Drug interaction between St John's wort and nevirapine.
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Biomedical subjects
Publications and source records attributed to E C van Gorp.
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Two weeks after rafting on a river in Thailand a Dutch 54-year-old male experienced chills and high fever. While rafting he had wounded his hand. Because of the history (water contact, the wound, high fever with chills), of the findings at examination (fever, conjunctivitis) and of the laboratory findings (leukocytosis, albuminuria, disturbance of liver enzymes), a clinical diagnosis of 'leptospirosis' was made. This was confirmed by serological tests and culturing of Leptospirae from the blood. Leptospirosis is a zoonosis, in man associated with certain occupations, water sports and inundations. The clinical picture varies from a mild febrile disease (sometimes pyrexia of unknown origin) to a severe condition with kidney and liver failure, bleeding tendency, lung oedema (Weil's syndrome). In travellers with fever, water contact, leukocytosis and neutrophilia, leptospirosis must be considered and specific diagnostic tests applied.
A prospective cohort study was performed in 50 patients with dengue haemorrhagic fever (DHF) to determine the potential role of the contact activation system and factor XI activation (intrinsic pathway) in the coagulation disorders in DHF. To establish whether TAFI (thrombin-activatable fibrinolysis inhibitor) was involved in the severity of the coagulation disorders, the TAFI antigen and activity levels were also determined. Markers of contact activation (kallikrein--C1-inhibitor complexes), the intrinsic pathway of coagulation (factor XIa--C1-inhibitor complexes) and TAFI were measured and correlated to thrombin generation markers (thrombin--anti-thrombin complexes (TAT), prothrombin fragment 1+2 (F1+2)) and a marker for fibrinolysis [plasmin--alpha 2--anti-plasmin complexes (PAP)]. Activation of the intrinsic pathway of coagulation was clearly demonstrated by elevated levels of factor XIa--C1-inhibitor complexes, without evidence of contact activation, reflected by undetectable kallikrein--C1-inhibitor complexes. Both TAFI antigen and activity levels were decreased in all patients, which may contribute to the severity of bleeding complications in DHF because of the impaired capacity of the coagulation system to protect the fibrin clot from fibrinolysis. These findings in a human viral infection model are in accordance with earlier findings in bacterial sepsis.
Infection, both bacterial and nonbacterial, may be associated with coagulation disorders, resulting in disseminated intravascular coagulation and multiorgan failure. In the last few decades a series of in vivo and in vitro studies has provided more insight into the pathogenetic mechanisms and the role of cytokines in these processes. Because of the growing interest in this field, the complexity of the subject, and the fact that many physicians must deal with a variety of infections, current data are reviewed on the association between infectious diseases and the coagulation system. Novel therapeutic intervention strategies that will probably become available in the near future are mentioned, along with those of special interest for infectious disorders for which only supportive care can be given.
The aging process is associated with increased coagulation and fibrinolysis parameters, resulting in an overall 'prethrombotic state'. This probably explains the increased baseline susceptibility of elderly patients to the development of thromboembolic disease. Additional factors such as major surgery or malignant disease multiply the risk of thromboembolism in this population. Even when adequate antithrombotic therapy is instituted, the mortality associated with thromboembolic disease remains considerable; this underlines the importance of adequate thromboembolic prophylaxis. At present, the use of low molecular weight heparins (LMWHs) in elderly immobile patients appears to be the most effective approach to prophylaxis. The use of compression stockings seems to be effective in the prevention of venous thrombosis, at least in moderate risk surgical patients. In patients undergoing orthopaedic surgery, additional prophylaxis (e.g. with an LMWH) is necessary. In the management of venous thrombosis, patients can initially be treated with a bodyweight-adjusted dosage of an LMWH. In patients with deep vein leg thrombosis or pulmonary embolism, oral anticoagulant therapy should be started as soon as possible, and should be continued for 6 months. However, before starting prophylaxis or therapy, an individual risk assessment should be performed in which the benefits and disadvantages are balanced. Most of the large trials that have studied the effects of thromboembolic prophylaxis have focused on postsurgical patients. However, it will be of great interest to develop more specific prophylactic and therapeutic regimens for different nonsurgical high risk subgroups of patients, particularly the elderly.
Three patients, two men aged 71 and one aged 73 years, were given artificial respiration because of acute respiratory failure. Subsequently they could not be weaned from artificial respiration, due to causes that were not immediately clear. It was ultimately found that the patients suffered from 'motor neuron disease', in two of them due to progressive spinal muscular atrophy, while the third, apart from loss of anterior horn motor cells, also had thoracic hydromelia. The patients died after termination of the artificial respiration.