tbuckley/cabot-search huggingface dataset:
ACE Gene Polymorphism in COPD
Authors: Nicholas S. Hopkinson, Annabel H. Nickol, John Payne, Emma Hawe, William D.-C. Man, John Moxham, Hugh Montgomery, Michael I. Polkey
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The study of Hopkinson and colleagues (1) showed that in patients with chronic obstructive pulmonary disease (COPD) the deletion allele (D) of the ACE polymorphism was associated with greater quadriceps strength compared with the insertion allele (I), and the authors suggested that this may also apply for exercise capacity. This is remarkable, because in healthy subjects it has consistently been reported that I, but not D, is positively associated with enhanced exercise and muscle performance (2). We have evaluated the ACE gene polymorphism, determined by polymerase chain reaction (3), in 95 patients with COPD (65 males and 30 females, aged 65 years, FEV1 39% of predicted) submitted to an 8-week pulmonary rehabilitation program comprising five exercise training sessions per week. ACE genotype distribution was comparable with that described by Hopkinson and colleagues (DD 32%; ID 50%; II 19%). Exercise capacity, measured by means of the maximal work load achieved during exhaustive incremental cycle ergometry (Wmax), was similar for all ACE genotypes at baseline (DD 57.5 W; II/ID 52.3 W), but I, and not D, was associated with an enhanced response to physical training (DD 6.0 9.8 W; II/ID 14.4 12 W; mean SD; p 0.04). It thus seems that exercise capacity, in contrast to muscle strength, is not associated with D in COPD. One could speculate that I is associated with enhanced improvement and/or preservation of endurance and D with better improvement and/or preservation of muscle strength. Unfortunately, in our study quadriceps strength was not measured. As in the study by Hopkinson and coworkers, no baseline association between ACE genotype and fat-free mass was found. However, this does not exclude the possibility that muscular properties other than variations in muscle mass are responsible for differences in muscle function. For example, I has been associated with increased proportions of fatigue-resistant slow-twitch fibers—and thus with decreased fast-twitch fiber proportions—in healthy subjects (4). In addition, impaired peripheral tissue oxygenation has been associated with D in COPD (5). It can therefore be hypothesized that a higher proportion of fast-twitch fibers underlies the D allele–associated preservation of muscle strength in the study by Hopkinson and colleagues, whereas in our study the I allele–associated increase in Wmax might be due to a higher proportion of slow-twitch fibers and/or better muscle oxygenation. To resolve this hypothesis, it is important that in future studies assessment of both muscle strength and endurance are included, in combination with muscle biopsy analysis of fiber types.
Receptors for secretin, calcitonin, parathyroid hormone (PTH)/PTH-related peptide, vasoactive intestinal peptide, glucagonlike peptide 1, growth hormone-releasing hormone, and glucagon belong to a newly discovered G-protein-linked receptor family
Authors: Gino V. Segre, Steven R. Goldring
Journal: Trends in Endocrinology and Metabolism (1993)
A “Customary and Necessary” Program — Medicaid and Health Care Reform
Authors: Sara Rosenbaum
Journal: New England Journal of Medicine (2010)

The recently passed U.S. health care reform law envisions a health care system that rests atop a four-legged stool consisting of employer-sponsored health plans, coverage purchased through state-based exchanges, Medicare, and Medicaid. Each leg faces important challenges, none more than Medicaid. Numerous issues confront the "new" Medicaid. Will states be able to achieve full coverage for eligible persons and align their operations smoothly with those of other coverage sources? Will coverage be adequate to the population's need? Will providers participate, and will the safety net be sustained? And perhaps above all, will states continue to operate Medicaid programs and share . . .
Coronary Artery Calcium Score and Risk Classification for Coronary Heart Disease Prediction
Authors: Tamar S. Polonsky, Robyn L. McClelland, Neal W. Jorgensen, Diane E. Bild, Gregory L. Burke, Alan D. Guerci, Philip Greenland
Journal: JAMA (2010)

The coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves classification of risk is unclear.To determine whether adding CACS to a prediction model based on traditional risk factors improves classification of risk.CACS was measured by computed tomography in 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2008. Participants with diabetes were excluded from the primary analysis. Five-year risk estimates for incident CHD were categorized as 0% to less than 3%, 3% to less than 10%, and 10% or more using Cox proportional hazards models. Model 1 used age, sex, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. We calculated the net reclassification improvement and compared the distribution of risk using model 2 vs model 1.Incident CHD events.During a median of 5.8 years of follow-up among a final cohort of 5878, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared with model 1 (net reclassification improvement = 0.25; 95% confidence interval, 0.16-0.34; P < .001). In model 1, 69% of the cohort was classified in the highest or lowest risk categories compared with 77% in model 2. An additional 23% of those who experienced events were reclassified as high risk, and an additional 13% without events were reclassified as low risk using model 2.In this multi-ethnic cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories.
Mechanisms of renal excretion of urobilinogen.
Authors: E. Bourke, M. D. Milne, G. S. Stokes
Journal: BMJ (1965)

Several arabinosyl-, xylosyl-, lyxosyl, 59-deoxy-, acyclo-, 2,29-anhydro-, 2,39-anhydro-29-deoxy-, 2,59-anhydro-, 6,59-cyclo-, and carbocyclic analogues of uridine with various 5-substitutions (fluoro, methyl, bromo, ethyl, benzyl, or benzyloxybenzyl) have been tested and compared with their corresponding ribo- and 29-deoxyribosides for their potency to inhibit uridine phosphorylase (UrdPase) from both mouse and human livers. The effect of the alpha- and beta-configurations of the glycosidic bond was also tested. Xylo-, lyxo-, 2,39-anhydro-29-deoxy-, 6,59-cyclo-, and carbocyclic uridines did not bind to the enzyme. Ribosides bound better than the corresponding 29-deoxyribosides, which were better than the 59-deoxyribosides. 29-alpha-Deoxyribosides bound to the enzyme, albeit less tightly than the corresponding beta-anomers. The acyclo- and 2,29-anhydrouridines were all potent inhibitors with the 2,29-anhydro- derivatives being the most potent. 2,59-Anhydrouridine bound to UrdPase less effectively than 2,29-anhydrouridine and acyclouridine. Arabinosyl uracil was at best a very poor inhibitor but binds better if a benzyl group is added at the 5-position of the pyrimidine ring. This binding was enhanced further by adding a 5-benzyloxybenzyl group. A similar enhancement of the binding with increased hydrophobicity at the 5-position of the pyrimidine ring was observed with ribosides, alpha- and beta-anomers of the 29-deoxyribosides, acyclonucleosides, and 2,29-anhydronucleosides. The inhibitory potencies of these compounds with UrdPase from human liver roughly parallel those obtained with UrdPase from mouse liver. It is concluded that the presence of a N-glycosidic bond as well as a properly oriented 39-hydroxyl group are prerequisites for a nucleoside ligand to bind to UrdPase. On the other hand, the presence of a 29- or 59-hydroxyl group or an N-glycosidic bond in the beta-configuration enhances but is not essential for binding. Furthermore, the potency of the binding of 2,29-anhydrouridines (fixed syn-isomers) in contrast to the complete lack of binding of the 6,59-cyclouridines (fixed anti-isomers) to UrdPase indicates that the binding of ligands to this enzyme is in the syn-conformation around the N-glycosidic bond.
Prostanoids and Leukotrienes in Experimental Feline Cholecystitis
Authors: Donald L. Kaminski, Hootan Daneshmand, Philip Dean, Yashwant G. Deshpande
Journal: Hepatology (1990)

Current information suggests that arachidonic acid metabolites are involved in the development of cholecystitis. The purpose of this study was to evaluate eicosanoid formation during the development of experimental cholecystitis in cats. Lysophosphatidylcholine is found in the gallbladders of patients with cholecystitis and is known to be a cytolytic, membrane-damaging substance. Anesthetized cats underwent gallbladder perfusion with and without 1.5 mmol/L lysophosphatidylcholine. Additional experiments were performed when calcium ionophore were added to the perfusates and experiments were performed when cats were treated with indomethacin and underwent perfusion with lysophosphatidylcholine. Changes in the gallbladder were determined by evaluating mucosal water transport as measured by determining the changes in concentration in a nonabsorbable marker, by protein secretion and by beta-glucuronidase accumulation in gallbladder tissue as an index of inflammation. Eicosanoid formation was evaluated by measuring perfusate concentrations and gallbladder homogenate concentrations by radioimmunoassay of prostaglandin E, 6 keto prostaglandin F1 alpha, leukotriene B4 and leukotriene C4. Lysophosphatidylcholine perfusion reversed the control patterns of absorption and produced water exsorption, produced an efflux of protein into the perfusate and increased beta-glucuronidase activity. These changes were accompanied by increased production of prostaglandin E and 6 keto prostaglandin F1 alpha in gallbladder perfusate and homogenate. The concentration of leukotriene C4 in gallbladder effusate was increased by lysophosphatidylcholine when compared with control values. Indomethacin inhibited the protein efflux, decreased beta-glucuronidase levels and decreased prostaglandin E and 6 keto prostaglandin F1 alpha formation when compared with values produced by lysophosphatidylcholine alone. Cyclooxygenase inhibition did not alter the secretion of water into the gallbladder or perfusate leukotriene C4 concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Roles of Mechanical Forces and Collagen Failure in the Development of Elastase-induced Emphysema
Authors: STEFANIDA KONONOV, KELLY BREWER, HIROAKI SAKAI, FRANCISCO S. A. CAVALCANTE, CHANDRAN R. SABAYANAGAM, EDWARD P. INGENITO, BÉLA SUKI
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Emphysema causes a permanent destruction of alveolar walls leading to airspace enlargement, loss of elastic recoil, decrease in surface area for gas exchange, lung hyperexpansion, and increased work of breathing. The most accepted hypothesis of how emphysema develops is based on an imbalance of protease and antiprotease activity leading to the degradation of elastin within the fiber network of the extracellular matrix. Here we report novel roles for mechanical forces and collagen during the remodeling of lung tissue in a rat model of elastase-induced emphysema. We have developed a technique to measure the stress–strain properties of tissue sections while simultaneously visualizing the deformation of the immunofluorescently labeled elastin–collagen network. We found that in the elastase treated tissue significant remodeling leads to thickened elastin and collagen fibers and during stretching, the newly deposited elastin and collagen fibers undergo substantially larger distortions than in normal tissue. We also found that the threshold for mechanical failure of collagen, which provides mechanical stability to the normal lung, is reduced. Our results indicate that mechanical forces during breathing are capable of causing failure of the remodeled extracellular matrix at loci of stress concentrations and so contribute to the progression of emphysema.
Iron supplementation generates hydroxyl radical in vivo. An ESR spin-trapping investigation.
Authors: M B Kadiiska, M J Burkitt, Q H Xiang, R P Mason
Journal: Journal of Clinical Investigation (1995)

Electron spin resonance (ESR) spectroscopy has been used to investigate hydroxyl radical generation in rats with chronic dietary iron loading. A secondary radical spin-trapping technique was used where hydroxyl radical forms methyl radical upon reaction with DMSO. The methyl radical was then detected by ESR spectroscopy as its adduct with the spin trap alpha-phenyl-N-t-butylnitrone (PBN). This adduct was detected in the bile of rats 10 wk after being fed an iron-loading diet and 40 min after the i.p. injection of the spin trap PBN dissolved in DMSO. Bile samples were collected into a solution of the ferrous stabilizing chelator 2,2'-dipyridyl in order to prevent the generation of radical adducts ex vivo during bile collection. Identification of the ESR spectrum of the major radical adduct as that of PBN/.CH3 provides evidence for the generation of the hydroxyl radical during iron supplementation. Desferal completely inhibited in vivo hydroxyl radical generation stimulated by high dietary iron intake. No radical adducts were detected in rats which were fed the control diet for the same period of time. This is the first evidence of hydroxyl radical generation in chronic iron-loaded rats.
Determination of glycosylated hemoglobins in neonatal blood by isoelectric focusing
Authors: M. D. Fitzgerald, M. N. Cauchi
Journal: American Journal of Hematology (1980)

Abstract Isoelectric focusing (IEF) with suitable „spacers”︁ can be used to distinguish glycosylated hemoglobins from HbA and HbF in adults and infants, respectively. Using this technique we have shown that there is a good correlation between glycosylated hemoglobins measured by IEF and column chromatography (r = 0.778, P &lt; 0.001). There was no significant difference in the rate of glycosylation between adult and cord blood hemolysates following incubation with glucose in vitro: In both instances there was an increase from the normal levels of about 5% to 26% through 31% after 18 hours of incubation. The levels of glycosylated hemoglobins in infants of varying gestation, neonates, and normal adults was remarkably constant, varying from 4.7 ± 1.1% to 6.1 ± 1.6%. These results show that IEF can be useful in the quantitation of glycosylated hemoglobins, particularly in the presence of hemoglobins (eg, HbF) where standard chromatographic techniques cannot be used. IEF has the added advantage of using small quantities of blood, and allows a number of samples to be tested at the same time, thus facilitating the identification of abnormal hemoglobins.
A randomized treatment duration-finding study of terbinafine in onychomycosis
Authors: J.G.VAN DER SCHROEFF, P.K.S. CIRKEL, M.B. CRIJNS, T.J.A.VAN DIJK, F.J. GOVAERT, D.A. GROENEWEG, D.J. TAZELAAR, R.F.E.DE WIT, J. WUITE
Journal: British Journal of Dermatology (1992)

Terbinafine is an allylamine antifungal compound shown to be effective in the oral treatment of onychomycosis. Because of the fungicidal acivity of the drug, a shorter duration of treatment, compared with the currently used oral treatment modalities, can be expected in onychomycosis of the toenail. In the present randomized study, the efficacy of oral terbinaifne treatment (250mg/day) was assessed for periods of 6.12, and 24 weeks. All patients were followed for up to 48 weeks after starting treatment. Of the 120 patients with toenail onychomycosis who entered the study, 98 were evaluable for efficacy. The involvement of the toenails was assessed both clinically and mycologically throughout the study. Evaluation at 24 weeks showed that complete cure of toenail onychomycosis was achieved in 67% of patients treated for 6 weeks, 82% treated for 12 weeks, and 85% treated for 24 weeks. At the end of a further 24 weeks of follow‐up, cure rates were 40%, 71% and 79%, respectively. The adverse effects of terbinafine were mostly mild‐to‐moderate gastrointestinal symptoms. Three patients discontinued treatment because of side‐effects. In conclusion, oral treatment with terbinafine is effective and generally well tolerated in patients with onychomycosis. Our results demonstrate that, for toenail onychomycosis, a treatment period of 12 weeks is sufficient.
Another Fraud Solicitor.
Authors: John M. Dodson
Journal: JAMA (1901)

Chicago, Feb. 15, 1901. <h3>To the Editor:</h3> —I learn that several physicians in Chicago have been victimized, as I was, recently by a scoundrel professing to be the representative of a newspaper subscription agency. I presume the firm which he professes to represent is a reputable one, although I wonder that they do not seem more interested in apprehending this man and prosecuting him, as he is not only collecting money in their name, but forging their signature to checks made out to the agency. As the magazines for which I subscribed failed to make their appearance some weeks after the visit of this agent, I addressed a letter to Moore's Agency, and received the following reply: Your favor of the 14th received, and in reply would say we have no agent by the name of W. R. Neal, and we do not offer any such list of magazines as
Thrombocytopenia Associated With Antiheparin Antibody
Authors: Timothy O. Wahl
Journal: JAMA (1978)

Thrombocytopenia developed in a 69-year-old woman receiving heparin sodium therapy for deep-vein thrombosis. Bone marrow and platelet survival studies suggested peripheral destruction of platelets. The serum factor associated with thrombocytopenia was shown to be an IgM immunoglobulin. Heparin-induced thrombocytopenia may be a common side effect of heparin therapy and should be evaluated to avoid serious consequences. (<i>JAMA</i>240:2560-2562, 1978)
Chlorpromazine-Type Cholangitis
Authors: Richard C. Mechanic, Lawrence Meyers
Journal: New England Journal of Medicine (1958)

SINCE the first case of cholangiolitic hepatitis and jaundice after the administration of chlorpromazine was reported by Zatuchni and Miller,1 numerous papers dealing with various aspects of this problem have appeared in the literature. Recent authors2 3 4 have considered the mechanism of production of this phenomenon to lie in hepatic sensitization to the drug, rather than any of its specific pharmacologic properties. A similar type of cholangitis was reported by Hanger and Gutman5 in 1940 in 12 patients who had been on arsphenamine therapy. Many other compounds have been associated with the appearance of this type of obstructive jaundice, among them . . .
Dead Souls — Comparing Dartmouth Atlas Benchmarks with CMS Outcomes Data
Authors: Michael L Langberg, Jeanne T Black
Journal: New England Journal of Medicine (2009)

The premise, based on the Dartmouth Atlas of Health Care, that geographic variations in end-of-life Medicare spending can be used to identify wasted resources was popularized by Peter Orszag, director of the Office of Management and Budget, who has said that “30 percent of Medicare's costs could be saved without negatively affecting health outcomes.”1 This belief has been propagated by well-meaning adherents seeking a means of financing the expansion of health coverage. Institutions such as Cedars-Sinai Medical Center in Los Angeles (where we work) and New York University (NYU) Medical Center have been portrayed as excessively costly,2 while “model systems” . . .
Linking Antibody Fc Domain to Endostatin Significantly Improves Endostatin Half-life and Efficacy
Authors: Tong-Young Lee, Robert M. Tjin Tham Sjin, Shahla Movahedi, Bissan Ahmed, Elke A. Pravda, Kin-Ming Lo, Stephen D. Gillies, Judah Folkman, Kashi Javaherian
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The half-life of the antiangiogenic molecule endostatin that has been used in clinical trial is short (∼2 h). In addition, ∼50% of the clinical grade endostatin molecules lack four amino acids at their NH2 termini. Lack of these amino acids gives rise to a molecule that is devoid of zinc, resulting in no antitumor activity. Our goal was to develop a new version of endostatin that does not show such deficiency. Experimental Design: A recombinant human endostatin conjugated to the Fc domain of IgG was constructed and expressed in mammalian cell culture. The presence of Fc has been shown by previous investigators to play a major role in increasing the half-life of the molecule. Fc-endostatin was tested in tumor-bearing mice, and its half-life was compared with the clinical grade endostatin. Results: The antitumor dose of Fc-endostatin was found to be ∼100 times less than the clinical grade endostatin. The half-life of Fc-endostatin in the circulation was found to be weeks rather than hours, as observed for endostatin alone. In addition, a U-shaped curve was observed for antitumor activity of endostatin as a function of endostatin concentration delivered to the animals. Conclusion: Fc-endostatin is a superior molecule to the original clinical endostatin. Due to its long half-life, the amount of protein required is substantially reduced compared with the clinically tested endostatin. Furthermore, in view of the U-shaped curve of efficacy observed for endostatin, we estimate that the requirement for Fc-endostatin is ∼700-fold less than endostatin alone. The half-life of endostatin is similar to that of vascular endothelial growth factor–Trap and Avastin, two other antiangiogenic reagents. We conclude that a new clinical trial of endostatin, incorporating Fc, may benefit cancer patients.
191 SPLENOHEPATIC INDEX IN ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY (ARFI) CAN INCREASE THE ACCURACY FOR PORTAL HYPERTENSION PREDICTION IN CIRRHOTIC PATIENTS?
Authors: I. Sporea, S. Bota, R. Sirli, A. Popescu, M. Danila, M. Sendroiu
Journal: Journal of Hepatology (2011)
Oat sensitization in children with atopic dermatitis: prevalence, risks and associated factors
Authors: P. Boussault, C. Léauté‐Labrèze, E. Saubusse, S. Maurice‐Tison, M. Perromat, S. Roul, A. Sarrat, A. Taïeb, F. Boralevi
Journal: Allergy (2007)

Background: Topical treatments of atopic dermatitis (AD) may be responsible for cutaneous allergies. Percutaneous sensitization to oat used in emollients/moisturizers has already been reported. Our objectives were to measure the prevalence of oat sensitization in AD children, to assess its relevance, and to look at related parameters. Methods: We recruited prospectively children with AD referred for allergy testing between June 2001 and December 2004. Atopy patch tests (APT) and skin prick tests (SPT) to oat proteins (1%, 3% and 5%) and to the European standard series were performed followed by oral food challenge (OFC) and repeated open application test (ROAT) in the oat‐sensitized group. Results: About 302 children were enrolled. Oat APT and SPT were positive in 14.6% and 19.2% of cases, respectively. Children under 2 years of age were more likely to have positive APT. In oat‐sensitized children, OFC and ROAT were positive in 15.6% (five of 32) and 28% (seven of 25) of cases, respectively. Thirty‐two percentage of oat cream users had oat‐positive atopy patch test (APT) vs 0% in the nonusers group. Conclusions: Oat sensitization in AD children seen for allergy testing is higher than expected. It may be the result of repeated applications of cosmetics with oats on a predisposed impaired epidermal barrier. We suggest avoiding topical‐containing oat proteins in infants with AD.