Distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene encoding the erythroid and kidney isoforms of anion exchanger 1 (AE1 or band 3) has a high prevalence in some tropical countries, particularly Thailand, Malaysia, the Philippines and Papua New Guinea (PNG). Here the disease is almost invariably recessive and can result from either homozygous or compound heterozygous SLC4A1 mutations.
The landmark HMG-CoA reductase inhibitor (statin) studies have practical lessons for clinicans. The 4S trial established the importance of treating the hypercholesterolaemic patient with cardiovascular heart disease. Next, WOSCOPS showed the benefit of treating healthy, high-risk hypercholesterolaemic men. CARE, a secondary prevention trial, showed the benefit of treating patients with cholesterol levels within normal limits. This was confirmed by the LIPID trial, another secondary prevention study, which enrolled patients with cholesterol levels 155-271 mg/dl (4-7 mmol/l). The importance of treating patients with established ischaemic heart disease, and those at high risk of developing heart disease, regardless of cholesterol level, was being realized. In the MIRACL trial, hypocholesterolaemic therapy was useful in the setting of an acute coronary syndrome, while the AVERT study showed that aggressive statin therapy is as good as angioplasty in reducing ischaemic events in patients with stable angina. By showing the value of fluvastatin after percutaneous intervention, LIPS confirmed that benefit is a class action of the statins. The HPS randomized over 20 000 patients, and showed beyond doubt the value of statins in reducing cardiovascular events in the high-risk patient. Although PROSPER showed benefit in treating the elderly patients above 70 years, statin therapy in this trial was associated with an increase in cancer incidence. The comparative statin trials, PROVE-IT, REVERSAL, Phase Z of the A to Z, ALLIANCE and TNT, all showed that high-dose statins will better reduce cardiovascular events in the high-risk patient, although the adverse effects of therapy will also be increased. ALLHAT-LLT, ASCOT-LLA and CARDS showed that for statin therapy to demonstrate a significant benefit, hypertensive or diabetic patients must be at sufficiently high risk of cardiovascular events. The emphasis is now on the risk level for developing cardiovascular events, and treatment should target the high-risk group and not the lipid level of the patient. No therapy is free of adverse effect. Treatment of those most at risk will bring the most benefit; treatment of those not at high risk of cardiovascular disease may expose patients who would not benefit much from therapy to its adverse effects.
To determine the incidence, types and risk factors for infection in systemic lupus erythematosus (SLE) patients in Kuala Lumpur, Malaysia, we retrospectively reviewed the medical records of 102 patients with definite SLE attending a specialist clinic. Details of major infections (pneumonia or severe infection requiring intravenous therapy) and minor infections, and their time of onset in relation to immunosuppressive therapy and disease flares were recorded. There were 77 major and 163 minor infections during 564 patient-years of follow-up. In the month following a course of pulse methylprednisolone, the incidence of major infection was 20 times higher and the incidence of minor infection was 10 times higher than at other periods (p < 0.0001). In the month after disease flare, the incidence of major infection was 10 times higher and the incidence of minor infection six times higher than at other times (p < 0.0001). After allowing for methylprednisolone therapy and disease flares, there was no increase in the rate of infections during treatment with azathioprine, oral or intravenous cyclophosphamide. There was no effect of renal involvement on infection rate.