Clinical applications of the camptothecins

In this paper, the pattern of induction of heat shock proteins (hsps) was studied in cultured Reuber H35 rat hepatoma cells by sequential application of different stressors. We analyzed whether a specific stress condition is able to induce an enhanced sensitivity to a subsequent application of a low dose of either the same or another stressor (self-sensitization and cross-sensitization, respectively). As a measure of sensitization, the stimulation of hsp induction was employed. Three different stressor conditions (heat shock, sodium arsenite and cadmium chloride) were used in doses which exerted a similar impact on overall protein synthesis. A synergistic effect in induction of the synthesis of various hsps was observed when a high stressor dose was followed by an 8-h incubation in a lower stressor dose in both self- and cross-sensitization experiments. The low-dose conditions used as second treatments did not induce any responses in non-pretreated cells. Studies in cultured cells have demonstrated stressor-specific hsp induction patterns. In this study we analyzed whether the pattern of hsps induced by the low-dose condition is characteristic for the first sensitizing stressor or for the secondary stressor applied in a low dose. The pattern of hsps which was induced above the level of the high-dose effect, due to the incubation with the secondary applied low-dose condition, was found to be characteristic for the secondary stressor and not for the sensitizing primary treatment. These results are of importance for an improved understanding of the regulation of heat shock protein synthesis in conditions of self- and cross-sensitization, as well as for a proper use of hsps as biomarkers of exposure to environmental stress.     

Clinical applications compared in implantology

On the basis of their own experience and of orientation reported by literature, the authors display how important it is for professional men who practise implantology or who approach it, to have the possibility of knowing several implantologic systems. Indeed, what we want to demonstrate is, that in different situations of edentulous, in relation to the quantity and the quality of the available bones, to the gnotologic situation and to the aesthetic functional result they aim to, corresponds the choice of one or several implantologic systems. In that sense the basic research occupies a role of vital importance, because only through the knowledge of chemical, chemical-physical and biomechanical characteristics it is possible to recognize some essential chemical entities for an implantologic approach. Thus the several diagnostic instrumental means available enable the surgeon to make an exact clinical diagnosis. The TAC, in this case, assumes a determinant role, because, in addition to supplying exact dimensional and qualitative informations, also occupies an important medico-legal aspect. The resolution of some forms of edentulous programmed like that, will subsequently be illustrated. Finally, a control hypothesis is proposed for the rearrangement, of peri-implant bone. On this account, the SPECT (single photon emission computerized tomography), through a semi-quantitative research, could provide some specific indications about the osteotropic implantation activity.     

Clinical applications of cytokines in pediatrics

The use of adjuvants for immunopotentiation has been investigated since the 1920s and a number of comprehensive reviews and monographs have been published on this subject. A recent trend in immunopotentiation has been the use of delivery systems which allow for sustained or controlled release of antigens and which induce prolonged immunity following a single dose. This concept has been termed either single-step or single-shot immunization. The delivery system has been modulated to potentiate the immune response either by delivering the antigen (and perhaps an adjuvant or adjuvants) either over a prolonged period of time or in a predetermined sequence or by incorporating substances with immunoadjuvant properties (e.g., lecithin and certain biodegradable polymers) as carriers within the delivery system. This Review focuses on the progress made in the design of delivery systems for immunopotentiation. Particular emphasis is given to delivery systems designed to achieve single-step immunization.     

Clinical applications of fundus reflection densitometry

Fundus reflection densitometry or retinal densitometry is a non-invasive technique to examine the visual photopigment kinetics in living eyes. The technique is based on the comparison of the reflected light from the fundus in a fully light adapted eye (when all visual photopigment has been bleached) with the reflected light following complete dark adaptation (when the retina contains its maximum amount of visual photopigment). The technique provides a measure of the density of visual photopigment, its time constant of regeneration, its distribution and spectral characteristics if measured at a series of wavelengths. Fundus reflection densitometry in the human eye was introduced 40 years ago. Presently, it is the only available technique from which direct and objective insight can be obtained into visual photopigment. This knowledge is particularly relevant in eyes where abnormalities of photoreceptor function are suspected. This paper summarizes the current knowledge of fundus reflection densitometry in the diseased and in the aging human retina, gathered over the last 30 years. Considerable improvements of the instrument for clinical purposes have been obtained, and are also discussed.     

Clinical applications of lactate dehydrogenase isoenzymes

A quantitative electrophoretic test for the determination of lactate dehydrogenase isoenzymes was applied to the analysis of human tissues, cells and fluids in order to obtain their normal isoenzyme patterns and to form a reference record. The same test was employed in the analysis of serum samples from patients with defined pathological conditions. The abnormal serum isoenzyme patterns were correlated with the tissue patterns, thus indicating the origin of the abnormality. This type of correlation, together with the clear demonstration of the actual isoenzymes and their quantitation, improves diagnostic discrimination and enhances the early detection of a biochemical abnormality that aids in the prevention of disease.     

Clinical applications of ultrasound contrast agents

Within the last decade safe and practical ultrasound contrast agents have been introduced. Most of these are based on gas-filled microbubbles, which markedly enhance Doppler signals and, in some cases, also gray-scale images. The clinical improvements expected from ultrasound contrast is reviewed. Tissue-specific contrast agents constitute another area of potential clinical significance. One particular agent is taken up by the reticulo-endothelial system and produces so-called acoustic emission signals when imaged. An introduction to the unique clinical applications of acoustic emission is given. Harmonic imaging is a new contrast-specific imaging modality, which utilizes the nonlinear properties of some agents in an attempt to alleviate current limitations of ultrasound contrast studies. Examples of harmonic images are presented.     

Clinical applications of magnetic resonance spectroscopy

Neurospectroscopy measures a neuronal marker, energy and redox state, specific fuels of tissue respiration, maturation, and possibly myelination. It provides diagnostic patterns of altered neurochemistry. Current clinical uses range from intensive care in neonates to dementia in the elderly and include tumor and stroke management, prognosis in hemorrhage and trauma, white matter, inflammatory diseases, and AIDS. Inborn errors, metabolic and systemic diseases, subclinical hepatic encephalopathy, hyponatremia, and "coma" have been elucidated. Automation, single-voxel MRS, chemical shift imaging, quality control, and outcome analyses are discussed. With no remaining impediments to clinical use, neurospectroscopy has changed the way we look at diseases of the brain.     

Clinical applications of transpulmonary contrast echocardiography

BACKGROUND: The recent development of new fluorocarbon-based echocardiographic contrast agents that are capable of opacification of the left-sided cardiac chambers after intravenous injection is a major new advance in diagnostic cardiac imaging. METHODS AND RESULTS: This is a review article focusing on these novel contrast agents, new echocardiographic imaging techniques to optimize their efficacy, and their clinical applications. Specific clinical applications of these agents are (1) enhancement of endocardial border definition to improve assessment of regional and global left ventricular function, (2) myocardial perfusion imaging by intravenous contrast echocardiography, (3) augmentation of spectral and color flow Doppler images, and (4) tissue-specific targeting of microbubbles for delivery of therapeutic agents. CONCLUSIONS: New intravenous contrast agents offer the possibility to assess myocardial perfusion echocardiographically. It is also possible to use these agents for delivery of therapeutic agents, including gene therapy.     

Clinical relevance of drug interactions with lithium

Although lithium continues to be regarded as the treatment of choice for bipolar disorders, the clinical use of this mood stabiliser is associated with an extremely narrow therapeutic range. Relatively minor increases in serum concentrations may induce serious adverse sequelae, and concentrations within the therapeutic range may result in toxic reactions. The safety of combining lithium with other medications, therefore, is a major concern, and extensive clinical experience has served to identify several significant drug interactions. Lithium removal from the body is achieved almost exclusively via renal means. As a result, any medication that alters glomerular filtration rates or affects electrolyte exchange in the nephron may influence the pharmacokinetic disposition of lithium. Concomitant use of diuretics has long been associated with the development of lithium toxicity, but the risk of significant interactions varies with the site of pharmacological action of the diuretic in the renal tubule. Thiazide diuretics have demonstrated the greatest potential to increase lithium concentrations, with a 25 to 40% increase in concentrations often evident after initiation of therapy. Osmotic diuretics and methyl xanthines appear to have the opposite effect on lithium clearance and have been advocated historically as antidotes for lithium toxicity. Loop diuretics and potassium-sparing agents have minor variable effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) have also been associated with lithium toxicity, although the relative interactive potential of specific NSAIDs is difficult to determine. Small prospective studies have demonstrated large interindividual differences in lithium clearance values associated with different NSAIDs. A growing body of evidence also suggests that ACE inhibitors may impair lithium elimination, but further investigations are needed to identify patients at risk. Anecdotal reports have linked numerous medications with the development of neurotoxicity without an apparent effect on the pharmacokinetic disposition of lithium. Antipsychotics, anticonvulsants and calcium antagonists have all be implicated in a sufficient number of case reports to warrant concern. As these medications have all been commonly coadministered with lithium, the relative risk of serious interactions appears to be quite low, but caution is advised.     

Clinical applications of fusion imaging in oncology

Recent developments in tumor imaging, made possible by advances in instrumentation and radiopharmaceuticals, has led to an increasing need for accurate anatomic correlation of single photon emission computed tomography (SPECT) and positron emission tomography (PET) images. Fusion imaging permits the functional strengths of SPECT and PET to be combined with the anatomic resolution of computed tomography (CT) and magnetic resonance imaging (MRI). Clinical applications of fusion imaging include the evaluation of brain tumors, lymphoma, hepatic lesions and monoclonal antibody studies. The continued development of these techniques will eventually allow fusion imaging to become a routine part of nuclear medicine practice.     

Clinical assessment applications of ambulatory biosensors.

Ambulatory biosensor assessment includes a diverse set of rapidly developing and increasingly technologically sophisticated strategies to acquire minimally disruptive measures of physiological and motor variables of persons in their natural environments. Numerous studies have measured cardiovascular variables, physical activity, and biochemicals such as cortisol in psychopathology and treatment research. The physiological concomitants of many behavior and medical disorders and the benefits of a multimethod assessment strategy provide strong rationales for clinical applications of ambulatory biosensor measurement. A number of psychometric dimensions of evaluation are important in clinical applications of biosensor measurement, including accuracy and validity, reliability and consistency, clinical utility, incremental validity and utility, sensitivity to change, generalizability, cost benefits, and the conditional nature of dimensions of biomeasure evaluation. The authors review ambulatory biosensor methods and make recommendations for use of the technology. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Clinical applications of functional MRI in neuropsychiatry

Clinical neuroimaging is due for yet another sea change as functional neuroimaging becomes increasingly powerful and available. Functional magnetic resonance imaging (fMRI) is perhaps the most promising of the emerging techniques. The following review helps us understand the physics, strengths, limitations, and promise of fMRI. The authors are all affiliated with the Brain Imaging Center at McLean Hospital and with the Departments of Neurology (Dr. Levin) and Psychiatry (Dr. Renshaw) at Harvard Medical School.     

Clinical applications of C-reactive protein in pediatrics

The body of literature concerning studies of the applications of CRP measurement in the pediatric population continues to grow. Based on current data serial CRP measurements appear to be most useful for monitoring patient response to therapy after the primary diagnosis of invasive infectious or inflammatory diseases, for monitoring patients after major surgical procedures and those with serious burns. Monitoring CRP over time may be used to assess for recrudescent disease, a secondary process or ineffective therapy. In addition CRP appears to be suited to most applications for which the ESR is used but offers many advantages. At present there are no objective outcome-based clinical trial data to justify using CRP values alone, whether elevated or normal, as a basis for management decisions regarding instituting or withholding antimicrobial therapy, or its early discontinuance for patients suspected of having neonatal sepsis, meningitis, bacteremia or pneumonia, regardless of immune status. In addition, because of significant inconsistencies among studies for which CRP has been applied to differential diagnosis of bacterial vs. viral diseases, including meningitis, acute otitis media and lower respiratory tract infection, we cannot recommend it for this purpose. Data do not support a role for CRP in differential diagnosis of acute appendicitis or for localizing urinary tract infections.     

Clinical applications of nuclear medicine in gastroenterology

This study describes the antibiotic resistance of 1961 staphylococcal strains that were isolated at the University Hospital of Vienna from July to December 1991. Staphylococcus aureus (SA) represented 43.2%; coagulase-negative (CNS) staphylococci 56.8%, three quarters of which were Staphylococcus epidermidis. Excepting netilmicin, the proportion of resistant strains to all antibiotics was higher with CNS than SA. Methicillin resistance (M(r)) was found in 11.8% of SA and 30.3% of CNS. Borderline oxacillin resistance (BOR) was noted in 7.4% of SA and 32.5% of CNS. It is important to note that severe or generalized infections due to M(r) staphylococci should be treated with glycopeptide antibiotics such as vancomycin or teicoplanin from the very beginning, whereas chemotherapy of those with BOR strains may also be carried out with beta lactamase-stable beta lactam antibiotics. Comparing the results of this study with those of the first half of 1991, the respective proportion of M(r) staphylococci was significantly lower than 23.6% for SA and 47.6% for CNS recorded then. As compared with the foregoing period, however, these strains demonstrated increased resistance frequencies to gentamicin (from 81.3 to 90%), amikacin (from 35.4 to 69%), netilmicin (35.4 to 55%), and ciprofloxacin (56.2 to 64%). This is taken as an indication for the epidemic spread of a clone of resistant strains.     

Clinical applications of composite and realtime megavoltage imaging

The versatility of electronic portal imaging devices (EPIDs) is best demonstrated by their ability to perform novel megavoltage imaging protocols, which are still pertinent to good radiotherapy practice. This paper examines two such techniques: composite and realtime imaging. Our EPID can be programmed to acquire and manipulate images very easily, allowing images from segmented treatment protocols to be mixed and displayed, giving a composite image of the effective treatment result. Its use for verifying the efficacy of spinal shielding using a segmented, offset collimator technique is described. By acquiring images very quickly, realtime imaging sequences can be obtained and used to analyse anatomical movement within a single treatment field. The technique is employed here to investigate movement in radical lung, breast, abdomen, pelvis and thyroid treatments. Our results show that the protocol is vital for treatment sites involving the lungs; changes up to 5 mm have been observed in the maximum lung depth for breast treatments, and displacements up to 16 mm for radical lung treatments. It is also useful in other anatomical sites for ensuring that no movement occurs.     

Clinical applications of neurotransmitter-receptor studies in geriatric neuropharmacology

The use of ligand-binding methods to study neurotransmitter-receptor sites has made its impact on almost all aspects of biological pursuits including research on aging and neurodegenerative diseases. In the past, most of the research in biochemical gerontology has largely centered around changes in various neurotransmitters and enzymatic activities. The molecular basis of aging and neurodegeneration at the level of neurotransmitter-receptor interactions has been highly appreciated in the last two decades as a result of receptor binding studies. It is now possible to obtain information about the regional distribution of neurotransmitter receptors in the brain, the pharmacological and biochemical characteristics of these sites, and the functional interrelationships between different neuronal systems in normal and pathological conditions. The passage of time after maturity is accompanied by measurable physiologic decline in virtually all systems. It is the aim of this work to discuss the practical aspects of neurotransmitter and/or drug (ligand)-receptor binding studies, highlighting some examples of their applications to geriatric neuropharmacology research, with special consideration to learning impairment and memory loss in normal and in pathological aging processes.     

Clinical applications of esophageal manometry and pH monitoring

In summary, GERD patients are usually well managed using a careful medical history, endoscopy, and empirical trials of antireflux medications. Extended esophageal pH monitoring is unnecessary in most patients but can be of considerable value in managing patients with typical or atypical symptoms who are refractory to standard therapy for GERD. Furthermore, the test can be useful in documenting abnormal reflux in an individual without esophagitis being evaluated for antireflux surgery. The test is done with compact, portable data loggers, miniature pH electrodes, and computerized data analysis. The pH electrode should be positioned 5 cm above the manometrically defined upper limit of the LES, and patients should undergo the test on an unrestricted diet. In terms of data analysis, the total percentage time of pH < 4 provides as much information as any other scheme of quantifying esophageal acid exposure, but symptom association is essential when evaluating atypical or sporadic symptoms. Enthusiasm for 24-h pH monitoring must, however, be tempered with an analysis of its proven clinical utility in patient management with its utility rightfully compared with that of an empirical trial of anti-reflux therapy. Ambulatory pH monitoring is probably most useful in examining patients without typical reflux symptoms or patients who have either partially or completely failed a trial of anti-reflux therapy. To date, there have not been any prospective, controlled clinical trials evaluating these uses. Suggested clinical indications for ambulatory pH monitoring are listed in Table 5 (53).     

Clinical applications of pharmacologic therapies for spinal cord injury

We review the evidence supporting the role of glucocorticosteroids, trilazad, and GM1 ganglioside in spinal cord injury and provide our critique of the published studies, along with our recommendations for pharmacologic therapy for this complex and difficult problem.     

Clinical applications of telehealth in mental health care.

This article introduces the concept of telehealth and examines how telehealth expands both provider and patient access to health care. Current clinical applications are presented including equipment, research, and examples of direct clinical care. The article focuses on store-and-forward and video teleconferencing technologies providing information about the equipment and research pertaining to the clinical use of the equipment. The status of behavioral telehealth programs in the United States is reviewed and two case examples are provided. The first example discusses a direct patient care system and the second a remote clinical supervision system. The article concludes with suggestions for determining the value of adding telehealth to existing clinical practices. (PsycINFO Database Record (c) 2010 APA, all rights reserved)