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Biomedical subjects

F Sabatini

Publications and source records attributed to F Sabatini.

At least 19 recordsLinked to original sources

UV hazard on a summer's day under Mediterranean conditions, and the protective role of a beach umbrella.

Mediterranean beaches are very crowded during summer and, because of the high values of solar UV radiation, the potential risk for human health is relevant. In this study, all-day measurements of biologically effective global and diffuse UV radiation for skin (UVBE(eryt)) and eye (UVBE(pker), UVBE(pconj), UVBE(cat)) disorders were carried out on differently tilted surfaces on a summer's day on a Mediterranean beach. The role played by beach umbrellas in protection from excessive sun exposure was also investigated. Erythema, photokeratitis and cataract seem to require almost the same exposure time to reach the risk threshold dose. Under full sunlight, the highest global and diffuse UV values are reached on surfaces normally oriented towards sunlight and on horizontal surfaces, respectively. Over vertical surfaces, at this northern hemisphere site, global and diffuse UV radiation reaches maxima values in the south-facing direction around noon, while maxima values are reached early in the morning and late in the afternoon over surfaces facing east and west, respectively. The quality of the beach umbrella's protection (efficiency in blocking solar UV radiation) varies with surface orientation; the highest efficiency for our specific site and geometrical conditions occurs over horizontal surfaces, with efficiency being least over vertical surfaces when incident radiation values are still relevant.

Bathing Beaches↗

Cytokine-activated bronchial epithelial cell pro-inflammatory functions are effectively downregulated in vitro by ciclesonide.

Ciclesonide, a new inhaled corticosteroid, is administered as a parent compound and converted in the airway mucosa into the active metabolite, desisobutyryl-(des-)ciclesonide. A study was designed to evaluate the ability of ciclesonide to modulate pro-inflammatory functions of human bronchial epithelial cell (HBEC) primary cultures being converted into des-ciclesonide. HBECs were stimulated with interleukin (IL)-4 and tumour necrosis factor (TNF)-alpha (20 ng/mL) in the presence of ciclesonide and intercellular adhesion molecule (ICAM)-1 expression, granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-8 release evaluated respectively by FACS and ELISA. Ciclesonide (3 microM) significantly inhibited ICAM-1 expression by stimulated HBECs, already after 3h and still after 48 h culture (p < 0.01). At all the concentrations tested ciclesonide inhibited ICAM-1 expression (p < 0.05). GM-CSF and IL-8 release by stimulated HBECs was also downregulated by ciclesonide (p < 0.05). All the ciclesonide activities tested appeared to be mainly due to a partial inhibition of the 'IL-4 + TNF-alpha-induced' and little or no involvement of the 'constitutive' cell functions. Des-ciclesonide was detected in 24 h culture HBEC supernatants using high-performance liquid chromatography, while no parental compound ciclesonide was present. These results show at cellular level the fast and prolonged activity of ciclesonide on pro-inflammatory functions of HBECs, a selective target of asthma therapy, involved in the activation of this new inhaled corticosteroid.

Adrenal Cortex Hormones↗

Early decrease in nasal eosinophil proportion after nasal allergen challenge correlates with baseline bronchial reactivity to methacholine in children sensitized to house dust mites.

BACKGROUND: Allergic rhinitis is induced by an IgE mediated inflammation after allergen exposure of the membranes lining the nose which, in predisposed individuals, may constitute a risk factor for the occurrence of asthma. OBJECTIVE: To detect early changes in nasal inflammation after allergen exposure, 11 children [9.0 (7, 11) yrs], sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and an age- and gender-matched control group (Ctr) were studied. METHODS: The following parameters were evaluated: i) pulmonary function; ii) bronchial reactivity to methacholine (MCh), expressed as Pd20MCh; iii) nasal brushing (NB) 'at baseline' and, on a separate day, 30 min after nasal allergen challenge (NAC). On NBs, the following markers of inflammation were evaluated: a) neutrophil and eosinophil proportion, b) 'intact to degranulated eosinophil' ratio, and c) expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR by nasal epithelial cells. RESULTS: 'At baseline', allergic children showed elevated nasal eosinophilia and increased ICAM-1 and HLA-DR expression (p<0.05), as compared to Ctr. In allergic children, nasal eosinophilia correlated with Pd20MCh (p=0.002). The significant decrease in nasal eosinophilia observed after NAC (p=0.002) was associated with a significant decrease in the 'intact to degranulated eosinophil' ratio (p=0.001). Interestingly, correlations were still present between Pd20MCh and 'post NAC' eosinophilia (p=0.004) or the NAC-induced decrease in eosinophilia (p=0.010). CONCLUSIONS: In children sensitized to HDM, experimental allergen exposure is followed by an early depletion of nasal eosinophils. The correlation between allergen-induced changes in nasal eosinophilia and bronchial reactivity to MCh further supports the concept of a tight link between upper and lower respiratory tract involvement in respiratory allergy.

Allergens↗

Cytokine release and adhesion molecule expression by stimulated human bronchial epithelial cells are downregulated by salmeterol.

Summary beta2-adrenoreceptor agonists are able to modulate various aspects of airway cell functions involved in the inflammatory and repair processes characterizing a variety of respiratory disorders. Human bronchial epithelial cells (HBECs), which can act as immune effector cells and express beta2-adrenoreceptors, were used to test the effects of different concentrations (0.1-100.0 nM) of salmeterol (Salm) on adhesion molecule expression and chemokine/cytokine release. HBECs, freshly isolated from resected bronchi at the time of surgery in ex-smokers with lung cancer, constitutively expressed over 3 times more ICAM-1 than VCAM-1 (P<0.05) and secreted greater amounts of IL-8 than of GM-CSF or RANTES (P<0.001). Stimulation of HBECs with IL-4, TNF-alpha or IL-4 plus TNF-alpha-upregulated ICAM-1 expression (P<0.05) and increased GM-CSF and IL-8 secretion (P<0.05). Similarly, VCAM-1 expression was significantly increased by IL-4 plus TNF-alpha, while RANTES release was significantly enhanced by IL-4 or by IL-4 plus TNF-alpha (P<0.05), but not by TNF-alpha alone (P>0.05). Dose-response curves showed that Salm, at concentration >1.0 nM, was effective in inhibiting adhesion molecule expression and cytokine release by HBECs (P<0.05). At a Salm concentration of 10 nM the degree of inhibition observed was similar for ICAM-1 and VCAM-1 expression (37.2 +/- 9.3% and 32.9 +/- 9.6%, respectively; P>0.05), but higher for RANTES (88.4 +/- 4.4%), as compared to IL-8 (21.8 +/- 7.0%) or GM-CSF (30.1 +/- 6.6%; P<0.05, each comparison). Thus, adhesion molecules and cytokines may be expressed/released at very different levels by unstimulated or stimulated HBECs and those activities appear to be modulated by Salm.

Adult↗

Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling.

Lung fibroblasts play a key role in the pathogenesis of airway inflammation and remodeling through the release of mediators and the expression of surface molecules connected with cell-cell and cell-extracellular matrix interaction. The aim of the study was to evaluate the inhibitory effect of two corticosteroids, mometasone furoate (MOM) and dexamethasone (DEX), respectively, on a variety of fibroblast functions: DNA synthesis and proliferation, expression of adhesion molecules [intercellular adhesion molecule-1 (ICAM-1, CD54) and hyaluronic cellular adhesion molecule (HCAM, CD44)] and release of chemokines/cytokines [monocyte chemoattractant protein (MCP)-1, eotaxin, interleukin (IL)-6 and transforming growth factor (TGF)-beta]. Cells from a human foetal lung fibroblast cell line (GM 06114) were stimulated with basic fibroblast growth factor (bFGF) or tumour necrosis factor (TNF)-alpha in the presence of different concentrations (0.01-100.0nM) of MOM or DEX. A significant increase in fibroblast DNA synthesis and proliferation was observed when the cells were stimulated with bFGF (p<0.05), whereas TNF-alpha induced a significant upregulation in ICAM-1 expression and in MCP-1, eotaxin and IL-6 release (p<0.05, each comparison). No changes in HCAM expression and in TGF-beta release were observed (p>0.05, each comparison). The addition of MOM or DEX at the beginning of the cell cultures induced a significant downregulation in fibroblast DNA synthesis and proliferation, ICAM-1 and HCAM expression and chemokine/cytokine release (p<0.05, each comparison). At all the concentrations tested, MOM was more effective than DEX in inhibiting ICAM-1 expression and MCP-1 release (p<0.05, each comparison), whereas no potency advantage for MOM was detected in DNA synthesis, cell proliferation, HCAM expression and in eotaxin, IL-6 and TGF-beta release (p>0.05, each comparisons). These results extend the profile of the anti-inflammatory activity of mometasone furoate to lung fibroblast functions involved in airway inflammation and remodeling.

Airway Obstruction↗

Nasal inflammation and bronchial reactivity to methacholine in atopic children with respiratory symptoms.

BACKGROUND: In atopic subjects, dysfunctions of the upper and lower airways frequently coexist and allergic rhinitis seems to constitute a risk factor for the occurrence of asthma in predisposed individuals. AIM OF THE STUDY: To evaluate whether in atopic subjects nasal inflammation could reflect changes in respiratory functions, 11 allergic children, sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and 10 nonatopic controls (ctrs) were studied. METHODS: All subjects underwent nasal brushing to detect percentages of nasal eosinophils (Eos %) and intercellular adhesion molecule-1 (ICAM-1) expression by nasal epithelial cells. In the same day pulmonary function tests, i.e. forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flows at 25-75% of the vital capacity (FEF25-75%) and methacholine (MCh) bronchial inhalation challenge were also evaluated. RESULTS: Pulmonary function parameters were not significantly different in allergic children and in ctrs (P > 0.05), while a significant increase in bronchial reactivity to MCh, expressed as Pd20 MCh, was detected in the former population (P < 0.05). As compared with ctrs, allergic children showed elevated Eos % and ICAM-1 expression (P < 0.05). When nasal inflammation and pulmonary function parameters were compared, a significant correlation was found between nasal Eos % and bronchial reactivity to MCh (P = 0.002). CONCLUSIONS: These data support the concept of significant links between upper and lower respiratory tract involvement in atopic children sensitized to HDM.

Adolescent↗

In allergic asthma experimental exposure to allergens is associated with depletion of blood eosinophils overexpressing LFA-1.

BACKGROUND: In atopic individuals, exposure to allergens is followed by recruitment of blood eosinophils in the target tissue. We investigated whether allergen inhalation challenge could result in depletion of blood eosinophils overexpressing adhesion molecules involved in eosinophil migration. METHODS: Blood eosinophils were isolated from seven atopic asthmatic patients and seven control subjects and the "at baseline" expression of lymphocyte function-associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1) and very late antigen-4 (VLA-4) was assessed by monoclonal antibody staining and flow cytometry analysis. Asthmatic patients underwent allergen challenge and the expression of LFA-1, Mac-1 and VLA-4 by blood eosinophils was again evaluated 3 h and 24 h after allergen challenge. RESULTS: As compared to controls, eosinophils from atopics showed at baseline enhanced LFA-1 expression (P=0.0012), but similar Mac-1 or VLA-4 expression (P > 0.1, each comparison). In atopics, the percentage and absolute number of blood eosinophils were significantly decreased 3 h after allergen challenge (P=0.001 and P=0.022, respectively) but returned to similar values to prechallenge values after an additional 21 h (P > 0.1). Allergen challenge was also followed by a significant decrease in LFA-1 expression by eosinophils, at 3 h (P=0.002) and at 24 h (P=0.038), while no changes in Mac-1 and VLA-4 were observed. A significant correlation between postchallenge decrease in LFA-1 expression and in blood eosinophilia, both expressed as percentage (r=0.88; P < 0.01) or absolute number (r=0.87; P < 0.01) was demonstrated at 3 h (r=0.88; P < 0.01) but not at 24 h (r=0.64, P > 0.05 and r=0.11; P > 0.05, respectively). CONCLUSION: In allergic asthma, an early recruitment of blood eosinophils overexpressing LFA-1 occurs in the first hours after allergen challenge.

Adolescent↗

Cysteinyl leukotrienes induce human eosinophil locomotion and adhesion molecule expression via a CysLT1 receptor-mediated mechanism.

BACKGROUND: The mechanisms involved in eosinophil recruitment by cysteinyl-leukotrienes (CysLTs) remain to be defined. OBJECTIVE: We investigated whether CysLTs LTC4, LTD4 and LTE4 could directly stimulate in vitro adhesion molecule expression and cell locomotion of blood eosinophils from atopic asthmatic donors. METHODS: Mab staining and FACS analysis were used to evaluate Mac-1 and LFA-1 expression on eosinophils before and after CysLTs stimulation. Eosinophil locomotion was tested using a 48-well Boyden microchamber. RESULTS: CysLTs, at the concentrations of 1 and 10 nM, were able to significantly up-regulate Mac-1 expression (P < 0.05, each comparison) but not LFA-1 expression (P > 0.05, each comparison). A dose-dependent, eosinophil chemotaxis was also induced by LTC4, LTD4 and LTE4 (0.1-10 nM) (P < 0.01, each comparison). Montelukast (0.01 nM to 10 nM), a specific CysLT1 receptor antagonist, significantly down-regulated LTC4, LTD4 and LTE4-induced Mac-1 expression (P < 0.01, each comparison) and the CysLT-induced eosinophil migration (P < 0.01, each comparison). In contrast, montelukast did not affect Mac-1 expression or cell migration when eosinophils were stimulated by the 'non-specific activators', such as fMLP or C5a (P > 0.05, each comparison). CONCLUSION: These data demonstrate that CysLTs are active in vitro in directly up-regulating human eosinophil functions involved in eosinophil recruitment. The down-regulation of Mac-1 expression and eosinophil chemotaxis by the potent and selective CysLT1 receptor antagonist montelukast indicated the specificity of the LTC4-, LTD4- and LTE4-induced response.

Acetates↗

Serum and synovial fluid concentration of vascular endothelial growth factor in juvenile idiopathic arthritides.

OBJECTIVE: To evaluate the role of vascular endothelial growth factor (VEGF) in the pathogenesis of local joint inflammation in juvenile idiopathic arthritis (JIA). METHODS: Sera from 50 patients affected with JIA and 10 age-matched healthy controls were tested with a commercial ELISA for VEGF. Corresponding synovial fluid (SF) concentrations of VEGF and p75 soluble tumour necrosis factor receptor (sTNFR) were evaluated in 20 active JIA patients. RESULTS: Serum concentrations of VEGF were significantly higher in patients with active polyarticular disease than in patients with active and inactive oligoarticular disease and healthy controls. In JIA patients, serum concentrations of VEGF displayed a significant correlation with a number of clinical and laboratory parameters of disease activity. VEGF concentrations in SF were significantly higher than those detected in corresponding sera. Moreover, a clear correlation was found between corresponding SF and serum VEGF concentrations. In SF, VEGF showed a strong positive correlation with p75 sTNFR. CONCLUSIONS: Concentrations of VEGF in SF in patients with JIA are higher than corresponding serum concentrations, suggesting that this pro-angiogenic factor may have a major role in the outgrowth of hyperplastic pannus and tissue damage at the site of tissue inflammation.

Adolescent↗

Fluticasone propionate downregulates nasal fibroblast functions involved in airway inflammation and remodeling.

BACKGROUND: Besides being highly effective in the treatment of allergic and nonallergic rhinitis with eosinophilia, intranasal corticosteroids appear to be useful in reducing nasal polypoid lesions and the likelihood of polyp recurrence after surgery. We evaluated the ability of fluticasone propionate to downregulate fibroblast functions related to nasal inflammation and remodeling. METHODS: Primary nasal polyp tissue-derived fibroblasts were stimulated with tumor necrosis factor (TNF)-alpha or interleukin (IL)-4 or basic fibroblast growth factor (bFGF) in the presence of fluticasone propionate (0.1-100 nM). Fibroblast proliferation, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression and eotaxin release were then evaluated. RESULTS: As compared with unstimulated cultures, a significant increase in fibroblast proliferation was observed when the cells were stimulated with bFGF (p < 0.05), but not with TNF-alpha or IL-4 (p > 0.05). TNF-alpha induced an upregulation of ICAM-1 expression (p < 0.05), which was not seen in fibroblasts cultured in the presence of IL-4 or bFGF. No changes in VCAM-1 expression were induced by TNF-alpha, IL-4 or bFGF, whereas both TNF-alpha and IL-4 increased eotaxin release (p < 0.05). Both bFGF-induced fibroblast proliferation and TNF-alpha-induced ICAM-1 expression were significantly reduced by fluticasone, starting at the dose of 1 and 10 nM, respectively (p < 0.05). Fluticasone at concentrations of 1-100 nM effectively inhibited eotaxin release by TNF-alpha- or IL-4-stimulated fibroblasts (p < 0.05). CONCLUSIONS: The pharmacologic activity of fluticasone in patients with chronic upper airway inflammatory disease may include inhibition of resident fibroblast functions involved in airway inflammation and remodeling.

Administration, Topical↗

Time-dependent changes in orally exhaled nitric oxide and pulmonary functions induced by inhaled corticosteroids in childhood asthma.

Exhaled nitric oxide levels are elevated in asthmatic children and decrease after inhaled steroid treatment. We evaluated the time-dependent changes in fractional exhaled nitric oxide concentration (FENO) and pulmonary function parameters following inhaled steroid therapy. Thirty-nine steroid-naive atopic patients (age 11.92+/-0.48 years) with mild intermittent asthma and 22 age-matched healthy controls were enrolled in the study; pulmonary functions and FE(NO) levels were measured. Low doses of inhaled steroids were prescribed to all asthmatic patients who were reevaluated in a second visit (between 10 and 40 days after the beginning of the treatment). At the enrolment, asthmatic patients had similar forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) values (p > 0.05) but reduced forced expiratory flows at 25-75% of the vital capacity (FEF(25-75%)) values, as compared to controls (p < 0.05). In addition, FE(NO) levels were significantly higher in asthmatics with respect to control subjects (30.8+/-3.0 and 4.0+/-0.5 ppb, respectively; p < 0.01). All asthmatics had FE(NO) levels higher than 8.8 ppb (i.e., > 2 standard deviations of the mean in controls). After steroid treatment, patients showed significant improvement of FEV1, FVC, and FEF(25-75%) (p = 0.0001; each comparison) and a reduction of FE(NO) levels (p = 0.0001). A weak significant correlation was found between percent decrease in FE(NO) levels and percent increase in FEV1 (r = 0.33, p = 0.04) or in FEF(25-75%) (r = 0.4, p = 0.01) after treatment. When changes in FE(NO) levels and in pulmonary function parameters were corrected for days of treatment, significant correlations were still present between percent decrease in FE(NO) levels and percent increase in FEV1 (r = 0.57, p = 0.0004) or percent increase in FEF(25-75%) (r = 0.45, p = 0.006). Sixteen of the 39 asthmatic patients were evaluated on two occasions after the beginning of treatment, at days 10 and 40. The significant reduction in FE(NO) levels (p < 0.01) and the significant increase in FEV1 and FEF(25-75%) values observed (p < 0.05) after 10 days did not further improve at day 40. These data show that it is possible to demonstrate early effects of low-dose inhaled steroids in asthmatic children using objective measurements of airway caliber and inflammation.

Administration, Inhalation↗

Exhaled nitric oxide levels in non-allergic and allergic mono- or polysensitised children with asthma.

BACKGROUND: Increased fractional exhaled NO concentrations (FENO) and blood/tissue eosinophilia are frequently reported in allergic children with mild asthma and are thought to reflect the intensity of the inflammation characterising the disease. The aim of this study was to investigate possible differences in FENO levels or in the intensity of the blood eosinophilia in allergic and non-allergic asthmatic children. METHODS: 112 children with stable, mild, intermittent asthma with a positive bronchial challenge to methacholine were consecutively enrolled in the study; 56 were skin prick test and RAST negative (non-sensitised) while 56 were sensitised to house dust mites (23 only to house dust mites (monosensitised) and 33 were sensitised to mites and at least another class of allergens (pollens, pet danders, or moulds)). Nineteen sex and age matched healthy children formed a control group. RESULTS: Compared with non-allergic patients, allergic children had a significantly higher rate of blood eosinophilia (p=0.0001) with no differences between mono- and polysensitised individuals. Forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), forced expiratory flow at 25-75% of vital capacity (FEF(25-75%)), and the degree of bronchial reactivity to methacholine were similar in non-atopic and atopic children, with no differences between mono- and polysensitised individuals. FENO levels measured by chemiluminescence analyser were higher in asthmatic children (15.9 (14.3) ppb) than in the control group (7.6 (1.6) ppb, p=0.04) and higher in allergic patients (23.9 (2.1) ppb) than in non-allergic patients (7.9 (0.8) ppb, p=0.0001), but there were no differences between mono- and polysensitised individuals (p>0.1). Significant correlations between blood eosinophilia and FENO levels were seen only in allergic (r=0.35, p<0.01) and in polysensitised individuals (r=0.45, p<0.05). CONCLUSIONS: In children with mild asthma, a similar degree of functional disease severity may be associated with a higher inflammatory component in allergic than in non-allergic subjects.

Adolescent↗

Fluticasone and salmeterol downregulate in vitro, fibroblast proliferation and ICAM-1 or H-CAM expression.

Beta2-adrenoreceptor agonists have pharmacological properties that may suggest an inhibitory effect on various aspects of the inflammatory and repair processes that characterize asthma. Since fibroblasts express beta2-adrenoreceptors, the effects of different concentrations (0.1-100 nM) of fluticasone propionate (FP), salmeterol (S) and their combination (FP+S) on lung fibroblast proliferation and adhesion molecule expression were evaluated. Stimulation of human foetal lung fibroblasts with a fibrogenic cytokine, basic fibroblast growth factor (bFGF), resulted in a [methyl-3H] thymidine ([3H]TdR) uptake, four-fold higher than that of control cultures (p=0.0001) and was significantly inhibited by S, at all the concentrations tested (0.1-100 nM; p<0.05). No changes in bFGF-induced cell proliferation were observed in the presence of FP (0.1-100 nM; p>0.05, all comparisons). In addition, the association FP+S did not improve the inhibitory activity of S alone (p>0.05, each comparison). An upregulation of intercellular adhesion molecule-1 (ICAM-1) expression was induced by tumour necrosis factor-alpha (TNF-alpha) (p=0.0004), but not by interleukin-4 (IL-4) (p>0.05), while none of the two cytokines were able to increase hyaluronic-cellular adhesion molecule (H-CAM) expression by lung fibroblasts (p>0.05). A significant downregulation of ICAM-1 or H-CAM expression was demonstrated in the presence of FP or S, at all concentrations tested (0.1-100 nM; p<0.01, each comparison). Interestingly, S (10 nM and 100 nM) was able to enhance the inhibitory activity of FP on ICAM-1 expression (p<0.01), but not on H-CAM expression (p>0.1). These results show that in human foetal lung fibroblasts, fluticasone propionate and salmeterol are effective in modulating in vitro, different lung fibroblast biological functions that are likely to be involved in airway remodelling.

Albuterol↗

Severe and near-fatal asthma in children and adolescents.

Near-fatal asthma attacks occur rather frequently in asthmatic patients during childhood and adolescence. Major risk factors appear to be the severity and/or treatment difficulties, which may be related to the characteristics of the disease but also to mistaken or delayed diagnosis, poor compliance to treatment, and psychosocial problems. Indeed, difficult-to-control asthma symptoms can be caused by other disorders mimicking asthma, by unidentified exacerbating factors, by low compliance with the prescribed therapy, by inability to use the devices correctly (metered-dose inhalers, dry powder inhalers, nebulizers) and by low perceptiveness of airway obstruction. Children and adolescents with severe, difficult-to-treat asthma should receive specialist assessment and follow-up. Pharmacologic intervention should be combined with a detailed education and action plan, designed to get the disease under control but also to meet patient' and parents desires.

Adolescent↗

Bronchoalveolar lavage and esophageal pH monitoring data in children with "difficult to treat" respiratory symptoms.

Gastroesophageal reflux (GER) may be associated with chronic or recurrent asthma-like symptoms secondary to bronchoconstrictor reflexes and/or inhalation of gastric content. The presence of lipid-laden alveolar macrophages has been proposed as an index to establish the degree of gastric aspiration. We evaluated 20 children with "difficult to treat" respiratory symptoms and a clinical history suggestive of GER. All children underwent 24-hr esophageal pH monitoring (pHm) and fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). The amount of lipid per single macrophage was determined by a semiquantitative method, using fluorescence microscopy to detect Nile-Red-stained BAL cells and calculating a lipid-laden macrophage index (LLMI). Eleven children had positive pHm recordings, suggesting the presence of GER (pH-positive patients), and 9 had negative pHm records (pH-negative patients). The pH-positive patients had higher percentages of neutrophils and higher LLMI than the pH-negative children (P < 0.05). There were no correlations between the pHm records and either % BAL neutrophils or LLMI in pH-positive or pH-negative patients (P > 0.05; each correlation). In contrast, a single correlation was found between % BAL neuytrophils and LLMI, both in the pH-positive and in the pH-negative patients (r = 0.72, P = 0.02 and r = 0.71, P = 0.04, respectively). These data demonstrate that a significant proportion of pH-positive patients with respiratory symptoms have BAL abnormalities that suggest airway inflammation and gastric content aspiration. However, the intensity of GER as indicated by pH monitoring does not correspond with BAL data in all patients.

Bronchoalveolar Lavage↗

Tumor necrosis factor induced adhesion molecule serum concentrations in Henoch-Schönlein purpura and pediatric systemic lupus erythematosus.

OBJECTIVE: Animal models of immune complex mediated tissue injury have shown that tumor necrosis factor (TNF) and TNF induced adhesion molecules play an important role in the pathogenesis of tissue damage mediated by IgG, but not in that mediated by IgA, immune complexes. We compared possible differences in the behavior of 2 TNF induced adhesion molecules (VCAM-1 and ICAM-1) in Henoch-Schönlein purpura (HSP), which is characterized by the formation of IgA immune complexes, versus systemic lupus erythematosus (SLE), which is mostly associated with the vascular deposition of IgG immune complexes. METHODS: Serum concentrations of soluble (s)VCAM-1 and ICAM-1 were determined by ELISA methods in 20 patients with pediatric SLE showing variably active disease, 20 active patients with active HSP, and 19 healthy controls. TNF-alpha as well as p55 and p75 soluble receptors (sTNF-R) were simultaneously tested by enzyme amplified sensitivity immunoassay in 22 patients (12 SLE, 10 HSP). RESULTS: Serum sVCAM-1 concentration was significantly higher in patients with SLE (mean +/- SD, 608 +/- 76 ng/ml), than in patients with HSP (501.9 +/- 63.3 ng/ml) and controls (446.8 +/- 139.2 ng/ml) (p < 0.001). In SLE patients, sVCAM-1 correlated positively with ESR (r = 0.45, p = 0.02) and negatively with C4 serum levels (r = -0.57, p = 0.004), platelets (r = -0.38, p = 0.03), and lymphocyte count (r = -0.42, p = 0.03). No differences in sICAM-1 serum concentrations were detected among SLE, HSP, or control groups. Soluble VCAM, but not sICAM-1, showed a positive correlation with TNF-alpha (r = 0.71, p = 0.01), p55 (r = 0.63, p = 0.02), and p75 (r = 0.7, p = 0.01) sTNF-R serum concentrations in SLE, but not in patients with HSP. CONCLUSION: Our study provides additional evidence of a possible differential involvement of TNF and TNF induced adhesion molecules in the pathogenesis of tissue damage between pediatric SLE and HSP.

Adolescent↗

[Cicatricial stenosis of colorectal anastomosis. Transanal treatment with circular stapler].

Anastomotic strictures complicating colorectal anastomoses can be difficult to treat. This condition must not be considered as an uncommon complication. In 20% of patients it may be a serious state that may require a therapy. Two patients treated successfully without complication with the transanal use of an CEEA stapler are presented. The staple cutter is safe and easy to use, and except for a conventional anoscope, no special equipment, including fluoroscope, is needed. On the basis of the successful results obtained, the procedure using staple cutter is recommended for the treatment of anastomotic stricture of the rectum.

Adenocarcinoma↗

[Coronary collateral circulation in coronary atherosclerosis (author's transl)].

The coronary collateral circulation of 162 patients suffering from atherosclerosis and coronary insufficiency (coronary artery disease) was studied. It was found to be present in 44 patients, or 27.1%; homocoronary in 9%, intercoronary in 90.9%. As other Authors have previously reported, anastomotic circulation is more developed when the coronary occlusion exceeds 75%. Not one of the 44 cases with normal coronary arteries or occlusion inferior to 75% presented collateral circulation. In addition, it was found to be present more frequently in cases with three branch lesions. The time of insurgence of coronary insufficiency seems to condition the development of anastomotic circulation which appears more frequently when the symptoms have been present for more than 5 years (43.9%). Anastomotic circulation is also found more frequently (48.4%) in patients who have suffered myocardial infarction and who have angina. Collateral circulation was not found in any of the 46 patients with unstable isolated angina; this seems to show the importance, in its pathogenesis, of the functional factor (spasm). In conclusion, we may say that anastomotic circulation is more developed: 1) in cases of severe occlusive lesions (in severe coronary occlusive disease/atherosclerosis) (85%);2) in three branch lesions; 3) in cases of long standing symptomatology; 4) in stable angina and in angina t infarction.

Angina Pectoris↗