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91.
92.
93.
Zhen-yu Wu Laurent P. Rivory Michael S. Roberts 《Journal of pharmacokinetics and pharmacodynamics》1993,21(6):653-688
Distribution of Evans Blue (EB), sucrose, and water into the isolated perfused rat hindlimb was studied under various conditions using the multiple indicator dilution (MID) technique. Statistical moment analyses of the outflow profiles for the EB, sucrose, and water were used to define the vascular, extravascular, and total water spaces, respectively. The varied perfusion conditions included albumin content (2, 4.7, and 7%), temperature (25, 37, and 42 C), perfusate flow rate (2, 4, 8, and 12 ml/min) and the presence/absence of red blood cells. The range of studies undertaken were chosen to represent the variety of conditions used in the preparation of both isolated animal and human limbs, the latter being particularly important in cytotoxic therapy for recurrent malignant melanoma. The distribution volumes of EB, sucrose, and water were dependent on the flow rate and the albumin content of perfusate. The normalized variances (CV
2
) of the markers were of the following order: sucrose (2.18) > water (1.58) > EB (0.68), indicating that some disequilibrium occurs during the capillary exchange of water and sucrose. It is suggested that a Krebs-Henseleit buffer containing 2% BSA is a suitable perfusate for most studies of the isolated rat hindlimb perfusion. The effect of albumin concentration manifests itself only at higher flows.We acknowledge the support of the National Heart Foundation (Queensland) and the Mayne Bequest Foundation. This study was conducted while the investigator (Z.Y. Wu) was in receipt of a WHO Research Training Grant. Professor M. S. Roberts also acknowledges the support of the Queensland and Northern New South Wales Lions Kidney & Medical Research Foundation. 相似文献
94.
This study looks at the relationship between anatomical concepts held by medical students and their clinical application, and develops a testable model of how students use basic science concepts for clinical problem-solving. According to the model, the essential prerequisites to solve a clinical problem using basic science information include the appropriate basic science knowledge, the ability to collect and interpret clinical information, with the key concept being the link that must then be made between clinical data and basic science. A detailed analysis of the individual components of the model should help to clarify and resolve some of the debate about the nature and balance of basic science and clinical education. A neurological diagnostic problem was used to test the assumptions of the model in a group of medical students who had minimal clinical experiences. There was no demonstrable relationship between anatomical knowledge as assessed by conventional tests and the diagnosis. There was a powerful relationship between measures of organization of knowledge and diagnosis, suggesting that the organization and development of concepts is the key to correct diagnosis. The findings have significant implications for assessment purposes and suggest that standard methods as generally practised may not measure the appropriate conceptual development and are not congruent with curricular objectives. Through the examination of its different learning outcome measures, the model may also be used to provide a profile of individual students or classes, which should help teachers and students deal with difficulties that may be experienced in learning to link clinical and basic science concepts. 相似文献
95.
ChanMA RMN DipN PGCEA Head of Mental Health & RudmanMA RMN RCNT DipNEd Tutor 《Journal of psychiatric and mental health nursing》1998,5(2):143-146
Debate about the best paradigm for mental health nursing is compounded by threats from mainstreaming and genericism. In nursing education, integrated practice may have been devalued in a matrix of reductionist disciplines. The 'gendered' nature of professional knowledge may create a schismatic and self-defeating attitude in nurses. Conversely, nurses may be exhorted to adopt a 'male' paradigm in order to gain academic credibility, in which the caring dimension may be lost. Other polarities such as ideological distinctions between treatment in hospital and care in the community lead to conceptual confusion. These schisms in care are detrimental to both professionals and users. The writers argue that these tensions may be addressed in an 'androgenous' model which presents a challenge to both value systems, rejects the dominance of schismatic models, and offers the potential for a new professional integrity. 相似文献
96.
97.
颞下颌关节的三维有限元法研究 总被引:1,自引:0,他引:1
本研究利用颞下颌关节CT扫描资料和计算机图像分析处理技术以及三维有限元方法相结合建立了髁状突的三维有限元模型,结果表明,此方法在技术上是可行的并将有助于颞下颌关节的临床和基础研究。 相似文献
98.
The glomerular capillary wall imposes a remarkably efficient barrier to the passage of proteins the size of albumin and larger. The development of heavy proteinuria signifies impairment of the function of this barrier. Because endogenous proteins of graded size are heterogeneous with respect to their molecular charge and undergo extensive tubular reabsorption, they are not useful for quantifying the extent of barrier dysfunction. An alternative approach is to determine the fractional clearance of uncharged and non-reabsorbable polymers of graded size. When combined with a hydrodynamic theory of solute transport through a heteroporous membrane, the intrinsic properties of healthy and diseased glomerular capillary walls can be inferred. This approach reveals the nephrotic range proteinuria that attends minimal change nephropathy to be associated with impairment of both the size- and charge-selective properties of glomerular capillary walls. 相似文献
99.
J. De Vry 《Psychopharmacology》1995,121(1):1-26
During the last decade, serotonin (5-HT)1A receptors have been a major target for neurobiological research and drug development. 5-HT1A receptors have been cloned and a variety of selective agonists, such as the aminotetraline 8-OH-DPAT and the pyrimidinylpiperazine ipsapirone, have become available. Demonstrations of apparent intrinsic activity of these ligands at 5-HT1A receptors, however, depend highly on the particular assay system. This may be due to the possible existence of receptor subtypes and to assay (or brain region)-dependent differences in receptor reserve and the nature of receptor-effector coupling. Nevertheless, the apparent intrinsic activity of 8-OH-DPAT seems to be higher (although possibly not yet maximal) than that of the pyrimidinylpiperazines. In the brain, 5-HT1A receptors are located presynaptically as somatodendritic receptors on 5-HT neurons and postsynaptically in particular limbic and cortical regions. Although it is generally accepted that presynaptic 5-HT1A receptors control 5-HT neuronal activity, recent evidence suggests an additional role of postsynaptic 5-HT1A receptors in cortex as part of a negative feedback loop. Anxiolytic and antidepressive properties of selective 5-HT1A receptor agonists have now been confirmed by clinical studies. Although it is well established that the latter properties depend on theagonistic activity of these compounds, theoptimal level of intrinsic activity is still a matter of debate and may be dependent on the clinical indication. Such compounds may also have antiaggressive effects, and possibly anticraving effects (manifested by their alcohol intake-reducing effects in dependent animals), but the specificity of these so-called anti-impulsivity effects is still controversial and not yet tested clinically. Anticataleptic, antiemetic and neuroprotective properties have been demonstrated in different species. Behavioral studies on the mechanisms underlying the anxiolytic and antidepressive effects have examined the relative contribution of pre-and postsynaptic 5-HT1A receptors by means of local cerebral application and lesion techniques. Most evidence points towards a critical involvement of presynaptic receptors in the anxiolytic effects of 5-HT1A receptor agonists (although a possible contribution of postsynaptic receptors cannot be excluded). With regard to the antidepressive properties, a case can be made for the reverse; i.e., a strong involvement of postsynaptic receptors and a questionable contribution of presynaptic receptors. However, as the therapeutic effects of those 5-HT1A receptor (partial) agonists which have been tested clinically require repeated administration, attention has been directed increasingly towards chronic studies. These studies have shown that a number of electrophysiological, biochemical, behavioral and endocrinological 5-HT1A receptor-related events adapt differentially to repeated or sustained administration. Thus, several hypotheses accounting for the delayed onset of action have been advanced. Among these, time-dependent downregulation /desensitization of eitherpre- orpostsynaptic 5-HT1A receptors, or cortical 5-HT2 receptors have received much attention. However, these hypotheses have their weaknesses, and it is argued thatfunctional sensitization of particular postsynaptic 5-HT1A receptor-mediated events remains a valuable alternate hypothesis. Basic research on the role of 5-HT1A receptors in psychopathology and in the therapeutic effects of clinically effective therapeutics, as well as on the mechanism of action of 5-HT1A receptor ligands, will enable rational design of ligands with particular profiles of intrinsic activity at different 5-HT1A receptor populations, and may contribute to a more efficient treatment of a multiplicity of brain disorders. 相似文献
100.
Yukiya Hashimoto Toshiko Koue Yuko Otsuki Masato Yasuhara Ryohei Hori Ken-ichi Inui 《Journal of pharmacokinetics and pharmacodynamics》1995,23(2):205-216
A simulation study was conducted to compare the cost and performance of various models for population analysis of the steady
state pharmacokinetic data arising from a one-compartment model with Michaelis-Menten elimination. The usual Michaelis-Menten
model (MM) and its variants provide no estimate of the volume of distribution, and generally give poor estimates of the maximal
elimination rate and the Michaelis-Menten constant. The exact solution to the Michaelis-Menten differential equation (TRUE)
requires a precise analysis method designed for estimation of population pharmacokinetic parameters (the first-order conditional
estimation method) and also considerable computational time to estimate population mean parameters accurately. The one-compartment
model with dose-dependent clearance (DDCL), in conjunction with the first-order conditional estimation or Laplacian method,
ran approximately 20-fold faster than TRUE and gave accurate population mean parameters for a drug having a long biological
half-life relative to the dosing interval. These findings suggest that the well-known MM and its variants should be used carefully
for the analysis of blood concentrations of a drug with Michaelis-Menten elimination kinetics, and that TRUE, in conjunction
with a precise analysis method, should be considered for estimating population pharmacokinetic parameters. In addition, DDCL
is a promising alternative to TRUE with respect to computation time, when the dosing interval is short relative to the biological
half-life of a drug.
This work was supported in part by the Epilepsy Research Foundation, the Nakatomi Foundation, and a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, and Culture of Japan. 相似文献