Markers of inflammation in exhaled breath condensate of young healthy smokers

INTRODUCTION: Although a strong correlation exists between long-term cigarette smoking, pulmonary inflammation, and COPD, efforts to identify populations at risk of acquiring COPD have so far been unsuccessful. To this end, noninvasive detection and monitoring of biomarkers of pulmonary inflammation in young healthy smokers may assist in this task. STUDY OBJECTIVES: The purpose of this study was to determine the concentrations of total protein, nitrites, interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha, and neutrophil chemotactic activity in exhaled breath condensate (EBC) collected from healthy college student smokers and nonsmokers. DESIGN: EBC was collected from 20 volunteers (9 nonsmokers and 11 smokers) during tidal breathing for 20 min. EBC was also collected from smokers 30 min after smoking one filtered cigarette. The concentrations of total protein, nitrite, IL-1beta, and TNF-alpha in EBC was determined by enzyme-linked immunosorbent assay. Neutrophil chemotactic activity in EBC was determined in vitro using the blind-well technique. RESULTS: The concentrations of total protein and nitrite, and neutrophil chemotactic activity were significantly higher in EBC of smokers in comparison to nonsmokers (p < 0.05). The concentrations of total protein and nitrite in the condensate of smokers did not change significantly after smoking one cigarette. The concentrations of IL-1beta and TNF-alpha in EBC were similar in nonsmokers and smokers. CONCLUSIONS: Concentrations of certain inflammatory mediators and neutrophil chemotactic activity are increased in EBC of young healthy smokers. Collection and analysis of EBC may assist in early detection of cigarette smoke-induced pulmonary inflammation and identifying populations at risk for acquiring COPD.     

Gastritis Promotes an Activated Bone Marrow-Derived Mesenchymal Stem Cell with a Phenotype Reminiscent of a Cancer-Promoting Cell

Background

Bone marrow-derived mesenchymal stem cells (BM-MSCs) promote gastric cancer in response to gastritis. In culture, BM-MSCs are prone to mutation with continued passage but it is unknown whether a similar process occurs in vivo in response to gastritis.

Aim

The purpose of this study was to identify the role of chronic gastritis in the transformation of BM-MSCs leading to an activated cancer-promoting phenotype.

Methods

Age matched C57BL/6 (BL/6) and gastrin deficient (GKO) mice were used for isolation of stomach, serum and mesenchymal stem cells (MSCs) at 3 and 6 months of age. MSC activation was assessed by growth curve analysis, fluorescence-activated cell sorting and xenograft assays. To allow for the isolation of bone marrow-derived stromal cells and assay in response to chronic gastritis, IRG/Vav-1^Cre mice that expressed both enhanced green fluorescent protein-expressing hematopoietic cells and red fluorescent protein-expressing stromal cells were generated. In a parabiosis experiment, IRG/Vav-1^Cre mice were paired to either an uninfected Vav-1^Cre littermate or a BL/6 mouse inoculated with Helicobacter pylori.

Results

GKO mice displayed severe atrophic gastritis accompanied by elevated gastric tissue and circulating transforming growth factor beta (TGFβ) by 3 months of age. Compared to BM-MSCs isolated from uninflamed BL/6 mice, BM-MSCs isolated from GKO mice displayed an increased proliferative rate and elevated phosphorylated-Smad3 suggesting active TGFβ signaling. In xenograft assays, mice injected with BM-MSCs from 6-month-old GKO animals displayed tumor growth. RFP+ stromal cells were rapidly recruited to the gastric mucosa of H. pylori parabionts and exhibited changes in gene expression.

Conclusions

Gastritis promotes the in vivo activation of BM-MSCs to a phenotype reminiscent of a cancer-promoting cell.     

Contribution of arachidonic acid metabolites derived via cytochrome P4504A to angiotensin II-induced neointimal growth

Angiotensin II and the arachidonic acid metabolite derived via cytochrome P450 20-hydroxyeicostetraenoic acid promote vasoconstriction and vascular smooth muscle cell (VSMC) proliferation. This study was conducted to determine if 20-hydroxyeicostetraenoic acid contributes to angiotensin II-induced neointimal formation in balloon-injured rat carotid artery. In anesthetized rats, the drugs were infused into the clamped segment of the injured right common carotid artery for 60 minutes. The drug solution and catheter were withdrawn, the common carotid artery was ligated, and blood flow was restored. Exposure of the injured artery to angiotensin II (200 nmol/L) or arachidonic acid (10 micromol/L) increased neointimal thickening at day 14 (intima/media ratio 0.71+/-0.14 with vehicle versus 1.65+/-0.10 with angiotensin II or 1.31+/-0.13 with arachidonic acid; P<0.05). Cytochrome P450 4A1 antisense, but not scrambled, oligodeoxynucleotide (100 nmol/L) reduced angiotensin II-induced or arachidonic acid-induced neointimal thickening (intima/media ratio 0.90+/-0.07 for angiotensin II and 0.95+/-0.06 for arachidonic acid). 20-hydroxyeicostetraenoic acid (0.5 micromol/L) also increased neointimal thickening of injured artery (intima/media ratio 1.15+/-0.03); this was not altered by cytochrome P450 4A1 antisense oligodeoxynucleotide. Angiotensin II, arachidonic acid, and 20-hydroxyeicostetraenoic acid also induced the expression of cytochrome P450 4A and increased the number of CD45-positive cells; the latter effect of angiotensin II and arachidonic acid, but not 20-hydroxyeicostetraenoic acid, was diminished by cytochrome P450 4A1 antisense oligodeoxynucleotide. These data suggest that arachidonic acid metabolites derived via cytochrome P450 4A, most likely 20-hydroxyeicostetraenoic acid, mediate angiotensin II-induced neointimal thickening in injured rat carotid artery.     

Activated Clotting Times in the Setting of Eptifibatide Use During Percutaneous Coronary Intervention

Background: Previous studies have demonstrated a prolongation of activated clotting times (ACT) with abciximab administration during percutaneous coronary interventions (PCI). The impact of the short acting glycoprotein (GP) IIb-IIIa inhibitor, eptifibatide, on ACT measurements has not been studied. Methods: Seventy consecutive patients undergoing PCI in the setting of eptifibatide administration were prospectively enrolled in a single center study. Eptifibatide was administered as two 180 g/kg boluses 10 minutes apart followed by a continuous infusion of 2.0 g/kg/min. In 15 patients (Group I), the initial eptifibatide and heparin boluses were separated by 5 minutes, and ACT's were assessed after each bolus as well as at 3 subsequent time points. In 55 patients (Group II), an ACT level was drawn 10 minutes after the initial heparin/eptifibatide bolus and 20 minutes following the second eptifibatide bolus. Two different ACT measuring devices—CoaguChek Pro DM and Hemochron 801—were used to examine the impact of eptifibatide on ACT values. Results: The devices differed in the reproducibility of their measurements, but the overall trends were consistent with both devices. The ACT value was unchanged after the initial eptifibatide bolus (with a delta of 0.6 seconds by CoaguChek Pro DM and 4.2 seconds by Hemochron). While the ACT value rose significantly after the heparin bolus, the second eptifibatide bolus did not result in any further rise in ACT values. Conclusions: Unlike abciximab, eptifibatide does not significantly prolong the ACT in patients undergoing PCI. This may have implications regarding the need for separate heparin dosing algorithms for patients undergoing PCI in the setting of different GPIIb-IIIa inhibitors.     

Weight reduction in the cardiac rehabilitation setting

BACKGROUND: Most patients with coronary heart disease are overweight. However, only minimal weight loss occurs with participation in a standard cardiac rehabilitation (CR) program. METHODS: The study investigated 82 patients with coronary heart disease who entered an outpatient CR program and completed 36 sessions of exercise over a 12-week period. The effects of a structured, nurse-coordinated, weight loss intervention during phase 2 CR were compared with those observed in a CR control group receiving usual care. RESULTS: The intervention group lost an average of 4.3 +/- 2.8 kg (P <.0001), as compared with a weight loss of 1.7 +/- 2.6 kg (P <.001) in the control group (P <.005 between groups). The effect of the weight loss intervention on total cholesterol (172 +/- 34 to 166 +/- 29 mg/dL) differed from the response in a control group receiving usual care (180 +/- 30 to 187 +/- 28 mg/dL) (P <.05 between groups). The weight loss group experienced a significantly greater improvement (P <.05) than the control group in the physical function score on the Medical Outcomes Study SF-36 questionnaire. A significant correlation was found between the number of weight loss sessions an individual attended and the amount of weight loss experienced (R = 0.39; P <.05). CONCLUSIONS: The current study demonstrated that a behavioral weight loss intervention is effective in reducing body weight in a CR setting. Participants in the intervention group experienced significantly greater improvements in body weight, body mass index, and total cholesterol than a control group. Additionally, participants in the weight loss program reported greater improvements in their physical function score than the control patients.     

The valve of choice in elderly patients and its influence on quality of life: a long-term comparative study

BACKGROUND AND AIM OF THE STUDY: Mechanical heart valves are preferred for younger patients in order to avoid valve structural deterioration, but bioprosthetic valves are favored for older patients to avoid long-term anticoagulation. With increasing patient longevity, controversy persists regarding the valve of choice in the 65- to 75-year-old population. With improving patient survival, long-term quality of life (QOL) is a critical element in helping to resolve this controversy. METHODS: A retrospective analysis was conducted of 1,104 consecutive patients, aged 65-75 years, who underwent valve replacement between July 1976 and December 1999. Valves implanted were either a Carpentier-Edwards (CE) porcine bioprosthesis (596 patients) or a St. Jude Medical (SJM) mechanical valve (508 patients), with and without concomitant coronary artery bypass grafting. QOL was assessed using the Short Form (SF-36) Health Survey for both groups at the time of follow up, which was 98.2% complete. Comparable patient groups were analyzed within quintiles by propensity score analysis. RESULTS: Operative mortality was 9.4% (n = 56) for CE patients, and 5.3% (n = 27) for SJM patients (p = 0.014). Propensity score analysis revealed no significant difference in operative mortality between groups in any of the five quintiles. Actuarial survival for hospital survivors favored SJM patients (p = 0.005). However, when compared within quintiles, there was no significant difference between groups. QOL summary scores were significantly higher for physical health (p = 0.007) for SJM patients, but similar between valve groups for mental health. Comparison within quintiles revealed no significant difference between the groups in either area. CONCLUSION: When comparing the outcomes of mechanical versus bioprosthetic valve replacement, considerable care must be exercised to ensure the clinically relevant similarity of groups. When evaluating comparable patient groups, there was no advantage in either survival or QOL for patients aged 65-75 years receiving a CE or SJM valve.     

Long-term outcome of patients with syncope associated with coronary artery disease and a nondiagnostic electrophysiologic evaluation

Syncope in the patient with structural heart disease and a nondiagnostic noninvasive workup is a generally accepted indication for an invasive electrophysiologic study. However, if the electrophysiologic evaluation is not highly sensitive, arrhythmic causes of syncope may not be discovered. In these patients, recurrent syncope and even sudden death may be observed at follow-up. Thus, we evaluated long-term follow-up in 68 consecutive patients who presented with syncope, coronary artery disease, and who had a negative invasive electrophysiologic evaluation. At a mean follow-up of 30 +/- 18 months (range 1 to 65), there have been 2 sudden deaths and 1 episode each of ventricular fibrillation and ventricular tachycardia in patients treated with an implantable cardioverter-defibrillator. All 4 arrhythmias occurred in patients with left ventricular fractions < or = 25%. Seventeen patients had recurrent presyncope or syncope. Bradycardia causing syncope was found in 8 of these patients. A bundle branch block at the initial evaluation predicted for the occurrence of bradycardia at follow-up. We conclude that in patients with coronary artery disease and syncope, noninducibility at electrophysiologic study predicts a lower risk of sudden death and ventricular arrhythmias. However, in patients with a reduced ejection fraction, the risk of sudden death and ventricular arrhythmias remains up to 10%/year and these patients may warrant treatment with implantable cardioverter-defibrillators. Recurrent syncope is common, and frequently a bradyarrhythmia is found to be the cause. Treatment of selected patients (especially those with bundle branch blocks) with permanent pacemakers may be justified.