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Biomedical subjects

E Middleton

Publications and source records attributed to E Middleton.

At least 91 records · Page 5Linked to original sources
PubMed1982

Role of parainfluenza virus-specific IgE in pathogenesis of croup and wheezing subsequent to infection.

In order to determine the role of parainfluenza virus-specific IgE antibody production and release of histamine in the pathogenesis of lower respiratory disease caused by parainfluenza virus infection, we studied 84 infants and children at the time of parainfluenza virus infection. Parainfluenza virus-IgE antibody was detected in samples of nasopharyngeal secretions by means of an enzyme-linked immunosorbent assay, and histamine content of nasopharyngeal secretions was determined by a fluorometric technique. Virus-specific IgE responses appeared earlier and were of greater magnitude in patients with croup, wheezing, and croup with wheezing caused by parainfluenza virus infection than in patients with parainfluenza virus-induced upper respiratory illness. Histamine was detectable in nasopharyngeal secretions of patients with parainfluenza virus-related croup significantly more often than in patients with upper respiratory illness caused by parainfluenza virus. These observations suggest a role for immunologic mechanisms in the pathogenesis of severe forms of respiratory illness caused by parainfluenza virus infection.

Antibodies, Viral↗
PubMed1981

The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection.

We studied the development of respiratory syncytial virus (RSV)-specific IgE and the release of histamine in nasopharyngeal secretions from 79 infants with various forms of respiratory illness due to RSV. RSV-IgE was measured by an enzyme-linked immunosorbent assay; specificity was confirmed by appropriate blocking experiments. Histamine content in the secretions was determined by fluorimetric methods. RSV-IgE was detectable in only one of 19 patients with RSV infection without wheezing, but was detectable in the majority of 60 patients with wheezing (P less than 0.01). Titers of RSV-IgE were significantly higher in patients with wheezing (P less than 0.05). Histamine was detectable in secretions of some patients with all forms of illness but was detected significantly more often (P = 0.05) and in higher concentrations in patients with wheezing. Peak titers of RSV-IgE and concentrations of histamine correlated significantly with the degree of hypoxia (P less than 0.001). Formation of RSV-specific IgE and release of histamine may adversely affect the outcome of RSV infection.

Age Factors↗
PubMed1981

Prednisolone disposition in steroid-dependent asthmatic children.

The pharmacokinetics of a 40-mg intravenous dose of prednisolone were determined in 10 steroid-dependent asthmatic children with highly variable prednisone requirements (5 mg every other day to 40 mg a day). Concentrations of prednisolone and cortisol in plasma over a 24-hr test period were measured by high-performance liquid chromatography. Eosinophil concentrations and the concentration-dependent protein binding of prednisolone were also determined. The mean (+/-SD) apparent half-life of prednisolone in these children was 2.5 +/- 0.5 hr. The mean total volume of distribution was 52.8 +/- 14.5 L/1.73 m2 and mean plasma clearance was 246 +/- 62 ml/min/1.73 m2. These pharmacokinetic parameters, as well as the protein binding and eosinopenic response, were similar to values from healthy and steroid-dependent asthmatic adults. The data were also similar in both responsive and relatively resistant patients. The pharmacokinetics and protein binding of prednisolone are not responsible for the highly variable prednisone requirement and clinical response of these children to prednisone therapy.

Aging↗
PubMed1980

Prednisolone disposition in steroid-dependent asthmatics.

A 40-mg intravenous dose of prednisolone was given as prednisolone phosphate to seven severe steroid-dependent asthmatics and to 13 healthy volunteers to determine if the large prednisone requirements of these patients were a function of the disease, cellular response, or rapid clearance of prednisolone. Plasma concentrations of prednisolone, prednisone, and cortisol were determined by high-performance liquid chromatography over an 8-hr test period. Circulating eosinophil concentrations were monitored concurrently. The apparent half-lifes of prednisolone in the asthmatics and normals were 3.33 +/- 0.71 and 3.25 +/- 0.58 hr (mean +/- SD). The apparent plasma clearances of prednisolone were 201 +/- 54 and 198 +/- 38 ml/min/1.73 m2 and the apparent volumes of distribution were 50.8 +/- 11.7 and 53.5 +/- 13.5 L/1.73 m2 for the asthmatic and normal groups, respectively. When the concentration-dependent binding of prednisolone to plasma protein was examined, no differences in the apparent clearances of unbound drug were found between the two groups. The eosinopenic response to prednisolone was similar in the steroid-dependent asthmatics and healthy normal volunteers. These studies indicate that binding, distribution, and clearance of prednisolone are not responsible for the large prednisone requirement of some steroid-dependent asthmatics. Differences in steroid-receptor sensitivity or in severity or pathophysiology of the disease state more likely account for the need for large prednisone dosages in these patients.

Adolescent↗
PubMed1980

A rational approach to asthma therapy.

Asthma is a common disease that can be very successfully managed in most cases by well-informed physicians and cooperative patients. A rational approach to therapy should begin with avoidance of all inciting agents insofar as possible. The second line of defense is optimal pharmacotherapy. Narcotics and sedatives are absolutely contraindicated in asthma because they depress the respiratory center. Also, the beta-adrenergic antagonists, such as propranolol and metaprolol, can precipate bronchospasm in some patients and so should be used with caution. In selected patients with clear-cut allergic asthma who fail to respond to environmental control and proper pharmacotherapy, consideration may be given to specific immunotherapy.

Adrenal Cortex Hormones↗
PubMed1978

Prostaglandin E and mitogenic stimulation of human lymphocytes in serum-free medium.

Sera used in cell cultures contain significant ammounts of prostaglandins (PGs). In order to avoid any effects of contaminating PGs, the present study employed a serum-free culture medium and confirmed the inhibitory effect of prostaglandin E (PGE) on the human lymphocyte activation which had been observed previously employing a serum-containing medium. PGE1 displayed a significantly stronger inhibitory effect on the cells than previously shown. Furthermore, reported enhancement of PGE synthesis by mitogen-activated lymphocytes could not be reproduced.

Cells, Cultured↗
PubMed1978

Plasma prostaglandin concentrations in allergic bronchial asthma.

Prostaglandin (PG) E plasma levels, measured by radioimmunoassay using anti-PGB1 antibody, were higher in asthmatic patients than in normal subjects. PGF levels measured with anti-PGF2alpha antibody, were not significantly different between normals and asthmatics. Plasma PGE/F ratios were elevated in the asthmatic patients. The results fail to support the hypothesis of decreased PGE or increased PGF production as an etiological factor in asthma.

Adolescent↗
PubMed1978

Prolonged oestrogenic and mitogenic activity of tamoxifen in the ovariectomized mouse.

A dose of tamoxifen (ICI 46,474), which has been found to inhibit the vaginal smear response to oestrogens, exerted prolonged oestrogenic effects in mice and increased the rate of cell proliferation in both the vagina and uterus. The vaginal epithelium became multilayered with stratified or cornified surface layers and the uterus developed gross cystic glandular hyperplasia. This demonstrates that ICI 46,474 is simply a weak oestrogen in the mouse.

Animals↗
PubMed1977

The molecular configuration of inulin: implications for ultrafiltration theory and glomerular permeability.

A space-filling model of the inulin molecule, based solely on physico-chemical data in the literature, indicates that the gross shape of the solvated molecule is a cylinder having semi-length 25 A and radius 10 A. The axial dimensions of this model very nearly equal the equivalent estimates (25 and 10.5 A) previously determined by studying restricted passage of inulin through artificial membranes of known pore size (E. Middleton, J. Membrane Biol. 20:347, 1975). The good agreement between these independent in-vitro studies--neither of which depends on ultrafiltration theory--strongly suggests that glomerular pore size is considerably greater than predicted by the theory.

Cell Membrane Permeability↗