Concurrent use of herbs may mimic, magnify, or oppose the effect of drugs. Plausible cases of herb-drug interactions include: bleeding when warfarin is combined with ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai (Angelica sinensis), or danshen (Salvia miltiorrhiza); mild serotonin syndrome in patients who mix St John's wort (Hypericum perforatum) with serotonin-reuptake inhibitors; decreased bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon when these drugs are combined with St John's wort; induction of mania in depressed patients who mix antidepressants and Panax ginseng; exacerbation of extrapyramidal effects with neuroleptic drugs and betel nut (Areca catechu); increased risk of hypertension when tricyclic antidepressants are combined with yohimbine (Pausinystalia yohimbe); potentiation of oral and topical corticosteroids by liquorice (Glycyrrhiza glabra); decreased blood concentrations of prednisolone when taken with the Chinese herbal product xaio chai hu tang (sho-salko-to); and decreased concentrations of phenytoin when combined with the Ayurvedic syrup shankhapushpi. Anthranoid-containing plants (including senna [Cassia senna] and cascara [Rhamnus purshiana]) and soluble fibres (including guar gum and psyllium) can decrease the absorption of drugs. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs.

A 1999 study found no decrease in breast-cancer mortality in Sweden, where screening has been recommended since 1985. We therefore reviewed the methodological quality of the mammography trials and an influential Swedish meta-analysis, and did a meta-analysis ourselves.

We investigated the relation between fetoplacental growth and the use of oral antihypertensive medication to treat mild-to-moderate pregnancy hypertension.

Vascular gene transfer potentially offers new treatments for cardiovascular diseases. It can be used to overexpress therapeutically important proteins and correct genetic defects, and to test experimentally the effects of various genes in a local vascular compartment. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) gene transfers have improved blood flow and collateral development in ischaemic limb and myocardium. Promising therapeutic effects have been obtained in animal models of restenosis or vein-graft thickening with the transfer of genes coding for VEGF, nitric-oxide synthase, thymidine kinase, retinoblastoma, growth arrest homoeobox, tissue inhibitor of metalloproteinases, cyclin or cyclin-dependent kinase inhibitors, fas ligand and hirudin, and antisense oligonucleotides against transcription factors or cell-cycle regulatory proteins. First experiences of VEGF gene transfer and decoy oligonucleotides in human beings have been reported. However, further developments in gene-transfer vectors, gene-delivery techniques and identification of effective treatment genes will be required before the full therapeutic potential of gene therapy in cardiovascular disease can be assessed.

Mitochondria have a pivotal role in cell metabolism, being the major site of ATP production via oxidative phosphorylation (OXPHOS); they have a critical role in apoptotic cell death; and they also contribute to human genetics since mitochondria have a functional genome separate from that of nuclear DNA. Defects of mitochondrial metabolism are associated with a wide spectrum of disease. An Important part of this spectrum is caused by mutations of mitochondrial DNA (mtDNA). These class I OXPHOS diseases are covered in part I of this two-part review. Dysfunction of mitochondrial OXPHOS has also emerged as an important component of a range of predominantly neurodegenerative diseases in which the mitochondrial abnormality is most probably secondary. These class II OXPHOS diseases are due to mutations of genes not encoding OXPHOS subunits or are caused by exogenous or endogenous OXPHOS toxins. Class II mitochondrial diseases and the mitochondrion's role in apoptosis are covered in part II (Lancet 2000; 355: 389-94).

The first part of this review (Lancet 2000; 355: 299) covered primary disorders of mitochondrial DNA (mtDNA). This section will cover nuclear-encoded defects of the oxidative phosphorylation (OXPHOS) system, including mtDNA mutations that are secondary to nuclear gene mutations and nuclear gene defects responsible for secondary OXPHOS deficiency (panel). The latter group of diseases are predominantly neurodegenerative. The mitochondrion's role in apoptosis and its contribution to the pathogenesis of neurodegenerative diseases are also covered.

After the introduction of effective Haemophilus influenzae type b (Hib) conjugate vaccines, clinical practice has driven the development of combination vaccines comprising Hib conjugates with the infant diphtheria-tetanus-pertussis (DTP) vaccines. However, when such combinations contain an acellular pertussis component (Pa), the antibody response to Hib is lower than that with separate injections and doubts have been raised about their efficacy. We believe that such concerns are unwarranted, since the serological correlates of efficacy previously applied for Hib polysaccharide vaccines seem inappropriate for Hib conjugates. Furthermore, our own studies have shown that the lower antibody responses are not associated with impaired function of the antibodies induced, nor, and possibly more importantly, with the induction of immune memory against Hib. Therefore, with the proviso that careful clinical surveillance of Hib disease is maintained, we encourage the introduction of DTPa-Hib combinations to facilitate the inclusion of Hib into the already crowded childhood immunisation schedule.

Randomised clinical trials are undertaken in the hope of showing positive benefits of a new treatment, but on occasion quite the opposite trend can occur, If the interim data suggest possible negative (harmful) effects of a new treatment. The handling of such emerging negative trends is among the most complicated and ethically challenging scenarios in monitoring clinical trials through repeated interim analyses. Statistical methods are helpful to detect the point of no likely beneficial effect, and the point that separates neutral results from harmful results. However, in practice the decision whether (and exactly when) to stop such a trial involves a complex of other issues that depends on the context of the disease, the treatment being assessed, and the current practice of medicine. Owing to this complexity, an Independent Data and Safety Monitoring Board (DSMB) is best suited to deal with such a situation. Prediction of whether a negative trend will emerge in any trial is not possible. Negative trends were not anticipated in the cardiovascular trials and the trials of lung-cancer prevention described here. In the light of these experiences, all trials and their DSMBs should consider ahead of time the possibility of unexpectedly harmful results, and should document appropriately the statistical guidelines and the decision-making process required to cope with such undesirable events.

Excessive bleeding may complicate cardiac surgery, and is associated with increased morbidity and mortality. Pharmacological strategies to decrease perioperative bleeding have been investigated in a large number of controlled trials, most of which have shown a decrease in blood loss. However, most studies lacked sufficient power to detect a beneficial effect on clinically more relevant outcomes. We did a meta-analysis of all randomised, controlled trials of the three most frequently used pharmacological strategies to decrease perioperative blood loss (aprotinin, lysine analogues [aminocaproic acid and tranexamic acid], and desmopressin).

Dermatomyositis is one of the idiopathic inflammatory myopathies with characteristic cutaneous manifestations including the heliotrope rash, Gottron's papules, cuticular changes including periungual telangiectasia, a photodistributed erythema or poikiloderma, and a scaly alopecia. Dermatomyositis has been linked to cancer, particularly ovarian cancer. Cancer-associated disease is more commonly found in older patients, and when present, is associated with a poor prognosis. A childhood form of the disease exists and is frequently complicated by the development of calcinosis. Dermatomyositis is a systemic disorder and whereas the skin and muscles are the most commonly affected organs, patients may have arthralgias, arthritis, oesophageal disease, or cardiopulmonary dysfunction. Recently described serological abnormalities, known as myositis-specific antibodies, add credence to the notion that this disorder is distinct from all other collagen-vascular diseases, and may lead to important discoveries about the pathogenesis of the inflammatory myopathies, which are not currently of practical use in the clinic or office. Management of the patient with myositis usually includes systemic corticosteroids with or without an immunosuppressive agent. Cutaneous disease is more difficult to manage, but antimalarials, methotrexate, and intravenous immunoglobulin are effective in small, often open-label, studies.

The Quality of Reporting of Meta-analyses (QUOROM) conference was convened to address standards for improving the quality of reporting of meta-analyses of clinical randomised controlled trials (RCTs).

In 2000 an estimated 66.8 million people worldwide will have glaucoma, 6.7 million of whom will be bilaterally blind from irreversible optic-nerve damage. Yet even in developed countries with public educational programmes that target glaucoma, half of the individuals with glaucoma remain undiagnosed. Patients with even mild visual impairment secondary to glaucoma may have difficulties with mobility, driving, and social interactions. Although glaucoma may be associated with increased eye pressures, its diagnosis does not rely on a specific level of eye pressure. Diagnosis of glaucoma often relies on examination of the optic disc and assessment of the visual field. The two most common types of glaucoma--primary open-angle glaucoma and primary angle-closure glaucoma--have different risk factors. Although similar medications can be used to treat these two types of glaucoma, the overall management of patients differs in important ways. Until recently, there were no randomised clinical trials that showed the effectiveness of lowering eye pressures with medications or surgery in patients with glaucoma. However, in 1998 a randomised clinical trial showed the benefit of lowering eye pressure in patients with glaucoma who had eye pressures of 24 mm Hg or less. Because glaucoma is treatable, and because the visual impairment from glaucoma is irreversible, early detection of the disease is critically important.