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Biomedical subjects

W J Matthews

Publications and source records attributed to W J Matthews.

34 records · Page 2Linked to original sources

Progression of cystic fibrosis lung disease as a function of serum immunoglobulin G levels: a 5-year longitudinal study.

Seventy children with cystic fibrosis were studied over a 5-year period to assess the relationship between serum immunoglobulin G levels and progression of cystic fibrosis lung disease. Patients were grouped according to their serum IgG values (low, normal, or high) and evaluated with serial pulmonary function testing, radiographic and immunologic studies, and clinical observation. The children with persistent hypogammaglobulinemia G showed significantly better lung function, better weight for age, fewer hospitalizations for pulmonary exacerbations, less colonization with Pseudomonas aeruginosa, and slower decline in pulmonary functions than did age-matched patients with normal or high IgG levels. Death occurred in five of eight (63%) patients with hypergammaglobulinemia, three of 30 (10%) with normogammaglobulinemia, and one of 32 (3%) with hypogammaglobulinemia. No deaths occurred in the 15 patients with persistent hypogammaglobulinemia. These data indicate that children with cystic fibrosis and hypogammaglobulinemia G have milder lung disease and slower deterioration in pulmonary function than do age-matched patients with normal or elevated immunoglobulin G values. The mechanisms accounting for this finding are unclear.

Agammaglobulinemia↗

Complement biosynthesis by human bronchoalveolar macrophages.

Complement production by bronchoalveolar macrophages recovered from 8 normal volunteers and 15 patients with a variety of lung diseases was measured functionally and immunochemically. While macrophages from all eight normals demonstrated the capacity to secrete hemolytically active C2 and factor B within 48 hr of culture at consistent rates, bronchoalveolar macrophages from patients secreted C2 and factor B in widely differing amounts, and in some cases, not at all. No functional, secreted C3 was detected from normal macrophage monolayers, although apparently native C3 protein was synthesized and secreted. In contrast, functional C3 was produced by macrophage monolayers from 3 of 15 patients. These findings suggest that complement production by the normal human bronchoalveolar macrophage differs from its progenitor cell, the blood monocyte, and that complement production by bronchoalveolar macrophages may be altered in different pulmonary diseases.

Adult↗

Management of pneumothorax in cystic fibrosis.

The increased longevity of patients with cystic fibrosis has resulted in a concomitant increase in the frequency with which pneumothorax is seen. While several approaches to this problem have been available from both a medical and surgical standpoint, unsettled questions remain regarding the efficacy of various modalities of therapy. A review of our own experience with 170 episodes of pneumothorax has provided a basis for proposing what appears to be a reasoned approach to therapy. During the past 12 years, 65 patients ages 5 to 32 years experienced 170 episodes of pneumothorax. Of the 211 trials of treatment, all yielded a high rate of initial resolution (70% to 100%) but rates of recurrence were high. The recurrence rates were: observation 60%, thoracentesis 79%, trochar thoracotomy 63%, tetracycline sclerosis 86%, and silver nitrate 43%. Quinacrine sclerosis yielded an acceptable recurrence rate of 12.5% and partial pleurectomy had no recurrence. There was no statistical difference in the pulmonary function parameters determined before pneumothorax and after chemical pleurodesis or partial pleurectomy. Based upon the data obtained in this review, we recommend that initial management of the pneumothorax include evacuation of the pneumothorax using a chest tube and then chemical pleurodesis using quinacrine sclerosis. In those cases where this pleurodesis fails, upper-partial pleurectomy with obliteration of pleural blebs via a limited thoracentesis is the treatment of choice. An occasional patient requires a concomitant lobectomy.

Adolescent↗

Immunochemical characterization of the mucoid exopolysaccharide of Pseudomonas aeruginosa.

Alginic acid-like mucoid exopolysaccharide was isolated from three strains of Pseudomonas aeruginosa obtained from the sputa of patients with cystic fibrosis. Purified mucoid antigens were greater than 99% uronic acid. With a hemagglutination assay, antibody responses to the mucoid exopolysaccharide were documented after immunization of rabbits with either whole mucoid organisms or purified mucoid exopolysaccharide. The mucoid antigen from one strain (no. 2192) was composed predominantly of a single serologic epitope shared among 40 alginate exopolysaccharides from different clinical isolates. The mucoid exopolysaccharide from the other two strains (nos. 1 and 258) had a serotype-specific determinant in addition to the common epitope. Analyses of antibody in sera from normal adults, children, and patients with cystic fibrosis culture-positive and culture-negative for mucoid P. aeruginosa showed a highly significant (P less than 0.001) association between increased hemagglutination titers and positive cultures for mucoid P. aeruginosa.

Adult↗

Clinical and bacteriological responses to three antibiotic regimens for acute exacerbations of cystic fibrosis: ticarcillin-tobramycin, azlocillin-tobramycin, and azlocillin-placebo.

In a randomized, double-blind study, cystic fibrosis patients 11-30 years of age with an acute exacerbation of their pulmonary disease were treated with either ticarcillin-tobramycin, azlocillin-tobramycin, or azlocillin-placebo for 10 days. There was significant improvement in Shwachman scores and pulmonary function tests. Concentrations of sputum bacteria were significantly reduced, but after therapy patients had a mean of 10(7) bacteria/ml of sputum. Pseudomonas was transiently eliminated in only one patient. The three regimens had similar impacts on pulmonary function and sputum bacterial concentration. Antibiotic resistance was noted more frequently in the azlocillin-placebo group, but this trend was not statistically significant. Improvement in pulmonary function did not correlate with bacteriological response. Four weeks after discharge, 62% of the improvement in forced expiratory volume in one second and 75% of the improvement in vital capacity remained, but concentrations of sputum bacteria had returned to pretreatment levels, and antibiotic-resistant bacteria persisted.

Acute Disease↗

Randomized, double-blind evaluation of azlocillin for the treatment of pulmonary exacerbations of cystic fibrosis.

Patients with cystic fibrosis hospitalized because of deterioration in their pulmonary disease were randomly assigned to receive ten days of intravenous antibiotic therapy with either ticarcillin plus tobramycin (previously the standard regimen at our hospital), azlocillin plus tobramycin or azlocillin plus placebo. Pulmonary function and microbiological responses were similar in the three treatment groups, although patients receiving azlocillin and placebo tended to have a smaller reduction in the concentration of bacteria in the sputum and a greater rate of acquisition of antibiotic-resistant organisms. Overall, in-hospital treatment was associated with a significant improvement in Shwachman score, pulmonary function tests, and PO2. Improvement was noted by day 5 of therapy, continued through day 10, and was partially maintained at follow-up clinic visit one month after discharge. There was also a statistically significant reduction in sputum bacterial concentration, but patients cultured at the conclusion of antibiotic therapy still had a mean of 10(7) cfu/ml in sputum. Pseudomonas aeruginosa, the principal pathogen recovered from sputum cultures in this study, was transiently suppressed to sub-detectable levels in only one patient. There was no correlation between microbiological response and change in any parameter of pulmonary function. By follow-up clinic visit, sputum bacteria had returned to pre-treatment levels, and antibiotic-resistant organisms persisted in all patients from whom they had been recovered during hospitalization.

Adolescent↗

Complement proteins C2, C4 and factor B. Effect of glycosylation on their secretion and catabolism.

Tunicamycin, an inhibitor of N-acetylglucosaminylpyrophosphopolyisoprenol-dependent glycosylation, was used to study the effect of glycosylation on the synthesis, post-translational modification, secretion and function of the complement proteins that are associated with the major histocompatibility complex in humans, mice and guinea pigs. Tunicamycin blocked glycosylation of pro-C4, C2 and factor B and inhibited secretion of the corresponding native complement proteins synthesized by guinea-pig peritoneal macrophages in tissue culture. In addition, underglycosylated pro-C4 was more rapidly catabolized intracellularly than the corresponding fully glycosylated pro-complement protein. C4 protein secreted by cells incubated with tunicamycin had approximately the same specific biological activity as the protein obtained from control culture media, suggesting that carbohydrate is not required for its activity in immune haemolysis. Direct studies of carbohydrate incorporation and the tunicamycin effect suggested an unequal distribution of sugar among the C4 subunits, with maximal incorporation of carbohydrate into alpha-, and less into the beta-chain of the native protein.

Animals↗

Pneumothorax in cystic fibrosis: management and outcome.

We reviewed our experience over the past 12 years to determine the best method of management, to determine the morbidity and the physiologic outcome of medical vs surgical treatment of pneumothorax complicating CF, and to assess the influence of age, sex, and Shwachman scores on survival. Sixty-five patients, ages ranging from 5 to 32 years (mean 18 years). Shwachman scores ranging from 25 to 87 (mean 57), and a male-female ratio of 1:1, experienced 170 pneumothoraces, 93 first episodes, and 77 recurrences, requiring 211 trials of management. All methods of management except needle aspiration resulted in a fair rate of resolution (70 to 100%), but recurrence rates were high for observation (60%), needle aspiration (79%), trocar thoracotomy (63%), tetracycline sclerosis (86%), and silver nitrate sclerosis (43%). The recurrence rates were 12.5% for quinacrine sclerosis and 0% for parietal pleurectomy. Quinacrine sclerosis and parietal pleurectomy were the most effective methods of management. There was no significant difference in pulmonary function before pneumothorax and after pleural sclerosis or parietal pleurectomy. Age, sex, and severity of pulmonary disease were all independent variables influencing prognosis. Severity of disease, rather than the occurrence of a pneumothorax, appears to be the major cause of death. We recommend that quinacrine sclerosis should be considered for management of the first pneumothorax, and parietal pleurectomy if it fails.

Adolescent↗

Mucoid Escherichia coli in cystic fibrosis.

Patients with cystic fibrosis commonly harbor in their lungs strains of Pseudomonas aeruginosa that have a mucoid coating considered virtually pathognomonic for the disease. We found that strains of Escherichia coli with a morphologically similar mucoid coating were present in the respiratory tracts of eight (11.8 per cent) of 68 patients with cystic fibrosis whose sputum cultures yielded Esch. coli, as compared with none of 89 patients without cystic fibrosis who had Esch. coli in sputum. Mucoid strains of Esch. coli were also recovered from the stools of five (11.1 per cent) of 45 patients with cystic fibrosis, as compared with one (0.7 per cent) of 150 patients without cystic fibrosis. The mucoid substances purified from Esch. coli were biochemically and antigenically distinct from those of P. aeruginosa. We conclude that the respiratory tract in cystic fibrosis offers an environment conducive to the production of a mucoid coating not only by P. aeruginosa but by other gram-negative bacilli as well.

Bacteriological Techniques↗

Hypogammaglobulinemia in patients with cystic fibrosis.

To investigate some aspects of immune function in cystic fibrosis, we measured serum immunoglobulins in 419 patients. Twenty-two per cent of the 154 patients less than 10 years old had hypogammaglobulinemia-G, whereas the older patients had normal or elevated serum immunoglobulins. A single mechanism accounting for the extraordinary prevalence of hypogammaglobulinemia in young patients with cystic fibrosis was not defined in studies of T and B-lymphocyte function in vitro or in studies of IgG metabolism in vivo. Analysis of objective clinical data, including arterial blood gases, chest roentgenograms, and bacteriologic cultures, indicated that the patients with hypogammaglobulinemia had significantly less severe lung disease than did age-matched patients with cystic fibrosis and normal or elevated IgG levels. We conclude that progression of lung disease may be due in part to a hyper-immune response.

Adolescent↗

Control of complement synthesis and secretion in bronchoalveolar and peritoneal macrophages.

The effect of inflammation on C (C2 and C4) biosynthesis by bronchoalveolar and peritoneal cells was studied with methods that detect changes in synthesis rates and qualitative changes in cell populations. Adherent bronchoalveolar macrophages produced less C2 and C4 than adherent peritoneal macrophages. However, the subset of cells capable of producing C was more than 20-fold greater in the peritoneal cell population than in the population of bronchoalveolar cells. The rate of synthesis per C producing bronchoalveolar macrophage was 5 to 10 times the rate by C producing peritoneal macrophages. In contrast, the effect of an inflammatory stimulus on C production was the result of a change in rate of synthesis per cell, not a change in the proportion of C producing cells. This stimulatory effect was exerted locally, not on a cell population harvested from a distant site. At least two mechanisms for local control of C levels in tissues have been identified--that is, a change in synthesis rate and a qualitative change in macrophage cell population. The capacity to alter C levels at a site of inflammation may be important for C dependent functions in host defenses.

Animals↗

Cyclophosphamide and cortisone acetate inhibit complement biosynthesis by guinea pig bronchoalveolar macrophages.

To explore mechanisms of drug-induced alterations in local host defenses in the lung, the capacity of guinea pig alveolar macrophages to synthesize the second (C2) and fourth (C4) components of complement was studied following treatment with cyclophosphamide and cortisone acetate. Administration of either drug significantly inhibited biosynthesis of C2 and C4 within 1 day. After 1 week of treatment, local complement synthesis was inhibited approximately 80%, although serum levels of the corresponding proteins were normal.

Animals↗

The effects of intercessory prayer, positive visualization, and expectancy on the well-being of kidney dialysis patients.

CONTEXT: Little replicable empirical evidence on the effectiveness of prayer is available. OBJECTIVE: To explore the effect of intercessory prayer, positive visualization, and outcome expectancy on a wide range of medical and psychological measures in critically ill patients. DESIGN: 2 x 3 (expectancy x treatment) factorial study. PARTICIPANTS: 95 adult male and female volunteer hemodialysis subjects with end-stage renal disease from an outpatient clinic in Miami, Fla. INTERVENTION: Participants were randomly assigned to 1 of the 6 treatment conditions. MAIN OUTCOME MEASURES: A total of 20 dependent measures (10 medically based and 10 psychological) were used to assess the subjects' overall well-being. Analysis of covariance was used to control for pre-treatment differences between groups. RESULTS: Subjects who expected to receive intercessory prayer reported feeling significantly better than did those who expected to receive positive visualization (F1.93 = 5.42; P < .02). No other statistically significant main effects or interactions were found for either expectancy, intercessory prayer, or positive visualization on the remaining dependent measures. Analysis of effect sizes on all dependent measures failed to indicate even a small magnitude of effect for intercessory prayer as contrasted with expectancy on the medical or psychological variables. CONCLUSIONS: The effects of intercessory prayer and transpersonal positive visualization cannot be distinguished from the effect of expectancy. Therefore, those 2 interventions do not appear to be effective treatments.

Adult↗