tbuckley/cabot-search huggingface dataset:
Immediate and late asthmatic responses induced by exercise in patients with reversible airflow limitation
Authors: B Speelberg, NJ van den Berg, CH Oosthoek, NP Verhoeff, WT van den Brink
Journal: European Respiratory Journal (1989)

The existence and prevalence of late asthmatic responses to exercise in patients is uncertain. We investigated whether the late falls of peak expiratory flow rate (PEFR) after exercise challenge were still significant after comparison with the corresponding clocktime PEFR on a control day. We examined 86 patients with reversible airflow limitation, 79 with asthma and 7 with chronic obstructive pulmonary disease (COPD), all under regular treatment with bronchodilators and/or anti-inflammatory agents. Patients were randomized for a control day and an exercise day and PEFR was recorded hourly. On the exercise day, each patient underwent an 8 minute bicycle ride at 90% of predicted heart-rate. An early and a late asthmatic response to exercise were considered to occur when PEFR decreased by 10% or more on the exercise day compared to the corresponding clocktime PEFR on the control day. Thirty-three patients (38%) had a 10% or greater fall of PEFR at 4 to 13 hours after exercise when PEFR was compared with the corresponding clocktime on a control day. Seven (8%) had an isolated late asthmatic response, and 26 (30%) had a dual asthmatic response. We conclude that true late asthmatic responses develop after exercise in a significant number of patients with well controlled reversible airflow limitation.
THE EFFECT OF HYPERCAPNIA ON ESTIMATED HEPATIC BLOOD FLOW, CIRCULATING SPLANCHNIC BLOOD VOLUME, AND HEPATIC SULFOBROMOPHTHALEIN CLEARANCE DURING GENERAL ANESTHESIA IN MAN*
Authors: Robert M. Epstein, Henry O. Wheeler, M. Jack Frumin, David V. Habif, Emanuel M. Papper, Stanley E. Bradley
Journal: Journal of Clinical Investigation (1961)
IL-22–producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17–producing TH17 T cells
Authors: Kristine E. Nograles, Lisa C. Zaba, Avner Shemer, Judilyn Fuentes-Duculan, Irma Cardinale, Toyoko Kikuchi, Michal Ramon, Reuven Bergman, James G. Krueger, Emma Guttman-Yassky
Journal: Journal of Allergy and Clinical Immunology (2009)
Predictors of treatment in patients with chronic hepatitis C infection-Role of patient versus nonpatient factors
Authors: Fasiha Kanwal, Tuyen Hoang, Brennan M.R. Spiegel, Seth Eisen, Jason A. Dominitz, Allen Gifford, Mathew Goetz, Steven M. Asch
Journal: Hepatology (2007)

Treatment with interferon and ribavirin is effective in patients with chronic infection with hepatitis C virus (HCV). Previous data indicate that treatment rates are suboptimal. We sought to identify patient and provider-level predictors of treatment receipt in HCV by conducting a retrospective cohort study of 5701 HCV patients in a large regional Veteran's Administration (VA) healthcare network. We also determined the degree of variation in treatment rates attributable to patient, provider, and facility factors. Three thousand seven hundred forty-three patients (65%) were seen by a specialist and 894 (15.7%) received treatment. Treatment rates varied from 6% to 29% across the 5 facilities included in the analysis. Patients were less likely to receive treatment if they were older [RR, 0.55; 95% CI, 0.45, 0.67), single (RR, 0.77; 95%CI, 0.67, 0.88), had hepatic dysfunction (RR, 0.73; 95%CI, 0.66, 0.89), had normal alanine aminotransferase (ALT) (RR, 0.73; 95%CI, 0.59, 0.89), had HCV genotype 1 (RR, 0.78; 95%CI, 0.71, 0.86), were African American with genotype 1 (RR, 0.78; 95% CI, 0.71, 0.86), or were anemic (RR, 0.70; CI, 0.60, 0.89). In addition, patients evaluated by less experienced providers were 77% less likely to receive treatment than those evaluated by more experienced providers. The patient, provider, and facility factors explained 23%, 25%, and 7% of variation in treatment rates, respectively. Conclusion: These data suggest that although patient characteristics are important predictors of treatment in HCV, a significant proportion of variation in treatment rates is explained by provider factors. These potentially modifiable provider-level factors may serve as high-yield targets for future quality improvement initiatives in HCV. (Hepatology 2007;46:1741–1749.)
Prevention and Treatment of Dysphagia and Aspiration After Chemoradiation for Head and Neck Cancer
Authors: David I. Rosenthal, Jan S. Lewin, Avraham Eisbruch
Journal: Journal of Clinical Oncology (2006)

Safe, successful swallowing depends on complex events affected by head and neck cancers and their treatment. This article reviews the swallowing process, how it is affected by chemoradiotherapy, and the evaluation, prevention, and treatment of swallowing disorders. Specific recommendations are made to promote maintenance and recovery of swallowing function.
Adherence to Protease Inhibitor Therapy and Outcomes in Patients with HIV Infection
Authors: David L. Paterson, Susan Swindells, Jeffrey Mohr, Michelle Brester, Emanuel N. Vergis, Cheryl Squier, Marilyn M. Wagener, Nina Singh
Journal: Annals of Internal Medicine (2000)

Background: Combination antiretroviral therapy with protease inhibitors has transformed HIV infection from a terminal condition into one that is manageable. However, the complexity of regimens makes adherence to therapy difficult. Objective: To assess the effects of different levels of adherence to therapy on virologic, immunologic, and clinical outcome; to determine modifiable conditions associated with suboptimal adherence; and to determine how well clinicians predict patient adherence. Design: Prospective, observational study. Setting: HIV clinics in a Veterans Affairs medical center and a university medical center. Patients: 99 HIV-infected patients who were prescribed a protease inhibitor and who neither used a medication organizer nor received their medications in an observed setting (such as a jail or nursing home). Measurements: Adherence was measured by using a microelectronic monitoring system. The adherence rate was calculated as the number of doses taken divided by the number prescribed. Patients were followed for a median of 6 months (range, 3 to 15 months). Results: During the study period, 45 397 doses of protease inhibitor were monitored in 81 evaluable patients. Adherence was significantly associated with successful virologic outcome (P < 0.001) and increase in CD4 lymphocyte count (P = 0.006). Virologic failure was documented in 22% of patients with adherence of 95% or greater, 61% of those with 80% to 94.9% adherence, and 80% of those with less than 80% adherence. Patients with adherence of 95% or greater had fewer days in the hospital (2.6 days per 1000 days of follow-up) than those with less than 95% adherence (12.9 days per 1000 days of follow-up; P = 0.001). No opportunistic infections or deaths occurred in patients with 95% or greater adherence. Active psychiatric illness was an independent risk factor for adherence less than 95% (P = 0.04). Physicians predicted adherence incorrectly for 41% of patients, and clinic nurses predicted it incorrectly for 30% of patients. Conclusions: Adherence to protease inhibitor therapy of 95% or greater optimized virologic outcome for patients with HIV infection. Diagnosis and treatment of psychiatric illness should be further investigated as a means to improve adherence to therapy.
Effect of oral terfenadine on bronchoconstrictor response to inhaled neurokinin A and histamine in asthmatic subjects
Authors: N Crimi, R Oliveri, R Polosa, G Pulvirenti, G Prosperini, F Palemo, A Mistretta
Journal: European Respiratory Journal (1993)

Neurokinin A (NKA) elicits a potent contractile effect in asthmatic airways. Its mechanism of action in bronchial asthma is still unknown. Recent work supports the view that NKA may stimulate mediator release from mast cells. To investigate the relative contribution of mast cell degranulation to the action of NKA, a randomized, double-blind study has been undertaken, to evaluate the effect of a potent and selective histamine H1-receptor antagonist, terfenadine (180 mg q.d., for three days), on bronchoconstriction provoked by inhaled NKA in six asthmatic subjects. Bronchial provocation tests with histamine were included in this study as control challenge. In the subjects studied, oral terfenadine, when compared to placebo, significantly increased the geometric mean (range) provocation dose of inhaled histamine required to reduce forced expiratory volume in one second (FEV1) by 20% of baseline (PD20) from 0.05 (0.03-0.08) mg (0.16 (0.10-0.26) mumol) to 1.19 (0.63-2.04) mg (3.88 (2.05-6.64) mumol). However, terfenadine failed to increase the airway responsiveness to NKA in all of the subjects studied, the geometric mean (range) PD15 NKA value being 0.94 (0.47-2.49) micrograms (8.36 (4.14-21.9 nmol) and 0.75 (0.48-1.59) micrograms (6.62 (4.23-14.0) nmol) after placebo and terfenadine, respectively. We conclude that NKA is a potent bronchoconstrictor agonist in asthma, being approximately 19 times more potent than histamine in molar terms. In this study on a small number of subjects, pharmacological intervention with oral terfenadine failed to achieve significant protection of the airways against the constrictor effect of NKA.(ABSTRACT TRUNCATED AT 250 WORDS)
Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy, chemoresistance inhibition, and cardioprotection
Authors: Yunuen Alfaro, Guadalupe Delgado, Alfonso Cárabez, Brenda Anguiano, Carmen Aceves
Journal: Molecular Cancer (2013)

Abstract Background Although mammary cancer (MC) is the most common malignant neoplasia in women, the mortality for this cancer has decreased principally because of early detection and the use of neoadjuvant chemotherapy. Of several preparations that cause MC regression, doxorubicin (DOX) is the most active, first-line monotherapeutic. Nevertheless, its use is limited due to the rapid development of chemoresistance and to the cardiotoxicity caused by free radicals. In previous studies we have shown that supplementation with molecular iodine (I 2 ) has a powerful antineoplastic effect in methylnitrosourea (MNU)-induced experimental models of MC. These studies also showed a consistent antioxidant effect of I 2 in normal and tumoral tissues. Methods Here, we analyzed the effect of I 2 in combination with DOX treatment in female Sprague Dawley rats with MNU-induced MC. In the first experiment (short) animals were treated with the therapeutic DOX dose (16 mg/kg) or with lower doses (8 and 4 mg/Kg), in each case with and without 0.05% I 2 in drinking water. Iodine treatment began on day 0, a single dose of DOX was injected (ip) on day 2, and the analysis was carried out on day 7. In the second experiment (long) animals with and without iodine supplement were treated with one or two injections of 4 mg/kg DOX (on days 0 and 14) and were analyzed on day 56. Results At all DOX doses, the short I 2 treatment induced adjuvant antineoplastic effects (decreased tumor size and proliferating cell nuclear antigen level) with significant protection against body weight loss and cardiotoxicity (creatine kinase MB, cardiac lipoperoxidation, and heart damage). With long-term I 2 , mammary tumor tissue became more sensitive to DOX, since a single injection of the lowest dose of DOX (4 mg/Kg) was enough to stop tumor progression and a second DOX4 injection on day 14 caused a significant and rapid decrease in tumor size, decreased the expression of chemoresistance markers (Bcl2 and survivin), and increased the expression of the apoptotic protein Bax and peroxisome proliferator-activated receptor type gamma. Conclusions The DOX-I 2 combination exerts antineoplastic, chemosensitivity, and cardioprotective effects and could be a promising strategy against breast cancer progression.
ANALYSIS OF GRAFT-<i>VERSUS</i>-HOST DISEASE IN SYRIAN HAMSTERS
Authors: J. Wayne Streilein
Journal: The Journal of Experimental Medicine (1972)

The so-called refractory state, one sequela of acute graft-versus-host disease, has been studied in adult (CB x MHA)F1 hybrid Syrian hamsters inoculated with sublethal numbers of MHA-anti-CB lymphoid cells. Intracutaneous challenge of these animals with 200 million MHA-anti-CB lymphoid cells after the acute syndrome subsided failed to evoke epidermal necrolysis, whereas a similar challenge administered to normal F1 recipients invariably resulted in lethal epidermolysis. Moreover, the gradual attrition of lymphatic tissues in these hosts and their fading capacity to display adequately immune lymphocyte transfer reactions in the skin coincided with increasing evidence of host refractoriness, suggesting a causal interrelationship. It was possible to circumvent refractoriness by challenging these animals intracutaneously with MHA-anti-CB cells if: (a) the hosts had been lethally irradiated and reconstituted with F1 hematopoietic cells, or (b) the intracutaneous inocula contained admixed F1 lymphoid cells. This evidence provides additional support for the hypothesis that in GVH disease donor lymphocytes attack primarily host lymphoid cells bearing offending homologous antigens. The GVH process can continue so long as these lymphocyte-bound antigens persist within the host, and will abate only as the aggregate host lymphatic mass is effectively destroyed (hamsters) or its antigenic determinants are masked by isoantibodies (rats, mice, man?). At this point, insufficient target tissues remain for rechallenge to incite significant recrudescence of the disease.
Skewed X chromosomal inactivation impacts T regulatory cell function in systemic sclerosis
Authors: Jasper C A Broen, Ingrid L M Wolvers-Tettero, Lenny Geurts-van Bon, Madelon C Vonk, Marieke J H Coenen, Robert Lafyatis, Timothy R D J Radstake, Anton W Langerak
Journal: Annals of the Rheumatic Diseases (2010)

Objectives To investigate the role of X chromosomal inactivation (XCI) in systemic sclerosis (SSc) and its effects on forkhead box P3 ( Foxp3 ) expression in T regulatory cells (Tregs). Methods 217 women with SSc and 107 healthy women (controls) were included in the study. From these subjects, DNA was isolated from total peripheral blood mononuclear cells, plasmacytoid dendritic cells, T cells, B cells, myeloid dendritic cells and monocytes after magnetic bead separation. All samples were assessed for skewed XCI patterns with the Human Androgen Receptor Assay. The outcome was assessed by linear regression. CD4+CD25+ cells were then isolated and intracellular Foxp3 expression was assessed by flow cytometry. Results Skewing was not associated with increased age in patients with SSc, in contrast to the control population (r=0.45, p&lt;0.0001). Taking this into account, a significantly higher frequency of skewed XCI was found in patients with SSc compared with controls (p=0.001). No difference in skewing was observed between the immune cell subsets. In addition, a higher concentration of Foxp3 + cells exhibiting a lower Foxp3 mean fluorescence intensity was found in the patients with SSc, with profound XCI skewing (both p&lt;0.001) associated with less efficient suppressive activity (p=0.012). Conclusions Skewed XCI plays a role in susceptibility to SSc, is not restricted and influences Foxp3 expression and the suppressive capacity of Tregs.
Epigastric pain in a man with previous subtotal gastrectomy
Authors: H-C Lai, C-C Tsai, C-L Feng, C-J Yu, J-W Chou, W-H Huang, C-H Hsu, K-S Cheng, C-Y Peng
Journal: Gut (2009)

A 68-year-old man presented to our hospital with a 2-day history of upper abdominal pain and non-bilious vomiting. Twenty years previously he had undergone a subtotal gastrectomy with Billroth II reconstruction because of a gastric ulcer. He denied alcohol consumption or trauma. Physical examination revealed that his upper abdomen was tender with muscle guarding and rebound tenderness. Laboratory tests showed the following: haemoglobin 11 g/dl (normal, 14–16 g/dl), white blood count 12.9×109/l …
Is amyloid A (AA) amyloidosis always secondary?
Authors: C P Maury, T Tornroth, O Wegelius
Journal: Annals of the Rheumatic Diseases (1985)

The case is reported of a patient with systemic AA amyloidosis associated with non-specific mesenteric lymphadenitis and chronic sideropenia. Renal, small bowel, and rectal biopsies showed amyloid deposits containing AA protein, as defined by potassium permanganate sensitivity and by reactivity with AA antiserum. Reversal of the nephrotic syndrome occurred during steroid-azathioprine therapy.
Effect of chest wall vibration on dyspnea during hypercapnia and exercise in chronic obstructive pulmonary disease.
Authors: L M Cristiano, R M Schwartzstein
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Vibration of chest wall inspiratory muscles during inspiration (in-phase) reduces breathlessness associated with hypercapnia and resistive loading in normal subjects and in patients with chronic obstructive pulmonary disease (COPD) at rest. To evaluate further the effect of chest wall vibration on breathlessness ("breathing discomfort") in patients, we studied 10 subjects 52 to 79 yr of age with severe dyspnea (mean FEV1, 0.75 L, 27% predicted). On a single day, we used two separate stimuli to produce mild to moderate breathlessness (BR): Protocol 1, steady-state hypercapnia; Protocol 2, exercise with a lower extremity ergometer. During each protocol, we applied in-phase chest wall vibration (CW) randomly alternating with one of two controls: deltoid vibration (DV) or no vibration (NV). During hypercapnia, CW significantly reduced BR (DV, 2.9 +/- 2.1; CW, 2.3 +/- 1.4; p < 0.05; NV, 3.3 +/- 2.1; CW, 2.6 +/- 2.0; p < 0.01) without significant changes in ventilation. During exercise, CW did not significantly alter BR relative to controls. These findings may be explained by the effect of vibration on the sense of respiratory effort and/or by improvement of the match between efferent motor commands and afferent information from the respiratory system. The lack of effect during exercise on BR suggests there may be a "therapeutic window" or range of conditions within which CW is effective in reducing dyspnea in patients with COPD.
Requirements for leukocyte adhesion molecules in nephrotoxic nephritis.
Authors: M S Mulligan, K J Johnson, R F Todd, T B Issekutz, M Miyasaka, T Tamatani, C W Smith, D C Anderson, P A Ward
Journal: Journal of Clinical Investigation (1993)

Requirements for leukocyte adhesion molecules as well as cytokines have been determined in the rat model of acute nephrotoxic nephritis. Proteinuria (at 24 h) and neutrophil accumulation in renal glomeruli (at 6 h) have been used as the endpoints. For full accumulation in glomeruli of neutrophils as well as full development of proteinuria, requirements have been demonstrated for TNF alpha, (but not IL-1), CD11b (but not CD11a), very late arising-4 (CD49d/CD29), and intercellular adhesion molecule-1 but not endothelial leukocyte adhesion molecule-1 (E-selectin). By immunohistochemical approaches, infusion of antibody to glomerular basement membrane induced glomerular upregulation of intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular adhesion molecule-1. Treatment of rats with anti-TNF alpha or soluble recombinant human TNF receptor-1 blocked this expression. Renal arterial infusion of TNF alpha induced glomerular expression of all three endothelial adhesion molecules, but infusion of IL-1 beta did not. These data suggest that, in neutrophil and complement-dependent anti-glomerular basement membrane-induced acute nephritis in rats, there are selective requirements for cytokines, beta 1 and beta 2 integrins, and endothelial adhesion molecules. These requirements contrast with those found in other vascular beds in which complement and neutrophil-induced vascular injury has been induced by deposition of immune complexes.
Transfected Mouse Melanoma Lines That Express Various Levels of Human Melanoma-Associated Antigen p97
Authors: C. D. Estin, U. Stevenson, M. Kahn, I. Hellstrom, K. E. Hellstrom
Journal: JNCI Journal of the National Cancer Institute (1989)

The gene for the human melanoma-associated antigen p97 has been introduced by cDNA transfection into cells from clone M2 of the K1735 mouse melanoma, which metastasizes to the lung when injected iv into syngeneic C3H/HeN mice. Tumor clones were established from the transfected cells and found to differ in the level of p97 expression. Their outgrowth in immunocompetent syngeneic mice was shown to inversely correlate with p97 antigen expression, and lines that express higher p97 levels elicited a stronger delayed-type hypersensitivity response when injected into the footpads of mice immune to p97. Five clones which expressed very high levels of p97 failed to grow in immunocompetent C3H/HeN mice while they formed tumors in nude (nu/nu) mice. The highest expressing clone, 2A, grew slightly faster than any of the other clones when cultured in vitro. Since several of the transfected clones were found to express a stable level of p97 and have consistent in vivo growth behavior, they provide a useful model for various forms of antigen-specific active and passive immunotherapy with the same agents as those intended for human application.
c-FLIP is involved in tumor progression of peripheral T-cell lymphoma and targeted by histone deacetylase inhibitors
Authors: Zhong Zheng, Shu Cheng, Wen Wu, Li Wang, Yan Zhao, Yang Shen, Anne Janin, Wei-Li Zhao
Journal: Journal of Hematology & Oncology (2014)

Peripheral T-cell lymphomas (PTCLs) are often aggressive tumors and resistant to conventional chemotherapy. Dysregulation of extrinsic apoptosis plays an important role on tumor cell sensitivity to chemotherapeutic agents. Cellular FLICE inhibitory protein (c-FLIP) is a key regulator of extrinsic apoptotic pathway. c-FLIP expression was assessed by real-time PCR and compared according to clinical parameters in patients with PTCLs. The relation of c-FLIP to tumor cell apoptosis mediated by histone deacetylases inhibitors (HDACIs) and the possible mechanism were examined in T-lymphoma cell lines and in a murine xenograft model. c-FLIP was overexpressed and associated with decreased tumor TRAIL/DR5 expression, elevated serum lactate dehydrogenase level and high-risk International Prognostic Index of the patients. In vitro, molecular silencing of c-FLIP by specific small-interfering RNA increased TRAIL/DR5 expression, enhanced T-lymphoma cell apoptosis and sensitized cells to chemotherapeutic agents. However, HDACIs valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) could downregulate c-FLIP expression and triggered extrinsic apoptosis of T-lymphoma cells, through inhibiting NF-κB signaling and interrupting P50 interaction with c-FLIP promoter. As Class I HDACIs, both VPA and SAHA inhibited HDAC1, resulting in P50 inactivation and c-FLIP downregulation. In vivo, oral VPA treatment significantly retarded tumor growth and induced in situ apoptosis, consistent with inhibition of HDAC1/P50/c-FLIP axis and increase of TRAIL/DR5 expression. c-FLIP overexpression in PTCLs protected tumor cells from extrinsic apoptosis and contributed to tumor progression. Although linking to chemoresistance, c-FLIP indicated tumor cell sensitivity to HDACIs, providing a potential biomarker of targeting apoptosis in treating PTCLs.