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Biomedical subjects

L Fabbri

Publications and source records attributed to L Fabbri.

At least 37 records · Page 2Linked to original sources
PubMed1997

Beta2-agonists prevent Th1 development by selective inhibition of interleukin 12.

Interleukin 12 (IL-12) plays a central role in the immune system by skewing the immune response towards T helper 1 (Th1) type responses which are characterized by high interferon-gamma and low IL-4 production. In this report we present evidence that beta2-agonists inhibit IL-12 production by both human monocytes in response to lipopolysaccharide (LPS) and dendritic cells stimulated via CD40. Inhibition of IL-12 production is selective, as other cytokines produced by monocytes are unaffected. IL-12 inhibition is dependent on beta2-adrenoceptor stimulation and correlates with increased levels of intracellular cAMP. In conjunction with their ability to suppress IL-12 production, when beta2-agonists are added at priming of neonatal T lymphocytes, they inhibit the development of Th1-type cells, while promoting T helper 2 (Th2) cell differentiation. Further, the in vivo administration of a therapeutic dose of salbutamol results in the selective inhibition of IL-12 production by whole blood lymphocytes stimulated in vitro with LPS. These findings provide new insight into the immunological consequences of the clinical use of beta2-agonists and may suggest new approaches for the treatment of Th1-mediated diseases.

Adrenergic beta-2 Receptor Agonists↗
PubMed1997

Serum levels of tumour necrosis factor alpha and other cytokines do not correlate with weight loss and anorexia in cancer patients.

Cancer anorexia-cachexia syndrome (CACS), which is characterized by progressive weight loss (WL) and anorexia (A), is present in 50% of advanced cancer patients and in 80% of terminally ill cancer patients. One of the most controversial aspects of CACS is its oetiopathogenesis; experimental studies have identified certain cytokines [Tumour necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), interleukin 6 (IL-6), and gamma interferon (gamma-IFN)] as possible co-factors in the onset of the syndrome. The aim of our study was to investigate the correlation between serum levels of circulating cytokines and severity of CACS. The following series of parameters was identified in 61 patients with advanced and terminal cancer: stage of disease; Karnofsky performance status (KPS) and clinical symptoms; biohumoral, anthropometric and immunological situation; level of circulating cytokines. All these parameters were evaluated for a possible link with WL/A. Our data do not show any significant correlation between circulating cytokines and WL/A. A direct correlation was identified between WL/A and nausea (P = 0.03 and P < 0.001, respectively) whereas inverse correlations were observed for both factors as regards arm circumference (P < 0.001 for both), wrist circumference (P < 0.001 for both), KPS (P < 0.001 and P = 0.003, respectively) and creatinine (P = 0.005 and P = 0.03, respectively). Other biochemical factors, such as haemoglobin, haematocrit, glycaemia, prealbumin, sodium and chlorine were also correlated with at least one of two clinical parameters in question. Unexpected results were seen in the increases in CD20 and CD4 and in the CD4/CD8 ratio. Serum levels of these cytokines do not, therefore, appear to be critical in the onset of CACS. On the contrary, our findings confirmed the clinico-laboratory picture that is characteristic of CACS. If we consider the possibility that CACS is provoked by an aspecific response of the host's defence mechanisms against prolonged neoplastic attack, the increase in CD4 (helper lymphocytes) could be linked to the persistent response.

Adult↗
PubMed1997

Evaluation of the cost of home care for terminally ill cancer patients.

The aim of this work was to carry out a cost evaluation of the home care programme for terminally ill cancer patients run by the Istituto Oncologico Romagnolo (I.O.R.) in the areas of Forlì, Cesena, Ravenna and Rimini (Romagna, Italy). To determine effective home care direct costs, we first selected 1 week of care as an observation unit. We then proceeded to assess the medical and nursing care units together with the clinical protocols administered for each patient. The Karnofsky Performance Status (KPS) was also assessed weekly. In this way, we calculated care costs for each patient and for each week as the sum of medical costs, nursing costs, treatment costs and other costs. A consecutive series of 574 patients were involved in the study from 1 April 1994 to 31 March 1995. A total of 5164 patient-weeks of care was provided, with an average cost per week of 177.6 Ecu. This weekly cost increased in the last 100 days of life (week -15 = 179.5 Ecu; week -8 = 188.3 Ecu; week -2 = 221.0 Ecu; P < 0.001). When single components were analysed in relation to total cost (treatment protocols, physician and nursing care) the increased global cost was found to be mainly attributable to the intensification in nursing care (21.8% of costs in week -15 vs 27.3% of costs in week -2). Examination of the relation between the cost of 1 week of care and KPS values clearly shows that healthcare costs increased as KPS decreased (from 152.2 Ecu with KPS > or = 60 to 292.6 Ecu with KPS < or = 20; P < 0.001). Home care costs were also seen to vary with some clinical characteristics and symptoms present when patients entered the study: asthenia, anorexia, nausea/vomiting, bedsores. Given the good results of home care for cancer patients in terms of quality of life, this method of cost accounting for home-care providers can help to monitor the rising cost of assistance and confirm the cost effectiveness of this type of care.

Adolescent↗
PubMed1997

Application of near-infrared reflectance spectrometry in the study of atopy. Part 1. Investigation of skin spectra.

An investigation into the existence of spectral differences and differences in response in terms of water and lipid content between normal and atopic skin is described. Since NIR radiation penetrates complex structured matrices down to a depth of 0.15-0.20 mm, it is evident that the method lends itself to spectral detection of skin components down to the deepest level. First the reproducibility of readings made with the instrument was tested and it was also checked whether the use of the probe caused changes in skin equilibrium due to occlusion. Analysis of the NIR spectra did not enable normal and atopic subjects to be distinguished unequivocally but provided important information on the use of NIR spectrometry in these subjects and insights into the stratum corneum. Although the responses of water and lipid structures could not be read directly from the spectra, it was possible to decompose the global spectral information into components by principal components analysis. It was possible to observe a fraction of variance associated in different ways with water.

Female↗
PubMed1997

Increased VIP-positive nerve fibers in the mucous glands of subjects with chronic bronchitis.

The presence and distribution of neuropeptide-containing nerves within bronchial surgical specimens has been investigated in bronchitic (n = 12) and in nonbronchitic subjects (n = 7). Lung tissue, obtained from patients undergoing thoracotomy for limited lung lesions, was processed immediately and analyzed for nerves using the streptavidin-biotin complex peroxidase method with antisera to the neural marker protein gene product 9.5 (PGP 9.5) and the neuropeptides vasoactive intestinal peptide (VIP), substance P (SP), calcitonin-gene related peptide (CGRP). There were no significant differences between the two groups with respect to the density of PGP 9.5-, SP-, or CGRP-positive nerves in both the locations assessed (smooth muscle layer and glands). The density of VIP-positive nerves was significantly higher in the glands of bronchitic than in nonbronchitic subjects. A negative relationship was found between the presence of airway inflammation, as indexed by mononuclear cell tissue infiltration, and the density of PGP 9.5-positive nerves in both smooth muscle and glands. Likewise, a relationship was found between the smoking history (packs/yr and age of onset of smoking) and the density of VIP-positive nerves in glands. These findings support a role for VIP in the hallmark of chronic bronchitis, i.e., sputum production.

Adult↗
PubMed1996

Methotrexate in the treatment of systemic glucocorticoid-dependent severe persistent asthma: a word of caution.

Methotrexate should not be prescribed to every systemic glucocorticoid-dependent asthmatic. In fact, while methotrexate may be advantageous in selected patients, every attempt to control asthma with regular anti-asthma agents should be made. Most studies on the effects of methotrexate in the treatment of systemic glucocorticoid-dependent asthmatics include small numbers of patients and are all of relatively short duration. Thus, large long-term multicentre trials are urgently needed. In these studies, a uniform accepted definition of systemic glucocorticoid-dependent asthmatics should be used. For the time being, we reinforce the recommendation of the NHLBI/ WHO panel that methotrexate and other systemic glucocorticoid sparing drugs should be considered experimental medications, and used only in selected patients under the supervision of an asthma specialist with previous experimental experience.

Asthma↗
PubMed1995

[Evaluation of the efficacy of oral sumatriptan in the management of migraine attacks. Clinical results].

This italian multicentre, double blind, parallel groups study compared the efficacy, safety and tolerability of oral sumatriptan, given as new film-coated tablet, with placebo in the acute treatment of migraine. 88 Patients received placebo and 162 patients received sumatriptan 100 mg (plus an optional dose 2 h later if the headache persisted plus a further optional dose for recurrence within 24 h). Sumatriptan was significantly more effective than placebo at releiving headache at 2 h (51% versus 31%, P = 0.003) and 4 h (71% versus 35%, P < 0.001). Fewer sumatriptan-treated patients required a second dose compared with placebo-treated patients (49% versus 74%, P < 0.001). Sumatriptan was more effective than placebo at relieving nausea, vomiting and photophobia/phonophobia. Few patients were evaluable for treatment of headache recurrence, and statistical analysis was not possible. More sumatriptan-treated patients than placebo-treated patients reported adverse events (29% versus 16%) but the difference was not statistically significant. More of these events were mild to moderate in severity, of short duration and resolved without treatment. Sumatriptan had no clinically significant effect on blood pressure, heart rate, electrocardiogram or laboratory test results. It is concluded that oral sumatriptan 100 mg, given as a film-coated, tablet, provides an effective and well-tolerated acute treatment for migraine.

Acute Disease↗
PubMed1994

Clinical prediction of survival is more accurate than the Karnofsky performance status in estimating life span of terminally ill cancer patients.

Predicting the survival of terminally ill cancer patients can help in informing patients and their families, in programming therapy and assistance models, and in utilising existing resources correctly. Clinical prediction of survival (CPS) and Karnofsky performance status (KPS) are two factors which have already been described in the literature. The aim of our study was to verify their respective predictive value with regard to actual survival. In our study of 100 consecutive patients, the CPS obtained a higher prediction accuracy than that reported previously (correlation coefficient with actual survival = 0.51) and than that obtained with KPS alone (correlation coefficient = 0.37). The median difference between predicted and expected survival was only 1 week. The resultant predictivity could be further improved by integrating other prognostic factors studied in larger prospective, multicentric studies.

Adolescent↗
PubMed1994

Predictive value of airways hyperresponsiveness and circulating IgE for identifying types of responses to toluene diisocyanate inhalation challenge.

Development of asthma after exposure to toluene diisocyanate (TDI) has been recognized in a variety of occupational settings. However, the pathogenesis of isocyanate-induced asthma remains controversial. In particular, the role of IgE in the development of TDI-induced asthma has remained uncertain. To investigate predictive factors for response to inhalation challenge with TDI, we analyzed data from 63 subjects referred for evaluation of respiratory symptoms thought to be related to TDI sensitization. All subjects underwent interview, routine phlebotomy, spirometry, methacholine challenge, and allergy skin testing prior to TDI challenge. Spirometry and methacholine challenge were repeated 1 day after TDI challenge. The cumulative dose of methacholine needed to produce a 20% decrease in FEV1 (PD20) was determined. A PD20 of 1.4 mg or more was considered normal. Subjects were challenged by exposure to 5 to 10 ppb TDI for up to 30 min in a 9 m3 exposure chamber. A positive response was a 20% or more decrease in FEV1 within 1 h (early) or beyond 1 h (late) after TDI exposure. Thirty-four subjects (54%) had a positive response, of whom 12 (35% of responders) had isolated early responses, 13 (38%) had isolated late responses, and the remainder had dual responses. Thirty-two individuals (51%) had a positive response to methacholine (AR+) prior to TDI challenge. AR+ was strongly associated with a positive TDI challenge: 23 AR+ subjects (72%) had a positive TDI challenge, compared with only 11 AR- subjects (35%) (p < 0.01). AR positivity did not predict the time of onset of TDI response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Toluene diisocyanate-stimulated release of arachidonic acid metabolites in the organ bath from guinea-pig airways.

This study was designed to evaluate whether metabolites of arachidonic acid play a role in the contractile response to toluene diisocyanate in isolated guinea pig airways. In control experiments we collected the supernatant from an organ bath over a time period of 2 h, after the addition of toluene diisocyanate (100 and 300 microM), and after the addition of toluene diisocyanate (300 microM) in the presence of indomethacin (5 microM). We measured prostaglandin E2, 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, thromboxane B2, leukotriene B4, leukotriene C4/D4/E4/F4 by radioimmunoassays. Levels of prostaglandin F2 alpha and 6-keto-prostaglandin F1 alpha increased significantly after addition of toluene diisocyanate in the absence of indomethacin. These results suggest that prostaglandins are involved in toluene diisocyanate-induced contractions in guinea-pig airways.

Animals↗
PubMed1993

Allergen exposure induces the activation of allergen-specific Th2 cells in the airway mucosa of patients with allergic respiratory disorders.

Biopsy specimens were obtained from the bronchial or the nasal mucosa of three patients with grass pollen-induced bronchial asthma or rhinitis 48 h after positive bronchial or nasal provocation test with grass pollen extract. T cell clones (TCC), derived from these and control specimens, were then assessed for their phenotype, allergen-specificity, profile of cytokine secretion and ability to provide B cell help for IgE synthesis. Out of 50 and 61 CD4+ TCC derived from the bronchial mucosa of the two patient with atopic asthma 11 (22%) and 19 (31%), respectively, showed both proliferation and cytokine production in response to grass pollen allergens under major histocompatibility complex-restricted conditions. Of these 21 (70%) exhibited a clear-cut type 2 T helper (Th2) profile and induced IgE synthesis in autologous peripheral blood B cells in the presence of grass allergens. All the other 9 grass-specific clones showed a Th0 pattern of cytokine secretion, but only 1 provided moderate help for IgE synthesis. In contrast, the majority of TCC, derived under the same experimental conditions from the bronchial mucosa of two nonatopic patients with toluene diisocyanate-induced asthma, were CD8+ and most of them produced interferon-gamma or interferon-gamma and interleukin-5, but not interleukin-4, in response to nonspecific stimulation. Of 22 CD4+ TCC3 (14%) derived from the grass-stimulated mucosa of the patient with allergic rhinitis, but none of those derived from the unstimulated nostril of the same patient, exhibited proliferation and cytokine production in response to grass allergens. All had a clear-cut Th2 profile and provided help for IgE synthesis by autologous B cells. These data indicate that inhalation of the relevant allergen results in the activation of allergen-specific Th2 lymphocytes in the airway mucosa of patients with allergic respiratory disorders. These cells may play a central role in determining the nature of the inflammatory response in the airways of atopic patients.

Adult↗
PubMed1993

Comparison of fluticasone propionate with beclomethasone dipropionate in moderate to severe asthma treated for one year. International Study Group.

BACKGROUND: High dose inhaled glucocorticosteroids are increasingly used in the management of patients with moderate to severe asthma. Although effective, they may cause systemic side effects. Fluticasone propionate is a topically active inhaled glucocorticosteroid which has few systemic effects at high doses. METHODS: Fluticasone propionate, 1.5 mg per day, was compared with beclomethasone dipropionate at the same dose for one year in patients with symptomatic moderate to severe asthma; 142 patients received fluticasone propionate and 132 received beclomethasone dipropionate. The study was multicentre, double blind and of a parallel design. For the first three months patients attended the clinic every four weeks and completed daily diary cards. For the next nine months they were only seen at three monthly intervals in the clinic. RESULTS: During the first three months diary card peak expiratory flow (PEF) rate and lung function measurements in the clinic showed significantly greater improvement in patients receiving fluticasone propionate (difference in morning PEF 15 l/min (95% CI 6 to 25)), and these differences were apparent at the end of the first week. The improved lung function was maintained throughout the 12 month period and the number of severe exacerbations in patients receiving fluticasone propionate was reduced by 8% compared with those receiving beclomethasone dipropionate. No significant differences between the two groups were observed in morning plasma cortisol levels, urinary free cortisol levels, or response to synthetic ACTH stimulation. In addition, both the rates of withdrawal and of adverse events were low, and there were fewer exacerbations of asthma with fluticasone propionate than beclomethasone dipropionate. CONCLUSIONS: This study shows that fluticasone propionate in a daily dose of 1.5 mg results in a significantly greater increase in PEF and asthma control than the same dose of beclomethasone dipropionate, with no increase in systemic or other side effects.

Administration, Topical↗
PubMed1993

Lack of increase or reduction in circulating platelet factor 4 and heparin-releasable platelet factor 4 in symptomatic patients with asthma.

We measured circulating platelet factor 4 (PF4) and heparin-releasable platelet factor 4 (HR-PF4) in 13 symptomatic patients suffering from bronchial asthma and in 10 matched normal controls. Neither a difference between patients and controls, nor a correlation between platelet count and HR-PF4 was found (PF4: controls 2.1 +/- 2.9; patients 3.6 +/- 4.4 ng/ml (n.s.); HR-PF4: controls 127 +/- 49, patients 101 +/- 34 ng/ml (n.s.). Therefore, the pathogenetic role of PF4 in the mechanism of bronchial asthma, elsewhere hypothesized, cannot definitely be established.

Adult↗
PubMed1991

Chemotherapy with 5-fluorouracil and streptozotocin in carcinoid tumors of gastrointestinal origin: experiences with 13 patients.

The Authors report their experiences on the treatment of 13 consecutive cases of gastro-intestinal carcinoid tumors observed over the last 11 years. The primary sites were as follows: intestine (5 cases), appendix (3 cases), colon (1 case) and peritoneum (4 cases); only 3 patients presented systemic signs. Ten patients in advanced phase were treated with a chemotherapeutic regimen containing 5-fluorouracil (5-Fu) and streptozotocin (STZ). One case was excluded from the study because of a concomitant gastric carcinoma. Of the 9 evaluable patients, two achieved partial remission (22%) with a duration of 18+ and 66 months respectively; 4 (44.5%) had stable disease for periods ranging from 7 to 40 months and 3 cases progressed. Severe toxicity (thrombocytopenia and diarrhea) occurred in 2 cases and disappeared with the suspension of therapy. The systemic signs disappeared with treatment and did not appear in 2 cases out of 3. The prospective of the employment of new drugs such as alpha-interferon and, above all, somatostatin provides hope that this uncommon disease may have an improved response rate to treatment in the future.

Adult↗
PubMed1990

[Clinical development of a drug for brain aging. Current limitations and future prospects].

The clinical development of any drug used in the treatment of brain-ageing, poses many methodological problems regarding the difficulty in defining precisely the pathology, both from the point of view of diagnostic and of terminology, the lack of specific parameters for assessing the therapeutic efficacy and the difficulty of establishing homogeneous trial sample, since the geriatric population is a very heterogeneous whole. The authors, in the light of the research done, state their methodology and give their directives; among them: common training for all the examiners, in order to make execution and classification of the tests extremely homogeneous the drug is evaluated through psychometric tests, which analyze the patient both physically and mentally.

Acetylcarnitine↗
PubMed1990

Methodology of a controlled clinical study for cerebral aging evaluation.

A multicentre study was planned and executed to evaluate the effect of acetyl-L-carnitine in the treatment of cerebral aging. Using 42 health centres, whose comparability of methodology was ensured through a training seminar and an instructional booklet on the psychometric battery of tests employed, some 400 elderly patients aged 60-80 years were enrolled using strict selection criteria. Treatment was run in four phases over 150 days. The first phase, serving as the baseline evaluation, defined through a battery of tests, consisted of 30-day placebo treatment. In the second phase of 45 days, daily treatment with 1500 mg acetyl-L-carnitine was given followed by a psychometric evaluation. For the next 45 days the same drug therapy was employed with a complete psychometric evaluation on the final day. In the last phase of 30 days the placebo was again administered and a final assessment made of the residual benefits of the 90-day treatment with acetyl-L-carnitine. Using this plan made it possible to evaluate the placebo effects, perform cross-study comparisons and demonstrate the effectiveness of the drug treatment.

Acetylcarnitine↗