Coronary artery perforations in the contemporary interventional era.

BACKGROUND: Coronary perforations represent a serious complication of percutaneous coronary intervention (PCI). METHODS: We performed a retrospective analysis of documented coronary perforations at Massachusetts General Hospital from 2000 to 2008. Medical records review and detailed angiographic analysis were performed in all patients. RESULTS: Sixty-eight cases of coronary perforation were identified from a total of 14,281 PCIs from March 2000 to March 2008 representing an overall incidence of 0.48%. The study cohort was predominantly male (61.8%), mean age 71+/-11 years with 78% representing acute cases (unstable angina: 36.8%, NSTEMI: 30.9%, STEMI: 10.3%). Coronary artery perforation occurred as a complication of wire manipulation in 45 patients (66.2%) with 88.9% of this group being hydrophilic wires, of coronary stenting in 11 (16.2%), of angioplasty alone in 6 (8.8%), and of rotational atherectomy in 8 (11.8%). The perforation was sealed with an angioplasty balloon alone in 16 patients (23.5%), and with stents in 14 patients (20.6%) (covered stents: 11.8% and noncovered stents: 8.8%). Emergency CABG was performed in 2 patients (2.9%). Five patients (7.4%) developed periprocedural MI. The in-hospital mortality rate was 5.9% in the study cohort. CONCLUSION: Coronary artery perforation as a complication of PCI is still rare as demonstrated in our series with an incidence of 0.48%. The predominant cause of coronary perforations in the current era of PCI is wire injury.

A comparison of the efficacy and tolerance of pancrelipase and placebo in the treatment of steatorrhea in cystic fibrosis patients with clinical exocrine pancreatic insufficiency.

OBJECTIVE: The safety and efficacy of Minimicrospheres, which are enteric-coated, delayed-release pancrelipase capsules, on fat absorption in pediatric/adolescent and adult cystic fibrosis (CF) patients was assessed. Exocrine pancreatic insufficiency, common in CF patients, causes steatorrhea due to insufficient release of pancreatic enzymes. METHODS: In the open-label phase, 97 CF patients with pancreatic insufficiency and steatorrhea were stabilized on a high-fat diet and administered pancrelipase. Seventy-four patients with >80% coefficient of fat absorption received placebo or pancrelipase in the double-blind phase. Fat intake and excretion, stool frequency and consistency, and clinical global improvement were recorded. RESULTS: Average daily fat intake was comparable between treatment groups within each age group (adults vs pediatric/adolescent), but placebo patients had a significant (p < 0.001) mean decrease in coefficient of fat absorption (adult, 36.9 percentage points; pediatric/adolescent, 34.9 percentage points) from open-label to double-blind treatment compared to pancrelipase patients (adult, 2 percentage points; pediatric/adolescent, 3.25 percentage points); this difference was caused by a greater (p < or = 0.001) increase in mean fecal fat excretion (grams per day) in the placebo groups compared to pancrelipase groups (adult: 61.9 vs 2.3; pediatric/adolescent: 45.4 vs 4.1). Change in mean stool frequency from open-label to double-blind phases was significantly different (p < or = 0.002) between treatment groups, with increases in placebo groups and no difference (adult) or decrease (pediatric/adolescent) in pancrelipase groups. Pancrelipase patients' stool consistency remained about the same from open-label to double-blind. Placebo patients' stool consistency decreased (became softer) from open-label pancrelipase to double-blind placebo. Clinical global improvement data showed that > or =83% of pancrelipase patients improved or remained unchanged. CONCLUSIONS: Enteric-coated, delayed-release (Minimicrospheres) pancrelipase capsules are an effective treatment for steatorrhea associated with pancreatic insufficiency in patients with cystic fibrosis.

Detecting and differentiating white from red coronary thrombus by angiography in angina pectoris and in acute myocardial infarction.

To determine the ability to detect thrombus by angiography, angioscopy was performed before angiography in patients undergoing interventional procedures and the data collected in a blinded fashion. These data demonstrated that the sensitivity of angiography to detect white thrombus was 50% and the specificity was 95%, whereas the sensitivity and specificity to detect red thrombus was 100%, respectively; the positive and negative predictive value of detecting thrombus in general was 89% and 83%, respectively.

Safety of repeated intermittent courses of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis.

OBJECTIVES: To determine the effect of repeated doses of aerosolized recombinant human deoxyribonuclease (rhDNase) on the development of anti-rhDNase antibodies, acute allergic reactions, and pulmonary function in patients with cystic fibrosis. DESIGN: A multicenter, open-label study in which 184 patients received 10 mg aerosolized rhDNase twice a day for 14 days followed by a 14-day washout period for a total of 6 treatment cycles. Serial determinations of anti-rhDNase antibodies and pulmonary functions were performed. RESULTS: Detectable anti-rhDNase antibodies developed in 16 (8.7%) patients. These patients had no changes in their symptoms from the time they entered the trial. Antibodies detected were all of the IgG isotype. Increases in both forced expired volume in 1 second and forced vital capacity were noted from the beginning to the end of each cycle of treatment returning to baseline during the off-treatment period of each cycle. Seropositivity to rhDNase was not associated with allergic reactions and had no relationship on improvement in pulmonary function. CONCLUSIONS: Development of anti-rhDNase antibodies occurred in a small number of patients and was not associated with side effects. Intermittent administration of rhDNase for 24 weeks to patients with cystic fibrosis was well tolerated and was not associated with anaphylaxis in any patient. Pulmonary function improved significantly during the 14-day cycles while rhDNase was administered and returned to baseline when rhDNase was discontinued.

Antibiotic use in cystic fibrosis.

Antibiotic administration is the mainstay of therapy for pulmonary disease in patients with cystic fibrosis (CF). The progressive nature of the pulmonary disease in CF shortens survival. New and potent antibiotics, more aggressive antibiotic therapy, and multiple routes of administration have contributed to improved survival among CF patients. Pseudomonas aeruginosa is the predominant bacterial pathogen in the lower airways of CF patients. Most of the efforts in treating the chronic pulmonary infection are directed toward this organism. Aerosol aminoglycoside delivery provides a safe and effective alternative method to parenteral administration for treating patients who require chronic antibiotic therapy. This article reviews strategies for choosing antibiotics and current opinions regarding antibiotic therapy for patients with CF.

Efficacy and safety of short-term administration of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis.

Chronic endobronchial bacterial infection evokes purulent airway secretions in patients with CF. The viscoelastic properties of these secretions is primarily due to the presence of polymerized DNA from degenerating leukocytes. Recombinant human DNase I (rhDNase) reduces the viscosity of CF sputum in vitro. To test the hypothesis that rhDNase would improve pulmonary function in children and adults with CF, we compared the efficacy and safety of 10-day administration of three doses of aerosolized rhDNase (0.6, 2.5, or 10.0 mg twice daily) in 181 outpatients using a randomized, placebo-controlled parallel design. Forced vital capacity (FVC) improved 10 to 12% (p < 0.05 to 0.001), and forced expiratory volume in one second (FEV1) improved 10 to 15% (p < 0.001) across all doses of rhDNase compared with placebo. The magnitude of effect was dose dependent for both FVC and FEV1 through study Day 21 (p < 0.001). rhDNase was associated with a decreased perception of dyspnea and an improved perception of well-being. No patients developed detectable anti-rhDNase antibodies or bronchial reactivity to rhDNase. Some patients experienced mild upper airway irritation, but no major adverse events were reported. Administration for 10 days of aerosolized rhDNase to pediatric and adult outpatients with CF improves lung function and is well tolerated. Although all three doses were efficacious, the greatest improvement in FEV1 and FEV1/FVC ratio was demonstrated in the 2.5 and 10.0 mg rhDNase treatment groups.

Efficacy of aerosolized tobramycin in patients with cystic fibrosis.

BACKGROUND: Direct aerosol delivery of aminoglycosides such as tobramycin to the lower airways of patients with cystic fibrosis may control infection with Pseudomonas aeruginosa and improve pulmonary function, with low systemic toxicity. We conducted a randomized crossover study to evaluate the safety and efficacy of aerosolized tobramycin in patients with cystic fibrosis and P. aeruginosa infections. METHODS: Seventy-one patients with stable pulmonary status were recruited from seven U.S. centers for the treatment of cystic fibrosis and randomly assigned to one of two crossover regimens. Group 1 received 600 mg of aerosolized tobramycin for 28 days, followed by half-strength physiologic saline (placebo) for two 28-day period. Group 2 received placebo for 28 days, followed by tobramycin for two 28-day periods. Pulmonary function, the density of P. aeruginosa in sputum, ototoxicity, nephrotoxicity, and the emergence of tobramycin-resistant P. aeruginosa were monitored. RESULTS: In the first 28-day period, treatment with tobramycin was associated with an increase in the percentage of the value predicted for forced expiratory volume in one second (9.7 percentage points higher than the value for placebo; P < 0.001), forced vital capacity (6.2 percentage points higher than the value for placebo; P = 0.014), and forced expiratory flow at the midportion of the vital capacity (13.0 percentage points higher than the value for placebo; P < 0.001). A decrease in the density of P. aeruginosa in sputum by a factor of 100 (P < 0.001) was found during all periods of tobramycin administration. Neither ototoxicity nor nephrotoxicity was detected. The frequency of the emergence of tobramycin-resistant bacteria was similar during both tobramycin and placebo administration. CONCLUSIONS: The short-term aerosol administration of a high dose of tobramycin in patients with clinically stable cystic fibrosis is an efficacious and safe treatment for endobronchial infection with P. aeruginosa.

Educating school personnel about asthma.

Teachers, administrators, and other nonmedical personnel are frequently responsible for managing students with asthma during school hours. We determined that the school secretary is the most likely person to manage asthma at school. We developed an educational program for both nonmedical and medical school personnel entitled "Asthma Management in the Schools." A questionnaire designed to evaluate knowledge and obtain information about asthma care at school was mailed to participants several weeks before they attended the program and was administered again after the program was presented. Nonmedical personnel had lower mean preclass test scores than nurses, but mean postclass test scores were similar. Programs designed to improve asthma care in school should meet the needs of nonmedical personnel.

Implementation of "Open Airways" as an educational intervention for children with asthma in an HMO.

This article describes the adaptation and implementation of an existing pediatric asthma-management educational program, Open Airways, for members of a large group practice health maintenance organization. Seventy-four children ages 4 to 14 years and their families were randomized into one of seven class cohorts as part of a larger study of pediatric asthma management. The Open Airways program was modified to increase the emphasis on behavioral change and medication information and to reflect the different sociodemographic makeup of the population, compared with that for which the program was developed. Of the 74 families, 62 attended at least one class, and 47 of these attended five or more classes. Evaluations after classes suggest an increase in parental confidence in managing their child's asthma and an earlier use of medications. Health care providers may be able to adapt similar programs for successful use with their populations.

Thrombolytic treatment of an acute anterior myocardial infarction based upon echocardiography and in the absence of electrocardiographic criteria.

Tissue plasminogen activator was administered intravenously to a patient with clinical features of, but without electrocardiographic criteria for, an acute myocardial infarction. The ultimate treatment decision was based upon echocardiographic findings diagnostic for an anteroseptal myocardial infarction. Subsequent coronary angiography demonstrated a severe proximal, but patent left anterior descending stenosis. The patient is now asymptomatic 3 months following thrombolytic therapy and coronary angioplasty.

Pulmonary function testing in children.

This article concentrates on those factors that are particularly important for performing and interpreting lung function tests in children. Specifically, technical considerations such as equipment, personnel, test performance, and bronchoprovocation procedures are discussed. Changes in lung function with growth and appropriate use of race-specific reference standards are emphasized, and references for standard and experimental pulmonary function tests are provided. Several examples illustrating the utility of pulmonary function testing in clinical situations in children with lung disease are provided as well.

Differentiation of ischemic from nonischemic cardiomyopathy with positron emission tomography.

This study was undertaken to determine whether positron emission tomography (PET) performed after the intravenous injection of 11C-palmitate permits differentiation of patients with ischemic from those with nonischemic dilated cardiomyopathy. PET was performed after intravenous injection of 11C-palmitate in 10 patients with ischemic and in 10 with nonischemic dilated cardiomyopathy. Regions of homogeneously severely depressed accumulation of 11C-palmitate, representing 15% or more of the expected myocardial cross-sectional area, were observed in 8 of 10 patients with ischemic but in none of 10 patients with nonischemic cardiomyopathy. Patients with nonischemic cardiomyopathy had marked spatial heterogeneity of the accumulation of palmitate throughout the left ventricular myocardium, whereas most tomographic sections from patients with ischemic cardiomyopathy accumulated 11C-palmitate more homogeneously in regions exclusive of discrete defects indicative of remote infarction. Thus, a larger number of discrete noncontiguous regions (17 +/- 5 compared with 12 +/- 4, p less than 0.001) and greater reduction of average 11C-palmitate content (59 +/- 6 compared with 64 +/- 10% maximal myocardial radioactivity, p less than 0.05) were seen in the tomographic reconstructions from patients with nonischemic than in those from patients with ischemic cardiomyopathy. These findings support the hypothesis that multiple myocardial infarctions underlie the process seen as dilated cardiomyopathy in patients with coronary artery disease. Our findings indicate that PET permits differentiation of patients with ischemic from those with nonischemic cardiomyopathy.

Quantitative 31P nuclear magnetic resonance analysis of metabolite concentrations in Langendorff-perfused rabbit hearts.

The quantitative analysis of the mobile high-energy phosphorus metabolites in isovolumic Langendorff-perfused rabbit hearts has been performed by 31P NMR utilizing rapid pulse repetition to optimize sensitivity. Absolute quantification required reference to an external standard, determination of differential magnetization saturation and resonance peak area integration by Lorentzian lineshape analysis. Traditionally accepted hemodynamic indices (LVDP, dp/dt) and biochemical indices (lactate, pyruvate) of myocardial function were measured concomitantly with all NMR determinations. Hemodynamically and biochemically competent Langendorff-perfused rabbit hearts were found to have intracellular PCr, ATP, GPC, and Pi concentrations of 14.95 +/- 0.25, 8.08 +/- 0.13, 5.20 +/- 0.58 and 2.61 +/- 0.47 mM respectively. Intracellular pH was 7.03 +/- 0.01. Cytosolic ADP concentration was derived from a creatine kinase equilibrium model and determined to be approximately 36 microM. Reduction of perfusate flow from 20 to 2.5 ml/min demonstrated statistically significant decreases in PCr, ATP, and pH as well as an increase in Pi that correlated closely with the independent hemodynamic and biochemical indices of myocardial function. The decrease in ATP and PCr concentrations precisely matched the increase in Pi during reduced flow. These results constitute the first quantitative determination of intracellular metabolite concentrations by 31P NMR in intact rabbit myocardium under physiologic and low flow conditions.

Tetanus toxoid as an antigen for delayed cutaneous hypersensitivity.

We studied the usefulness of tetanus toxoid (TT) as a skin test antigen in assessing cellular immune function. Hospitalized patients were skin tested with four antigens, and the response rates between these antigens were compared. Candida and mumps antigens resulted in significantly more positive responses than did TT or PPD. The response rate to the TT significantly declined in older patients, suggesting these persons may not be adequately immunized against tetanus. We found TT is not as useful as Candida or mumps antigens in the evaluation of cellular immune function in a hospitalized population but it may have some usefulness in the evaluation of energy. Negative skin test results may convert to positive after patients receive an immunizing dose of TT, as shown by our data. In addition, there were several patients with a positive response to TT and negative responses to the other common skin test antigens.