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PubMed2004

Drug immunosuppression therapy for adult heart transplantation. Part 2: clinical applications and results.

This review describes the clinical application of classical immunosuppressive drugs as well as that of more recent drugs. All current immunosuppressive drugs target T-cell activation, and cytokine production and clonal expansion, or both. Immunosuppressive protocols can be broadly divided into induction therapy, maintenance immunosuppression, and treatment of acute rejection episodes.

Acute Disease↗

PubMedDate not supplied

Large animal models of congestive heart failure: a critical step in translating basic observations into clinical applications.

Congestive heart failure (CHF) is a clinical syndrome in which pathophysiologic underpinnings include left ventricular (LV) dysfunction, remodeling, and increased neurohormonal activation. Accordingly, large animal constructs must be developed that mimic this disease process in order to define new pharmacologic and surgical treatment strategies. Multiple large animal species have been used for these purposes. For instance, canine coronary artery microembolization has been used to generate ischemia-induced LV dilation and dysfunction. Sheep have been subjected to total acute coronary artery occlusion to evaluate ischemia-induced mitral valve insufficiency. Rapid ventricular pacing has been used in both dogs and pigs to reproduce the characteristics of dilated cardiomyopathy. Each model is associated with advantages and disadvantages. Therefore findings derived from the study of large animal models of LV failure must be carefully evaluated. With proper interpretation, important insights into the pathogenesis of CHF may be realized. Furthermore, these models may be used in conjunction with imaging modalities such as magnetic resonance imaging, single photon emission computed tomography, and positron emission tomography to elucidate the identification of cellular and extracellular alterations associated with LV failure. Thus large animal models of CHF are critical components in the effort to translate basic observations into beneficial clinical applications.

Animals↗

PubMed1996

New Antifolates: Pharmacology and Clinical Applications.

Many new antifolate compounds with unique clinical properties are currently in clinical development. Some of these agents have been rationally designed to circumvent known mechanisms of resistance to methotrexate, the most useful and extensively studied antifolate in clinical practice. Resistance to methotrexate can result from decreased active transport into cells, decreased polyglutamation resulting in enhanced drug efflux from cells, mutations in dihydrofolate reductase which reduce drug binding affinity, and increased expression of dihydrofolate reductase due to gene amplification or increased translational efficiency. As a consequence, the newer antifolates may differ from methotrexate because of increased lipid solubility, improved cellular uptake or increased ability to undergo polyglutamation. Several of these newer agents also uniquely target specific folate-dependent enzymes such as thymidylate synthase or glycinamide ribonucleotide transformylase. Antifolates currently in clinical development include trimetrexate, edatrexate, piritrexim, ZD1694, lometrexol, AG337, LY231514 and 1843U89. This report summarizes the basic pharmacology and potential clinical applications of these promising new agents.

Journal Article↗

PubMed1990

Clinical application of laser flare-cell meter.

Clinical application of the laser flare-cell meter was described. The instrument was developed for concurrent quantitative determinations of the flare and number of cells in the aqueous humor. Diurnal variations were demonstrated in the aqueous flare, and also an increase in the flare with increasing age. The effects of drugs on aqueous humor dynamics were also studied. Orally administered 500 mg of carbonic anhydrase inhibitor reduced the aqueous humor formation by one-third. Concurrent study with the laser flare-cell meter and slit-lamp microscopy in uveitis cases has revealed that the former instrument is superior to the latter in making a quantitative evaluation of inflammation in the anterior segment of the eye. A follow-up study of postoperative inflammation was performed in patients undergoing extracapsular cataract extraction with posterior chamber intraocular lens implantation. Cases with uneventful postoperative course showed intense flare on the first postoperative day followed by a rapid decrease. Cases with inflammation and fibrin had high aqueous flare which showed an increase even before detection of fibrin in the aqueous by slit-lamp microscopy. Topical 0.5% indomethacin treatment was shown to be effective in suppressing the postoperative increase in aqueous flare but had little effect on cell count. In cases undergoing Argon laser trabeculoplasty, the aqueous flare in the treated eyes was determined to be significantly higher than that in the fellow eyes for four weeks postoperatively (P less than 0.05). The laser flare-cell meter has made it possible to determine the flare and number of cells in the aqueous humor quantitatively. This capability differentiates the instrument from the slit-lamp microscope as well as the instruments previously developed for similar purposes. The laser flare-cell meter is a newly developed useful tool to investigate the pathophysiology of the eye.

Acetazolamide↗

PubMed1993

[Clinical application of the fascia lata flap].

The clinical application of the musculo-cutaneous flap of musculus tensor fascia lata has been limited because it includes muscle and it is very thick. To correct this disadvantage, the ascending branch of the lateral femoral circumflex artery, which is the supplying artery, is dissected up to its entrance into the tensor muscle of the fascia lata, then the upper, middle and lower branches were identified, and the upper and middle branches are ligated, followed by resection of the muscle, resulting in a fascia lata flap supplied by the lower branch only. The flap contains the lateral femoral cutaneous nerve. It is a good flap to repair a defect of skin and to restore sensory function at the same time. It has been used in 15 cases with good effect.

Adolescent↗

PubMed2001

Radiolabeled amino acids: basic aspects and clinical applications in oncology.

As the applications of metabolic imaging are expanding, radiolabeled amino acids may gain increased clinical interest. This review first describes the basic aspects of amino acid metabolism, then continues with basic aspects of radiolabeled amino acids, and finally describes clinical applications, with an emphasis on diagnostic value. A special focus is on (11)C-methionine, (11)C-tyrosine, and (123)I-iodomethyltyrosine, because these have been most used clinically, although their common affinity for the L-transport systems may limit generalization to other classes of amino acids. The theoretic and preclinical background of amino acid imaging is sound and supports clinical applications. The fact that amino acid imaging is less influenced by inflammation may be advantageous in comparison with (18)F-FDG PET imaging, although tumor specificity is not absolute. In brain tumor imaging, the use of radiolabeled amino acids is established, the diagnostic accuracy of amino acid imaging seems adequate, and the diagnostic value seems advantageous. The general feasibility of amino acid imaging in other tumor types has sufficiently been shown, but more research is required in larger patient series and in well-defined clinical settings.

Amino Acids↗

PubMed1994

Embolotherapy: agents, clinical applications, and techniques.

For embolization to be successful, three factors must be addressed: embolic agent selection, clinical application, and technical skill. The major embolic agents used include stainless steel coils, absorbable gelatin pledgets and powder, polyvinyl alcohol foam, ethanol, and glues. Each of these agents acts at different levels in the arterial system; for example, coils are equivalent to surgical ligation and occlude medium to small arteries, whereas liquid agents and the smaller diameter particles occlude at the arteriolar level or the capillary bed. The type of agent selected should also be determined according to clinical application, which includes trauma, tumors, male infertility, impotence, and vascular malformations. It may be better to occlude an artery only temporarily, particularly in trauma patients, and absorbable gelatin material is preferred for this application. Conversely, permanent occlusion of arteries with either ethanol or polyvinyl alcohol foam particles may be necessary in the treatment of tumors. To use embolotherapy effectively, the interventional radiologist must be experienced, familiar with the underlying pathologic processes, and knowledgeable with regard to the role of other specialties in the treatment of the disease process presented.

Adhesives↗

PubMed2005

Clinical applications of DNase I, a genetic marker already used for forensic identification.

This review primarily summarizes the clinical applications of deoxyribonuclease I (DNase I). Human DNase I exhibits polymorphism at both the protein and DNA level, and thus is potentially one of the best biochemical markers for forensic practice. Clinically, DNase I activity in serum can be used as a novel diagnostic marker for the early detection of acute myocardial infarction and transient myocardial ischemia. Furthermore, the DNase I gene is considered to be one of the susceptibility genes for gastric and colorectal carcinoma, and myocardial infarction. Over the last decade since the discovery of the utility of its genetic polymorphism for forensic purposes, research on DNase I has expanded into clinical applications.

Biomarkers↗

PubMed2006

Cell and tissue engineering and clinical applications: an overview.

Most human tissues do not regenerate spontaneously; this is why cell therapies and tissue engineering are promising alternatives. The principle is simple: cells are collected in a patient and introduced in the damaged tissue or in a tridimentional porous support and harvested in a bioreactor in which the physico-chemical and mechanical parameters are controlled. Once the tissues (or the cells) are mature they may be implanted. In parallel, the development of biotherapies with stem cells is a field of research in turmoil given the hopes for clinical applications that it brings up. Embryonic stem cells are potentially more interesting since they are totipotent, but they can only be obtained at the very early stages of the embryo. The potential of adult stem cells is limited but isolating them induces no ethical problem and it has been known for more than 40 years that bone marrow does possess the regenerating functions of blood cells. Finally, the properties of foetal stem cells (blood cells from the umbilical cord) are forerunners of the haematopoietic system but the ability of these cells to participate to the formation of other tissues is more problematic. Another field for therapeutic research is that of dendritic cells, antigen presenting cells. Their efficiency in cell therapy relies on the initiation of specific immune responses. They represent a promising tool in the development of a protective immune response against antigens which the host is usually unable to generate an efficient response (melanomas, breast against cancer, prostate cancer, ..). Finally, gene therapy, has been nourishing high hopes but few clinical applications can be envisaged in the short term, although potential applications are multiple (haemophilia, myopathies, ..). A large number of clinical areas stand as candidates for clinical applications: leukaemia and cancers, cardiac insufficiency and vascular diseases, cartilage and bone repair, ligaments and tendons, liver diseases, ophthalmology, diabetes, neurological diseases (Parkinson, Huntington disease, ..), .. Various aspects of this new regenerative therapeutic medicine are developed in this work.

Animals↗

PubMed2003

Clinical applications of strain rate imaging.

Myocardial strain (epsilon) is a dimensionless index of change in myocardial length in response to an applied force. epsilon Rate (SR) is the rate of change of length and is usually obtained as the time derivative of the epsilon signal. In echocardiography, SR is calculated as the difference between 2 velocities normalized to the distance between the 2 velocities. SR imaging (SRI) has a theoretic advantage over Doppler tissue imaging in that SRI is relatively immune to cardiac translational motion and tethering. Therefore, SRI may be superior to Doppler tissue imaging in quantitative assessment of regional myocardial function and may find clinical application in the interrogation of coronary artery disease. The high frame rates of SRI have also renewed interest in timings of global and regional mechanical events, and their potential clinical applications. The high temporal resolution allows SRI to depict regional systolic and diastolic asynchrony. Ongoing clinical trials will determine the sensitivity, specificity, and accuracy of SRI parameters for a variety of clinical conditions. Potential clinical applications include investigation of ischemia (at rest and with stress), myocardial viability, and altered global and regional systolic and diastolic function in cardiomyopathies. Suboptimal signal quality remains a major limitation of strain imaging, and advances in data acquisition and postprocessing capabilities will help determine its future incorporation into standard regional myocardial assessment.

Blood Flow Velocity↗

PubMed2001

Fetal DNA in maternal plasma: emerging clinical applications.

OBJECTIVE: To review the potential clinical diagnostic applications of fetal DNA analysis in maternal plasma or serum for noninvasive prenatal diagnosis and screening. DATA SOURCES: We conducted a MEDLINE search of articles published between January 1970 and March 2000 using the key terms "fetal DNA," "plasma," and "serum." METHODS OF STUDY SELECTION: All 369 articles describing the detection of fetal DNA in maternal plasma were reviewed. RESULTS: The diagnostic use of circulating fetal DNA in maternal plasma is currently limited to genes that are present in the fetus but not in the mother. From a clinical perspective, the most advanced application is for noninvasive detection of fetal rhesus D (Rh[D]) genotype. The results of studies performed by four different groups showed that prenatal diagnosis of fetal Rh(D) status by molecular analysis of maternal plasma or serum is routinely possible beginning in the second trimester. Noninvasive fetal genotyping should be useful for the treatment of sensitized Rh(D)-negative women whose partners are heterozygous for the Rh(D) gene because no further diagnostic or therapeutic procedures are necessary if the fetus is Rh(D) negative. Future clinical applications of fetal DNA may be in its use as a screening test for Down syndrome, preeclampsia, or preterm labor. However, these applications currently rely on the detection of Y chromosomal sequences and consequently are limited presently to male fetuses. CONCLUSION: The recent discovery of high concentrations of fetal DNA in maternal plasma represents a promising noninvasive approach to prenatal diagnosis. Compared with the analysis of the cellular fraction of maternal blood, the analysis of fetal DNA extracted from maternal plasma has the advantage of being rapid, robust, and easy to perform. The fetal DNA detected is limited to the current pregnancy. However, universal fetal gene sequences must be identified that allow analysis of genetic material from both male and female fetuses. Study of fetal DNA in maternal plasma can improve our understanding of fetomaternal biology and physiology. The long-term effects of maternal exposure to relatively high amounts of foreign DNA are unknown but represent an exciting area for future inquiry.

DNA↗

PubMed1982

Clinical applications of perceived exertion.

The purpose of this paper is to review those studies related to the clinical applications of perceived exertion. The Borg Scale has been used most widely to evaluate the subjective response of patients during graded exercise tests. More recently, ratings of perceived exertion (RPE) have been shown to be an accurate predictor of aerobic capacity. Appraisal of angina pectoris during exercise is discussed relative to its interaction with effort perceptions. Two groups of investigators have recently studied the validity of using stress-test perceptions to control exercise intensity during training. Caution is suggested when perceptual prescriptions are based upon estimation techniques in exercise tests but require production techniques by patients in exercise programs. One investigation was reviewed to illustrate the use of perceptual information in solving occupational problems: three lifting techniques were compared relative to perceptual acceptability, the recommended squat technique being the least acceptable. A variety of sport applications were discussed: perception of pace, sex differences in perception of effort, perceptual recovery from exercise, and the new Borg Category-Ratio Scale in the measurement of anaerobic stress and several recommendations were made for future study of clinical applications of perceived exertion.

Exercise Test↗

PubMed1997

[Recent clinical applications of MR medicine as functional medical imaging in the brain and heart].

This paper reviewed recent clinical applications of MR medicine as functional imaging in the brain and heart. Functional and metabolic imaging of brain and heart can be evaluated by the development of fast MR technique (fast SE, echo planar imaging, etc) and chemical shift imaging. The clinical applications of MR medicine to the brain are follows. 1. higher nerve activity assessment using functional MRI, 2. brain perfusion imaging by dynamic contrast MRI, 3. brain diffusion imaging and 4. brain metabolic function by 1H and 31P-MRS. Those of MR medicine to the heart are as follows. 1. left ventricular function assessment by snapshot and/or echo planar imaging. 2. regional wall motion assessment by magnetic tagging, 3. myocardial perfusion imaging by dynamic contrast MRI, 4. coronary flow reserve assessment and 5. cardiac metabolic function by 31P and 1H MRS. Most of these data are thought to be compatible with nuclear medicine technique such as PET and SPECT. In the future, MR medicine may be used as the tool of functional and metabolic diagnosis in addition to anatomical diagnosis in the field of cerebral and cardiac disorders.

Brain↗

PubMed1997

Anthropomorphic breast measurement: protocol and results in 50 women with aesthetically perfect breasts and clinical application.

This paper presents a simple protocol for the measurement and evaluation of the difficult physiognomy of the female breast and the application of the protocol in clinical practice. The protocol includes measurement of the breast and its landmarks and their relevant position from fixed skeletal points. Volume was measured with the Grossman-Roudner device. The protocol provides a useful tool in the accurate evaluation of patients preoperatively and in the assessment of surgical results. The protocol is compared with the two previously reported protocols. The paper presents the anthropomorphic measurements of 50 women with aesthetically perfect breasts utilizing this protocol. Aesthetically perfect was defined as a nonptotic breast in which no common aesthetic procedure would be considered appropriate (excluding augmentation) to enhance the breast's form. Results were compared with those reported in the two previous studies. The paper presents the clinical correlation obtained by statistical analysis of the results of the measurements of the 50 women. Although the results of the measurements indicate the range and variance in the aesthetically perfect breast, there still was a statistically significant correlation of some of the parameters of the breast and torso shape to breast volume. This correlation can be used preoperatively to predict desired breast shape and volume in breast augmentation, reduction, and reconstruction. Clinical application of the concepts proposed will lead to better surgical goal orientation and improve evaluation of surgical results. A formula for calculating appropriate breast size based on torso parameters is presented.

Adolescent↗

PubMed2001

[Clinical application of gated SPECT imaging to regional function assessment: current status and limitations].

It is likely that clinical applications of ECG-gated single-photon emission computed tomography (SPECT) are established in nuclear cardiology practice because of the improved diagnostic accuracy of gated SPECT imaging for the detection of coronary artery disease and because this technique enables not only simultaneous assessment of myocardial perfusion and function but also improvement of risk stratification of coronary patients. Although a gated approach with SPECT imaging has been demonstrated to have high reproducibility and reliability for quantifying global function, there are several limitations in appropriate processing of 4-dimensional data for quantitative assessment of regional function. Even if limited spatial and temporal resolutions and a lack of attenuation and scatter corrections are disregarded, sufficient data collection, image-quality control, and precise application of algorithms to gated SPECT data are prerequisite. The results of several kinds of quantitative analysis of regional cardiac function, such as regional wall motion (distance deviation of the inner myocardial border), regional ejection fraction, percent wall thickening, and percent count increase with or without self-normalization have been reported. Further clinical application of quantitative regional function assessment by a gated SPECT technique, however, requires standardization of data acquisition, data analysis, and data presentation with appropriate quantitative parameters; production of a standard map using quantitative values; and validation study by comparison with results of visual analysis and other modalities in a large-scale patient population.

Algorithms↗

PubMed1989

[The clinical application and the problems in future for the ventricular assist device].

In an attempt to save patients with severe cardiac pump failure to which no emergency methods of treatment show effect even with various medications or machinery assisted circulation, the ventricular assisted device (VAD) has come more and more in need today as it provides patients with a temporary cardiac function and serves as a life-prolongation means, eventually aiming at patients' return to normal daily life. In Japan, basic researches for development of VAD have been proceeding since 1960. We have been pursuing researches in the related scientific field since 1980 with the theme of clinical application of VAD and have completed the total system of VAD in August, 1982. In October 1982, we succeeded for the first time in Japan in weaning a patient from the VAD. Until April, 1988 we had managed clinical applications of VAD in 121 cases. Based on this experience, I have presented here a result of our clinical analysis of these cases and have come up with the problems surrounding the clinical application of VAD.

Adolescent↗

PubMed1992

Clinical applications of cytometry: 6th annual meeting.

The Sixth Annual Clinical Applications of Cytometry Meeting was held September 11-14, 1991, in Charleston, SC. Attendance reached a record 470. The meeting provides a forum for interactions among investigators who utilize cytometry as a tool in their clinical immunology, cell biology, hematology, and cancer investigations. Clinical laboratory directors and their technical staff find the meeting of practical value because of the presentation of new applications that they can take home to their own laboratories. The emphasis of the meeting is on advances in the application of cytometry to clinical problems. Often, advances result from new dyes or reagents or improved instrumentation. Sometimes they result from advances in biology that make the studies possible. Occasionally a new way of looking at the same data provides a useful answer. In every case, the effort is to provide a reliable, straightforward way to quantitate biologic information in order to provide improved diagnosis or treatment of human disease.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Intravascular stents. Status of development and clinical application.

A variety of intravascular stents are currently under investigation and in various stages of achieving governmental approval for clinical application. The Palmaz balloon-expandable stent has recently been approved for use in the iliac arteries based on specific indications for application. Stents are generally described according to their method of deployment and are either balloon-expandable or self-expanding. Clinical application has been proved in the iliac arteries, where the use of stents has greatly enhanced the treatment of patients with total occlusions, complex dissections, and restenoses. Additionally, there is promise that stents will enhance the percutaneous treatment of renal artery ostial lesions, infrainguinal arterial lesions, and strictures in large veins. Clearly, the increasing application of intravascular stents has ushered in a new era of percutaneous intervention.

Arterial Occlusive Diseases↗