Effect of environmental and clinical factors on lung function and respiratory symptoms in adolescents with alpha1-antitrypsin deficiency

Individuals identified in the Swedish neonatal alpha1-antitrypsin (AAT) screening study were followed prospectively from their first to their eighteenth year of life. The aim of this study was to analyse the effect of environmental factors, i.e. active and passive smoking, and of clinical factors on lung function and the occurrence of respiratory symptoms in AAT-deficient adolescents. The study group consisted of 88 protease inhibitor (Pi)ZZ and 40 PiSZ adolescents. Medical history including respiratory symptoms, and active and passive smoking were recorded at each follow-up up to the age of 18 y. Lung function tests were performed at the present check-up. At the age of 18 y, both forced expiratory volume in one second (FEV ) and FEV1/vital capacity (VC) were significantly lower in the smoking than in the non-smoking subgroup, and significantly more smokers than non-smokers reported the presence of phlegm. The mean FEV1/VC ratio was lower for those presently exposed to parental smoking. Multiple linear regression analysis indicated that clinical liver disease in early life, active smoking and parental smoking were independent determinants of FEV1/VC. The results suggest that marginal deviations in lung function and the symptom of phlegm among AAT-deficient adolescents occur characteristically early in the subgroup of smokers. Parental smoking may contribute to decreased lung function.     

Acute neurohumoral and cardiovascular effects of idarubicin in leukemia patients

To examine the nature of asthma in the elderly, we compared older (group 1: 65 years or older, n = 50) with younger patients (group 2: <40 years, n = 99) and to determine the influence of long-standing disease, elderly asthmatics with early onset (group A: onset before 40, n = 22) were compared with patients developing symptoms later in their lives (group B: onset after 40, n = 22). Blood eosinophilia and IgE value >/=100 IU/l were more frequent in younger patients. Short symptom-free periods were more frequent among older asthmatics (78.5 vs. 45.4%, p < 0.001). Only 31.2% of older patients had only mild symptoms. Requirement of systemic steroids was higher in the elderly population. The worst FEV1 was lower in older patients (54.4 +/- 17.3 vs. 71.8 +/- 18.5%, p 相似文献   

Bioelectrical impedance analysis of body composition in patients with pulmonary emphysema

In this study we utilized bioelectrical impedance analysis (BIA) to compare the body composition of 36 stable pulmonary emphysema (PE) patients with 19 healthy controls. We compared the PE patients and healthy controls in terms of fat-free mass (FFM) and body fat (BF) as percentages of ideal body weight (FFM/IBW, BF/IBW). FFM/IBW and BF/IBW were significantly lower in the PE patients than in the controls (75.0 +/- 9.8% vs. 85.2 +/- 7.3%, p < 0.001 and 11.8 +/- 6.4% vs. 16.7 +/- 7.7%, p < 0.05, respectively). We divided the PE patients into two subgroups according to FFM, then investigated the relationships between FFM and skeletal muscle strength, and between FFM and respiratory muscle strength. In patients with reduced FFM (FFM < 43.5 kg) grip strength as an index of skeletal muscle strength was significantly lower than in patients without reduced FFM (FFM > or = 43.5 kg) (25.7 +/- 7.8 kg vs. 36.2 +/- 7.2 kg, p < 0.005). As indexes of respiratory muscle strength, maximal expiratory pressure (PEmax) and maximal inspiratory pressure (PImax) were lower in the patients with reduced of FFM, but not to a statistically significant degree (49.6 +/- 20.8 cm H2O vs. 58.7 +/- 23.9 cm H2O and 40.5 +/- 19.2 cm H2O vs. 50.2 +/- 22.1 cm H2O, respectively). In the PE patients, FFM correlated closely with vital capacity (r = 0.528, p < 0.001), forced vital capacity (FVC) (r = 0.531, p < 0.001), FEV1.0 (r = 0.554, p < 0.001), FEV1.0/FVC (r = 0.467, p < 0.005), RV/TLC (r = -0.395, p < 0.05), DLco (r = 0.770, p < 0.001), and DLco/VA (r = 0.622, p < 0.001). However no correlation was observed between BF and any of the measures of lung function. The findings of our study suggest that FFM correlates with skeletal muscle strength, respiratory muscle strength and some measures of lung function in patients with PE, and that assessments of body composition are valuable to their clinical management.     

Pulmonary hemodynamics in the obstructive sleep apnea syndrome. Results in 220 consecutive patients

We have investigated pulmonary hemodynamics in a large series of consecutive, unselected patients with obstructive sleep apnea syndrome (OSAS). The aims of this study were to evaluate the frequency of pulmonary artery hypertension (PH) in OSAS and to analyze, as far as possible, its mechanisms. Two hundred twenty patients were included on the basis of a polysomnographic diagnosis of OSAS (apnea+hypopnea index > 20). PH, defined by a resting mean pulmonary artery mean pressure (PAP) of at least 20 mm Hg, was observed in 37 of 220 patients (17%). Patients with PH differed from the others with regard to pulmonary volumes (vital capacity [VC], FEV1) and the FEV1/VC ratio that were significantly lower (p < 0.001); PaO2 (64.4 +/- 9.3 vs 74.7 +/- 10.1 mm Hg; p < 0.001); PaCO2 (43.8 +/- 5.4 vs 37.6 +/- 3.9 mm Hg; p < 0.001), apnea+hypopnea index (100 +/- 33 vs 74 +/- 32; p < 0.001), and mean nocturnal arterial oxygen saturation (SaO2) (88 +/- 6% vs 94 +/- 2%; p < 0.001). Patients with PH were also more overweight (p < 0.001). Multiple regression analysis showed that 50% of the variance of PAP could be predicted by an equation including PaCO2 (accounting for 32% of the variance), FEV1 (12%), airway resistance (4%), and mean nocturnal SaO2 (2%). In conclusion, PH is observed, in agreement with previous studies, in less than 20% of OSAS patients. PH is strongly linked to the presence of an obstructive (rather than restrictive) ventilatory pattern, hypoxemia, and hypercapnia, and is generally accounted for by an associated obstructive airways disease. In this regard, the severity of OSAS plays only a minor role.     

Cardiac pacing following surgery for acquired heart disease

BACKGROUND: This study is comprised of 3493 consecutive patients who underwent open heart surgery at our institution. Data on all patients were collected prospectively. METHODS: In 45 patients (Group P) (1.3%), a permanent pacemaker (PP) was inserted postoperatively. For the purpose of the study, these patients were compared to 3448 patients (Group NP) who did not require insertion of a PP after surgery. Mean follow-up was 33 months (range 1.5 to 66). RESULTS: We found Group P patients were older (64.8 +/- 11.0 vs 61.0 +/- 11.0 years, p < 0.05), had a higher proportion of elderly (> 70 years) 36% vs 19%, p = 0.01), and of female patients (48.8% vs 22.7%, p < 0.001) compared to Group NP. Group P also had a higher incidence of preoperative rhythm abnormalities (26.6% vs 5.7%, p < 0.0001), redo surgery (13.3% vs 4.6%, p = 0.02), aortic valve surgery (48.8% vs 10.8%, p < 0.001), and tricuspid valve surgery (repair 3, replacement 1) (8.8% vs 0.5%, p < 0.001), in addition to a higher proportion of patients in whom cold (vs warm) blood cardioplegia was used (68.8% vs 52.3%, p = 0.03). Indication for postoperative PP was sick sinus syndrome (SSS) in nine patients; atrial fibrillation in eight patients; atrioventricular block (AVB) in 27 patients; and combined AVB/SSS in 1 patient. There were no operative deaths in Group P. Necessity for PP after heart surgery had a significant impact on resource utilization resulting in prolonged ventilation (3.1 +/- 7.5 vs 1.4 +/- 3.3 days, p < 0.01), intensive care unit (5.1 +/- 10.2 vs 2.5 +/- 4.0 days, p < 0.01), and postoperative hospital stay (18.0 +/- 13.4 vs 8.1 +/- 9.4 days, p < 0.01). CONCLUSIONS: By multivariate logistic regression (odds ratio and p value in parentheses), aortic valve surgery (8.23, p = 0.001), the absence of preoperative sinus rhythm (5.60, p = 0.001), postoperative myocardial infarction (3.46, p = 0.024), and female gender (2.52, p = 0.003), were found to be independent predictors for PP requirement post surgery.     

Risk factors for coronary atherosclerosis. Comparison between two Argentine regions

The prevalence of risk factors for coronary atherosclerosis were studied in two population samples, Northeast (Posadas, n = 498) and South (Viedma, C. Rivadavia and Cipolletti, n = 652) of 20 years and older, males and females. The diet in the Northeast (n = 102) contained more monounsaturated acids and polyunsaturated acids than the one in the South (n = 62), 9.5 +/- 4.1 vs. 8.1 +/- 3.5% TCV (Total Caloric Value) (P < 0.02) and 8.1 +/- 4.1 vs. 6.2 +/- 3.0% TCV (P < 0.001) respectively. The P/S relationship was greater in the Northeast, 1.02 +/- 0.44 vs. 0.85 +/- 0.50 (P < 0.001). Total cholesterol (TC) in the Northeast was less than in the South, in males 176 +/- 41 vs. 213 +/- 43 mg/dl (P < 0.001); CLDL (LDL cholesterol) 109 +/- 37 vs. 141 +/- 41 mg/dl (P < 0.001). The most frequent risk factors in the South vs. Northeast (males) were: TC > or = 240 mg/dl, 26.7% vs. 9.5% (P < 0.001); LDL-C > or = 160 mg/dl, 30.3% vs. 10.9% (P < 0.001); Cig > or = 10/d (equal or more than 10 cigarettes per day), 30.0% vs. 16.4% (P < 0.001). The hypertension prevalence (HTA, 160/95), in males, was higher in the Northeast than in the South, 23.7% vs. 11.5% (P < 0.001). BMI > 27 Kg/m2 was higher in the women of Northeast than in the South, 38.4% vs. 24.2% (P < 0.001). In the males of the Northeast, the combination Cig > or = 10/d and HTA, 4.1 vs 0.9% was more common; in the South Cig > or = 10/d and LDL-C > or = 160 mg/d, 8.2% vs. 1.8% (P < 0.001) was more common. The differences in the prevalence of the risk factors between the population samples indicate the need to plan the prevention of coronary atherosclerosis locally.     

Salmeterol compared with slow-release terbutaline in nocturnal asthma. A multicenter, randomized, double-blind, double-dummy, sequential clinical trial. French Multicenter Study Group

The aim of the multicenter, randomized, double-blind, double-dummy, parallel-group clinical trial with a 2-week treatment period was to compare the efficacy and safety of salmeterol (50 micrograms twice daily) with slow-release (SR) terbutaline (5 mg orally, twice daily) in nocturnal asthma. A total of 159 asthmatic adults (FEV, 50-90% of predicted value; sex ratio: 0.87) with at least two nocturnal awakenings during a 7-d run-in period was included in the study. Patients were centrally randomized with a national computer network (Minitel). The main variable (number of awakening-free nights during the last week of treatment) was analyzed according to a sequential method with the one-sided triangular test. The number of awakening-free nights (+/- SD) was significantly higher in the salmeterol group: 5.3 +/- 2.4 vs 4.6 +/- 2.3 (P = 0.006). Salmeterol was significantly more effective than SR-terbutaline in the following factors: number of patients without any awakening during the last week of treatment (50% vs 27%, P = 0.003), mean morning PEF (351 +/- 109 l/min-1 vs 332 +/- 105 l/min-1, P = 0.04), PEF diurnal variation 6 +/- 10% vs 11 +/- 12%, P = 0.01), overall assessment of efficacy by the patient and the investigator (P = 0.001 and 0.005, respectively), and daily rescue salbutamol intakes (P = 0.004). In the salmeterol group, significantly fewer patients reported adverse events (16% vs 29%, P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up

It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a double-blind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2.4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2.39 +/- 0.02 vs 2.32 +/- 0.02 mmol/l, P = 0.037) and phosphate (0.97 +/- 0.06 vs 0.75 +/- 0.05 mmol/l, P = 0.011) increased and the index of phosphate excretion (0.03 +/- 0.03 vs 0.19 +/- 0.02, P < 0.001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64.8 +/- 11.8 vs 17.4 +/- 1.8 ng/ml, P < 0.001; procollagen type I carboxyterminal propeptide (PICP), 195.3 +/- 26.4 vs 124.0 +/- 15.5 ng/ml, P = 0.026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8.9 +/- 1.2 vs 3.3 +/- 0.5 ng/ml, P < 0.001; urinary hydroxyproline, 0.035 +/- 0.006 vs 0.018 +/- 0.002 mg/100 ml glomerular filtration rate, P = 0.009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306 +/- 45.3 vs 88.7 +/- 22.5 ng/ml, P < 0.001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1.194 +/- 0.058 vs 1.133 +/- 0.046 g/cm2, P = 0.015), femoral neck (1.009 +/- 0.051 vs 0.936 +/- 0.034 g/cm2, P = 0.004), Ward's triangle (0.881 +/- 0.055 vs 0.816 +/- 0.04 g/cm2, P = 0.019) and the trochanteric region (0.869 +/- 0.046 vs 0.801 +/- 0.033 g/cm2, P = 0.005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < -1.0 S.D.) increased more than in those with normal bone mass (lumbar spine 11.5 vs 2.1%, P = 0.030, and femoral neck 9.7 vs 4.2%, P = 0.055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk.     

Additive effect of nitroglycerine inhalation on beta2-agonist-induced bronchodilatation in asthmatics

The current treatment of airway obstruction using beta-agonists and theophylline is designed to increase intracellular level of cAMP. Experimental data show that cGMP and cAMP induce functionally additive relaxation of airways. Nitrates relax smooth muscle through the activation of guanylate cyclase. We wondered whether an additive effect of nitroglycerin (NTG) on beta2-agonist-induced bronchodilatation was present in asthmatic patients. To this aim we evaluated the acute bronchodilating effect of inhaled salbutamol (200 mu g MDI) in 10 asthmatics, pre-treated with inhaled NTG or placebo, in a double-blind cross-over design. FEV1 after NTG was higher than that obtained after placebo (2197 +/- 175 vs. 1981 +/- 155 ml, P <0.001). Mean FEV1 obtained 5 min after salbutamol was higher when patients were pre-treated with NTG than placebo (2694 +/- 217 vs 2440 +/- 228 ml respectively, P <0.001). The bronchodilatation due to salbutamol was identical whether NTG or placebo was inhaled first, respectively at 458 +/- 68 and 497 +/- 44 ml after 5 min. After 15 min FEV1 was higher than baseline, but no significant difference was still present between the value observed after pre-treatment with NTG or placebo (2554 +/- 235 and 2551 +/- 205 ml respectively). In conclusion, in asthmatics nebulized NTG produces a moderate and short-lasting bronchodilatation, which is additive with that produced by salbutamol.     

Changes in the pancreatic and respiratory functions in cystic fibrosis. The influence of the time of the evolution of the disease

BACKGROUND: Cystic fibrosis is the most frequent congenital disease in Caucasian and is transmitted by recessive autosomic inheritance. It is characterized by affection of different glands of exocrine secretion, particularly the pancreas and the lung. The aim of this study was to analyze the degree of alteration of pulmonary and pancreatic exocrine function in a group of patients with cystic fibrosis in relation to the time of disease evolution. METHODS: Twenty-one patients between 9 and 31 years of age were studied; 11 with an evolution of lower than or equal to 158 months and 10 with an evolution of higher than 158 months (median of the total patients). To study pancreatic exocrine function the BT-PABA test immunoreactive serum trypsin test were used. To evaluate respiratory function FEV1, FVC, FEV1/FVC ratio and PaO2 were used. RESULTS: The results obtained demonstrated that in the group with a lower time of evolution the diagnosis had been carried out at earlier ages (17 +/- 17 months versus 84 +/- 60 months; p = 0.002) and presented a significantly more altered pancreatic exocrine function (BT-PABA: 13 +/- 12% versus 35 +/- 23%; p = 0.013). However, respiratory function was altered in the group with longer time of evolution (FEV1: 68 +/- 20% versus 36 +/- 23%; p = 0.003; FVC: 74 +/- 9 versus 52 +/- 25%; p = 0.013; FEV1/FEV: 77 +/- 19 versus 50 +/- 9%; p < 0.001; PaO2: 84 +/- 16 versus 58 +/- 11%; p < 0.001). CONCLUSIONS: Pancreatic exocrine function is most intensely affected in patients diagnosed with cystic fibrosis at earlier and with shorter times of evolution while patients who have the longest time of evolution and who were diagnosed later in life presented greater changes in respiratory function.     

Dyspnoea and exercise intolerance during cardiopulmonary exercise testing in patients with univentricular heart. The effects of chronic hypoxaemia and Fontan procedure

BACKGROUND: Patients with univentricular hearts have decreased exercise tolerance and may demonstrate exertional dyspnoea. It is not known if chronic hypoxaemia exacerbates exercise intolerance and contributes to symptomatic limitation. The extent to which surgical correction of a right-to-left shunt by a Fontan-type procedure can increase exercise tolerance by reducing arterial deoxygenation is not well documented. The cardiopulmonary exercise responses and the symptomatic status in two groups of univentricular patients, those who are cyanotic and those who are acyanotic with Fontan-type circulation, were compared. METHODS AND FINDINGS: Cardiopulmonary exercise testing was performed in 10 univentricular patients with rest or stress-induced cyanosis (age 30.5 +/- 2.3 [SE] years; 5 men) who had palliative or no surgery and eight patients (age 29.4 +/- 1.5 years; 4 men) with Fontan-type circulation. Peak oxygen consumption was comparable in both groups of univentricular patients (21.7 +/- 2.5 vs 21.0 +/- 1.9 ml.kg-1.min-1, P = 0.85) but was less than an age-matched group of 10 healthy subjects (34.7 +/- 1.9 ml.kg-1.min-1, P < 0.001 for both). Arterial oxygen saturation was 90.6% at rest in the cyanotic patients compared with 95.1% in the Fontan patients (P < 0.001) and at peak exercise, 66.2% compared with 90.5% (P < 0.001). Using a modified Borg scale (0-10), the symptoms of dyspnoea and fatigue were also assessed during exercise in the patient groups. The Borg scores for dyspnoea in the cyanotic and the corrected univentricular patients were, respectively, as follows: Stage 1: 0.5 vs 1.7; P= 0.04; Stage 2: 1.8 vs 2.3, P = 0.5; Stage 3: 3.0 vs 3.5, P = 0.7; Peak Exercise: 4.9 vs 4.8, P = 0.9. In addition, the Borg scores for fatigue were: Stage 1: 0.4 vs 1.6, P = 0.08; Stage 2: 2.0 vs 2.2, P = 0.9; Stage 3: 3.0 vs 4.3, P = 0.5; Peak Exercise: 4.9 vs 5.4, P = 0.5. The major limiting symptom at peak exercise was dyspnoea in four cyanotic patients compared with one in the Fontan group (Chi-square 0.982, P > 0.10). The arterial oxygen desaturation at peak exercise in the cyanotic patients limited by dyspnoea was not different from those limited by fatigue (67.5 +/- 10.1% vs 66.7 +/- 13.7%, P = 0.92). Exercise tolerance was also not related to the arterial oxygen saturation at peak exercise (r = 0.47, P = 0.17) in these patients. CONCLUSIONS: Despite correction with Fontan-type surgery, the exercise tolerance and symptoms of these univentricular patients remained similar to those who were cyanosed. Cyanotic patients have adjusted to chronic hypoxaemia and it does not appear to determine the exercise tolerance or the genesis of dyspnoea in these patients. Further randomized prospective studies are required to investigate the long-term benefits of Fontan-type procedures in these patients on exercise tolerance, symptoms and prognosis.     

Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial

STUDY OBJECTIVES: To determine whether obese, apparently healthy individuals experience dyspnea at rest and, if so, whether their pulmonary function test (PFT) profile and maximal respiratory pressures are different from obese, healthy subjects without dyspnea. DESIGN: Prospective, open. SETTING: Pulmonary function test laboratory, Veterans Administration Medical Center. PATIENTS: Twenty-three obese male subjects (each with a body mass index [BMI] of > 28 kg/m2) with an FEV1 level and an FEV1/FVC ratio > or = 80% of predicted and no coexisting conditions. Fifteen complained of dyspnea, where eight denied having it, at rest. MEASUREMENTS AND RESULTS: Standard PFT parameters and maximum static inspiratory (P(Imax)) and expiratory (P(Emax)) mouth pressures were determined. Subjects with dyspnea had similar age and height but larger body weight (113.9+/-5.0 vs 97.4+/-2.6 kg, p = 0.03) and BMI (37.4+/-1.6 vs 31.8+/-0.7 kg/m2, p = 0.02) than subjects without dyspnea, and a greater number of them were current or previous smokers. Forced expiratory flow at 75% vital capacity (54.9+/-6 vs 75.5+/-7% predicted, p = 0.05), maximum voluntary ventilation (MVV; 90.2+/-3.8 vs 107.8+/-9.3% predicted, p = 0.05), and P(Emax) (77+/-2 vs 97.8% predicted, p = 0.007) were significantly reduced in the group of subjects with dyspnea. Large airway function (FVC, FEV1, and FEV1/FVC ratio), lung volumes, and gas exchange parameters were similar between the two groups. CONCLUSIONS: Some obese, but otherwise healthy, individuals experience dyspnea at rest. Reduced P(Emax) and MVV combined with greater body mass and peripheral airway disease are most likely responsible for the sensation of dyspnea in these individuals.     

Differential suppression of dialysis patients' lymphocyte IFN-gamma production by glucocorticoids and cyclosporine

IFN-gamma is a potent pro-inflammatory cytokine involved in the immunologic rejection of transplanted organs. Having previously demonstrated differential suppressive effects of methylprednisolone (MP), prednisolone (P) and cyclosporine (CsA) on dialysis patients' lymphocyte proliferative responses to phytohaemagglutinin (PHA), we studied the effects of these drugs on dialysis patients' lymphocyte IFN-gamma production during mitogenic and allogeneic (MLR) stimulation. The mean +/- SEM 50% inhibitory concentration (ng/ml) on cell proliferation was significantly lower for MP than P in PHA-stimulated haemodialysis (HD) patients' (35 +/- 7 vs 152 +/- 25, P < 0.001) and peritoneal dialysis (PD) patients' (35 +/- 11 vs 134 +/- 33, P = 0.001) cultures and in HD patients' MLR cultures (15 +/- 3 vs 48 +/- 9, P < 0.001). The mean +/- SEM fractional responses (PHA or MLR + drug/PHA or MLR) in culture supernatant IFN-gamma concentrations were significantly lower with 10(-7) M concentrations of MP than P in HD (0.19 +/- 0.05 vs 0.31 +/- 0.06, P = 0.01) and PD (0.30 +/- 0.11 vs 0.46 +/- 0.11, P < 0.05) PHA cultures and in HD MLR cultures (0.15 +/- 0.04 vs 0.28 +/- 0.07, P = 0.01). CsA (400 ng/ml) alone not only caused less than 50% inhibition of IFN-gamma production in 15/27 HD PHA, 6/14 PD PHA and 4/13 HD MLR cultures, but actually stimulated it in 9 HD and 5 PD PHA cultures. The results suggest that: (1) MP has greater immunosuppressive potential than P for renal transplant recipients; (2) the stimulation of IFN-gamma by CsA in some patients could be harmful in patients with initial allograft dysfunction; and (3) pre-transplant in-vitro assessment of recipients' PBMC responsiveness to glucocorticoids and CsA may help individualize the post-transplant immunosuppressive regimen.     

Eosinophil cationic protein in the asthmatic infant: correlation with the clinic and pulmonary function

PATIENTS AND METHODS: Serum eosinophil cationic protein (ECP) was measured in 99 chronic asthmatic patients (51 males and 48 females) with a mean age of 10.59 years and correlated with the number of eosinophils, lung function, symptoms in the last 6 months and clinical scoring (that reflecting the clinical situation during the last 15 days). RESULTS: Serum ECP showed a significant correlation with the total number of eosinophils (p < 0.001, R = 0.44), clinical scoring (p < 0.05, R = 0.26), number of inhaled beta 2-agonist doses needed in the last 15 days (p < 0.05, R = 0.26), forced expiratory volume during 1 second (FEV1; p < 0.01, R = -0.27), forced vital capacity (FVC; p < 0.05, R = -0.23), maximal mid-expiratory flow (FEF25-27; p < 0.001, R = -0.37). However, there was no significant correlation between the total number of eosinophils and the clinical situation of the children or the FEV1, but we found a significant correlation with the FEF25-27. Patients with ECP < 20 had better results on lung function tests than patients with ECP > 20 (FEV1: 108.89 +/- 17.7 vs 100.5 +/- 22 (p < 0.05), FEF25-27: 93.81 +/- 24.4 vs 75.21 +/- 24.5 (p < 0.001). CONCLUSIONS: The findings of this study suggest that the ECP level is a good marker of the situation of asthma in childhood. The levels of ECP will probably be able to help us to evaluate the degree of bronchial inflammation that neither the clinical state nor the lung function define completely.     

Therapy of post-renal transplantation hyperlipidaemia: comparative study with simvastatin and fish oil

BACKGROUND: Recipients of renal transplantation (RT) exhibit disturbances of serum lipids and apoproteins that may contribute to their cardiovascular morbidity and mortality. In our renal transplant department the hypercholesterolaemia prevalence at the first and fifth year of RT is 70.0% and 81.2%, respectively. Lipid-lowering therapy has been utilized in many Transplant Units. The aim of our study was to evaluate post-RT hyperlipidaemia control with simvastatin or fish oil. METHODS: Forty-three RT patients (26 men and 17 women) with persistent hypercholesterolaemia and stable graft function which were resistant to a lipid-lowering diet (American Heart Association Step Two) were randomized into two groups and treated for 3 months with simvastatin (S) (10mg/day; n = 25) and fish oil (F) (6 g/day; n = 18). Total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), lipoprotein a (Lp(a)), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) were monitored and at the study baseline they were similar between the two groups. RESULTS: No side effects were detected after 3 months of therapy. In group S, the concentrations of TC (271 +/- 46 mg% vs 228 +/- 49 mg%; P < 0.001), TG (180 +/- 78 vs 134 +/- 45; P < 0.01), LDL-C (177 +/- 40 vs 144 +/- 43; P < 0.01) and Apo B (96 +/- 18 vs 82 +/- 16; P < 0.001) were significantly reduced, and Apo A1 concentration had increased (135 +/- 24 vs 149 +/- 30; P < 0.01). In group F, the concentrations of TC (266 +/- 25 vs 240 +/- 31; P < 0.001), TG (203 +/- 105 vs 156 +/- 72; P = 0.02) and HDL-C (63 +/- 15 vs 53 +/- 12; P < 0.01) were significantly reduced. CONCLUSIONS: We concluded that low-dose simvastatin and fish oil are both effective and safe in correcting post-RT hyperlipidaemia. Further prospective studies with larger follow-up are needed to clarify whether this therapy has an impact on cardiovascular morbidity and mortality in RT patients.     

Normal phosphate transport in cells from the S2 and S3 segments of Hyp-mouse proximal renal tubules

An intrinsic phosphate (Pi) transport defect in the proximal tubule (PT) presumably underlies X-linked hypophosphatemic rickets. We recently reported normal Pi transport in the S1 segment of the Hyp mouse PT. Whether Pi wasting results from an abnormality in the S2 or S3 segment remains unknown. Thus, we compared Pi transport in S2 and S3 immortalized cells from transgenic (simian virus 40) normal and Hyp mice. These cells display biochemical features of PT cells, including alkaline phosphatase- and hormone- stimulated cAMP activity as well as gluconeogenesis. Moreover, kinetic studies in S2 cells reveal a similar Km[0.26 +/- 0.03 (+/-SEM) vs. 0.22 +/- 0.03 mM] and maximum velocity (Vmax; 5.5 +/- 0.66 vs. 5.9 +/- 0.72 nmol/mg x 5 min) in normal and Hyp mice, respectively. Km and Vmax were also similar in cells from the S3 segment; however, the Vmax values in S3 cells in normal and Hyp mice (2.8 +/- 0.45 and 3.0 +/- 0.56 nmol/mg x 5 min) were reduced in both animal models compared to those in S2 cells (P < 0.001), whereas the Km values in S3 cells from normal and Hyp mice (0.10 +/- 0.02 and 0.11 +/- 0.04 mM) were increased relative to those in S2 cells (P < 0.001). These data indicate that Pi transport throughout the PT of Hyp mice is intrinsically normal. Such observations exclude the presence of a nascent defect in renal Pi transport in the kidneys of Hyp mice and support the hypothesis that a humoral abnormality underlies X-linked hypophosphatemic rickets.     

Effect of age upon airway obstruction and reversibility in adult patients with asthma

OBJECTIVE: In a cross-sectional study we evaluated the effect of aging (separately from that of duration of disease) on airway obstruction and reversibility by comparing two groups of non-smoker patients with asthma. METHODS: We compared two groups of patients: group A, which had 50 subjects (8 men and 42 women) aged 59.7+/-4.6 years (mean +/- SD), and group B, comprised of 51 subjects (19 men and 32 women) who were 35.7+/-7.4 years old. The groups were selected because of comparable baseline degree of obstruction (FEV1 % of predicted, 67.8+/-20.3 in group A; 73.0+/-19.6 in group B, NS) and duration of the disease (14.0+/-11.7 years vs 11.2+/-9.1, NS). Spirometric examination, with a bronchodilator test, was performed and subjects not reaching 85% of predicted were submitted to a 4-week course of inhaled steroids. RESULTS: Although a higher number of subjects from group B responded to the acute bronchodilator test (p < 0.001), the maximum response achievable with treatment (steroid or bronchodilator) (deltaFEV1 expressed as the percent of predicted) was not statistically different between groups (12.0+/-17.5 vs 16.0+/-23.9). The mean FEV1 attainable after treatment (deltaFEV1%PT) was significantly lower in the older group (p = 0.0006). Within groups, the baseline FEV1% did not correlate with age; it was inversely correlated with the duration of the disease (p < 0.03 and p < 0.01, respectively). In both groups deltaFEV1 was inversely related with the baseline FEV1, whereas FEV1%PT was correlated with the duration of the disease, with a slope nearly doubled in group B (p < 0.001). CONCLUSIONS: Both the process of aging and the prolonged exposure to disease effects are important factors in determining the functional characteristics of chronic asthma: In particular, aging is associated not only with a reduced acute responsiveness to bronchodilators, but also with a reduced slope of the duration-FEV1%PT relationship that suggests a slowing of the rate of loss of reversibility of uncertain biological meaning.     

Serial lung function and elastic recoil 2 years after lung volume reduction surgery for emphysema

STUDY OBJECTIVE: To evaluate serial lung function studies, including elastic recoil, in patients with severe emphysema who undergo lung volume reduction surgery (LVRS). To determine mechanism(s) responsible for changes in airflow limitation. METHODS: We studied 12 (10 male) patients aged 68+/-9 years (mean+/-SD) 6 to 12 months prior to and at 6-month intervals for 2 years after thoracoscopic bilateral LVRS for emphysema. RESULTS: At 2 years post-LVRS, relief of dyspnea remained improved in 10 of 12 patients, and partial or full-time oxygen dependency was eliminated in 2 of 7 patients. There was significant reduction in total lung capacity (TLC) compared with pre-LVRS baseline, 7.8+/-0.6 L (mean+/-SEM) (133+/-5% predicted) vs 8.6+/-0.6 L (144+/-5% predicted) (p=0.003); functional residual capacity, 5.6+/-0.5 L (157+/-9% predicted) vs 6.7+/-0.5 L (185+/-10% predicted) (p=0.001); and residual volume, 4.9+/-0.5 L (210+/-16% predicted) vs 6.0+/-0.5 L (260+/-13% predicted) (p=0.000). Increases were noted in FEV1, 0.88+/-0.08 L (37+/-6% predicted) vs 0.72+/-0.05 L (29+/-3% predicted) (p=0.02); diffusing capacity, 8.5+/-1.0 mL/min/mm Hg (43+/-3% predicted) vs 4.2+/-0.7 mL/min/mm Hg (18+/-3% predicted) (p=0.001); static lung elastic recoil pressure at TLC (Pstat), 13.7+/-0.5 cm H2O vs 11.3+/-0.6 cm H2O (p=0.008); and maximum oxygen consumption, 8.7+/-0.8 mL/min/kg vs 6.9+/-1.5 mL/min/kg (p=0.03). Increase in FEV1 correlated with the increase in TLC Pstat/TLC (r=0.75, p=0.03), but not with any baseline parameter. CONCLUSION: Two years post-LVRS, there is variable clinical and physiologic improvement that does not correlate with any baseline parameter. Increased lung elastic recoil appears to be the primary mechanism for improved airflow limitation.     

Electrocardiographic and clinical predictors of torsades de pointes induced by almokalant infusion in patients with chronic atrial fibrillation or flutter: a prospective study

The aim of this study was to identify predictors of torsades de pointes (TdP) in patients with atrial fibrillation (AF) or flutter exposed to the Class III antiarrhythmic drug almokalant. TdP can be caused by drugs that prolong myocardial repolarization. One hundred patients received almokalant infusion during AF (infusion 1) and 62 of the patients during sinus rhythm (SR) on the following day (infusion 2). Thirty-two patients converted to SR. Six patients developed TdP. During AF, T wave alternans was more common prior to infusion (baseline) in patients developing TdP (50% vs 4%, P < 0.01). After 30 minutes of infusion 1, the TdP patients exhibited a longer QT interval (493 +/- 114 vs 443 +/- 54 ms [mean +/- SD], P < 0.01), a larger precordial QT dispersion (50 +/- 74 vs 27 +/- 26 ms, P < 0.05), and a lower T wave amplitude (0.12 +/- 0.21 vs 0.24 +/- 0.16 mV, P < 0.01). After 30 minutes of infusion 2, they exhibited a longer QT interval (672 +/- 26 vs 489 +/- 74 ms, P < 0.001), a larger QT dispersion in precordial (82 +/- 7 vs 54 +/- 52 ms, P < 0.01) and extremity leads (163 +/- 0 vs 40 +/- 34 ms, P < 0.001), and T wave alternans was more common (100% vs 0%, P < 0.001). Risk factors for development of TdP were at baseline: female gender, ventricular extrasystoles, and treatment with diuretics; and, after 30 minutes of infusion: sequential bilateral bundle branch block, ventricular extrasystoles in bigeminy, and a biphasic T wave. Patients developing TdP exhibited early during almokalant infusion a pronounced QT prolongation, increased QT dispersion, and marked morphological T wave changes.