tbuckley/cabot-search huggingface dataset:
Long-Term Ambulatory Peritoneal Insulin Infusion of Brittle Diabetes with Portable Pumps: Comparison with Intravenous and Subcutaneous Routes
Authors: J L Selam, A Slingeneyer, B Hedon, P Mares, J J Beraud, J Mirouze
Journal: Diabetes Care (1983)

This work compares different routes of insulin infusion via portable pumps with chronically implanted catheters and evaluates the long-term feasibility of the technique. Six severely unstable (i.e., uncontrolled by optimized intensive insulin therapy) diabetic individuals (age range: 35 +/- 4 yr; duration: 11 +/- 2 yr) were selected. Promedos pumps (Siemens A. G., Erlangen, West Germany) were exclusively used because of their portability and long-life insulin reservoir (1-mo duration with U40 acidic Hoechst insulin). Each patient underwent three randomized 1-mo periods of insulin infusion: subcutaneous (s.c.), intravenous (i.v.), and intraperitoneal (i.p.) before the catheter was left indefinitely in one of these sites. Diabetic control was improved and insulin doses reduced whatever the route of infusion, although the s.c. route gave slightly higher values. These results did not deteriorate with time: mean blood glucose was 126 +/- 3 mg/dl and HbA1 was 8.3 +/- 0.6% after 10-18 mo of constant infusion versus 237 +/- 35 mg/dl and 10.0 +/- 0.8%, respectively, under conventional therapy. From a practical point of view, the i.p. route seems preferable since all s.c. catheters provoked local reactions after less than 1 mo and the two chronic i.v. catheters obstructed after 8 and 9 mo. All other incidents were minor and curable without removal of the catheters. All patients argued improvement of both diabetes and quality of life and no one has resigned so far. Thus, the i.p. infusion technique seems beneficial to unstable diabetic individuals and adaptable to long-term therapy, although intensive education and careful follow-up are necessary.
Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD.
Authors: V M Keatings, A Jatakanon, Y M Worsdell, P J Barnes
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The role of glucocorticoids in the treatment of chronic obstructive pulmonary disease (COPD) is controversial. We have previously described high numbers of neutrophils and high concentrations of the inflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha), and of the cell activation markers eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), myeloperoxidase (MPO), and human neutrophil lipocalin (HNL) in COPD patients as compared with controls, and have postulated that the cytokines TNF-alpha and IL-8 play a role in propagating the inflammatory response in COPD. We have now studied the effects of inhaled and oral glucocorticoids on these inflammatory indices in induced sputum. Initially, we studied the effect of a 2-wk course of inhaled budesonide (800 mg twice daily for 2 wk) in 13 patients with severe COPD (mean FDV1: 35% predicted). There was no clinical benefit in either lung function or symptom scores, and no significant change in the inflammatory indices as measured by total and differential cell counts and concentrations of TNF-alpha eosinophil activation markers ECP and EPO, and neutrophil activation markers MPO and HNL. Because the lack of anti-inflammatory effect might have been due to poor drug delivery as a result of severe airflow limitation, we undertook a study examining the antiinflammatory effect of oral prednisolone (30 mg daily for 2 wk) in patients with COPD and undertook the same measurements in 10 patients with atopic asthma. Sputum eosinophil numbers, ECP, and EPO were significantly reduced in the asthmatic patients but were not modified in COPD. This confirms the clinical impression that inhaled steroids have little antiinflammatory effect, at least in the short term in this group of patients, and suggests that the inflammatory process in COPD is resistant to the antiinflammatory effect of glucocorticoids.
Statistical analysis of the lactulose/breath hydrogen test in the measurement of orocaecal transit: its variability and predictive value in assessing drug action.
Authors: D H Staniforth, D Rose
Journal: Gut (1989)

The variability in the orocaecal transit time as measured by the lactulose/breath hydrogen method has been studied for three conditions: lactulose given with a meal, subjects sitting; lactulose given with a meal, subjects semirecumbent; lactulose given in aqueous solution, subjects semirecumbent. Thirty three healthy subjects attended on up to 12 occasions. It was found that administration of the lactulose with a meal significantly reduced the variability (p less than 0.05) and that adoption of the semirecumbent position further reduced variability. A power analysis was used to predict the number of subjects who would be required to show a given percentage change in orocaecal transit time at specified probabilities and powers. A graph and a table for use in the prediction of subject numbers at a probability of 5% and for powers of 50-99% is presented. A dose response curve for metoclopramide using the lactulose/breath hydrogen method is given for doses of 10, 15, and 20 mg.
Role of Financial Relationships in Economic Analyses of Targeted Therapies in Oncology Remains Unclear
Authors: Henry Jacob Conter
Journal: Journal of Clinical Oncology (2012)

TO THE EDITOR: In their systematic review of financial relationships and their effects on the results of cost-effectiveness studies, Valachis et al examined the qualitative conclusions of such studies and determined that funding from manufacturers introduces bias. However, conclusions of cost-effectiveness analyses depend on both the calculated cost outcome (eg, cost per quality-adjusted life year) and the threshold value used as the reference standard. Conceivably, two cost-effectiveness analyses could report the same cost per qualityadjusted life year for a new therapy, but arrive at contradictory conclusions on the basis of their concept of what should be considered cost-effective. Valachis et al do not provide data relating to the opportunity cost estimates determined by their included studies. So readers are left wondering whether a sufficient fundamental research bias exists in industry-sponsored cost-effectiveness analyses to support the authors’ call for so-called balanced funding for future analyses, or if this favorable difference merely represents enthusiastic conclusions from those who support higher cost-effectiveness thresholds.
Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field
Authors: S. Ogino, A. T. Chan, C. S. Fuchs, E. Giovannucci
Journal: Gut (2010)

Colorectal cancer is a complex disease resulting from somatic genetic and epigenetic alterations, including locus-specific CpG island methylation and global DNA or LINE-1 hypomethylation. Global molecular characteristics such as microsatellite instability (MSI), CpG island methylator phenotype (CIMP), global DNA hypomethylation, and chromosomal instability cause alterations of gene function on a genome-wide scale. Activation of oncogenes including <i>KRAS</i>, <i>BRAF</i> and <i>PIK3CA</i> affects intracellular signalling pathways and has been associated with CIMP and MSI. Traditional epidemiology research has investigated various factors in relation to an overall risk of colon and/or rectal cancer. However, colorectal cancers comprise a heterogeneous group of diseases with different sets of genetic and epigenetic alterations. To better understand how a particular exposure influences the carcinogenic and pathologic process, somatic molecular changes and tumour biomarkers have been studied in relation to the exposure of interest. Moreover, an investigation of interactive effects of tumour molecular changes and the exposures of interest on tumour behaviour (prognosis or clinical outcome) can lead to a better understanding of tumour molecular changes, which may be prognostic or predictive tissue biomarkers. These new research efforts represent ‘molecular pathologic epidemiology’, which is a multidisciplinary field of investigations of the inter-relationship between exogenous and endogenous (eg, genetic) factors, tumoural molecular signatures and tumour progression. Furthermore, integrating genome-wide association studies (GWAS) with molecular pathological investigation is a promising area (GWAS-MPE approach). Examining the relationship between susceptibility alleles identified by GWAS and specific molecular alterations can help elucidate the function of these alleles and provide insights into whether susceptibility alleles are truly causal. Although there are challenges, molecular pathological epidemiology has unique strengths, and can provide insights into the pathogenic process and help optimise personalised prevention and therapy. In this review, we overview this relatively new field of research and discuss measures to overcome challenges and move this field forward.
Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions
Authors: Matteo Fumagalli, Uberto Pozzoli, Rachele Cagliani, Giacomo P. Comi, Stefania Riva, Mario Clerici, Nereo Bresolin, Manuela Sironi
Journal: The Journal of Experimental Medicine (2009)

Many human genes have adapted to the constant threat of exposure to infectious agents; according to the "hygiene hypothesis," lack of exposure to parasites in modern settings results in immune imbalances, augmenting susceptibility to the development of autoimmune and allergic conditions. Here, by estimating the number of pathogen species/genera in a specific geographic location (pathogen richness) for 52 human populations and analyzing 91 interleukin (IL)/IL receptor genes (IL genes), we show that helminths have been a major selective force on a subset of these genes. A population genetics analysis revealed that five IL genes, including IL7R and IL18RAP, have been a target of balancing selection, a selection process that maintains genetic variability within a population. Previous identification of polymorphisms in some of these loci, and their association with autoimmune conditions, prompted us to investigate the relationship between adaptation and disease. By searching for variants in IL genes identified in genome-wide association studies, we verified that six risk alleles for inflammatory bowel (IBD) or celiac disease are significantly correlated with micropathogen richness. These data support the hygiene hypothesis for IBD and provide a large set of putative targets for susceptibility to helminth infections.
Biotype as determinant of natural immunising effect of cholera
Authors: J.D. Clemens, F. van Loon, D.A. Sack, M.R. Rao, F. Ahmed, J. Chakraborty, B.A. Kay, M.R. Khan, M. Yunus, J.R. Harris, J.D. Clemens, M.R. Rao, D.A. Sack, J.R. Harris, J.D. Clemens, M.R. Rao, A-M. Svennerholm, J. Holmgren
Journal: The Lancet (1991)
Ancestry-related assortative mating in Latino populations
Authors: Neil Risch, Shweta Choudhry, Marc Via, Analabha Basu, Ronnie Sebro, Celeste Eng, Kenneth Beckman, Shannon Thyne, Rocio Chapela, Jose R Rodriguez-Santana, William Rodriguez-Cintron, Pedro C Avila, Elad Ziv, Esteban Gonzalez Burchard
Journal: Genome biology (2009)

While spouse correlations have been documented for numerous traits, no prior studies have assessed assortative mating for genetic ancestry in admixed populations.Using 104 ancestry informative markers, we examined spouse correlations in genetic ancestry for Mexican spouse pairs recruited from Mexico City and the San Francisco Bay Area, and Puerto Rican spouse pairs recruited from Puerto Rico and New York City. In the Mexican pairs, we found strong spouse correlations for European and Native American ancestry, but no correlation in African ancestry. In the Puerto Rican pairs, we found significant spouse correlations for African ancestry and European ancestry but not Native American ancestry. Correlations were not attributable to variation in socioeconomic status or geographic heterogeneity. Past evidence of spouse correlation was also seen in the strong evidence of linkage disequilibrium between unlinked markers, which was accounted for in regression analysis by ancestral allele frequency difference at the pair of markers (European versus Native American for Mexicans, European versus African for Puerto Ricans). We also observed an excess of homozygosity at individual markers within the spouses, but this provided weaker evidence, as expected, of spouse correlation. Ancestry variance is predicted to decline in each generation, but less so under assortative mating. We used the current observed variances of ancestry to infer even stronger patterns of spouse ancestry correlation in previous generations.Assortative mating related to genetic ancestry persists in Latino populations to the current day, and has impacted on the genomic structure in these populations.
Good clinical practice: a way to better drugs.
Authors: E F Hvidberg
Journal: BMJ (1989)

best kind."IRecently the Wolfson Research Laboratories have invited all general practitioners with desktop instruments for measuring plasma cholesterol concentration to participate in a national quality assessment programme'2; local biochemistry or haematology laboratories will be in a good position to provide advice about other schemes and back up services.Desktop microanalysers have come of age, but the far reaching consequences of their uncontrolled use have not been fully grasped by the early adopters of this new tech- nology.If a new technology is really essential in modern primary health care it must be introduced in a patient centred way that researches the risks, benefits, and opportunity costs so that what the government calls "customers" can at least know that their doctors are striving for an informed pro- fessional view of what is in their best interests and applying it responsibly.Internal and external quality control of bio- medical assays and the risks of cross infection from other diagnostic equipment are important issues for general practi- tioners and primary care nursing staff today.
Inhibition of nitric oxide and reactive oxygen species production improves the ability of a sunscreen to protect from sunburn, immunosuppression and photocarcinogenesis
Authors: P.A.J. Russo, G.M. Halliday
Journal: British Journal of Dermatology (2006)

Journal Article Inhibition of nitric oxide and reactive oxygen species production improves the ability of a sunscreen to protect from sunburn, immunosuppression and photocarcinogenesis Get access P.A.J. Russo, P.A.J. Russo Discipline of Medicine (Dermatology), Melanoma and Skin Cancer Research Institute, Sydney Cancer Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW 2006, Australia Search for other works by this author on: Oxford Academic Google Scholar G.M. Halliday G.M. Halliday Discipline of Medicine (Dermatology), Melanoma and Skin Cancer Research Institute, Sydney Cancer Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW 2006, Australia Gary Halliday. E‐mail: garyh@med.usyd.edu.au Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 155, Issue 2, 1 August 2006, Pages 408–415, https://doi.org/10.1111/j.1365-2133.2006.07339.x Published: 01 August 2006 Article history Accepted: 09 February 2006 Published: 01 August 2006
<i>ANGPT2</i> Genetic Variant Is Associated with Trauma-associated Acute Lung Injury and Altered Plasma Angiopoietin-2 Isoform Ratio
Authors: Nuala J. Meyer, Mingyao Li, Rui Feng, Jonathan Bradfield, Robert Gallop, Scarlett Bellamy, Barry D. Fuchs, Paul N. Lanken, Steven M. Albelda, Melanie Rushefski, Richard Aplenc, Helen Abramova, Elena N. Atochina-Vasserman, Michael F. Beers, Carolyn S. Calfee, Mitchell J. Cohen, Jean-Francois Pittet, David C. Christiani, Grant E. O'Keefe, Lorraine B. Ware, Addison K. May, Mark M. Wurfel, Hakon Hakonarson, Jason D. Christie
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Acute lung injury (ALI) acts as a complex genetic trait, yet its genetic risk factors remain incompletely understood. Large-scale genotyping has not previously been reported for ALI.To identify ALI risk variants after major trauma using a large-scale candidate gene approach.We performed a two-stage genetic association study. We derived findings in an African American cohort (n = 222) using a cardiopulmonary disease-centric 50K single nucleotide polymorphism (SNP) array. Genotype and haplotype distributions were compared between subjects with ALI and without ALI, with adjustment for clinical factors. Top performing SNPs (P < 10(-4)) were tested in a multicenter European American trauma-associated ALI case-control population (n = 600 ALI; n = 2,266 population-based control subjects) for replication. The ALI-associated genomic region was sequenced, analyzed for in silico prediction of function, and plasma was assayed by ELISA and immunoblot.Five SNPs demonstrated a significant association with ALI after adjustment for covariates in Stage I. Two SNPs in ANGPT2 (rs1868554 and rs2442598) replicated their significant association with ALI in Stage II. rs1868554 was robust to multiple comparison correction: odds ratio 1.22 (1.06-1.40), P = 0.0047. Resequencing identified predicted novel splice sites in linkage disequilibrium with rs1868554, and immunoblots showed higher proportion of variant angiopoietin-2 (ANG2) isoform associated with rs1868554T (0.81 vs. 0.48; P = 0.038).An ANGPT2 region is associated with both ALI and variation in plasma angiopoietin-2 isoforms. Characterization of the variant isoform and its genetic regulation may yield important insights about ALI pathogenesis and susceptibility.
Inhibition of T lymphocyte activation in mice heterozygous for loss of the IMPDH II gene
Authors: Jing Jin Gu, Sander Stegmann, Karen Gathy, Robert Murray, Josee Laliberte, Lanier Ayscue, Beverly S. Mitchell
Journal: Journal of Clinical Investigation (2000)

Inosine 5′-monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in the de novo synthesis of guanine nucleotides, which are also synthesized from guanine by a salvage reaction catalyzed by the X chromosome–linked enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Since inhibitors of IMPDH are in clinical use as immunosuppressive agents, we have examined the consequences of knocking out the IMPDH type II enzyme by gene targeting in a mouse model. Loss of both alleles of the gene encoding this enzyme results in very early embryonic lethality despite the presence of IMPDH type I and HPRT activities. Lymphocytes from IMPDH II+/– heterozygous mice are normal with respect to subpopulation distribution and respond normally to a variety of mitogenic stimuli. However, mice with an IMPDH II+/–, HPRT–/o genotype demonstrate significantly decreased lymphocyte responsiveness to stimulation with anti-CD3 and anti-CD28 antibodies and show a 30% mean reduction in GTP levels in lymphocytes activated by these antibodies. Furthermore, the cytolytic activity of their T cells against allogeneic target cells is significantly impaired. These results demonstrate that a moderate decrease in the ability of murine lymphocytes to synthesize guanine nucleotides during stimulation results in significant impairment in T-cell activation and function.
Effects of Resistance Exercise Training and Nandrolone Decanoate on Body Composition and Muscle Function among Patients Who Receive Hemodialysis
Authors: Kirsten L. Johansen, Patricia L. Painter, Giorgos K. Sakkas, Patricia Gordon, Julie Doyle, Tiffany Shubert
Journal: Journal of the American Society of Nephrology (2006)

Patients who are on hemodialysis commonly experience muscle wasting and weakness, which have a negative effect on physical functioning and quality of life. The objective of this study was to determine whether anabolic steroid administration and resistance exercise training induce anabolic effects among patients who receive maintenance hemodialysis. A randomized 2 x 2 factorial trial of anabolic steroid administration and resistance exercise training was conducted in 79 patients who were receiving maintenance hemodialysis at University of California, San Francisco-affiliated dialysis units. Interventions included double-blinded weekly nandrolone decanoate (100 mg for women; 200 mg for men) or placebo injections and lower extremity resistance exercise training for 12 wk during hemodialysis sessions three times per week using ankle weights. Primary outcomes included change in lean body mass (LBM) measured by dual-energy x-ray absorptiometry, quadriceps muscle cross-sectional area measured by magnetic resonance imaging, and knee extensor muscle strength. Secondary outcomes included changes in physical performance, self-reported physical functioning, and physical activity. Sixty-eight patients completed the study. Patients who received nandrolone decanoate increased their LBM by 3.1 +/- 2.2 kg (P < 0.0001). Exercise did not result in a significant increase in LBM. Quadriceps muscle cross-sectional area increased in patients who were assigned to exercise (P = 0.01) and to nandrolone (P < 0.0001) in an additive manner. Patients who exercised increased their strength in a training-specific fashion, and exercise was associated with an improvement in self-reported physical functioning (P = 0.04 compared with nonexercising groups). Nandrolone decanoate and resistance exercise produced anabolic effects among patients who were on hemodialysis. Further studies are needed to determine whether these interventions improve survival.
Proteomic Profiling Reveals Autoimmune Targets in Sarcoidosis
Authors: Anna Häggmark, Carl Hamsten, Emil Wiklundh, Cecilia Lindskog, Cecilia Mattsson, Eni Andersson, Ingrid E. Lundberg, Hans Grönlund, Jochen M. Schwenk, Anders Eklund, Johan Grunewald, Peter Nilsson
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: There is a need to further characterize the antibody repertoire in relation to sarcoidosis and potentially related autoantigens.Objectives: We investigated bronchoalveolar lavage (BAL) and serum samples from patients with sarcoidosis and healthy and diseased control subjects to discover sarcoidosis-associated autoantigens.Methods: Antigen microarrays built on 3,072 protein fragments were used to screen for IgG reactivity in 73 BAL samples from subjects with sarcoidosis, subjects with asthma, and healthy subjects. A set of 131 targets were selected for subsequent verification on suspension bead arrays using 272 additional BAL samples and 141 paired sera. Reactivity to four antigens was furthermore analyzed in 22 unprocessed BAL samples from patients with fibrosis and 269 plasma samples from patients diagnosed with myositis.Measurements and Main Results: Reactivity toward zinc finger protein 688 and mitochondrial ribosomal protein L43 were discovered with higher frequencies in patients with sarcoidosis, for mitochondrial ribosomal protein L43 especially in patients with non–Löfgren syndrome. Increased reactivity toward nuclear receptor coactivator 2 was also observed in patients with non–Löfgren syndrome as compared with patients with Löfgren syndrome. The antigen representing adenosine diphosphate–ribosylation factor GTPase activating protein 1 revealed high reactivity frequency in all sample groups but with significantly higher level of IgG reactivities in patients with sarcoidosis.Conclusions: Autoantigen reactivity was present in most BAL and serum samples analyzed, and the results revealed high interindividual heterogeneity, with most of the reactivities observed in single individuals only. Four proteins are here proposed as sarcoidosis-associated autoimmune targets and of interest for further validation in independent cohorts.