Drugs

Brogden, Rex; Faulds, Diana

doi: 10.2165/00003495-199142050-00010pmid: 1723379

Yazici, H.; Barnes, C.

doi: 10.2165/00003495-199142050-00006pmid: 1723375

Behçet’s syndrome is a disease of unknown aetiology classified among the vasculitides. It runs a course of exacerbations and remissions which gradually abate with time. Eye disease, the most frequent cause of serious morbidity, may lead to blindness in 20% of those affected. The syndrome may occasionally be fatal due to vasculitis leading to arterial occlusion, ruptured arterial aneurysms or pulmonary vasculitis, or involvement of the central nervous system.

Fraiser, Lucy; Kanekal, Sarathchandra; Kehrer, James

doi: 10.2165/00003495-199142050-00005pmid: 1723374

Cyclophosphamide, an orally active alkylating agent, is widely used to treat a variety of malignant and nonmalignant disorders. Although it has some tumour selectivity, it also possesses a wide spectrum of toxicities. The requirement of metabolic activation before cyclophosphamide exerts either its therapeutic or toxic effects is well established, but has not led to effective countermeasures. Clinically, damage to the bladder (haemorrhagic cystitis), immunosuppression (when not desired) and alopecia are the most significant toxicities associated with cyclophosphamide. Cardiotoxicity is also a possibility when very high doses are given. Preventing these toxicities has focused on modifications of the treatment regimens and, in the case of haemorrhagic cystitis, the administration of a drug which is excreted in the urine where it inactivates the bladder-toxic species. As treatment regimens for cancer become more effective in prolonging a patient’s life, and as cyclophosphamide receives increasing use for nonmalignant disorders, the potential for cyclophosphamide-induced cancers, particularly in the bladder, must be recognised. Although the toxicities associated with cyclophosphamide are serious, this agent remains a highly effective drug in many situations. Research on the pathways which play an important role in activating this drug may improve our ability to target particular diseases and decrease unwanted side effects.

Norris, J.

doi: 10.2165/00003495-199100425-00004pmid: 1726212

Much of the published data concerning the outcome in patients with transient ischaemic attacks and stroke was produced before the development of computerised tomography, and when the risk factors for cerebrovascular disease were different in quality and quantity. Outcome data also depend on the definition of the original disorders, which remain controversial and are often poorly described.

Verstraete, M.

doi: 10.2165/00003495-199100425-00006pmid: 1726214

Of the major risk factors for atherosclerosis, high factor VII and fibrinogen levels, genetic predisposition, gender and age cannot be influenced. Reduction of high blood pressure reduces the cerebral but not the coronary vascular risk and correction of dyslipidaemia correlates with cardiovascular risk. Other major risk factors (tobacco consumption, obesity, sedentary lifestyle and diabetes) can also be modified.

Verhaeghe, R.

doi: 10.2165/00003495-199100425-00008pmid: 1726216

Prophylactic therapy with antiplatelet drugs aims to improve both the general prognosis of patients and the local progression of peripheral arterial disease. A recent meta-analysis of 28 trials revealed that the proportional risk reduction in serious vascular events is similar to that in cardio- and cerebrovascular disease. A decreased incidence of vascular complications was also found in a meta-analysis of 4 trials with ticlopidine, and a recent Swedish study [Swedish Ticlopidine Multicentre Study (STIMS)] confirmed that long term ticlopidine reduces both mortality and cardio- and cerebrovascular morbidity.

Dechant, Kerry; Faulds, Diana

doi: 10.2165/00003495-199142050-00009pmid: 1723378

Mehta, Minesh; Bastin, Kenneth; Wiersma, Susan

doi: 10.2165/00003495-199142050-00004pmid: 1723373

Wilms’ tumour (nephroblastoma, renal embryoma) is the fifth most common paediatric malignancy, arising from the embryonal tissue of kidneys and first formally described by Max Wilms in his classic 1899 monograph. Until the early part of this century, Wilms’ tumour was associated with a less than 20% survival rate. The current survival rate exceeds 80%, primarily due to large multi-institutional trials such as the National Wilms’ Tumor Study (NWTS). These studies have refined and defined the roles of surgery, chemotherapy, and radiation in treating Wilms’ tumour, based on staging and histology. The dramatic improvement in the prognosis for children with Wilms’ tumour, especially over the past 20 years, represents a landmark achievement in the history of paediatric oncology.

Criqui, M.; Langer, R.; Fronek, A.; Feigelson, H.

doi: 10.2165/00003495-199100425-00005pmid: 1726213

Previous reports have indicated an excess of mortality from coronary heart disease (CHD), cardiovascular disease (CVD), and all causes in subjects with large-vessel peripheral arterial disease (LV-PAD). However, there is little information available concerning the risk of nonfatal events (morbidity) in this patient group.

Badimon, L.; Badimon, J.; Cohen, M.; Chesebro, J.; Fuster, V.

doi: 10.2165/00003495-199100425-00003pmid: 1726211

Angiography in patients with unstable angina or myocardial infarction with subtotal coronary occlusion often reveals eccentric stenoses with irregular borders, suggesting ruptured atherosclerotic plaques and thrombosis, as documented by angioscopy and at autopsy. We have studied these processes in an ex vivo perfusion chamber, an in vivo swine model, and in human subjects. Our results, and those of other investigators, suggest that specific local risk factors at the time of plaque disruption influence the degree of thrombogenicity and, therefore, the various clinical syndromes. These risk factors can be divided into 2 groups: local vessel wall-related factors, and local (focal action) systemic factors. These risk factors include the following: 1) Rheological factors. It has been demonstrated that the more severe the stenotic lesion after plaque rupture, the higher the local shear rate with enhanced platelet deposition and thrombus formation; platelet deposition and thrombosis are particularly likely if the rupture includes the apex of the stenotic plaque, because of the high shear rate induced. 2) Degree of plaque damage. Plaque rupture produces a rough surface and stimulates an occlusive thrombus, which is enhanced depending on the degree of damage or amount of collagen type I and macrophage-dependent tissue factor exposed. 3) Residual thrombus. After spontaneous or pharmacological reperfusion, the surface of the residual thrombus is very thrombogenic and may contribute to reocclusion; this is partially due to thrombin bound to fibrin in the original thrombus. 4) Systemic factors. There is clinical and experimental evidence to suggest that 3 systemic factors at the time of plaque rupture may enhance thrombogenicity. Firstly, the levels of epinephrine (adrenaline) [i.e. in stress, smoking, early acute myocardial infarction], secondly, the level of serum cholesterol, and thirdly, impaired fibrinolysis resulting from high serum lipoprotein(a).