Outpatient management of chronic suppurative otitis media without cholesteatoma in children.

Prolonged antipseudomonal parenteral antibiotic therapy combined with daily aural toilet has been effective in resolving long standing ear discharge in children with chronic suppurative otitis media. However, such treatment suffered from the disadvantages of prolonged hospitalization. We conducted a prospective study to investigate the feasibility and efficacy of exclusive outpatient treatment of children with chronic suppurative otitis media without cholesteatoma who had failed ototopical/oral antimicrobial therapy. The treatment consisted of daily aural toilet (suction and debridement) and twice daily parenteral ceftazidime (50 mg/kg/dose). Thirty-seven children were included. The duration of discharge from the ear before treatment was 6 to 121 months (median, 30 months). Aerobic cultures yielded Pseudomonas aeruginosa in 97%, often with other organisms. The management and follow-up were performed jointly by otolaryngology and infectious diseases physicians using the hospital ambulatory services. The route of ceftazidime administration (intravenous or intramuscular) was chosen according to the parents' and patients' convenience. Discharge stopped within 3 to 20 days (median, 8 days) in all children but one. Seventy-six percent of the 29 children available for follow-up 12 months after treatment were still free of discharge. Our results demonstrate that a regiment combining daily aural toilet and twice daily parenteral ceftazidime is highly efficacious in resolving ear discharge in children with chronic suppurative otitis media without cholesteatoma and that such a regimen does not require hospitalization.     

Safety and immunogenicity of oral tetravalent human-rhesus reassortant rotavirus vaccine in neonates.

We conducted a prospective randomized double blind study to determine: (1) the safety and immunogenicity of live oral tetravalent human-rhesus rotavirus reassortant vaccine in neonates; and (2) whether a second dose at the age of 6 to 8 weeks enhances the immunogenicity. Two hundred forty healthy neonates were enrolled and received vaccine (183) or placebo (57) on the second day of life. At the age of 6 to 8 weeks 133 received placebo and 88 received a second dose of vaccine. Medical events were noted within 10 days from vaccine administration in 6 of 183 (3.3%) vaccine recipients vs. 0 of 57 placebo recipients (P = 0.34) after the first dose and in 8 of 88 (9%) vs. 4 of 133 (3%) after the second dose (P = 0.069); none was severe and all were of short duration. Seroresponse of any type (detectable IgA or 4-fold increase of titer to rhesus rotavirus was 9% for the placebo, vs. 52 and 46% for those who received one and two doses of vaccine, respectively. However, neutralizing antibodies against human serotypes 1, 2 and 3 were not raised successfully in vaccinated infants when compared with placebo recipients. The same pattern was found when geometric mean titers were compared. Vaccine take was better when cord blood titers were low. At the age of 1 year the vaccinees had more often high titers for antirhesus rotavirus antibodies (> 640) than the placebo recipients (49% vs. 0%; P < 0.001). NO difference was found between the groups in neutralizing antibodies to human serotypes 1, 2 and 3 rotavirus.(ABSTRACT TRUNCATED AT 250 WORDS)     

What proteins are present in polyethylene glycol precipitates from rheumatic sera?

The proteins present in 4% polyethylene glycol (PEG) precipitates of 10 normal sera and 60 samples from patients with rheumatic diseases were studied. A variety of immunochemical methods were used, including estimation of the percentages of total serum proteins precipitated by PEG, gel filtration analyses of the precipitates, and affinity chromatography with protein A and anti-immunoglobulin columns. Substantial amounts of protein were precipitated from normal sera. Many non-immunoglobulin proteins were precipitated from patients' sera, including fibronectin, haptoglobin, albumin, transferrin, and alpha 1-antitrypsin. Affinity chromatography with anti-immunoglobulin columns bound non-immunoglobulin proteins from PEG precipitates, but the protein A affinity column did not do so. The view that circulating antibody-antigen complexes alone are precipitated by 4% PEG is too simplistic; many non-immunoglobulin proteins are involved. They may either bind to immune complexes or be coprecipitated owing to non-specific protein aggregation.     

Safety and immunogenicity of Haemophilus type b-tetanus protein conjugate vaccine, mixed in the same syringe with diphtheria-tetanus-pertussis vaccine in young infants

As new vaccines are developed there is increasing interest in reducing the number of injections given to children by combining vaccines in one syringe. We studied the safety and immunogenicity of Haemophilus influenzae type b-tetanus protein conjugate vaccine (PRP-T) administered at ages 2, 4 and 6 months mixed in the same syringe with DTP vaccine and its effects on the seroresponse to DTP vaccine. A group of 112 healthy 2-month-old infants received DTP-PRP-T or DTP-placebo mixed immediately before immunization in the same syringe. The addition of PRP-T to DTP did not increase the rate of local or systemic reactions. After the first, second and third dose, the PRP-T recipients showed a geometric anti-PRP antibody mean of 0.13, 2.31 and 6.40 micrograms/ml vs. 0.07, 0.05 and 0.05 micrograms/ml among the DTP-placebo recipients, respectively. Of the PRP-T recipients, 94 and 98% attained antibody concentration of greater than or equal to 0.15 micrograms/ml protein after the second and third dose, respectively, and 65 and 94% attained a concentration of greater than or equal to 1.0 micrograms/ml after the second and third dose, respectively. At the age of 1 year 94 and 52% of the DTP-PRP-T recipients vs. 12% and 0% of the placebo recipients still maintained titers of greater than or equal to 0.15 and greater than or equal to 1.0 micrograms/ml, respectively. The administration of DTP in the same syringe with PRP-T did not affect significantly the antibody response to diphtheria and tetanus toxoid and to pertussis agglutinins. It is concluded that PRP-T vaccine could be administered in the same syringe as DTP.     

Homogeneously staining region in anthracycline-resistant HL-60/AR cells not associated with MDR1 amplification.

Anthracycline-resistant HL-60/AR cells and their drug-sensitive HL-60/S counterparts were characterized by karyotypic analysis and examined for the overexpression of DNA and mRNA sequences coding for P-glycoprotein (Pgp). The HL-60/S cells were karyotypically stable over a 5-year period of study (1986-1991), except for an additional small Giemsa-positive band noted at 7q22 in cultures harvested in 1987, but not in 1986. This change did not affect drug sensitivity. The drug-resistant HL-60/AR cells examined in 1986, 1987, and 1991 demonstrated a very stable karyotype. The most striking feature was a large homogeneously staining region in the long arm of chromosome 7 (7q11.2), and translocation of the remainder of the long arm to another centromere. Other changes in the HL-60/AR cells included inversion in 9q, partial deletion of the short arm of chromosome 10p, addition of material to the p arm of der(16), loss of chromosome 22, and the appearance of a new marker chromosome. Both HL-60/S and the HL-60/AR cells were found not to amplify DNA or mRNA sequences coding for the Pgp. Thus, although the HL-60/AR cells possess the classical multidrug resistance phenotype and demonstrate a homogeneously staining region near the region of the MDR1 gene, their resistance is due to mechanisms other than those coded for by MDR1.     

Epidemiology and laboratory diagnosis of infection with viral and bacterial pathogens in infants hospitalized for suspected sepsis

A prospective study was conducted to determine the frequency and distribution of bacterial and viral pathogens in infants hospitalized with suspected sepsis and to evaluate the potential of virus detection for improving patient management. A causative organism was detected in 157 (67%) of 233 previously healthy infants less than 3 months of age, who had been hospitalized for suspected sepsis: 19 (8%) had bacterial infections, 135 (58%) had viral infections, and 3 (1%) had mixed viral-bacterial infections. Viral infections occurred in a seasonal pattern: enteroviruses were responsible for most of the hospitalizations during summer and fall (65/110; 63%) and respiratory syncytial and influenza A viruses were responsible for most of the infections during winter (44/81; 55%). In contrast, bacterial infections were not seasonally distributed. Virus was detected in 33% of the 138 infected infants within 24 hours, and in 64% within 3 days. We conclude that viral infections are prevalent among infants hospitalized for suspected sepsis, and most can be detected early enough to influence patient management.     

A syndrome including thumb malformations, microcephaly, short stature, and hypogonadism.

We report on eight patients from seven different families affected with a syndrome which includes thumb defects, short stature, microcephaly, and mental retardation. Most of the patients had additional malformations, in particular amenorrhoea and azoospermia in the adults. There were no haematological manifestations and the chromosomes were normal without evidence of breakage even after stimulation. In five of the cases the probands' mother received hormonal treatment before or at the beginning of her pregnancy or both. The syndrome may be inherited as an autosomal recessive trait since the patients included both males and females and their parents were related in most cases. In addition, supporting this possibility, they all originated from a small village which may be considered as an isolate. However, in all cases but one, only one person was affected in each family and there was a significant apparent excess of healthy sibs of the probands. These observations may be the result of the variability of the syndrome or a more complex type of inheritance.     

Genetic testing for hearing loss: different motivations for the same outcome

Autism is a complex genetic disorder. Chromosome 15 is of particular interest in this disorder, because of previous reports of individuals with autism with chromosomal abnormalities in the 15q11-q13 region. Transmission disequilibrium between polymorphisms in this region and autism has been also been reported in some, but not all studies. Recently, a novel maternally expressed gene, ATP10C, was characterized and mapped to the chromosome 15q11-q13 region, 200 kb distal to UBE3A. It encodes a putative aminophospholipid translocase likely to be involved in the asymmetric distribution of proteins in the cell membrane. Preferential maternal expression has been demonstrated in fibroblasts and brain. Because of its physical location and imprinting pattern, ATP10C was considered to be a candidate gene for chromosome 15-associated autism. In an effort to find the genes responsible for autism in this chromosomal region, 1.5 kb of the 5' flanking region, as well as the coding and splicing regions of ATP10C, were screened for sequence variants. Several polymorphic markers including five nonsynonymous SNPs were identified. To investigate transmission disequilibrium between ATP10C and autism, a family-based association study was conducted for 14 markers in 115 autism trios. No significant transmission disequilibrium was found, suggesting ATP10C is unlikely to contribute strongly to susceptibility to autism in these families. However, due to limited power to detect genes of modest effect, the possible functional role of the nonsynonymous SNPs and the functional implications of the SNPs identified from 5' flanking region and intron 2 splicing region may be evaluated in further studies.