A prospective study of 104 patients was undertaken to determine the frequency of severe heparin-induced thrombocytopenia in patients receiving either bovine lung or porcine mucosal heparin. One of 54 patients randomized to receive bovine heparin and two of 50 patients randomized to receive porcine heparin developed heparin-induced thrombocytopenia (platelet count less than 100,000/microliters). Although three previous studies suggest a remarkably high frequency of bovine heparin-induced thrombocytopenia, or a high frequency compared to porcine heparin, our study supports other evidence that clinically important, severe heparin-induced thrombocytopenia (platelet count less than 100,000/microliters) occurs in 10 percent of patients or less receiving heparin, and that there is no significant difference of occurrence between bovine and porcine heparin.

Previous studies have shown that labetalol, a new alpha- and beta-adrenergic antagonist, is relatively safe for the treatment of hypertension in patients with chronic obstructive pulmonary disease (COPD). This multicenter study was designed to evaluate its effects in hypertensive patients with asthma and propranolol sensitivity. Hypertension was successfully controlled in 18 of 21 patients who received labetalol in increasing doses, up to 1,200 mg/day. The decrease in mean FEV1 (1.5 percent) two hours after the highest dose of labetalol was not statistically significant, although there was a gradual decline in mean baseline FEV1 during the four-week treatment period. Antihypertensive agents other than adrenergic antagonists should be considered for the management of hypertension in patients with asthma, especially those with marked reversibility of airflow. If treatment with beta-adrenergic antagonists is indicated, labetalol is recommended over other currently available agents.

Many patients with irreversible chronic obstructive pulmonary disease (COPD) claim symptomatic improvement with steroid therapy, despite a lack of objective improvement in their spirometric data. To determine if steroids actually increase the exercise capacity of these individuals, 13 clinically stable patients (mean age, 63 +/- 4 years; 12 male patients) were given methylprednisolone (32 mg once daily) or placebo in a randomized double-blind crossover fashion. Spirometric data and minute ventilation, oxygen consumption (VO2), carbon dioxide production, and heart rate during incremental exercise were measured at each visit. Methylprednisolone did not produce a significant change in any of the measured parameters. Three patients had an increase in maximal VO2 of greater than 2 ml/kg/min during therapy with methylprednisolone, while two experienced a decline in maximal VO2 of similar magnitude. The change in exercise capacity was unrelated to the change in the forced expiratory volume in one second in individual patients (r = 0.08). We conclude that in the absence of any improvement in the usual tests of airway mechanics, steroid therapy does not improve exercise performance in patients with COPD.

In unilateral parenchymal pulmonary disease, arterial oxygenation decreases when the patient is positioned such that the abnormal lung is dependent; however, few studies have evaluated the effect of the body position on oxygenation in patients with unilateral or asymmetric pleural effusions. To our knowledge, no previous study has evaluated the possible transient effects of changing position on the level of arterial oxygen saturation (SaO2) in such patients. Accordingly, we studied ten normoxic patients spontaneously breathing room air, who had asymmetric pleural effusions as documented by chest x-ray film and physical examination. We monitored pulse, respiratory rate, and blood pressure every five minutes and SaO2 by ear oximetry continuously while patients were in the following positions: sitting; supine; and left and right lateral decubitus. The mean SaO2 was 95 percent and 94.3 percent in the sitting and supine positions, respectively. Mean SaO2 fell to 93.4 percent when the patients were positioned so that the side with the largest pleural effusion was dependent. When the side with the pleural effusion was down, the mean SaO2 was significantly lower than in either the sitting position or with the side with the pleural effusion up. We could find no significant relationship between the size of the pleural effusion and the amount of arterial oxygen desaturation. We conclude that there is a decrease in SaO2 in normoxic patients when the side with the larger pleural effusion is dependent; however, this decreased SaO2 does not appear to be clinically significant in patients with normal SaO2.

Long-term ambulatory Holter-monitoring was used to evaluate the arrhythmogenic effects of beta 2-agonist therapy, alone and in combination with a xanthine derivative, theophylline or enprofylline. Twenty patients (mean age 51 years) with mild-to-moderate obstructive lung disease (bronchial asthma or chronic bronchitis), but without concomitant ischemic heart disease were studied. Compared with beta 2-agonist therapy alone, both combined regimens were associated with a small but significant increase in the frequency of ventricular arrhythmias. Few serious arrhythmias were observed, however, and the clinical significance of these findings is thought to be minor. Although adenosine has been suggested to have an antiarrhythmic effect, a difference between theophylline and enprofylline in the effect on adenosine (theophylline but not enprofylline being an adenosine antagonist) would appear to be of less cardiac relevance in patients without ischemic heart disease.

Twenty-six patients undergoing coronary bypass graft surgery were randomized in two groups. In group 1, 14 patients were subjected to inspiratory pressure support during spontaneous ventilation (IPSSV) and 12 patients in group 2 were treated with conventional ventilation (CV). The outcome of IPSSV was a definite advantage over the conventional ventilation. The patients in IPSSV group needed +/- 3 h of pressure support before tracheal extubation. The other patients in CV group 2 needed +/- 6 h of mechanical ventilation before being weaned off the ventilator.

The present study investigated the effects of oxygen therapy upon human information processing for hypoxemic COPD patients. Each of ten patients was admitted to a general clinical research center for a two-day period. In a randomly counter-balanced factorial design, patients breathed either room air or enriched oxygen for either six hours or 20 minutes prior to testing. The tests evaluated speed of information processing, ability to detect correct sequence of tones, and serial memory. In addition, patients were evaluated on critical flicker fusion and story recall. The results suggested that acute oxygen therapy does not reverse information processing deficits observed in hypoxemic COPD patients.

The effect of theophylline on the penetration of an inhaled radioaerosol in the lung, bronchial clearance, and tracheal mucociliary transport rate (TMTR) was investigated in 13 healthy volunteers. Following a randomized, double-blind, crossover protocol, subjects ingested 4 mg/kg twice daily of theophylline or placebo for three days which resulted in stable, low therapeutic serum levels. Aerosol penetration, assessed by the skew of the initial distribution of lung radioactivity, was more peripheral (p less than 0.025) with theophylline, indicating bronchodilation that was not detectable by standard pulmonary function tests. The TMTR increased in ten of 13 subjects after theophylline, but not to a significant level. Bronchial clearance was not significantly different with theophylline despite the longer clearance pathway created by the increased peripheral aerosol deposition. This finding suggests that mucus transport rates in the intrapulmonary airways were increased by theophylline.

Eighteen asymptomatic postmenopausal women volunteered to ingest 2 ml of 100-proof vodka per kg of body weight in orange juice on one night and a placebo on another. Overnight sleep monitoring was performed immediately thereafter. Alcohol ingestion caused reduction in total sleep time from 329 to 281 minutes and a decrease in rapid eye movement sleep. There was no difference from placebo in the number of episodes of apnea or hypopnea, or in the frequency, length, or severity of oxygen desaturation. In contrast to the effects of alcohol ingestion in men, the effects on breathing and oxygenation are minimal during the sleep of women if this amount of alcohol is ingested.

Breathing patterns in six normal awake subjects were monitored noninvasively during progressive hypoxia accomplished with the administration of nitrogen at 2, 4, 6, and 8 L/min by nasal cannula. The lowest value of arterial oxygen saturation (SaO2) of 88 +/- 4 percent (mean +/- SD) was achieved with nitrogen at 8 L/min. At baseline, tidal volume (VT) and frequency were fairly regular; with nitrogen at 2 and 4 L/min, some subjects showed minor fluctuations of VT. At 6 and 8 L/min, periodic breathing with marked oscillations of VT, apneas, hypopneas, and intermittent large tidal breaths were consistently observed. Inspired oxygen concentration fluctuated because of the variations of tidal breaths provoked when periodic breathing took place and enhanced fluctuation in SaO2. A randomized, double-blind crossover design was used to assess the effect of pretreatment with naloxone on this periodicity. In contrast to the irregular breathing pattern observed with pretreatment with placebo, the breathing pattern after pretreatment with naloxone was regular during nasal administration of nitrogen except at 8 L/min, when minor fluctuations in VT with occasional hypopneas and large tidal breaths occurred. On another day, irregular and periodic breathing with apneas or hypopneas (or both) produced by nasal nitrogen at 8 L/min was eliminated or blunted by short-term intravenous administration of naloxone. On another day, electroencephalographic monitoring corroborated visual observations made in the previous studies that the hypoxic subjects were awake during the breathing alterations. Thus, awake adults develop irregular and periodic breathing during induction of mild hypoxia produced by nasal administration of nitrogen. The irregularity in breathing appears to be mediated through release of endorphins, since the effect is blunted or eliminated by pretreatment or short-term treatment with naloxone.

The aim of this study was to investigate the effects of nebulized ipratropium in patients with acute asthma in order to determine whether it augments the bronchodilator effect of a beta agonist drug. A total of 28 patients with acute asthma were randomly allocated to treatment every six hours with either 1 mg nebulized fenoterol (group A) or 1 mg fenoterol and 0.5 mg ipratropium (group B). There was no significant difference between the mean FEV1 of the two groups prior to treatment and increasing the dose of fenoterol from 1 mg to 2 mg did not increase the response. However the mean change in FEV1 after 48 hours (expressed as a percentage of the predicted maximal response) was 40.1 +/- 7.2 percent in group A and 54.3 +/- 9.2 percent in group B (p less than 0.005). It was concluded that the response of patients with acute asthma to fenoterol was significantly enhanced by the addition of the anticholinergic agent ipratropium bromide.

To assess the effect of conventional chest physiotherapy and mechanical chest vibration on arterial blood gas levels, spirometry, and sputum production, we studied 20 stable outpatients with chronic obstructive lung disease. All patients had severe obstructive ventilatory defects with a mean FEV1/FVC ratio of 30 percent and all produced moderate amounts of sputum. Patients were randomized and received chest physiotherapy or mechanical vibration for 20 minutes. Arterial blood gas levels and spirometry obtained 20 minutes and 40 minutes after completion of the treatment did not show any significant change compared to the baseline. We conclude that neither chest physiotherapy nor chest mechanical vibration improved gas exchange, flow rates, or clearance of secretions in stable outpatients with severe chronic obstructive lung disease.

The efficacy of propafenone hydrochloride, a new antiarrhythmic agent, was evaluated in the treatment of chronic stable ventricular arrhythmias. Twenty-five patients who had suffered a myocardial infarction three months or longer before the trial were studied. All exhibited a minimum mean frequency of 30 ventricular ectopic beats per hour over at least two 24-hour Holter monitoring periods with the last recorded tape serving as a control. The mean decrease in ventricular ectopic activity with propafenone was 65.62 percent (p = less than 0.001). Side effects were infrequent, minimal, and of no clinical consequence. Oral propafenone was found to be an effective drug for reducing the level of chronic ventricular ectopy, as reflected by a short-term trial.

Ninety patients with stage-3 non-small cell lung cancer were given vindesine (3 mg/sq m) plus mitomycin (10 mg/sq m). Data on response are available for 84 adequately treated individuals (93 percent). For patients who had received no prior chemotherapy, the rate of major objective response was 36 percent (20/55). For previously treated patients the rate of major response was 17 percent (5/29). The drugs were routinely administered in the outpatient department without difficulty. Moderate or severe myelosuppression, neurotoxic, nephrotoxic, or pulmonary toxic effects, nausea, and vomiting occurred in less than 15 percent of all studied patients. Three-drug extravasation ulcerations occurred in 1,129 administrations of chemotherapy (0.3 percent). There were two treatment-related deaths, one from sepsis and one from the combination of mitomycin-induced pulmonary and renal toxic effects. The combination of vindesine plus mitomycin is an active, well-tolerated outpatient regimen for patients with non-small cell lung cancer who have not previously received chemotherapy. Further trials are warranted to compare this regimen to other active combinations and to use it as a component of a program of treatment using alternating regimens of chemotherapy.

The literature is unclear as to whether theophylline loading doses should be based on total body weight (TBW) or ideal body weight (IBW). The objective of this study was to determine the most appropriate body weight for estimation of volume of distribution (Vd) in calculating theophylline loading dose in patients with acute bronchospasm. Fifty-four adult patients with acute bronchospasm requiring intravenous (IV) theophylline therapy were entered into the study. Patients were randomized into three theophylline loading dose groups based on (1) TBW, (2) IBW, and (3) adjusted body weight (ABW). Initial serum theophylline concentrations were used to determine an IV loading dose to reach a plasma concentration of 12 to 15 micrograms/ml. Percent prediction error was used to determine the appropriateness of each dosing group. Volumes of distribution were also determined for each group. There was a statistically significant difference at p less than 0.01 in the percent prediction error when patients in the TBW group were compared to the IBW and ABW groups. A statistically significant difference in the Vd was observed between the TBW and IBW group (p less than 0.01). We conclude that IBW is more appropriate than TBW or ABW for determining theophylline loading dose in patients with acute bronchospasm.

Recently, several transmembrane calcium-channel blockers have been used in experimental models to investigate the mechanisms through which Ca++ ions contribute to the regulation of the contractile response of airway smooth muscle and to determine the therapeutic use of these drugs in bronchial asthma. Since the data from these studies are inconsistent and inconclusive, we studied the effect of diltiazem, a calcium-channel blocker previously not examined to our knowledge, on histamine- and carbachol-induced bronchoconstriction in healthy and in asymptomatic allergic bronchial asthma. The study was performed in a double-blind, randomized, placebo-controlled fashion, using a single oral dose of 60 mg of diltiazem. Airway reactivity to histamine and carbachol expressed by PD35SGaw was significantly but weakly attenuated by diltiazem in the asthmatic, but not in the normal subjects. Baseline lung function was not significantly influenced by diltiazem. We concluded that the effect of diltiazem on unspecific airway hyperresponsiveness in asthmatic subjects is too weak to justify a recommendation as therapy.

Atopic asthma is associated with diminished cell-mediated immunity and elevated levels of IgE, both of which may be caused by imbalances of T-lymphocyte subsets. We analyzed the response of peripheral blood T-cell subsets to two commonly used corticosteroid preparations as a probe of T-cell subset regulation. We administered prednisone (P) 60 mg or 20 mg, beclomethasone dipropionate (BDP) aerosol, 336 micrograms, placebo, or BDP vehicle in a double-blind protocol to 15 atopic asthmatic patients and ten nonatopic subjects. No difference was found between the groups of the baseline number of T-cells with T4, T8, M1, and Ia antigens, nor the ratio of T4+ (helper) to T8+ (suppressor) cells. Five hours after administration of BDP aerosol, BDP vehicle, and oral placebo, there was no change of these values in either the atopic or in the nonatopic group. In contrast, P, 20 and 60 mg, caused a fall of T4/T8 ratio in the atopic, but not in the nonatopic population. Atopic asthma is not associated with baseline imbalances of peripheral blood T-cell subsets, but is associated with an abnormal response to systemic, but not inhaled corticosteroid.