tbuckley/cabot-search huggingface dataset:
Relation between adverse events associated with allopurinol and renal function in patients with gout
Authors: J Vazquez-Mellado
Journal: Annals of the Rheumatic Diseases (2001)

<h3>BACKGROUND</h3> Because serious adverse reactions to allopurinol have been related to a reduce creatinine clearance rate and prolonged half life of oxypurinol, it has been recommended that the dose should be adjusted according to the rate of creatinine clearance. However, in some patients with gout the dose is not sufficient to reduce serum levels of uric acid (⩽390 μmol/l) and to halt disease progression. <h3>OBJECTIVE</h3> To determine the prevalence of adverse reactions attributable to allopurinol in patients with primary gout according to dose and creatinine clearance rate. <h3>METHODS</h3> Data on 120 patients with gout receiving allopurinol, in whom the starting dose was adjusted according to creatinine clearance rate and later increased in some patients to control the disease, were retrospectively reviewed. Two groups were compared: group A, 52 patients receiving creatinine clearance adjusted maintenance doses of allopurinol and group B, 68 patients receiving non-adjusted higher maintenance doses of allopurinol. <h3>RESULTS</h3> During follow up 57% required higher allopurinol doses than those recommended according to their creatinine clearance rate. Only five (4%) of 120 consecutive patients developed allopurinol related adverse reactions: four minor skin reactions and one allopurinol hypersensitivity syndrome (AHS). Three of these (including the case of AHS) occurred in group A and two in group B (p=NS). The duration of allopurinol treatment was the same in both groups (group A: 2.3 (3.3) years; group B: 3.7 (4.8) years). No patient in group A, but 44% in group B had a creatinine clearance rate of &lt;50 ml/min. None of the patients received concomitant diuretics, ampicillin, or azathioprine. <h3>CONCLUSIONS</h3> No increase was seen in the prevalence of adverse reactions to allopurinol in patients who received higher allopurinol maintenance doses than those recommended according to creatinine clearance rate.
Sociodemographic factors and vestibular schwannoma: a Danish nationwide cohort study
Authors: J. Schuz, M. Steding-Jessen, S. Hansen, S.-E. Stangerup, P. Caye-Thomasen, C. Johansen
Journal: Neuro-Oncology (2010)

Vestibular schwannoma (VS) (or acoustic neuroma) accounts for about 5%–6% of all intracranial tumors; little is known about the etiology. We investigated the association between various sociodemographic indicators and VS in a cohort of 3.26 million Danish residents, with 1087 cases identified in 35 308 974 person-years under risk, with data accrued from 1993 to 2006. Complete ascertainment of cases was ensured by using population-based and clinical cancer registries. Information on sociodemographic indicators was obtained on an annually updated individual level from Statistics Denmark. Log-linear Poisson regression models were used to estimate incidence rate ratios (IRRs). Linear regression models were used to examine the association between sociodemographic indicators and tumor size. We found that IRRs decreased gradually with decreasing level of education, with values of 0.62 (95% CI: 0.49–0.78) for men and 0.62 (95% CI: 0.50–0.77) for women with a basic education compared with a higher education. Similar results were found for disposable income. Marital status was associated with a higher incidence of VS in men but not women; nonmarried men with a basic education had an IRR of 0.34 (95% CI: 0.23–0.50) compared with married men with a higher education. Lower incidence rates were also observed among unemployed or early-retirement pensioners, whereas there were no differences in incidence rates across the broad groups of occupations and across the types of districts. Sociodemographic indicators were not associated with the tumor size. The magnitude of the differences in incidence rates across the groups of different socioeconomic indicators suggests a high potential for earlier diagnosis of VS by improving the awareness of early symptoms.
PPAR as a new therapeutic target in inflammatory bowel diseases
Authors: L Dubuquoy
Journal: Gut (2006)

The peroxisome proliferator activated receptor gamma(PPARgamma) is a nuclear receptor highly expressed in the colon and playing a key role in bacterial induced inflammation. Regulation of colon inflammation by this receptor has been well demonstrated in many experimental models of colitis but also in patients with ulcerative colitis, characterised by impaired expression of PPARgamma confined to their colon epithelial cells. Recent data showing that PPARgamma was the major functional receptor mediating the common aminosalicylate activities in inflammatory bowel diseases (IBD) have also reinforced the roles of this receptor in the control of intestinal inflammation. The aims of this review are to discuss the potential roles of PPARgamma in the physiopathology of IBD, as well as the emerging therapeutic strategies targeting this receptor.
The 1 alpha-hydroxylase locus is not linked to calcium stone formation or calciuric phenotypes in French-Canadian families.
Authors: P Scott, D Ouimet, Y Proulx, M L Trouvé, G Guay, B Gagnon, L Valiquette, A Bonnardeaux
Journal: Journal of the American Society of Nephrology (1998)

Calcium urolithiasis is often associated with increased intestinal absorption and urine excretion of calcium, and has been suggested to result from increased vitamin D production. The role of the enzyme 1 alpha-hydroxylase, the rate-limiting step in active vitamin D production, was evaluated in 36 families, including 28 sibships with at least a pair of affected sibs, using qualitative and quantitative trait linkage analyses. Sibs with a verified calcium urolithiasis passage (n = 117) had higher 24-h calciuria (P = 0.03), oxaluria (P = 0.02), fasting and postcalcium loading urine calcium/creatinine (Ca/cr) ratios (P = 0.008 and P = 0.002, respectively), and serum 1,25(OH)2 vitamin D levels (P = 0.02) compared with nonstone-forming sibs (n = 120). Markers from a 9-centiMorgan interval encompassing the VDD1 locus on chromosome 12q13-14 (putative 1 alpha-hydroxylase) were analyzed in 28 sibships (146 sib pairs) of single and recurrent stone formers and in 14 sibships (65 sib pairs) with recurrent-only (> or = 3 episodes) stone-forming sibs. Two-point and multipoint analyses did not reveal excess in alleles shared among affected sibs at the VDD1 locus. Linkage of stone formation to the VDD1 locus could be excluded, respectively, with a lambda d of 2.0 (single and recurrent stone formers) and 3.25 (recurrent stone formers). Quantitative trait analyses revealed no evidence for linkage to 24-h calciuria and oxaluria, serum 1,25(OH)2 vitamin D levels, and Ca/cr ratios. This study shows absence of linkage of the putative 1 alpha-hydroxylase locus to calcium stone formation or to quantitative traits associated with idiopathic hypercalciuria. In addition, there is coaggregation of calciuric and oxaluric phenotypes with stone formation.
Phase III Study of Weekly High-Dose Infusional Fluorouracil Plus Folinic Acid With or Without Irinotecan in Patients With Metastatic Colorectal Cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986
Authors: C.-H. Köhne, E. van Cutsem, J. Wils, C. Bokemeyer, M. El-Serafi, M.P. Lutz, M. Lorenz, P. Reichardt, H. Rückle-Lanz, N. Frickhofen, R. Fuchs, H.-G. Mergenthaler, T. Langenbuch, U. Vanhoefer, P. Rougier, R. Voigtmann, L. Müller, B. Genicot, Ö. Anak, B. Nordlinger
Journal: Journal of Clinical Oncology (2005)

To demonstrate that adding irinotecan to a standard weekly schedule of high-dose, infusional fluorouracil (FU) and leucovorin (folinic acid [FA]) can prolong progression-free survival (PFS).Four hundred thirty patients with measurable or assessable metastatic colorectal cancer were randomly assigned to receive either FA 500 mg/m(2) as a 2-hour infusion and FU 2.6 g/m(2) by intravenous 24-hour infusion, both administered weekly for 6 weeks, followed by a 2-week rest (Arbeitsgemeinschaft für Internistische Onkologie [AIO] arm, n = 216), or a similar schedule but with FU 2.3 or 2.0 g/m(2) preceded by irinotecan 80 mg/m(2) administered over 30 minutes (experimental group, n = 214).The median PFS time in the experimental group was 8.5 months (95% CI, 7.6 to 9.9 months) compared with 6.4 months (95% CI, 5.3 to 7.2 months) in the AIO arm (P < .0001). The median overall survival time was increased from 16.9 to 20.1 months (P = .2779). The objective response rate was 62.2% (95% CI, 55.0% to 69.5%) in the experimental group and 34.4% (95% CI, 27.5% to 41.3%) in the AIO arm (P < .0001).The addition of irinotecan to the standard AIO FU/FA regimen was associated with a highly significant improvement in PFS and response rate and was well tolerated. The results of this study confirm that irinotecan in combination with high-dose infusional FU/FA is a reference first-line treatment.
Rheumatoid arthritis bone erosion volumes on CT and MRI: reliability and correlations with erosion scores on CT, MRI and radiography
Authors: U. M. Dohn, B. J Ejbjerg, M. Hasselquist, E. Narvestad, M. Court-Payen, M. Szkudlarek, J. Moller, H. S Thomsen, M. Ostergaard
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> To investigate intramodality and intermodality agreements of CT and MRI erosion volumes in metacarpophalangeal (MCP) joints in rheumatoid arthritis (RA), and to compare the volumes with erosion scores for CT, MRI and radiography. <h3>Methods:</h3> In total, 17 patients with RA and four healthy controls underwent unilateral CT, MRI and radiography of second to fifth MCP joints in one hand. Erosion volumes (using OSIRIS software) and scores were determined from CT, MRI and radiography (scores only). <h3>Results:</h3> CT, MRI and radiography detected 77, 62 and 12 erosions, respectively. On CT, the mean erosion volume was 26 mm<sup>3</sup> (median 10; range 0 to 248) and 30 mm<sup>3</sup> (18; 1 to 163) on MRI. Total erosion volumes (per patient/control) were 97 mm<sup>3</sup> (29; 0 to 485) on CT and 90 mm<sup>3</sup> (46; 0 to 389) on MRI. For volumes, Spearman correlation coefficients were 0.96 to 0.99 (CT vs CT), 0.95 to 0.98 (MRI vs MRI) and 0.64 to 0.89 (CT vs MRI), all p&lt;0.01. MRI erosion volumes correlated with the Outcome Measures in Rheumatology Clinical Trials/Rheumatoid Arthritis Magnetic Resonance Imaging Score (OMERACT RAMRIS) erosion scores (0.91 to 0.99; p&lt;0.01) and the Sharp/van der Heijde erosion score (0.49 to 0.63; p&lt;0.01). <h3>Conclusion:</h3> Very high intramodality and high intermodality agreements of CT and MRI erosion volumes were found, encouraging further testing in longitudinal studies. A close correlation with CT and MRI erosion volumes supports the OMERACT RAMRIS erosion score as a valid measure of joint destruction in RA.
Diabetes-induced Coronary Vascular Dysfunction Involves Increased Arginase Activity
Authors: Maritza J. Romero, Daniel H. Platt, Huda E. Tawfik, Mohamed Labazi, Azza B. El-Remessy, Manuela Bartoli, Ruth B. Caldwell, Robert W. Caldwell
Journal: Circulation Research (2007)

Increases in arginase activity have been reported in a variety of disease conditions characterized by vascular dysfunction. Arginase competes with NO synthase for their common substrate arginine, suggesting a cause and effect relationship. We tested this concept by experiments with streptozotocin diabetic rats and high glucose (HG)-treated bovine coronary endothelial cells (BCECs). Our studies showed that diabetes-induced impairment of vasorelaxation to acetylcholine was correlated with increases in reactive oxygen species and arginase activity and arginase I expression in aorta and liver. Treatment of diabetic rats with simvastatin (5 mg/kg per day, subcutaneously) or L-citrulline (50 mg/kg per day, orally) blunted these effects. Acute treatment of diabetic coronary arteries with arginase inhibitors also reversed the impaired vasodilation to acetylcholine. Treatment of BCECs with HG (25 mmol/L, 24 hours) also increased arginase activity. This effect was blocked by treatment with simvastatin (0.1 micromol/L), the Rho kinase inhibitor Y-27632 (10 micromol/L), or L-citrulline (1 mmol/L). Superoxide and active RhoA levels also were elevated in HG-treated BCECs. Furthermore, HG significantly diminished NO production in BCECs. Transfection of BCECs with arginase I small interfering RNA prevented the rise in arginase activity in HG-treated cells and normalized NO production, suggesting a role for arginase I in reduced NO production with HG. These results indicate that increased arginase activity in diabetes contributes to vascular endothelial dysfunction by decreasing L-arginine availability to NO synthase.
Is a Retrovirus Implicated in Familial Prostate Cancer?
Authors: Vicki Brower
Journal: JNCI Journal of the National Cancer Institute (2009)

Three years ago, researchers discovered a retrovirus that appeared to be more common in the tumors of men with familial prostate cancer than in those with sporadic prostate cancer. Since then, the virus, XMRV, has become the focus of a growing number of studies in the U.S. and elsewhere. Not everyone agrees that XMRV is involved in familial prostate cancer, but there is little doubt that the discovery has attracted the attention of viral researchers. That’s partly because XMRV is one of a very few authentic, known human retroviruses, said Stephen Goff , Ph.D., who heads a laboratory studying retrovirus replication at Columbia University in New York. Although retroviruses have long been implicated in animal cancers, only three — human T-lymphotropic viruses 1 and 2 and human immunodefi ciency virus — have been linked to cancer
Patching the Heart
Authors: Lei Ye, Wolfram-Hubertus Zimmermann, Daniel J Garry, Jianyi Zhang
Journal: Circulation Research (2013)

Transplantation of engineered tissue patches containing either progenitor cells or cardiomyocytes for cardiac repair is emerging as an exciting treatment option for patients with postinfarction left ventricular remodeling. The beneficial effects may evolve directly from remuscularization or indirectly through paracrine mechanisms that mobilize and activate endogenous progenitor cells to promote neovascularization and remuscularization, inhibit apoptosis, and attenuate left ventricular dilatation and disease progression. Despite encouraging results, further improvements are necessary to enhance current tissue engineering concepts and techniques and to achieve clinical impact. Herein, we review several strategies for cardiac remuscularization and paracrine support that can induce cardiac repair and attenuate left ventricular dysfunction from both within and outside the myocardium.
Erythrokeratoderma variabilis-like ichthyosis in Chanarin-Dorfman syndrome
Authors: R.M. Pujol, M. Gilaberte, A. Toll, L. Florensa, J. Lloreta, M.A. Gonzalez-Ensenat, J. Fischer, A. Azon
Journal: British Journal of Dermatology (2005)

Journal Article Erythrokeratoderma variabilis‐like ichthyosis in Chanarin–Dorfman syndrome Get access R.M. Pujol, R.M. Pujol Departments of Dermatology and Pathology, Hospital del Mar, IMAS, Passeig Maritim 25–29, 08003 Barcelona, Spain Ramon M. Pujol. E‐mail: rpujol@imas.imim.es Search for other works by this author on: Oxford Academic Google Scholar M. Gilaberte, M. Gilaberte Departments of Dermatology and Pathology, Hospital del Mar, IMAS, Passeig Maritim 25–29, 08003 Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar A. Toll, A. Toll Departments of Dermatology and Pathology, Hospital del Mar, IMAS, Passeig Maritim 25–29, 08003 Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar L. Florensa, L. Florensa Departments of Dermatology and Pathology, Hospital del Mar, IMAS, Passeig Maritim 25–29, 08003 Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar J. Lloreta, J. Lloreta Departments of Dermatology and Pathology, Hospital del Mar, IMAS, Passeig Maritim 25–29, 08003 Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar M.A. González‐Enseñat, M.A. González‐Enseñat Department of Dermatology, Hospital Sant Joan de Deu, Barcelona, Spain Search for other works by this author on: Oxford Academic Google Scholar J. Fischer, J. Fischer Centre National de Génotypage, Evry, France Search for other works by this author on: Oxford Academic Google Scholar A. Azon A. Azon Department of Dermatology, Hospital Universitari Sant Joan, Reus, Spain Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 4, 1 October 2005, Pages 838–841, https://doi.org/10.1111/j.1365-2133.2005.06828.x Published: 01 October 2005 Article history Accepted: 13 March 2005 Published: 01 October 2005
Cholesterol net transport, esterification, and transfer in human hyperlipidemic plasma.
Authors: P E Fielding, C J Fielding, R J Havel, J P Kane, P Tun
Journal: Journal of Clinical Investigation (1983)

Cholesterol esterification, cholesteryl ester transfer between lipoproteins, and cholesterol transport between lipoproteins and cultured cells have been measured in the plasma of 22 patients with primary hyperlipidemia and 10 normolipidemic subjects. In hyperbetalipoproteinemia, increase in plasma low density lipoprotein levels was associated with a reduction of cholesteryl ester transfer rates, and with a reversal of the normal direction of sterol transport between fibroblasts and their plasma culture medium. Instead of net transport from cells to medium there was a net uptake of sterol from plasma by the cells, despite a level of plasma lecithin/cholesterol acyltransferase activity that was within the normal range. In dysbetalipoproteinemia, esterification rates were increased above normal levels, but cholesteryl ester transfer was reduced and the direction of sterol transport between the cells and plasma medium was reversed, as in the hyperbetalipoproteinemic group. In hypertriglyceridemia, those subjects with cardiovascular disease showed a metabolic pattern similar to the hyperbetalipoproteinemic group. The subjects in this group without symptoms of cardiovascular disease showed a normal direction of sterol transport, normal or raised rates of cholesteryl ester transfer between lipoproteins, and an increased rate of sterol esterification in plasma that decreased towards normal levels as plasma triglyceride levels decreased. Despite their quite distinct metabolic patterns there was no consistent difference between the two hypertriglyceridemic groups in triglyceride or cholesterol levels, very low density lipoprotein composition, or electrophoretic or isoelectric focussing patterns. All hypertriglyceridemic subjects with documented cardiovascular disease showed reversed cell-plasma sterol transport and all subjects without such disease showed a normal direction of cell-plasma sterol transport. The results of this study indicate major and reproducible abnormalities in plasma cholesterol metabolism in several groups of subjects with genetically distinct hyperlipidemias, who are at risk for atherosclerotic vascular disease. The possible predictive value of sterol metabolic measurements in the analysis of cardiovascular disease is discussed.
Prenatal Organochlorine and Methylmercury Exposure and Memory and Learning in School-Age Children in Communities Near the New Bedford Harbor Superfund Site, Massachusetts
Authors: Sara T.C. Orenstein, Sally W. Thurston, David C. Bellinger, Joel D. Schwartz, Chitra J. Amarasiriwardena, Larisa M. Altshul, Susan A. Korrick
Journal: Environmental Health Perspectives (2014)

Background: Polychlorinated biphenyls (PCBs), organochlorine pesticides, and methylmercury (MeHg) are environmentally persistent with adverse effects on neurodevelopment. However, especially among populations with commonly experienced low levels of exposure, research on neurodevelopmental effects of these toxicants has produced conflicting results.Objectives: We assessed the association of low-level prenatal exposure to these contaminants with memory and learning.Methods: We studied 393 children, born between 1993 and 1998 to mothers residing near a PCB-contaminated harbor in New Bedford, Massachusetts. Cord serum PCB, DDE (dichlorodiphenyldichloroethylene), and maternal peripartum hair mercury (Hg) levels were measured to estimate prenatal exposure. Memory and learning were assessed at 8 years of age (range, 7–11 years) using the Wide Range Assessment of Memory and Learning (WRAML), age-standardized to a mean ± SD of 100 ± 15. Associations with each WRAML index—Visual Memory, Verbal Memory, and Learning—were examined with multivariable linear regression, controlling for potential confounders.Results: Although cord serum PCB levels were low (sum of four PCBs: mean, 0.3 ng/g serum; range, 0.01–4.4), hair Hg levels were typical of the U.S. fish-eating population (mean, 0.6 μg/g; range, 0.3–5.1). In multivariable models, each microgram per gram increase in hair Hg was associated with, on average, decrements of –2.8 on Visual Memory (95% CI: –5.0, –0.6, p = 0.01), –2.2 on Learning (95% CI: –4.6, 0.2, p = 0.08), and –1.7 on Verbal Memory (95% CI: –3.9, 0.6, p = 0.14). There were no significant adverse associations of PCBs or DDE with WRAML indices.Conclusions: These results support an adverse relationship between low-level prenatal MeHg exposure and childhood memory and learning, particularly visual memory.Citation: Orenstein ST, Thurston SW, Bellinger DC, Schwartz JD, Amarasiriwardena CJ, Altshul LM, Korrick SA. 2014. Prenatal organochlorine and methylmercury exposure and memory and learning in school-age children in communities near the New Bedford Harbor Superfund Site, Massachusetts. Environ Health Perspect 122:1253–1259; http://dx.doi.org/10.1289/ehp.1307804
DRD2 Promoter Region Variation as a Predictor of Sustained Response to Antipsychotic Medication in First-Episode Schizophrenia Patients
Authors: Todd Lencz, Delbert G. Robinson, Ke Xu,, Jenny Ekholm, Serge Sevy, Handan Gunduz-Bruce, Margaret G. Woerner, John M. Kane, David Goldman, Anil K. Malhotra
Journal: American Journal of Psychiatry (2006)

All antipsychotics act on the dopamine D(2) receptor. The present study extends prior pharmacogenetic investigations of the D(2) receptor gene (DRD2) by examining, in first-episode schizophrenia patients, promoter region variation as a predictor of response time to two first-line atypical antipsychotics.Patients experiencing their first episode of schizophrenia (N=61) were genotyped for two DRD2 promoter region polymorphisms (A-241G and -141C Ins/Del) and were randomly assigned to receive 16 weeks of treatment with either risperidone or olanzapine. Time until sustained response (two consecutive ratings without significant positive symptoms) for rare allele carriers versus wild types was examined by using Kaplan-Meier curves.Relative to wild type homozygotes, G carriers (A-241G) exhibited a significantly faster time until response, whereas -141C Del carriers took a significantly longer time to respond. Diplotype analysis revealed similar results.These findings suggest that variation in the D(2) receptor gene can, in part, explain variation in the timing of clinical response to antipsychotics in patients with first-episode schizophrenia.
Priority Setting for Pandemic Influenza: An Analysis of National Preparedness Plans
Authors: Lori Uscher-Pines, Saad B Omer, Daniel J Barnett, Thomas A Burke, Ran D Balicer
Journal: PLoS Medicine (2006)

The authors provide a targeted review of national pandemic influenza plans from the developed and developing world, describing national variations in prioritization of vaccines and antiviral medications.