AimsPeak oxygen uptake (VO 2 ) is diminished in patients with heart failure with preserved ejection fraction (HFpEF) suggesting impaired cardiac reserve. To test this hypothesis, we assessed the haemodynamic response to exercise in HFpEF patients. Methods and resultsEleven HFpEF patients (73 + 7 years, 7 females/4 males) and 13 healthy controls (70 + 4 years, 6 females/7 males) were studied during submaximal and maximal exercise. The cardiac output (Q c , acetylene rebreathing) response to exercise was determined from linear regression of Q c and VO 2 (Douglas bags) at rest, 30% and 60% of peak VO 2 , and maximal exercise. Peak VO 2 was lower in HFpEF patients than in controls (13.7 + 3.4 vs. 21.6 + 3.6 mL/kg/min; P , 0.001), while indices of cardiac reserve were not statistically different: peak cardiac power output ConclusionContrary to our hypothesis, cardiac reserve is not significantly impaired in well-compensated outpatients with HFpEF. The abnormal haemodynamic response to exercise (decreased peak VO 2 , increased DQ c /DVO 2 slope) is similar to that observed in patients with mitochondrial myopathies, suggesting an element of impaired skeletal muscle oxidative metabolism. This impairment may limit functional capacity by two mechanisms: (i) premature skeletal muscle fatigue and (ii) metabolic signals to increase the cardiac output response to exercise which may be poorly tolerated by a left ventricle with impaired diastolic function.--

Background Sedentary aging has deleterious effects on the cardiovascular system, including decreased left ventricular compliance and distensibility (LVCD). Conversely, Masters level athletes, who train intensively throughout adulthood, retain youthful LVCD. Objectives To test the hypothesis that preservation of LVCD may be possible with moderate lifelong exercise training. Methods Healthy seniors (n = 102) were recruited from predefined populations, screened for lifelong patterns of exercise training, and stratified into 4 groups: “sedentary” (<2 sessions/week); “casual” (2 to 3 sessions/week); “committed” (4 to 5 sessions/week); and “competitive” Masters level athletes (6 to 7 sessions/week). Right heart catheterization and echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion to define LV pressure–volume relationships and Frank-Starling curves. Results Peak oxygen uptake and LV mass increased with escalating doses of lifelong exercise, with little change in systolic function. At baseline, LV distensibility was greater in committed (21%) and competitive (36%) exercisers than in sedentary subjects. Group LV stiffness constants (sedentary: 0.062 ± 0.039; casual: 0.079 ± 0.052; committed: 0.055 ± 0.033; and competitive: 0.035 ± 0.033) revealed 1) increased stiffness in sedentary subjects compared to competitive athletes, whereas lifelong casual exercise had no effect; and 2) greater compliance in committed” exercisers than in sedentary or casual exercisers. Conclusions Low doses of casual, lifelong exercise do not prevent the decreased compliance and distensibility observed with healthy, sedentary aging. In contrast, 4 to 5 exercise sessions/week throughout adulthood prevent most of these age-related changes. As LV stiffening has been implicated in the pathophysiology of many cardiovascular conditions affecting the elderly, this “dose” of exercise training may have important implications for prevention of cardiovascular disease.

Aging results in marked abnormalities of cardiovascular regulation. Regular exercise can improve many of these age-related abnormalities. However, it remains unclear how much exercise is optimal to achieve this improvement or whether the elderly can ever improve autonomic control by exercise training to a degree similar to that observed in healthy young individuals. Ten healthy sedentary seniors [71 +/- 3 (SD) yr] trained for 12 mo; training involved progressive increases in volume and intensity. Static hemodynamics were measured, and R-wave-R-wave interval (RRI), beat-to-beat blood pressure (BP) variability, and transfer function gain between systolic BP and RRI were calculated at baseline and every 3 mo during training. Data were compared with those obtained in 12 Masters athletes (68 +/- 3 yr) and 11 healthy sedentary young individuals (29 +/- 6 yr) at baseline. Additionally, the adaptation of these variables after completion of identical training loads was compared between the seniors and the young. Indexes of RRI variability and baroreflex gain were decreased in the sedentary seniors but preserved in the Masters athletes compared with the young at baseline. With training in the seniors, baroreflex gain and resting BP showed a peak adaptation after moderate doses of training following 3-6 mo. Indexes of RRI variability continued to improve with increasing doses of training and increased to the same magnitude as the young at baseline after heavy doses of training for 12 mo; however, baroreflex gain never achieved values equivalent to the young at baseline, even after a year of training. The magnitude of the adaptation of these variables to identical training loads was similar (no interaction effects of age x training) between the seniors and the young. Thus RRI variability in seniors improves with increasing "dose" of exercise over 1 yr of training. In contrast, more moderate doses of training for 3-6 mo may optimally improve baroreflex sensitivity, associated with a modest hypotensive effect; however, higher doses of training do not lead to greater enhancement of these changes. Seniors retain a similar degree of "trainability" as young subjects for cardiac autonomic function to dynamic exercise.

In 2005, Candida nivariensis, a yeast species genetically related to Candida glabrata, was described following its isolation from three patients in a single Spanish hospital. Between 2005 and 2006, 16 fungal isolates with phenotypic similarities to C. nivariensis were submitted to the United Kingdom Mycology Reference Laboratory for identification. The strains originated from various clinical specimens, including deep, usually sterile sites, from patients at 12 different hospitals in the United Kingdom. PCR amplification and sequencing of the D1D2 and internal transcribed spacer 1 (ITS1) regions of the nuclear ribosomal gene cassette confirmed that these isolates from the United Kingdom are genetically identical to C. nivariensis. Biochemically, C. glabrata and C. nivariensis are distinguished by their differential abilities to assimilate trehalose. However, in contrast to the original published findings, we found that C. glabrata isolates, but not C. nivariensis isolates, are capable of assimilating this substrate. Antifungal susceptibility tests revealed that C. nivariensis isolates are less susceptible than C. glabrata isolates to itraconazole, fluconazole, and voriconazole and to have significantly higher flucytosine MICs than C. glabrata strains. Finally, C. nivariensis could be rapidly distinguished from the other common pathogenic fungus species by pyrosequencing of the ITS2 region. In the light of these data, we believe that C. nivariensis should be regarded as a clinically important emerging pathogenic fungus.

An increased "dose" of endurance exercise training is associated with a greater maximal oxygen uptake (Vo2max), a larger left ventricular (LV) mass, and improved heart rate and blood pressure control. However, the effect of lifelong exercise dose on metabolic and hemodynamic response during exercise has not been previously examined. We performed a cross-sectional study on 101 (69 men) seniors (60 yr and older) focusing on lifelong exercise frequency as an index of exercise dose. These included 27 who had performed ≤ 2 exercise sessions/wk (sedentary), 25 who performed 2-3 sessions/wk (casual), 24 who performed 4-5 sessions/wk (committed) and 25 who performed ≥ 6 sessions/wk plus regular competitions (Masters athletes) over at least the last 25 yr. Oxygen uptake and hemodynamics [cardiac output, stroke volume (SV)] were collected at rest, two levels of steady-state submaximal exercise, and maximal exercise. Doppler ultrasound measures of LV diastolic filling were assessed at rest and during LV loading (saline infusion) to simulate increased LV filling. Body composition, total blood volume, and heart rate recovery after maximal exercise were also examined. Vo2max increased in a dose-dependent manner (P < 0.05). At maximal exercise, cardiac output and SV were largest in committed exercisers and Masters athletes (P < 0.05), while arteriovenous oxygen difference was greater in all trained groups (P < 0.05). At maximal exercise, effective arterial elastance, an index of ventricular-arterial coupling, was lower in committed exercisers and Masters athletes (P < 0.05). Doppler measures of LV filling were not enhanced at any condition, irrespective of lifelong exercise frequency. These data suggest that performing four or more weekly endurance exercise sessions over a lifetime results in significant gains in Vo2max, SV, and heart rate regulation during exercise; however, improved SV regulation during exercise is not coupled with favorable effects on LV filling, even when the heart is fully loaded.

Filamentous fungi and yeasts are increasingly isolated from respiratory secretions of patients with cystic fibrosis (CF), and persistent fungal colonization of the airways of such patients is thought to exacerbate lung damage. While many independent studies have identified Aspergillus fumigatus complex as the principal colonizing fungus in CF, increased awareness of the role of fungi in CF pathology coupled with improved mycological culture and identification methods have resulted in a number of other fungi being isolated and reported from CF sputum samples, including A. terreus, members of the Pseudallescheria boydii/Scedosporium apiospermum complex, Exophiala dermatitidis, Paecilomyces and Penicillium species. However, the range of fungal pathogens isolated and the relative prevalence of individual species vary widely between reports from different geographical CF centres, and as yet no standardized method for the mycological examination of CF sputum samples has been adopted. Here, we examine the potential contribution of the mycological methods employed to examine CF respiratory secretions relative to the variability in the fungal biota reported. The role of direct microscopic examination of respiratory samples and the impact of the culture conditions used on the detection of specific fungal pathogens are addressed, and the potential significance of isolation of yeast species from CF patient airways is discussed.

Rapid identification of yeast isolates from clinical samples is particularly important given their innately variable antifungal susceptibility profiles. We present here an analysis of the utility of PCR amplification and sequence analysis of the hypervariable D1/D2 region of the 26S rRNA gene for the identification of yeast species submitted to the United Kingdom Mycology Reference Laboratory over a 2-year period. A total of 3,033 clinical isolates were received from 2004 to 2006 encompassing 50 different yeast species. While more than 90% of the isolates, corresponding to the most common Candida species, could be identified by using the AUXACOLOR2 yeast identification kit, 153 isolates (5%), comprised of 47 species, could not be identified by using this system and were subjected to molecular identification via 26S rRNA gene sequencing. These isolates included some common species that exhibited atypical biochemical and phenotypic profiles and also many rarer yeast species that are infrequently encountered in the clinical setting. All 47 species requiring molecular identification were unambiguously identified on the basis of D1/D2 sequences, and the molecular identities correlated well with the observed biochemical profiles of the various organisms. Together, our data underscore the utility of molecular techniques as a reference adjunct to conventional methods of yeast identification. Further, we show that PCR amplification and sequencing of the D1/D2 region reliably identifies more than 45 species of clinically significant yeasts and can also potentially identify new pathogenic yeast species.

Candida africana was previously proposed as a new species within the Candida albicans species complex, together with C. albicans and C. dubliniensis, although further phylogenetic analyses better support its status as an unusual variant within C. albicans. Here we show that C. africana can be distinguished from C. albicans and C. dubliniensis by pyrosequencing of a short region of ITS2, and we have evaluated its occurrence in clinical samples by pyrosequencing all presumptive isolates of C. albicans submitted to the Mycology Reference Laboratory over a 9-month period. The C. albicans complex constituted 826/1,839 (44.9%) of yeast isolates received over the study period and included 783 isolates of C. albicans, 28 isolates of C. dubliniensis, and 15 isolates of C. africana. In agreement with previous reports, C. africana was isolated exclusively from genital specimens, in women in the 18-to-35-year age group. Indeed, C. africana constituted 15/251 (6%) of "C. albicans" isolates from female genital specimens during the study period. C. africana isolates were germ tube positive, grew significantly more slowly than C. albicans and C. dubliniensis on conventional mycological media, could be distinguished from the other members of the C. albicans complex by appearance on chromogenic agar, and were incapable of forming chlamydospores. Here we present the detailed evaluation of epidemiological, phenotypic, and clinical features and antifungal susceptibility profiles of United Kingdom isolates of C. africana. Furthermore, we demonstrate that C. africana is significantly less pathogenic than C. albicans and C. dubliniensis in the Galleria mellonella insect systemic infection model.