Search PubMed⌕ Search

Biomedical subjects

E Griffiths

Publications and source records attributed to E Griffiths.

At least 19 recordsLinked to original sources

Dietetic guidelines on food and nutrition in the secondary prevention of cardiovascular disease - evidence from systematic reviews of randomized controlled trials (second update, January 2006).

AIM: To update dietetic guidelines based on systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention). METHODS: The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to January 2005 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomized controlled trials relating to diet and secondary prevention of CVD. Each review was critically appraised by at least two members of the UK Heart Health and Thoracic Dietitians Group. The quality and results of each review were discussed and summarized at a group meeting. RESULTS: Evidence-based strategies that reduce cardiovascular events in those with CVD include reduction in saturated fat and substitution with unsaturated fats. Individuals who have suffered a myocardial infarction may also benefit from adopting a Mediterranean type diet and increasing intake of omega 3 fats, but it is not clear whether they are beneficial for all patients with CVD. There is no systematic review evidence to support the use of antioxidant vitamins supplements, low glycaemic index diets, or homocysteine lowering therapies in this group. CONCLUSION: There remains good evidence that reducing saturated fat reduces morbidity in patients with CVD. This advice is consistent for most manifestations of CVD, with the addition of Mediterranean dietary advice and increased omega 3 fats for those who have had a myocardial infarction.

Antioxidants↗

Dietetic guidelines: diet in secondary prevention of cardiovascular disease (first update, June 2003).

AIM: To update dietetic guidelines summarizing the systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention). METHODS: The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to November 2002 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomised controlled trials relating to diet and secondary prevention of CVD. Two members of the UK Heart Health and Thoracic Dietitians Group critically appraised each review. The quality and results of each review were discussed and summarized in a meeting of the whole group. RESULTS: Providing evidence-based dietary information (including increasing omega-3 fat intake) to all people who have had a myocardial infarction will save more lives than concentrating dietary advice on just those in need of weight loss or lipid lowering. The practice of prioritizing dietetic time in secondary prevention to those with raised lipids is out of date since the advent of statin therapy. However, effective dietary advice for those with angina, stroke, peripheral vascular disease or heart failure is less clear. CONCLUSION: There is good systematic review evidence that dietary advice to those with coronary heart disease can reduce mortality and morbidity as well as modify some risk factors. Dietary advice that does this most effectively should be prioritized.

Cardiovascular Diseases↗

Report of a WHO workshop on the standardization and control of antivenoms.

A workshop to discuss progress in the standardization and control of antivenoms, organized by the Quality Assurance and Safety of Biologicals Unit of WHO, was held at the National Institute for Biological Standards and Control, Potters Bar, England, 7-9 February 2001. This was the first meeting convened by the WHO on this subject since 1979 and it brought together experts from academic institutions, antivenom manufacturers and national regulatory authorities from 21 countries. The meeting reviewed antivenom production and quality control measures and special consideration was given to the current crisis in antivenom production and supply in sub-Saharan Africa. The importance of snake bite and scorpion stings as public health issues was re-emphasised. The majority of commercial antivenoms are raised against snake or scorpion venoms.The review of antivenom production methods indicated that the vast majority of commercial antivenoms were still produced by traditional technology in horses, although some antisera were raised in sheep and rabbits. Methods used for plasma fractionation included salt and heat coagulation, caprylic acid stabilization or ion exchange chromatography, as well as immunoglobulin digestion with pepsin to produce F(ab')(2) or with papain to produce Fab fragments. The meeting agreed that there was much room for improving the production, quality control and safety profile of these products and that lessons could be learnt from the experience gained with the preparation of human immunoglobulins. Many basic assumptions, such as the need to remove Fc fragments by enzyme digestion and to freeze-dry antivenom preparations, required critical re-examination and more attention should be given to clinical trials as a means of assessing efficacy and safety and of defining the average initial dose. The Workshop also discussed concerns about the risks of transmitting infectious agents to humans via animal blood products, especially those posed by viruses or prions and it was agreed that this aspect needed attention. However, there was no documented or even suspected example of this ever having occurred in the case of antivenom treatment. Current WHO Requirements for the production and control of antivenoms and for immune sera of animal origin date from the late 1960s. The Workshop recommended that these be updated to take account of the progress that had taken place in the production and quality control of biologicals in recent years. In addition, the Workshop discussed the need for better standardization of both the venoms and antivenoms, but concluded that international standards and reference materials were not appropriate in the antivenom field due to the considerable variation in venom characteristics from the same species from region to region. Instead, it was recommended that national or regional standards be prepared and used.

Animals↗

The global impact of vaccines containing aluminium adjuvants.

Immunization against childhood vaccine-preventable diseases has arguably had the greatest impact on the health of children of any public health intervention. Many of the vaccines used in the Expanded Programme on Immunization (EPI) have contained aluminium-based adjuvants. As such, these adjuvants have played a vital role in enabling the basic vaccines to be used effectively. DTP global supply is fragile and could easily be upset through the loss of even one major vaccine manufacturer. Non-aluminium adjuvants could not readily replace aluminium adjuvants. New generation vaccines will probably need new generation adjuvants. The impact of vaccines with adjuvants is discussed. Having provided decades of reliable, safe service in their relatively simple chemical formulations, adjuvants are likely to be with us, in one form or another, for the indefinite future.

Adjuvants, Immunologic↗

Ensuring vaccine safety in immunization programmes--a WHO perspective.

Ever since vaccines were firstly used against smallpox, adverse events following immunization have been reported. As immunization programmes expand to reach even the most remote communities in the poorest countries, it is likely that many more events will be temporally linked with vaccine administration. Furthermore, the profound shift in the general public and media interest in adverse events may lead to undue concerns and allegations which may ultimately jeopardize immunization programmes world-wide. While the health professional has understood this issue for some time, the public and the media have now also become all too aware of the significance of vaccine-related adverse events. The familiar vaccines, well-tested over decades, have not changed--but the perception regarding their safety has shifted. Claims outrageous or reasonable are being made against both the old and the newly-introduced vaccines. At the same time, the immunological and genetic revolution of the last decade may well bring to our notice some hypothetical risks that need to be addressed at pre-clinical level. WHO has been at the leading edge to guarantee vaccine safety for the last 30 years and will continue to do so. The Organization's plans for the next decade and beyond include the Safe Injection Global Network (SIGN), the development and introduction of safer technologies, and the prevention, early detection and management of AEFIs. The new technologies include needle-containing injection devices such as the autodisable syringe, as well as mucosal and transcutaneous immunization. Training will continue to be at the centre of WHO's efforts, limiting human error to a minimum. Mechanisms have been set in place to detect and respond to new and unforeseen events occurring. Above all, there is a willingness to respond to new climates and new technologies so that the Organization is in the best position to ensure safe immunization for all the world's children.

Drug Contamination↗

CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling.

The regulation of tyrosine phosphorylation and associated signalling through antigen, growth-factor and cytokine receptors is mediated by the reciprocal activities of protein tyrosine kinases and protein tyrosine phosphatases (PTPases). The transmembrane PTPase CD45 is a key regulator of antigen receptor signalling in T and B cells. Src-family kinases have been identified as primary molecular targets for CD45 (ref. 4). However, CD45 is highly expressed in all haematopoietic lineages at all stages of development, indicating that CD45 could regulate other cell types and might act on additional substrates. Here we show that CD45 suppresses JAK (Janus kinase) kinases and negatively regulates cytokine receptor signalling. Targeted disruption of the cd45 gene leads to enhanced cytokine and interferon-receptor-mediated activation of JAKs and STAT (signal transducer and activators of transcription) proteins. In vitro, CD45 directly dephosphorylates and binds to JAKs. Functionally, CD45 negatively regulates interleukin-3-mediated cellular proliferation, erythropoietin-dependent haematopoieisis and antiviral responses in vitro and in vivo. Our data identify an unexpected and novel function for CD45 as a haematopoietic JAK phosphatase that negatively regulates cytokine receptor signalling.

Animals↗

Bacterial toxins and enteral feeding of premature infants at risk for necrotizing enterocolitis.

Concordance between gram-negative enteric and other toxin-producing bacteria in blood and stool culture, endotoxin (lipopolysaccharide), and interleukin 6 (IL-6) was measured in 60 preterm infants (600-1600 g) as a clinical index in neonatal necrotizing enterocolitis (NEC). Escherichia coli, Klebsiella, Enterobacter, and Clostridium spp, identified by routine bacteriology, were each strongly associated with elevated concentrations of endotoxin (P < 0.01) in stool filtrates with Clostridium spp most strongly associated with NEC disease. Stool filtrate endotoxin (endotoxin units [EU] per gram) measured by a Limulus amebocyte lysate assay was age-dependent. Samples from stage I NEC (61%) and infants with advanced disease (67%) had notably elevated levels of stool endotoxin (>10 ln EU/g) compared with NEC-negative (47%) samples tested. Plasma and stool IL-6 generally tested at the low, nonmeasurable limit of the enzyme-linked immunosorbent assay (ELISA) for NEC-negative (88%) and stage I NEC (93%), although a small proportion of samples (25%) from infants with stage II or II NEC had elevated stool concentrations of IL-6. We conclude that identification of toxin-producing organisms and endotoxin elevations in stool filtrates are more useful than circulating levels of endotoxin in plasma in predicting mucosally limited disease in the gastrointestinal tract. The prognostic value of monitoring stool endotoxin in infants with overgrowth of gram-negative bacteria has implications for therapeutic strategies for patients with early and advanced stages of disease. Monitoring inflammatory cytokines (IL-6) in relation to endotoxin values in stool appears of limited clinical value in controlling this devastating disease in preterm neonates.

Bacterial Toxins↗

Assuring the quality, safety, and efficacy of DNA vaccines.

Scientists in academia whose research is aimed at the development of a novel vaccine or approach to vaccination may not always be fully aware of the regulatory process by which a candidate vaccine becomes a licensed product. It is useful for such scientists to be aware of these processes as the development of a novel vaccine could be problematic owing to the starting material often being developed in a research laboratory under ill-defined conditions. This paper examines the regulatory process with respect to the development of a DNA vaccine. DNA vaccines present unusual safety considerations that must be addressed during preclinical safety studies, including adverse immunopathology, genotoxicity through integration into a vaccinees chromosomes, and the potential for the formation of anti-DNA antibodies.

Animals↗

WHO Expert Committee on Biological Standardization: highlights of the 50th meeting, October 1999.

Biological medicines, which include vaccines, blood products and biological therapeutics, have historically played a dominant role in improving world health and are expected to make an increasingly important contribution to public health in the 21st century. Recent scientific and biotechnological developments have opened the way to novel products, new production methods and to highly sensitive assay procedures. However, the nature of biologicals, and especially new vaccines, blood products and therapeutics, raises particular questions regarding their standardization and quality control. These relate both to efficacy and to safety not only for the individual recipient but also for the population at large. Such advances highlight the complex issues surrounding standardization and control of biologicals, issues that need to be addressed on an international level.

Biological Factors↗

Sepsis: the critical role of iron.

Sepsis is a global problem which is exacerbated by increasing bacterial resistance to antibiotics. However, mechanisms of natural resistance can be extremely effective, and need to be exploited, but the availability of iron is critical for controlling bacterial growth. The diagnosis of sepsis and possible strategies for limiting iron availability are discussed.

Animals↗

New challenges in assuring vaccine quality.

In the past, quality control of vaccines depended on use of a variety of testing methods to ensure that the products were safe and potent. These methods were developed for vaccines whose safety and efficacy were based on several years worth of data. However, as vaccine production technologies have developed, so have the testing technologies. Tests are now able to detect potential hazards with a sensitivity not possible a few years ago, and an increasing array of physicochemical methods allows a much better characterization of the product. In addition to sophisticated tests, vaccine regulation entails a number of other procedures to ensure safety. These include characterization of starting materials by supplier audits, cell banking, seed lot systems, compliance with the principles of good manufacturing practices, independent release of vaccines on a lot-by-lot basis by national regulatory authorities, and enhanced pre- and post-marketing surveillance for possible adverse events following immunization. These procedures help assure vaccine efficacy and safety, and some examples are given in this article. However, some contaminants of vaccines that can be detected by newer assays raise theoretical safety concerns but their presence may be less hazardous than not giving the vaccines. Thus risk-benefit decisions must be well informed and based on scientific evidence.

Humans↗