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Biomedical subjects

L Casali

Publications and source records attributed to L Casali.

At least 19 recordsLinked to original sources
PubMed2005

Management of multidrug-resistant tuberculosis in Italy.

SETTING: SMIRA (Italian Study on Anti-Tuberculosis Drug Resistance) network, 46 major clinical units and 22 laboratories nationwide in Italy. OBJECTIVES: To determine the main features, adherence to WHO guidelines and the outcomes of multidrug-resistant tuberculosis (MDR-TB) patients enrolled from January 1995 to December 1999. DESIGN: Observational study, preceded by proficiency testing, according to WHO recommendations. Results were stratified by appropriate and inappropriate regimens (< three active drugs). Analysis of the outcomes was performed according to adequacy of treatment. Analysis of risk factors and factors predicting treatment outcomes was performed using univariate and multivariate analysis (level of significance P < 0.05). RESULTS: One hundred and twenty-seven MDR patients were diagnosed. The overall success rate was low (39%). Seventy per cent of cases were treated with at least three active drugs. Factors predicting treatment success were new MDR-TB cases (OR 3.45; 95% CI 1.22-9.78; P < 0.05) and treatment for > or = 12 months (OR 5.03; 95% CI 1.65-15. 31; P < 0.05). Immigration and HIV infection were the main risk factors among new MDR-TB cases. CONCLUSION: The best available treatment should be provided to all newly diagnosed MDR-TB patients, avoiding the use of poorly modified regimens. MDR-TB patients should be referred to highly specialised centres.

Adult↗
PubMed2004

The role of climate on the geographic variability of asthma, allergic rhinitis and respiratory symptoms: results from the Italian study of asthma in young adults.

BACKGROUND: Variations in the prevalence of respiratory symptoms according to geo-climatic factors could provide important clues to the knowledge of the aetiology of asthma. METHODS: Geo-climatic variations in the prevalence of current asthma, allergic rhinitis and chronic cough, and phlegm were assessed on a random sample of 18 873 subjects (response rate = 72.7%) from different climatic regions of Italy. An ecological analysis, supported by robust statistical methods, was employed to investigate potential trends. RESULTS: The prevalence of all symptoms was significantly heterogeneous throughout the peninsula. Only asthma-like symptoms showed a north-south trend: the prevalence increased at a decreasing latitude [odds ratio (OR) varies from 0.92 to 0.96, P < 0.05], at a decreasing distance from the sea (OR: 0.90-0.93 for 30 km distance, P < 0.05), at higher annual mean temperatures (OR: 1.11-1.14, P < 0.05) and at smaller annual temperature ranges (OR: 0.94-0.95, P < 0.05). Of the geo-climatic variables considered, temperature range had the greatest influence on most asthma-like symptoms. No association was found between geo-climatic variables and allergic rhinitis or chronic cough and phlegm. CONCLUSIONS: Asthma prevalence seems to be significantly affected by climate as asthma-like symptoms were more common in central-southern Italy, with a Mediterranean climate, than in areas with a continental climate (northern Italy).

Adult↗
PubMed2002

A 10-year survey of Mycobacterium tuberculosis isolates in Pavia and their drug resistance: a comparison with other Italian reports.

A retrospective review was made of the bacteriological and medical records of patients with culture-confirmed pulmonary tuberculosis who attended the IRCCS San Matteo Polyclinic of Pavia, between 1990 and 2000. Altogether, 279 patients were included in the survey: 220 new cases and 59 prior treatment cases. Resistance to at least one drug, and resistance to both isoniazid and rifampicin (MDR) were more common among previously treated patients than among new cases (86.4% vs. 34.1%, and 44% vs. 5.9%, respectively). While the frequency of resistance to any drug showed no variation in the period examined, a trend toward a progressive decrease in the frequency of primary MDR-TB was observed (from 11.9% in 1990-1992 to 1.3% in 1998-2000). The level of resistance observed in our study suggests that all isolates of Mycobacterium tuberculosis should be tested for drug susceptibility, especially when obtained from patients who report a previous episode of the disease.

Drug Resistance, Multiple, Bacterial↗
PubMed2002

Efficacy and safety of short course (5-day) moxifloxacin vs 7-day ceftriaxone in the treatment of acute exacerbations of chronic bronchitis (AECB).

The aim of this multicenter, open, randomized study was to compare the efficacy and tolerability of a 5-day treatment course with oral moxifloxacin (MXF) vs a 7-day course with i.m. ceftriaxone (CRO) in 476 patients with acute exacerbations of chronic bronchitis (AECB), and to conduct a cost minimization analysis of the two treatments from the perspectives of both the Italian National Health Service (INHS) and society. The study was conducted in Italy. Clinical success rates at test-of-cure in the 423 patients of the PP (Per Protocol) population (primary efficacy parameter) were 90.6% and 89.0% for MXF and CRO, respectively. Statistical non-inferiority of MXF vs CRO was confirmed. Similar results were found between study drugs on the secondary efficacy parameters, including success at end-of-treatment (95.3% for MXF vs 92.9% for CRO), success at test-of-cure in bacteriologically-positive patients (94.1% vs 90.7%) and eradication/presumed eradication rates (91.7% vs 93.3%). ITT (Intention-to-Treat) analysis confirmed these data. There was a low incidence of adverse events (10.8% vs 9.1%). During a 6-month follow-up period, relapse rates were lower for MXF vs CRO (23.3% vs 28.3%; p > .05). Compared with CRO, MXF was associated with cost savings per patient ranging from Euro226.57 (INHS perspective) to Euro448.23 (societal perspective), with lower hospitalization rate the major variable contributing to reduced costs. MXF appears to be an ideal candidate for AECB treatment.

Acute Disease↗
PubMed2002

Prevalence of resistance to anti-tuberculosis drugs: results of the 1998/99 national survey in Italy.

OBJECTIVE: To determine the prevalence of resistance to the main anti-tuberculosis drugs in newly and previously treated tuberculosis patients in Italy and to evaluate the contribution of foreign-born and human immunodeficiency virus (HIV) positive cases to drug resistance. METHODS: Methods and definitions were derived from the WHO/IUATLD Global Project on Anti-tuberculosis Drug Resistance Surveillance. Univariate and multivariate analysis was used to study prevalence rates of drug resistance in risk groups. RESULTS: In a national survey in Italy, 810 initial isolates of Mycobacterium tuberculosis (683 from new cases, 115 from retreatment cases and 12 from patients whose treatment history was unknown/dubious) were analysed. Low prevalence of drug and multidrug resistance was found in the new cases (isoniazid 2.9%; rifampicin 0.8%; multidrug resistance 1.2%; any drug resistance 12.3%). The prevalence of resistance to isoniazid and rifampicin was significantly higher in immigrants and HIV-positive subjects, respectively. A high prevalence of drug resistance was found in cases with previous treatment failure or default (isoniazid 5.2%; rifampicin 4.3%; multidrug resistance 36.5%; any drug resistance 61.7%). RECOMMENDATIONS: Special efforts are necessary to monitor trends in drug resistance and to ensure favourable treatment outcomes among immigrants and HIV-positive tuberculosis cases.

Antitubercular Agents↗
PubMed2001

Variations in serum levels of interleukin (IL)-1beta, IL-2, IL-6, and tumor necrosis factor-alpha during specific immunotherapy.

BACKGROUND: Cytokine production by T helper cells is essential for the induction and maintenance of allergic inflammation in the bronchial mucosa. According to recent views, specific immunotherapy (SIT) favors the differentiation of T lymphocytes into cells of the Th1 rather than those of the Th2 subset. OBJECTIVE: To determine whether or not SIT induces a decrease in the inflammatory reaction by studying eventual variations in the serum levels of IL-1beta, IL-2, IL-6, and TNF-alpha in allergic subjects during SIT. METHODS: Serum levels of IL-1beta, IL-2, IL-6, and TNF-alpha were determined before and after 3, 6, and 9 months of SIT by an immunoradiometric assay (IRMA) in 11 adults with perennial allergic asthma and/or rhinitis caused by house dust mites and in 6 nonatopic healthy volunteers. RESULTS: Median serum IL-1beta and TNF-alpha levels of the patients were significantly higher at baseline than those of the controls and decreased during SIT to values similar to or lower (P < .01) after 6 months of SIT for TNF-alpha than those of the controls. Median serum IL-2, significantly lower at baseline than in the controls, increased during SIT to a level similar to that of the controls. Although the median values of IL-1beta and TNF-alpha in the patients tended to decrease and those of IL-2 to increase during SIT, the differences were not significant; the correlation coefficients (r) of the serum levels of IL-1beta IL-6, and TNF-alpha versus duration of SIT were negative, while that of IL-2 was positive. CONCLUSIONS: Decreases in median serum IL-1beta and TNF-alpha levels during SIT, together with the increases in serum IL-2 and IL-6, compared with those of the controls furnish evidence supporting a reduction in the inflammatory response in the course of SIT.

Adult↗
PubMed2001

Variations in the prevalence across countries of chronic bronchitis and smoking habits in young adults.

The present work aims to assess the international variation in the prevalence of chronic bronchitis and its main risk factor, smoking habits, in young adults of 35 centres from 16 countries. Respiratory symptoms and pulmonary function were assessed in 17,966 subjects (20-44 yrs), randomly selected from the general population, in the frame of the European Community Respiratory Health Survey. The median prevalence of chronic bronchitis was 2.6%, with wide variations across countries (p<0.001; 0.7-9.7%). The prevalence of current smokers ranged 20.1-56.9%, (p<0.001) with a median value of 40%. Current smoking was the major risk factor for chronic bronchitis, especially in males. Its effect increased according to number of pack-yrs: in males, the odds ratio of chronic bronchitis was 3.51 (95% confidence interval (CI) 2.31-5.32) in 1-14 pack-yrs smokers and increased to 17.32 (9.97-30.11) in > or = 45 pack-yrs smokers with respect to nonsmokers. Only 30% of the geographical variability in prevalence could be explained by differences in smoking habits, suggesting that other environmental and/or genetic factors may play an important role. In conclusion, chronic bronchitis is a substantial health problem even in young adults. The impressive prevalence in current smokers in most countries highlights the need to improve the quality of prevention.

Adult↗
PubMed2001

Lung cancer resection: the prediction of postsurgical outcomes should include long-term functional results.

STUDY OBJECTIVES: To assess (1) the possibility of predicting long-term postoperative lung function, and (2) the usefulness of maximal oxygen consumption (O(2)max) as a criterion for operability and as a predictor of long-term disability. DESIGN: Prospective study. SETTING: Outpatients and inpatients of a university hospital. PARTICIPANTS: Sixty-two consecutive patients (mean +/- SD age, 62 +/- 8 years; 51 male and 11 female patients) were preoperatively evaluated for lung cancer resection (pneumonectomy or bilobectomy [n = 14] and lobectomy [n = 48]). MEASUREMENTS: Clinical examination and recorded respiratory symptoms and spirometry results before surgery and 6 months after surgery. If predicted postoperative FEV(1) (ppoFEV(1)) was < 40%, patients underwent exercise testing; if O(2)max was between 10 mL/kg/min and 20 mL/kg/min, patients underwent a split-function study. RESULTS: All the patients with ppoFEV(1) > or = 40%-even those patients (26%) with FEV(1) < 80%-underwent thoracotomy without further tests. Seven patients with ppoFEV(1) < 40% underwent exercise testing, and three of them underwent a split-function study. Nine patients (15%; including six patients with COPD and one patient with asthma) had immediate postoperative complications (pneumonia [n = 5] and respiratory failure [n = 4]); seven of these patients had ppoFEV(1) > or = 40%. ppoFEV(1) significantly underestimated the actual postoperative FEV(1) (poFEV(1); p < 0.001) 6 months after pneumonectomy or bilobectomy but was reliable for actual poFEV(1) after lobectomy. Two patients with predicted postoperative O(2)max > 10 mL/kg/min became oxygen dependent and had marked limitation of daily living. CONCLUSIONS: ppoFEV(1) > or = 40% reliably identifies patients not requiring further tests and not at long-term risk of respiratory disability. O(2)max, effective for defining the immediate surgical risk, is not useful in predicting long-term disability.

Female↗
PubMed2001

Virulence of Mycobacterium tuberculosis affects interleukin-8, monocyte chemoattractant protein-1 and interleukin-10 production by human mononuclear phagocytes.

Microbial virulence and cytokine-mediated immune responses to Mycobacterium tuberculosis infection are important determinants of the pathogenesis of human tuberculosis. To determine the interrelationship between mycobacterial virulence and cytokine induction, human monocytes and monocyte-derived macrophages were infected with attenuated (H37Ra) and virulent (H37Rv and CH306) strains of M. tuberculosis and the amount of proinflammatory [interleukin (IL)-8 and monocyte chemoattractant protein (MCP)- 1] and inhibitory (IL- 10) cytokines was measured in the culture supernatants by enzyme-linked immunosorbent assay (ELISA). Infection with live bacilli induced de novo synthesis of IL-8, MCP-1 and IL-10, since cytokine release was abolished when cells were preincubated with the protein synthesis inhibitor cycloheximide. A differential production of antiinflammatory and inhibitory cytokines was observed. The amount of IL-8 and MCP-1 release was inversely related to strain virulence, the attenuated H37Ra strain being more prone than virulent strains to induce secretion of chemokines. In contrast, virulent strains induced greater amounts of the inhibitory cytokine IL-10. Efficient upregulation of IL-10 synthesis, but not of chemokines, required infection of cells with live bacilli, since heat killing of organisms or challenge with soluble mycobacterial products completely abrogated the effect. Moreover, cells infected with virulent strains produced IL-10 even at a very low bacillus-to-cell ratio and secreted IL-10 continuously during the 96 h that followed infection. The results suggest that the degree of virulence affects host cell responses to M. tuberculosis infection. Continued production of IL-10 may be one of the means by which M. tuberculosis downregulates acute local inflammatory reactions, favoring the development of tuberculosis.

Cells, Cultured↗
PubMed2000

HLA-Gm/kappam interaction in sarcoidosis. Suggestions for a complex genetic structure.

The aetiology of sarcoidosis is still unknown. Environmental exposures are believed to interact with genetic factors in determining the pattern of sarcoidosis presentation, progression and prognosis. The frequency of serological polymorphism of immunoglobulin G heavy chain (Gm) and kappa light chain (kappam) markers in 107 patients with biopsy-proven sarcoidosis and in 227 controls, and their interactions with histocompatibility leukocyte antigen (HLA) class I, II, and III markers, were studied. A "protective" effect of the Gm(3 5*) phenotype in the sarcoid group versus controls (p-value for number of specificities tested (p(c))=0.05, odds ratio 0.15) and a reduced frequency of Gm(3 23 5*) in patients with advanced chest radiographic stage (Chi-squared (two degrees of freedom)(chi2(2df) 17.61, p(c)=0.0058) were observed. With reference to epistatic interactions, the combination Gm(3 23 5*)/BfS had a "protective" effect towards stage II (chi2(2dt) 13.86, p(c)=0.043). Finally, correspondence analysis defined two clusters: HLA-DR4, C4BQ0, Gm(1, 3, 17 23 5*, 21, 28) and BfF associated with stage II, and HLA-DR3, C4AQ0, kappam(1) and Gm(3 23 5*) associated with stage I. These data further support the hypothesis that sarcoidosis results from an interplay of environmental factors and genes, each contributing to the susceptibility/resistance to and/or the clinical heterogeneity of the disease. In addition, these data provide the first evidence of an interaction between immunoglobulin G heavy chain/kappa light chain markers and histocompatibility leukocyte antigen class III genes in a disease.

Adult↗
PubMed2000

Genetic aspects in sarcoidosis.

Sarcoidosis is an immune-mediated, multiorgan, granulomatous disorder thought to be triggered by an intricate combination of environmental and genetic factors. Two robust lines of evidence support the hypothesis of a genetic component in the pathogenesis of sarcoidosis: racial variation in its epidemiology and familial clustering of cases. The relationship between epidemiology and environmental factors affecting variations in sarcoidosis incidence/prevalence and presentation are reviewed, as well as strategies to be pursued in the search for susceptibility genes for the disorder. Pathogenic processes leading to sarcoid granuloma formation and maintenance have prompted investigators interested in the genetics of sarcoidosis to focus mainly on major histocompatibility complex genes, and indeed a remarkable amount of data has been accumulated during the last two decades. Whilst in contrast with some autoimmune disorders a clear association between human leukocyte antigen (HLA) and sarcoidosis is still a controversial issue, there is, however, a general agreement that some HLA genes are related to phenotypic variations of the disease. Some genetic investigators have focused on T-cell receptor genes, immunoglobulin genes, angiotensin converting enzyme gene, chemokine genes and others. From a review of studies performed in different racial and ethnic groups, a reasonable suggestion arises that genetic factors are the major determinant in the racial variations in the epidemiology of the disorder. This assumption is, however, so far limited by lack of studies considering both genetic and environmental factors simultaneously.

Environmental Exposure↗
PubMed2000

Increased frequency of CFTR gene mutations in sarcoidosis: a case/control association study.

A complete screening of the CFTR gene by DGGE and DNA sequencing was performed in patients with sarcoidosis. In 8/26 cases, missense and splicing CFTR gene mutations were found, a significant difference over controls (9/89) from the same population (P = 0.014). The odds ratio for a person with a CFTR gene mutation to develop the disease is 3.95 (1.18 < OR < 13.26). Seven different CFTR gene mutations were observed: R75Q, R347P, 621 + 3 A/G, 1898 + 3 A/G, L997F, G1069R, and a novel mutation which was detected in this study, I991V. R75Q mutation was present in 3/26 patients, a significant increase (P = 0. 01) in cases over controls, indicating its preferential association with sarcoidosis. A trend towards disease progression was observed in patients with CFTR gene mutations compared to patients without mutations. These data suggest that CFTR gene mutations predispose to the development of sarcoidosis.

Adult↗
PubMed1999

Micellar electrokinetic chromatography for analyzing active site specificity of Pseudomonas aeruginosa elastase.

The geometry of the catalytic site of Pseudomonas aeruginosa elastase was reexamined, exploiting the specific feature of micellar electrokinetic chromatography (MEKC), i.e., its ability to detect a decrease of intact substrate and simultaneous formation of reaction products. We carried out a detailed investigation using two tri- and six tetra-peptide 4-nitroanilides (NA) differing from each other by only one or more amino acids as stable substrates. The kinetic cleavage parameters Km and k(cat) determined by MEKC and the catalytic efficiency Km/k(cat) values calculated allowed us to better define the substrate specificity of this proteinase.

Amino Acids↗
PubMed1999

Prospective multicentre study on the evaluation of antituberculosis treatment results in Italy: comparison of the culture- versus the smear-based methods. National AIPO Tuberculosis Study Group.

Cohort analysis of treatment outcomes is the most informative technique to evaluate the tuberculosis (TB) control programme. The aim of the study was to assess treatment outcomes comparing the smear- versus the culture-based methods, using data on TB patients treated under programme conditions in Italy. This was a prospective monitoring study based on the standardized collection of forms from a representative sample of Italian TB Units. The forms, with individual data, were reviewed and analysed on a quarterly basis according to the principles of cohort analysis, using both the smear- and culture-based methods. The complete bacteriological profile of patients was analysed at diagnosis and at completion of treatment. Nine hundred and ninety-two TB cases were notified. Among 681 pulmonary cases, 368 cases were culture-confirmed at diagnosis (333 new and 35 retreatment cases, 293 being sputum smear positive, 79.6%). At the end of treatment, out of the 333 new culture-confirmed cases, 136 (40.8%) were defined "cured" using the culture-based method and 108 (32.4%) using the smear-based method (p<0.05, chi2 test). The culture-based method is the recommended tool to evaluate pulmonary tuberculosis treatment results. Culture allows a more precise definition of a "cured" patient in both sputum smear positive and negative tuberculosis cases.

Antitubercular Agents↗
PubMed1999

Late pulmonary sequelae after childhood bone marrow transplantation.

BACKGROUND: Respiratory function in transplanted children is important because of the long life expectancy of bone marrow transplant recipients, particularly children. Attention is now being focused on the late sequelae of treatment on organ system function. A few papers have been published but available data are somewhat conflicting. METHODS: A cross sectional study aimed at evaluating the late effects of transplantation on lung function was performed in a group of 52 young patients who were given autologous or allogeneic bone marrow transplants during childhood for haematological malignancies. RESULTS: No patients reported chronic respiratory symptoms. The distribution of respiratory function patterns showed that only 62% of patients had respiratory function within the normal limits; 23% had a restrictive pattern and 15% had isolated transfer factor impairment. The percentage of patients with lung function abnormalities was higher in those who (1) received a bone marrow transplant after two or three complete remissions compared with those who were transplanted immediately after the first remission (54% vs 21%; p < 0.02), (2) underwent allogeneic bone marrow transplantation rather than an autologous transplantation (45% vs 26%; p = 0.06), and (3) had a pulmonary infection compared with those without (56% vs 26%; p = 0.07). CONCLUSIONS: In spite of the absence of chronic respiratory symptoms there is a high prevalence of children with late pulmonary sequelae after bone marrow transplantation. Regular testing is recommended after transplantation, in particular in subjects at higher risk of lung injuries, such as those receiving transplants after more than one remission, those receiving allogeneic transplants, and those having suffered from pulmonary infections. When lung function abnormalities become apparent, long term follow up is necessary to see whether they become clinically relevant. All patients should remain non-smokers after transplantation and should have active early and aggressive treatment for respiratory illnesses.

Adolescent↗