Enzyme-replacement therapy has been assessed as a treatment for patients who have mucopolysaccharidosis I (alpha-L-iduronidase deficiency). We aimed to investigate the humoral immune response to recombinant human alpha-L-iduronidase among these patients.

The clearest advantage of new generation, atypical antipsychotics is a reduced risk of extrapyramidal side-effects (EPS), compared with conventional compounds. These findings might have been biased by the use of the high-potency antipsychotic haloperidol as a comparator in most of the trials. We aimed to establish whether the new drugs induce fewer EPS than low-potency conventional antipsychotics.

Ulceration of the foot in diabetes is common and disabling and frequently leads to amputation of the leg. Mortality is high and healed ulcers often recur. The pathogenesis of foot ulceration is complex, clinical presentation variable, and management requires early expert assessment. Interventions should be directed at infection, peripheral ischaemia, and abnormal pressure loading caused by peripheral neuropathy and limited joint mobility. Despite treatment, ulcers readily become chronic wounds. Diabetic foot ulcers have been neglected in health-care research and planning, and clinical practice is based more on opinion than scientific fact. Furthermore, the pathological processes are poorly understood and poorly taught and communication between the many specialties involved is disjointed and insensitive to the needs of patients.

Primary pulmonary hypertension (PPH) is a rare disorder characterised by raised pulmonary-artery pressure in the absence of secondary causes. Precapillary pulmonary arteries are affected by medial hypertrophy, intimal fibrosis, microthrombosis, and plexiform lesions. Most individuals present with dyspnoea or evidence of right heart failure. Echocardiography is the best non-invasive test to screen for suspected pulmonary hypertension. The discovery of mutations in the coding region of the gene for bone morphogenetic protein receptor 2 in patients with familial and sporadic PPH may help not only to elucidate pathogenesis but also to direct future treatment options. The pathogenesis is not completely understood, but recent investigations have revealed many possible candidate modifier genes. Without treatment, the disorder progresses in most cases to right heart failure and death. With current therapies such as epoprostenol, progression of disease is slowed, but not halted. Many promising new therapeutic options, including prostacyclin analogues, endothelin-1-receptor antagonists, and phosphodiesterase inhibitors, improve clinical function and haemodynamic measures and may prolong survival.

Every year, millions of people travel abroad, exposing themselves to various diseases. Advice on risk avoidance and on self-medication is not always successful; sometimes travellers return home ill or become unwell soon afterwards. There are many possible causes for such illnesses, and physicians should try to establish whether the disease is specifically associated with the recent journey. The approach to assessment of the ill traveller should make use not only of signs and symptoms, but also of geography and epidemiology. Travellers with fever need immediate attention to rule out serious and potentially life-threatening conditions. Faced with a difficult diagnosis, physicians should consult with experts in tropical and travel medicine.

Hysterectomy is a common and effective treatment for menorrhagia but is associated with substantial post-operative convalescence time and morbidity. In the early 1990s endometrial resection or ablation became a well-established day-case alternative for the surgical treatment of menorrhagia. Both endometrial resection and ablation require general anaesthesia, a high level of skill in hysteroscopic surgery, and can be long procedures. More recently, various new techniques have been developed that can be done in an outpatient setting under local anaesthesia and with a low risk of complications. The effectiveness of most new second-generation ablation technologies has not been confirmed in randomised trials and it is possible that these techniques will not prove to be as effective or as safe as originally thought.

In the past decade, our understanding of the genetic basis, pathogenesis, and natural history of pancreatitis has grown strikingly. In severe acute pancreatitis, intensive medical support and non-surgical intervention for complications keeps patients alive; surgical drainage (necrosectomy) is reserved for patients with infected necrosis for whom supportive measures have failed. Enteral feeding has largely replaced the parenteral route; controversy remains with respect to use of prophylactic antibiotics. Although gene therapy for chronic pancreatitis is years away, our understanding of the roles of gene mutations in hereditary and sporadic pancreatitis offers tantalising clues about the disorder's pathogenesis. The division between acute and chronic pancreatitis has always been blurred: now, genetics of the disorder suggest a continuous range of disease rather than two separate entities. With recognition of pancreatic intraepithelial neoplasia, we see that chronic pancreatitis is a premalignant disorder in some patients. Magnetic resonance cholangiopancreatography and endoscopic ultrasound are destined to replace endoscopic retrograde cholangiopancreatography for many diagnostic indications in pancreatic disease.

More than a decade ago, a mammography screening programme for women aged 50-69 years was initiated in the Netherlands. Our aim was to assess the effect of this programme on breast-cancer mortality rates.

The four steps for giving travellers the foundation for healthy journeys are to assess their health, analyse their itineraries, select vaccines, and provide education about prevention and self-treatment of travel-related diseases. This process takes time. Since there is a risk of information overload, travellers should leave the clinic with some written advice for reinforcement. The order of these steps can be tailored to what best suits the travel clinic, but vaccinating early in the process allows monitoring for adverse reactions. Face-to-face discussion is vital for explaining the use and side-effects of medications. Those who provide a travel medicine service should be seeing many travellers and should seek specialist training. In 2003, the International Society of Travel Medicine introduced a certificate of knowledge examination in travel medicine. We cannot make travellers bullet-proof but it is possible to make them bullet-resistant. The pre-travel visit should minimise health risks specific to the journey, give travellers the capability to handle most minor medical problems, and allow them to identify when to seek local care during the trip or on return.

In both ageing men and women, there is an increasing incidence of lower urinary tract symptoms (LUTS) which are increasing. These infections have many possible causes, including smooth muscle dysfunction, neurological factors and benign prostatic hyperplasia. Up to 15% to 25% of men aged 50-65 years have LUTS of sufficient severity to interfere with their quality of life. Although benign prostatic hyperplasia is an important cause of these symptoms, and can have serious consequences, clinicians should be aware of these other causes so that the appropriate diagnosis is made before invasive treatments are started. New medical treatments, including alpha-adrenergic blocking agents and 5 alpha-reductase inhibitors mean that many men without complications such as infection, bleeding, or chronic retention, and with mild to moderate symptoms, should be managed in primary care. Combined local protocols between primary and secondary care will help to establish which men with persistent symptoms or complications need referral for a urological opinion to determine the need for further investigation and more invasive forms of management. We review the pathophysiology of the disease, and current approaches to investigation and management of this common problem.

Coeliac disease is caused by a genetically determined, specific immune response to antigens present in wheat gluten. This immune response may be focused on a limited region of the alpha gliadin component of gluten, and previous studies have suggested that the generation of epitopes for recognition by CD4+ T cells requires deamidation of the protein by tissue transglutaminase. However, it had not previously been shown that candidate epitope peptides could be generated from gluten in vivo, or that these epitopes were selective products of physiological digestion of gluten by tissue transglutaminase.

The sequencing of chromosome 21 and the use of models of Down's syndrome in mice have allowed us to relate genes and sets of genes to the neuropathogenesis of this syndrome, and to better understand its phenotype. Research in prenatal screening and diagnosis aims to find methods to identify fetuses with Down's syndrome, and reduce or eliminate the need for amniocentesis. Other areas of active research and clinical interest include the association of Down's syndrome with coeliac disease and Alzheimer's disease, and improved median age of death. Medical management of the syndrome requires an organised approach of assessment, monitoring, prevention, and vigilance. Improvements in quality of life of individuals with Down's syndrome have resulted from improvements in medical care, identification and treatment of psychiatric disorders (such as depression, disruptive behaviour disorders, and autism), and early educational interventions with support in typical educational settings. Approaches and outcomes differ throughout the world.

Body piercing is increasing in popularity around the world. In this review, I describe the history, origins, and peculiarities of various forms of body piercing, and procedures involved, variations in healing time, legal aspects and regulations, and complications and side-effects. I have also included a discussion of the motivation for and psychological background behind body piercing. In presenting research results, I aim to raise awareness of the many risks associated with body piercing. In presenting psychological data, I intend to create an understanding of the multifaceted and often intense motivations associated with body piercing, and, thus, to diminish any prejudices held by health professionals against people with piercings.

Recent breakthroughs in the treatment of psoriasis have led to improved understanding of the pathogenesis of this disease. Activation of T lymphocytes leading to release of cytokines results in proliferation of keratinocytes. Several new biological therapies have been developed, which target specific steps in the pathogenesis of psoriasis. With these new treatments, variable degrees of clearing occur. Initial data suggest improved safety over older agents such as methotrexate and ciclosporin, but long-term data are necessary. Enhancements in topical therapy and phototherapy have also increased the armamentarium of treatments available for this disorder.

Human papillomavirus (HPV) is believed to be the most important cause of cervical cancer. Recent studies suggest that long duration use of oral contraceptives increases the risk of cervical cancer in HPV positive women.

Epidemiologically, screening is justified by the importance of the disease and the lack of prospects for primary prevention, but evidence from natural history is unhelpful since men are more likely to die with, rather than from, prostate cancer. The available screening tests do not always detect men whose lesions could result in future morbidity or mortality. Evidence is limited for the benefits of treatment for localised cancers detected through screening, whereas the evidence for harm is clear. Observational evidence for the effect of population screening programmes is mixed, with no clear association between intensity of screening and reduced prostate cancer mortality. Screening for prostate cancer cannot be justified in low-risk populations, but the balance of benefit and harm will be more favourable after risk stratification. Prostate cancer screening can be justified only in research programmes designed to assess its effectiveness and help identify the groups who may benefit.

Gastro-oesophageal reflux disease (GORD) is a common chronic disorder that has severe impact on quality of life and often requires continuous acid-suppression therapy. Proton-pump inhibitors (PPIs) are extremely effective but expensive, and do not restore the normal antireflux barrier at the gastro-oesophageal junction. Antireflux surgery, even with the laparoscopic approach, has not proven more cost-effective than maintenance therapy with PPIs. Postoperative morbidity is substantial, especially when procedures are done outside expert centres. In the past few years several endoscopic techniques have been developed to treat chronic GORD on an outpatient basis. These techniques include radiofrequency-energy delivery and endoscopic suturing, although other approaches are now under development. STARING POINT: Two prospective open-label studies have recently reported 1-year follow-up of GORD patients treated either by radiofrequency-energy delivery (G Triadafilopoulos and colleagues Gastrointest Endosc 2002; 55:149-56) or endoscopic suturing (Z Mahmood and colleagues Gut 2003; 52:34-39). In a US multicentre trial, Triadafilopoulos and colleagues delivered radiofrequency energy to the cardia and distal oesophagus in patients with chronic heartburn, regurgitation or both (the Stretta procedure). All patients were on continuous acid-suppression therapy, but none had severe oesophagitis or hiatus hernia of more than 2 cm. At 12 months, 94 patients available for follow-up showed significant improvement in GORD symptoms, quality of life, and oesophageal acid-exposure. The need for PPI therapy fell from 98% to 30% of patients. In the Mahmood study, 26 similar patients had endoscopic suturing in a single centre. After 1 year, symptoms and quality of life improved and the need for PPIs was reduced to 36% from 100%. In both studies, only minor complications occurred, none of which required specific therapeutic intervention. WHERE NEXT? An effective outpatient procedure to treat chronic GORD would represent a major step forward. However, further studies are needed before an endoscopic approach can be adopted, as none of the published trials are well-controlled studies. Longer follow-up is needed to ensure that relapses do not occur rapidly, complications do not occur more frequently with less skilled operators, or that endoscopic-induced changes do not complicate or compromise subsequent antireflux surgery. Comparative studies of the cost-effectiveness of endoscopic therapy should also include medical strategies such as intermittent or on-demand PPI therapy.