Hemoptysis due to migration of a fractured Kirschner wire.

We report a rare complication related to the insertion of Kirschner wires for stabilization of an acromioclavicular separation. Five years after placement of the Kirschner wires, the patient presented with hemoptysis. On review of chest radiographs, a fractured wire was found to have migrated from the acromioclavicular joint, through the hemithorax and into the trachea.

Refractory hypoxemia due to intrapulmonary shunting associated with bronchioloalveolar carcinoma.

Bronchioloalveolar carcinoma caused severe refractory hypoxemia due to intrapulmonary shunting in a patient. Preoperative evaluation by occlusion of the pulmonary lobar artery supplying the tumor showed normalization of the arterial oxygen saturation. Resection of the involved lobe corrected the intrapulmonary shunting, and the patient required no further supplemental oxygen. However, with recurrence of the tumor over the next 6 months the patient became progressively more hypoxemic and died.

Breathing pattern during acute respiratory failure and recovery.

The objective of this study was to compare the breathing pattern of patients who failed to wean from mechanical ventilation to the pattern during acute respiratory failure. We hypothesized that a similar breathing pattern occurs under both conditions. Breathing pattern, mouth occlusion pressure (P[0.1]) and maximum inspiratory pressure (P[I,max]) were measured in 15 patients during acute respiratory failure, within 24 h of the institution of mechanical ventilation, and in 49 patients during recovery, when they were ready for discontinuation from mechanical ventilation. The following indices were calculated: rapid shallow breathing index (respiratory frequency/tidal volume (fR/VT)); rapid shallow breathing-occlusion pressure index (ROP = P[0.1 x fR/VT]); P(0.1)/P(I,max); and effective inspiratory impedance (P[0.1]/VT/(inspiratory time (tI)). Patients who failed to wean (n=11) had a similar ROP,fR/VT and P(0.1)/P(I,max) to those with acute respiratory failure despite a significantly reduced P(0.1)/VT/tI, the value of which was comparable to that of patients who weaned successfully (n=38). The P(I,max) of patients who failed to wean was similar to that of patients who weaned successfully. We conclude that patients who failed to wean had a breathing pattern similar to that during acute respiratory failure, despite a reduced mechanical load on the respiratory muscles and a relatively adequate inspiratory muscle strength. This suggests that strategies that enhance respiratory muscle endurance may facilitate weaning.

Acute hemorrhagic leukoencephalitis during treatment for disseminated tuberculosis in a patient with AIDS.

A 45-year-old man with the acquired immune deficiency syndrome (AIDS) developed disseminated Mycobacterium tuberculosis infection and was started on isoniazid, rifampin, pyrazinamide and ethambutol. The treatment was interrupted because of side effects. On resumption of treatment be developed a rapidly progressive neurological illness characterized by left hemiparesis, right gaze preference, convulsions, coma, evidence of cerebral edema on computed tomography scan and death 9 days later. Autopsy showed the presence of miliary tuberculosis affecting the lungs, liver, spleen, lymph nodes and bone marrow. The brain showed evidence of acute hemorrhagic leukoencephalitis (AHL)-the first such case in a patient with AIDS. We speculate that treatment-induced lysis of mycobacteria with concomitant release of mycobacterial lipoproteins may have activated T-lymphocytes to cause AHL in this patient.

Resolution of recurrent atelectasis in spinal cord injury patients with administration of recombinant human DNase.

Atelectasis occurs frequently in patients with spinal cord injury (SCI). Impaired cough leads to ineffective clearance of secretions. If the secretions cannot be cleared and become thick and purulent, atelectasis may occur. Recombinant human DNase (rhDNase) has been shown to decrease purulent sputum viscosity in vitro. We report two SCI patients with respiratory failure due to recurrent atelectasis from purulent secretions in whom conventional treatment methods had failed. Administration of rhDNase resulted in successful resolution of atelectasis. These results suggest the need for a controlled clinical trial.

Acquired laryngomalacia as a cause of obstructive sleep apnea.

We describe a patient who, 4 years after a radical neck dissection and radiotherapy, presented with obstructive sleep apnea; upon bronchoscopy, he was found to have acquired laryngomalacia. Inspiration induced upper airway obstruction due to a large flaccid epiglottis, large aryepiglottic folds, and edema of the supraglottic area. We suggest that acquired laryngomalacia can lead to obstructive sleep apnea. Patients with obstructive sleep apnea after radical neck dissection need to be evaluated for laryngomalacia with fiberoptic laryngobronchoscopy. Examination of the upper airway is useful to determine the nature and extent of any upper airway collapse.

Drug-induced pulmonary edema in a patient infected with human immunodeficiency virus.

Adverse reactions to drugs are common in patients infected with the human immunodeficiency virus (HIV). In these patients pulmonary reactions to drugs may be difficult to differentiate from opportunistic pulmonary infections. We report a HIV-infected patient who on two occasions developed acute pulmonary edema related to the administration of ibuprofen.

Chronic respiratory failure due to bilateral vocal cord paralysis managed with nocturnal nasal positive pressure ventilation.

A patient with bilateral vocal cord paralysis developed chronic respiratory failure. Treatment with nocturnal inspiratory positive airway pressure via nasal mask improved symptoms and reduced hypercapnia.

Conversion of COPD patients from multiple to single dose theophylline. Serum levels and symptom comparison.

The objective of the present study was to determine if patients with COPD who were taking Theo-Dur bid or tid (total dose 400 to 900 mg per day) could be safely switched to Uni-Dur, 800 mg given qd at bedtime. Twenty-eight patients were enrolled in the study, and 23 completed the study. The mean daily dose of theophylline prior to the study was 828 mg, while the mean dose after three weeks of Uni-Dur therapy was 783 mg. The mean serum theophylline level 10.5 +/- 3.6h after the last Theo-Dur dose was 10.5 mg/L. After three weeks of Uni-Dur therapy, the mean theophylline level at 8:00 AM was 14.6 mg/L, while the mean theophylline level at 8:00 PM was 9.9 mg/L. This latter level did not differ significantly from that obtained at the start of the study 10.5 +/- 3.6 h after the last dose of Theo-Dur. After three weeks of Uni-Dur therapy, the peak expiratory flow rate, the FEV1, and the FVC were not significantly changed from those at the initial evaluation. Twenty-one of the 23 patients ended up receiving 800 mg Uni-Dur qd. From this study, we conclude that once daily theophylline dosing with Uni-Dur compared with bid or tid dosing with Theo-Dur produces similar theophylline levels and pulmonary function, and most COPD patients who are taking 400 to 900 mg Theo-Dur daily can be managed with 800 mg Uni-Dur once daily at bedtime.

Exercise performance of polycythemic chronic obstructive pulmonary disease patients. Effect of phlebotomies.

The purpose of this study was to determine the effects of phlebotomy on the exercise tolerance and right and left ventricular ejection fraction of polycythemic patients with chronic obstructive pulmonary disease. Ten patients with COPD (mean FEV1 = 1.32 +/- 0.55 L) and polycythemia (mean Hct = 62 +/- 3 percent) were studied before and after their hematocrits had been reduced to approximately 50 percent. Post-phlebotomy the maximal oxygen consumption increased from 1.09 +/- 0.34 L/min to 1.26 +/- 0.43 L/min (p less than 0.05) and the maximum workload increased from 56.5 +/- 32.6 watts to 74.5 +/- 23.4 watts (p less than 0.05). The increase in the exercise tolerance appeared to be primarily due to an increased cardiac output at Emax. There was no relationship between the increases in the upright exercise capacity and changes in the supine ejection fractions of the right or left ventricular either at rest or during exercise.

Exercise-induced changes in left ventricular function after phlebotomy in patients with polycythemic COPD.

The exercise capacity of polycythemic COPD patients has been shown to improve after phlebotomy, possibly because of reduction of ventricular afterload by decreased blood viscosity, resulting in increased cardiac output. Ten patients with polycythemic COPD and mean hematocrit 62% were studied at rest and during exercise before and after reduction of mean hematocrit to 50% by repeated phlebotomy. Pulmonary function was evaluated by physiologic exercise testing on a bicycle ergometer. Cardiac function was evaluated by rest and exercise RNVG. Significant increase in exercise tolerance and maximal oxygen uptake at peak exercise, with significant reduction in mean systemic BP, were demonstrated. Ejection fractions did not change, but dV/dt for ejection from the left ventricle at peak exercise improved significantly. Mean SV counts, ESV counts, and EDV counts were measured and the fractional increase with exercise compared for prephlebotomy and postphlebotomy, assuming that resting volumes would not change. ESV counts and EDV counts were both proportionately, though not significantly, reduced postphlebotomy. The data tend to support the hypothesis that the afterload on the left ventricle is reduced, with resulting improved myocardial contractility and left ventricular function. Improved peripheral oxygen uptake may also be a factor.

Effect of dimethyl sulphoxide on mitochondrial biogenesis in regenerating rat liver and Saccharomyces cerevisiae.

Effect of dimethyl sulphoxide (DMSO) on mitochondrial biogenesis in regenerating rat liver and cells of Saccharomyces cerevisiae during aerobiosis has been studied by monitoring the cytochrome oxidase activity. A single dose of DMSO (275 mg/100-125 g body wt) to normal rats stimulated cytochrome oxidase activity in liver mitochondria while the same dose to partial hepatectomized rats inhibited the enzyme activity. Administration of low dose of DMSO (92 mg/100-125 g body wt) to partial hepatectomized rats did not alter the enzyme activity. Anaerobic cells of S. cerevisiae on aerobiosis for 2 hr attained cytochrome oxidase activity level on par with aerobic cells. Inclusion of DMSO (275 mg/100 ml) in the growth medium of S. cerevisiae during respiratory adaptation exerted partial inhibitory effect on the formation of cytochrome oxidase at 2 hr period, while the 10-fold concentration inhibited the enzyme formation completely. However, the inhibitory effect of DMSO on enzyme formation was abolished on prolonged growth (18 hr and above), while these doses had no influence on cytochrome oxidase in aerobic cells of S. cerevisiae. The results imply that DMSO may be exerting its effect on the assembly of subunits into active enzyme complex during mitochondrial biogenesis.

Evidence for the presence of DNA primase in mitochondria of Saccharomyces cerevisiae.

Chromatography of a DNA polymerase preparation from mitochondria of Saccharomyces cerevisiae on DNA-cellulose column, using Tris-HCl (pH 7.5) buffer containing 0.6 M NaCl as eluent, was found to yield a fraction exhibiting DNA primase-like activity free of DNA polymerase. This fraction could support the synthesis of 12-15 residue-long oligoribonucleotides on single-stranded natural or synthetic DNA templates. The oligoribonucleotides could be further elongated by incorporation of deoxyribonucleotides in the presence of Klenow fragment.

Effect of radiation therapy on bronchial obstruction due to bronchogenic carcinoma.

We evaluated the effect of radiation therapy in 57 patients with obstruction of a large bronchus with NSCC. Response with aeration of the atelectatic lung was seen in 12 patients (21 percent). Three patients (5 percent) showed partial response with persistent partial atelectasis, and nine patients (16 percent) showed good response with complete aeration of the atelectatic lung. In these patients the response appeared to be related to the dose of radiation. All of the patients who responded received more than 50 Gy. The difference in the response rate related to the dose of radiation was statistically significant (p less than 0.05). The rates were similar with all histologic types of NSCC. Regardless of the clinical response observed, bronchoscopy performed two to four months after completion of radiation therapy in 14 patients revealed persistent endobronchial tumor. There was no significant relationship between the persistence of endobronchial tumor, the dose of radiation therapy, and the tumor's histologic type. Of the 12 patients with radiographic improvement in atelectasis, fibrotic changes developed in four (33 percent) patients and pneumonitis in two (17 percent). Progression of disease with distant metastases occurred in 58 percent (seven) of the 12 patients who showed a clinical response of their bronchial obstruction. The median time to survival was nearly identical in responders and nonresponders.

Dimethyl sulfoxide elicited increase in cytochrome oxidase activity in rat liver mitochondria in vivo and in vitro.

A single intraperitoneal injection of dimethyl sulfoxide (275 mg/100 g body wt.) to rats stimulated cytochrome oxidase activity in liver mitochondria 2-5-fold. The enzyme activity remained at this level for as long as 5 days post-injection. There was however only 10.5% increase in the content of cytochromes a and a3 (as determined spectrophotometrically) in the same period in response to DMSO injection. The addition of either DMSO or dimethyl sulfate (a metabolite of DMSO) to isolated liver mitochondria also caused 2-3-fold increase in cytochrome oxidase activity. The results indicate that enhancement in cytochrome oxidase activity in liver mitochondria after administration of DMSO to rats is on account of activation of cytochrome oxidase caused by structural alterations in mitochondrial membranes rather than de novo synthesis of cytochrome oxidase.

Transudative pleural effusions.

A transudative pleural effusion develops when the systemic factors influencing the formation or absorption of the pleural fluid are altered. The pleural surfaces are not involved by the primary pathologic process. The diagnosis of transudative effusion is simple to establish by examining the characteristics of the pleural fluid. Transudates have all of the following three characteristics: The ratio of the pleural fluid to the serum protein is less than 0.5. The ratio of the pleural fluid to the serum LDH is less than 0.6. The pleural fluid LDH is less than two thirds the upper limit of normal for the serum LDH. Among the conditions that produce transudative pleural effusion, congestive heart failure is by far the most common. Pulmonary embolism, cirrhosis of the liver with ascites, and the nephrotic syndrome are the other common causes. Management of transudative pleural effusions involves managing the primary disease. Refractory, massive effusions can be controlled by tetracycline pleurodesis.

Comparison of the effects of labetalol and hydrochlorothiazide on the ventilatory function of hypertensive patients with mild chronic obstructive pulmonary disease.

Labetalol is a new adrenergic antagonist with both alpha- and beta-blocking effects. The effects of labetalol and hydrochlorothiazide on the hypertension and ventilatory function of patients with both hypertension and mild reversible chronic pulmonary disease were compared. In this double-blind study, 20 patients were randomly allocated to receive increasing doses of labetalol (100 to 400 mg three times a day) or hydrochlorothiazide (25 to 50 mg three times a day) over a four-week treatment period. Patients returned at weekly intervals for spirometry baseline, two hours after receiving the medication for the following week, and five minutes after an exercise test. Each treatment reduced the blood pressure significantly and to a comparable degree. There was no significant decrease in ventilatory function two hours after administration of the drug at any visit for either drug. Ventilatory function did not deteriorate significantly following exercise with either drug. With labetalol there was a progressive statistically significant decline in baseline forced expiratory volume in one second from 1,860 +/- 190 ml to 1,685 +/- 190 ml during the four-week study period, although no patient became symptomatic from shortness of breath. We conclude that labetalol is an effective antihypertensive agent that does not adversely effect ventilatory function immediately, but that may lead to a decline in ventilatory function when administered long-term.

Improved exercise tolerance of the polycythemic lung patient following phlebotomy.

The present study evaluated the effects of therapeutic phlebotomy on the exercise tolerance and the maximal carbon dioxide output of polycythemic patients with chronic obstructive pulmonary disease. Fifteen maximal exercise studies were performed before and after phlebotomy in patients with moderate to severe chronic obstructive pulmonary disease (mean forced expiratory volume in one second [FEV1]= 970 ml). After phlebotomy there were no significant differences in pulmonary function, blood gases, oxygen consumption, or carbon dioxide production at rest. However, after phlebotomy there was a significant increase in the exercise tolerance of the patients. The mean workload, the duration of exercise, the maximal oxygen consumption, the maximal carbon dioxide production, and the ventilation at maximal exercise all increased significantly. The improved exercise tolerance after phlebotomy appeared due to an increased cardiac output generated mainly through an increased stroke volume. We hypothesize that the increased stroke volume was due to a higher ejection fraction of the right ventricle secondary to a lower pulmonary artery pressure. This study provides further evidence that patients with chronic obstructive pulmonary disease who have polycythemia benefit by therapeutic interventions that maintain their hematocrits below 55 percent.