheumatoid arthritis: a case-control study of human vagotomy
Authors: C. Carlens, L. Brandt, L. Klareskog, J. Lampa, J. Askling
Journal: Annals of the Rheumatic Diseases (2006)

Recent data suggest remarkable effects of vagus stimulation (reduction) and vagotomy (exacerbation) on acute inflammation in rats, the so-called "inflammatory reflex". Its role in humans remains unknown. Therefore, the aim was to explore whether surgical vagotomy in humans would affect the risk of a prototype inflammatory disease, rheumatoid arthritis. This was a case–control study. Assessment of the relative risk (RR) of developing rheumatoid arthritis after surgical vagotomy during 1964–2001 in 63 092 prevalent rheumatoid arthritis cases versus 125 404 matched controls from the general population and in 2548 incident rheumatoid arthritis cases versus 24 357 matched controls from the general population, respectively, was done. For comparison, we assessed RRs for hospitalisation for gastric disorders not including vagotomy. Data on exposures and rheumatoid arthritis were retrieved from population-based and prospectively recorded Swedish registers. A pre-rheumatoid arthritis vagotomy was not significantly associated with an increased risk for rheumatoid arthritis (RR = 1.17, 95% CI 0.97 to 1.40). RRs in the same range were observed for several other pre-rheumatoid arthritis gastric conditions that do not include vagotomy (eg, gastric ulcer RR = 1.21, 95% 1.11 to 1.33). Vagotomy has no specific effect on the risk of developing rheumatoid arthritis in humans. Gastroduodenal ulcers occur more often than expected even before the occurrence of rheumatoid arthritis.
Controlled Delivery of High vs Low Humidity vs Mist Therapy for Croup in Emergency Departments
Authors: Dennis Scolnik, Allan L. Coates, Derek Stephens, Zelia Da Silva, Elana Lavine, Suzanne Schuh
Journal: JAMA (2006)

Children with croup are often treated with humidity even though this is not scientifically based, consumes time, and can be harmful. Although humidity using the traditional blow-by technique is similar to room air and no water droplets reach the nasopharynx, particles sized for laryngeal deposition (5-10 microm) could be beneficial.To determine whether a significant difference in the clinical Westley croup score exists in children with moderate to severe croup who were admitted to the emergency department and who received either 100% humidity or 40% humidity via nebulizer or blow-by humidity.A randomized, single-blind, controlled trial conducted between 2001 and 2004 in a tertiary care pediatric emergency department.A convenience sample of 140 previously healthy children 3 months to 10 years of age with Westley croup score of more than 1 or 2 or higher (scoring system range, 0-17); 21 families refused participation.Thirty-minute administration of humidity using traditional blow-by technique (commonly used placebo, n = 48), controlled delivery of 40% humidity (optimally delivered placebo, n = 46), or 100% humidity (n = 46) with water particles of mass median diameter 6.21 microm.A priori defined change in the Westley croup score from baseline to 30 and 60 minutes in the 3 groups.Groups were comparable before treatment. At 30 minutes the difference in the improvement in the croup score between the blow-by and low-humidity groups was 0.03 (95% confidence interval [CI], -0.72 to 0.66), between low- and high-humidity groups, 0.16 (95% CI, -0.86 to 0.53), and between blow-by and high-humidity groups, 0.19 (95% CI, -0.87 to 0.49). Results were similar at 60 minutes. Differences between groups in pulse and respiratory rates and oxygen saturation changes were insignificant, as were proportions of excellent responders; proportions with croup score of 0 at study conclusion; and proportions receiving dexamethasone, epinephrine, or requiring additional medical care or hospitalization.One hundred percent humidity with particles specifically sized to deposit in the larynx failed to result in greater improvement than 40% humidity or humidity by blow-by technique. This study does not support the use of humidity for moderate croup for patients treated in the emergency department.ClinicalTrials.gov Identifier: NCT00230841.