No abstract

No abstract

S. Roberts is supported by the NIHR Manchester Biomedical Research Centre.

Primary biliary cirrhosis (PBC) is a chronic cholestatic disorder characterised by an immunological, and often granulomatous, attack on bile ducts leading to fibrosis, cirrhosis, liver failure and death. Animal and human studies suggest that oxidant stress plays a key role in progression of other liver diseases, but no comprehensive investigation has been performed previously in PBC. A wide range of lipid peroxidation and antioxidant markers were measured in the blood and urine of 41 patients with histologically confirmed PBC. Lipid peroxidation markers were significantly elevated [plasma and urinary 8-isoprostane, P<0.001; plasma malondialdehyde (MDA), P=0.007] compared to age- and sex-matched controls. The most striking antioxidant depletion occurred with plasma total glutathione where levels were significantly reduced (30% of controls). Total serum antioxidant levels were decreased (P=0.013) and serum selenium and vitamin A were also lower (both P<0.001); vitamins C and E were normal. Most patients had early disease biochemically and were Child-Pugh grade A. Urinary 8-isoprostane correlated positively with Ludwig stage and markers of hepatic injury and cholestasis. This study clearly demonstrates that oxidant stress, as reflected in a comprehensive spectrum of lipid peroxidation and antioxidant markers, is a significant feature of early-stage PBC.

This audit has shown that patients managed by the Manchester protocol using serial PIIINP measurement and selective liver biopsy were not disadvantaged in comparison with those managed according to AAD guidelines; they were subjected to sevenfold fewer liver biopsies without evidence that important liver toxicity was missed in the process. If PIIINP monitoring were widely adopted, methotrexate would become a more acceptable option for many patients who are dissuaded from considering it because of the threat of repeated liver biopsy; it would also result in significant savings to the healthcare budget.

AMH may exhibit assay-specific preanalytical instability. Robust protocols for the development and validation of commercial AMH assays are required.

Although large, prospective, multicentre studies are indicated, we have clearly demonstrated that individualized, AMH-guided, controlled ovarian hyperstimulation protocols significantly improved positive clinical outcomes, reduced the incidence of complications and reduced the financial burden associated with assisted reproduction.

Delay in the presentation of symptoms and in referral of patients for surgical opinion remains an important problem in colorectal cancer. Factors influencing patients to consult early include advice from close family or other associates and abdominal pain or vomiting, or both, as one of the early symptoms. More localised rectal symptoms and loss of weight are often associated with long delay. The "classic" symptom pictures are not often seen in the early stages of the disease. Few identifiable factors were associated with delay in referral for surgical opinion. Doctors who examine their patients (rectally or otherwise) refer them sooner. In the districts studied delay in instituting definitive treatment after consultant referral does not seem to be a major problem. There is some evidence that delay is associated with stage of the disease at presentation.