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At least 55 records · Page 3Linked to original sources

Clinical application of drug pump for spasticity, pain, and restorative neurosurgery: other clinical applications of intrathecal baclofen.

Intrathecal baclofen has been successfully used for control of severe spasticity. Baclofen, an agonist of GABA-B receptor, has other potential effects on pain and recovery from coma. Sporadic episodes of dramatic recovery from persistent vegetative state are reported after intrathecal administration of baclofen. There are also reports on the use of baclofen for neuropathic pain including post-stroke central pain syndrome. Baclofen is also used for control of dystonia due to cerebral palsy or reflex sympathetic dystrophy. On the other hand, epidural spinal cord stimulation has been used for pain, spasticity, dystonia, or attempt to improve deteriorated consciousness, though the effects seem variable and modest. Similarity between baclofen and spinal cord stimulation is interesting in that both involves in spinal GABAergic system. The GABAergic system in the spinal cord plays a pivotal role in various clinical effects of these procedures.

Baclofen↗

Platelet function after total artificial heart replacement: clinical application and experiment.

Clinical application of artificial blood pumps for mechanical circulatory support has been hampered by thromboembolic events. The underlying mechanisms are complicated and may differ from patient to patient. Because the calf is commonly used for artificial heart studies, the object was to determine the value of data gained in an animal model. To this end, the average of 10 calf experiments was compared with three clinical applications of an orthotopically implanted total artificial heart in patients with terminal heart failure. Platelet reactivity was investigated in vitro by collagen-induced whole blood aggregometry, radioimmunoassay methods, and scanning electron microscopy over a 10-day period. An analogous periodicity of platelet function was found in human and animal recipients. Improvement of platelet function preceded that of platelet counts in the early postoperative phase. Exaggerated responses to aggregative agents were observed at days 3 and 7. On the basis of our data, we believe that we can comment about the prospective course of the function and number of human platelets, which may contribute to the identification of critical phases of such treatment, during total artificial heart replacement.

Adult↗

Retroviral gene transfer to primitive normal and leukemic hematopoietic cells using clinically applicable procedures.

Clinical uses of gene transfer to bone marrow transplants require the establishment of a reproducible method for infecting large numbers of very primitive hematopoietic cells at high efficiency using cell-free retrovirus-containing media. In this study we report the results of experiments with preparations of a high-titer (2-5 x 10(7)/ml) helper-free recombinant neo(r) retrovirus that indicate this goal can now be achieved based on measurements of gene transfer efficiencies to cells referred to as long-term culture initiating cells (LTC-IC) because they give rise to clonogenic cells after greater than or equal to 5 wk in long-term culture (LTC). Intermittent, repeated exposure of normal human marrow mononuclear cells to virus-containing supernatant over a 3-d period of cell maintenance on an IL-3/granulocyte colony-stimulating factor (G-CSF) producing stromal layer resulted in gene transfer efficiencies to LTC-IC of 41%; a level previously obtainable only using co-cultivation infection techniques. Marrow cells enriched greater than or equal to 500-fold for LTC-IC (1-2% pure) by flow cytometry showed gene transfer efficiencies of 27% when infected in a similar fashion over a shorter period (24 h), but in the presence of added soluble IL-3 and G-CSF without stromal feeders, and this increased to 61% when Steel factor was also present during the infection period. By using a less highly enriched population of LTC-IC obtained by a bulk immunoselection technique applicable to large-scale clinical marrow harvests, gene transfer efficiencies to LTC-IC of 40% were achieved and this was increased to 60% by short-term preselection in G418. Southern analysis of DNA from the nonadherent cells produced by these LTC over a 6-wk period provided evidence of clonal evolution of LTC-IC in vitro. Leukemic chronic myelogenous leukemia LTC-IC were also infected at high efficiency using the same supernatant infection strategy with growth factor supplementation. These data demonstrate the feasibility of using cell-free virus preparations for infecting clinical marrow samples suitable for transplantation, as well as for further analysis of human marrow stem cell dynamics in vitro.

Base Sequence↗

Interferons: mechanisms of action and clinical applications.

PURPOSE OF REVIEW: Interferons are pleiotropic cytokines that exhibit important biologic activities, including antiviral, antitumor, and immunomodulatory effects. These cytokines have found important applications in clinical medicine, including the treatment of certain malignancies. The purpose of this review is to provide an update on basic and clinical research in the interferon field. RECENT FINDINGS: Significant advances have recently occurred in the field of type I interferon signal transduction. It is well known that the interferons transduce signals via activation of multiple signaling cascades, involving Jak kinases, signal transducer and activator of transcription proteins, Map kinases, and IRS and Crk proteins. Recent evidence indicates that the p38 Map kinase pathway plays an important role in type I interferon signaling in malignant cells and that its function is required for type I interferon-dependent gene transcription and generation of the antiproliferative of type I interferons. In clinical oncology, interferon-alpha remains an active and useful agent in the treatment of several malignant disorders, and efforts are underway to improve its efficacy by using different schedules and combinations with other agents. SUMMARY: This review summarizes the mechanisms of signal transduction of interferons and the emerging new concepts in this area. An update on the clinical applications of interferons in oncology is also provided, and potential translational applications, reflecting recent advances in the field, are discussed.

Adaptor Proteins, Signal Transducing↗

[Pharmacokinetics of anti-arrhythmics. 2. Clinical applications].

The clinical usage of antiarrhythmic drugs may pose problems which could be solved by the direct application of the basic principles of pharmacokinetics. These problems involve the calculation of intravenous infusion rates and or oral dosages. Examples are provided by the rate of initial infusion of lignocaine in order to obtain a concentration within the therapeutic range, the eventual adjustment of this rate of infusion and the calculation of a loading dose. As regards the oral route, the calculation of the doses of procainamide is taken as an example. The estimation of the serum procainamide is a method for determining whether the dose should be increased or whether the drug is ineffective when no clinical result is observed. The pharmacokinetics of the main antiarrhythmic drugs are reviewed; procainamide, quinidine, propanolol, phenytoin, disopyramide. The therapeutic dose, clearance, extraction coefficient, bioavailability and half-life are the object of particular study. The fractioning of the dose and the total dose in a 24 hour period depend on these factors. The effects of cardiac, renal and hepatic failure on the clearance of each drug are recalled. These pharmacokinetic principles help the clinician not only in the prescription of an antiarrhythmic drug but also in deciding on the indications for drug serum concentration, estimations which are particularly useful in some difficult clinical situations, and in interpreting the results.

Administration, Oral↗

[Evaluation on ISGP classification of endometrial hyperplasia in clinical application].

To evaluate clinical application of International Society of Gynecologic Pathologists Classification of endometrial hyperplasia 424 patients with endome trial hyperplasia were treated in our hospital from Sept. 1989 to Feb. 1995. Our of these cases, 339 were simple hyperplasia, 28 were complex hyperplasia and 57 atypical hyperplasia. We made an analysis of the cases of complex and atypical hyperplasia in terms of the ISGP classification. The total rate of curettage was 63.5%. The agreement rate for pathologic diagnoses before and after operation was 78%. Under the age of 40, 18 patients had atypical hyperplasia and 15 of them underwent hysterectomy. Eight patients had complex hyperplasia and 3 of them underwent hysterectomy. Above the age of 40, 39 patients had atypical hyperplasia and 30 of them had uterus removed. Twenty patients had complex hyperplasia and 12 of them had uterus removed. These suggest that the ISGP pathologic diagnostic method is good to avoid overdiagnosis and overtreatment. Yet, diagnostic curettage is still the best means in diagnosis before operation.

Adult↗

[Some new clinical applications of rhinomanometry].

Clinical applications of active anterior rhinomanometry of the oscillation type had been carried out for the purposes other than the conventional uses of rhinomanometry. 1. Effect of acupuncture upon the nasal resistance to airflow: Among 8 acupuncture points which were recorded in Chinese traditional medical literatures as effective for improving nasal breathing, Ingxiang point had been proved to possess definite effect of lowering the nasal resistance to air-flow in patients with congestion of nasal mucosa, whereas in other acupuncture points this effect was not certain. 2. The severity of snoring before and after treatment could be determined objectively by the measurement of nasal resistance to air-flow and the breathing pattern of the patient.

Acupuncture Points↗

Lasting accelerative effects of 1 Hz and 20 Hz electrical stimulation on cortical spreading depression: relevance for clinical applications of brain stimulation.

Clinical applications of brain stimulation have been increasing during the last decade; however, the mechanisms of action remain unknown. One proposed mechanism of action is that repetitive stimulation modulates cortical excitability. Herein, we explore the question of whether repetitive electric stimulation increases cortical excitability as indexed by the cortical spreading depression. Twenty-four Wistar rats were divided into three groups according to the treatment: sham, 1-Hz and 20-Hz stimulation. Stimulation was applied to the left frontal cortex through a pair of epidurally implanted silver-wire electrodes. The cortical spreading depression-features were analysed at three time points (one day before, one day after and 2 weeks after treatment) in both the stimulated and unstimulated hemisphere. A 3 x 2 x 3 factorial anova with repeated measures showed significant differences in the main effect of time (P < 0.0001), hemisphere (P = 0.0002) and stimulation group (P = 0.008). The interaction between time vs. hemisphere vs. stimulation group was also significant (P < 0.0001). Posthoc analysis demonstrated that 1-Hz and 20-Hz repetitive electrical stimulation significantly increased the velocity of cortical spreading depression in the stimulated hemisphere. Furthermore, 20-Hz stimulation showed a greater effect on cortical spreading depression compared to 1-Hz stimulation. The results show that 1-Hz and 20-Hz repetitive electrical stimulation results in an increase in cortical spreading depression velocity that is associated with the frequency and the hemisphere of stimulation. Furthermore, the effects are found to be long lasting. We believe that these findings have strong relevance to support the clinical application of therapies involving electrical stimulation for diseases of reduced cortical excitability.

Analysis of Variance↗