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Biomedical subjects

D A Mahler

Publications and source records attributed to D A Mahler.

At least 73 records · Page 4Linked to original sources

Intratumoral Bacillus Calmette-Guérin immunotherapy prior to surgery for carcinoma of the lung: results of a prospective randomized trial.

A prospective randomized trial of preoperative intratumoral therapy with Bacillus Calmette-Guérin (BCG) was conducted in non-small cell lung cancer patients. Eighty-eight patients (48 BCG-treated and 40 control subjects) were entered into the study; three control subjects were removed from data analysis because histology revealed pathology other than non-small cell lung cancer. There were no differences between BCG-treated and control patients in sex, age, cigarettes smoked per day, pack-years of cigarette smoking, white blood cell count, or number of peripheral blood lymphocytes. Toxicity of BCG was limited to transient malaise and fever (average peak temperature, 38.7 degrees C). There was no significant difference in outcome (recurrence or survival) between BCG-treated and control groups with Stage I or Stage III tumors; there were too few Stage II tumors for separate statistical analysis. Outcome was not affected within or between the two treatment groups by tuberculin skin test status. Combining both treatment groups, Stage III patients had a worse outcome than did Stage I-II patients, non-squamous cell tumor patients (large cell and adenocarcinoma) had worse outcomes than did squamous cell tumor patients, and men had a worse outcome than women. We conclude that, although preoperative intratumoral BCG therapy is safe, it does not lengthen disease-free interval or prolong survival in patients with non-small cell lung cancer.

Bacterial Vaccines↗

Physiologic changes in rowing performance associated with training in collegiate women rowers.

To evaluate the physiologic changes in rowing performance during the training season, selected cardiorespiratory variables were measured three times at 3-month intervals in seven collegiate women rowers during incremental exercise on the rowing ergometer. Values for maximal oxygen consumption (VO2 max) and peak power production increased by 14% and 18%, respectively, over the 6-month period. Maximal heart rate was unchanged with training. Oxygen-pulse increased significantly (+ 14%) during the training season, while the ventilatory equivalent for oxygen did not change. Oxygen consumption as a percent of VO2 max and heart rate at the anaerobic threshold (AT) decreased during the first 3 months of predominantly aerobic training, but increased significantly in the last 3 months with greater anaerobic conditioning. The changes demonstrated by physiologic testing corresponded to the particular type of training emphasized during the 6-month period. Serial measurements of VO2 max and AT can be used to assess the benefits of specific training. Based on these results, individual guidelines for aerobic and anaerobic conditioning can be developed using the heart rate response at the AT.

Adult↗

Volumetric responses of right and left ventricles during upright exercise in normal subjects.

We evaluated the volumetric responses of the right and left ventricles to upright exercise using two noninvasive methods, first-pass radionuclide angiocardiography and the CO2 rebreathing technique, in nine normal subjects. Right (RV) and left (LV) ventricular ejection fractions, heart rate, and cardiac index were determined at rest and during steady-state exercise on the bicycle ergometer at 50% of maximal O2 consumption. From these data, stroke volume index (SVI), end-diastolic volume index (EDVI), and end-systolic volume index (ESVI) were derived. SVI increased from 40 +/- 7 ml/m2 at rest to 59 +/- 13 ml/m2 with exercise (P less than 0.001). RVEDVI increased significantly from 82 +/- 16 ml/m2 at rest to 95 +/- 21 ml/m2 during exercise (P = 0.008), while there was no significant change in RVESVI with exercise. Changes in LVEDVI and LVESVI during upright exercise were similar to the right ventricle. The increase in systolic blood pressure during exercise, along with no change in LVESVI, indicated enhanced ventricular contractility. The normal augmentation in SVI during submaximal exercise was due to both the Frank-Starling mechanism and an increased contractile state. Application of these or similar techniques may be useful in evaluating ventricular performance in patients with cardiorespiratory dysfunction.

Blood Pressure↗

Sustained-release theophylline reduces dyspnea in nonreversible obstructive airway disease.

Although orally administered theophylline has been prescribed widely in patients with nonreversible airway obstruction, symptomatic benefit has not been established. To assess the effects of orally administered theophylline on dyspnea, we performed a randomized, double-bind, crossover, placebo-theophylline clinical trial in 12 ambulatory male patients with moderate to severe nonreversible airway obstruction. Dyspnea was rated using 2 clinical indexes based on 3 components affecting breathlessness: functional impairment, magnitude of task that evokes dyspnea, and the associated magnitude of effort. Dyspnea and physiologic parameters were measured on 4 occasions: at baseline, 4 wk after initial treatment, a second baseline after a 2-wk washout period, and 4 wk after the second medication. For the 12 patients, mean age (+/- SD) was 60 +/- 7 yr, forced expiratory volume in one second was 1.36 +/- 0.67 L (mean, 40% of predicted), and arterial oxygen tension was 71 +/- 10 mmHg. During the treatment phase, all patients had a therapeutic theophylline blood level (range, 12 to 19 micrograms/ml). Theophylline significantly decreased the components of functional impairment (p = 0.02) and magnitude of task (p = 0.02) relating to dyspnea, as well as the overall dyspnea rating (p = 0.01). There were no significant differences between placebo and theophylline therapy for spirometry, arterial blood gas tensions, and the 12-min walking distance. Thus, sustained-release theophylline significantly reduced dyspnea in these ambulatory patients with moderate to severe nonreversible airway obstruction without altering lung function, gas exchange, or exercise performance.

Administration, Oral↗

Determination of cardiac output at rest and during exercise by carbon dioxide rebreathing method in obstructive airway disease.

We evaluated the accuracy of the CO2 rebreathing method (CO2rb) for measuring cardiac output at rest and during steady-state exercise in 15 patients (mean +/- SD age, 59.7 +/- 7.5 yr) with obstructive airway disease. At rest, there was a significant correlation between direct Fick and CO2rb methods using measured arterial PCO2 (r = 0.70; p = 0.002), but not with using end-tidal PCO2 (r = 0.38; p = NS). During exercise, there was greater correlation with CO2rb using arterial PCO2 (r = 0.79; p = 0.001) than using end-tidal PCO2 (r = 0.63; p = 0.007) compared with the direct Fick determination. Correlation between the CO2rb and direct Fick methods was greater with moderate air-flow obstruction (n = 6) than with severe airway disease (n = 9), and the CO2rb method was more accurate during exercise than at rest. The CO2rb method using either end-tidal or arterial PCO2 underestimated the direct Fick measurement in 13 of 15 patients at rest, which may reflect inadequate equilibration between alveolar and oxygenated mixed venous PCO2. However, no consistent error was observed during exercise when higher CO2 production and an increased venoarterial PCO2 difference would diminish potential inaccuracies. We concluded that the CO2rb technique is an acceptable method for measuring cardiac output during exercise in patients with moderate and severe obstructive airway disease as long as arterial PCO2 is directly measured rather than estimated from end-tidal PCO2.

Aged↗

Mechanical and physiological evaluation of exercise performance in elite national rowers.

We describe the scientific basis for evaluating the biomechanics and associated physiological requirements of exercise performance in elite national rowers. Computer-assisted analysis of high-speed cinematography has demonstrated that efficiency in rowing is related to the relative proximity between peak force and the perpendicular position of the oar. Physiological testing has indicated that near maximal levels of oxygen consumption are required during "all out" rowing, involving both aerobic and anaerobic metabolism. Serial testing has been performed on elite oarsmen throughout the year in order to evaluate the individual benefits of a training program and to establish guidelines for future training. Successful application of the scientific analysis of rowing performance requires that the athlete, coach, and investigator work closely together in an effort to increase the average velocity of the boat.

Adult↗

Relationship between oxygen uptake and oxygen transport in stable patients with chronic obstructive pulmonary disease. Physiologic effects of nitroprusside and hydralazine.

This study was designed to determine whether alterations in systemic oxygen transport induced by the use of vasodilators for pulmonary hypertension would simultaneously affect oxygen uptake in patients with chronic obstructive pulmonary disease (COPD). Six stable patients with moderate to severe COPD were studied during resting conditions, nitroprusside infusion, a second control period, and after administration of hydralazine. Systemic oxygen transport fell with nitroprusside infusion (523 +/- 94 to 418 +/- 78 ml/min/m2, p less than 0.05). With this there was a fall in oxygen uptake (135 +/- 11 to 119 +/- 12 ml/min/m2, p less than 0.05), but only a minimal increase in oxygen extraction. In contrast, systemic oxygen transport was augmented in all patients when hydralazine was administered (444 +/- 121 to 840 +/- 157 ml/min/m2, p less than 0.05). There was also a net increase in oxygen uptake in these patients (122 +/- 19 to 148 +/- 21 ml/min/m2, p less than 0.05). We postulate that these clinically stable patients have a resting oxygen uptake that may become dependent on systemic oxygen transport whenever the latter decreases. This phenomenon has been described previously only in patients with adult respiratory distress syndrome, and it is important to consider when designing studies of pharmacologic therapy for COPD complicated by pulmonary hypertension.

Aged↗

Right ventricular performance and central circulatory hemodynamics during upright exercise in patients with chronic obstructive pulmonary disease.

A combined hemodynamic and radionuclide approach was used to evaluate right ventricular performance during upright exercise in 12 male patients with chronic obstructive pulmonary disease. To assess the influence of intrathoracic pressure on hemodynamic parameters, pleural pressure was measured using an esophageal balloon. Mean age was 58.5 +/- 6.7 yr (+/- SD), and all had dyspnea on physical exertion. For the group, forced expiratory volume in one second (FEV1) was 1.04 +/- 0.40 L and arterial oxygen-tension (PaO2) was 77 +/- 11 mmHg. During steady-state, upright exercise on the bicycle ergometer at 58% of maximal oxygen consumption (VO2 max): (1) mean pulmonary artery pressure (Ppa) and pulmonary vascular resistance index (PVRI) increased significantly; (2) right ventricular ejection fraction (RVEF) failed to augment appropriately (less than 5% increase); and (3) right ventricular end-diastolic volume index (RVEDVI) increased significantly, whereas right ventricular end-systolic volume index (RVESVI) did not change. A diminished pulmonary vascular bed, the change in PaO2, and possibly increased alveolar pressure appeared to contribute to the increased load placed on the right ventricle. Both RVEDVI and RVESVI were significantly correlated with Ppa at rest and during exercise. In 2 of the 12 patients, stroke volume index and left ventricular end-diastolic volume index showed minimal change with exercise. VO2max was correlated with the FEV1 (r = 0.75; p = 0.01) as well as resting (r = -0.60; p = 0.02) and exercise (r = -0.61; p = 0.02) PVRI. These results suggest that exercise performance may be limited by right ventricular dysfunction in addition to respiratory impairment in some patients with chronic airway disease.

Aged↗

The measurement of dyspnea. Contents, interobserver agreement, and physiologic correlates of two new clinical indexes.

To improve the clinical measurement of dyspnea, we developed a baseline dyspnea index that rated the severity of dyspnea at a single state and a transition dyspnea index that denoted changes from that baseline. The scores in both indexes depend on ratings for three different categories: functional impairment; magnitude of task, and magnitude of effort. At the baseline state, dyspnea was rated in five grades from 0 (severe) to 4 (unimpaired) for each category. The ratings for each of the three categories were added to form a baseline focal score (range, 0 to 12). At the transition period, changes in dyspnea were rated by seven grades, ranging from -3 (major deterioration), to +3 (major improvement). The ratings for each of the three categories were added to form a transition focal score (range, -9 to +9). In 38 patients tested with respiratory disease, interobserver agreement was highly satisfactory for both indexes. The baseline focal score had the highest correlation (r = 0.60; P less than 0.001) with the 12-minute walking distance (12 MW), while significant, but lower, correlations existed for lung function. For the transition focal score, there was a significant correlation only with the 12 MW (r = 0.33; p = 0.04). These results indicate that dyspnea can receive a direct clinical rating that provides important information not disclosed by customary physiologic tests.

Aged↗

Comparison of 6-min "all-out" and incremental exercise tests in elite oarsmen.

A high aerobic capacity is an important criterion for rowing success. Two exercise protocols, the 6-min "all-out" (6M-AO) and progressive incremental (PI) tests, have been used to evaluate physiological performance in rowers and to select team members. We measured heart rate (HR), minute ventilation (VE), oxygen consumption (VO2), and carbon dioxide production (VCO2) every 30 s, and obtained ratings of perceived exertion (RPE) from 12 candidates for the 1983 United States Men's Lightweight Rowing Team. Testing was randomized and each oarsman performed a different test on the rowing ergometer on consecutive days. For the group, age was 23 +/- 2 yr (mean +/- SD), height was 183 +/- 3 cm, and weight was 72.2 +/- 1.4 kg. Peak physiological values were achieved in the first 2 min of exercise for the 6M-AO test, but in the last 2 min for the PI test. There were no statistically significant differences among peak values for HR, VE, VO2, VCO2, and RPE with each test. The peak ventilatory equivalent for oxygen (VE/VO2) was also similar. The onset of anaerobic metabolism was observed at 83 +/- 4% of peak VO2 during the PI test, while anaerobic metabolism has been shown to occur within the first minute of the 6M-AO test. We conclude that physiological values at peak exercise were similar for the 6M-AO and PI tests. Because the onset of anaerobic metabolism can only be determined by noninvasive means using the PI test, this method of testing is preferable for the physiological assessment of rowing performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Exercise impairment in chronic obstructive pulmonary disease.

This article reviews factors that may limit exercise performance in patients with COPD. These factors include alteration in pulmonary mechanics, respiratory muscle fatigue, impairment in pulmonary gas exchange, abnormal perception of breathlessness and ventilatory control, cor pulmonale, and poor nutritional status. The clinical application of exercise testing in patients with COPD and the role of various therapeutic modalities in altering exercise performance in COPD are discussed.

Diaphragm↗

The physiology of endurance exercise. The marathon.

The metabolic demands of competitive marathon running require the development and integration of the respiratory, cardiovascular, and musculoskeletal systems. Environmental factors such as ambient temperature, humidity, and wind resistance can affect running performance. In addition to training, racing strategy, fluid ingestion, and dietary manipulation are specific and practical methods that can be used to augment marathon performance.

Adolescent↗

Positional dyspnea and oxygen desaturation related to carcinoma of the lung. Up with the good lung.

Body position can lead to respiratory symptoms and affect gas exchange in disease states. We describe a patient with carcinoma of the left lung in whom dyspnea and oxygen desaturation developed in the right lateral position only. Fiberoptic bronchoscopic study demonstrated a tumor mass protruding into the left main-stem bronchus, which caused further narrowing when the patient turned on his right side.

Bronchoscopy↗

Ventilatory responses at rest and during exercise in marathon runners.

Diminished ventilatory responsiveness to hypercapnia and hypoxia has been reported in athletes, but whether reduced chemosensitivity might lessen hyperpnea during exercise and facilitate performance is unknown. To evaluate ventilatory control and its possible role in athletic performance, we prospectively measured ventilatory responses to hypercapnia and hypoxia at rest and ventilatory equivalents for carbon dioxide (VE/VCO2) and oxygen (VE/VO2) during exercise in 20 accomplished marathon (42.2 km) runners (RUN) and 20 control subjects (CON). The athletes (mean age 27.8, range 18-41 yr) were all experienced runners with a mean best marathon time of 2 h, 36 min (range 2:14-2:55). There were no significant differences in the ventilatory responses at rest to hypercapnia (RUN, 2.23 +/- 0.73 vs. CON, 2.61 +/- 1.05 l X min-1 X Torr-1) and hypoxia (RUN, 0.57 +/- 0.40 vs. CON, 0.88 +/- 0.72 l X min-1 X 1% desat-1) (mean +/- SD). Similarly, there were no significant differences in VE/VCO2 and VE/VO2 between the two groups. Good correlation (r = 0.68; P less than 0.01) was observed between hypercapnic response at rest and exercise ventilation (VE/VCO2) in RUN. However, both hypercapnic and hypoxic ventilatory responses correlated poorly with marathon running time. These results demonstrate no differences in ventilatory responses at rest and during exercise between marathon runners and control subjects. The range of ventilatory responsiveness observed in this group of marathon runners indicates that a spectrum of ventilatory control is present in well-trained endurance athletes.

Adult↗

Respiratory muscle fatigue after marathon running.

Respiratory muscle fatigue has been demonstrated in the laboratory as well as in pathological states, but whether it occurs in healthy individuals under physiological conditions is unknown. To determine whether fatigue of the respiratory muscles may develop with endurance exercise, we measured spirometry and respiratory muscle strength and endurance in four runners before and after completion of a marathon race (42.2 km). Strength was assessed by measuring maximal inspiratory (PImax) and expiratory (PEmax) pressures and transdiaphragmatic pressure during inspiratory capacity (PdiIC); endurance was determined by measuring maximal voluntary ventilation (MVV). After marathon running (mean time, 3 h 24 min) there was no change in forced vital capacity, inspiratory capacity, or flow rates from prerace values. Decreases were observed between pre- and postrace PImax (165.8 +/- 11.0 vs. 138.5 +/- 7.6 cmH2O; P less than 0.01) PEmax (240.0 +/- 20.4 vs. 173.0 +/- 22.6 cmH2O; P less than 0.05), PdiIC (78.8 +/- 11.6 vs. 63.3 +/- 7.0 cmH2O; P less than 0.10), and MVV (178 +/- 24.2 vs. 161.2 +/- 23.2 l/min; P less than 0.005). The decrements in respiratory muscle strength and endurance suggest the development of respiratory muscle fatigue after marathon running.

Adult↗

Clinical and roentgenographic features of nosocomial pulmonary disease due to Mycobacterium xenopi.

We describe 19 cases of pulmonary disease due to Mycobacterium xenopi, a nosocomial infection related to the hospital water system. Pre-existing lung disease and prolonged environmental exposure during previous hospitalizations were apparent predisposing factors. Twelve patients had respiratory symptoms, including three with hemoptysis, at the time an abnormal chest roentgenogram was obtained. The predominant radiographic presentation of lung diseases caused by M. xenopi was a nodular or mass shadow, but cavitary disease and multiple nodular densities were also frequently observed. One subject had a solitary pulmonary nodule, and surgical resection was performed. In 12 patients who were skin tested with both M. xenopi sensitin and PPD-tuberculin, induration was consistently greater with M. xenopi. Initial isolates of M. xenopi were uniformly sensitive in vitro to 2.0 microgram of streptomycin, 1.0 microgram of isoniazid, and 10.0 microgram of para-aminosalicylic acid. In general, disease due to M. xenopi was successfully treated with standard antituberculosis drugs.

Aged↗

Lung function after marathon running at warm and cold ambient temperatures.

using maximal expiratory flow-volume curves we studied the effects of endurance exercise on lung function in 46 and 41 runners before and after completion of a marathon race (42.2 km) at different ambient temperatures. There was a significant decrease (-3.9%; -5.9%) in the post-race forced vital capacity in runners at each marathon. The mean values for forced expiratory volume in one second did not change. Post-race peak flow at 50% of forced vital capacity were significantly decreased in runners participating in subfreezing conditions (-2 degrees C to -4 degrees C), but were unchanged when the ambient temperature was above freezing. These data demonstrated that healthy persons may develop bronchoconstriction during endurance exercise in subfreezing temperatures. The decrement in forced vital capacity noted in marathon runners competing at above freezing temperatures may be related to fuel metabolism and running performance.

Adolescent↗