tbuckley/cabot-search huggingface dataset:
Contribution of cAMP-phosphodiesterase inhibition and sensitization of the contractile proteins for calcium to the inotropic effect of pimobendan in the failing human myocardium.
Authors: M Böhm, I Morano, B Pieske, J C Rüegg, M Wankerl, R Zimmermann, E Erdmann
Journal: Circulation Research (1991)

Previous studies have shown reduced effects of cAMP-dependent positive inotropic agents in the failing human myocardium; thus other cAMP-independent mechanisms of action may be useful to increase force of contraction in this condition. The purpose of this investigation was to determine whether a positive inotropic effect of the cAMP-phosphodiesterase (PDE) inhibitor pimobendan is observed in the failing human myocardium and to study whether other factors, such as an increase in the Ca2+ sensitivity of myofilaments, play a functional role in the increase in force of contraction. Pimobendan produced a positive inotropic effect in isolated preparations from nonfailing donor hearts; however, in moderately (New York Heart Association class II-III, NYHA II-III) and severely (NYHA IV) failing myocardium, this effect was reduced. In addition, in NYHA IV specimens pimobendan inhibited the crude cAMP-PDE (crude PDE) and the isoenzymes I-III (PDE I-III) in a concentration-dependent way. As judged from the IC50 values found in this tissue for the inhibition of PDE III and of crude PDE, the potency of the compound was 18.1 times greater on PDE III. Consistent with a cAMP-PDE-dependent mechanism of action, the positive inotropic effect was potentiated by isoproterenol and inhibited by adenosine in failing myocardium. In failing myocardium, pimobendan also increased the sensitivity of skinned cardiac fibers to Ca2+ and shifted the Ca(2+)-tension relation to the left. This sensitizing effect began at 0.01 mumol/l in NYHA II-III and NYHA IV and rose to about 200% at 300 mumol/l in both groups. In contrast, the demethylated metabolite UD-CG 212 Cl failed to produce positive inotropic effects in failing myocardium alone, but in the presence of isoproterenol, it exerted an increase in force of contraction. The potency of UD-CG 212 Cl for PDE III inhibition in NYHA IV was greater than that of pimobendan. The metabolite pronouncedly decreased the sensitivity of skinned cardiac fibers to Ca2+ at 30-300 mumol/l in NYHA II-III and NYHA IV. It is concluded that in the failing human heart pimobendan inhibited PDE III and sensitized contractile proteins for Ca2+. Both effects appear to be involved in the positive inotropic effect of the compound, because its metabolite, UD-CG 212 Cl, had no effect on force of contraction and on the Ca2+ sensitivity of skinned cardiac fibers but inhibited PDE III even more potently than pimobendan.(ABSTRACT TRUNCATED AT 400 WORDS)
Preoperative Chemotherapy in Patients with Colorectal Liver Metastasis: Experience of Group of Gastrointestinal Tumours of Rimini
Authors: Tamburini Emiliano, Veneroni Luigi, Rudnas Britt, Nicoletti Stefania Vittoria Luisa, Palini Gian Marco, Drudi Fabrizio, Paratore Filippo, Fantini Manuela, Della Chiesa Laura, Crescentini Giacomo, Donati Gabriele, Cavagna Enrico, Francioni GianFranco, Tassinari Davide
Journal: Annals of Oncology (2014)
REPEATED ADJUVANT CHEMOTHERAPY WITH PHENYLALANINE MUSTARD OR 5-FLUOROURACIL, CYCLOPHOSPHAMIDE, AND PREDNISONE WITH OR WITHOUT RADIATION, AFTER MASTECTOMY FOR BREAST CANCER
Authors: D.L. Ahmann, P.W. Scanlon, H.F. Bisel, J.H. Edmonson, S. Frytak, W.S. Payne, J.R. O'Fallon, R.G. Hahn, J.N. Ingle, M.J. O'Connell, J. Rubin
Journal: The Lancet (1978)
On the bioavailability of oral and subcutaneous 2-chloro-2'-deoxyadenosine in humans: alternative routes of administration.
Authors: J Liliemark, F Albertioni, M Hassan, G Juliusson
Journal: Journal of Clinical Oncology (1992)

PURPOSE The antimetabolite 2-chloro-2'-deoxyadenosine (CdA) is a promising alternative to alkylating agents for the treatment of lymphoproliferative disorders. Its use, however, is hampered by the need for intravenous (IV) administration. The aim of the present study was to determine the bioavailability of subcutaneously (SC) and orally administered CdA, and to establish an oral dose of CdA that could supersede IV administration. PATIENTS AND METHODS A previously developed high-performance liquid chromatography method was used for the determination of plasma CdA concentrations in 13 patients. Ten patients were treated on alternate days with 0.14 mg/kg/d CdA as a 2-hour IV infusion or by a SC injection. Three of these patients were also given 0.14 mg/kg CdA orally in enteric-coated capsules. Ten patients were administered CdA orally that was dissolved in phosphate-buffered saline (PBS) after treatment with 20 mg omeprazole 1 and 6 hours before the administration of CdA. RESULTS The bioavailability of SC CdA was 102% +/- 28% (mean +/- SD), and the bioavailability of CdA administered in enteric-coated capsules was 19%, 24%, and 60%. In the three patients who were given 0.14 mg/kg orally dissolved in PBS, the bioavailability was 48% +/- 8%, whereas in the seven patients who received 0.28 mg/kg, the bioavailability was 55% +/- 17%. In the 10 patients who were treated with the CdA solution orally, the coefficients of variation of the areas under the curve (AUCs) after oral and IV administration were similar. Thus, oral administration did not add to the interindividual variability. CONCLUSIONS We conclude that orally administered CdA can supersede IV infusion if the dose is doubled. SC administration gives a high peak concentration of short duration with an AUC identical to that of IV infusion. Thus, SC injection can also be used as an alternative to IV infusion.
Hydroxyethyl Starch 130/0.42 versus Ringer's Acetate in Severe Sepsis
Authors: Anders Perner, Nicolai Haase, Anne B. Guttormsen, Jyrki Tenhunen, Gudmundur Klemenzson, Anders Åneman, Kristian R. Madsen, Morten H. Møller, Jeanie M. Elkjær, Lone M. Poulsen, Asger Bendtsen, Robert Winding, Morten Steensen, Pawel Berezowicz, Peter Søe-Jensen, Morten Bestle, Kristian Strand, Jørgen Wiis, Jonathan O. White, Klaus J. Thornberg, Lars Quist, Jonas Nielsen, Lasse H. Andersen, Lars B. Holst, Katrin Thormar, Anne Lene Kjældgaard, Maria L. Fabritius, Frederik Mondrup, Frank C. Pott, Thea P. Møller, Per Winkel, Jørn Wetterslev
Journal: New England Journal of Medicine (2012)

Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis.In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization.Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline.Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.).
MRI of the pharynx and treatment efficacy of a mandibular advancement device in obstructive sleep apnoea syndrome
Authors: B.M. Sanner, M. Heise, B. Knoben, M. Machnick, U. Laufer, R. Kikuth, W. Zidek, B. Hellmich
Journal: European Respiratory Journal (2002)

In obstructive sleep apnoea syndrome (OSAS), prosthetic mandibular advancement devices (MAD) seem to be a promising treatment alternative to conventional continuous positive airway pressure therapy. Unfortunately, while they are effective in some patients, they are ineffective in others or may even worsen OSAS. At present, it is not known whether predictors can be defined which allow for estimation of the potential effect of oral appliances on the severity of OSAS. Clinical and polysomnographical efficacy of a MAD was evaluated in 15 patients with OSAS. In addition, ultrafast magnetic resonance imaging (MRI) of the pharynx was performed in 13 of these patients at rest during transnasal shallow respiration and during performance of the Muller manoeuvre, both with and without the MAD, and the site of closure was determined. The MAD reduced the mean apnoea/hypopnoea index (AHI) from 19.8±14.5 to 7.2±7.4·h −1 . Seven subjects (53.8%) had at least a 50% reduction in AHI to a value &lt;10·h −1 with the MAD, whereas the MAD was ineffective in six patients. Five of the seven treatment responders had no significant pharyngeal obstruction during the manoeuvre with the device, while all of them had pharyngeal obstruction when not equipped with the device. Four of the six patients with treatment failure had a single velopharyngeal obstruction and two a combined obstruction of the velo‐ and glossopharynx during the Muller manoeuvre while wearing the device. The results of this study suggest that airway patency during the Muller manoeuvre while wearing a mandibular advancement device may be predictive of the success of obstructive sleep apnoea syndrome treatment with a mandibular advancement device.
Outcomes of mechanically ventilated hematology patients with invasive pulmonary aspergillosis
Authors: Gaston Burghi, Virginie Lemiale, Amélie Seguin, Jérôme Lambert, Claire Lacroix, Emmanuel Canet, Anne-Sophie Moreau, Patricia Ribaud, David Schnell, Eric Mariotte, Benoît Schlemmer, Elie Azoulay
Journal: Intensive Care Medicine (2011)
Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial
Authors: Stefan Z Wiktor, Madeleine Sassan-Morokro, Alison D Grant, Lucien Abouya, John M Karon, Chantal Maurice, Gaston Djomand, Alain Ackah, Kouao Domoua, Auguste Kadio, Achy Yapi, Patrice Combe, Odette Tossou, Thierry H Roels, Eve M Lackritz, Doulourou Coulibaly, Kevin M De Cock, Issa-Malick Coulibaly, Alan E Greenberg
Journal: The Lancet (1999)
Multiple defects in muscle glycogen synthase activity contribute to reduced glycogen synthesis in non-insulin dependent diabetes mellitus.
Authors: A W Thorburn, B Gumbiner, F Bulacan, G Brechtel, R R Henry
Journal: Journal of Clinical Investigation (1991)

To define the mechanisms of impaired muscle glycogen synthase and reduced glycogen formation in non-insulin dependent diabetes mellitus (NIDDM), glycogen synthase activity was kinetically analyzed during the basal state and three glucose clamp studies (insulin approximately equal to 300, 700, and 33,400 pmol/liter) in eight matched nonobese NIDDM and eight control subjects. Muscle glycogen content was measured in the basal state and following clamps at insulin levels of 33,400 pmol/liter. NIDDM subjects had glucose uptake matched to controls in each clamp by raising serum glucose to 15-20 mmol/liter. The insulin concentration required to half-maximally activate glycogen synthase (ED50) was approximately fourfold greater for NIDDM than control subjects (1,004 +/- 264 vs. 257 +/- 110 pmol/liter, P less than 0.02) but the maximal insulin effect was similar. Total glycogen synthase activity was reduced approximately 38% and glycogen content was approximately 30% lower in NIDDM. A positive correlation was present between glycogen content and glycogen synthase activity (r = 0.51, P less than 0.01). In summary, defects in muscle glycogen synthase activity and reduced glycogen content are present in NIDDM. NIDDM subjects also have less total glycogen synthase activity consistent with reduced functional mass of the enzyme. These findings and the correlation between glycogen synthase activity and glycogen content support the theory that multiple defects in glycogen synthase activity combine to cause reduced glycogen formation in NIDDM.
Mitral valve prolapse in the dog: a model of mitral valve prolapse in man
Authors: H Pedersen
Journal: Cardiovascular Research (2000)

Time for primary review 31 days. 

Mitral valve prolapse (MVP), i.e. abnormal systolic protrusion of mitral valve leaflets into the left atrium, is a common cause of severe mitral regurgitation (MR) requiring operation in people living in industrialized nations [1,2]. MVP has been reported to have many causes but in the majority of cases it is a primary condition (called primary MVP in this paper) characterized by a progressive myxomatous degeneration of the mitral valve leaflets and chordae tendineae [1–3]. The disease typically emerges in adolescence but complications such as severe MR usually do not occur until middleage or senescence [1–3]. An animal model with a shorter course of disease could be useful in several ways, for instance, by making it feasible to evaluate the effects of different drugs on disease progression. Despite this, no animal model of primary MVP has been described so far.

From pathological studies, it has long been known that most dogs develop myxomatous mitral valve disease with age and that this disease is very similar macroscopically as well as microscopically to primary MVP in humans [4,5]. Traditionally, however, the canine disease has been given names other than MVP, including endocardiosis and chronic valvular disease. Recently, a number of studies, including many based on well-defined echocardiographic criteria for the diagnosis of MVP, have increased our understanding of this disease in the dog. The purpose of this article is to compare the knowledge which has been accumulated about myxomatous mitral valve disease/MVP in the dog with knowledge of primary MVP in humans.

Pathologically, primary MVP in humans is very similar to canine myxomatous mitral valve disease [4,5]. In both species, the principal macroscopic findings are enlarged, thickened leaflets, interchordal hooding and elongated chordae tendineae (Fig. 1A, B) [4–9]. In addition, affected … 

* Corresponding author. Tel.: +45-35-282-526; fax: +45-35-282-525 hdp{at}kvl.dk
A SEARCH FOR DYSENTERY CARRIERS AMONG SOLDIERS COMING FROM GALLIPOLI AND EGYPT
Authors: J. O. W. Barratt
Journal: BMJ (1916)

_2The other two cases were not given as much as 10 grains of emetine.No. 17 was discharged as cured after seven grain doses, and No, 30 relapsed after a course of 8 grains.Table III gives the records of these two cases.TABLE III.Treatment.Consecutive Negative Examinations.
EFFECTS OF DIETARY FATS ON HUMAN ERYTHROCYTE FATTY ACID PATTERNS*
Authors: John W. Farquhar, Edward H. Ahrens
Journal: Journal of Clinical Investigation (1963)

an increase that is small when compared to dietary effects on other tissues (1-6).But, interpretation of any changes in fatty acid composition of erythrocytes, however small, must take account of three special features of red cell composition (7). 1) Erythrocyte lipids are made up mainly of free cholesterol and phospholipids (Figure 1, left).
Why should women have lower reference limits for haemoglobin and ferritin concentrations than men?
Authors: D H. Rushton
Journal: BMJ (2001)

The need to transport oxygen and remove carbon dioxide from animal tissue is a fundamental requirement of life, independent of age or sex.1 The role of iron in humans and many other mammals is central to this process. 2 3 Haemoglobin concentration and red blood cell count are important diagnostic indicators for anaemia in humans and animals.

In prepubertal humans no major differences can be found between the sexes in red blood cell count or haemoglobin and serum ferritin concentrations.4 Only after the onset of menstruation does a difference emerge.4 Not until 10 years after the menopause does this situation revert in women, when the haemoglobin concentration becomes similar to that of aged matched men. 4 5 This situation is compounded by the fact that modern women have a different reproductive history from those in the past. They reach sexual maturity at an earlier age, have fewer pregnancies, and breast feed for shorter periods; as such they menstruate for more years than women in the past. Menstruation is the principal cause of iron loss in women.6–8 Furthermore, 90% of UK females of childbearing age do not achieve the recommended daily intake of elemental iron (14.8 mg) from their diet.9 Evaluation of the haemoglobin concentration and red blood cell count of women from Canada, Central America, China, and the United States shows that this situation is widespread. 4 10–14 Women worldwide are at risk of being in a negative iron balance, and by current criteria if their haemoglobin concentration is less than 115 g/l they are deemed to be anaemic, whereas in men the cut-off point is 130 g/l.15

As far as the authors are aware, of the primates only humans show a sex difference in haemoglobin concentration and red blood …
A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1)
Authors: R. Booton, P. Lorigan, H. Anderson, S. Baka, L. Ashcroft, M. Nicolson, M. O'Brien, D. Dunlop, K. O'Byrne, V. Laurence, M. Snee, G. Dark, N. Thatcher
Journal: Annals of Oncology (2006)
Single-Dose Packaging of Meningococcal Vaccine
Authors: W. Paul McKinney
Journal: JAMA (1988)

<h3>To the Editor.—</h3> While the risk to immunocompetent persons for acquiring meningococcal meningitis in the United States is low, an increased risk for this potentially fatal infection is recognized in several areas of the world. Most recently, pretravel immunization has been recommended by the Centers for Disease Control for Americans traveling to (1) New Delhi<sup>1</sup>; (2) the so-called meningitis belt of sub-Saharan Africa<sup>2</sup>(stretching from Mauretania in the west to Ethiopia in the east); (3) Saudi Arabia following the 1987 pilgrimages to Mecca and Medina<sup>3</sup>; and (4) Nepal, especially for Himalayan trekkers.<sup>4</sup> Meningococcal vaccine administered as a single 0.5-mL subcutaneous dose has been shown to have 85% to 95% clinical efficacy in preventing illness due to serogroup A, the most common cause of epidemics outside the United States.<sup>2</sup>Vaccine reactions are usually mild and consist mainly of local erythema for 24 to 48 hours, with
Identification of <i>Plasmodium falciparum</i> Erythrocyte Membrane Protein 1 (PfEMP1) as the Rosetting Ligand of the Malaria Parasite <i>P. falciparum </i>
Authors: Qijun Chen, Antonio Barragan, Victor Fernandez, Annika Sundström, Martha Schlichtherle, Anders Sahlén, Johan Carlson, Santanu Datta, Mats Wahlgren
Journal: The Journal of Experimental Medicine (1998)

Severe Plasmodium falciparum malaria is characterized by excessive sequestration of infected and uninfected erythrocytes in the microvasculature of the affected organ. Rosetting, the adhesion of P. falciparum–infected erythrocytes to uninfected erythrocytes is a virulent parasite phenotype associated with the occurrence of severe malaria. Here we report on the identification by single-cell reverse transcriptase PCR and cDNA cloning of the adhesive ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1). Rosetting PfEMP1 contains clusters of glycosaminoglycan-binding motifs. A recombinant fusion protein (Duffy binding-like 1–glutathione S transferase; Duffy binding-like-1–GST) was found to adhere directly to normal erythrocytes, disrupt naturally formed rosettes, block rosette reformation, and bind to a heparin-Sepharose matrix. The adhesive interactions could be inhibited with heparan sulfate or enzymes that remove heparan sulfate from the cell surface whereas other enzymes or similar glycosaminoglycans of a like negative charge did not affect the binding. PfEMP1 is suggested to be the rosetting ligand and heparan sulfate, or a heparan sulfate–like molecule, the receptor both for PfEMP1 binding and naturally formed erythrocyte rosettes.
Diabetes Does Not Influence Treatment Decisions Regarding Revascularization in Patients With Stable Coronary Artery Disease
Authors: Arno Breeman, Michel E. Bertrand, Jan Paul Ottervanger, Sanne Hoeks, Mattie Lenzen, Udo Sechtem, Victor Legrand, Menko-Jan de Boer, William Wijns, Eric Boersma
Journal: Diabetes Care (2006)

To evaluate whether in stable angina preference for coronary revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) is influenced by diabetes status and whether this has prognostic implications.A total of 2,928 consecutive patients with stable angina who were enrolled in the prospective Euro Heart Survey on Coronary Revascularization were studied. Multivariable analyses were applied to evaluate the relation between diabetes, treatment decision, and 1-year outcome.Diabetes was documented in 587 patients (20%) who had more extensive coronary disease. Revascularization was intended in 74% of patients with diabetes and in 77% of those without diabetes. In patients selected for revascularization, CABG was intended in 35% of diabetic and in 33% of nondiabetic patients. Multivariable analyses did not change these findings, but in some subgroups diabetes influenced treatment decisions. For example, diabetic subjects with mild heart failure had more often intended revascularization (91%) than those without diabetes (67%, P < 0.001). Treatment decisions in patients with more extensive (left main, multivessel, or proximal left anterior descending artery) disease were not influenced by diabetes status. Diabetes was not associated with an increased incidence of all-cause death, nonfatal cerebrovascular accident, or nonfatal myocardial infarction at 1 year, regardless of preferred treatment. The incidence of the combined end points was 7.3% in diabetic and 6.8% in nondiabetic patients (adjusted hazard ratio 1.0 [95% CI 0.7-1.4]).In stable angina, treatment decisions regarding revascularization or the choice for CABG or PCI were not influenced by the presence of diabetes. Diabetes was not associated with a poor prognosis.
Percutaneous Coronary Intervention of Functionally Nonsignificant Stenosis
Authors: Nico H.J. Pijls, Pepijn van Schaardenburgh, Ganesh Manoharan, Eric Boersma, Jan-Willem Bech, Marcel van’t Veer, Frits Bär, Jan Hoorntje, Jacques Koolen, William Wijns, Bernard de Bruyne
Journal: Journal of the American College of Cardiology (2007)