In this 'double-blind', randomized, placebo-controlled phase II trial, we compared an altered peptide ligand of myelin basic protein with placebo, evaluating their safety and influence on magnetic resonance imaging in relapsing-remitting multiple sclerosis. A safety board suspended the trial because of hypersensitivity reactions in 9% of the patients. There were no increases in either clinical relapses or in new enhancing lesions in any patient, even those with hypersensitivity reactions. Secondary analysis of those patients completing the study showed that the volume and number of enhancing lesions were reduced at a dose of 5 mg. There was also a regulatory type 2 T helper-cell response to altered peptide ligand that cross-reacted with the native peptide.

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The associations with environmental factors are consistent with the hypothesis that more crowded houses, increased family size and birth order, which may possibly increase early exposure to infections, may offer protection from subsequent development of eczema.

Atopy is strongly and inversely related to family size, a pattern which is plausibly assumed to reflect a protective effect of early infection. The current study tested this hypothesis by case-referent analysis of an adult cohort in the UK.The study established that atopy, defined by prick tests to common aeroallergens, was less common among those from larger families after adjustment for potentially confounding factors. In particular, a higher number of brothers appeared to offer protection. The current authors attempted to explain this distribution by examining contemporary family-doctor records of early childhood infections; and by a number of other indirect indices of early-life "hygiene".The sibling effect was unexplained by evidence of infection with either hepatitis A or Helicobacter pylori, or by counts of infections or antibiotic prescriptions in early life. There was a significant and independent negative association between the number of gastrointestinal infections before the age of 5 yrs and the odds of atopy. Dog ownership and home moving in early life also displayed potentially protective associations.Although the current study replicates the finding that atopy is inversely associated with family size this could not be explained by documentary or serological evidence of early infection. The findings support the suggestion that the "sibling effect" in atopy may not simply reflect protection by early infection. Eur Respir J 2003; 22: 956-961.

Background: It is suggested that the inverse relationship between allergic disease and family size reflects reduced exposure to early life infections, and that antibiotic treatment in childhood diminishes any protective effect of such infection. Methods: A birth cohort study was undertaken in 642 children recruited before birth and seen annually until the age of 8 years. Reported infections and prescribed antibiotics by the age of 5 years were counted from GP records and comparisons were made with a previous study of their parents. Results: At the age of 8 years, 104 children (19%) were atopic, 79 (13%) were currently wheezy and 124 (21%) had seasonal rhinitis. 577 children (97%) had at least three infections recorded by age 5, a figure much higher than that of their parents (69%). By the age of 5 only 11 children (2%) had never received a prescription for antibiotics; the corresponding figure for the parents was 24%. Higher numbers of infections were recorded for firstborn children. After adjusting for parental atopy and birth order, there was no association between infection counts and atopy (OR 1.01 (95% CI 0.99 to 1.03) per infection). Significant positive associations were found for wheeze and seasonal rhinitis. An increased risk of current wheeze was found for each antibiotic prescription (adjusted OR 1.07 (95% CI 1.03 to 1.10)) but not for atopy. This was primarily explained by prescriptions for respiratory infections. Similar patterns were observed for seasonal rhinitis. Conclusions: Despite very high rates of recorded early life infections and antibiotic prescriptions, no plausibly causative relationships were found with subsequent respiratory allergies.