Biomedical subjects

M Bugiani

Publications and source records attributed to M Bugiani.

At least 37 records · Page 2Linked to original sources

PubMed2002

Cerebral white matter involvement in children with mitochondrial encephalopathies.

In childhood mitochondrial encephalopathies the common MRI features are bilateral symmetric abnormalities in basal nuclei and brainstem. The presence of diffuse white matter abnormality has been described only in a few cases. Among a series of 110 children with mitochondrial encephalopathies, 8 patients with MR imaging consistent with a leukoencephalopathy were retrospectively evaluated. Diagnosis was based on the recognition of the biochemical defect in muscle homogenate. H-MR spectroscopic imaging was performed in six of them. Biochemical analysis demonstrated a defect of respiratory chain complexes in six patients: complex I in two cases, complex II in two, complex IV in one, multiple complexes defect in one. Pyruvate dehydrogenase deficiency was demonstrated in two patients. MRI showed severe involvement of the brain white matter without significant basal nuclei or brainstem abnormalities. Two patients developed large cystic areas since onset; in two others progressive vacuolisation of affected white matter was seen later in the course of the disease. One patient with pyruvate dehydrogenase deficiency also presented with a diffuse cortical polymicrogyria. H-MR spectroscopic imaging showed a decrease of N-acetylaspartate, choline and creatine with lactate accumulation in five patients, and was normal in one. These findings suggest that mitochondrial disorders should be included in the differential diagnosis of white matter disorders.

Atrophy↗

PubMed2001

Infantile Alexander disease: spectrum of GFAP mutations and genotype-phenotype correlation.

Heterozygous, de novo mutations in the glial fibrillary acidic protein (GFAP) gene have recently been reported in 12 patients affected by neuropathologically proved Alexander disease. We searched for GFAP mutations in a series of patients who had heterogeneous clinical symptoms but were candidates for Alexander disease on the basis of suggestive neuroimaging abnormalities. Missense, heterozygous, de novo GFAP mutations were found in exons 1 or 4 for 14 of the 15 patients analyzed, including patients without macrocephaly. Nine patients carried arginine mutations (four had R79H; four had R239C; and one had R239H) that have been described elsewhere, whereas the other five had one of four novel mutations, of which two affect arginine (2R88C and 1R88S) and two affect nonarginine residues (1L76F and 1N77Y). All mutations were located in the rod domain of GFAP, and there is a correlation between clinical severity and the affected amino acid. These results confirm that GFAP mutations are a reliable molecular marker for the diagnosis of infantile Alexander disease, and they also form a basis for the recommendation of GFAP analysis for prenatal diagnosis to detect potential cases of germinal mosaicism.

Adolescent↗

PubMed2001

The role of metals in autoimmune vasculitis: epidemiological and pathogenic study.

BACKGROUND: A possible relationship between Silica (Si) exposure and antineutrophil cytoplasm antibodies (ANCA)-associated vasculitis has been reported. Furthermore, tuberculosis (TBC) has been frequently described in patients with silicosis, and TBC infection shares with ANCA-associated vasculitis the formation of granulomas. Therefore, an intriguing network including Silica, Vasculitis, TBC and ANCA might be hypothesized. The aim of this work was to further investigate these correlations using both epidemiological and pathogenic approaches. METHODS: Study I--epidemiological study. A case-control study to compare the occupational histories of 31 cases of biopsy proven vasculitis (18 pauci-immune crescentic glomerulonephritis, 9 microscopic polyangitis, 4 Wegener's granulomatosis) with those of 58 age, sex and residence-matched controls (affected by other kidney diseases), was performed. Occupational Health physicians designed an appropriate questionnaire in order to evaluate a wide spread of exposures and calculate their entity by the product of Intensity x Frequency x Duration. Study II--tuberculosis association. A case-control study to evaluate the frequency of a previous history of tuberculosis (TBC) in 45 patients with vasculitis and 45 controls were performed. Study III--ANCA positivity. A case-control study to evaluate the presence of ANCA was performed by testing blood samples of 64 people with previous professional exposure and 65 sex/age matched patients hospitalized in a General Medicine Unit. Furthermore, the same evaluation was made in a pilot study in 16 patients with ongoing or previous TBC. Study IV--experimental study. The oxygen free radicals (OFR) and IL-12 production (both involved in the pathogenesis of vasculitis) from human phagocytic cells stimulated with an amorphous (diatomaceous earth) and a crystalline (quartz) form of Si at the doses of 10 and 100 microg ml(-1) was evaluated. RESULTS: Study I--a positive history of exposure to Si resulted in significantly more present in cases (14/31 = 45%) than in controls (14/58 = 24%, P = 0.04, OR = 2.4) and no other significant exposure association was found (including asbestos, mineral oil, formaldehyde, diesel and welding fumes, grain and wood dust, leather, solvents, fungicides, bitumen, lead and paint). Study II--past TBC infection was significantly more present in patients with vasculitis (12/45 = 26%) than in controls (4/45 = 8%, P < 0.05). Study III--ANCA was present in 2/64 exposed people (vs. 0/65 controls, P = NS) and 0/16 patients with TBC. Study IV--both amorphous and crystalline Si forms represented a stimulus for OFR and IL-12 production, but quartz resulted as a greater inductor. CONCLUSIONS: We conclude that Si exposure might be a risk factor for ANCA-associated vasculitis, possibly enhancing endothelial damage by phagocyte generation of oxygen free radicals and Th1 differentiation by an excessive IL-12 phagocyte production. Frequency of TBC was significantly higher in vasculitis patients. ANCA was not frequent in the preliminary examination of people with previous professional exposure or patients with TBC, but the number of samples evaluated is too small to allow conclusions.

Adult↗

PubMed2001

Screening for tuberculosis and latent tuberculosis infection among undocumented immigrants at an unspecialised health service unit.

SETTING: Practical or cost-effective strategies to identify undocumented immigrants with latent tuberculosis infection and to deliver treatment for latent TB infection are still unavailable. OBJECTIVES: To compare completion rates of screening procedures for TB infection and disease among undocumented immigrants at specialised (TB) and unspecialised health services in Italy. DESIGN: A TB unit (TBU) and an unspecialised health service unit for migrants (MHCU) served as recruitment sites for recent undocumented immigrants from TB endemic areas. The screening included a symptom questionnaire, a tuberculin skin test and a chest X-ray. RESULTS: Of 1318 eligible subjects, 1232 (93.4%) accepted the screening. Screening was completed by 993 (80.6%) individuals overall, 86.5% and 71.4% at the TBU and MHCU services, respectively. In a multivariate analysis model, the only variable associated with an increased probability of completing screening was being enrolled at the TBU site (OR 2.5, 95%CI 1.8-3.5; P < 0.001). Three hundred and ninety-two subjects (39.4%) had a TST test of > or = 10 mm. Eight cases of active tuberculosis were detected, with a calculated prevalence of disease of 650/100,000. CONCLUSIONS: Undocumented immigrants to Italy can be screened for TB at an unspecialised health service unit, although not as efficiently as at a specialised TB unit.

Emigration and Immigration↗

PubMed2000

Neuronal ceroid lipofuscinosis: detection of atypical forms.

The neuronal ceroid lipofuscinoses (NCL) are progressive neurodegenerative diseases occurring in infancy and adulthood. Atypical forms of these diseases have been described and are particularly represented in the late-infantile and juvenile onset groups. Recent progress in biochemistry and molecular genetics has identified some of these variants as separate disease entities while disclosing the phenotypic variability of some classic forms. We report the results of a retrospective analysis performed on a series of 27 NCL patients, 15 of which were atypical as to clinical and/or pathological findings. Most of such patients, belonging to the late-infantile onset group and displaying homogeneous clinical-pathological features, were suggestive for CLN6. The two atypical juvenile NCL patients had features which resembled the "protracted form" of the disease. Given their relative frequency, strict clinical and pathological criteria are still the most useful tools for identifying and characterizing atypical forms and for defining phenotype-genotype correlations.

Adult↗

PubMed2000

Brainstem encephalitis resulting from Epstein-Barr virus mimicking an infiltrating tumor in a child.

A case of a child with subacute neurologic features and imaging findings consistent with a brainstem encephalitis that was discovered to be related to a primary central nervous system infection caused by Epstein-Barr virus is presented. A brainstem tumor was initially suspected, but a correct diagnosis was formulated on the basis of the favorable clinical course and the detection of positive Epstein-Barr virus serology. In contrast to a prompt recovery of neurologic signs the neuroimaging alterations persisted for a longer time. The present report emphasizes the possible role of Epstein-Barr virus in the pathogenesis of infectious neurologic disorders in childhood, underlining the unusual presentation of a brainstem encephalitis, and considers the discrepancy between the course of neurologic features and the evolution of imaging alterations.

Antibodies, Viral↗

PubMed2000

Microbiological confirmation of tuberculosis cases at diagnosis and at the end of treatment in Italy.

Microbiological findings at diagnosis and at the end of treatment are relevant for evaluating tuberculosis (TB) treatment programmes. The objectives of this study were to describe the microbiological findings at diagnosis and at the end of treatment in pulmonary and extrapulmonary TB patients treated under programme conditions in Italy. The study was a prospective monitoring activity based on the collection of standard recording and reporting forms from a representative sample of Italian TB Units. The forms with individual data were reviewed and analysed on a quarterly basis, 9 months after enrolment. The complete bacteriological profile of patients was analysed at diagnosis and at the completion of treatment. Individual data on 992 patients were analysed. At diagnosis 320 (32.2%) of cases were pulmonary sputum smear positive, 361 (36.4%) pulmonary smear negative or not done and 311 (33.4%) extrapulmonary; 424 (42.7%) of all TB cases were culture confirmed at diagnosis (368, 50.2%, of pulmonary cases); 575 (84.4%) of pulmonary cases had a culture done at diagnosis and 156 (22.9%) at the end of treatment (p < 0.001); 572 (84%) had a sputum smear done at diagnosis and 164 (24.1%) at the end of treatment (p < 0.001). Although the rate of bacteriologically confirmed cases is similar to that of other European countries, the bacteriological confirmation at diagnosis and, particularly, at the end of treatment, is sub-optimal. The importance of further disseminating national guidelines among physicians managing TB is emphasized, in order to achieve a higher proportion of TB cases bacteriologically confirmed at diagnosis and monitored at the end of treatment.

Antitubercular Agents↗

PubMed2000

Supervised preventive therapy for latent tuberculosis infection in illegal immigrants in Italy.

In a multicenter, prospective, randomized, open-label study of isoniazid-preventive therapy (IPT) for latent tuberculosis infection, illegal immigrants from countries where tuberculosis is highly endemic were enrolled at two clinical sites in Northern Italy. Of 208 eligible subjects, 82 received supervised IPT at a dose of 900 mg twice weekly for 6 mo (Regimen A), 73 received unsupervised IPT 900 mg twice weekly for 6 mo (Regimen B), and 53 received unsupervised IPT 300 mg daily for 6 mo (Regimen C). Supervised IPT was delivered at either one tuberculosis clinic or one migrant clinic. The probability of completing a 26-wk regimen was 7, 26, and 41% in Regimens A, B, and C, respectively (p < 0.005, Log- rank test calculated using Kaplan-Meier plots). The mean time to dropout was 3. 8, 6, and 6.2 wk in Regimens A, B, and C, respectively (p = 0.003 for regimen A versus either Regimens B or C). Treatment was stopped in five subjects (2.4%) because of adverse events. The rate of completion of preventive therapy for latent tuberculosis infection among illegal immigrants was low. Supervised, clinic-based administration of IPT significantly reduced adherence. Alternative strategies to implement preventive therapy in illegal immigrants are clearly required.

Adolescent↗

PubMed1999

A new questionnaire for the repeat of the first stage of the European Community Respiratory Health Survey: a pilot study.

In the early 1990s a multicentre survey on asthma was performed on the young adult population (European Community Respiratory Health Survey - ECRHS). This study is to be repeated in order to estimate changes in the prevalence of asthma-like symptoms during the last decade and to assess the social and economic costs of the disease and their variations among countries. The self-administered questionnaire devised for this purpose is a two-page questionnaire. The first page contains the same items as those used in the first survey with four additional questions related to: 1) the frequency and severity of asthma attacks; 2) the presence of chronic bronchitis; 3) smoking habits; and 4) a visual analogue scale assessing perception of outdoor pollution. The second page aims to collect information regarding the direct and indirect costs of asthma. The influence of the length of the questionnaire on the response rate was assessed in a pilot study in Italy. Two random samples of 150 subjects received either the one-page questionnaire (first page) or the two-page questionnaire. The response rate was compared with that obtained from the first postal wave in the 1991-1992 survey. Although the response rate was unchanged when using the one-page questionnaire (45% versus 45%), it decreased by 7% when the two-page questionnaire was used (38% versus 45%). On the basis of these results, no problem should arise if four more questions are added to the one-page questionnaire. The slight reduction in the response rate of the two-page questionnaire is worrying but could be corrected by the use of telephone interviews.

Adult↗

PubMed1999

Cost-comparison of different management policies for tuberculosis patients in Italy. AIPO TB Study Group.

Although in developing countries the treatment of tuberculosis (TB) cases is among the most cost-effective health interventions, few studies have evaluated the cost-effectiveness of TB control in low-prevalence countries. The aim of the present study was to carry out an economic analysis in Italy that takes into account both the perspective of the resource-allocating authority (i.e. the Ministry of Health) and the broader social perspective, including a cost description based on current outcomes applied to a representative sample of TB patients nationwide (admission and directly observed treatment (DOT) during the initial intensive phase of treatment); a cost-comparison analysis of two alternative programmes: current policy based on available data (scenario 1) and an hypothetical policy oriented more towards outpatient care (scenario 2) (both scenarios included the option of including or not including DOT outside hospital admission, and incentives) were compared in terms of cost per case treated successfully. Indirect costs (such as loss of productivity) were included in considerations of the broader social perspective. The study was designed as a prospective monitoring activity based on the supervised collection of forms from a representative sample of Italian TB units. Individual data were collected and analysed to obtain a complete economic profile of the patients enrolled and to evaluate the effectiveness of the intervention. A separate analysis was done for each scenario to determine the end-point at different levels of cure rate (50-90%). The mean length of treatment was 6.6 months (i.e. patients hospitalized during the intensive phase; length of stay was significantly higher in smear-positive patients and in human immunodeficiency virus (HIV) seropositive patients). Roughly six direct smear and culture examinations were performed during hospital admission and three during ambulatory treatment. The cost of a single bed day was US$186.90, whereas that of a single outpatient visit ranged, according to the different options, from US$2.50 to US$11. Scenario 2 was consistently less costly than scenario 1. The cost per case cured for smear-positive cases was US$16,703 in scenario 1 and US$5946 in scenario 2. The difference in cost between the cheapest option (no DOT) and the more expensive option (DOT, additional staff, incentives) ranged from US$1407 (scenario 1, smear-negative and extrapulmonary cases) to US$1814 (scenario 2, smear-positive cases). The additional cost to society including indirect costs ranged from US$1800 to US$4200. The possible savings at the national level were in the order of US$50 million per year. In conclusion, cost-comparison analysis showed that a relatively minor change in policy can result in significant savings and that the adoption of DOT will represent a relatively modest economic burden, although the real gain in effectiveness resulting from DOT in Italy requires further evaluation.

Cost Control↗

PubMed1998

Doses and models in risk assessment analysis for bronchial hyperresponsiveness.

The aims of this study are: (1) to evaluate whether the estimates of the association of risk factors with bronchial hyperresponsiveness (BHR) depends on the accumulated dose administered in challenge tests; and (2) to verify whether a model developed for survival studies (Weibull regression) is suited to analyze methacholine dose-response curves. For these purposes, 863 challenge tests, from EC Respiratory Health Survey in Italy, up to a cumulative dose of 6 mg methacholine, were analyzed by Weibull regression and by traditional methods (logistic model and linear model), both before and after truncation of the curves at 2 mg. With all methods the main risk factors for BHR were respiratory symptoms and atopy while age and airway caliber exerted a protective action. Our results confirmed that in epidemiological surveys 2 mg methacholine is enough to fully appreciate the effect of risk factors on BHR and showed that the Weibull model explains the observed variability better than linear and logistic regressions.

Adult↗

PubMed1998

Predictors of survival in a group of patients with chronic airflow obstruction.

This article shows the results of a 10-year follow-up study conducted on a cohort of 870 patients affected by severe chronic airflow obstruction (CAO) on spirometric tests. The main aims of the study were to identify those factors associated with reduced survival in CAO patients and to evaluate the effectiveness of a care program on patients' survival. The analysis compared the survival time and causes of death between patients who showed adherence and patients who did not show adherence to the care program. The most important results can be summarized as follows: (1) CAO patients have a high mortality rate for acute respiratory failure, cor-pulmonale, and lung cancer; (2) patient's age at the time of selection to enter follow-up influences the death hazard; (3) patients who need long-term oxygen treatment (LTOT) have a higher death hazard than those who don't need it; (4) the higher is FEV1 or PaO2 value at the time of selection, the lower the death hazard; (5) patients who need, and regularly take, long-term oxygen treatment have a lower death hazard compared to those who need it, but do not take it properly; and (6) patients with a partial reversible airway obstruction (pRAO) who regularly attend the clinic for planned check-ups, have a lower death hazard compared to those who have the same characteristics, but do not show adherence to the care program. These results indicate that an organized program to treat severe CAO patients may improve their survival.

Adult↗

PubMed1998

Fatal familial insomnia: genetic, neuropathologic, and biochemical study of a patient from a new Italian kindred.

Fatal familial insomnia (FFI) is an inherited prion disease linked to a mutation at codon 178 of the PRNP gene that results in aspartic acid to asparagine substitution, in coupling phase with methionine at position 129. The disease is characterized clinically by insomnia with disturbances of the autonomic, endocrine, and motor systems and neuropathologically by selective degeneration of the thalamus. Phenotypic variability is well known and has been linked to homozygosity or heterozygosity at PRNP codon 129. We report the clinical, neuropathologic, and biochemical findings and genomic analysis of a patient with FFI from a new Italian kindred. Although homozygous for methionine at codon 129, this patient showed some clinical and pathologic features most commonly found in heterozygotes.

Blotting, Western↗

PubMed1998

An undetected burden of asthma in Italy: the relationship between clinical and epidemiological diagnosis of asthma.

This study aimed to compare questions and tests used in asthma epidemiology with clinical diagnosis of current asthma and to assess the extent of undiagnosed asthma in Italy. Thus, 811 attenders to the second stage of the European Community Respiratory Health Survey were classified by panels of respiratory physicians as current asthmatics or not. Among those with a clinical diagnosis of asthma (n=105), 69% reported current wheezing and 68% asthma in their lifetime (ever asthma), while asthma attacks in the previous year and/or current treatment for asthma (self-reported current asthma) were mentioned by only 37%. Thirty two per cent did not mention asthma at any time, but nevertheless presented a rate of hospitalization close to that of people with self-reported current asthma. On the other hand, almost no subjects labelled nonasthmatics by clinicians (n=706) presented self-reported current asthma (99.7%), while some reported ever asthma (5%) or current wheezing (9%). A model simulation showed that, in its usual range (0-15%), asthma prevalence is markedly overestimated by the question on wheezing and underestimated by the questions on self-reported current asthma, with respect to clinical judgement. Prevalence estimates close to those obtained by clinical judgement were achieved by combining asthma-like symptoms in the previous year with the results of lung function and allergological tests, but especially by using the single question on ever asthma. In conclusion, the present results suggest that the question on ever asthma gives prevalence estimates close to those obtained by clinical judgement and that asthma is greatly underdiagnosed in Italy.

Adult↗

PubMed1998

An antibody raised against a conserved sequence of the prion protein recognizes pathological isoforms in human and animal prion diseases, including Creutzfeldt-Jakob disease and bovine spongiform encephalopathy.

Antibodies to the prion protein (PrP) have been critical to the neuropathological and biochemical characterization of PrP-related degenerative diseases in humans and animals. Although PrP is highly conserved evolutionarily, there is some sequence divergence among species; as a consequence, anti-PrP antibodies have a wide spectrum of reactivity (from strong immunopositivity to lack of reactivity) when challenged with PrP from diverse species. We have produced an antibody (anti-PrP95-108) raised against a synthetic peptide corresponding to residues 95 to 108 of human PrP and have characterized it by epitope mapping, Western immunoblot analysis, and immunohistochemistry. The antibody recognizes not only human PrP isoforms but also pathological PrP from all species tested (ie, cattle, sheep, hamsters, and mice). This is probably due to the fact that the epitope recognized by this antibody includes residues 100 to 108 of human PrP, a sequence that is also present in PrP of several other species. Thus, this reagent is valuable not only for the study of human prion diseases but also for analysis of the possible relationship between human and animal disorders.

Amino Acid Sequence↗

PubMed1997

Effectiveness of anthracycline against experimental prion disease in Syrian hamsters.

Prion diseases are transmissible neurodegenerative conditions characterized by the accumulation of protease-resistant forms of the prion protein (PrP), termed PrPres, in the brain. Insoluble PrPres tends to aggregate into amyloid fibrils. The anthracycline 4'-iodo-4'-deoxy-doxorubicin (IDX) binds to amyloid fibrils and induces amyloid resorption in patients with systemic amyloidosis. To test IDX in an experimental model of prion disease, Syrian hamsters were inoculated intracerebrally either with scrapie-infected brain homogenate or with infected homogenate coincubated with IDX. In IDX-treated hamsters, clinical signs of disease were delayed and survival time was prolonged. Neuropathological examination showed a parallel delay in the appearance of brain changes and in the accumulation of PrPres and PrP amyloid.

Amyloid↗

PubMed1997

Inadequate antiasthma drug use in the north of Italy.

A multicentre survey of prevalence, determinants and management of asthma (the European Community Respiratory Health Survey (ECRHS)) has shown that the ratio of subjects declaring current use of antiasthmatic drugs to those reporting asthma attacks in the previous 12 months was particularly low (0.54) in the north of Italy. In this study, we used a standardized clinical interview to gather a more detailed insight into the issue of asthma undertreatment in the north of Italy. A total of 1,104 subjects were interviewed, 116 of whom had been defined as asthmatic by the family doctor. Fifty subjects had current asthma and 66 had a history of previous asthma. A considerable percentage (26%) of subjects with current asthma were not being treated with antiasthmatic therapy. Even when only patients with severe asthma were considered, the percentage of untreated patients was still high (21%). Forty two per cent of subjects used inhaled beta2-agonists alone, 28% inhaled steroids plus beta2-agonists, 2% inhaled steroids alone and 2% other drugs. Only 19% of the asthmatics on treatment, 85% of whom had more severe asthma, received daily treatment. Only 65% of the subjects who had received antiasthmatic drug prescriptions declared they had taken all the drugs prescribed; this percentage was 74% when respiratory symptoms were worsening. Of the patients with past asthma, 18% had taken antiasthmatic drugs. Most of these patients were those who had had more severe asthma. In conclusion, antiasthmatic drugs are underused in the north of Italy, at least in part due to low compliance.

Adult↗

PubMed1996

[The sweat test. The proposal to revise the concept of the "grey zone"].

The results of the sweat tests performed in Turin CF Centre in the last four years were reviewed. The opportunity of changing the range of doubt, commonly situated between 40 and 70 mEq/l Cl-, has been considered. The sweat test appears worth to be repeated only for values > 60, unless clinical signs and symptoms persist.

Cystic Fibrosis↗