Flecainide and propafenone are effective in suppressing both ventricular and supraventricular tachyarrhythmias, but their efficacy is often limited by dose-related side effects. This study was performed to evaluate noninvasively the effects of intravenous flecainide and propafenone on left ventricular systolic function indices in a selected population of 40 subjects (28 men and 12 women; mean age, 25 years) with normal cardiac structure and performance. Echocardiographic indexes of global systolic pump function (ejection fraction [EF] and percentage of fractional shortening [percent FS]) as well as monodimensional parameters of the intraventricular septum (IVS) and left ventricular posterior wall (PW) contractility (percent systolic thickening [percent th] and systolic excursion [ex]) were assessed in all subjects at baseline, immediately after, and in the early recovery (15 min) after randomized injection of either flecainide or propafenone. Heart rate and blood pressure did not significantly change after both drugs. A significant increase (p < 0.001) in left ventricular systolic internal diameter was observed after both flecainide and propafenone; simultaneously a significant decrease of percent FS (p < 0.001), EF (p < 0.001), PW percent thickening (th) (p < 0.001), and PWex (p < 0.001 after flecainide and p < 0.01 after propafenone) was recorded. These changes were comparable and promptly reversible. In analyzing individual data, a marked systolic dysfunction was observed in two patients after intravenous flecainide (percent FS from 37 percent to 17 percent and from 42 percent to 13 percent; EF from 55 percent to 40 percent and from 65 percent to 35 percent, respectively) and in one patient after intravenous propafenone (percent FS from 30 percent to 15 percent; EF from 58 percent to 35 percent). We conclude that both intravenous flecainide and propafenone exhibit mild negative inotropic effects leading to a moderate and reversible reduction of left ventricular systolic performance; however, in some cases, a dramatic impairment of systolic pump function may occur, suggesting careful use of both drugs as first-line agents also in normal subjects; finally, the true incidence of this deleterious effect is still unknown.

We have measured caloric intake, energy expenditure, and the thermogenic effect of food in ten patients with stable COPD who had a history of involuntary weight loss over several years and were malnourished (< 85 percent ideal body weight). Each patient completed a 7-day food record. Indirect calorimetry was performed in the resting postabsorptive state. After placement of a nasoenteric tube, patients were randomly assigned to be refed or sham-fed (mean +/- SD, 16 +/- 3 days), following which, metabolic measurements were repeated. Indirect calorimetry was also performed before and after a large meal in each patient. Home caloric intake was 135 +/- 23 percent of resting energy expenditure. Resting energy expenditure was 94 +/- 16 percent of that predicted by the Harris-Benedict equation and did not change significantly during inpatient refeeding. Refeeding resulted in weight gain (2.4 +/- 1.9 kg, p < 0.02). A large meal caused substantial increases in energy expenditure (24 +/- 18 percent), carbon dioxide production (39 +/- 18 percent), and oxygen consumption (23 +/- 16 percent). We conclude that stable malnourished COPD patients consume adequate calories to meet average energy requirements and are not hypermetabolic. Inpatient refeeding by nocturnal nasoenteric infusion is well tolerated and results in weight gain, but the thermogenic effect of a large meal poses a considerable metabolic and ventilatory load that could precipitate acute respiratory failure.

In the 1970s, three randomized trials, each involving approximately 10,000 male subjects, were carried out to determine the value of lung cancer screening in cigarette smokers. These studies have been widely interpreted as providing strong evidence that screening does not contribute to decreased death rates, and, accordingly, the American Cancer Society firmly recommends against lung cancer screening. No randomized trial, however, has evaluated screening for lung cancer in women, who currently comprise 39% of the lung cancer population. The trials performed at Memorial-Sloan Kettering and at Johns Hopkins were designed so that subjects were randomized to either a single screen (annual chest x-ray alone) or a dual screen (annual chest x-ray and every-4-month sputum cytology) group. While the results of both revealed no difference in mortality between the groups, these studies were designed to examine the value of sputum cytology, and no conclusion regarding the efficacy of chest x-rays can be inferred. In the Mayo Lung Project, patients were randomized to a screened group in which a chest x-ray and sputum cytology were obtained every 4 months or to a control group in which an annual chest x-ray and cytology were simply recommended. The results indicate that after 6 years, more lung cancers were detected among the 4,618 men in the screened group (206 cases, 4.46%) than in the 4,593 men in the control group (160 cases, 3.48%). The screened group showed a superiority over the control subjects in resectability rate (46% vs 32%) and 5-year survival (33% vs 15%). However, the number of cancer deaths was slightly greater in the screened (122) than in the control group (115), and, consequently, the mortality rates were not significantly different among the groups. An "overdiagnosis bias" has been suggested to account for the increased number of lung cancers detected in the screened vs the control population in the Mayo Lung Project. This explanation is statistically plausible, but, given the status of lung cancer as the most lethal of malignancies, is biologically unlikely. An alternative hypothesis is that chance alone might have accounted for the observed 0.98% difference in lung cancer detection rates. Were this the case, then 46 additional cases would have been detected in the control group had this chance event not occurred.(ABSTRACT TRUNCATED AT 400 WORDS)

The primary purpose of this study was to compare the efficacy of 1.4 percent sodium citrate with heparin, 4 U/ml, for maintaining radial artery catheter patency in patients in the medical ICU.

The purpose of this study was to determine whether supplemental oxygen-induced decreases in ventilation (VE) and mouth occlusion pressure (P0.1) in patients with COPD are related to the ventilatory or P0.1 responses to hypoxia (delta VE/delta SaO2, delta P0.1/delta SaO2). We measured these responses in 14 patients with a (mean +/- SD) FEV1 of 0.95 +/- .41 L. The VE and P0.1 were also measured while the patients sequentially breathed either room air or supplemental oxygen (1-2 L/min) for 10 min in a randomized single blind fashion. The mean (+/- SEM) SaO2 increased from 90.8 +/- 0.99 percent to 95.2 +/- 0.46 percent and the VE decreased during oxygen breathing from 12.3 +/- 0.46 to 11.6 +/- 0.47 L/min (p < 0.03). However, the individual changes in VE were not significantly related to the corresponding changes in SaO2 (CHG SaO2), (delta VE/delta SaO2), or (delta VE/SaO2) (CHG SaO2). Similarly, the P0.1 decreased from 2.50 +/- 0.27 to 2.26 +/- 0.20 cm H2O (p < 0.05), but the individual changes in P0.1 were not significantly related to (CHG SaO2), (delta P0.1/delta SaO2), or (delta PO.1/delta SaO2) (CHG SaO2).

A new long-acting bronchodilator prodrug, bambuterol hydrochloride, was tested in a randomized, crossover, and double-blind study in elderly asthmatic patients (aged 64 to 82 years). They received placebo and 5-mg, 10-mg, and 20-mg tablets once daily for a week at each dose. The plasma concentration of the active metabolite, terbutaline, increased linearly with the dose of drug (p < 0.001). Peak expiratory flow rate increased with dose in the morning (p < 0.001 for 10-mg and 20-mg doses) and afternoon (p < 0.05 for 10 mg; p < 0.001 for 20 mg) and was different from placebo for the 10-mg/d and 20-mg/d regimens. The use of supplemental inhaled beta 2-adrenergic agonist therapy was reduced during the night for the 10-mg (p < 0.05) and 20-mg (p < 0.01) doses in comparison to placebo. No significant effects of treatment on blood pressure and pulse were demonstrated. Tremor and palpitations were mild and related to the dose. These data suggest that treatment once daily with bambuterol hydrochloride in a dose of 10 or 20 mg improves pulmonary function and is well tolerated as bronchodilator therapy in elderly patients with asthma.

The efficacy and safety of orally administered clarithromycin and erythromycin in the treatment of community-acquired pneumonia were assessed in a multicenter, double-blind, randomized study. Two hundred sixty-eight patients were randomized to receive either clarithromycin, 250 mg twice a day, or erythromycin stearate, 500 mg 4 times a day, for 7 to 14 days. Efficacy was evaluable in 173 patients (92 for clarithromycin, 81 for erythromycin). No statistically significant difference in clinical success rate (cure or improvement) was observed between the two groups (clarithromycin, 97 percent; erythromycin, 96 percent). Both groups had identical radiologic response (97 percent with resolution or improvement). Similarly, no statistically significant difference in bacteriologic response toward the target pathogens was observed among evaluable patients (clarithromycin, 23/26; erythromycin, 17/17; p value = 0.287). Clinical response toward Mycoplasma and Chlamydia pneumonia was comparable between the two groups (clarithromycin, 15/16; erythromycin, 10/11). However, patients receiving erythromycin had a twofold higher incidence of adverse events, mostly related to the gastrointestinal system, and were five times more likely to withdraw from therapy because of drug-related adverse events. These results show that clarithromycin is as effective as erythromycin in the outpatient treatment of community-acquired pneumonia. Furthermore, the lower incidence of adverse events associated with clarithromycin indicates that it is more acceptable to patients and, therefore, can enhance compliance.

Cold air may worsen asthmatic bronchoconstriction but can lessen breathlessness in normal individuals. Patients with COPD sometimes report improvement in their dyspnea in cold weather. We examined the effect of breathing cold air on exercise tolerance and the perception of breathlessness in 19 patients with stable COPD (age [+/- SD], 63 +/- 6 years; FEV1, 0.99 +/- 0.28 L) in a randomized open study. Patients exercised on a cycle ergometer breathing either room or cold air (-13 degrees C), breathlessness being assessed by Borg scaling. Peak exercise performance improved when breathing cold air (mean +/- SE), 46 +/- 6 W compared with 37 +/- 7 W (p < 0.05) while end-exercise breathlessness fell from 4.6 +/- 0.4 compared with 4.1 +/- 0.5 (p < 0.05) when breathing cold air. End-exercise ETCO2 was higher breathing cold air (6.1 +/- 0.3 kPa compared with 5.5 +/- 0.3 kPa) (p < 0.005). There was no difference in breathlessness at equivalent levels of ventilation. Cold air reduces breathlessness in COPD, probably by inducing relative hypoventilation.

To compare the effectiveness of administration of albuterol by nebulizer or by a metered-dose inhaler having a holding chamber attachment (hereafter "inhaler") for treatment of acute asthma in an emergency department (ED).

It has been suggested that the defective cyclic AMP-dependent Cl- secretion and the increased Na+ absorption from airway epithelia in cystic fibrosis (CF) may lead to dehydrated secretions and impaired mucociliary clearance. Beta 2-adrenergic agonists are unable to stimulate the Cl- transport in the airways in CF while being able to do so in normal airways. Thus, we questioned whether the beta 2-adrenergic agonist, terbutaline, would improve mucociliary clearance in patients with CF as it does in healthy subjects.

The purpose of this study was to evaluate and compare the clinical effects, safety, and economic cost of propofol and midazolam in the sedation of patients undergoing mechanical ventilation in the ICU. Eighty-eight critically ill patients were studied and randomly allocated to receive short-term (less than 24 h), medium-term (24 h to 7 days), and prolonged (more than 7 days) continuous sedation with propofol (n = 46) or midazolam (n = 42). Mean doses required were 2.36 mg/kg/h for propofol and 0.17 mg/kg/h for midazolam. Patients in the group receiving propofol showed a percentage of hours of sedation at the desired level (grade 2, 3, 4, or 5 on the Ramsay scale) of 93 percent, compared with 82 percent (p < 0.05) in the group receiving midazolam. Both agents were considered safe with respect to the induction of adverse reactions during their use in prolonged sedation. Recovery after interrupting sedation was significantly faster in patients treated with propofol than in those sedated with midazolam (p < 0.05). Recovery of total consciousness was predictable according to sedation time in propofol-treated subgroups (r = 0.98, 0.88, and 0.92, respectively), while this correlation was not observed in the midazolam-treated group. In the subgroup with sedation of less than 24 h, propofol provided a cost savings of approximately 2,000 pesetas (pts) per patient, due to shorter stays in the ICU. We conclude that propofol is a sedative agent with the same safety, higher clinical effectiveness, and a better cost-benefit ratio than midazolam in the continuous sedation of critically ill patients.

Using radiolabeled, monodispersed aerosols (99mTc-iron oxide) and gamma camera analysis, we measured the efficacy of cough for clearing mucus from the airways of the lung following inhalation of the bronchodilator ipratropium bromide (IB) (Atrovent, Boehringer Ingelheim, Inc), a drug that has been shown to have no effect on mucociliary clearance in COPD. Clearance of radiolabeled aerosol was studied over a 2.5-h period on three separate days, a control day with no coughing, and two study days during which the patient performed controlled cough maneuvers over the course of clearance measurements following IB or placebo therapy (double blind, crossover). Fifteen patients, age > 45 years, with stable moderate-to-severe airway obstruction (mean FEV1/FVC = 0.45) were studied. IB diminished the effectiveness of cough for clearing the radiolabeled particles from the airways. This effect of IB on cough clearance may be due to (1) changes in the airflow dynamics induced by bronchodilation or (2) altered rheology or depth of airway secretions.

Intrapleural bupivacaine has been reported to be effective for analgesia following cholecystectomy and thoracic surgery. Twenty patients who had a posterolateral thoracotomy were studied in a randomized, double-blind, placebo-controlled fashion. Patients were assigned to receive intrapleural administration of either 0.5 percent bupivacaine or saline solution every 4 h for 12 doses postoperatively, as well as narcotic analgesics as needed for additional pain control. Pain was assessed using a visual analogue scale. Narcotic analgesic use, duration of hospitalization, and the development of complications were recorded. There were nine evaluable patients who received bupivacaine, and ten patients who received placebo. The age, sex, and type of operation were similar in the two groups, and the procedures were performed by the same two surgeons. The mean pain score at 24 h postoperatively was 5.8 +/- 0.8 in the bupivacaine group and 6.0 +/- 0.6 in the placebo group. At 48 h, the scores were 4.6 +/- 0.8 in the bupivacaine group and 5.1 +/- 0.9 in the placebo group. The mean dose of morphine sulfate or equianalgesic dose of meperidine during the first 24 h was 13.9 +/- 3.7 mg in the bupivacaine group and 12.6 +/- 1.8 mg in the placebo group, and during the next 24 h it was 40.0 +/- 13.4 mg in the bupivacaine group and 38.0 +/- 9.2 mg in the placebo group. The mean duration of hospitalization was 12.8 +/- 3.2 days in the bupivacaine group and 12.1 +/- 2.9 days in the placebo group. Two patients who received bupivacaine and three patients who received placebo had development of pneumonia or atelectasis postoperatively. There was no statistically significant difference in any parameter between those who received bupivacaine and those who received placebo. Thus, there was no subjective or objective clinical benefit of this method of postoperative analgesia compared with placebo following posterolateral thoracotomy.

To assess the accuracy of room-temperature thermodilution cardiac output measurements from the side port (SP) of the introducer catheter through which the pulmonary artery flotation catheter is inserted.

In an effort to isolate the effect of theophylline on sleep from the effect of asthma, we examined the impact of oral theophylline on sleep quality in normal, nonasthmatic subjects. Ten healthy, nonsmoking, male subjects ranging in age from 23 to 35 were studied. The subjects were randomly divided into two groups and studied in a double-blinded, crossover designed protocol. Each group underwent two consecutive nights in the sleep laboratory. Group one received four doses of 300 mg of sustained-release theophylline at 12-h intervals prior to the study night. Group two received a placebo. After 14 days, the patients crossed over to the other group, and the procotcol was repeated. The mean serum theophylline level on the morning following the study night was 7.85 +/- SD 2.12 micrograms/ml, with a range of 5.1 to 12.1 microns/ml. The analysis of variance for a crossover design showed no order effect. The analysis for drug effect showed that theophylline administration resulted in a statistically significant adverse effect on arousals per sleep hour (19.3 vs 15.9 for placebo, p = .006) and total sleep time (370.9 min vs 399.45 min for placebo, p = .015). Comparing the sum of ranks data, theophylline was found to have a significant adverse effect on sleep quality (p = .036). We conclude that low doses of oral theophylline result in a significant disturbance in sleep quality in normal nonasthmatic subjects.

Bronchial mucosa inflammation is a hallmark of asthma. Epithelial damage due to inflammatory process may contribute to induce a pattern of rapid and shallow breathing (RSB). Probably due to its effects on inflammatory process, beclomethasone dipropionate (BDP) decreases bronchial hypersensitivity (BH), as assessed in terms of histamine concentration causing a 20 percent FEV1 decrease from saline solution (PC20FEV1); however, no data are available on the effect of BDP on RSB. We studied 32 asymptomatic asthmatic subjects with a severe to moderate levels of BH (PC20FEV1 0.01 to 1.7 mg/ml). After they were randomly assigned to one month of either BDP (2 mg daily, 17 patients) or placebo (15 patients), they inhaled progressively doubling concentrations of histamine phosphate by tidal breathing method. With histamine in seven BDP-treated and in five placebo-treated patients, decrease in FEV1 > or = 20 percent from saline solution was paralleled by a significant decrease in tidal volume (VT), inspiratory time (Ti), and expiratory time (Te), and increase in respiratory frequency (RF). In the remaining patients, histamine failed to change the breathing pattern. In the seven RSB patients, BDP resulted in a smaller VT decrease (p < 0.02) and a smaller RF increase (p < 0.02) with histamine. The five RSB placebo-treated patients were then given one month BDP (2 mg daily): inhaled BDP, but not placebo, resulted both in a significant increase in PC20FEV1 and modulation in histamine-induced changes in breathing pattern. We conclude that high doses of BDP seem to be able to modulate histamine-induced RSB, an effect that might be linked to reversal of airway inflammation.

The efficacy of 8 weeks of treatment with 4 mg of nedocromil sodium 4 times daily in the management of partially reversible chronic airflow obstruction was evaluated in a randomized, double-blind, placebo-controlled crossover trial at Repatriation General Hospital, Western Australia. Sixty-seven patients with a mean forced expiratory volume in 1 s (FEV1) of 0.99 L, which improved by 21.8 percent after beta 2-adrenergic bronchodilator, took part in the full 24-week study. After a 4-week run-in period, in addition to their regular therapy comprised of inhaled or oral bronchodilators and steroids (which remained unchanged), patients were randomly allocated to receive treatment with nedocromil sodium or placebo for 8 weeks. This was followed by a 4-week washout, and then the patients were given the alternative test treatment to that given in the first period for another 8 weeks. Compared with placebo, patients receiving nedocromil sodium had improvement in their morning and evening peak flow rates, symptom scores for cough, sleep disturbance, and overall treatment efficacy. Hence, treatment with nedocromil sodium should be considered for patients with partially reversible chronic airflow obstruction not fully controlled with bronchodilators and steroids.

The efficacy of ofloxacin, rifampicin and isoniazid was prospectively compared with the regimen of ethambutol, rifampicin and isoniazid for the primary treatment of pulmonary tuberculosis in 124 patients. All drugs were given orally daily for nine months. Culture conversion rates three months after starting treatment were 98 percent in the ofloxacin group and 94 percent in the ethambutol group; by six months all patients in both groups were culture-negative. Significant radiological improvement of pulmonary infiltrates was observed in 83 percent of the ofloxacin group and 85 percent of the ethambutol group one year after starting treatment. No relapse in either group was observed during a two-year follow-up period after the cessation of chemotherapy. Ofloxacin appears to be as useful as ethambutol in the treatment of pulmonary tuberculosis when either drug is combined with isoniazid and rifampicin.

A generalized decision tree or clinical algorithm for treatment of high-risk elective surgical patients was developed from a physiologic model based on empirical data. First, a large data bank was used to do the following: (1) describe temporal hemodynamic and oxygen transport patterns that interrelate cardiac, pulmonary, and tissue perfusion functions in survivors and nonsurvivors; (2) define optimal therapeutic goals based on the supranormal oxygen transport values of high-risk postoperative survivors; (3) compare the relative effectiveness of alternative therapies in a wide variety of clinical and physiologic conditions; and (4) to develop criteria for titration of therapy to the endpoints of the supranormal optimal goals using cardiac index (CI), oxygen delivery (DO2), and oxygen consumption (VO2) as proxy outcome measures. Second, a general purpose algorithm was generated from these data and tested in preoperatively randomized clinical trials of high-risk surgical patients. Improved outcome was demonstrated with this generalized algorithm. The concept that the supranormal values represent compensations that have survival value has been corroborated by several other groups. We now propose a unique approach to refine the generalized algorithm to develop customized algorithms and individualized decision analysis for each patient's unique problems. The present article describes a preliminary evaluation of the feasibility of artificial intelligence techniques to accomplish individualized algorithms that may further improve patient care and outcome.

Formoterol solution aerosol has proved to be a fast and long-acting beta 2-sympathicomimetic drug in many clinical trials. The physical stability, however, was such that storage needed to be at 4 degrees C to 8 degrees C before first use; afterwards, the aerosol could be used for another three months at room temperature. To improve the stability, new ways have been investigated to formulate ann aerosol with improved shelf life and thus more convenient storage conditions, which was reached with a formoterol suspension aerosol. Equivalent single doses between the two formulations revealed no differences in onset or duration of action. In a double-blind, randomized parallel group multicenter study, organized in the Netherlands, 186 patients with stable asthma and reversible airway obstruction were treated either with one puff of 12 micrograms twice daily of formoterol metered dose inhaler (MDI) supension (SP) or a same dose of solution (SL) aerosol for 12 weeks to study the efficacy and tolerability of both presentations after a longer period of use. The following criteria of effectiveness were used: the FEV1 values on the mornings of the control days at 0, +4, +8, and + 12 weeks, the peak flow values (PEF) in the mornings and in the evenings before, and 1/2 to 1 h after treatment, the number of asthma attacks at night and during the day, the number of extra puffs at night and during day, and the subjective impression of patients and investigator.