Pediatric AIDS.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
S Abramson
Publications and source records attributed to S Abramson.
Cystic fibrosis in childhood: pulmonary, paranasal sinus, and skeletal manifestations.
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Adolescent↗
Complement activation and vascular injury in systemic lupus erythematosus.
The deposition of immune complexes within blood vessel walls results in the potential for complement activation and the release of chemotactic factors, such as fragments of C5 (C5fr). The generation of C5fr results in the intravascular aggregation of neutrophils with subsequent leukostatic occlusion of the pulmonary arterioles. The generation of C5fr may contribute to the pathogenesis of adult respiratory distress syndrome and other diseases. Studies were undertaken to determine the role of circulating complement derived peptides and intravascular neutrophil activation in systemic lupus erythematosus.
Antigen-Antibody Complex↗
Non-steroidal anti-inflammatory drugs: how do they work?
Current dogma holds that non-steroidal anti-inflammatory drugs (NSAIDs) act by inhibition of the synthesis and release of prostaglandins. However, NSAIDs also inhibit the activation of neutrophils, which provoke inflammation by releasing products other than prostaglandins. We now report that NSAIDs (for example, indomethacin, piroxicam) inhibit activation of neutrophils by inflammatory stimuli such as C5-derived peptides and leukotriene B4 even when cyclooxygenase products generated in suspensions of stimulated neutrophils (prostaglandin E and thromboxanes) are present. Sodium salicylate (3mM) greatly inhibited aggregation of neutrophils but had no effect on aggregation of platelets or production of thromboxane induced by arachidonate. Sodium salicylate and other NSAIDs also inhibit calcium movements (45Ca uptake, changes in fluorescence of chlortetracycline and Quin-2). Aspirin, sodium salicylate, indomethacin, and piroxicam also enhanced the post-stimulation rise in intracellular cyclic AMP. NSAIDs therefore inhibit early steps in neutrophil enhance intracellular levels of cyclic AMP.
Adult↗
Complement activation during systemic lupus erythematosus. C3a and C5a anaphylatoxins circulate during exacerbations of disease.
To determine whether activated complement components appear in the circulation of patients with systemic lupus erythematosus (SLE), we measured C5a and C3a by radioimmunoassay. Mean C5a concentration in the plasma of acutely ill SLE patients was 46.0 ng/ml, compared with 17.1 ng/ml in normal controls (P less than 0.01). Mean C3a concentration in patients with severe disease was 526 ng/ml, compared with 134 ng/ml in controls (P less than 0.01). In patients with moderately active SLE, the mean C3a concentration, but not the mean C5a concentration, was also elevated. In addition, C3a was elevated in 15 or 21 patients with active SLE, whereas low levels of C3 or C4 were noted in only 7 of these 21 patients. We conclude that the measurement of complement-derived anaphylatoxins may be useful in the management of patients with SLE. In addition, we suggest that these circulating mediators may contribute to the pathogenesis of vascular injury in patients with the disease.
Complement Activation↗
Primary pulmonary tuberculosis in infancy: a resurgent disease in the urban United States.
Primary pulmonary tuberculosis in infancy still exists in the urban United States, reflecting new immigrations from less developed areas. The clinical diagnosis may be difficult and routine chest radiographs may be confusing. We found magnification high KV filtered radiography to be very useful in delineating the primary complex and its effect on the tracheobronchial tree. Twelve infants and small children with primary pulmonary tuberculosis were seen in the years 1978-1984.
Female↗
"Missing" femoral condyle: an unusual sequela to neonatal osteomyelitis and septic arthritis.
Growth deformities of the distal femur and unusual gait disturbances were observed in four girls who had had neonatal osteomyelitis and septic arthritis. In each case apparent absence or hypoplasia of one of the femoral condyles, as seen on plain radiographs, was associated with marked genu varum or genu valgum. Arthrography showed the apparently missing condyle to be present in a cartilaginous form, with preservation of the articular surfaces. Based on these findings, surgical treatment was limited to corrective osteotomy.
Arthritis, Infectious↗
Microcolon of prematurity: a form of functional obstruction.
Six premature infants (birth weights 920-1320 g) developed marked abdominal distension after birth, and contrast enema examination showed a microcolon. Four of the six were born to mothers with toxemia who received magnesium sulfate. Bilious emesis was absent in all six, despite marked distension and failure to pass meconium. None of the patients had aganglionosis or cystic fibrosis; five of six were followed without surgery and recovered spontaneously. The sixth had perforation 8 hr after contrast enema and required bowel diversion; this infant also survived. This appears to be an equivalent form in small premature infants of the "small-left-colon syndrome" seen in term infants. Surgery should be reserved for complications; it is not necessarily indicated by the finding of a microcolon in such patients.
Colon↗
Salmonella bacteremia in systemic lupus erythematosus. Eight-year experience at a municipal hospital.
Non-endemic Salmonella bacteremia tends to occur in patients with chronic disease. We reviewed all cases of Salmonella infection documented in adults at Bellevue Hospital during the years 1975-1982. Unexpectedly, the most frequent underlying disease found among bacteremic patients was systemic lupus erythematosus (SLE). Patients with SLE accounted for 6 of 30 Salmonella bacteremias as compared with 13 of 2,388 non-Salmonella gram-negative bacteremias. Salmonella was the single most frequent gram-negative isolate from the blood of SLE patients. All lupus patients with Salmonella infection were bacteremic. In contrast, isolates from blood represented only 23% of all Salmonella infections documented in the non-lupus population. Presentation was characterized by fever (greater than 103 degrees F) and abdominal pain. Four of the 6 patients were hypocomplementemic. All were receiving immunosuppressive therapy. We conclude that SLE patients in a municipal hospital setting are at increased risk for Salmonella sepsis. This should be considered when empiric antibiotic therapy is initiated.
Adolescent↗
Potential errors in the diagnosis and surgical management of neonatal jaundice.
Despite advances and refinements in diagnostic techniques, distinguishing between cholestatic syndromes and extrahepatic biliary atresia is not always possible. Because there are inherent errors in all diagnostic studies including nuclear scanning, ultrasonography, and liver biopsy some infants presumed to have biliary atresia will come to surgery when, in fact, the bile ducts are partially or completely patent. The decision to proceed with a portoenterostomy or to terminate the procedure depends upon the appearance of the liver and histology of the biopsy.
Biopsy, Needle↗
Modes of action of aspirin-like drugs.
Current dogma holds that nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibition of the synthesis and release of prostaglandins. However, NSAIDs also inhibit the activation of neutrophils, which provoke inflammation by releasing products other than prostaglandins. We now report that NSAIDs (e.g., indomethacin, piroxicam) inhibit activation of neutrophils by inflammatory stimuli, such as C5-derived peptides and leukotriene B4, even when cyclooxygenase products generated in suspensions of stimulated neutrophils (prostaglandin E and thromboxanes) are present. Sodium salicylate (3 mM) greatly inhibited aggregation of neutrophils but had no effect on aggregation of platelets or production of thromboxane induced by arachidonate. Sodium salicylate and other NSAIDs also inhibit calcium movements (45Ca uptake, changes in fluorescence of chlortetracycline and quin-2). Aspirin, sodium salicylate, indomethacin, and piroxicam also enhanced the poststimulation increase in intracellular cyclic AMP. NSAIDs therefore inhibit early steps in neutrophil activation as reflected by their capacity to inhibit movements of Ca and to enhance intracellular levels of cyclic AMP.
Anti-Inflammatory Agents↗
Inhibition of neutrophil activation by nonsteroidal anti-inflammatory drugs.
Nonsteroidal anti-inflammatory drugs are thought to prevent inflammation in rheumatoid arthritis by inhibiting prostaglandin synthesis. This observation does not explain, however, why nonsteroidal anti-inflammatory drugs are able to control inflammation caused by other mediators. To determine whether nonsteroidal anti-inflammatory drugs also exert an effect on neutrophil activation, in vitro and in vivo studies were undertaken. Aggregation, superoxide anion generation, and lysosomal enzyme release were assessed. The nonsteroidal anti-inflammatory drugs were found to inhibit these neutrophil responses, but the patterns of inhibition varied from drug to drug. These findings suggest that nonsteroidal anti-inflammatory drugs may have direct effects on neutrophil activation that are independent of their shared inhibition of prostaglandin synthesis.
Anti-Inflammatory Agents↗
Effects of non-steroidal anti-inflammatory agents on human neutrophil functions in vitro and in vivo.
Human blood neutrophils exposed to appropriate stimuli aggregate, degranulate and generate superoxide anion (O2-). These responses are anteceded by mobilization of membrane-associated calcium, monitored as a decrease in fluorescence of cells preloaded with chlortetracycline (CTC). We studied the effects, both in vitro and in vivo, of non-steroidal anti-inflammatory agents (aspirin, indomethacin, ibuprofen and piroxicam) on these neutrophil responses to three stimuli: a chemoattractant, N-formyl-methionyl-leucyl-phenylalanine (FMLP); a tumor promotor, phorbol myristate acetate (PMA); and a lectin, concanavalin A (Con A). The effects of these drugs were compared with those of two polyenoic inhibitors of arachidonate metabolism: eicosatrienoic acid (ETI) and eicosatetraynoic acid (ETYA). The pattern of inhibition of neutrophil functions varied both with inhibitor and the nature of the stimulus. Thus, aspirin, piroxicam, ETYA and ETI inhibited neutrophil aggregation, degranulation, and O2- generation in response to FMLP, whereas ibuprofen inhibited only aggregation and degranulation and indomethacin only inhibited aggregation. None of the agents inhibited aggregation or degranulation induced by PMA or Con A: only piroxicam inhibited O2- generation in response to PMA or Con A. ETI and ibuprofen inhibited decrements of CTC fluorescence induced by FMLP, but whereas ETI inhibited the CTC response to PMA or Con A, ibuprofen was without effect. The agents had varying effects on binding of the stimulus [( 3H]FMLP, [3H]Con A), but these did not correlate with neutrophil responses to the ligands. Neutrophils from subjects taking therapeutic doses of ibuprofen, indomethacin, or piroxicam showed profiles of inhibited responses to FMLP similar to those observed with these agents in vitro. These data suggest that, although non-steroidal anti-inflammatory agents may inhibit discrete neutrophil functions both in vitro and in vivo, their effects do not duplicate those of polyenoic inhibitors of arachidonate metabolism. Moreover, since the susceptibility of neutrophils differed not only with respect to each inhibitor, but also to the stimulus, it is unlikely that all neutrophil responses are necessarily linked by a common pathway that is blocked by inhibitors of arachidonic acid metabolism.
5,8,11,14-Eicosatetraynoic Acid↗
The inactivation of the polymorphonuclear leukocyte by non-steroidal anti-inflammatory drugs.
When human neutrophils (PMNs) are activated by appropriate stimuli, they aggregate, generate superoxide anion (O2-) and secrete lysosomal enzymes. Pre-incubation of PMNs in vitro with the cyclo-oxygenase (COx) inhibitor piroxicam (50 microM) before stimulation with the chemotactic peptide f-met-leu-phe (FMLP, 10(-7)M) inhibited all of these responses. The COx inhibitor ibuprofen inhibited FMLP-induced aggregation and lysozyme secretion, leaving O2- generation unaffected. Binding of 3H-FMLP was inhibited by piroxicam. When the plant lectin concanavalin A (Con-A, 30 micrograms/ml) or the tumor promoter phorbol myristate acetate (PMA, 50 micrograms/ml) was used as a stimulus, ibuprofen had no effect on PMN response, while piroxicam inhibited only O2- generation. To determine whether such inhibition might also occur in vivo, we tested neutrophil aggregation and O2- generation in response to FMLP in 26 normal subjects. These subjects were then administered therapeutic doses of piroxicam (20 mg/day), ibuprofen (2400 mg/day) or indomethacin (100 mg/day), and neutrophil functions were retested after 3 days. Piroxicam inhibited FMLP-induced aggregation by 31% (5.2 cm2/min versus 3.6 cm2/min, P less than 0.004) and O2- generation by 35% (15.8 nmol cytochrome c reduced versus 10.2 nmol, P less than 0.002). Ibuprofen inhibited FMLP-induced aggregation by 44% (5.2 versus 3.0, P less than 0.03) but had no effect on O2- production. Indomethacin inhibited FMLP-induced aggregation (6.4 versus 2.9, P less than 0.01) but had no effect on O2- generation.(ABSTRACT TRUNCATED AT 250 WORDS)
Anti-Inflammatory Agents↗
The diagnosis and management of renal inflammatory processes in children.
Renal inflammatory processes in children often present a diagnostic and therapeutic dilemma. Since the advent of improved diagnostic imaging techniques these lesions can be appreciated and defined better. An analysis of 12 children with renal inflammatory lesions treated at our institution clearly outlines the pathological spectrum of these lesions and provides a format for their diagnosis and management.
Abscess↗
The neutrophil in rheumatoid arthritis: its role and the inhibition of its activation by nonsteroidal antiinflammatory drugs.
The activation of the polymorphonuclear leukocyte (PMN) in rheumatoid arthritis produces toxic products that include lysosomal enzymes, stable prostaglandins, and leukotrienes and causes the release of superoxide anion. These products produce the inflammatory response, damage cell membranes, and degrade hyaluronic acid. The inhibition of prostaglandin synthetase by NSAIDs does not, by itself, account for their effectiveness in preventing inflammation in rheumatoid arthritis. In vivo and in vitro experiments were conducted to determine if NSAIDs also exert an effect on neutrophil activation. The NSAIDs tested inhibited discrete PMN functions dependent upon the stimulus tested. The antiinflammatory effects of NSAIDs cannot be entirely explained by their inhibition of prostaglandin synthetase and may, in part, be due to other direct effects upon inflammatory cell activation.
Anti-Inflammatory Agents↗
Superoxide anion generation by human neutrophils exposed to monosodium urate.
We studied the capacities of naked and protein-coated monosodium urate (MSU) crystals to stimulate superoxide anion (O(2)) release by human polymorphonuclear leukocytes (PMN). Uncoated MSU estimated significant O(2) production by cytochalasin B-treated PMN. Precoating MSU with IgG caused an increase in mean O(2) production, whereas precoating heated MSU with serum or plasma inhibited O(2) release. Unheated MSU crystals, which activate complement to a greater extent than heated crystals, also provoked O(2) generation, an effect again abrogated by precoating with serum but not with plasma. Coincubation of unheated MSU and plasma resulted in an enhancement of O(2) generation. The results of these experiments support the hypothesis that adsorbed proteins modulate the phlogistic potential of MSU and that the surface activation of humoral mediators contributes to the local inflammatory response.
Adsorption↗
The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid systems.
The precise relationship between the stem cells for the lymphoid system and those for the blood-forming system is unclear. While it is generally assumed that the hemopoietic stem cell, the spleen colony-forming unit (CFU-S), is also the stem cell for the lymphoid system, there is little evidence for this hypothesis. To investigate the stem cells in these two systems, we irradiated bone marrow cells to induce unique chromosome aberrations in the stem cell population and injected them at limiting dilution into stem cell-deficient recipients. Several months (between 3 and 11) were allowed for the injected cells to repopulate the hemopoietic system. At that time, the bone marrow, spleen, and thymus were examined for a high frequency of cells having the same unique chromosome aberration. The presence of such markers shows that the marker was induced in a cell with extensive proliferative capacity, i.e., a stem cell. In addition, the splenic lymphocytes were stimulated with phytohemagglutinin (PHA) or lipopolysaccharide (LPS) to search for unique chromosomes in dividing T and B cells, respectively. Finally, bone marrow cells were injected into secondary irradiated recipients to determine if the marker occurred in CFU-S and to determine whether or not the same tissue distributions of marked cells could be propogated by bone marrow cells in a second recipient. After examination of 28 primary recipients, it was possible to identify three unique patterns of stem cell regeneration. In one set of mice, a unique chromosome marker was observed in CFU-S and in PHA- and LPS-stimulated cultures. These mice provide direct evidence for a pluripotent stem cell in bone marrow. In addition, two restricted stem cells were identified by this analysis. In three recipients, abnormal karyotypes were found only in myeloid cells and not in B and T lymphocytes. These mice presumably received a marked stem cell restricted to differentiate only into myeloid progeny. In three other recipients, chromosome aberrations were found only in PHA-stimulated cells; CFU-S and cells from LPS cultures did not have cells with the unique chromosome. This pattern suggests that bone marrow contains cells committed to differentiation only into T lymphocytes. For each of the three types of stem cells, secondary recipients had the same cellular distribution of marked cells as the primary recipients. This observation provides further evidence that unique markers can be induced in both pluripotent and restricted stem cells.
Age Factors↗