Validation of a viral and bacterial inactivation step during the extraction and purification process of porcine collagen.

In the last few years, regulations for biomolecule production, and especially for extraction and purification of animal molecules such as collagen, have been reinforced to ensure the sanitary safety of the materials. To be authorized to market biomaterials based on collagen, manufacturers now have to prove that at least one step of their process is described in guidelines to inactivate prion, viruses, and bacteria. The present study focuses on the inactivation step performed during the extraction and purification of porcine type I atelocollagen. We chose to determine the reduction factor of a 1 M NaOH step on porcine parvovirus and four bacterial strains inactivation. During the extraction step, we deliberately inoculated the collagen suspension with the different microorganisms tested. Then, 1 M NaOH was added to the suspension for 1 hour at 20 degrees C. We demonstrated that this treatment totally inactivated S. aureus, P. aeruginosa, C. albicans and A. niger which are bacterial strains responsible of severe human pathology. The reduction factors reached more than 4 logs for B. cereus spores and 4 logs for the porcine parvovirus. are encouraging as those two microorganisms are known to be very resistant to inactivation.

Randomized trial of interferon beta-1a in chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: To test the safety and efficacy of interferon beta-1a (IFN-beta) in treatment-resistant chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). BACKGROUND: Current treatment regimens leave 4% to 30% of patients with CIDP with moderate or severe disability. IFN-beta has been reported as beneficial in one treatment-resistant patient. METHODS: Ten consecutive treatment-resistant patients were randomized in a double-blind, crossover design to receive placebo or IFN-beta (3 MIU for 2 weeks and then 6 MIU for 10 weeks) subcutaneously three times weekly, followed by 4 weeks without treatment, and then the opposite treatment for 12 weeks. The primary outcome measure was "clinically important" improvement by specified amounts in any three of eight clinical measures: timed 10-m walk, Ambulation Index, expanded Medical Research Council sum score, nine-hole peg test time, Functional Independence Measure, Hammersmith Motor Ability, a new Guy's Neurological Disability Scale, and the EuroQoL quality-of-life scale. These and motor median nerve conduction studies were measured before and after 12 weeks of each treatment. RESULTS: Clinically important improvement was observed in one patient while taking IFN-beta and two patients while taking placebo. There was no significant difference between IFN-beta and placebo in the change in any of the individual clinical or neurophysiological measures between the beginning and end of treatment. There were no serious adverse events. CONCLUSION: This trial shows that IFN-beta is safe but not efficacious in treatment-resistant CIDP.

The epidemiology of multiple sclerosis in Devon: a comparison of the new and old classification criteria.

OBJECTIVES: To determine the prevalence of multiple sclerosis in Devon and compare the new McDonald classification guidelines with the Poser criteria currently used. METHODS: All patients known to have multiple sclerosis and alive and resident within the chosen area on 1 June 2001 were included in the study. Seven sources of case ascertainment were used and each patient was classified according to both the Poser criteria and the McDonald guidelines. RESULTS: The prevalence of multiple sclerosis in Devon was 118 per 100,000 (definite and probable cases, Poser criteria) in a population of 341,796, on the prevalence day. The prevalence of definite and possible cases, as classified by the new McDonald guidelines, was slightly lower at 117 per 100,000. Clinical demographics of the prevalent population were similar to those of other studies in the United Kingdom. CONCLUSIONS: This is first survey to use the new recommended guidelines and compare these criteria with the Poser classification. The difficulties encountered with applying the new criteria in research are highlighted, as are the differences between the new and old criteria. This study reports one of the highest prevalences in the south of the UK, adding support for a north-south divide being a step effect rather than a latitudinal gradient.

Randomized controlled trial of brain-derived neurotrophic factor in Guillain-Barré syndrome: a pilot study.

Brain-derived neurotrophic factor (BDNF) has the theoretical potential to protect neurones from axonal degeneration. The objective of this study was to discover whether brain-derived neurotrophic factor is safe in Guillain-Barré syndrome, and to make preliminary observations of its efficacy. This was a parallel group randomized controlled trial of subcutaneous brain-derived neurotrophic factor 25 microg/kg daily compared with placebo for up to 24 weeks or until patients could walk without aid. Six patients received brain-derived neurotrophic factor, of whom three had serious adverse events including one death. Four patients received placebo, of whom two had serious adverse events including one death. The rate and extent of recovery were similar in the two groups. This pilot study did not detect any serious adverse events attributed to brain-derived neurotrophic factor treatment.

Immunoadsorption inferior to plasma exchange in a patient with chronic inflammatory demyelinating polyradiculoneuropathy.

Staphylococcal protein A immunoadsorption and plasma exchange were compared for treating chronic inflammatory demyelinating polyradiculoneuropathy. In a single patient, plasma exchange had a more beneficial effect than immunoadsorption on clinical outcome measures. Serum IgM antibody activity to peripheral nerve fell significantly following plasma exchange. Serum IgM and IgA fell more and IgG less after plasma exchange than after immunoadsorption. The superior efficacy of plasma exchange to immunoadsorption in this case may have been the result of removal of an IgM antibody.

Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy.

This multicenter, randomized, double-blind, crossover trial compared a six week course of oral prednisolone tapering from 60 mg to 10 mg daily with intravenous immunoglobulin (IVIg) 2.0 g/kg given over one to two days for treating chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Twenty-four of the thirty-two randomized patients completed both treatment periods. Both treatments produced significant improvements in the primary outcome measure, change in an 11-point disability scale two weeks after randomization. There was slightly, but not significantly, more improvement after IVIg than with prednisolone, the mean difference between the groups in change in disability grade being 0.16 (95% CI = -0.35 to 0.66). There were also slightly, but not significantly, greater improvements favoring IVIg in the secondary outcome measures: time to walk 10 meters after two weeks and improvement in disability grade after six weeks. Results may have been biased against IVIg by the eight patients who did not complete the second arm of the trial. A serious adverse event (psychosis) attributable to treatment occurred in one patient while on prednisolone and in none with IVIg.