M O Farber

Indiana University East, Ричмонд, Indiana, United States

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Publications (60)299.26 Total impact

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    ABSTRACT: Adult athletes have a higher prevalence (11%-50%) of exercise-induced bronchoconstriction (EIB) and airways hyperresponsiveness (AHR) than the population at large (7%-11%): reports describing EIB/AHR in adolescent athletes are scant. Hypotheses: 1) a minimum AHR prevalence of 20% would be revealed in a group of high school athletes; 2) demographic data would predict AHR; 3) AHR-positive athletes would preferentially choose low ventilation sports. Eucapnic voluntary hyperpnea (EVH) was used to test for AHR in 23% of all athletes (79 of 343) of a midwestern high school. The AHR was defined by at least a 10%, 20%, or 25% decline in FEV1, FEF25-75, or PEFR at 1, 5, 10, or 15-min post-EVH, respectively. Results: 30 of 79 (38%) tested positive for AHR; demographic data tended to predict AHR, as correlations between the total number of years exercised with the greatest decline in FEV1 and the total number of days exercised with the greatest decline in FEV1 following the EVH challenge tended to be significant (r = 0.354; p = 0.055 and r=0.314; p = 0.091, respectively); and 69% of AHR-positive students played only low ventilation sports. CONCLUSION: AHR prevalence was 38% in athletes of a midwestern high school; demographic data tended to predict AHR; those with AHR preferentially play low ventilation sports.
    Journal of Asthma 09/2004; 41(5):567-74. DOI:10.1081/JAS-120037658 · 1.80 Impact Factor
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    ABSTRACT: To compare diameter and cross-sectional area measurements with volume measurements in the assessment of lung tumor growth with serial computed tomography (CT). Patients with lung cancer who underwent at least one pair of chest CT examinations 25 or more days apart before treatment and with a tumor size of T1 (< or =3-cm diameter) at the initial CT examination were identified. A total of 63 patients (62 men, one woman) who underwent 93 pairs of CT examinations were included. Images obtained at each examination were displayed, and the maximum diameter, cross-sectional area, and volume of the tumor were measured. For each measurement, the change between examinations was assessed to determine whether the change reached a detection threshold for growth, as determined in a prior study with simulated tumors. Results were then compared between measurement methods, with volume change serving as the reference standard, by calculating Spearman rank-order coefficients between examinations. Tumor size or section width were also evaluated with the two-tailed Fisher exact probability test to determine if they affected agreement about tumor growth between measurement methods. Thresholds were as follows: diameter, 2.1 mm with hand-held calipers and 0.68 mm with electronic calipers; area, 9.4%; volume, 16.5%. The median time between examinations was 92 days (range, 25-1,221 days). Median diameter increased from 19.3 mm to 23.0 mm (19.2%), median area from 207 mm(2) to 267 mm(2) (29.0%), and median volume from 1,652 mm(3) to 2,443 mm(3) (47.9%). Growth assessment with these diameter (as assessed with hand-held and electronic calipers) and area thresholds disagreed with those obtained with volume in 34 (37%), 26 (28%), and 25 (27%) of the 93 pairs of CT examinations, respectively. Of diameter assessments with the hand-held caliper threshold, 28 (30%) were false-negative; false-negative results occurred with this diameter threshold and area threshold with examination intervals as long as 1 year. Growth assessment of T1 lung tumors on serial CT scans with nonvolumetric measurements frequently disagrees with growth assessment with volumetric measurements.
    Radiology 06/2004; 231(3):866-71. DOI:10.1148/radiol.2313030715 · 6.87 Impact Factor
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    ABSTRACT: Athletes have a high prevalence (11-50%) of exercise-induced asthma, which may be caused by the hyperventilation accompanying repetitive bouts of strenuous exercise. We hypothesized that recreational exercisers would display a similar trend. Eucapnic voluntary hyperventilation (EVH) bronchoprovocation (breathing 21% O2, 5% CO2, and 74% N2 at 60% of MVV for 5 minutes) was performed to determine the prevalence of airways hyperresponsiveness (AHR) in adults (n=212, 146 males, mean +/- standard deviation, age 32 +/- 10 years) who exercised regularly (10 +/- 10 years, 31 +/- 28% of their lives): none had a previous diagnosis of asthma. AHR was defined by at least a 10%, 20%, or 25% decline in FEV1, FEF(25-75), or PEFR, respectively, by spirometry at 1, 5, 10, and 15 minutes post-EVH. Forty-one of 212 (19%) tested positive for AHR: 20 of 41 (49%) were positive by FEV1, 28 of 41 (68%) by FEF(25-75), and 27 of 41 (66%) by PEFR. Comparing responders with nonresponders: pre-EVH lung function was equivalent, except for FEV1, which was reduced (p<0.05) in responders (96 +/- 13 vs. 102 +/- 12% predicted). Mean maximal negative deflections for responders were: for FEV1, -17 +/- 7%; FEF(25-75), -31 +/- 10%; PEFR, -38 +/- 11%. Ranges of decline for responders were: FEV1, -10 to -33%; FEF(25-75), -20 to -59%; PEFR, -25- to -70%. We conclude that in these regular exercisers, the prevalence of AHR is high and comparable with some athletic populations.
    Journal of Asthma 06/2003; 40(4):349-55. DOI:10.1081/JAS-120018634 · 1.80 Impact Factor
  • E T Mannix · C A Hage · M O Farber
    Medicine &amp Science in Sports &amp Exercise 05/2002; 34(5). DOI:10.1097/00005768-200205001-00744 · 3.98 Impact Factor
  • M O Farber · E T Mannix
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    ABSTRACT: Malnutrition is common among individuals suffering from hypoxemic chronic obstructive pulmonary disease (COPD), advanced HIV disease, and in patients with chronic, severe congestive heart failure. Although increased morbidity and mortality has been associated with weight loss in these conditions, the pathophysiology of malnutrition remains somewhat unclear for each. In COPD, the primary postulated mechanism is hypermetabolism resulting in elevated total caloric expenditure arising from increased airway resistance, increased O2 cost of ventilation, increased dietary induced thermogenesis, inefficient substrate use and perhaps, increased levels of proinflammatory cytokines. In AIDS, postulated mechanisms include hypermetabolism arising from increased activation of proinflammatory cytokines, along with futile cycling of fatty acids and de novo lipogenesis early in the course of HIV infection; intestinal malabsorption and anorexia also play a role in many inflicted individuals. In cardiac cachexia, dietary and metabolic factors, and levels and activity of cytokines, thyroid hormone, catecholamines and cortisol have been suggested as being responsible for causing weight loss in a most cases.
    Neurologic Clinics 03/2000; 18(1):245-62. · 1.40 Impact Factor
  • Mark O. Farber · Edward T. Mannix
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    ABSTRACT: Malnutrition is common in patients with chronic, severe CHF with as many as 50% of these patients experiencing significant weight loss as the disease progresses. In the past, various dietary and metabolic factors have been examined as mediators of the cachectic response in CHF. More recently, studies have implicated proinflammatory cytokines, thyroid hormone, catecholamines, and cortisol as agents that may be associated with weight loss in this disease process. Gastrointestinal malabsorption, hypermetabolism, and anorexia also have been noted as potential mediators of cardiac cachexia.
    Neurologic Clinics 02/2000; 18(1):245-262. DOI:10.1016/S0733-8619(05)70188-2 · 1.40 Impact Factor
  • E T Mannix · F Manfredi · M O Farber
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    ABSTRACT: Studies documenting the increased incidence of exercise-induced bronchospasm (EIB) in figure skaters have employed a method that incorporates on-ice exercise with rink-side spirometry. The literature suggests that bronchial provocation challenge testing is better than exercise testing for identifying EIB. To test this hypothesis in figure skaters, a unique athletic population that trains and competes in cold air, we compared these two methods in the same individuals. Two challenge tests were performed on a group of competitive figure skaters (n = 29, 26 female subjects; mean+/-SD age = 12.3+/-3.5 years): (1) rink-side (temperature = 14 degrees C, humidity = 60%) spirometry before and 1, 5, 10, and 15 min after 5 min of intense skating; and (2) eucapnic voluntary hyperventilation (EVH), breathing 5% CO2, 21% O2, balance N2 at a rate of 60% of maximum voluntary ventilation (not to exceed 70 L/min) for 5 min (temperature = 18 degrees C, humidity = 50%), with an identical pretest and posttest spirometry schedule. EIB was defined as at least one of the following: a > or =10% decline in Fev1; a > or = 20% decline in maximum midexpiratory flow rate; or a > or = 25% decline in peak expiratory flow rate. Sixteen of 29 skaters (55%) developed EIB: 9 were positive by on-ice testing; 12 were positive by EVH testing; 5 were positive on both tests; on-ice testing missed 7 skaters with EIB; EVH testing missed 4 with EIB. In the group of figure skaters studied, EVH challenge testing was better at identifying EIB than on-ice exercise testing. However, these data suggest that evaluation for EIB in athletes who train and compete in the cold should include exercise testing in cold air along with a challenge test such as EVH to increase the yield of positive responders.
    Chest 03/1999; 115(3):649-53. DOI:10.1378/chest.115.3.649 · 7.48 Impact Factor
  • E T Mannix · F Manfredi · M O Farber
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    ABSTRACT: BACKGROUND AND OBJECTIVES: Thirty to 50% of all COPD patients experience tissue wasting that may be caused by hypermetabolism, but the cause of the perturbed metabolic state is unclear. We hypothesized that the elevated O2 cost of ventilation (O2 COV) may be a contributing factor. All of the data are presented as means (+/-SEM). Ten hypoxemic (a PaO2 of 54+/-3 mm Hg) stable COPD patients (an FEV1/FVC ratio of 42+/-4%) and five healthy control subjects were studied. The patients were divided into two groups based on nutritional status. Group 1 (n = 6) was malnourished (a body mass index [BMI] of 17.6+/-0.7 kg/m2), and group 2 (n = 4) was normally nourished (a BMI of 26.0+/-3 kg/m2). The O2 COV was determined by measuring the change in the oxygen consumption (VO2) and the minute ventilation (VE) caused by CO2-induced hyperventilation. RESULTS AND CONCLUSIONS: Group 1 had an elevated O2 COV when compared to group 2 and the control group, respectively: 16.4+/-1.0 vs 9.7+/-1.0 and 2.4+/-0.2 mL O2/L of VE (p < 0.05). The VO2 at rest was higher for group 1 than for group 2 and the control group, respectively: 4.5+/-0.3 vs 3.1+/-0.5 and 3.4+/-0.2 mL/kg/min (p < 0.05). The resting energy expenditure (REE) % predicted for group 1 was also higher than group 2 and the control group, respectively: 125+/-3% vs 87+/-7% and 97+/-2% (p < 0.05). Significant correlations were observed that implicate the increased O2 COV as a cause of tissue wasting: O2 COV vs BMI (r = -0.79; p = 0.007), O2 COV vs REE % predicted (r = 0.66; p = 0.039), and REE % predicted vs BMI (r = -0.83; p = 0.003). The O2 COV was also correlated with lung function: FEV1/FVC vs O2 COV (r = -0.84; p = 0.002). We conclude that in these COPD patients the O2 COV is associated with an increased metabolic rate which, in turn adversely affects the nutritional status.
    Chest 03/1999; 115(3):708-13. DOI:10.1378/chest.115.3.708 · 7.48 Impact Factor
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    ABSTRACT: Cardiopulmonary exercise testing (CPET) is a well recognized tool for the functional assessment of patients with cardiovascular and pulmonary disorders. The exercise response of asthmatics has been well characterized but the exercise response of patients with occupational asthma is less well understood. In this report we describe the clinical utility of CPET by characterizing the cardiovascular and pulmonary responses to exercise in patients with occupational asthma (OA) and a closely related entity, reactive airways dysfunction syndrome (RADS). We evaluated clinical and cardiopulmonary exercise data (mean +/- SD) from patients with OA (n = 22, age = 40.1 +/- 8.9 years, 14 males) and RADS (n = 23, age = 37.7 +/- 9.7 years, 18 males) who exhibited comparable pulmonary function. Oxygen uptake, CO2 output, ventilatory parameters, cardiac hemodynamics, O2 delivery, 12 lead EKG, systemic BP, and O2 saturation were monitored at rest and during cycle ergometer exercise. Compared with the RADS group, OA patients demonstrated higher resting dead-space ventilation (41 +/- 8 vs 35 +/- 9%, p = 0.04), reduced exercise capacity (94 +/- 32 vs 122 +/- 47 W, p = 0.01), higher respiratory quotients at 50 W (0.98 +/- 0.14 vs 0.91 +/- 0.08, p = 0.04), decreased power output past attainment of the anaerobic threshold (28.1 +/- 17.1 vs 44.7 +/- 15.1 W, p = 0.002) and a strong tendency for lower anaerobic thresholds (53 +/- 9 vs 60 +/- 14% pred VO2max, p = 0.06). In the 2 groups with occupational bronchial hyperreactivity, each with mild disease severity, OA patients exhibited greater decrements in cardiovascular conditioning when compared with the RADS group, perhaps because of the more prolonged, chronic respiratory insult experienced by the OA group. These data indicate that CPET in patients with work-related bronchial hyperreactivity is of significant utility in the impairment evaluation process.
    Journal of Investigative Medicine 07/1998; 46(5):236-42. · 1.69 Impact Factor
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    ABSTRACT: Studies in healthy human subjects subjected to lower body positive pressure (LBPP) have failed to elucidate many of the physiologic effects of this maneuver. In 7 healthy, well-hydrated men we studied the following responses to LBPP (35 mm Hg, 1 hour, supine position): systemic and renal hemodynamics; urine volume (UV), urine osmolality (Uosm), and urine sodium level (UNaV); free water (CH20) and osmolar (Cosm) clearances; plasma renin activity (PRA); levels of aldosterone (PA), cortisol (CORT), norepinephrine (NE), atrial natriuretic peptide (ANP), and vasopressin (AVP); osmolality (Posm); and serum sodium level. Subjects were restudied on a control day with zero trouser pressure. The recorded changes (p < 0.05) when comparing the LBPP day with the control day were as follows: fractional Na+ reabsorption increased (98.7% +/- 0.2% to 99.3% +/- 0.1%) and UNaV decreased (0.19 +/- 0.03 mEq/min to 0.10 +/- 0.01 mEq/min), with concomitant increases in PRA (1.7 +/- 0.2 ng/ml/90 min to 4.5 +/- 1.8 ng/ml/90 min), PA (7.7 +/- 0.7 ng/dl to 9.3 +/- 1.5 ng/dl), and CORT (13.0 +/- 2.6 mg/dl to 19.2 +/- 3 mg/dl); the increase in blood pressure with LBPP (96 +/- 3 mm Hg to 112 +/- 4 mm Hg) was greater than that during control conditions. Renal plasma flow tended to display an interactive pattern across days, with a slight decline during LBPP (5%) and a slight elevation under control conditions (9%). On the LBPP day only, filtered Na+ declined (15 +/- I mEq/min to 12 +/- 1 mEq/min) as a function of reduced glomerular filtration rate (112 +/- 5 ml/min to 91 +/- 7 ml/min), blood volume decreased (by 2.7% +/- 0.7%), CO decreased (5.5 +/- 0.3 L/min to 4.7 +/- 0.3 L/min), and stroke volume declined (101 +/- 6 ml to 84 +/- 3 ml). On both days, NE increased (control, 221 +/- 23 pg/ml to 340 +/- 33 pg/ml; LBPP, 236 +/- 17 pg/ml to 369 +/- 31 pg/ml) and ANP increased (control, 47 +/- 7 pg/ml to 97 +/- 21 pg/ml; LBPP, 49 +/- 10 pg/ml to 104 +/- 30 pg/ml). We concluded that LBPP reduces renal sodium excretion. The mechanism for this reduction is not known, although it did occur in association with an increase in plasma renin activity, which in turn results from mechanical reduction of renal perfusion, stress-related CORT stimulation, a reflex-based elevation in peripheral vascular resistance leading to a reflex increase in plasma renin activity, or a combination of these.
    Journal of Laboratory and Clinical Medicine 12/1996; 128(6):585-93. DOI:10.1016/S0022-2143(96)90131-6 · 2.80 Impact Factor
  • E T Mannix · A Healy · M O Farber
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    ABSTRACT: Hypotheses: 1) figure skaters possess average aerobic power; 2) on-ice training would not improve aerobic power of supramaximal endurance; 3) off-ice training plus on-ice training would improve aerobic power and supramaximal endurance. This was a prospective, controlled study in which we monitored ice skaters before, during and after two different 10 week training programs. Athletes training for competition sanctioned by the United States Figure Skating Association. 15 figure skaters (12 females) enrolled at an ice skating academy were randomly placed in two study groups. Grp 1 maintained on-ice training and Grp 2 supplemented on-ice with cycle ergometer training. Maximum O2 consumption (VO2peak) during cycle ergometer exercise, anaerobic threshold, HR, supramaximal exercise time and the lactate (LACT) response to exercise. (*, p < 0.05), Grp 1: VO2peak, pre = 44.2 +/- 2.2 ml/[kg.min], post = 41.4 +/- 1.6 ml/[kg.min]; VO2peak% (% predicted), pre = 100 +/- 5%, post = 92 +/- 4%; anaerobic threshold as % VO2peak (AT%), pre = 74 +/- 3%, post = 73 +/- 3%; Supramaximal Time, pre = 0.87 +/- 0.12 min, post = 0.94 +/- 0.12 min; lower LACT occurred at VO2peak and supramaximal exercise following on-ice training. Grp 2: VO2peak, pre = 50.7 +/- 3.6 ml/[kg.min], post = 55.9 +/- 3.3 ml/[kg.min]*; VO2peak%, pre = 110 +/- 7%, post = 121 +/- 6%*; AT%, pre = 80 +/- 2%, post = 83 +/- 2%*; Supramaximal Time, pre = 1.31 +/- 0.18 min, post = 2.69 +/- 0.66 min*; lower LACT occurred at 50%, 75% and VO2peak following training. 1) Grp 1 plus Grp 2 had average aerobic power (VO2peak = 105 +/- 3% of predicted) prior to the study; 2) on-ice training did not affect aerobic power or supramaximal endurance, while off-ice training improved these parameters; 3) the LACT response detected training adaptations.
    The Journal of sports medicine and physical fitness 09/1996; 36(3):161-8. · 0.97 Impact Factor
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    ABSTRACT: Ethylene oxide (EO) is commonly used to sterilize heat-sensitive products used by hospital patients and personnel. Ethylene chlorohydrin (EC), a by-product, is considered highly toxic. We report a cluster of 12 operating-room nurses and technicians who developed symptoms after a 5-month exposure to high levels of EO and EC in disposable surgical gowns. All patients reported a rash on the wrist where contact was made with the gowns, headaches, and hand numbness with weakness. Ten of 12 patients complained of memory loss. Neurologic evaluation revealed neuropathy on examination in nine of the 12 patients, elevated vibration threshold in four of nine, abnormal pressure threshold in 10 of 11, atrophy on head MRI in three of 10, and neuropathy on conduction studies in four of 10. Neuropsychological testing demonstrated mild cognitive impairment in four of six patients. Sural nerve biopsy in the most severely affected patient showed findings of axonal injury. Several patients in this group display signs of peripheral and CNS dysfunction following exposure to EO. Possible mechanisms of neurotoxicity include direct exposure of peripheral nerves through cutaneous absorption and central involvement through inhalation and vascular dissemination. The frequency of central and peripheral nervous system symptoms, supported by objective testing in these EO-exposed patients, suggests other healthcare personnel may be at similar risk.
    Neurology 05/1996; 46(4):992-8. DOI:10.1212/WNL.46.4.992 · 8.29 Impact Factor
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    E T Mannix · M O Farber · P Palange · P Galassetti · F Manfredi
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    ABSTRACT: Many highly trained athletes experience exercise-induced bronchospasm (EIB): studies describing EIB in figure skaters, who may be at increased risk of EIB due to rink temperatures (7 to 10 degrees C), have not been published. We studied professionally coached figure skaters (n = 124) for EIB by spirometry at rinkside immediately before a simulated long program and at 0 to 1, 5, 10, and 15 min postexercise. Postexercise spirometry revealed the presence of EIB (a decrease from baseline in FEV1 of at least 10%) in 43 skaters, while the remainder (n = 81, control group) remained relatively stable. Pre-exercise FEV1, FVC, and FEV1/FVC ratio were not different between groups. The EIB group had significantly lower FEV1 vs baseline at each measurement following exercise: baseline, 3.08 +/- 0.13; 0 to 1 min postexercise, 2.81 +/- 0.13 (p < 0.05); 5 min postexercise, 2.77 +/- 0.14 (p < 0.05); 10 min postexercise, 2.78 +/- 0.13 (p < 0.05); 15 min postexercise, 2.78 +/- 0.13 (p < 0.05). The EIB group also had lower FVC: baseline, 3.48 +/- 0.16; 0 to 1 min postexercise, 3.16 +/- 0.15 (p < 0.05); 5 min postexercise, 3.19 +/- 0.15 (p < 0.05); 10 min postexercise, 3.27 +/- 0.16 (p < 0.05); 15 min postexercise, 3.26 +/- 0.16 (p < 0.05). Control subjects, however, experienced no decline in these variables. In conclusion, the incidence of EIB in the figure skaters measured during this investigation (43 of 124 = 35%) is greater than that of the population at large and other highly trained athletes, signifying that screening for EIB and therapeutic follow-up are reasonable considerations for participants in this sport.
    Chest 02/1996; 109(2):312-5. · 7.48 Impact Factor
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    ABSTRACT: Inadequate O2 supply may impair intramuscular oxidative metabolism and O2 availability may modulate ATP production within exercising muscle. Therefore, we studied ATP flux from anaerobic glycolysis, the creatine kinase reaction, and oxidative phosphorylation using 31P-magnetic resonance spectroscopy kinetic data collected during exercise. We examined six chronic obstructive pulmonary disease (COPD) patients with severe hypoxemia (group 1), seven COPD patients with mild hypoxemia (group 2), and seven healthy control subjects. Exercise (90-s isometric contraction of the gastrocnemius-soleus muscle group, 40% of max) was performed on room air for all subjects; for COPD patients, it was repeated during supplemental O2 at identical power outputs, with 60-min rest between the two sets. In group 1 (air vs. O2), oxidative phosphorylation ATP production was lower (P < 0.05), anaerobic glycolysis ATP production was higher (P < 0.05), and anaerobic glycolysis plus creatine kinase ATP production tended to be higher (P = 0.06). In group 2, no differences were observed across conditions. Assuming that mitochondrial size, density, function, and redox state were not affected by acute changes in the inspired O2 fraction, reduced O2 availability is the remaining factor that could have limited oxidative ATP production during hypoxemia. In conclusion, in severely hypoxemic COPD patients, O2 availability apparently limits intramuscular oxidative metabolism because acute hypoxemia increases anaerobic and decreases aerobic ATP production.
    Journal of Applied Physiology 06/1995; 78(6):2218-27. · 3.06 Impact Factor
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    ABSTRACT: We evaluated the effect of supplemental O2 on energy metabolism of hypoxemic humans by measuring O2 uptake (VO2) kinetics and other cardiorespiratory parameters in nine male chronic obstructive pulmonary disease (COPD) patients and seven age-matched control subjects (on air and on 30% O2) at rest and during moderate cycle ergometer exercise. Heart rate, ventilation, VO2, CO2 output, respiratory exchange ratio, O2 cost of work, and work efficiency were measured with a computerized metabolic cart; O2 deficit and VO2 time courses were calculated. In COPD patients, 30% O2 breathing resulted in 1) reduction of O2 deficit (from 488 +/- 34 ml in air to 398 +/- 27 ml in O2; P < 0.05) and phase 2 VO2 time constant (from 116 +/- 13 s in air to 74 +/- 12 s in O2; P < 0.05); 2) a smaller steady-state increment in CO2 output than in room air (315 +/- 17 ml/min in O2 vs. 358 +/- 27 ml/min in air; P < 0.02), which resulted in a lower exercise respiratory exchange ratio (0.75 +/- 0.02 in O2 vs. 0.80 +/- 0.02 in air; P < 0.02); and 3) reduced steady-state ventilation (22.6 +/- 1.0 l/min in O2 vs. 25.4 +/- 1.1 l/min in air; P < 0.05). In conclusion, 30% O2 breathing accelerated exercise VO2 kinetics in mildly hypoxemic COPD patients. The observed VO2 kinetics improvement with O2 supplementation is consistent with an enhancement of aerobic metabolism in skeletal muscles during moderate exercise.
    Journal of Applied Physiology 06/1995; 78(6):2228-34. · 3.06 Impact Factor
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    ABSTRACT: Inspiratory muscle fatigue, a common event in patients in the intensive care unit, is under multifactorial control. To test the hypothesis that systemic oxygenation is a factor in this event, we subjected five healthy males (age 42 +/- 3 yr) to continuous inspiratory pressure (75% of maximal inspiratory pressure, -95 +/- 5 cmH2O) with the use of a controlled breathing pattern while they breathed normoxic (21% O2), hyperoxic (30% O2), and hypoxic (13% O2) mixtures. Inspiratory muscle endurance (IME; time that pressure could be maintained) and other cardiorespiratory parameters were monitored. Room air IME (3.3 +/- 0.4 min) was shortened (P < 0.05) during 13% O2 breathing (1.6 +/- 0.4 min) but was unaffected during 30% O2 breathing (4.0 +/- 0.6 min). Inspiratory loading lowered the respiratory exchange ratio (RER) during the 21 and 30% O2 trials (1.02 +/- 0.01 to 0.80 +/- 0.03% and 1.05 +/- 0.05 to 0.69 +/- 0.01%, respectively) but not during the 13% O2 trials (1.03 +/- 0.03 to 1.06 +/- 0.07%). At the point of fatigue during the 13% O2 trials, RER was lower compared with the same time point during the 21 and 30% O2 trials. A significant relationship was observed between IME and RER (r = -0.73, P = 0.002) but not between IME and any of the other measured variables. We conclude that 1) hypoxemia impairs the ability of the inspiratory muscles to sustain a mechanical challenge and 2) substrate utilization of the respiratory muscles shifts toward a greater reliance on lipid metabolism when O2 is readily available; this shift was not observed when the O2 supply was reduced.
    Journal of Applied Physiology 11/1993; 75(5):2188-94. · 3.06 Impact Factor
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    ABSTRACT: We investigated the influence of a right shift of the oxyhemoglobin dissociation curve on tissue oxygenation in two groups of anesthetized rabbits subjected to short periods of graded hypoxia: Group 1 (n = 5) with elevated P50 due to increased RBC 2,3-diphosphoglycerate and adenosine triphosphate and Group 2 (n = 5) with normal P50. Hemoglobin fell progressively in all animals due to blood letting for necessary measurements. During 16% inspired O2 (FIO2), both groups remained stable. During 13% FIO2, arterial pO2 was the same in both groups, but only in Group I did it fall below the crossover point (C.O.P.), which was raised by the high P50. Arterial pH and arterial-venous O2 content difference remained within the normal range in both groups throughout the experiment. During 13% FIO2, animals with high P50 showed a fall in cardiac output and oxygen consumption while animals with normal P50 remained stable. We postulate that when systemic O2 content is sufficiently reduced and tissue O2 extraction is maximal, the O2 needs of the myocardium perfused with a pO2 below the C.O.P. cannot be met: under these conditions cardiac output and systemic O2 consumption fall, presumably due to a reduction in coronary blood flow.
    Journal of Surgical Research 08/1993; 55(1):9-13. DOI:10.1006/jsre.1993.1101 · 1.94 Impact Factor
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    ABSTRACT: It is known that the O2 COV in COLD is high; O2 administration to these patients lowers airway resistance, a major determinant of the COV. Thus, O2 should lower the COV. We measured the COV in ten stable COLD patients and five normal control subjects breathing room air and 30 percent O2. Results indicate that the COV of our patients was elevated above that of control subjects, was related to disease severity, and was decreased with 30 percent O2. The COV of control subjects also was lowered by O2. At rest, O2 lowered VE, VEQ O2 and HR. During submaximal exercise O2 lowered VE, reduced VEQ O2 and extended total exercise time. An inverse correlation was noted between COV and maximal O2 uptake. Thus, in stable COLD, the COV is elevated in proportion to the degree of airway obstruction, inversely related to exercise capacity and lowered by O2 administration.
    Chest 05/1992; 101(4):910-5. DOI:10.1378/chest.101.4.910 · 7.48 Impact Factor
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    ABSTRACT: A recent study on stable, hypoxemic, COLD patients in which ANP was stimulated by LBPP demonstrated that in these individuals elevation of ANP does not exert a "normal" suppressing effect on the PRA-PA axis. Accordingly, we exercised ten comparable COLD patients, another maneuver known to stimulate ANP and to elicit cardiorespiratory responses substantially different from those observed with LBPP. Patients were studied breathing room air and on 40 percent O2 to determine whether the level of oxygenation would modify ANP secretion. Basal levels of ANP on room air were markedly elevated above controls (269 +/- 65 SE vs 70 +/- 20 pg/ml, p less than 0.05); PRA (13.0 +/- 5.4 ng/ml/90 min) and PA (8.6 +/- 3.5 ng/100 ml) were elevated (greater than 2 SD over control levels of 8.1 +/- 1.3 and 2.6 +/- 0.7) in 6/10 and 2/10 patients, respectively. During exercise while breathing O2, only ANP increased; PRA and PA remained unchanged when breathing air and O2. Comprehensive statistical analyses failed to demonstrate a negative relationship between ANP and PRA or ANP and PA. We conclude that in patients with advanced COLD, ANP response to moderate exercise is significantly affected by correction of hypoxemia. This effect may be mediated through changes in airway resistance and consequently cardiac filling pressure.
    Chest 03/1992; 101(2):341-4. DOI:10.1378/chest.101.2.341 · 7.48 Impact Factor
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    ABSTRACT: Atrial volume, pressure, and heart rate are considered the most important modulators of atrial natriuretic peptide (ANP) release, although their relative role is unknown. Continuous positive-pressure breathing in normal humans may cause atrial pressure and atrial volume to go in opposite directions (increase and decrease, respectively). We utilized this maneuver to differentially manipulate atrial volume and atrial pressure and evaluate the effect on ANP release. Effective filling pressure (atrial pressure minus pericardial pressure) was also monitored, because this variable has been proposed as another modulator of ANP secretion. We measured right atrial (RA) pressure, RA area, esophageal pressure (reflection of pericardial pressure), and RA and peripheral venous ANP in seven healthy adult males at rest and during continuous positive-pressure breathing (19 mmHg for 15 min). Continuous positive-pressure breathing decreased RA area (mean +/- SE, *P less than 0.05) 13.6 +/- 1.1 to 10.5 +/- 0.8* cm2, increased RA pressure 4 +/- 1 to 16 +/- 1* mmHg, increased esophageal pressure 2 +/- 1 to 12 +/- 1* mmHg, and increased effective filling pressure 2 +/- 0 to 4 +/- 1* mmHg. RA ANP increased from 67 +/- 17 to 91 +/- 18* pmol/l and peripheral venous ANP from 43 +/- 4 to 58 +/- 6* pmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
    Journal of Applied Physiology 11/1991; 71(4):1340-5. · 3.06 Impact Factor

Publication Stats

963 Citations
299.26 Total Impact Points


  • 2004
    • Indiana University East
      Ричмонд, Indiana, United States
  • 1984–2003
    • Indiana University-Purdue University Indianapolis
      • Department of Medicine
      Indianapolis, Indiana, United States
  • 1988–1993
    • Richard L. Roudebush VA Medical Center
      Indianapolis, Indiana, United States
    • Indiana University Bloomington
      Bloomington, Indiana, United States
  • 1989–1992
    • University of Louisville
      Louisville, Kentucky, United States
  • 1982–1991
    • The American University of Rome
      Roma, Latium, Italy
  • 1983
    • Spokane VA Medical Center
      Spokane, Washington, United States
  • 1977
    • St. Vincent Hospital
      Green Bay, Wisconsin, United States
  • 1976
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States