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CURRENT SCIENCE REVIEWS By Joe Bruman April 1997 p. 1 of 3 Litvan I et al;Brain 1997;120:65-74: Review of clinical distinctions between progressive supranuclear palsy (PSP) and related disorders, including PD. In that case, the principal difference is that PD responds to levodopa. Leiguarda R et al;Brain 1997;120:75-90: Seeking clinical distinctions, authors studied 45 PD patients plus 34 with related disorders for apraxia (impaired coordination in gesturing movements). They found some correlation, but no definite marker. Rascol O et al;Brain 1997;120:103-110: Using SPECT to observe regional cerebral blood flow, authors tested 12 normal subjects, 12 PD patients deprived of medication, and 16 normally medicated PD patients, with standardized movement tasks. In the unmedicated (and akinetic) group, the ipsilateral cerebellar hemisphere is overactive, suggesting an autonomous compensation for failure of the basal ganglia-cortical loop. Weiss P et al;Brain 1997;120:91-102: Exploring the root of multi-component movement (e.g., walking) impairment, authors carefully compared 15 PD patients with an age- matched healthy control group. They conclude that programming is intact, but transition between successive components is hesitant. Brown P;Lancet, 22 Feb 1997:533-535: Active muscle emits sound, audible with an ordinary stethoscope, with one peak around 40-50 Hz, both in normal subjects and in PD patients when medicated. But in unmedicated PD patients, the tone is replaced by an (infrasonic) vibration of 10 Hz, evidently arising in the sensorimotor cortex. (My guess is, this is the autonomous attempt to "detour" the failed cortico-striatal pathway.) Booij I et al;J Neur N'Surg Psych 1997:62:133-140: A newly available radiotracer permits SPECT (Single-Photon-Emission Computed Tomography) to be used in a same-day, outpatient protocol, for early detection of PD. Application to comparable groups of early-stage PD patients, advanced PD patients, and healthy controls, showed differences in dopamine uptake patterns that offer a useful diagnostic tool. Johansson F et al;J Neur N'Surg Psych 1997;62:125-132: Study of 20 advanced-PD patients who had postero-ventral pallidotomy revealed pronounced improvement in dyskinesia, moderate improvement in tremor, and little or no effect on bradykinesia. Authors conclude that PVP "may" be useful for patients with severe motor fluctuations and "may" allow increased levodopa dosage, to alleviate off-state bradykinesia. Sonders M et al;J Neurosci 1997;17:960-974: Using frog eggs cloned to express the human dopamine transporter hDAT, authors studied its electrical effects on simulated dopamine uptake. Thomaidu D et al;J Neurosci 1997;17:1075-1085: In prenatal and neonatal rat brains, apoptosis is most prominent in the proliferating epithelium of the cerebral cortex, and is related to progression of the cell cycle. CURRENT SCIENCE REVIEWS By Joe Bruman April 1997 p.2 of 3 Jordan J et al;J Neurosci 1997;17:1397-1405: The tumor suppressor gene p53 has been suspected before to induce neuronal apoptosis. Authors used cultured rat neurons, genetically altered to overexpress p53 as an immune reaction, and confirmed the suspicion. Pappolla M et al;J Neurosci 1997;17:1683-1690: Oxidative stress, mediated by free radicals, is known as a factor in Alzheimer's disease. The pineal hormone melatonin, an antioxidant, decreases with aging and is markedly reduced in AD. Lab tests showed melatonin to be remarkably effective in preventing death of cultured neuroblastoma cells. (Might the effect also apply in PD? JRB) BMJ, 1 Mar 1997:625 (news item): Although fetal pig cell transplants are finding success in PD trials, the British government has been cautious about any interspecies transplant, partly because of the fear that a retrovirus may gain a foothold in the human population. (A retrovirus is one that, like the HIV viruses, reproduces by subverting the host's DNA.) One such porcine retrovirus was found capable of infecting other mammalian species, with greater risk if host immunity is suppressed. Zhang F et al;Science, 28 Feb 1997:1318-1319: In experiments on the relatively simple sea slug (Aplysia), authors found that a growth factor active in embryonic development may also permit modification of adult neurons, raising hope for new therapy in neurodegenerative diseases such as PD. Cuthbertson B, Noble D;BMJ, 8 Mar 1997:689-690: Dopamine (not levodopa) has been popular for 20 years, in dosage less than that used in PD, both as a diuretic in suspected kidney failure and as a vasodilator in shock. In view of numerous adverse effects and scanty knowledge, authors are dubious and propose large-scale formal trials. Federico F et al;J Neur N'Surg Psych 1997:62:239-242: Looking for diagnostic distinctions, authors used MRI and Proton Magnetic Resonance Spectroscopy (1-H-MRS), a related technique, to compare concentration of certain brain metabolites in 8 PD patients and 5 PSP patients. They found significant differences that were not discernible by MRI or PET alone. Gnanalingham K et al;J Neur N'Surg Psych 1997;62:245-252: Authors applied a battery of motor and cognition tests to 16 patients with Lewy body dementia, 15 with PD, 25 with AD, and 22 healthy controls. They found a useful distinction between LBD and AD but not between LBD and PD. Rice G et al;J Neur N'Surg Psych 1997;62:282-284: In a placebo-controlled, double-blind, crossover test on 20 patients having cerebellar tremor from various causes, authors tried ondansetron, already known to alleviate cerebellar vertigo, and found it improved tremor (in spiral copying test) as well. CURRENT SCIENCE REVIEWS By Joe Bruman April 1997 p.3 of 3 Daniele A et al;J Neur N'Surg Psych 1997;62:288-289: Authors report a woman of 63, who had PD 23 yr, and who developed cognitive impairment and obsessive-compulsive behavior following an ischemic stroke in the left putamen. Hestnes A et al;J Neur N'Surg Psych 1997;62:289: Dementia like that in AD occurs in nearly all Downs patients, and in about 15% of PD patients. Since Downs is clearly hereditary, authors studied postmortem substantia nigra of 27 Downs patients, but didn't find the Lewy bodies associated with PD. Contrary to previous reports, they conclude there is no link between Downs and PD. Tachibana H et al;Arch Neur 1997;54:296-302: Authors measured cognitive response times in 28 PD patients and 28 controls, via EEG and eye-motion sensors, finding that the PD group slows more with advancing age than the controls. Louis E et al;Arch Neur 1997;54:260-264: Authors tracked survival of 1690 elderly New York City residents without PD and 288 PD patients, also divided into demented and non-demented groups. Judging roughly from the plotted results, in the range 80yr to 100yr, PD patients died about 8 to 10 yr earlier. Dementia was not a major factor in the healthy group, but shortened the life-span in the PD group. Lancet, 16 Mar 97:784 (news item): The heavy hand of the FDA is descending on usage of "extensively processed" or "novel" human tissues or cells, e.g., PD transplants. Wang Y et al;Lancet, 15 Mar 97:777: A woman given perphenazine for post-surgical pain developed tardive dyskinesia. She then got tetrabenazine for that, but developed depression and parkinsonism. So they did a postero-ventral pallidotomy, and it worked as well as it normally does for levodopa-induced dyskinesia in PD. Turkka J et al;Neur 1997;48:662-667: Selegiline (Eldepryl), with or without levodopa, in a double-blind trial on 52 PD patients who were followed for median 6 yr, reduced autonomic response to various tests, suggesting increased risk of orthostatic hypotension. Durif F et al;Neur 1997;48:658-662: Authors tried low-dose clozapine (Clozaril) against apomorphine- induced dyskinesia in 7 PD patients, concluding that it may help reduce levodopa-induced dyskinesia in addition to its customary antipsychotic effect. Gorell J et al;Neur 1997;48:650-658: Authors surveyed 144 PD patients and 464 comparable controls having varied long-term occupational exposure to iron, copper, manganese, mercury, zinc, or lead, singly or in combination. They found weak (partial) correlation with PD for copper, manganese, lead, and some of the combinations, and negative (protective) indication for mercury and zinc. J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks CA 91403