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Biomedical subjects

A K Pierce

Publications and source records attributed to A K Pierce.

At least 37 records · Page 2Linked to original sources

Early bacterial clearance from murine lungs. Species-dependent phagocyte response.

Two sets of phagocytic cells are available to defend the lung against inhaled bacteria. Both resident alveolar macrophages and granulocytes from the circulation have been observed in pulmonary air spaces after the deposition of bacteria; their functional roles, however, have been defined. We rendered mice selectively granulocytopenic with heterologous antiserum in order to ascertain the relative contributions of these two groups of cells in intrapulmonary bacterial killing. The clearance of Staphylococcus aureus was unimpaired in granulocytopenic animals, confirming the primary role of the alveolar macrophages in the killing of these organisms. In contrast, granulocytopenic animals cleared only 10.0+/-7.0% of an inoculum of Klebsiella pneumoniae compared with 33.0+/-4.0% clearance in normal animals (P < 0.02), and Pseudomonas aeruginosa proliferated to 513% of baseline levels in granulocytopenic animals, whereas normal mice cleared 26.8+/-10.6% of the inoculum. These findings indicate that circulating granulocytes play a major role in the clearance of the latter two organisms. This variation in cellular response to different bacterial species suggests that the defense of the lung against pathogenic bacteria is more complex than has been previously assumed.

Aerosols↗

Use of probenecid in ticarcillin-induced hypokalemia.

Probenecid has been suggested as a prophylactic treatment of penicillin-induced hypokalemia, the proposed mechanism being that penicillin will be prevented from acting as a nonreabsorbable anion binding potassium and resulting in increased urinary losses. A rapidly occurring hypokalemia, unresponsive to intravenous replacement of potassium, can be explained by redistribution rather than urinary wastage. We report a case where probenecid was administered for ticarcillin-induced hypokalemia without any significant benefits.

Child↗

Animal model of neutropenia suitable for the study of dual-phagocyte systems.

When two sets of phagocytic cells participate simultaneously in the inflammatory process and bacterial killing, the relative contribution of each cell type is difficult to ascertain. The use of cell-specific antibody will permit selective depletion of one phagocyte population. We describe an experimental model of granulocytopenia which utilizes the immunoglobulin G fraction of an antigranulocyte serum. This material markedly depleted circulating polymorphonuclear leukocytes (PMN); within 2 h after injection of antigranulocyte globulin, PMN counts were at 19% of original levels and remained significantly depressed for 24 h. Granulocyte recruitment was also impaired, with only 5 x 10(3) PMN appearing in the lungs in response to an aerosol of Klebsiella, compared to 4.17 x 10(5) PMN in control animals (P less than 0.01). Most importantly, alveolar macrophages retained normal viability (97% versus 94% for control value, P not significant) normal phagocytic function, and normal bactericidal capacity. Antigranulocyte globulin is thus a valuable tool for the study of bacterial defense mechanisms.

Agranulocytosis↗

Pharyngeal aspiration in normal adults and patients with depressed consciousness.

A sensitive technic using indium111 chloride was devised to investigate the occurrence of pharyngeal aspiration. Twenty normal subjects and 10 patients with depressed consciousness were studied. Forty-five per cent of the normal subjects aspirated during deep sleep. Normal subjects who did not aspirate were noted to sleep poorly. Seventy per cent of the patients with depressed consciousness aspirated. Aspiration of pharyngeal secretions occurs frequently in patients with depressed sensorium and also in normal adults during deep sleep. Bacterial pneumonia may result when aspirated bacteria are not effectively cleared. This may result when clearance mechanisms are impaired or when they are overwhelmed by large volumes of aspirated secretions.

Adult↗

Controlled oxygen administration in acute respiratory failure in chronic obstructive pulmonary disease: a reappraisal.

Controlled oxygen therapy may aggravate carbon dioxide retention during acute exacerbations of chronic obstructive pulmonary disease (COPD). Of 50 consecutive patients with COPD and acute respiratory failure, 13 required intubation because of carbon dioxide narcosis. With discriminant analysis of their arterial oxygen tension (PaO2) and pH on admission, a diagram separated patients into those at high risk and those at low risk for carbon dioxide narcosis. This diagram was then used to predict carbon dioxide narcosis in 73 patients with COPD and acute respiratory failure who were treated with controlled oxygen. In 16 of these patients carbon dioxide narcosis developed. Thirteen (81 per cent) were predicted by the diagram to be at high risk for this complication. Only two (4 per cent) patients judged by the diagram to be at low risk for carbon dioxide narcosis required mechanical ventilation. Utilizing an oxygen tension (PO2), carbon dioxide tension (PCO2) diagram a patient's ventilatory response was compared to that of ambulatory patients with COPD. These data suggest that hypoxemia and acidosis are more discriminatory for "carbon dioxide narcosis" than hypercapnia.

Acute Disease↗

Lung clearance of Staphylococcus aureus strains with differing protein A content: protein A effect on in vivo clearance.

We have studied the clearance from murine lungs of two strains of Staphylococcus aureus, one possessing high and the other possessing low levels of protein A.S. aureus FDA 209 and S. aureus Wood 46 were assayed for their ability to bind mouse immunoglobulin G, using an indirect radioimmunoassay. S. aureus FDA 209 binding of mouse immunoglobulin was significantly greater than that of S. aureus Wood 46 (118,909 versus 37,845 cpm). Clearance of these two strains from the lung after a 30-min aerosol inoculation period was not significantly different. The percentage of bacteria remaining in the lung was 49.2 and 55.0% at 2h, 31.8 and 33.2% at 3 h, and 25.4 and 17.2% at 4 h for protein A-rich and protein A-poor strains, respectively (P greater than 0.20 at each time). These data suggest that the previously demonstrated in vitro antiphagocytic effect of protein A may not be relevant to pulmonary clearance mechanisms.

Animals↗

Cardiovascular effects of positive end-expiratory pressure in dogs.

Our purpose was to reexamine the relationship of the fall in cardiac output and blood pressure which occurs during positive end-expiratory pressure (PEEP) to changes in transmural right atrial and left atrial filling pressures. Closed-chest dogs, half with pulmonary edema, were studied during spontaneous breathing and inspiratory positive-pressure breathing (IPPB) with 0-15 cmH2O PEEP. Mean esophageal pressure accurately reflected changes in pericardial pressure and was used to estimate extracardiac pressure. We found that cardiac output fell approximately 50% and blood pressure fell 20% during 15 cmH2OPEEP in spite of well maintained transmural right atrial and left atrial (or pulmonary artery wedge) pressures suggesting a primary or reflex depression of atrial or ventricular function.

Anesthesia↗

An examination of the microbiologic flora of normal lung of the dog.

We examined the hypothesis that normal lung is sterile. A laboratory animal, the dog, was chosen so that sample size could be maximized. Controls were used to eliminate the possible artifactual presence of bacteria in the lung. Thirty-seven per cent of lung samples contained aerobic bacteria with a mean concentration of 1.3 X 10(3) organisms per g of tissue. Seventy-four per cent of identical bacterial isolates were found in the pharynx of the same animal. We concluded that viable bacteria are aspirated into normal lung where they may survive for at least limited intervals.

Animals↗

The effect of complement depletion on lung clearance of bacteria.

We have investigated the effect of hypocomplementemia on early pulmonary clearance of four species of bacteria. The experiments were performed in an inbred animal model to minimize immunologic variability. Complement was depleted by cobra venom factor, and activity in serum was monitored with a phagocytic assay. Bacterial specific antibodies were examined by an indirect radioimmunoassay, and animals with high levels of activity were excluded from anaysis. 4 h after aerosolization with Streptococcus pneumoniae, complement-depleted animals had cleared only 75% of the initial number of organisms, whereas saline-treated controls cleared 91% (P less than 0.01). Aerosolization with Pseudomonas aeruginosa was followed at 4 h by a twofold greater growth of organisms in the complement-depleted animals (446% of original deposition) as compared to the saline-treated controls (211% of original deposition) (P less than 0.02). Clearance of Klebsiella pneumoniae and Staphylococcus aureus were similar in complement-depleted animals and saline-treated controls. These experiments suggest that hypocomplementemia predisposes to bacterial pneumonia and may explain the high incidence of pulmonary infections in patients having impaired complement activity. Our results further indicate that varying defense mechanisms may be involved with clearing the lung of differing bacterial species.

Animals↗

Pulmonary complications of general surgery.

1. Patients should be divided preoperatively into low- or high-risk categories, depending on their probability of developing postoperative pulmonary complications. The evaluation should include spirometry as well as an assessment of the previously defined risk factors. 2. Patients in a low-risk category need only instruction in deep breathing pre- and postoperatively. Routine use of supplemented oxygen postoperatively is reasonable until it can be demonstrated whether such is necessary. 3. High-risk patients should be as free as possible of respiratory secretions at the time of surgery. A regimen for this purpose includes cessation of smoking, and administration of inhaled bronchodilators followed by chest percussion and postural drainage. 4. High-risk patients should be carefully instructed in deep breathing and coughing preoperatively. A mechanical device such as an incentive spirometer may be beneficial in this regard. If it is not possible to achieve spontaneous deep breathing, an attempt to accomplish this by IPPB may be undertaken. The tidal volume desired should be ordered. If IPPB does not result in large tidal volumes, it should be discontinued. 5. The deep breathing procedure found to be most successful preoperativelly should be continued postoperatively. 6. The patient should be as mobile as possible while in bed and ambulated as soon as is feasible. 7. Patients with preoperative expiratory flows of less than 20% of predicted values or with chronic hypercapnia should be carefully observed for postoperative ventilatory failure.

Anesthesia↗

Determinants of lung bacterial clearance in mice after acute hypoxia.

Net lung bacterial clearance in normal mice is determined by the balance of in vivo bacterial multiplication on the one hand, and the defense mechanisms of mucociliary clearance and phagocytosis and killing by the oxygen-dependent alveolar macrophage on the other. The bactericidal function of the macrophage is the major component of the defense mechanism. The effect of acute hypoxia on the defense mechanism was studied in mice exposed to aerosols of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae. Physical clearance was not impaired by acute hypoxia, and bacterial replication was not stimulated by the low oxygen atmosphere. Clearance of Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli was impaired during acute hypoxia due to decreased phagocytosis or killing by the alveolar macrophage. The important human pathogen Streptococcus pneumoniae was cleared normally in the presence of acute hypoxia. This observation suggests that an oxygen-independent clearance mechanism is important in lung defense against the pneumococcus. This may be a separate mechanism within the alveolar macrophage or a system as yet unidentified.

Aerosols↗

Leukocytic response to inhaled bacteria.

Using histologic techniques, we have quantified the amount of infiltration of bronchi and alveoli by polymorphonuclear leukocytes during the 4 hours after an aerosol inoculation of mice with bacteria. Although the lungs of animals challenged with Staphylococcus aureus differed little from those of animals exposed only to a water aerosol, the lungs of animals exposed to Klebsiella pneumoniae or to Escherichia coli demonstrated significantly greater polymorphonuclear leukocyte infiltrations in bronchi and alveoli 2 and 4 hours afer exposure. These results suggest that the polymorphonuclear leukocyte may contribute to the early defense of the lung against some bacteria.

Aerosols↗

Intravascular coagulation associated with the adult respiratory distress syndrome.

In seven of 30 consecutive patients with the adult respiratory distress syndrome, disseminated intravascular coagulation (DIC) developed. Increasing respiratory dysfunction characterized by decreased effective static compliance and increased hypoxemia coincided with the development of DIC. Patients in whom DIC developed were characterized by a high incidence of bleeding, gangrene of the extremities, renal dysfunction, mortality and autopsy evidence of fibrin microthrombi in the lungs, kidney and skin. In 12 of 23 patients who did not meet the criteria for DIC, the platelet count decreased by at least 50 per cent of the initial values at some time during their illness. Fibrin microthrombi were found in the lungs in the majority of the patients subjected to autopsy. These data support the concept that depostion of platelet on damaged pulmonary capillary endothelium may be more common in the adult respiratory distress syndrome than the DIC syndrome.

Adult↗

Comparison of spontaneous and positive-pressure breathing in supine normal subjects.

Distribution of ventilation (V) and perfusion (Q) was studied with 133Xe in eight supine, normal subjects comparing spontaneous breathing (SB) and intermittent positive-pressure breathing (IPPB). Tidal volume, inspiratory flow, and breathing frequency measured during SB were closely matched during automatically triggered IPPB. V and Q in the lung bases (adjacent to the diaphragm) were decreased relative to other regions during SB and further diminished by IPPB at similar volumes. During IPPB, basilar V and Q improved when tidal volume was increased; however; spontaneous hyperinflation resulted in significantly higher basilar V and Q than large tidal volumes delivered by IPPB. Thus, changes in lung volumes and gas exchange in the supine posture are attributable to impaired V and Q in the bases but not in dependent (posterior) regions. IPPB further reduces basilar V and Q, possibly due to loss of interdependence resulting from diminished respiratory muscle contraction. These findings may explain atelectasis during prolonged IPPB in supine patients. Although large tidal volumes improve basilar V during IPPB, spontaneous deep breaths are more effective and may prevent atelectasis better than IPPB at similar tidal volumes.

Humans↗

Pulmonary aspiration of gastric contents.

A retrospective analysis of 50 patients who had been observed to aspirate gastric contents was performed to define better the course of patients with this syndrome. The patients invariably had a disturbance of consciousness, most commonly due to sedative drug overdose or general anesthesia. The onset of clinical signs occurred prompty after aspiration and tended to be similar in all patients, irrespective of their subsequent course or outcome. These findings usually included fever, tachypnea, diffuse rales, and serious hypoxemia. Cough, cyanosis, wheezing, and apnea were each seen in approximately one third of the cases. Apena, shock, and early severe hypoxemia were particularly ominous events. Initial roentgenograms revealed diffuse or localized alveolar infiltrates, which progressed during the next 24 to 36 hours. Subsequent clinical courses followed 3 patterns: 12 per cent of the patients died shortly after aspiration; 62 per cent had rapid clinical and radiologic improvement, with clearing, on average, within 4.5 days; 26 per cent demonstrated rapid improvement, but then had clinical and radiographic progression associated with recovery of bacterial pathogens from the sputum and a fatal outcome in more than 60 per cent. Treatment from the outset by adrenocortical steroids or antimicrobial agents had no demonstrable effect on the outcome. The clinical features of aspiration of gastric contents are characteristic and distinguish it from other forms of aspiration-related lung disease.

Apnea↗

Determinants of lung bacterial clearance in normal mice.

The determinants of the lung clearance of Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus were studied in normal mice after exposure to an aerosol of viable bacteria and 99mTc-labeled dead bacteria. The fraction of bacteria in lungs that remained viable 4 h after exposure were: S. pneumoniae, 7.3%; K. pneumoniae, 121%; E. coli, 88.5%; S. aureus, 27.6%. The rate of physical removal of bacterial particles (Kmc) was determined from the change in lung 99mTc counts with time: Kmc ranged between 7 and 12%/h and and was similar in all species. The rate of mucociliary clearance and of intrapulmonary bacterial killing (Kk + Kmc) was calculated from the change in bacterial counts with time in animals that had received tetracycline to inhibit bacterial multiplication. Kk, the rate of intrapulmonary killing, was obtained by subtraction of Kmc from (Kk + Kmc). The calculated values for Kk were: S. pneumoniae, - 87%/h; K. pneumoniae, - 17%/h; E. coli, - 18%/h; S. aureus, - 22%/h. The rate of intrapulmonary bacterial multiplication (Kg) was estimated from the relationship of bacterial counts in tetracycline and nontetracycline-treated animals, assuming that tetracycline altered only Kg. Kg, expressed as the doubling time, was: S. pneumoniae, 310 min; K. pneumoniae, 217 min; E.coli, 212 min; S. aureus, infinity (no multiplication). The data indicate that the marked differences in the clearance of these species from the normal mouse lung result from the interaction of differing rates of in vivo bacterial multiplication and killing.

Aerosols↗

The radiographic resolution of Streptococcus pneumoniae pneumonia.

To determine the characteristics of the radiographic resolution of bacteremic Streptococcus pneumoniae pneumonia we examined serial chest roentgenograms in 72 patients. Consolidation disappeared in all patients by eight to 10 weeks; volume loss (9 per cent), plural disease (9 per cent), and stranding (19 per cent) often persisted beyond eight weeks. Resolution occurred earlier in patients less than 50 years old (P less than 0.05) and in the absence of alcoholism and underlying airways disease regardless of age (P less than 0.05). Delayed clearing occurred when these complicating factors were present in patients over 50. Lung cancer was not responsible for delayed resolution of pneumonia. We conclude that an appropriate interval for serial radiographic examinations after therapy for pneumococcal pneumonia is six weeks.

Aging↗