EPIDEMICS
Telehealth systems have a large potential for informing public health authorities in an early stage of outbreaks of communicable disease. Influenza and norovirus are common viruses that cause significant respiratory and gastrointestinal disease worldwide. Data about these viruses are not routinely mapped for surveillance purposes in the UK, so the spatial diffusion of national outbreaks and epidemics is not known as such incidents occur. We aim to describe the geographical origin and diffusion of rises in fever and vomiting calls to a national telehealth system, and consider the usefulness of these findings for influenza and norovirus surveillance.
Data about fever calls (5- to 14-year-old age group) and vomiting calls ([greater than or equal to]5-year-old age group) in school-age children, proxies for influenza and norovirus, respectively, were extracted from the NHS Direct national telehealth database for the period June 2005 to May 2006. The SaTScan space-time permutation model was used to retrospectively detect statistically significant clusters of calls on a week-by-week basis. These syndromic results were validated against existing laboratory and clinical surveillance data.
We identified two distinct periods of elevated fever calls. The first originated in the North-West of England during November 2005 and spread in a south-east direction, the second began in Central England during January 2006 and moved southwards. The timing, geographical location, and age structure of these rises in fever calls were similar to a national influenza B outbreak that occurred during winter 2005-2006. We also identified significantly elevated levels of vomiting calls in South-East England during winter 2005-2006.
Spatiotemporal analyses of telehealth data, specifically fever calls, provided a timely and unique description of the evolution of a national influenza outbreak. In a similar way the tool may be useful for tracking norovirus, although the lack of consistent comparison data makes this more difficult to assess. In interpreting these results, care must be taken to consider other infectious and non-infectious causes of fever and vomiting. The scan statistic should be considered for spatial analyses of telehealth data elsewhere and will be used to initiate prospective geographical surveillance of influenza in England.
- "Tracking the spatial diffusion of influenza and norovirus using telehealth data: a spatio-temporal analysis of syndromic data" Duncan L Cooper , Gillian E Smith , Martyn Regan , Shirley Large and Peter Groenewegen BMC Medicine 2008, 6:16doi:10.1186/1741-7015-6-16
PHARMACOLOGY
For most drug-metabolizing enzymes (DMEs), the functional consequences of genetic polymorphisms have been examined. Variants leading to reduced or increased enzymatic activity as compared to the wild-type alleles have been identified. This review tries to define potential fields in the therapy of major medical conditions where genotyping (or phenotyping) of genetically polymorphic DMEs might be beneficial for drug safety or therapeutic outcome.
The possible application of genotyping is discussed for depression, cardiovascular diseases and thromboembolic disorders, gastric ulcer, malignant diseases and tuberculosis. Some drugs used for relief of these ailments are metabolized with participation of genetically polymorphic DMEs including CYP2D6, CYP2C9, CYP2C19, thiopurine-S-methyltransferase, dihydropyrimidine dehydrogenase, uridine diphosphate glucuronosyltransferase and N-acetyltransferase type 2.
Current evidence suggests that taking genetically determined metabolic capacities of DMEs into account has the potential to improve individual risk/benefit relationship. However, more prospective studies with clinical endpoints are needed before the paradigm of 'personalized medicine' based on DME variants can be established.
- "The clinical role of genetic polymorphisms in drug-metabolizing enzymes" D Tomalik-Scharte, A Lazar, U Fuhr and J Kirchheiner. The Pharmacogenomics Journal (2008) 8, 4-15; doi:10.1038/sj.tpj.6500462; published online 5 June 2007
CELL CULTURES
Cholesterol synthesis in animals is controlled by the regulated transport of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum to the Golgi, where the transcription factors are processed proteolytically to release active fragments. Transport is inhibited by either cholesterol or oxysterols, blocking cholesterol synthesis. Cholesterol acts by binding to the SREBP-escort protein Scap, thereby causing Scap to bind to anchor proteins called Insigs.
Here, we show that oxysterols act by binding to Insigs, causing Insigs to bind to Scap. Mutational analysis of the six transmembrane helices of Insigs reveals that the third and fourth are important for Insig's binding to oxysterols and to Scap.
These studies define Insigs as oxysterol-binding proteins, explaining the long-known ability of oxysterols to inhibit cholesterol synthesis in animal cells.
- "Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Oxysterols block transport by binding to Insig" Arun Radhakrishnan. PNAS PNAS April 17, 2007 vol. 104 no. 16 pp. 6511-6518
