Resting respiratory variables and exercise capacity in adult patients with cystic fibrosis.

INTRODUCTION: Cystic fibrosis (CF) is the most common life-limiting, recessively inherited disease in the white population, associated with significantly high morbidity and mortality rates; CF pulmonary disease, assessed by pulmonary function tests, arterial blood gases and the Schwachman score, remains the most prevalent in terms of morbidity in the adult CF population. OBJECTIVES: The aim of the present study was to evaluate the relationship between resting respiratory variables and exercise capacity in adult patients with CF. RESULTS: Study investigations undertaken in 18 CF patients and 11 healthy volunteers showed that among the resting lung function parameters, inspiratory capacity (IC) at rest was the only significant predictor of VO(2) peak (r=0.67, p<0.007) and VO(2)/t-slope (r=0.86, p<0.0001). The percentage of predicted FEV(1) in adult CF patients was 77+/-33% pred. vs 104+/-16% pred. in healthy subjects (p<0.006); the corresponding percentage of IC at rest was 82+/-36% pred. in patients vs 116+/-20% pred. in healthy (p<0.003). CF patients presented with a significantly prolonged rapid breathing after exercise (32br per minute at recovery for CF vs 22 for healthy; p<0.001), as well as a shortened inspiratory time. CONCLUSION: Adult patients with CF show a limited exercise capacity with lower peak oxygen consumption and prolonged oxygen kinetics. Interestingly, decreased IC qualified as the only significant predictor of exercise capacity in our study.

Leptin alterations in the course of sepsis in humans.

Neuroendocrine response to sepsis may be divided into acute and prolonged phase. As leptin is implicated in the stress response, leptin's profile during both phases, and the possible relationships between leptin and the neuroendocrine response to sepsis were investigated. Thirty adult patients with sepsis in an intensive care unit were studied. Blood samples were collected at the acute and the prolonged phases. In acute sepsis, leptin levels were higher in patients than in controls (10.2 +/- 2.5 vs. 4.1 +/- 1.2 ng/ml, p =0.01) and correlated positively with insulin levels and insulin resistance. A decline in leptin levels was found during prolonged sepsis (from 10.2 +/- 2.5 to 6.2 +/- 1.7 ng/ml, p=0.001), which was not related to survival (p=0.913). At the onset of sepsis, leptin levels increased in correlation with insulin and insulin resistance, possibly indicating a cause-effect relationship. However, the decline in leptin levels during the prolonged phase of sepsis was not related either to survival or to metabolic and hormonal changes.

Exercise-induced flow limitation, dynamic hyperinflation and exercise capacity in patients with bronchial asthma.

It is known that, in stable asthmatics at rest, tidal expiratory flow limitation (EFL) and dynamic hyperinflation (DH) are seldom present. This study investigated whether stable asthmatics develop tidal EFL and DH during exercise with concurrent limitation of maximal exercise work rate (WRmax). A total of 20 asthmatics in a stable condition and aged 32+/-13 yrs (mean+/-SD) with a forced expiratory volume in one second (FEV1) of 101+/-21% of the predicted value were studied. Only three patients exhibited an FEV1 below the normal limits. On a first visit, patients performed a symptom-limited incremental (20 W.min(-1)) bicycle exercise test. On the second visit, the occurrence of EFL (using the negative expiratory pressure technique) and DH (via reduction in inspiratory capacity) were assessed at rest and when cycling at 33, 66 and 90% of their predetermined WRmax. FEV1 was measured to detect exercise-induced asthma, 5 and 15 min after stopping exercise at 90% WRmax. Only one patient showed EFL at rest, whereas 13 showed EFL and DH during exercise. In these 13 asthmatics, exercise capacity was significantly reduced (WRmax 75+/-9% pred) compared to the seven non-EFL patients (WRmax 95+/-13% pred). Moreover, a significant correlation of WRmax (% pred) to the change in inspiratory capacity (percentage of resting value) from rest to 90% WRmax was found. Tidal EFL during exercise was not associated with exercise-induced asthma, which was detected in only three patients. In conclusion, tidal expiratory flow limitation and dynamic hyperinflation during exercise are common in stable asthmatics with normal spirometric results and without exercise-induced asthma, and may contribute to reduction in exercise capacity.

Dynamic hyperinflation and tolerance to interval exercise in patients with advanced COPD.

Dynamic hyperinflation (DH) contributes importantly to the limitation of constant-load exercise (CLE) in patients with chronic obstructive pulmonary disease (COPD). However, its role in the limitation of interval exercise (IE) remains to be explored. The change (Delta) in inspiratory capacity (IC) was measured to reflect changes in DH in 27 COPD patients (forced expiratory volume in one second mean+/-SEM % predicted: 40+/-3) at the end of a symptom-limited CLE test at 80% of peak work capacity (WRmax) and an IE test at 100% WRmax (30 s of work, alternated with 30 s of unloaded pedalling). At the limit of tolerance in both IE and CLE, patients exhibited similar DH (DeltaIC: 0.39+/-0.05 L and 0.45+/-0.05 L, respectively). However, exercise endurance time (t end) for IE (32.7+/-3.0 min) was significantly greater than for CLE (10.3+/-1.6 min). The IE t end correlated with resting IC, expressed as % pred normal. At 30 and 90% of total IE t end, DeltaIC (0.43+/-0.06 and 0.39+/-0.05 L, respectively) and minute ventilation (31.1+/-1.6 and 32.7+/-2.2 L.min(-1), respectively) were not significantly different. Resting hyperinflation helps to explain the limitation of interval exercise. Implementation of interval exercise for rehabilitation should provide important clinical benefits because it prolongs exercise endurance time and allows sustaining higher stable ventilation.

Numerical aberrations of chromosomes 9 and 11 detected by FISH in Greek bladder cancer patients.

BACKGROUND: Bladder cancer is a genetically heterogeneous disease. The chromosomal aberrations observed are non-random and they are often correlated with disease progression. Several environmental risk factors have also been reported to be implicated in the pathogenesis of this disease. The aim of this study was to evaluate, by FISH technique, the numerical aberrations of chromosomes 9 and 11 in Greek bladder cancer patients and to correlate them with grade and histological stage of the tumors. MATERIALS AND METHODS: FISH with a-satellite DNA probes specific for chromosomes 9 and 11 were applied to 35 primary bladder tumors directly processed for cytogenetic study. RESULTS: Numerical aberrations of chromosome 9 were observed in 23 out of 27 tumors (85.18%). Monosomy 9 was detected in 12 cases (44.45%) and polysomy in 11 cases (40.74%). Statistical analysis showed that polysomy 9 was linked to histological stage (p = 0.024) and grade (p = 0.01) of the tumors, while monosomy 9 was correlated with tumor stage (p = 0.050). Numerical aberrations of chromosome 11 were observed in 25 out of 35 cases (71.43%). Polysomy was detected in 24 cases (68.57%), while only one case (2.86%) had monosomy 11. Polysomy 11 was found mainly in high-grade and advanced-stage tumors. CONCLUSION: Numerical aberrations of chromosome 9 could be a potential biomarker for bladder cancer screening. Further studies must be carried out to investigate gene alterations reflected by numerical aberrations of chromosomes 9 and 11 also contributing to the classification of this disease.

Cytogenetic data as a prognostic factor in multiple myeloma patients: involvement of 1p12 region an adverse prognostic factor.

BACKGROUND: Multiple myeloma (MM) is charecterized by great clinical heterogeneity. Among known prognostic factors the cytogenetic abnormalities are thought to be of major importance. The aim of this study was to correlate certain chromosomal abnormalities with immunoglobulin isotype and survival in MM patients. PATIENTS AND METHODS: Forty-nine Greek MM patients, homogeneously treated with conventional-dose chemotherapy, were cytogenetically studied by direct culture of bone marrow cells and G-banding technique. RESULTS: Twenty-four patients had a normal karyotype while the remaining 25 patients presented numerical and structural abnormalities. Recurrent structural abnormalities were observed. Translocations involving the 14q32 region were observed in 8 cases, while 6 cases exhibited a del(1)(p12). We confirmed the negative impact of chromosomal abnormalities on the overall survival of MM patients and we also showed that t(11;14) had a worse impact on disease outcome as compared to t(14q32) with an unidentified partner chromosome. The presence of del(1) (p12) significantly worsened the prognosis in MM patients. No correlations existed between the association of immunoglobulin isotype with survival or certain chromosomal changes. CONCLUSION: Further studies are indicated at the molecular level to clarify the exact role and the prognostic value of 1p12 involvement in MM patients.

Respiratory muscles and weaning failure.

Weaning failure is, unfortunately, a rather common phenomenon for mechanically-ventilated patients (especially those with chronic obstructive pulmonary disease (COPD)), and the respiratory muscles play a pivotal role in its development. Weaning fails whenever an imbalance exists between the ventilatory needs and the neurocardiorespiratory capacity. This can happen if there is an increase in the energy demands of the respiratory muscles, a decrease in the energy available, a decrease in neuromuscular competence, or if the respiratory muscles pose an impediment to the heart and blood flow. The imbalance created will lead to weaning failure through the development of respiratory muscle fatigue, hypercapnia, dyspnoea, anxiety and organ dysfunction.