To pog rap h ic Map pingMarihuana abuse, especially that which is chronic, continues to generate public and medical concern,' and investigations into the pharmacological, physiological and behavioral effects of this substance ~o n t i n u e .~-~ It is perhaps perplexing t o realize that even though natural marihuana and synthetic delta-9-tetrahydrocannabinol (hereafter both are referred to as THC) exert obvious psychoactive effects, the neurophysiological concomitants of acute THC exposure are incompletely understood and effective CNS measures of chronic use in humans are lacking. In particular, electroencephalographic correlates of l o n g term marihuana use have not been reported.Clinical EEG studies of marihuana use began over four decades ago. The first appeared in 1945 and 1946 and both were limited to visual inspection of bipolar occipital waking activity secured before and after volunteers (who were heavy daily THC users) smoked from one to four marihuana cigarettes. In neither study were any specific effects of acute THC exposure noted. In another early investigation' conducted in 1958, Ames gave ten presumably THC-naive medical staff volunteers EEGs and other tests before and after receiving a single dose of concentrated marihuana extract. Using bipolar parasagittal and temporal montages, no THC-specific EEG changes were detected and only minor frequency alterations, which varied across s u bj ec t s , we re seen . S u bseq u en t studies in which clinical EEG tracings were visually analyzed before and after volunteers (usually experienced THC users) smoked or orally ingested either natural or concentrated THC preparations, again failed to identify specific EEG effects of acuteTHC exposure. However, three of the above s t u d i e~~~~' '~ reported visual recognition o f a subtle slowing of alpha frequency in some subjects following THC exposure, and one of them13 reported a post THC increase in alpha amplitude as well. In noneof thestudies mentioned above did acute THC exposure produce clinical abnormalities in the EEG. Studies of chronic heavy THC users in other culture^^^"^ also have failed to demonstrate THC related clinical EEG abnormalities of any kind Other early studies are either atypical or present other problems for review. I n a complex study of considerable interest, Koukkou and Lehmanl6,l7 have attempted to demonstrate EEG spectral shifts following THC induced disturbances of mood, sensory experience, o r perceptual alterations as contrasted with periods when these phenomena were not present. The study did not address the issue of THC related changes in background EEG characteristics. In a different vein, data obtained in a study" requiring EEG recordings under an eyes-open condition are not comparable to findings derived from the majority of studies using the traditional eyesclosed recording approach. M i r a~~~c l a i m e d to discern significant EEG changes in two very

Two brothers presented in their mid-forties with movement disorders including atypical parkinsonism, choreiform movements, stereotypies, ataxia and dysarthria. Both brothers showed putaminal lucencies on imaging and, in the proband, a deficiency of the pyruvate dehydrogenase complex (PDHC) was found on skin fibroblast assay.

Background. Cardiovascular disease is the major cause of death in the end-stage renal disease population. Novel risk factors such as homocysteine (Hcy) are of considerable interest in this group as hyperhomocysteinaemia is highly prevalent in the setting of renal impairment. Folic acid-vitamin B group therapies are only partially effective treatments. Hcy is highly protein-bound and thus poorly dialysed. Dialyzers with albumin-leaking properties have been shown to result in lowering of plasma Hcy. As the FX-class (Advanced Fresenius Polysulfone dialyzer) has greater clearance of larger molecular weight substances but is non-albumin-leaking, we explored the capacity of this new technology membrane to reduce plasma Hcy levels. Methods. A prospective randomized cross-over trial in 35 prevalent haemodialysis patients, one group receiving 12 weeks dialysis using FX dialyzer then 12 weeks with standard high flux dialysis (SHF) and the other group SHF followed by FX dialyzer. All patients received vitamin B 6 25 mg and folic acid 5 mg daily throughout the study. Results. The primary outcome was plasma Hcy pre-dialysis at week 12. FX vs SHF showed no significant difference, 25±6.6 vs 25.9±5.8 mg/l, Á95% CI ¼ À2.77 to 4.59, P ¼ 0.31. There was a nonsignificant trend toward a decrease in Hcy in both groups (27.43±7.68 to 25.91±5.78 mmol/l for SHF, P ¼ 0.23 and 26.0±4.58 to 25.0±6.61 mmol/l for FX, P ¼ 0.28). Analysis by repeated measures method demonstrated a statistically significantly lower Hcy with FX vs SHF dialyzer (adjusted b ¼ À1.30, 95% CI ¼ À2.41 to À0.19, P ¼ 0.022). K t /V urea was higher in FX vs SHF (1.35±0.18 vs 1.22±0.2; P ¼ 0.013). Folate and B 6 levels did not change. Conclusions. The primary outcome analysis did not show any significant difference in pre-Hcy comparing FX and SHF membranes. Although our secondary analysis demonstrated a statistically significant difference between membranes, the magnitude of the difference (1.3 mmol/l) is not clinically significant. Thus the use of the FX dialyzer did not result in a clinically significant benefit in relation to improving pre-dialysis Hcy compared with standard high-flux dialysis.

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