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2921. Nuclear weapons, a continuing threat to health.
32,000 nuclear weapons, with a destructive force equivalent to several thousand megatons of conventional explosive, are still deployed. The risk of nuclear war by accident may have increased and new threats include war between newly declared nuclear-weapon-states and the construction by terrorist groups of crude but effective devices. Health workers have drawn attention in the past to the likely major health consequences of the use of nuclear weapons. An opportunity for their global elimination under a nuclear weapons convention arises with the current review conference in New York of the nuclear Non-Proliferation Treaty--a crucial event for efforts to bring about a world free of nuclear weapons.
2922. Platelets.
Platelets, derived from megakaryocyte cytoplasm, have a critical role in normal haemostasis, and in thrombotic disorders. The development of megakaryocytes is controlled by thrombopoietin, which binds to c-mpl on the surface of platelets and megakaryocytes. Platelet membrane glycoproteins mediate binding to subendothelial tissue and aggregation into haemostatic plugs. Thrombocytopenia and disorders of platelet function cause petechiae and mucocutaneous bleeding. Drugs causing specific inhibition of platelet function are important in the treatment of cardiovascular and cerebrovascular disease.
2923. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Prostate Cancer Trialists' Collaborative Group.
来源: Lancet. 2000年355卷9214期1491-8页
In advanced prostate cancer, androgen suppression (AS) by surgery or drugs controls testicular hormone secretion, and the further addition of an antiandrogen such as nilutamide, flutamide, or cyproterone acetate is referred to as maximum androgen blockade (MAB). The aim of this overview was to compare the effects on the duration of survival of MAB and of AS alone.
2924. White cells 2: impact of understanding the molecular basis of haematological malignant disorders on clinical practice.
The molecular basis of many leukaemias is now known, allowing precise diagnosis. Treatment of chronic myeloid leukaemia is now possible by targeting of the BCR-ABL tyrosine kinase. The underlying molecular abnormalities in acute leukaemias allow the outlook for individual patients to be assessed at diagnosis and therapy tailored accordingly. Analysis of V(H) genes in B-cell malignant disorders allows these to be placed in the hierarchy of B-cell development and may provide prognostically valuable information.
2925. Epilepsy in elderly people.
The prevalence and incidence of epilepsy are highest in later life with around 25% of new cases occurring in elderly people, many of whom will have concomitant neurodegenerative, cerebrovascular, or neoplastic disease. Difficulties accepting the diagnosis are frequently compounded by its unpredictable nature. Those affected commonly lose confidence and independence. Seizures in older people can result in physical injury, adding to low morale. Complete control is achievable in around 70% of patients with antiepileptic drug treatment. Optimum management requires rapid investigation, accurate diagnosis, effective treatment, sympathetic education, and assured support. The emergence of seizure disorders in old age places an increasing burden on health-care facilities and costs. A coordinated programme among health-care workers is advised to maintain the independence and improve the quality of life of this vulnerable patient population.
2928. The taxanes: an update.
The taxanes are anticancer cytotoxics that stabilise cellular microtubules. Two members, paclitaxel and docetaxel have substantial activity. One or both agents are widely accepted as evidence-based components of therapy for advanced breast, lung, and ovarian carcinomas. Paclitaxel has recently been approved in the USA for the adjuvant treatment of early stage node-positive breast carcinoma.
2929. Red cells I: inherited anaemias.
Examination of the genetic mechanisms underlying the thalassaemias has led to a clearer understanding of the control of eukaryotic genes in general. Inherited disorders of haemoglobin synthesis are an important cause worldwide of morbidity and mortality, and place a large burden on patients, families, and ultimately communities. The haemoglobin disorders can be controlled, by counselling and prenatal diagnosis. Treatment is usually symptomatic, though bone-marrow transplantation for beta-thalassaemia may be successful in suitable patients.
2931. White blood cells 1: non-malignant disorders.
Disorders of white cells are very common in clinical practice. White-cell development and numbers are controlled by a mixture of external stimuli including cytokines, matrix proteins, and accessory cells. Several different white-cell lineages are recognised; each has a role in host defence. Both white-cell deficiency and overproduction can lead to disease. Some forms of inherited white-cell deficiency are potentially treatable with gene therapy.
2932. Directly observed therapy and treatment adherence.
Direct observation of patients taking their medication is a strategy to improve completion rates for tuberculosis treatment, but the programmes to implement this approach consist of a complex array of inputs aimed at influencing adherence. Policy makers need a clear understanding of these inputs to succeed. We systematically identified and reviewed published reports of direct observation therapy (DOT) programmes and compared inputs with WHO's short-course DOT programme. DOT programmes frequently consist of more than the five elements of WHO's strategy, including incentives, tracing of defaulters, legal sanctions, patient-centred approaches, staff motivation, supervision, and additional external funds. Focusing on direct observation as a key factor in the promotion of adherence seems inappropriate. Multiple components might account for the success of DOT programmes, and WHO should make these explicit.
2933. Red cells II: acquired anaemias and polycythaemia.
Iron deficiency affects 30% of the world's population. Iron metabolism is tightly regulated, with both gut transport and storage being coordinated. Hereditary haemochromatosis due to mutations in the HFE gene leads to increased absorption of iron and multiple end-organ damage. Myelodysplastic disorders are acquired clonal stem-cell disorders that cause ineffective erythropoiesis. Aplastic anaemia is caused by an intrinsic defect of haemopoietic stem cells; both inherited and acquired forms occur. Primary polycythaemia is a myeloproliferative disorder, a non-malignant stem-cell disease.
2934. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer.
Despite more than 70 randomised trials, the effect of chemotherapy on non-metastatic head and neck squamous-cell carcinoma remains uncertain. We did three meta-analyses of the impact of survival on chemotherapy added to locoregional treatment.
2935. Chiral switches.
Developments in synthetic and analytical chemistry have provided the tools to differentiate between two enantiomers (mirror images) of drugs or between the parent compound and metabolite(s) with respect to desired and undesired pharmacological effects. Several drugs are now marketed or being developed as single enantiomers in place of a previous racemic mixture, a process known as "chiral switching". It is easier to understand "pure" as opposed to "mixture" pharmacology but whether the promise of chiral (and metabolite) switches will translate into real clinical advances remains to be seen.
2936. Influenza virus neuraminidase inhibitors.
Neuraminidase promotes influenza virus release from infected cells and facilitates virus spread within the respiratory tract. Several potent and specific inhibitors of this enzyme have been developed, and two (zanamivir and oseltamivir) have been approved for human use. Unlike amantadine and rimantadine that target the M2 protein of influenza A viruses, these drugs inhibit replication of both influenza A and B viruses. Zanamivir is delivered by inhalation because of its low oral bioavailability whereas oseltamivir is administered by mouth. Early treatment with either drug reduces the severity and duration of influenza symptoms and associated complications. Both agents are effective for chemoprophylaxis. Because of a broader antiviral spectrum, better tolerance, and less potential for emergence of resistance than is seen with the M2 inhibitors, the neuraminidase inhibitors represent an important advance in the treatment of influenza.
2937. Scabies and pediculosis.
Scabies and pediculosis are ubiquitous, contagious, and debilitating parasitic dermatoses. They have been known since antiquity and are distributed worldwide. Clusters of infestation occur-for example, scabies affecting immunocompromised individuals or patients and staff in hospitals and nursing homes for the elderly, and pediculosis affecting schoolchildren or homeless people. Associations with other disorders are common: infections with human T-cell leukaemia/lymphoma virus I (HTLV-I) and HIV are associated with scabies, and trench fever and exanthematous typhus with pediculosis. Specific forms of scabies, including bullous scabies or localised crusted scabies, may be misdiagnosed. Moreover, definitive parasitic diagnosis can be difficult to obtain, and the value of new techniques remains to be confirmed. Difficulties in management have returned scabies and pediculosis to the limelight.
2938. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview.
High blood glucose concentration may increase risk of death and poor outcome after acute myocardial infarction. We did a systematic review and meta-analysis to assess the risk of in-hospital mortality or congestive heart failure after myocardial infarction in patients with and without diabetes who had stress hyperglycaemia on admission.
2939. Prenylation inhibitors in renal disease.
Members of the superfamily of Ras GTPase signalling proteins (monomeric G proteins) require post-translational carboxy-terminal prenylation to function. Prenylation is the covalent attachment of a hydrophobic prenyl group (either farnesyl or geranylgeranyl), which localises the GTPase to cell membranes. Ras proteins exert substantial control on cell proliferation and gene-transcription events, and prenylation inhibitors are now included in clinical trials for cancer. Many renal diseases are highly proliferative and are driven by a range of profibrotic cytokines. We hypothesise that inhibition of prenylation could be of substantial therapeutic benefit in such diseases, providing greater selectivity against abnormal cytokine-driven proliferation and fibrogenesis than current treatments available to nephrologists.
2940. Therapeutic monoclonal antibodies.
The therapeutic potential of monoclonal antibodies (mAb) was quickly realised after the hybridoma technique allowed their development in the mid 1970s. Chimeric humanised and fully humanised mAb can now be made by recombinant engineering. About a quarter of all biotech drugs in development are mAb, and around 30 products are in use or being investigated. Licensed products are available for inhibition of alloimmune and autoimmune reactivity, and for antitumour, antiplatelet, or antiviral therapy. Short-term side-effects are tolerable and as expected, although long-term safety remains to be elucidated. The cost-effectiveness and quality-of-life benefits of the use of mAb in patients who are usually seriously and chronically ill also needs studying. The therapeutic use of mAb is now established, and is perhaps the first example of how the "new biology" and the understanding of underlying molecular mechanisms has benefited patients.
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