Prevalence of transfusion-acquired hepatitis C in an Australian bleeding disorders population.

In Australia prior to 1992, many patients with bleeding disorders were exposed to hepatitis C through blood products. However, the incidence, complications and response to treatment of chronic hepatitis C (CHC) in this population are poorly characterized. The aim of this study was to examine the prevalence of CHC and response to treatment in an Australian bleeding disorders population. Demographic data, virological data and liver disease status from these 700 patients with inherited bleeding disorders were analysed. Of these 700 patients, 424 (61%) had been tested for CHC infection and 219 (52%) were hepatitis C antibody positive, with the prevalence approaching 100% in patients with severe bleeding disorders. Of 219 patients, 73 (33%) had received treatment for their infection with a response rate of 33/73 (45%) across all genotypes. Of 219 patients, 34 (16%) had spontaneous viral clearance. When measured with transient elastography, 44/98 (45%) patients with CHC had significant liver fibrosis and 15/98 (15%) had liver cirrhosis. Of 130 patients, 38 (29%) with CHC infection had no evidence of follow-up with an appropriate clinician in the past 2 years. This study demonstrates that testing for CHC in this population is incomplete and treatment rates are low. Given the substantial morbidity and mortality associated with CHC and new therapeutic options becoming available, it seems important to reengage patients to diagnose, offer treatment and monitor this infection.

A novel short isoform of the D3 dopamine receptor generated by alternative splicing in the third cytoplasmic loop.

The mouse D3 dopamine receptor has been cloned from olfactory tubercle cDNA using polymerase chain reaction and has been found to exist in two alternatively spliced forms. These two mRNA isoforms differ by the presence or absence of 63 base pairs (bp), which encode 21 amino acids in the putative third cytoplasmic loop of the receptor. The longer form corresponds to the previously reported rat D3 dopamine receptor, to which it bears sequence homology of 94%. Northern blot analysis shows the mouse D3 receptor to be most abundant in the olfactory tubercle. Expression studies show the novel short D3 isoform to bind dopaminergic ligands with a D3-like pharmacological profile. Polymerase chain reaction analysis on different mouse brain regions shows the long and short D3 receptors to be present in the same tissues, the longer form invariably being the predominant one. Analysis of the gene for the mouse D3 dopamine receptor shows that no separate exon encodes the 63-bp stretch and reveals the presence of a consensus sequence for an acceptor site at the 3' end of the 63-bp stretch. This suggests that an internal acceptor site in the exon coding for the distal part of the third cytoplasmic loop directs alternative splicing of the D3 dopamine receptor.