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[Development of a new inspection diagnostic method: genetic screening of cancer].

Wilms' tumor gene WT1 mRNA is a new marker of leukemic blast cells for AML, ALL, and CML. The minimal residual disease(MRD) of leukemia can be detected at frequencies as low as 1 in 10(3) to 10(4) normal bone marrow cells and 1 in 10(5) normal peripheral blood mononuclear cells by means of the quantitation of WT1 mRNA (WT1 assay) using reverse transcriptase-polymerase chain reaction. Thus, the WT1 assay makes it possible to rapidly assess the effectiveness of treatment and to evaluate the degree of eradication of leukemic cells in individual leukemia patients. Furthermore, the WT1 assay can continuously assess the disease progression of myelodysplastic syndrome(MDS) and predict the evolution of MDS to overt AML within 6 months. Moreover, WT1 protein is highly immunogenic, thus, WT1 peptide-based cancer immunotherapy is effective.

Genetic Testing↗

Genetic population structure and call variation in a passerine bird, the satin bowerbird, Ptilonorhynchus violaceus.

Geographic variation in vocalizations is widespread in passerine birds, but its origins and maintenance remain unclear. One hypothesis to explain this variation is that it is associated with geographic isolation among populations and therefore should follow a vicariant pattern similar to that typically found in neutral genetic markers. Alternatively, if environmental selection strongly influences vocalizations, then genetic divergence and vocal divergence may be disassociated. This study compared genetic divergence derived from 11 microsatellite markers with a metric of phenotypic divergence derived from male bower advertisement calls. Data were obtained from 16 populations throughout the entire distribution of the satin bowerbird, an Australian wet-forest-restricted passerine. There was no relationship between call divergence and genetic divergence, similar to most other studies on birds with learned vocalizations. Genetic divergence followed a vicariant model of evolution, with the differentiation of isolated populations and isolation-by-distance among continuous populations. Previous work on Ptilonorhynchus violaceus has shown that advertisement call structure is strongly influenced by the acoustic environment of different habitats. Divergence in vocalizations among genetically related populations in different habitats indicates that satin bowerbirds match their vocalizations to the environment in which they live, despite the homogenizing influence of gene flow. In combination with convergence of vocalizations among genetically divergent populations occurring in the same habitat, this shows the overriding importance that habitat-related selection can have on the establishment and maintenance of variation in vocalizations.

Animals↗

[Nurses and doctors in the management of arrhytmic complications: the case of electric storm in patients with an implantable cardioverter defibrillator].

The evolution of arrhythmologic technology introduced new therapeutic opportunities for cardiology patients. Competence, continuity of care, integration and collaboration between medical doctors and nurses allow a safe management of short and long term complications. A typical example of a new arrhythmic complication is the "electrical storm" or "arrhythmic warm up" in patients implanted with a cardioverter-defibrillator (ICD). The definition and epidemiology of the electrical storm stress the relevance of this clinical situation; its dramatic emergency involves several aspects of nursing care, clinical, prognostic, ethical and deontological. The definition and implementation of an integrated protocol for the treatment of this condition is described and ethical and unresolved questions are rised. One of these problems is the recommendation to offer the patient the opportunity to receive information about the option of inactivating the ICD.

Adrenergic beta-Antagonists↗

Neuropsychological functioning in human immunodeficiency virus type 1 seropositive children infected through neonatal blood transfusion.

The neuropsychological development of 15 human immunodeficiency virus type 1 (HIV-1) seropositive children infected through neonatal blood transfusion was compared with that of a control group of 33 HIV-1 seronegative children who had also received blood transfusions as neonates. Human immunodeficiency virus type 1 infection was identified on the basis of a callback blood testing. Two thirds of the HIV-1-infected children were asymptomatic at time of enrollment in the study of development. The children were administered two psychological batteries approximately 8 months apart. The results indicated that the two serostatus groups did not differ in overall intelligence, even as long as 8 years after HIV-1 infection. Significant group differences, though slight, were found on school achievement and on tasks that require motor speed, visual scanning, and cognitive flexibility. Continued longitudinal study of this cohort will be important in characterizing the evolution of neuropsychological deficits.

Acquired Immunodeficiency Syndrome↗

[Therapeutic application of anesthetic blocks in weever-fish stings].

Five cases of weaver-fish sting (weaver Trachinus) are described. All patients presented severe pain and peripheral vascular disorders. In 4 cases the sting was in the upper limb and treated with brachial plexus axillary block. One patient had been stung in the foot and treated with epidural continuous block with catheter: In all cases bupivacaine 0.5% was employed and evolution was good 24-48 hours later. We conclude that anesthetic blocks should be included in the symptomatic treatment of those cases, that is: steroids, antihistaminics, calcium, analgesic agents, antibiotics, and antitetanic vaccine.

Adult↗

[Relation of fluctuations in the physiological traits of a continuous Saccharomyces cerevisiae culture to the cell division cycle].

Such physiological characteristics of a continuous Saccharomyces cerevisiae culture as the rate of O2 uptake and CO2 evolution, the rate at which the medium was acidified, were found to vary. When the flow rate was increased from 0.05 to 0.1 h-1, the period of variations also rose (from 3 to 33 h) and two maxima were detected in the quantity of budding cells within one 33-h period of the variations. These findings indicate that the variations do not depend on changes in the physiology of the cell in the course of its division cycle.

Cell Cycle↗

Biosensors and the clinical laboratory.

Aside from the economic factors that make biosensors attractive, on-board signal conditioning and signal processing improve the limits of detection and simplify use of the devices. The present discussion summarizes the breadth of biosensor design and application, and the requirements of clinical assay detection. Current sensor research is aimed toward extending the lower limits of detection for nonradioactive immunoassays. The clinical laboratory is in a state of change; operating and instrumentation costs will affect the delivery of diagnostics. Technology will assume a major role in reshaping the clinical laboratory. Biosensors promise to deliver the diagnostic tools for the evolution that is now in progress. The clinical laboratory will no doubt continue to perform chemical profiling and the more specialized tests. The successful implementation of solid-state sensor technology promises to simplify immunoassay procedures, as the autoanalyzer did some 20 years ago for the profiling of blood metabolites. It is likely that more tests will be performed in physicians' offices with the advent of highly automated and cost-effective biosensors. By the use of this technology, practitioners of critical care medicine will be able to assume greater responsibility for diagnostic testing.

Clinical Laboratory Techniques↗

[Campylobacter neonatal enteritis (author's transl)].

Authors communicate four cases of bloody diarrhea in neonates, with Campylobacter fetus jejuni in the stools. In one case, the same bacteria was isolated from the mother and, in another case, existed possibility of a cross-infection. The mildness of the evolution is marked, specially in those cases in which maternal feeding was continued. Some diagnostic and epidemiological aspects, concerning the neonatal period, are commented.

Campylobacter Infections↗

Selective binding of soluble Abeta1-40 and Abeta1-42 to a subset of senile plaques.

Alzheimer's disease is characterized by the progressive accumulation of amyloid-beta protein (Abeta) in senile plaques and cerebral amyloid angiopathy. It is not known whether the plaque growth is a continuous and homogeneous process or whether some plaques have a more rapid evolution. As plaques grow by the deposition of Abeta, we used an in situ binding technique to analyze the deposition of fluorescein-conjugated and biotinylated Abeta1 40 and Abeta1-42 in cryosections of brains from Alzheimer's disease patients. Only a subset of senile plaques but all cerebrovascular Abeta deposits were labeled by both Abeta1-40 and Abeta1-42. Striking differences in binding were observed among adjacent plaques. Quantitative analysis showed that on average 60% of all plaques were labeled with Abeta1-42 and 31% of all plaques were labeled with Abeta1-40 (n=7; P<0.001). Confocal laser scanning microscopy of double-labeled sections revealed that the newly deposited Abeta was only partially co-localized to pre-existing Abeta and apolipoprotein E and was not co-localized to heparan sulfate proteoglycan. Abeta binding was preserved after glycolytic pretreatment with periodic acid. Our results suggest that at a given time point only a subset of active senile plaques accumulate A(beta) and that plaque growth may be conditioned by the presence of other distinct plaque components different from Abeta, apolipoprotein E or heparan sulfate proteoglycan.

Aged↗

The introduction of evidence-based medicine as a component of daily practice.

Evidence-based medicine is an increasingly important concept in continuing medical education and medical school curricula. To cope with the rapid evolution of medicine, physicians need to remain abreast of the many new therapies and diagnostic tools that affect their practices. Unfortunately, along with the many changes there is also a surplus of relevant written material. Physicians are unable to read all of this information due to time constraints. Instead, they must choose information efficiently. Tools are needed to facilitate this process. Over a two-month period, a demonstration model was carried out at the Ottawa General Hospital to encourage faculty, residents, and students to incorporate evidence-based medicine into their daily practice. A study was conducted to investigate the level and type of information required by these individuals in a clinical setting. A literature searching service was introduced six months after the formal introduction of evidence-based medicine in the Department of Medicine. The logistics of and recommendations for providing such a service are presented in this paper.

Decision Making, Computer-Assisted↗

Managed care glossary update.

The vocabulary and acronyms of managed care continue to change in tandem with the industry's rapid growth and evolution. This article defines many key terms used to describe how health care is purchased, delivered and financed under the latest types of managed care arrangements.

Managed Care Programs↗

The podiatric examination.

With the evolution of the AIDS epidemic into a relatively chronic disease, practitioners will continue to see an increase in the number of patients infected with HIV for the diagnosis and management of podiatric pathology. A thorough history and physical examination, taken with a complete knowledge base of HIV implications, will enhance the ability to form the strategies required to treat the manifestations of this disease and to request appropriate referrals. Laboratory studies and other diagnostic techniques have been developed and increased in specificity to allow for earlier and more precise identification of the presenting pathology. A continuously expanding choice of medications is available for treatment. The clinical presentations of HIV infection in the foot involve nearly all organ systems. This article reviews the podiatric role as part of the medical team in the diagnosis and treatment of patients infected with HIV.

AIDS-Related Opportunistic Infections↗

Preliminary report: parenteral Lorazepam in induced epileptic states in man.

The anticonvulsive effect of Lorazepam -- one of the newer diazepines -- has been tested in 10 patients with induced epileptic conditions under continuous polygraphic control. The quantitative analysis of the paroxysmal discharges -- i.e. the evolution of the "paroxysmal index" -- shows that 5 mg IV Lorazepam normalize the tracings in 2.3 minutes. Parenteral Lorazepam inhibits pharmacologically-induced electroencephalographic abnormalities in man. Its action is slightly delayed. No effect on cardiac or respiratory function, or muscle tone was noted.

Adolescent↗

Evolution of canine parvovirus--a need for new vaccines?

Canine parvovirus (CPV) is a new virus, which is continuing to evolve, giving rise to new antigenic types and virus mutants that spread through the dog population. The most successful mutants, from an evolutionary perspective, appear to be selected by improved binding to the CPV receptor, the canine transferrin receptor, and by an extended host range, which for the newer antigenic types now includes both the dog and the cat. The new viruses also show antigenic differences that can be defined by binding of certain monoclonal antibodies; they also differ in their reactivity in virus neutralisation tests, using immune sera raised against the various antigenic types. These differences may influence the susceptibility of young animals to infection at the time when the level of maternally derived antibody decreases to the minimum protective titre. This minimum protective titre may vary depending on the infecting virus type. There is, however, a high degree of cross-protection between the virus types and the true relevance of the differences in neutralisation titer is currently not known.

Animals↗

Sleep and the time course of motor skill learning.

Growing evidence suggests that sleep plays an important role in the process of procedural learning. Most recently, sleep has been implicated in the continued development of motor-skill learning following initial acquisition. However, the temporal evolution of motor learning before and after sleep, the effects of different training regimens, and the long-term development of motor learning across multiple nights of sleep remain unknown. Here, we report data for subjects trained and retested on a sequential finger-tapping task across multiple days. The findings demonstrate firstly that following initial training, small practice-dependent improvements are possible before, but not following the large practice-independent gains that develop across a night of sleep. Secondly, doubling the quantity of initial training does not alter the amount of subsequent sleep-dependent learning that develops overnight. Thirdly, the amount of sleep-dependent learning does not correlate with the amount of practice-dependent learning achieved during training, suggesting the existence of two discrete motor-learning processes. Finally, whereas the majority of sleep-dependent motor-skill learning develops during the first night of sleep following training, additional nights of sleep still offer continued improvements.

Adult↗

Monte Carlo simulation of early molecular evolution in the RNA World.

The origin of life remains a highly speculative field, mainly due to the shortage of our knowledge on prebiotic chemistry and basic understanding on the essence of life. In this context, computer simulation is expected to play an important role. For instance, the scenario concerning the genesis of the widely accepted RNA World remains blurry, though we have gathered some circumstantial evidence and fragmented knowledge on several supposed stages, including formation of polynucleotides from a prebiotic nucleotide pool, emergence of RNA replicases (RNA molecules catalyzing their own replication), and evolution of RNA replicases. It is highly valuable to simulate the stages as a continuous process to evaluate the plausibility of the supposition and study the rules involved. Here we construct a computer simulation on the process using Monte Carlo method. It demonstrates that primordial RNA replicases may appear and spread in a nucleotide pool provided they could recognize their own sequence and their complements as catalytic targets, and then may evolve to more efficient RNA replicases. Apart from its indication on the genesis of the RNA World, the vivid simulation of emergence of the "first replicative molecules" and their subsequent evolution is impressive and may help to get insight into "how could self-replication and Darwinian evolution, two key features of life, emerge in a non-life background?" thus improve our understanding of "what is life" when studying origins of life.

Biological Evolution↗

The context of human genetic evolution.

The debate on modern human origins has often focused on the relationship between genes and fossils. Although more and more genetic evidence has been accumulating in favor of a recent African origin for modern humans, it has been assumed by many that the fossil evidence remains ambiguous. On the contrary, it has been clear for some time that the fossil evidence does not support the multiregional model: Fossils and archeology indicate a pattern of multiple dispersals from and beyond Africa, against which the genetic data can be compared. The continuing value of paleobiology is in complementing genetic information by revealing the context of human evolution: locating the dispersals and extinctions of populations in time and space, correlating these events with the environmental forces that shaped them, and providing an increasingly detailed understanding of the morphology and technology of early humans.

Animals↗

The evolution of myocardial ischaemia during percutaneous transluminal coronary angioplasty.

Balloon inflation during percutaneous transluminal coronary angioplasty is a useful human model of acute coronary occlusion and regional myocardial ischaemia. We assessed the prevalence and duration of ischaemia during successive sixty-second balloon inflations in sixteen patients undergoing routine single vessel angioplasty by continuous six lead electrocardiography and cross-sectional echocardiography. The influence of rate-pressure product on the evolution of ischaemia was also evaluated. ST segment elevation developed in fourteen of the patients within 19 +/- 12 seconds and returned to baseline within 20 +/- 9 seconds of deflation. Reciprocal ST segment depression occurred in four patients, only one of whom had multivessel disease. Wall motion abnormalities on echocardiography occurred in all sixteen patients and were seen significantly earlier than electrocardiographic changes. Thus, dyskinesis developed 15 +/- 5 seconds after balloon inflation and disappeared 13 +/- 3 seconds following balloon deflation. Time to onset of ischaemia by both methods remained constant during successive balloon inflations. Rate pressure product prior to balloon inflation correlated inversely with time to onset of ischaemia detected by either technique: r = -0.73, P less than 0.05 (ECG), r = -0.65, P less than 0.05 (echocardiography). Nevertheless, evidence of ischaemia developed within 30 seconds in all patients regardless of rate-pressure product. This investigation indicates that electrocardiography and cross-sectional echocardiography have similar sensitivity for the detection of acute ischaemia during coronary angioplasty although echocardiographic change is seen significantly earlier. Resting myocardial oxygen consumption, as reflected by rate-pressure product, is an important determinant of time to onset of ischaemia following balloon inflation.

Angioplasty, Balloon↗