Primary pulmonary hypertension (PPH) is a progressive disease characterised by raised pulmonary vascular resistance, which results in diminished right-heart function due to increased right ventricular afterload. PPH occurs most commonly in young and middle-aged women; mean survival from onset of symptoms is 2-3 years. The aetiology of PPH is unknown, although familial disease accounts for roughly 10% of cases, which suggests a genetic predisposition. Current theories on pathogenesis focus on abnormalities in interaction between endothelial and smooth-muscle cells. Endothelia-cell injury may result in an imbalance in endothelium-derived mediators, favouring vasoconstriction. Defects in ion-channel activity in smooth-muscle cells in the pulmonary artery may contribute to vasoconstriction and vascular proliferation. Diagnostic testing primarily excludes secondary causes. Catheterisation is necessary to assess haemodynamics and to evaluate vasoreactivity during acute drug challenge. Decrease in pulmonary vascular resistance in response to acute vasodilator challenge occurs in about 30% of patients, and predicts a good response to chronic therapy with oral calcium-channel blockers. For patients unresponsive during acute testing, continuous intravenous epoprostenol (prostacyclin, PGI2) improves haemodynamics and exercise tolerance, and prolongs survival in severe PPH (NYHA functional class III-IV). Thoracic transplantation is reserved for patients who fail medical therapy. We review the progress made in diagnosis and treatment of PPH over the past 20 years.

The pathophysiology of transient global amnesia (TGA) has been obscure since the definition of this syndrome more than 30 years ago. Current hypotheses include migraine, seizure, or transient cerebral arterial ischaemia. However, none of these potential mechanisms explain both the absence of other neurological signs or symptoms during TGA, and its frequent precipitating activities: many of which would be expected to result in marked increases in venous return from the arms to the superior vena cava. Patients with TGA also commonly have a Valsalva manoeuvre at the onset of attacks. I suggest that a Valsalva manoeuvre, blocking venous return through the superior vena cava, may allow brief retrograde transmission of high venous pressure from the arms to the cerebral venous system, resulting in venous ischaemia to the diencephalon or mesial temporal lobes and to TGA.

A summary of new findings regarding alterations of magnesium (Mg2+) and phosphorus (P) metabolism are reviewed for the clinician caring for patients in general wards. Alterations in serum concentrations of Mg2+ and P are frequently observed in acute or very ill patients in emergency rooms or intensive-care areas. A significant proportion of these alterations are iatrogenic. Most of the symptoms related are non-specific, and usually they are associated with changes in concentration of other ions. The need to measure Mg2+ and P routinely and to define better the real abnormal values is stressed. Correction of the abnormalities must be early in the course of the alterations.

Seizures are commonly encountered in patients who do not have epilepsy. Factors that may provoke such seizures include organ failure, electrolyte imbalance, medication and medication withdrawal, and hypersensitive encephalopathy. There is usually one underlying cause, which may be reversible in some patients. A full assessment should be done to rule out primary neurological disease. Treatment of seizures in medically ill patients is aimed at correction of the underlying cause with appropriate short-term anticonvulsant medication. Phenytoin is ineffective in the management of seizures secondary to alcohol withdrawal, and in those due to theophylline or isoniazid toxicity. Control of blood pressure is important in patients with renal failure and seizures. Non-convulsive status epilepticus should be considered in any patient with confusion or coma of unclear cause, and electroencephalography should be done at the earliest opportunity. Most ill patients with secondary seizures do not have epilepsy, and this should be explained to patients and their families. Only those patients with recurrent seizures and uncorrectable predisposing factors need long-term treatment with anticonvulsant medication.

Lyme borreliosis (Lyme disease) is often said to be associated with "protean" manifestations, a reference to the ancient god Proteus, who could assume many forms and thus elude his pursuers. This legendary quality has clouded our understanding of Lyme borreliosis by giving Borrelia burgdorferi infection a mythical aura of its own. This review shows that this illness, while incompletely understood, is far more palpable than Proteus and is (in most cases) much more readily subdued. The clinical presentations of Lyme borreliosis do differ in North America and Eurasia, possibly due to the differing pathogenicity of distinct genospecies of Borrelia burgdorferi. The most common manifestation, however, in both continents is erythema migrans. Diagnosis should rest on a careful history and objective clinical findings, supported by appropriately chosen laboratory tests. Reports of coinfection with other tick-borne diseases should prompt a fresh look at Lyme borreliosis. Assertions about "protean manifestations" of B burgdorferi infection should be reappraised. Advances in laboratory techniques are welcome but culture remains the gold standard for the diagnosis--and no laboratory test result should substitute for careful clinical observation and critical analysis.

Acid-base disorders are common clinical problems resulting from a wide variety of pathophysiological conditions, including newly recognised acquired and genetic causes. The history and physical examination and measurement of blood and urinary indices allow identification of the underlying cause of these disorders in most cases. Treatment directed at correction of electrolyte abnormalities and the underlying cause for the disorder is essential for preventing the acute and long-term metabolic consequences of acid-base derangements.

Acute exacerbations of underlying COPD are a common cause of respiratory deterioration. Developments have been made in preventive measures, but admission to hospital for acute exacerbations can be expected to remain common. Several expert consensus guidelines have been published to define the appropriate management of COPD patients. These consensus guidelines generally agree, but all acknowledge a lack of large well-controlled clinical studies, especially studies focusing on the management of acute exacerbations. Consequently, many potential controversies exist about the details of managing patients with acute exacerbations. Although studies of many fundamental aspects of management are still needed, the results of controlled clinical trials are sufficient to emphasise the importance of a careful clinical assessment, supplemental oxygen, inhaled bronchodilators to partially improve airway obstruction, corticosteroids to decrease the likelihood of treatment failures and to speed recovery, antibiotics, especially in severe patients, and non-invasive positive-pressure ventilation for treatment of acute ventilatory failure in selected patients.

When the British HIV-1 Association (BHIVA) guidelines on the treatment of HIV-seropositive individuals with antiretrovirals were published in The Lancet in April 1997, it was clear that they would require updating on a frequent basis. The guidelines have been useful in ensuring that viral-load testing and combination therapy is widely available in the UK. However, standards of treatment are rapidly changing as new evidence becomes available. Since formulation of the guidelines, data from two large clinical endpoint studies have been presented that show superior clinical benefit for the use of triple therapy compared with dual therapy in treatment of both naive individuals and patients who have been given zidovudine. Here we update the BHIVA guidelines with a consensus drawn from a wide range of UK medical opinion. The guidelines include input from groups representing individuals living with HIV-1. A more detailed reflection of these views may be found in publications such as the National AIDS Manual and the AIDS Treatment Project's Doctor fax.

Abnormalities in serum calcium concentration may have profound effects on neurological, gastrointestinal, and renal function. Maintenance of the normal serum calcium is a result of tightly regulated ion transport by the kidney, intestinal tract, and bone, mediated by calcaemic hormones especially parathyroid hormone and 1,25-dihydroxyvitamin D3. Abnormalities in calcium transport that result in uncompensated influx into, or efflux from, the extracellular fluid, will result in hypercalcaemia or hypocalcaemia, respectively. When possible the biologically important ionised calcium concentration should be measured. A variety of common disorders are responsible for abnormalities in the serum calcium. Treatment of both hypercalcaemia and hypocalcaemia is dependent on the underlying disorder, the magnitude of the deviation of the serum calcium, and the severity of symptoms. Fortunately, in the case of hypercalcaemia, there is a broad selection of effective medications, especially the bisphosphonates. Treatment of hypocalcaemia relies on the provision of calcium and often vitamin D. In this article we review the mechanisms responsible for abnormalities in calcium homoeostasis, the differential diagnosis of hypercalcaemia and hypocalcaemia, and appropriate therapy.

The role of postoperative radiotherapy in treatment of patients with completely resected non-small-cell lung cancer (NSCLC) remains unclear. We undertook a systematic review and meta-analysis of the available evidence from randomised trials.

Disorders of serum sodium are both the most common and probably most the poorly understood electrolyte disorders in clinical medicine. In the past few years increased knowledge about the non-osmotic release of vasopressin and the cloning of vasopressin receptors and of vasopressin-regulated water channels (AQP2) has enhanced our understanding of these disorders. Also controversies surrounding the treatment of hyponatraemic patients have led to well-accepted therapeutic guidelines.

It is likely that the pathophysiology of diabetic nephropathy involves an interaction of metabolic and haemodynamic factors. Relevant metabolic factors include glucose-dependent pathways such as advanced glycation, increased formation of polyols, and activation of the enzyme, protein kinase C. Specific inhibitors of the various pathways are now available, enabling investigation of the role of these processes in the pathogenesis of diabetic nephropathy and potentially to provide new therapeutic approaches for the prevention and treatment of diabetic nephropathy. Haemodynamic factors to consider include systemic hypertension, intraglomerular hypertension, and the role of vasoactive hormones, such as angiotensin II. The mainstay of therapy remains attaining optimum glycaemic control. Antihypertensive therapy has a major role in slowing the progression of diabetic nephropathy. Agents that interrupt the renin-angiotensin system such as angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists may be particularly useful as renoprotective agents in both the hypertensive and normotensive context.

In a logical, stepwise approach to patients presenting with hypokalaemia or hyperkalaemia the clinician must first recognise circumstances in which the dyskalaemia represents a clinical emergency because therapy then takes precedence over diagnosis. If a dyskalaemia has been present for a long time, there is an abnormal renal handling of K+. The next step to analyse is the rate of excretion of K+ and, if necessary, its two components (urine flow rate and K+ concentration in the cortical collecting duct [CCD]) analysed independently. If the K+ concentration in the CCD is not in the expected range, its basis should be defined at the ion-channel level in the CCD from clinical information that can be used to deduce the relative rates of reabsorption of Na+ and Cl- in the CCD. This analysis provides the basis for diagnosis and may indicate where non-emergency therapy should then be directed.