Pleurodesis by autologous blood, doxycycline, and talc in a rabbit model.

BACKGROUND: Management of recurrent spontaneous pneumothorax or symptomatic pleural effusion often uses thoracoscopic pleurodesis, about which many questions remain. Both effectiveness and toxicity of agents currently used for pleurodesis were evaluated in a rabbit model. METHODS: Agents administered were autologous blood 1 mL/kg, talc slurry (70 mg x mL(-1) x kg(-1)), and doxycycline 10 mg/mL, given through a chest tube to 30 rabbits. Controls had only chest tubes inserted. At 30 days surfaces were graded by gross observation and histologic examination. Blood and lung tissue from all animals were analyzed for enzymes and blood chemistries. RESULTS: Gross observations showed mediastinal thickening and adhesions with doxycycline, and threadlike adhesions with talc. Autologous blood was only slightly more effective than a chest tube alone. Talc significantly increased angiotensin converting enzyme activity in serum, whereas doxycycline changed liver function enzymes and produced tissue toxicity. CONCLUSIONS: Doxycycline produced effective pleurodesis but yielded remarkably severe local effects. The distant sequelae of talc and doxycycline pleurodesis-histologic changes in the contralateral lung and serum enzyme elevations-suggests undesirable systemic effects for the commonly used agents, and autologous blood exhibited no significant pleurodesis, short-term. The search for the ideal agent for chemical pleurodesis continues.

Oral clonidine in patients with asthma: no significant effect on airway reactivity.

Fifteen patients with asthma were randomized into a double-blind, placebo controlled, crossover trial evaluating whether clonidine increased airway resistance. After meeting entry criteria [demonstration of 20% improvement in any two of the following pulmonary function tests after bronchodilator therapy: FVC, FEV1, or forced expiratory flow over the mid-50% of the vital capacity(FEF(25-75)], patients were evaluated on two subsequent visits, receiving sequential doses of clonidine 0.1 mg (maximum cumulative dose 0.3 mg) or placebo in a random fashion. They returned to clinic after a 36-48 hour washout period at which time they received the opposite treatment. The end points were three doses of clonidine or placebo, decrease in blood pressure to < or = 90 mm mercury systolic, and/or < 70 mm mercury diastolic, or a 20% fall in FEV1. Airway reactivity was proved utilizing methacholine on each clinic visit, and blood pressures were monitored continuously during the study period. There were no significant differences in the provocative concentrations of methacholine inducing a 20% fall in FEV1 (PD20) between baseline (1.92), clonidine (1.10), and placebo (1.69). (Numbers in parentheses indicate PD20 values in cumulative dose units).

Effects of dopamine on T-lymphocyte proliferative responses and serum prolactin concentrations in critically ill patients.

OBJECTIVES: Dopamine is currently used in the ICU for its vasopressor, renal vasodilating, and cardiac inotropic properties. Animal studies have shown both endocrine and T-lymphocyte alterations with dopamine agonist administration. The relationships between exogenous dopamine and patient hormonal and lymphocyte proliferative responses have not been evaluated in the critically ill patient. These findings furnished the impetus for the present study. DESIGN: Prospective, controlled, clinical study. PATIENTS AND METHODS: All patients admitted to the ICU at Truman Medical Center were evaluated for admission into the protocol, excluding patients whose medications or diseases produced effects in the study-dependent variables. Before institution of dopamine therapy, blood samples were taken for T-cell analysis and prolactin measurement. Daily, early morning blood samples were taken if the dopamine infusion was > 5 micrograms/kg/min for 4 hrs during that 24-hr period. An early morning postdopamine sample was taken on the first day after dosage discontinuation. Control blood samples for determination of T-cell and prolactin responses were drawn from ICU patients who did not receive dopamine. A severity-of-disease score (Acute Physiology and Chronic Health Evaluation [APACHE II] score) was recorded for all patients. MAIN RESULTS: Serum prolactin concentrations decreased > 90% (p < .001) within hours in all patients receiving dopamine infusions at study dose limit or above. The in vitro T-cell proliferative response to concanavalin A decreased (a transitory response) in patients receiving a dopamine infusion (p < .001). Dopamine infusions in medical ICU patients produced an immediate and profound reduction in serum prolactin concentrations in both males and females. An immediate transitory decrease in patient T-cell response to concanavalin A stimulation in vitro was seen in patients receiving dopamine. CONCLUSIONS: The data suggest the possibility of altered endocrine and immune function as a corollary of therapeutic concentrations of dopamine in critically ill patients.

Pulmonary effects of ischemic limb reperfusion: evidence for a role for oxygen-derived radicals.

OBJECTIVE: To evaluate the lung as a reperfusion target after limb ischemia-reperfusion, and to measure specifically the oxygen radical response to this reperfusion. DESIGN: Paired simple randomized, with continuous interval data in dependent variable and both continuous and nominal independent variables. SUBJECTS AND INTERVENTION: Sprague-Dawley male rats (n = 195) were anesthetized and both hind limbs occluded for 3.75 hr, the overnight LD50. Alveolar lavage was performed on the animals 1 hr after reperfusion or on survivors 20 hr after reperfusion. Groups were either undosed or pretreated with alpha-tocopherol as an antioxidant (50 mg/kg.day) 2 days before ischemia. MEASUREMENTS AND MAIN RESULTS: Luminol-enhanced chemiluminescence was measured in both phorbol myristate acetate-stimulated and unstimulated macrophages. Nanomoles of superoxide radicals per 10(6) alveolar cells/min were also measured using a cytochrome c reduction assay. A significant (p less than .01, Student's t-test), time-dependent increase in response of cells from ischemic-reperfused rats was seen. Pretreatment with antioxidant had no effect at 1 hr, but significant differences were seen in the 20-hr survivors. CONCLUSIONS: These studies show that alveolar lavage cells, 95% macrophages, reflect the reperfusion of ischemic-reperfused hind limbs by a significant increase in oxygen radical activity, an effect partly suppressed in antioxidant-dosed survivors.

Use of intrapleural streptokinase in the treatment of thoracic empyema.

The incidence of pleural effusions in bacterial pneumonia may exceed 40%, a factor that may be related to increased morbidity and mortality. Options in the treatment of complicated pleural effusions or empyema, when unresponsive to closed tube drainage, include repositioning of the indwelling tube thoracostomy or insertion of additional chest tubes, instillation of intrapleural streptokinase, and surgical intervention. The authors describe the course of three patients wherein the use of intrapleural streptokinase was efficacious in effecting prompt drainage of previously inadequately evacuated empyema, thus eliminating the necessity for further invasive intervention.

Congenital unilateral absence of a pulmonary artery: a report of two adult cases.

Congenital unilateral absence of a pulmonary artery (UAPA) is a rare anomaly that is generally diagnosed in childhood and frequently associated with other cardiovascular abnormalities. Two patients with unilateral absence of a pulmonary artery first diagnosed as adults are reported. Our two cases demonstrate that presentation of UAPA may range from an incidental finding to chronic, life-threatening symptoms. Because UAPA may require urgent intervention, physicians should be alerted to the possibility of this entity presenting later in life.

Changing spectrum of hemoptysis. Underlying causes in 148 patients undergoing diagnostic flexible fiberoptic bronchoscopy.

A retrospective study to examine the underlying causes of hemoptysis in patients undergoing diagnostic bronchoscopy was conducted. We found hemoptysis to be caused by bronchitis in 55 (37%) of 148, bronchogenic carcinoma in 28 (19%) of 148, tuberculosis in 10 (7%) of 148, and bronchiectasis in 1 (1%) of 148 patients. Compared with previous studies, it appears that hemoptysis is less likely to be caused by bronchiectasis or tuberculosis while hemoptysis caused by bronchitis has increased proportionately. The rate of occurrence of hemoptysis caused by bronchogenic carcinoma has not changed significantly. All patients with underlying bronchogenic carcinoma had a positive smoking history and abnormal chest roentgenogram. The rate of hemoptysis was not a good indicator of the underlying disease.

Theophylline and diaphragmatic contractility. Investigation of a dose-response relationship.

Our study evaluated whether a dose-response relationship exists for theophylline and diaphragmatic contractility within the usual therapeutic range for theophylline. The study, involving 16 patients with mild to moderate chronic obstructive pulmonary disease, was done in a randomized, placebo-controlled, double-blind, crossover fashion. We found no statistically significant effect of theophylline on diaphragmatic contractility at mean theophylline concentrations of 5.13, 12.07, and 18.6 micrograms/ml.

Toxic pneumonitis from mixing household cleaners.

In the past year we have seen three cases of life-threatening toxic pneumonitis caused by exposure to mixtures of household ammonia and bleach. This particular mixture forms intermediary chloramine compounds that cause toxic pneumonitis. Each patient had a prolonged hospitalization and was left with symptomatic residual roentgenographic changes. Exposure to mixtures of household ammonia and bleach may be a frequent cause of acute pneumonitis that is not well recognized.

The effect of erythromycin on theophylline pharmacokinetics in chronic bronchitis.

We examined theophylline pharmacokinetics for changes caused by the addition of erythromycin in patients with chronic bronchitis and obstructive pulmonary disease. Twelve hospitalized patients were randomized in a crossover fashion to receive aminophylline and either erythromycin or placebo. After the eighth dose, plasma was analyzed for theophylline, using the enzyme-mediated immunoassay technique. A 6-h urine collection was analyzed for theophylline metabolites, using high-pressure liquid chromatography. Erythromycin significantly decreased mean theophylline clearance by 22% from 4.9 L/min to 3.87 L/min (p less than 0.05). Mean peak theophylline levels increased 28% from 11.9 micrograms/ml to 15.3 micrograms/ml (p = 0.05). No change in urine theophylline metabolites was found. Patients with chronic bronchitis and obstructive pulmonary disease who begin erythromycin while receiving a preexisting therapeutic theophylline regimen experience a significant elevation of theophylline concentration, which predisposes to theophylline toxicity. For those patients with theophylline levels at the higher end of the therapeutic range (15 to 20 micrograms/ml), we recommend an initial 25% reduction in theophylline dosage when erythromycin is added. Serum theophylline levels should be monitored for further refinement of dosage.