Use of anticholinergic drugs in older patients. / Bruk av legemidler med antikolinerg virkning hos eldre.

Many medicines prescribed for older patients have an unintended anticholinergic effect in addition to the primary intended effect. This may lead to adverse reactions such as dizziness and memory loss, particularly in older people. Before prescribing new medicines, it is therefore important to assess the total anticholinergic burden by means of specific screening tools, such as AGS Beers Criteria® and the STOPP/START criteria. If the anticholinergic burden is high, drugs should be replaced or discontinued.

[Contraception for women taking antiepileptic drugs]. / Prevensjon for kvinner som bruker antiepileptika.

Most women of fertile age want safe contraception. This is especially important for women with epilepsy, as some antiepileptic drugs may have harmful effects on the foetus. When hormonal contraception is combined with antiepileptic drugs, it is essential to be aware that certain antiepileptic drugs may reduce the efficacy of hormonal contraceptives and vice versa, which may result in a reduced effect for both drugs. Non-hormonal contraception, such as the copper coil and barrier methods may, however, be used safely in this patient group.

Evolutionary history and functional characterization of three large genes involved in sporulation in Bacillus cereus group bacteria.

The Bacillus cereus group of bacteria is a group of closely related species that are of medical and economic relevance, including B. anthracis, B. cereus, and B. thuringiensis. Bacteria from the Bacillus cereus group encode three large, highly conserved genes of unknown function (named crdA, crdB, and crdC) that are composed of 16 to 35 copies of a repeated domain of 132 amino acids at the protein level. Bioinformatic analysis revealed that there is a phylogenetic bias in the genomic distribution of these genes and that strains harboring all three large genes mainly belong to cluster III of the B. cereus group phylogenetic tree. The evolutionary history of the three large genes implicates gain, loss, duplication, internal deletion, and lateral transfer. Furthermore, we show that the transcription of previously identified antisense open reading frames in crdB is simultaneously regulated with its host gene throughout the life cycle in vitro, with the highest expression being at the onset of sporulation. In B. anthracis, different combinations of double- and triple-knockout mutants of the three large genes displayed slower and less efficient sporulation processes than the parental strain. Altogether, the functional studies suggest an involvement of these three large genes in the sporulation process.

Reference genes for quantitative, reverse-transcription PCR in Bacillus cereus group strains throughout the bacterial life cycle.

Quantitative reverse-transcription PCR (RT-qPCR) has become a major tool to better understand the biology and pathogenesis of bacteria. One prerequisite of valid RT-qPCR data is their proper normalization to stably expressed reference genes. To identify and evaluate reference genes suitable for normalization of gene expression data in Bacillus cereus group strains, mRNA levels of eleven candidate reference genes (rpsU, nifU, udp (UDP-N-acetylglucosamine 2-epimerase), BT9727_5154/BC_5475, BT9727_4034/BC_4293, BT9727_4549/BC_4813, pspA, gatB_Yqey (gatB_Yqey domain containing protein), helicase (SWF/SNF family protein), adk and pta) and a target gene (BT9727_3305/BC3547+BC3546) were quantified by RT-qPCR at different time points throughout the entire life cycle of the wild-type B. cereus ATCC 14579 and Bacillus thuringiensis subsp. konkukian 97-27, a phylogenetically closely related strain to Bacillus anthracis. The programs geNorm and Normfinder were used to calculate expression stabilities and identified the genes gatB_Yqey, rpsU and udp as the most stably expressed reference genes. Compared to this combination or the sets of reference genes as recommended by geNorm or Normfinder, normalization using a traditional housekeeping gene (adk) alone resulted in significantly different gene expression results and in a significant overestimation of the target gene transcription. Normalization of the data to the reference gene gatB_Yqey alone showed no or only small differences to the reference gene combinations indicating that gatB_Yqey may be used as a single reference gene when investigating rather large changes in mRNA transcription. Otherwise, a combination of the stably expressed reference genes is recommended. In conclusion, the present study underlines the importance of normalization to stably expressed reference genes and presents valid endogenous controls suitable for normalization of transcriptional data throughout the life cycle of B. cereus group strains.

How many antibiotic prescriptions are unsubsidised in New Zealand?

AIMS: To determine the proportion of prescriptions for antibiotics which were unsubsidised, in one town in one year, and to use this to develop a model which could be used to estimate the number of unsubsidised prescriptions. METHODS: Data on all prescriptions for antibiotics during 2002 were extracted from pharmacy computers in one town. Data were obtained from PharmHouse database on all subsidised prescriptions from the town pharmacies during 2002. (The PharmHouse database is a subset of the New Zealand Health Information System database and contains records of all the claims for medicines dispensed within New Zealand.) These were compared and the proportion of unsubsidised prescriptions for each antibiotic calculated. Weighted linear regression was used to develop a model of the relationship between the percentage of each drug subsidised, and patient and prescription characteristics obtainable in PharmHouse. RESULTS: 64.4% of antibiotic dispensings in the study town were subsidised, and therefore captured by the PharmHouse database. The proportion varied substantially between different antibiotics. For particular drugs, the proportion of drugs unsubsidised could be predicted by the price of the drug, the number of days it was prescribed for, and the number of patients aged under six who received subsidised prescriptions. CONCLUSIONS: Previous studies using PharmHouse data are likely to have significantly underestimated the extent of drug use. Further research is needed on whether this model can help to estimate the extent of unsubsidised prescriptions.

Unusual group II introns in bacteria of the Bacillus cereus group.

A combination of sequence and structure analysis and reverse transcriptase PCR experiments was used to characterize the group II introns in the complete genomes of two strains of the pathogen Bacillus cereus. While B. cereus ATCC 14579 harbors a single intron element in the chromosome, B. cereus ATCC 10987 contains three introns in the chromosome and four in its 208-kb pBc10987 plasmid. The most striking finding is the presence in B. cereus ATCC 10987 of an intron [B.c.I2(a)] located on the reverse strand of a gene encoding a putative cell surface protein which appears to be correlated to strains of clinical origin. Because of the opposite orientation of B.c.I2(a), the gene is disrupted. Even more striking is that B.c.I2(a) splices out of an RNA transcript corresponding to the opposite DNA strand. All other intragenic introns studied here are inserted in the same orientation as their host genes and splice out of the mRNA in vivo, setting the flanking exons in frame. Noticeably, B.c.I3 in B. cereus ATCC 10987 represents the first example of a group II intron entirely included within a conserved replication gene, namely, the alpha subunit of DNA polymerase III. Another striking finding is that the observed 3' splice site of B.c.I4 occurs 56 bp after the predicted end of the intron. This apparently unusual splicing mechanism may be related to structural irregularities in the 3' terminus. Finally, we also show that the intergenic introns of B. cereus ATCC 10987 are transcribed with their upstream genes and do splice in vivo.