Randomised controlled trial of gabapentin in Complex Regional Pain Syndrome type 1 [ISRCTN84121379]

Background  

Complex Regional Pain Syndrome type one (CRPS I) or formerly Reflex Sympathetic Dystrophy (RSD) is a disabling syndrome, in which a painful limb is accompanied by varying symptoms. Neuropathic pain is a prominent feature of CRPS I, and is often refractory to treatment. Since gabapentin is an anticonvulsant with a proven analgesic effect in various neuropathic pain syndromes, we sought to study the efficacy of the anticonvulsant gabapentin as treatment for pain in patients with CRPS I.     

Somatic cell mutations at the glycophorin a locus in erythrocytes of radiation workers from the Sellafield nuclear facility

The glycophorin A (GPA) somatic mutation assay for N0 and NN mutant erythrocytes was performed on 245 current and 48 retired workers who had been occupationally exposed to radiation at the British Nuclear Fuels plc facility at Sellafield. A positive association with increasing age was found for current workers for both N0 and NN frequencies of 0.14 +/- 0.05 x 10(-6) (P = 0.012) and 0.25 +/- 0.07 x 10(-6) (P = 0.0003) per year, respectively. No association with age was found for the retired workers. In a comparison of ever-smokers with never-smokers, no difference was observed for N0 frequencies for current workers, but a significantly higher frequency was found for ever-smokers in the retired group (P = 0.001). NN mutant frequencies were slightly higher in ever-smokers than in never-smokers for both current and retired workers, but in neither case was the increase significant. In age-adjusted analyses for N0 mutant frequencies, a slight positive radiation dose response was found for current workers (1.6 +/- 3.8 x 10(-6) per Sv), for retired workers (2.9 +/- 2.5 x 10(-6) per Sv), and in the combined analysis (2.6 +/- 2.2 x 10(-6) per Sv), but in no case did this reach significance. Similar analyses for NN mutant frequencies revealed a positive dose response for current workers (4.7 +/- 4.6 x 10(-6) per Sv) and a negative response for retired workers (-2.4 +/- 3.6 x 10(-6) per Sv) that was maintained in the combined analysis (-1.4 +/- 2.8 x 10(-6) per Sv), but none of these slopes was significantly different from zero. The results suggest that the GPA mutation assay is insufficiently sensitive to be used as a biological marker of low-dose chronic exposure and provide further evidence that, in contrast to high acute radiation exposure, protracted exposure is much less effective at inducing somatic mutations in vivo.     

Polymorphisms of the DNA repair gene XRCC1 and the frequency of somatic mutations at the glycophorin A locus in newborns

Essential oils extracted from the three medicinal plants; Helichrysum italicum, Ledum groenlandicum and Ravensara aromatica, together with their mixture were tested for their genotoxic and antigenotoxic activities against urethane, a well-known promutagen. We have adopted the somatic mutations and recombination test (SMART) in the wings of Drosophila melanogaster. Three days old larvae, trans-heterozygous for two genetic markers mwh and flr, were treated by essential oil and/or urethane. A negative control corresponding to solvent was also used. Our results do not show any significant effect of the oils tested but they reduce the mutation ratio resulting from urethane. The mixture of the three oils at equal volume seems to be the most effective. The antimutagenic effect of these oils could be explained by the interaction of their constituents with cytochrome P-450 activation system leading to a reduction of the formation of the active metabolite. The effect could also be attributed to certain molecules that are involved in these oils.     

Modular architecture of the hexameric human mitochondrial DNA helicase

We have probed the structure of the human mitochondrial DNA helicase, an enzyme that uses the energy of nucleotide hydrolysis to unwind duplex DNA during mitochondrial DNA replication. This novel helicase shares substantial amino acid sequence and functional similarities with the bacteriophage T7 primase-helicase. We show in velocity sedimentation and gel filtration analyses that the mitochondrial DNA helicase exists as a hexamer. Limited proteolysis by trypsin results in the production of several stable fragments, and N-terminal sequencing reveals distinct N and C-terminal polypeptides that represent minimal structural domains. Physical analysis of the proteolytic products defines the region required to maintain oligomeric structure to reside within amino acid residues approximately 405-590. Truncations of the N and C termini affect differentially DNA-dependent ATPase activity, and whereas a C-terminal domain polypeptide is functional, an N-terminal domain polypeptide lacks ATPase activity. Sequence similarity and secondary structural alignments combined with biochemical data suggest that amino acid residue R609 serves as the putative arginine finger that is essential for ATPase activity in ring helicases. The hexameric conformation and modular architecture revealed in our study document that the mitochondrial DNA helicase and bacteriophage T7 primase-helicase share physical features. Our findings place the mitochondrial DNA helicase firmly in the DnaB-like family of replicative DNA helicases.     

Chromosomal abnormalities among offspring of childhood-cancer survivors in Denmark: a population-based study

Ionizing radiation and many cancer drugs have the potential to produce germ-cell mutations that might lead to genetic disease in the next generation. In a population-based study, we identified, from records in the Danish Cancer Registry, 4,676 children treated for cancer. Their 6,441 siblings provided a comparison cohort. The results of a search of the Central Population Register identified 2,630 live-born offspring of the survivors and 5,504 live-born offspring of their siblings. The occurrence of abnormal karyotypes diagnosed in these offspring and also in any pregnancies terminated following prenatal diagnosis of a chromosome abnormality was determined from the Danish Cytogenetic Registry. After exclusion of hereditary cases and inclusion of the prenatal cases, after correction for expected viability, the adjusted proportion of live-born children in survivor families with abnormal karyotypes (5.5/2,631.5 [0.21%]) was the same as that among the comparison sibling families (11.8/5,505.8 [0.21%]). There were no significant differences in the occurrence of Down syndrome (relative risk [RR]=1.07; 95% CI 0.16-5.47) or Turner syndrome (RR=1.32; 95% CI 0.17-7.96) among the children of cancer survivors, compared with the children of their siblings. These reassuring results are of importance to the survivors, to their families, and to genetic counselors.     

Herd-level risk factors associated with the presence of Phage type 21/28 E. coli O157 on Scottish cattle farms

Background  

E. coli O157 is a bacterial pathogen that is shed by cattle and can cause severe disease in humans. Phage type (PT) 21/28 is a subtype of E. coli O157 that is found across Scotland and is associated with particularly severe human morbidity.