tbuckley/cabot-search huggingface dataset:
Recent infections are associated with decreased risk of rheumatoid arthritis: a population-based case-control study
Authors: Maria E C Sandberg, Camilla Bengtsson, Lars Klareskog, Lars Alfredsson, Saedis Saevarsdottir
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Do recent infections affect the risk of rheumatoid arthritis (RA)? <h3>Methods</h3> We used the population-based case-control study EIRA (N=6401) on incident RA and healthy controls, matched for sex, age, calendar period and area of residence. Gastroenteritis, urinary tract infection, genital infection, prostatitis, sinusitis, tonsillitis and pneumonia during the 2 years before inclusion in the study were investigated. Conditional logistic regression was used to calculate OR, adjusting for smoking and socioeconomic status. <h3>Results</h3> Infections in the gastrointestinal and urogenital tract before clinical onset were associated with a lowered risk of RA: gastroenteritis (OR=0.71 (95% CI 0.63 to 0.80)), urinary tract infections (OR=0.78 (95% CI 0.68 to 0.90)) and genital infections (OR=0.80 (95% CI 0.64 to 1.00)), while a non-significant association of similar magnitude was observed for the less common prostatitis (OR=0.64 (95% CI 0.38 to 1.08)). In contrast, no associations were observed for sinusitis, tonsillitis or pneumonia. <h3>Conclusions</h3> Gastrointestinal and urogenital infections, but not respiratory infections, are associated with a significantly lowered risk of RA. The results indicate that infections in general do not affect the risk for RA, but that certain infections, hypothetically associated with changes in the gut microbiome, could diminish the risk.
Differential Effects of Combined Ad5-Δ24RGD and Radiation Therapy in <i>In vitro</i> versus <i>In vivo</i> Models of Malignant Glioma
Authors: Martine L.M. Lamfers, Sander Idema, Lisette Bosscher, Stan Heukelom, Sharif Moeniralm, Ida H. van der Meulen-Muileman, Renée M. Overmeer, Paul van der Valk, Victor W. van Beusechem, Winald R. Gerritsen, W. Peter Vandertop, Clemens M.F. Dirven
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The integrin-targeted conditionally replicating adenovirus Ad5-Δ24RGD has been shown to possess strong oncolytic activity in experimental tumors and is currently being developed toward phase I clinical evaluation for ovarian cancer and malignant glioma. Previously, we reported that combination therapy of Ad5-Δ24RGD with irradiation led to synergistic antitumor activity in s.c. glioma xenografts. In the current study, the underlying mechanism of action to this synergy was studied and the effects of combined therapy were assessed in an orthotopic glioma model. Experimental Design and Results: Sequencing studies in U-87 monolayers showed that delivery of irradiation before Ad5-Δ24RGD infection led to a greater oncolytic effect than simultaneous delivery or infection before irradiation. This effect was not due to enhanced virus production or release. Experiments using a luciferase-encoding vector revealed a small increase in transgene expression in irradiated cells. In tumor spheroids, combination therapy was more effective than Ad5-Δ24RGD or irradiation alone. Staining of spheroid sections showed improved penetration of virus to the core of irradiated spheroids. Mice bearing intracranial tumors received a combination of Ad5-Δ24RGD with 1 × 5 Gy total body irradiation or with 2 × 6 Gy whole brain irradiation. In contrast to the in vitro data and reported results in s.c. tumors, addition of radiotherapy did not significantly enhance the antitumor effect of Ad5-Δ24RGD. Conclusions: Combined treatment with Ad5-Δ24RGD and irradiation shows enhanced antitumor activity in vitro and in s.c. tumors, but not in an orthotopic glioma model. These differential results underscore the significance of the selected tumor model in assessing the effects of combination therapies with oncolytic adenoviruses.
Flat-Fixed Dosing of Irinotecan
Authors: Floris A. de Jong, Ron H. J. Mathijssen, Rujia Xie, Jaap Verweij, Alex Sparreboom
Journal: Clinical Cancer Research (2004)

Abstract Purpose: In a previous analysis, it was shown that body-surface area (BSA) is not a predictor of irinotecan pharmacokinetic parameters. Here, we prospectively evaluated the effects of administering a flat-fixed irinotecan dose to cancer patients, regardless of BSA. Experimental Design: Twenty-six cancer patients (12 females) received a fixed irinotecan dose of 600 mg, given as a 90-min i.v. infusion. Plasma concentrations of irinotecan and its metabolites SN-38 (7-ethyl-10-hydroxycamptothecin) and SN-38G (SN-38 glucuronide) were measured during the first cycle and analyzed using nonlinear mixed-effect modeling. Data were compared with those obtained in 47 cancer patients (19 females) who received irinotecan at a BSA-normalized dose of 350 mg/m2. Results: The interindividual variability in irinotecan clearance (25.9% versus 25.1%; P = 0.93), in relative extent of conversion to SN-38 (47.8% versus 42.7%; P = 0.24), and in relative extent of SN-38 glucuronidation (71.2% versus 72.4%; P = 0.95) were not significantly different between the two dose groups. Variance differences in irinotecan-mediated hematological side effects were also similar between the 600 mg and 350 mg/m2 groups (P &amp;gt; 0.14). Conclusions: These findings suggest that flat-fixed dosing of irinotecan does not result in increased pharmacokinetic/pharmacodynamic variability and could be safely used to supplant current dosing strategies based on BSA.
Increased Production of Urea Hydrogen Peroxide from Maillard Reaction and a UHP-Fenton Pathway Related to Glycoxidation Damage in Chronic Renal Failure
Authors: Akira Moh, Noriyuki Sakata, Shigeo Takebayashi, Kayoko Tateishi, Ryoji Nagai, Seikoh Horiuchi, Junichi Chihara
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Urea hydrogen peroxide (UHP) is a stable form of H2O2 and cytotoxic agent. This study describes examination of UHP formation from collagen glycation and relevant glycoxidative damage in chronic renal failure (CRF). Renal fibers were incubated with 50 mM ribose in either serum ultrafiltrate or phosphate-buffered saline in the presence of various concentrations of urea. UHP was determined by a modified ferrous oxidation in xylenol orange (FOX) assay. The presence of urea resulted in an increase in the generation of UHP in a dose-dependent manner of urea in these incubation systems. Pentosidine levels analyzed by HPLC also increased in a dose-dependent manner of urea. Blocking experiments showed that pentosidine and carboxymethyllysine formation was significantly enhanced by hydroxyl radical generated from UHP via Fenton reaction. The renal and cardiac levels of UHP, pentosidine, and carboxymethyllysine in patients with CRF, including seven predialysis and eight hemodialysis subjects, were significantly higher than that in controls (n = 16). The renal and cardiac levels of UHP closely correlated with the levels of renal and cardiac pentosidine and carboxymethyllysine and inversely correlated with left ventricle ejection fraction in CRF patients. This study provides evidence, for the first time, that UHP can be produced from Maillard reaction. Increased UHP in chronic renal failure enhances the formation of pentosidine and carboxymethyllysine via Fenton reaction (UHP-Fenton pathway).
TCT-244 Impact of Intensive Statin Therapy on Plaque Characteristics as Assessed by Serial Optical Coherence Tomography
Authors: Takashi Akasaka, Kenichi Komukai, Takashi Kubo, Atsushi Tanaka, Hironori Kitabata, Yoshiki Matsuo, Yasushi Ino, Kohei Ishibashi, Takashi Tanimoto, Takashi Ymano, Tomoyoshi Yamaguchi, Makoto Orii, Kunihiro Shimamura, Yasutsugu Shiono, Kumiko Hirata, Toshio Imanishi
Journal: Journal of the American College of Cardiology (2012)
Low Penetrance, Broad Resistance, and Favorable Outcome of Interleukin 12 Receptor β1 Deficiency
Authors: Claire Fieschi, Stéphanie Dupuis, Emilie Catherinot, Jacqueline Feinberg, Jacinta Bustamante, Adrien Breiman, Frédéric Altare, Richard Baretto, Françoise Le Deist, Samer Kayal, Hartmut Koch, Darko Richter, Martin Brezina, Guzide Aksu, Phil Wood, Suliman Al-Jumaah, Miquel Raspall, Alberto José da Silva Duarte, David Tuerlinckx, Jean-Louis Virelizier, Alain Fischer, Andrea Enright, Jutta Bernhöft, Aileen M. Cleary, Christiane Vermylen, Carlos Rodriguez-Gallego, Graham Davies, Renate Blütters-Sawatzki, Claire-Anne Siegrist, Mohammad S. Ehlayel, Vas Novelli, Walther H. Haas, Jacob Levy, Joachim Freihorst, Sami Al-Hajjar, David Nadal, Dewton de Moraes Vasconcelos, Olle Jeppsson, Necil Kutukculer, Klara Frecerova, Isabel Caragol, David Lammas, Dinakantha S. Kumararatne, Laurent Abel, Jean-Laurent Casanova
Journal: The Journal of Experimental Medicine (2003)

The clinical phenotype of interleukin 12 receptor β1 chain (IL-12Rβ1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rβ1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rβ1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most.
Multiple Serotonergic Brainstem Abnormalities in Sudden Infant Death Syndrome
Authors: David S. Paterson, Felicia L. Trachtenberg, Eric G. Thompson, Richard A. Belliveau, Alan H. Beggs, Ryan Darnall, Amy E. Chadwick, Henry F. Krous, Hannah C. Kinney
Journal: JAMA (2006)

ContextThe serotonergic (5-hydroxytryptamine [5-HT]) neurons in the medulla oblongata project extensively to autonomic and respiratory nuclei in the brainstem and spinal cord and help regulate homeostatic function. Previously, abnormalities in 5-HT receptor binding in the medullae of infants dying from sudden infant death syndrome (SIDS) were identified, suggesting that medullary 5-HT dysfunction may be responsible for a subset of SIDS cases.ObjectiveTo investigate cellular defects associated with altered 5-HT receptor binding in the 5-HT pathways of the medulla in SIDS cases.Design, Setting, and ParticipantsFrozen medullae from infants dying from SIDS (cases) or from causes other than SIDS (controls) were obtained from the San Diego Medical Examiner's office between 1997 and 2005. Markers of 5-HT function were compared between SIDS cases and controls, adjusted for postconceptional age and postmortem interval. The number of samples available for each analysis ranged from 16 to 31 for SIDS cases and 6 to 10 for controls. An exploratory analysis of the correlation between markers and 6 recognized risk factors for SIDS was performed.Main Outcome Measures5-HT neuron count and density, 5-HT1A receptor binding density, and 5-HT transporter (5-HTT) binding density in the medullary 5-HT system; correlation between these markers and 6 recognized risk factors for SIDS.ResultsCompared with controls, SIDS cases had a significantly higher 5-HT neuron count (mean [SD], 148.04 [51.96] vs 72.56 [52.36] cells, respectively; P&lt;.001) and 5-HT neuron density (P&lt;.001), as well as a significantly lower density of 5-HT1A receptor binding sites (P≤.01 for all 9 nuclei) in regions of the medulla involved in homeostatic function. The ratio of 5-HTT binding density to 5-HT neuron count in the medulla was significantly lower in SIDS cases compared with controls (mean [SD], 0.70 [0.33] vs 1.93 [1.25] fmol/mg, respectively; P = .001). Male SIDS cases had significantly lower 5-HT1A binding density in the raphé obscurus compared with female cases (mean [SD], 16.2 [2.0] vs 29.6 [16.5] fmol/mg, respectively; P = .04) or with male and female controls combined (mean [SD], 53.9 [19.8] fmol/mg; P = .005). No association was found between 5-HT neuron count or density, 5-HT1A receptor binding density, or 5-HTT receptor binding density and other risk factors.ConclusionsMedullary 5-HT pathology in SIDS is more extensive than previously delineated, potentially including abnormal 5-HT neuron firing, synthesis, release, and clearance. This study also provides preliminary neurochemical evidence that may help explain the increased vulnerability of boys to SIDS.
Increased Risk of Stroke and Transient Ischemic Attack in 5-Year Survivors of Hodgkin Lymphoma
Authors: Marie L. De Bruin, Lucille D. A. Dorresteijn, Mars B. van't Veer, Augustinus D. G. Krol, Helena J. van der Pal, Arnoud C. Kappelle, Willem Boogerd, Berthe M. P. Aleman, Flora E. van Leeuwen
Journal: JNCI Journal of the National Cancer Institute (2009)

Information on clinically verified stroke and transient ischemic attack (TIA) following Hodgkin lymphoma is scarce. We quantified the long-term risk of cerebrovascular disease associated with the use of radiotherapy and chemotherapy in survivors of Hodgkin lymphoma and explored potential pathogenic mechanisms.We performed a retrospective cohort study among 2201 five-year survivors of Hodgkin lymphoma treated before age 51 between 1965 and 1995. We compared incidence rates of clinically verified stroke and TIA with those in the general population. We used multivariable Cox regression techniques to study treatment-related factors and other risk factors. All statistical tests were two-sided.After a median follow-up of 17.5 years, 96 patients developed cerebrovascular disease (55 strokes, 31 TIAs, and 10 with both TIA and stroke; median age = 52 years). Most ischemic events were from large-artery atherosclerosis (36%) or cardioembolisms (24%). The standardized incidence ratio for stroke was 2.2 (95% confidence interval [CI] = 1.7 to 2.8), and for TIA, it was 3.1 (95% CI = 2.2 to 4.2). The risks remained elevated, compared with those in the general population, after prolonged follow-up. The cumulative incidence of ischemic stroke or TIA 30 years after Hodgkin lymphoma treatment was 7% (95% CI = 5% to 8%). Radiation to the neck and mediastinum was an independent risk factor for ischemic cerebrovascular disease (hazard ratio = 2.5, 95% CI = 1.1 to 5.6 vs without radiotherapy). Treatment with chemotherapy was not associated with an increased risk. Hypertension, diabetes mellitus, and hypercholesterolemia were associated with the occurrence of ischemic cerebrovascular disease, whereas smoking and overweight were not.Patients treated for Hodgkin lymphoma experience a substantially increased risk of stroke and TIA, associated with radiation to the neck and mediastinum. Physicians should consider appropriate risk-reducing strategies.
Home therapy for deep vein thrombosis and pulmonary embolism in cancer patients
Authors: S. Siragusa, C. Arcara, A. Malato, R. Anastasio, M.R. Valerio, F. Fulfaro, L. Lo Coco, S. Grimaudo, G. Bajardi, V. Abbadessa, N. Gebbia
Journal: Annals of Oncology (2005)
Ventricular elastic modulus as a function of age in the Syrian golden hamster.
Authors: R L Kane, T A McMahon, R L Wagner, W H Abelmann
Journal: Circulation Research (1976)

Analysis of passive right and left ventricular pressure-volume curves for hearts of 72 Syrian golden hamsters studied in vitro showed increases in ventricular weight, volume, and compliance at mid-age. Both ventricles were filled by syringe pumps at a constant rate. Ventricular compliance (dV/dP) was determined by electronic differentiation of the intraventricular pressures and formation of the ratio (dV/dt)/(dP/dt) as a continuous function of intraventricular pressure between 0 and 30 mm Hg. By relating, with justification, the left ventricle to a thin-walled elastic sphere, ventricular elastic moduli, E, for different ages were compared at constant levels of myocardial wall stress, sigma. The elastic modulus E proved to be a linear function of sigma. The slope of the E-sigma plot yielded a stiffness constant, K, for each age group. Body weight, heart weight, end-diastolic volume, and dV/dP all varied by more than 200% up and then down as a function of age, but K was not a significant function of age. These results suggest that the aging heart does not normally undergo substantial alterations in passive properties that affect the muscle cells and fibers themselves, but rather that the observed changes in compliance are primarily attributable to alterations in ventricular size.
Communication With the Radiologist
Authors: Barry H. Martin
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Today was typical. I read skull x-ray films of a patient with a diagnosis of bunions and films of the feet of a patient with nosebleeds. I appeal to my medical colleagues to communicate with their friendly radiologist. A few words of pertinent clinical information will permit a more reasoned analysis of roentgenograms. Some clinicians seem to think that a diagnosis arrived at in a vacuum is more reliable than otherwise. I promise not to be confused by the facts. It is sometimes difficult to judge the age or importance of isolated roentgenographic findings outside of the clinical setting, ie, abdominal calcification or atypical gas shadow, vertebral body compression, certain pulmonary densities, and bone infarcts. I hasten to add that many physicians are pleased to consult and cooperate for the common good. This letter is addressed to the silent minority. The x-ray film requisition form is available
The changing pattern of miliary tuberculosis
Authors: J. Jacques, J. M. Sloan
Journal: Thorax (1970)

Over the past 20 years there has been a striking change in the clinical pattern of miliary tuberculosis, which is now more common in adults than in children. This is shown by a comparative study of the necropsy records of such cases seen in the same group of hospitals in the years 1946-9 and 1966-9. In the early period miliary tuberculosis occurred in 1·7% of necropsies, 54% of patients being under 20 years of age and suffering from a classical form of miliary tuberculosis. By 1966-9 the incidence had fallen to 0·47% of necropsies, but now all the patients seen were over 30 years of age, the majority having a `cryptic9 clinical presentation. The percentage of patients diagnosed during life fell dramatically between the two periods and in the latter period most cases were only diagnosed at necropsy. While the incidence of childhood miliary tuberculosis has been reduced, it is now important to consider this diagnosis in adults with a variety of non-specific symptoms.
Vandetanib for the Treatment of Patients With Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer
Authors: Samuel A. Wells, Jessica E. Gosnell, Robert F. Gagel, Jeffrey Moley, David Pfister, Julie A. Sosa, Michael Skinner, Annetta Krebs, James Vasselli, Martin Schlumberger
Journal: Journal of Clinical Oncology (2010)

Purpose There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC. Methods Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST [Response Evaluation Criteria in Solid Tumors]). Results Thirty patients received initial treatment with vandetanib 300 mg/d. On the basis of investigator assessments, 20% of patients (ie, six of 30 patients) experienced a confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53% of patients (ie, 16 of 30 patients) experienced stable disease at ≥ 24 weeks, which yielded a disease control rate of 73% (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50% or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. The most common adverse events were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). Conclusion In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy.
Racing problems in the U.S.A.
Authors: G. Jaggard
Journal: British Journal of Sports Medicine (1976)

The major problems of racing in the United States at the present time are caused by too much racing. This has led to too few horses and small fields. Consequently many owners and trainers are trying to enter their horses too frequently and to race them when they are not really fit to run. The desire to race horses as frequently as possible has led to constant pressure from horsemen through their organizations for so called "permissive medication". Started in the state of Colorado approximately ten years ago this has grown until finally there are only a few states, notably New York and New Jersey that have resisted the pressure. The drug that gave the opening wedge to permissive medication was phenylbutazone, but this in many states has led to the inclusion of other drugs including analgesics and drugs that veterinarians claim are needed for therapeutic purposes. Some states have endeavoured to control phenylbutazone medication by quantitation and while lower limits cause little difficulty, maximum allowable limits have caused problems and are not practical. While there has been no publicity to my knowledge about frusemide (furosemide, lasix) the abuse of this drug for so called "bleeders" is an example that may seriously interfere with drug detection in urine and its use should be confined to proven "bleeders" (i.e. horses suffering from epistaxis). Pre-race blood testing began roughly ten years ago at the harness tracks and has been resisted by our flat tracks rather successfully up to the present time. The blood testing methods and those used by the same laboratories in post-race urine testing is inadequate and will not detect many illegal drugs.