tbuckley/cabot-search huggingface dataset:
Preventing Nephropathy Induced by Contrast Medium
Authors: Brendan J. Barrett, Patrick S. Parfrey
Journal: New England Journal of Medicine (2006)

A 71-year-old man with type 2 diabetes and hypertension is referred for coronary angiography. Medications include metformin and a thiazide. Before the angiogram, his serum creatinine level is 1.8 mg per deciliter (160 μmol per liter), yielding an estimated glomerular filtration rate of 40 ml per minute per 1.73 m2 of body-surface area. What can be done to reduce the risk that an angiographic contrast agent will worsen his kidney function?
Statin Use Reduces Decline in Lung Function
Authors: Stacey E. Alexeeff, Augusto A. Litonjua, David Sparrow, Pantel S. Vokonas, Joel Schwartz
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Decreased lung function has been linked to increased inflammation and oxidative stress. Statins have demonstrated antiinflammatory and antioxidant properties.We investigated the effect of statin use on decline in lung function in the elderly, and whether smoking modified this effect.Our study population included 2,136 measurements on 803 elderly men from the Normative Aging Study whose lung function (FVC and FEV(1)) was measured two to four times between 1995 and 2005. Subjects indicated statin use and smoking history at each visit. We used mixed linear models to estimate the effects of each covariate, adjusting for subject and possible confounders.For those not using statins, the estimated decline in FEV(1) was 23.9 ml/year (95% confidence interval [CI], -27.8 to -20.1 ml/yr), whereas those taking statins had an estimated 10.9-ml/year decline in FEV(1) (95% CI, -16.9 to -5.0 ml/yr). We also examined the effect of statins with smoking by dividing the cohort into four groups: never-smokers, longtime quitters (quit >or= 10 yr ago), recent quitters (quit < 10 yr ago), and current smokers. We found a significant three-way interaction between time since first visit, statin use, and smoking status (P < 0.001). Within each smoking category, the effect of statins was always estimated to be beneficial, but the size of the improvement in the decline rate varied among smoking groups. We found similar results for FVC decline.Our results indicate that statin use attenuates decline in lung function in the elderly, with the size of the beneficial effect modified by smoking status.
Antigenic variation of Borrelia hermsii.
Authors: H G Stoenner, T Dodd, C Larsen
Journal: The Journal of Experimental Medicine (1982)

At least 24 different serotypes were detected in populations of Borrelia hermsii that originated from a single organism. These serotypes were identified by staining with specific fluoresceinated antisera prepared against cloned populations of living organisms of each type. In the order of decreasing frequency, the 10 types more often encountered were 7, which was clearly dominant, and 2, 17, 24, 13, 2, 1, 21, 11, and 12. Each of the 24 types were shown to change to 7 or more other serotypes. Spirochetemia in mice was persistent, and relapses occurred when the concentration of organisms was sufficient for detection by visual means. After mice were inoculated with a single organism, peak spirochetemia usually occurred on day 4, after which clearance of organisms occurred, and an apparently pure population was replaced by a mixed population consisting of as many as seven variants. These types persisted for 2-3 d before being replaced by other types. Conversions occurred constantly and were independent of relapses. The rate of conversion in mice treated with cyclophosphamide to delay antibody production was comparable to that of controls. Spontaneous conversion was clearly demonstrated in tubes of fortified Kelly's medium inoculated with a single organism of type 7 or 21. 11 different variants appeared in eight cultures of type 21 by the time growth had reached 4 X 10(6)-10(7) organisms/ml. The rate of spontaneous change was estimated to be or approximately 10(-4)-10(-3) per cell per generation.
Phase I Pharmacokinetic Study of the Safety and Tolerability of Lapatinib (GW572016) in Combination with Oxaliplatin/Fluorouracil/Leucovorin (FOLFOX4) in Patients with Solid Tumors
Authors: Wandena S. Siegel-Lakhai, Jos H. Beijnen, Walter L. Vervenne, Henk Boot, Marianne Keessen, Melissa Versola, Kevin M. Koch, Deborah A. Smith, Lini Pandite, Dirk J. Richel, Jan H.M. Schellens
Journal: Clinical Cancer Research (2007)

Abstract Purpose: This phase I study was designed to determine the optimally tolerated regimen (OTR), safety, and clinical activity of lapatinib in combination with FOLFOX4 [oxaliplatin/leucovorin/5-fluorouracil (5-FU)] in patients with solid tumors. Furthermore, the pharmacokinetics of lapatinib, oxaliplatin, and 5-FU when given alone and in combination were evaluated. Experimental Design: This study was conducted in two parts. Part 1 was designed to determine the OTR and part 2 was the pharmacokinetic part of the study. Lapatinib was administered once daily for the entire duration of the study. Leucovorin and oxaliplatin were given concurrently over 2 h as an i.v. infusion, after which 5-FU was given as a bolus followed by continuous infusion over 22 h on day 1. 5-FU and leucovorin administration were repeated in an identical manner on day 2. Cycles were repeated every 2 weeks. Once the OTR was determined, it was to become the dose level for patients included in the pharmacokinetic part of the study. Results: A total of 34 patients was treated in this study. No dose-limiting toxicities were observed and the OTR was established at 1,500 mg/d lapatinib in combination with the standard FOLFOX4 regimen. Nonhematologic toxicities consisted mainly of nausea, diarrhea, vomiting, fatigue, neuropathy, and mucositis. The most important hematologic toxicity was neutropenia. No drug-drug interactions between lapatinib and the FOLFOX4 regimen were observed. Conclusion: Lapatinib can be safely administered in combination with the standard FOLFOX4 regimen. Further studies are warranted to explore the potential additive antitumor effect of lapatinib in combination with the FOLFOX4 regimen.
Polyclonal B cell activation in lupus-prone mice precedes and predicts the development of autoimmune disease.
Authors: D M Klinman
Journal: Journal of Clinical Investigation (1990)

Polyclonal B cell activation is an early feature of autoimmune disease in humans and mice with systemic lupus erythematosus. The contribution of polyclonal activation to the progression of autoimmunity is unclear, however, since it precedes the development of end-organ damage by months or years. To examine this issue, 109 autoimmune-prone (NZB X NZW)F1 X NZB backcross mice were hemi-splenectomized at 10 wk and the number and antigenic specificity of their Ig-secreting B cells quantitated by ELISA spot assay. Of the 61 mice that had polyclonally increased numbers of Ig-secreting cells/spleen, 31 died by 6 mo. In contrast, 0/48 backcross mice with normal numbers of Ig-secreting B cells at 10 wk died over the same period (P less than 0.001). Polyclonally activated mice also developed proteinuria earlier and more frequently than littermates with normal numbers of Ig-secreting cells (P less than 0.001). As adults, backcross mice with proteinuria expressed repertoires skewed towards the production of anti-DNA antibodies. At 10 wk these same mice expressed repertoires marked by polyclonal activation rather than preferential anti-DNA production. These findings indicate that autoimmune disease in SLE is accompanied by the autoantigen-driven production of autoantibodies but is preceded and predicted by polyclonal B cell activation.
The enteric serotonergic system is altered in patients with diverticular disease
Authors: Martina Böttner, Martina Barrenschee, Ines Hellwig, Jonas Harde, Jan-Hendrik Egberts, Thomas Becker, Dimitri Zorenkov, Thilo Wedel
Journal: Gut (2012)

<h3>Objective</h3> Disturbances of the enteric serotonergic system have been implicated in several intestinal motility disorders. Patients with diverticular disease (DD) have been reported to exhibit abnormal intestinal motility and innervation patterns. Gene expression profiles of the serotonergic system and distribution of the serotonin type 4 receptor (5HT-4R) were thus studied in patients with DD. <h3>Design</h3> Colonic specimens from patients with DD and controls were subjected to quantitative PCR for serotonin receptors 2B, 3A, 4, serotonin transporter and synthesising enzyme tryptophan hydroxylase. Localisation of 5HT-4R was determined by dual-label immunocytochemistry using smooth muscle actin (α-SMA) and pan-neuronal markers (PGP 9.5) and quantitative analysis was carried out. Site-specific gene expression analysis of 5HT-4R was assessed within myenteric ganglia and muscle layers. Correlation of 5HT-4R with muscarinic receptors 2 and 3 (M2R, M3R) messenger RNA expression was determined. <h3>Results</h3> 5HT-4R mRNA expression was downregulated in the tunica muscularis and upregulated in the mucosa of patients with DD, whereas the other components of the serotonergic system remained unchanged. 5HT-4R was detected in ganglia and muscle layers, but was decreased in the circular muscle layer and myenteric ganglia of patients with DD. 5HT-4R mRNA expression correlated with M2R/M3R mRNA expression in controls, but not in patients with DD. <h3>Conclusions</h3> The serotonergic system is compromised in DD. Altered expression of 5HT-4R at mRNA and protein levels may contribute to intestinal motor disturbances reported in patients with DD. The findings support the hypothesis that DD is associated and possibly promoted by an enteric neuromuscular pathology.
Homozygous/Compound Heterozygous Triadin Mutations Associated With Autosomal-Recessive Long-QT Syndrome and Pediatric Sudden Cardiac Arrest
Authors: Helene M. Altmann, David J. Tester, Melissa L. Will, Sumit Middha, Jared M. Evans, Bruce W. Eckloff, Michael J. Ackerman
Journal: Circulation (2015)

Long-QT syndrome (LQTS) may result in syncope, seizures, or sudden cardiac arrest. Although 16 LQTS-susceptibility genes have been discovered, 20% to 25% of LQTS remains genetically elusive.We performed whole-exome sequencing child-parent trio analysis followed by recessive and sporadic inheritance modeling and disease-network candidate analysis gene ranking to identify a novel underlying genetic mechanism for LQTS. Subsequent mutational analysis of the candidate gene was performed with polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing on a cohort of 33 additional unrelated patients with genetically elusive LQTS. After whole-exome sequencing and variant filtration, a homozygous p.D18fs*13 TRDN-encoded triadin frameshift mutation was discovered in a 10-year-old female patient with LQTS with a QTc of 500 milliseconds who experienced recurrent exertion-induced syncope/cardiac arrest beginning at 1 year of age. Subsequent mutational analysis of TRDN revealed either homozygous or compound heterozygous frameshift mutations in 4 of 33 unrelated cases of LQTS (12%). All 5 TRDN-null patients displayed extensive T-wave inversions in precordial leads V1 through V4, with either persistent or transient QT prolongation and severe disease expression of exercise-induced cardiac arrest in early childhood (≤3 years of age) and required aggressive therapy. The overall yield of TRDN mutations was significantly greater in patients ≤10 years of age (5 of 10, 50%) compared with older patients (0 of 24, 0%; P=0.0009).We identified TRDN as a novel underlying genetic basis for recessively inherited LQTS. All TRDN-null patients had strikingly similar phenotypes. Given the recurrent nature of potential lethal arrhythmias, patients fitting this phenotypic profile should undergo cardiac TRDN genetic testing.
Injuries in martial arts: a comparison of five styles
Authors: M N Zetaruk, M A Violán, D Zurakowski, L J Micheli
Journal: British Journal of Sports Medicine (2004)

Objective: To compare five martial arts with respect to injury outcomes. Methods: A one year retrospective cohort was studied using an injury survey. Data on 263 martial arts participants (Shotokan karate, n = 114; aikido, n = 47; tae kwon do, n = 49; kung fu, n = 39; tai chi, n = 14) were analysed. Predictor variables included age, sex, training frequency (⩽3 h/week v &gt;3 h/week), experience (&lt;3 years v ⩾3 years), and martial art style. Outcome measures were injuries requiring time off from training, major injuries (⩾7 days off), multiple injuries (⩾3), body region, and type of injury. Logistic regression was used to determine odds ratios (OR) and confidence intervals (CI). Fisher’s exact test was used for comparisons between styles, with a Bonferroni correction for multiple comparisons. Results: The rate of injuries, expressed as percentage of participants sustaining an injury that required time off training a year, varied according to style: 59% tae kwon do, 51% aikido, 38% kung fu, 30% karate, and 14% tai chi. There was a threefold increased risk of injury and multiple injury in tae kwon do than karate (p&lt;0.001). Subjects ⩾18 years of age were at greater risk of injury than younger ones (p&lt;0.05; OR 3.95; CI 1.48 to 9.52). Martial artists with at least three years experience were twice as likely to sustain injury than less experienced students (p&lt;0.005; OR 2.46; CI 1.51 to 4.02). Training &gt;3 h/week was also a significant predictor of injury (p&lt;0.05; OR 1.85; CI 1.13 to 3.05). Compared with karate, the risks of head/neck injury, upper extremity injury, and soft tissue injury were all higher in aikido (p&lt;0.005), and the risks of head/neck, groin, and upper and lower extremity injuries were higher in tae kwon do (p&lt;0.001). No sex differences were found for any of the outcomes studied. Conclusions: There is a higher rate of injury in tae kwon do than Shotokan karate. Different martial arts have significantly different types and distribution of injuries. Martial arts appear to be safe for young athletes, particularly those at beginner or intermediate levels.
Effects of asymptomatic ischemia on long-term prognosis in chronic stable coronary disease.
Authors: A C Yeung, J Barry, J Orav, E Bonassin, K E Raby, A P Selwyn
Journal: Circulation (1991)

BACKGROUND Ischemia on ambulatory electrocardiographic monitoring has been shown to adversely affect short-term prognoses in patients with unstable angina, after myocardial infarction, and with chronic stable angina. METHODS AND RESULTS In this long-term study, we followed 138 patients (mean age, 59 +/- 9 years) with chronic stable angina and positive exercise tests for cardiac events (e.g. death, myocardial infarction, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft surgery). In 105 patients, ambulatory electrocardiographic monitoring was performed after all antianginal medication was withheld for 48 hours. In 26 patients, the diagnostic tests were repeated while on their usual medication. In addition to the 105 patients, 33 patients had their monitoring performed only while on their usual medication. During 37 +/- 17 months of follow-up, there were nine deaths, nine myocardial infarctions, and 35 revascularization procedures. In patients monitored off medication, Cox survival analysis showed that the occurrence of ischemia on electrocardiographic monitoring was the most significant predictor of death and myocardial infarction in the subsequent 2 years (p = 0.02) and all adverse events for 5 years (p = 0.009). Patients who were monitored on medication and did not have ischemia (n = 18) appeared to have more adverse events than patients who had no ischemia while being monitored off medication (n = 43). CONCLUSIONS Asymptomatic ischemia on ambulatory electrocardiographic monitoring in patients with stable angina predicts death and myocardial infarction for 2 years and all adverse events for 5 years. Monitoring performed while on medication may show no ischemia; however, this may not indicate low risk of future coronary events.
Effect of Esthetic Outcome After Breast-Conserving Surgery on Psychosocial Functioning and Quality of Life
Authors: Jennifer F. Waljee, Emily S. Hu, Peter A. Ubel, Dylan M. Smith, Lisa A. Newman, Amy K. Alderman
Journal: Journal of Clinical Oncology (2008)

Purpose Although breast-conserving surgery (BCS) is often assumed to result in minimal deformity, many patients report postoperative breast asymmetry. Understanding the effect of asymmetry on psychosocial functioning is essential for patients to make an informed choice for surgery. Patients and Methods All women who underwent BCS at the University of Michigan Medical Center (Ann Arbor, MI) during a 4-year period were surveyed using a mailed questionnaire (N = 714; response rate = 79.5%). Women were queried regarding five aspects of psychosocial functioning: quality of life (QOL), depression, fear of recurrence, stigmatization, and perceived change in health status. Postoperative breast asymmetry was assessed using items from the Breast Cancer Treatment and Outcomes Survey. Multiple regression was used to examine the relationship between breast asymmetry and each outcome, controlling for age, time from surgery in years, race, education level, disease stage, surgical treatment, and the occurrence of postoperative complications. Results Women with pronounced breast asymmetry were significantly more likely to feel stigmatized as a result of their breast cancer treatment (odds ratio [OR] = 4.58; 95% CI, 2.77 to 7.55) and less likely to report unchanged or improved health after treatment (OR = 0.43; 95% CI, 0.27 to 0.66). Minimal breast asymmetry was associated with higher QOL scores (86.3 v 82.4, P &lt; .001). Finally, women with pronounced breast asymmetry were more likely to exhibit depressive symptoms (minimal asymmetry, 16.2%; moderate asymmetry, 18.0%; pronounced asymmetry, 33.7%, Wald test = 16.6; P = .002). Conclusion Pronounced breast asymmetry after BCS is significantly correlated with poor psychosocial functioning. Identifying patients at risk for postoperative asymmetry at the time of consultation may allow for improved referral for supportive counseling, prosthetics, and reconstruction.
Differential effects of nitric oxide synthase inhibitors in an in vivo allergic rat model
Authors: M.K Tulic, J.L Wale, P.G Holt, P.D Sly
Journal: European Respiratory Journal (2000)

The in vivo role of nitric oxide in inflammatory cell migration, vascular permeability and the development of hyperresponsiveness to methacholine (MCh) was studied in rats 24 h following ovalbumin (OVA) challenge. The NO synthase (NOS) inhibitors N(G)-mono-methyl-L-arginine (L-NMMA; nonselective), aminoguanidine (two-fold inducible NOS-selective), N(omega)-nitro-L-arginine methyl ester (L-NAME; 2000-fold endothelial cell NOS-selective) or S-methyl-L-thiocitrulline (100-fold neuronal NOS-selective) were administered (100 mg x kg(-1) s.c.) to OVA-sensitized Piebald-Virol-Glaxo rats on 3 consecutive days during which they were challenged with allergen (1% OVA). Responses to inhaled MCh were measured in anaesthetized animals 24 h after OVA challenge. Cellular inflammation and vascular permeability were assessed using bronchoalveolar lavage (BAL) fluid collected 30 min after administration of Evans blue (50 mg x kg(-1) i.v.). OVA challenge in sensitized animals induced hyperresponsiveness to MCh, inflammatory cell influx and increased leakage of Evans blue into the BAL fluid (n=9, p&lt;0.001). Aminoguanidine was effective in inhibiting the allergen-induced cellular influx and microvascular leakage (n=9, p&lt;0.001) without altering responses to MCh. This effect was reserved by L-arginine. L-NAME (n=5, p&lt;0.01) and S-methyl-L-thiocitrulline (n=6, p&lt;0.001) further potentiated the allergen-induced hyperresponsiveness without altering cellular inflammation. L-NMMA attenuated both the OVA-induced cellular influx and Evans blue leakage (n=8, p&lt;0.001) as well as further potentiating the hyperresponsiveness to MCh (p&lt;0.05). From these studies, it is suggested that, in allergic Piebald-Virol-Glaxo rats, nitric oxide production by inducible nitric oxide synthase plays a role in the migration of inflammatory cells and increase in vascular permeability following allergen challenge, whereas nitric oxide produced by the constitutively expressed neuronal nitric oxide synthase limits hyperresponsiveness to methacholine.
Creatine Metabolism in Arthritis
Authors: J. E. Dawson, H. B. Salt
Journal: Annals of the Rheumatic Diseases (1952)

The results published by Granirer (1949) of his investigation of creatinuria in patients with rheumatoid arthritis and osteo-arthritis appeared especially interesting, as few such studies had previously been recorded.The extensive work of Wang (1939) on creatine metabolism included a study of only three arthritic patients.All of these were regarded as having significant creatinuria of varying degree, but this was attributed by Wang to the accompanying muscular atrophy.Pemberton and Buckman (1920) had earlier studied forty cases of arthritis in men,'with the conclusion that about one-half of these showed an abnormally high value for blood " creatine ", but that only three of the cases showed creatinuria.In the control series of nine normal men, no creatinuria was found.Granirer's results were obtained from adult male and female subjects and yielded the following mean values for the 24-hr urinary creatine excretion: 675 mg. for ten osteo-arthritics 185 mg. for ten elderly healthy controls 176 mg. for ten patients with rheumatoid arthritis 161 mg. for ten young healthy controls.These findings, together with a consideration of normal levels of creatinuria previously postulated by certain other workers, led Granirer to conclude that creatinuria is a normal process in the adult male and female; that patients with active rheumatoid arthritis have also a normal creatinuria; and that in patients with osteo-arthritis there exists the possibility of an abnormal excretion of creatine.It is well known that creatine is an integral factor in the activity of muscle and in the cycle of carbohydrate metabolism, although the amount of creatine excreted in the urine depends rather on a process of disposal of creatine present in excess of that required for metabolic needs.The nature and purpose of the process of disposal of the excess creatine are still obscure (Peters and Van Slyke, 1946), though it has been noted by various investigators (quoted by Boland, 1950) that a marked increase in creatinuria was found during the early phase of cortisone and ACTH administration, which increase may or may not continue during the period of treatment.Using an improved method (Peters, 1942) for the determination of creatine 23 copyright.