tbuckley/cabot-search huggingface dataset:
Corticosteroid-induced Improvement in the PC<sub>20</sub> of Adenosine Monophosphate Is More Closely Associated with Reduction in Airway Inflammation than Improvement in the PC<sub>20</sub> of Methacholine
Authors: MAARTEN Van Den BERGE, HUIB A. M. KERSTJENS, RONALD J. MEIJER, DOROTHEA M. DE REUS, GERARD H. KOËTER, HENK F. KAUFFMAN, DIRKJE S. POSTMA
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

It has been suggested in cross-sectional studies that provocation with adenosine 5 ′ -monophosphate (AMP) more closely reflects the inflammatory process in asthma than does provocation with methacholine or histamine. We investigated whether the steroid-induced improvement in the provocative concentration of AMP producing a 20% decline in FEV1 (PC20 AMP) is more closely associated with the concomitant reduction in airway inflammation than is the improvement in PC20 methacholine. In 120 asthmatic patients, we measured PC20 methacholine and PC20 AMP as well as sputum induction and nitric oxide (NO) in exhaled air before and after 2 weeks of treatment with corticosteroids. Improvement in PC20 AMP was solely related to reduction in airway inflammation (i.e., change in the number of sputum eosinophils, lymphocytes, epithelial cells, and concentration of NO in exhaled air). In contrast, improvement in PC20 methacholine was related to both reduction in airway inflammation (i.e., change in the number of sputum eosinophils and lymphocytes) and increase in FEV1 %predicted. The total explained variance of the improvement in bronchial hyperresponsiveness was greater for AMP than for methacholine (36% versus 22%, respectively). We conclude that PC20 AMP is more sensitive to changes in acute airway inflammation than is PC20 methacholine, further reinforcing the notion that PC20 AMP can be a useful tool for monitoring the effects of antiinflammatory therapy.
Preclinical Antilymphoma Activity of a Humanized Anti-CD40 Monoclonal Antibody, SGN-40
Authors: Che-Leung Law, Kristine A. Gordon, John Collier, Kerry Klussman, Julie A. McEarchern, Charles G. Cerveny, Bruce J. Mixan, Wyne P. Lee, Zhonghau Lin, Patricia Valdez, Alan F. Wahl, Iqbal S. Grewal
Journal: Cancer Research (2005)

SGN-40 is a humanized IgG1 antihuman CD40 that is currently in a phase I clinical trial for the treatment of multiple myeloma. As surface CD40 expression on B-lineage cells is maintained from pro-B cells to plasma cells, SGN-40 may be applicable to treatment of other B-cell neoplasias, including non-Hodgkin's lymphoma. In this study, we examined potential in vitro and in vivo anti-B-lineage lymphoma activity of SGN-40. Recombinant SGN-40 was expressed and purified from Chinese hamster ovary cells and characterized based on binding affinity, specificity, and normal B-cell stimulation. The ability of SGN-40 to target neoplastic B cells was examined in vitro by proliferation inhibition, cytotoxicity, and antibody-dependent cell cytotoxicity assays and in vivo by human lymphoma xenograft models. Recombinant SGN-40 showed high affinity, Kd of approximately 1 nmol/L, and specific binding to CD40. Whereas SGN-40 was a weak agonist in stimulating normal B-cell proliferation in the absence of IL-4 and CD40L, it delivered potent proliferation inhibitory and apoptotic signals to, and mediated antibody-dependent cytotoxicity against, a panel of high-grade B-lymphoma lines. These in vitro antilymphoma effects were extended to disseminated and s.c. xenograft CD40 tumor models. In these xenograft models, the antitumor activity of SGN-40 was comparable with that of rituximab. The preclinical in vitro and in vivo antilymphoma activity of SGN-40 observed in this study provides a rationale for the clinical testing of SGN-40 in the treatment of CD40+ B-lineage lymphomas.
Intestinal Blood Flow in Patients With Chronic Heart Failure
Authors: Anja Sandek, Alexander Swidsinski, Wieland Schroedl, Alastair Watson, Miroslava Valentova, Ralph Herrmann, Nadja Scherbakov, Larissa Cramer, Mathias Rauchhaus, Anke Grosse-Herrenthey, Monika Krueger, Stephan von Haehling, Wolfram Doehner, Stefan D. Anker, Juergen Bauditz
Journal: Journal of the American College of Cardiology (2014)
Visualization of Patients’ Skin Lesions on Their Smartphones
Authors: Thomas Hubiche, Laure Valério, Franck Boralevi, Emmanuel Mahe, Christine Bodemer Skandalis, Alice Phan, Pascal del Giudice
Journal: JAMA Dermatology (2015)

A New Step During Dermatology VisitsSmartphones are a new potential source of medical data. 1,2During dermatology appointments, we have observed an increasing number of patients presenting a picture of their skin lesions during the visit.The utility of the information provided by pictures on smartphones has not been evaluated.To assess their utility, we determined the proportion of patients whose smartphone photographs provided information relevant to their diagnosis.11-20 21-30 31-40 41-50 51-60 61-70 >70 Yes No Yes No Bad Average Good To show the picture to the physician Flare up of the skin disease Modification of a chronic skin disease Modification of skin lesions Nonmedical purpose (family picture...
Clinical and genetic features of 20 Japanese patients with vascular-type Ehlers-Danlos syndrome
Authors: Y. Shimaoka, T. Kosho, M. Wataya-Kaneda, M. Funakoshi, T. Suzuki, S. Hayashi, Y. Mitsuhashi, T. Isei, Y. Aoki, K. Yamazaki, M. Ono, K. Makino, T. Tanaka, E. Kunii, A. Hatamochi
Journal: British Journal of Dermatology (2010)

Vascular-type Ehlers-Danlos syndrome (vEDS) is a severe autosomal dominant inherited disorder resulting from mutations within the α1 type III collagen gene (COL3A1). The majority of published mutations are base changes leading to the substitution of single glycine residues within the triple-helical domain of type III collagen. Although clinical characteristics and mutations in the COL3A1 gene have been analysed for some patients from Europe and America, similar analyses have not yet been performed for Japanese patients with vEDS.To analyse the genetic and phenotypic findings in Japanese patients with vEDS.We analysed the clinical features of 20 unrelated individuals with vEDS. To quantify type III collagen production, the fibroblasts were cultured with (3) H-proline, and the radiolabelled collagenous proteins were analysed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis and fluorography. Mutations in COL3A1 were detected by sequence analysis of cDNA from patients' fibroblasts and subsequently by a genomic DNA sequence analysis.Thin and translucent skin with extensive bruising and hypermobility of the small joints were observed in about 90% of the patients, whereas the prevalence of serious clinical findings such as rupture/dissection/aneurysm of the arteries (30%) or rupture of the gastrointestinal tract (25%) was relatively low. Sequence analyses of the COL3A1 gene demonstrated heterozygous point mutations leading to glycine substitution in only nine patients (45%), while heterozygous splice-site mutations at the junction of the triple-helical exons were observed in the remaining 11 patients (55%). The average type III collagen production level in the cultured dermal fibroblasts was 14·6% of the normal value. The types of complication were not associated with specific mutations in COL3A1.The analysis in the present series revealed a low frequency of patients presenting with serious clinical findings such as arterial rupture/arterial dissection/aneurysm and perforation or rupture of the gastrointestinal tract, and revealed a higher prevalence of splice-site mutations at the junction of the triple-helical exons than of glycine substitution mutations in COL3A1.
Peritraumatic Dissociation and Posttraumatic Stress Disorder Following Motor Vehicle Accidents
Authors: Robert J. Ursano, Carol S. Fullerton, Richard S. Epstein, Brian Crowley, Kelley Vance, Tzu-Cheg Kao, Andrew Baum
Journal: American Journal of Psychiatry (1999)

This study examined the relation between peritraumatic dissociation and posttraumatic stress disorder (PTSD) in victims of motor vehicle accidents.Victims of serious motor vehicle accidents (N = 122) were assessed for peritraumatic dissociation with the Peritraumatic Dissociative Experiences Questionnaire-Rater Version and followed longitudinally to assess acute and chronic PTSD (1 month and 3 months after the accident) with the Structured Clinical Interview for DSM-III-R.The most common peritraumatic dissociative symptom was time distortion (56.6%). Subjects with peritraumatic dissociation were 4.12 times more likely than those without to have acute PTSD and 4.86 times more likely to develop chronic PTSD. The risk was independent of risk associated with the presence of PTSD before the accident.Peritraumatic dissociation is common following motor vehicle accidents and is a risk factor for acute and chronic PTSD, independent of risk associated with prior PTSD.
Abstract 2072: Multiple Platelet Aggregation Genes Are Identified by Genome-wide Association Meta-analyses
Authors: Andrew D Johnson, Lisa R Yanek, Ming-Huei Chen, Aldi T Kraja, Martin G Larson, Rosa Lin, Geoffrey H Tofler, Diane M Becker, Qiong Yang, Michael A Province, Christopher J O'Donnell, Lewis C Becker
Journal: Circulation (2009)

Platelet aggregation plays an important role in arterial thrombosis. While a few candidate gene polymorphisms have been previously associated with platelet aggregation, a genome-wide association study (GWAS) has not been reported. We hypothesized that meta-analysis of results from multiple GWAS would discover new genes contributing to aggregation. In two separate GWAS conducted in white participants, the Framingham Heart Study (FHS) Offspring cohort and GeneSTAR (GS), platelet rich plasma (PRP) was isolated from fasting blood samples. Subjects with CAD or anti-coagulant or anti-platelet medication were excluded. PRP samples were treated with varying doses of agonists (collagen, ADP, epinephrine) and lag time, biphasic responses and maximal aggregation were measured. Genotyping was conducted with Affymetrix 500K + 50K MIPs arrays (FHS) and Illumina 1M arrays (GS). After genotyping QC, both cohorts used MACH software to impute 2.54 million common SNPs based on the HapMap. The imputed SNP dosages were used i...
Cerebral Blood Flow and Mental Processes in Schizophrenia
Authors: P F Liddle, K J Friston, C D Frith, R S J Frackowiak
Journal: Journal of the Royal Society of Medicine (1992)

The patterns of cerebral blood flow associated with three syndromes of schizophrenic symptoms are compared with the loci of cerebral activation in normal subjects during the performance of mental processes implicated in the three syndromes. The psychomotor poverty syndrome, which has been shown to involve a diminished ability to generate words, is associated with decreased perfusion of the dorsolateral prefrontal cortex at a locus which is activated in normal subjects during the internal generation of words. The disorganization syndrome, which has been shown to involve impaired suppression of inappropriate responses (eg in the Stroop test), is associated with increased perfusion of the right anterior cingulate gyrus at a location activated in normal subjects performing the Stroop test. The reality distortion syndrome, which evidence suggests arises from disordered internal monitoring of activity, is associated with increased perfusion in the medial temporal lobe at a locus activated in normal subjects during the internal monitoring of eye movements.
Prevalence of severe asthma in the hospital of Montes Claros- MG
Authors: Roseane Caldeira, Márjorie Rodrigues
Journal: European Respiratory Journal (2012)

Introduction: Asthma attacks can be triggered by respiratory infections, environmental pollutants, sudden temperature changes, among other factors, being directly related to an increased likelihood of hospitalization. Every year occurs 370.000 hospitalizations for asthma in Brazil and this is the fourth leading cause of hospitalization in the public health system.  Aims: To investigate the prevalence of severe asthma in hospitalized patients in the University Hospital in the city of Montes Claros-MG.  Methods: Descriptive and retrospective study. We have analyzed 111 medical records of patients admitted in the University Hospital from January 2008 to June 2011, due to the exacerbation of asthma. Through the use of a form, informations have been collected from the medical records of 50 patients with severe asthma.  Results:  The prevalence of severe asthma was 45%. Of the 50 patients with severe asthma, the average was 15 years. 60% were female, 52% had other hospitalizations due to asthma. 82% of the cases had asthma diagnosed before the admission. Of these, 44% of subjects were doing regular treatment and 31% used inhaled corticosteroids associated with bronchodilator. Regarding the hospitalization, the average of admission time was 4.6 days. Related to the climate was observed that most of the patients were admitted in the fall (40%) or in the winter (26%).  Conclusions:  The study showed high prevalence of severe asthma and that there is a failure in primary care related to the treatment and the education of asthmatic patients because of the frequency of asthma exacerbations hospitalizations. Moreover, few patients do regular treatment, which causes low life quality, absenteeism from school and work and risk of death.
Irreversible airways obstruction on spirometry, does it equate to a diagnosis of COPD?
Authors: Dennis Wat, Sarah Haines, Linda Lukehirst, Joan McWean, Onnor Hampson, Kamlesh Mohan
Journal: European Respiratory Journal (2012)

Introduction: Irreversible airways obstruction and a post-bronchodilator FEV1/FVC ratio of   Aims: To study the prevalence and characteristics of lung diseases in patients with irreversible airways obstruction.  Methods: The diagnosis of all patients with irreversible airways obstruction seen in our service between August 2011 and January 2012 seen respiratory physicians was retrospectively reviewed. Respiratory diagnosis was made based on clinical history, physiology testing and radiology.  Results: There were a total of 486 referrals; 446 (92%) have COPD and 40 (8%) have bronchiectasis. No other obstructive lung diseases were diagnosed. There are no significant differences between the demographics of the COPD and bronchiectasis groups.  Conclusions: Current guidelines define irreversible airways obstruction as COPD and many of the therapeutic management strategies for COPD are based on the degree of airway obstruction. We have shown that a proportion of patients with irreversible airways obstruction have bronchiectasis. Hence any patients with irreversible airways diseases who are refractory to maximised COPD management should prompt a review of the diagnosis.
Role of technetium 99m-labeled monoclonal antibody in the management of melanoma patients.
Authors: M J Blend, S G Ronan, D J Salk, T K Gupta
Journal: Journal of Clinical Oncology (1992)

PURPOSE A study was performed to assess the usefulness of a radiolabeled monoclonal antibody (MoAb; technetium 99m NR-ML-05 Fab) as a detecting agent, as well as to evaluate its role in the overall decision-making process in the management of cutaneous malignant melanoma. PATIENTS AND METHODS Twelve patients with histologically confirmed primary cutaneous melanoma and palpable regional nodes were injected with MoAb NR-ML-05 Fab, radiolabeled with 20 to 30 mCi of 99mTc. Whole-body anterior and posterior images were obtained. Left and right lateral views of the head and anterior and posterior views of the chest, abdomen, pelvis, and extremities were obtained, as were selected single-photon emission computed tomographic (SPECT) views of regional lymph nodes and areas of known or suspected lesions. RESULTS In nine of 12 patients, clinical and/or MoAb evolution identified 30 discrete sites of suspected melanoma. The remaining three patients showed no positive sites, and there was no evidence of metastatic melanoma. All 30 sites were examined microscopically, and melanoma was confirmed histologically in 23. The remaining seven were negative. MoAb imaging detected 21 (true-positive) but failed to detect two (false-negative) lesions. Sensitivity was 91% (21 of 23); positive predictive value was 95% (21 to 22). CONCLUSIONS MoAb imaging seems to provide an excellent way to obtain information with regard to the metastatic status of melanoma patients. Immunocytochemistry showed that MoAb (NR-ML-05) is as sensitive as the S-100 antibody and probably more sensitive than the commercially available antimelanoma antibody HMB-45.
Imiquimod a new adjuvant for telomerase peptide vaccine: A phase I trial in patients with inoperable pancreatic cancer
Authors: S. L. Bernhardt, T. A. Buanes, M. Møller, J. A. Eriksen, G. Geudernack
Journal: Journal of Clinical Oncology (2005)

9623 Background Telomerase is a key enzyme in the process of immortalization of cancer cells and as such it holds a pivotal role in carcinogenesis. The catalytic subunit of telomerase, hTERT is expressed in 85–90% of pancreatic cancers. We have previously demonstrated that vaccination of inoperable pancreatic cancer patients with the telomerase peptide GV1001 in combination with GM-CSF, results in a high frequency of immune responders (75%). Recently it has been focus on imiquimod, an immune modulator, as a potential new adjuvant for peptide vaccination. Imiquimod acts via stimulation of Toll-like receptor 7 on antigen presenting cells, resulting in production of the cytokines IL-12, INF- α and INF-β, and thus creates a broader inflammatory response than GM-CSF. Methods The present study was performed to determine safety and immunogenecity of GV1001 using imiquimod as an adjuvant. Fourteen patients with non-resectable pancreatic cancer, were recruited into a phase I trial. The patients were vaccinated eight times over a 10 week regimen. Imiquimod (Aldara, 3M) was applied on the skin at the injection site 24 and 3 hours before intradermal injection of GV1001. The patients were evaluated on a regular basis: biochemically, radiologically and clinically. Immune responses were measured as skin reaction (DTH) and T-cell responses in vitro. Patients were offered monthly booster vaccinations as follow up treatment. Results Immune response was detected in 5 (35.7%) of the 13 evaluable patients (at least finishing week 4). One additional patient became immune responder after the second booster vaccination, resulting in an overall response rate of 46%. Conclusion The study documented that the use of Imiquimod in combination with GV1001 was well tolerated; there were no signs of toxicity, nor serious adverse events. Moore data is necessary to determine wether imiquimod may be used alone or in combination with GM-CSF, as adjuvant for peptide vaccination. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GemVax GemVax GemVax GemVax GemVax
Pregnancy: A risk for developing tuberculosis? A national cohort and self-controlled case series study using UK primary care data
Authors: Dominik Zenner, Michelle Kruijshaar, Nick Andrews, Ibrahim Abubakar
Journal: European Respiratory Journal (2011)

Introduction:  Tuberculosis (TB) incidence has increased in the UK over the last decade. The study of TB in pregnancy is important because of adverse outcomes in mother and child. The aim of this study was to analyse the epidemiology of TB in pregnancy in the UK, and establish, whether pregnancy is an independent risk factor for TB in order to inform prevention and early detection strategies.   Methods:  Using a cohort based on the UK General Practitioner Research Database (GPRD), incidence rates (IR) and rate ratios (IRR) of TB events in three time periods were compared using Poisson regression: pregnancy, a period of 6 months post-partum, and outside of pregnancy. In addition TB risk was calculated using a nested self-controlled case series (SCCS) analysis which implicitly adjusts for time-bounds covariates.   Results:  Combined pregnancy and post-partum TB rates (15.4 per 100,000 person years, py) were significantly higher than rates outside of pregnancy (9.1 per 100,000 py, p=0.02). Compared to risk outside of pregnancy, TB risk was not significantly increased during pregnancy (IRR 1.29, CI 0.82-2.03), but significantly increased post-partum (IRR 1.95, CI 1.24-3.07), adjusting for age, region and deprivation. These observations were confirmed in the SCCS (IRR 1.62, CI 1.01-2.58 and 1.03, CI 0.64-1.65).   Conclusions:  There is a significantly increased post-partum TB risk and this is very likely pregnancy-related, but occurs post-partum due to administrative, diagnostic or immunological delays. Our results can be used to raise clinicians9 awareness and inform targeted public health policy measures to minimise this risk.
Pharmacokinetics of mycophenolic acid (MPA) and determinants of MPA free fraction in pediatric and adult renal transplant recipients. German Study group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients.
Authors: L T Weber, M Shipkova, T Lamersdorf, P D Niedmann, M Wiesel, A Mandelbaum, L B Zimmerhackl, E Schütz, O Mehls, M Oellerich, V W Armstrong, B Tönshoff
Journal: Journal of the American Society of Nephrology (1998)

Dosage guidelines for mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), are still preliminary in children. This study compares the pharmacokinetics of MPA and its major metabolite MPA glucuronide (MPAG) in pediatric renal transplant recipients receiving 600 mg MMF/m2 body surface area twice a day to those of adults on the currently recommended oral dose of 1 g of MMF twice a day. Concentration-time profiles of 18 children (age, 10.7+/-0.72 yr; range, 5.9 to 15.3 yr) and 10 adults were investigated 1 and 3 wk after transplantation. Plasma concentrations of MPA and MPAG were measured by reverse-phase HPLC. Because MPA is extensively bound to serum albumin and only the free fraction is presumed to be pharmacologically active, the MPA free fraction was also analyzed by HPLC after separation through ultrafiltration. The areas under the concentration-time curves (AUC0-12) of total and free MPA throughout the 12-h dosing interval in children were, in general, comparable to the corresponding data in adult patients. The mean AUC0-12 of MPA and free MPA did not change significantly over the first 3 wk after transplantation, but there was substantial intra- and interindividual variation. MPAG-AUC0-12 values in children with primary renal transplant dysfunction were threefold higher than in those with functioning transplants. Renal impairment had no consistent effect on total MPA-AUC0-12 values, but the MPA free fraction in children (median, 1.65%; range, 0.40 to 13.8%) was significantly (r2=0.46) modulated by renal transplant function and serum albumin levels. In conclusion, concentration-time profiles of pediatric renal transplant recipients administered 600 mg MMF/m2 body surface area twice a day are comparable to those in adults on 1 g MMF twice a day in the first 3 wk after transplantation. Renal impairment and decreased serum albumin levels led to an increase in the free fraction of MPA and the free MPA-AUC0-12 values. Because the pharmacologic activity of MPA is a function of unbound drug concentration, these findings might be relevant for the pharmacodynamic effects of MPA.