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Biomedical subjects

M Pollack

Publications and source records attributed to M Pollack.

At least 37 records · Page 2Linked to original sources

Prehospital use of intravenous verapamil.

Verapamil was introduced into a hospital-based urban/rural advanced life support (ALS) system for intravenous (IV) use in patients with symptomatic supraventricular tachyarrhythmias. During this trial period, IV verapamil was given to 24 patients, 12 (50%) of which benefited from its use. IV verapamil produced no harmful effects, and there was only one reported adverse effect (nausea) related to its administration. IV verapamil may be useful in the prehospital care of patients with symptomatic supraventricular tachyarrhythmias.

Adult

The effect of Pseudomonas aeruginosa cytotoxin and toxin A on human polymorphonuclear leukocytes.

After exposure to cytotoxin or toxin A of Pseudomonas aeruginosa, the ultrastructure of resting and phagocytosing human polymorphonuclear leukocytes (PMNL) and of cells of P. aeruginosa strain 1348A was studied by transmission (TEM) and scanning (SEM) electronmicroscopy, and by light microscopy (LM) after histochemical staining of cytoplasmic granules. Cytotoxin caused marked clumping and destruction of PMNL, pyknotic nuclear changes with bleb formation, and release of cytoplasmic granules; phagocytosis was markedly diminished. In contrast, after exposure to toxin A, PMNL phagocytosed actively, but their cytoplasmic pseudopodia were markedly irregular and their nuclei pyknotic. Colloidal-gold-labelled cytotoxin showed an affinity for the cytoplasmic membranes, nuclei and granules of PMNL. Cytotoxin had no apparent effect on cells of P. aeruginosa strain 1348A but there was polar separation of the cytoplasmic membrane in bacteria exposed to toxin A. Cytotoxin and toxin A appear to be important in the pathogenesis of infections caused by P. aeruginosa.

ADP Ribose Transferases

Human monoclonal antibodies that recognize conserved epitopes in the core-lipid A region of lipopolysaccharides.

Epstein-Barr virus (EBV)-transformed human B lymphocytes were fused with a murine-human heteromyeloma to produce stable hybrid cell lines that secreted human monoclonal antibodies (mAbs) of the IgM class that recognized conserved epitopes in the core-lipid A region of lipopolysaccharides (LPS). Three of the mAbs reacted with epitopes on the lipid A moiety, while a fourth recognized a determinant in the core oligosaccharide. The lipid A-specific mAbs cross-reacted with heterologous rough LPS and with lipid As released by acid hydrolysis of different intact (smooth) LPS. Carbohydrate groups in the O-side chain and core oligosaccharide of isolated, smooth LPS restricted antibody access to antigenic sites on lipid A. Yet, one lipid A-reactive mAb recognized its epitope on the surfaces of a variety of intact bacteria. These findings confirm the presence of highly conserved epitopes in the core-lipid A complex and prove the existence of human B cell clones with the potential for secreting high avidity IgM antibodies that react with these widely shared determinants. Such human mAbs might provide protective activity against disease caused by diverse gram-negative bacteria.

Animals

Functionally distinct monoclonal antibodies reactive with enzymatically active and binding domains of Pseudomonas aeruginosa toxin A.

Monoclonal antibodies (MAbs) are described which react with two discrete structural domains of Pseudomonas aeruginosa toxin A and which have two distinct functional profiles. The MAbs designated T3-1C7 and T4-1F2 reacted with a 46,000-dalton peptide similar to the putative B or binding fragment of toxin A. These antibodies neutralized the cytotoxic and lethal properties of toxin but had no effect on its ADP-ribosyl transferase activity. T4-1F2 interfered with the binding of toxin A to membrane receptors on mouse fibroblasts (L cells), although the epitope for the antibody appears to be distinct from the actual receptor binding site. The MAb designated T2-1H2 reacted with intact toxin A and with a cloned, enzymatically active carboxy-terminal polypeptide similar to the toxin A fragment. This MAb neutralized the ADP-ribosyl transferase activity of activated holotoxin and of the cloned peptide, but inhibited neither binding of toxin to membrane receptors nor its cytotoxic and lethal actions. The complementary specificity and function of these MAbs confirm the functional specialization of discrete structural domains within the toxin A molecule. Our findings suggest the greater antitoxic potential of antibodies that block binding, compared with those which inhibit the enzymatic activity of toxin A.

ADP Ribose Transferases

Functionally active monoclonal antibody that recognizes an epitope on the O side chain of Pseudomonas aeruginosa immunotype-1 lipopolysaccharide.

A murine monoclonal antibody (MAb) was prepared against Pseudomonas aeruginosa immunotype-1 (It-1) lipopolysaccharide (LPS). The MAb bound It-1 LPS in the enzyme-linked immunosorbent assay and in the immunodiffusion and immunoblotting assays, agglutinated and opsonized It-1 bacteria, and protected against challenge with live It-1 organisms in a murine burn infection model. All of these activities were immunotype specific. Correlation of the opsonic and protective properties of the MAb with its recognition site on the LPS O side chain confirmed that such immunotype-specific determinants are important targets for protective antibodies in Pseudomonas disease. The functional equivalence of this MAb and polyclonal antibodies from hyperimmune plasma underscores the therapeutic potential of single MAbs which recognize critical determinants in the LPS O side chain.

Animals

Morphine-augmented cholescintigraphy in the diagnosis of acute cholecystitis.

Cholescintigraphy is a sensitive procedure for diagnosing or excluding acute cholecystitis. However, when rapid diagnosis is critical, the requirement for delayed images (4 hr or more after injection) to minimize the false-positive rate diminishes its utility. We prospectively evaluated 40 cholescintigraphic examinations that did not visualize the gallbladder 1 hr after injection of 99mTc diisopropyliminodiacetic acid. These examinations were then augmented by administration of IV morphine, followed by an additional 30 min of imaging. After the morphine, 18 of these examinations demonstrated visualization of the gallbladder; none subsequently required surgical exploration. Of the remaining 22, who demonstrated persistent nonvisualization of the gallbladder post-morphine, 11 were explored surgically and found to be abnormal. The 11 others were treated medically. Low-dose morphine administered when the gallbladder fails to visualize after 1 hr is a useful adjunct to conventional cholescintigraphy because it reduces the time required to obtain a diagnostic result and decreases the number of false-positive results.

Acute Disease

Unexplained persistent lymphadenopathy in homosexual men and the acquired immune deficiency syndrome.

Ninety-three homosexual men with persistent lymphadenopathy were followed at the Memorial Sloan-Kettering Cancer Center for a mean period of 20.8 months. Histories and serologic evidence of a number of previous infections were common, but the lymphadenopathy was not due to recognizable infections or neoplastic disease. Leukopenia, lymphopenia, granulocytopenia, monocytopenia, decreased ratios of T-helper to T-suppressor cells, decreased natural killer cell activity and increased serum immunoglobulin concentrations were common. Lymph node biopsies showed reactive hyperplasia without any unique histopathologic features. Antibody to the human T-lymphotropic virus-III (HTLV-III or LAV), a newly described retrovirus believed to be the etiologic agent of the acquired immune deficiency syndrome (AIDS), was detected in 91.4%. Over a 3-year period, 11 cases of AIDS were recognized in these patients: Kaposi's sarcoma developed in 7 and opportunistic infections in 4. The lymphadenopathy resolved in six patients and the others remained unchanged. Although most of these patients are asymptomatic and remain well, the risk of AIDS in this group of men was higher than in other groups of homosexual men in New York.

Acquired Immunodeficiency Syndrome

Elevation of platelet associated antibody levels in patients with chronic idiopathic thrombocytopenic purpura expressing the B8 and/or DR3 allotypes.

The HLA type DR3 was present in 11 of 26 patients with Chronic Idiopathic Thrombocytopenic Purpura (ITP), a significantly increased frequency (p less than 0.05). Levels of platelet associated immunoglobulin M(PAIgM) were significantly higher in the B8 and/or DR3 positive group of chronic ITP patients than in the B8 DR3 negative patients despite similar clinical outcomes. Other immunologic parameters assessed, including serum immunoglobulin levels, rate of catabolism of transfused IgG, and antibody coated autologous red cell clearances were similar for both groups. These results suggest that there is an immunobiologic abnormality associated with the B8 DR3 allotypes which may result in a predisposition not only to chronic ITP, but also to a significant increase in PAIgM. These results are in accord with studies linking autoantibody with B8 DR3.

Adolescent

HLA typing in bartter syndrome.

The mode of inheritance of Bartter syndrome is unclear; however, autosomal recessive inheritance seems likely. A consistent genetic marker of the carrier state likewise remains elusive. HLA typing was done in a family in whom six of 12 sibs have the syndrome. No significant HLA-syndrome linkage was found. This is in contrast to another familial hypokalemic syndrome in which a significant HLA association was found.

Bartter Syndrome

Cardiopulmonary abnormalities in severe acute respiratory failure.

Serial cardiopulmonary variables were recorded over 4 days in 23 children with severe acute respiratory failure. In all patients, pulmonary artery catheters were inserted within 24 hours of the diagnosis of respiratory failure, and all required greater than 10 cm H2O positive end-expiratory pressure to achieve adequate oxygenation. Eight patients died (35% mortality). Evaluation of systemic hemodynamic variables indicated that survivors had higher blood pressures than nonsurvivors, although neither group was in the hypotensive range. Systemic vascular resistance was lower in the nonsurvivors. Cardiac function as evaluated by cardiac index, right ventricular stroke work index, and left ventricular stroke work index was similar in both groups. Survivors demonstrated elevations in mean pulmonary artery pressure and pulmonary vascular resistance during the first 36 hours, with gradual improvement thereafter. In contrast, pulmonary artery pressure and resistance increased progressively in patients who died. Intrapulmonary shunt fractions remained high in the nonsurvivors despite the use of up to 25 cm H2O PEEP. Cardiac function and oxygen delivery were well maintained in both groups despite the high levels of PEEP.

Acute Disease

Blind use of the double-lumen plugged catheter for diagnosis of respiratory tract infections in critically ill children.

Transtracheal aspiration, percutaneous lung biopsy, and tracheal aspiration can be dangerous and/or unreliable methods for obtaining specimens of pulmonary secretions for culture. Using a blind technique, we evaluated the efficacy of a double-lumen catheter (DLC) with a polyethylene glycol plug in obtaining specimens of respiratory tract secretions for culture, and compared these results with simultaneously obtained cultures of tracheal aspirates. Twenty-seven intubated children already receiving antibiotic therapy were studied. Sixteen (59%) DLC specimens were sterile, as opposed to only 6 (22%) tracheal aspirates. Only 2 (8%) of the DLC specimens were contaminated. Two DLC specimens yielded significant bacterial growth (at least 10(5) colony-forming units/ml). Using DLC culture data, there was an 81% success rate in making decisions concerning antibiotic selection. We conclude that blind use of the DLC is a safe and reliable method of obtaining pulmonary secretion specimens for culture.

Adolescent

Immunization with Pseudomonas aeruginosa high-molecular-weight polysaccharides prevents death from Pseudomonas burn infections in mice.

High-molecular-weight polysaccharides from the extracellular slime of Pseudomonas aeruginosa were evaluated as immunogens in Pseudomonas burn infections in mice. Immunization with immunotype 1 or 2 polysaccharides induced a strong immunotype-specific and weak cross-reactive antibody response but protected mice against burn infections caused by either immunotype. Passive protection was provided by rabbit antiserum to immunotype 1 polysaccharide against burn infection by the homologous organism. Pseudomonas high-molecular-weight polysaccharides are potentially effective vaccines in burn infections.

Animals

Immunochemical characterization of high-molecular-weight polysaccharide from Fisher immunotype 3 Pseudomonas aeruginosa.

A high-molecular-weight polysaccharide (PS) was isolated from the culture supernatant of a Fisher immunotype 3 (IT-3) strain of Pseudomonas aeruginosa. Consistent with previously reported findings for IT-1 and IT-2 PS, the preparation of IT-3 PS was found to be an immunogenic, nontoxic form of the O polysaccharide side chain on the lipopolysaccharide (LPS). The IT-3 PS was mainly carbohydrate in composition. It was serologically and chemically identical to LPS O side chain, but distinct from that structure in molecular size and immunogenicity. The IT-3 PS was nontoxic in mice and guinea pigs, nonpyrogenic in rabbits, and greater than 1,000-fold less reactive than IT-3 LPS in gelation of the Limulus amoebocyte lysate. Preliminary analyses by gas-liquid chromatography and 13C nuclear magnetic resonance have established the structural identity of IT-3 high-molecular-weight PS and the IT-3 O side chain. IT-3 PS was immunogenic in rabbits and mice. After active immunization, mice were protected against P. aeruginosa IT-3 intraperitoneal infection and burn wound sepsis. IT-3 PS also elicited protection against challenge with an IT-5 strain of P. aeruginosa, indicating that low-level contamination of the IT-3 PS with IT-3 LPS was not responsible for the immunogenic activity. These findings demonstrate the feasibility of preparing nontoxic immunogenic IT-3 PS capable of eliciting serotype-specific protective antibodies, employing methods similar to those previously described for the isolation of PS from other P. aeruginosa immunotypes.

Animals

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Health Services Administration

Clinical significance of serum antibody responses to exotoxin A and type-specific lipopolysaccharides in patients with Pseudomonas aeruginosa infections.

Serum antibodies to Pseudomonas aeruginosa exotoxin A and immunotype-specific lipopolysaccharides were evaluated as diagnostic and prognostic markers in patients with Pseudomonas disease. Hemagglutination titers to exotoxin A were 1:1,024 or higher and/or showed a fourfold acute-to-convalescent increase in 17 of 25 (68 percent) patients infected with Pseudomonas compared with only one of seven (15 percent) colonized (p = 0.01) and two of 24 (8 percent) culture-negative patients (p less than 0.001). By comparison, hemagglutination titers to the lipopolysaccharide of patients' Pseudomonas isolates were 1:1,024 or higher or showed a fourfold increase in only four of 17 (24 percent) infected patients and in none of six (0 percent) colonized patients (p = 0.96). Serial antibody titers to exotoxin A provided serologic confirmation of invasive disease, distinguished infection from colonization, and, in the case of decreasing titers, indicated successful therapy. It is concluded that serum antibodies to exotoxin A are useful serologic markers for the clinical assessment of Pseudomonas infections in man.

ADP Ribose Transferases