Analysis of quality of life before and after heart transplantation.
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Biomedical subjects
Publications and source records attributed to S Valente.
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This phase II study was designed to verify the activity and safety of an intensive epirubicin/ifosfamide schedule in untreated soft tissue sarcoma (STS) patients by using both the agents at the identified maximal tolerated doses. 39 adult patients were treated with epirubicin at 55 mg/m2, on days 1 and 2 (total dose per cycle 110 mg/m2) combined with ifosfamide at 2.5 g/m2 days 1-4 (total dose per cycle 10 g/m2), with equidose mesna uroprotection and G-CSF support. Treatment was given on an ambulatory basis, at 3-week intervals. The overall objective response (OR) rate was 59% (95% confidence interval, CI, 43-72%), with 5 complete responses (13%) at 18 partial responses (46%); 12 partial responders were rendered disease-free following surgery. The median survival time was 19 months, being 23 and 13 months, respectively, for responding and non-responding patients. The median time to response was 40 days (range 21-60). Treatment-related toxicity was overall acceptable. The OR of 59% was the highest ever reported in our consecutive studies in advanced STS, confirming that improved therapeutic efficacy can be obtained with intensified regimens in such a disease; both the response duration and survival were also longer. The observed activity proved to be interesting with regard to the high response rate in the lung (86%), as well as the proportion of patients rendered disease-free by early surgery after the achievement of a partial response (55%). Both these findings may be important in the multimodality approach to patients with lesions potentially resectable for cure.
Epidermal growth factor (EGF) has been detected by radioimmunoassay (RIA) in different body fluids such as serum, amniotic fluid, and urine. Human tumor tissues with EGF receptors (EGF-Rc) may be saturated with EGF, which may be of prognostic value. An RIA was envisaged to measure human epidermal growth factor (hEGF) levels using EGF-Rc as capture agent and a monoclonal antibody anti-hEGF (MAb anti-hEGF) labeled with 125Iodine as a marker for this binding. The purpose of this work was to study the feasibility of MAb anti-hEGF to detect the receptor binding sites and to investigate the interaction between MAb anti-hEGF and the EGF-Rc. Various binding experiments were performed to study possible interference and interactions in the complex MAb anti-hEGF and the receptor. Affinity constants were determined by means of Scatchard plot analysis to interpret the complex stability challenged with other compounds for a better understanding of the interaction process. Binding constants were of the same order for all the ligands tested separately involving the EGF-Rc, but were significantly higher (t = 15.7, p < 0.05) for hEGF in its binding to MAb anti-hEGF. It was possible with equilibrium studies and competition experiments to evaluate the interaction of EGF and MAb anti-hEGF with the EGF receptor. This observation makes the MAb anti-hEGF a potential tracer for the quantitation of receptors in vitro, and possibly for the detection of membrane receptors on tumor cells in vivo.
AIMS: Three cases of chronic periapical periodontitis including focal areas with malakoplakia changes are reported. METHODS AND RESULTS: These areas included both von Hansemann-type macrophages and periodic acid-Schiff-positive, iron- and calcium-containing concretions. Some concretions corresponded to spherules with a targetoid configuration, thus fitting the morphological criteria for classical Michaelis-Gutmann bodies. CONCLUSION: The vast majority of the cases of malakoplakia that have been reported in the literature corresponded to a characteristic, fairly homogeneous lesion, but a few instances of focal malakoplakia have been described in various chronic conditions. These considerations support the opinion that the local conditions for the production of Michaelis-Gutmann bodies may occur focally in diseases characterized by macrophage accumulation.
Static and dynamic lung volumes, arterial blood gases, alveolar ventilation and ventilation-perfusion (VA/Q) relationships were studied in 14 mild asthmatic patients and in 7 normal subjects (as controls) before and after fenoterol inhalation. Multiple nitrogen washout curves were analyzed by a bicompartmental distribution model, in order to assess the distribution of ventilation and VA/Q mismatch. At baseline, asthmatics showed mild airway obstruction and gas exchange impairment [forced expiratory volume in 1 s (FEV1) = 79% pred; PaO2 = 87.4; alveolar-arterial oxygen tension gradient (AaPO2) = 22.9 mm Hg]. By analysing nitrogen washout curves, an alveolar slow space representing 45.1% of total lung volume (vs. 36.8% in normals; p = 0.044) was identified; its alveolar ventilation per minute per unit lung volume (VA2/L2) was lower than in normals (p = 0.01). beta-Agonist inhalation by the asthmatics, which reversed airway obstruction (FEV1 = 98% pred.; p < 0.001) and improved gas exchange (PaO2 = 92.6 mm Hg, p < 0.001; AaPO2 = 16.8 mm Hg, p = 0.003), led to a highly significant increase in VA2/L2 (p = 0.001). The improvement in PaO2 was associated with the increase in VA2/L2 (r2 = 0.39; p = 0.017), but not with the increase in FEV1. Lastly, the changes in FEV1 and VA2/L2 were not correlated with each other. We conclude that even in mild stable asthma there is substantial unevenness of ventilation, detectable by bicompartmental analysis of nitrogen washout curves, which is responsible for gas exchange impairment and is not related to common spirometric parameters. In addition, the improvement in gas exchange is probably due to the effect of fenoterol on the tributary airways of the alveolar slow compartment. This effect can be assessed by this simple method, which can be used in clinical pharmacology studies and in the follow-up of asthmatic patients.
In this paper, we present data on the prevalence of sinusitis and its relationship to bronchial asthma in 120 young male asthmatics evaluated without exacerbations of their disease. All patients reported respiratory symptoms during the preceding year, and in the most of them (74%), the severity of asthma was mild. Sinusitis was observed in 52 patients (43.3%), and the maxillary sinus was involved in 36 asthmatics. Sixteen of 52 patients with sinusitis had never had nasal symptoms of rhinitis. In all patients, physical examination of the lung was negative for wheezing. All patients had FEV1 (forced expiratory volume/forced vital capacity x 100 in 1 second of expiration) values in the normal range, and bronchial hyperresponsiveness was detected in 101 asthmatics (84.2%). One hundred sixteen patients (96.6%) were found to be skin reactors. We did not find statistical differences between asthmatics with or without sinusitis with regard to severity of asthma, basal lung function, and bronchial hyperresponsiveness. We suggest that antibiotic therapy for sinusitis should be given only to asthmatics with worsening respiratory symptoms and obvious signs of chronic sinusitis.
PURPOSE: The goal of this trial was to determine the maximum tolerable dose when carboplatin (CBDCA) was administered in continuous infusion concurrently with radiotherapy in patients with nonsmall cell lung cancer. METHODS AND MATERIALS: From October 1989 to July 1993, 54 patients were studied (male/female ratio: 44 to 10), median age was 62 years. Two patients had Stage II cancer, 22 had Stage IIIA, 24 had Stage IIIB, and 6 had Stage IV. Carboplatin was given for 96 h, starting at a dose of 30 mg/m2/day: 13 patients received 30 mg/m2/day (group A), 12 patients received 50 mg/m2/day (group B), 12 patients received 70 mg/m2/day (group C), 10 patients received 90 mg/m2/day (group D), and 7 patients 110 mg/m2/day (group E). The radiation dose was 50.40 Gy delivered to the target volume in 5.3 weeks. RESULTS: Fifty-three of 54 patients were evaluable for toxicity and 52 out of 54 for response. Toxicity (Miller score): Myelotoxicity: in groups A and B it was almost absent; in groups C and D it was moderate (leukopenia G1-2: 45.4% patients; trombocytopenia G1-2: 22.7%, G3: 9%; anemia G1-2: 9%); only in group E was it severe (leukopenia G1 and G3 16.6% respectively; trombocytopenia G3: 33.3%, G4: 16.6%; anemia G1-2: 50%). Nephrotoxicity was present only in one patient of group E and was Grade 3. Nausea and vomiting were related to CBDCA dose. One patient in Group E died of intractable toxicity 3 days after the end of infusion; then the study was closed. The limiting toxicity dose was shown to be 110 mg/m2/day given for 96 h. Clinical response rate: Twenty-six of 52 patients had major response, 24 had minor response, and only 2 patients had progression of disease. SURGERY: Twenty-one of 52 tumors were judged resectable: 18 patients had complete tumor resection, 1 had exploratory thoracotomy, and 2 patients refused surgery. Pathological response rate: Five patients had pathologic state T0 or Tis. CONCLUSIONS: These results indicate that the maximum tolerable dose of CBDCA infusion for 96 h is 90 mg/m2/day, and this schedule seems to produce an appreciable response rate. Therefore, we have started a Phase II trial, which will permit us to define the true efficacy of this schedule.
Iodine-123 metaiodobenzylguanidine (123I-MIBG) radioaerosol is of potential use in the investigation of the neuroadrenergic function of the lungs; however, before the method can be successfully employed the following issues need to be clarified: (1) Does the nebulization affect the radiochemical purity of 123I-MIBG? (2) Is the pulmonary distribution of inhaled 123I-MIBG homogeneous in normal subjects? (3) Does the pulmonary clearance of inhaled 123I-MIBG reflect the functional status of the neuroadrenergic system of the lungs? In this study we performed: (1) a chromatographic study of nebulized 123I-MIBG; (2) a quantitative evaluation of the lung distribution of 123I-MIBG radioaerosol in normal subjects as compared with that of technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) and (3) an assessment of 123I-MIBG lung clearance both under control conditions and after pharmacologically induced beta-blockade, again compared with 99mTc-DTPA. For these purposes, eight normal subjects were divided randomly into an "MIBG group" and a "DTPA group" (four subjects each) and submitted to three scintigraphic studies each: a baseline study, and studies after the administration of a low (80 mg) and a high (160 mg) dose of propranolol. Radiochemical purity of nebulized 123I-MIBG ranged between 97.18% and 98.70%. The lung distribution of 123I-MIBG, as judged by the aerosol penetration index, was identical to that of 99mTc-DTPA under all study conditions. The 123I-MIBG clearance rate was slower than that of 99mTc-DTPA under baseline conditions (135+/-32 min vs 69+/-27 min, P<0.01) and increased significantly after propranolol administrations, while the 99mTc-DTPA clearance did not change. The following conclusions were drawn: (1) the nebulization does not affect the radiochemical purity of 123I-MIBG; (2) the lung distribution of 123I-MIBG is homogeneous in normal subjects; (3) the pulmonary clearance of 123I-MIBG reflects the functional status of the neuroadrenergic system of the lungs. Thus this scintigraphic method is suitable for research and perhaps for future clinical use.
STUDY OBJECTIVES: Scintigraphic prediction of the residual pulmonary function following a lobectomy is not widely employed; its accuracy is poorly known. This study aims at determining the accuracy and the clinical value of the scintigraphic prediction of postlobectomy residual function. PATIENTS AND INTERVENTIONS: In this study, 41 patients with bronchial carcinoma underwent a perfusion lung scintigraphy before lobectomy; the functional contribution of each single lobe was computed by an indirect method proposed by Wernly et al.; the results of the scintigraphic prediction were compared with those of the pulmonary function tests performed 1 month after surgery. MEASUREMENTS AND RESULTS: The linear regression analyses of predicted and observed values of FVC and FEV1 showed significant correlations (R2=0.607 and 0.749, respectively); however, an evident scatter of data was obtained, as quantified by the values of imprecision (20.70% and 18.11%, respectively) and global inaccuracy (25.50% and 22.90%, respectively). The estimates of both FVC and FEV1 were significantly better in right lung lobectomies than in left lung lobectomies (mean imprecision and global inaccuracy: 15.43% and 14.94% for the right lung, and 27.27% and 29.00% for the left lung). CONCLUSIONS: The scintigraphic prediction of postlobectomy residual function is easily implemented by the method herein employed; it has a greater margin of uncertainty than that of pneumonectomy, especially for left lobectomies; however, the use of some safety thresholds for predicted values of FEV1 (1.2 L for upper lobectomies and 1 L for lower lobectomies) guarantees a safe clinical use of the test.
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The aim of this study was to determine the equivalence of single doses of two nedocromil sodium/salbutamol combined formulations, namely (a) metered dose inhaler (MDI) (nedocromil sodium 4 mg + salbutamol 0.2 mg) and (b) nebulizer solution (nedocromil sodium 10 mg + salbutamol 1.5 mg), in a group of healthy volunteers. The plasma pharmacokinetic profiles of nedocromil sodium and the pharmacodynamic effect (bronchodilation) of salbutamol were evaluated. Twelve healthy volunteers entered this randomized, cross-over study. All subjects completed the pharmacokinetic section of the study. Nine of them completed also the pharmacodynamic part of the study. After preliminary controls, treatments were administered on separate days and in random order. Blood samples were collected 5, 10, 20, 30, 45 min, 1, 1.5, 2, 3 and 4h after test medication. Specific airways resistance (sRaw) was measured 5, 10, 20, 30, 40, 50 and 60 min following test treatment administration. The pharmacokinetic profiles of nedocromil sodium were evaluated using the maximum plasma concentration (Cmax), the time to peak plasma concentration (tmax) and the area under the curve from 0 to infinity (AUCzero-->infinity), derived from the plasma concentration/time curves. The bronchodilating effect of the two test treatments were evaluated as sRaw percentage change at each time point, maximum sRaw percentage change (sRawMAX) and area under the curve (AUC) of sRaw percentage change plotted against the time of recording. The mean pharmacokinetic results for MDI and nebulizer solution were, respectively: Cmax = 7.59 ng.ml-1 +/- 4.99 and 9.64 ng.ml-1 +/- 5.22 (p = 0.36), tmax = 0.21 hour +/- 0.08 and 0.28 hour +/- 0.14 (p = 0.19), AUCzero-->infinity = 6.28 ng.ml-1.h +/- 2.91 and 12.91 ng.ml-1.h +/- 4.12 (p = 0.008), while the mean pharmacodynamic results were: sRawMAX = -37.91% +/- 13.77 and -39.69% +/- 9.69 (p = 0.69), AUC = -1465.5 delta %.h +/- 799.3 and -1683.4 delta %.h +/- 496.3 (p = 0.45). No statistically significant differences between treatments were found also for sRaw percentage change at each time point. The absorption of nedocromil sodium was proportional to the two administered nominal doses and similar to values obtained after administration of nedocromil sodium alone. The two combined formulations of nedocromil sodium and salbutamol produce an equivalent bronchodilating effect. These results confirm the pharmacological equivalence of the two products, whichever may be used according to specific therapeutic needs.
PURPOSE: To identify factors affecting the short-term prognosis of patients with acutely exacerbated chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: The 590 patients having COPD as primary disease who were hospitalized in the pneumology unit of a university hospital from 1981 to 1990 were studied. A standardized protocol for the treatment of acutely exacerbated COPD was adopted for all the patients. The patient records were retrospectively analyzed by two observers, and 23 clinical and laboratory variables defining the patient status on admission were collected. Age and arterial gas data were also taken into account, and the outcome mortality was recorded. Interobserver reproducibility was tested by computing the kappa coefficient and Spearman's rho for dichotomous and continuous variables, respectively. The relationship of clinical and laboratory factors to the outcome was assessed first by univariate analysis and then by a logistic regression analysis assessing the independent predictive role of variables previously shown to be univariately correlated with mortality. RESULTS: The mortality rate was 14.4%. The logistic regression analysis identified four independent predictors of death: age (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.04 to 1.11), alveolar-arterial oxygen gradient greater than 41 mm Hg (OR 2.33; 95% CI 1.39 to 3.90), ventricular arrhythmias (OR 1.91; 95% CI 1.10 to 3.31), and atrial fibrillation (OR 2.27; 95% CI 1.14 to 4.51). CONCLUSIONS: Patients with acutely exacerbated COPD having a high risk of death can be identified at the time of admission. Variables reflecting heart dysfunction are important determinants of this risk. Among pulmonary function data, only alveolar-arterial oxygen gradient contributes to the predictive model.
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A 70-year-old male patient presenting with a cutaneous node of the genal region that was first diagnosed as basal cell carcinoma is described. Owing to the following observation, the authors were prompted to a diagnosis of cutaneous odontogenic sinusitis: a) examination of the lesion which emitted pus upon gentle squeezing; b) presence in the vestibular fornix of a large fibrous cord; c) the serious conditions of the mouth and the radiologic results of homolateral sinusitis. The importance of the sinusitis picture, and the necessity to completely remove all bacteria foci prior to surgery on the abdominal aorta the patient was scheduled to undergo, prompted the authors to avulse the cutaneous lesion with tooth extraction, after a "Caldwell-Luc" operation of the homolateral paranasal sinus. Full restitutio ad integrum was achieved.
The scintigraphic prediction of residual pulmonary function after pneumonectomy has been validated in a number of studies while scintigraphy is not standardized in case of lobectomy. This study was aimed at investigating the accuracy of the scintigraphic prediction of post-lobectomy lung function using Wernly method. We examined 43 patients with bronchial carcinoma: 20 of them underwent pneumonectomy and 23 underwent lobectomy. The pulmonary function data (vital capacity, CV, and forced expiratory volume in one second, VEMS) predicted by quantitative lung scan were compared with those observed in the postoperative follow-up. A good correlation between predicted and observed data was obtained in both the pneumonectomized group (r = 0.77 and 0.78 for CV and VEMS, respectively; p < 0.005) and the lobectomized group (r = 0.74 and 0.79 for CV and VEMS, respectively: p < 0.005). It can be concluded that the method used for the scintigraphy prediction of post-lobectomy pulmonary function is as accurate as the post-pneumonectomy method and can be used reliably in the clinical practice.
The effect on B-lymphocytes of butyric acid, a metabolic by-product formed by selected anaerobic bacteria of the subgingival plaque and present in mM amounts in the crevicular fluid of patients affected by adult periodontitis was investigated. A dose-dependent inhibition of both mitogenesis and Ig production in B-cells challenged with formalinized Staphylococcus aureus, strain Cowan I (SAC), was observed. A role of this molecule in the downregulation of the local immune response in periodontal patients is proposed.
Norepinephrine (NE) is one of the many biologically active substances that are metabolized by the lung. The norepinephrine uptake in the lung has been widely investigated in animal studies in order to detect abnormalities of the endothelial cells. 131I- or 123I-labelled metaiodobenzylguanidine (MIBG) is a radioactive tracer that shares several metabolic pathways with NE; it has been used instead NE or both in animal and in human studies for the same purposes. It has been definitely demonstrated that MIBG lung uptake following intravenous administration is a reliable marker of minimal endothelial cell lesions and it allows one to investigate several conditions involving damage to the lung vasculature such as adult respiratory distress syndrome, post-actinic lung fibrosis or chemotherapic lung toxicity. MIBG could also potentially be used as a tracer of the neuroadrenergic system of the airways, once it has been deposited in the whole branches of the bronchial tree. With this in mind we evaluated the feasibility of the administration of MIBG in radioaerosol form. We first performed a chromatographic study on [123I]MIBG aliquots aerosolized for variable lengths of time (2-30 minutes). Radiochemical purity was always over 96%, thus demonstrating that aerosolization does not significantly modify the stability of the tracer. We then compared both the lung clearance curves and the scintigraphic images in two groups of normal subjects who respectively underwent [123I]MIBG and 99mTc-DTPA radioaerosol dynamic scintigraphy. We found that MIBG clearance to be significantly lower than that of DTPA (135 +/- 32 minutes versus 69 +/- 27 minutes, p < 0.01), probably due to its being trapped in the adrenergic nerve endings of the airways. The pulmonary distribution of both tracers was homogeneous, as demonstrated by the correspondence of the values for the aerosol penetration index in both groups of subjects. Such results warrant further research and pharmacologic tests.