Inpatient management of gout in a New Zealand hospital: a retrospective audit.

AIM: To review inpatient management of acute gout in a New Zealand hospital. METHODS: A retrospective file review of all acute episodes of gout at Hutt Hospital, Wellington, New Zealand over a 1 year period. RESULTS: In the course of a year, there were 90 admissions for, or complicated by, acute gout. In 31 cases, gout was the primary diagnosis. Median length of stay was 5 days and readmissions were common. The majority of patients (87%) were known to have gout before admission, yet only 50% of these patients were on uric acid lowering treatment. Serum urate was measured in only 60% of patients with a mean level of 0.471 mmol/L. Treatment for the acute attack was evenly split between monotherapy (49%) and polytherapy (49%). Treatment modalities used were: prednisone (61%), non-steroidal anti-inflammatories (40%), colchicine (40%), adrenocorticotrophic hormone (ACTH) (15%) and intrarticular steroids (7%). Patients were generally treated in a timely manner with few patients experiencing delays. Patients seen by the Rheumatology Department were more likely to receive polytherapy, be treated with intra-articular steroids or ACTH and to start allopurinol. The 'treat-to-target' approach to the management of elevated serum urate was mentioned in only 9% of cases. CONCLUSION: There was considerable variability in the investigation and management of acute gout, with significant deviation from published protocols. The 'treat-to-target' approach to the management of elevated urate has not yet been widely adopted by the physicians in this New Zealand hospital.

DNA vaccines in sheep: CTLA-4 mediated targeting and CpG motifs enhance immunogenicity in a DNA prime/protein boost strategy.

DNA vaccines have proven to be an efficient means of inducing immune responses in small laboratory animals; however, their efficacy in large out-bred animal models has been much less promising. In addressing this issue, we have investigated the ability of ovine cytotoxic lymphocyte antigen 4 (CTLA-4) mediated targeting and ruminant specific CpG optimised plasmids, both alone and in combination, to enhance immune responses in sheep to the pro cathepsin B (FhCatB) antigen from Fasciola hepatica. In this study, CTLA-4 mediated targeting enhanced the speed and magnitude of the primary antibody response and effectively primed for a potent memory response compared to conventional DNA vaccination alone, which failed to induce a detectable immune response. While the CpG-augmentation of the CTLA-4 targeted construct did not further enhance the magnitude or isotype profile of the CTLA-4 induced antibody titres, it did result in the induction of significant antigen-specific, lymphocyte-proliferative responses that were not observed in any other treatment group, showing for the first time that significant cellular responses can be induced in sheep following DNA vaccination. In contrast, CpG-augmentation in the absence of CTLA-4 mediated targeting failed to induce a detectable immune response. This is the first study to explore the potential adjuvant effects of ruminant specific CpG motifs on DNA vaccine induced immune responses in sheep. The ability of CpG-augmented CTLA-4 mediated targeting to induce both humoral and cellular immune responses in this study suggests that this may be an effective approach for enhancing the efficacy of DNA vaccines in large out-bred animal models.

Cloning and expression of the major secreted cathepsin B-like protein from juvenile Fasciola hepatica and analysis of immunogenicity following liver fluke infection.

The functions of the cathepsin B-like proteases in liver flukes are unknown and analysis has been hindered by a lack of protein for study, since the protein is produced in small amounts by juvenile flukes. To circumvent this, we isolated and characterized a cDNA encoding the major secreted cathepsin B from Fasciola hepatica. The predicted preproprotein is 339 amino acids in length, with the mature protease predicted to be 254 amino acids long, and shows significant similarity to parasite and mammalian cathepsin B. Only one of the two conserved histidine residues required for cathepsin B exopeptidase activity is predicted to be present. Recombinant preproprotein was produced in yeast, and it was shown that the recombinant proprotein can undergo a degree of self-processing in vitro to the mature form, which is active against gelatin and synthetic peptide substrates. The recombinant protein is antigenic in vaccinated rats, and antibodies to the protein are detected early after infection of rats and sheep with F. hepatica. The kinetics of the response to cathepsin B and cathepsin L after infection of sheep and rats confirm the temporal expression of these proteins during the life cycle of the parasite.