Effect of elastic loading on mouth occlusion pressure during CO2 rebreathing in man

In 7 normal subjects, mouth occlusion pressure was evaluated as an index of neural drive to the respiratory muscles during CO2 rebreathing, with and without the addition of 2 degrees of elastic loads. During control and loaded rebreathing, changes in both mouth occlusion pressure and ventilation were linearly related to changes in end-tidal PCO2. With elastic loading, the slope of occlusion pressure versus end-tidal PCO2 response consistently increased from control values in all subjects and was greater with the higher load in 6 of 7 subjects. The ventilatory response to elastic loading was variable and inconsistent owing to the variable increase in frequency of breathing, the tidal volume always being diminished. In normal subjects, both mouth occlusion pressure and ventilation appeared to assess neural drive to the respiratory muscles in response to CO2 rebreathing; with elastic loading, only occlusion pressure continued to reflect neuromuscular output. This increased pressure response could have been mediated by neural reflex and/or intrinsic muscle mechanisms. The data suggest that mouth occlusion pressure may be a useful parameter for evaluating neuromuscular control mechanisms under conditions of increased lung elastance.     

Associations between breathing pattern during submaximal exercise and exercise capacity in patients with pulmonary emphysema

We sought to clarify the factors associated with exercise capacity in patients with pulmonary emphysema. Exercise capacities of 20 men with pulmonary emphysema were evaluated by bicycle ergometery, and the results were used to divide the subjects into two groups: high exercise capacity (n = 10) and low exercise capacity (n = 10). Pulmonary-function tests were done, emphysema scores were computed from CT scans, breathing pattern was recorded during submaximal exercise (up to 20 watts), and index of rapid shallow breathing was computed. Neither FEV1 nor airway resistance differed between the two groups, and patients with lower exercise capacity tended to have lower tidal volumes and higher values of the index of rapid shallow breathing during submaximal exercise. Functional residual capacity measured by body plethysmography and emphysema scores were inversely associated with exercise capacity. We speculate that among patients with pulmonary emphysema and a given degree of airway obstruction, a high functional residual capacity causes breathing during submaxinal exercise to be rapid and shallow, and that this rapid and shallow breathing makes ventilation inefficient, increases the work of breathing, and limits exercise capacity.     

Effects of negative pressure assisted ventilation on dyspnoeic sensation and breathing pattern

Although negative pressure assisted ventilation with an assist-control mode may have a potential therapeutic role in the treatment of severe dyspnoea, the effects of negative pressure assisted ventilation with the assist-control mode on dyspnoea and breathing patterns have not been examined. We examined the effects of negative pressure assisted ventilation with the assist-control mode on dyspnoea and breathing patterns produced by a combination of resistive loading and hypercapnia in nine healthy subjects breathing spontaneously. Subjects were asked to rate their sensation of respiratory discomfort using a visual analogue scale. Negative pressure assisted ventilation caused a significant reduction in sensation of respiratory discomfort from a visual analogue scale score of 74 (55-91) (median (range)) before negative pressure assisted ventilation to 34 (15-53) during negative pressure assisted ventilation (p<0.01). During negative pressure assisted ventilation, there were significant changes in breathing patterns characterized by an increase in tidal volume and a decrease in respiratory frequency, while neither minute ventilation nor end-tidal carbon dioxide tension changed. Our results indicate that negative pressure assisted ventilation with the assist-control mode is effective in relief of dyspnoea and that negative pressure assisted ventilation influences the control of breathing to minimize respiratory discomfort.     

Physiological model of CO2 output during incremental exercise

In this study, a physiological model to explain the pathway of CO2 output during incremental exercise was examined by referring to experimental data. Since CO2 output (VCO2) shows multiple correlations with mixed venous CO2 pressure (PvCO2) and arterial CO2 pressure (PaCO2), the increase in the difference between PvCO2 and PaCO2 was considered to be involved in the increase in VCO2. In order to better understand the influence of CO2 pressure, VCO2 was divided into the expiratory CO2 phase (non-lactic VCO2), which was unrelated to lactic acid increase and the expiratory CO2 phase (excess VCO2), which was related to lactic acid increase. As a result, the non-lactic VCO2 significantly correlated to PvCO2. When non-lactic VCO2 was zero, the value of PvCO2 was 43.7 mmHg. This was higher than the resting PaCO2 value. On the other hand, as PaCO2 showed an almost constant value in the low load phase and showed a low value in the high load phase, it was believed that the low value of PaCO2 was related to the excess VCO2 that appeared in the high load phase. The CO2 excess, which was obtained by adding excess VCO2 in terms of the lapse of exercise time, correlated significantly with an increase in lactate in the blood. Based on the results, a model was constructed to illustrate the pathway of CO2 output. The key points of the model were as follows: (1) the use of the blood CO2 dissociation curve as the vector to transport CO2 from tissue to lungs, (2) the standard value of PaCO2 was established in order to divide non-lactic VCO2 and excess VCO2, (3) the dextroversion of the blood CO2 dissociation curve due to lactic acid was connected to excess VCO2, and (4) a decrease in PaCO2 was related to excess VCO2 derived from tissue.     

Breathing pattern and additional work of breathing in spontaneously breathing patients with different ventilatory demands during inspiratory pressure support and automatic tube compensation

OBJECTIVE: To identify predictors of hypoglycemic and hyperglycemic episodes in hospitalized patients with diabetes with special attention to the effectiveness of sliding scale insulin regimens. DESIGN: Prospective cohort study. SETTING: Urban university hospital. PARTICIPANTS: One hundred seventy-one adults with diabetes mellitus as a comorbid condition admitted consecutively to medical inpatient services during a 7-week period. MEASUREMENTS: Demographic, clinical, and laboratory data from inpatient medical records. MAIN OUTCOMES: Rates of hypoglycemic (capillary blood glucose, < or = 3.3 mmol/L [< or = 60 mg/dL]) and hyperglycemic (capillary blood glucose, > or = 16.5 mmol/L [> or = 300 mg/ dL]) episodes. RESULTS: Of the patients, 23% experienced hypoglycemic episodes, and 40% experienced hyperglycemic episodes. The overall rates of hypoglycemic and hyperglycemic episodes were 3.4 and 9.8 per 100 capillary blood glucose measurements, respectively. Independent predictors of hypoglycemic episodes included African American race (relative risk [RR], 2.13) and low serum albumin level (RR, 1.92 per 100-g/L decrease); corticosteroid use was associated with a reduced risk of hypoglycemic episodes (RR, 0.32; P < .05). Independent predictors of hyperglycemic episodes included female gender (RR, 1.67), severity of illness (RR, 1.22 per 10 Acute Physiology and Chronic Health Evaluation III units), severe diabetic complications (RR, 2.32), high admission glucose level (RR, 1.33 per 5.5 mmol/L), admission for infectious disease (RR, 2.14), and corticosteroid use (RR, 3.74; P < .05). Of 171 patients, 130 (76%) were placed on a sliding scale insulin regimen. When used alone, sliding scale insulin regimens were associated with a 3-fold higher risk of hyperglycemic episodes compared with individuals following no pharmacologic regimen (RRs, 2.85 and 3.25, respectively; P < .05). CONCLUSIONS: Suboptimal glycemic control is common in medical inpatients with diabetes mellitus. The risk of suboptimal control is associated with selected demographic and clinical characteristics, which can be ascertained at hospital admission. Although sliding scale insulin regimens are prescribed for the majority of inpatients with diabetes, they appear to provide no benefit; in fact, when used without a standing dose of intermediate-acting insulin, they are associated with an increased rate of hyperglycemic episodes.     

Effect of hypoxia on the pressure developed by inspiratory muscles during airway occlusion

Patients with colitis and ileocolitis of unknown etiology from two previously reported series have been combined and the follow-up studies have been extended to compare the long term postoperative courses of ulcerative colitis (UC) and Crohn's disease of the colon (CDC). The combined and updated series of 176 patients, 99% of whom could be traced, provided a mean postoperative follow-up period for UC of 14 years (5 to 31) and CDC of 13.1 years (5 to 36). There were highly significant associations between generally accepted clinical and distributional features of UC and CDC and microscopic findings generally regarded as reliable for each. However, because of spectrum of features was found in each entity, neither clinical and distributional nor microscopic features alone are sufficient for diagnosis in every case. There were no differences in gross or disease-related mortality in UC and CDC whatever the method of diagnosis. After anastomotic procedures in CDC a recurrence rate of 73% was found. After proctocolectomy the ileostomy revision rate (considering all types of those which required further excision of ileum) was higher in CDC than UC whether the diagnoses were based on microscopic, clinical, or combined criteria, but the differences reached statistical significance only in the comparison of "clinical UC", with "clinical CDC". Moreover, after the first 2 postoperative years, the risk of having an ileostomy revision in UC and CDC (combined criteria) per patient year follow-up was virtually identical and there were no cases of short bowel syndrome. Differences in the clinical courses of UC and CDC after colectomy and ileostomy are of degree and do not reflect the ultimate course or potential for rehabilitation. Decisions regarding surgical therapy should be made independent of the diagnosis of UC or CDC.     

Effect of local exercise and vessel occlusion on fibrinolytic activity

Arterial occlusion of the upper limb did not affect the fibrinolytic activity in the venous blood of that limb; venous occlusion associated with venous distension resulted in a marked rise in activity. Local fibrinolytic activity was increased substantially by active exercise; passive exercise induced a smaller increase. Active exercise undertaken during arterial occlusion did not result in a rise in activator level. It is concluded from these results that blood flow into the venous system rather than accumulation of metabolites is responsible for the increased release of activator into the blood during local exercise and vessel occlusion.     

Changes in maximal exercise ventilation and breathing pattern in boys during growth: a mixed cross-sectional longitudinal study

The aim of this mixed cross-sectional longitudinal study covering a total age range of 11-17 years, i.e. the entire pubertal growth period, was (1) to specify the changes in maximal breathing pattern during incremental exercise; (2) to determine what parts of the changes are due to anthropometric characteristics, physical fitness and inspiratory or expiratory muscle strength; and (3) to determine if the role of these variables is identical before, during and after pubertal growth spurt. This study was conducted in 44 untrained schoolboys separated into three groups, with an initial age of 11.2 +/- 0.2 years for group A, 12.9 +/- 0.25 years for group B, and 14.9 +/- 0.26 years for group C. These children were subsequently followed for 3 years, during the same time period each year. The maximal inspiratory and expiratory pressures (PI max and PE max) were used as an index of the respiratory muscle strength. During an incremental exercise test, maximal ventilation (VE max), tidal volume (VT max), breathing frequency (fmax), inspiratory and expiratory times (tI max and tE max) and mean inspiratory flow (VT/tI max) were measured at maximal oxygen uptake (VO2max). Our study showed that there was a marked increase with age in VE max, VT max, and VT/tI max, and no significant changes in fmax, tI max and tE max. PI max and PE max showed a general trend towards an increase between 11 and 17 years. The study of the linear correlations between maximal breathing pattern and the anthropometric characteristics, physical fitness and inspiratory or expiratory muscle strength showed that, in the three groups of children, (1) lean body mass was the major determinant of VE max, VT max and VT/tI max and the relationships were significantly different before, during and after the pubertal growth spurt; (2) physical fitness was the main determinant of tI max, tE max and fmax before and after the pubertal growth spurt; and (3) maximal respiratory strength did not play a significant role. In conclusion, this mixed cross-sectional longitudinal study showed, at maximal exercise, a significant increase in VE max during growth due only to a significant increase in VT max and VT/tI max, and that the relationships of anthropometric characteristics and physical fitness with maximal breathing pattern change during growth.     

Rib cage mechanics during quiet breathing and exercise in humans

During exercise, large pleural, abdominal, and transdiaphragmatic pressure swings might produce substantial rib cage (RC) distortions. We used a three-compartment chest wall model (J. Appl. Physiol. 72: 1338-1347, 1992) to measure distortions of lung- and diaphragm-apposed RC compartments (RCp and RCa) along with pleural and abdominal pressures in five normal men. RCp and RCa volumes were calculated from three-dimensional locations of 86 markers on the chest wall, and the undistorted (relaxation) RC configuration was measured. Compliances of RCp and RCa measured during phrenic stimulation against a closed airway were 20 and 0%, respectively, of their values during relaxation. There was marked RC distortion. Thus nonuniform distribution of pressures distorts the RC and markedly stiffens it. However, during steady-state ergometer exercise at 0, 30, 50, and 70% of maximum workload, RC distortions were small because of a coordinated action of respiratory muscles, so that net pressures acting on RCp and RCa were nearly the same throughout the respiratory cycle. This maximizes RC compliance and minimizes the work of RC displacement. During quiet breathing, plots of RCa volume vs. abdominal pressure were to the right of the relaxation curve, indicating an expiratory action on RCa. We attribute this to passive stretching of abdominal muscles, which more than counterbalances the insertional component of transdiaphragmatic pressure.     

Evaluation of right ventricular systolic pressure during incremental exercise by Doppler echocardiography in adults with atrial septal defect

STUDY OBJECTIVES: Pulmonary hypertension is the most important complication in patients with atrial septal defect (ASD), but its role in limiting exercise has not been examined. This study sought to evaluate exercise performance in adults with ASD and determine the contribution of elevated pulmonary artery pressure in limiting exercise capacity. DESIGN: We used Doppler echocardiography during exercise in 10 adults (aged 34 to 70 years) with isolated ASD (New York Heart Association class I, II) and an equal number of matched control subjects. Incremental exercise was performed on an electrically braked upright cycle ergometer. Expired gases and VE were measured breath-by-breath. Two-dimensional and Doppler echocardiographic images were obtained at rest prior to exercise to determine ASD size, stroke volume (SV), shunt ratio (Qp:Qs), right ventricular outflow tract (RVOT) size, and right ventricular systolic pressure at rest (RVSPr). Doppler echocardiography was repeated at peak exercise to measure right ventricular systolic pressure during exercise (RVSPex). RESULTS: Resting echocardiography revealed that RVOT was larger (21+/-4 vs 35+/-8 mm, mean+/-SD; p=0.0009) and RVSPr tended to be higher (17+/-8 vs 31+/-8 mm Hg; p=0.08) in ASD; however, left ventricular SV was not different (64+/-23 vs 58+/-23 mL; p>0.05), compared with control subjects. Despite normal resting left ventricular function, ASD patients had a significant reduction in maximum oxygen uptake (VO2max) (22.9+/-5.4 vs 17.3+/-4.2 mL/kg/min; p=0.005). RVSPex was higher (19+/-8 vs 51+/-10 mm Hg; p=0.001) and the mean RVSP-VO2 slope (1+/-2 vs 18+/-3 mm Hg/L/min; p=0.003) and intercept (17+/-4 vs 27+/-4 mm Hg; p=0.05) were higher in the ASD group. VO2max correlated inversely with both RVSPr (r=-0.69; p=0.007) and RVSPex (r=-0.67; p=0.01). CONCLUSION: These findings suggest that adults with ASD have reduced exercise performance, which may be associated with an abnormal increase in pulmonary artery pressure during exercise.     

Muscle oxygenation during incremental arm and leg exercise in men and women

The purpose of this study was to compare the rates of muscle deoxygenation in the exercising muscles during incremental arm cranking and leg cycling exercise in healthy men and women. Fifteen men and 10 women completed arm cranking and leg cycling tests to exhaustion in separate sessions in a counterbalanced order. Cardiorespiratory measurements were monitored using an automated metabolic cart interfaced with an electrocardiogram. Tissue absorbency was recorded continuously at 760 nm and 850 nm during incremental exercise and 6 min of recovery, with a near infrared spectrometer interfaced with a computer. Muscle oxygenation was calculated from the tissue absorbency measurements at 30%, 45%, 60%, 75% and 90% of peak oxygen uptake (VO2) during each exercise mode and is expressed as a percentage of the maximal range observed during exercise and recovery (%Mox). Exponential regression analysis indicated significant inverse relationships (P < 0.01) between %Mox and absolute VO2 during arm cranking and leg cycling in men (multiple R = -0.96 and -0.99, respectively) and women (R = -0.94 and -0.99, respectively). No significant interaction was observed for the %Mox between the two exercise modes and between the two genders. The rate of muscle deoxygenation per litre of VO2 was 31.1% and 26.4% during arm cranking and leg cycling, respectively, in men, and 26.3% and 37.4% respectively, in women. It was concluded that the rate of decline in %Mox for a given increase in VO2 between 30% and 90% of the peak VO2 was independent of exercise mode and gender.     

Effect of sleep on changes in breathing pattern accompanying sigh breaths

We studied the effect of sleep on the characteristics of sigh breaths and the associated changes in breathing pattern in breaths following spontaneous sighs in 4 unrestrained dogs with an intact upper airway. The sigh breath was characterized by its large tidal volume (VT), long TI and TE in comparison with the control breath. The volume of the sigh breath was larger in awake sighs than in those recorded during non-REM (NREM) and REM sleep. The strength of Hering-Breuer reflex as determined by duration of the post-sigh apnea was similar in NREM and REM sleep. Sighs occurring during wakefulness, NREM and REM sleep were associated with augmented activity of the parasternal muscles during inspiration, and a persistent tonic abdominal muscle activity during the expiratory period. Breathing pattern in the post-sigh period was characterized by a smaller VT and longer TE in the first post-sigh breath in all sleep states (compared with the control breath), but the pattern returned to control level within the second or third post-sigh breath in both NREM and REM sleep. Sighs did not precipitate periodic breathing or other forms of abnormal breathing patterns in either wakefulness or sleep. We conclude that the respiratory control mechanisms stabilizing breathing after a sigh in the awake dog are intact in NREM and REM sleep.     

Measurement of mouth occlusion pressure as an index of respiratory centre output in man

Peptostreptococcus anaerobius strain VPI 4330-1 was used as the test organism in an evaluation of the bactericidal effect of anaerobic broth exposed to air. The test organism, grown under anaerobic conditions in Trypticase soy broth, was diluted in buffered salt solution, and about 2 x 10(4) cells were suspended in 10 ml of an aerated broth. Ninety percent of the cells were killed within 15 min in actinomyces broth and within 50 min in Trypticase soy broth. All cells survived for 2 h in fluid thioglycolate medium. Addition of DABCO [1,4-diazabicyclo (2.2.2) octane] or mannitol to Trypticase soy broth did not influence the death rate of the organism, whereas superoxide dismutase decreased the death rate. Addition of catalase or manganese dioxide to the broth kept all the cells viable for 2 h. Of the three broth media tested, actinomyces broth reduced oxygen at the highest rate and Trypticase soy broth reduced it at the slowest rate. Hydrogen peroxide could be demonstrated in actinomyces broth and in Trypticase soy broth but not in fluid thioglycolate medium. In addition to catalase, manganese dioxide also removed all hydrogen peroxide from Trypticase soy broth, and superoxide dismutase significantly decreased the concentration of hydrogen peroxide in the broth. The results suggest that hydrogen peroxide mediated the toxic effect of atmospheric oxygen in these broth media.     

Influence of drive and timing mechanisms on breathing pattern and ventilation during mental task performance

Assessment of multiple respiratory measures may provide insight into how behavioral demands affect the breathing pattern. This is illustrated by data from a study among 44 subjects, in which tidal volume, respiration rate, minute ventilation and indices of central drive and timing mechanisms were assessed via inductive plethysmography, in addition to end-tidal PCO2. After a baseline, three conditions of a memory comparison task were presented. The first two conditions differed only with regard to the presence or absence of feedback of performance (NFB and FB). In the third 'all-or-nothing' (AON) condition, subjects only received a monetary bonus, if their performance exceeded that of the previous two conditions. Minute ventilation increased from baseline to all task conditions, and from NFB and FB to AON. Respiration rate increased in all task conditions, but there were no differences between task conditions. Tidal volume decreased during NFB, but was equal to baseline during FB and AON. Of the respiratory control indices, inspiratory flow rate covaried much more closely with minute ventilation than duty cycle. The task performance induced a minor degree of hyperventilation. The discussion focusses on how behavioral demands affect respiratory control processes to produce alterations in breathing pattern and ventilation.     

Relationship between mouth occlusion pressure and electrical activity of the diaphragm: effects of flow-resistive loading

We determined the relationship between mouth occlusion pressure and diaphragmatic electromyography during CO2 rebreathing with and without inspiratory flow resistance. Diaphragmatic electromyography was measured as a moving time average; occlusion pressures were measured 150 msec after onset of an inspiratory effort against a closed airway (P.15). P.15 versus diaphragmatic electromyographic plots during CO2 rebreathing with and without inspiratory flow resistance were linear. In 3 subjects the slope of P.15 versus diaphragmatic electromyography was unchanged with inspiratory flow resistance whereas in 3 others the slope increased, indicating greater inspiratory force for a given degree of diaphragmatic activity. We concluded that under unloaded conditions P.15 is a reliable index of respiratory neural output but may no longer reflect only inspiratory motoneuron drive during mechanical loading.     

Physiological effects of variations in spontaneously chosen crank rate during incremental upper-body exercise

The aims of the present study were: first, to assess the interindividual variations of a spontaneously chosen crank rate (SCCR) in relation to the power developed during an incremental upper body exercise on an arm ergometer set at a constant power regime, and second, to compare heart rate (HR) responses, expired minute ventilation (V[E]) and oxygen consumption (VO2) when the pedal rates were chosen spontaneously (T[SCCR]) or set at +/- 10% of the freely chosen rates (T[+10%] and T[-10%], respectively). The mean pedal rate values were linearly related (P < 0.01) with the power developed during arm cranking (r = 0.96), although large variations of pedalling rate strategies were observed between subjects. Maximal power (MP) and time to exhaustion values were significantly higher (P < 0.05) during T(SCCR) than during T(+10%) and T(-10%). Peak VO2 values were significantly higher (P < 0.05) in T(+10%) than in T(SCCR) and T(-10%). The increase in HR, V(E), and VO2 mean values, in relation to the increase in the power developed, was significantly higher (P < 0.05) when the pedal rate was set at plus 10% of the SCCR (T[+/-10%]) than in the two other conditions. The findings of the present study suggest that the use of an electromagnetically braked ergometer, which automatically adjusts the resistance component to maintain a constant work rate, should be used in order to achieve the highest MP values during an incremental upper body exercise. A 10% increase of the SCCR should be used in order to provide the highest peak VO2 value.     

Effect of occlusion on cell proliferation during epidermal healing

Sphincter of Oddi dysfunction (SOD) is an obstructive syndrome of the papilla not resulting from a stone. It may cause recurrent biliary type pain to cholecystectomized patients. SOD is caused by sphincter dyskinesia or benign stenosis. Diagnosis is usually based on symptoms, serum biochemistry, endoscopic retrograde cholangiopancreatography and Sphincter of Oddi manometry. The latter is the best means of evaluating Sphincter of Oddi dynamics. However, because of the many inconveniences of Sphincter of Oddi manometry and of its high morbidity rate, it is seldom used. Non invasive techniques, such as cholescintigraphy, have been developed to replace Sphincter of Oddi manometry in diagnosing SOD. Patients can be cured by sphincterotomy. Certain drugs could also be effective but few controlled studies have been carried out of date.     

Maximum rate of change in oesophageal pressure assessed from unoccluded breaths: an option where mouth occlusion pressure is impractical

A nested polymerase chain reaction (PCR) assay was used to determine the levels of cytomegalovirus (CMV) genomes in cells of CSF from 19 patients with AIDS and 12 human immunodeficiency virus type I (HIV-1) seronegative individuals with various neurologic disorders. Five AIDS patients had autopsy-proven CMV encephalitis (CMVE) and 14 patients had no evidence of CMV-related CNS manifestations. CSF cells from AIDS patients with confirmed CMVE harbored viral genomes at a median value of 3,333/10(5) cells (range, 1,667 to 5,333/10(5) cells; mean, 3,558/10(5) cells) compared with a median value of 125/10(5) cells (range, 9 to 1,000/10(5) cells; mean, 281/10(5) cells) for AIDS patients with CMV-unrelated symptoms and a median value of 1.9/10(5) cells (range, 0 to 562/10(5) cells; mean, 52/10(5) cells) for HIV-1 seronegative control subjects. A subset of CSF samples was assessed using a modified single round amplification PCR with a detection limit of 500 viral copies. CMV DNA was detected in all four specimens from AIDS patients with proven CMVE, in two of five AIDS patients without CMVE, and in none of five seronegative control subjects. Quantitation of CMV genomes in CSF cells is indicative of latent or productive CMV infection and is a reliable means for diagnosis of CMVE in patients with AIDS. Detection of a cutoff value of cellular CMV genomes by means of nonquantitative PCR may identify patients at risk for CMV infection of the CNS.     

Treadmill exercise duration and dyspnea recovery time in chronic obstructive pulmonary disease: effects of oxygen breathing and repeated testing

OBJECTIVES: To evaluate biochemical outcome after definitive radiotherapy as a function of family history groupings. METHODS: Biochemical freedom from disease for 920 men treated for prostate cancer with external beam radiation alone between March 1987 and December 1997 was compared according to hereditary/familial history (PFH) and sporadic family history. To adjust for known predictors of biochemical outcome, 97 PFH patients were randomly matched 2:1 to 194 sporadic patients according to age, grade, pretreatment prostate-specific antigen level, and palpation stage and compared in terms of biochemical outcome. Cox multivariate regression analyses were also performed to identify independent predictors of outcome in the two patient populations. RESULTS: In both patient populations, univariate analysis of biochemical outcome demonstrated no difference according to family history groupings. After adjusting for known predictors of biochemical outcome, multivariate analysis confirmed the nonsignificant univariate findings. CONCLUSIONS: No difference was found in this study between patients with a PFH (combined hereditary and familial) and patients with the sporadic form of prostate cancer. Recent published reports are conflicting and the question of whether a genetic change influencing prostate cancer causation is associated with factors altering treatment response should be addressed using a multi-institutional, carefully documented, prospective family history data collection and outcome analysis.     

Effect of theophylline on substrate metabolism during exercise

We tested the hypothesis that adenosine is involved in regulating substrate metabolism during exercise. Seven trained cyclists were studied during 30 minutes of exercise at approximately 75% maximal oxygen uptake (VO2max). Lipid metabolism was evaluated by infusing [2H5]glycerol and [1-13C]palmitate, and glucose kinetics were evaluated by infusing [6,6-2H]glucose. Fat and carbohydrate oxidation were also measured by indirect calorimetry. The same subjects performed two identical exercise tests, but in one trial theophylline, a potent adenosine receptor antagonist, was infused for 1 hour before and throughout exercise. Theophylline did not increase whole-body lipolysis (glycerol rate of appearance [Ra]) or free fatty acid (FFA) release during exercise, but fat oxidation was lower than control values (9.5 +/- 3.0 v 18.0 +/- 4.2 micromol x min(-1) x kg(-1), P < .01). Glucose Ra was not affected by theophylline infusion, but glucose uptake was lower (31.6 +/- 4.1 v 40.4 +/- 5.0 micromol x min(-1) x kg(-1), P < .05) and glucose concentration was higher (6.4 +/- 0.6 v 5.8 +/- 0.4 mmol/L, P < .05) than in the control trial. Total carbohydrate oxidation (302.3 +/- 26.2 v 265.5 +/- 11.7 micromol x min(-1) x kg(-1), P < .06), estimated muscle glycogenolysis (270.7 +/- 23.1 v 225.1 +/- 9.7 micromol x min(-1) x kg(-1), P < .05), and plasma lactate concentration (7.9 +/- 1.6 v 5.9 +/- 1.1 mmol/L, P < .001) were also higher during the theophylline trial. These data suggest that adenosine may play a role in stimulating glucose uptake and restraining glycogenolysis but not in limiting lipolysis during exercise.