The influence of hepatic impairment on the pharmacokinetics of paliperidone.

OBJECTIVES: This study assessed the impact of hepatic impairment on the pharmacokinetics (PK) of paliperidone and its enantiomers. METHODS: A single 1 mg dose of paliperidone immediate-release (IR) was administered to subjects with moderate hepatic impairment (n = 10) and demographically matched individuals with normal hepatic function (n = 10). RESULTS: Plasma protein binding was lower in hepatically impaired subjects resulting in a 27% higher unbound fraction of paliperidone compared with healthy individuals. After correcting for the difference in plasma protein binding, unbound exposures were comparable between groups. All other PK parameters were similar between the two groups. Paliperidone IR was equally well tolerated in both groups. CONCLUSIONS: The impact of moderate hepatic impairment on paliperidone PK is not considered clinically relevant as the PK profile of unbound paliperidone is similar for subjects with moderate hepatic impairment and those with normal hepatic function. Dosage adjustments of paliperidone are not required in subjects with mild or moderate hepatic impairment.

[Retrobulbar optic neuritis associated with Infliximab]. / Neuritis óptica desmielinizante tras tratamiento con Infliximab.

CASE REPORT: We report the case of a 76-year-old woman who attended our hospital because of a sudden loss of visual acuity in her left eye. The problem appeared to be that of retrobulbar optic neuritis. However, the age of the patient together with the simultaneous use of Infliximab to treat her rheumatoid arthritis, suggests the demyelination may have been associated with the Infliximab use. DISCUSSION: TNFa inhibitors (including Infliximab) are associated with demyelinating diseases including optic neuritis.

Position-specific effect of ribonucleotides on the cleavage activity of human topoisomerase II.

Beyond the normal DNA transactions mediated by topoisomerase II, we have recently demonstrated that the cleavage activity of the two human topoisomerase II isoforms is several-fold stimulated if a ribonucleotide rather than a deoxyribonucleotide is present at the scissile phosphodiester in one strand of the substrate. Here we show that ribonucleotides exert a position-specific effect on topoisomerase II-mediated cleavage without altering the sequence specificity of the enzyme. Ribonucleotides located within the 4 bp cleavage stagger stimulate topoisomerase II-mediated cleavage, whereas ribonucleotides located outside the stagger in general have an inhibitory effect. Results obtained from competition experiments indicate that the position-specific effect of ribonucleotides on topoisomerase II activity is caused by altered substrate interaction. When cleavage is performed with substrates containing one ribonucleotide in both strands or several ribonucleotides in one strand the effect of the individual ribonucleotides on cleavage is not additive. Finally, although topoisomerase II recognizes substrates with longer stretches of ribonucleotides, an RNA/DNA hybrid where one strand is composed entirely of RNA is not cleaved by the enzyme. The positional effect of ribonucleotides on topoisomerase II-mediated cleavage shares many similarities to the positional effect exerted by either abasic sites or base mismatches, demonstrating a general influence of DNA imperfections on topoisomerase II activity.

[Multiple sphincterotomies in the surgical treatment of cataracts in narrow pupils]. / Esfinterotomías múltiples en la cirugía de la catarata en pupila estrecha.

Deficient mydriasis of diverse etiology renders extracapsular cataract extraction and posterior chamber intraocular lens implantation technically difficult. Several techniques are available to improve surgical results when this problem is present. We have used multiple sphincterotomies in 6 patients with narrow pupils undergoing cataract extraction. We discuss the indications, intraoperative complications and postoperatory evolution of these cases.

Phenotypic characterization of the marine pathogen Photobacterium damselae subsp. piscicida.

The taxonomic position of Photobacterium damselae subsp. piscicida, the causative agent of fish pasteurellosis, is controversial as this organism has also been described as 'Pasteurella piscicida'. To clarify the taxonomic position of the pathogen, a total of 113 P. damselae subsp. piscicida strains and 20 P. damselae subsp. damselae strains, isolated from different geographical areas and from the main affected fish species, were analysed using 129 morphological and biochemical tests, including the commercial API 20E and API CH50 test systems. For comparison, the type strains of other Photobacterium species (i.e. Photobacterium leiognathi and Photobacterium angustum) were included in the analyses. The results were statistically analysed by unweighted pair group average clustering and the distance between the different clusters was expressed as the percentage disagreement. The analyses showed that, based on morphological and biochemical identification tests, P. damselae subsp. piscicida is related to other Photobacterium species. However, it is clearly distinguishable from P. damselae subsp. damselae and no phenotypic evidence was found to include P. damselae subsp. piscicida as a subspecies in the species P. damselae.

Epidemiology of hepatitis C in Belgium: present and future.

Based on currently available epidemiological data, Belgium appears to belong to the low endemicity countries for hepatitis C, with an estimated annual incidence of 3/100,000 clinical cases; a survey among the Flemish population showed an overall seroprevalence of 0.87% (1993-1994). There was no statistically significant difference in anti-HCV prevalence between men and women. A significant increase of the anti-HCV prevalence with increasing age was observed. In the French Community there was an overall seroprevalence of 0.6%. Developing surveillance for hepatitis C has proven to be difficult, since it requires confirmation tests. Techniques detecting hepatitis C antibodies in saliva will replace the need for serum samples, making prevalence studies more accessible.

Application of AFLP for taxonomic and epidemiological studies of Photobacterium damselae subsp. piscicida.

A collection of 106 Photobacterium damselae subsp. piscicida strains and 19 Photobacterium damselae subsp. damselae strains, including reference and type strains, were genetically characterized using AFLP. The total genomic DNA of each bacterial strain was digested using restriction endonucleases HindIII and TaqI. Using numerical analysis, six clusters were recognized. The largest cluster (n = 106) contained the majority of the strains tested and consisted exclusively of Photobacterium damselae subsp. piscicida. The Photobacterium damselae subsp. damselae strains fell outside this cluster. DNA-DNA hybridization experiments showed 77% DNA binding between the two subspecies, indicating a close genetic relationship. This clearly demonstrates the applicability of AFLP in studying the taxonomic position of Photobacterium damselae subsp. piscicida. In addition, AFLP proved to be a useful genotypic technique for epidemiological surveys of the pathogen, since it was able to discriminate between Mediterranean and Japanese Photobacterium damselae subsp. piscicida isolates.

Esfinterotomías múltiples en la cirugía de la catarata en pupila estrecha / Multiple sphincterotomies in the surgical treatment of cataracts in narrow pupils

Deficient mydriasis of diverse etiology renders extracapsular cataract extraction and posterior chamber intraocular lens implantation technically difficult. Several techniques are available to improve surgical results when this problem is present. We have used multiple sphincterotomies in 6 patients with narrow pupils undergoing cataract extraction. We discuss the indications, intraoperative complications and postoperatory evolution of these cases