Co-morbidities in children presenting with chronic suppurative otitis media--a South African study.

BACKGROUND: Chronic suppurative otitis media (CSOM) is common among children in southern Africa. Managing associated co-morbidities may result in earlier disease resolution. METHODS: Children <13 years of age with otorrhoea lasting >4 weeks were recruited to the study. Each child underwent a full clinical examination, a blood count, an HIV test and CD4 cell count, if found to be infected. RESULTS: The study included 86 children, and the median age was 4.6 years. HIV infection was present in 45 of 83 children (54.2%), of which 23 (51.1%) were receiving antiretroviral treatment at the time of presentation. Underweight was present in 22 of 85 (25.9%) children and in 17 of the 45 (37.8%) HIV-infected children. One or more clinical signs (not aural-related) were found in 46 of 86 (53.4%) children. Cholesteatoma was found in 23 of 113 (20.4%) ears, and 9 of 86 (10.5%) children had serious associated aural or intracranial complications. CONCLUSIONS: A high percentage of children with CSOM have associated pathology that needs to be diagnosed to optimally manage CSOM.

A sensitized mutagenesis screen identifies Gli3 as a modifier of Sox10 neurocristopathy.

Haploinsufficiency for the transcription factor SOX10 is associated with the pigmentary deficiencies of Waardenburg syndrome (WS) and is modeled in Sox10 haploinsufficient mice (Sox10(LacZ/+)). As genetic background affects WS severity in both humans and mice, we established an N-ethyl-N-nitrosourea (ENU) mutagenesis screen to identify modifiers that increase the phenotypic severity of Sox10(LacZ/+) mice. Analysis of 230 pedigrees identified three modifiers, named modifier of Sox10 neurocristopathies (Mos1, Mos2 and Mos3). Linkage analysis confirmed their locations on mouse chromosomes 13, 4 and 3, respectively, within regions distinct from previously identified WS loci. Positional candidate analysis of Mos1 identified a truncation mutation in a hedgehog(HH)-signaling mediator, GLI-Kruppel family member 3 (Gli3). Complementation tests using a second allele of Gli3 (Gli3(Xt-J)) confirmed that a null mutation of Gli3 causes the increased hypopigmentation in Sox10(LacZ/+);Gli3(Mos1/)(+) double heterozygotes. Early melanoblast markers (Mitf, Sox10, Dct, and Si) are reduced in Gli3(Mos1/)(Mos1) embryos, indicating that loss of GLI3 signaling disrupts melanoblast specification. In contrast, mice expressing only the GLI3 repressor have normal melanoblast specification, indicating that the full-length GLI3 activator is not required for specification of neural crest to the melanocyte lineage. This study demonstrates the feasibility of sensitized screens to identify disease modifier loci and implicates GLI3 and other HH signaling components as modifiers of human neurocristopathies.

A comparison of the pharmacokinetics of Aspen Ceftriaxone and Rocephin in community-acquired meningitis.

BACKGROUND: Community-acquired bacterial meningitis (CABM) is a life-threatening condition that is common among immunocompromised individuals. Intravenous ceftriaxone, of which Rocephin (ROC) is the originator brand, is recommended as first-line therapy in South Africa. Despite concerns regarding therapeutic equivalence with generic agents, this is the first study that has been conducted comparing clinical pharmacokinetics (PK) of a generic ceftriaxone formulation with the originator. OBJECTIVE: To compare the PK and safety of Aspen Ceftriaxone (AC) and ROC in the treatment of adult CABM.Methods. A total of 63 eligible patients were randomised 1:1 to receive 2 g of either medication twice daily for a duration based on the identity of the causative organism and their physician's clinical judgment. The primary endpoint of this study was the comparison of clinical PK, specifically the concentrations of each drug in the cerebrospinal fluid with corresponding paired plasma samples. While this study was underpowered to assess efficacy, safety could be evaluated on the basis of reported adverse events. RESULTS: The two patient groups were epidemiologically similar. There were no statistically significant differences in PK between either agent, nor any difference with regard to safety. CONCLUSION: AC can be considered as equivalent to ROC with regard to PK and safety in patients with CABM.