In 1903, Leishman and Donovan separately described the protozoan now called Leishmania donovani in splenic tissue from patients in India with the life-threatening disease now called visceral leishmaniasis. Almost a century later, many features of leishmaniasis and its major syndromes (ie, visceral, cutaneous, and mucosal) have remained the same; but also much has changed. As before, epidemics of this sandfly-borne disease occur periodically in India and elsewhere; but leishmaniasis has also emerged in new regions and settings, for example, as an AIDS-associated opportunistic infection. Diagnosis still typically relies on classic microbiological methods, but molecular-based approaches are being tested. Pentavalent antimony compounds have been the mainstay of antileishmanial therapy for half a century, but lipid formulations of amphotericin B (though expensive and administered parenterally) represent a major advance for treating visceral leishmaniasis. A pressing need is for the technological advances in the understanding of the immune response to leishmania and the pathogenesis of leishmaniasis to be translated into field-applicable and affordable methods for diagnosis, treatment, and prevention of this disease.

Highly active antiretroviral therapy (HAART) can induce a characteristic lipodystrophy syndrome of peripheral fat wasting and central adiposity. HIV-1 protease inhibitors are generally believed to be the causal agents, although the syndrome has also been observed with protease-inhibitor-sparing regimens. Here, we postulate that the mitochondrial toxicity of the nucleoside-analogue reverse-transcriptase inhibitors plays an essential part in the development of this lipodystrophy, similar to the role of mitochondrial defects in the development of multiple symmetrical lipomatosis.

Progress in nuclear medicine has always been a function of technological advances, and applications in neurology and psychiatry illustrate the point. Improvements in radiation detectors now allow for three-dimensional and quantitative mapping of the distribution of a labelled compound in the human brain. New ligands permit the study of specific functioning signals of the blood/brain barrier, blood flow, metabolism (oxygen, glucose, aminoacids), and neurotransmission (dopamine, benzodiazepine, serotonin receptors). The picomolar sensitivity of nuclear medicine can now be coupled to a wide group of ligands which offer specific information that can be obtained in no other way in the living patient.

Ursodeoxycholic acid (UDCA) is the only approved treatment for primary biliary cirrhosis, but its effect on disease progression and survival is uncertain. The aim of this study was to clarify the efficacy of UDCA in primary biliary cirrhosis.

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