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Biomedical subjects

E L Mills

Publications and source records attributed to E L Mills.

14 recordsLinked to original sources
PubMed1990

The sequelae of Haemophilus influenzae meningitis in school-age children.

BACKGROUND: Previous data on the consequences of Haemophilus influenzae type b meningitis for school-age children have been inconsistent, and much of the information on risk factors has been inconclusive. The present study was designed to evaluate the sequelae of this disease with a protocol for the comprehensive assessment of neuropsychological function. METHODS: Ninety-seven school-age children (mean age, 9.6 years), each of whom had a school-age sibling, were recruited from a survey of the medical records of 519 children treated for H. influenzae type b meningitis between 1972 and 1984 (at a mean age of 17 months) at the children's hospitals of Toronto, Ottawa, and Montreal. Of the 97 children, 41 had had an acute neurologic complication. Sequelae were assessed by comparing the index children with their nearest siblings on the basis of standardized measures of cognitive, academic, and behavioral status. RESULTS: Only 14 children (14 percent) had persisting neurologic sequelae: sensorineural hearing loss in 11 (unilateral in 6 and bilateral in 5), seizure disorder in 2, and hemiplegia and mental retardation in 1. Although the total sample of index children scored slightly below the siblings in reading ability, the 56 children without acute-phase neurologic complications (58 percent) were indistinguishable from their siblings on all measures. The differences between the groups were small even for the 41 pairs in which the index child had had an acute neurologic complication (mean full-scale IQ, 102 for the index children vs. 109 for the siblings). Sequelae were also associated with lower socioeconomic status and a lower ratio of glucose in cerebrospinal fluid to that in blood at the time of the meningitis. Behavioral problems were more prominent in index boys than index girls and in those who were older at the time of testing, but sex and age were not related to cognitive or academic sequelae. CONCLUSIONS: We find a favorable prognosis for the majority of children who are treated for meningitis caused by H. influenzae type b.

Adolescent↗
PubMed1990

Comparative studies of microscopically determined aggregation, degranulation, and light transmission after chemotactic activation of adult and newborn neutrophils.

Changes in the light transmission of suspensions of activated neutrophils are widely used to measure the dynamics of neutrophil aggregation. Such studies have suggested, for example, that aggregation is irreversible for human newborn neutrophils but fully reversible for adult cells. We have evaluated aggregation directly by microscopic particle counting and compared it with changes in light transmission (delta T) and with release from three granule subsets for neutrophils activated with N-formyl-methionyl-leucyl-phenylalanine (FMLP). Maximal increases in %T in response to 0.5 micromol/L FMLP were approximately 25% larger for newborn than for adult neutrophils, and were only partially reversible by 8 minutes, while %T increases for adult neutrophils were fully reversible. However, measurements of neutrophil aggregation using light microscopy showed that both newborn and adult neutrophils fully deaggregated. A further independence of delta T from aggregation was found by pretreating adult neutrophils with cytochalasin B (5 micrograms/mL) in the presence of 0.5% gelatin, a pretreatment that blocked FMLP-induced neutrophil aggregation while allowing large increases in %T and degranulation. In response to FMLP, newborn neutrophils released more enzyme from each granule subset than did adult neutrophils. Our results suggest that cellular events associated with neutrophil activation (other than aggregation) are implicated in light transmission responses and that these differ for adults and newborns. These results also suggest that reports of neutrophil aggregation should be based on direct particle counting methods rather than on %T responses.

Adult↗
PubMed1979

Deficient alternative complement pathway activity in newborn sera.

Neonatal susceptibility to overwhelming bacterial infection is commonly attributed to a relative deficiency in serum opsonic activity. However, few studies have compared the functional capacity of the classical complement pathway with that of the alternative complement pathway in the neonate. The opsonic activity of nine maternal infant serum pairs were studied by determining percent uptake of radiolabeled Escherichia coli. Seven mother-infant paired sera were studied using E. coli strains known to be opsonized via the alternative complement pathway: the mean percent uptake of E. coli opsonized in neonatal sera was 16.8%; of those opsonized in maternal sera, 54%; and of those opsonized in control sera, 45% (P less than 0.005). Two E. coli strains requiring the classical complement pathway for opsonization were phagocytized equally well in maternal and infant sera of seven mother-infant pairs. Determination of anti-O hemagglutination inhibition (HI) antibody titers in six maternal sera for one classical complement pathway activating and one alternative complement pathway strain showed no correlation between percent phagocytosis and HI antibody titer. These data would suggest that serum levels of classical pathway components are probably adequate for opsonization of E. coli via the classical pathway, but that low alternative complement pathway activity in neonatal sera may contribute to the newborn's increased susceptibility to bacterial sepsis.

Complement Activation↗
PubMed1979

Bactericidal and metabolic function of polymorphonuclear leukocytes.

The bactericidal and metabolic function of the phagocytic system requires integration of several complex humoral and cellular factors responding to different regulators. Polymorphonuclear leukocytes are highly mobile cells, capable of phagocytosis of bacteria or fungi with formation of a "cellular digestive system" containing reactive oxygen radicals, hydrogen ions, and digestive enzymes. The unique metabolism of oxygen in neutrophils results in release of energy as light (chemiluminescence) a response closely associated with microbiol killing. Neonatal neutrophils cope with normal bacterial challenges in vitro as efficiently as adult neutrophils; however, these cells have decreased capacity for locomotion, decreased deformability, decreased phagocytosis in low serum concentrations, and decreased chemiluminescence. These subtle defects in function can be amplified by exaggerated challenge which may be related to a higher incidence of sepsis during the neonatal period.

Adult↗
PubMed1979

The microbiology of serous and mucoid otitis media.

One hundred forty-four serous and mucoid effusions were cultured for aerobic bacteria, Mycoplasma pneumoniae, and virus. Thirty percent of all effusions yielded an unequivocally positive culture for aerobic bacteria. Although serous effusions were culture positive as often as mucoid effusions, Haemophilus influenzae was isolated predominantly from serous effusions and Staphylococcus epidermidis predominantly from mucoid samples. Only one of 73 effusions yielded a viral isolate (Herpesvirus hominis). None of 33 effusions yielded M pneumoniae, and only one of 17 effusions yielded an anaerobe (Propionibacterium). These findings suggest that aerobic bacteria may play a role in the pathogensis of serous and mucoid otitis media.

Bacterial Infections↗
PubMed1979

The chemiluminescence response and bactericidal activity of polymorphonuclear neutrophils from newborns and their mothers.

Chemiluminescence (CL) was measured in the polymorphonuclear neutrophils (PMN) of 18 normal term infants, their mothers, and controls during phagocytosis of opsonized zymosan particles. Chemiluminescence was significantly lower in the PMN of newborns in comparison with the PMN of their mothers and of the controls. Depressed bactericidal activity was demonstrated in newborn PMN, in comparison with the activity of the PMN of their mothers and controls, when challenged with Escherichia coli at large bacteria-PMN ratios. Uptake of radio-labeled bacteria by PMN was identical in newborns, mothers, and controls, which indicates that reduced CL was not a result of impaired ingestion. Therefore, PMN of normal term infants have both depressed oxidative metabolic responsiveness as measured by CL and depressed bactericidal capacity.

Adult↗
PubMed1978

Phagocytosis of Candida albicans by human leukocytes: opsonic requirements.

The kinetics of phagocytosis of Candida albicans by human polymorphonuclear leukocytes was studied. The basis for these studies was a phagocytic assay with use of C. albicans radiolabeled with [3H]adenine. After incubation of leukocytes with C. albicans, extracellular C. albicans was separated from phagocytes by centrifugation through Ficoll-Hypaque suspensions (specific density, 1.175 g/cm3). Recovery of leukocytes by this technique was greater than or equal to 85%. The initial rate of phagocytosis was more rapid than that previously reported for bacteria. Ethylenediaminetetraacetate, vinblastine, ethylmaleimide, NaF, and ice bath temperature completely inhibited phagocytosis. Colchicine had no effect, and NaN3 was partially inhibitory. Pooled sera possessed low titers (greater than or equal to 1:40) of heat-stable opsonins. The opsonic activity of pooled sera was shown to depend primarily upon complement activated through both the alternative and classical pathways. Decomplemented hyperimmune sera were opsonic at high dilutions (greater than or equal to 1:160), and complement amplified the initial rate of ingestion seen with hyperimmune sera.

Candida albicans↗
PubMed1978

The effect of hemodialysis on neutrophil chemotactic responsiveness.

After several hemodialysis treatments, neutrophil chemotactic responsiveness is commonly depressed. The median chemotactic index of 34 patients was 21, compared with 47 for 21 controls tested simultaneously. The depressed chemotactic responsiveness was not restored to normal when leukocytes were washed and resuspended in normal plasma, neither did plasma from patients with depressed chemotaxis affect control neutrophils.

Chemotaxis, Leukocyte↗
PubMed1978

The chemiluminescence response of human platelets.

Human platelets and platelet particulate fractions were found to emit a burst of chemiluminescence during incubation with arachidonic acid. The magnitude of light emission was directly related to the number of platelets in the reaction mixture and varied little for the same individual from day to day. The chemiluminescence response of platelets was localized to the particulate fraction and was almost totally oxygen dependent. In addition to arachidonate, seven other polyunsaturated fatty acids, including several that are not prostaglandin precursors, also induced platelet chemiluminescence.A correlation was sought between chemiluminescence and platelet prostaglandin synthesis. Platelets incubated in low concentrations of aspirin, or platelets from subjects who had ingested aspirin, had markedly decreased arachidonic acid-induced chemiluminescence. Salicylic and sulfosalicylic acid had no inhibitory effect. A time-response curve of aspirin inhibition of arachidonate-induced chemiluminescence closely paralleled a time-response curve of aspirin inhibition of malondialdehyde production. Linoleic acid-induced platelet chemiluminescence was also markedly inhibited using aspirin-incubated platelets or platelets from subjects who had ingested aspirin. These studies implicate activation of the enzyme prostaglandin synthetase in the arachidonate-induced platelet chemiluminescence. They provide evidence that linoleic acid may also specifically activate platelet cyclooxygenase to produce electronically excited species capable of light emission.

Arachidonic Acids↗
PubMed1977

Comparison of phagocytic and chemiluminescence response of human polymorphonuclear neutrophils.

The phagocytic activity and the chemiluminescence response of human polymorphonuclear neutrophils were studied with normal human serum used as opsonin for S. typhimurium and S. aureus. When serum was heated, chelated with ethyleneglycol tetraacetic acid (EGTA), or absorbed with zymosan, there were reduction of phagocytic activity for S. aureus and a comparable reduction of chemiluminescence; a 50 per cent decrease in phagocytosis by neutrophils corresponded to a 50 per cent reduction in the chemiluminescence response. In contrast, S. typhimurium was successfully phagocytized in serum treated with MgEGTA (complement--alternate pathway intact; classic pathway blocked), and chemiluminescence was reduced by only 20 per cent under the same conditions. Both neutrophil phagocytic and chemiluminescence responses for S. typhimurium were abolished when serum was heated at 56 degrees C. or adsorbed with zymosan. These findings suggest that both phagocytosis and chemiluminescence in neutrophils are interrelated, and the chemiluminescence response of neutrophils may be a reliable assay for measuring serum opsonic activity.

Egtazic Acid↗
PubMed1976

Experimental otitis media due to Streptococcus pneumoniae: immunopathogenic response in the chinchilla.

Acute otitis media was produced in 110 chinchillas by inoculation of type 23 Streptococcus pneumoniae directly into the middle ear cavity by tympanotomy. During the first three days after inoculation, inflammatory cells were seen in the mucoperiosteum of the middle ear. After four to seven days, there was purulent exudation in the middle ear cavity, and 40% of the animals had pneumococcal meningitis and/or bacteremia. The middle ears were sterile in five of 28 animals sacrificed during the second week and in six of seven animals sacrificed at six weeks, although subepithelial changes persisted in the mucoperiosteum. Levels of antibody to S. pneumoniae in serum were measured by radioimmunoassay; mean values were 6.1 ng of pneumococcal antibody nitrogen/ml in 28 uninfected control animals and 16.5 ng of antibody nitrogen/ml in 29 animals sacrificed two weeks after inoculation (P less than 0.025). Opsonic activity of serum against S. pneumoniae was evaluated in infected and uninfected chinchillas. The opsonic titer was significantly higher in infected animals sacrificed at six weeks than in uninfected controls. Although pneumococcal polysaccharide antigen was found by counterimmunoelectrophoresis in 25 of 30 middle ear effusions, it could not be detected in the serum from infected animals. Methods for infection and sacrifice of chinchillas yielded reproducible results. This model should permit evaluation of the pathologic response to other serotypes of S. pneumoniae and possibly to prophylactic and therapeutic regimes.

Animals↗
PubMed1976

Chemiluminescence response of phagocytizing human monocytes.

Chemiluminescence (CL) occurs as a consequence of phagocytosis of bacteria or inert particles by human polymorphonuclear neutrophils. This phenomenon appears to be related to the production of singlet oxygen and/or electronically excited carbonyl groups which relax with light emission. We report that human monocytes also produce CL after phagocytosis of opsonized bacteria, fungi, or zymosan particles. Monocytes produce approximately one-third of the CL produced by polymorphonuclear neutrophils for all three particles, reflecting possible metabolic differences between cells of these types. Addition of exogenous superoxide dismutase reduced the peak production of CL by 65% for cells of both types, whereas raising the temperature of the cultures from 25 to 37 C approximately doubled the peak CL responses.

Candida albicans↗