Nuclear medicine provides the surgeon with important diagnostic and functional information on specific organs and with therapy for a limited set of diseases. Clinical applications of nuclear medicine are beginning to guide surgeons to specific locations, notably to sentinel lymph nodes in patients with cancer. The role of radionuclide diagnosis in oncology has been covered earlier in this Lancet series, so here is a surgeon's perspective on sentinel node and other oncological applications and on the surgical value of nuclear medicine in non-malignant diseases.

After tuberculosis and leprosy, Buruli-ulcer disease (caused by infection with Mycobacterium ulcerans) is the third most common mycobacterial disease in immunocompetent people. Countries in which the disease is endemic have been identified, predominantly in areas of tropical rain forest; the emergence of Buruli-ulcer disease in West African countries over the past decade has been dramatic. Current evidence suggests that the infection is transmitted through abraded skin or mild traumatic injuries after contact with contaminated water, soil, or vegetation; there is one unconfirmed preliminary report on possible transmission by insects. The clinical picture ranges from a painless nodule to large, undermined ulcerative lesions that heal spontaneously but slowly. Most patients are children. The disease is accompanied by remarkably few systemic symptoms, but occasionally secondary infections resulting in sepsis or tetanus cause severe systemic disease and death. Extensive scarring can lead to contractures of the limbs, blindness, and other adverse sequelae, which impose a substantial health and economic burden. Treatment is still primarily surgical, and includes excision, skin grafting, or both. Although BCG has a mild but significant protective effect, new vaccine developments directed at the toxins produced by M. ulcerans are warranted. In West Africa, affected populations are underprivileged, and the economic burden imposed by Buruli-ulcer disease is daunting. Combined efforts to improve treatment, prevention, control, and research strategies (overseen by the WHO and funded by international relief agencies) are urgently needed.

We review the concept and importance of functional somatic symptoms and syndromes such as irritable bowel syndrome and chronic fatigue syndrome. On the basis of a literature review, we conclude that a substantial overlap exists between the individual syndromes and that the similarities between them outweigh the differences. Similarities are apparent in case definition, reported symptoms, and in non-symptom association such as patients' sex, outlook, and response to treatment. We conclude that the existing definitions of these syndromes in terms of specific symptoms is of limited value; instead we believe a dimensional classification is likely to be more productive.

Nuclear medicine therapy uses unsealed radioactive sources for the selective delivery of radiation to tumours or target organs. For benign disorders such as thyrotoxicosis and arthritis radionuclide therapy provides an alternative to surgery or medical treatment. In cancer treatment, it often combines the advantage of target selectivity (like brachytherapy or external beam radiotherapy) with that of being systemic, as with chemotherapy, and it may be used as part of a therapeutic strategy with curative intent or for disease control and palliation. Toxicity is generally limited to the haematopoietic tissue and few side-effects are observed. When cure is feasible, the long-term consequences of radionuclide therapy (eg, fertility disorders and leukaemia or other secondary cancers) do compare favourably with the risks associated with and accepted for chemotherapy and radiotherapy.

Nuclear medicine imaging has contributed significantly to diagnosis, treatment planning, and the evaluation of response to treatment in patients with cancer since the development of modern techniques in the 1970s. Diagnostic applications such as the bone scan continue to be the most common use in oncology because of their high sensitivity but the contribution of nuclear medicine to oncology can perhaps be best understood in the context of patient management. Staging of newly presenting cancer patients and restaging for treatment planning are reviewed here. For treatment response and disease recurrence nuclear medicine provides information non-invasively. The studies can be repeated with few side-effects and with low radiation absorbed doses. Results can be directly correlated with clinical laboratory data. The goals of biologically characterising an individual patient's tumour and predicting his or her response to treatment are within reach.

Respiratory syncytial virus (RSV), long recognised as the major viral pathogen of the lower respiratory tract of infants, has also been implicated in severe lung disease in adults, especially the elderly. This fact, and the demonstration that passive prophylaxis with either polyclonal or monoclonal antibody to RSV prevents severe lung disease in high-risk infants and children, has led to renewed interest in the immune mechanisms surrounding protection, and the development of vaccines

Nuclear medicine imaging techniques can help in patient evaluation where infectious and non-infectious inflammatory disorders are suspected. When selected and tailored to the clinical situation, most techniques already in use or available soon provide information with high sensitivity. However, almost all currently available techniques lack the specificity to discriminate between infectious and non-infectious inflammation. In undiagnosed fever, this non-specificity may be an advantage since fever of unknown origin is caused by infection in only about 25% of cases, but in the postoperative patient the reliable differentiation between infection and sterile inflammation is highly relevant to clinical management. The range of radiopharmceuticals to investigate infectious and non-microbial inflammatory disorders is expanding and developments in protein/peptide chemistry and in labelling technology should lead to agents with very high specific activities. Nuclear medicine has to add specificity to its already high sensitivity if it is to distinguish both categories of inflammatory disorder.

Although the literature is filled with information about the prevalence and incidence of back pain in general, there is less information about chronic back pain, partly because of a lack of agreement about definition. Chronic back pain is sometimes defined as back pain that lasts for longer than 7-12 weeks. Others define it as pain that lasts beyond the expected period of healing, and acknowledge that chronic pain may not have well-defined underlying pathological causes. Others classify frequently recurring back pain as chronic pain since it intermittently affects an individual over a long period. Most national insurance and industrial sources of data include only those individuals in whom symptoms result in loss of days at work or other disability. Thus, even less is known about the epidemiology of chronic low-back pain with no associated work disability or compensation. Chronic low-back pain has also become a diagnosis of convenience for many people who are actually disabled for socioeconomic, work-related, or psychological reasons. In fact, some people argue that chronic disability in back pain is primarily related to a psychosocial dysfunction. Because the validity and reliability of some of the existing data are uncertain, caution is needed in an assessment of the information on this type of pain.

Pemphigus and bullous pemphigoid are distinct autoimmune blistering diseases that are characterised by the presence of autoantibodies directed against specific adhesion molecules of the skin and mucous membranes. The comparison and contrast of molecular mechanism of blister formation of these two diseases provide a rational diagnostic and therapeutic approach to affected patients.

High blood lactate concentration (hyperlactacidaemia) in trauma or sepsis is thought to indicate tissue hypoxia and anaerobic glycolysis even when blood pressure, cardiac output, and urine output are within clinically acceptable ranges. However, mechanisms of lactate generation by well-oxygenated tissues have received little attention. Within cells, oxidative and glycolytic energy production can proceed in separate, independent compartments. In skeletal muscle and other tissues, aerobic glycolysis is linked to ATP provision for the Na+-K+ pump, the activity of which is stimulated by epinephrine. In injured patients, hypokalaemia may reflect increased Na+,K+-ATPase activity. We propose that increased blood lactate often reflects increased aerobic glycolysis in skeletal muscle secondary to epinephrine-stimulated Na+,K+-ATPase activity and not anaerobic glycolysis due to hypoperfusion. The hypothesis explains why hyperlactacidaemia often neither correlates with traditional indicators of perfusion nor diminishes with increased oxygen delivery. When other variables have returned to normal, continued attempts at resuscitation based on elevated blood lactate may lead to unnecessary use of blood transfusion and inotropic agents in an effort to increase oxygen delivery and lactate clearance.

Outcome in acute respiratory distress syndrome (ARDS) is influenced by a number of factors, including the nature of the precipitating condition and the extent to which multiorgan failure ensues. Most studies of potential therapeutic interventions have been unsuccessful due to the enrollment of limited numbers of patients with a wide variety of pathologies of varying severity. Moreover, the value of initiating single-agent interventions at varying time points in what is an evolving and complex inflammatory process must be questioned. Mortality may therefore represent an inappropriate end-point for clinical trials, which are increasingly focusing on ventilator-free days. Despite these uncertainties, survival appears to be improving, possibly due to the application of supportive techniques in a protocol-driven fashion to patients in whom the underlying condition has been rigorously treated.

Effective, feasible interventions to prevent perinatal transmission of HIV-1 in developing nations are an urgent necessity. Scientific issues of concern include a need to identify other effective antiretroviral agents; to define the shortest effective course of therapy; to assess interventions other than antiretroviral agents; and to investigate interventions that may reduce HIV-1 transmission via breastfeeding. Sound scientific design is fundamental to all research studies. Ethical standards must guide such studies and include the necessity that the problem studied be a health priority in the host country; that the highest standard of care attainable in the country be assured to participants; that the health-care resources of the country not be harmed; that the informed consent of participants be obtained; and that a process of discussion ensure that a successful intervention will be considered for implementation. There are circumstances in which a no-antiretroviral comparison may be ethically justified.