Drugs
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Tumour markers can aid in areas such as diagnosis, surveillance of recurrence, staging and prognosis. This article focuses on 2 tumour markers, alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG). These tumour markers have been examined for their utility as prognostic indicators in 2 different manners. ⋯ In some diseases, issues relating to timing of marker sampling when examining marker decline need to be studied in greater detail. Hopefully, marker decline studies can be duplicated in the other diseases, to document a potential role in determining outcome. Further studies are needed to test the ability to alter therapy in attempts to improve survival while decreasing toxicity to patients.
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Surgical site infections (SSI) remain a major source of postoperative morbidity. The preventive effect of antimicrobial drugs on postoperative infections is without debate. The common basis of accepted indications for prophylaxis is available evidence of effect. ⋯ Overconsumption in terms of invalid indications or use of drugs with too broad a spectrum of activity should be eliminated by adhering to accepted guidelines. Practical suggestions are given to optimise timing, such as simple reminders on the daily operating programme, the display of prophylaxis regimens according to type of surgery in table format in the operating room and having the anaesthetist note the complete drug regimen on the patient's anaesthesia record. Such measures will help to optimise antibiotic prophylaxis and restrict if to the operating room where it belongs.
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Cardiopulmonary bypass (CPB) is associated with defective haemostasis which results in bleeding and the requirement for allogenic blood product transfusions in many patients undergoing open heart surgery (OHS) and/or coronary artery bypass graft surgery (CABG) with CPB. Conservation of blood has become a priority during surgery because of shortages of donor blood, the risks associated with the use of allogenic blood products and the costs of these products. Aprotinin is a serine protease inhibitor isolated from bovine lung tissue which acts in a number of interrelated ways to provide an antifibrinolytic effect, inhibit contact activation, reduce platelet dysfunction and attenuate the inflammatory response to CPB. It is used to reduce blood loss and transfusion requirements in patients with a risk of haemorrhage and has clear advantages over placebo or no treatment. High dose aprotinin significantly reduces postoperative blood loss compared with aminocaproic acid and desmopressin, and decreases transfusion requirements compared with desmopressin. Results are less consistent with tranexamic acid: high dose aprotinin either reduces blood loss significantly more than, or to an equivalent level to, tranexamic acid. A variety of other lower aprotinin dosage regimens consistently result in similar reductions in blood loss to aminocaproic acid or tranexamic acid. Data from clinical trials indicate that aprotinin is generally well tolerated, and the adverse events seen are those expected in patients undergoing OHS and/or CABG with CPB. Hypersensitivity reactions occur in <0.1 to 0.6% of patients receiving aprotinin for the first time. The results of original reports indicating that aprotinin therapy may increase myocardial infarction rates or mortality have not been supported by more recent studies specifically designed to investigate this outcome. However, a tendency to early vein graft occlusion with aprotinin has been shown and care with anticoagulation and vessel grafts is required. No comparative tolerability data between aprotinin and the lysine analogues, aminocaproic acid and tranexamic acid, are available. ⋯ Comparative tolerability and cost-effectiveness data for aprotinin and the lysine analogues are required to more fully assess their individual roles in reducing blood loss and transfusion requirements in patients undergoing CPB during OHS and/or CABG. However, clinical evidence to date supports the use of aprotinin over its competitors in patients at high risk of haemorrhage, in those for whom transfusion is unavailable or in patients who refuse allogenic transfusions.
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In recent years, the concept has emerged that the host's inflammatory response contributes substantially to the development of septic shock and organ failure. Experimental observations prompted large scale randomised clinical trials with a variety of agents such as glucocorticoids, ibuprofen, antiendotoxin monoclonal antibodies, antagonists of platelet-activating factor, of bradykinin or of interleukin-1 receptor, and monoclonal anti-tumour necrosis factor (TNF) antibodies or soluble dimeric TNF receptor fusion proteins. ⋯ Many lessons have been learned from these studies. and certain mistakes in their study design will be avoided in the future. Our understanding of the pathophysiology of sepsis and septic shock is increasing markedly; potential new treatment strategies are available and could be explored to improve the outcome of patients with sepsis.
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The biguanide drugs metformin and phenformin have been linked in the past to lactic acidosis, a metabolic condition associated with high rates of mortality. Although concern over the hyperlactataemic effect of phenformin led to the withdrawal of this drug from clinical practice in the 1970s, the situation with metformin has been less clear. ⋯ Overall, it appears that mortality in patients receiving metformin who develop lactic acidosis is linked to underlying disease rather than to metformin accumulation, and that metformin can no longer be considered a toxic drug in this respect. These findings are likely to be of considerable relevance to the management of patients with type 2 (non-insulin-dependent) diabetes mellitus, especially where such patients are elderly.