Variations on the musical brain.
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Biomedical subjects
Publications and source records attributed to J D Warren.
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BACKGROUND: Although 'senile' chorea is commonly listed in the differential diagnosis of chorea, the condition is poorly defined. Indeed, the existence of such an entity is debated. There are few contemporary prospective studies of sporadic chorea in the elderly. METHODS: Detailed prospective study of patients presenting with undiagnosed chorea over a three year period to a Movement Disorder Clinic. RESULTS: Twelve patients, aged 50 to 89 years, were identified. The final diagnoses were Huntington's disease, confirmed on genetic testing in six, antiphospholipid antibody syndrome in two, and hypocalcaemia, tardive dyskinaesia and basal ganglia calcification in each of the three remaining cases. Only one patient remained undiagnosed despite extensive investigation. CONCLUSIONS: The majority of patients with 'senile' chorea actually have Huntington's disease even in the absence of a family history. Rarer causes of chorea still need to be considered in the elderly when Huntington's disease has been excluded by DNA analysis.
A case is reported of a 63-year-old woman with thalamic syndrome as the presenting feature of an unruptured cerebral aneurysm. Unruptured aneurysm is a rare cause of thalamic syndrome; the possible mechanisms of production of the sensory disturbance are discussed.
1. To investigate the morphology and physiology of vertical medium-lead burst neurons with downward on-directions (DMLBs), we impaled midbrain axons and recorded their discharge patterns in relation to spontaneous saccades of alert, behaving squirrel monkeys. Selected axons were injected with horseradish peroxidase and morphologically characterized. 2. DMLBs emitted bursts of impulses that preceded rapid eye movements by approximately 5 ms. Parameters of the burst (duration and number of spikes) were highly correlated with parameters of the saccadic eye movement (duration and amplitude of the downward displacement of the eyes). 3. Somata of DMLBs were recovered in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF, n = 14), and in the interstitial nucleus of Cajal (NIC, n = 2). Fibers originating from riMLF DMLBs projected, usually ipsilaterally, to the NIC as well as in the inferior rectus and the superior oblique subdivisions of the oculomotor complex. The axons of NIC DMLBs projected to the ipsilateral riMLF, NIC, and the mesencephalic reticular formation but not to the oculomotor complex. 4. Our data demonstrate that some DMLBs can provide extraocular motoneurons of both eyes with the pulse of activity they display during downward saccades. In addition, such neurons can supply the NIC with one of the signals that this nucleus is thought to integrate to extract an estimate of the vertical eye position. Finally, our data demonstrate the existence of DMLBs that do not establish direct connections with oculomotoneurons.
Dysthyroid exophthalmopathy (orbitopathy) results from an enlargement of extraglobal orbital structures, producing ocular proptosis, optic nerve compression, and corneal exposure. Treatment with corticosteroids and radiation may be beneficial; refractory cases require surgical decompression of the orbit. Transantral orbital decompression was described by Walsh and Ogura and has been performed in over 350 patients at this institution. A review of 305 patients with long-term follow-up was performed. Visual acuity improved or was maintained at preoperative levels in over 95% of the patients, with ocular recession ranging from 1 to 12 mm (average: 4 mm). Postoperative ocular balance of relative exophthalmos was to within 1 mm in 76% of the patients and to within 2 mm in approximately 90% of the patients. Normal postoperative extraocular muscle balance was present in 99 patients. Immediate postoperative diplopia was noted in 206 patients. Long-term follow-up revealed that in 137 of these patients, diplopia resolved or responded to conservative management. Extraocular muscle surgery was required for correction in 69 patients. Twenty-seven patients had postoperative complications. These included 16 patients with hypesthesia of the infraorbital nerve, 5 patients with sinusitis, 3 patients who had incomplete decompression, 2 patients with oral antral fistulae, and 1 patient who had CSF rhinorrhea. Five patients, despite surgery, radiation, and steroid therapy progressed to blindness. We conclude that this procedure is effective and carries few complications. Orbital imaging, using computed tomography or magnetic resonance sequence with reconstructive capabilities, permits early diagnosis and treatment of dysthyroid compression optic neuropathy.
9,10-Anthracenedicarboxaldehyde bis[(4,5-dihydro-1H-imidazol-2-yl)hydrazone] (bisantrene, VI-1) showed anticancer activity in mice vs. both leukemias and solid tumors. Increases in life span vs. the following neoplasms were: P-388 leukemia, 137%; B-16 melanoma, 122%; Lieberman plasma cell tumor, greater than 85%; colon tumor 26, 150%; Ridgway osteogenic sarcoma, 85%. There were significant numbers of long-term survivors. Both DNA and RNA synthesis were strongly inhibited. The drug was resistant to biodegradation and was bound strongly to tissues; in monkeys the half-life for disappearance from serum was 6 days. Related hydrazones were synthesized, and structure-activity relationships are discussed. Two routes to ring-substituted anthracene-9,10-dicarboxaldehyde intermediates were developed.
Eleven quinazolinylformamidines and quinazolinediylbisformamidines were synthesized and investigated for antihypertensive activity in spontaneous hypertensive rats. Several compounds showed moderate antihypertensive activity at 100 mg/kg po. The same compounds were not hypotensive in the normotensive dog.
Twelve 4-substituted semicarbazone derivatives of o- and p-chloro- as well as 2,6-dichlorobenzaldehyde were synthesized and investigated for antihypertensive activity in spontaneously hypertensive rats. Several of the compounds synthesized (viz. 1, 6, 7, and 15) exhibited potent antihypertensive effects when orally administered. The same compounds were not hypotensive in the normotensive dog.
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Successful organ transplantation depends on adequate preservation of cellular function. We tested the effect of four commonly used donor organ preservation fluids on the ability of cultured bovine pulmonary artery endothelial cells to release endothelium-derived relaxing factor (EDRF). Columns of endothelial cells grown on microcarrier beads were exposed to either University of Wisconsin (Belzer's) solution, Marshall's preservation fluid, Euro-Collins solution, or a blood-based preservation fluid at 4 degrees C for 6 hours, and then to Krebs-Henseleit buffer at 37 degrees C for 1 hour. They were then stimulated with boluses of bradykinin, and the EDRF released was detected by bioassay. The release of EDRF from endothelial cells previously exposed to a preservation fluid was compared with the release of EDRF from control columns of cells perfused throughout at 37 degrees C with Krebs-Henseleit buffer. Previous exposure to any of the three non-blood-based preservation fluids did not attenuate bradykinin-stimulated EDRF release. By contrast, previous perfusion with the blood-based solution completely inhibited EDRF release (p less than 0.01, ANOVA), an effect attributable to the acidity of the solution. Donor organ preservation fluids differ in their effect on endothelial cell function, and this has important implications for lung and for other organ transplantation.
A rapid method is described for extraction and cleanup of raw and processed milk for determination of aflatoxins M1 and M2 by using a C18 Sep-Pak/silica gel cleanup column combination. Aflatoxins are separated by normal phase liquid chromatography and their concentrations are determined by fluorescence detection in a silica gel-packed flow cell. Recoveries ranged from 99 to 103% with coefficients of variation less than 2% for M1 levels of 0.117-1.17 ng/mL added to raw milk. Similar recoveries were obtained for M2. The coefficient of variation for analysis of 5 subsamples of naturally contaminated milk was less than 1%. Agreement with the official method is satisfactory. Each sample requires less than 25 mL solvent and 10 min actual handling time. Sample chromatograms show no interferences in the M1-M2 elution region and no late-eluting peaks, which permits spacing injections at 13-20 min intervals. Aflatoxin levels as low as 0.03 ppb may be determined by this procedure. Extracts have also been analyzed by thin layer chromatography.