Biomedical subjects
Publications and source records attributed to M Lippmann.
The present report describes a patient who had severe obstructive lung disease in association with acquired hypogammaglobulinemia. Evidence obtained by bronchoalveolar lavage is presented that suggests that his lung disease resulted from both a marked increase in elastase load and a reduction in protease inhibitor function.
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Forty patients (A.S.A. class I or II), 18 to 75 years of age, who were undergoing elective surgery were studied to determine the clinical and subclinical neuromuscular blocking effects of two antibiotics, tobramycin and gentamicin and to compare these effects with those produced by cefazolin, an aminoglycoside not known to produce paralysis. Patients were prospectively and randomly assigned in approximately equal numbers to one of four groups: group A received 1 mg/kg of tobramycin; group B, 1 mg/kg of gentamicin; group C, 500 mg of cefazolin; or group D, control (no antibiotic). Antibiotics were administered intravenously 45 minutes immediately preceding the study. The ulnar nerve was stimulated supramaximally and neuromuscular function was measured electromyographically. Anesthesia was induced with thiopental, 4 mg/kg IV, and maintained with endotracheal enflurane 1.0% to 1.5% (inspired) and N2O-O2 (2 L:1 L) after intubation. Succinylcholine (1 mg/kg) was administered after induction of anesthesia and the magnitude and duration of neuromuscular block monitored. d-Tubocurarine (0.1 mg/kg) was given 5 to 10 minutes after full recovery from succinylcholine and repeated as required. At the end of the operation, atropine, 0.02 mg/kg, and neostigmine, 0.4 mg/kg, were used to reverse the block. Base line neuromuscular data, duration of block of succinylcholine, and potency, duration of block, recovery rate, train-of-four fade, tetanic trend, response to double stimuli, post-tetanic effect, and reversibility of the subsequent d--tubocurarine-induced neuromuscular block were not significantly different (p less than 0.01) between any two groups. Tobramycin, gentamicin, and cefazolin, in recommended single doses, lack clinical neuromuscular blocking and subclinical relaxant-potentiating effects.
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To test the hypothesis that adult respiratory-distress syndrome (ARDS) is related to increased activity of the proteolytic enzyme elastase released from neutrophils in the lung, we determined the differential white-cell count, the elastolytic activity, the source of elastase, and the concentration and activity of the endogenous protease inhibitor alpha-1-antiprotease (alpha-1-AP) in bronchoalveolar lavage fluid from 23 patients with ARDS and from 55 patients without this syndrome. Neutrophil predominance (> 80 per cent) was observed in 18 of 23 patients with ARDS. High elastolytic activity of neutrophil origin was found in 12 of 23 patients with ARDS (52 per cent), in none of 16 normal nonsmokers (P < 0.01), in two of 17 normal smokers, and in three of 22 patients with chronic obstructive pulmonary disease. Although there were no significant differences in alpha-1-AP concentrations, its activity was reduced in eight of nine patients with ARDS and high elastolytic activity. We conclude that in many patients with ARDS, high levels of neutrophil elastolytic activity in the lungs are associated with reduced alpha-1-AP function.
Ninety-eight patients completed a double-blind, multidose, randomized parallel study in which buprenorphine (Temgesic) was compared to morphine. Drugs were administered at approximately equipotent intramuscular doses for a maximum of three days for the relief of moderate to severe postoperative pain. The two drugs exhibited similar profiles with pain relief evident at 1/2 hour, peaking at 1 hour, and decreasing to slight relief at 4-5 hours, with no significant differences for time to remedication. The most frequent side effect was somnolence. One patient suffered sudden chest pain shortly after an injection of morphine, and one patient had moderate hypoventilation after buprenorphine; both patients recovered uneventfully. Overall, both drugs provided good or excellent analgesia in 80 per cent of the patients in this unique multidose/observational study. Thus, these data and the reported lack of withdrawal symptoms and the absence of physical dependence liability suggest that buprenorphine may have a role in the management of chronic pain.
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It is often difficult to distinguish pulmonary embolism from worsening underlying disease in the setting of severe chronic obstructive lung disease. We describe three patients with severe COPD and angiographically documented pulmonary embolus to stress that standard clinical and radioisotopic studies were of little value in establishing a diagnosis. All patients had acute increases in alveolar ventilation immediately following the embolus with a reduction in previously elevated levels of PaCO2, as well as hypoxemia. Such changes in arterial blood gases in the patient with severe COPD should suggest pulmonary embolus rather than increased obstruction.
The effects of one hour exposures of healthy nonsmoking human volunteers to submicrometer H2SO4 droplets via nasal mask on tracheobronchial mucociliary particle clearance were studied using two different sized monodisperse gamma-tagged Fe2O3 test aerosols. The larger sized Fe2O3 aerosol, 7.5 micrometers AMAD, was deposited primarily in the larger bronchial airways, while the smaller 4 micrometers AMAD aerosol had a much greater fraction deposited in the smaller and more distal conductive airways. Thoracic retention of the Fe2O3 aerosols as a function of time after a brief inhalation was measured with external collimated radiation detectors. At the highest H2SO4 exposure, 1,000 micrograms/m3, there was a pronounced transient slowing of bronchial mucociliary clearance of both the 7.5 and 4 micrometers Fe2O3. On the other hand, at the lowest H2SO4 concentration, 100 micrograms/m3, there was a marked acceleration of the clearance of the 7.5 micrometers Fe2O3, but a slowing of the clearance of the 4 micrometers Fe2O3. Thus, submicrometer H2SO4, which deposits primarily in the distal airways, can slow mucociliary clearance in those airways. In the larger airways, where its deposition is minimal, the H2SO4 can, at the same time, accelerate mucus transport.
A relatively inexpensive method for the noninvasive in vivo detection of ferrimagnetic particles within the lungs of a large laboratory animal, viz., the donkey, is described. The particles were neutron activated prior to inhalation, which permitted a comparison of two different retention measurements for the same particles, i.e., a well-characterized radiological-detection method concurrent with the newer magnetic-field technique. The long-term clearance of the particles from the lung was monitored in terms of the reduction in initial remanent field following magnetization, and the reduction in gamma-ray flux reaching the collimated scintillation detectors. Comparison of the measurements confirmed that the reduction of the initial remanent-field values with time was due to particle clearance rather than a change of the iron state to a nonmagnetic form. This validates previous reports that particle clearance studies can be performed using remanent magnetic-field measurement techniques. However, remanent magnetic-field measurements require careful design and interpretation, since they are highly sensitive to the distribution of the particles within the effective viewing field.
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Submicrometer H2SO4 droplets can affect pulmonary functions in humans. The lowest concentration which has been reported to produce a statistically significant effect on pulmonary mechanics is 1 mg/m3. Effects on tracheobronchial mucociliary clearance of inert particles were observed in our laboratory at much lower concentrations. For ten nonsmoking humans exposed for one hour via nasal mask to 0.1 mg/m3 of H2SO4, the mean bronchial clearance half-time was reduced by 38% (p less than 0.02) while for 1 mg/m3, it was increased by 48% (p less than 0.03). Four donkeys exposed for 1 hour daily to 0.1 mg/m3 for six months developed clearance abnormalities which persisted for at least three months after the last exposure. The patterns of mucociliary clearance responses to H2SO4 are similar to those seen previously in humans and donkeys following exposure to cigarette smoke, a known causal factor for chronic bronchitis.
Regional deposition of inhaled particles was studied experimentally in a hollow cast of the human larynx-tracheobronchial tree extending through the first six branching levels, and in twenty-six non-smoker human volunteers in vivo. Results of the hollow cast study indicated a linear dependence of particle deposition efficiency on the Stokes number for aerosols with aerodynamic diameters greater than 2 micrometers. Alveolar and total respiratory tract in vitro deposition in healthy non-smokers was minimal for particles of approximately 0.4 micrometers, and alveolar deposition for mouthpieces inhalations peaked for particles of approximately 3 micrometers. A new anatomic parameter, the bronchial deposition size (BDS), is introduced to permit the classification of various individuals and populations according to their tracheobronchial deposition efficiencies. The average BDS's were 1.20 cm for 26 healthy non-smokers, 1.02 cm for 46 cigarette smokers, 0.90 cm for 19 clinical patients being treated for obstructive lung disease and 0.60 cm for six severely disabled patients.
The realistic study of article deposition in model systems of the tracheobronchial tree requires that respiratory patterns and airflow profiles mimic those occurring in vivo. This paper describes a variable-opening mechanical larynx which was designed for use in deposition studies performed under cyclic flow conditions.
A modified method for nebulization was developed for use with relatively small (20 mL) amounts of feed liquid, in this case, a suspension of radioactively tagged polystyrene (CMD = 2.87 micron, sigma g = 1.25). The method may be easily adapted for use in producing other aerosols where only this quantity of suspension material is available.
The effects of pancuronium 0.08 mg kg-1, metocurine 0.4 mg kg-1 and tubocurarine 0.4 mg kg-1 on vascular tone were studied in 26 patients undergoing open heart surgery during total cardiopulmonary bypass. With a fixed rate of perfusion, arterial pressure is related directly to total peripheral resistance, while the volume of blood remaining in the extracorporeal reservoir is related inversely to vascular capacity, which depends primarily on venous tone. Pancuronium increased the reservoir volume (average of 780 +/- SEM 250 ml (P less than 0.01). We conclude that under certain circumstances pancuronium constricts capacitance vessels in man.