Comparative PET studies of the kinetics and distribution of cocaine and cocaethylene in baboon brain.

Recent studies have suggested that cocaethylene, an active metabolite of cocaine found in blood and postmortem brain of individuals self-administering cocaine and alcohol, may play a role in the increased toxicity seen when coadministering these 2 drugs. We have used positron emission tomography (PET) and carbon-11 (t1/2:20.4 min) labeled cocaine and cocaethylene to compare the short-term kinetics of cocaine and cocaethylene in baboon brain. The regional uptake of [11C]cocaine cocaethylene in baboon brain. The regional uptake of [11C]cocaine ([11C]COC) and [11C]cocaethylene ([11C]CE), 5-8 mCi and 4-6 micrograms, in baboon brain (n = 7) were similar but clearance from whole brain (global, GL) and from striatum (SR), thalamus (TH), and cerebellum (CB) was slower for cocaethylene. Steady-state distribution volumes (DV) were not significantly different in the striatum but were greater for cocaethylene in the thalamus, cerebellum, and whole brain. Debenzoylation of cocaethylene proceeded at about one-third the rate of cocaine, as determined by in vitro incubation of labeled cocaethylene and labeled cocaine with baboon plasma and with purified horse butyryl-cholinesterase (EC 3.1.1.8). Even though the slower clearance of cocaethylene could lead to longer tissue exposures and potentially accentuated or different physiological effects relative to cocaine, the difference between the 2 drugs is not large. Thus it is more likely that the direct actions of cocaine and alcohol on some organs, rather than cocaethylene, account for this enhanced toxicity.     

Antiarrhythmic activity of 17 beta-aminoestratrienes. Comparison of 3-ols and 3-acetates with the corresponding 3-(3-amino-2-hydroxypropyl) ethers

The antiarrhythmic efficacy of 17 beta-amino- and 17 beta-amino-16 alpha-hydroxyestratrien-3-ols and 3-acetates (group 1) was compared with the efficacy of corresponding 3-[2-hydroxy-3-(isopropylamino)propyl] and 3-[2-hydroxy-3-(tert-butylamino)propyl] ethers (group II), substituents which are usually associated with beta-adrenoceptor blocking activity. Group I compounds exerted potent antiarrhythmic activity against both aconitine-induced arrhythmias in mice and ischemia-induced arrhythmias in rats and reduced the maximum following frequency of isolated guinea pig atria. Electrophysiological studies indicated that their mechanism of action is due to an ability to reduce the fast inward sodium current in cardiac cells (class I antiarrhythmic action). Group II compounds were inactive in the aconitine and atrial tests and electrophysiological studies confirmed that they were devoid of class I activity. However, these compounds, like both class I antiarrhythmic and beta-adrenoceptor blocking drugs, were active against ischemia-induced arrhythmias. Group II compounds, unlike group I compounds, exerted nonspecific beta-adrenoceptor blocking actions, which may account for their activity in the rat test. It was concluded that introduction of the 3-substituted ether group did not confer any advantage over the parent 3-ol or 3-acetate compounds.     

Convergence substitution for paralysed horizontal gaze.

Three patients with paralysed horizontal gaze are presented. Involuntary use of convergence to assist horizontal gaze was noted as a late feature. All patients showed (1) unilateral or bilateral horizontal gaze palsy (two patients had one and a half syndrome, the other had bilateral nuclear sixth nerve palsies), (2) adduction of both eyes on attempted gaze into the paralysed field, (3) miosis which coincided with adduction. Convergence substitution should be considered in the differential diagnosis of gaze induced strabismus.     

Incidence of inflammatory bowel disease in north west Greece: rarity of Crohn's disease in an area where ulcerative colitis is common.

Ulcerative colitis (UC) and Crohn's disease (CD) are generally regarded as diseases of affluent societies of the Western World, although their frequency in less affluent areas is not well established. This retrospective study therefore, assesses the incidence of UC and CD in a semirural area of north west Greece during the 10 year period 1982-1991. By the 31 December 1991, 61 patients had met standard diagnostic criteria for UC (annual incidence 4.0/10(5), 95% confidence intervals 3.0 to 5.0/10(5)) and only five patients met the diagnostic criteria for CD (annual incidence 0.3/10(5), 95% confidence intervals 0.1 to 0.8/10(5)) in this area of 157,214 inhabitants. UC incidence was lowest in the first three years at 1.8/10(5) per annum and subsequently increased to 4.8 and 5.1/10(5) per annum for the successive four and three year periods respectively. UC incidence was slightly higher in men. A third of all cases of UC had pancolitis while a quarter had only proctitis. More than one half were categorised as having moderate or severe colitis. Three quarters of the patients resided in urban areas. The incidence of CD was a twelfth of the UC incidence, which is in considerable contrast with most Western countries where the incidence of CD is usually no less than a third that for UC. The rarity of CD points to the absence of aetiological environmental factors specific for CD.     

Detecting cumulative trauma disorders in workers performing repetitive tasks

On-site testing of 157 poultry processors disclosed that 50% had three or more abnormal upper extremity findings out of a total of 22 possibles. The average worker had five to six abnormal findings. Impaired pinch strength, decreased vibration sensitivity in the fingertips, and reports of current numbness were the most prevalent. Of workers with signs, 25% reported no symptoms, whereas only 8% of workers reported symptoms but had no signs. The investigators concluded that this measurement method has utility for assessments of worker populations to determine prevalence of CTDs and, potentially, for preclinical detection of these disorders to permit early intervention, reduce medical costs, and minimize disability. The need for accurate measurement to enhance early detection and prevention is discussed.