Chronic bacterial inflammation induces prostatic intraepithelial neoplasia in mouse prostate.

BACKGROUND: Although the aetiology of prostate cancer remains unknown, we hypothesised that chronic bacterial insult has a major role in prostate carcinogenesis. METHODS: Male C3H/HeOuJ mice, infected with phosphate-buffered saline or Escherichia coli bacteria, were killed at 5 days, or at 12 or 26 weeks. Harvested prostate tissues were evaluated for inflammatory responses and immunostained for neoplastic transformation markers. RESULTS: All infected mice developed bacterial prostatitis. Control mice had no prostate infections or inflammation. Mice infected for 5 days showed foci of acute inflammation with infiltrating neutrophils and epithelial necrotic debris in the prostatic glandular lumen. All mice infected for 12 weeks had evidence of chronic inflammation with dense inflammatory infiltrates in the stroma. The prostatic epithelium showed varying degrees of atypical hyperplasia with increased epithelial cell layers and cytological atypia. At 26 weeks, the dysplastic changes were more pronounced and mimicked a prostatic intraepithelial neoplasia and high-grade dysplasia. Prostatic glands exhibiting reactive dysplasia had a stronger staining for oxidative DNA damage, increased epithelial cell proliferation, and a decrease in androgen receptor, GSTP1, p27(Kip1), and PTEN expression, when compared with control prostate glands. CONCLUSION: These data demonstrate that chronic inflammation induces focal prostatic glandular atypia and suggest a potential linkage between inflammation and prostatic neoplasia.

Differences in skeletal muscle between men and women with chronic heart failure.

Men with chronic heart failure (CHF) have alterations in their skeletal muscle that are partially responsible for a decreased exercise tolerance. The purpose of this study was to investigate whether skeletal muscle alterations in women with CHF are similar to those observed in men and if these alterations are related to exercise intolerance. Twenty-five men and thirteen women with CHF performed a maximal exercise test for evaluation of peak oxygen consumption (VO(2)) and resting left ventricular ejection fraction, after which a biopsy of the vastus lateralis was performed. Twenty-one normal subjects (11 women, 10 men) were also studied. The relationship between muscle markers and peak VO(2) was consistent for CHF men and women. When controlling for gender, analysis showed that oxidative enzymes and capillary density are the best predictors of peak VO(2.) These results indicate that aerobically matched CHF men and women have no differences in skeletal muscle biochemistry and histology. However, when CHF groups were separated by peak exercise capacity of 4.5 metabolic equivalents (METs), CHF men with peak VO(2) >4.5 METs had increased citrate synthase and 3-hydroxyacyl-CoA dehydrogenase compared with CHF men with peak VO(2) <4.5 METs. CHF men with a lower peak VO(2) had increased capillary density compared with men with higher peak VO(2). These observations were not reproduced in CHF women. This suggests that differences may exist in how skeletal muscle adapts to decreasing peak VO(2) in patients with CHF.

Effects of exercise training on chronotropic incompetence in patients with heart failure.

OBJECTIVE: To describe the effects of exercise training on chronotropic incompetence in patients with stable heart failure, as measured by their inability to achieve a peak exercise heart rate greater than 85% of maximum. BACKGROUND: Exercise intolerance and chronotropic incompetence are characteristic of patients with heart failure. Exercise training improves exercise capacity in these patients; however, to what extent reversal of chronotropic incompetence contributes to such a response remains uncertain. METHODS: Fifty-one patients undergoing standard medical therapy were randomly assigned to a 24-week exercise training program or a no exercise control group. Twenty-one of 26 patients assigned to the exercise group and 22 of 25 control patients completed the study. Peak oxygen consumption, resting and exercise plasma norepinephrine level, and quality of life (Living With Heart Failure Questionnaire) were assessed. RESULTS: A significant (P <.05) increase in peak heart rate was observed in the exercise group (9 +/- 3 beats/min) when compared with the control group (1 +/- 3 beats/min). Among exercise-trained patients with chronotropic incompetence at baseline (n = 14), the increase in peak heart rate at week 24 was 12 +/- 3 beats/min. Peak oxygen consumption was significantly (P <.05) increased in the exercise group (204 +/- 57 mL/min) versus the control group (72 +/- 33 mL/min). Health-related quality of life was not significantly changed with exercise training. Twenty-four weeks of exercise training induced a greater (P <.05) reduction in plasma norepinephrine at rest and during exercise in patients with a nonischemic cardiomyopathy versus those with ischemic cardiomyopathy. CONCLUSIONS: Exercise training results in an increase in peak heart rate and partial reversal of chronotropic incompetence among patients with stable heart failure. These responses contribute, in part, to the exercise training-induced increase in exercise capacity that occurs in these patients.

Capillary density of skeletal muscle: a contributing mechanism for exercise intolerance in class II-III chronic heart failure independent of other peripheral alterations.

OBJECTIVES: The study was conducted to determine if the capillary density of skeletal muscle is a potential contributor to exercise intolerance in class II-III chronic heart failure (CHF). BACKGROUND: Previous studies suggest that abnormalities in skeletal muscle histology, contractile protein content and enzymology contribute to exercise intolerance in CHF. METHODS: The present study examined skeletal muscle biopsies from 22 male patients with CHF compared with 10 age-matched normal male control patients. Aerobic capacities, myosin heavy chain (MHC) isoforms, enzymes, and capillary density were measured. RESULTS: The patients with CHF demonstrated a reduced peak oxygen consumption when compared to controls (15.0+/-2.5 vs. 19.8+/-5.0 ml x kg(-1) x min(-1), p <0.05). Using cell-specific antibodies to directly assess vascular density, there was a reduction in capillary density in CHF measured as the number of endothelial cells/fiber (1.42+/-0.28 vs. 1.74+/-0.35, p = 0.02). In CHF, capillary density was inversely related to maximal oxygen consumption (r = 0.479, p = 0.02). The MHC IIx isoform was found to be higher in patients with CHF versus normal subjects (28.5+/-13.6 vs. 19.5+/-9.4, p <0.05). CONCLUSIONS: There was a significant reduction in microvascular density in patients with CHF compared with the control group, without major differences in other usual histologic and biochemical aerobic markers. The inverse relationship with peak oxygen consumption seen in the CHF group suggests that a reduction in microvascular density of skeletal muscle may precede other skeletal muscle alterations and play a critical role in the exercise intolerance characteristic of patients with CHF.

Leukocytosis in acute pulmonary embolism.

PURPOSE: The purpose of this investigation is to assess the level of leukocytosis in acute pulmonary embolism (PE). BACKGROUND: Limited data exist regarding leukocytosis in acute PE. One reason that the prevalence of leukocytosis in acute PE is unknown, despite an extensive number of investigations of PE, may relate to the fact that acute PE is usually associated with other conditions that themselves may cause leukocytosis. METHODS: Hospital records of 386 patients with a diagnosis of acute PE were reviewed retrospectively. Patients with no other possible or definite cause of leukocytosis were analyzed separately. A diagnosis of PE was made by a high-probability interpretation of the ventilation/perfusion lung scan or pulmonary angiogram. RESULTS: Among patients with PE in whom other possible or defined causes for leukocytosis were eliminated, 52 of 266 (20%) had a WBC count > 10,000/mm3. None had a WBC count that was > or = 20,000/mm3. Patients with the pulmonary hemorrhage/infarction syndrome had an increased WBC count in 32 of 183 (17%) vs 20 of 83 (24%) in patients who did not have pulmonary hemorrhage/infarction syndrome (not significant). CONCLUSION: A modest leukocytosis may accompany (and possibly be caused by) PE. Its presence should not dissuade the clinician from objectively pursuing the diagnosis of PE.

Caloric expenditure during cardiac rehabilitation.

PURPOSE: The purpose of this study was to describe estimated caloric expenditure among patients in a maintenance cardiac rehabilitation program relative to a stated goal of approximately 300 kcal/session or 1,000 kcal/week. Additionally, we assessed the validity of several different methods for estimating caloric expenditure. METHODS: The caloric expenditure for an exercise session was evaluated in 30 of 65 patients exercising in a maintenance cardiac rehabilitation program. Patients exercised using a treadmill, dual-action ergometer, upright stepper, or reclining stepper. The kilocalorie expenditure was assessed by three different techniques. The first used liquid crystal display (LCD) readings from the equipment (LCD method), the second combined both the American College of Sports Medicine metabolic equations for treadmill walking and the LCD values from the other equipment (Combined method), and the third measured oxygen consumption (VO2 method). RESULTS: The caloric expenditure for the LCD, Combined, and VO2 methods were 247 +/- 83, 245 +/- 80, and 230 +/- 88 kcal, respectively. Agreement between methods using intraclass correlation analysis was r = 0.84 (0.68 to 0.92, 95% confidence intervals) for LCD versus VO2 and r = 0.88 (0.77 to 0.94, 95% confidence intervals) for Combined versus VO2 method. CONCLUSIONS: Most patients (83%) in a maintenance cardiac rehabilitation program exercise below 300 kcal per session, a level believed to be necessary to illicit favorable changes in cardiovascular health. Additionally, the Combined method provides a reasonable estimate of kilocalorie expenditure. Use of kilocalorie expenditure should be considered in the cardiac rehabilitation setting as a fourth component in the exercise prescription.

Exercise training in heart failure.

Patients with heart failure challenge the clinician with a constellation of difficult clinical, pathophysiologic, and psychologic issues. As a result, until recently, exercise training was not considered a safe and effective treatment strategy to be used in these patients. However, in the past 10 years, data from both randomized and nonrandomized trials showed that regular exercise training in patients with stable Class II and III heart failure can safely improve exercise tolerance, attenuate an overactivated sympathetic nervous system, partially reverse skeletal muscle abnormalities, and enhance health-related quality of life. These outcomes are achievable with a relatively moderate dose of physical activity, such as 30 to 60 minutes of walking or cycling 3 to 5 days per week at an intensity equivalent to 60% to 70% of peak oxygen consumption. Sufficiently powered trials are needed to assess morbidity, mortality, and cost-effectiveness endpoints relative to exercise training in patients with heart failure.

Exercise testing and training of patients with heart failure due to left ventricular systolic dysfunction.

Reducing the exercise intolerance and symptoms experienced by patients with chronic heart failure remains an important focus in their clinical care. A clear shortcoming exists; however, with respect to an appreciation that in addition to standard medical therapy, selected patients with stable heart failure also can benefit from a moderate exercise training program. Improvements in central transport, regional blood flow, and skeletal muscle histology and biochemistry all likely account for the increase in exercise capacity and delay in fatigue that these patients experience. Additionally, the autonomic imbalance that is characteristic of these patients is improved. Although the number of patients with heart failure participating in an exercise program is increasing, much work still exists relative to incorporating this treatment method into the care plans established by physicians and physician extenders.

Responses to arm exercise in patients with compensated heart failure.

PURPOSE: This study compares the responses of 20 male patients (mean age 51 +/- 11 years) with stable heart failure during peak and submaximal arm and leg exercise. METHODS: On day 1, subjects completed two symptom-limited graded exercise tests, one with their arms and one with their legs. On day 2, subjects performed arm only and leg only exercise at a matched power output of 30 Watts (W). Ten age-matched healthy subjects served as controls. RESULTS: During peak arm exercise power output, oxygen consumption (VO2), ventilation, and rate-pressure product were higher in healthy subjects than in patients with heart failure. However, when a subject's peak VO2 or power output during arm exercise was expressed as a percentage of that achieved during peak leg exercise, no significant differences were noted between patients with heart failure and healthy subjects. Among both groups, rate-pressure product, VO2, ventilation, the ventilatory equivalent for O2, and respiratory exchange ratio were all higher when exercising at 30 W with the arms versus 30 W with the legs. Also, in patients with heart failure heart rate was higher (+6 min-1) and stroke volume index lower (-4 mL/m2) during submaximal arm than leg exercise. CONCLUSIONS: Although peak exercise capacity (Watts, VO2) during arm exercise is lower in patients with heart failure than healthy subjects, when expressed as a percentage of peak leg capacity, the extent of the exercise intolerance they experience during arm exercise does not differ from healthy subjects.

Exercise training in patients with heart failure. A randomized, controlled trial.

OBJECTIVE: To assess the benefit of exercise training in patients with heart failure caused by left ventricular systolic dysfunction and to further describe the physiologic changes associated with exercise training in these patients. DESIGN: Randomized, controlled trial. SETTING: Urban outpatient clinic. PATIENTS: 40 men with compensated heart failure who were receiving standard medical therapy were randomly assigned to an exercise-training group or to a control group that did not exercise. Fifteen of the 21 patients assigned to exercise training and 14 of the 19 patients assigned to the control group completed the study. INTERVENTION: Patients assigned to exercise training participated in a program of three exercise sessions per week for 24 weeks. MEASUREMENTS: Symptom-limited exercise tests with gas exchange analysis done just before randomization, at week 12, and at week 24. RESULTS: At week 24, the following changes (mean +/- SE) were seen in patients in the exercise group and patients in the control group, respectively; exercise duration, 2.8 +/- 0.6 minutes and 0.5 +/- 0.5 minutes; peak oxygen consumption (VO2), 231 +/- 54 L/min and 58 +/- 38 L/min; peak ventilation, 12 +/- 3 L/min and -4 +/- 3 L/min; peak heart rate, 10 +/- 4 beats/min and -2 +/- 4 beats/min; and peak power output, 20 +/- 6 W and 2 +/- 5 W. Differences between the increases occurring in the exercise group and the changes occurring in the control group were significant (P < 0.05). Among patients in the exercise group, 85% of the increase in peak VO2 occurred by week 12, and 46% of the increase in peak VO2 was caused by the increase in peak heart rate. CONCLUSION: Exercise training does not appear to be contraindicated in patients with compensated heart failure. Exercise training improved exercise tolerance, as measured by increases in peak VO2, exercise duration, and power output. This improved exercise tolerance was caused in part by an increase in peak heart rate.

Cardiorespiratory responses during exercise in competitive in-line skaters.

This study describes the cardiorespiratory responses of 12 male (age = 30 +/- 6 yr) competitive in-line skaters during peak and submaximal skating. We hypothesized that velocities of 22.5 and 27.4 km.h-1 would elicit heart rate (HR) and oxygen consumption (VO2) responses consistent with the American College of Sports Medicine's guidelines for developing cardiorespiratory fitness. Using a 644-m indoor cement course, subjects completed 10 trials comprised of various velocities, stroke frequencies, and body positions. At 22.5 km.h-1, HR and VO2 were 74 and 51% of peak, respectively. At 27.4 km.hr-1, HR and VO2 were 85 and 72% of peak, respectively. When compared to the College's guidelines, regression analysis revealed a leftward shift in the VO2-HR relationship, evidenced by a disproportionately higher HR at a VO2 approximating 60 vs 80% of peak. At 22.5 km.h-1 our skaters self-selected a stroke frequency which resulted in less of an increase in both HR and VO2, when compared to the imposed stroke frequencies of 50 min-1 and 70 min-1. Also, skating at 27.4 km.h-1 in the bent vs upright position resulted in less of an increase in HR and VO2. Competitive in-line skaters are capable of safely skating at velocities sufficient to stimulate an increase in cardiorespiratory fitness. These athletes select a stroke frequency and utilize a body position which results in favorable HR and VO2 responses.