Middle ear abnormalities at age 5 years in relation with early onset otitis media and number of episodes, in the Inuit population of Nunavik, Quebec, Canada.

Otitis media (OM) and their sequelae are a major health issue in the Inuit population of Nunavik, Quebec. Hypotheses of the study were: (i) early onset OM leads to repeated OM; (ii) repeated OM episodes leads to middle ear abnormalities (MEA) at age 5 years, (iii) pneumococcal conjugate vaccines (PCVs) may reduce multiple OM and MEA. Immunisation cards, medical records and audiology screening tests at age 5 years in a sample of 610 children born in 1994-2010 in 3 communities were reviewed. Children were classified into three categories using a score based on audiology screening tests: no abnormality, minor, or major MEA. The average number of OM episodes before age 5 years was 5.0 and 30% had minor and 17% major MEA at age 5 years. Community residency predicted both frequent (≥ 8) OM episodes and MEA. Early onset OM (age <6 months) was a predictor of frequent OM (RR = 1.71; 95%CI: 1.50-1.95) whereas PCV (≥1 dose ≥ age 2 months) has no significant effect. Frequent OM episodes were associated with major MEA (RR = 2.16; 95%CI: 1.20-3.85). Although associations were not statistically significant, there was a trend towards a protective effect of PCV administration on frequent OM and minor MEA, but not major MEA. In conclusion, results support an association between early onset OM, frequent OM and MEA that could represent a causal pathway.

Prevalence of middle ear abnormalities from otitis media in relation with pneumococcal vaccine use in the Inuit population of Nunavik, province of Quebec, Canada.

BACKGROUND: Otitis media (OM) constitutes an important public health problem in the Inuit population of Nunavik, Northern Quebec. One of the objectives of the childhood pneumococcal vaccination program is to reduce OM burden. The program was implemented in 2002, and 7-, 10-, and 13-valent conjugate vaccines were used sequentially, with doses offered at 2, 4, 6 and 12-18 months, respectively. OBJECTIVE: To assess the prevalence of middle ear abnormalities at age 5 years in relation with exposure to different pneumococcal conjugate vaccines. METHODS: Immunization cards and audiology screening tests at age 5 years of children born in 1994-2010 were reviewed. Children were classified according to the vaccine schedule recommended for their birth cohort or to the vaccines they actually received. Log-linked binomial regression models were used to assess the relative abnormalities risk according to different vaccination schedules. RESULTS: Among 3517 children with complete documentation, the prevalences of minor and major abnormalities were 29% and 18%, respectively. Minor abnormalities frequency was higher in unvaccinated children (34%) and lower in children vaccinated with PCV7 (22%), PCV7 + PCV10 (17%), PCV10 (15%) and PCV10 + PCV13 (18%). No substantial differences among vaccine schedules were observed for major abnormalities. CONCLUSIONS: Pneumococcal conjugate vaccination was associated with a decreased frequency of middle ear abnormalities although no effect was seen for major abnormalities which may be trigger by OM with early onset. Clinicaltrials.gov registration number: NCT01694329.

Expression of CTLA-4 (CD152) in peripheral blood T cells of children with influenza virus infection including encephalopathy in comparison with respiratory syncytial virus infection.

Influenza virus and respiratory syncytial virus (RSV) are the most common causes of acute severe respiratory infection in children during the winter. There have been few reports about peripheral blood T cell activation in vivo in influenza virus infection and conflicting results concerning peripheral blood T cells activation in RSV infection. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, CD152) is a receptor present on T cells that plays a critical role in the down-regulation of antigen-activated immune responses. To clarify the status of peripheral blood T cells, we investigated intracellular CTLA-4 expression in T cells in patients with influenza virus and RSV infection. We collected blood samples from 15 patients with influenza virus infection, including three with complications of influenza virus-associated encephalopathy and 18 patients with RSV infection, as well as 44 healthy children. We determined the intracellular expression of CTLA-4 in CD4+ and CD8+ T cells by flow cytometry. There were no significant differences in the percentages of intracellular CTLA-4-positive CD4+ T cells and CD8+ T cells by age. The percentages of intracellular CTLA-4-positive CD4+ T cells in the patients with influenza virus infection were significantly higher than those in healthy children (P < 0.01). In particular, the patients with influenza virus-associated encephalopathy had sevenfold higher percentages of CTLA-4-positive CD4+ T cells than influenza patients without encephalopathy (P < 0.05). The patients with influenza virus-associated encephalopathy had increased percentages of CTLA-4-positive CD8+ cells at the acute stage in comparison with the convalescent stage and in control subjects (P < 0.01, respectively). RSV patients showed no increase in CTLA-4-positive CD4+ T cells or CD8+ T cells. The immunological status of peripheral T cell activation is substantially different in influenza virus infection and RSV infection. The patients with RSV infection did not show any increase in CTLA-4-positive peripheral blood T cells. There was a remarkable increase in intracellular CTLA-4 in CD4+ and CD8+ T cells in influenza virus-associated encephalopathy. Down-regulation of antigen-activated peripheral blood T cell activation might play an important role in the pathogenesis of influenza virus-associated encephalopathy and host defence against influenza virus infection.

Outcome of acute lymphoblastic leukemia in children with AL90 regimen: impact of response to treatment and sex difference on prognostic factors.

BACKGROUND: In our previous studies, the outcome of high-risk ALL was still poor. In the present study, all children with ALL were classified into three groups and treated with a new regimen (AL90). PATIENTS AND METHODS: Between 1990 and 1996, 220 children with ALL, treated with the AL90 regimen, were classified into three risk groups: low, intermediate, and high: LR, IR, and HR, respectively. The protocol consisted of three- to five-drug induction, consolidation with intermediate-dose methotrexate and/or cytarabine, mercaptopurine and cyclophosphamide, four-drug intensification, and sequential maintenance therapies. Only intrathecal chemotherapy was used for CNS prophylaxis in the LR group, whereas cranial irradiation was added for the IR and HR groups. RESULTS: The number of eligible patients was 91: LR group, 71: IR group, and 58: HR group. Complete remission (CR) was obtained in > 98% of the LR and IR groups, while only 88% achieved CR in the HR group. The 5-year event-free survival (EFS) rate was 67.4% in all patients: 70.4% in the LR group, 71.7% in the IR group, and 57.5% in the HR group. With respect to the previous study, EFS in the HR group who showed positive residual leukemia at 14 days was improved, whereas EFS in boys versus girls was significantly lower (48.8% : 85.7%, P = 0.02). CONCLUSIONS: In high-risk ALL, the rate of induction failure was high and boys had a worse outcome, calling for improvements in induction therapy and a specific approach for boys.

Longitudinal observations (1987-1997) on the prevalence of middle ear disease and associated risk factors among Inuit children of Inukjuak, Nunavik, Quebec, Canada.

The prevalence of middle ear disease in 2-6 year old children in 1997 was compared with that observed in 1987 in the same Inuit community in northern Quebec. Risk and protective factors associated with middle ear disease were also assessed. A total of 122 children participated. The assessments included: otological examination, cerumen sampling for analysis of organochlorine compounds, medical file review, and parent questionnaire regarding environmental and lifestyle factors. Comparison of ear examination results in 1997 and 1987 showed that there had been no change in the prevalence of chronic otitis media [9.4% to 10.8%] and proportion of ear drums with minimal scarring [45.6% to 45.4%], an increase in the proportion of normal ear drums [23.9% to 39.0%], a decrease the proportion with maximal scarring [17.8% to 2.0%] and little difference in the rate of serous otitis media [3.3% to 2.8%]. Factors found to be significantly associated with middle ear disease included: number of persons/bedroom, number of siblings with a history of ear disease, age at first, second and third visit to the nursing station for ear problems, and type of milk (formula vs. non-formula) in bottle fed children.

Treatment of childhood acute myelogenous leukemia with allogeneic and autologous stem cell transplantation during the first remission: a report from the Kyushu-Yamaguchi Children's Cancer Study group in Japan.

A total of 64 newly diagnosed acute myelogenous leukemia patients (except FAB M3 and/or Down syndrome) under 18 years of age were consecutively enrolled into the study. Patients having an HLA-identical sibling (allo group) were assigned to undergo allogeneic bone marrow transplantation (allo BMT) in the first complete remission (CR). Others (non-allo group) were assigned to undergo autologous peripheral blood stem cell transplantation (PBSCT) or autologous BMT (auto BMT). Conditioning regimen was busulfan + melphalan for all transplantation. Of 64 patients (allo group 24; non-allo group 40), 59 (92.2%) achieved a CR. Eighteen relapses occurred (allo group 4; non-allo group 14) and 6 died during the first CR. The 5-year event-free survival (EFS) rate was 53.3 +/- 6.4% at a median follow-up period of 45 months. The 5-year EFS rates of allo and non-allo groups were 70.8 +/- 9.3% and 43.0 +/- 8.1%, respectively (p = .08). The EFS rates at 5 years post-transplant for allo BMT from an HLA-identical sibling (n = 18), PBSCT (11), and auto BMT (6) were 88.1 +/- 7.9%, 41.6 +/- 19.7%, and 83.3 +/- 15.2%, respectively. The outcome of allo BMT was superior to that of autograft. Auto BMT rather than PBSCT might contribute to a long-term survival in case of no available HLA-identical siblings.

Recombinant chromosome 18 resulting from a maternal pericentric inversion.

We report on a newborn girl with duplication of 18q12.2-->18qter and deficiency of 18p11.2-->18pter which resulted from meiotic recombination of the maternal pericentric inversion, inv(18)(p11.2q12.2). Her clinical manifestations were compatible with those of partial trisomy 18q syndrome. We review the previously reported 9 cases in 8 families of rec(18) resulting from recombination of a parental pericentric inversion.

Alkylation reaction of phosphorus oxyacids.

Alkylation reactions of phosphorus oxyacids (i.e. phosphoric acid, phosphorous acid, hypophosphorous acid) were examined by means of several methods for the synthesis of the corresponding esters. These reactions were applied to the synthesis of oligonucleotide having phosphotriester bond or phosphonate diester bond.

Hearing loss due to aging (presbycusis).

Presbycusis is the progressive hearing loss caused by histologic changes due to aging. Schuknecht described four histopathologic types of presbycusis and correlated these findings to audiometric data. In a retrospective study, some strict criteria were set to distinguish the "pure" cases of presbycusis in a group of 1,181 subjects, 50 years of age and older, seen in our Audiology Clinic over one year; 91 subjects were found to meet these criteria. An attempt was made to fit the pure tone threshold curves into the types described by Schuknecht and correlate these curves to speech discrimination, tone decay, recruitment, age and sex of these subjects. It was found that: (a) only 50% of these audiograms could be fitted into the described histopathologic types, suggesting that in 50% of the subjects, presbycusis was caused by more than one degenerative process; (b) in 86% of subjects, speech discrimination was excellent or good in quiet; this test therefore may not reflect the difficulties presbycusis have in understanding speech under adverse auditory conditions; (c) subjects with flat pure tone threshold curves had generally good discrimination; (d) no differences were found between males and females; and (e) tests for tone decay and recruitment showed that in most cases the hearing loss was due to cochlear pathology, but these data do not exclude the possibility of central auditory involvement.

In vivo induction of endogenous retroviruses in BALB/c mouse hepatocytes by successive treatments with carbon tetrachloride and bromodeoxyuridine.

The effects of bromodeoxyuridine (BrdUrd) incorporation into hepatocytes of carbon tetrachloride (CCl4)-induced regenerating liver of BALB/c mice on the induction of endogenous retroviruses was examined. From the nucliec acid hybridization studies, the maximum levels of hybridization were obtained for both N- and X-tropic BALB/c endogenous retrovirus specific [3H]-cDNAs with liver RNA from animals receiving BrdUrd at 40 and 44 h post-CCl4 treatment, and killed on the fourth day following BrdUrd injection. Media from NIH-3T3 (Swiss mouse) and mink cell cultures, infected with liver homogenates from animals treated as above, gave significant levels of reverse transcriptase activity. The observations made in the present study show that BrdUrd incorporation into cell DNA can cause induction of both N- and X-tropic endogenous retroviruses in BALB/c mouse hepatocytes in vivo, and such induction is probably a transient event.