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Biomedical subjects

H Faden

Publications and source records attributed to H Faden.

At least 73 records · Page 4Linked to original sources

Otitis media in children. I. The systemic immune response to nontypable Hemophilus influenzae.

Twenty-one infants experienced 29 episodes of otitis media with effusion caused by nontypable Hemophilus influenzae (NTHI) during 2 y of observation. Bactericidal antibody was detected in acute serum of 26% of the subjects at a mean titer of 0.8 +/- 0.3 (log2) and was observed in convalescent serum of all of the individuals at a mean titer of 4.0 +/- 0.3 (log2, P less than .001). The serum bactericidal antibody response was not age-dependent (r = .08, P greater than .05). Serum concentrations of bactericidal antibody remained stable for the entire observation period in 90% of the children. The presence of serum bactericidal antibody correlated significantly with a reduction in the number of bacteria present in the middle ear fluid (P less than .025). Eight children experienced a second episode of otitis media with effusion caused by a different serotype of NTHI. All those who lacked bactericidal antibody against the organism causing the second episode possessed bactericidal antibody against the first strain at the time of the second episode. These data suggest that the immune response to NTHI in otitis media with effusion is type-specific. The occurrence of second episodes of otitis media with effusion due to different strains of NTHI in the face of preexisting heterologous bactericidal antibody suggests a lack of NTHI in the face of preexisting heterologous bactericidal antibody suggests a lack of cross-protection.

Antibodies, Bacterial↗

Otitis media in children: local immune response to nontypeable Haemophilus influenzae.

Twenty children experienced 30 episodes of otitis media with effusion due to nontypeable (NT) Haemophilus influenzae in the first 2 years of life. The local and systemic immune responses to homologous strains of NT H. influenzae were determined by an immunodot assay. Strain-specific immunoglobulin G (IgG) antibody predominated in the middle ear fluid (MEF). It was detected in 91% of the children, compared with IgM in 48% (P less than 0.005), IgA in 52% (P less than 0.005), and secretory IgA in 18% (P less than 0.005). The titer (log2) of NT H. influenzae-specific IgG antibody (mean +/- standard error, 8.2 +/- 0.1) exceeded the titers of IgM (3.4 +/- 0.1), IgA (3.7 +/- 0.1), and secretory IgA (1.2 +/- 0.3). NT H. influenzae-specific antibody was detected exclusively in MEFs of individuals who possessed homologous serum antibody. Although antibody titers in MEF declined over time, serum antibody titers remained stable. These data suggest that immunity to NT H. influenzae in the middle ear, in part, reflects systemic immunity. Whereas local antibody disappears after resolution of the infection, systemic antibody persists.

Antibodies, Bacterial↗

Recovery of a unique bacterial organism in human middle ear fluid and its possible role in chronic otitis media.

The middle ear fluids of 10 children with persistent otitis media with effusion (OME) were found to contain an unclassified, slow-growing, gram-positive organism. Large gram-positive cocci, often present as diplococci or tetrads, were readily seen in each effusion. Culture of the fluid on a blood agar plate required 2 to 5 days of incubation at 37 degrees C and yielded a slow-growing coccus in pure culture in 70% of cases and in mixed culture in 30% of cases. The organism in question was unique and could be distinguished from aerococci, gemellas, enterococci, and micrococci. It grew in 6.5% saline and on bile esculin agar. It did not grow at 45 degrees C or anaerobically. It was uniformly catalase and hippurate positive. It gave negative reactions with tellurite, tetrazolium, and pyruvate and did not utilize any of the carbohydrates tested. Reactions to bile esculin were variable. The episodes of OME associated with the bacterium in question were asymptomatic, had been present from 1 to 8 months, and occurred in children who had previously experienced OME. The middle ear fluids were typically serous or seromucinous and contained inflammatory cells. The data suggest that the gram-positive coccus is a newly described middle ear pathogen and may be responsible, in part, for persistent middle ear effusion. The characteristically slow growth of the organism in vitro could hinder recovery of the organism from clinical specimens and may therefore have prevented its earlier recognition.

Child, Preschool↗

Release of leukotriene C4 in respiratory tract during acute viral infection.

Groups of children with wheezing during respiratory illness, children without wheezing during respiratory illness, and appropriately matched healthy children were tested for the presence and concentration of leukotriene C4 (LTC4) in nasopharyngeal secretions, employing the techniques of reverse-phase high-pressure liquid chromatography and radioimmunoassay. Although most wheezing children had LTC4 in nasopharyngeal secretions, the concentration of LTC4 among wheezing children who shed respiratory viruses was found to be consistently elevated (mean 1520 +/- 228 pg/0.1 mL) compared with values in wheezing children without evidence of viral infection (mean 709 +/- 147 pg/0.1 mL). In sharp contrast, little or no LTC4 activity was detected in healthy children (mean 106 +/- 77 pg/0.1 mL). These observations suggest that respiratory viruses are stimuli for the release of mediators of inflammation such as LTC4. Thus development of virus-induced bronchospasm may be related in part to direct mucosal cell-virus interaction and the release of pharmacologically active mediators in the respiratory tract.

Acute Disease↗

Chemiluminescent response of neutrophils from patients with inflammatory bowel disease.

The activity of inflammatory bowel disease (IBD) is often difficult to monitor by currently available laboratory tests. The oxidative metabolic activity of Ficoll-Hypaque separated human neutrophils was determined in a luminol-dependent chemiluminescence assay and compared to the white blood cell (WBC) count and the erythrocyte sedimentation rate (ESR) among 13 subjects with inflammatory bowel disease. Clinical disease activity was assessed with a standardized scoring system and judged to be mild in five subjects and absent (remission) in the other eight subjects. The chemiluminescent response of neutrophils was increased among 12 persons compared to that of healthy subjects. In contrast, the WBC count and ESR were abnormal only among two and four individuals, respectively. The widespread abnormality in neutrophil chemiluminescence, even among subjects classified as being in remission, suggests that chemiluminescence determinations may provide a means to monitor longitudinal changes in disease activity.

Adolescent↗

In-vivo effects of clindamycin on neutrophil function.

Neutrophil functions were evaluated in 13 normal subjects who had received 300 mg of clindamycin orally four times each day for two days. The mean serum concentration of clindamycin was 1.6 mg/l. Intracellular killing of a clindamycin-resistant strain of Staphylococcus aureus increased from 38% to 45%, P less than 0.005, during clindamycin therapy. In contrast, clindamycin therapy did not significantly alter chemotaxis, phagocytosis, chemiluminescence of neutrophils, or the ability of serum to generate chemotactic factor and opsonize particles of yeast. The potentially synergistic relationship between clindamycin and neutrophils may prove to be valuable for the treatment of staphylococcal infections in patients with defects in oxygen-dependent mechanism of neutrophil-mediated bacterial killing such as in chronic granulomatous disease.

Adult↗

Fatal disseminated adenovirus infection featuring liver necrosis and prolonged viremia in an immunosuppressed child with malignant histiocytosis.

Truly disseminated adenovirus disease is rare and appears to be limited to patients with severe combined T and B cell deficiency. This report describes an 18-month-old child with malignant histiocytosis treated with chemotherapy who developed a fatal disseminated type 2 adenovirus infection. Histologic changes in the tissues of multiple organs as well as the presence of typical crystalline structures in sections of the liver seen with electron microscopy provided evidence of viral replication. Adenovirus was recovered from the involved organs and from daily serum samples obtained over a 2-week period prior to death. The possibility that the child may have had virus associated histiocytic disease prior to chemotherapy is discussed.

Adenoviridae Infections↗

Interaction of polymorphonuclear leukocytes and viruses in humans: adherence of polymorphonuclear leukocytes to respiratory syncytial virus-infected cells.

The nature of neutrophil-respiratory syncytial virus (RSV) interaction was investigated by assessing factors that influence neutrophil adherence to RSV-infected tissue culture monolayers. The adherence of neutrophils to infected cells was directly proportional to the degree of RSV replication as evidenced by infectious virus production, cytopathological changes, or viral antigen appearance. Sixty-one percent of the neutrophils adhered to the RSV-infected cells as compared with 52.7% on noninfected monolayers (P less than 0.05). The addition of RSV-specific antibody markedly increased polymorphonuclear leukocyte adherence to 88.5% (P less than 0.001). Complement in the absence of antibody augmented polymorphonuclear leukocyte adherence, but to a lesser degree, 69.0% (P less than 0.025). Arachidonic acid metabolism appeared to play a critical role in the adherence process; thromboxane was the single most important arachidonic acid metabolite. Inhibition of thromboxane synthesis reduced antibody-dependent polymorphonuclear leukocyte adherence on RSV-infected cells to 52.3% (P less than 0.025). These observations suggest a role for neutrophils in RSV infection. It is proposed that neutrophils may participate in RSV infection at the site of viral replication through the attachment to infected cells and the subsequent release of mediators of inflammation.

Antigens, Viral↗

Immune response to respiratory syncytial virus: prevention of syncytia formation by human serum during in vitro infection.

Human serum specimens containing respiratory syncytial virus (RSV)-specific neutralizing antibody were found to prevent the formation of syncytia when applied to HEp-2 tissue culture monolayers which had been infected with RSV 12 h previously. This was evidenced by the demonstration of RSV-infected cells without any syncytia formation in the monolayers treated with RSV antibody-positive serum. On the other hand, widespread syncytia formation was observed with antibody-negative control serum. The inhibitory effects of RSV antibody progressively declined when applied beyond 12 h after infection. Protection of the monolayer against syncytia formation occurred only in the presence of antibody and was quickly lost after the serum was removed. The titer of antisyncytial antibody correlated with the titer of neutralization antibody.

Adult↗

Virus-induced complement activation and neutrophil-mediated cytotoxicity against respiratory syncytial virus (RSV).

Complement-dependent neutrophil-mediated cytotoxicity (CDNC) was determined by specific release of 51-chromium (51Cr) from respiratory syncytial virus infected HEp2 cells in a microcytotoxicity assay. There was significant release of 51Cr from RSV infected cells as compared to uninfected cells in the presence of complement (C) and neutrophils (PMN). The degree of cytotoxicity was dependent upon the concentration of C used in the assay. Such cytotoxicity was effectively abolished after heat-inactivation of complement. Complement deficient in C4 did not induce cytotoxicity. Similarly, inhibitors of C1 or C3 blocked CDNC. The maximal CDNC was observed at 37 degrees C with little or no response at 4 degrees C. Lymphocytes and monocytes mediated complement-dependent cytotoxicity very poorly in comparison to PMN. Evidence of complement activation by infected cells was demonstrated by the detection of C3 fixed to RSV infected cells by indirect immunofluorescence. Treatment of C with EDTA or heat prevented subsequent attachment of C3 to the infected cells. These in vitro observations suggest an initial activation of complement by RSV infected cells and subsequent lysis by PMN. It is proposed that this process may play a role in the elimination of virus in the early phase of infection in the absence of specific antibody or sensitized lymphocytes.

Complement Activation↗

Activation of oxidative and arachidonic acid metabolism in neutrophils by respiratory syncytial virus antibody complexes: possible role in disease.

The effect of respiratory syncytial virus (RSV) antibody complexes on the metabolism of human neutrophils was determined by examining the generation of luminol-dependent chemiluminescence, superoxide, and thromboxane B2. Incubation of neutrophils with RSV antibody complexes resulted in a significant increase in the production of chemiluminescence. The increase in chemiluminescence appeared to be due to (1) active phagocytosis of RSV antibody complexes as evidenced by 70% inhibition with cytochalasin B (P less than 0.001) or (2) increased superoxide production as evidenced by 40% inhibition with superoxide dismutase (P less than 0.001). The generation of superoxide was confirmed by specific analysis in a superoxide dismutase-inhibitable ferricytochrome c reduction assay. Of particular importance was the observation that RSV antibody complexes induced the release of significant quantities of thromboxane B2 from neutrophils as determined by radioimmunoassay. Oxygen radicals and/or products of arachidonic acid metabolism may, in part, mediate the pathogenesis of RSV infection through direct tissue damage and bronchoconstriction.

Adult↗

In-vivo effects of clindamycin on neutrophil function--a preliminary report.

Neutrophil functions were evaluated in six normal subjects who had received 300 mg of clindamycin orally four times each day for two days. The mean serum concentration was 1.0 mg/l at the time of neutrophil collection. Clindamycin increased phagocytosis of a clindamycin-resistant staphylococcus from 0.8 to 1.0 organism per polymorphonuclear leukocyte (P less than 0.05). The proportion of killed intracellular bacteria increased from 23.8% to 29.8%. Zymosan-induced chemiluminescence was reduced from 130 X 10(3) to 86 X 10(3) counts per 0.2 min (P less than 0.05). Chemotaxis was unaffected. These preliminary results demonstrate measurable effects of clindamycin on neutrophil functions in the host; however, further studies are needed in order to confirm the observed changes.

Adult↗

Renal and Auditory toxic effects of amikacin in children with cancer.

Amikacin sulfate was given to 21 febrile children with neutropenia and cancer for 9 +/- 3 days. Peak serum amikacin levels ranged between 13 and 32 microgram/mL, and trough levels were consistently less than 2 microgram/mL. Renal toxic effects were detected in two children (9.5%) and were extremely mild. Two additional children (16.5%) experienced mild, transient, unilateral, high-frequency hearing losses. The lack of serious renal and auditory impairment suggests that children are at less risk than adults from aminoglycoside therapy.

Adolescent↗

Prophylactic antibiotics in pediatrics cardiovascular surgery: current practices.

A survey of 23 pediatric cardiovascular surgery programs demonstrated uniform use of prophylactic antibiotics for open-heart operations. Only 65% of the programs used prophylaxis for repair of patent ductus arteriosus. Cephalosporins were the most frequently used antibiotics, but aminoglycosides in combination with penicillins were used in approximately 25% of the operations. Antibiotics were most often started prior to operation (89.7%) and continued for less than five days. These data demonstrate that the use of prophylaxis in pediatric cardiovascular operations conforms to current guidelines.

Anti-Bacterial Agents↗

A comparison of the penetration characteristics of cephapirin and cephalothin into right atrial appendage, muscle, fat, and pericardial fluid of pediatric patients undergoing open-heart operation.

Thirty-two pediatric patients having open-heart operation received a single dose of either cephalothin or cephapirin intravenously, 30 mg per kilogram of body weight, in the operating room, for prophylaxis before the chest cavity was opened. Samples of right atrial appendage, pericardial fluid, muscle, fat, and plasma were obtained at various time intervals after injection of the antibiotics, and assayed for cephalosporin concentration. The concentration-time profiles of cephalothin and cephapirin in atrial appendage, muscle, fat, and plasma were identical. Cephapirin produced higher total and free concentrations in pericardial fluid compared with cephalothin. This presumably was due to the lower protein binding of cephapirin. Antibiotic concentrations above the minimal inhibitory concentration for Staphylococcus aureus and S. epidermidis were present in myocardial tissue for at least 90 minutes after the dose was administered. These data support the need to administer these antibiotics shortly before surgical intervention and, if the operation is prolonged, the need to administer a second dose of antibiotic.

Adipose Tissue↗

Effect of respiratory syncytial virus and virus-antibody complexes on the oxidative metabolism of human neutrophils.

The effect of respiratory syncytial virus (RSV) or mixtures of RSV and its specific antibody on the oxidative metabolic activity of human polymorphonuclear leukocytes was studied by the technique of luminol-dependent chemiluminescence. Peripheral blood neutrophils obtained from normal healthy donors were used. RSV alone failed to induce any chemiluminescent response by the neutrophils. However, mixtures of RSV and RSV antibody-positive serum regularly elicited significant neutrophil chemiluminescence. Ultracentrifugation, electron microscopy, and Raji cell immune complex assays of virus-antibody mixtures suggested that the neutrophil chemiluminescent response was related to the presence of specific immune complexes of RSV antigen-antibody. Heat inactivation of the serum significantly reduced the polymorphonuclear leukocyte chemiluminescence, and the response also appeared to be dependent on the dose of the virus and the antibody in the reaction mixture. It is proposed that interaction between the neutrophil and RSV-specific immune complexes may contribute to the pathogenesis of RSV infection via the possible release of metabolic products from the activated neutrophils.

Adult↗