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Biomedical subjects

T Todisco

Publications and source records attributed to T Todisco.

At least 19 recordsLinked to original sources

Prediction of pulmonary immunodeficiency in chronic bronchitis by cutaneous hypoergy to multitest.

Multitest (Pasteur Mérieux) is a plastic disposable device used to assess delayed cutaneous hypersensitivity (DCH) to seven antigens. Hypoergy to Multitest is believed to reflect a status of compromised cell-mediated immunity. Among the many possible pathogenic factors of chronic bronchitis, immunodepression has been little investigated. Indeed, whether lower immunodefence is the cause or the consequence of chronic bronchitis is still a subject of debate. The aim of the study was to evaluate DCH in a large group of patients with chronic obstructive pulmonary disease (COPD) and in a control group, in order to relate DCH (expressed as score, mm) to clinical and functional impairment. One hundred patients with COPD in stable conditions and not undergoing treatment with immunomodulating drugs (mean age, yr, M +/- SD: 66.1 +/- 6.5) and 40 normal controls in the same age range were admitted to the study. Evaluated parameters were: symptoms scores, physical examination, lung function tests and Multitest. Fifty-three percent of the COPD patients were hypoergic compared with 14% of controls. The Multitest score was 10 +/- 10 (mm M +/- SD) in COPD compared with 17 +/- 9 in controls. The Multitest score was significantly related to age (r = -0.45) in the control group, but not in COPD patients. DCH to only three of the seven antigens may predict a response to Multitest, with a sensitivity of 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Role of bromhexine in exacerbations of bronchiectasis. Double-blind randomized multicenter study versus placebo.

The effectiveness of bromhexine in the treatment of patients with bronchiectasis, in a stage of clinical exacerbation, was assessed in a double-blind, placebo-controlled trial involving 88 in-patients. Bronchiectasis was diagnosed by bronchography and/or CT scan. Bromhexine or matched placebo was administered as 30-mg capsules three times daily per os. Ceftazidine, 1 g i.m., was given to all patients once a day for the first week only. Bromhexine seemed to improve the clinical picture, with significantly positive trends for expectoration, quantity of sputum and auscultatory findings. It also increased the FEV1 and was well-tolerated. Both patients and investigators judged it efficacious.

Adult

Defective candidacidal activity of alveolar macrophages and peripheral blood monocytes from patients with chronic obstructive pulmonary disease.

We investigated the in vitro candidacidal activity of alveolar macrophages (AM) and peripheral blood monocytes (PBM) from normal subjects or from patients with chronic obstructive pulmonary disease (COPD) displaying defective skin test delayed-type hypersensitivity (DTH) reactivity to seven antigens including Candida albicans. The results showed that cells from patients with COPD were significantly less effective than cells from control subjects in the killing of C. albicans. To explore whether the observed functional impairment could be reversed, interferon-gamma (IFN-gamma) was added to AM and PBM from patients with COPD, alone or in the presence of lipopolysaccharide (LPS) as a suboptimal stimulus. The cells were cultured for 24 h and then assayed for anti-Candida activity. After IFN-gamma treatment, the fungicidal activity of cells from patients with COPD was comparable to that of unstimulated AM or PBM from healthy donors. Treatment with IFN-gamma plus LPS resulted in a further enhancement in the killing of C. albicans. To gain more insight into the mechanisms involved in the modulation of killing, we evaluated the possible stimulating activity of IFN-gamma plus LPS treatment on the secretion of tumor necrosis factor (TNF) and interleukin-1 (IL-1), two cytokines produced by activated macrophages and capable of stimulating natural effectors. The results showed that IFN-gamma plus LPS can indeed stimulate TNF and IL-1 secretion by AM and PBM from patients with COPD. Therefore, a precise role can reasonably be ascribed to these soluble factors in the observed augmentation of candidacidal activity as ascertained by treatment with IFN-gamma plus LPS.

Aged

Fate of human albumin microsphere and spherocyte radioaerosols in the human tracheobronchial tree.

Human albumin microspheres (99mTc-HAM; 7-25 microns) and spherocytes (99mTc-S; 4-4.5 mu) are particles used for lung mucociliary clearance (MCC) measurements. If radiolabelled HAM aerosols are sent through an airway model to a screen, they appear peripherally distributed, whereas S present a more central and homogeneous distribution. The radioscanning evaluation of particle sedimentation in saline-filled tubes shows quite a different behavior pattern for S, HAM, and surfactant-coated HAM (S-C HAM). In these experimental conditions, S-C HAM and HAM floating properties were better than those of S. This could be explained by physical-chemical factors. Looking for the fate of organic particles after inhalation, we performed multiple bronchial biopsies in seven bronchitic patients, 2 h following inhalation of HAM and S. Scanning electron microscopy revealed that most of S was floating on the mucus layer, while HAM appeared deeply imbedded inside the mucus and partially digested. The same study performed on three bronchitic patients after S-C HAM inhalation, shows that S-C HAM float like S. In vitro, the time-course of tryptic digestion is similar for HAM and for S. However, in vivo, the different location of each particle on the bronchial surface might lead to a different digestion by trypsin and by PZ-peptidase, which are dosable in pathologic mucus. In our opinion, if HAM are coated with surfactant, this should improve the mucus-HAM interaction, thus helping to control variability in lung radioaerosol MCC studies.

Aerosols

Viral and Mycoplasma pneumoniae pneumonias in school-age children: three-year follow-up of respiratory function.

We studied the evolution of respiratory function during and for 3 years after the acute onset of viral and Mycoplasma pneumoniae pneumonias in 13 school-age children. A mixed type transient ventilatory defect (restrictive and obstructive, but mainly restrictive) with large and small airway involvement was observed during the acute phase of the pneumonias. Residual small airway involvement was found over the next 12 months, but no pulmonary function abnormalities were present after 3 years. At that time, one of the 13 subjects displayed bronchial hyperreactivity to distilled water mist challenge. The authors concluded that viral and Mycoplasma pneumoniae pneumonia in previously healthy school-age children does not cause impaired lung function in later childhood.

Adenovirus Infections, Human

Normal reference values for regional pulmonary peripheral airspace epithelial permeability. Influence of pneumonectomy and the smoking habit.

Peripheral airspace epithelial permeability (PAEP) to diethylentriaminopentacetate (DTPA), an index of pulmonary integrity, was measured in 3 groups of subjects for different purposes: (1) to establish vertical regional reference values; (2) to determine the physiological role of acute doubling of total pulmonary blood flow; (3) to quantify the pulmonary epithelial damage in smokers and the possibility of lung protection by an agent stimulating surfactant production. This study broadens previous knowledge of PAEP. First of all, regional reference values are given for young normal nonsmoking subjects and the existence of a vertical gradient of PAEP is confirmed. Furthermore, this study shows that this gradient is independent of the vertical blood flow gradient, since an acute increase of total blood flow in pneumonectomized patients does not modify the regional distribution of PAEP. Finally, it is confirmed that the cigarette smoker's lung is more permeable than the controls and that probably a drug-stimulating surfactant production gives some protection against damage due to chronic smoking.

Adult

Ability of retinoic and ascorbic acid to interfere with the binding of benzo(a)pyrene to DNA in explants from donors with bronchial cancer.

The capability of ascorbic acid (AA) and transretinoic acid (RA) to interfere with 3H-benzo(a)pyrene [B(a)P] binding to DNA has been evaluated in cultured bronchial mucosa explants from patients with bronchial cancer. The results show that the DNA-bound 3H-B(a)P is smaller in treated cultures than in controls. To explain this finding, it is proposed that AA, acting as antioxidant, inhibits the oxidative degradation of B(a)P, and that RA, a lipophilic compound interacting with the lipid components of mixed function oxidases, could modify the activities of these enzymes. Both vitamins decrease the concentration of ultimate carcinogen metabolites, which can interact with DNA. Furthermore, the treatment with RA does not increase DNA synthesis, while AA inhibits 3H-thymidine incorporation.

Antineoplastic Combined Chemotherapy Protocols

Modulation of anti-Candida activity of human alveolar macrophages by interferon-gamma or interleukin-1-alpha.

The fungicidal and bactericidal activities of human alveolar macrophages (AM) and peripheral blood monocytes (PBM) from 18 healthy volunteers were evaluated. The results showed that AM were able to phagocytize and kill Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus. However, killing of the bacteria was already complete in 2 h, whereas killing of Candida required 4 to 6 h despite an early phagocytosis of yeast cells. The fungicidal activity of freshly collected AM and PBM was also tested after effector cell exposure to interferon-gamma (IFN-gamma), interleukin-1-alpha (IL-1 alpha), endotoxin lipopolysaccharide (LPS), or interleukin 2 (IL-2). It was found that treatment with IFN-gamma, IL-1 alpha, or LPS significantly augmented macrophage and PBM candidacidal activity, whereas the addition of IL-2 was ineffective. We also evaluated killing of C. albicans by AM cultured in vitro for different times. While phagocytosis was apparently unaffected, the candidacidal activity progressively decreased over the in vitro culture period, an effect that was largely reversed by cell exposure to IFN-gamma, IL-1 alpha, or LPS. In an experimental model in which mice infected with an agerminative C. albicans strain (PCA-2) resisted lethal microbial challenge, freshly harvested AM showed increased cytotoxic activity to Aspergillus fumigatus in vitro as well as enhanced IL-1 production. In conclusion, present data confirm the crucial role of AM in the surveillance of bacterial and fungal infections and indicate that treatment of these cells with IFN-gamma or IL-1 alpha is able to enhance their antimicrobial capability.

Adult

Sarcoidosis: an alveolar macrophage disease?

The Authors focus on new functions of alveolar macrophages (AM) from patients with active pulmonary sarcoidosis. They show that sarcoid AM present a candidacidal activity higher than normal controls, probably due to an enhanced phagocytic efficiency. Furthermore, after LPS stimulation cultured sarcoid AM secrete larger amount of interleukin 1 (IL-1) and of tumor necrosis factor (TNF) than normal controls. In conclusion, a new key role is emerging for sarcoid AM: not only an antigen-presenting cell, but a cell with a great primitive potential in modulating the inflammatory process.

Bronchoalveolar Lavage Fluid

Effects of dipyridamole on the hypoxemic pulmonary hypertension of patients with chronic obstructive pulmonary disease.

Based on the hypothesis that blood platelets contribute to the pathogenesis of hypoxemic pulmonary hypertension in patients with chronic obstructive pulmonary disease (COPD), the effect of a prolonged treatment with dipyridamole, a platelet-inhibiting drug, on hypoxemic pulmonary hypertension was evaluated in a double-blind cross-over study. Eight patients with COPD, pulmonary hypertension [mean systolic pressure 52.2 +/- (SD) 9.7 mm Hg; mean diastolic pressure 25.8 +/- (SD) 6.8 mm Hg] and shortened platelet regeneration time [mean 5.2 +/- (SD) 1.2 days] received, in a cross-over random sequence, the following two 3-month treatments: (a) dipyridamole 100 mg and acetylcysteine 100 mg every 6 h; (b) acetylcysteine, 100 mg every 6 h. Dipyridamole significantly prolonged the platelet regeneration time [mean 6.5 +/- (SD) 1.0 days; p less than 0.05]. There was no significant effect on diastolic pulmonary pressure. However, systolic pressure was significantly (p less than 0.05) lower after dipyridamole [46.8 +/- (SD) 16 mm Hg] than after placebo [56.1 +/- (SD) 14 mm Hg]. These results suggest that dipyridamole can slow the progression of hypoxemic pulmonary hypertension in patients with COPD.

Aged

Pulmonary epithelial permeability in ARDS and cardiogenic pulmonary oedema.

Clearance of inhaled 99mTechnetium-labelled diethylene triamine pentacetate (99mTc-DTPA) from the lung, an index of pulmonary alveolar epithelial permeability (PAEP), was measured in 13 patients with cardiogenic interstitial pulmonary oedema (CIPO) and in 7 patients with adult respiratory distress syndrome (ARDS). Thirty-five normal subjects (22 nonsmokers and 13 smokers) were evaluated as controls. Half-time clearance (t0.5) values in ARDS patients (mean +/- SD: 15 +/- 2 min) were significantly lower than in CIPO patients (62 +/- 9 min). This PAEP increase in ARDS was impressive, even in comparison to heavy smokers. Loss of the PAEP vertical gradient (apical PAEP greater than base PAEP) was observed in both cardiogenic and ARDS lungs and among smokers.

Adolescent

Radioisotopic method for nasal mucociliary function evaluation.

In 13 healthy young adults, nasal mucociliary transport velocity was measured by means of albumine microsphere labeled with Tc99m as a tracer. M + ISD of clearance velocity values and of the half time radioactivity (T1/2) resulted to be respectively 1.02 + 0.22 cm/min and 1.07 + 0.24 min. A significant correlation (P less than 0.05) between half time clearance (T1/2) values of the radioactive particles and the mucociliary velocity ones could be detected, making T1/2 a reliable and rapidly obtainable parameter for determining nasal mucociliary function. Advantages and disadvantages of the different techniques are discussed.

Adult

Biodegradability of inhaled organic particles in patients with chronic bronchitis.

2 h after the inhalation of monodispersed 99mTc-labeled autologous spherocytes and of commercial human albumin microspheres (HAM), 7 patients with chronic bronchitis underwent bronchofibroscopy. The fate of organic particles along the tracheobronchial tree was verified by scanning electron microscopy and the proteolytic activity (trypsin and PZ peptidase) in mucus samples was assessed. Significant proteolytic activity was detected in bronchial secretions. Thereafter in vitro digestion of labeled spherocytes and HAM was verified after exposure to increasing concentrations of trypsin. While in vitro a similar time-course of tryptic digestion of both particles was observed, in vivo spherocytes seem to be less vulnerable to enzymatic digestion. These findings add another unexpected variable, which may influence the reproducibility of radioaerosol lung mucociliary clearance measurements, and improve its standardization.

Aerosols