Interferon beta-1a in ulcerative colitis: a placebo controlled, randomised, dose escalating study.

BACKGROUND: and aims: Administration of interferon (IFN)-beta may represent a rational approach to the treatment of ulcerative colitis through its immunomodulatory and anti-inflammatory effects. The present study was performed to evaluate the efficacy and tolerability of IFN-beta-1a. METHODS: Patients (n=18) with moderately active ulcerative colitis were randomised to receive IFN-beta-1a or placebo. IFN-beta-1a was started at a dose of 22 micro g three times a week subcutaneously, and the dose was increased at two week intervals to 44 micro g and then to 88 micro g if no response was observed. The maximum duration of treatment was eight weeks. End points were clinical treatment response, defined as a decrease of at least 3 points from baseline in the ulcerative colitis scoring system (UCSS) symptoms score and induction of endoscopically confirmed remission. RESULTS: Baseline characteristics and disease severity were similar in both groups. Data from 17 patients are included in this report (10 patients in the IFN-beta-1a group and seven patients in the placebo group). Clinical response was achieved in five patients (50%) in the IFN-beta-1a group and in one (14%) in the placebo group (P=0.14). Remission was achieved in three patients in the IFN-beta-1a group and in none in the placebo group (p=0.02). Most adverse reactions associated with IFN-beta-1a were influenza-like symptoms or injection site reactions, and were mild or moderate in severity. CONCLUSIONS: IFN-beta-1a may represent a promising novel treatment approach in ulcerative colitis.

The management of chronic pain in Switzerland: a comparative survey of Swiss medical specialists treating chronic pain.

Chronic pain management by Swiss specialist physicians with the primary hypothesis that pain clinic practitioners conform better to good practice (interdisciplinarity, diagnostic/therapeutic routines, quality control, education) than other specialists treating chronic pain was surveyed. Management of all types of chronic pain by pain clinic practitioners and rheumatologists, oncologists or neurologists was compared via a mailed questionnaire survey (n=125/group). Two hundred and twenty-nine (46%) of 500 mailed questionnaires were returned with similar group return rates. Eighty-six percent of responders find chronic pain therapy very difficult/difficult; they estimate only 45% of these patients achieve good outcomes. Twenty-three per cent of responders belong to an interdisciplinary pain centre, but 72% of chronic pain patients are treated by responders alone. Fifty-nine percent never/only occasionally use therapeutic algorithms, 38% use formal pain diagnostic procedures, 20% have a pain quality control programme. Fifty-one percent lack past pain education, 37% do not attend continuing pain education, 69% agree that pain education is their greatest need. Pain clinic practitioners are more interdisciplinary and use more pain diagnostics than other specialists. They are matched by oncologists in education and success in therapeutic escalation, and bettered by them in algorithm use. Pain clinic practitioners and oncologists bring particular-differing-skills to chronic pain management compared to rheumatologists and neurologists. Chronic pain management diversity may result from differences in malignant and benign pain, and its generally being provided by the speciality treating the underlying cause. This survey identifies targets for improvement in areas fundamental to good chronic pain practice: interdisciplinarity, diagnostic/therapeutic tools, quality management and education.

Molecular cloning, characterization and localization of PfPK4, an eIF-2alpha kinase-related enzyme from the malarial parasite Plasmodium falciparum.

PfPK4, a protein kinase gene from the human malarial parasite Plasmodium falciparum, has been cloned utilizing oligonucleotide probing. The gene encodes a protein of a predicted length of 1123 amino acids, and within this amino acid sequence all the conserved regions characteristic of protein kinases can be identified. The catalytic kinase domain possesses highest identities (34-37%) with eukaryotic initiation factor-2alpha (eIF-2alpha) kinases, especially haem-regulated inhibitory (HRI) protein kinases. There are two kinase inserts in PfPK4, located at positions common to eIF-2alpha kinases. The first insert separates kinase subdomains IV and VI by 559 amino acids, and the second subdomains VII and VIII by 41 amino acids. Both inserts are larger than their homologues in eIF-2alpha kinases. The sequence of PfPK4 has one putative haemin-binding site. The recombinant protein, expressed in Escherichia coli, phosphorylates a synthetic peptide representing a substrate of eIF-2alpha kinases. Autophosphorylation and substrate phosphorylation are inhibited by haemin. Thus PfPK4 appears to be the first protozoan protein kinase related to eIF-2alpha kinases and might be the first non-mammalian HRI kinase. Western blots indicated that the protein is expressed as major forms of 80 and 90 kDa. Whereas the 80 kDa form is present throughout the intraerythrocytic development and in merozoites, the two 90 kDa forms are only found in mature parasites. One of the latter is also present in the membrane fraction of erythrocytes harbouring segmenters. Confocal microscopy detected the protein distributed throughout the trophozoite, whereas it was found in discrete foci (punctate distribution) in segmenters. PfPK4 co-localizes with P. falciparum 83 kDa antigen/apical membrane antigen-1 at the apical complex in segmenters and merozoites, but does not co-localize with rhoptry-associated protein-1.