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Biomedical subjects

W E Regelmann

Publications and source records attributed to W E Regelmann.

At least 19 recordsLinked to original sources

Aerosol scintigraphy in the assessment of therapy for cystic fibrosis.

Thirteen patients with cystic fibrosis (aged 11 to 32 years) who were hospitalized for exacerbation and who had sputum cultures positive for Pseudomonas organisms were treated initially for 4 days with bronchodilators and physiotherapy followed by the addition of antibiotic (14 days, n = 8) or placebo (14 days, n = 4; 7 days, n = 1). Tc-99m DTPA aerosol scintigraphy was performed on the day before bronchodilators and physiotherapy, on the day before antibiotic or placebo, and on the day after completion of antibiotic or placebo therapy. Scintigrams were evaluated for change in the number of nonventilated segments and change in the number of bronchial deposits of aerosol. Sixty-nine percent of patients showed improvement after bronchodilators and physiotherapy alone. Sixty-two percent showed further improvement after antibiotic or placebo was added; this improvement was independent of whether antibiotic or placebo was administered (P greater than 0.1). These aerosol scintigraphy results failed to demonstrate that the effectiveness of bronchodilators and physiotherapy is enhanced by antibiotics in the treatment of cystic fibrosis exacerbations.

Adult

The association of pauciarticular juvenile arthritis and myasthenia gravis.

We encountered two children with fluorescent antinuclear antibody-positive pauciarticular juvenile arthritis who later developed myasthenia gravis. Acetylcholine receptor binding, blocking, and modulating antibodies, retrospectively tested on frozen serum, yielded negative results before the onset of myasthenic symptoms but all yielded strongly positive results coincident with the onset of weakness. In both children, myasthenia gravis responded to thymectomy, and one child had a beneficial response to plasmapheresis. Although, to our knowledge, only two patients with juvenile arthritis and myasthenia gravis have been described in the past, the presence of two additional children with both diseases in a single clinic population suggests that the association may be more prevalent than previously suspected.

Adolescent

Pseudomonas aeruginosa variants isolated from patients with cystic fibrosis are killed by a bactericidal protein from human polymorphonuclear leukocytes.

The susceptibility of paired mucoid and nonmucoid variants of Pseudomonas aeruginosa isolated from 13 patients with cystic fibrosis (CF) to killing by a 55,000-Da bactericidal protein (BP55) from human polymorphonuclear leukocytes was studied. Mucoid and nonmucoid variants were equally sensitive to killing by BP55 at both pH 5.6 and pH 7.2. Eleven of the isolates were resistant to the bactericidal activity of 10% normal human serum but were as sensitive as the serum-sensitive isolates to BP55. Similarly, the 15 isolates with lipopolysaccharides (LPS) containing O-polysaccharide side chains (smooth LPS) were as sensitive to BP55 as those isolates with rough LPS.P. aeruginosa isolates from patients in poor clinical condition were more likely to have LPS of the smooth type and to be resistant to killing by 10% human serum than the isolates from patients in good clinical condition. We have concluded that the susceptibility of the P. aeruginosa isolates from patients with CF to killing by BP55 does not correlate with mucoid or nonmucoid variations, with the presence or absence of smooth LPS, or with the sensitivity or resistance to killing by normal human serum.

Adolescent

Increased monocyte oxidase activity in cystic fibrosis heterozygotes and homozygotes.

Freshly isolated monocytes from cystic fibrosis (CF) heterozygotes and homozygotes had significantly increased oxygen uptake and superoxide formation after surface glycoprotein stimulation than did monocytes from age- and sex-matched controls. Lack of differences among the genotypes in inhibition by simple sugars of the concanavalin A-stimulated superoxide production and lack of differences in concanavalin A-binding surface proteins suggested that different regulation of the oxidase pathway produced the increased oxygen uptake and superoxide formation in CF patients and carriers. This regulatory role is consistent with the predicted structure of the CF gene product. The results support the hypothesis that the mononuclear phagocytes of CF heterozygotes have a significantly increased ability to kill intracellular microbes and may confer a selective advantage to the host.

Adolescent

Reduction of sputum Pseudomonas aeruginosa density by antibiotics improves lung function in cystic fibrosis more than do bronchodilators and chest physiotherapy alone.

We evaluated patients with cystic fibrosis (CF) and moderate obstructive lung disease in pulmonary exacerbation in a double-blind placebo-controlled trial to determine the contribution of antibiotic-mediated reduction in sputum bacterial density to clinical improvement. For the first 4 days of study, all patients received bronchodilating aerosols and chest physiotherapy but no antibiotics. During this time, the patients showed significant improvement in mean FVC, FEV1, and maximal midexpiratory flow rate (FEF25-75). In 12 of 13 trials, the patients showed no significant increases in the density of Pseudomonas aeruginosa during these first 4 days. In these 12 trials, the patients were stratified by their initial FVC and randomized to receive either parenteral tobramycin and ticarcillin (n = 7) or placebo (n = 5), in addition to continued aerosol and chest physiotherapy. In the remaining trial, the patient had a significant rise in the density of P. aeruginosa and was assigned to the antibiotic group. During the next 14 days of therapy, the antibiotic group showed significantly (p less than 0.01) greater reductions in log10 colony-forming units (cfu) of P. aeruginosa per gram of sputum and greater increases in FVC, FEV1, and FEF25-75 than did the placebo group. The degree of decrease in log10 cfu P. aeruginosa/g sputum correlated significantly (p less than 0.001) with the degree of improvement in FVC, FEV1, and FEF25-75.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Distribution of cells bearing "rheumatic" antigens in peripheral blood of patients with rheumatic fever/rheumatic heart disease.

Cell surfaces of some peripheral blood cells from individuals with a history of rheumatic fever/rheumatic heart disease (RHD) have been demonstrated by the use of monoclonal antibodies to be antigenically distinct from the majority of the population. Our study examines the distribution of cells bearing these "rheumatic" antigens in 23 subjects with rheumatic fever/RHD of Maori, Polynesian and Caucasian ancestry and 182 members of their families (rheumatic fever/RHD families) as well as in 46 members of families in which no member had been demonstrated to have had rheumatic fever/RHD (control families). Mononuclear cells from the blood of all cooperating family members were prepared and non-T cells isolated by sheep red blood cell rosette depletion. The binding of monoclonal antibodies 83S19.23 and D8103 to non-T cells was measured using an immunoperoxidase technique. Subjects with rheumatic fever/RHD had a significantly higher proportion of cells binding the antibodies than the unaffected members of all families. Unaffected members of rheumatic fever/RHD families had significantly higher levels of such rheumatic cells than control families. An increase in the proportion of rheumatic cells with age was noted in unaffected members of rheumatic fever/RHD families but not in rheumatic fever/RHD subjects of control families. A level of 13% 83S19.23 positive non-T cells optimally discriminated between rheumatic and nonrheumatic individuals. The relative risk for rheumatic fever/RHD with 13% or greater positive cells was 9.48. The negative predictive value of having less than 13% positive cells was 98.3%. In the population studied, 83S19.23 seems especially capable of identifying those with low risk for rheumatic fever/RHD.

Aging

Cytokines and immunoglobulin in rheumatic heart disease: production by blood and tonsillar mononuclear cells.

Rheumatic fever and rheumatic heart disease are considered to result from abnormal immune responses after Group A streptococcal pharyngitis. Production of interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF), interleukin 2 (IL-2) and immunoglobulin (Ig) by blood and tonsillar mononuclear cells from rheumatic or healthy children was measured after stimulation in vitro by pokeweed mitogen (PWM) or the streptococcal extracellular product, blastogen A (BLA). Tonsillar cells from patients with rheumatic heart disease produced significantly less IL-1, TNF, IL-2, and Ig than control tonsillar cells. In contrast, blood mononuclear cell cultures from rheumatic children produced more TNF and IL-2 than controls. Our findings suggest that abnormal regulation of cytokine and Ig production may contribute to the pathogenesis of acute rheumatic fever and rheumatic heart disease.

Cells, Cultured

Lyme disease in children.

Lyme disease is an increasing health risk for children. Pediatricians should become familiar with the different clinical syndromes caused by the Borrelia burgdorferi. Appropriate antibiotic therapy must be initiated and follow-up of these children should be a part of the management as some may develop (tertiary) chronic borreliosis. Lyme disease should be considered in the diagnostic work-up of heart block, childhood arthritis and in undiagnosed peripheral and central nervous system disease. Serologic tests appear to be quite specific and sensitive in children with late stage disease in our experience. Newer diagnostic tests to detect infection during the early stage will optimize the management of Lyme disease and further decrease the incidence of long-term sequelae.

Anti-Bacterial Agents

Cell surface markers and cellular immune response associated with rheumatic heart disease: complex segregation analysis.

A series of functional and cell surface markers associated with a significantly increased risk of rheumatic heart disease were analyzed for the contribution of genetic factors in their presence. Peripheral blood lymphocytes from nine large kindreds from the New Zealand Maori, Polynesian, and Caucasian populations were isolated, purified, and evaluated with lymphocyte surface markers (monoclonals 83S.19.23 and D8103), as well as studied for blastogenic response to a purified group A streptococcal extracellular product, blastogen A. Segregation analysis of blastogenic response and percent of cells positive for these cell surface markers was consistent with genetic control by single major genes; however, the contribution by polygenes varied by marker, indicating heterogeneity of genetic control of identification of cell surface glycoproteins and blastogenic response to streptococcal products.

Antibodies, Monoclonal

Augmentation of cytotoxic activity by mitogens in rheumatic heart disease.

Natural killer cell activity and alterations in cytotoxicity after culture with streptococcal blastogen A and phytohemagglutinin (PHA) were examined in patients with inactive rheumatic heart disease (RHD) and control patients. Natural cytotoxic activity of mononuclear cells (MNC) did not differ between RHD and control patients with either peripheral blood or tonsils. In cultured blood MNC the level of cytotoxic activity stimulated by blastogen A was significantly greater in patients with RHD at all effector:target cell ratios. These differences in cytotoxic activity were not observed with cultured tonsillar MNC. In similar experiments with a different group of patients, culture with PHA or blastogen A both produced a significantly greater increase in cytotoxic activity in blood MNC from patients with RHD. The increase was significantly lower with PHA than with blastogen A. The ability of mitogens to differentially augment cytotoxic activity in cells from the blood of patients with RHD implies that a population of cells exists in these patients that could be activated during acute rheumatic fever to play a role in pathogenesis.

Adolescent

Compartmentalization of cells bearing "rheumatic" cell surface antigens in peripheral blood and tonsils in rheumatic heart disease.

Monoclonal antibodies that recognize "rheumatic" antigens of peripheral blood non-T cells were used to study the compartmentalization of such cells in peripheral blood and tonsils of individuals with rheumatic heart disease (RHD) and suitable control subjects. The peripheral blood of most (71%) of the 42 individuals with RHD contained cells reacting with monoclonal antibody 83S19.23 or 256S.10, whereas these cells were present in only 17% of the 41 control subjects (P less than .02). However, none of 21 individuals with RHD had such cells in their tonsils, although they were present in the tonsils of 50% of the 40 control subjects (P less than .03). These results may reflect a failure in RHD or organ-specific homing of cells with the epitopes recognized by the antibodies. The presence of these cells in tonsils may be important in the immune response to streptococcal pharyngeal infection, and their absence in RHD may be involved in the unusual immune responses characteristic of this disease.

Adolescent

Oxidative response of human neutrophils, monocytes, and alveolar macrophages induced by unopsonized surface-adherent Staphylococcus aureus.

In contrast to results with bacterial suspensions, phagocytosis of unopsonized bacteria readily occurs when bacteria are adhered to glass or plastic surfaces. However, in contrast to neutrophils, alveolar macrophages produced much less DNA denaturation as measured by acridine orange metachromasia of phagocytized Staphylococcus aureus. We have studied the phagocytosis of unopsonized surface-adherent S. aureus and the subsequent production of reactive oxygen species by peripheral blood neutrophils, monocytes, and alveolar macrophages. Phagocyte-free systems were then used to show the relationship of the reactive oxygen species produced by neutrophils and alveolar macrophages and the denaturation of unopsonized S. aureus DNA with acridine orange. Peripheral blood neutrophils, monocytes, and alveolar macrophages from normal human volunteers were added to vials with adherent S. aureus without opsonin. Bacterial uptake and luminol- and lucigenin-dependent chemiluminescence were measured. Neutrophils developed much greater luminol-dependent chemiluminescence than monocytes or alveolar macrophages. Compared with neutrophils and monocytes, alveolar macrophages developed significantly greater concentrations of superoxide, as measured by lucigenin-dependent chemiluminescence and ferricytochrome c reduction. These findings suggested that products of the myeloperoxidase-hydrogen peroxide-halide pathway were generated when peripheral blood neutrophils were stimulated and that alveolar macrophages primarily produced superoxide. When these reactive oxygen species were generated in phagocyte-free systems containing S. aureus, products of the myeloperoxidase-hydrogen peroxide-halide pathway produced denaturation of S. aureus DNA, whereas superoxide did not. Thus, differences in reactive oxygen species produced during phagocytosis may be related to the different capacities of neutrophils and alveolar macrophages to denature unopsonized adherent S. aureus DNA.

Acridine Orange

Lymphocyte subpopulations in rheumatic heart disease.

Monoclonal antibodies and indirect immunofluorescence techniques were used to compare the distribution of lymphocyte subpopulations of tonsil and peripheral blood from patients with rheumatic heart disease and age and socioeconomically matched patients undergoing tonsillectomy for chronic recurrent tonsillitis, but who had no evidence of rheumatic fever or rheumatic heart disease. The proportions of B cells (BA-1+), total T cells (Lyt-3), inducer/helper T cells (T4+) and cytotoxic/suppressor T cells (T8) were determined. No significant differences were apparent between rheumatic heart disease and control groups in resting cells from tonsils or blood. Cells undergoing proliferation in response to streptococcal blastogen A were identified by similar techniques. These tonsillar preparations from patients with rheumatic heart disease generated a smaller proportion of T8+ cultured cells and a greater T4/T8 ratio of cultured cells in response to group A streptococcal blastogen A than did nonrheumatic subjects.

Adenoids

Interference with granulocyte function by Staphylococcus epidermidis slime.

The interaction of Staphylococcus epidermidis slime with human neutrophils (PMN) was examined by using isolated slime and allowing bacteria to elaborate slime and other extracellular products in situ. S. epidermidis slime was found to contain a chemoattractant. Incubation of PMN with 50 micrograms or more of slime per ml inhibited subsequent chemotaxis of the PMN to n-formyl-methionyl-leucyl-phenylalanine by 27% and to zymosan-activated serum by 44 to 67% with increasing slime concentrations. S. epidermidis slime stimulated little degranulation of untreated PMN. After pretreatment of PMN with 5 micrograms of cytochalasin b per ml, slime predominantly induced release of specific granule contents (33.8% lactoferrin release by 250 micrograms of slime per ml versus 10% myeloperoxidase release by 250 micrograms of slime per ml). By a surface phagocytosis assay, PMN uptake of radiolabeled S. epidermidis which were incubated for 18 h on a plastic surface for slime expression was less than that for S. epidermidis adhered to the plastic for 2 h or grown in unsupplemented nutrient broth. These results suggest that S. epidermidis slime interaction with PMN may be potentially detrimental to host defense and may contribute to the ability of this organism to persist on surfaces of foreign bodies in the vascular or central nervous system.

Chemotaxis, Leukocyte

Increased monocyte chemiluminescence in cystic fibrosis patients and in their parents.

We examined the chemiluminescence response of peripheral blood monocytes from patients with cystic fibrosis (CF) and their asymptomatic parental carriers of the CF gene to three different types of stimulation. We found that monocytes from both patients and carriers have increased luminol-dependent chemiluminescence in the first 25 min after stimulation by adherence to glass. These results are consistent with the hypothesis that monocytes from both CF heterozygotes and homozygotes respond to adhesion with increased oxygen radical formation. The increased adherence-induced monocyte chemiluminescence of the parental carriers did not vary with age or length of exposure of the parents to a child with CF. Also, repeated exposure to medications and respiratory secretions of CF patients was not associated with an increase in adherence-induced monocyte chemiluminescence of their nonbiologically related caretakers. Thus, this observed increase in chemiluminescence is not simply secondary to the medications or respiratory dysfunction seen in the patients with CF. Patients with other types of obstructive lung disease did not show increased adherence-induced monocyte chemiluminescence. We conclude that increased early phase adherence-induced monocyte chemiluminescence occurs in patients with cystic fibrosis and the obligate carriers of the CF gene independent of environmental influences.

Adolescent

Aerosol penetration ratio: a new index of ventilation.

Superimposition of nuclear medicine scintigrams and standard radiographs provides a unique opportunity for merging functional information intrinsic to nuclear medicine images with the high resolution anatomic detail of radiographs. A newly developed image processing system allows the merging of two separate films of greatly varying sizes to form a single composite image. Subsequent quantitative analysis of the composite image may be performed. Using the superimposition technique, [99mTc]DTPA aerosol ventilation scans (4.5 X 4.5 cm) were superimposed upon chest radiographs (35.6 X 43.2 cm) in 17 cystic fibrosis (CF) patients. Subsequent quantification of the area of nuclear scan ventilation and the radiographic lung area was then performed. A new quantitative radiologic index of ventilation, the aerosol penetration ratio (APR), was defined. Linear correlation of aerosol penetration ratio with residual volume (RV) as percent of total lung capacity (TLC) measured by body plethysmography was good. We conclude that the APR has validity as a physiologic parameter which localized regional excessive residual volume and correlates well with RV/TLC, the "gold standard" pulmonary function index of obstructive airway disease.

Adolescent

Effect of extracellular slime substance from Staphylococcus epidermidis on the human cellular immune response.

Staphylococcus epidermidis infection of plastic catheters is often associated with heavy deposits of slime. To test whether this slime affects the human cellular immune response, its effect on the lympho-proliferative response of mononuclear cells to polyclonal stimulators was measured. Slime drastically reduces this response. Its inhibitory action was not immediate but took place over a few days and resulted in destruction of affected cells. The effect is dose related. This inhibition of cellular response may contribute to S epidermidis infection of implanted prostheses.

Adhesiveness