Few randomised controlled trials have sufficient power to show clear advantages of different designs of cervical-smear collection devices. We studied by systematic review whether the design of cervical-smear devices affects rates of inadequate smears and detection of disease and whether the presence of endocervical cells in the smear affects detection of disease.

Erectile dysfunction can be devastating for men and for their partners. A good sexual history and focused physical examination can provide clues as to whether the underlying cause is psychogenic or organic. Diagnostic investigation should be tailored to the clinical picture. Oral medications now represent first-line therapy. Penile injection therapy and vacuum constrictive devices are reasonable choices for men in whom oral therapy falls or is contraindicated. The penile prosthesis provides a reliable long-term solution with high satisfaction rates. Psychotherapy may be indicated. Physicians can have a positive impact on the quality of life of patients by providing a non-judgmental and supportive environment for discussion and management of impotence.

In the long QT syndromes (LQTS), malfunction of ion channels impairs ventricular repolarisation and triggers a characteristic ventricular tachyarrhythmia: torsade de pointes. Symptoms in the LQTS (syncope or cardiac arrest) are caused by this arrhythmia. In congenital LQTS, mutations in the genes encoding for ion channels cause this channel malfunction. Six genotypes (LQT1 to LQT6) have been identified, and attempts are being made to correlate different mutations with clinical signs and specific therapy. In acquired LQTS, channel malfunction is caused by metabolic abnormalities or drugs. The list of drugs that may impair ion-channel function expands continuously. Moreover, attributes that increase the risk for drug-induced torsade (eg, female sex, recent heart-rate slowing, or hypokalaemia) and electrocardiographic "warning signs" are recognised. Recent data suggest that patients with an acquired LQTS have some underlying predisposition to proarrhythmia. Mutations causing "silent" forms of congenital LQTS, in which the patient remains free of arrhythmias until exposed to drugs that further impair repolarisation, are now recognised.

Associations of birthweight with leg length and trunk length are similar. Childhood exposures rather than in-utero programming may underlie specific associations seen between leg length and mortality.

This review of the effectiveness of treatment for acute stroke and methods of secondary prevention shows that the highest priority for providers of a stroke service must be to establish a stroke unit and multidisciplinary team that delivers organised stroke care. Acute ischaemic stroke patients should be immediately started on aspirin 300 mg daily, and, if possible, many of them should be entered into further trials of thrombolysis and other promising treatments. After the acute phase, aspirin should be continued in a lower dose, 75 mg daily; smoking should be discouraged; high blood pressure treated initially with a diuretic; and fibrillating ischaemic stroke/transient ischaemic attack survivors anticoagulated long-term with warfarin or given aspirin if anticoagulation is not sensible. Statins are probably indicated in patients who already have symptomatic coronary heart disease. Adding dipyridamole to aspirin, substituting clopidogrel for aspirin, and carotid endarterectomy are all expensive interventions to prevent stroke, but if ways could be found to focus them on those patients at especially high risk, they would become more affordable.

WHO estimate that by the beginning of the next century major unipolar depression will be one of the most important causes of ill health overall. Whereas the cause of depression is still obscure, it is becoming clear that a number of diverse factors are likely to be implicated, both genetic and environmental. Effective treatment of depression similarly involves a variety of methods, from electro-convulsive therapy to inter-personal psychotherapy. The pathophysiology of depression is gradually becoming accessible through research strategies, such as functional neuroimaging paired with mood altering interventions.

Permissive hypercapnia (acceptance of raised concentrations of carbon dioxide in mechanically ventilated patients) may be associated with increased survival as a result of less ventilator-associated lung injury. Conversely, hypocapnia is associated with many acute illnesses (eg, asthma, systemic inflammatory response syndrome, pulmonary oedema), and is thought to reflect underlying hyperventilation. Accumulating clinical and basic scientific evidence points to an active role for carbon dioxide in organ injury, in which raised concentrations of carbon dioxide are protective, and low concentrations are injurious. We hypothesise that therapeutic hypercapnia might be tested in severely ill patients to see whether supplemental carbon dioxide could reduce the adverse effects of hypocapnia and promote the beneficial effects of hypercapnia. Such an approach could also expand our understanding of the pathogenesis of disorders in which hypocapnia is a constitutive element.

Influenza is the most frequent cause of acute respiratory illness requiring medical intervention because it affects all age groups and because it can recur in any individual. During the past three decades, efforts to prevent and control influenza have focused primarily on the use of inactivated influenza vaccines in elderly people and in individuals with chronic medical conditions that put them at risk for complications. However, the continuing impact of influenza in these and other population groups has motivated the development of novel approaches for prevention and control of influenza. Several important advances in the field of influenza have occurred in the last few years. An experimental live, attenuated, intranasally administered trivalent influenza vaccine was shown to be highly effective in protecting young children against influenza A H3N2 and influenza B. New antiviral drugs based on the structure of the neuraminidase molecule were assessed in clinical trials and found to be effective against influenza A and B viruses. The expected use of these new antiviral agents has accelerated the development of rapid point-of-care diagnostic tests. The availability of new diagnostic tests, new antiviral drugs, and new vaccines will undoubtedly alter our approaches to influenza control and have an impact on clinical practice.

Bed rest is not only used in the management of patients who are not able to mobilise, but is also prescribed as a treatment for a large number of medical conditions, a procedure that has been challenged. We searched the literature for evidence of benefit or harm of bed rest for any condition.

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.