Faculty Bibliography

BACKGROUND: Microalbuminuria (MA) is thought to be a marker of widespread vascular damage. It is associated with increased mortality in diabetes mellitus, hypertension and acute myocardial infarction. The aim of the present study was to evaluate the prognostic significance of MA in non-diabetic acute stroke patients. MATERIAL AND METHODS: We studied 52 patients (mean age 69.3 +/- 12.5 years) diagnosed with ischemic stroke confirmed by computed tomography, who were admitted to the Stroke Unit within 24 hours after the onset of symptoms. The control group consisted of 37 age- and gender-matched subjects (mean age 65.2 +/- 5.7 years), examined 3 to 18 months after ischemic stroke. We excluded patients with diabetes mellitus, positive urinalysis, proteinuria, hepatic or renal insufficiency, neoplastic disease or clinical signs of infection. The severity of the neurological deficit was assessed by the Scandinavian Stroke Scale (SSS). The albumin excretion rate was measured in daily urine collection on the second day of hospitalization, using the immunonephelometric method. The patients were followed up for three months. RESULTS: MA was found in 24 of 52 (46.1%) acute stroke patients and in 5 of 37 (13.5%) controls (p<0.05). Patients with MA scored lower on the SSS than patients without MA, both on admission and later. We found a correlation between the daily excretion of albumin and the severity of neurological deficit on admission, as expressed by the SSS score (r = -0.48, p<0.05). The 90-day mortality rate was higher in patients with MA as compared to patients without MA (45.8% vs 7.1%). Patients with MA scored lower on the Barthel Index on Day 90 (median: 65 vs 100, p<0.01). CONCLUSIONS: We found that MA can be detected in about 46% of non-diabetic patients with acute ischemic stroke. Measuring the albumin excretion rate may be a reliable predictor of increased mortality 3 months after stroke

OBJECTIVE: Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood. METHOD: To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1 ) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity). RESULTS: Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites, just three (anterior cingulate, right inferior parietal lobule, and the caudate/lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film. CONCLUSIONS: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.

Although associations between cholesterol and coronary heart disease (CHD) are well accepted, the association between cholesterol and stroke remains unclear. Epidemiological studies suggest lack of apparent correlation between cholesterol and cerebrovascular events, however meta-analyses of secondary prevention trials tested statins (HMG-CoA reductase inhibitors) efficacy in reducing cholesterol revealed a powerful statistically significant effect to reduce stroke as well as CHD (32%). Mechanism for stroke reduction can be connected with nonlipid mechanism of statins action: modifying endothelial function and inflammatory responses, plaque stabilisation and inhibition of plaque progression and thrombus formation in the intracranial and extracranial carotid arteries. Stroke events may be also reduced partially as a consequence of CHD reduction

BACKGROUND:The aim of this study was to determine the existence of, and possible mechanisms for, chronic cocaine use-induced neurotoxicity in the human brain. Because in vivo magnetic resonance spectroscopy (MRS) provides a noninvasive way to detect biochemical and physiological changes in the brain, we sought to specifically determine the neurochemical adaptations in chronic cocaine-dependent subjects. METHODS:Twenty-one cocaine users and 13 non-drug-using, age-matched normal volunteers were recruited for an in vivo proton MRS study. Following screening that included physical examination, histories, and blood testing, cocaine group subjects received a spectral scan on a 1.5-T GE Signa scanner. Spectra were obtained from the left basal ganglia and/or the left thalamus from subjects in both groups using an rf bird-cage type head coil with single-voxel localization. RESULTS:The level of N-acetyl aspartate in the region of left thalamus was lower (17%) in the chronic cocaine user group but not in the region of left basal ganglia, compared with the control group. CONCLUSIONS:These results suggest that chronic cocaine use may induce abnormal neurochemical activity and a state of neuronal dysregulation and/or neurotoxicity. It will now be important to determine if these alterations are reversible during withdrawal and what the functional implications of this observation are with respect to cognitive function and drug relapse.

As the applications of functional magnetic resonance imaging (fMRI) expand, there is a need for the development of new strategies for data extraction and analysis that do not require the presentation of stimuli in a repeated on/off pattern. A description and evaluation of a method and computer algorithm for the detection and analysis of brain activation patterns following acute drug administration using fMRI are presented. A waveform analysis protocol (WAP) input function has been developed that is based upon the single-dose pharmacokinetics of a drug of interest. As a result of this analysis, regional brain activation can be characterized by its localization and intensity of activation, onset of action, time to peak effect, and duration of action. A global statistical test for significant drug effects based upon the probability of a voxel being activated by a saline vehicle injection is applied to grouped data on a voxel by voxel basis. Representative data are presented using nicotine as a prototypical agent. Using this method, statistically significant drug-induced brain activation has been identified in several key cortical and subcortical brain regions.

OBJECTIVE: Nicotine is a highly addictive substance, and cigarette smoking is a major cause of premature death among humans. Little is known about the neuropharmacology and sites of action of nicotine in the human brain. Such knowledge might help in the development of new behavioral and pharmacological therapies to aid in treating nicotine dependence and to improve smoking cessation success rates. METHOD: Functional magnetic resonance imaging, a real-time imaging technique, was used to determine the acute CNS effects of intravenous nicotine in 16 active cigarette smokers. An injection of saline followed by injections of three doses of nicotine (0.75, 1.50, and 2.25 mg/70 kg of weight) were each administered intravenously over 1-minute periods in an ascending, cumulative-dosing paradigm while whole brain gradient-echo, echo-planar images were acquired every 6 seconds during consecutive 20-minute trials. RESULTS: Nicotine induced a dose-dependent increase in several behavioral parameters, including feelings of "rush" and "high" and drug liking. Nicotine also induced a dose-dependent increase in neuronal activity in a distributed system of brain regions, including the nucleus accumbens, amygdala, cingulate, and frontal lobes. Activation in these structures is consistent with nicotine's behavior-arousing and behavior-reinforcing properties in humans. CONCLUSIONS: The identified brain regions have been previously shown to participate in the reinforcing, mood-elevating, and cognitive properties of other abused drugs such as cocaine, amphetamine, and opiates, suggesting that nicotine acts similarly in the human brain to produce its reinforcing and dependence properties.