Home About us Contact
|
Home About us Contact | ||
|
|
||
Ethical Reasons (ethical + reason)
Selected AbstractsIn defense of clinical judgment , and mechanical predictionJOURNAL OF BEHAVIORAL DECISION MAKING, Issue 5 2006Jason Dana Abstract Despite over 50 years of one-sided research favoring formal prediction rules over human judgment, the "clinical-statistical controversy," as it has come to be known, remains something of a hot-button issue. Surveying the objections to the formal approach, it seems the strongest point of disagreement is that clinical expertise can be replaced by statistics. We review and expand upon an unfortunately obscured part of Meehl's book to try to reconcile the issue. Building on Meehl, we argue that the clinician provides information that cannot be captured in, or outperformed by, mere frequency tables. However, that information is still best harnessed by a mechanical prediction rule that makes the ultimate decision. Two original studies support our arguments. The first study shows that multivariate prediction models using no data other than clinical speculations can perform well against statistical regression models. Study 2, however, showed that holistic predictions were less accurate than predictions made by mechanically combining smaller judgments without input from the judge at the combination stage. While we agree that clinical expertise cannot be replaced or neglected, we see no ethical reason to resist using explicit, mechanical rules for socially important decisions. Copyright © 2006 John Wiley & Sons, Ltd. [source] Inflammatory bowel disease pathogenesis: therapeutic implicationsJOURNAL OF DIGESTIVE DISEASES, Issue 1 2005Claudio FIOCCHI The pathogenesis of inflammatory bowel disease (IBD) is complex, involving environmental, genetic, microbial, and immune factors. Therefore, treatment should target components that either predispose to or mediate the chronic inflammatory response of IBD. At the moment it is assumed that all components are necessary to have the typical manifestations of IBD but, in reality, it is unclear to what extent each factor contributes to the disease process, and whether some are more important than others. In addition, some factors are not practical targets; for example, environmental factors are poorly defined, too numerous, and require changes that cannot be implemented by the physician or the patient alone. The same is true for genetic factors that are still not amenable to therapeutic manipulations for technical and ethical reasons. This leaves microbial and immune factors as the two categories that can be selected for therapeutic intervention and where all current treatments are focused. The commensal gut flora can be qualitatively or quantitatively modified with antibiotics, probiotics, or diet, and a better characterization of enteric bacteria strains should help greatly in developing more effective therapies. Most current drugs are focused on inhibiting pro-inflammatory molecules produced by immune cells, including biological agents that block specific cytokines such as tumor necrosis factor-alpha. It is anticipated that combination therapies targeting multiple pathogenic components will prove more effective than those blocking single components of IBD pathogenesis. [source] INFECTIVE DOSE OF FOODBORNE PATHOGENS IN VOLUNTEERS: A REVIEWJOURNAL OF FOOD SAFETY, Issue 1 2001MAHENDRA H. KOTHARY ABSTRACT Risk assessment and impact of foodborne pathogens on the health of different populations was one of the goals identified in the Presidential Food Safety Initiative three-year plan. This entailed estimation of dose-response relationship for foodborne pathogens to humans, either by feeding studies or from outbreaks. For certain pathogens, such as Listeria monocytogenes and Escherichia coli O157:H7, there are no feeding studies due to ethical reasons, and the results from outbreaks are normally used to estimate the infectious dose. The focus of this review is to compile dose-response information in volunteers for several foodborne pathogens including Salmonella, Shigella spp., Campylobacter jejuni, Vibrio spp., Escherichia coli, Cryptosporidium parvum and Entamoeba coli. The infectious dose for different serovars of Salmonella and strains of E. coli was quite large (> 105 organisms), while the infectious dose for some Shigella spp. seemed to be as low as less than 10 organisms. Toxigenic V. cholerae (O1 and O139 serotypes) were infective at a dose of 104 organisms; a non-O1 strain was infective at a much higher dose (106 organisms). C. jejuni, C. parvum and Entamoeba coli appeared to have infectious doses as low as 500 organisms, 10 oocysts, and 1 cyst, respectively. The infectious dose and the dose response are dependent upon the strains used, and the age and physical condition of the individuals, and can therefore show wide variations. In addition, since many of the volunteer studies are carried out by feeding the organisms in a nonfood matrix after neutralizing the stomach acidity, results obtained may not reflect the true dose response. [source] Ototoxic eardrops and tympanic membrane perforations: Time for a change?JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 8 2005Harvey Coates Abstract: Until recently the only available antibiotic eardrops for treatment of the discharging middle ear and mastoid cavity have been potentially ototoxic. With the advent of non-ototoxic fluoroquinolone eardrops, consensus panels in the USA, Canada and the UK have advocated the preferential use of these agents in the open middle ear. However, in Australia, no fluoroquinolone topical agent is approved for use with tympanic membrane perforations, and when used as an ,off label' eardrop, none is on the Pharmaceutical Benefits Scheme. This creates an ethical dilemma, particularly with best practice management of chronic suppurative otitis media in indigenous children. Despite concerns regarding resistance issues with ototopical use of systemic antibiotics, bacterial resistance has not been documented in major studies. For equity and ethical reasons, Australian regulatory authorities should consider approving a sterile non-ototoxic eardrop for use in the open middle ear. [source] Profiling of vitreous proteomes from proliferative diabetic retinopathy and nondiabetic patientsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 22 2007Taeoh Kim Abstract Diabetes can lead to serious microvascular complications like proliferative diabetic retinopathy (PDR), which is the leading cause of blindness in adults. The proteomic changes that occur during PDR cannot be measured in the human retina for ethical reasons, but could be reflected by proteomic changes in vitreous humor. Thus, we considered that comparisons between the proteome profiles of the vitreous humors of PDR and nondiabetic controls could lead to the discovery of novel pathogenic proteins and clinical biomarkers. In this study, the authors used several proteomic methods to comprehensively examine vitreous humor proteomes of PDR patients and nondiabetic controls. These methods included immunoaffinity subtraction (IS)/2-DE/MALDI-MS, nano-LC-MALDI-MS/MS, and nano-LC-ESI-MS/MS. The identified proteins were subjected to the Trans-Proteomic Pipeline validation process. Resultantly, 531 proteins were identified, i.e., 415 and 346 proteins were identified in PDR and nondiabetic control vitreous humor samples, respectively, and of these 531 proteins, 240 were identified for the first time in this study. The PDR vitreous proteome was also found to contain many proteins possibly involved in the pathogenesis of PDR. The proteins described provide the most comprehensive proteome listing in the vitreous humor samples of PDR and nondiabetic control patients. [source] In vitro neuromuscular activity of snake venomsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2002Wayne C Hodgson Summary 1.,Snake venoms consist of a multitude of pharmacologically active components used for the capture of prey. Neurotoxins are particularly important in this regard, producing paralysis of skeletal muscles. These neurotoxins can be classified according to their site of action (i.e. pre- or post-synaptic). 2.,Presynaptic neurotoxins, which display varying phospholipase A2 activities, have been identified in the venoms of the four major families of venomous snakes (i.e. Crotalidae, Elapidae, Hydrophiidae and Viperidae). The blockade of transmission produced by these toxins is usually characterized by a triphasic effect on acetylcholine release. Considerable work has been directed at identifying the binding site(s) on the presynaptic nerve terminal for these toxins, although their mechanism of action remains unclear. 3.,Post-synaptic neurotoxins are antagonists of the nicotinic receptor on the skeletal muscle. Depending on their sequence, post-synaptic toxins are subdivided into short- and long-chain toxins. These toxins display different binding kinetics and different affinity for subtypes of nicotinic receptors. Post-synaptic neurotoxins have only been identified in venoms from the families Elapidae and Hydrophiidae. 4.,Due to the high cost of developing new antivenoms and the reluctance of many companies to engage in this area of research, new methodologies are required to test the efficacy of existing antivenoms to ensure their optimal use. While chicken eggs have proven useful for the examination of haemorrhagic venoms, this procedure is not suited to venoms that primarily display neurotoxic activity. The chick biventer cervicis muscle has proven useful for this procedure, enabling the rapid screening of antivenoms against a range of venoms. 5.,Historically, the lethality of snake venoms has been based on murine LD50 studies. Due to ethical reasons, these studies are being superseded by in vitro studies. Instead, the time taken to produce 90% inhibition of nerve-mediated twitches (i.e. t90) in skeletal muscle preparations can be determined. However, these two procedures result in different rank orders because they are measuring two different parameters. While murine LD50 determinations are based on ,quantity', t90 values are based on how ,quick' a venom acts. Therefore, knowledge of both parameters is still desirable. 6.,In vitro neuromuscular preparations have proven to be invaluable tools in the examination of snake venoms and isolated neurotoxins. They will continue to play a role in further elucidating the mechanism of action of these highly potent toxins. Further study of these toxins may provide more highly specific research tools or lead compounds for pharmaceutical agents. [source] | |||||||||||||