Expert opinion on investigational drugs
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Endotoxic shock, or Gram-negative septic shock, can occur as a component of Gram-negative sepsis and is characterised by hypotension, poor tissue perfusion and multi-organ dysfunction. Despite antibiotic therapy and intensive care management, the morbidity and mortality rates of Gram-negative septic shock remain high. Endotoxin mediates its effects through interaction with receptors on the surface of a variety of host cells. ⋯ Examination of the literature regarding pharmacological agents used to treat endotoxic shock often yields confusing and contradictory results. The reasons for these mixed results include differences in models, drug dosages, dosing methods and intervals and timing of administration relative to disease duration and severity. However, despite mixed results, several of the drugs discussed in this paper offer promise in the therapy of an often frustrating and lethal condition.
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Sickle cell anaemia, a chronic and often debilitating disease, results from homozygosity for a single amino acid substitution in the beta-globin subunit of the haemoglobin molecule. Sickle haemoglobin (HbS), the product of this mutation, polymerises when deoxygenated, thus damaging the red blood cell and causing vaso-occlusive complications and haemolytic anaemia. Most cases of sickle cell anaemia are found in Africa. ⋯ Hydroxyurea is given to severely affected sickle cell anaemia patients in an attempt to prevent painful episodes, reduce hospital days, improve the patients' overall quality of life, and perhaps to prevent or provide some degree of end-organ damage stabilisation. Other novel therapies, such as bone marrow transplantation and gene therapy, pursue a cure. For these novel therapies to be effective on a global basis they must be amenable to underdeveloped and poorer countries of the world.
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Expert Opin Investig Drugs · Jun 1999
Levobupivacaine: a new safer long acting local anaesthetic agent.
The choice of local anaesthetic is influenced by several factors; it must provide effective anaesthesia and analgesia for the duration of the procedure and meet the expectations for post-operative pain management. Of primary concern is patient safety. Bupivacaine, currently the most widely used long acting local anaesthetic agent in both surgery and obstetrics, generally has a good safety record but its use has resulted in fatal cardiotoxicity, usually after accidental intravascular injection. ⋯ Nevertheless, levobupivacaine has been shown to have less effect on myocardial contractility and QTc prolongation, early signs of cardiotoxicity, than bupivacaine in healthy subjects. In clinical use levobupivacaine has been shown to be equally efficacious as bupivacaine at comparable doses and concentrations, and has been found to produce similar anaesthetic characteristics (onset, duration and density of block). As levobupivacaine now becomes commercially available, the database available with which to make efficacy and safety comparisons with other local anaesthetics will increase, and the true value of this new long acting local anaesthetic should become even more apparent.
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Organ transplantation is considered the most effective treatment for end-stage organ failure; currently it is limited by a severe worldwide shortage of human donor organs. This has led to investigation of the potential use of animals as organ donors. For a number of reasons, the pig represents the most likely organ donor candidate. ⋯ Strategies aimed at preventing this initial rejection have been largely successful in experimental models. This has allowed attention to turn towards an understanding of the immunological barriers comprising the next phase of xenograft rejection, termed acute vascular rejection. This delayed rejection process appears to be a humoral event, and it is likely that the control of antibody synthesis will play a pivotal role in overcoming the current barrier to successful xenotransplantation.
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The annual meeting of the American Diabetes Association highlighted considerable progress in the field. Prominent presentations focused on a number of new emerging therapeutics, as well as new avenues of research that may provide greater insight into the aetiology of the disease. This update provides coverage of some of the more interesting portions of the meeting.