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Biomedical subjects

Irvin Mayers

Publications and source records attributed to Irvin Mayers.

17 recordsLinked to original sources

Effects of nocturnal noninvasive mechanical ventilation on heart rate variability of patients with advanced COPD.

BACKGROUND: Cardiovascular comorbidities have a negative impact on the health status and prognosis of patients with COPD. We determined whether nocturnal noninvasive (positive) mechanical ventilation (NIMV) can improve heart rate variability (HRV), decrease circulating natriuretic peptide levels, and improve functional performance of patients with very advanced COPD. METHODS: A randomized, double-blind, parallel controlled trial was conducted in 23 participants with stable but advanced COPD. Participants received standard medical therapy plus nocturnal NIMV or standard medical therapy plus sham NIMV for 3 months. RESULTS: After 3 months of NIMV therapy, the 24-h triangular interpolation of N-N intervals increased from 322 to 473 ms (p = 0.034), the 24-h HRV index (HRVI) increased from 21.8 to 29.9 ms (p = 0.035), nocturnal HRVI increased from 6.1 to 8.0 ms (p = 0.026), and the SD of the average N-N interval increased from 37 to 41 ms (p = 0.020). None of these indexes changed significantly in the control group. Additionally, compared with the control group, the pro-atrial natriuretic peptide levels declined significantly in the NIMV group (p = 0.013). CONCLUSIONS: NIMV applied nocturnally over 3 months may improve HRV, reduce circulating natriuretic peptide levels, and enhance the functional performance of patients with advanced but stable COPD. While not definitive due to small sample size, these data suggest that nocturnal NIMV may reduce the impact of cardiac comorbidities in COPD patients.

Aged↗

Inhaled nitric oxide treatment of patients with pulmonary tuberculosis evidenced by positive sputum smears.

Endogenous nitric oxide (NO) has antimycobacterial properties. We tested the hypothesis that exogenous (inhaled) NO can be safely delivered and can accelerate airway disinfection for pulmonary tuberculosis patients treated with standard therapy. Exogenous NO administered at 80 ppm for 72 h can be safely delivered but does not accelerate airway disinfection.

Administration, Inhalation↗

The use of noninvasive mechanical ventilation for the treatment of acute exacerbations of chronic obstructive pulmonary disease in Canada.

BACKGROUND: Noninvasive mechanical ventilation (NIMV) is accepted as a life-saving treatment for patients presenting to the emergency department and other acute care settings with severe exacerbations of chronic obstructive pulmonary disease (COPD). OBJECTIVES: It was hypothesized that there is marked national variability in the use of NIMV. Therefore, the use of NIMV for COPD exacerbations in urban centres across Canada was evaluated. METHODS: All Canadian hospitals affiliated with a university training program were surveyed, and a request for involvement in this survey was posted on the Canadian Society of Respiratory Therapy professional practice listserv. Survey information was received from all 33 sites (100%) that were contacted. RESULTS: Marked differences in the application of NIMV were identified across all regions in Canada, ranging from requiring extensive monitoring in the intensive care unit to application on a general internal medical unit with intermittent noninvasive blood pressure monitoring. There were sites that rarely used NIMV for COPD exacerbations and others where it was routine practice. CONCLUSIONS: NIMV is a life-saving treatment for acute exacerbations of COPD. Despite clear clinical evidence, its use has not penetrated throughout all the larger urban hospitals in Canada. This may be more problematic in sites without 24 h respiratory therapy support. There are barriers to the routine application of NIMV that can be overcome using established guidelines and available evidence.

Acute Disease↗

Nitric oxide and cyclic GMP increase the expression of matrix metalloproteinase-9 in vascular smooth muscle.

Interactions and possible cross talk between inducible nitricoxide synthase (iNOS), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9), were studied in rat aortic vascular smooth muscle cells stimulated with bacterial lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), and phorbol 12-myristate13-acetate (PMA). The expression and activity of iNOS, COX-2, and MMP-9 were characterized at the transcriptional, protein, and enzyme activity levels. The NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) was used to investigate the effects of NO on COX-2 and MMP-9 at the transcriptional level. The measurements of mRNAs for these enzymes using real-time polymerase chain reaction (PCR) showed that COX-2 mRNA was up-regulated 2.3-fold, whereas MMP-9 mRNA up-regulation was 11.7-fold in the presence of LPS, IFN-gamma, and PMA. Real-time PCR results indicated that L-NAME exerted an inhibitory effect on COX-2 and MMP-9 mRNA synthesis. Both superoxide dismutase (SOD) and the SOD mimetic Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (MnTMPyP) did not modify significantly the up-regulation of these enzymes, indicating that neither superoxide nor peroxynitrite are involved in this mechanism. Furthermore, NO-mediated up-regulation of MMP-9 was cGMP-dependent since 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase, blocked, in a concentration-dependent manner, the increased expression of MMP-9, an effect reversed by 8-bromo-cGMP, a soluble analog of cGMP. Our findings suggest that NO and cGMP are necessary to up-regulate the expression of MMP-9.

Animals↗

Pulmonary and systemic nitric oxide measurements during CCK-5-induced panic attacks.

Nitric oxide (NO) plays a major role in cardiopulmonary regulation as illustrated by the alterations of the NO system described in cardiopulmonary illnesses. Recent studies have found an association between panic disorder and cardiovascular death and illness, as well as pulmonary diseases. Our objective was to investigate whether pulmonary or systemic NO production was altered during induced panic attacks (PAs). We used a double-blind placebo-controlled crossover design with randomization of the order of an injection of placebo and pentagastrin, a cholecystokinin-B receptor agonist that induces PAs in healthy volunteers (HVs). A total of 17 HVs experienced a PA after pentagastrin challenge. Exhaled NO and NO metabolites were measured by chemiluminescence. During pentagastrin-induced PAs, HVs displayed significant decreases in plateau concentrations of NO exhaled, which were associated with proportional increases in minute ventilation. There were no significant changes in pulmonary or systemic NO production. These results suggest that the decrease in exhaled NO concentration observed during pentagastrin-induced PAs is related to the associated hyperventilation, rather than to any change in lung NO production. This study is the first to evaluate changes in NO measurements during acute anxiety.

Adult↗

Increased matrix metalloproteinase activity after canine cardiopulmonary bypass is suppressed by a nitric oxide scavenger.

OBJECTIVES: We tested whether nitric oxide scavenging with a ruthenium-based compound (AMD6221) would improve hemodynamics and alter nitric oxide synthase and matrix metalloproteinase activities in a canine model of cardiopulmonary bypass. METHODS: Dogs were randomized to either cardiopulmonary bypass (n = 12) or control (n = 12) groups. They were further randomized to receive a continuous infusion of AMD6221 or placebo. Cardiopulmonary bypass was maintained for 90 minutes, and then, 4 hours later, dogs were killed. Cardiac, lung, and brain sections were snap frozen in liquid nitrogen for determination of nitric oxide synthase, matrix metalloproteinase 2, and matrix metalloproteinase 9 activities. RESULTS: After cardiopulmonary bypass, 3 of 6 placebo-treated (cardiopulmonary bypass-placebo) and 0 of 6 AMD6221-treated (cardiopulmonary bypass-6221) animals required phenylephrine infusion to maintain a predetermined blood pressure (P <.05). Total fluid administration was lower in the cardiopulmonary bypass-6221 group compared with that in the cardiopulmonary bypass-placebo group (983 +/- 134 vs 1617 +/- 254 mL, respectively; P <.005). After cardiopulmonary bypass, matrix metalloproteinase 2 and matrix metalloproteinase 9 activities in the lung, left ventricle, and left atrium were decreased in the cardiopulmonary bypass-6221 group compared with that in the cardiopulmonary bypass-placebo group (P <.05). Ca(2+)-independent nitric oxide synthase activity and matrix metalloproteinase 2 activity in the brain were also lower (P <.05) in the cardiopulmonary bypass-SCV group. Finally, neutrophil expression of CD18, an adhesion complex, was lower at 4 hours after cardiopulmonary bypass in the cardiopulmonary bypass-6221 group compared with that in the cardiopulmonary bypass-placebo group (38 +/- 27 vs 81 +/- 11; P <.05). CONCLUSIONS: We found that (1) infusion of an nitric oxide scavenger, AMD6221, was associated with improved predefined hemodynamics; (2) cardiopulmonary bypass increased activities of Ca(2+)-independent nitric oxide synthase and matrix metalloproteinases in multiple organs; and (3) AMD6221 could ameliorate the increased generation of nitric oxide and increased matrix metalloproteinase activities.

Animals↗

Distribution of nitric oxide synthase in normal and cirrhotic human liver.

Chronic liver disorders represent a serious health problem, considering that 300 million people worldwide are hepatitis B virus carriers, and 8,000-10,000 patients per year, in the U.S. alone, die as a result of liver failure caused by hepatitis C infection. Nitric oxide synthase (NOS) regulates hepatic vasculature; however, the patterns of expression and activity of NOS proteins in healthy and diseased human livers are unknown. Sections of diseased (n = 42) and control livers (n = 14) were collected during orthotopic liver transplants and partial hepatectomy. The diseased sections included alcoholic cirrhosis, viral hepatitis, cholestasis, acute necrosis, and uncommon pathologies including alpha(1)-anti-trypsin disorder. The endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were studied by using the citrulline assay, Western immunoblot, immunohistochemistry, and in situ hybridization. The systemic generation of plasma NO metabolites was measured by HPLC. In control livers, Ca(2+)-dependent and -independent NOS activities were identified by Western analysis as eNOS and iNOS, respectively. The eNOS was uniformly distributed in the hepatocytes and also detected in the endothelium of hepatic arteries, terminal hepatic venules, sinusoids, and in biliary epithelium. The iNOS was detected in hepatocytes and localized mainly in the periportal zone of the liver acinus. This pattern of distribution of eNOS and iNOS in normal liver was confirmed by in situ hybridization. In diseased livers, there was a significant increase in Ca(2+)-independent NOS with the corresponding strong appearance of iNOS in the cirrhotic areas. The eNOS was translocated to hepatocyte nuclei. Thus, eNOS and iNOS proteins are differentially expressed in healthy human liver, and this expression is significantly altered in cirrhotic liver disorders.

Blotting, Western↗

Predictors of survival following in-hospital adult cardiopulmonary resuscitation.

BACKGROUND: This study was undertaken to provide up-to-date survival data for Canadian adult in-patients following attempted resuscitation from cardiac or respiratory arrest. We hope that objective data might encourage more meaningful dialogue between physicians, patients and their families regarding resuscitation wishes. METHODS: We reviewed all records of adult cardiopulmonary arrest that occurred between Jan. 1, 1997, and Jan. 31, 1999, at the 3 main teaching hospitals in Edmonton. We then abstracted data from the full inpatient medical records to describe patient characteristics, type of arrest and survival details. The family physicians of survivors were contacted to confirm the outcomes. We included only adults admitted to hospital but not to a critical care bed. RESULTS: There were 247 arrests during the study period; 143 (57.9%) were witnessed, and 104 (42.1%) were unwitnessed). Of the patients whose arrests were witnessed, 48.3% (95% confidence interval [CI] 39.8%-56.8%) were able to be resuscitated, 22.4% (95% CI 1 5.8%-30.1%) survived to hospital discharge, and 18.9% (95% CI 12.8%-26.3%) were able to return home. Survival was highest after primary respiratory arrest and lowest after pulseless electrical activity or asystole. Of the patients with unwitnessed arrests, 21.2% (95% CI 13.8%-30.3%) were able to be resuscitated, but only 1 patient (1.0% [95% CI 0.0%-5.2%]) survived to hospital discharge and was able to return home. This patient survived an unwitnessed respiratory arrest. No patient who had an unwitnessed cardiac arrest survived to discharge. Most of the respiratory arrests were witnessed (93.1%), and most of the pulseless electrical activity or asystole arrests were unwitnessed (54.6%). We did not find age or sex to be independent predictors of survival. However, the risk of not returning home was higher among patients whose arrest occurred between 2301 and 0700 than among those whose arrest was between 0701 and 1500 (adjusted OR 3.2, 95% CI 1.0-10.1). Survival was significantly decreased after pulseless ventricular tachycardia or ventricular fibrillation arrest (adjusted OR 4.2, 95% CI 1.4-12.5) and even more so after pulseless electrical activity or asystole arrest (adjusted OR 21.0, 95% CI 6.2-71.7) than after respiratory arrest. INTERPRETATION: Overall, survival following cardiopulmonary resuscitation in hospital does not appear to have changed markedly in 40 years. The type of arrest is highly predictive of survival, whereas age and sex are not.

Adult↗

Long-term compliance rates to continuous positive airway pressure in obstructive sleep apnea: a population-based study.

STUDY OBJECTIVES: To determine long-term compliance rates to continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnea enrolled in a comprehensive CPAP program in the community. DESIGN: Prospective cohort longitudinal study. SETTING: University sleep disorders center. PATIENTS: Two hundred ninety-six patients with an apnea-hypopnea index (AHI) > or = 20/h on polysomnography. INTERVENTIONS: A CPAP device equipped with a monitoring chip was supplied. Within the first week, daily telephone contacts were made. Patients were seen at 2 weeks, 4 weeks, 3 months, and 6 months. RESULTS: Of the 296 subjects enrolled, 81.1% were males. Mean +/- SD AHI was 64.4 +/- 34.2/h of sleep; age, 51 +/- 11.7 years; and body mass index, 35.2 +/- 7.9 kg/m(2). The mean duration of CPAP use was 5.7 h/d at 2 weeks, 5.7 h/d at 4 weeks, 5.9 h/d at 3 months, and 5.8 h/d at 6 months. The percentage of patients using CPAP > or = 3.5 h/d was 89.0% at 2 weeks, 86.6% at 4 weeks, 88.6% at 3 months, and 88.5% at 6 months. There was a decrease in the Epworth Sleepiness Scale (ESS) score of 44% by 2 weeks of therapy. The patients continue to improve over the follow-up period, with the lowest mean ESS score observed at 6 months. With multiple regression analysis, three variables were found to be significantly correlated with increased CPAP use: female gender, increasing age, and reduction in ESS score. CONCLUSION: A population-based CPAP program consisting of consistent follow-up, "troubleshooting," and regular feedback to both patients and physicians can achieve CPAP compliance rates of > 85% over 6 months.

Cohort Studies↗

Can continuous positive airway pressure therapy improve the general health status of patients with obstructive sleep apnea?: a clinical effectiveness study.

STUDY OBJECTIVES: To determine the short-term and long-term impacts of continuous positive airway pressure (CPAP) therapy on health-related quality of life (HRQL) in patients with obstructive sleep apnea (OSA). DESIGN: Prospective longitudinal cohort study. SETTING: University sleep disorders center. PATIENTS: Three hundred sixty-five patients with an apnea-hypopnea index (AHI) > or = 20 per hour of sleep and 358 patients with an AHI of < 20. INTERVENTIONS: All patients with AHIs > or = 20 received CPAP therapy; those with AHIs < 20 did not. The HRQL of all study participants was measured using the 36-item medical outcomes study short form (SF-36) questionnaire at baseline and then at 3 and 12 months of follow-up. RESULTS: Although the SF-36 scores were similar at baseline, after 3 months of therapy, the CPAP group had higher adjusted emotional summary scores than did those who did not receive CPAP therapy (score increase, 1.72; 95% confidence interval [CI], 0.08 to 3.37). These improvements were maintained for 12 months. The gains in the SF-36 scores were most striking in the vitality domain (score increase, 10.52; 95% CI, 7.04 to 14.00 U increment). The severe OSA group (ie, AHIs > or = 40) experienced the largest benefit. Their adjusted vitality scores were 12.3 U higher (95% CI, 8.0 to 16.6) than those persons without OSA (ie, AHIs < 5). CONCLUSIONS: CPAP therapy was associated with marked short-term and long-term improvements in the vitality of patients with moderate-to-severe OSA in the community. These findings suggest that CPAP therapy is effective in improving the long-term HRQL of patients with OSA.

Female↗

To all members.

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Canada↗

The current status of autotitrating continuous positive airway pressure systems in the management of obstructive sleep apnea.

BACKGROUND: Autotitrating continuous positive airway pressure (APAP) devices have the potential to address some of the disadvantages of titration and treatment with conventional continuous positive airway pressure (CPAP). Information on the performance of APAP in clinical use is still comparatively limited. OBJECTIVE: To assess the status of APAP devices in the management of obstructive sleep apnea (OSA) by reviewing evidence of their efficacy, effectiveness and costs. METHODS: A systematic search of electronic databases and a review of selected comparative studies on the use of APAP in the diagnosis, titration and treatment of OSA was undertaken. Cost analysis using data applicable to the management of OSA in Edmonton, Alberta was performed. RESULTS: Thirty-three studies met the selection criteria: three on the use of APAP in diagnosing OSA; six on APAP for titration; 14 that considered short-term treatment outcomes; and 10 that addressed longer-term treatment of OSA. In most studies, patients suffering from cardiac, pulmonary and other medical conditions were excluded. Available data suggested some potential for the use of APAP in the diagnosis of OSA, but further validation is needed. In titration, estimated treatment pressures tended to be lower with APAP than with the manual titration of CPAP. Although lower treatment pressures were achieved with APAP, there was no significant difference in clinical outcome measures between APAP and CPAP. Estimates of costs suggested that APAP may provide savings in some scenarios. CONCLUSIONS: APAP shows promise in the management of OSA; however, given the exclusion of some categories of patients from trials of this technology, caution is still required in its use.

Continuous Positive Airway Pressure↗

Internet-based asthma education - a novel approach to compliance: a case report.

Asthma costs Canadians over 1.2 billion dollars per annum and, despite advances, many asthmatic patients still have poor control. An action plan, symptom diary and measurement of peak expiratory flow have been shown to improve clinical outcomes. Effective educational interventions are an important component of good care. However, many rural sites lack not only access to education but physician care as well. It is reasonable, therefore, that an Internet-based asthma management program may be used as an approach. In the present case report, a novel approach that may increase access in these poorly serviced areas is presented. In an Internet-based asthma management program, patients are reviewed by a physician, receive education and are given a unique password that provides program access. Patients record symptoms and peak expiratory flow rates. The present case report shows that a patient can be assisted through an exacerbation, thus averting emergency intervention and stabilizing control, even when travelling on another continent.

Aged↗