Books on the topic 'GBS infection'

Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are both immune-mediated diseases of the peripheral nervous system that typically present with symmetric, progressive muscle weakness, areflexia, and sensory symptoms or signs. GBS evolves rapidly with a nadir at 2–4 weeks usually with an antecedent viral illness, while CIDP progresses more slowly over months to years. GBS is sometimes complicated by life-threatening respiratory failure or dysautonomia. Onset of GBS and relapse of CIDP can occur during pregnancy or postpartum. But with appropriate supportive care and immunotherapy, maternal and fetal outcome in both conditions is typically excellent. The exception is fetal outcome in GBS triggered by maternal CMV or Zika infection transmitted to the fetus. Full-term vaginal delivery and regional anesthesia are preferred in maternal GBS and CIDP, but if C-section and general anesthesia are indicated, non-depolarizing agents such as succinylcholine should be avoided.

Group B Streptococcus (GBS) is a leading cause of early neonatal infection and neonatal mortality, with long-term adverse neurodevelopmental outcomes in up to 50% of survivors of GBS meningitis. GBS has a likely underappreciated role in causing preterm birth and stillbirth. GBS colonizes the vagina and gastrointestinal tract of the pregnant woman, and transmission to the infant occurs during or just before delivery. Although the majority of these infants do not develop invasive disease, maternal colonization is a prerequisite for early onset disease (0–6 days of life, most commonly associated with sepsis and respiratory distress) and a significant risk factor for late onset disease (7–89 days of life, most commonly associated with sepsis and meningitis). The introduction of intrapartum antibiotic prophylaxis has resulted in significant declines in the incidence of early onset disease but provides no protection against late onset disease.

This chapter describes the microbiology of clostridial infection as it applies to Emergency Medicine, and in particular the Primary FRCEM examination. The chapter outlines the key details of the source, clinical features, and principles of treatment and prevention of clostridial colitis, clostridial gas gangrene, and tetanus. This chapter is laid out exactly following the RCEM syllabus, to allow easy reference and consolidation of learning.

Verocytotoxin (VT)-producing Escherichia coli (VTEC), also known as Shiga toxin producing E. coli (STEC), are zoonotic agents, which cause a potentially fatal illness whose clinical spectrum includes diarrhoea, haemorrhagic colitis, and the haemolytic uraemic syndrome (HUS). VTEC are of serious public health concern because of their association with large outbreaks and with HUS, which is the leading cause of acute renal failure in children. Although over 200 different OH serotypes of VTEC have been associated with human illness, the vast majority of reported outbreaks and sporadic cases of VTEC-infection in humans have been associated with serotype O157:H7.VTs constitute a family of related protein subunit exotoxins, the major ones implicated in human disease being VT1, VT2, and VT2c. Following their translocation into the circulation, VTs bind to endothelial cells of the renal glomeruli, and of other organs and tissues via a specific receptor globotriosylceramide (Gb 3), are internalized by a process of receptor-mediated endocytosis, and cause subcellular damage that results in the characteristic microangiopathic disease observed in HUS.The incubation period of VTEC-associated illness is about 3–5 days. After ingestion VTEC (especially of serotype O157:H7) multiply in the bowel and colonize the mucosa of probably the large bowel with a characteristic attaching and effacing (AE) cytopathology. Colonization is followed by the translocation of VTs into the circulation and the subsequent manifestation of disease.The majority of patients with uncomplicated VTEC infection recover fully with general supportive measures. Historically, the case-fatality rate was high for HUS. However, improvement in the treatment of renal failure and the attendant biochemical disturbances has substantially improved the outlook, although long-term sequelae may develop.Ruminants, especially cattle, are the main reservoirs of VTEC. Infection is acquired through the ingestion of contaminated food, especially under-cooked hamburger, through direct contact with animals, via contaminated water or environments, or via personto-person transmission.The occurrence of large outbreaks of food-borne VTEC-associated illness has promoted close scrutiny of this zoonoses at all levels in the chain of transmission, including the farm, abattoir, food processing, packaging and distribution plants, the wholesaler, the retailer and the consumer. While eradication of VTEC O157 at the farm may not be an option, interventions to increase animal resistance or to decrease animal exposure are being developed and validated. Hazard Analysis and Critical Control Programmes are being implemented in the processing sector and appear to be associated with temporal decreases in VTEC serotype O157 illness in humans. Education programmes targeting food handling procedures and hygiene practices are being advocated at the retail and consumer level. Continued efforts at all stages from the farm to the consumer will be necessary to reduce the risk of VTEC-associated illness in humans.

The collection contains the scientific works of the All-Russian Scientific and Practical conference «Epidemiological surveillance of current infections: new threats and challenges», held by the FBIS «Academician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology» of Rospotrebnadzor in honor of the 100th anniversary of the outstanding scientist I. N. Blokhina, who headed the Institute for 44 years. Leading scientists and specialists from 57 scientific and practical institutions of Rospotrebnadzor, healthcare, education and other organizations from 32 regions of Russia and foreign countries took part in the compilation of the materials. The materials of the collection present the results of scientific research on the epidemiology of current infections, including the use of GIS technologies, methods of molecular epidemiology and bioinformatics, achievements in the field of diagnostics, molecular genetic and molecular biological studies of pathogens of bacterial and viral nature, in the study of human immune defense mechanisms, means of ensuring biological safety, general and population ecology of microorganisms of various biosystems, a number of aspects of biotechnology of immunobiological drugs, etc A separate section of the collection is devoted to new threats to the safety of the population, among them the most relevant is the pandemic of a new coronavirus infection. The collection contains materials on the results of studies on the pathogenesis, epidemiology, clinic and diagnosis of COVID-19. The conference materials will be useful for both scientific and practical employees of Rospotrebnadzor institutions, other ministries and departments involved in the work of the system of anti-epidemic protection of the population, as well as epidemiologists, microbiologists, virologists, biotechnologists, etc. working in various fields of science, education and practical health care. Scientific articles are published in the author’s edition.

Antiglomerular basement membrane (anti-GBM) disease may present as rapidly progressive glomerulonephritis alone, or in the presence of a secondary pulmonary insult (e.g. smoking or other toxicity, or infection) in combination with lung haemorrhage. Rarely it presents as lung disease alone (with haematuria) or as subacute glomerulonephritis. The major differential diagnoses are small vessel vasculitis, which is a more common cause of pulmonary haemorrhage with rapidly progressive glomerulonephritis, and causes of simultaneous pulmonary and renal failure. For most of these, the lung lesion is not pulmonary haemorrhage. The diagnosis often most quickly, most sensitively, specifically and usefully made by renal biopsy, but immunoassays showing a high titre of anti-GBM antibodies in the setting of severe renal disease are also useful. Borderline and even normal anti-GBM titres are not so specific or reliable in some forms of the disease though.

The spectrum of “poststreptococcal” movement disorders and other behavioral abnormalities has expaanded and the array of neuropsychiatric features associated with rheumatic fever (RF) has been broadened. However, it is difficult to establish a causal link between Group A Streptococcus (GAS) and neuropsychiatric symptoms beyond RF, which has fuelled a long-lasting, and still unsolved, debate as to whether putative “poststreptococcal” disorders such as the PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection) phenotype are distinct entities or not. This chapter provides an up-to-date overview of the conditions that are well established (Sydenham’s chorea) or proposed (poststreptococcal tic and obsessive-compulsive disorders) as secondary to an immune response toward GAS.

“Can’t intubate, can’t oxygenate” crises and aspiration of gastric contents are important hazards in anaesthesia, and may result in the death of relatively young and healthy patients. Airway difficulties may manifest at the end of anaesthesia as well as at induction and are commoner in emergency departments and intensive care settings than during anaesthesia in operating rooms. Elements of poor management characterize the majority of airway complications. Emergency cricothyroidotomy performed by anaesthetists is associated with a high rate of failure. Other important hazards associated with anaesthesia may involve excessive or inadequate levels of oxygen or carbon dioxide in the blood, hypertension or hypotension, hypothermia or hyperthermia (including malignant hyperpyrexia), hypovolaemia, embolism of gas or thrombus, awareness, infection, and injury to the peripheral or central nervous system, or the eyes. Stroke and postoperative cognitive dysfunction may be particularly devastating for patients. These hazards are typically increased in low- and middle-income countries. The World Federation of Societies of Anaesthesiologists and the World Health Organization have endorsed international standards for a safe practice of anaesthesia, which are structured to reflect different levels of resource. The Lifebox Foundation seeks to improve the safety of surgery and anaesthesia in resource-constrained areas, notably by closing the substantial global gap in pulse oximetry. Several hazards are integral to the occupation of anaesthesia, including certain infections, increased rates of suicide, and medico-legal risks. In the end, the best way to mitigate these risks is through focusing on the safety of our patients.

The stories behind drug discovery are fascinating, full of human and scientific interest. This is a book on the history of drug discovery that highlights the intellectual splendor of discoverers as well as the human frailty associated them. History is replete with examples of breakthrough medicines that have saved millions of lives. Ether as an anesthetic by Morton; penicillin as an antibiotic by Fleming; and insulin as an anti-diabetic by Banting are just a few examples. The discoverers of these medicines are doubtlessly benefactors to mankind--for instance, without penicillin, 75% of us probably would not be alive because some of our parents or grandparents would have succumbed to infections. Dr. Jack Li, a medicinal chemist who is intimately involved with drug discovery, has assembled an astounding amount of facts and information behind important drugs through extensive literature research and interviews with many inventors of the drugs including Viagra and Lipitor. There have been many myths and inaccuracies associated with those legendary drugs. The inventors perspectives afforded this book an invaluable accuracy and insight because history is not history unless it is true. The text is supplemented by many anecdotes, pictures and postage stamps. Both specialist and layman will find Laughing Gas, Viagra, and Lipitor informative and entertaining. Students in chemistry, pharmacy, and medicine, workers in healthcare and high school science teachers will find this book most useful.

Crescent formation refers to the appearance of proliferating cells in Bowman’s space in response to severe glomerular inflammation. Any aggressive ‘nephritic’ diseases that cause basement membrane breaks may provoke this. Specific serum proteins appear to be responsible for provoking crescent formation as it is largely abolished by defibrination in animal models. The cells in the crescent are initially mostly hypertrophying and proliferating parietal epithelial cells that normally line Bowman’s capsule. Foci of proliferation of these cells (extracapillary proliferation) are the first steps of crescent formation. Monocytes are frequently seen in established crescents. At this stage recovery of glomerular structure and function is possible in many circumstances. However, if Bowman’s capsule is ruptured, fibroblast ingress followed by fibrosis and glomerulosclerosis are likely. Crescentic nephritis is a histological description, but it fits closely with the clinical picture of rapidly progressive glomerulonephritis (RPGN), in which renal function is lost over days to weeks. The diseases most likely to cause this clinical picture are small vessel vasculitis, anti-GBM disease, lupus nephritis, and post-infectious glomerulonephritis. Any ‘nephritic’ disease may provoke crescent formation, but it is frequently encountered in immunoglobulin A nephropathy/Henoch–Schönlein purpura, and in post-infective glomerulonephritis. Recognizing the clinical picture is important as aggressive immunosuppression can be effective in saving glomerular function in some of the conditions causing it.

Individuals appear to be predisposed to antiglomerular basement membrane (anti-GBM) disease by carrying a predisposing human leucocyte antigen type, DRB1*1501 being identified as the highest risk factor, and there are likely to be other predisposing genes or influences on top of which a relatively rare ‘second hit’ leads to the development of autoimmunity. In anti-GBM disease this appears to have a self-perpetuating, accelerating component, that may be to do with antibodies and altered antigen presentation. Lymphocyte depletion may also predispose to the disease. A number of second hits have been identified and they seem to share a theme of damage to the glomerulus. There may be a prolonged (months to years) and usually subclinical phase in anti-GBM disease in which usually relatively low level antibody titres are associated with variable haematuria, sometimes minor pulmonary haemorrhage, but often no symptoms. Damage to the lung seems to determine whether there is a pulmonary component to the disease. Without pulmonary damage caused typically by smoking, inhalation of other fumes, and potentially infection or oxygen toxicity, the disease remains an isolated kidney disease. Antibodies appear to be an important component of the disease, but cell-mediated immunity is also critical to the clinical picture. In animal models, cell-mediated immunity triggered by the GBM antigen can cause severe renal damage in the absence of pathogenic antibody. The development of specific antibody also requires T-cell sensitization and help, and suppressing the response is likely to require suppressing both antibody and cell-mediated immunity. Antibodies recognize one major and some other epitopes, which are now well described. T-cell epitopes are becoming better understood. Evidence from animal models also suggests that the damage in anti-GBM disease is dependent on complement, macrophages, and neutrophils.

Cyclophosphamide and plasma exchange are the standard of care in rapidly progressive glomerulonephritis or lung haemorrhage caused by antiglomerular basement membrane (anti-GBM) disease, and it is unusual to encounter patients at earlier stages. Steroids are universally used in addition. There is some evidence that plasma exchange may not be a critical part of treatment at an earlier stage. There is no more than anecdotal evidence for other therapies. Slower-onset therapies such as antibodies to B cells are rarely appropriate. If untreated, patients with severe anti-GBM disease will not recover renal function and are at risk of pulmonary haemorrhage. Evidence for the pathogenicity of circulating anti-GBM antibodies provides rationale for removal of circulating antibodies as rapidly as possible, whilst simultaneously inhibiting their synthesis. This was behind the introduction of the combination of plasma exchange with immunosuppressive therapy in mid 1970s, which revolutionized outcomes. Plasmapheresis aims to remove circulating pathogenic antibodies against GBM and possibly other mediators; cyclophosphamide prevents further synthesis of autoantibodies; and steroids act as anti-inflammatory agents to attenuate the glomerular inflammatory response initiated by anti-GBM antibodies. It is clear from experimental models and occasional observations in man that the anti-cell mediated effects of current therapies are important too. Outcomes vary, but in general patient survival is now good, while renal survival remains poor, in many series less than 50% at 1 year. Treatment is toxic and after an early peak in deaths due to pulmonary haemorrhage, secondary infections are the next threat. It may therefore be best not to immunosuppress patients with a very poor renal prognosis who appear to be at low risk of pulmonary haemorrhage. Treatment can usually be curtailed after 3 months without recurrence. ANCA and anti-GBM antibodies occur together in some patients. This is typically an older group which often has features of vasculitis, and the anti-GBM response may often be secondary. Longer treatment as for small vessel vasculitis is usually indicated.

♦ Fat embolism syndrome is defined as the presence of globules of fat in the lungs and in other tissues and occurs occasionally in long bone fractures♦ Reflex sympathetic dystrophy is characterized by intense prolonged pain, vasomotor disturbance, delayed functional recovery, and trophic changes♦ Avascular necrosis typically affects intra-articular bone after fracture and can occur in up to 70% of displaced talar neck fractures♦ Immobility associated with recovery from fracture is associated with deep vein thrombosis, which carries a risk of pulmonary embolism, and should be treated with anti-coagulants♦ Gas gangrene is a rapidly-spreading infection of devitalized tissue, removal of the affected area and treatment with penicillin is required♦ Compartment syndrome within a closed compartment can result in tissue ischaemia and necrosis followed by fibrosis and muscle contracture

Mechanical ventilation is indicated when the patient’s ability to ventilate the lung and/or effect gas transport across the alveolar capillary interface is compromised to point that harm is imminent. In practice, this means addressing one or more of three fundamental pathophysiological processes—loss of proper ventilatory control, ventilatory muscle demand-capability imbalances, and/or loss of alveolar patency. A fourth general indication involves providing a positive pressure assistance to allow tolerance of an artificial airway in the patient unable to maintain a patent and protected airway. The decision to initiate mechanical ventilation usually involves an integrated assessment that should include mental status, airway protection capabilities, ventilatory muscle load tolerance, spontaneous ventilatory pattern, and signs of organ dysfunction from either acidosis and/or hypoxaemia. Providing mechanical ventilatory assistance can be life-sustaining, but it is associated with significant risk, including ventilator-induced lung injury, infection, and need for sedatives/paralytics, and must be applied only when indications justify the risk.

Alterations in respiratory function and gas exchanges are frequently seen in patients during anaesthesia and in the post-operative period. Mechanical ventilation and drugs such as neuromuscular blocking agents can alter normal function of the respiratory system and cause damage to lungs. Protective ventilation strategies should always be adopted intra-operatively in mechanically-ventilated patients. A neuromuscular monitoring-guided use of decurarizating agents and post-operative adequate analgesia techniques are recommended to avoid post-operative residual curarization and pain. Pneumonia is the most frequent infective complication, but at the moment there are no recommended clinical tools (scoring systems) to identify patients at high. A fast-track surgical approach and early can decrease the risk. Early mobilization and prophylactic low molecular weight heparins use have a well-documented efficacy on prevention of pulmonary embolism. There is still no general consensus on the widespread use of early NIV in post-operative patients, although in selected high-risk patients it could help respiratory recovery and reduce complications.

The Oxford Handbook of General Practice offers hands-on advice to help with any day-to-day problems that might arise in general practice, and covers the entire breadth and depth of general practice in concise, quick-reference topics. It starts by exploring the definition of general practice, and moves on to practical advice on practice management, consulting with patients, social aspects of primary care, and prescribing and managing medicines. It gives practical advice on all clinical areas of general practice, including minor surgery, healthy living, chronic disease and elderly care, cardiology and vascular disease, respiratory medicine, endocrinology, gastrointestinal medicine, renal medicine and urology, musculoskeletal problems, neurology, dermatology, infectious disease, haematology and immunology, breast disease, gynaecology, sexual health and contraception, pregnancy, child health, ear, nose, and throat medicine, ophthalmology, mental health, cancer care, palliative care, and emergencies in general practice. It is written for general practitioners (GP), GPs in training, medical students, and allied health professionals working in the community.

This chapter reviews advances in pathogenesis; European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria with clinical, laboratory, and ultrasound criteria for classification as polymyalgia rheumatica (PMR); the heterogeneity and overlap between PMR, inflammatory arthritis, and large-vessel vasculitis as illustrated by representative cases; recent guidelines on early and correct recognition, investigations, and management of PMR; the scope of disease-modifying agents; socio-economic impact, outcomes, and patient experience in PMR. It also discusses areas for future research including clinical trials with biological agents and newer steroid formulations, standardized outcome assessments, and the search for better biomarkers in PMR. PMR is one of the common inflammatory rheumatic diseases of older people and represents a frequent indication for long-term glucocorticoid (GC) therapy. It is characterized by abrupt-onset pain and stiffness of the shoulder and pelvic girdle muscles. Its management is subject to wide variations of clinical practice and it is managed in primary or secondary care by general practitioners (GPs), rheumatologists, and non-rheumatologists. The evaluation of PMR can be challenging, as many clinical and laboratory features may also be present in other conditions, including other rheumatological diseases, infection, and neoplasia. PMR is usually diagnosed in the primary care setting, but standard clinical investigations and referral pathways for suspected PMR are unclear. The response to standardized therapy is heterogeneous, and a significant proportion of patients do not respond completely. There is also an overlap with inflammatory arthritis and large-vessel vasculitis for which adjuvant disease-modifying medications are often used. Prolonged corticosteroid therapy is associated with a variety of side effects, especially when high-dose glucocorticoid therapy is employed. Giant cell arteritis (GCA) is also often linked to PMR. It is a vasculitis of large- and medium-sized vessels causing critical ischaemia. GCA is a medical emergency because of the high incidence of neuro-ophthalmic complications. Both conditions are associated with a systemic inflammatory response and constitutional symptoms. The pathogenesis is unclear. The initiating step may be the recognition of an infectious agent by aberrantly activated dendritic cells. The key cell types involved are CD4+ T cells and macrophages giving rise to key cytokines such as interferon-γ‎ (implicated in granuloma formation), PDGF (intimal hyperplasia), and interleukin (IL)-6 (key to the systemic response). The pathogenesis of PMR may be similar to that of GCA, although PMR exhibits less clinical vascular involvement. The mainstay of therapy is corticosteroids, and disease-modifying therapy is currently indicated in relapsing disease.

Syphilis, a chronic, sexually transmitted disease caused by the extracellular spirochete Treponema pallidum, has exhibited a remarkable resurgence in recent years. Despite the existence of inexpensive, easily administered, and highly effective antibiotic treatments, maternal and neonatal syphilis infections continue to be a major global public health problem. In addition to its potential to cause morbidity in the mother, untreated gestational syphilis (GS) can lead to serious adverse outcomes in the offspring, including stillbirth, prematurity, low birth weight, and neonatal death. Congenital syphilis (CS) is regarded as a missed opportunity during the antenatal care of the mother, resulting from socioeconomic, demographic, and behavioral factors that promote mother-to-child transmission (MTCT) of syphilis. This chapter emphasizes emerging concepts about screening aimed at controlling the ongoing epidemic, including serological screening of mother and infant, newer paradigms of “reverse screening,” clinical presentation, therapy, and long-term neurodevelopmental disabilities that must be a component of follow-up care.

Any public debate about air pollution starts with the premise that air pollution cannot be good for you, so we should have less of it. However, it is much more difficult to determine how much is dangerous, and even more difficult to decide how much we are willing to pay for improvements in measured air pollution. Recent UK estimates suggest that fine particulate pollution causes about 6500 deaths per year, although it is not clear how many years of life are lost as a result. Some deaths may just be brought forward by a few days or weeks, while others may be truly premature. Globally, household pollution from cooking fuels may cause up to two million premature deaths per year in the developing world. The hazards of black smoke air pollution have been known since antiquity. The first descriptions of deaths caused by air pollution are those recorded after the eruption of Vesuvius in ad 79. In modern times, the infamous smogs of the early twentieth century in Belgium and London were clearly shown to trigger deaths in people with chronic bronchitis and heart disease. In mechanistic terms, black smoke and sulphur dioxide generated from industrial processes and domestic coal burning cause airway inflammation, exacerbation of chronic bronchitis, and consequent heart failure. Epidemiological analysis has confirmed that the deaths included both those who were likely to have died soon anyway and those who might well have survived for months or years if the pollution event had not occurred. Clean air legislation has dramatically reduced the levels of these traditional pollutants in the West, although these pollutants are still important in China, and smoke from solid cooking fuel continues to take a heavy toll amongst women in less developed parts of the world. New forms of air pollution have emerged, principally due to the increase in motor vehicle traffic since the 1950s. The combination of fine particulates and ground-level ozone causes ‘summer smogs’ which intensify over cities during summer periods of high barometric pressure. In Los Angeles and Mexico City, ozone concentrations commonly reach levels which are associated with adverse respiratory effects in normal and asthmatic subjects. Ozone directly affects the airways, causing reduced inspiratory capacity. This effect is more marked in patients with asthma and is clinically important, since epidemiological studies have found linear associations between ozone concentrations and admission rates for asthma and related respiratory diseases. Ozone induces an acute neutrophilic inflammatory response in both human and animal airways, together with release of chemokines (e.g. interleukin 8 and growth-related oncogene-alpha). Nitrogen oxides have less direct effect on human airways, but they increase the response to allergen challenge in patients with atopic asthma. Nitrogen oxide exposure also increases the risk of becoming ill after exposure to influenza. Alveolar macrophages are less able to inactivate influenza viruses and this leads to an increased probability of infection after experimental exposure to influenza. In the last two decades, major concerns have been raised about the effects of fine particulates. An association between fine particulate levels and cardiovascular and respiratory mortality and morbidity was first reported in 1993 and has since been confirmed in several other countries. Globally, about 90% of airborne particles are formed naturally, from sea spray, dust storms, volcanoes, and burning grass and forests. Human activity accounts for about 10% of aerosols (in terms of mass). This comes from transport, power stations, and various industrial processes. Diesel exhaust is the principal source of fine particulate pollution in Europe, while sea spray is the principal source in California, and agricultural activity is a major contributor in inland areas of the US. Dust storms are important sources in the Sahara, the Middle East, and parts of China. The mechanism of adverse health effects remains unclear but, unlike the case for ozone and nitrogen oxides, there is no safe threshold for the health effects of particulates. Since the 1990s, tax measures aimed at reducing greenhouse gas emissions have led to a rapid rise in the proportion of new cars with diesel engines. In the UK, this rose from 4% in 1990 to one-third of new cars in 2004 while, in France, over half of new vehicles have diesel engines. Diesel exhaust particles may increase the risk of sensitization to airborne allergens and cause airways inflammation both in vitro and in vivo. Extensive epidemiological work has confirmed that there is an association between increased exposure to environmental fine particulates and death from cardiovascular causes. Various mechanisms have been proposed: cardiac rhythm disturbance seems the most likely at present. It has also been proposed that high numbers of ultrafine particles may cause alveolar inflammation which then exacerbates preexisting cardiac and pulmonary disease. In support of this hypothesis, the metal content of ultrafine particles induces oxidative stress when alveolar macrophages are exposed to particles in vitro. While this is a plausible mechanism, in epidemiological studies it is difficult to separate the effects of ultrafine particles from those of other traffic-related pollutants.