Wolfe Tone’s death: Suicide or assassination?

The final events of Wolfe Tone’s short and stormy life are fairly common knowledge. He was captured on board the French flagshipHoche when the vessel surrendered to a superior British naval force off Lough Swilly on October 10, 1798. Despite his protests that he was entitled to normal prisoner-of-war treatment, he was brought in irons a month later to Dublin. A court martial was hurriedly convened and he was found guilty of treason on Saturday November 10 and condemned to be hanged two days later. According to the generally accepted version of subsequent events he cut his own throat early on the Monday morning. The assistant surgeon of the 5th Dragoon Guards dressed the wound “ — but only with a view to prolong life until the fatal hour of one o’clock”. This surgeon was Benjamin Lentaigne, a Royalist emigre from France. Despite the pleas of John Philpott Curran, a leading advocate of the day, the military authorities refused to allow any consultation with a civil surgeon. Was this just bloody mindedness or was there an even more sinister reason? Two possibilities come to mind. One was that the wound had been so incompetently treated that a consultant would have been forced to make adverse comments, the other that the throat wound was not due to a cutting injury but, to a bullet fired either deliberately or accidently and a knife or razor was then used to try and camouflage the original trauma. In 1812 Lentaigne published a pamphlet in Latin in which he made reference to an unusual neck would stating that “— the bullet passed through his throat...” There is no direct evidence that the victim was Tone, why did the writer not make this clear? It may be he was reluctant to expose the medico-military inefficiency or callousness or to jeopardise his son’s career. Whatever the true facts, the verdict must remain the Scots one of “Not proven”.     

The effect of pressurized carbon dioxide as a temporary plasticizer and foaming agent on the hot stage extrusion process and extrudate properties of solid dispersions of itraconazole with PVP-VA 64.

The aim of the current research project was to explore the possibilities of combining pressurized carbon dioxide with hot stage extrusion during manufacturing of solid dispersions of itraconazole and polyvinylpyrrolidone-co-vinyl acetate 64 (PVP-VA 64) and to evaluate the ability of the pressurized gas to act as a temporary plasticizer as well as to produce a foamed extrudate. Pressurized carbon dioxide was injected into a Leistritz Micro 18 intermeshing co-rotating twin-screw melt extruder using an ISCO 260D syringe pump. The physicochemical characteristics of the extrudates with and without injection of carbon dioxide were evaluated with reference to the morphology of the solid dispersion and dissolution behaviour and particle properties. Carbon dioxide acted as plasticizer for itraconazole/PVP-VA 64, reducing the processing temperature during the hot stage extrusion process. Amorphous dispersions were obtained and the solid dispersion was not influenced by the carbon dioxide. Release of itraconazole from the solid dispersion could be controlled as a function of processing temperature and pressure. The macroscopic morphology changed to a foam-like structure due to expansion of the carbon dioxide at the extrusion die. This resulted in increased specific surface area, porosity, hygroscopicity and improved milling efficiency.     

HLA-DPB1 gene polymorphism and multiple sclerosis: a large case-control study in the southwest of France

The polymorphism at the HLA-DPB1 locus has been characterized in a large number of patients with multiple sclerosis (n = 112) and in healthy controls (n = 115). Both patients and controls lived in the southwest of France (in the Pyrénées Atlantiques) and had similar ethnic background. The typing procedure involved the selective amplification of the second exon of the DPB1 locus by polymerase chain reaction, followed by hybridization of the amplified DNA with 14 sequence-specific oligonucleotide probes. Individual alleles were identified by the pattern of hybridization of the different probes. The distribution of the DPB1 alleles was not significantly different in multiple sclerosis patients and controls (p = 0.11). This does not corroborate the reported association of multiple sclerosis with the primed lymphocyte typing (PLT)-defined DPw4 specificity and is not in favour of a role played by polymorphic residues of the DP molecule in susceptibility to multiple sclerosis.     

Usher syndrome: clinical findings and gene localization studies

The issue of genetic heterogeneity is a critical problem in the localization of the gene(s) for Usher syndrome. Based on the data obtained on families studied to date, the differences between type I and type II Usher syndrome appear quite distinct with regard to auditory and vestibular function. Although the majority of families can be confidently diagnosed as typical type I or type II, clinical investigations revealed four families with findings that did not fit into either of the two more common subtypes. These findings emphasize the critical importance of an in-depth clinical analysis concomitant with the linkage investigation to assure accurate subtyping of Usher syndrome. Based on an analysis of only those families with definite type I or type II Usher syndrome, approximately 17% of the genome can be excluded as a potential site of the gene for type I, and 14% can be excluded as the site for the type II gene. This study will continue until the Usher gene(s) is successfully localized.