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Corticosteroid pharmacokinetics in the inner ear fluids: an animal study followed by clinical application.

OBJECTIVE: Autoimmune disease (e.g., Cogan syndrome) and other inflammatory inner ear diseases may ravage the labyrinth if not treated aggressively with antiinflammatory medication. Corticosteroids are the mainstay of treatment, yet, partly because of the existence of the blood-labyrinthine barrier, the ideal drug, dose, and route of administration are currently unknown. STUDY DESIGN: In the present study, we established cochlear fluid pharmacokinetic profiles of hydrocortisone, methylprednisolone, and dexamethasone in the guinea pig following oral, intravenous, and topical (intratympanic) administration. High-performance liquid chromatography was used to determine the drug concentrations, and comparisons were made with simultaneous pharmacokinetic profiles from blood and cerebrospinal fluid. RESULTS: Our findings demonstrated a much higher penetration of all three drugs into the cochlear fluids following topical application as compared with systemic administration, with methylprednisolone showing the best profile. DISCUSSION: The results suggested that intratympanic administration of corticosteroids might be more efficacious while avoiding high blood levels and therefore the deleterious side effects of systemic use. CLINICAL APPLICATION: Thirty-seven patients with various inner ear disorders causing sensorineural hearing loss were subsequently treated using intratympanic corticosteroids, 20 with dexamethasone, and 17 with methlyprednisolone. Patients with immune-mediated hearing losses showed the best results, with notable improvement also seen in several cases of a "sudden deafness." No benefit was seen in patients with cochlear hydrops or those with sudden deterioration of a preexisting hearing loss. Three patients developed a transient otitis media related to the treatments, easily controlled with antibiotics. There were no cases of treatment-induced hearing loss and no permanent tympanic membrane perforations. CONCLUSIONS: Overall injection of intratympanic corticosteroids for the treatment of hearing loss in inner ear disorders appears to be both safe and highly effective for certain disorders. The concept of this technique is supported by animal experimental data. The findings from the present study warrant further clinical application and experimental investigation.

Administration, Oral↗

Clinical applications of the Process Model of Family Functioning.

This paper discusses clinical applications of the Process Model of Family Functioning. It provides a framework for conducting and systematically recording a family assessment, and can help clinicians achieve and use improved control of clinical sessions to increase their diagnostic and therapeutic effectiveness. Ways of using FAM-III, a self-report test derived from the model, to confirm or amplify a clinical assessment and to assist or monitor therapeutic interventions are discussed. Viewing psychological and family systems theories as complementary, the model provides a rationale for integrating both sets of theories to achieve a more pluralistic view of pathogenesis and a more selective choice of therapies. An extended example illustrates the concurrent use of individual and family therapies. Other topics discussed include the role of family strengths, the derivation of therapeutic goals, moving from content to perceive underlying structure and process, making the conceptual shift from group-of-two to conceptualizing the family as a group (system) in equilibrium.

Adolescent↗

Clinical application of controlled stress to the healing extensor tendon: a review of 112 cases.

The purposes of this article are to describe an early passive motion program for the healing extensor tendon and to report the results and trends noted in a review of 112 complex extensor tendon injuries treated with this therapeutic technique. The rationale for this technique is based on a review of the physiologic response of healing tendon to controlled stress. Clinical application is dependent on a biomechanical study of extensor tendon excursion, which allows the therapist to apply controlled stress to the healing tendon with precision. The early passive motion technique is considered in terms of physiology, biomechanics, clinical application, and results. The author concludes that early controlled passive motion for the complex extensor tendon injury in zones V, VI, VII, T IV, and TV is a safe and effective rehabilitation technique that reduces complications associated with extensor tendon injury and repair.

Biomechanical Phenomena↗

Paraspinal muscle EMG fatigue testing with two methods in healthy volunteers. Reliability in the context of clinical applications.

OBJECTIVE: Comparison of the accuracy of surface electromyogram for back muscle endurance assessment with two different tests. DESIGN: Test-retest measurements in 16 healthy volunteers on two separate occasions for each test under controlled conditions. BACKGROUND: Back muscle endurance is considered important in low back pain rehabilitation. Reliability of paraspinal muscle endurance assessment is a pre-requisite for accurate and meaningful clinical applications of the technique. METHODS: All participants performed each test twice. A direct comparison was made between two popular fatigue testing methods, the modified Biering-Sørensen and a 60% maximum voluntary isometric contraction in the upright position during which time fatigue was assessed from the electromyogram spectral and amplitude analysis. RESULTS: Reproducibility of initial median frequency was excellent for both tests. Normalised median frequency slope values were more reliable with the 60% maximum voluntary contraction upright test. The clinical applicability of these measures in detecting significant differences after patient rehabilitation is recommended. Root mean square had very large between-day error for both tests.

Adult↗

Potential clinical applications of rhGM-CSF in acute myeloid leukemia based on its biologic activity and receptor interaction.

BACKGROUND AND OBJECTIVE: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multilineage hemopoietic growth factor that stimulates proliferation, differentiation, and survival of progenitor cells, enhances the functional activities of mature myeloid effector cells, and plays a key role in host defense and the inflammatory process. Although the clinical use of rhGM-CSF in patients affected by lymphoid malignancies is widely accepted, its utility and safety in the management of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is still controversial. The three main schedules adopted for clinical application of GM-CSF in AML are as follows: A) post-chemotherapy, in order to shorten the duration of neutropenia and/or monocytopenia; B) prechemotherapy to recruit blast cells into active cell cycle phases, and to increase their sensitivity to cell cycle-dependent cytotoxic drugs; C) as a mobilizing agent to induce the release of progenitor cells from bone marrow into circulation (peripheral blood progenitor cell transplantation-PBPC). The objective of this paper is to analyze the potential clinical applications of rhGM-CSF in AML. EVIDENCE AND INFORMATION SOURCES: The material examined in the present review includes several personal papers in this field and articles and abstracts published in journals covered by the Science Citation Index. STATE OF THE ART: Based on current knowledge, it may be argued that rhGM-CSF should be used only in a subset of AML patients at high risk of infection mortality, including elderly subjects, and/or in those AML patients who relapse or are resistant to induction treatment. However, the risk of stimulating the leukemic clone following GM-CSF therapy should be kept in mind when using this growth factor in the clinical setting, even though the great majority of the reported papers on this subject have shown that GM-CSF therapy does not affect relapse rates, frequency of remissions or patient life expectancy. PERSPECTIVES: It is likely that new data from controlled clinical trials will clarify the therapeutic role of GM-CSF in myeloid-derived malignancies, allowing the establishment of consensus guidelines for its use.

Acute Disease↗

Umbilical cord blood as a source of hematopoietic stem cells: from research to clinical application.

The clonogenic capacity of human umbilical cord blood (UCB) has been evaluated in several studies which found high numbers of primitive hematopoietic progenitor cells. Recently, UCB progenitor cells were shown to possess significant advantages over bone marrow (BM) in terms of proliferative capacity and immunologic reactivity. Therefore UCB has come to be considered an attractive source of hematopoietic stem cells for both research and clinical applications. UCB has been used in the treatment of diseases potentially curable by bone marrow transplantation (BMT). Seventy-one transplants have been performed world-wide using UCB cells, and the results have been reported to the International Cord Blood Transplant Registry (ICBTR). Since UCB cells appear to be less alloreactive than BM cells, studies have been carried out to determine the most successful procedures for collection and fractionation of UCB and to quantify precisely the progenitor/stem cell content. The different techniques for quantifying progenitor/stem cells as well as the results of related and unrelated UCB treatments will be reviewed. Further clinical applications of UCB involving gene therapy and stem cell expansion will be discussed.

Blood Banks↗

Knowledge retention and clinical application after continuing education.

The authors investigate the knowledge retention and clinical application of physical assessment skills by nurses who participated in a required continuing education workshop. Tools were developed to measure the specific application of workshop concepts. Results support the underlying objectives of nursing staff development, which are to increase knowledge and improve skills.

Adult↗

Inhaled nitric oxide: clinical applications, indications, and toxicology.

PURPOSE: Although the analogy of nitric oxide (NO) to Endothelium-derived Relaxing Factor remains controversial, medical use of exogenous NO gas by inhalation has grown exponentially. This review presents the mechanisms of action of inhaled NO in pulmonary hypertension, hypoxaemia, inflammation and oedema, as well as its therapeutic and diagnostic indications with emphasis on acute respiratory distress syndrome (ARDS) and toxicology. SOURCE: Two medical databases (Current Contents, Medline) were searched for citations containing the above-mentioned key words to December 1996. Moreover, many presentations in congresses such as 4th International Meeting of Biology of Nitric Oxide, 52nd and 53rd Annual Meeting of Canadian Anaesthetists' Society or 10th Annual Meeting of European Association of Cardiothoracic Anaesthesiologists were used. PRINCIPAL FINDINGS: Inhaled NO is now recognized as an invaluable tool in neonatal and paediatric critical care, and for heart/lung surgery. Other clinical applications in adults, such as chronic obstructive pulmonary disease and ARDS, require a cautious approach. The inhaled NO therapy is fairly inexpensive, but it would seem that it is not indicated for everybody with regards to the paradigm of its efficiency and potential toxicity. The recent discovery of its anti-inflammatory and extrapulmonary effects open new horizons for future applications. CONCLUSION: Clinical use of inhaled NO was mostly reported in case series, properly designed clinical trials must now be performed to establish its real therapeutic role. These trials would permit adequate selection of the cardiopulmonary disorders, and subsequently the patients that would maximally benefit from inhaled NO therapy.

Administration, Inhalation↗

[Digital dental radiographic technique and its clinical application].

OBJECTIVE: To investigate the digital dental radiographic technique and its clinical application. METHODS: One hundred and five dental films were taken in 88 cases with the digora digital radiographic system and studied. RESULTS: The digora system has more advantages than the conventional dental radiographic technique. The image plate was used instead of the films and shorten exposure time. It had high exposure tolerances and image processing functions. CONCLUSIONS: This new imaging system applied in the clinics and research work can play an important role in improving the diagnostics.

Humans↗

A physiologic model of the dehydroepiandrosterone to estrogen conversion system in the fetoplacental unit. II. Preliminary clinical application--the dehydroepiandrosterone loading test.

A dehydroepiandrosterone (DHEA) loading test (DLT) is described. The results of 19 DHEA loading tests in as many third-trimester obstetric patients are presented. Analysis involves inspection of the raw data and the application of the physiologic model of the DHEA to estrogen conversion system described in the preceding paper (Part I). The DLT results show that within the population studied, the conversion rate of DHEA to estrogens is lower in patients with placental insufficiency than in normal patients (N = 5, p = 0.002) or in patients with various complications of pregnancy who deliver normally grown, undistressed infants (N = 6, p = 0.001). Routine clinical application must await more extensive evaluation to preclude the existence of forms of placental insufficiency not detected by this means, or normal states resulting in "false-positive" tests. These initial clinical results are intended primarily to demonstrate the potential clinical applicability of the physiologic model described in Part I.

Dehydroepiandrosterone↗

[Study of sensory memory reflected by mismatch negativity and its clinical application].

The event-related brain potential called Mismatch negativity (MMN) reflects the auditory detection system which automatically detects subtle change in the surrounding acoustic environment. This system is based on the pre-attentive mechanism of comparison mechanism between the neural trace of background sounds stored in sensory memory and incoming sound change. This "memory trace theory" has raised the importance of MMN. The features of sound information are extracted from the incoming sound in sensory memory, and is integrated into an auditory unit within the temporal window of 160-170 ms. Since the MMN itself is basically free from the influence of attention and requires no task for measurement, MMN can be applied to various clinical studies. There are two generators, the temporal MMN reflecting the change detection in sensory memory and the frontal MMN reflecting the attentional switch. Therefore, MMN has various clinical applications including memory disturbance and attention disorder. For example, reduced amplitude of MMN is a robust finding in schizophrenia. Some basic MMN studies and their promising clinical applications are described here.

Acoustic Stimulation↗

[Clinical application of gene technology for diagnosis and treatment of leukemia].

Recently, clinical application of gene technology in oncology and hematology has been markedly advanced. Pathogenesis of leukemic transformation has been thought that it was resulted from cumulation of activation or mutation in oncogenes or onco-suppressor genes. As a matter of fact, many specific chromosomal abnormalities in leukemias have been thought to be due to production of chimeric fusion gene by translocation and activation in some kinds of oncogenes under specific regulatory genes after translocation. In addition to those, inactivation of onco-suppressor genes, such as RB gene or p53 gene, may be also related to leukemogenesis in some leukemias. Laboratory examinations using molecular technology are being necessary for clinical diagnosis and treatment in many hematological disorders. The examinations detecting rearrangement of major BCR or minor BCR in Ph1 positive leukemias, TCR in T cell malignancy, immunoglobulin in B cell malignancy, PML-RAR alpha fusion gene in APL have become routine for diagnosis of some leukemias. Moreover, these examinations are useful for judgement of treatment effects and evaluation of minimal residual diseases. In this paper, we also discuss the usefulness and importance of these technology especially in stem cell transplantation and cytokine therapy, and the future possibility in this technology for gene therapy.

Cytokines↗

[Quantitation of telomerase activity using the polymerase chain reaction-based enzyme immunoassay and its clinical application].

OBJECTIVE: To investigate detective methodology of telomerase activity and its clinical application. METHODS: The telomerase activity was quantitated by polymerase chain reaction-base enzyme immunoassay (PCR-EIA). The TS primer was biotinylated (TS-B), and CX primer was digoxigeninated (CX-D). The amplicons containing TS-B were combined with microtiter plate coated streptavidin, then combined with anti-digoxigenin antibody labeled with POD and finally reacted to tetramethylbenzidine substrate solution. RESULTS: Telomerase activity measured by the PCR-EIA method was comparable to that obtained from TRAP-silver stain protocol. The CV of the PCR-EIA method was 4.138%. Telomerase activity was detected in 90% of various tumer tissues. In control tissues, telomerase activity was detected only in 7.1%. CONCLUSION: The PCR-EIA method offers a rapid, quantitative, and nonisotopic assay for the determination of telomerase activity. It is simpler than silver stain protocol. The detection of telomerase activity may play a significant role in the diagnosis of clinical tumors.

Colorectal Neoplasms↗

Analysis of surface electrocardiograms in atrial fibrillation: techniques, research, and clinical applications.

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Neither the natural history of AF nor its response to therapy is sufficiently predictable by clinical and echocardiographic parameters. The purpose of this article is to describe technical aspects of novel electrocardiogram (ECG) analysis techniques and to present research and clinical applications of these methods for characterization of both the fibrillatory process and the ventricular response during AF. Atrial fibrillatory frequency (or rate) can reliably be assessed from the surface ECG using digital signal processing (extraction of atrial signals and spectral analysis). This measurement shows large inter-individual variability and correlates well with intra-atrial cycle length, a parameter which appears to have primary importance in AF maintenance and response to therapy. AF with a low fibrillatory rate is more likely to terminate spontaneously and responds better to antiarrhythmic drugs or cardioversion, whereas high-rate AF is more often persistent and refractory to therapy. Ventricular responses during AF can be characterized by a variety of methods, which include analysis of heart rate variability, RR-interval histograms, Lorenz plots, and non-linear dynamics. These methods have all shown a certain degree of usefulness, either in scientific explorations of atrioventricular (AV) nodal function or in selected clinical questions such as predicting response to drugs, cardioversion, or AV nodal modification. The role of the autonomic nervous system for AF sustenance and termination, as well as for ventricular rate responses, can be explored by different ECG analysis methods. In conclusion, non-invasive characterization of atrial fibrillatory activity and ventricular response can be performed from the surface ECG in AF patients. Different signal processing techniques have been suggested for identification of underlying AF pathomechanisms and prediction of therapy efficacy.

Atrial Fibrillation↗

Experiments re: clinical application of reflex modulation audiometry.

Two experiments were conducted on normal hearing adults to assess the audiometric test potential of reflex modulation (RM) when administered according to the descending method of limits. RM describes the inhibitory effect of a tone upon a subsequently occurring eyeblink reflex. Although RM conducted according to the method of constant stimuli has already been shown to produce RM results which agree well with voluntary audiometry in normal and hearing-impaired adults and children, the present concern is with the potential clinical application of RM, and in this regard the descending method may offer certain distinct advantages. In study one, a 2-kHz tone was presented at several descending intensities, whereas in study two, four different frequencies (0.5, 1.2, and 4 kHz) were presented in concurrent fashion, but again, the intensity of the complete set was decreased in successive steps. Sensitivity in both cases was 10 to 15 dB SL. Implications for the clinical application of RM audiometry are discussed.

Adult↗

[Clinical application of improved percutaneous tracheostomy with dilatational technique].

OBJECTIVE: To evaluate clinical application of improved percutaneous tracheostomy with dilatational technique. METHODS: In 55 patients an improved percutaneous tracheostomy was used, and in another 52 patients an old technique of percutaneous tracheostomy was used. RESULTS: The cost of the improved percutaneous tracheostomy was only (216.0+/-4.4) yuan, operation time was (5.0+/-3.5) minutes, while the cost of the old method was (3 011.0+/-5.3) yuan, and operation time was (10.0+/-6.9) minutes. The difference between them was significant (t=23.60, 4.76, both P<0.001), but there were no differences in the time of bleeding and healing (both P>0.05). CONCLUSION: The improved percutaneous tracheostomy was more expeditious, costless, better healing, scar smaller. Therefore, it is useful in emergency care, and it can take the place of classical tracheostomy.

Adult↗

Non-interventional cardiac diagnostics: computed tomography, magnetic resonance and real-time three-dimensional echocardiography. Techniques and clinical applications.

New cardiovascular imaging modalities, including computed tomography (CT), magnetic resonance (MR) imaging and real-time three-dimensional echocardiography, have great potential for providing important and additional information concerning cardiac function and pathology. With significant and extremely fast technical improvements, non-invasive cardiac imaging has become a focal point in the diagnosis of cardiac disease. Thereby CT has been shown to allow the visualization of coronary arteries concerning calcifications, significant stenoses and coronary plaques, whereas MR imaging demonstrated its ability to evaluate cardiac morphology and function as well as perfusion imaging and viability assessment. As CT and MR, real-time three-dimensional echocardiography has increasingly progressed in the last years offering the potential for routine clinical application, e.g. in the evaluation of valve disease, the assessment of left ventricular thrombi or the guidance of intracardiac catheter placement. This article will provide a brief overview of each technique, possible clinical applications and their perspectives. Because both, CT and MR, have been successfully applied to visualize the coronary arteries, this article focuses on the abilities and limitations of CT and MR coronary artery imaging.

Coronary Disease↗

Cut-off values of blessed dementia rating scale and its clinical application in elderly Taiwanese.

Although the Blessed Dementia Rating Scale (BDRS), a clinical screening instrument, has been applied extensively, no suitable cut-off values and clinical application have been proposed, particularly in mild cognitive impairment (MCI), the precursor of dementia. The BDRS, Mini Mental State Examination (MMSE), and Clinical Dementia Rating Scale (CDR) were administrated in people aged 65 years and above, who were enrolled from southern Taiwan with multistep stratified random sampling and followed-up for 2 years. All subjects (total number = 3,027), with new onset of MCI (defined as CDR = 0.5) in the first year and dementia (defined as CDR > or = 1) in the second and third years were subjected to statistical analysis. In distinguishing normal from MCI, except in the literate group aged 65-74 years, MMSE was superior to BDRS, with cut-off values of 1 in both literate groups aged 65-74 years and > or = 75 years, and 1.5 and 2 in less educated groups aged 65-74 and > or = 75 years, respectively. In distinguishing MCI from dementia, BDRS had cut-off values of 2.5 in both literate groups aged 65-74 and > or = 75 years, and 2.5 and 3 in less educated groups aged 65-74 and > or = 75 years, respectively. These values were better than those for MMSE in all groups. BDRS might be considered as a better tool than MMSE to screen for MCI and dementia in the increasing proportion of literate elderly aged 65-74 years in the aging population.

Aged↗