Search

Objectives: The Glu to Lys change at codon 200 (E200K) of the PRNP gene is the most frequent mutation associated to genetic Creutzfeldt-Jakob disease (CJD) and the only one responsible for geographical clusters. Patients carrying this mutation develop disease at different ages and show variable clinical phenotypes that are not affected by the methione/valine polymorphism at codon 129 of the PRNP gene suggesting the influence of other factors. The objective of this study is to look for genes other than PRNP that might be responsible of this variability., Methods: We searched for other genes by performing genome-wide analyses (GWA) on 19 patients with genetic CJD and 18 healthy subjects carrying the E200K mutation of PRNP and belonging to the Calabrian cluster in Italy. We then validate this result in 32 patients with E200K CJD from non-cluster areas and 259 patients with sporadic CJD referred to the Italian CJD national registry., Results and Conclusions: We identified two single nucleotide polymorphisms on the CYP4X1  gene locus as candidate disease modifiers in patients with E200K CJD of the cluster area and confirmed this finding in 32 patients with E200K CJD from non-cluster areas and 259 patients with sporadic CJD. Our results indicate that the CYP4X1  gene modulates the onset of disease in patients with E200K genetic and sporadic CJD. This finding improves our understanding on the pathogenesis of CJD, suggests new targets for developing novel therapeutic strategies and might be useful for the stratification of patients in future preventive treatment trials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: In this study we compared duplex Doppler sonography, conventional angiography and CT angiography for the evaluation of hepatic arterial complications following orthotopic liver transplantation (OLT)., Material and Methods: CT angiography, with Maximum Intensity Projection (MIP) and Volume Rendering reconstructions, was performed in 11 patients with well-grounded suspect of hepatic artery stenosis or thrombosis after routine duplex Doppler examination. Eight patients underwent conventional angiography., Results: CT detected three out of four duplex doppler false positives and confirmed the diagnostic suspect in four cases. In two cases it showed a shift of the blood flow towards the splenic artery with hepatic hypoperfusion. In one case a wrong delay rendered the study unuseful. In seven out of eight patients conventional angiography confirmed CT angiography findings. DISCUSSION. The follow up of OLT arterial complications is now performed with duplex doppler sonography; this technique has a satisfactory sensitivity and specificity, but far from 100%. Therefore in some patients the diagnosis of arterial obstruction might be delayed, with the risk of serious complications; in other cases with ultrasonographic false positive findings, useless angiographic examinations are performed. In our experience CT angiography proved to be a precious tool, which might be included in the diagnostic algorithm of arterial complications after OLT. Particularly CT angiography seems to be suitable for the cases of discordance between clinical and duplex doppler findings, to improve the overall diagnostic accuracy., Conclusion: In our experience CT-angiography proved to be accurate and satisfactory as a second step examination after duplex-doppler in the diagnostic algorythm of adult OLT arterial complications.

Two patients with histologically unequivocal Hodgkin's disease (HD) (lymphocyte-depleted type, stage IIIA, and mixed cellularity variety, stage IVA) were found to have, respectively, a serum IgGk M-component and pure Bence Jones proteinuria of the lambda type. Unlike most of the previously reported patients with HD-associated monoclonal gammopathy (MG), they had simultaneous occurrence of HD and M-components, and no evidence of concurrent multiple myeloma or any other related B-lymphoproliferative disorder was found either at presentation or at postmortem examination. Both M-components were demonstrated before starting any cytotoxic treatment, and their appearance was unrelated to other disorders which may be associated with persistent antigenic overstimulation. In both patients the size of the M-components was reduced significantly by treatment for HD. Such findings make these patients of interest for exploring the significance of the coexistence of HD with MG.

The protein patterns of the serum, cerebrospinal fluid and urine from 32 patients with definite multiple sclerosis and 30 control patients with neurological non-demyelinating disorders were simultaneously analyzed by means of high-resolution agarose gel electrophoresis combined with immunofixation. About one-third (31%) of the patients with multiple sclerosis were found to excrete monoclonal free light chains of immunoglobulins, i.e., Bence Jones proteins, in the urine without any concurrent immunoproliferative disease. Bence Jones proteinuria, at concentration generally not exceeding 0.2 g/24 hours, was demonstrated exclusively in multiple sclerosis patients in a phase of active disease (44% of the cases) or in chronic progressive disease (25% of the cases). The results of the study suggest that the presence of Bence Jones protein in the urine from multiple sclerosis patients may be utilized as an indicator of disease activity.

The fortuitous report of the change of serum electrophoretic pattern from the oligoclonal to the monoclonal type in a patient with Hodgkin's disease has been the starting point for some considerations about the physiopathological and clinical significance of the oligoclonal serum pattern. The AA. carry out a critical review of the ordinary electrophoretic methods, underlining some problems related to a good visualization of the oligoclonal serum pattern.