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Biomedical subjects

G Moscato

Publications and source records attributed to G Moscato.

At least 37 records · Page 2Linked to original sources

T-cell interleukin-6 receptor binding in interferon-beta-1b-treated multiple sclerosis patients.

Multiple sclerosis (MS) is a T-cell-mediated autoimmune demyelinating disease of the central nervous system, associated with an altered cytokine network. We previously assayed peripheral blood T-lymphocyte binding for two prototypic cytokines, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and found that T cells from MS patients had significantly more TNF-alpha and IL-6 receptors than those from healthy controls. In the present work, paralleling a previous one on T-cell TNF-alpha binding, we studied the effect of interferon (IFN)-beta-1b treatment on T-lymphocyte IL-6 binding in patients with relapsing-remitting MS. T cells from MS patients had significantly (P < 0.001) higher amounts of IL-6 receptors than those from controls [292 +/- 6 vs. 228 +/- 8 (mean +/- SEM) receptors per cell, respectively], whereas the ligand-receptor affinity values were similar in the two groups [26.2 +/- 0.7 and 25.7 +/- 0.4 (mean +/- SEM) pmoles/l, respectively]. After a 3-month IFN-beta-1b treatment, they showed a significant decrease in IL-6 binding [266 +/- 7 (mean +/- SEM) receptors per cell]. After 6 and 9 months, T-cell IL-6 B(max) values were even lower [258 +/- 8 and 251 +/- 8 (mean +/- SEM) receptors per cell]. Since an increased IL-6 binding might be linked to a lymphocyte activation, our data give further support for an enhanced immune response in patients with MS. Our data seem to demonstrate that the major effects of IFN-beta-1b treatment result in a decrease of T-cell activation.

Adult↗

Decreases in T-cell tumor necrosis factor alpha binding with interferon beta treatment in patients with multiple sclerosis.

OBJECTIVE: To investigate the effects of interferon beta treatment on T-cell tumor necrosis factor alpha (TNF-alpha) binding (which is a possible marker for T-cell-dependent immune function) in patients with multiple sclerosis. DESIGN: The TNF-alpha binding on T lymphocytes from patients with stable relapsing-remitting multiple sclerosis was assayed before and 3 and 6 months after the start of treatment with interferon beta. SETTING: The study was performed on ambulatory patients in a tertiary care center. PATIENTS: Eighteen patients with clinically definite stable relapsing-remitting multiple sclerosis (13 women and 5 men; mean [+/-SD] age, 32.6+/-7.1 years) were selected consecutively. Clinical status was defined according to the Expanded Disability Status Scale. All patients were treated with 8 x 10(6) U of interferon beta-1b subcutaneously every other day. Eighteen age- and sex-matched healthy subjects, with no family history of neuropsychiatric disorders, served as controls. RESULTS: T lymphocytes from untreated patients with multiple sclerosis had significantly more TNF-alpha receptors than those from controls (mean+/-SE, 837+/-33 vs 135+/-5 receptors per cell). After 3 months of treatment with interferon beta-1b, they showed a significant decrease (P<.001) in TNF-alpha binding (452+/-29 receptors per cell). After 6 months, T-cell TNF-alpha maximal receptor numbers were even lower (345+/-35 receptors per cell). CONCLUSION: Given that increased TNF-alpha binding might be linked to lymphocyte activation, our data demonstrate that a major effect of interferon beta-lb treatment is to decrease T-cell activation.

Adjuvants, Immunologic↗

T-cell interferon gamma receptor binding in interferon beta-1b-treated patients with multiple sclerosis.

OBJECTIVE: To investigate the effects of interferon beta treatment on T-cell interferon gamma binding (which is a possible marker for T-cell-dependent immune function) in patients with multiple sclerosis (MS). DESIGN: Assay interferon gamma binding on T lymphocytes from patients with stable relapsing-remitting MS before, 3 months after, and 6 months after initiating interferon beta-1b treatment. SETTING: The study was performed on ambulatory patients in a tertiary care center, where patients were diagnosed as having definite MS. PATIENTS: Eighteen patients with clinically definite, stable, relapsing-remitting MS (13 women and 5 men; mean age [+/-SD] 32.6+/-7.1 years) were selected consecutively. Clinical status was defined according to the Kurtzke Expanded Disability Status Scale. All patients were treated with 8 x 10(6) IU interferon beta-1b subcutaneously every other day. Eighteen age- and sex-matched healthy subjects with no family history of neuropsychiatric disorders formed the control group. RESULTS: T lymphocytes from untreated patients with MS had significantly smaller amounts of interferon gamma receptors than those from control subjects (638+/-7 [SE] vs 707+/-11 [SE] receptors per cell). After 3 months of interferon beta-1b treatment, they showed a significant increase in interferon gamma binding (681+/-9 [SE] receptors per cell). After 6 months, T-cell interferon gamma maximal receptor values were even higher (700+/-7 [SE] receptors per cell), only slightly lower than those of control subjects. CONCLUSION: Given that reduced interferon gamma binding might be related to lymphocyte activation, our data seem to demonstrate that the major effect of interferon beta-lb treatment is a decrease in T-cell activation.

Adjuvants, Immunologic↗

Serum eosinophil cationic protein (sECP) in subjects with a history of asthma symptoms with or without rhinitis.

BACKGROUND: Serum eosinophil cationic protein (sECP) has been proposed as a marker of disease activity in bronchial asthma. The study aimed to evaluate the role of sECP in screening asthmatics in a group of subjects with asthma and rhinitis symptoms, and the relationship between sECP and clinical and functional parameters of asthma. METHODS: A total of 185 subjects with asthma symptoms, 149 of them with rhinitis as well, underwent skin tests, spirometry, methacholine (MCH) test, blood sampling for eosinophil percentage (bEOS%) and sECP determination, and nasal secretions smear for eosinophil percentage (nEOS%) determination; PEF values, symptoms, and medication over a period of 4 weeks after sampling for sECP quantitation were recorded on a diary. RESULTS: A total of 99 (53%) subjects received a diagnosis of asthma (asthmatics), and 86 did not (nonasthmatics). In asthmatics, neither sECP nor bEOS% was significantly different from nonasthmatics. In asthmatics, sECP was higher in subjects with increased than in those with normal daily PEF variability (16.4, 6.8-24.4 vs 5.3, 3.9-8.4 microg/l; P<0.001). sECP was higher in moderate persistent asthma than in intermittent asthma (24.8, 10.6-53 vs 8.4, 5.6-14.1; P<0.05). In nonasthmatics (73 with a history of rhinitis), both sECP and bEOS% correlated with nEOS% (rho=0.35; P<0.01 and rho=0.53; P<0.001). CONCLUSIONS: In adults with asthma symptoms with or without rhinitis, sECP did not distinguish asthmatics from nonasthmatics. In asthmatics, sECP was associated with PEF variability and symptom severity. In subjects with asthma and rhinitis, as well as in subjects with only rhinitis, sECP levels are possibly influenced by nasal inflammation.

Adolescent↗

Occupational asthma: a longitudinal study on the clinical and socioeconomic outcome after diagnosis.

AIM: To evaluate the clinical outcome and socioeconomic consequences of occupational asthma (OA). SUBJECTS AND METHODS: Twenty-five patients with OA both to high- and low-molecular-weight agents (3 and 22, respectively) confirmed by specific inhalation challenge were followed up for 12 months after the diagnosis. Upon diagnosis, each patient received a diary on which to report peak expiratory flow rate (PEFR), symptoms, drug consumption, expenses directly or indirectly related to the disease, as well as information regarding personal socioeconomic status. At each follow-up visit (1, 3, 6, and 12 months), the patients underwent clinical examination, spirometry, methacholine (Mch) challenge, and assessment of diary-derived parameters and socioeconomic status. Asthma severity (AS) was classified into four levels, based on symptoms, drug consumption, and PEFR variability. RESULTS: At 12 months, 13 patients (group A) had ceased exposure; the remaining 12 patients (group B) continued to be exposed. At diagnosis, FEV1 percent and provocative dose causing a 20% fall in FEV1 (PD20) of Mch were lower in group A than in group B; patients of group A were also characterized by significantly higher basal AS levels. At 12 months, no significant variation in FEV1 percent or PD20 was found for either group, while AS levels improved in both groups, the change being more marked for group A than group B. Pharmaceutical expense at 12 months significantly (p < 0.05) decreased, as compared with the first month, in group A, whereas it tended to increase in group B. In group A, 9 of 13 subjects had reported a deterioration of their socioeconomic status as compared with 2 of 12 in group B (p < 0.01). A significant loss of income was registered in patients of group A (median 21.45, 25th to 75th percentiles 16.9 to 25.8 Italian liras x 10(6) on the year preceding diagnosis and 15.498, 10.65 to 21.087 Italian liras x 10(6) on the year after diagnosis; p < 0.01), whereas no significant change was seen for patients in group B. CONCLUSIONS: In OA, cessation of exposure to the offending agent results in a decrease in asthma severity and in pharmaceutical expenses, but it is associated with a deterioration of the individual's socioeconomic status (professional downgrading and loss of work-derived income). There appears to be a great need for legislation that facilitates the relocation of these patients.

Adult↗

Effect of 1-year treatment with interferon-beta1b on thyroid function and autoimmunity in patients with multiple sclerosis.

OBJECTIVE: Interferon-beta (IFN-beta) is a widely used therapy for multiple sclerosis (MS), a demyelinating disease of the central nervous system. This study has evaluated the effect on thyroid function and autoimmunity of a 1-year treatment with IFN-beta1b in patients with MS. PATIENTS: We studied 31 patients (age 34+/-7 years, 21 women) with relapsing-remitting MS during IFN-beta1b treatment of 1 year duration. Systematic thyroid assessment and measurements of serum interleukin-6 (IL-6) levels were performed at baseline and every 3 months during treatment. RESULTS: Sixteen percent of the patients had autoimmune thyroiditis before IFN-beta1b, all positive for anti-peroxidase antibodies. The overall incidence of thyroid dysfunction was 33% over 1 year (10% hyperthyroidism, 23% hypothyroidism). Thyroid autoimmunity developed in 5/26 patients (19%), in one case without dysfunction. In addition to autoantibody positivity at baseline, female gender and the presence of an ultrasound thyroid pattern suggestive of thyroiditis were identified by multiple logistic regression as additional risk predictors for the development of thyroid dysfunction. During IFN-beta1b treatment, serum IL-6 levels rose in a consistent biphasic pattern; there was, however, no difference between patients with or without incident thyroid abnormalities. CONCLUSIONS: We conclude that IFN-beta1b therapy can induce multiple alterations in thyroid function, some of which are unrelated to thyroid autoimmunity. IL-6 measurement is not useful to identify patients prone to develop thyroid abnormalities. Though thyroid dysfunction is generally subclinical and often transient, systematic thyroid assessment should be performed during IFN-beta1b treatment.

Adjuvants, Immunologic↗

Styrene-induced alterations in the respiratory tract of rats treated by inhalation or intraperitoneally.

Although exposure to styrene occurs primarily via inhalation, the action of this agent on the respiratory tract has scarcely been investigated. This article describes morphological and biochemical changes occurring in the respiratory tract of rats after either inhalation of styrene vapors (300 ppm, 6 h/d, 5 d/wk, for 2 wk) or systemic (ip) treatment with 40 or 400 mg/kg styrene for 3 consecutive days. Electron microscopy analysis showed diffuse cell damage involving the tracheal, bronchiolar, and alveolar epithelium. In the tracheal epithelium, several cell types were affected. Ciliated cells presented vacuolation, detachment of cilia, blebbing of the apical cytoplasm, and compound cilia. Most secretory cells showed scant secretory granules and blebbings. Dense bodies and fibrillary inclusions were seen in intermediate and basal cells. Styrene also caused alterations of cytoplasmic components in type II pneumocytes and bronchiolar cells as well as thickness of the alveolar wall. These abnormalities were accompanied by depletion of glutathione (GSH) in the lung tissue. Pneumotoxic effects of systemic administration of styrene were dose dependent and tended to be more severe than those seen in the animals exposed for longer periods to styrene by inhalation. Metabolic activation of styrene and subsequent cell damage induced by the reactive metabolite styrene oxide may be involved in the sequence of events culminating in the toxic insult to the respiratory tract.

Administration, Inhalation↗

Occupational asthma and rhinitis caused by 1,2-benzisothiazolin-3-one in a chemical worker.

We report a case of occupational asthma and rhinitis caused by inhalation of 1,2-benzisothiazolin-3-one, an additive used as a microbicidal in detergent production, in a 26-year-old man employed in a chemical factory producing detergents. The subject's task consisted of pouring raw materials into the recipient of a machine which mixed the substances. Two months after the beginning of this job the patient complained of rhinitis and asthma at the workplace. The specific challenge test with 1,2-benzisothiazolin-3-one, one of the raw materials to which the subject was exposed, provoked an immediate prolonged asthmatic response and nasal symptoms, whereas exposure to other agents (e.g., alpha-amylase, alcalase or bezalkonium chloride) to which the patient was also exposed at work did not. To our knowledge this is the first case of occupational asthma and rhinitis caused by this compound.

Adult↗

Allergic and Irritant Glove-related Diseases in Health Care Workers and Their Prevention.

Because the widespread use of gloves by health care workers has induced an increase of both irritant and type I or type IV allergic glove-related diseases, the Italian Society of Preventive Medicine for Health Care Workers set up a working group to collect information about glove composition and to standardize procedures for the diagnosis and prevention of glove-related disease and job-fitness evaluation of employees who will be wearing gloves. In addition, the group made recommendations for educational programs focusing not only on users but also on purchasers, who presently favor glove selection for economic reasons. The group's recommendations are summarized in a consensus document, but cannot be considered definitive. More research is needed to achieve answers to questions raised by the working group, indicated in the consensus document. In particular, diagnostic criteria must be standardized to plan multicenter studies to verify the real extent of the problem, and further studies are needed to verify whether limit values for substances contained in the gloves (e.g., latex proteins, residual chemicals) can be established.

Journal Article↗

Comparison between peak expiratory flow and forced expiratory volume in one second (FEV1) during bronchoconstriction induced by different stimuli.

To evaluate the sensitivity of peak expiratory flow (PEF), obtained by portable peak flow meter, in detecting mild changes in airway caliber as assessed by forced expiratory volume in 1 sec (FEV1), we studied 184 subjects who underwent different bronchial challenge tests for suspected bronchial asthma. We measured FEV1 and PEF during bronchoconstriction induced by different stimuli: allergen, methacholine, toluene diisocyanate vapors, exercise, or distilled water inhalation; a total of 186 tests were examined. Before and at different times after challenge, FEV1 was measured, and immediately after, PEF was obtained by Mini-Wright or Assess Peak Flow Meter; each time FEV1 and PEF were taken as the best of three satisfactory tracings. The median FEV1 change from baseline value of all steps in the different challenge tests was 7.5% (range: 0-66%). The correlation coefficients between FEV1 and PEF percent changes in different challenge tests were low (Spearman's p: 0.27-0.69), with high scattering of the data. The concordance between classes of percent changes in FEV1 and PEF was also low (Cohen's weighted kappa: 0.28-0.42). In subjects with a FEV1 fall > 15% after challenge, the median PEF change after bronchoconstriction was lower than the corresponding FEV1 change [17% (0-52) vs. 27% (17-66)]. When different cutoff limits of PEF percent change were considered, the sensitivity of PEF to detect a significant change in FEV1 (15 or 20% change) during bronchoconstriction was low; specificity was in general higher than sensitivity. We conclude that PEF and FEV1 changes are poorly related during mild bronchoconstriction induced by different stimuli. The low sensitivity of PEF to detect mild changes in airway caliber may represent a limit in the use of PEF in the day-to-day monitoring of asthma.

Allergens↗

Clinical evaluation of occupational asthma.

In this paper, the procedures in the assessment of occupational asthma (OA) are discussed. Only the most common subtype of OA is considered here, i.e. that in which symptoms appear after a latency period from the beginning of exposure. OA is characterized by variable bronchial obstruction, and variable bronchial hyperresponsiveness caused by specific agents inhaled at work. The clinical investigation of OA is a stepwise approach which includes a comprehensive history together with physiological and immunological studies. The first step is to identify symptoms and relate exposure at work to the presence in the workplace of substances known to provoke OA. The presence of bronchial asthma must then be confirmed; this is achieved by assessing the reversibility of bronchial obstruction and/or the presence of nonspecific bronchial hyperreactivity and/or the presence of significant peak expiratory flow (PEF) variability. The relationship between work and symptoms may first be assessed by means of serial measurements of PEF and of nonspecific bronchial hyperreactivity during periods at work and away from work. When the suspected agent is a high-molecular-weight (HMW) or a low-molecular-weight (LMW) agent known to act through an immunoglobulin E (IgE)-mediated mechanism, skin tests and/or research for specific IgE should be performed. In case of sensitization, where a relationship between asthma and work has been demonstrated by means of serial monitoring of PEF, a diagnosis can be made. If the suspected agent is a LMW agent, a specific inhalation challenge test in the laboratory or at the workplace is necessary.

Asthma↗

Bronchial responsiveness to ultrasonic "fog" in occupational asthma due to low molecular weight chemicals.

BACKGROUND: In a previous work we have demonstrated that the use of an indirect stimulus such as ultrasonically nebulized distilled water (UNDW, "fog") challenge, in addition to methacholine, in the assessment of occupational asthma due to TDI improves our ability in detecting sensitized subjects. OBJECTIVE: In the present study we aimed to determine the validity of "fog" in the assessment of occupational asthma induced by various low molecular weight substances. METHODS: Fourty subjects exposed to low molecular weight substances with work-related respiratory symptoms underwent methacholine, UNDW and specific bronchial challenge tests. Diagnosis of occupational asthma was made in 20 of 40 patients who developed bronchoconstrictive responses to the specific challenges (reactors). Sensitivity and specificity of UNDW alone, of methacholine alone, and of the combination of the two tests were determined at two different cutpoints of PD20FEV1 of methacholine, with the results of the specific challenge as the "gold standard". RESULTS: Frequency and severity of bronchial hyperresponsiveness both to UNDW and to methacholine were significantly higher in reactors than in nonreactors. Ultrasonically nebulized distilled water had higher specificity (80% versus 60%) but lower sensitivity (65% versus 75% to 90%) than methacholine. As compared with methacholine alone, the combination in series of the two challenges (both challenges positive) substantially improved specificity (85% versus 60%). CONCLUSIONS: In conclusion, in the assessment of low molecular weight chemical-induced asthma diagnosed with the specific challenge as the "gold standard," UNDW challenge proves more specific than methacholine for occupational asthma, but it is considerably less sensitive. The combination of the two challenges results in very high sensitivity and high specificity for occupational asthma, therefore, although further investigations are required for the definitive diagnosis, it should be regarded as a useful means to confirm objectively a suggestive history.

Adult↗