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Biomedical subjects

T W Chick

Publications and source records attributed to T W Chick.

At least 19 recordsLinked to original sources

Neutrophil responses to intravascular pneumococcal sonicate.

Leukopenia and pulmonary leukostasis are prominent features in patients succumbing to pneumococcal (PNC) infections. We examined mechanisms involved in recruitment of polymorphonuclear neutrophils (PMNs) into pulmonary capillaries and alveolae after PNC sonicate injection. We showed that by 15 min postinjection, PMN chemotactic activity was found in bronchoalveolar lavage (BAL) fluids and increased with time until the end point of the study at 90 min. Accompanying the increased chemotactic activity in BAL fluids was a decrease in circulating PMNs more pronounced in the femoral artery (FA) than the pulmonary artery (PA). Superoxide anion (O2-) production by peripheral PMNs was depressed following PNC sonicate injection, and comparison of FA and PA showed that FA PMNs produced less O2- than PA PMNs. PA PMNs also showed enhanced random migration when compared to the depressed random migration of FA PMNs. This study demonstrated that an intravascular challenge of PNC sonicate was associated with increased chemotactic activity for PMNs in BAL fluid. Fewer PMNs and altered PMN function resulted from passage through the pulmonary microvasculature after PNC sonicate injection.

Animals

Effects of acid-base status on acute hypoxic pulmonary vasoconstriction and gas exchange.

To investigate the relationship between hypoxic pulmonary vasoconstriction and respiratory and metabolic acidosis and respiratory alkalosis, the pulmonary gas exchange and pulmonary hemodynamic responses were measured in anesthetized, paralyzed, and mechanically ventilated dogs in two sets of experiments (series A, n = 6; series B, n = 10). The animals were treated with acute hypoxia, CO2 inhalation, hyperventilation, and dinitrophenol in various combinations. Multiple regression analysis indicated that mean pulmonary arterial pressure (Ppa) was significantly correlated with end-tidal PO2, mixed venous PO2, and the mean pulmonary capillary pH (average of arterial and mixed venous pH) as independent variables [series A: r = +0.999, standard error of estimate (SEE) = 0.4 mmHg; series B: r = +0.98, SEE = 1.4 mmHg]. Similar analyses of mean values published by other authors from an acute study on humans with exercise at sea level and simulated altitudes of 10,000 and 15,000 ft also indicated a good relationship (n = 14, r = +0.98, SEE = 2.1 mmHg). The mean data (n = 19) obtained in Operation Everest II at various exercise loads and simulated altitudes gave a correlation of r = +0.87, SEE = 6.1 mmHg. These empirical analyses suggest that variations in the rise of Ppa with hypoxia can be accounted for in vivo by the superimposed acid-base status. Furthermore, ventilation-perfusion inhomogeneity, as estimated in the dogs from end-tidal and arterial O2 and CO2 differences and assuming no true shunt or diffusion impairment, was highly correlated with Ppa and mean pulmonary capillary pH (r = +0.999 in series A, r = +0.77 in series B). The human data from the above studies also showed significant correlations between Ppa and directly measured ventilation-perfusion (standard deviation of perfusion obtained from inert gas measurements). These observations indicate that the beneficial effects of hyperventilation during hypoxia may be related to the marked alkalosis that serves to reduce Ppa and improve pulmonary gas exchange efficiency.

2,4-Dinitrophenol

A multivariate model for the prediction of relapse after outpatient treatment of decompensated chronic obstructive pulmonary disease.

PURPOSE: To develop and validate a multivariate model for predicting relapses after treatment of decompensated chronic obstructive pulmonary disease in an emergency department. METHODS: A 5-year survey was conducted, including training and validation periods. Stepwise logistic regression was used to develop a multivariate predictive model using clinical data obtained at the time of each visit. A relapse was defined as an unscheduled return to the emergency department within 48 hours. SITE: The study was conducted in the emergency department of the Albuquerque (New Mexico) Veterans Affairs Medical Center. SUBJECTS: The subjects were 289 patients with documented chronic obstructive pulmonary disease. MEASUREMENTS AND MAIN RESULTS: During the first 3 years, there were 705 visits in which the patient was treated and released from the emergency department. Relapse occurred 82 times (11.6%). Logistic regression showed that the following variables had an effect on the risk of relapse: the relapse rate for previous visits, a previous visit within 7 days, long-term home oxygen therapy, the number of doses of nebulized bronchodilators, the administration of aminophylline, and the use of antibiotics and prednisone at the time of discharge from the emergency department. During the next 2 years, the 48-hour relapse rate was 9.9% (47 of 476 discharges). When the model was fitted to these data, all of the original variables contributed to the prediction of relapse except antibiotic use and long-term home oxygen therapy. The logistic model was used to categorize each visit during the validation phase. The relapse rate for "high-risk" visits was significantly higher than that for "low-risk" visits (18.4% vs 6.1%). The method identified 57.4% of visits that ended in relapse at 48 hours. CONCLUSIONS: A multivariate model can be used to identify patients with a poor prognosis after the outpatient treatment of decompensated chronic obstructive pulmonary disease.

Ambulatory Care

A multivariate model for predicting hospital admissions for patients with decompensated chronic obstructive pulmonary disease.

PURPOSE: To develop a method for predicting hospital admissions for patients with decompensated chronic obstructive pulmonary disease treated in an emergency department. METHODS: A 4-year survey including training and validation periods was conducted. Stepwise logistic regression was used to develop a multivariate model using information from the patient's previous visits and results of baseline pulmonary function tests. MEASUREMENTS AND MAIN RESULTS: During the first 2 years, there were 693 visits to the emergency department for decompensated chronic obstructive pulmonary disease. The patient was admitted to the hospital on 210 occasions (30.3%). Logistic regression showed that the probability of admission was related to the following: the admission and relapse rates for previous visits, the proportion of previous discharges from the emergency department in which "conservative therapy" was given, the highest baseline post-bronchodilator forced expiratory volume in 1 second within 3 years of entry, and the highest baseline pre-bronchodilator forced expiratory volume in 1 second-vital capacity ratio. A relapse was defined as an unscheduled return to the emergency department within 48 hours. "Conservative therapy" was any treatment regimen that did not include parenteral medications. During the next 2 years, the model was validated with patients not previously treated at this medical center. Seventy-six (28.3%) of 269 episodes resulted in hospital admission. The logistic model was used to categorize each visit during the validation phase. "High-risk" visits had calculated probabilities of admission greater than .208, while "low-risk" visits had values that were less. The admission rate for 98 low-risk visits (8.2%) was much lower than the rate for 171 high-risk visits (39.8%). CONCLUSIONS: A multivariate model can be used to identify patients with decompensated chronic obstructive pulmonary disease who are unlikely to need hospitalization. This model could be used to select episodes of decompensated chronic obstructive pulmonary disease for treatment at home.

Aged

Treatment of decompensated chronic obstructive pulmonary disease in the emergency department--correlation between clinical features and prognosis.

STUDY OBJECTIVE: Patients with decompensated chronic obstructive pulmonary disease (COPD) are at high risk of relapse after treatment in an emergency department. The purpose of this study was to determine if the risk of relapse correlates with the clinical features of the disease. PATIENTS: Three hundred fifty-two patients with documented COPD who were treated for dyspnea in the ED of the Albuquerque Veterans Administration Medical Center over a three-year period. METHODS: We reviewed the clinical features and pulmonary function tests of the patients, who were considered to have COPD if the baseline prebronchodilator one-second forced expiratory volume (FEV1) was less than 80% predicted, and less than 80% of the forced vital capacity and inhaled bronchodilators failed to increase the FEV1 to levels of more than 80% predicted. Visits for pneumonia, pneumothorax, pleural effusion, or pulmonary emboli were excluded. A relapse was defined as an unscheduled revisit to the ED within 14 days of initial treatment. Data were entered into a microcomputer data base and analyzed by a commercial statistical package. RESULTS: Of 877 visits in which the patient was treated and released from the ED, 281 (32.0%) resulted in relapse and were considered unsuccessful Compared with successful visits, unsuccessful visits were characterized by a shorter duration of dyspnea (P = .002), a lower entry FEV1 (P = .027), a lower discharge FEV1 (P = .040), a greater number of treatments with nebulized bronchodilators (P = .009), more frequent use of parenteral adrenergic drugs (P = .006), and less frequent use of oral prednisone on discharge (P = .016). Patients with one or more relapse visits during the study period (relapsers) differed from nonrelapsers in several respects. Relapsers had a greater bronchodilator response on baseline FEV1 than nonrelapsers (P = .047). Nevertheless, relapsers required more bronchodilator treatments in the ED (P less than .001); were treated more frequently with parenteral adrenergic drugs (P less than .001), IV glucocorticoids (P less than .001), and oral prednisone (P less than .001); and recovered less of their baseline FEV1 (P less than .014). CONCLUSION: Bronchodilator response on baseline pulmonary function testing appears to identify patients with COPD who have a poor prognosis after emergency treatment. Their poor response to intensive bronchodilator treatment suggests that loss of bronchodilator response may be involved in the pathogenesis of respiratory decompensation.

Aged

The effect of aging on submaximal exercise performance and recovery.

The upward drift of gas exchange variables during 70% maximal exercise and recovery half-times in aged and young subjects of equivalent age-predicted aerobic capacity was measured. In the aged subjects, upward drift of VE, VO2, and HR was reduced compared with the young group. The recovery of VE, VCO2, and VO2 was slowed in the aged. However, at 10 minutes post-exercise, VCO2, VO2, and HR had returned to similar relative values for both groups; in the young subjects VE remained elevated at the end of recovery. The reduced upward drift of gas exchange variables and HR during exercise in aged subjects is consistent with an attenuated response of glycogenolysis and lactate production to adrenergic stimulation and/or to selective loss of type II skeletal muscle fibers. The slowed recovery of VE, VCO2, and VO2 in elderly persons is consistent with age-related reduced CO2 chemosensitivity, delaying elimination of the exercise-induced CO2 load.

Adult

Cardiopulmonary responses to acute hypoxia, head-down tilt and fluid loading in anesthetized dogs.

The separate and combined acute effects of hypoxia (HY-11% O2), head-down tilt (HD-30 degrees) and fluid loading (FL-1.0 L saline) on hemodynamics and pulmonary gas exchange were determined in 17 anesthetized, mechanically ventilated dogs. Both during HY and normoxia (NO), the total respiratory compliance was decreased by HD, attributable to pulmonary vascular congestion. The reductions in compliance were twice as great with FL, indicating pulmonary interstitial edema, which was supported by histological observation of lung tissue. Pressure-flow relationships in the pulmonary circulation indicated that superimposing HD on HY doubled the increase in vascular resistance due to HY alone, while in the systemic circulation the resistance was returned to below NO by HD. A significant positive correlation between the changes in blood volume and pulmonary artery pressure for experimental transitions suggests that a shift in blood volume from systemic to pulmonary circulations and changes in total blood volume probably contributed substantially to these apparent changes in resistance. Pulmonary gas exchange efficiency, whether expressed in terms of shunt or ventilation/perfusion distribution from arterial-end-tidal PCO2 and PO2 differences, showed a significant inverse relationship with pulmonary driving pressure for the experimental conditions imposed. No clear synergistic effects of HY on HD were evident in contributing to pulmonary edema when superimposed prior to FL, but after FL this risk must be considered.

Acute Disease

Rate-adaptive cardiac pacing in children using a minute ventilation biosensor.

Chronotropic integrity is required for a normal cardiac output response to exercise. We evaluated a rate-adaptive ventricular demand pacemaker (Telectronics, META-MV) which uses minute ventilation as the sensed physiological variable for adjusting pacing rate, in seven young patients with a mean age of 11.4 years. All patients had clinically significant bradycardia related to complete heart block (n = 4) or sinus node dysfunction (n = 3). For the entire group, paced heart rates increased from 70 +/- 10 beats/min to 151 +/- 19 beats/min with exercise testing. The onset of rate adaptation took less than 30 seconds. Changes in paced rate were linearly related to workload, VO2 (5.9 to 20.7 mL/min/kg) and minute ventilation (8-65 L/min). The decline in pacing rate after exercise was related directly to the gradual decrease in minute ventilation and VO2. Our data show that minute ventilation closely and accurately reflects the metabolic demands of varying workloads in children and can be used to achieve physiological, rate-adaptive pacing.

Adult

Training-induced skeletal muscle adaptations are independent of systemic adaptations.

To isolate the peripheral adaptations to training, five normal subjects exercised the nondominant (ND) wrist flexors for 41 +/- 11 days, maintaining an exercise intensity below the threshold required for cardiovascular adaptations. Before and after training, intracellular pH and the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) were measured by 31P magnetic resonance spectroscopy. Also maximal O2 consumption (VO2 max), muscle mass, and forearm blood flow were determined by graded systemic exercise, magnetic resonance imaging, and venous occlusion plethysmography, respectively. Blood flow, Pi/PCr, and pH were measured in both forearms at rest and during submaximal wrist flexion at 5, 23, and 46 J/min. Training did not affect VO2 max, exercise blood flow, or muscle mass. Resting pH, Pi/PCr, and blood flow were also unchanged. After training, the ND forearm demonstrated significantly lower Pi/PCr at 23 and 46 J/min. Endurance, measured as the number of contractions to exhaustion, also was increased significantly (63%) after training in the ND forearm. We conclude that 1) forearm training results in a lower Pi/PCr at identical submaximal work loads; 2) this improvement is independent of changes in VO2 max, muscle mass, or limb blood flow; and 3) these differences are associated with improved endurance and may reflect improved oxidative capacity of skeletal muscle.

Adaptation, Physiological

Recovery of gas exchange variables and heart rate after maximal exercise in COPD.

Studies of the limited exercise capacity in patients with COPD have not assessed the recovery phase, although the phenomenon of increased oxygen uptake after exercise has been thoroughly investigated in normal subjects. Therefore, we compared the recovery of gas exchange variables and HR after maximal cycle ergometry in 16 patients with varying severities of airflow obstruction and ten aged control subjects. Aerobic capacity was reduced in the patients with COPD, and the rates of recovery of VE, VO2, VCO2, excess VCO2, and HR were all significantly slower in the patients with COPD than in the controls. When expressed as the half-time for recovery, patients with COPD had values which were approximately twice that of control subjects for gas exchange and HR. The extent of recovery was similar in patients and controls. We conclude that in patients with COPD, postexercise relative hyperpnea and hypermetabolism are significantly prolonged. In addition, impaired elimination of increased body stores of carbon dioxide may contribute to impaired adjustment to acid-base disorders in these patients.

Aged

Intravenous and oral corticosteroids for the prevention of relapse after treatment of decompensated COPD. Effect on patients with a history of multiple relapses.

To determine if a regimen of intravenous and oral corticosteroids reduces the relapse rate after treatment of decompensated COPD in the ED, 30 patients were studied. Forty-five visits in which intravenous and oral corticosteroids were given (T visits) were compared with an equal number of matched visits in which they were withheld (N visits). No differences were noted between T and N visits with respect to clinical findings, laboratory results and other forms of therapy. Treatment with corticosteroids reduced the relapse rate within 24 h of discharge. At 48 h, the cumulative relapse rate for T visits (8.9 percent) was significantly lower than for N visits (33.3 percent; p = 0.005). For patients with a history of multiple relapses, a regimen consisting of intravenous and oral corticosteroids reduces the risk of relapse after ED treatment of decompensated COPD.

Acute Disease

Aminophylline in the outpatient management of decompensated chronic obstructive pulmonary disease.

The objective of this study was to determine if IV aminophylline reduces the risk of relapse after treatment of decompensated COPD in an ED. Forty-six visits in which IV aminophylline was given (T visits) were compared with an equal number of visits in which it was withheld (N visits) with respect to pretreatment serum theophylline level, number of treatments with nebulized bronchodilators and use of parenteral beta-adrenergic drugs, IV corticosteroids and prednisone. The difference in 48-h relapse rates for T and N visits was examined by McNemar's test. No differences were found between T and N visits with respect to vital signs, pretreatment FEV1, arterial blood gas values, hematocrit level or blood leukocyte count. The 48-h relapse rate for T visits (22.2 percent) was significantly higher than for N visits (6.7 percent; p = 0.035). Aminophylline does not appear to be beneficial for outpatients with decompensated COPD and may be harmful.

Aged

Effects of acute hypoxia on cardiopulmonary responses to head-down tilt.

Six male subjects were exposed on two separate occasions to simulated microgravity with 28 degrees head-down tilt (HD) for 1 h with baseline followed by recovery at + 17 degrees head-up. Pulmonary ventilation, gas exchange, spirometry, and central and cerebral blood flow characteristics were compared while breathing ambient air (PIO2 = 122 mm Hg) and reduced FIO2 equivalent to 14,828 ft (PIO2 = 81 mm Hg). With hypoxia (HY), the increased tidal volume served to attenuate the drop in arterial saturation by reducing deadspace ventilation. Arterial and mixed venous PO2 values, estimated from peripheral venous samples and cardiac output (CO), were both maintained during HD in HY. Mixed venous PO2 was elevated by an increase in CO associated with a reduction in systemic resistance. Changes in spirometric indices during HD were not accentuated by HY, making the presence of interstitial edema unlikely. Cerebral flow and resistance showed minor reductions with HD. Tissue oxygenation and cardiopulmonary function were not notably effected by HD during HY, but a combination of these two stressors may predispose subjects to subsequent orthostatic intolerance during initial recovery.

Acute Disease

Subsensitivity of beta responses during therapy with a long-acting beta-2 preparation.

The question whether some tolerance or subsensitivity of various beta receptors develops during therapy with long-acting oral beta-2 agents has practical and theoretical importance. We applied a strong beta-2 stimulus (terbutaline, 5.0 mg orally) at weekly intervals for up to three weeks in 19 stable asthmatics and bronchitics while commencing 5.0 mg terbutaline three times daily. The evening dose was omitted before each morning challenge. Challenges were continued at one and two weeks off terbutaline in some patients to test return of beta function. Patients received no ephedrine for two weeks before the study but were allowed aminophylline or isoproterenol inhalations up to 18 and 4 hr before challenges, respectively. Pulmonary function, pulse, and blood pressure were monitored at 0, 60, 120, and 180 min, and metabolic parameters measured at 0 and 180 min. There was significant drug tolerance in the drop and minimum diastolic pressure reached, rise in lactate, cyclic AMP, and blood glucose, and drop in eosinophils. Peak FEV1 and V50 dropped slightly, but vital capacity and minimal airway resistance did not change significantly. During continuous therapy this slight bronchial subsensitivity is probably obscured by elevated baseline function. It might assume importance during periods of excessive inhaler use or abrupt drug withdrawal.

Asthma

Pulmonary dysfunction after lymphangiography.

Pulmonary function tests were done on 15 patients before and after bipedal lymphangiography. Lymphangiography was associated with an approximate 10 per cent reduction in lung volume. This phenomenon persisted for 48 to 72 hours. The probable mechanism for this reduction is closure of terminal airways or alveolar ducts or both and is reversible by beta-adrenergic drugs. The reduction does not correlate with the severity of pre-existing pulmonary disease. The degree of pulmonary impairment can be assessed roughly by measurement of the vital capacity. An operation can be performed safely 3 to 5 days after lymphangiography.

Aged

Comparative bronchodilator responses to atropine and terbutaline in asthma and chronic bronchitis.

We have compared bronchodilator responses to atropine and terbutaline in 39 chronic bronchitics and 16 stable asthmatics. Fasting subjects were given either 1.05 mg atropine of 5.0 mg terbutaline orally. Pulmonary function was assessed using the peak responses, namely: three 60-minute intervals for terbutaline and three 30-minute intervals for atropine. A subgroup of five reactive bronchitis patients was given a placebo with no response. Areas under the percent response-time interval curve were compared. Both patient groups responded to the same degree to atropine and terbutaline with respect to reduction of airway resistance. However, the FEV1 and V50 responses to terbutaline were markedly enhanced compared to atropine in the asthmatics while equal to the atropine response in the bronchitis patients. Thus, atropine appears to exert its effect upon both large and small airways in bronchitis, but predominantly on large airways in asthma. The results are consistent with a state of enhanced vagal tone in small airways in bronchitis compared to asthma, but other explanations are conceivable.

Airway Resistance

Apparent theophylline half-life fluctuations during treatment of acute left ventricular failure.

The administration of theophylline in a 63-year-old man with arteriosclerotic heart disease and chronic bronchitis is discussed to illustrate the pharmacokinetics of theophylline in an abnormal host state. The case demonstrates that clearly acute congestive heart failure and its treatment may dramatically affect the kinetics of theophylline elimination. Possible explanations for this phenomenon are presented, and the therapeutic implications are discussed.

Administration, Oral