Showing papers in "British Medical Bulletin in 2003"

Hazards of heavy metal contamination.

Abstract: The main threats to human health from heavy metals are associated with exposure to lead, cadmium, mercury and arsenic. These metals have been extensively studied and their effects on human health regularly reviewed by international bodies such as the WHO. Heavy metals have been used by humans for thousands of years. Although several adverse health effects of heavy metals have been known for a long time, exposure to heavy metals continues, and is even increasing in some parts of the world, in particular in less developed countries, though emissions have declined in most developed countries over the last 100 years. Cadmium compounds are currently mainly used in re-chargeable nickel-cadmium batteries. Cadmium emissions have increased dramatically during the 20th century, one reason being that cadmium-containing products are rarely re-cycled, but often dumped together with household waste. Cigarette smoking is a major source of cadmium exposure. In non-smokers, food is the most important source of cadmium exposure. Recent data indicate that adverse health effects of cadmium exposure may occur at lower exposure levels than previously anticipated, primarily in the form of kidney damage but possibly also bone effects and fractures. Many individuals in Europe already exceed these exposure levels and the margin is very narrow for large groups. Therefore, measures should be taken to reduce cadmium exposure in the general population in order to minimize the risk of adverse health effects. The general population is primarily exposed to mercury via food, fish being a major source of methyl mercury exposure, and dental amalgam. The general population does not face a significant health risk from methyl mercury, although certain groups with high fish consumption may attain blood levels associated with a low risk of neurological damage to adults. Since there is a risk to the fetus in particular, pregnant women should avoid a high intake of certain fish, such as shark, swordfish and tuna; fish (such as pike, walleye and bass) taken from polluted fresh waters should especially be avoided. There has been a debate on the safety of dental amalgams and claims have been made that mercury from amalgam may cause a variety of diseases. However, there are no studies so far that have been able to show any associations between amalgam fillings and ill health. The general population is exposed to lead from air and food in roughly equal proportions. During the last century, lead emissions to ambient air have caused considerable pollution, mainly due to lead emissions from petrol. Children are particularly susceptible to lead exposure due to high gastrointestinal uptake and the permeable blood-brain barrier. Blood levels in children should be reduced below the levels so far considered acceptable, recent data indicating that there may be neurotoxic effects of lead at lower levels of exposure than previously anticipated. Although lead in petrol has dramatically decreased over the last decades, thereby reducing environmental exposure, phasing out any remaining uses of lead additives in motor fuels should be encouraged. The use of lead-based paints should be abandoned, and lead should not be used in food containers. In particular, the public should be aware of glazed food containers, which may leach lead into food. Exposure to arsenic is mainly via intake of food and drinking water, food being the most important source in most populations. Long-term exposure to arsenic in drinking-water is mainly related to increased risks of skin cancer, but also some other cancers, as well as other skin lesions such as hyperkeratosis and pigmentation changes. Occupational exposure to arsenic, primarily by inhalation, is causally associated with lung cancer. Clear exposure-response relationships and high risks have been observed.

Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment.

Abstract: While characterization of pathogenetic mechanisms underlying major depression is a fundamental aim of neuroscience research, an equally critical clinical goal is to identify biomarkers that might improve diagnostic accuracy and guide treatment selection for individual patients. To this end, a synthesis of functional neuroimaging studies examining regional metabolic and blood flow changes in depression is presented in the context of a testable limbic-cortical network model. 'Network' dysfunction combined with active intrinsic compensatory processes is seen to explain the heterogeneity of depressive symptoms observed clinically, as well as variations in pretreatment scan patterns described experimentally. Furthermore, the synchronized modulation of these dysfunctional limbic-cortical pathways is considered critical for illness remission, regardless of treatment modality. Testing of response-specific functional relationships among regional 'nodes' within this network using multivariate approaches is discussed, with a perspective aimed at identifying biomarkers of treatment non-response, relapse risk and disease vulnerability. Characterization of adaptive and maladaptive functional interactions among these pathways is seen as a critical step towards future development of evidenced-based algorithms that will optimize the diagnosis and treatment of individual depressed patients.

Noise pollution: non-auditory effects on health

Abstract: Noise is a prominent feature of the environment including noise from transport, industry and neighbours. Exposure to transport noise disturbs sleep in the laboratory, but not generally in field studies where adaptation occurs. Noise interferes in complex task performance, modifies social behaviour and causes annoyance. Studies of occupational and environmental noise exposure suggest an association with hypertension, whereas community studies show only weak relationships between noise and cardiovascular disease. Aircraft and road traffic noise exposure are associated with psychological symptoms but not with clinically defined psychiatric disorder. In both industrial studies and community studies, noise exposure is related to raised catecholamine secretion. In children, chronic aircraft noise exposure impairs reading comprehension and long-term memory and may be associated with raised blood pressure. Further research is needed examining coping strategies and the possible health consequences of adaptation to noise.

Executive functions and their disorders.

Abstract: The term executive function defines complex cognitive processing requiring the co-ordination of several subprocesses to achieve a particular goal. Neuropsychological evidence suggests that executive processing is intimately connected with the intact function of the frontal cortices. Executive dysfunction has been associated with a range of disorders, and is generally attributed to structural or functional frontal pathology. Neuroimaging, with PET and fMRI, has confirmed the relationship; however, attempts to link specific aspects of executive functioning to discrete prefrontal foci have been inconclusive. Instead, the emerging view suggests that executive function is mediated by dynamic and flexible networks, that can be characterised using functional integration and effective connectivity analyses. This view is compatible with the clinical presentation of executive dysfunction associated with a range of pathologies, and also with evidence that recovery of executive function can occur after traumatic brain injury, perhaps due to functional reorganisation within executive networks.

Global burden of maternal death and disability

Abstract: Sound information is the prerequisite for health action: without data on the dimensions, impact and significance of a health problem it is neither possible to create an advocacy case nor to establish strong programmes for addressing it. The absence of good information on the extent of the burden of maternal ill-health resulted in its relative neglect by the international health community for many years. Maternal deaths are too often solitary and hidden events that go uncounted. The difficulty arises not because of lack of clarity regarding the definition of a maternal death, but because of the weakness of health information systems and consequent absence of the systematic identification and recording of maternal deaths. In recent years, innovative approaches to measuring maternal mortality have been developed, resulting in a stronger information base. WHO, UNICEF and UNFPA estimates for the year 2000 indicate that most of the total 529,000 maternal deaths globally occur in just 13 countries. By contrast, information on the global burden of non-fatal health outcomes associated with pregnancy and childbearing remains patchy and incomplete. Nonetheless, initial estimates based on systematic reviews of available information and confined to the five major direct pregnancy-related complications indicate a problem of considerable magnitude.

Beyond the Numbers: reviewing maternal deaths and complications to make pregnancy safer

Abstract: 'Whose faces are behind the numbers? What were their stories? What were their dreams? They left behind children and families. They also left behind clues as to why their lives end so early 1 ' Avoiding maternal deaths is possible, even in resource-poor countries, but requires the right kind of information on which to base programmes. Knowing the level of maternal mortality is not enough; we need to understand the underlying factors that led to the deaths. Each maternal death or case of life-threatening complication has a story to tell and can provide indications on practical ways of addressing its causes and determinants. Maternal death or morbidity reviews provide evidence of where the main problems in overcoming maternal mortality and morbidity may lie, produce an analysis of what can be done in practical terms and highlight the key areas requiring recommendations for health sector and community action as well as guidelines for improving clinical outcomes. The information gained from such enquiries must be used as a prerequisite for action.

Sporadic and familial CJD: classification and characterisation

Abstract: Prion diseases are unique transmissible neurodegenerative diseases that have diverse phenotypes and can be familial, sporadic, or acquired by infection. Recent findings indicate that the PrP genotype and the PrP(Sc) type have a major influence on the disease phenotype in both sporadic and familial human prion diseases. This review attempts to classify and characterise sporadic and familial Creutzfeldt-Jakob disease (CJD) as a function of these two disease determinants. Based on the genotype at codon 129 on both PRNP alleles, the size of protease resistant PrP(Sc) fragments and disease phenotype, we divide sporadic CJD into six subtypes: sCJDMM1/sCJDMV1, sCJDVV2, sCJDMV2, sCJDMM2, sCJDVV1, and sporadic fatal insomnia (sFI). Familial CJD is classified into many haplotypes based on the PRNP mutation and codon 129 (and other polymorphic codons) on the mutant allele. The clinical and pathological features are summarised for each sporadic CJD subtype and familial CJD haplotype.

Environmental pollution and the global burden of disease

Abstract: Exposures to environmental pollution remain a major source of health risk throughout the world, though risks are generally higher in developing countries, where poverty, lack of investment in modern technology and weak environmental legislation combine to cause high pollution levels. Associations between environmental pollution and health outcome are, however, complex and often poorly characterized. Levels of exposure, for example, are often uncertain or unknown as a result of the lack of detailed monitoring and inevitable variations within any population group. Exposures may occur via a range of pathways and exposure processes. Individual pollutants may be implicated in a wide range of health effects, whereas few diseases are directly attributable to single pollutants. Long latency times, the effects of cumulative exposures, and multiple exposures to different pollutants which might act synergistically all create difficulties in unravelling associations between environmental pollution and health. Nevertheless, in recent years, several attempts have been made to assess the global burden of disease as a result of environmental pollution, either in terms of mortality or disability-adjusted life years (DALYs). About 8-9% of the total disease burden may be attributed to pollution, but considerably more in developing countries. Unsafe water, poor sanitation and poor hygiene are seen to be the major sources of exposure, along with indoor air pollution.

Indoor air pollution: a global health concern.

Abstract: Indoor air pollution is ubiquitous, and takes many forms, ranging from smoke emitted from solid fuel combustion, especially in households in developing countries, to complex mixtures of volatile and semi-volatile organic compounds present in modern buildings. This paper reviews sources of, and health risks associated with, various indoor chemical pollutants, from a historical and global perspective. Health effects are presented for individual compounds or pollutant mixtures based on real-world exposure situations. Health risks from indoor air pollution are likely to be greatest in cities in developing countries, especially where risks associated with solid fuel combustion coincide with risk associated with modern buildings. Everyday exposure to multiple chemicals, most of which are present indoors, may contribute to increasing prevalence of asthma, autism, childhood cancer, medically unexplained symptoms, and perhaps other illnesses. Given that tobacco consumption and synthetic chemical usage will not be declining at least in the near future, concerns about indoor air pollution may be expected to remain.

Health hazards and waste management

Abstract: Different methods of waste management emit a large number of substances, most in small quantities and at extremely low levels. Raised incidence of low birth weight births has been related to residence near landfill sites, as has the occurrence of various congenital malformations. There is little evidence for an association with reproductive or developmental effects with proximity to incinerators. Studies of cancer incidence and mortality in populations around landfill sites or incinerators have been equivocal, with varying results for different cancer sites. Many of these studies lack good individual exposure information and data on potential confounders, such as socio-economic status. The inherent latency of diseases and migration of populations are often ignored. Waste management workers have been shown to have increased incidence of accidents and musculoskeletal problems. The health impacts of new waste management technologies and the increasing use of recycling and composting will require assessment and monitoring.

Perinatal psychiatric disorders: a leading cause of maternal morbidity and mortality.

Abstract: The Confidential Enquiry into Maternal Deaths 1997 to 1999 finds that psychiatric disorder, and suicide in particular, is the leading cause of maternal death. Suicide accounted for 28% of maternal deaths. Women also died from other complications of psychiatric disorder and a significant minority from substance misuse. Some of the findings of the Confidential Enquiry confirm long established knowledge about postpartum psychiatric disorder. The findings highlight the severity and early onset of serious postpartum mental illness and of the risk of recurrence following childbirth faced by women with a previous history of serious mental illness either following childbirth or at other times. These findings led to the recommendation that all women should be asked early in their pregnancy about a previous history of serious psychiatric disorder and that management plans should be in place with regard to the high risk of recurrence following delivery. Other findings of the Enquiry were new and challenged some of the accepted wisdoms of obstetrics and psychiatry. It is likely that the suicide rate following delivery is not significantly different to other times in women's lives and for the first 42 days following delivery may be elevated. This calls into question the so-called 'protective effect of maternity'. The overwhelming majority of the suicides died violently, contrasting with the usual finding that women are more likely to die from an overdose of medication. Compared to other causes of maternal death, the suicides were older and socially advantaged. The Enquiry findings suggest that the risk profile for women at risk of suicide following delivery may be different to that in women at other times and in men. None of the women who died had been admitted at any time to a Mother and Baby Unit and their psychiatric care had been undertaken by General Adult Services. None of the women who died had had a previous episode correctly identified and none had had adequate plans for their proactive care. The conclusion is that there is a need for both Psychiatry and Obstetrics to acknowledge the substantial risk that women with a previous psychiatric history of serious mental illness face following delivery.

TSE strain variation.

Abstract: Studies in mice have revealed considerable strain variation in the agents causing transmissible spongiform encephalopathies (TSEs). TSE strains interact with genetic factors in the host (in particular PrP genotype) to influence characteristics of the disease such as incubation period and neuropathology. TSE strains can retain their identity after propagation in different host species or PrP genotypes, showing that these agents carry their own strain-specific information. It is not known whether this information resides in specific self-perpetuating modifications of PrP, or whether a separate informational molecule is required. Strain typing in mice can be used to explore links between TSEs occurring naturally in different species. Such studies have demonstrated that the strain causing BSE in cattle has also infected domestic cats and exotic ungulates. Most importantly, the BSE strain has also been isolated from patients with variant CJD. In contrast, different TSE strains are associated with sporadic CJD and sheep scrapie.

Contribution of environmental factors to cancer risk

Abstract: Environmental carcinogens, in a strict sense, include outdoor and indoor air pollutants, as well as soil and drinking water contaminants. An increased risk of mesothelioma has consistently been detected among individuals experiencing residential exposure to asbestos, whereas results for lung cancer are less consistent. At least 14 good-quality studies have investigated lung cancer risk from outdoor air pollution based on measurement of specific agents. Their results tend to show an increased risk in the categories at highest exposure, with relative risks in the range 1.5-2.0, which is not attributable to confounders. Results for other cancers are sparse. A causal association has been established between exposure to environmental tobacco smoke and lung cancer, with a relative risk in the order of 1.2. Radon is another carcinogen present in indoor air which may be responsible for 1% of all lung cancers. In several Asian populations, an increased risk of lung cancer is present in women from indoor pollution from cooking and heating. There is strong evidence of an increased risk of bladder, skin and lung cancers following consumption of water with high arsenic contamination; results for other drinking water contaminants, including chlorination by-products, are inconclusive. A precise quantification of the burden of human cancer attributable to environmental exposure is problematic. However, despite the relatively small relative risks of cancer following exposure to environmental carcinogens, the number of cases that might be caused, assuming a causal relationship, is relatively large, as a result of the high prevalence of exposure.

Near misses: a useful adjunct to maternal death enquiries

Abstract: In developed countries where maternal death is rare, the factors surrounding the death are often peculiar to the event and are not generalizable, making analysis of maternal deaths less useful. Near misses are defined as pregnant women with severe life-threatening conditions who nearly die but, with good luck or good care, survive. Incorporation of near misses into maternal death enquiries would strengthen these audits by allowing for more rapid reporting, more robust conclusions, comparisons to be made with maternal deaths, reinforcing lessons learnt, establishing requirements for intensive care and calculating comparative indices. The survival of a pregnant woman is dependent on the disease, her basic health, the health care facilities and personnel of the health care system. The criteria currently used to identify a near miss vary greatly. However, areas with similar health care facilities, medical records and personnel should be able to agree on suitable criteria, making their incorporation into maternal death enquiries feasible.

Contaminants in drinking water.

Abstract: An adequate supply of safe drinking water is one of the major prerequisites for a healthy life, but waterborne disease is still a major cause of death in many parts of the world, particularly in children, and it is also a significant economic constraint in many subsistence economies. The basis on which drinking water safety is judged is national standards or international guidelines. The most important of these are the WHO Guidelines for Drinking Water Quality. The quality of drinking water and possible associated health risks vary throughout the world with some regions showing, for example, high levels of arsenic, fluoride or contamination of drinking water by pathogens, whereas elsewhere these are very low and no problem. Marked variations also occur on a more local level within countries due, for example, to agricultural and industrial activities. These and others are discussed in this chapter.

Acquired prion disease: iatrogenic CJD, variant CJD, kuru

Abstract: Human prion diseases can be classified as sporadic, hereditary or acquired. The cause of sporadic Creutzfeldt-Jakob disease (CJD) is unknown, hereditary cases are associated with mutations of the prion protein gene (PRNP) and acquired forms are caused by the transmission of infection from human to human or, as a zoonosis, from cattle to human. Although acquired forms of human prion disease are rare, the transmission of a fatal and untreatable neurological disorder has had major implications for public health and public policy.

Air pollution and infection in respiratory illness.

Abstract: The detrimental effects of air pollution on health have been recognized for most of the last century. Effective legislation has led to a change in the nature of the air pollutants in outdoor air in developed countries, while combustion of raw fuels in the indoor environment remains a major health hazard in developing countries. The mechanisms of how these pollutants exert their effects are likely to be different, but there is emerging evidence that the toxic effects of new photochemical pollutants such as nitrogen dioxide are likely to be related to infection. This review discusses the relationship between air pollution and infection and will explore some of the mechanisms of how both could act synergistically to cause respiratory illnesses especially in exacerbating symptoms in individuals with pre-existing respiratory conditions such as asthma and chronic obstructive pulmonary disease.

Pre-eclampsia and the hypertensive disorders of pregnancy

Abstract: Pre-eclampsia is a multisystem disorder, of unknown aetiology, usually associated with raised blood pressure and proteinuria. Although outcome for most women and their babies is good, it remains a major cause of morbidity and mortality. A wide range of interventions for prevention and treatment of pre-eclampsia have been evaluated in randomized trials. This evidence provides the basis for a rational approach to care. Overall, there is insufficient evidence for any firm conclusion about the effects of any aspect of diet or lifestyle during pregnancy. Antiplatelet agents are associated with a 19% reduction in the risk of pre-eclampsia (relative risk 0.81; 95% CI 0.75, 0.88), a 7% reduction in the risk of preterm birth (RR 0.93; 95% CI 0.89, 0.98), a 16% reduction in the risk of stillbirth or neonatal death (RR 0.84; 95% CI 0.74, 0.96) and an 8% reduction in the risk of a small for gestational age baby (RR 0.92; 95% CI 0.85, 1.00). For mild to moderate hypertension, trials evaluating bed rest are too small for reliable conclusions about the potential benefits and hazards. Antihypertensive agents halve the risk of progression to severe hypertension (RR 0.52; 95% CI 0.41, 0.64), but with no clear effect on pre-eclampsia (RR 0.99; 95% CI 0.84, 1.18), or any other substantive outcome. For severe hypertension, there is no good evidence that one drug is any better than another. Plasma volume expansion for severe pre-eclampsia seems unlikely to be beneficial, although the trials are small. The optimum timing of delivery for pre-eclampsia before 34 weeks is unclear. Magnesium sulphate more than halves the risk of eclampsia (RR 0.41; 95% CI 0.29, 0.58) and probably reduces the risk of maternal death (RR 0.54; 95% CI 0.26, 1.10). It is also the drug of choice for treatment of eclampsia.

Ambient air pollution and health

Abstract: The adverse health effects of air pollution became widely acknowledged after severe pollution episodes occurred in Europe and North America before the 1960s. In these areas, pollutant levels have decreased. During the last 15 years, however, consistent results, mainly from epidemiological studies, have provided evidence that current air pollutant levels have been associated with adverse long- and short-term health effects, including an increase in mortality. These effects have been better studied for ambient particle concentrations but there is also substantial evidence concerning gaseous pollutants such as ozone, NO(2) and CO. Attempts to estimate the impact of air pollution effects on health in terms of the attributable number of events indicate that the ubiquitous nature of the exposure results in a considerable public health burden from relatively weak relative risks.

Skilled attendants for pregnancy, childbirth and postnatal care

Abstract: This paper sets out the rationale for ensuring that all pregnant women have access to skilled health care practitioners during pregnancy and childbirth. It describes why increasing access to a skilled attendant, especially at birth, is not only based on legitimate demand and clinical common sense, but is also cost-effective and feasible in resource-poor countries. Skilled attendants need to be supported by a health system providing a legal and policy infrastructure, an effective referral system and the supplies that are necessary for effective care. A skilled attendant providing skilled care will help achieve the goals of reducing both maternal and child mortality. Health care professionals as individual practitioners, leaders and informers have an important role in making this a reality.

Trafficking, turnover and membrane topology of PrP.

Abstract: Cell biological studies of PrP have contributed enormously to our understanding of prion diseases. Like other membrane proteins, PrP(C) is post-translationally processed in the endoplasmic reticulum and Golgi on its way to the cell surface after synthesis. Cell surface PrP(C) constitutively cycles between the plasma membrane and early endosomes via a clathrin-dependent mechanism, a pathway consistent with a suggested role for PrP(C) in cellular trafficking of copper ions. PrP molecules carrying mutations linked to inherited prion diseases display several abnormalities in their biochemical properties, maturation, and localisation that may explain their pathogenicity. Recent results have clarified the role of the proteasome in degradation of PrP, and the properties of a transmembrane form of PrP which may play a neurotoxic role in prion diseases.

Neuropathology of prion diseases

Abstract: In prion diseases, neuropathology has remained the most important tool to give a definite diagnosis, and neuropathological research has contributed significantly to our current pathogenetic understanding. Immunohistochemistry for the disease-associated prion protein (PrP(Sc)) is indispensable for the neuropathological confirmation of prion diseases. The amount and distribution of PrP(Sc) deposits do not always correlate with type and severity of local tissue damage. PrP(Sc) deposition occurs only where neuronal parenchyma is present; in scarred infarctions with prominent gliosis, PrP(Sc) does not accumulate. Early, severe and selective loss affects a subset of inhibitory GABAergic neurons both in human and experimental prion diseases. The central pathogenetic cascade includes oxidative stress to neurons and their apoptosis. New patterns of PrP(Sc) immunoreactivity include granular ganglionic and tiny adaxonal PrP(Sc) deposits in peripheral nervous tissue, and dendritic cells and macrophages in vessel walls, suggesting that mobile haematogenous cells may be involved in spread of prions.

Introduction to the transmissible spongiform encephalopathies or prion diseases.

Abstract: Sheep scrapie has been known for at least 200 years and was described as a transmissible disease over 100 years ago. Since then, three groups of transmissible spongiform encephalopathies or TSE diseases have been identified in humans including familial, infectious and sporadic types. The discovery of the prion protein (PrP) in the 1980s greatly accelerated knowledge of the biology and pathogenesis of TSE diseases as this protein was found to play a critical role in disease susceptibility and the TSE species-barrier and may also be a component of the infectious agent itself. Nevertheless, the nature of the TSE agents remains an enigma. Proof of the protein-only hypothesis may require generation of biologically active transmissible agent in a cell-free environment where a virus cannot replicate. Conversely, proof of a viral aetiology will require identification and isolation of a candidate virus. Further understanding of the structure of the disease-associated protease-resistant PrP should help elucidate the mechanism of PrP conversion from the normal to the abnormal form. Such information should open up new approaches to both diagnosis and therapy.

PrP knock-out and PrP transgenic mice in prion research.

Abstract: Spongiform encephalopathies such as scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle or Creutzfeldt-Jacob disease (CJD) and Gerstmann-Straussler-Scheinker syndrome (GSS) in humans is caused by a transmissible agent designated prion. The 'protein only' hypothesis proposes that the prion consists partly or entirely of a conformational isoform of the normal host protein PrP(C), designated PrP(*)(1) and that the abnormal conformer, when introduced into the organism, causes the conversion of PrP(C) into a likeness of itself. PrP(*) may be congruent with PrP(Sc), a protease-resistant, aggregated conformer of PrP that accumulates mainly in brain of almost all prion-infected organisms. PrP(C) consists of a flexible N-terminal half, comprising Cu(2+)-binding octapeptide repeats, and a globular domain consisting of three alpha-helices, one short antiparallel beta-sheet and a single disulphide bond. It is anchored at the outer cell-surface by a glycosyl phosphatidylinositol (GPI) tail and is present in almost all tissues, however, mainly in brain. Compelling linkage between the prion and PrP was established by biochemical and genetic data and led to the prediction that animals devoid of PrP should be resistant to experimental scrapie and fail to propagate infectivity. This prediction was indeed borne out, adding substantial support to the 'protein only' hypothesis. In addition, the availability of PrP knock-out mice provided an approach to carry out reverse genetics on PrP, both in regard to prion disease and to its physiological role.

The impact of environmental pollution on congenital anomalies.

Abstract: Major congenital anomalies are diagnosed in 2-4% of births. In this paper we review epidemiological studies that have specifically looked at congenital anomalies as a possible outcome of community exposure to chemical exposures associated with environmental pollution. These include studies of drinking water contaminants (heavy metals and nitrates, chlorinated and aromatic solvents, and chlorination by-products), residence near waste disposal sites and contaminated land, pesticide exposure in agricultural areas, air pollution and industrial pollution sources, food contamination, and disasters involving accidental, negligent or deliberate chemical releases of great magnitude. We conclude that there are relatively few environmental pollution exposures for which we can draw strong conclusions about the potential to cause congenital anomalies and, if so, the chemical constituents implicated, to provide an evidence base for public health and clinical practice. A precautionary approach should be adopted at both community and individual level. In order to prevent congenital anomalies, one must reduce exposure to potential teratogens before pregnancy is recognized (i.e. preconceptionally and in the first few weeks of pregnancy). It is a challenge to develop effective strategies for preconceptional care within the primary care framework. Prenatal service providers and counsellors need to be aware of the uncertainties regarding environmental pollution when addressing parental concerns.

Safe motherhood: a brief history of the global movement 1947-2002.

Abstract: The health of mothers has long been acknowledged to be a cornerstone of public health and attention to unacceptably high level of maternal mortality has been a feature of global health and development discussions since the 1980s. However, although a few countries have made remarkable progress in recent years, the reality has not generally followed the rhetoric. Health and development partners have failed to invest seriously in safe motherhood and examples of large-scale and sustained programmes are rare. Safe motherhood has tended to be seen as a subset of other programmes such as child survival or reproductive health and is often perceived to be too complex or costly for under-resourced and overstretched health care systems that have limited capacity. Despite this, a consensus has emerged about the interventions needed to reduce maternal mortality and there are good examples (historical and contemporary) of what can be achieved within a relatively short time period. The activities of both grassroots organizations and international health and development agencies have helped to build political will and momentum. Further progress in improving maternal health will require outspoken and determined champions from within the health system and the medical community, particularly the obstetricians and gynaecologists, and from among decision-makers and politicians. But in addition, substantial and long-term funding--by governments and by donor agencies--is an essential and still missing component.

Language systems in normal and aphasic human subjects: functional imaging studies and inferences from animal studies

Abstract: The old neurological model of language, based on the writings of Broca, Wernicke and Lichtheim in the 19th century, is now undergoing major modifications. Observations on the anatomy and physiology of auditory processing in non-human primates are giving strong indicators as to how speech perception is organised in the human brain. In the light of this knowledge, functional activation studies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are achieving a new level of precision in the investigation of language organisation in the human brain, in a manner not possible with observations on patients with aphasic stroke. Although the use of functional imaging to inform methods of improving aphasia rehabilitation remains underdeveloped, there are strong indicators that this methodology will provide the means to research a very imperfectly developed area of therapy.

Biochemistry and structure of PrPC and PrPSc

Abstract: In a brief historical description, it is shown that the prion model was developed from the biochemical and biophysical properties of the scrapie infectious agent. The biochemical properties of the prion protein which is the major, if not only, component of the prion are outlined in detail. PrP is a host-encoded protein which exists as PrP C (cellular) in the non-infected host, and as PrP Sc (scrapie) as the major component of the scrapie infectious agent. An overview of the purification techniques is given. Although chemically identical, the biophysical features of PrP Sc are drastically different in respect to solubility, structure, and stability; furthermore, specific lipids and a polyglucose scaffold were found in prions, whereas for nucleic acids their absence could be proven. The structure of recombinant PrP in solution is known from spectroscopic studies and with high resolution from NMR analysis. Structural models of PrP Sc were derived recently from electron microscopic analysis of two-dimensional crystals. Conformational transitions of PrP in vitro were studied with different techniques in order to mimic the natural PrP C to PrP Sc conversion. Spontaneous transitions can be induced by solvent changes, but at present infectivity cannot be induced in vitro. The early history of the prion model is the history of the biochemical and biophysical properties of the scrapie infectious agent. In searching for a virus, no viral features were found; however, highly enigmatic properties of the infectious agent were demonstrated, such as absence of particles in the electron microscope, no immune response during the infection, and high resistance of the agent against chemical and physical treatment. As early as 1966 from inactivation studies using ionising and UV-irradiation, Alper et al 1 concluded that the target size of the scrapie infectious agent (50‐150 kDa) is too small for a virus but more characteristic of a protein. Many experimental results were left unexplained until Prusiner took up the inactivation studies and performed systematic analysis using not only chemical and physical, but also enzymatic procedures. He summarized the results under two groups: (i) procedures which modify or destroy nucleic acids do not inactivate scrapie infectivity; and (ii) procedures which modify or destroy proteins inactivate the infectivity. From that, he came to the conclusion that the scrapie infectious agent could not be a virus but a novel

Bovine spongiform encephalopathy (BSE) and its epidemiology

Abstract: Since the recognition of BSE in 1986, over 180,000 cattle in the UK have developed the disease and 1-3 million are likely to have been infected with the BSE agent, most of which were slaughtered for human consumption before developing signs of the disease. The origin of the first case of BSE is unknown, but the epidemic was caused by the recycling of processed waste parts of cattle, some of which were infected with the BSE agent, to other cattle in feed. Control measures have resulted in the consistent decline of the epidemic in the UK since 1992. Cattle and feed exported from the UK have seeded smaller epidemics in other European countries, where control measures were applied later. If the control measures now in place to protect public and animal health are well enforced, the epidemic in cattle should be largely under control and any remaining risk to humans through the consumption of beef should be very small.