Oesophageal motility disorders comprise various abnormal manometric patterns which usually present with dysphagia or chest pain. Some, such as achalasia, are diseases with a well defined pathology, characteristic manometric features, and good response to treatments directed at the pathophysiological abnormalities. Other disorders, such as diffuse oesophageal spasm and hypercontracting oesophagus, have no well defined pathology and could represent a range of motility changes associated with subtle neuropathic changes, gastro-oesophageal reflux, and anxiety states. Although manometric patterns have been defined for these disorders, the relation with symptoms is poorly defined and the response to medical or surgical therapy unpredictable. Hypocontracting oesophagus is generally caused by weak musculature commonly associated with gastro-oesophageal reflux disease. Secondary oesophageal motility disorders can be caused by collagen vascular diseases, diabetes, Chagas' disease, amyloidosis, alcoholism, myxo-oedema, multiple sclerosis, idiopathic pseudo-obstruction, or the ageing process.

The US National Cancer Institute alert in February, 1999, stated that concomitant chemotherapy and radiotherapy should be considered for all patients with cervical cancer. Our aim was to review the effects of chemoradiotherapy on overall and progression-free survival, local and distant control, and acute and late toxicity in patients with cervical cancer.

The introduction of sensitive thyrotropin assays and free thyroid hormone measurements has simplified the interpretation of thyroid function tests. However, important pitfalls and difficult cases still exist. In this review, thyroid function test results are grouped into six different patterns. We propose that if assays for thyrotropin, free T3, and free T4 are all done, knowledge of these patterns coupled with clinical details and simple additional tests allow a diagnosis to be made in almost all cases.

The advent of insulin almost 80 years ago revolutionised treatment of diabetes and must be one of the most outstanding achievements of twentieth century medicine. Since then, there has been an ever-increasing awareness and acceptance of the need to achieve and sustain near-normoglycaemia to delay onset and retard progression of diabetic angiopathy. Physiological insulin replacement is therefore central to management of patients with diabetes who are unable to make [corrected] insulin. Insulin formulations, treatment strategies, and methods and routes of delivery have changed much, with more and more options for monitoring the effect on blood glucose concentrations. Patients with type 1 and type 2 diabetes need insulin much more aggressively than previously. Parallel developments in glucose-sensing technologies are welcomed as an integral part of safe and optimum implementation of insulin replacement therapy.

Kidney stones are common in industrialised nations: up to 15% of white men and 6% of all women will develop one stone, with recurrence in about half these people. Risk factors for formation of stones include urinary promoters (calcium, urate, cystine, and sodium) and urinary inhibitors (magnesium, citrate, and nephrocalcin). Acute renal colic can be precipitated by dehydration and reduced urine output, increased protein intake, heavy physical exercise, and various medicines. Such colic manifests as severe loin pain and can be accompanied by frequent urination, dysuria, oliguria, and haematuria. Documentation of stone characteristics is extremely important: type, size, location, and underlying metabolic abnormalities. Such details can be obtained with a combination of biochemical investigations, microscopic examination of urine under polarised light, and an intravenous pyelogram. Ultrasonography and plain abdominal radiographs are also useful, especially for patients unable to tolerate an intravenous pyelogram. Acute therapy includes complete pain relief, rehydration, and encouragement of diuresis. Long-term management encompasses education of patients with regard to diet and fluid intake, control of calciuria, citrate replacement, and treatment of any underlying urinary-tract infection or metabolic abnormality. Stones smaller than 5 mm normally pass spontaneously, whereas larger stones, as big as 2 cm, are best treated with extracorporeal shock-wave lithotripsy. All physicians should have a clear understanding of the pathogenesis and clinical management (acute treatment and prevention of recurrence) of renal stone disease.

To help patients to fully participate in shared decision making is becoming an important goal in clinical practice and one which is receiving increasing attention in terms of the requisite skills and technological development. We discuss the potential application of decision analysis-a specific technology that has been introduced into clinical practice but to date only within research contexts-and examine the usefulness and feasibility of the technique for patients, particularly in settings where clinical presentations are diverse and characterised by uncertainty.

There is a potential role for antisense oligonucleotides in the treatment of disease. The principle of antisense technology is the sequence-specific binding of an antisense oligonucleotide to target mRNA, resulting in the prevention of gene translation. The specificity of hybridisation makes antisense treatment an attractive strategy to selectively modulate the expression of genes involved in the pathogenesis of diseases. One antisense drug has been approved for local treatment of cytomegalovirus-induced retinitis, and several antisense oligonucleotides are in clinical trials, including oligonucleotides that target the mRNA of BCL2, protein-kinase-C alpha, and RAF kinase. Antisense oligonucleotides are well tolerated and might have therapeutic activity. Here, we summarise treatment ideas in this field, summarise clinical trials that are being done, discuss the potential contribution of CpG motif-mediated effects, and look at promising molecular targets to treat human cancer with antisense oligonucleotides.

There is little knowledge about Latin American social medicine in the English-speaking world. Social medicine groups exist in Argentina, Brazil, Chile, Colombia, Cuba, Ecuador, and Mexico. Dictatorships have created political and economic conditions which are more adverse in some countries than others; in certain instances, practitioners of social medicine have faced unemployment, arrest, torture, exile, and death. Social medicine groups have focused on the social determinants of illness and early death, the effects of social policies such as privatisation and public sector cutbacks, occupational and environmental causes of illness, critical epidemiology, mental health effects of political trauma, the impact of gender, and collaborations with local communities, labour organisations, and indigenous people. The groups' achievements and financial survival have varied, depending partly on the national context. Active professional associations have developed, both nationally and internationally. Several groups have achieved publication in journals and books, despite financial and technical difficulties that might be lessened through a new initiative sponsored by the US National Library of Medicine. The conceptual orientation and research efforts of these groups have tended to challenge current relations of economic and political power. Despite its dangers, Latin American social medicine has emerged as a productive field of work, whose findings have become pertinent throughout the world.

Before chromosomal analysis became available, the diagnosis of Turner's syndrome was based on the characteristics independently described by Otto Ullrich and Henry Turner, such as short stature, gonadal dysgenesis, typical, visible dysmorphic stigmata, and abnormalities in organs, which present in individuals with a female phenotype. Today, Turner's syndrome or Ullrich-Turner's syndrome may be defined as the combination of characteristic physical features and complete or part absence of one of the X chromosomes, frequently accompanied by cell-line mosaicism. The increasing interest in Turner's syndrome over the past two decades has been motivated both by the quest for a model by which the multi-faceted features of this disorder can be understood, and the endeavour to provide life-long support to the patient. New developments in research allow patients with Turner's syndrome to have multidisciplinary care.

Epidemics of meningococcal disease in Africa are commonly detected too late to prevent many cases. We assessed weekly meningitis incidence as a tool to detect epidemics in time to implement mass vaccination.

Overview analysis involving 18000 women with breast cancer in 47 randomised trials showed that prolonged chemotherapy significantly reduces the risk of relapse and death compared with no chemotherapy. Here we express the size of the benefit in terms of quality-adjusted survival time gained.

As our knowledge of type 1 (insulin-dependent) diabetes increases, so does our appreciation for the pathogenic complexity of this disease and the challenges associated with its treatment. Many new concepts about the pathogenesis of this disorder have arisen. The role of genetics versus environment in disease formation has been questioned, and the basis on which type 1 diabetes is characterised and diagnosed is the subject of much debate. Additionally, the care and treatment of patients with type 1 diabetes has seen a rapid evolution; with genetically engineered insulins, glucose monitoring devices, and algorithms all contributing to a decrease in disease-related complications. We focus this seminar on these changing views, and offer a new perspective on our understanding of the pathogenesis of type 1 diabetes and on principles for therapeutic management of patients with this disorder.

Bacteria that adhere to implanted medical devices or damaged tissue can encase themselves in a hydrated matrix of polysaccharide and protein, and form a slimy layer known as a biofilm. Antibiotic resistance of bacteria in the biofilm mode of growth contributes to the chronicity of infections such as those associated with implanted medical devices. The mechanisms of resistance in biofilms are different from the now familiar plasmids, transposons, and mutations that confer innate resistance to individual bacterial cells. In biofilms, resistance seems to depend on multicellular strategies. We summarise the features of biofilm infections, review emerging mechanisms of resistance, and discuss potential therapies.

The identification of genes that place individuals at high risk of breast, ovarian, and colorectal cancer has greatly advanced our understanding of cancer predisposition over the past decade. This knowledge has received much attention from the media, and referrals to geneticists and surgeons, and requests for genetic testing, have risen. We review the published evidence for the management of people at increased risk of hereditary cancers, to draw attention to areas of uncertainty and to discuss implications for primary care. We focus on common inherited cancers, since they will have the greatest effect on clinical practice over the next decade. Cancer genetics offers a model of how information on the genetics of other common diseases could affect primary care in the future. Strategies to support the integration of genetic medicine in primary care are needed to enable primary-care practitioners to identify individuals at raised genetic risk and to reassure patients for whom genetic testing and increased surveillance offer little benefit.

Haematology represents a prime example of how rapidly immunology is moving towards the bedside. The diagnosis of blood disease has been modified by the "cluster of differentiation" (CD) nomenclature of leucocyte surface antigens, and the molecular genetics of the immune system has had a major effect on the diagnosis and treatment of blood malignancies. Lymphoid tumours represent a fertile area of interaction between immunology and haematology: B-cell malignancies are associated with dysregulation of the immune system, and antigen exposure might have an important role in the development of lymphoid malignant clones that interact with the microenvironment to avoid apoptosis and acquire better growing conditions. Understanding the pathophysiology of immune-mediated blood diseases has paved the way to the successful use of immunosuppressive agents, and the unravelling of the mechanisms of lymphocyte signal transduction and the relations between lymphocyte activation and apoptosis are allowing new therapeutic approaches. Paradoxically, lymphoid tumours are an excellent model to test the efficacy of manipulating the immune system for the purpose of tumour eradication.