Bronchodilator response to salbutamol after spontaneous recovery from nonspecific bronchial provocation tests in asthma

Assessment of airway responsiveness by bronchoprovocation and bronchodilatation tests is important in the diagnostic work-up protocol of bronchial asthma and it would be convenient to undertake both tests on the same occasion. However, it is not known whether this can be done accurately. Therefore, this study evaluated the effect of a prior bronchial provocation test on the bronchodilator response to salbutamol after spontaneous recovery of the forced expiratory volume in one second (FEV1) in a group of asthmatic subjects. On two separate occasions at the same time of day, concentration-response studies with inhaled histamine or methacholine, or a sham challenge with normal saline were carried out in a blinded, randomized manner. Changes in airway calibre were followed as FEV1 and agonist responsiveness expressed as the provocative concentration causing a 20% fall in FEV1 (PC20). After either spontaneous recovery or a fixed-duration wait of 45 min (when appropriate), the subjects received 2x100 microg of salbutamol from a metered dose inhaler with a spacer. The bronchodilator response to salbutamol was expressed as a percentage of initial FEV1 (deltaFEV1% init). Bronchial challenge with both agonists failed to alter significantly the airway response to salbutamol, with the deltaFEV1% init mean value (range) being 16.9% (9.0-31.9) and 17.5% (11.6-31.2) on the sham and histamine/methacholine challenge day respectively. It was shown that the degree of bronchodilatation achieved after salbutamol 200 microg is not affected by prior bronchoprovocation testing when enough time is allowed for the airways to recover spontaneously to baseline forced expiratory volume in one second. Thus evaluation of airway responsiveness by both bronchial provocation tests and bronchodilator testing can be assessed reliably within a few hours in asthmatic patients.     

Prevalence and correlates of echocardiographic determined left ventricular hypertrophy in 2318 asymptomatic middle-aged men: the ECCIS project. Epidemiolgia e Clinica della Cardiopatia Ischemica Silente

BACKGROUND: Serum levels of eosinophil cationic protein are an indirect measure of airway inflammation in asthma. It is proposed that the extent to which broncho-constriction or airway inflammation contributes to airflow obstruction in acute asthma may determine responsiveness to bronchodilator therapy. OBJECTIVE: To test the hypothesis that subjects with acute asthma exacerbations who respond poorly to inhaled bronchodilator treatment may have more marked airway inflammation than those who respond well to identical therapy. METHODS: Forty-eight asthmatic children who visited the emergency room due to acute exacerbations were studied. Serum levels of eosinophil cationic protein were measured at the time of acute exacerbations and of clinical remissions. At acute exacerbation, FEV1 was assessed before and after the administration of aerosolized salbutamol. RESULTS: The mean serum level of eosinophil cationic protein at acute exacerbation (41.1 +/- 12.8 micrograms/L) was significantly higher (P < .01) than that at clinical remission (30.0 +/- 8.5 micrograms/L) in the study population. The level at acute exacerbation was even higher in group A (n = 18: postbronchodilator FEV1 < 75% predicted) than in group B (n = 30: postbronchodilator FEV1 > or = 75% predicted), whereas both groups showed similar levels at clinical remission. The level at acute exacerbation correlated positively with severity of exacerbation (r = .47, P < .01) and negatively with bronchodilator responses (r = -.56, P < .01). This negative correlation was valid among subjects with a similar degree of exacerbation. CONCLUSION: A higher level of eosinophil cationic protein at acute asthma exacerbation was associated not only with more severe exacerbation but also with a lower degree of bronchodilator responsiveness. This suggests that degree of airway inflammation may be one determinant of degree of responsiveness to initial bronchodilator therapy at acute asthma exacerbation.     

Follicular fluid immunoreactive-inhibin concentrations in relation to follicular diameter and estradiol-17 beta, progesterone and testosterone concentrations in individual ovarian follicles in buffalo, Bubalus bubalis

BACKGROUND: Mycophenolate mofetil reduces episodes of biopsy-proven acute cellular rejection or treatment failure in the first year after kidney transplantation; however, limited data exist regarding the efficacy after lung transplantation. METHODS: In a 2-center, nonrandomized concurrent cohort study (level III evidence), we analyzed the incidence of biopsy-proven acute cellular rejection (International Society for Heart and Lung Transplantation grade > or=A2) and decrement in pulmonary function during the first 12 months after successful lung transplantation. All patients received induction immunosuppression with antithymocyte globulin (< or=5 days' duration), cyclosporine and prednisone, in addition to either mycophenolate mofetil (2.0 g/d) [n=11] or azathioprine (1 to 2 mg/kg per day) [n=11]. RESULTS: During the first 12 months after lung transplantation, the mycophenolate mofetil group experienced significantly fewer episodes of acute cellular rejection than the azathioprine group (0.26+/-0.34 vs 0.72+/-0.43 episodes/100 patient-days [mean+/-SD], p < 0.01; 95% CI for the difference=0.126 to 0.813). The change in forced expiratory volume -1 second [deltaFEV1] (liters) between the 3rd and 12th months after lung transplantation was analyzed for the two treatment groups. For this interval, deltaFEV1 for the mycophenolate mofetil group was +0.158+/-0.497 L vs -0.281+/-0.406 L for the azathioprine group (p < 0.05; 95% CI for difference=+0.0356 to 0.843). During the first year, there was 1 death in each group attributed to bronchiolitis obliterans syndrome with concurrent pneumonia. There were no differences in incidence of cytomegalovirus or bacterial infections between the treatment groups; however, a higher prevalence of aspergillus sp airway colonization in bronchoalveolar lavage fluid was observed for the mycophenolate mofetil group (p < .05). The prevalence of bronchiolitis obliterans syndrome at 12 months was 36% for the azathioprine group vs 18% for the mycophenolate mofetil group (p=NS). CONCLUSIONS: Our preliminary experience with mycophenolate mofetil after lung transplantation suggests a decreased incidence of biopsy-proven acute cellular rejection. Furthermore, less decline in FEV1 after 12 months may suggest a reduced incidence or delayed onset for development of bronchiolitis obliterans syndrome. Prospective randomized trials with low beta error (level I evidence) should be performed to assess the efficacy of mycophenolate mofetil vis-à-vis acute allograft rejection and bronchiolitis obliterans syndrome.     

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   

Role of neutral endopeptidase in exercise-induced bronchoconstriction in asthmatic subjects

The membrane-bound metalloproteinase, neutral endopeptidase (NEP), is a degrading enzyme of both bronchoconstrictor and bronchodilator peptides within the airways. To examine the role of NEP in exercise-induced bronchoconstriction (EIB) in asthmatic subjects, we used inhaled thiorphan, a NEP inhibitor, as pretreatment to a 6-min standardized exercise challenge. Thirteen clinically stable asthmatic subjects participated in this double-blind, placebo-controlled, crossover study that was performed on 2 days separated by 48 h. Thiorphan was administered by two inhalations of 0.5 ml containing 1.25 mg/ml. Subsequently, exercise was performed on a bicycle ergometer at 40-50% of predicted maximal voluntary ventilation while inhaling dry air (20 degrees C, relative humidity 6%). The airway response to exercise was measured by forced expiratory volume in 1 s (FEV1) every 3 min, up to 30 min postexercise challenge, and was expressed both as the maximal percent fall in FEV1 from baseline and as the area under the time-response curve (AUC) (0-30 min). The acute effects of both pretreatments on baseline FEV1 were not different (P > 0.2), neither was there any difference in maximal percent fall in FEV1 between thiorphan and placebo (P > 0.7). However, compared with placebo, thiorphan reduced the AUC by, on average, 26% [AUC (0-30 min, +/-SE): 213.6 +/- 47.7 (thiorphan) and 288.6 +/- 46.0%fall.h (placebo); P = 0.047]. These data indicate that NEP inhibition by thiorphan reduces EIB during the recovery period. This suggests that bronchodilator NEP substrates, such as vasoactive intestinal polypeptide or atrial natriuretic peptide, modulate EIB in patients with asthma.     

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.     

Airways remodeling is a distinctive feature of asthma and is related to severity of disease

PURPOSE: Airways remodeling, evaluated as the subepithelial layer thickness, was compared in asthmatic patients with that of healthy subjects, and was related to clinical grading of disease, presence of atopy, and length of asthmatic history. SUBJECTS AND METHODS: Thirty-four patients with stable asthma (mean age+/-SD: 26.5+/-9.2 years; 10 female) treated with only inhaled beta2-agonists and eight healthy volunteers (mean age+/-SD: 24.6+/-2.5 years; four female) were recruited for the study. Twenty-seven of 34 asthmatics had atopy. Eleven patients had newly diagnosed conditions (duration of disease < or = 1 year), nine patients had long asthmatic history (> 1 year and < or = 10 years), and 14 had prolonged asthmatic history (> 10 years). Bronchial responsiveness to methacholine (M) was expressed as provocative concentration of M causing a 20% fall in FEV1 (PC20) (mg/mL). Degree of asthma severity was assessed using a 0- to 12-point score based on symptoms, bronchodilator use, and daily peak expiratory flow variability over a 3-week period. Bronchoscopy and bronchial biopsy were performed successfully for all subjects; the subepithelial layer thickness, in biopsy samples, was measured from the base of bronchial epithelium to the outer limit of reticular lamina. RESULTS: In asthmatics, baseline FEV1 values (percent of predicted) ranged from 75.7 to 137.0%, and PC20 M ranged from 0.15 to 14.4 mg/mL. According to the asthma severity score, 14 asthmatics were classified as having mild disease, 14 as having moderate disease, and six as having severe disease. The mean values of subepithelial layer thickness were 12.4+/-3.3 microm (range, 6.8 to 22.1 microm) in asthmatics, and 4.4+/-0.5 microm (range, 3.8 to 5.2 microm) in healthy subjects (p<0.001). Subepithelial layer thickness of those with severe asthma differed significantly from that of patients with moderate and mild asthma (16.7+/-3.1 microm vs 12.1+/-2.7 microm and 10.8+/-2.4 microm, p<0.01 and p<0.003, respectively). Moreover, in asthmatics, degree of thickening was positively correlated to asthma severity score (Spearman rank correlation coefficient [rs]=0.581; p<0.001), and negatively correlated with baseline FEV1 (rs=-0.553; p<0.001) and PC20 M (rs=-0.510; p<0.01). No difference was found between degree of thickening observed in atopic asthmatics, compared with that of nonatopic asthmatics, or between degree of thickening in patients with different lengths of asthmatic history. Lastly, multiple regression analysis revealed that asthma severity score was the significant predictive factor for thickness of subepithelial layer. CONCLUSIONS: We confirmed that airways remodeling is a very distinctive and characteristic pathologic finding of asthma. We also demonstrated that it is related to the clinical and functional severity of asthma, but not to atopy or length of asthmatic history.     

Attenuation of neutrophil and endothelial activation by intravenous morphine in patients with acute myocardial infarction

To investigate the effects of morphine on neutrophil and endothelial activation, we measured serum levels of intercellular adhesion molecule-1 (ICAM-1), L-selectin, and neutrophil endopeptidase 24.11 (NEP) in 38 patients with acute myocardial infarction (group 1) and 16 control subjects (group 2). In group 1, all the patients underwent blood sampling at initial presentation and 10 minutes later. Twenty of them had 3 mg of morphine administered intravenously immediately after the first sampling (group 1A) and the other 18 after a second sampling (group 1B). The serum levels of ICAM-1 and L-selectin were both significantly higher in groups 1A and 1B than in group 2. In group 1A, the ICAM-1 decreased significantly at second blood samplings (310 +/- 28 vs 368 +/- 30 ng/ml; p <0.001), whereas in group 1B there was no significant change in ICAM-1 (357 +/- 33 vs 359 +/- 26 ng/ml; p = NS). In group 1A, the L-selectin decreased significantly at second blood samplings (2.3 +/- 1.2 mg/L, p <0.001 vs baseline), whereas in group 1B there was no significant change in L-selectin (3.9 +/- 1.0 mg/L, p = NS vs baseline). There was no significant difference in baseline NEP activities between groups 1A and 1B (4.89 +/- 1.22 vs 5.14 +/- 1.57 nmol/mg protein; p = NS). However, the NEP activities at second blood samplings decreased significantly in group 1A (9.88 +/- 1.86 nmol/mg protein, p <0.001 vs baseline), whereas no significant changes were observed in group 1B (5.09 +/- 1.62 nmol/mg protein, p = NS vs baseline). In conclusion, morphine increased NEP activities and thus attenuated shedding of L-selectin and ICAM-1.     

Measuring hospital performance: are we asking the right questions?

The aim of this randomized cross-over trial was to evaluate the dose effect and systemic absorption of epinephrine nebulized at 2 and 5 mg in comparison with salbutamol (5 mg). Thirteen asthmatic patients (29 +/- 15 years, 4 men and 9 women) were randomly assigned to receive one nebulization of each of the three treatment regimens at 24 h interval. The evaluation concerned forced expiratory volume in 1 second (FEV1), heart rate, respiratory rate and arterial pressure. All measurements were done at baseline, every 15 minutes during the first hour, and hourly thereafter until return to baseline FEV1. Serum potassium was measured at baseline (T0) and sixty minutes after (T60). Plasma levels of epinephrine were measured at T0, T20, T60. Fifteen minutes after the beginning of nebulization FEV1 improved significantly over baseline in the three groups. These changes were similar in the three groups until T45, while FEV1 improvement was significantly greater in A5 and S groups than A2 group (+640 +/- 470 ml, +721 +/- 349 ml, +406 +/- 306 ml in A5, S and A2 groups respectively, p < 0.01). Bronchodilation lasted significantly longer with salbutamol than with epinephrine (p < 0.05). No side effects were recorded in spite of substantial and dose-dependent systemic absorption of epinephrine. CONCLUSION: Increasing epinephrine doses produces greater bronchodilation without additional side effects. However this bronchodilation lasts shorter than with salbutamol.     

Lung epithelial permeability and bronchial responsiveness in subjects with stable asthma

Lung epithelial permeability of asthmatic patients has been reported to be similar or lower than that of healthy subjects and to be correlated or not to bronchial hyperresponsiveness. To clarify these discrepancies, we evaluated 99mTc-DTPA pulmonary clearance in a group of carefully selected asthmatic patients with mild, stable asthma (n = 13; seven women; mean age +/- SD = 27.69 +/- 6.63 years), and compared them with a group of healthy, nonsmoking subjects (n = 8; six women; mean age +/- SD = 24.38 +/- 5.15 years). Selection criteria for asthmatics were as follows: baseline FEV1 > or = 80% of predicted values, no bronchial infections, and/or no asthma attacks during 4 weeks prior to study and peak expiratory flow rate variability lower than 20%, over a period of 3 weeks. Patients controlled symptoms with beta 2-adrenergic drugs only, regularly or on demand. Mean baseline FEV1 (+/-SD) as percent of predicted was 102.38 +/- 13.97 and 112.88 +/- 18.36, respectively (p < 0.05). In the asthmatic group, bronchial responsiveness to methacholine (PC20 M FEV1) ranged between 0.55 and 28.5 mg/mL. Mean value (+/-SD) of DTPA clearance from lungs to blood (evaluated on the first 10 min out of 30 min of the curves) in the asthmatic group was not different from that of control group (68.31 +/- 21.46 and 69.5 +/- 15.73). In the asthmatic patients, there was no correlation between PC20 M values and DTPA T1/2 min of the whole lung, nor between PC20 M and inner and outer lung clearance zones. Moreover, both in asthmatics and healthy subjects, DTPA clearance of outer (alveolar) zones was significantly faster than that of inner (bronchial) zones (57.69 +/- 19.94 vs 102.08 +/- 38.19, p < 0.001, and 59.75 +/- 12.49 vs 103.5 +/- 31.86, p < 0.003, respectively). Our data show that DTPA clearance in patients with stable asthma is similar to that found in healthy subjects; it is not correlated to degree of bronchial responsiveness and occurs more rapidly in the outer zones than in the inner zones, both in asthmatic patients and in healthy subjects. Thus, to date, DTPA clearance index is not a valid tool for identifying and/or monitoring asthmatic patients.     

N-acetylcysteine attenuates endotoxin-induced leukocyte-endothelial cell adhesion and macromolecular leakage in vivo

OBJECTIVE: To determine the influence of N-acetylcysteine on endotoxin-induced leukocyte-endothelial cell adhesion, vascular leakage, and venular microhemodynamics. DESIGN: Randomized, blinded, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Thirty male Wistar rats. INTERVENTIONS: After pretreatment with N-acetylcysteine (150 mg/kg; n = 40; group A) or 0.9% saline solution (n = 10; group B) animals were given an intravenous infusion of endotoxin (Escherichia coli lipopolysaccharide 026:B6; 2 mg/kg/hr) over 120 mins. Animals in the control group (n = 10; group C) received a volume-equivalent infusion of 0.9% saline solution. MEASUREMENTS AND MAIN RESULTS: Leukocyte adherence, red cell velocity (VRBC), vessel diameters, venular wall shear rate, and macromolecular leakage were determined in mesenteric postcapillary venules using in vivo videomicroscopy at baseline and at 30, 50, 90, and 120 mins after the start of the endotoxin challenge. Endotoxin exposure induced a marked increase in adherent leukocytes (group B: baseline, 391 +/- 24 cells/mm2; 120 mins, 1268 +/- 131 cells/mm2; p < .01). N-acetylcysteine pretreatment attenuated the adherence of leukocytes during endotoxemia (baseline, 366 +/- 28 cells/mm2; 120 mins, 636 +/- 49 cells/mm2; p < .01 vs. baseline; p < .01 vs. group B). Leukocyte adherence in control animals (group C) did not increase significantly. Administration of N-acetylcysteine did not influence the decrease in VRBC observed during endotoxemia. In group B1 VRBC decreased during the infusion of endotoxin from 2.0 +/- 0.2 mm/sec at baseline to 1.1 +/- 0.2 mm/ sec after 120 mins (p < .01 vs. baseline; p < .05 vs. group C), and in group A from 2.2 +/- 0.2 mm/sec to 1.1 +/- 0.1 mm/sec after 120 mins (p < .01 vs. baseline; p < .05 vs. group C). In group C, VRBC remained unchanged (baseline, 1.7 +/- 0.2 mm/sec; at 120 mins, 1.5 +/- 0.2 mm/sec). The venular diameters remained unchanged in all groups during the entire study period. After 120 mins, the venular wall shear rate decreased from 502 +/- 62 secs-1 at baseline to 272 +/- 46 sec-1 in group B (p < .01), and from 563 +/- 45 secs-1 at baseline to 283 +/- 31 secs-1 in group A (p < .01). No differences in venular wall shear rate were observed between these groups. In group C, the venular wall shear rate remained unchanged (baseline, 457 +/- 54 secs-1; at 120 mins, 409 +/- 51 secs-1). Macromolecular leakage, expressed as perivenular/intravenular fluorescence intensity after injection of fluorescence-labeled albumin, increased from 0.29 +/- 0.03 to 0.58 +/- 0.03 (p < .01) during the infusion of endotoxin in group B. In contrast, pretreatment with N-acetylcysteine diminished the extravasation of albumin (baseline, 0.27 +/- 0.01; at 120 mins, 0.37 +/- 0.02; p < .01 vs. baseline; p < .01 vs. group B). CONCLUSION: These results demonstrate that N-acetylcysteine attenuates endotoxin-induced alterations in leukocyte-endothelial cell adhesion and macromolecular leakage, suggesting N-acetylcysteine might be therapeutic in the prevention of endothelial damage in sepsis.     

Lack of correlation between bronchoconstrictor response and bronchodilator response in a population-based study

Bronchodilator and bronchoconstrictor responsiveness have been considered physiological opposites in patients with obstructive airways disease. Provocation challenges have been replaced by bronchodilator tests in the assessment of cases of severe airways obstruction. The aim of this study was to examine the relationship between bronchoconstrictor and bronchodilator responsiveness, and their supposed interchangeability, in a general population. From the Vlagtwedde-Vlaardingen follow-up study, 101 adults were recruited (mean (SD) age 55 (11) yrs, 67 males and 34 females, and 31 were smokers). All completed a questionnaire on airways symptoms. Bronchoconstrictor and bronchodilator responsiveness were assessed with cumulative dose-response curves, using histamine and terbutaline, respectively. Thus, it was possible to relate histamine sensitivity of the airways (the concentration of histamine, at which forced expiratory volume in one second (FEV1) falls by 10% (PC10)) to the maximal bronchodilator response (delta FEV1) and the sensitivity to the bronchodilator (cumulative dose of inhaled terbutaline at which FEV1 increases by 10% (RD10)). Subjects with a bronchoconstrictor response (PC10 < or = 16 mg x mL(-1); n=38) had more respiratory symptoms than those without (n=63) (40 versus 21%) and also lower baseline FEV1 values (90 versus 96% predicted), but had comparable bronchodilator responsiveness. Subjects with a bronchodilator response (delta FEV1 > or = 9% of the predicted value; n=13) did not differ from those without (n=88) for all parameters, including symptoms, allergy and pulmonary function. In those with a bronchoconstrictor response, there was a weak but significant correlation between the PC10 and RD10 (rho=-0.32), but not between PC10 and delta FEV1. This study suggests that bronchoconstrictor and bronchodilator responsiveness are not highly correlated, even in subjects with airways obstruction. Symptoms were associated with the presence of a bronchoconstrictor, but not a bronchodilator, response. We conclude that bronchoconstrictor and bronchodilator responsiveness are two different phenotypic markers that are not interchangeable in epidemiological studies.     

Countertransference in the nurse-patient relationship: a review of the literature

The connection between lipids and the rate of progression of chronic renal disease was retrospectively examined in 70 patients who were divided into 2 groups according to their baseline creatinine clearance (CCr): Group 1 (Gp1) contained 30 patients with CCr 60-40 mL/min followed for 40.0 +/- 13.3 months; Group 2 (G2) contained 40 patients with CCr 39-15 mL/min followed for 39.0 +/- 18.2 months. The following parameters were considered: basal and final CCr proteinuria per unit of CCr (UProt/CCr); the difference between final and basal UProt/CCr (delta UProt/CCr); the change in CCr/month (delta CCr); baseline triglycerides (TG), total (TC), HDL (HDLC) and LDL (LDLC) cholesterol, Apo AI, Apo B, Lp(a). Besides in basal CCr the 2 groups significantly differed in the final CCr, final UProt/CCr, delta UProt/CCr, delta CCr. No differences were observed concerning lipid parameters except for Lp(a) (G1 14.8 +/- 13.6, G2 28.7 +/- 27.4 mg/dL; p < 0.05). Baseline TG (G1 184.1 +/- 61.3, G2 187.5 +/- 72.1 mg/dL) and Apo B (only G2 1.05 +/- 0.32 g/L) were significantly higher than normal subjects and the Apo AI/Apo B ratio (G1 1.42 +/- 0.43, G2 1.33 +/- 0.45) were significantly lower than in normal subjects. delta CCr, while inversely correlated in both groups with delta UProt/CCr (p < 0.01), only in G2 did it correlate directly with the Apo AI/Apo B ratio (p < 0.05) and inversely with Apo B and LDLC (p < 0.05). Although a correlation between Lp(a) and delta CCr was not found, 20/22 patients (3/5 G1, 17/17 G2) with a level > 30 mg% ran a progressive course. A natural progression of CRI, heralded by an increasing UProt, is highly frequent when baseline CCr is < 40 mL/min; only then lipids seem to add a burden to the renal damage.     

Accelerated lung function decline in swine confinement workers

We conducted a longitudinal study to determine the annual rate decline in pulmonary function measurements in male swine confinement workers. For comparison, a grain farming group and a nonfarming rural-dwelling control group were also chosen for the longitudinal study. Two hundred seventeen swine confinement workers, 218 grain farmers, and 179 nonfarming control subjects had valid pulmonary function measurements at the baseline observation conducted in 1990 to 1991 and at the second observation conducted in 1994 to 1995. The swine confinement workers were younger (mean age=38.3+/-11.7 [SD] years) than the nonfarming control subjects (42.6+/-10.4 years) and the grain farmers (44.5+/-11.9 years). When stratified by age, nonfarming control subjects had the lowest mean annual rate decline in FEV1 and FVC in all age categories. The swine confinement workers had the largest annual rate decline in FEV1 and FVC, and this was most obvious in the middle age categories. After controlling for age, height, smoking, and baseline pulmonary function, swine confinement workers had excess annual decline of 26.1 mL in FEV1 (p=0.0005), 33.5 mL in FVC (p=0.0002), and 42.0 mL/s in forced expiratory flow between 25% and 75% of FVC (FEF[25-75%]) (p=0.02) over nonfarming control subjects. Grain farmers had excess annual decline of 16.4 mL in FEV1 (p=0.03), 26.7 mL in FVC (p=0.002), and 11.2 mL/s in FEF(25-75%) (p=0.38) over control subjects. These findings suggest that workers engaged in the swine industry and grain farmers appear prone to accelerated yearly losses in lung function and may therefore be at risk for the future development of chronic airflow limitation.     

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.     

QRS prolongation measured by a new computerized method: a sensitive marker for detecting exercise-induced ischemia

This study compared thallium stress testing and exercise changes in QRS duration using a computerized 'optic scanner' in three groups. Group 1 consisted of 108 subjects with positive exercise ECG tests by ST-T segment criteria and with proven coronary artery disease. Group 2 included 19 subjects with nondiagnostic exercise ECG ST-T changes and with proven coronary artery disease. Group 3 was formed by 38 healthy controls. Group 1: Mean increase in exercise QRS width of 12.4 +/- 14 ms. Group 3: Mean decrease in exercise QRS width of 4.9 +/- 9.3 ms (p < 0.0001). Group 2: Mean QRS prolongation of 7.8 +/- 9.2 ms, which was significantly different from the controls (p < 0.0001) but not from group 1. When compared to thallium stress testing, exercise QRS prolongation had a sensitivity of 93%, specificity of 71%, relative risk of 5, and positive predictive value of 86%. QRS duration measurement can improve the diagnostic accuracy of the exercise ECG stress test.     

Presyncope during progressive hypovolaemia simulated by lower body negative pressure is not prevented by high-dose naloxone

STUDY OBJECTIVE: We set the hypothesis that follow-up surveys of occupational asthma (OA) could now show better improvement in the asthmatic condition because of a more prolonged interval since removal from exposure than in previously reported studies. PATIENTS/METHODS: Ninety-nine subjects with OA were assessed and were separated into two groups according to the duration of cessation of exposure: (1) group removed for > or = 5 years: 48 subjects studied 8.9+/-2.2 years after cessation of exposure; (2) group removed for <5 years: 51 subjects with OA, comparable in terms of history and functional results at time of diagnosis, with a time lapse from last exposure of 3.1+/-1.2 years. On the follow-up visit, questionnaires including information on the current and previous use of inhaled steroids, spirometry, and methacholine tests were administered and results were compared with those obtained at the time of diagnosis. RESULTS: At the follow-up visit, no significant changes in spirometry were observed in the two groups. However, a significant improvement in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) from a mean value of 1.5 to 3.7 mg/mL was documented (p<0.001). The proportion of subjects having normal PC20 at the follow-up visit was significantly higher in the group removed from exposure for >5 years than in the group removed for < or = 5 years (16/33 vs 8/42; p=0.01). Stepwise logistic regression showed that follow-up PC20 could be predicted from baseline PC20 (p<0.001, odds ratio [OR]=4.1, 95% confidence interval [CI]=1.8 to 9.1), duration of exposure (p=0.04, OR=0.9, 95% CI=0.8 to 1.0), the interval since removal from exposure (p=0.002, OR=1.7, 95% CI=1.2 to 2.5), and the type of agent; subjects with OA due to high-molecular-weight agent showed a less favorable outcome (p=0.04, OR=0.2, 95% CI=0.03 to 1.0). Current and past treatments with inhaled steroids were not significant predictors. CONCLUSION: Results obtained in the group of this study removed for >5 years show better prognostic figures than those reported in most previous studies. Comparison with the group removed for a shorter interval and the stepwise logistic regression analysis suggest that the longer duration of the interval from cessation of exposure appears to be a factor determining this difference.     

Molecular and immunopathology studies of oncogenes and tumor-suppressor genes in bladder cancer

The aim of the study was to evaluate glucose tolerance, B cell secretion and hepatic clearance of insulin during the process of aging. 100 subjects of both sexes, in age range of 17 to 92 years and with BMI < 27 kg/m2 were studied. All subjects were divided in 4 groups according to age: 18 patients were in age from 17 to 59 years (group I--mean 46 +/- 12 (SD) years, 23 patients in age from 60 to 69 years (group II--mean 64 +/- 3 years), 33 patients in age from 70 to 79 years (group III--mean 75 +/- 3 years), 26 patients in age from 80 to 92 years (group IV--mean 84 +/- 4 years). In all participants oral glucose tolerance test (75 g) and the i.v. glucagon test (1 mg) were carried out and blood glucose, serum insulin (IRI) and C-peptide (CP) were measured. Hepatic clearance of insulin was calculated from the serum CP/IRI ratio. With advanced age the increase in fasting glycaemia (group I 4.25 +/- 0.6, group IV 4.7 +/- 0.5 mM, p = 0.02) and after applied stimuli, and a decrease in fasting (group I 0.6 +/- 0.2, group IV 0.35 +/- 0.13 nM, p < 0.05) and stimulated serum CP with no differences in serum IRI concentrations between groups was observed. Consequently the serum CP/IRI ratio decreased from 10 +/- 3.8 in group I to 5.4 +/- 1.7 in group IV (p < 0.05) indicating reduced insulin clearance in liver, probably as a compensatory adaptation to the deterioration of B cell secretory activity.     

Limited myocardial contractile reserve and chronotropic incompetence in patients with chronic Chagas' disease: assessment by dobutamine stress echocardiography

OBJECTIVES: To determine whether dobutamine stimulation in patients with Chagas' disease may uncover abnormal contractile responses as seen in ischemic myocardium. BACKGROUND: Segmental left ventricular (LV) dysfunction in the absence of coronary atherosclerosis is frequently seen in patients with chronic Chagas' heart disease. Myocardial ischemia and coronary microcirculation abnormalities have been found in animal models and in humans with Chagas' disease. In addition, chagasic sera may contain autoantibodies against human beta-adrenergic receptors. METHODS: Two groups of patients with Chagas' disease were studied by echocardiography: group 1 (n = 12) without and group 2 (n = 14) with LV segmental wall motion abnormalities (mostly apical aneurysm). Ten normal subjects served as control subjects. We performed qualitative assessment of wall motion and quantitative evaluation of LV cavity under baseline conditions and after dobutamine stimulation. RESULTS: Patients with Chagas' disease exhibited a blunted inotropic and chronotropic response to dobutamine stimulation. After dobutamine, fractional area change in Chagas' group 1 (54.7+/-6.6%; SD) and in group 2 (35.1+/-12.1%) were significantly lower than control group (66.7+/-2.5%; p < 0.001). In addition, in 6 of 14 group 2 patients, dobutamine induced a biphasic response with improvement at low dose and deterioration at peak dose, as seen in patients with coronary artery disease. Although the three groups had similar basal mean heart rates and attained a similar mean peak dobutamine doses, both groups of patients with Chagas' disease had a significantly blunted mean heart rate effect after dobutamine (p < 0.0001). CONCLUSIONS: Thus, dobutamine stimulation unmasks a chronotropic incompetence and a blunted myocardial contractile response in chagasic patients, even in those with no overt manifestation of heart disease.     

FK 506 'rescue' immunosuppression for obliterative bronchiolitis after lung transplantation

PRELIMINARY EXPERIENCE: In a consecutive case series (level V evidence) involving 10 recipients of unilateral lung transplantation (LT) with bronchiolitis obliterans, in conjunction with Fujisawa protocol 93-0-003, the physiologic responses to FK 506 (tacrolimus) "rescue" immunosuppression were assessed. Recipients were 22+/-18 months post-LT and demonstrated progressive allograft dysfunction that was refractory to pulsed-dose methylprednisolone therapy. All recipients received induction immunosuppression with Minnesota antilymphocyte globulin (10 to 15 mg/kg/d) for 5 to 10 days, cyclosporine (CsA) (whole-blood Abbott TDX fluorescence polarization immunoassay (Abbott Inc, Abbott Park, IL)=600 to 800 ng/mL), azathioprine (2 mg/kg/d), and prednisone (tapered to 0.2 mg/kg/d). The "rescue" regimen consisted of oral FK 506 adjusted to maintain a whole-blood Abbott IMX microparticle enzyme immunoassay (Abbott Inc, Abbott Park, IL) of 10 to 15 ng/mL with an initial increase in prednisone (1.0 mg/kg/d) during conversion that was subsequently tapered to 0.2 mg/kg/d. Spirometry was performed monthly in accordance with accepted American Thoracic Society criteria. Recipients were classified in accordance with the International Society for Heart and Lung Transplantation (ISHLT) "Working Formulation for Standardization of Nomenclature and for Clinical Staging of Chronic Dysfunction in Lung Allografts" as stages Ib (n=2), IIb (n=4), and IIIb (n=4) upon entry to the protocol. The deltaFEV1/month relationships during CsA- and FK 506-based regimens were analyzed by linear regression and compared by signed rank test (p<0.05). RESULTS: The deltaFEV1/month slopes were -0.0687+/-0.0221 and +0.0300+/-0.033 L/mo (mean+/-SEM) for CsA and FK 506, respectively (p=0.037). Although no significant spirometric improvement was noted in most recipients, no further decline in FEV1 occurred after conversion to FK 506. Recipients with less severe chronic dysfunction (ie, obliterative bronchiolitis [OB] stages Ib and IIb) stabilized their spirometric indexes at higher levels. Two recipients with OB stage IIIb died of hypercapnic respiratory failure at 6 and 8 months after conversion. CONCLUSIONS: The deltaFEV1/mo slopes stabilized after FK 506 conversion. Earlier conversion may be beneficial in stabilizing FEV1 at a higher plateau. Significant economic impact may be anticipated with FK 506 compared to alternative cytolytic strategies for OB. However, multicenter prospective controlled investigations are necessary to further address the potential role of FK 506 after LT (level I evidence). Furthermore, the ISHLT "Staging of OB Syndrome" may have significant clinical implications vis-à-vis prognosis and potential therapies.