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PubMed2004

Leaching behaviour of pharmaceuticals in soil-testing-systems: a part of an environmental risk assessment for groundwater protection.

The leaching behaviour of six selected pharmaceuticals was tested in different soils. Leaching experiments are a part of environmental risk assessment to estimate the distribution and fate of these pharmaceuticals in the environment. Based on the results of this assessment their mobility in soil and their potential to contaminate groundwater was evaluated. When assessing the leaching behaviour of these compounds, the influence of the properties (e.g. grain size distribution, pH, Corg) of different soils has to be taken into account. The test results indicated that the leaching potential found could be rated as low for diazepam, ibuprofen, ivermectin and carbamazepine. Therefore, contamination of the groundwater with these substances seems to be unlikely if the groundwater level is covered with sufficient layers of the soils investigated. Clofibric acid and iopromide were very mobile under the experimental conditions and thus, groundwater contamination would be possible if the soil is exposed to these pharmaceuticals, i.e. wastewater irrigation. These results are more or less in agreement with groundwater monitoring data found in the literature for ibuprofen and diazepam which were in general not present in groundwater, while clofibric acid and iopromide were frequently detected. However, a discrepancy was found for carbamazepine, since it occurs very often in groundwater. This discrepancy might be explained by the fact that the leaching tests were performed with soil, whereas in reality the groundwater contamination occurs mainly over river sediments and sub soil from receiving waters.

Carbon↗
PubMed2003

B-type natriuretic peptide: physiologic role and assay characteristics.

The discovery of cardiac natriuretic peptides two decades ago has lead to considerable research to investigate their biochemical and physiological properties. Clearly the heart is not just a pump but is also an endocrine organ that together with the kidneys control volume overload. The natriuretic peptides are a group of structurally similar but genetically distinct peptides that exhibit diverse actions in cardiovascular, renal, and endocrine homeostasis. Atrial natriuretic peptide (ANP) and brain (or B-type) natriuretic peptide (BNP) are of myocardial cell origin. BNP is released mainly from the left ventricle in response to volume overload and has become the first biochemical marker for the identification of individuals with congestive heart failure (CHF). The development of assays, including rapid point-of-care tests, has made BNP measurement a clinical reality.

Atrial Natriuretic Factor↗
PubMed2002

An evaluation of a virtual reality airway simulator.

UNLABELLED: In this research, we sought to test the hypothesis that the AccuTouch Flexible Bronchoscopy Simulator (Simulator) is an effective way to teach clinicians the psychomotor skills necessary to use the fiberoptic bronchoscope as an instrument for intubating the trachea of a pediatric patient. Pediatric residents with no prior experience in fiberoptic bronchoscopy were studied. Residents performed fiberoptic intubation on children undergoing general anesthesia. Tapes of these intubations were analyzed for: time to visualization of the carina, and number and time that the bronchoscope tip hit the mucosa. Residents were then trained on the Simulator. Performance of fiberoptic intubation on a subsequent child was compared. Training on the Simulator was the only instruction that the residents received between the two cases. A control group of residents performed two consecutive intubations without training on the Simulator between cases. Residents studied an average of 17 cases, and spent 39 min on the Simulator. Performance was markedly improved after the Simulator. Time to completion of successful intubation with a bronchoscope was reduced from 5.15 to 0.88 min (P < 0.001). The number of times that the tip of the bronchoscope hit the mucosa was reduced from 21.4 to 3.0 (P < 0.001). The amount of time that the resident spent viewing the mucosa decreased from 2.24 to 0.19 min (P < 0.001). The percent of time viewing the channel of the airway increased from 58.5% to 80.4% (P = 0.004). This bronchoscopy simulator was very effective in teaching residents the psychomotor skills necessary for fiberoptic intubation. Significant improvement was seen in time to completion of endotracheal intubation, as well as other performance indicators. IMPLICATIONS: This research showed that the AccuTouch Bronchoscopy Simulator is an effective way to teach the psychomotor skills necessary to intubate the trachea of patients using a fiberoptic bronchoscope. The residents that practiced on the Simulator dramatically improved their skills compared with a control group of residents.

Anesthesia↗
PubMed1976

The role of the chief resident: expectations and reality.

The job expectations of 35 incoming chief residents were tested by questionnaire when they attended a weekend workshop on leadership and were reexamined after they has had six months' experience on their jobs. Such personal qualities as a sense of humor and persistence and such administrative skills as the ability to exercise authority and set objectives significantly increased in importance six months after these residents began work. The authors recommend educational programs in administration for chief residents.

Humans↗
PubMed2006

Preclinical pharmacokinetics: an approach towards safer and efficacious drugs.

Lack of efficacy and toxicity are considered to be major reasons for drug failures and pharmacokinetics governs them to a large extent. Compound with favorable pharmacokinetics is more likely to be efficacious and safe. Therefore, the preclinical pharmacokinetic evaluation should be comprehensive enough to ensure that compounds do not fail in the clinic. Preclinical ADME screening facilitates early elimination of weak candidates and directs the entire focus of the drug development program towards fewer potential lead candidates. Hence, it is mandatory that the pre-clinical candidates are subjected to as many possible reality checks. Reliance on in-vitro tests should be minimized because they do not represent the real physiological environment but rather slow down the pace of a drug discovery program. Compounds can be straight away subjected to in-vivo high throughput screens such as cassette dosing, cassette analysis or rapid rat screen etc. Candidates with the desired in-vivo pharmacokinetic profile may be further profiled in-vitro, using assays such as metabolic stability, reaction phenotyping, CYP-450 inhibition and induction, plasma protein binding etc. in human microsomes, human recombinant CYP-450 enzymes and human plasma. This also provides an early indication of whether the compound which worked in animals would work in human as well. In-vitro metabolic stability profile is a qualitative as well as quantitative comparison of metabolism of a compound in human and animal models. It helps in identifying the right model for toxicity studies. Extensive metabolism is generally considered a liability as it limits the systemic exposure and shortens the half-life of a compound. Several strategies such as reduction of lipophilicity, modification and / or blocking of metabolically soft spots and use of enzyme inhibitors; have been developed to combat metabolism. In spite of several concerns, the fact that active metabolites of several marketed drugs have been developed as drugs with better efficacy, safety and pharmacokinetics profile; cannot be denied. Therefore, instead of considering metabolic instability a liability it can be exploited as a tool for discovering better drugs. It is equally important to identify the metabolic pathways of the drug candidates by conducting in-vitro CYP450 reaction phenotyping assays. The identification of drug metabolizing enzymes involved in the major metabolic pathways of a compound helps in predicting the probable drug-drug interactions in human. Compounds with more than one metabolic pathway have less likelihood of clinically significant drug interactions. In-vitro CYP450 inhibition and induction screens are used to evaluate the potential of compound towards drug - drug interactions and the most prone candidates may either be discarded or taken ahead with a caution. It is known that only unbound drug is pharmacologically active and therefore the assessment of bound fraction by the estimation of plasma protein binding of a compound is another important parameter to be explored in-vitro. In addition to the process of 'weeding out' weak candidates early in the drug discovery process, it is equally important to identify the probable causes of poor ADME exhibited by some compounds as this information is useful to medicinal chemists for improving upon backbones that exhibit un favorable pharmacokinetic profile. Toxicity study is the foundation of an INDA (Investigational new drug application) and therefore, the final selection of a compound can be performed only after proper toxicological evaluation in animal models. Toxicokinetics forms an integral part of toxicity study and is used to assess the exposure of candidates in toxicity models and correlate the drug levels in blood and various tissues with the toxicological findings. Although in-vivo screening of compounds in animal models and in-vitro assays in human recombinant CYP-450 enzymes help in drug candidate selection, both approaches have their own limitations. There is no certainty that the selected candidates will exhibit the desired target PK profile in human and real human PK remains suspense until the compound enters Phase-1 clinical trial. The recognition of human micro dosing, (HMD) by medicines and healthcare products regulatory agency (MHRA) and European agency for evaluation of medicinal products [EMEA] is a stepping stone in the direction of obtaining human PK data early in the preclinical stage. This would gradually shift the focus of early drug development away from animal studies directly towards safe and ethical studies in human yielding more relevant and reliable pharmacokinetic data. HMD would provide an answer to the growing public demand for a reduction in the use of animals for pharmaceutical development.

Animals↗
PubMed2000

What the Internet means for the medical device industry.

The Internet is dramatically changing the structure of the industry. For the first time, direct communication between all suppliers and all hospitals is available. The Internet-based electronic market place not only provides the ability to choose products from a standardized catalogue, but also to send orders direct to suppliers' enterprise resource planning systems. One-to-one marketing is also becoming a reality. Medical device manufacturers are advised to test the different electronic sales and marketing initiatives that are now available.

Equipment and Supplies↗
PubMed2003

[Effects of field viewing angles on object judgement [correction of jubgerent] in virtual environment].

OBJECT: To investigate the effect of viewing angle on human judgement reliability for objects in virtual environment. METHOD: Firstly, pre-tests were done with the PC virtual reality ergonomic system to determine difference among observed object and values of viewing angle. Then, one factor, 4-levels full random experiments were done with 45 health human subjects (male and female nearly 1:1). RESULT: It was shown that the reliability of human judgement was significantly influenced by the setting of the viewing angle of virtual environment, and the object judgement including size and angle judgement was the best when the viewing angle of virtual environment was 60 degrees. CONCLUSION: When virtual reality was used in ergonomic design, operation training and other related research, the effect of field viewing angle should be taken into consideration, and 60 degrees is recommended to be optimal for human judgment task.

Adult↗
PubMed1993

Scabies research: another dimension.

The life cycle of canine scabies has been studied extensively. Currently studies are focusing on mite behavior, physiological requirements, host specificity, mite survival, and clinical complications of scabies. Investigations are giving insight into immunologic responses to infestation and cross-reactivity with house dust mites. A diagnostic blood test or vaccine may become a future reality, if a unique antibody response can be isolated. Can scabies transmit the human immunodeficiency virus (HIV)? This controversial area needs prompt definitive exploration.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Genetic discrimination and health insurance: a call for legislative action.

Fear of genetic discrimination in health insurance is a growing reality. Individuals who might otherwise choose genetic testing may decline it based on their fear that they or their family members will not be able to obtain or maintain health insurance coverage. This commentary notes the evolving legislative efforts to address genetic discrimination in health insurance and urges physicians to help move this legislative agenda forward.

Genetic Diseases, Inborn↗
PubMed2001

Implementing a virtual reality paradigm in human anatomy/physiology college curricula.

Modes of instruction in the college course called Human Anatomy/Physiology are changing. Due to ethical concerns and the ever-increasing source of new physiological data, there is a need for enhancements to assist the instructor and student. The computer science of virtual reality (VR) provides a method to electronically educate, train, prototype, test and evaluate new enhancements to the college curricula. This study detailed the modeling and simulation of a skeletal human hand with degrees of freedom of movement, which provided the students with a physiological representation of some of the movements of the hand. The primary objectives of the study were to assess the use of the VR simulation by college students and to assess the potential learning outcomes of students in their use of the VR simulation. The simulation was implemented into classes of Human Anatomy/Physiology as an adjunct enhancement for the students' use. The expectation centered on the constructivist theory that students develop an analytic outlook to the various articulations of the human skeleton. Positive results were shown based on the answers to the questionnaire, summary and post-test taken by the students, after their use of the VR simulation. The results supported the constructivist theory that critical thinking took place. The results showed that the virtual reality simulation enhanced the learning ability of the students. The recommendations of the study include future experimentation to be done on increasing the number of VR simulations, incorporating the VR simulations into undergraduate courses, testing the outcomes, and following the progression of students into graduate programs that are using VR simulations. Faculty and administration are advised to consider implementing the paradigm of VR simulations in undergraduate courses of Human Anatomy/Physiology.

Anatomy↗
PubMed2005

Metacognitive development of deaf children: lessons from the appearance-reality and false belief tasks.

'Theory of mind' development is now an important research field in deaf studies. Past research with the classic false belief task has consistently reported a delay in theory of mind development in deaf children born of hearing parents, while performance of second-generation deaf children is more problematic with some contradictory results. The present paper is aimed at testing the metacognitive abilities of deaf children on two tasks: the appearance-reality paradigm designed by Flavell, Flavell and Green (1983) and the classic false belief inference task (Wimmer & Perner, 1983; Hogrefe, Wimmer & Perner, 1986). Twenty-eight second-generation deaf children, 60 deaf children of hearing parents and 36 hearing children, aged 5 to 7, were tested and compared on three appearance-reality and three false belief items. Results show that early exposure to language, be it signed or oral, facilitates performance on the two theory of mind tasks. In addition, native signers equal hearing children in the appearance-reality task while surpassing them on the false belief one. The differences of performance patterns in the two tasks are discussed in terms of linguistic and metarepresentational development.

Adult↗
PubMed2004

Validation of a six-task simulation model in minimally invasive surgery.

BACKGROUND: The content validity of currently available inanimate simulation models is questionable, because some tasks seem too far from clinical reality. The aim of this study was to validate a simulation model with six tasks commonly used in clinical practice (6-TSM) for the acquisition of psychomotor skills in minimally invasive surgery (MIS). METHODS: This was a prospective randomized trial comparing the 6-TSM to a previously described three-task training method (3-TTM). All first, second, and third postgraduate year surgical residents were eligible. The 6-TSM included clipping and dividing of a vessel, excision of lesion, appendectomy, mesh repair, suturing perforation, and hand-sewn anastomosis. The outcome measures of 6-TSM included accuracy error, tissue damage, sliding knot, leak, operating time, and dangerous movements. After completion of training, 6-TSM and 3-TTN residents were tested by the Minimally Invasive Surgical Trainer-Virtual Reality (MIST-VR). Criterion-related and construct validity, responsiveness, test-retest, and interrater reliability were assessed. RESULTS: During six months, 17 residents underwent training with the 6-TSM or the 3-TTM as allocated. The mean duration of training with 6-TSM and 3-TTM was similar (7.8 vs 8.1 h). The criterion-related validity of the 6-TSM was shown by significantly increased skill improvement in the 6-TSM residents, as compared with the 3-TTM residents at MIST-VR. Construct validity the of 6-TSM was shown by the finding that the experts' baseline was superior to the residents' baseline. The responsiveness of the 6-TSM was shown by the significantly increased skill improvement of the 6-TSM residents in sliding knot, leak, and operating time. The test-retest reliability of the 6-TSM was good (> 0.80), except for accuracy error and dangerous movements (Cronbach's intraclass correlation coefficient alpha: 0.57, p < 0.0001; 0.62, p < 0.0001, respectively). The interrater reliability of the 6-TSM was good (>0.80) except for leak (Kendall's concordance coefficient tau_b:0.76, p = 0.06 for hand-sewn anastomosis) and dangerous movements (tau_b:0.72, p = 0.08 for suturing perforation and tau_b:0.68, p = 0.10 for hand-sewn anastomosis). The perresident cost for 6-TSM was 769 dollars. CONCLUSIONS: The 6-TSM is a valid and reliable learning tool for surgical residents' acquisition of laparoscopic motor skills.

Clinical Competence↗
PubMed1994

Assessment of developmental toxicity: neuropsychological batteries.

Assessment of change in behavioral functioning in children as a function of neurotoxicity is not a trivial undertaking. Psychological tests, widely (though erroneously) considered to be the "gold standard" for measurement of behavior in humans, are not adequate for the task; they tap the structure of cognition, not the behavioral repertoire, and cannot (alone) address developmental change. Comprehensive neurobehavioral assessment must be undertaken within a multidisciplinary assessment strategy incorporating knowledge of brain and brain development, cognitive processes and their development, brain-behavior relationships, and detailed knowledge of neurotoxicants, their action and the exposure thereto. Initial assessment batteries must be adequately broad ranging and must incorporate strategies and data for evaluating the impact of predictable nonbrain variables; they must also be cost efficient to respond to the realities of funding and the exigencies of field testing. Measures of neuropsychological outcome are optimally characterized as they relate to behavioral domains specified in terms of the competencies of infants and children of different ages; relevant information is derived from demographic, socioeconomic, medical, developmental, and educational sources, as well as from detailed observational data and performance on psychological tests. Two levels of assessment are proposed.

Brain Diseases↗
PubMed2003

Haptic subjective vertical shows context dependence: task and vision play a role during dynamic tilt stimulation.

Perceiving one's vertical is an integral part of efficiently functioning in an environment physically polarized along that dimension. How one determines the direction of gravity is not a task left only to inertial sensors, such as the vestibular organs, rather as numerous studies have shown, this task is influenced visually and somatosensorily. In addition, there is evidence that higher order cognitive effects such as expectancies and context are critical in perception of the vertical. One's ability to integrate these various inputs during normal activity is not generally questioned, one's doubts being satisfied by observing a waiter navigating a crowded restaurant with a tray balanced on one hand, neither tripping or dropping an entree. But how these various sources are integrated is still debated. Most research focuses on subjective vertical perception used visual matching/alignment tasks, verbal reports, or saccadic eye movements as a dependent measure. Although a motor task involving a joystick or indicator to be aligned with gravity without visual feedback is used much less frequently, there is good evidence that individuals easily orient limbs to an external gravity-aligned coordinate axis while being statically tilted. By exposure to a dynamic situation, the central nervous system should be no more challenged by the task of determining the subjective vertical than during static conditions, because our spatial orientation systems were likely selected for just that. In addition, the sensitive calibration between visual and other sensory input also must have been key to its selection. This sensory interaction can be tested by changing the relation between the various sources. With the advent of virtual reality technology, a complex and "natural" visual stimulus is achievable and is easily manipulable. How one tests perception of verticality is also a pertinent question when researching spatial orientation systems. The system's performance may be better indicated by a task of higher relevance to its normal function. In other words, the dependent measure can be made more or less relevant to real-world tasks. With an experimental design that attempts to mimic natural conditions, the current study focuses on two main topics. First, how does manipulation of the visual inputs during passive roll-tilt affect one's sense of body orientation? And second, how does changing the task used to measure subjective vertical affect one's performance?

Darkness↗
PubMedDate not supplied

An inquiry into the positive personal and social effects of old age stereotypes among the elderly.

Much has been written or inferred about the detrimental consequences of old age stereotypes for elderly individuals. This paper presents and tests an alternative perspective called relative advantage. As the reciprocal counterpart of relative deprivation theory, this perspective claims that such stereotypes may be psychologically and sociologically functional for the old to believe. Using the results of the 1975 Louis Harris--NCOA "The Myth and Reality of Aging in America" survey, two hypotheses were tested: 1) those who feel other older individuals are worse off than themselves will have higher life satisfaction scores than those perceiving others to be as well or better off; 2) these imputations of others' difficulties correlate with one's likelihood to support and join coalitions on behalf of the old and to approve government taxing of all age groups to support them. The evidence presented raises some dysfunctional implications of debunking aging myths.

Adaptation, Psychological↗
PubMed1999

A virtual reality module for intravenous catheter placement.

BACKGROUND: Virtual reality (VR) is a potential tool for technical skills training. We tested the validity and instructional effectiveness of a prototype VR module for learning intravenous (i.v.) catheter placement. METHODS: First-year medical students (n = 37), third-year medical students (n = 14), and surgical residents (n = 9) attempted two pretest i.v.s into each other, used the VR module for 12 minutes, and subsequently attempted two posttest i.v.s. Success or failure were recorded for each attempt. For each successful attempt, time and global rating of i.v. insertion were also recorded. RESULTS: The pretest success rate was significantly different between groups (chi square = 28.71, P <0.01). VR success rate was not significantly different between groups (F(2,57) = 1.47, ns). Although there was improvement in all groups during VR training (F(2,114) = 44.16, P <0.01), this did not result in improvement in posttest performance. CONCLUSIONS: Significant differences between groups were observed in performance of i.v. insertion in physical reality. However, no significant difference was observed in performance in VR. Thus, performance in VR demonstrated neither construct nor concurrent validity. While performance improved in VR, transfer of skill from VR to physical reality was not observed. Additional development and testing of VR as a training tool is warranted before its widespread use can be recommended.

Catheterization↗
PubMed1998

Mouse mutagenesis: from gene to phenotype and back again.

Screens for genetic mutations have been instrumental in identifying genes needed to execute particular biological processes. They have also helped to resolve the function of individual genes. Now the notion of large-scale mutagenesis screens in mouse, an experimental model for humans, is becoming a reality.

Animals↗
PubMed1991

[Organ transplantation and laboratory tests].

The media has recently been featuring organ transplantation from various viewpoints. Furthermore, Novel Prizes 1990 for Medical & Physiological fields were awarded to Drs. JE Murray and ED Thomas, both pioneers of clinical transplantation. Our topic has been timely indeed. This symposium mainly dealt with laboratory tests vs. various types of organ transplantation. In reality though, only kidney and bone marrow transplantations have been practiced in Japan; thus, Dr. I Yokoyama, University of Pittsburgh, discussed liver transplantation. First, Dr. K Uchida lectured on the recent advancement of immunosuppressive drugs and improvement in the clinical outcome of kidney transplantation. Serum creatinine determination is the only parameter for rejection besides renal biopsy. Drs. K Miyamura & Y Morishima discussed about PCR method to detect MRD (minimal residual diseases). There are positive relationships between the remaining leukemic cells and the relapse of leukemia even though the patients are in clinical remission. Dr. H Funada dealt with the importance of "sterile room treatment" for bone marrow transplantation. It protects patients from infection, minimizes GVHD and prolongs survival time after transplantation. Dr. Yokoyama stressed the importance of back-up system, i.e. drug-monitoring, coagulation tests, pathological examination, biochemical tests, blood transfusion services for successful liver transplantations. Dr. T Fukunishi discussed the importance of developing the organ donor and coordinator system to promote kidney transplantation from cadaver. He also dealt with virus antibody tests for selecting donors. All discusssions stressed on the importance of the 24-hour laboratory back-up system performing emergency tests but no specific laboratory test for organ transplantation was necessary.

Clinical Laboratory Techniques↗