Successful treatment of empyema thoracis with polymethylmethacrylate antibiotic-impregnated beads in the guinea pig

Two hundred nine Duncan-Harley guinea pigs had intrathoracic inoculation with 10(8) Staphylococcus aureus, accompanied by blood and umbilical tape. One hundred fifty-two animals were excluded because of clinical recovery, early death, or complications related to intrathoracic polymethylmethacrylate (PMMA) bead placement. The remaining 57 animals had clinical signs of empyema thoracis and were the subjects of this study. Group I animals (N = 24) served as the controls and had no therapy. Group II animals (N = 14) were treated by intrathoracic placement of placebo PMMA beads. Group III animals (N = 19) were treated by intrathoracic placement of tobramycin sulfate-impregnated PMMA beads. There were no differences between the groups in pleural reaction or pneumonia scores. These findings demonstrate a similar host response to the established infection. Group III, however, had a higher sterilization rate than Groups I and II (p less than 0.05), a finding underlining the therapeutic effect of tobramycin-treated PMMA beads. We conclude that intrathoracic local antimicrobial therapy with slow-release tobramycin-impregnated PMMA beads may enhance empyema treatment by increasing the rate of local sterilization. More experiments are necessary to assess the efficacy of this potentially important therapeutic arm for the treatment of thoracic empyema.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.