CNV and nervous system diseases - what's new?

Several new genomic disorders caused by copy number variation (CNV) of genes whose dosage is critical for the physiological function of the nervous system have been recently identified. Dup(7)(q11.23) patients carry duplications of the genomic region deleted in Williams-Beuren syndrome, they are characterized by prominent speech delay. The phenotypes of Potocki-Lupski syndrome and MECP2 duplication syndrome were neuropsychologically examined in detail, which revealed autism as an endophenotype and a prominent behavioral feature of these disorders. Tandem duplication of LMNB1 was reported to cause adult-onset autosomal dominant leukodystrophy. PAFAH1B1/LIS1 and YWHAE, which were deleted in isolated lissencephaly (PAFAH1B1/LIS1 alone) and Miller-Dieker syndrome (both genes), were found to be duplicated in patients with developmental delay. Finally, two novel microdeletion syndromes affecting 17q21.31 and 15q13.3, as well as their reciprocal duplications, were also identified. In this review, we provide an overview of the phenotypic manifestation of these syndromes and the rearrangements causing them. Copyright (C) 2009 S. Karger AG, Base

Histopathology of the gut in rheumatic diseases

The gastrointestinal tract regulates the trafficking of macromolecules between the environment and the host through an epithelial barrier mechanism and is an important part of the immune system controlling the equilibrium between tolerance and immunity to non-self-antigens. Various evidence indicates that intestinal inflammation occurs in patients with rheumatic diseases. In many rheumatic diseases intestinal inflammation appears to be linked to dysbiosis and possibly represents the common denominator in the pathogenesis of different rheumatic diseases. The continuative interaction between dysbiosis and the intestinal immune system may lead to the aberrant activation of immune cells that can re-circulate from the gut to the sites of extraintestinal inflammation as observed in patients with ankylosing spondylitis. The exact contribution of genetic factors in the development of intestinal inflammation in rheumatic diseases needs to be clarified

The Immune System

Modern biotherapy has been in use for some 30 years. The first types of biotherapy were nonspecific stimulators of the immune response, but advances in genetic engineering are allowing the mass production of pure biological products which are now being tested as pharmaceutical agents. Biotherapy connotes the administration of products (1) that are coded by the mammalian genome; (2) that modify the expression of mammalian genes; or (3) that stimulate the immune system. In this chapter the discussion of the immune system will be limited primarily to topics relevant to cancer or autoimmune diseases. Because understanding the new biological agents requires an understanding of both the immune response and the molecular basis of oncogenesis, this chapter first presents a summary of the structure and function of the immune system. Following a discussion of immune responses, and the cells involved in these responses, will be a discussion on the current concepts of oncogenesis, particularly oncogenes and growth factors. Because research efforts are beginning to identify many biological proteins as having a role in autoimmune and other diseases, a brief introduction to autoimmune diseases is also included at the end of the chapter

Crop protection in organic agriculture - a simple matter?

This report was presented at the UK Organic Research 2002 Conference. Crop protection strategies in organic agriculture and horticulture aim to prevent pest, disease and weed problems through optimisation of the cropping system as a whole. Choice of crops and varieties within the rotation and use of appropriate husbandry practices are critical to the success of the system and direct curative action against pests and diseases is rarely necessary. Research is urgently needed to determine strategies for control of key pests and diseases in organic systems if UK organic agriculture is to expand to meet increasing consumer demand. This paper describes current prevention and control strategies for pests, diseases and weeds in UK organic agriculture and identifies problems that are currently limiting expansion of the industry

Glucocorticoids—All-Rounders Tackling the Versatile Players of the Immune System

Glucocorticoids regulate fundamental processes of the human body and control cellular functions such as cell metabolism, growth, differentiation, and apoptosis. Moreover, endogenous glucocorticoids link the endocrine and immune system and ensure the correct function of inflammatory events during tissue repair, regeneration, and pathogen elimination via genomic and rapid non-genomic pathways. Due to their strong immunosuppressive, anti-inflammatory and anti-allergic effects on immune cells, tissues and organs, glucocorticoids significantly improve the quality of life of many patients suffering from diseases caused by a dysregulated immune system. Despite the multitude and seriousness of glucocorticoid-related adverse events including diabetes mellitus, osteoporosis and infections, these agents remain indispensable, representing the most powerful, and cost-effective drugs in the treatment of a wide range of rheumatic diseases. These include rheumatoid arthritis, vasculitis, and connective tissue diseases, as well as many other pathological conditions of the immune system. Depending on the therapeutically affected cell type, glucocorticoid actions strongly vary among different diseases. While immune responses always represent complex reactions involving different cells and cellular processes, specific immune cell populations with key responsibilities driving the pathological mechanisms can be identified for certain autoimmune diseases. In this review, we will focus on the mechanisms of action of glucocorticoids on various leukocyte populations, exemplarily portraying different autoimmune diseases as heterogeneous targets of glucocorticoid actions: (i) Abnormalities in the innate immune response play a crucial role in the initiation and perpetuation of giant cell arteritis (GCA). (ii) Specific types of CD4+ T helper (Th) lymphocytes, namely Th1 and Th17 cells, represent important players in the establishment and course of rheumatoid arthritis (RA), whereas (iii) B cells have emerged as central players in systemic lupus erythematosus (SLE). (iv) Allergic reactions are mainly triggered by several different cytokines released by activated Th2 lymphocytes. Using these examples, we aim to illustrate the versatile modulating effects of glucocorticoids on the immune system. In contrast, in the treatment of lymphoproliferative disorders the pro-apoptotic action of glucocorticoids prevails, but their mechanisms differ depending on the type of cancer. Therefore, we will also give a brief insight into the current knowledge of the mode of glucocorticoid action in oncological treatment focusing on leukemia

Vaccines: Propaganda and Practice

Vaccines are a cost effective, time tested means of reducing morbidity and mortality. As more and more new vaccines are introduced and more diseases come under the purview of ‘vaccination net’, the routine immunization program is sidelined.\ud This is compounded by vaccination practices in private health care system and anti vaccine propaganda and confusing pro vaccine propaganda. The primary purpose of the vaccine is shifting from prevention of diseases to monetary gains for the health care providers and manufacturers. There is a need to regulate the vaccination practices in the private health care system especially in the developing countries. The regulatory process should educate not only the community but also the health care providers and take adequate measures to control the ‘vaccine market forces

The Occupational Safety and Health Act of 1970 and the Law of Torts

INTRODUCTION: A patients needs and the seriousness of the disease are not the only factors that determine referral to hospital. The objective of this study was to analyse whether locum doctors (LDs) have a different pattern of referral to hospital from regular GPs (RGPs). METHODS: All hospital referrals for one year (n = 5566 patients) from two Norwegian rural primary health care (PHC) centres to the nearby district hospital were analysed with regard to ICD-10 diagnosis groups. A major difference between the PHCs was that one had a continuous supply of LDs while the other had a stable group of RGPs. The equal-sized communities were demographically and socio-culturally similar. RESULTS: The PHC centre mainly operated by short-term LDs referred a relatively high number of patients to the district hospital within the diagnosis groups of chapter VI Diseases of the nervous system (proportionate referral rate 210%; p = 0.010), and chapter IX Diseases of the circulatory system (proportionate referral rate 130%; p = 0.048), and a comparatively low number of patients for the diagnostic groups in chapter X Diseases of the respiratory system (p = 0.018), and chapter XIV Diseases of the genitourinary system (p = 0.039), compared with the norm of the district hospitals total population. The number and proportion of the total number of referrals, adjusted for population size, did not differ between the two rural communities. The LD-run PHC centre differed significantly from the total norm in 5 out of 19 ICD chapters, equal to 41% of the patients. CONCLUSIONS: Only one significant difference in hospital referrals related to ICD-diagnoses groups were found between the studied rural PHC centres, but the LD-run PHC differed from the total norm. These differences could neither be explained from the districts consumption of somatic hospital care nor the demographical differences, but were related to staffing at the PHC, that is LDs or RGPs. The analysis also revealed that possible under- and/or over-diagnosing of certain diseases occurred, both having potential medical consequences for the patient, as well as increasing healthcare expenditure