Paracetamol (acetaminophen, N-acetyl-p-aminophenol, 4-hydroxyacetanilide) is the most common cause of acute liver failure in developed countries. There are a number of factors which potentially impact on the risk of an individual developing hepatotoxicity following an acute paracetamol overdose. These include the dose of paracetamol ingested, time to presentation, decreased liver glutathione, and induction of cytochrome P450 (CYP) isoenzymes responsible for the metabolism of paracetamol to its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI). In this paper, we review the currently published literature to determine whether induction of relevant CYP isoenzymes is a risk factor for hepatotoxicity in patients with acute paracetamol overdose. Animal and human in vitro studies have shown that the CYP isoenzyme responsible for the majority of human biotransformation of paracetamol to NAPQI is CYP2E1 at both therapeutic and toxic doses of paracetamol. Current UK treatment guidelines suggest that patients who use a number of drugs therapeutically should be treated as “high-risk” after paracetamol overdose. However, based on our review of the available literature, it appears that the only drugs for which there is evidence of the potential for an increased risk of hepatotoxicity associated with paracetamol overdose are phenobarbital, primidone, isoniazid, and perhaps St John’s wort. There is no evidence that other drugs often quoted as increasing risk, such as carbamazepine, phenytoin, primidone, rifampicin, rifabutin, efavirenz, or nevirapine, should be considered risk factors for hepatotoxicity in patients presenting with acute paracetamol overdose.
A drilling or a fishing jar is used in the bottomhole assembly (BHA) of a drill string to free the string should it become stuck during the drilling operation. Because many expensive sensors are now incorporated in downhole tools, it is necessary to predict the damaging effect of jarring on these downhole sensors accurately. In addition, BHA's are becoming tncreasingly complex and are difficult to analyze by closed-form methods. For such reasons, the finite-element method (FEM) was used in this study to predict the dynamic response of a drill string to jarring.
A wide range of new treatments have been investigated for the management of overactive bladder; few, however, have been evaluated extensively in neurogenic urinary incontinence. Further studies are required to determine the optimal dosing regimes and formulations for individual sub-populations of neurogenic bladder patients and to determine the cost-effectiveness of these interventions. With the current experience available, two treatment algorithms for a subset of patients with neurological disease have also been proposed, which suggest at which stage of management and in which patients individual therapies for neurogenic urinary incontinence could be used.
This paper presents field performance results for a new type of bearing seal for rock bits. The new seal design is found to be effective in significantly reducing abrasive wear at the sealing interface by virtue of its unique geometry that simultaneously introduces a hydrodynamic lubricant film and prevents the ingress of abrasives at the sealing interface. This has resulted in longer seal life and overall improvements in the rock-bit performances by a significant reduction in early seal failures.
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