Dramatic clinical response to ultra-high dose IVIg in otherwise treatment resistant inflammatory neuropathies

Background Intravenous immunoglobulin (IVIg) has short and long-term efficacy in both chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy with conduction block (MMNCB). There is potential for under and over-treatment if trial regimens are strictly adhered to in clinical practice where titrating dose to clinical response is recommended. Methods We report the response to high-dose IVIg (>2 g/kg/6 weeks) in a subgroup of patients with definite CIDP or MMNCB who were unresponsive to ‘usual’ dosing. IVIg frequency and dosing was determined for each individual by subjective and objective outcome measures for impairment, grip strength, and activity and participation. Results Six patients (three with chronic inflammatory demyelinating polyneuropathy (CIDP), three with MMN) were included. Two patients (one CIDP and one MMNCB) returned to full-time work on fractionated IVIg doses of 5 g/kg/month and 9 g/kg/month. Patient three (CIDP) failed numerous other immunosuppressants but responded to short-term fractionated 4 g/kg/month of IVIg. Patient four has severe, refractory, childhood-onset CIDP, remains stable but dependent currently on 6.9 g/kg/month of IVIg. Patients five and six, both with MMNCB, required short term 4.5–5 g/kg/month to recover significant bilateral hand strength. No IVIg-related adverse events occurred in any individual. Conclusions These six cases demonstrate the safety and effectiveness of a treatment approach that includes individualised but evidence-based clinical assessment and, when necessary, high-doses of IVIg to restore patients’ strength and ability to participate in activities of daily activities. Careful patient selection is important

Discovery of a polyomavirus in European badgers (Meles meles) and the evolution of host range in the family Polyomaviridae.

Polyomaviruses infect a diverse range of mammalian and avian hosts, and are associated with a variety of symptoms. However, it is unknown whether the viruses are found in all mammalian families and the evolutionary history of the polyomaviruses is still unclear. Here, we report the discovery of a novel polyomavirus in the European badger (Meles meles), which to our knowledge represents the first polyomavirus to be characterized in the family Mustelidae, and within a European carnivoran. Although the virus was discovered serendipitously in the supernatant of a cell culture inoculated with badger material, we subsequently confirmed its presence in wild badgers. The European badger polyomavirus was tentatively named Meles meles polyomavirus 1 (MmelPyV1). The genome is 5187 bp long and encodes proteins typical of polyomaviruses. Phylogenetic analyses including all known polyomavirus genomes consistently group MmelPyV1 with California sea lion polyomavirus 1 across all regions of the genome. Further evolutionary analyses revealed phylogenetic discordance amongst polyomavirus genome regions, possibly arising from evolutionary rate heterogeneity, and a complex association between polyomavirus phylogeny and host taxonomic groups

Prevalence of depressive disorders in the elderly

Community-based mental health studies have revealed that the point prevalence of depressive disorders in the elderly population of the world varies between 10% and 20%, depending on cultural situations. A retrospective study based on analysis of various study reports was conducted, to determine the median prevalence rates of depressive disorders in the elderly population of India and various other countries in the world. All the studies that constituted the sample were conducted between 1955 and 2005. Included are only community-based, cross-sectional surveys and some prospective studies that had not excluded depression at baseline. These studies were conducted on a homogenous community of the elderly population in the world, who were selected by a simple random sampling technique. After applying the inclusion and exclusion criteria on published and indexed articles, 74 original research studies that surveyed a total of 487 275 elderly individuals, in the age group of 60 years and above, residing in various parts of the world, were included for the final analysis. The median prevalence rate and its corresponding interquartile range were calculated. The chi-square test and chi-square for linear trend were applied. A P value of <.05 was considered as statistically significant. The median prevalence rate of depressive disorders in the world for the elderly population was determined to be 10.3% (interquartile range [IQR], 4.7%-16.0%). The median prevalence rate of depression among the elderly Indian population was determined to be 21.9% (IQR, 11.6%–31.1%). Although there was a significant decrease in the trend of world prevalence of geriatric depression, it was significantly higher among Indians, in recent years, than the rest of the world

Transfer of genetic therapy across human populations: molecular targets for increasing patient coverage in repeat expansion diseases

Allele-specific gene therapy aims to silence expression of mutant alleles through targeting of disease-linked single-nucleotide polymorphisms (SNPs). However, SNP linkage to disease varies between populations, making such molecular therapies applicable only to a subset of patients. Moreover, not all SNPs have the molecular features necessary for potent gene silencing. Here we provide knowledge to allow the maximisation of patient coverage by building a comprehensive understanding of SNPs ranked according to their predicted suitability toward allele-specific silencing in 14 repeat expansion diseases: amyotrophic lateral sclerosis and frontotemporal dementia, dentatorubral-pallidoluysian atrophy, myotonic dystrophy 1, myotonic dystrophy 2, Huntington’s disease and several spinocerebellar ataxias. Our systematic analysis of DNA sequence variation shows that most annotated SNPs are not suitable for potent allele-specific silencing across populations because of suboptimal sequence features and low variability (&gt;97% in HD). We suggest maximising patient coverage by selecting SNPs with high heterozygosity across populations, and preferentially targeting SNPs that lead to purine:purine mismatches in wild-type alleles to obtain potent allele-specific silencing. We therefore provide fundamental knowledge on strategies for optimising patient coverage of therapeutics for microsatellite expansion disorders by linking analysis of population genetic variation to the selection of molecular targets