T cells are crucial for the control of cytomegalovirus (CMV) in infected individuals. Although CMV-specific T cells can be quantified by various methods, clear correlates of protection from CMV disease have not been defined. However, responses to the pp65 protein are believed to play an important role. Here, the proportions of interferon γ–producing T cells following ex vivo activation with pools of overlapping peptides representing the pp65 and immediate early (IE)-1 proteins were determined at multiple time points and related to the development of CMV disease in 27 heart and lung transplant recipients. Frequencies of IE-1–specific CD8 T cells above 0.2 and 0.4% at day 0 and 2 wk, respectively, or 0.4% at any time during the first months discriminated patients who did not develop CMV disease from patients at risk, 50–60% of whom developed CMV disease. No similar distinction between risk groups was possible based on pp65-specific CD8 or CD4 T cell responses. Remarkably, CMV disease developed exclusively in patients with a dominant pp65-specific CD8 T cell response. In conclusion, high frequencies of IE-1 but not pp65-specific CD8 T cells correlate with protection from CMV disease. These results have important implications for monitoring T cell responses, adoptive cell therapy, and vaccine design.
Our study establishes a histomorphologic basis for classification and interpretation of angioscopic findings. Yellow plaque color is closely related to degenerated plaque or atheroma and is associated with unstable coronary syndromes.
The ventilatory equivalent for CO2 defines ventilatory efficiency largely independent of metabolism. An impairment of ventilatory efficiency may be caused by an increase in either anatomical or physiological dead space, the latter being the most important mechanism in the hyperpnoea of heart failure, pulmonary embolism, pulmonary hypertension and the former in restrictive lung disease. However, normal values for ventilatory efficiency have not yet been established. We investigated 101 (56 men) healthy volunteers, aged 16-75 years, measuring ventilation and gas exchange at rest (n = 64) and on exercise (modified Naughton protocol, n = 101). Age and sex dependent normal values for ventilatory efficiency at rest defined as the ratio ventilation:carbon dioxide output (VE:VCO2), exercise ventilatory efficiency during exercise, defined as the slope of the linear relationship between ventilation and carbon dioxide output (VE vs VCO2 slope), oxygen uptake at the anaerobic threshold and at maximum (VO2AT, VO2max, respectively) and breathing reserve were established. Ventilatory efficiency at rest was largely independent of age, but was smaller in the men than in the women [VE:VCO2 50.5 (SD 8.8) vs 57.6 (SD 12.6) P < 0.05]. Ventilatory efficiency during exercise declined significantly with age and was smaller in the men than in the women (men: (VE vs VCO2 slope = 0.13 x age + 19.9; women: VE vs VCO2 slope = 0.12 x age + 24.4). The VO2AT and VO2max were 23 (SD 5) and 39 (SD 7) ml O2 x kg x min(-1) in the men and 18 (SD 4) and 32 (SD 7) in the women, respectively, and declined significantly with age. The VO2AT was reached at 58 (SD 9)% VO2max. Breathing reserve at the end of exercise was 41% and was independent of sex and age. It was concluded from this study that ventilatory efficiency as well as peak oxygen uptake are age and sex dependent in adults.
BackgroundRespiratory muscle (RM) function predicts prognosis in non-cachectic patients with chronic heart failure (CHF). We hypothesized that weakness of RM (maximum inspiratory mouth occlusion pressure, Pimax) is a function of body mass index, and that outcome is more a function of BMI than of Pimax or ventilatory drive (P0.1).Subjects and methodsWe enrolled 249 CHF patients (11.2 % female, median age 54.2 years) at the German Heart Institute Berlin. Patients were in NYHA classes I/II/III/IV by n = 16/90/108/35. All patients underwent tests of pulmonary function, RM (Pimax, P0.1), cardiopulmonary exercise testing (peakVO2, VE/VCO2-slope), and right heart catheterization.ResultsMean follow-up time was 18 (1–36) months, 47 patients (18.9 %) died or underwent cardiac assist implantation. Pimax correlated weakly with BMI (r = 0.19), peakVO2 (r = 0.15), and FEV1 (r = 0.34, all p < 0.02), and was lower in females compared to males (3.9 ± 1.7 vs. 6.6 ± 2.7 kPa; p < 0.001). P0.1 correlated with pulmonary pressure (rho = 0.2; p < 0.01) and peakVO2 (rho = −0.14; p < 0.02). Neither Pimax [hazard ratio (HR) 0.98; confidence interval (CI) 0.88–1.08] nor P0.1 (HR 0.52; 0.06–4.6) predicted survival. Multivariate regression analysis revealed gender, BMI, and FEV1 as cofactors of Pimax, with only BMI (HR 0.87; CI 0.80–0.95) predicting survival independently. The lowest quintile in BMI had the worst outcome (log-rank χ² = 13.5, p = 0.009).SummaryIn CHF patients including cachexia and NYHA IV, Pimax does not predict survival. Pimax depends on gender, BMI, FEV1, and peakVO2, with only BMI and peakVO2 predicting survival. The impaired Pimax in CHF might be a result of catabolism and weight loss and is not a predictive factor in itself.
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