Significant variability in response to inhaled corticosteroids for persistent asthma.

Background: A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy.

Objective: The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs.

Methods: A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma.

IFN-gamma synergizes with TNF-alpha but not with viable H. pylori in up-regulating CXC chemokine secretion in gastric epithelial cells.

Helicobacter pylori colonizes the gastric epithelial surface and induces epithelial cells to increase production of the neutrophil attractant IL-8. Little is known about the role of the gastric epithelium in regulating mucosal T cell trafficking. We therefore characterized constitutive and regulated epithelial expression of the CXC chemokines IP-10, I-TAC and Mig, which specifically attract CXCR3 expressing CD4(+) T cells.

Quality control within the Asthma Clinical Research Network.

Quality control and assurance are very important issues for multicenter clinical investigation. Although such investigation usually states that those factors are part of the investigation, at best this occurs to a minimal extent. Indeed, to ensure the best possible investigatory results with the least amount of variance between centers, the Asthma Clinical Research Network (ACRN) instituted strict written criteria that were continually overviewed.

CD4+ Th1-cells predominate in low-grade B-cell lymphoma of gastric mucosa-associated lymphoid tissue (MALT type).

Background: Little is known about the function of T cells in the inflammatory infiltrate in Helicobacter pylori-associated gastritis and B-cell lymphoma of mucosa-associated lymphoid tissue (MALT type). Previous studies have proposed a dominant Th1-type response in low-grade MALT lymphoma consistent with the Th1 response observed in H. pylori-associated gastritis.

Significance of human papillomavirus in sinonasal papillomas.

Recent investigations have suggested human papillomavirus (HPV) to be involved in the development of sinonasal papillomas (SNP). Forty-three patients operated for SNP were studied to determine the prevalence of HPV-DNA sequences in these tumours and to evaluate their value as a prognostic parameter. The original sections of all cases were reviewed and reclassified according to the WHO.

[Fulminant liver failure after administration of the herbal antidepressant Kava-Kava].

History And Clinical Findings: A 60 year-old woman was admitted to hospital because of jaundice, fatigue, weight loss over several months and icteric skin. Because of progressive liver failure, concomitant renal failure and progressive encephalopathy she was transferred to an intensive care unit.

Investigations: Biochemical tests revealed acute liver failure with high levels of total and conjugated bilirubin (30 mg/dl) as well as aspartate aminotransferase (921 IU/l) and alanine aminotransferase (1350 IU/l) concentrations.

Signaling lymphocytic activation molecule (SLAM) regulates T cellular cytotoxicity.

Signaling lymphocytic activation molecule (SLAM) is a CD2-related surface receptor expressed by activated T cells and B cells. SLAM is a self ligand and enhances T cellular proliferation and IFN-gamma production. A defective SLAM associated protein (SAP) causes X-linked lymphoproliferative syndrome (XLP), a frequently lethal mononucleosis based on the inability to control EBV.

Evaluation of persistent torticollis following adenoidectomy.

Post-operative neck complaints are not an uncommon finding following adenotonsillectomy. However, non-traumatic subluxation of the atlantoaxial joint (Grisel's syndrome) should be considered in cases of persistent neck pain and stiffness. An early diagnosis and adequate treatment of this rare condition is mandatory to prevent potentially serious complications.

Evaluation of blood vessels and edema in the airways of asthma patients: regulation with clarithromycin treatment.

Background: Although airway angiogenesis and edema have been proposed to contribute to the airway remodeling process in patients with asthma, there are few studies looking at these structural components in the airway tissue of asthma patients. Mycoplasma infection may be associated with chronic asthma and has been shown to induce angiogenesis and edema in a murine model.

Participants And Measurements: We evaluated blood vessels and edema by immunohistochemistry in endobronchial biopsy samples from 10 normal control subjects and 15 patients with mild-to-moderate asthma before and after a 6-week treatment with clarithromycin (n = 8) or placebo (n = 7).

Neurokinin-1 receptor antagonists block acute cocaine-induced horizontal locomotion.

Systemic exposure to neurokinin-1 receptor antagonists CP099994 or LY306740 prior to cocaine administration (10 mg/kg i.p.) blocks acute, cocaine-induced horizontal locomotion.

Substance P modulates cocaine-evoked dopamine overflow in the striatum of the rat brain.

To study the role of the neuropeptide substance P in modulating some of the effects of cocaine in the striatum, we administered cocaine to rats and measured preprotachykinin-A (PPT-A) messenger RNA and substance P peptide in the nigrostriatal pathway. We also measured the effect of a neurokinin-1 (NK-1) receptor antagonist on striatal cocaine-evoked dopamine overflow by in vivo microdialysis in freely moving animals. Acute administration of cocaine to naive rats (15 mg/kg of body weight) increased preprotachykinin-A mRNA levels in the dorsal and ventral aspects of the caudate putamen 4 hours after the intraperitoneal injection of cocaine.

Discrete cleavage motifs of constitutive and immunoproteasomes revealed by quantitative analysis of cleavage products.

Proteasomes are the main proteases responsible for cytosolic protein degradation and the production of major histocompatibility complex class I ligands. Incorporation of the interferon gamma--inducible subunits low molecular weight protein (LMP)-2, LMP-7, and multicatalytic endopeptidase complex--like (MECL)-1 leads to the formation of immunoproteasomes which have been associated with more efficient class I antigen processing. Although differences in cleavage specificities of constitutive and immunoproteasomes have been observed frequently, cleavage motifs have not been described previously.

Colonic epithelial cells induce endothelial cell expression of ICAM-1 and VCAM-1 by a NF-kappaB-dependent mechanism.

Epithelial cells are positioned in close proximity to endothelial cells. A non-contact coculture system was used to investigate whether colonic epithelial cells activated with various cytokines are able to provide signals that can modulate ICAM-1 and VCAM-1 expression on endothelial cells. Coculture of human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1) with TNF-alpha/IFN-gamma-stimulated human colon epithelial cell lines led to a significant up-regulation of endothelial ICAM-1 and VCAM-1 expression.

Distal lung dysfunction at night in nocturnal asthma.

We have previously shown that patients with nocturnal worsening of asthma (nocturnal asthma) exhibit increased parenchymal inflammation at night. To evaluate the functional significance of this parenchymal inflammation, 10 subjects with nocturnal asthma (NA), four subjects with non-nocturnal asthma (NNA), and four normal control subjects underwent bronchoscopy with measurement of peripheral airways resistance (Rp) at 4:00 P.M.

Safety and reproducibility of sputum induction in asthmatic subjects in a multicenter study.

The safety of sputum induction and the reproducibility of measurements in induced sputum in multicenter studies is unknown. We examined the safety of sputum induction in a two-visit, six-center study in 79 subjects with moderate to severe asthma (mean +/- SD FEV(1) 71 +/- 12% predicted, 67% taking inhaled corticosteroids). In addition, we compared the reproducibility of markers of inflammation in induced sputum with the reproducibility of the FEV(1) and the methacholine PC(20).

Inhaled corticosteroid reduction and elimination in patients with persistent asthma receiving salmeterol: a randomized controlled trial.

Context: Inhaled long-acting beta(2)-agonists improve asthma control when added to inhaled corticosteroid (ICS) therapy.

Objective: To determine whether ICS therapy can be reduced or eliminated in patients with persistent asthma after adding a long-acting beta(2)-agonist to their treatment regimen.

Design And Setting: A 24-week randomized, controlled, blinded, double-dummy, parallel-group trial conducted at 6 National Institutes of Health-sponsored, university-based ambulatory care centers from February 1997 through January 1999.

Long-acting beta2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial.

Context: Long-acting beta(2)-agonists are prescribed for patients with persistent asthma and are sometimes used without inhaled corticosteroids (ICSs). No evidence exists, however, to support their use as monotherapy in adults with persistent asthma.

Objective: To examine the effectiveness of salmeterol xinafoate, a long-acting beta(2)-agonist, as replacement therapy in patients whose asthma is well controlled by low-dose triamcinolone acetonide, an ICS.

Decreased steroid responsiveness at night in nocturnal asthma. Is the macrophage responsible?

As peripheral blood mononuclear cells from patients with nocturnal asthma (NA) exhibit reduced steroid responsiveness at 4:00 A.M. as compared with 4:00 P.

Effect of polymorphism of the beta(2)-adrenergic receptor on response to regular use of albuterol in asthma.

Background: Regular use of inhaled beta-adrenergic agonists may have adverse effects in some asthma patients. Polymorphisms of the beta(2)-adrenergic receptor (beta(2)-AR) can affect its regulation; however, results of smaller studies of the effects of such polymorphisms on response to beta-agonist therapy have been inconsistent.

Methods: We examined the possible effects of polymorphisms at codons 16 (beta(2)-AR-16) and 27 (beta(2)-AR-27) on response to albuterol by genotyping 190 asthmatics who had participated in a trial of regular versus as-needed albuterol use.

IL-4, IL-13, and dexamethasone augment fibroblast proliferation in asthma.

Background: IL-4 and IL-13 have been shown to be critical for expression of the asthma phenotype in a murine model and may modulate human fibroblast function.

Objective: We hypothesized that IL-4 and IL-13 would increase airway fibroblast proliferation and reduce the ability of dexamethasone to decrease this proliferation.

Methods: Six subjects with severe asthma, 5 subjects with mild asthma, and 5 healthy subjects underwent bronchoscopy with endobronchial biopsy.

A link between chronic asthma and chronic infection.

Background: Asthma is a prevalent disease with marked effects on quality of life and economic societal burden. However, the cause of asthma and its pathophysiology are not completely defined. Recently, the possibility that chronic infection may play a role has been suggested.

Microfluidic tectonics: a comprehensive construction platform for microfluidic systems.

A microfluidic platform for the construction of microscale components and autonomous systems is presented. The platform combines liquid-phase photopolymerization, lithography, and laminar flow to allow the creation of complex and autonomous microfluidic systems. The fabrication of channels, actuators, valves, sensors, and systems is demonstrated.