Innovative training posts.
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Attitude of Health Personnel↗
Biomedical subjects
R Tyler
Publications and source records attributed to R Tyler.
Restricted use of antibiotic prophylaxis for recurrent acute otitis media in the era of penicillin non-susceptible Streptococcus pneumoniae.
OBJECTIVE/INTERVENTION: To compare the annual rates of acute otitis media (AOM) episodes, antibiotic days, and ventilating tube insertion during the first 3 years of life before and after a practice change to restrict use of antibiotic chemoprophylaxis for recurrent AOM. METHODS SETTING: The sole pediatric private practice in a rural Kentucky community. PATIENTS: Population-based sample of all children born consecutively in two different 13 month intervals. Cohort 1 (n=251) was born before and Cohort 2 (n=274) was born after restricted use of chemoprophylaxis and documented emergence of widespread penicillin non-susceptible Streptococcus pneumoniae (PNSP). DESIGN: Retrospective case cohort comparison. MAIN OUTCOME MEASURES: Suppurative AOM diagnosed by validated experienced otoscopists using stringent tympanic membrane criteria. RESULTS: Children were mostly white with the majority (50-65%) enrolled in daycare during each year. The first episode of AOM was experienced by 6 and 12 months of age in 64 and 86%, respectively. Rates of children with recurrent AOM in Cohorts 1 and 2 were 28 and 31% in Year 1, 17 and 23% in Year 2, and 7 and 10% in Year 3, respectively. Rates of new onset AOM and persistent AOM episodes were similar between cohorts in the first 2 years. Number of days of antibiotic prophylaxis were reduced from 11.2 to 3.4 days in Year 1, from 11.9 to 2.6 days in Year 2, and from 6.9 to 0.7 days in Year 3, respectively (P<0.0001 for each year). Total antibiotic days for Years 1, 2 and 3 were reduced commensurately with prophylactic days from 61.7 to 55.5 days (nonsignificant), from 56.3 to 45.8 days (P=0.047), and from 38.7 to 25.7 days (P<0.0001), respectively. For each year a non-significant trend for increased ventilating tube placement from Cohort 1 to Cohort 2, respectively, was observed, 2 versus 2.2%, 4 versus 5.8%, and 0.8 versus 2.6%. Daycare attendance and white race were consistently significant risk factors for AOM and recurrent AOM. CONCLUSIONS: In the era of PNSP, restricted use of antibiotic chemoprophylaxis for recurrent AOM was not associated with significantly increased rates of new onset AOM episodes or tube placement in the first 24 months of life. Total antibiotic days were also significantly reduced in Cohort 2 during Years 2 and 3.
Acute Disease↗
Expression and characterization of truncated forms of humanized L243 IgG1. Architectural features can influence synthesis of its oligosaccharide chains and affect superoxide production triggered through human Fcgamma receptor I.
The properties of IgG and its subcomponents are being exploited to generate new therapeutics with selected biological activities. In this study, a series of truncated, humanized IgG1 antibodies was expressed in Chinese hamster ovary cells, to evaluate the contribution of structural components to glycosylation and function. The series includes L243 IgG1 (alpha-MHC Class II) lacking a CH3 domain pair (DeltaCH3-IgG1), single-chain Fv fusion proteins with Fc or a hinge-CH2 domain, Fc with/out a hinge, and a single CH2 domain. Glycosylation of IgG Fc is important for recognition by effector ligands such as Fcgamma receptors. HPLC analysis of released and pyridylaminated oligosaccharides indicates that intact IgG1 and scFvFc antibodies are galactosylated and sialylated to levels similar to those observed previously for normal human IgG1. The truncated forms express increased levels of digalactosylated (30-83%) or sialylated (9-21%) oligosaccharide chains with the highest levels observed for the single CH2 domain. These data show which architectural components influence IgG glycosylation processing and that the (CH3)2 pair is particularly influential. When MHC Class II bearing (JY) cells were sensitized with L243 DeltaCH3-IgG1, scFvFc, or scFvhCH2 they elicited superoxide production, from U937 cells, at levels of 35-45% relative to that obtained for intact L243 IgG1 (100%). Mild reduction and alkylation of the hinge disulphide bonds of scFvhCH2 greatly decreased its capacity to trigger superoxide production. Thus, the L243 scFvhCH2 homo-dimer constitutes the minimal truncated form that binds the MHC Class II antigen and triggers superoxide production through FcgammaRI.
Amino Acid Sequence↗
Increasing bacterial resistance in pediatric acute conjunctivitis (1997-1998).
We sought to determine the current level of resistance in Haemophilus influenzae and Streptococcus pneumoniae, the primary pathogens of pediatric conjunctivitis. Between January 1997 and March 1998, we prospectively cultured acute conjunctivitis in 250 ambulatory pediatric patients from rural Kentucky whose average age was 24.3 months. In those 250 cases, 106 H. influenzae (42% of the total) and 75 S. pneumoniae (30% of the total) pathogens were isolated, with no growth or no pathogen resulting in 79 cases (32% of the total). Beta-lactamase was detected in 60 (69%) of 87 tested strains of H. influenzae. Among 65 isolates of S. pneumoniae tested for penicillin susceptibility, 44 (68%) were susceptible, 17 (26%) were resistant, and 4 (6%) were intermediate. Conjunctivitis with acute otitis media was observed in 97 patients (39%), and H. influenzae was recovered in 57% of these 97 cases. As for in vitro activity, ciprofloxacin, ofloxacin, and tetracycline were the most active; and gentamicin, tobramycin, polymyxin B-trimethoprim, and polymyxin B-neomycin were intermediately active. Sulfamethoxazole possessed no activity against either pathogen. Beta-lactamase production was detected in 69% of H. influenzae strains, which still remains the primary causative pathogen of both conjunctivitis and conjunctivitis-otitis syndrome. Penicillin-nonsusceptible S. pneumoniae was observed in 32% of 65 patients with S. pneumoniae conjunctivitis, with most strains being penicillin resistant.
Anti-Bacterial Agents↗
Psychopathology, mother-child interaction, and infant development: substance-abusing mothers and their offspring.
The course of severe depressive symptoms from pregnancy to 6 months postpartum, as well as the occurrence of severe paranoid symptoms prenatally, were examined by the Millon Clinical Multiaxial Inventory I and the Beck Depression Inventory, in 78 women who were heavy, chronic cocaine users and who retained custody of their children after birth. Six months postpartum, the quality of caregiving was observed and assessed in the home, and the children were assessed on the Bayley MDI Index in the laboratory. Mothers who were depressed and paranoid prenatally, regardless of whether the depression continued to 6 months postpartum, were less sensitive in caregiving than women without severe symptoms of paranoia or depression during pregnancy or those who reported only depression that lifted by 6 months postpartum. Mothers who were depressed prenatally and continued to be depressed by 6 months postpartum, regardless of the presence or absence of paranoia, had infants who earned lower Bayley MDI scores than the offspring of women without severe psychological symptoms or women whose depression had lifted. Severe depressive symptoms during pregnancy, if they did not continue to 6 months postpartum, did not appear to adversely influence either caregiving or infant functioning.
Adult↗
A comparison of language achievement in children with cochlear implants and children using hearing aids.
English language achievement of 29 prelingually deaf children with 3 or more years of cochlear implant (CI) experience was compared to the achievement levels of prelingually deaf children who did not have such CI experience. Language achievement was measured by the Rhode Island Test of Language Structure (RITLS), a measure of signed and spoken sentence comprehension, and the Index of Productive Syntax (IPSyn), a measure of expressive (signed and spoken) English grammar. When the CI users were compared with their deaf age mates who contributed to the norms of the RITLS, it was found that CI users achieved significantly better scores. Likewise, we found that CI users performed better than 29 deaf children who used hearing aids (HAs) with respect to English grammar achievement as indexed by the IPSyn. Additionally, we found that chronological age highly correlated with IPSyn levels only among the non-CI users, whereas length of CI experience was significantly correlated with IPSyn scores for CI users. Finally, clear differences between those with and without CI experience were found by 2 years of post-implant experience. These data provide evidence that children who receive CIs benefit in the form of improved English language comprehension and production.
Achievement↗
Placement with substance-abusing mothers vs. placement with other relatives: infant outcomes.
Evaluating a subset of participants from a larger research project concerning comprehensive drug treatment services for pregnant substance-abusing women and their offspring, this investigation compared those mothers who retained custody of their infants following delivery with those who lost custody and whose infants were placed in the care of other relatives. There were no differences between the groups with respect to maternal demographics, substance abuse (as assessed by self-report prenatally and urine toxicology screens at birth), or mental health status, or with respect to newborn characteristics (including gestational age, birthweight, medical risk status). Further, caregiving behaviors of mothers and relative caregivers showed no significant differences at 6 months. Infants who remained in the care of their biological mothers, however, demonstrated better cognitive development than infants in the care of relatives at 6 months. There was also a discrepancy in terms of safety at 6 months, in that there were three deaths and two reported cases of suspected child abuse/neglect among infants in the care of their mothers, and no deaths and no reports of suspected abuse among infants in relative foster care.
Adult↗
Chlamydia pneumoniae in acute otitis media.
BACKGROUND: Aerobic bacterial pathogens are recovered from 65 to 85% of patients with acute otitis media (AOM). Although Chlamydia pneumoniae is a common pathogen of pediatric pneumonia, it has rarely been cultured from children with chronic otitis media and its role in AOM is unknown. METHODS: We cultured for C. pneumoniae in tympanocentesis aspirates and nasopharyngeal swabs from 101 consecutive, otherwise healthy children with AOM or refractory AOM. A control group of 50 similarly aged, healthy children was evaluated for nasopharyngeal carriage of C. pneumoniae. Specimens were also evaluated by PCR for C. pneumoniae. RESULTS: C. pneumoniae was recovered by tympanocentesis in 8 (8%) of 101 children with AOM. Among the 8 children with C. pneumoniae-positive-AOM, 5 had C. pneumoniae detected by PCR in middle ear fluid, none had C. pneumoniae recovered by nasopharyngeal culture or PCR and 5 were younger than 16 months. C. pneumoniae was the sole pathogen isolated in 2 patients. Copathogens included beta-lactamase-positive positive Haemophilus influenzae (2), beta-lactamase positive Moraxella catarrhalis (1), penicillin-resistant Streptococcus pneumoniae (2) and penicillin-susceptible S. pneumoniae (1). C. pneumoniae was recovered from nasopharyngeal culture in 2 additional patients with C. pneumoniae-negative AOM and in none of 50 healthy control children, although 2 controls were positive by PCR from the nasopharynx. CONCLUSIONS: This is the first study to report the isolation of C. pneumoniae in middle ear fluid of children with AOM.
Acute Disease↗
A report of a child with a deletion (9)(q34.3): a recognisable phenotype?
We report a case of a male infant who presented with congenital anomalies and was found to have a de novo deletion in the terminal region of the long arm of chromosome 9. He died at the age of 17 weeks of cardiorespiratory failure owing to RSV positive bronchiolitis. A review of previously published reports documented one previous report of a patient with a deletion of (9)(q34.3) and multiple congenital anomalies. Comparison with the previously reported case suggests that the phenotype observed constitutes a clinically recognisable pattern of malformations.
Abnormalities, Multiple↗
Speech perception by prelingually deaf children and postlingually deaf adults with cochlear implant.
We review recent data from the University of Iowa obtained from prelingually deaf children over 3 years using feature-extraction versions of the Nucleus cochlear implant, and from postlingually deaf adults using the compressed-analog Ineraid, a feature-extraction version of Nucleus, and a continuous interleaved sampling version of the Clarion cochlear implant. Both adults and children were followed over a 3-year period. Average results are shown where each patient is represented at each point in time. Results for the children show continued improvement over the 3-year period, with some children obtaining maximum scores possible on the easier closed-set tests. Substantial improvements in audiovisual enhancement were provided by the cochlear implant. Results from the adults show maximum gains within the first year of implant use, although some patients show continued improvements after 2 years of implant use. Adults who have been deaf for several years and who receive their implant when they are older tend not to perform as well as adults who have been deaf for only a few years or receive their implant when they are younger.
Adult↗
Human immunodeficiency virus among the homeless in Miami: a new direction for the HIV epidemic.
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Adult↗
Estrogen, progesterone, and vascular reactivity: potential cellular mechanisms.
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Endothelium, Vascular↗
Control of IgG/Fc glycosylation: a comparison of oligosaccharides from chimeric human/mouse and mouse subclass immunoglobulin Gs.
Oligosaccharide profiles were obtained for chimeric mouse-human antibodies corresponding to each of the human IgG subclasses 1-4, and mouse IgG2b antibodies each expressed in the mouse J558L cell line. These antibodies have specificity for the NIP hapten and form a matched set of IgGs. An IgG4 chimeric antibody (B72.3) produced in the chinese hamster ovary (CHO-K1) cell line was also analysed for carbohydrate. Additionally aglycosylated mutants of this IgG4 (B72.3) and anti-NIP mouse IgG2b were analysed. The total lack of carbohydrate found in the aglycosylated site-directed mutants human chimeric IgG4 B72.3 (Asn 297-->Gln) and mouse IgG2b (Asn 297-->Ala) demonstrates that there are no N-glycosylation sites other than Asn 297. Therefore glycosylation profiles for all the IgGs analysed reflect carbohydrate attached to this site. Factors such as cell type (A), template direction by the IgG heavy chains (B) and culture conditions (C) are shown to influence IgG glycosylation profiles. (A) The anti-NIP IgG antibodies expressed by the J558L cell line may have one or two Gal (alpha 1-->3) Gal residues per oligosaccharide unit, indicative of the presence of (alpha 1-->3) galactosyl transferase in the J558L mouse cell line. (B) The galactosylation profiles obtained for the IgG heavy chains, in particular the preference for galactosylation of the Man (alpha 1-->6) arm rather than the Man (alpha 1-->3) arm, contrary to the beta-galactosyltransferase specificity, suggest that the polypeptide chain may act as a template to influence the extent of galactosylation and hence the proportions of each oligosaccharide incorporated. The IgG2 antibody does not display this galactosylation preference. (C) The extent of galactosylation appears to be influenced by the growth conditions, with the highest levels of galactosylation being found for IgG produced by cells grown in still cultures, rather than cells grown as ascites or in hollow fibre bioreactors. It is concluded that though the profile of glycosylation is controlled predominantly by the glycosylation activity of the cell in which the IgG is expressed, differences between the IgG heavy chain templates of the various subclasses and culture conditions can also influence glycosylation.
Animals↗
Culturally tailored HIV-AIDS risk-reduction messages targeted to African-American urban women: impact on risk sensitization and risk reduction.
African-American women recruited from low-income housing projects in Chicago (N = 106) were randomly assigned to view 1 of 3 20-min videotapes: a standard public health service tape on prevention of acquired immunodeficiency syndrome (AIDS), the same public health service tape but matching presenter and participant ethnicity and sex, or a tape that included the same content but was framed in a context specifically intended to increase cultural relevance. Participants who viewed the tapes presented by African-American women were significantly more sensitized to AIDS and were more likely to have discussed AIDS with friends, to be tested for human immunodeficiency virus (HIV) antibodies during the follow-up interval, and to request condoms at follow-up. These results support the use of culturally sensitive AIDS prevention messages targeted to specific populations, particularly to promote HIV-antibody testing.
Acquired Immunodeficiency Syndrome↗
Glycosylation of human IgG subclass and mouse IgG2b heavy chains secreted by mouse J558L transfectoma cell lines as chimeric antibodies.
Oligosaccharide profiles for monoclonal chimeric mouse-human and mouse IgG2b antibodies produced in the mouse J558L cell line have been determined. These chimeric antibodies share the same mouse light chain and VH region and have a single, complex, oligosaccharide moiety attached to residue 297 of the heavy chain. Since the panel of chimeric antibodies included each of the human IgG subclasses and a set of IgG3 proteins having single residue differences, it was possible to evaluate the contributions of the protein template, the cell line, and the culture conditions to glycosylation. The study shows that the J558L cell line glycosylates human heavy chains with oligosaccharides characteristic of mouse immunoglobulins. This includes a galactose alpha 1-->3 galactose structure not found in human IgG and for which most humans have naturally occurring "anti-Gal" antibodies. The extent of galactosylation was very dependent on the culture conditions and was maximal for still culture. The findings have significance for the production of antibodies for in vivo administration.
Animals↗
Does an antibody molecule act as a template directing (determining) its glycosylation?
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Animals↗
A truncated P element is inserted in the transcribed region of the Cu,Zn SOD gene of an SOD "null" strain of Drosophila melanogaster.
The decreased Cu,Zn SOD activity (less than 5%) in a "null" SODCA1 Drosophila melanogaster strain isolated in our laboratory is due to the insertion of a truncated P element into the transcribed region of the Cu,Zn SOD gene. Using a cDNA Cu,Zn SOD probe from a wild type D. melanogaster (F allele) we isolated an EcoRI Cu,Zn SOD clone from an EMBL3 genomic library of the SODCA1 strain, subcloned it, restriction-mapped and partially sequenced it. The 2.5 kb clone consists of a wild-type 1.84 kb EcoRI fragment containing the Cu,Zn SOD gene previously isolated in our laboratory, with an insertion of 0.68 kb derived (by an internal deletion) from an autonomous, 2.9 kb P element. The insertion starts 21 bp upstream from the coding sequence and causes an 8 bp target site duplication characteristic of P elements. A point mutation in the second exon results in a replacement of Asn by Lys at position 96, confirming that the mature protein encoded by the SOCCA1 is the same one encoded by the S allele, commonly found in natural populations. The diminished expression of SODCA1 allele is most possibly due to a reduction of the rate of transcription attributable to the insertion of the P element.
Alleles↗
Virucidal activity of disinfectants: studies with the poliovirus.
The activity of various disinfectants against poliovirus (Sabin 1 an) was assessed using surface and suspension tests. The surface test showed that 2% glutaraldehyde and high concentrations of hypochlorites (9200 ppm avCl2) were effective (i.e. greater than or equal to 4 log10 reduction) against a dried virus suspension in 1 min. Diluted aldehydes ('Sporicidin' and 'Gigasept'), lower hypochlorite concentrations (1000 ppm avCl2) and peroxides (3%) were less effective while 70% ethanol showed variable results; 70% isopropanol was ineffective in 10 min. In the suspension tests hydrogen peroxide (3% and 6%) and 70% ethanol were ineffective in 1 min.
Disinfectants↗