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Biomedical subjects

T Todisco

Publications and source records attributed to T Todisco.

At least 19 recordsLinked to original sources
PubMed2002

An open, comparative pilot study of thiamphenicol glycinate hydrochloride vs clarithromycin in the treatment of acute lower respiratory tract infections due to Chlamydia pneumoniae.

The aim of this study was to evaluate the efficacy and tolerability of thiamphenicol glycinate hydrochloride (TGH) i.m. versus clarithromycin in acute lower respiratory infections due to Chlamydia pneumonia. 113 patients with suspected pneumonia were screened. 40 patients with IgM and/or IgA titers > or = 1:16 and/or IgG titers > or = 1:512 were assigned to 10 days of treatment with TGH 1500 mg daily or clarithromycin 1000 mg daily. 34 patients were considered a clinical success. 33 patients were a radiological success. 22 patients showed a decrease in IgG values. 3 patients had an increase in IgG values. Blood/urine values presented no clinically significant variations. Clinical efficacy was similar in both treatment groups. These are the first results confirming in vivo the recent in vitro evidence that TGH is effective against acute lower respiratory tract infections due to C. pneumoniae, thus representing an alternative therapy to clarithromycin.

Administration, Oral↗
PubMed2000

Basis for nebulized antibiotics: droplet characterization and in vitro antimicrobial activity versus Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.

The aims of this study were to (1) quantify the particle size characteristics of several antibiotics considered suitable for aerosol therapy after aerosolization with the PARI IS/2 nebulizer (Pari GmbH, Sarnberg, Germany) and (2) determine the degree to which in vitro antimicrobial activity of these antibiotics is maintained after nebulization. The aerosolized drugs were tobramycin sulfate, streptomycin, and imipenem, with saline solution as the control. Mean mass aerodynamic diameter of the nebulized drugs was 3.25 microns for tobramycin, 2.26 microns for imipenem, and 2.38 microns for streptomycin. In vitro tests showed that tobramycin and imipenem were unaltered in their bacteriostatic activity against strains of Escherichia coli (American Type Culture Collection [ATCC] 25922) and Staphylococcus aureus (ATCC 29213) as well as against Pseudomonas aeruginosa (ATCC 27853) with minimal inhibitory concentration (MIC) values less than 0.3 microgram/mL. Nebulized streptomycin showed significantly higher MIC values against P. aeruginosa (ATCC 27853). These results suggest that tobramycin and imipenem may be prescribed as an aerosol generated by jet nebulization (PARI IS/2) to treat S. aureus, E. coli, and P. aeruginosa infections without any risk of altering the drugs minimum bacteriostatic activity by the nebulization process. Aerosolization of streptomycin with this nebulizer may not be as effective against P. aeruginosa because it seems to alter the bacteriostatic activity.

Aerosols↗
PubMed2000

Myasthenic inspiratory vocal cord dysfunction: efficacy of nasal continuous positive airway pressure treatment.

Myasthenic vocal cord dysfunction (VCD), presenting with severe inspiratory stridor, was successfully treated with nasal continuous positive airway pressure (nCPAP), thus giving the medical staff time to make the diagnosis and avoiding intubation or tracheostomy. An important sign leading to diagnosis was the very high MEF(50)/MIF(50) ratio calculated from the flow-volume loop. nCPAP treatment induced prompt remission of stridor and a sharp reduction in the MEF(50)/MIF(50) ratio from 9.90 to 1.36. A review of the literature has shown that VCD with inspiratory stridor is an unusual onset symptom of myasthenia gravis and that nCPAP treatment may avoid emergency oral/tracheal intubation and tracheostomy. After diagnosis, the patient underwent thymectomy, and today, 3 years later, he is well without any further therapy.

Adult↗
PubMed1996

Nasal-continuous positive airway pressure in the treatment of near-drowning in freshwater.

In patients who have experienced near-drowning, hypoxemia is the major clinical consequence. We report two cases of patients who have experienced near-drowning in freshwater who were successfully treated with nasal-continuous positive airway pressure (N-CPAP) plus oxygen therapy. Both patients presented a radiographic appearance of bilateral pulmonary edema. We suggest the use of N-CPAP as an easier and less costly alternative to tracheal intubation for treating near-drowning in patients who are breathing spontaneously and who have not experienced loss of consciousness.

Adolescent↗
PubMed1995

A phase II trial of combined chemotherapy and surgery in stage IIIA non-small cell lung cancer.

A poor prognosis for patients with Stage IIIA clinical N2 treated by surgery alone has led clinical researchers to find a new treatment modality to improve the curative potential of surgery. Many Phas II trials have been carried out with induction chemo- or chemo-radiotherapy prior to surgery. From June 1988 to July 1991, 46 patients with non-small cell lung cancer (NSCLC) Stage IIIA clinical N2 entered a Phase II induction-chemotherapy trial. Patients received 2-3 cycles of high-dose cisplatin and etoposide. Forty-five were evaluable for response; the response rate was 82% (37/45: 3 CR, 34 PR). Toxicity was primarily hematologic. Surgical resection was performed in 35 patients; radical resection was possible in 28 patients (62%); three patients were incompletely resected and two patients were only explored. Three deaths were surgery-related. Median survival was 24.5 months with a 2-year survival of 53%. Cisplatin with etoposide is an active and safe induction chemotherapy regimen for NSCLC Stage IIIA N2 with a high response rate. The median survival seems to be prolonged and therefore, randomized trials are needed to compare this approach with other treatment modalities.

Aged↗
PubMed1995

Effect of bamiphylline on tracheobronchial mucus clearance in subjects with smokers' simple chronic bronchitis.

A double-blind study versus placebo was performed to assess the effect of bamiphylline, a new xanthylic derivative, on tracheobronchial mucus clearance (TBMC) in smokers with simple chronic bronchitis and impaired mucus clearance as compared to normal controls. Twenty patients were enrolled and divided into two randomized groups. The first group was treated with bamiphylline (600 mg b.d.) for 15 days, while the second group received placebo with the same oral dosage regimen. Complete clinical-functional examinations were made before and after the test period to establish the effects of treatment. At the end of the study, only the group treated with bamiphylline showed a net increase in mucus clearance (mean radioaerosol elimination 28 +/- 7% before treatment and 38 +/- 11% after treatment; p < 0.01) and an improvement in the clinical score and pulmonary function parameters, in particular the residual volume (RV = 3.41 +/- 0.75 liters before treatment and 2.7 +/- 0.6 after treatment; p < 0.01) and the forced expiratory volume at 1 s (FEV1 = 2.37 +/- 0.7 liters before treatment and 2.88 +/- 0.5 after treatment; p < 0.05). No side effects or adverse reactions that could be attributed to the study drug were observed.

Aged↗
PubMed1994

Encapsulation of Cryptococcus neoformans regulates fungicidal activity and the antigen presentation process in human alveolar macrophages.

Our previous studies have shown that unstimulated alveolar macrophages (AM) play a predominant role as antigen-presenting cells in Cryptococcus neoformans infections, while the function as effector cells seems to be of minor relevance. The present study focuses on the role of encapsulation of C. neoformans on fungicidal activity and the antigen presentation process of AM. Fungicidal activity in unstimulated AM occurs to a higher degree when the acapsular strain is employed, but this is impaired compared with other natural effectors, such as peripheral blood monocytes (PBM) and polymorphonuclear (PMN) cells. Cryptococcus-laden AM also induce a higher proliferative response in autologous CD4+ lymphocytes when the acapsular strain is used compared with encapsulated yeast. The enhanced blastogenic response is, in part, ascribed to an augmented IL-2 production by T cells. In addition, higher levels of interferon-gamma (IFN-gamma), but not IL-4, are produced by the responding T cells, when the acapsular strain is used compared with the encapsulated yeast. Moreover, IFN-gamma is able to induce fungicidal activity in AM against the encapsulated yeast and augments killing activity of the acapsular strain. This phenomenon is not mediated by nitric oxide production, but is correlated with an enhancement of fungicidal activity of cytoplasmic cationic proteases. We speculate that encapsulation of C. neoformans could down-regulate the development of the immune response mediated by Cryptococcus-laden AM at lung level.

Adult↗
PubMed1994

Role of human alveolar macrophages as antigen-presenting cells in Cryptococcus neoformans infection.

The contribution of human alveolar macrophages (AM) from normal subjects in Cryptococcus neoformans infection was investigated. AM were able to efficiently phagocytize the fungus after opsonization, but killing activity did not occur at an effector-to-target ratio of 10:1 in a 6-h incubation since there was an inhibition of phagosome-lysosome fusion. Moreover, the role of AM as antigen-presenting cells was investigated. Cryptococcus-laden AM were co-cultured with autologous T lymphocytes and lymphoproliferation was determined; a massive blastogenic response of alpha/beta TCR-bearing T lymphocytes was observed. The response started after 1 day of co-culture and was triggered and regulated by IL-1 produced by AM in response to C. neoformans. Finally, the antigen-presentation process was associated with HLA class II DR molecules. This finding suggests that AM play a key role in the lung as antigen-presenting cells and, through the secretion of IL-1, regulate proliferation and activation of T lymphocytes, which are important in mediating pulmonary clearance. We speculate that in immunodepressive conditions, the impairment of AM functions could contribute to the spread of C. neoformans infection from the lung.

Adult↗
PubMed1994

Macrophage activation by N-acetyl-cysteine in COPD patients.

The effect of in vivo and in vitro N-acetylcysteine (NAC) treatment on destructive activity of macrophages against Candida from COPD patients has been evaluated. Patients received NAC (600 mg) or placebo orally 3 times a day for 15 days and bronchoalveolar lavage (BAL) fluid and peripheral blood were collected before and at the conclusion of treatment. In our system, NAC treatment was not able to modulate antifungal activity of alveolar macrophages, peripheral blood monocytes (PBM), and polymorphonuclear leukocytes. On the contrary, in vitro NAC treatment at appropriate doses (10 micrograms/ml) significantly enhanced antifungal activity of PBM from COPD patients. This phenomenon is mediated by augmented phagocytic activity and phagosome-lysosome fusion. The lack of correlation between in vivo and in vitro studies could be ascribed to differences in the intracellular concentration of the drug that in vivo does not reach levels capable of inducing macrophage activation. We speculate that in COPD patients who undergo long-term NAC treatment, appropriate schedules and doses of the drug could augment resistance against microbial infections which are often life-threatening in these patients.

Acetylcysteine↗
PubMed1993

Mild prematurity and respiratory functions.

Pulmonary function tests and bronchial reactivity to methacholine (MCH) were measured in 34 randomly selected prematures (21 males, 13 females; mean age 11.6 years; mean gestational age 34.9 weeks; mean birth weight 1980 g) and in 34 siblings (22 males, 12 females; mean age 12.5 years, mean gestational age 39.5 weeks; mean birth weight 3030 g). None had suffered neonatal respiratory distress syndrome or had been artificially ventilated. Prematurely born children had a residual volume (RV) and residual volume/total lung capacity (RV/TLC) significantly (P < 0.01) increased compared to controls, although the mean values of both groups were still within the upper limits of normal. Furthermore, an increase of closing volume/vital capacity and closing capacity/total lung capacity (CC/TLC) was observed in most patients with increased RV and RV/TLC. No significant difference was observed for bronchial responsiveness to MCH between prematurely born and control children (11.8% and 5.9% of hyperreactive subjects, respectively). Maternal smoking during pregnancy was prevalent in prematures with impaired respiratory functions. In conclusion clinically normal children of smoking mothers who have survived prematurity but present some respiratory function impairment compared to their born-at-term siblings, should be fully informed and protected from risk factors for chronic obstructive pulmonary disease (COPD) in adult life.

Bronchial Hyperreactivity↗
PubMed1993

Altered platelet function associated with the bronchial hyperresponsiveness accompanying nocturnal asthma.

BACKGROUND: Nocturnal awakening is a common feature of bronchial asthma, and yet the mechanisms underlying this phenomenon are poorly understood. We investigated whether nocturnal awakening is associated with changes in platelet function with the use of a variety of markers of platelet activation. METHODS: Ten patients with a history of nocturnal asthma and 10 age- and sex-matched healthy control subjects were studied at 10:00 PM, 4:00 AM, and 10:00 AM on 2 consecutive days. The following parameters were tested: forced expiratory volume in 1 second (FEV1), log dose of methacholine inducing a 20% fall in FEV1, platelet count and volume, platelet aggregation induced by collagen or activating factor, and plasma and intraplatelet levels of beta-thromboglobulin and platelet factor 4. RESULTS: We have demonstrated that altered platelet function and platelet activation occurs at 4:00 AM in patients with nocturnal asthma and is associated with the maximum increases in bronchial reactivity. Such changes were not observed in 10 control subjects. Platelet dysfunction has been detected as a reduced aggregatory response of platelets to collagen and platelet activating factor such that up to 5 times more platelet activating factor and 1.5 times more collagen were required to elicit a threshold aggregatory response in asthmatic subjects when compared with control subjects; this difference was evident at all time points tested. Furthermore, at 4:00 AM there were significantly lower levels of intraplatelet beta-thromboglobulin corresponding to the maximum reduction in peak expiratory flow and to the maximal increase in bronchial responses to inhaled methacholine. CONCLUSIONS: These results suggest that platelet activation accompanies nocturnal asthma and further suggest that platelets may play a role in this common clinical condition.

Adult↗
PubMed1993

Inhibition of candidacidal activity of polymorphonuclear cells by alveolar macrophage-derived factor from lung cancer patients.

Culture supernatants of alveolar macrophages (AM) from lung cancer patients are able to inhibit the candidacidal activity of polymorphonuclear cells (PMN) in vitro. This phenomenon is ascribed to a factor secreted in the culture medium by unstimulated AM from tumor-bearing patients, but not from normal subjects. The inhibitor does not apparently affect the phagocytic activity of PMN, but the superoxide release during phagocytosis is significantly impaired when cells are pretreated with supernatants containing the factor. The secretion of the inhibitor seems to be restricted to the pulmonary compartment of lung cancer patients, since culture supernatants of peripheral blood monocytes (PBM) from the same subjects are not capable of depressing the candidacidal activity of PMN. The AM-derived factor is not inactivated after exposure to heat (60 degrees C) and when supernatants are analyzed by HPLC, the inhibitory activity is recovered in the fractions corresponding to a low molecular weight (800 D). In conclusion, AM from lung cancer patients are able to produce a factor capable of inhibiting the antimicrobial activity of PMN. This could account, at least in part, for the enhanced susceptibility to local infections observed in lung cancer patients.

Biological Factors↗
PubMed1993

Mechanism of intracellular candidacidal activity mediated by calcium ionophore in human alveolar macrophages.

In the present study, we investigated the effect of in vitro treatment with calcium ionophore (A23187) on candidacidal activity of human alveolar macrophages (AM) from normal subjects. In vitro incubation of AM with A23187 results in a significant dose-dependent enhancement of candidacidal activity. The availability of Ca2+ and Mg2+ ions in the culture medium is crucial for phagocytosis and killing to occur, but appears irrelevant for the binding between Candida albicans and AM. Enhancement of the killing effect mediated by A23187 does not correlate with increased phagocytic activity; in fact, the availability of ions is required for the phagocytic event, but an increase of cations does not correlate with enhancement of this activity. On the contrary, the augmentation of killing activity correlates with increased production of superoxide anion. Moreover, soluble material endowed with candidacidal activity has been extracted from cytoplasmic granules of AM both unstimulated and following A23187 treatment in vitro. Indeed, the granules extracted contain cationic proteases and, when isolated from stimulated cells, appear to be significantly more cytotoxic for C. albicans with respect to those obtained from unstimulated AM. In conclusion, the results reported here show that the phagocytic and killing events are ion dependent and the enhancement of intracellular candidacidal activity mediated by A23187 in AM is correlated with an augmented anti-Candida activity of cation-activated proteases.

Adult↗
PubMed1992

99mTc-DTPA-surfactant inhalation in adult respiratory distress syndrome (ARDS): a new diagnostic-therapeutic tool.

ARDS is a life-threatening pulmonary disease with a rapidly progressive decline due mainly to multi-organ failure. Death occurs in 50-75% of ARDS cases. The diagnosis and therapy should start in the first six days of this fatal disease when mortality is at its lowest level. The 99mTc-DTPA-measured pulmonary alveolar epithelial permeability (PAEP) is strikingly increased in ARDS even in comparison to heavy smokers. Furthermore, surfactant inhalation has been shown to be of therapeutic value. In five ARDS patients with increased PAEP (T0.5 = 12% pred.) 20 mg/kg of aerosolized surfactant determined a dramatic improvement in blood gases and PAEP (51.8% pred.) No patient remained dependent on ventilatory treatment.

Administration, Inhalation↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗