tbuckley/cabot-search huggingface dataset:
The effects of cyclosporine and prednisone on serum lipid and (apo)lipoprotein levels in renal transplant recipients.
Authors: L B Hilbrands, P N Demacker, A J Hoitsma, A F Stalenhoef, R A Koene
Journal: Journal of the American Society of Nephrology (1995)

Disturbances of lipid metabolism are frequently encountered after renal transplantation and have been ascribed to the use of cyclosporine (CsA) and corticosteroids, but the individual contribution of each of these drugs remains uncertain. The individual effects of CsA and prednisone (Pred) on serum lipid and (apo)lipoprotein levels were compared in a prospective randomized trial. All patients received CsA and Pred during the first 3 months after transplantation. Subsequently, they were allocated to either withdrawal of Pred or conversion from CsA to azathioprine (Aza). Serum lipids and (apo)lipoproteins, including lipoprotein(a) (Lp(a)), were measured at regular intervals during the first year after renal transplantation. Analysis of variance for repeated measures of the first year results showed higher values for serum triglycerides (P < 0.001) and lower high-density lipoprotein (HDL) cholesterol levels (P < 0.05) in the CsA monotherapy group (N = 59) as compared with the AzaPred group (N = 63). At 1 yr after transplantation, CsA-treated patients had significantly higher Lp(a) levels (CsA: median, 105 (interquartile range 42 to 340) mg/L; Aza-Pred: 46 (25 to 176) mg/L; P < 0.05). The withdrawal of Pred in the CsA group resulted in a large fall in HDL cholesterol (27 +/- 30% at 5 months after transplantation) and an increase in triglycerides (49 +/- 73% at 6 months). A reversion of these changes was observed in patients who were retreated with Pred. Multiple linear regression analysis showed an independent correlation between the use of Pred and HDL cholesterol level, whereas the use of CsA was independently associated with the concentration of Lp(a).(ABSTRACT TRUNCATED AT 250 WORDS)
Renal trauma and the intravenous urogram
Authors: C D H Oakland, J M Britton, C A C Charlton
Journal: Journal of the Royal Society of Medicine (1987)

A retrospective analysis of all patients with blunt abdominal trauma associated with haematuria admitted to one hospital (Royal United, Bath) in a 10-year period was conducted to establish the contribution of the intravenous urogram (IVU) in their management. Eighty-one case records were analysed. Of 35 IVUs performed in patients with microscopic (reagentstrip positive) haematuria, only one was abnormal. In contrast, 27 IVUs performed in patients with macroscopic (naked eye) haematuria revealed 17 major injuries and 5 previously unrecognized congenital abnormalities. It is concluded that an IVU is an unnecessary and non-contributory investigation in patients with microscopic haematuria and guidelines are suggested for the role of IVU in patients with blunt abdominal trauma associated with haematuria.
Biosimilars for psoriasis: preclinical analytical assessment to determine similarity
Authors: A. Blauvelt, A.D. Cohen, L. Puig, R. Vender, J. van der Walt, J.J. Wu
Journal: British Journal of Dermatology (2015)

Biosimilars, sometimes called 'generic biologics', are no longer a vision for the future but a present-day reality. Drug manufacturers and regulatory authorities are charged with ensuring that these products are safe and effective. Because biologically produced medications are large, complex proteins, many factors affect the quality of the end product, including glycosylation and presence of impurities, and thus many factors need to be compared between an emerging biosimilar and its originator biologic. Indeed, preclinical analytical assessments to determine similarity to an originator biologic are critical and are considered to be the foundation for regulatory approval of biosimilars. Here, the science behind the preclinical development of biosimilars is discussed by members of the International Psoriasis Council, and suggestions are put forth to try to ensure that future biosimilars are produced in a high quality and standardized manner.
Cementless Fixation of the Tibial Component for the ICLH Knee
Authors: M A R Freeman, J D Blaha, G W Bradley, H P Insler
Journal: Journal of the Royal Society of Medicine (1982)

The use of polymethylmethacrylate bone cement in joint replacement surgery is not without drawbacks. Certain hazards have been appreciated and the bone cement interface may not be as stable in the long run as was once felt. This paper reports the results in 52 knees which were replaced using the uncemented ICLH (Imperial College/London Hospital) tibial component; the average follow up was two years (range six months to four years). The results were compiled with regard to pain as well as clinical examination and X-ray evaluation. The results were comparable to those achieved in knees replaced using bone cement. Roentgenographic evaluation revealed no evidence of loosening nor sinkage of any of these prostheses. Considerations in the development of a knee prosthesis to be utilized without bone cement and the operative technique employed to implant such a prosthesis are presented. The merits of such a system are discussed.
Exome Sequencing Of African American Siblings With Activated, B-Cell Like Diffuse Large B-Cell Lymphoma
Authors: Loretta J. Nastoupil, Rini Pauly, Leon Bernal-Mizrachi, Michael R Rossi, Jean Koff, Bhakti Dwivedi, David L. Jaye, Christopher R. Flowers, Jeanne Kowalski
Journal: Blood (2013)
Efficacy and tolerability of proactive treatment with topical corticosteroids and calcineurin inhibitors for atopic eczema: systematic review and meta-analysis of randomized controlled trials
Authors: J. Schmitt, L. von Kobyletzki, Å. Svensson, C. Apfelbacher
Journal: British Journal of Dermatology (2010)

Long-term low-level topical anti-inflammatory therapy has been suggested as a new paradigm in the treatment of atopic eczema (AE).To determine the efficacy and tolerability of topical corticosteroids and calcineurin inhibitors for flare prevention in AE.Systematic review of randomized controlled trials reporting efficacy of topical corticosteroids and/or topical calcineurin inhibitors for flare prevention in AE. Identification of relevant articles by systematic electronic searches (Cochrane Library, Medline) supplemented by hand search. Primary efficacy endpoint: proportion of participants experiencing at least one flare during proactive anti-inflammatory treatment. Relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated and pooled by pharmaceutical agent using random-effects meta-analysis. Sensitivity analysis included meta-regression to explore the influence of study-specific covariates.Nine articles reporting on eight vehicle-controlled trials were included. Three, four and one trial(s) evaluated proactive therapy with topical tacrolimus, fluticasone propionate and methylprednisolone aceponate, respectively. Each agent under study was more efficacious to prevent flares than vehicle. Meta-analysis suggested that topical fluticasone propionate (RR 0·46, 95% CI 0·38-0·55) may be more efficacious to prevent disease flares than topical tacrolimus (RR 0·78, 95% CI 0·60-1·00). Meta-regression indicated robustness of these findings. Proactive anti-inflammatory therapy was generally well tolerated. The trials identified, however, do not allow firm conclusions about long-term safety.Vehicle-controlled trials indicate efficacy of proactive treatment with tacrolimus, fluticasone propionate and methylprednisolone aceponate to prevent AE flares. Indirect evidence from vehicle-controlled trials suggests that twice weekly application of the potent topical corticosteroid fluticasone propionate may be more efficacious to prevent AE flares than tacrolimus ointment. Head to head trials should be conducted to confirm these results. Future studies are also needed to evaluate the long-term safety of proactive treatment of AE.
Mechanisms for the positive inotropic effect of alpha 1-adrenoceptor stimulation in rat cardiac myocytes.
Authors: D Fedida, R A Bouchard
Journal: Circulation Research (1992)

alpha 1-Adrenoceptor activation can enhance myocardial contractility, and two possible inotropic mechanisms are an increase in myofilament Ca2+ sensitivity and action potential prolongation, which can increase net Ca2+ entry into cells. In adult rat ventricular myocytes (bath Ca2+, 1 mM; stimulated at 0.2-0.5 Hz), the drug 4-aminopyridine and the whole-cell voltage clamp have been used to control Ca2+ entry and differentiate between the two mechanisms. At 22-23 degrees C the specific alpha 1-adrenoceptor agonist methoxamine (100 microM) prolonged action potential duration at 50% repolarization from 55 +/- 2 to 81 +/- 5 msec, delayed time to peak contraction, and increased shortening amplitude from 5.3 +/- 0.6 to 7.8 +/- 1 microns (n = 18). Reduction of the transient outward current and other K+ currents by methoxamine was the major cause of action potential prolongation in rat myocytes with little change in the L-type calcium current. Block of the transient outward current with 2 mM 4-aminopyridine prolonged action potential duration from 52 +/- 6 to 98 +/- 12 msec and increased unloaded cell shortening from 2.9 +/- 0.4 to 6.6 +/- 0.6 microns (n = 4). Subsequently, methoxamine no longer increased cell shortening, although significant potentiation of twitch amplitude was still seen after a brief rest interval. In voltage-clamp experiments, with 70-500-msec pulses, although membrane currents were reduced, methoxamine had no positive inotropic effect and reduced cell shortening from 5.3 +/- 0.7 to 4.97 +/- 0.8 microns at pulse potentials positive to -40 mV. Similar alpha 1-adrenoceptor responses were observed at 35 degrees C during action potential and voltage-clamp experiments, which could be blocked by 10 microM prazosin. In myocytes loaded with the Ca2+ indicator indo-1, alpha 1-adrenoceptor stimulation or 4-aminopyridine both increased cell contraction and intracellular Ca2+ transients by similar amounts. As in unloaded cells, prior exposure to 4-aminopyridine prevented any inotropic effect of methoxamine without changing the systolic intracellular Ca2+ transient. The results indicated that under our experimental conditions positive inotropy in rat cardiomyocytes on exposure to alpha 1-adrenoceptor agonists was strongly correlated with the action potential prolongation that accompanied K+ current reduction. In addition, modulation of K+ channels could occur independent of changes in contractility and/or [Ca2+]i.
Forced Expiratory Maneuvers in Very Young Children
Authors: MARCUS H. JONES, STEPHANIE D. DAVIS, DEBORAH GRANT, KATHY CHRISTOPH, JEFFREY KISLING, ROBERT S. TEPPER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The application of negative expiratory pressure (NEP) to the airway opening during forced expiratory maneuvers has recently been described as a noninvasive method to assess whether flow limitation is achieved in adults. This methodology has great potential for extending the measurement of forced expiratory maneuvers to young children who may not produce maximal efforts as reproducibly as adults. We used NEP to assess flow limitation in 10 children between 3 and 5 yr of age. NEP was well tolerated by all subjects. With the application of NEP, there was not a step increase in flow, a finding consistent with flow limitation for the subjects. In addition to visual inspection, we proposed a method to quantify the change in flow during a short NEP. The flow–volume curves obtained with and without NEP were visually the same, other than the flow transients produced by NEP. The calculated values of FVC and FEF25–75 were not significantly different when measured from flow– volume curves with and without NEP. There was a statistically significant increase in FEV1 with NEP; however, the group mean increase in FEV1 was less than 2%. We conclude that NEP may be a useful technique to determine whether flow limitation has been achieved in young children performing forced expiratory maneuvers.
Phase II Study Of Anti-CD19 Antibody Drug Conjugate (SAR3419) In Combination With Rituximab: Clinical Activity and Safety In Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (NCT01470456)
Authors: Bertrand Coiffier, Catherine Thieblemont, Sophie de Guibert, Jehan Dupuis, Vincent Ribrag, Réda Bouabdallah, Franck Morschhauser, Guillaume Cartron, Steven Le Gouill, Olivier Casasnovas, Harald Holte, Laurence Hatteville, Chiara Zilocchi, Corina Oprea, Hervé Tilly
Journal: Blood (2013)
Occurrence of qnrA-positive clinical isolates in French teaching hospitals during 2002–2005
Authors: E. Cambau, C. Lascols, W. Sougakoff, C. Bébéar, R. Bonnet, J.-D. Cavallo, L. Gutmann, M.-C. Ploy, V. Jarlier, C.-J. Soussy, J. Robert
Journal: Clinical Microbiology and Infection (2006)
Perpetual length of respiratory muscles during breathing
Authors: Jenny Jagers, Michael Ji, Paul Easton
Journal: European Respiratory Journal (2013)

Introduction: Where is resting respiratory muscle length at Functional Residual Capacity (FRC) in comparison to the innate length of each muscle? It is unknown whether end expiratory/pre-inspiratory length of muscles at equilibrium i.e. length at FRC, is below, above or identical to inherent muscle length when ambient system tension is removed. Therefore we studied canines during nondepolarizing paralysis to determine the perpetual resting length of respiratory muscles.  Methods: With approval by Animal Ethics Board, sonomicrometry and EMG were implanted in the costal (COS) and crural (CRU) diaphragm, transversus abdominis (TA), parasternal (PARA) and external intercostal (EXT). After recovery, the animals were studied awake, recording flow, CO2, muscle length, and EMG per breath during room air, before and after flaccid paralysis. Results are shown before, during, and after paralysis.  Results: For N= 4 dogs (wt 29.8kg) studied after 50 days, all muscles lengthened significantly with onset of paralysis. During paralysis, lengthening was: COS 1.69%, CRU 1.5%, TA 3.30%, PARA 1.99% and EXT 1.68% respectively. All lengths reverted to the original shorter baseline with resolution of paralysis.  Summary: Perpetual resting length of respiratory muscles at equilibrium, is universally shorter than inherent muscle length without normal system tension. That is, each breath initiated from FRC begins from a “pre-shortened” muscle length compared to inherent muscle length.
Deficient production of IFN-stimulated genes upon rhinovirus infection in cystic fibrosis airway epithelial cells
Authors: Elisabeth Kieninger, Marjolaine Vareille, Marco P. Alves, Brigitte S. Kopf, Thomas Geiser, Sebastian L. Johnston, Michael R. Edwards, Nicolas Regamey
Journal: European Respiratory Journal (2011)

Background:  Rhinoviruses (RVs) are important triggers of pulmonary exacerbations and possible contributors to long-term respiratory morbidity in cystic fibrosis (CF), but mechanisms leading to RV-induced CF exacerbations are poorly understood. We recently described deficient innate immune responses to RV infection in CF characterized by impaired type I and III interferon (IFN) production and increased virus replication.  To study downstream effects of impaired IFN induction we investigated the expression of IFN-stimulated genes (ISGs) which are important for the production of antiviral proteins.   Methods:  Epithelial CF and non-CF cell lines (UNCCF2T/UNCN2T, CFBE41o-/16HBE14o-) were cultured and infected with RV-16 and -1B at a MOI of 2. Induction of ISGs including MxA, 29,59-OAS, viperin and NOS2 was assessed by RT-PCR. Exogenous IFN-β and -λ were added before and after infection.   Results:  Expression of all ISGs was induced in CF and control cells upon virus infection. CF cells expressed 100-1000 times less ISGs than control cells (all p   Conclusions:  ISG induction upon RV infection is deficient in CF indicating a profound impairment of the early innate antiviral response. Addition of exogenous IFN restores antiviral pathways in CF, suggesting a potential use of IFNs in the prevention or treatment of RV-induced CF exacerbations.
Left atrial volume to distinguish idiopathic pulmonary arterial hypertension from pulmonary hypertension due to left heart disease
Authors: Stephen Crawley, Martin Johnson, Andrew Peacock
Journal: European Respiratory Journal (2011)

Introduction:  It can be difficult to distinguish pulmonary arterial hypertension (which will respond to disease targeted therapy) from pulmonary hypertension due to left heart disease (PHLHD). Current practice is to use right heart catheterisation (RHC) to distinguish between the two conditions. We explored the use of left atrial volume (LAV) obtained via cardiac magnetic resonance imaging (CMR) as an alternative to RHC.   Methods:  Patients being admitted for diagnostic assessment underwent CMR and RHC. LA volume was assessed using standard 2- and 4-chamber CMR views and the biplane area-length method, and indexed to the body surface area. RHC was then performed within 72 hours. IPAH was defined as per current guidelines. Patients with mean PAP >25mmHg and PAWP >15mmHg at RHC were considered to have PHLHD.   Results:  Between Jan 2009 and Feb 2011 we diagnosed 31 patients with IPAH (mPAP 47±10, PAWP 7±4 mmHg) and 19 patients with PHLHD (mPAP 43±8, PAWP 22±6 mmHg). LAV was significantly lower in IPAH compared with PHLHD (24±9 ml/m 2  vs 66±19 ml/m 2 , p 2  as the cutoff, we could distinguish IPAH from PHLHD with 97% sensitivity and 100% specificity. The area under the ROC curve was 0.99.   Conclusion:  Left atrial volume of 43 ml/m 2  recorded by CMR may be a useful means of distinguishing between IPAH and PHLHD, avoiding the need for catheterisation.
Optimal Transfusion Trigger in Surgical Patients With Coronary Artery Disease
Authors: Steven M. Frank, Aslam Ejaz, Timothy M. Pawlik
Journal: JAMA Surgery (2015)

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Ten-year survival and late sequelae in testicular cancer patients treated with cisplatin, vinblastine, and bleomycin.
Authors: G Stoter, A Koopman, C P Vendrik, A Struyvenberg, D T Sleyfer, P H Willemse, H Schraffordt Koops, A T van Oosterom, W W ten Bokkel Huinink, H M Pinedo
Journal: Journal of Clinical Oncology (1989)

This 10-year follow-up study of 91 patients with disseminated testicular nonseminomatous cancer, treated with cisplatin, vinblastine, and bleomycin (PVB) induction chemotherapy and vinblastine plus bleomycin maintenance chemotherapy for a planned period of 2 years, shows a 63% cure rate. The predominant long-term sequelae are neurological and sexual dysfunction in 68% and 40% of patients, respectively. Two patients died of myocardial infarction. Sixteen percent of patients developed hypertension, 23% Raynaud's phenomenon, and 25% ototoxicity. Despite the long-term side effects, 90% of the patients who responded to a questionnaire are fully employed. This study shows that the maintenance chemotherapy has contributed to the incidence and/or degree of neurotoxicity, hypertension, and renal function disturbance.
LSC 2013 abstract - Influence of AECOPD to monocytes apoptosis and chemotaxis and macrophages phagocytosis
Authors: Mindaugas Vaitkus, Simona Lavinskiene, Kristina Bieksiene, Jolanta Jeroch, Raimundas Sakalauskas
Journal: European Respiratory Journal (2013)

Background:  Monocytes/macrophages are associated with inflammation during chronic obstructive pulmonary disease (COPD).   Aim:  To assess influence of AECOPD to monocytes apoptosis and chemotaxis and macrophages phagocytosis.   Methods:  Forty five patients during AECOPD and the same after recovery from exacerbation as well as 20 healthy individuals were enrolled to this study. Monocytes from peripheral blood and macrophages from sputum were isolated by high density gradient centrifugation and magnetic labeling system. Annexin-V FITC was used to detect apoptotic monocytes. IL-8 was used as a chemoatractant to investigate chemotaxis and labeled  S. aureus  bacteria were used for macrophages phagocytosis assay.   Results:  Peripheral blood monocytes apoptosis was significantly reduced and chemotaxis enhanced in patients during AECOPD compared with stable COPD and HI (p    Conclusion:  Our results show, that reduced monocytes apoptosis and increased chemotaxis are important mechanisms for enhanced inflammatory cells migration and accumulation to the airways. Decreased sputum macrophages phagocytosis lets us suggest that defective pathogen removal may prolong chronic inflammation.
Abstract 2407: Increased Arteriolar Resistance Of Heart Failure Is Associated With Rho-Independent Inhibition Of MLCP.
Authors: Mohammed A Azam, Judith Hoefer, Mohammed Abdul Momen, Steffen Sebastian Bolz, Mansoor Husain
Journal: Circulation (2008)

Background: The clinical syndrome of heart failure (HF) is caused by decreased cardiac output, and is both compensated for and exacerbated by increased systemic vascular resistance (SVR). We posit that a mechanistic understanding of the vasomotor abnormalities that accompany HF may enable new diagnostic and therapeutic tools. Objective: To determine the molecular mechanisms underlying increased resistance of mesenteric arteries (MAs) in a mouse model of HF. Methods &amp; Results: In a mouse left anterior descending (LAD)-ligation model of myocardial infarction (MI)-induced HF, echocardiography and hemodynamics documented markedly increased SVR. Isolated perfused MAs manifested dramatic, early (1 wk), and sustained (12 wk) increases in myogenic responses (MR). Vasoconstrictor responses to S1P and ET-1 were also increased in MAs of HF but not SHAM mice. At wk 6, aorta and MA were analyzed for levels and or activity of Rho/GTP-Rho, a key mediator of enhanced vasoconstrictor responses. We also measured total and phosphorylated levels of: MYPT1 (Thr850), the myosin targeting subunit of myosin light chain phosphatase (MLCP), an end-regulatory molecule of smooth muscle contraction; CPI-17 (Thr38), an inhibitor of MLCP; and (iv) myosin light chain itself (MLC; Ser19). When phosphorylated, MYPT1 inhibits MLCP, limiting its dephosphorylation of MLC, and thus prevents relaxation. Given our results with respect to ET-1 and S1P, we were surprised to find significantly decreased levels of total and GTP-Rho in MAs and aorta of HF as compared to SHAM mice. By contrast, increased levels of phosphorylated-MYPT1, CPI-17 and MLC were found in HF. Conclusion: These data implicate a heretofore unrecognized mechanism of ‘Rho-independent’ inhibition of MLCP in the increased SVR, MR, and vasoconstrictor responses observed in the MI model of HF in mice.