tbuckley/cabot-search huggingface dataset:
Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis
Authors: F Chopin, P Garnero, A le Henanff, F Debiais, A Daragon, C Roux, J Sany, D Wendling, C Zarnitsky, P Ravaud, T Thomas
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Background:</h3> Rheumatoid arthritis (RA) is associated with systemic bone loss, subchondral bone erosion and cartilage degradation under the control of pro-inflammatory cytokines, including tumour necrosis factor α (TNFα). Therefore, we tested the hypothesis that administration of infliximab, an anti-TNFα drug in the treatment of RA, would modulate systemic and local bone resorption and reduce cartilage degradation. <h3>Methods:</h3> We performed a prospective study of a multicentric cohort of 48 women, mean (SD) age 54.2 (12.1) years old, with severe RA for 11.4 (7.8) years, who started infliximab after failure of other disease-modifying antirheumatic drugs. At baseline and 6, 22 and 54 weeks after initiating Infliximab therapy we measured the following biochemical markers: pro-collagen serum type I N-terminal propeptide (PINP), a marker of bone formation; serum C-terminal cross-linked telopeptide of type I collagen (CTX-I), a marker of cathepsin K-mediated bone collagen degradation believed to reflect systemic bone resorption; serum C-terminal cross-linked telopeptide of type I collagen (ICTP), an index of matrix metalloprotease (MMP) mediated type I collagen degradation reflecting preferential joint metabolism; and urinary CTX-II a biochemical markers of cartilage degradation. Total hip and lumbar spine bone mineral density (BMD) was assessed at baseline, and after 6 and 12 months by dual-energy x-ray absorptiometry (DXA). No patient received bisphosphonates while 77% were under oral glucocorticoids. <h3>Results:</h3> BMD remained stable over 1 year. Serum CTX-I levels rapidly decreased by 19% and 28% at week 6 and week 22, respectively (analysis of variance (ANOVA) p = 0.032) values returning to pre-treatment level at week 54. By contrast, ICTP levels progressively declined with a maximal 25% decrease at week 54 (ANOVA p = 0.028). By contrast, PINP levels remained stable over time, which led to a 30 to 40% improvement in bone remodelling balance, as assessed by the ratios PINP/CTX and PINP/ICTP (p&lt;0.05). There was no significant change of urinary CTX-II in the whole population, but a slight decrease (ANOVA p = 0.041) in those with pre-treatment levels above the upper limit of normal range. <h3>Conclusions:</h3> In summary, the improvement in the formation/resorption marker ratio suggests beneficial systemic and local bone effects of infliximab in patients with RA.
Infertility among male UK veterans of the 1990-1 Gulf war: reproductive cohort study
Authors: Noreen Maconochie, Pat Doyle, Claire Carson
Journal: BMJ (2004)

On the basis of nuclear Overhauser enhancement and 1H chemical shift data obtained in aqueous solution, a model is proposed for the interaction of beta-avoparcin and epi-beta-avoparcin with acetyl-D-alanyl-D-alanine (Ac-D-Ala-D-Ala) and diacetyl-L-lysyl-D-alanyl-D-alanine (Ac2-L-Lys-D-Ala-D-Ala). For the beta-avoparcin: Ac2-L-Lys-D-Ala-Ala complex, the COOH-terminal end of the tripeptide is located near the NH2 terminus of the antibiotic with the tripeptide extending across the peptide backbone of beta-avoparcin toward its COOH-terminal end. In our proposed structure, the three amino acid residues of the peptide span the entire length of the antibiotic, and the aliphatic side chain of the lysine residue extends over the D-ring of beta-avoparcin. The structure of the epi-beta-avoparcin:Ac2-L-Lys-D-Ala-D-Ala complex was found to be similar to the beta-avoparcin complex at the binding site for the lysine residue at the COOH-terminal end of the antibiotic, but differed in the interactions at the NH2 terminus. These results are consistent with the similarities in the COOH-terminal conformations and the differences in conformations at the NH2 terminus found for beta-avoparcin and epi-beta-avoparcin which were described in the preceding paper [Fesik, S. W., I. M. Armitage, G. A. Ellestad, and W. J. McGahren, Mol. Pharmacol. 25:275-280 (1984)]. The association constants (measured by UV methods) for both beta-avoparcin:peptide complexes were greater than those measured for epi-beta-avoparcin and correlated with their differences in antibacterial activity. Epi-beta-avoparcin exhibited no measurable binding to the dipeptide: however, a significant affinity was measured for the tripeptide, indicating that the interactions with the NH2 terminus of the antibiotics provide binding energy for the antibiotic peptide complex but that the COOH-terminal end of the antibiotics also plays an important role in the binding interaction. These results are interesting in light of the similarities in the structural and conformational features at the COOH terminus for all of the glycopeptide antibiotics.
Local Intraluminal Infusion of Biodegradable Polymeric Nanoparticles
Authors: Luis A. Guzman, Vinod Labhasetwar, Cunxian Song, Yangsoo Jang, A. Michael Lincoff, Robert Levy, Eric J. Topol
Journal: Circulation (1996)

Background Several perfusion balloon catheters are under investigation for local drug delivery; however, sustained tissue drug levels are difficult to achieve with these techniques. To overcome this problem, sustained-release, biodegradable nanoparticles represent a potential alternative for prolonged local delivery. Methods and Results A biodegradable polylactic-polyglycolic acid (PLGA) copolymer was used to formulate nanoparticles. Fluorescent-labeled nanoparticles were intraluminally administered in a single, 180-second infusion after balloon injury in the rat carotid model. Localization and retention at different time points and biocompatibility of nanoparticles were evaluated. To evaluate the potential of the system in the prevention of neointimal formation, dexamethasone was incorporated into the particles and delivered locally as above. Nanoparticles were seen in the three layers of the artery at 3 hours and 24 hours. At 3 days, they were mainly present in the adventitial layer, decreasing at 7 days, with no fluorescent activity at 14 days. The PLGA nanoparticles appeared to be fully biocompatible. In the dexamethasone nanoparticle study, a significant amount of dexamethasone was present in the treated segment for up to 14 days after a single infusion, with no plasma levels detected after the first 3 hours. There was a 31% reduction in intima-media ratio in animals treated with local dexamethasone nanoparticles compared with control. Conclusions Nanoparticles successfully penetrated into the vessel wall and persisted for up to 14 days after a short, single intraluminal infusion. Local administration of nanoparticles with incorporated dexamethasone significantly decreased neointimal formation. This methodology appears to have important potential for clinical applications in local drug delivery.
Immune cells in term and preterm labor
Authors: Nardhy Gomez-Lopez, Derek StLouis, Marcus A Lehr, Elly N Sanchez-Rodriguez, Marcia Arenas-Hernandez
Journal: Cellular and Molecular Immunology (2014)

Labor resembles an inflammatory response that includes secretion of cytokines/chemokines by resident and infiltrating immune cells into reproductive tissues and the maternal/fetal interface. Untimely activation of these inflammatory pathways leads to preterm labor, which can result in preterm birth. Preterm birth is a major determinant of neonatal mortality and morbidity; therefore, the elucidation of the process of labor at a cellular and molecular level is essential for understanding the pathophysiology of preterm labor. Here, we summarize the role of innate and adaptive immune cells in the physiological or pathological activation of labor. We review published literature regarding the role of innate and adaptive immune cells in the cervix, myometrium, fetal membranes, decidua and the fetus in late pregnancy and labor at term and preterm. Accumulating evidence suggests that innate immune cells (neutrophils, macrophages and mast cells) mediate the process of labor by releasing pro-inflammatory factors such as cytokines, chemokines and matrix metalloproteinases. Adaptive immune cells (T-cell subsets and B cells) participate in the maintenance of fetomaternal tolerance during pregnancy, and an alteration in their function or abundance may lead to labor at term or preterm. Also, immune cells that bridge the innate and adaptive immune systems (natural killer T (NKT) cells and dendritic cells (DCs)) seem to participate in the pathophysiology of preterm labor. In conclusion, a balance between innate and adaptive immune cells is required in order to sustain pregnancy; an alteration of this balance will lead to labor at term or preterm.
The multichain interleukin 2 receptor. A target for immunotherapy in lymphoma, autoimmune disorders, and organ allografts [clinical reference]
Authors: T. A. Waldmann
Journal: JAMA (1990)

<h3>SELECTED CASE</h3> A 24-YEAR-OLD black man developed nodules on the face and the anterior part of the chest. The nodules were non-tender and a biopsy showed epidermal infiltration with lymphoid cells that possessed convoluted nuclei. The patient also had repeated infections and sepsis and was referred to the National Institutes of Health. A second lymph node biopsy revealed malignant lymphoma recognized to represent human T-cell lymphotropic virus type I (HTLV-I)-related adult T-cell leukemia/lymphoma (ATL). This diagnosis was supported by the finding of high titers of antibodies to HTLV-I in the peripheral blood and the identification of HTLV-I provirus in the genome of the patient's malignant peripheral blood lymphocytes. The patient developed overt leukemia, with a total peripheral white blood cell count of 27 × 10<sup>9</sup>/L, 75% of which were malignant lymphocytes. He also had hypercalcemia and elevated serum levels of alkaline phosphatase and lactic dehydrogenase, typical features of
Lenalidomide, adriamycin, and dexamethasone (RAD) in patients with relapsed and refractory multiple myeloma: a report from the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myelom)
Authors: Stefan Knop, Christian Gerecke, Peter Liebisch, Max S. Topp, Uwe Platzbecker, Orhan Sezer, Christina Vollmuth, Karina Falk, Axel Glasmacher, Uwe Maeder, Hermann Einsele, Ralf C. Bargou
Journal: Blood (2009)
Thrombosis after Travel
Authors: Kenneth J Rothman
Journal: PLoS Medicine (2006)

Traveling has always been a risky venture. In times gone by, the traveler left the security of home to face myriad dangers, including accidents, storms, infectious disease, malnutrition, and assault. Consider the choices faced by travelers from New York to San Francisco before the transcontinental railroad traversed North America in 1869. They had to choose between a harsh overland route by wagon train through forbidding territory, a sailing expedition around Cape Horn through some of the most treacherous waters on earth, or the most dangerous route, by sea to Panama, and then a trek by canoe, mule, and foot through mosquito-infested jungles in the hope of booking passage by ship from the Pacific side. By comparison, today's traveler would seem to have little to worry about.
THE TREATMENT OF GONORRHEAL RHEUMATISM BY AN ANTIGONOCOCCUS SERUM.
Authors: JOHN ROGERS
Journal: JAMA (1906)

Cases of gonorrheal arthritis can be grouped roughly in three classes—those which are mild and recover quickly; those which are severe and run a prolonged course, and those few which continue indefinitely. From what is known of other infectious diseases, it is very evident that the prolonged cases of this infection must lack the antibodies which naturally exist or are produced in the vast majority of individuals. If these antibodies could be provided artifically recovery ought at least to be accelerated, and with the specific object of thus benefiting the patient whose history is given in Case 8, I proposed the scheme to Dr. John Torrey, the bacteriologist in the experimental laboratory of Cornell University Medical College. He follows this clinical report with one describing the details in the manufacture of an anti-gonococcus serum. The gonococcus is somewhat peculiar in its pathogenic limitation to man. Inoculations of pure cultures of
STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL
Authors: John B. Nelson
Journal: The Journal of Experimental Medicine (1936)

Fetal membrane and tissue culture suspensions of the coccobacilliform bodies are infective for normal fowl. Intranasal injection is commonly followed by a coryza which is serially transmissible and communicable by direct contact. The specific bodies are generally demonstrable in the nasal exudate of birds infected either by injection or contact. Compared with the original strain of the coryza of slow onset the reaction produced by these suspensions is often less vigorous; the incidence of apparent cases, characterized by a nasal discharge, being 97 per cent and 53 per cent, respectively. The apparent cases are similarly characterized by a long incubation period and a tendency towards chronicity.
Adenosine receptors, heart rate, and cardioprotection
Authors: M MANGONI
Journal: Cardiovascular Research (2004)

a paper by Fabritz et al. [1] investigates the effects of controlled overexpression of the A 3 adenosine receptor (A 3 AR) in the mouse heart.Their findings will feed further the current debate on the use of adenosine receptors (AR) as targets for gene therapy aimed at protecting the myocardium against ischemic damage.Furthermore, Fabritz et al. report interesting observations on the functional role of adenosine receptors in the regulation of heart rate.
Approved and unapproved use of immunoglobulins in Iceland
Authors: Bryndís Ester Ólafsdóttir, Davíð Þór Þorsteinsson, Rannveig Einarsdóttir, Björn Rúnar Lúðvíksson, Gerður Gröndal, Kristján Erlendsson, Ásgeir Haraldsson
Journal: Journal of Allergy and Clinical Immunology (2013)
Brain differences, anthropological stories, and educational implications
Authors: Christy Hammer, R. Valentine Dusek
Journal: Behavioral and Brain Sciences (1996)

Abstract Geary's anthropological assumptions are questioned as he uses literature influenced by sociobiology to back the claim that Female humans do not engage in environmental orientation. Yet, female gatherers or migrators do need and use spatial skills. Geary's exploration of gender differences in math skills is speculation that hasharmful, ungrounded, and misleading educational implications and applications, particularly in light of research on the status of gender equity in education.
Validation of the difference in urine and blood carbon dioxide tension during bicarbonate loading as an index of distal nephron acidification in experimental models of distal renal tubular acidosis.
Authors: T D DuBose, C R Caflisch
Journal: Journal of Clinical Investigation (1985)

Recent classifications of the several pathophysiologic types of distal renal tubular acidosis (secretory, voltage dependent, and gradient) have been based on the response of acidification parameters to a series of provocative maneuvers in vivo and in vitro. A reduction in the difference in urine and blood CO2 tension during bicarbonate loading (U-B pCO2 gradient), a widely applied parameter, has been employed as an index of reduced distal nephron proton secretion. This study was designed to test the validity of the U-B pCO2 gradient in a variety of experimental models of distal renal tubular acidosis by measuring and comparing disequilibrium pH (a direct technique to detect H+ secretion in situ) with the pCO2 in the papillary collecting duct of the rat in vivo during bicarbonate loading. Chronic amiloride, lithium chloride, and amphotericin-B administration, and the post-obstructed kidney models were employed. Amiloride resulted in an acidification defect which did not respond to sulfate infusion (urine pH = 6.15 +/- 0.08), and was associated with an obliteration of the acid disequilibrium pH (-0.26 +/- 0.05- -0.08 +/- 0.03) and reduction in papillary pCO2 (116.9 +/- 3.2 - 66.9 +/- 2.5 mmHg). The defect induced by lithium administration responded to Na2SO4 (urine pH = 5.21 +/- 0.06) but was similar to amiloride with respect to the observed reduction in disequilibrium pH (-0.04 +/- 0.02) and pCO2 (90.3 +/- 3.0 mmHg). The post-obstructed kidney model was characterized by an abnormally alkaline urine pH unresponsive to sulfate (6.59 +/- 0.06) and a reduction in disequilibrium pH (+0.02 +/- 0.06) and pCO2 (77.6 +/- 3.6 mmHg). Amphotericin-B resulted in a gradient defect as characterized by excretion of an acid urine after infusion of sodium sulfate (5.13 +/- 0.06). Unlike other models, however, amphotericin-B was associated with a significant acid disequilibrium pH (-0.11 +/- 0.05) and an appropriately elevated urine pCO2 (119.8 +/- 6.4 mmHg) which did not differ from the respective values in control rats. Thus, these findings support the use of the U-B pCO2 as a reliable means of demonstrating impaired distal nephron proton secretion in secretory and voltage-dependent forms of distal renal tubular acidosis (RTA) and supports the view that proton secretion is not impaired in gradient forms of distal RTA.
Comparison of Effective and Ineffective Target Sites That Demonstrate Concealed Entrainment in Patients With Coronary Artery Disease Undergoing Radiofrequency Ablation of Ventricular Tachycardia
Authors: Frank Bogun, Marwan Bahu, Bradley P. Knight, Raul Weiss, Walter Paladino, Mark Harvey, Rajiva Goyal, Emile Daoud, K. Ching Man, S. Adam Strickberger, Fred Morady
Journal: Circulation (1997)

Background Concealed entrainment has been useful in guiding catheter ablation of monomorphic ventricular tachycardia in patients with coronary artery disease. However, not all sites with concealed entrainment result in successful ablation of the targeted ventricular tachycardia. The purpose of this prospective study was to identify factors at sites that demonstrate concealed entrainment that differentiate effective from ineffective target sites. Methods and Results In 14 consecutive patients with hemodynamically stable monomorphic ventricular tachycardia and coronary artery disease, radiofrequency ablation of 26 ventricular tachycardias was performed. Ablation was attempted at 46 sites that demonstrated concealed entrainment. Twenty-five of the targeted ventricular tachycardias (96%) were successfully ablated. The positive predictive value of concealed entrainment for successful ablation was 54%; it increased to 72% in the presence of a stimulus-QRS interval/ventricular tachycardia cycle length ratio of ≤70%, to 82% in the presence of a match of the stimulus-QRS and electrogram-QRS interval, and to 89% in the presence of isolated middiastolic potentials that could not be dissociated from ventricular tachycardia during entrainment. Conclusions The positive predictive value of concealed entrainment for identification of successful ablation sites in patients with sustained ventricular tachycardia and coronary artery disease can be significantly enhanced by the presence of associated mapping criteria, particularly an isolated mid diastolic potential that cannot be dissociated from the tachycardia.
Faldaprevir combined with pegylated interferon alfa-2a and ribavirin in treatment-naïve patients with chronic genotype1 HCV: SILEN-C1 trial
Authors: Mark S. Sulkowski, Tarik Asselah, Jacob Lalezari, Peter Ferenci, Hugo Fainboim, Barbara Leggett, Fernando Bessone, Stefan Mauss, Jeong Heo, Yakov Datsenko, Jerry O. Stern, George Kukolj, Joseph Scherer, Gerhard Nehmiz, Gerhard G. Steinmann, Wulf O. Böcher
Journal: Hepatology (2013)

Abstract Faldaprevir (BI 201335) is a potent, hepatitis C virus (HCV) NS3/4A protease inhibitor with pharmacokinetic properties supportive of once-daily (QD) dosing. Four hundred and twenty-nine HCV genotype (GT)-1 treatment-naïve patients without cirrhosis were randomized 1:1:2:2 to receive 24 weeks of pegylated interferon alfa-2a and ribavirin (PegIFN/RBV) in combination with placebo, faldaprevir 120 mg QD with 3 days of PegIFN/RBV lead-in (LI), 240 mg QD with LI, or 240 mg QD without LI, followed by an additional 24 weeks of PegIFN/RBV. Patients in the 240 mg QD groups achieving maintained rapid virologic response (mRVR; viral load [VL] &lt;25 IU/mL at week 4 and undetectable at weeks 8-20) were rerandomized to cease all treatment at week 24 or continue receiving PegIFN/RBV up to week 48. VL was measured by Roche TaqMan. Sustained virologic response (SVR) rates were 56%, 72%, 72%, and 84% in the placebo, faldaprevir 120 mg QD/LI, 240 mg QD/LI, and 240 mg QD groups. Ninety-two percent of mRVR patients treated with faldaprevir 240 mg QD achieved SVR, irrespective of PegIFN/RBV treatment duration. Eighty-two percent of GT-1a patients who received faldaprevir 240 mg QD achieved SVR versus 47% with placebo. Mild gastrointestinal disorders, jaundice resulting from isolated unconjugated hyperbilirubinemia, and rash or photosensitivity were more common in the active groups than with placebo. Discontinuations resulting from adverse events occurred in 4%, 11%, and 5% of patients treated with 120 mg QD/LI, 240 mg QD/LI, and 240 mg QD of faldaprevir versus 1% with placebo. Conclusion: Faldaprevir QD with PegIFN/RBV achieved consistently high SVR rates with acceptable tolerability and safety at all dose levels. The 120 and 240 mg QD doses are currently undergoing phase 3 evaluation.
Lack of funding prevents human-animal stem cell research in UK
Authors: S. Mayor
Journal: BMJ (2009)

Lack of funding has prevented progress in UK stem cell research that is based on creating human-animal hybrid clones, despite legislation that allows the technique being passed a year ago, researchers warned this week.

Two of the three UK researchers who were granted licences last year to conduct research with human-animal hybrid stem cells, Stephen Minger at King’s College, London, and Lyle Armstrong at Newcastle University’s centre for life, said that they had been unable to initiate or continue with early studies because research councils had turned down grant applications.

Dr Minger, senior lecturer in stem cell biology at King’s College, London, said that the Medical Research Council had turned down an application by his department for about £1m (€1.1m; $1.5m) to cover a three year project.

The aim was to develop stem cell lines from people with genetic forms …
Drug misuse and sharing of needles in Scottish prisons.
Authors: D H Kennedy, G Nair, L Elliott, J Ditton
Journal: BMJ (1991)

More than a half of the people in Scotland with known HIV infection are drug injectors.1 Two recent studies have suggested that injecting with a consequent risk of HIV transmission is prevalent among drug misusers in prison.2There is also concern over the lack of treatment for drug misuse in prison.4 Drug misusers attending needle exchange centres seem able to maintain a low level of risk behaviour,5 although their attendance may be interrupted by imprisonment.3 Little is known about their drug taking, injecting, and sharing of needles in prison.
A NEW METHOD OF TREATING NEURALGIA OF THE TRIGEMINUS BY THE INJECTION OF ALCOHOL INTO THE GASSERIAN GANGLION
Authors: JULIUS GRINKER
Journal: JAMA (1913)

The greatest advance in the treatment of trifacial neuralgia was made when Schlosser, a Munich ophthalmologist, announced his method of injecting alcohol into the branches of the trigeminus nerve at their exit from the cranium. Ostwalt in Europe, and Kiliani and Hauck in America somewhat later adopted what was practically the same method with slight modifications. As the technic was extremely difficult, only the chosen few who had learned it directly of the master, after serving with him a more or less prolonged apprenticeship, were in a position to utilize it in their practice. It was not, therefore, until Levy and Baudouin of Paris had discovered a comparatively easy technic that the alcohol-injection treatment of trifacial neuralgia had become a distinct addition to the physician's therapeutic armamentarium.  Though this has become the generally accepted method of treating true trifacial neuralgia, there are cases in which the benefits of the method