The treatment of tremor.
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Biomedical subjects
Publications and source records attributed to K Burton.
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The polarization properties of light diffracted from single-skinned fibers of skeletal muscles have been examined under conditions in which the bathing solution pH and the ionic strength are changed. For fibers in the relaxed state, we observe large decreases in both the total depolarization signal, r, and the total diffraction birefringence signal, delta nT, upon pH change from 7.0 to 8.0 at normal ionic strength. However, if the ionic strength is raised, then the r-value change as the pH changes from pH 7.0 to pH 8.0 is much smaller. If the rigor state is achieved at pH 8.0, and 0 mM ATP under either of the ionic strength conditions, the fiber can still be stretched. Rigor stiffness for this state is only approximately 20% that of the value of the stiffness at pH 7.0 rigor. Electron micrographs obtained under this pH 8.0 rigor state show that the overlap region can be decreased upon stretching the fiber, signifying a different kind of weaker-binding rigor state. Optically, the weaker-binding rigor state has a lower depolarization signal and larger form birefringence than the strong-binding rigor state. To convert from one type of rigor state (pH 7.0) to the other rigor state (pH 8.0), or vice versa, the fiber must first be relaxed. Apparently, either of the rigor states can block the full impact of the pH effect.
Two patients with acquired dystonia were studied by computed imaging techniques and found to have lesions predominantly involving the putamen. The implications of these findings are discussed, and it is concluded that, for the genesis of dystonia, a relative increase of other inputs to the pallidum may be important, such as those from the caudate and subthalamic nuclei.
Light diffraction patterns produced by Limulus striated muscle fibers were examined. Segments of fibers were glycerinated, fixed or bathed in relaxing solution. Profiles of the intensity of a diffracted order vs. the angle of incidence of the laser beam often exhibited narrow peaks with the fiber at rest length. The incident angles at which the intensity of left and right orders is greatest are used to calculate the sarcomere length, supporting the notion that regions of the fiber are organised into Bragg reflecting planes. These profiles developed subpeaks and broadened upon stretch of the fiber. The broad angle scan profiles are suggested to result from a decrease in the regular packing of myofibrils as the fiber is lengthened. The angular width of the subpeaks is used to estimate the thickness of clusters of myofibrils. The variation in sarcomere length along the fiber, as determined by the 0th to 1st diffraction order spacing, was dependent upon the fiber preparation. Glycerinated fibers and those bathed in relaxing solution showed more variation than fixed fibers. The variation of sarcomere length is compared to the variation in thick filament lengths in Limulus reported by Dewey et al. (1982). These results are compared to those obtained from frog fiber segments.
Optical ellipsometry studies of single, skinned muscle fibers conducted on the diffraction orders have yielded spectra that are sensitive to the state of the fiber. The linearly polarized light field vector becomes elliptically polarized as it passes through the fiber and may be collected at the diffraction orders. Fibers that have been subjected to extraction of myosin (0.6 M KCl) retain a weak diffraction pattern and exhibit a substantially decreased depolarization of incident linearly polarized light. A significant decrease in polarization is seen in skinned fibers that are subject to an increase in pH from 7.0 to 8.0. This increase in pH results in a decrease of approximately 30% in the depolarization angle of single fibers. The major decrease in depolarization angle that we observe at pH 8.0 is consistent with the notion that as cross-bridges move out from the shaft of the thick filament, their ability to cause depolarization of the incident linearly polarized light decreases. This interpretation is also consistent with the work of Ueno and Harrington where the decrease in the ability to cross-link S-1 and S-2 to the thick filament at pH 8.2 suggests cross-bridge movement away from the thick filament. A large decrease in birefringence, seen after treatment of skinned fibers with alpha-chymotrypsin, appears to be related to the breakdown of myosin into rod, S-1, heavy meromyosin, and light meromyosin.
From 1972 to 1983 the Duke University Department of Anesthesiology designed, built, and maintained most of its own operating room patient monitoring equipment. Construction of a new hospital facility in 1980 provided the opportunity to design and test a new computer-based system, the Duke Automatic Monitoring Equipment (DAME) System. The system consist of microcomputer-based instrumentation on monitoring carts, which communicate with a central minicomputer that allows selection of different software monitoring packages based on the needs of the patient. Multiple problems, including frequent total monitoring failures during surgery, plagued the DAME System in its first year of operation. Despite resolution of many of these problems, user acceptance was poor because of the large size and weight of the monitoring carts, the inadequate quality of displayed physiological waveforms, and inability to overcome the difficulties of the man-machine interface. Because the remaining problems could not be rectified with the existing monitoring carts, a new generation of monitors was designed. The smaller, multiprocessor microDAME was designed to be as automatic and user tolerant as possible. It would omit much of the flexibility that had proved undesirable in the DAME system. When the microDAME was nearly completed, however, departmental research in that area ceased. It remains for others to apply our experiences to further improve operating room patient monitors.
The depolarization signal of the diffraction patterns from muscle fibers includes information that differs from that of transmission birefringence experiments. Although both the birefringence studies and the phase shift studies of Yeh et al. (Yeh, Y, and G. Pinsky, 1983, Biophys. J., 42:83-90; Yeh, Y., M. E. Corcoran, R. J. Baskin, and R. L. Lieber, 1983, Biophys. J., 44:343-351) include inseparable intrinsic and form contributions, the present analysis shows that the magnitude of the E-field components of diffracted light is affected only by the intrinsic contribution. We have analyzed the amplitude portion of the data of which the phase shift portion had previously been reported (Yeh, Y., M. E. Corcoran, R. J. Baskin, and R. L. Lieber, 1983, Biophys. J., 44:343-351). For the relaxed-to-rigor transition, these field amplitudes also exhibit changes when ATP concentration is decreased. The observed decrease in optical depolarization upon rigor is consistent with the idea that optically anisotropic elements move away from the myosin thick filament under such conditions.
Previous studies with mesulergine (CU 32-085) demonstrated safety and efficacy in short-term observations of patients with Parkinson's disease. We compared mesulergine with bromocriptine in 20 patients with Parkinson's disease. Eighteen patients completed the randomized, double-blind, crossover study. Clinical assessments employed the UBC scale and "Mini-Mental State" examination; neurophysiologic measurements were undertaken on wrist rigidity and speed and accuracy of hand movement, and toxicity screening tests were compared. There were no significant differences between the effects of mesulergine (mean dosage, 27.4 mg/d) and bromocriptine (mean dosage, 40.8 mg/d).
A non-invasive, indirect method for measuring spinal cord mixed afferent-efferent conduction is described. The method is based upon eliciting late reflex responses labelled R1 and R2 from voluntarily contracting thenar and tibialis anterior muscles by preferentially stimulating median and common peroneal sensory nerve fibres. The mean onset latencies of R1 measured 27.5 msec and 30.6 msec recorded from hand and leg muscles respectively. R2 mean onset latencies measured 46.0 msec and 65.1 msec respectively. R1 has characteristics similar to an H-reflex. R2 is a long-loop reflex of unknown pathway assumed to involve similar circuits and rostral turn around points when elicited by both arm and leg stimulation. Mean spinal cord conduction time between the seventh cervical and fifth lumbar spinous processes, is given by (formula; see text) It measured 7.95 msec and the calculated mean conduction velocity was 57.9 +/- 5.7 m/sec.
The therapeutic use of dopamine agonists for Parkinson's disease, clinical guidelines for their introduction into antiparkinson regimens, and their range of adverse effects are reviewed. The role played by the dopaminomimetic ergots in elucidating dopamine receptor function, and laboratory methods that identify dopamine agonists, are also examined.
Dopamine agonists have yielded two important advances to our understanding of the basal ganglia--they have facilitated the subdivision of different classes of dopamine receptors, and they have established the fact that important dopaminergic effects can be achieved by activation of dopamine receptors in a manner that is unrelated to anoxal impulse traffic in dopaminergic neurons--a phenomenon similar in its diffuse, slow, characteristics to an endocrine effect. The tangible clinical benefit of dopamine agonists has been evident in patients with prominent dyskinesia or wearing off reactions. It is possible that earlier use of agonists, in low doses combined with similarly low doses of levodopa, may improve the long term treatment of Parkinson's disease, but as yet there is no firm evidence. In the future, we can expect to see agonists with more prolonged effects, deriving from the formation of active metabolites. We can also hope to gain further insight into the correlations between the various animal models of dopaminomimetic activity, and specific aspects of drug efficacy and toxicity in parkinsonian patients. Such information should allow the design of improved pharmacotherapy.
We studied posthemiplegic hemidystonia in an adult, and generalized dystonia in two children. CT and magnetic resonance imaging (MRI) studies in the adult revealed infarction of the contralateral putamen and, to a much lesser extent, the head of the caudate nucleus. Both children had subacute encephalopathies (possible Leigh's disease), and CT revealed bilateral putamen lesions when generalized dystonia was the predominant clinical disorder. These cases and other reports of symptomatic dystonia suggest that lesions of the putamen correlate with dystonia.
The approach to treatment of Parkinson's disease depends on the severity of symptoms at presentation and the response to previous therapy. The pharmacotherapy of Parkinson's disease is discussed with respect to management of cardinal symptoms, management of associated features, and future directions for therapy.
Convulsive status epilepsy is a medical emergency with significant mortality and morbidity. This retrospective survey reports the use of non-anaesthetic doses of thiopentone, given either by intravenous or rectal infusion. The regime was effective in controlling convulsive status without significant complications. It is suggested that this regime can be used safely when standard doses of diazepam (or clonazepam), and/or phenytoin, fail to effect immediate control of convulsive status, and before anaesthetic agents are administered.
The uptake and retention of purine bases and of uracil requires both a protonmotive force and intracellular conversion to nucleotides. Inhibition of uptake by arsenate does not imply that ATP is required for the transport process because arsenate caused a rapid fall in the level of 5-phosphoribosyl 1-pyrophosphate. A mutation defective in high-affinity adenine transport has been identified and is designated purP. This mutation has been found to lie in the neighbourhood of mtl. Competition experiments indicate that at least two other systems are used to transport guanine, xanthine and hypoxanthine.
The 13 questions to which 173 rheumatic outpatients most frequently wished to know the answer were made the basis of a structured interview. Two lengths of interview were conducted in a controlled trial (short being of 2 minutes' duration, long ranging from 4 to 11 minutes). Sixty patients referred directly from their general practitioners, and not being in any of the remedial professions, were randomly assigned to one of the 2 groups. They were tested by an independent observer immediately after interview, and one month later at their return appointment, by means of a questionnaire that covered the 13 items of information given to all the patients. The longer interview resulted in significantly more information being retained. Of individual questions only 3 scored significantly better with the longer interview--that about the reasons for x-rays immediately after interview, and the role of heredity and the place of rest at delayed recall.
Three Laotian refugee children with chronic pulmonary complaints and findings were found to have pulmonary paragonimiasis during a one-year period in Chicago. These patients ranged from 8 to 11 years of age and the diagnosis was delayed five to six months in two children because of the unfamiliarity of American physicians with signs and symptoms of this disorder. Clinical manifestations included chronic cough for up to two years, apparent hemoptysis in two patients, lack of fever or sweats, and family history negative for tuberculosis. Physical findings included rales and dullness to percussion, clubbing (one patient), and lack of fever or respiratory distress. All three patients showed interstitial infiltrates on chest roentgenogram whereas two had multiple small cystic areas. Moderate eosinophilia was present. Paragonimus westermani ova were found in stools of two patients, in sputum of two patients, and in bronchoscopic specimens in one patient. All patients demonstrated striking clinical and radiologic improvement following treatment with bithionol (50 mg/kg every other day for 15 doses), which was well tolerated. Lung fluke infestation must be considered in Indochinese refugee children with apparent hemoptysis or chronic pulmonary symptoms, and sputum and stool should be examined for P westermani ova.
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