tbuckley/cabot-search huggingface dataset:
A Randomized Trial Comparing Continuous Subcutaneous Insulin Infusion of Insulin Aspart Versus Insulin Lispro in Children and Adolescents With Type 1 Diabetes
Authors: Stuart A. Weinzimer, Christine Ternand, Campbell Howard, Cheng-Tao Chang, Dorothy J. Becker, Lori M.B. Laffel
Journal: Diabetes Care (2008)

OBJECTIVE—The safety and efficacy of insulin aspart continuous subcutaneous insulin infusion (CSII) was compared with that of insulin lispro CSII in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS—Children and adolescents aged 4–18 years with diagnosed type 1 diabetes ≥1 year previously and treated with insulin analog in a CSII ≥3 months were randomly assigned 2:1 to 16 weeks of insulin aspart CSII (n = 198) or insulin lispro CSII (n = 100) in this open-label, parallel-group, multicenter study. Standard diabetes safety and efficacy parameters were assessed. RESULTS—Baseline demographics, subject characteristics, and diabetes history were similar between treatment groups. After 16 weeks of treatment, insulin aspart CSII was noninferior to insulin lispro CSII as measured by change in A1C from baseline (aspart, −0.15 ± 0.05%; lispro, −0.05 ± 0.07% [95% CI of the treatment difference −0.27 to 0.07]; P = 0.241). No significant differences between treatment groups were observed in fasting plasma glucose, hyperglycemia, and rates of hypoglycemic episodes. At week 16, 59.7% of subjects in the aspart group and 43.8% of subjects in the lispro groups achieved age-specific American Diabetes Association A1C goals (&amp;lt;8.5% for subjects aged &amp;lt;6 years; &amp;lt;8% for subjects aged 6–18 years) (P = 0.040, corrected for baseline). Daily insulin dose (units per kilogram) was significantly lower at week 16 for subjects treated with aspart compared with those treated with lispro (0.86 ± 0.237 vs. 0.94 ± 0.233, P = 0.018). CONCLUSIONS—Insulin aspart was as safe and effective as insulin lispro for use in a CSII in children and adolescents with type 1 diabetes.
FAILURE OF PROGESTERONE TO ENLARGE SEBACEOUS GLANDS IN THE FEMALE RAT.
Authors: F. J. EBLING
Journal: British Journal of Dermatology (1961)

Journal Article FAILURE OF PROGESTERONE TO ENLARGE SEBACEOUS GLANDS IN THE FEMALE RAT. Get access F. J. EBLING F. J. EBLING Department of Zoology, Sheffield University Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 73, Issue 2, 1 February 1961, Pages 65–68, https://doi.org/10.1111/j.1365-2133.1961.tb14409.x Published: 01 February 1961
IL-10 attenuates TNF- -induced NF B pathway activation and cardiomyocyte apoptosis
Authors: S. Dhingra, A. K. Sharma, R. C. Arora, J. Slezak, P. K. Singal
Journal: Cardiovascular Research (2009)

AimsWe have recently reported that tumour necrosis factor-α (TNF-α) increases oxidative stress and apoptosis in cardiomyocytes by upregulating p38 mitogen-activated protein (MAP) kinase (MAPK) phosphorylation. Interleukin-10 (IL-10) blocked these effects of TNF-α by upregulating extracellular signal-regulated kinase 1/2 (ERK 1/2) MAPK phosphorylation. However, the precise site of this IL-10 action is still unknown, and this is investigated in the present study.
Heterogeneity of antibody response to human platelet transfusion.
Authors: K K Wu, J S Thompson, J A Koepke, J C Hoak, R Flink
Journal: Journal of Clinical Investigation (1976)

To study the antibody response to human platelet transfusions, nine thrombocytopenia patients with bone marrow failure were given 6 U (3X10(11)) of random platelet concentrates twice a week. Before transfusion, none of the patients had preexisting antibodies detectable with lymphocytotoxicity, platelet aggregation, or capillary leukoagglutination techniques. After receiving 18-78 U of platelets, they became refractory to further transfusions of random platelets and alloantibodies were detectable. Two patterns of antibody response could be identified. In three patients, the sera were not lymphocytotoxic with a panel of standard cells in which all the known HLA antigens in the first and second series were represented at least once. Yet, they caused platelet aggregation with 30, 24, and 60%, respectively, of a donor population studied. The aggregating activities were inhibited by antihuman IgG but not by antihuman IgA or antihuman IgM antiserum. The aggregating antibodies could be absorbed out with donor platelets but not lymphocytes or granulocytes. Antibodies from two of these patients aggregated platelets of their respective siblings matched for both HLA haplotypes. Transfusion of platelets from these two siblings did not increase the platelet count while platelets obtained from aggregation-negative donors did. The sera from the remaining six patients were lymphocytotoxic with 15-100% of the panel of standard cells. They also had aggregating antibodies, which could be absorbed out by both platelets and lymphocytes, suggesting that they were HLA antibodies. These data suggest that the development of platelet-specific antibodies may play an important role in the immunological rejection of isologous platelets, and should be considered in the selection of donors for patients who are refractory to platelets from random donors.
Post-ischaemic neovascularization and inflammation
Authors: J.-S. Silvestre, Z. Mallat, A. Tedgui, B. I. Levy
Journal: Cardiovascular Research (2008)

Four principal processes-vasculogenesis, angiogenesis, arteriogenesis, and collateral growth-characterize tissue repair and remodelling in acute and chronic ischaemic vascular diseases. The relative importance of each process remains unclear, but it is likely that they may complement each other. In addition, these processes are driven by distinct, but partially overlapping, cellular and molecular pathways. In particular, inflammation might be one of the most important stimuli for initiation of vessel growth in the setting of ischaemia. Here, we summarize the current knowledge on the inflammatory response in the context of ischaemia and review the major factors that may be involved in inflammation-induced, post-ischaemic neovascularization.
Ultrasound-Mediated Gene and Drug Delivery Using a Microbubble-Liposome Particle System
Authors: Young Il Yoon, Yong-Su Kwon, Hee-Sang Cho, Sun-Hee Heo, Kyeong Soon Park, Sang Gyu Park, Soo-Hong Lee, Seung Il Hwang, Young Il Kim, Hwan Jun Jae, Gook-Jun Ahn, Young-Seok Cho, Hakho Lee, Hak Jong Lee, Tae-Jong Yoon
Journal: Theranostics (2014)

Theranostic agents present a promising clinical approach for cancer detection and treatment.We herein introduce a microbubble and liposome complex (MB-Lipo) developed for ultrasound (US) imaging and activation.The MB-Lipo particles have a hybrid structure consisting of a MB complexed with multiple Lipos.The MB components are used to generate high echo signals in US imaging, while the Lipos serve as a versatile carrier of therapeutic materials.MB-Lipo allows high contrast US imaging of tumor sites.More importantly, the application of high acoustic pressure bursts MBs, which releases therapeutic Lipos and further enhances their intracellular delivery through sonoporation effect.Both imaging and drug release could thus be achieved by a single US modality, enabling in situ treatment guided by real-time imaging.The MB-Lipo system was applied to specifically deliver anti-cancer drug and genes to tumor cells, which showed enhanced therapeutic effect.We also demonstrate the clinical potential of MB-Lipo by imaging and treating tumor in vivo.
The beneficial effect of lisinopril on left ventricular remodelling after a first myocardial infarction is modulated by age. The GISSI-3 echo database
Authors: Roberto Latini, Gianluigi Nicolosi, Aldo P. Maggioni, Maria G. Franzosi, Simona Barlera, Serge Masson
Journal: Journal of the American College of Cardiology (1996)
Can Patient-Reported Outcome Measures Identify Cancer Patients' Most Bothersome Issues?
Authors: Claire F. Snyder, Amanda L. Blackford, Neil K. Aaronson, Symone B. Detmar, Michael A. Carducci, Michael D. Brundage, Albert W. Wu
Journal: Journal of Clinical Oncology (2011)

Patient-reported outcome (PRO) questionnaires are being investigated for their ability to aid in individual patient management. We evaluated whether PROs can identify patients' most bothersome quality-of-life issues and compared approaches for interpreting PRO scores.This secondary data analysis included 130 patients with cancer (mean age, 57 years; 71% female) receiving outpatient palliative chemotherapy. Patients completed a PRO (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire [QLQ-C30]) at up to three consecutive visits and reported one or two of their most bothersome function and symptom issues from categories based on QLQ-C30 domains. We compared two approaches for interpreting PRO scores and identified which way better identified patients' most bothersome issues: worst scores in absolute terms or worst change from the previous time point.For patients reporting one bothersome issue, absolute scores identified it correctly 91% of the time for both function and symptoms versus change scores' accuracy of 40% for function and 26% for symptoms. For patients reporting two bothersome issues, absolute scores identified at least one correctly 98% of the time for both function and symptoms versus change scores' 63% for function and 62% for symptoms. Absolute scores identified both issues correctly 42% of the time for function and 66% of the time for symptoms versus change scores' performance of 23% for both function and symptoms.Absolute scores identify patients' most bothersome quality-of-life issues better than change scores. These results support the use of PROs in clinical practice and suggest that clinicians may want to focus on the worst absolute scores when examining PRO score reports.
Downregulation of epithelial apoptosis and barrier repair in active Crohn's disease by tumour necrosis factor antibody treatment
Authors: S Zeissig
Journal: Gut (2004)

Barrier dysfunction is an important feature contributing to inflammation and diarrhoea in Crohn's disease (CD). Recently, tumour necrosis factor alpha (TNF-alpha) antibodies were recognised as effective in steroid refractory CD. The aim of this study was to characterise the effects of this therapy on the epithelial barrier.Forceps biopsies were obtained from the sigmoid colon before and 14 days after TNF-alpha antibody therapy in 11 patients treated for chronic active CD (Crohn's disease activity index >150). Epithelial apoptoses were measured after terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (TUNEL) and 4',6-diamidino-2-phenylindole staining. Epithelial resistance was determined by alternating current impedance analysis in miniaturised Ussing chambers. Occludin, claudin 1, and claudin 4 expression was quantified in immunoblots.The epithelial apoptotic ratio was 2.1 (0.2)% in controls and increased to 5.3 (1.0)% in CD. TNF-alpha antibody therapy decreased the apoptotic ratio to 2.9 (1.0)% (normalised in 10 of 11 patients). In parallel, epithelial resistance was lower in CD than in controls (24 (3) v 42 (3) Omegaxcm(2)) and improved to 34 (3) Omegaxcm(2) after therapy. Occludin, claudin 1, and claudin 4 were not affected by TNF-alpha antibody therapy. In support of a functional role of epithelial apoptoses in CD, a similar decrease in resistance of -40% was observed when the apoptotic rate was selectively upregulated from 2.6% to 5.4% with camptothecin in HT-29/B6 cells.Epithelial apoptoses were upregulated in the colon in CD and restored to normal in 10 of 11 patients by TNF-alpha antibody therapy. This is the structural correlate of epithelial barrier dysfunction measured as epithelial resistance while expression of tight junction proteins did not contribute to this therapeutic effect.
Dendritic Cell–Activating Vaccine Adjuvants Differ in the Ability to Elicit Antitumor Immunity Due to an Adjuvant-Specific Induction of Immunosuppressive Cells
Authors: Yushe Dang, Wolfgang M. Wagner, Ekram Gad, Lauren Rastetter, Carmen M. Berger, Gregory E. Holt, Mary L. Disis
Journal: Clinical Cancer Research (2012)

We questioned whether the vaccine adjuvant combination of TLR-7 ligand agonist, imiquimod, with granulocyte macrophage colony-stimulating factor (GM-CSF) would result in enhanced dendritic cell recruitment and activation with increased antigen-specific immunity as compared with either adjuvant used alone.
Tetracycline Resistance Of Group A Beta Hemolytic Streptococci
Authors: Henry A. Kuharic
Journal: JAMA (1960)

This study was undertaken to determine whether any group A streptococci isolated from clinical sources are now resistant to tetracycline antibiotics. Over a seven-month period in 1959 and 1960, 218 strains were isolated from a number of hospitals and clinical laboratories, and 42 strains (20%) were found to be resistant to tetracycline and demethylchlortetracycline. The majority of strains were isolated from patients with clinical infections, and some failed to respond to treatment with tetracyclines. Asymptomatic carriers were also noted. In the light of other recent reports, these results were taken to indicate that tetracyclines should probably not be used for prophylaxis of rheumatic fever, and should not be used for the therapy of streptococcal sore throats unless it is known that the infecting streptococcus is susceptible.
Do Treatment Improvements in PTSD Severity Affect Substance Use Outcomes? A Secondary Analysis From a Randomized Clinical Trial in NIDA's Clinical Trials Network
Authors: Denise A. Hien, Huiping Jiang, Aimee N.C. Campbell, Mei-Chen Hu, Gloria M. Miele, Lisa R. Cohen, Gregory S. Brigham, Carrie Capstick, Agatha Kulaga, James Robinson, Lourdes Suarez-Morales, Edward V. Nunes
Journal: American Journal of Psychiatry (2009)

The purpose of the analysis was to examine the temporal course of improvement in symptoms of posttraumatic stress disorder (PTSD) and substance use disorder among women in outpatient substance abuse treatment.Participants were 353 women randomly assigned to 12 sessions of either trauma-focused or health education group treatment. PTSD and substance use assessments were conducted during treatment and posttreatment at 1 week and after 3, 6, and 12 months. A continuous Markov model was fit on four defined response categories (nonresponse, substance use response, PTSD response, or global response [improvement in both PTSD and substance use]) to investigate the temporal association between improvement in PTSD and substance use symptom severity during the study's treatment phase. A generalized linear model was applied to test this relationship over the follow-up period.Subjects exhibiting nonresponse, substance use response, or global response tended to maintain original classification; subjects exhibiting PTSD response were significantly more likely to transition to global response over time, indicating maintained PTSD improvement was associated with subsequent substance use improvement. Trauma-focused treatment was significantly more effective than health education in achieving substance use improvement, but only among those who were heavy substance users at baseline and had achieved significant PTSD reductions.PTSD severity reductions were more likely to be associated with substance use improvement, with minimal evidence of substance use symptom reduction improving PTSD symptoms. Results support the self-medication model of coping with PTSD symptoms and an empirical basis for integrated interventions for improved substance use outcomes in patients with severe symptoms.
Diagnosing Adult Attention Deficit Hyperactivity Disorder: Are Late Onset and Subthreshold Diagnoses Valid?
Authors: Stephen V Faraone, Joseph Biederman, Thomas Spencer, Eric Mick, Kate Murray, Carter Petty, Joel J Adamson, Michael C Monuteaux
Journal: American Journal of Psychiatry (2006)

Objective: Diagnosing attention deficit hyperactivity disorder (ADHD) in adults is difficult when diagnosticians cannot establish an onset before the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve DSM’s diagnosis threshold. Method: The authors addressed the validity of DSM-IV’s age-at-onset and symptom threshold criteria by comparing four groups of adults: 127 subjects with full ADHD who met all DSM-IV criteria for childhood-onset ADHD, 79 subjects with late-onset ADHD who met all criteria except the age-at-onset criterion, 41 subjects with subthreshold ADHD who did not meet full symptom criteria for ADHD, and 123 subjects without ADHD who did not meet any criteria. The authors hypothesized that subjects with late-onset and subthreshold ADHD would show patterns of psychiatric comorbidity, functional impairment, and familial transmission similar to those seen in subjects with full ADHD. Results: Subjects with late-onset and full ADHD had similar patterns of psychiatric comorbidity, functional impairment, and familial transmission. Most children with late onset of ADHD (83%) were younger than 12. Subthreshold ADHD was milder and showed a different pattern of familial transmission than the other forms of ADHD. Conclusions: The data about the clinical features of probands and the pattern of transmission of ADHD among relatives found little evidence for the validity of subthreshold ADHD among such subjects, who reported a lifetime history of some symptoms that never met DSM-IV’s threshold for diagnosis. In contrast, the results suggested that late-onset adult ADHD is valid and that DSM-IV’s age-at-onset criterion is too stringent.
Nasal Administration of Recombinant Rat α3(IV)NC1 Prevents the Development of Experimental Autoimmune Glomerulonephritis in the WKY Rat
Authors: John Reynolds, Evangelia I. Prodromidi, Jason K. Juggapah, Danielle S. Abbott, Kathryn A. Holthaus, Raghu Kalluri, Charles D. Pusey
Journal: Journal of the American Society of Nephrology (2005)

Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture’s disease, can be induced in Wistar Kyoto (WKY) rats by immunization with either collagenase-solubilized rat glomerular basement membrane (GBM) or the recombinant NC1 domain of the α3 chain of type IV collagen [α3(IV)NC1]. EAG is characterized by circulating and deposited anti–glomerular basement membrane antibodies, focal necrotizing glomerulonephritis with crescent formation, and glomerular infiltration by T cells and macrophages. Previous studies have demonstrated that oral administration of collagenase-solubilized GBM to WKY rats prevented the development of EAG. Nasal administration of specific autoantigens has been reported to be more effective than oral administration in other models of autoimmune disease. The main aim of this study was to investigate further the concept of mucosal tolerance in EAG by examining the effect of nasal administration of recombinant rat α3(IV)NC1. Groups of WKY rats with EAG, induced by immunization with recombinant rat α3(IV)NC1, were given α3(IV)NC1 nasally on 3 consecutive days before immunization, at total cumulative doses of 25, 100, or 250 μg per rat. A dose-dependent effect was observed on the development of EAG. A dose of 25 μg had no effect on disease; 100 μg resulted in a moderate reduction in the severity of nephritis; and 250 μg led to a marked reduction in circulating and deposited antibodies, albuminuria, severity of glomerular abnormalities, and numbers of glomerular CD8+ T cells and macrophages. In addition, there was a reduction in the proliferative response of splenocytes from rats in the high dose group (250 μg) to α3(IV)NC1 in vitro. The results from this study clearly demonstrate for the first time that mucosal tolerance in EAG can be induced by nasal administration of recombinant rat α3(IV)NC1 and that this approach is effective in the prevention of crescentic glomerulonephritis. Further work using new antigen-specific treatment strategies may provide a novel approach to the treatment of patients with anti–glomerular basement membrane disease.
One Thousand and One Nights
Authors: Sarah N Mourra
Journal: Annals of Internal Medicine (2011)

On Being a Doctor4 October 2011One Thousand and One NightsSarah N. Mourra, MDSarah N. Mourra, MDFrom Yale School of Medicine, New Haven, CT 06510.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-7-201110040-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In the beginning, she was the same age, the same height, and the same weight as the young doctor. She had come into the hospital for a broken foot that, somehow in all the commotion, suddenly became leukemia. She wore strange hats and swore she would write a book when all of this was finished.“I'm going to call it How I Beat Luke and Mia,” she proclaimed one day. She said things like these because she loved making the young doctor laugh, which was more thrilling than talking about her swollen feet and nausea. When her pillow became covered ... Author, Article, and Disclosure InformationAffiliations: From Yale School of Medicine, New Haven, CT 06510.Corresponding Author: Sarah N. Mourra, MD, Department of Psychiatry, Yale School of Medicine, 300 George Street, New Haven, CT 06510; e-mail, sarah.[email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 October 2011Volume 155, Issue 7Page: 475-476KeywordsComputed axial tomographyFallsHand strengthHeartNauseaWheelchairs ePublished: 4 October 2011 Issue Published: 4 October 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations of N-region insertions during V(D)J recombination
Authors: Lisa Gangi-Peterson, David H. Sorscher, Jon W. Reynolds, Thomas B. Kepler, Beverly S. Mitchell
Journal: Journal of Clinical Investigation (1999)

Template-independent nucleotide additions (N regions) generated at sites of V(D)J recombination by terminal deoxynucleotidyl transferase (TdT) increase the diversity of antigen receptors. Two inborn errors of purine metabolism, deficiencies of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP), result in defective lymphoid development and aberrant pools of 2′-deoxynucleotides that are substrates for TdT in lymphoid precursors. We have asked whether selective increases in dATP or dGTP pools result in altered N regions in an extrachromosomal substrate transfected into T-cell or pre–B-cell lines. Exposure of the transfected cells to 2′-deoxyadenosine and an ADA inhibitor increased the dATP pool and resulted in a marked increase in A–T insertions at recombination junctions, with an overall decreased frequency of V(D)J recombination. Sequence analysis of VH-DH-JH junctions from the IgM locus in B-cell lines from ADA-deficient patients demonstrated an increase in A–T insertions equivalent to that found in the transfected cells. In contrast, elevation of dGTP pools, as would occur in PNP deficiency, did not alter the already rich G–C content of N regions. We conclude that the frequency of V(D)J recombination and the composition of N-insertions are influenced by increases in dATP levels, potentially leading to alterations in antigen receptors and aberrant lymphoid development. Alterations in N-region insertions may contribute to the B-cell dysfunction associated with ADA deficiency.