tbuckley/cabot-search huggingface dataset:
Effect of encouragement on walking test performance.
Authors: G H Guyatt, S O Pugsley, M J Sullivan, P J Thompson, L Berman, N L Jones, E L Fallen, D W Taylor
Journal: Thorax (1984)

Walking tests, frequently used to document effects of treatment on exercise capacity, have never been standardised. We studied the effects of encouragement on walking test performance in a randomised study that controlled for the nature of the underlying disease, time of day, and order effects. We randomised 43 patients with chronic airflow limitation or chronic heart failure or both to receive or not receive encouragement as they performed serial two and six minute walks every fortnight for 10 weeks. Simple encouragement improved performance (p less than 0.02 for the six minute walk), and the magnitude of the effect was similar to that reported for patients in studies purporting to show beneficial effects of therapeutic manoeuvres. Age and test repetition also affected performance. These results demonstrate the need for careful standardisation of the performance of walking tests, and suggest caution in interpreting studies in which standardisation is not a major feature of the study design.
Terbutaline and the Prevention of Nocturnal Hypoglycemia in Type 1 Diabetes
Authors: Benjamin A. Cooperberg, Suzanne M. Breckenridge, Ana Maria Arbelaez, Philip E. Cryer
Journal: Diabetes Care (2008)

Bedtime administration of 5.0 mg of the beta(2)-adrenergic agonist terbutaline prevents nocturnal hypoglycemia but causes morning hyperglycemia in type 1 diabetes. We tested the hypothesis that 2.5 mg terbutaline prevents nocturnal hypoglycemia without causing morning hyperglycemia.This was a randomized double-blind crossover pilot study (placebo, 2.5 mg terbutaline, and 5.0 mg terbutaline) in 15 patients with type 1 diabetes.Mean +/- SE nadir nocturnal plasma glucose concentrations were 87 +/- 14 mg/dl following placebo, 100 +/- 14 mg/dl following 2.5 mg terbutaline, and 122 +/- 13 mg/dl following 5.0 mg terbutaline (P < 0.05 vs. placebo). Nadir levels were <50 mg/dl in 5, 2, and 0 patients (P < 0.05 vs. placebo), respectively. Morning levels were 113 +/- 18, 127 +/- 17, and 183 +/- 19 mg/dl (P < 0.02 vs. placebo), respectively.Terbutaline may be shown to be effective and safe in the prevention of nocturnal hypoglycemia in type 1 diabetes in a suitably powered randomized controlled trial.
Comparison of cumulative and non-cumulative techniques to measure dose-response curves for beta agonists in patients with asthma.
Authors: J Britton, A Tattersfield
Journal: Thorax (1984)

It has been suggested that the use of a cumulative technique to obtain bronchodilator dose-response curves will cause a greater response than a non-cumulative technique, because sequential doses of drug will penetrate further into the lung. To test this hypothesis we have compared cumulative and non-cumulative dose-response curves for inhaled isoprenaline in 10 subjects with stable asthma, measuring FEV1, forced vital capacity (FVC), and peak expiratory flow rate (PEFR). With both techniques there was an increased response with increasing doses of isoprenaline for all the dose-response curves except for the non-cumulative PEFR response, which reached a plateau with the 20 micrograms dose. The area under the dose-response curve for FEV1 was significantly greater after cumulative administration of isoprenaline than with the non-cumulative technique. The increase in FVC and PEFR tended to be greater with the cumulative technique but the differences were not significant. This study confirms that the airway response to an inhaled beta agonist may be greater when a cumulative inhalation technique is used.
Expiratory flow limitation during mechanical ventilation detected by the forced oscillation method
Authors: M Vassiliou, R Peslin, C Saunier, C Duvivier
Journal: European Respiratory Journal (1996)

We have previously observed large phasic variations of respiratory mechanical impedance in chronic obstructive pulmonary disease (COPD) patients mechanically-ventilated for acute respiratory failure, and postulated that they were due to expiratory flow limitation (EFL). The aim of this study was to test that assumption experimentally and to assess the value of impedance for automatic and noninvasive detection of EFL during mechanical ventilation. The study was performed: 1) in a mechanical analogue, including a flow-limiting element; and 2) in eight anaesthetized and paralysed rabbits, before and during histamine infusion. In both instances, EFL was obtained by lowering the expiratory pressure, using a computer-controlled ventilator; the absence of flow increase when expiratory pressure was further lowered was taken as evidence of EFL. Impedance was measured by applying 15 Hz oscillations at the airway opening. Its real (Re) and imaginary (Im) parts were measured separately during the inspiratory and the expiratory phases, and their differences were related to the mean inspiratory modulus. With the analogue, EFL was accompanied by large decreases both of Re and Im during the expiratory phase. In the rabbits, phasic variations of Re were variable in sign and were not significantly different with and without EFL. In contrast, EFL systematically and specifically decreased Im during the expiratory phase. A threshold of -50% provided a sensitivity of 96% and a specificity of 100% for detecting EFL. The observed phasic variations may be explained by airway wall shunt properties. The study suggests that a large decrease of the imaginary part of impedance during the expiratory phase is a sensitive and specific index of expiratory flow limitation during artificial ventilation.
Effects of psoralen plus UVA radiation (PUVA) on HIV-1 in human beings: A pilot study
Authors: Thomas D. Horn, Warwick L. Morison, Homayoon Farzadegan, Barbara Z. Zmudzka, Janusz Z. Beer
Journal: Journal of the American Academy of Dermatology (1994)

Laboratory data document the activation of the HIV-1 genome on exposure to UV radiation, including PUVA. The overall effects of UV radiation exposure on HIV-1 infection in human beings are unknown.Our purpose was to observe CD4 cell counts and quantitative markers of HIV-1 load in late-stage HIV-1-infected human beings receiving PUVA for various cutaneous diseases.Samples of peripheral blood were obtained on days 0, 14, 30, and 60 of PUVA administered in therapeutic doses. Number of CD4+ T lymphocytes was determined by flow cytometry, and HIV-1 load was measured by semiquantitative polymerase chain reaction for viral genome in peripheral blood mononuclear cells, semiquantitative RNA-polymerase chain reaction for HIV-1 RNA in serum, and determination of p24 in serum.No significant changes in the measurements were observed.This study did not detect a deleterious effect on CD4 cell count or HIV-1 load during 2 months of PUVA treatment for patients in late stages of infection, with low CD4 cell counts and high HIV-1 loads.
PEYER'S PATCHES: AN ENRICHED SOURCE OF PRECURSORS FOR I<scp>G</scp>A-PRODUCING IMMUNOCYTES IN THE RABBIT
Authors: Susan W. Craig, John J. Cebra
Journal: The Journal of Experimental Medicine (1971)

The proliferative and differentiative potential of Peyer's patch, peripheral blood, and popliteal lymph node cells was assessed by allogeneic cell transfer followed by quantitation of donor immunocytes by immunofluorescence. It was found that Peyer's patches are a highly enriched source of cells which have the potential to proliferate and differentiate into IgA-producing immunocytes and that the Peyer's patch cells are far more efficient in seeding the gut of irradiated recipient rabbits with donor cells that give rise to immunoglobulin-producing cells than cells from peripheral blood or popliteal lymph nodes.
Suramin Therapy for Patients With Symptomatic Hormone-Refractory Prostate Cancer: Results of a Randomized Phase III Trial Comparing Suramin Plus Hydrocortisone to Placebo Plus Hydrocortisone
Authors: Eric J. Small, Mark Meyer, M. Ernest Marshall, Leonard M. Reyno, Frederick J. Meyers, Ronald B. Natale, Peter F. Lenehan, Liang Chen, William J. Slichenmyer, Mario Eisenberger
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Suramin is a novel agent that has demonstrated preliminary evidence of antitumor activity in hormone-refractory prostate cancer (HRPC). A prospective randomized clinical trial was designed to evaluate pain and opioid analgesic intake as surrogates for antitumor response in HRPC patients with significant, opioid analgesic–dependent pain. PATIENTS AND METHODS: A double-blind, placebo-controlled trial randomized patients to receive a 78-day, outpatient regimen of either suramin plus hydrocortisone (HC, 40 mg/d) or placebo plus HC. Treatment assignment was unblinded when either disease progression or dose-limiting toxicity occurred; placebo patients were allowed to cross-over to open-label suramin plus HC. In addition to pain and opioid analgesic intake, prostate-specific antigen (PSA) response, time to disease progression, quality of life, performance status, and survival were compared. RESULTS: Overall mean reductions in combined pain and opioid analgesic intake were greater for suramin plus HC (rank sum P = .0001). Pain response was achieved in a higher proportion of patients receiving suramin than placebo (43% v 28%; P = .001), and duration of response was longer for suramin responders (median, 240 v 69 days; P = .0027). Time to disease progression was longer (relative risk = 1.5; 95% confidence interval, 1.2 to 1.9) and the proportion of patients with a greater than 50% decline in PSA was higher (33% v 16%; P = .01) in patients who received suramin. Neither quality of life nor performance status was decreased by suramin treatment, and overall survival was similar. Most adverse events were of mild or moderate intensity and were easily managed medically. CONCLUSION: Outpatient treatment with suramin plus HC is well tolerated and provides moderate palliative benefit and delay in disease progression for patients with symptomatic HRPC.
Brugada Syndrome
Authors: C. Antzelevitch, P. Brugada, J. Brugada, R. Brugada, W. Shimizu, I. Gussak, A.R. Perez Riera
Journal: Circulation Research (2002)

The Brugada syndrome has gained wide recognition throughout the world and today is believed to be responsible for 4% to 12% of all sudden deaths and approximately 20% of deaths in patients with structurally normal hearts. The incidence of the disease is on the order of 5 per 10 000 inhabitants and, apart from accidents, is the leading cause of death of men under the age of 50 in regions of the world where the inherited syndrome is endemic. This minireview briefly summarizes the progress made over the past decade in our understanding of the clinical, genetic, cellular, ionic, and molecular aspects of this disease.
Mechanism of generation of body surface electrocardiographic P-waves in normal, middle, and lower sinus rhythms.
Authors: W J Eifler, E Macchi, H J Ritsema van Eck, B M Horacek, P M Rautaharju
Journal: Circulation Research (1981)

We used comprehensive electrophysiological/anatomical digital computer models of atrial excitation and the human torso to study the mechanisms of generation of body surface P-waves in normal sinus rhythm, and in middle and lower sinus rhythm. Simulated atrial surface isochrone maps for normal sinus rhythm support the validity of the atrial excitation model. The results suggest that the presence of specialized internodal tracts containing fast-conducting fibers is not essential to account for propagation of excitation in apparent preferential directions from the sinoatrial (SA) node to the atrioventricular node. However, in the absence of fast conducting fibers, a slowly conducting segment in the intercaval region is necessary to achieve proper excitation of the interatrial septum. P-wave notches occur in the absence of specialized fast conducting atrial tracts and anisotropies due to fiber orientation. These notches are due to the atrial geometry and the separate contributions of the right atrium, left atrium, and interatrial septum to the P-waves, and become more pronounced as the pacemaker site shifts downward in the SA node. Thus, slight changes in the origin of excitation, which result in subtle changes in the atrial excitation isochrones, produce significant and complex changes in the simulated body surface P-waves.
Community acquired acute bacterial and atypical pneumonia in Saudi Arabia.
Authors: N Y Kurashi, A al-Hamdan, E M Ibrahim, H Y al-Idrissi, T H al-Bayari
Journal: Thorax (1992)

Rational treatment of pneumonia requires knowledge of the likely aetiological diagnosis in any community. Little is known about the pattern and outcome of pneumonia in Saudi Arabia.A total of 567 pneumonic episodes in adult patients from the Al-Qassim area were reviewed retrospectively.Patients had a mean age of 42.7 years, with 103 patients (18%) aged 13 to 20 years and 103 (18%) aged 60 or more. Almost two thirds of the episodes (64%) occurred in men. An aetiological diagnosis was established in 351 (62%) cases, with 145 episodes being due to pneumococcal infection and 129 to Mycoplasma pneumonia. Inhospital mortality was 6% (35 patients). Age over 60 years, aspiration pneumonia, and Gram negative infection were the only factors that independently predicted adverse outcome on adjusted mortality analysis.This analysis of pneumonia in the Al-Qassim area indicates the pattern and prognosis of acute bacterial and atypical pneumonia that requires admission to hospital in the central region of Saudi Arabia. It should provide a basis for developing rational treatment for community acquired pneumonia in Saudi Arabia.
Costimulator deficient antigen presentation by an endothelial cell line induces a nonproliferative T cell activation response without anergy.
Authors: J D St Louis, J A Lederer, A H Lichtman
Journal: The Journal of Experimental Medicine (1993)

The ability of endothelial cells to activate helper T (Th) cells by antigen presentation was studied using the murine endothelial cell line SVEC4-10 and antigen-specific murine T cell clones. SEVEC4-10 cells constitutively express vascular cell adhesion molecule 1 but not intercellular adhesion molecule 1. Interferon gamma (IFN-gamma) treatment of these cells induced class II major histocompatibility complex (MHC) expression and antigen-presenting capabilities, but did not alter surface integrin expression. IFN-gamma-treated SVEC4-10 cells were competent at mediating antigen-dependent cytokine production and proliferation of a Th2 clone. In contrast, endothelial antigen presentation to Th1 cells did not stimulate T cell proliferation. The addition of MHC mismatched spleen cells as a source of costimulatory molecules resulted in the ability of the endothelial cells to stimulate Th1 cell proliferation in an antigen-specific manner. The failure of the endothelial cell line alone to support Th1 cell proliferation correlated with the failure to stimulate interleukin 2 (IL-2) gene expression. T cell exposure to the endothelial cells plus antigen resulted in upregulation of IL-2 receptors and an enhanced response to subsequent antigen presentation by splenic antigen-presenting cells. Despite the lack of functional costimulators for IL-2 expression, antigen presentation by the endothelial cell line did not induce Th1 cell anergy, indicating that costimulator deficiency for IL-2 expression is not obligatorily linked to anergy induction. Thus, endothelial cells are capable of presenting antigens to helper T lymphocytes, but stimulate only partial T cell responses. These partial responses may serve to selectively stimulate transmigration of antigen-specific T cells and may enhance functional responses upon subsequent, extravascular antigen exposure.
The Wilms' Tumor Antigen Is a Novel Target for Human CD4+ Regulatory T Cells: Implications for Immunotherapy
Authors: Cynthia Lehe, Hazem Ghebeh, Abdullah Al-Sulaiman, Ghofran Al Qudaihi, Khaled Al-Hussein, Fahad Almohareb, Naeem Chaudhri, Fahad Alsharif, Hazza Al-Zahrani, Abdelghani Tbakhi, Mahmoud Aljurf, Said Dermime
Journal: Cancer Research (2008)

Abstract Compelling evidences indicate a key role for regulatory T cells (Treg) on the host response to cancer. The Wilms' tumor antigen (WT1) is overexpressed in several human leukemias and thus considered as promising target for development of leukemia vaccine. However, recent studies indicated that the generation of effective WT1-specific cytotoxic T cells can be largely affected by the presence of Tregs. We have generated T-cell lines and clones that specifically recognized a WT1-84 (RYFKLSHLQMHSRKH) peptide in an HLA-DRB1*0402–restricted manner. Importantly, they recognized HLA-DRB1*04–matched fresh leukemic cells expressing the WT1 antigen. These clones exerted a T helper 2 cytokine profile, had a CD4+CD25+Foxp3+GITR+CD127− Treg phenotype, and significantly inhibited the proliferative activity of allogeneic T cells independently of cell contact. Priming of alloreactive T cells in the presence of Tregs strongly inhibited the expansion of natural killer (NK), NK T, and CD8+ T cells and had an inhibitory effect on NK/NK T cytotoxic activity but not on CD8+ T cells. Furthermore, priming of T cells with the WT1-126 HLA-A0201–restricted peptide in the presence of Tregs strongly inhibited the induction of anti–WT1-126 CD8+ CTL responses as evidenced by both very low cytotoxic activity and IFN-γ production. Moreover, these Treg clones specifically produced granzyme B and selectively induced apoptosis in WT1-84–pulsed autologous antigen-presenting cells but not in apoptotic-resistant DR4-matched leukemic cells. Importantly, we have also detected anti–WT1-84 interleukin-5+/granzyme B+/Foxp3+ CD4+ Tregs in five of eight HLA-DR4+ acute myeloid leukemia patients. Collectively, our in vitro and in vivo findings strongly suggest important implications for the clinical manipulation of Tregs in cancer patients. [Cancer Res 2008;68(15):6350–9]
Evolution of alcohol dehydrogenase genes in peonies (Paeonia): phylogenetic relationships of putative nonhybrid species
Authors: T. Sang, M. J. Donoghue, D. Zhang
Journal: Molecular Biology and Evolution (1997)

Alcohol dehydrogenase genes were amplified by PCR, cloned, and sequenced from 11 putative nonhybrid species of the angiosperm genus Paeonia. Sequences of five exons and six intron regions of the Adh gene were used to reconstruct the phylogeny of these species. Two paralogous genes, Adh1A, and Adh2, were found; an additional gene, Adh1B, is also present in section Moutan. Phylogenetic analyses of exon sequences of the Adh genes of Paeonia and a variety of other angiosperms imply that duplication of Adh1 and Adh2 occurred prior to the divergence of Paeonia species and was followed by a duplication resulting in Adh1A and Adh1B. Concerted evolution appears to be absent between these paralogous loci. Phylogenetic analysis of only the Paeonia Adh exon sequences, positioning the root of the tree between the paralogous genes Adh1 and Adh2, suggests that the first evolutionary split within the genus occurred between the shrubby section Moutan and the other two herbaceous sections Oneapia and Paeonia. Restriction of Adh1B genes to section Moutan may have resulted from deletion of Adh1B from the common ancestor of sections Oneapia and Paeonia. A relative-rate test was designed to compare rates of molecular change among lineages based on the divergence of paralogous genes, and the results indicate a slower rate of evolution within the shrubby section Moutan than in section Oneapia. This may be responsible for the relatively long branch length of section Oneapia and the short branch length between section Moutan and the other two sections found on the Adh, ITS (nrDNA), and matK (cpDNA) phylogenies of the genus. Adh1 and Adh2 intron sequences cannot be aligned, and we therefore carried out separate analyses of Adh1A and Adh2 genes using exon and intron sequences together. The Templeton test suggested that there is not significant incongruence among Adh1A, ITS, and matK data sets, but that these three data sets conflict significantly with Adh2 sequence data. A combined analysis of Adh1A, ITS, and matK sequences produced a tree that is better resolved than that of any individual gene, and congruent with morphology and the results of artificial hybridization. It is therefore considered to be the current best estimate of the species phylogeny. Paraphyly of section Paeonia in the Adh2 gene tree may be caused by longer coalescence times and random sorting of ancestral alleles.
Pharmacokinetics and safety of ixazomib plus lenalidomide–dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study
Authors: Neeraj Gupta, Yeow Tee Goh, Chang-Ki Min, Jae Hoon Lee, Kihyun Kim, Raymond S. M. Wong, Chor Sang Chim, Michael J. Hanley, Huyuan Yang, Karthik Venkatakrishnan, Ai-Min Hui, Dixie-Lee Esseltine, Wee Joo Chng
Journal: Journal of Hematology & Oncology (2015)

The oral proteasome inhibitor ixazomib is under phase 3 clinical investigation in multiple myeloma (MM) in combination with lenalidomide–dexamethasone. This study was conducted to investigate the pharmacokinetic and safety profiles of ixazomib, administered with lenalidomide–dexamethasone, in East Asian patients with relapsed/refractory MM. Adult patients with measurable disease who had received 1–3 prior lines of therapy received oral ixazomib on days 1, 8, and 15, lenalidomide (25 mg) on days 1–21, and dexamethasone (40 mg) on days 1, 8, 15, and 22, in 28-day cycles. Primary objectives were to characterize ixazomib plasma pharmacokinetics, determine the recommended phase 2/3 dose, and evaluate safety and tolerability. Forty-three patients were enrolled. No dose-limiting toxicities were reported for the first six patients receiving ixazomib (4.0 mg), confirming this as the recommended phase 2/3 dose. Ixazomib was rapidly absorbed with a median T max of 1.5 h on day 1 and 2.0 h on day 15 of cycle 1 and had a geometric mean terminal half-life of 6.1 days. Twenty-one (49 %) patients had at least one drug-related grade ≥3 adverse event (AE); the most common were neutropenia (19 %), diarrhea (14 %), and thrombocytopenia (12 %). Twenty-eight of 43 (65 %) response-evaluable patients had at least a partial response. The recommended phase 2/3 dose for ixazomib was determined to be 4.0 mg. The all-oral combination of ixazomib plus lenalidomide–dexamethasone appeared active and well tolerated at 4.0 mg. Consequently, East Asian patients enrolled in phase 3 studies are receiving the same ixazomib dose as patients in other regions. This study is registered at NCT01645930 .