Objective To compare the methodological quality and conclusions in Cochrane reviews with those in industry supported meta-analyses and other meta-analyses of the same drugs. Design Systematic review comparing pairs of meta-analyses that studied the same two drugs in the same disease and were published within two years of each other. Data sources Cochrane Database of Systematic Reviews (2003, issue 1), PubMed, and Embase. Data extraction Two observers independently extracted data and used a validated scale to judge the methodological quality of the reviews. Results 175 of 1596 Cochrane reviews had a meta-analysis that compared two drugs. Twenty four meta-analyses that matched the Cochrane reviews were found: eight were industry supported, nine had undeclared support, and seven had no support or were supported by non-industry sources. On a 0-7 scale, the median quality score was 7 for Cochrane reviews and 3 for other reviews (P < 0.01). Compared with industry supported reviews and reviews with undeclared support, Cochrane reviews had more often considered the potential for bias in the review-for example, by describing the method of concealment of allocation and describing excluded patients or studies. The seven industry supported reviews that had conclusions recommended the experimental drug without reservations, compared with none of the Cochrane reviews (P = 0.02), although the estimated treatment effect was similar on average (z = 0.46, P = 0.64). Reviews with undeclared support and reviews with not for profit support or no support had conclusions that were similar in cautiousness to the Cochrane reviews. Conclusions Industry supported reviews of drugs should be read with caution as they were less transparent, had few reservations about methodological limitations of the included trials, and had more favourable conclusions than the corresponding Cochrane reviews.

In an effort to develop a porcine model of Alzheimer's disease we used handmade cloning to produce seven transgenic Göttingen minipigs. The donor fibroblasts had been stably transfected with a plasmid cassette containing, as transgene, the cDNA of the neuronal variant of the human amyloid precursor protein gene with the Swedish mutation preceded by beta-globin sequences to induce splicing and a human PDGF beta promoter fragment to drive transcription. Transgene insertion had occurred only at the GLIS3 locus where a single complete copy of the transgene was identified in intronic sequences in opposite direction. Similar and robust levels of the transgene transcript were detected in skin biopsies from all piglets and the sequence of full-length transcript was verified. Consistent with PDGF beta promoter function, high levels of transgene expression, including high level of the corresponding protein, was observed in brain tissue and not in heart or liver tissues. A rough estimate predicts that accumulation of the A beta peptide in the brain may develop at the age of 1-2 years.

We describe a new human isoform, GFAP⑀, of the intermediary filament protein GFAP (glial fibrillary acidic protein). GFAP⑀ mRNA is the result of alternative splicing and a new polyadenylation signal, and thus GFAP⑀ has a new C-terminal protein sequence. This provides GFAP⑀ with the capacity for specific binding of presenilin proteins in yeast and in vitro. Our observations suggest a direct link between the presenilins and the cytoskeleton where GFAP⑀ is incorporated. Mutations in GFAP and presenilins are associated with Alexander disease and Alzheimer's disease, respectively. Accordingly, GFAP⑀ should be taken into consideration when studying neurodegenerative diseases.

The iodine intake level of the population is of major importance for the occurrence of thyroid disorders in an area. The aim of the present study was to evaluate the importance of drinking water iodine content for the known regional differences in iodine intake in Denmark and for the iodine content of infant formulas.Iodine in tap water obtained from 55 different locations in Denmark varied from <1.0 to 139 mg/l. In general the iodine content was low in Jutland (median 4.1 mg/l) with higher values on Sealand (23 mg/l) and other islands. Preparation of coffee or tea did not reduce the iodine content of tap water with a high initial iodine concentration. A statistically significant correlation was found between tap water iodine content today and the urinary iodine excretion measured in 41 towns in 1967 (r = 0.68, P < 0.001). The correlation corresponded to a basic urinary iodine excretion in Denmark of 43 mg/24 h excluding iodine in water and a daily water intake of 1.7 l. The iodine content of infant formulas prepared by addition of demineralized water varied from 37 to 138 mg/l (median 57 mg/l, n = 18). Hence the final iodine content would depend heavily on the source of water used for preparation.We found that iodine in tap water was a major determinant of regional differences in iodine intake in Denmark. Changes in water supply and possibly water purification methods may influence the population iodine intake level and the occurrence of thyroid disorders.