The management of side-effects during therapy for hepatitis C.

The results of interferon and ribavirin combination therapy for chronic hepatitis C infection have substantially improved in recent years, such that the majority of patients in randomized-controlled trials now achieve a sustained virological response. However, adverse effects are commonplace, often disabling and may lead to interruption or cessation of therapy with subsequent loss of efficacy. Constitutional, neuropsychiatric and haematological reactions have proved particularly troublesome. In this review, we discuss these adverse effects in more detail and highlight recent advances in their management.

Gene therapy for pancreatic and biliary malignancies.

Advances in our understanding of the molecular genetics of pancreatic and biliary cancers have given us new targets for therapy using molecular and genetic approaches. Replacement of tumour suppressor gene function using adenoviruses to transfer wild-type p53 and p16 genes can produce dramatic anti-tumour effects, both in vitro and in vivo. Blockade of dominant oncogene function using dominant negative technology may have a particular application for mutated K-ras which occurs almost ubiquitously in pancreatic adenocarcinoma. Genetic prodrug activation therapy using tumour-selective gene promoters to drive the expression of so-called suicide genes is showing remarkable promise. Targeted delivery of such therapeutic constructs may also be possible through knowledge of the expression of surface receptors by particular tumour cell types. Genetic immunomodulation using cytokine genes as well as specific vaccines against tumour-associated antigens are now being brought into clinical trials.

Diagnosis and treatment of chronic hepatic encephalopathy.

Neuropsychiatric abnormalities affecting patients with chronic liver disease are termed chronic hepatic encephalopathy. They involve neurotransmitter changes, rather than a structural disorder of the brain. Diagnosis is based on clinical findings, and electroencephalographic and psychometric testing. There is no 'specific' treatment, but there are a number of non-specific measures that can be used.

The impact of climate change on the soil/moisture regime of Scottish mineral soils.

The likely impact of climate change on the moisture regime of Scottish soils and consequently on agriculture and land use has been addressed using a novel Geographic Information Systems (GIS) approach. Current estimates of changes in summer precipitation by the year 2030 are 0% with an associated uncertainty of +/- 11%. This study considers the worst case scenario of a decrease in rainfall by 11% which will lead to some low rainfall areas experiencing an increased drought risk, particularly on lighter soils. Wet areas with heavy soils could benefit from an increase in the accessibility period for machinery. As the major agricultural land in Scotland is located on the relatively dry east coast where localised problems due to drought are not uncommon even under the present climate, the detrimental effects of a decrease in rainfall for the whole of Scotland are therefore likely to outweigh the benefits. Approximately 8% of Scotland has been identified in this study as soil/climate combinations which will be susceptible to drought should summer rainfall decrease by 11% and summer temperature increase by 1.4 degrees C.

The effects of cromakalim on ATP-sensitive potassium channels in insulin-secreting cells.

1. The single-channel current recording technique has been used to investigate the effects of cromakalim, diazoxide and ATP, separately and combined, on the opening of ATP-sensitive potassium channels in the insulin-secreting cell-line RINm5F. The actions of these drugs have been studied using the permeabilized open-cell variation of the patch-clamp technique. 2. In the absence of internal ATP, cromakalim (80-200 microM) was unable to open ATP-sensitive K+ channels but when ATP was present both cromakalim and diazoxide caused channel openings. 3. Interactions between ATP and cromakalim seemed competitive. Concentrations of cromakalim in the range 80-200 microM readily activated channels inhibited by 0.1 mM ATP, but had no effects when the concentration of ATP was increased to 0.5-2 mM. Only when the concentration of cromakalim was increased to 400-800 microM could opening of 0.5-2 mM ATP-inhibited channels be regularly observed. In the continued presence of cromakalim (400-800 microM), an increase in the internal concentration of ATP from either 0.25 to 0.5 mM or 1 to 2 mM, inhibited cromakalim-activated K+ channels. 4. Activation of ATP-inhibited K+ channels was abolished by replacing ATP with ATP gamma S and cromakalin had no effects on ATP gamma S-inhibited channels. This suggests that cromakalim may open KATP channels in insulin-secreting cells by a mechanism which involves protein phosphorylation.