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Biomedical subjects

R B Dreisin

Publications and source records attributed to R B Dreisin.

At least 19 recordsLinked to original sources

Allergic bronchopulmonary curvulariosis.

A patient with clinical and roentgenographic findings suggestive of allergic bronchopulmonary disease who presented with recurrent pulmonary infiltrates with peripheral eosinophilia was identified. Sputum cultures were positive for Curvularia lunata. Total serum IgE was elevated, and intracutaneous skin testing with C. lunata was positive. Serum precipitins against C. lunata were present with specific IgE and IgG antibody indexes elevated. These studies provide further Immunologic characterization of this uncommon disorder.

Adult↗

The purification and identification of circulating immune complexes in tuberculosis.

Circulating immune complexes (CIC) have been documented in patients with tuberculosis. Like most other disease-related CIC, the composition of CIC in tuberculosis is unknown. Using the new technique of conglutinin affinity chromatography, we isolated and purified CIC from 6 patients with mycobacterial disease and compared these with CIC from 6 patients with other disorders. The CIC material from both groups was found by Ouchterlony analysis to be similar, containing IgG, IgA, and variable amounts of Clq, C3, and C4. Relative purity was confirmed by the absence of other serum components such as fibrinogen, alpha 1-antiprotease, alpha 2-macroglobulin, and transferrin; trace amounts of albumen were present in all samples. On sucrose density ultracentrifugation, CIC material from both groups demonstrated a well-defined major peak in the 9S to 12S range and a much smaller peak at 7S. After dissociation of CIC at pH 2.8, only a broad band in the 7S region was noted. Ouchterlony analysis demonstrated a positive precipitation reaction between CIC and rabbit anti-BCG in 5 of 6 patients with tuberculosis and 1 of 6 patients without tuberculosis. Anti-BCG activity was demonstrated by precipitation inhibition in 5 of 6 tuberculous and 2 of 6 nontuberculous samples. In all but one of the tuberculous samples tested, these reactions were confined to the 9S to 12S fraction. We conclude that some of the CIC found in patients with tuberculosis are composed of immunoglobulin, complement, and antigen derived from Mycobacterium tuberculosis.

Adult↗

Enhanced thrombin and plasmin activity with exercise in man.

We measured products of thrombin and plasmin action and of the platelet release reaction during exercise to determine if the well-known effect of exercise on in vitro coagulation and fibrinolytic tests reflects activity of these systems in vivo. Plasma fibrinopeptide A, produced by thrombin-mediated proteolysis of fibrinogen, increased with graded treadmill and cycle exercise to postexercise levels of 20--30 times resting values. Fibrin/fibrinogen-related D antigen increased in a similar fashion with peak levels at maximal O2 uptake. Plasma-activated partial thromboplastin times fell as fibrinopeptide A levels increased. Unheated fibrin plate lysis areas increased as D antigen concentrations rose, indicating increased release of plasminogen activator. In contrast to activation of the soluble coagulation and fibrinolytic systems, platelet counts and plasma levels of beta-thromboglobulin, a platelet release protein, did not change significantly with exercise. The effect of exercise on thrombin and plasmin was not influenced by prior physical training, but appeared to be less with cycle exercise than with treadmill exercise.

Blood Coagulation↗

Adverse effects of lidocaine and methylparaben on tracheal ciliary activity.

The effect of standard concentrations of lidocaine HCl and methylparaben (preservative) on the ciliary activity of ferret tracheal rings in organ culture was assessed. Pure lidocaine concentrations as low as 0.5% caused complete ciliostasis which was reversible after removal of the drug. One percent and two percent effects were not completely reversible. Pure methylparaben concentrations as low as 0.06 mg/ml paralyzed cilia; and, at concentrations of 0.5 mg/ml or higher, adverse effects were not completely reversible. When lidocaine and methylparaben were combined at the same ratio used in commercial preparations, their ciliotoxic effects were additive. These data suggest that topical respiratory anesthesia may result in prolonged ciliary paralysis.

Animals↗

The use of fluorescent labeled antigen to follow the fate of instilled immune complexes in the rabbit lung.

To follow the fate of exogenously introduced immune complexes in the rabbit lung, a direct labeling method was devised. Bovine serum albumin was incubated with fluorescein isothiocyanate, washed and then bound at equivalence with antibovine serum albumin. Immune complexes thus prepared are injected into a rabbit airway and the animal was sacrificed. Using chilled alcohol fixative and paraffin embedding 4 micrometer sections were prepared for light and fluorescent microscopy. This technique readily verifies that labeled antigen is taken up by alveolar macrophages. Electron microscopy using ferritin-antiferritin complexes corroborate these light findings.

Animals↗

Rapidly fatal pulmonary fibrosis: the accelerated variant of interstitial pneumonitis.

We sought to explore immunological factors in patients who died with rapidly fatal fibrosing lung diseases (Hamman-Rich syndrome). A retrospective review of cases of interstitial lung disease showed 12 recent deaths from Hamman-Rich syndrome. The mean age was 62, men outnumbering women 3 : 1. Five patients had proved collagen vascular disease (rheumatoid arthritis three, lupus two). Four others had a history of allergic disorders, syphilis, chronic eosinophilia, or hypersensitivity reactions. One patient showed disappearance of immunofluorescence as fibrosis advanced, which has not previously been reported. The study suggests a possible aetiological link between disorders of immunity and Hamman-Rich syndrome. The evidence also supports the notion that Hamman-Rich syndrome is an accelerated variant of the more indolent interstitial pneumonias.

Adult↗

The routine use of positive end-expiratory pressure after open heart surgery.

Because atelectasis of the left lower lobe is a frequent complication of open heart surgery, we evaluated the efficacy of routine therapy with positive end-expiratory pressure (PEEP) to prevent this complication. Twenty-four patients were randomly assigned to either a group receiving therapy with PEEP (ten patients) or to a group with no PEEP (14 patients). The two groups could not be distinguished by age, weight, the forced expiratory volume in one second (FEV1), the ratio of FEV1 over the forced vital capacity, the time on the pump, the units of blood transfused, the tidal volume, or the hours of mechanical ventilation. There was no significant roentgenographic difference between the two groups in either the degree or frequency of left lower lobe atelectasis. While the arterial-alveolar ratios tended to improve over time in those patients receiving therapy with PEEP, this improvement was not clinically significant. No complications were encountered with the use of PEEP. We conclude that the routine use of PEEP following open heart surgery is safe but offers no advantage over standard ventilatory techniques.

Cardiac Surgical Procedures↗

Sulfhydryl-mediated depression of ciliary activity: an adverse effect of acetylcysteine.

Although N-acetyl-L-cysteine (Mucomyst) is an effective mycolytic, numerous investigations have failed to demonstrate a consistent improvement in pulmonary mechanics following its use. In order to determine whether its beneficial mucolytic activity might be counterbalanced by a deleterious direct effect on cilia, we studied its effect on the activity of ciliated epithelium in the ferret tracheal organ culture system. N-acetyl-L-cysteine consistently caused progressive time-dependent ciliostasis at concentrations clinically employed, with complete ciliary paralysis within 8 hr. The effect was only partially reversed by the removal of the drug. Control preparations retained full ciliary activity for 3 to 12 weeks. In order to determine the active site on the N-acetyl-L-cysteine molecule, we investigated the ciliostatic effects of five of its chemical analogs. Isomolar N-acetyl-L-alanine was not ciliostatic, indicating the necessity of a sulfhydryl group for activity. Ciliostasis was independent of isomeric structure, acetylation, and chain length, as evidenced by the similar ciliostatic effects of L-cysteine, D-cysteine, 2-mercaptoethylamine, and N-acetyl-L-homocysteine. We conclude that N-acetyl-L-cysteine induces partially reversible ciliostasis of tracheal epithelium via its sulfhydryl group; prolonged use of this drug may impair mucociliary clearance.

Acetylcysteine↗

Complement fragments, alveolar macrophages, and alveolitis.

Mechanisms of neutrophil infiltration into the rabbit alveolus have been investigated. Complement activation in the circulation induced pulmonary vascular margination but not a significant level of alveolar infiltration. Instillation of C5 fragments into the airways, however, attracted neutrophils into the alveolar airspaces. The anaphylatoxin-inactive fragment of C5, C5a des Arg, was found to be much more active in this regard than C5a. Furthermore, these fragments were shown to induce the production of a neutrophil-directed chemoctactic factor from pulmonary macrophages, raising the question of whether the C5a des Arg was acting directly to attract neutrophils or indirectly via the macrophage. To substantiate a possible role for C5 and C5 fragments in alveolitis, active C5 was demonstrated in lavage fluids, and macrophage-derived C5 cleaving enzymes have been described. Finally, a route of neutrophil infiltration via migration through the alveolar capillary wall into the interstitium is proposed, and subsequent penetration of the alveolar epithelium out into the airspace. (Am J Pathol 97:93--110, 1979).

Alveolitis, Extrinsic Allergic↗

Circulating immune complexes in the idiopathic interstitial pneumonias.

We determined circulating immune complex levels and their correlation with pulmonary histopathology, immunofluorescence and steroid responsiveness in 24 patients with idiopathic interstitial pneumonias. Levels were elevated in all but three of 16 patients with cellular disease, but in none of eight with diffuse fibrosis (P less than 0.001). Granular deposition of IgG, usually with elevated levels, but in only 11 per cent of those with normal levels (P less than 0.001). The radiographic and physiologic response to corticosteroid therapy was better in patients with initially elevated levels than in those with normal levels (P less than 0.03). Circulating immune complexex are present in patients with cellular idiopathic interstitial pneumonias, have a pathogentic role in this disease and may identify a patient population that is potentially steroid responsive.

Adrenal Cortex Hormones↗

Immunofluorescent patterns in the idiopathic interstitial pneumonias.

Immunologic mechanisms have been implicated in the pathogenesis of the IIP's. Thirty five patients with IIP were divided into three groups: group I, seven subjects with DIP; group II, thirteen with UIP; and group III, fifteen with mural fibrosis. Lung biopsies were exposed to fluorescein-conjugated antisera to IgG, IgA, IgE, IgM, C3, fibrinogen, and albumin. In group I, all patients demonstrated IgG and C3 in a granular pattern lining alveolar walls. Similarly, in group II, all had IgG and 10 had C3 within alveolar walls. In contrast, only two group III subjects demonstrated IgG and none C3. Only one of 19 control subjects hav alveolar wall immunoglobulin and C3 deposition. The incidence of positive rheumatoid and antinuclear factors was similar in all three study groups. These data suggest that immune complex deposition may play a role in the pathogenesis of the cellular interstitial pneumonias and that once mural fibrosis supervenes, these complexes are no longer present.

Adult↗