Clinical commentary: the law of unintended ethics.
Criticizes Ronald Green's parental-based approach to genetic testing and counseling of children for its failure to address the clinical realities of genetic practice.
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Criticizes Ronald Green's parental-based approach to genetic testing and counseling of children for its failure to address the clinical realities of genetic practice.
For the near term, control of the AIDS epidemic depends entirely upon altering the human behavior which results in HIV transmission. How best to achieve the required changes has been controversial with approaches ranging from education/information only, to a vast array of largely unproven voluntary behavior modification techniques, to mandatory testing and restrictive measures. Given the complexity of human behavior and the reality of a still uncontrolled epidemic, at least among poor urban drug using minorities, there is a legitimate role for most approaches and any promising behavior modification strategy deserves evaluation. However, because voluntarism will not work for some individuals, society still must choose between effective public health law--including restrictive measures--now, and a much larger reservoir of HIV infection and more deaths from AIDS for many generations to come.
The discovery of the occult brainstem neurotoxicity subsequent to widespread deployment of artemisinin derivatives has created particular problems. That is, the clinical setting for artemisinin use is problematic for accomplishing what ordinarily would be addressed in phase I-II clinical trials. Nevertheless, it is clear that an urgent and vital need exists for the deployment and widespread availability of artemisinins. The work done to date has already yielded a substantial body of evidence that, while incomplete, provides guidelines for artemisinin use to minimize the risk of these drugs while preserving their much-needed efficacy. The evidence thus far shows that route of administration, oil/water solubility and concentration-duration of drug level, are critical determinants of toxicity and can be given appropriate consideration in the clinical decisions regarding route, choice of drug used, and drug regimens. In this regard, an oral, water-soluble drug with moderately rapid clearance may be the most attractive choice in the absence of significant differences in efficacy. The same body of evidence clearly shows that toxicity can, and does, develop with no obvious or useful clinical marker. Therefore, the development and validation of a test that can reliably detect the onset of injury, at a reversible stage, is a critical path task for any future development in this class. More complete understanding of mechanisms, kinetics, and molecular targets of neurotoxicity, will certainly be forthcoming. A continuing, more generalized use of these drugs, however, cannot be fully endorsed without a useful, practical clinical test of toxicity. The requirement is especially critical in light of the reality that those patients receiving artemisinin derivatives live in high risk environments and are likely to receive repeated courses of therapy with little likelihood of close, post marketing surveillance.
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This present review gives an overview on Linkage disequilibrium (LD), its measures and its different utilizations in human genetics studies. In the first part, we provide a detailed and a simplified presentation focusing on the definition of LD, its measures and the major software for its evaluation. Thereafter, we describe and discuss the biological and evolutionary mechanisms which create, remodel, maintain or destroy LD in human population. Consensus has now emerged on the pattern of LD in the genome which has a block-like organization with block of high disequilibrium interrupted by recombination hotspots. However, no standard method exists for the determination of such blocks and, more importantly, for the identification of TagSNP. This would yield inconsistencies between different studies of the same genes, compromising the practical use of TagSNP in association studies. The ACE gene is used to illustrate this. Will it be possible to identify consensus TagSNP that could be used consistently in all populations for testing association of candidate genes in common diseases? What is the part of myth and reality in what is called "individualized medicine"? We conclude that further LD studies are needed to get clear insights into this matter.
During the last few years computerised perimetry has become a clinical reality. This new technique eliminates the operator's error, ensures reproducibility of test procedures and parameters and makes visual field testing of large numbers of patients possible. Great differences exist between computerised perimeters. Differences in hardware for example, the way in which stimuli or field charts are produced may be striking but even more important are differences in software, especially test algorithms. The results obtained with some instruments and test programmes are of such high quality that the same level of performance may be almost impossible to obtain with manual perimetry, at least in a clinical setting. Nevertheless, improvements can be expected in the future particularly in adaptive tests and in computerised interpretation of the fields.
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BACKGROUND: The benefit of performing chemotherapy on soft tissue sarcomas remains controversial. The present study deals with the in vitro characterisation of the influence of 3 antitumoral agents on the growth of 8 sarcoma cell lines. MATERIALS AND METHODS: Cell growth was monitored by means of the MTT colorimetric assay, which was further validated by a direct cell counting method. The three drugs tested included doxorubicin (ADR), cisplatin (DDP) and dacarbazine (DTIC). ADR was tested at 10(-5) M, 10(-6) M and 10(-7) M; DDP at 10(-5) M, 10(-6) M and 10(-7) M; and DTIC at 10(-3) M, 10(-4) M and 10(-5) M. A combination of the three drugs was also tested in order to ascertain whether a synergistic effect on cell growth inhibition could be obtained. A potential antineoplastic agent-induced influence on cell growth was determined 3 days after the addition of the diverse drug(s) to the culture media. The cell concentration was specifically adapted to each cell line. The 8 cell lines included 3 leiomyosarcomas, 1 malignant mixed Müllerian tumour, 3 rhabdomyosarcomas and 1 fibrosarcoma. RESULTS: The results show that of the three drugs tested, ADR was the most efficient in terms of the level of cell growth inhibition obtained and the number of cell lines whose growth was significantly inhibited. Of the three drugs, the least active was DDP. A significant synergistic effect was observed when the three drugs were added together to the culture medium. This synergistic effect was evident at the lowest doses tested for each drug. Whatever the histopathological type, the 8 cell lines exhibited a wide range of response to chemotherapy. CONCLUSIONS: The present study shows that the inhibition induced by 10(-7) M ADR, 10(-7) M DDP and 10(-5) M DTIC on sarcoma cell line growth is significantly more efficient than if each agent is tested individually. The in vitro methodology used here fits in with clinical reality because it enables sarcoma cell heterogeneity to be taken into account.
Allergy to the gelatin used as a plasma filler product has not been recognised until now. Methods used have not been validated but are composed of specific serum IgE, skin tests and histamine release by leucotrienes. The clinical observation that we report has the merit of showing the reality of an allergy that is dependent on plasma filler products due to development of a protocol which includes firstly, during anaphylactic shock, measurement of the mediators of immediate hypersensitivity and secondly, after the clinical accident, test of the activation of basophils by flow cytometry (TAB) and measurement of leucotrienes.
Until now, radical cystectomy has been considered the most effective treatment for invasive bladder cancer. However, it fails to cure more than 50% of patients and can result in a mediocre quality of life. In an effort to improve cure rates, combined modality regimens have been investigated. Despite the preliminary results of early clinical trials, randomized trials have most often failed to show any benefit from neoadjuvant or adjuvant chemotherapy or radiotherapy. One of the major progress brought by radiotherapy has been the wide use of conservative treatment in several cancer, and in the recent years promising results with concomitant radiochemotherapy have been published. Use of the conservative approach in bladder cancer now appears to be a tangible reality for selected patients, but these combined modalities have not yet been tested in randomized trials.
The laser videodisc-based Sentence Gist Recognition (SGR) test consists of sets of topically related sentences that are cued by short film clips. Clients respond to test items by selecting picture illustrations and may interact with the talker by using repair strategies when they do not recognize a test item. The two experiments, involving 40 and 35 adult subjects, respectively, indicated that the SGR may better predict subjective measures of speechreading and listening performance than more traditional audiologic sentence and nonsense syllable tests. Data from cochlear implant users indicated that the SGR accounted for a greater percentage of the variance for selected items of the Communication Profile for the Hearing-Impaired and the Speechreading Questionnaire for Cochlear-Implant Users than two other audiologic tests. As in previous work, subjects were most apt to ask the talker to repeat an utterance that they did not recognize than to ask the talker to restructure it. It is suggested that the SGR may reflect the interactive nature of conversation and provide a simulated real-world listening and/or speechreading task. The principles underlaying this test are consistent with the development of other computer technologies and concepts, such as compact discinteractive and virtual reality.
BACKGROUND: Most quantitative tests do not perfectly discriminate between subjects with and without a given disease and their results do not always allow certainty about disease status for diagnostic or screening purposes. We propose a method to construct a three-zone partition for quantitative tests to avoid the binary constraint of a 'black or white' decision that often does not fit the reality of clinical or screening practice. This partition intentionally includes a grey zone between positive and negative conclusions. METHODS AND RESULTS: We show that the width of this grey zone depends on the difference between the means of test results for subjects with and without the disease, the variability of the test results and its components (biological, measurement), and the level of the misclassification risks (false positive, false negative) required by the context of use. We illustrate the method by application to the tuberculin skin test and iron deficiency markers in children. CONCLUSION: This method can be used both to display the discriminatory performance of a quantitative test in a variety of contexts and to scrutinize its components of variability. Due to the simplicity of the graphical representations, the grey zone approach may be useful during the development of quantitative tests and the publication of their performance.
We describe a comprehensive software-oriented approach to virtual reality-based neuroscientific systems in order to establish an easy to use framework for neuroscientific assessment and treatment. We have defined a process model and implemented the NeuroVRAC authoring tool for design and execution of experiments in virtual environments. Our system enables the modeling of virtual world objects and the definition of events, which are used to control the experimental process. We have included the virtual test person concept to enhance the sense of presence during the execution of virtual reality-based neuroscientific experiments.
With regard to an observation of anaphylaxis after a mosquito bite, we have shown by new immunobiological parameters and clinical investigations: Skin tests, specific IgE, Tests of Activation of basophils by flow cytometry (on basophils and total blood) and measurement of Leucotriene LTC4, the objective reality of the mechanism of IgE-dependent hypersensitivity (HS). This observation is correlated with rare work in support of true IgE-mediated allergy to mosquito 9 authors having used skin tests, PK in 1984 and immunoblot.
BACKGROUND: A number of studies have investigated several aspects of feasibility and validity of performance assessments with virtual reality surgical simulators. However, the validity of performance assessments is limited by the reliability of such measurements, and some issues of reliability still need to be addressed. This study aimed to evaluate the hypothesis that test subjects show logarithmic performance curves on repetitive trials for a component task of laparoscopic cholecystectomy on a virtual reality simulator, and that interindividual differences in performance after considerable training are significant. According to kinesiologic theory, logarithmic performance curves are expected and an individual's learning capacity for a specific task can be extrapolated, allowing quantification of a person's innate ability to develop task-specific skills. METHODS: In this study, 20 medical students at the University of Basel Medical School performed five trials of a standardized task on the LS 500 virtual reality simulator for laparoscopic surgery. Task completion time, number of errors, economy of instrument movements, and maximum speed of instrument movements were measured. RESULTS: The hypothesis was confirmed by the fact that the performance curves for some of the simulator measurements were very close to logarithmic curves, and there were significant interindividual differences in performance at the end of the repetitive trials. CONCLUSIONS: Assessment of perceptual motor skills and the innate ability of an individual with no prior experience in laparoscopic surgery to develop such skills using the LS 500 VR surgical simulator is feasible and reliable.
In view of the ever-increasing HIV/AIDS epidemic in sub-Saharan Africa, the expansion of HIV-1 voluntary counselling and testing (VCT) as an integral part of prevention strategies and medical research is both a reality and an urgent need. As the availability of HIV-1 VCT grows two limitations need to be addressed, namely: low rates of HIV-1 serostatus disclosure to sexual partners and negative outcomes of serostatus disclosure. Results from a study among men, women and couples at an HIV-1 VCT clinic in Dar es Salaam, Tanzania are presented. The individual, relational and environmental factors that influence the decision to test for HIV-1 and to share test results with partners are described. The most salient barriers to HIV-1 testing and serostatus disclosure described by women include fear of partners' reaction, decision-making and communication patterns between partners, and partners' attitudes towards HIV-1 testing. Perception of personal risk for HIV-1 is the major factor driving women to overcome barriers to HIV-1 testing. The implications of findings for the promotion of HIV-1 VCT programmes, the implementation of partner notification policies and the development of post-test support services are discussed.
Cognitive deficits have been hypothesized to be differentially related to the negative, positive and disorganization dimensions of schizophrenia symptoms. In this article, we quantitatively review the published literature on the relationships between symptom dimensions in schizophrenia and performance on the two most widely applied tests of executive functioning and sustained attention, the Wisconsin Card Sorting Test (WCST) and the Continuous Performance Test (CPT). Meta-analyses were conducted on studies that reported correlational data for the relations between performance on these tests and scales of positive and negative symptoms. The more recent distinction between disorganization and reality distortion was also taken into account. The results showed statistically significant relationships of negative symptoms with worse performance on the WCST and the CPT. Disorganization symptoms showed a significant positive correlation with perseverations on the WCST, but not with CPT performance. In contrast, reality distortion symptoms and general scores for all positive symptoms did not correlate with either measure. Although some correlations were statistically significant, the observed associations between psychiatric symptoms and cognitive performance were typically weak, suggesting relative independence of these disease processes.
Public concern about genetic discrimination, particularly access to insurance following genetic testing, has been reported in the literature. This paper aims to separate myths from realities regarding genetic discrimination in life insurance and to underline the positive aspects of allowing insurers access to relevant genetic information for underwriting purposes. We present a review of the literature pertinent to discrimination in life insurance and a comparative analysis of industries guidelines. There are few reported cases in the literature of validated genetic discrimination. However, the benefits to be gained by allowing insurers access to relevant genetic data could justify fostering a more active role in the use of genetic information by insurance companies.