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Biomedical subjects

F Gigliotti

Publications and source records attributed to F Gigliotti.

At least 109 records · Page 6Linked to original sources
PubMed1987

Effect of inhaled histamine on occlusion pressure and breathing pattern in asthmatic patients.

In animals, histamine inhalation is known to increase either respiratory frequency or respiratory drive by stimulation of airway vagal sensitive endings. However, it is not well known whether these changes are concomitant in man. In order to elucidate this point, we carried out the present investigation in thirty-five asthmatic patients who underwent bronchial provocation test by progressively doubling the dose of inhaled histamine. Bronchial reactivity to histamine allowed two populations of patients to be defined: group I with moderate and group II with mild, increased reactivity. In the twenty-three group I patients, neuromuscular inspiratory drive, assessed by mouth occlusion pressure (P0.1), was found to be significantly increased while no significant changes in breathing pattern were noted. In the twelve group II patients histamine did not modify P0.1 or breathing pattern. However, we were able to separate in group I a sub-group of ten patients, as with atopic asthma, in which histamine-induced increase in P0.1 was paralleled by rapid and shallow breathing (RSB). Changes in P0.1 and breathing pattern did not depend on baseline airway calibre. In group I, after bronchoconstriction had been reversed by inhaling a beta 2-agonist bronchodilator agent (fenoterol), P0.1 decreased significantly and RSB was found to be reversed; however, these changes were not interrelated. We concluded that: in asthmatics, histamine-induced increase in P0.1 is not necessarily paralleled by, nor related with, change in breathing pattern and in atopics a 'sensitization' of vagal receptors could account for the concomitance of enhanced P0.1 with RSB.

Administration, Inhalation↗
PubMed1987

Inspiratory impedance during histamine-induced bronchoconstriction in patients with bronchial asthma.

Histamine inhalation provocation tests were performed in 18 asymptomatic asthmatic patients with progressively increasing doses of a pressurized aerosol of histamine phosphate. Forced expiratory volume in 1 s (FEV1), total neuromuscular output, assessed by mouth occlusion pressure (P0.1), mean inspiratory flow (VT/Ti), and the P0.1/(VT/Ti) ratio, which represents an index of effective inspiratory impedance of the respiratory system, were measured. With histamine, compared to control, FEV1 decreased and P0.1/(VT/Ti) increased (p less than 0.01 for both). After bronchoconstriction was reversed by administration of a beta 2-agonist bronchodilator (fenoterol), a significant decrease in P0.1/(VT/Ti) (p less than 0.001) and a significant increase in FEV1 (p less than 0.01) were noted as compared to histamine. With histamine, change in P0.1/(VT/Ti) was found to be related to its pre-histamine value (p less than 0.01). Furthermore, with histamine and fenoterol, changes in P0.1/(VT/Ti) and concurrent changes in FEV1 were found to be significantly related (p less than 0.001). From these data we calculated that the P0.1/(VT/Ti) ratio provides a useful tool in the clinical assessment of histamine-induced bronchospasm.

Adult↗
PubMed1987

Experimental Pneumocystis carinii pneumonia in the ferret.

Pneumocystis carinii pneumonia (PCP) was provoked in the ferret, Mustela pulorius furo, by immunosuppression with daily long-term administration of cortisone acetate, 10-20 mg/kg subcutaneously for 9 to 10 weeks, Microscopically P. carinii was observed in the lungs of all 11 treated animals: mild to moderate in five and extensive disease in six. The histopathological features of PCP in the ferret included interstitial pneumonitis, scant mononuclear cell alveolitis, with abundant cysts and trophozoites visible in a focal distribution. There were few neutrophils present. Electron microscopy showed large numbers of both cysts and trophozoites in close association with type I cells. No bacterial pathogens were isolated from the lungs of immunosuppressed animals but an unexplained eosinophilic enteritis was present in treated animals. P carinii pneumonia developed without significant body weight loss during corticosteroid administration, unlike previously described studies using corticosteroid-treated rodents. Ferrets thus appear to be a 'steroid resistant' animal, like man, and therefore a more suitable model for immunological studies of host response to PCP than rodents. This new model also has practical advantages over previously described animal models of PCP, including larger lung and airway size.

Animals↗
PubMed1986

Development of murine monoclonal antibodies to Pneumocystis carinii.

Relatively little is known about the antigenic structure of Pneumocystis carinii and the immunopathogenesis of pneumonitis caused by P. carinii. To begin to define the antigenic character of the surface of this organism, we have produced murine monoclonal antibodies that react with the surface of P. carinii (obtained from rats), as detected by immunofluorescence and immunoelectron microscopy. Immunoblot analysis revealed that the six antibodies described in this report bound an antigen with an apparent molecular mass of 90,000-95,000 daltons. Although all six monoclonal antibodies bound P. carinii obtained from rats, only one (5E12) was also able to bind P. carinii obtained from rabbits, ferrets, and a human; this result demonstrated that isolates of P. carinii obtained from different species are not antigenically identical.

Animals↗
PubMed1986

Breathing pattern and neuromuscular drive during CO2 rebreathing in normal man and in patients with COPD.

In 11 normal subjects and in 10 patients with chronic obstructive pulmonary disease we evaluated breathing pattern and mouth occlusion pressure (PO.1), while breathing room air and during reinhalation of a hypercapnic hyperoxic gas mixture. In the breathing pattern we analyzed the time and volume components of the respiratory cycle: tidal volume (VT), inspiratory time (Ti), expiratory time (Te), total time of respiratory cycle (Ttot); mean inspiratory flow (VT/Ti) and Ti/Ttot ratios, respiratory frequency (RF) and instantaneous ventilation (VE). In the normal subjects, increase in VE during rebreathing mainly depended on an increase in both VT and VT/Ti without significant changes in Ti. During CO2 rebreathing the patients exhibited a lesser increase in VE compared to normals, due to a lesser increase in VT. However, expressing VT in percent of resting inspiratory capacity showed that VT attained at the end of rebreathing (VTmax) was similar to that noted in the normal subjects at the same minute of rebreathing. Furthermore, percent increase in VE, VT, VT/Ti and PO.1 between resting value and that at 56 mm Hg (delta %), were significant in both groups with a major increase in the normal subjects for VE and VT/Ti. In comparison, delta % decreases in both Te and Ttot were found to be significant only in the normal subjects. VT/Ti was related to VE in a similar way in the two groups. In contrast, in the normal subjects, Ti/Ttot did not increase with increasing VE. During rebreathing increase in PO.1 was found to be similar in the normal subjects and in patients. However, for a given neuromuscular drive VE and VT/Ti were greater in the normal subjects than in the patients. These data show that in the patients as a whole no significant changes in breath intervals occur during CO2 rebreathing. Furthermore, in patients, in spite of a similar increase in neuromuscular drive, the efficiency by which inspiratory muscle output (PO.1) is converted into VT/Ti was found to be reduced.

Adult↗
PubMed1986

Effects of histamine and reproterol inhalation on mouth occlusion pressure in patients with bronchial asthma.

Both vagal and non-vagal afferences from the lung or chest wall contribute to increasing neural drive to the respiratory muscles, but only the former are known to change the breathing pattern by increasing respiratory frequency (RF) during bronchoconstriction. In order to evaluate the relative contribution of vagal and non-vagal afferences to increasing neural drive to the respiratory muscles in 14 asymptomatic asthmatic patients known to be responsive (decrease in FEV1 greater than 20% of the control values) to previous bronchial provocation test (BPT) with aerosolized histamine, we evaluated FEV1, breathing pattern and neuromuscular drive, as assessed by mouth occlusion pressure (PO.1), under control conditions, during BPT with progressive doubling doses of inhaled histamine (H) and 5 min after inhalation of a bronchodilator agent (Reproterol) (B). During HBPT FEV1 exhibited a significant decrease (p less than 0.01) while PO.1 was found to increase significantly (p less than 0.01). However, no significant changes were noted in breathing pattern. After B FEV1 returned to control values while PO.1, even if significantly reduced (p less than 0.01), did not. Changes in PO.1 were found to be significantly related to changes in FEV1 both during HBPT and B (p less than 0.05). The data suggest that in these patients non-vagal afferences, linked to the abnormalities of thoraco-pulmonary mechanics, could play a major role in changing neural drive to the respiratory muscles.

Adult↗
PubMed1985

Failure of monoclonal antibodies to core glycolipid to bind intact smooth strains of Escherichia coli.

To study the ability of antibody to the core glycolipid (CGL) region of lipopolysaccharide (LPS) to bind intact gram-negative bacterial cells, we produced monoclonal antibodies that bind LPS from the Escherichia coli rough mutant J5. Four representative monoclonal antibodies that bound four distinct epitopes on the CGL region of LPS were studied. All four antibodies bound both isolated J5 LPS and intact J5 bacterial cells, but none of the antibodies bound to intact cells of E. coli O111:B4 or K1:O7. Binding of the monoclonal antibodies to isolated LPS from these latter two smooth strains was variable. These results confirm the presence of shared antigenic sites in the CGL region of heterologous LPS molecules but indicate that these sites are not necessarily available on smooth gram-negative bacteria for binding by antibody to CGL.

Antibodies, Bacterial↗
PubMed1984

Efficacy of topical antibiotic therapy in acute conjunctivitis in children.

We studied 102 children aged 1 month to 18 years in a randomized, double-blind trial designed to determine both the natural history of bacterial conjunctivitis and whether topical antibiotic therapy is beneficial. Affected eyes were treated four times a day for 7 days with drug (polymyxin-bacitracin ophthalmic ointment) or placebo. Eighty-four patients had proved bacterial conjunctivitis (Haemophilus influenzae 61, Streptococcus pneumoniae 22, both one); 66 of these received only topical therapy. By 3 to 5 days, 21 of 34 (62%) patients receiving topical antibiotic were clinically cured, whereas only nine of 32 (28%) patients given placebo were cured (P less than 0.02). By 8 to 10 days, 31 (91%) of the patients given antibiotic and 23 (72%) of the placebo group were cured (P = NS). The bacterial pathogen was eradicated by day 3 to 5 in 71% and by day 8 to 10 in 79% of patients given antibiotic, compared to 19% and 31% of the placebo group (P less than 0.001). Acute bacterial conjunctivitis is a self-limited disease, but topical antibiotic therapy with polymyxin-bacitracin shortens the duration of clinical disease and enhances eradication of the causative organism from the conjunctiva.

Acute Disease↗
PubMed1984

Reproducible production of protective human monoclonal antibodies by fusion of peripheral blood lymphocytes with a mouse myeloma cell line.

The production of monoclonal antibodies of human origin may represent a significant advance in immunotherapy for disease in humans. Although human monoclonal antibody has been produced from human lymphocytes by fusion with human myeloma cell lines or by Epstein-Barr viral transformation, fusion of postimmunization human lymphocytes with a mouse myeloma cell line is a relatively simple and reproducible alternative. Mouse-human hybrid cell lines were obtained in 205 (53%) of the microtiter wells initially seeded. Thirty-one (15%) of these hybrid cell lines secreted antibody of predefined specificity. Cloning was attempted with eight of the hybrid cell lines, and long-term antibody production was established in four of the lines: two hybridomas secreted antibody to the capsule of Haemophilus influenzae type b, one secreted antibody to tetanus toxoid, and one secreted antibody to diphtheria toxin. The production of mouse-human hybridomas appears to be a reliable method for obtaining human monoclonal antibody of predefined specificity.

Animals↗
PubMed1984

Comparative effects of SCH 1000 and fenoterol after histamine-induced bronchoconstriction in asymptomatic asthmatics.

In 16 asymptomatic asthmatics a functional study was carried out under controlled conditions during histamine bronchial provocation test (HBPT) and after bronchodilation test with either SCH 1000 or fenoterol by evaluating both SRAW and the slope of the alveolar plateau of nitrogen washout curve (N2 ph III). During HBPT, 9 of 16 subjects showed a central response (increase in RAW and SRAW only), whereas in the remaining 7 subjects histamine induced a mixed response due to an increase in both SRAW and N2 ph III. No differences between the two groups were observed in age and functional data during controlled conditions. Doses of delivered histamine were not significantly different. In 5 of 9 central responders to HBPT, SCH 1000 induced a decrease in SRAW only, whereas in 3 of the remaining 4 fenoterol caused both central and peripheral bronchodilation (decrease in both SRAW and N2 ph III). All mixed responders to HBPT showed a mixed bronchodilation during SCH 1000 (three subjects) or fenoterol (the remaining four). These data seem to indicate that the mechanism of bronchodilation induced by SCH 1000 is related to that of histamine-induced bronchoconstriction. Moreover, bronchodilation due to fenoterol could be related to a vagal modulation or be a systemic direct effect.

Adult↗
PubMed1983

Monoclonal antibodies. Clinical relevance to pediatrics.

Monoclonal antibodies are identical antibodies with the same binding specificity that can be generated in unlimited amounts by construction of continuous cultures of single antibody-secreting cells. These cell lines are produced by cell fusion of lymphocytes of an animal that produces desired antibody to cells of a myeloma tumor cell line, which confers, on the antibody-producing hybrid cell, immortality and the ability to grow as a tumor in animals. Monoclonal antibodies can be produced to complex, impure antigens. The antibodies are replacing conventional, polyclonal antisera in immunologic assays and are being widely applied to the study of the pathogenesis and to the diagnosis and treatment of childhood diseases.

Animals↗
PubMed1983

Effects of steroid therapy on pulmonary involvement in sarcoidosis.

In eleven patients with stage II-III pulmonary sarcoidosis as assessed by mediastinoscopy or open lung biopsy, we carried out a functional study by evaluating static and dynamic pulmonary volumes, diffusing lung properties (TLCO, KCO), and mechanical properties: resistance of the airway, flow-volume curve, pressure-volume curve, flow-pressure curve, and dynamic compliance. In 7 of 11 patients a clinical and functional follow-up during steroid treatment over a period of 5 months to 3 years was also performed. Before treatment diffusing properties were in the normal range in 6 of 11 subjects, reduced in 4, and increased in 1. Elastic properties studied in 8 patients were in the normal range, whereas peripheral airway involvement was noted in 4 nonsmokers. During the follow-up the changes noted in diffusing lung properties on the whole parallelled the clinical and radiologic improvement or relapses after cessation of therapy. In contrast, no changes in elastic properties or lung volume were noted. We concluded that steroid treatment seems to improve parenchymal lung involvement in most cases as shown by the increase in diffusing lung properties.

Adult↗
PubMed1982

Protection from infection with Haemophilus influenzae type b by monoclonal antibody to the capsule.

Monoclonal antibodies to Haemophilus influenzae type b were produced by fusing splenic lymphocytes from immunized C57BL/6 mice with the mouse myeloma line P3-X63-Ag8.653. The antibody produced by one hybridoma (5M1H9) bound the capsular polysaccharide, as determined by a radiolabeled antigen-binding assay. The antibody was of the IgM class and was bactericidal in vitro with complement. The protective and therapeutic capacity of antibody 5M1H9 was examined in the infant rat model of H. influenzae type b disease. Antibody (0.1 ml), either undiluted or diluted 1:2, 1:10, or 1:100, administered 4 hr before intraperitoneal injection of 10(4)-10(5) H. influenzae type b organisms protected 100%, 90%,. 55% and 10% of the animals, respectively. To determine the efficacy of antibody 5M1H9 in treating established infection, antibody was given at 24-hr intervals after intraperitoneal injection of bacteria. Delayed administration of antibody 5M1H9 was effective in reducing both the level and incidence of bacteremia.

Animals↗
PubMed1982

Protective human hybridoma antibody to tetanus toxin.

Postimmunization human B lymphocytes and mouse myeloma cells were fused to produce interspecies hybridomas secreting human antibody of predefined specificity with an initial frequency comparable to intraspecies fusion. After 13 mo in culture, one clone continued to secrete high titers of human IgG antitetanus toxin antibody. This antibody binds to the B fragment of tetanus toxin and protects mice against tetanus. The demonstration of in vivo protection with a human monoclonal antibody is an important first step towards the ultimate goal of human administration of monoclonal antibodies for the prevention and therapy of human infections.

Antibodies, Monoclonal↗
PubMed1981

Etiology of acute conjunctivitis in children.

To determine the etiology of acute conjunctivitis in children seen in pediatric practice, 99 patients with conjunctivitis and 102 age-and season-matched controls were cultured for aerobic bacteria including Haemophilus influenzae, and for viruses, Chlamydia trachomatis, and mycoplasmas. Agents statistically associated with conjunctivitis included H. influenzae (42% vs 0%), Streptococcus pneumoniae (12% vs 3%), and adenoviruses (20% vs 0%). One of these three etiologic agents was isolated from 71 (72%) of the patients. Simultaneous infection with two pathogens was uncommon. Staphylococcus aureus was equally prevalent in diseased and control eyes; one strain of C. trachomatis was isolated from a control eye. Although there were variations in the clinical features of viral and bacterial conjunctivitis, differentiation in an individual patient was difficult. An adenovirus was isolated from 11 (65%) of 17 patients who had pharyngitis in addition to conjunctivitis. H. influenzae was isolated from 14 (74%) of 19 children who had both otitis and conjunctivitis. Adenovirus conjunctivitis was common in the fall and H. influenzae in winter.

Acute Disease↗
PubMedDate not supplied

Respiratory muscle overloading and dyspnoea during bronchoconstriction in asthma: protective effects of fenoterol.

Whether, and to what extent, beta 2-agonists protect against respiratory muscle overloading and breathlessness during bronchoconstriction remains to be defined in patients with asthma. In a double blind placebo-controlled study, 100 micrograms of fenoterol were administered to six stable asthmatics before a bronchial provocation test, performed by inhaling doubling concentrations of histamine from a Devilbiss 646 nebulizer. We recorded breathing pattern (tidal volume VT, inspiratory time TI, total time of the respiratory cycle TTOT), inspiratory capacity (IC), dynamic pleural pressure swing (Pplsw), total lung resistance (RL) and FEV1. VT was expressed both in actual values and as % of IC. Changes in VT (%IC) during histamine inhalation reflected changes in dynamic end-inspiratory lung volume (EILV). Pplsw was expressed as % of maximal (the most negative in sign) pleural pressure, obtained under control conditions during a sniff manoeuvre (Pplsn). Pplsw (%Pplsn) is an index of inspiratory muscle effort. The test ended when the concentration of histamine which caused a decrease in FEV1 of > or = 40% post-saline was reached. Dyspnoea rating was scored by a modified Borg scale. At the ultimate degree of bronchoconstriction (UDB) with histamine: (i) decrease in FEV1 was similar after placebo and fenoterol, while increase in RL was lower after fenoterol (P < 0.005); (ii) VT(%IC) increased less after fenoterol (P < 0.027); (iii) increases in Pplsw (%Pplsn) was lower after fenoterol (P < 0.001); (iv) delta Borg (from saline) was lower (P < 0.01) after fenoterol; (v) differences in delta Borg, from placebo to fenoterol, related to concurrent changes in VT(%IC) (r2 = 0.67). In conclusion, at UDB 100 micrograms of fenoterol produced a beneficial effect on the degree of inspiratory muscle loading and breathlessness, an effect greater than it would be expected from measuring FEV1 alone.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Reactivity of antibodies to core glycolipid with gram-negative bacteria.

Studies of the cross-reactivity of antibodies to core glycolipid with assorted isolated, heterologous lipopolysaccharides (LPSs) confirm the conservation of core glycolipid epitopes among gram-negative bacterial species. However, the accessibility of core glycolipid epitopes to antibody in the intact bacterial cell may be affected by the cell surface structure. In studies with 125I-labeled monoclonal antibodies to core glycolipid that cross-react with isolated LPS, the degree to which antibodies can bind to LPS in the outer membrane of intact, viable, gram-negative bacterial cells was found to vary with the strain of bacteria tested. Sequestration of bacterial cell-bound LPS from antibody was confirmed in a smooth strain of Escherichia coli by means of immunoelectron microscopy. The inability of antibody to bind to membrane-bound LPS suggests that such sequestered LPS may also be unable to effect toxicity in the infected host until liberated by bacterial cell breakdown.

Antibodies, Bacterial↗