Cerebral blood flow relationships associated with a difficult tone recognition task in trained normal volunteers

Tone recognition is partially subserved by neural activity in the right frontal and primary auditory cortices. First we determined the brain areas associated with tone perception and recognition. This study then examined how regional cerebral blood flow (rCBF) in these and other brain regions correlates with the behavioral characteristics of a difficult tone recognition task. rCBF changes were assessed using H2(15)O positron emission tomography. Subtraction procedures were used to localize significant change regions and correlational analyses were applied to determine how response times (RT) predicted rCBF patterns. Twelve trained normal volunteers were studied in three conditions: REST, sensory motor control (SMC) and decision (DEC). The SMC-REST contrast revealed bilateral activation of primary auditory cortices, cerebellum and bilateral inferior frontal gyri. DEC-SMC produced significant clusters in the right middle and inferior frontal gyri, insula and claustrum; the anterior cingulate gyrus and supplementary motor area; the left insula/claustrum; and the left cerebellum. Correlational analyses, RT versus rCBF from DEC scans, showed a positive correlation in right inferior and middle frontal cortex; rCBF in bilateral auditory cortices and cerebellum exhibited significant negative correlations with RT These changes suggest that neural activity in the right frontal, superior temporal and cerebellar regions shifts back and forth in magnitude depending on whether tone recognition RT is relatively fast or slow, during a difficult, accurate assessment.      

CORRELATION BETWEEN THE NUMBER OF MITOTIC FIGURES AND THE PERCENTAGE OF Ki67-POSITIVE CELLS IN NON-HODGKIN’S LYMPHOMAS

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Role of 5-HT1A autoreceptors in the mechanism of action of serotoninergic antidepressant drugs: recent findings from in vivo microdialysis studies

Summary— Although a new generation of selective serotonin reuptake inhibitors (SSRIs) has been introduced in therapeutics as antidepressant drugs, a two to four week lag period still occurs between starting treatment with SSRIs and the onset of therapeutic effects in man. In vivo cerebral microdialysis can be used to measure extracellular concentrations of serotonin (5-hydroxytryptamine, 5-HT), which reflect intrasynaptic events. With the coupling of this new experimental method to very sensitive analytical assays such as liquid chromatography with electrochemical detection, it has recently been possible to obtain two major arguments supporting the hypothesis that somatodendritic 5-HT_1A autoreceptors situated in the raphe nuclei play an important role in the mechanism of action of SSRIs. First, in the rat, single administration of SSRIs at low doses comparable to those used therapeutically increases extracellular 5-HT concentrations in the vicinity of the cell body and the dendrites of serotoninergic neurones of the raphe nuclei. This effect is more marked than that observed in regions rich in nerve endings (frontal cortex). The magnitude of the activation of the serotoninergic neurotransmission depends on the brain area studied and the dose of the SSRIs administered to rats. This could be explained by simultaneous activation of somatodendritic 5-HT_1A autoreceptors by endogenous 5-HT in the raphe nuclei, thereby limiting the corticofrontal effects of the antidepressant. Second, SSRIs cause a larger increase in extracellular 5-HT concentrations in the nerve endings when administered chronically: 5-HT autoreceptors may have gradually desensitized during the 2–4 weeks of treatment with SSRIs. Preliminary studies of patients with depression appear to confirm these experimental results, as co-administration of a 5-HT_1A autoreceptor antagonist and a SSRI accelerated the onset of the antidepressant effect (< 1 week).     

SCREENING AND TREATMENT FOR HYPERUPIDAEMIA IN NON-INSULIN-DEPENDENT DIABETES: A PROSPECTIVE ASSESSMENT OF 350 PATIENTS

SUMMARY This report presents experiences in screening 350 non-insulin-dependent diabetics for hypercholesterolemia and results of 1 year's treatment. Mean serum total cholesterol was 6.4 mmol/l at screening; 46 patients whose initial total serum cholesterol was above 7.0 mmol/l attended for detailed assessment and treatment. Mean total cholesterol concentrations fell between screening and review (7.8 vs 7.1 mmol/l, P<0.01). Levels fell below 7.0 mmol/l in 13 patients with diet alone. After excluding patients with secondary dyslipidaemia (including poor diabetic control), 10 patients received lipid-lowering drug treatment. Total cholesterol and triglyceride concentrations fell significantly and the HDL/non- HDL cholesterol ratio improved on treatment. Screening diabetic patients identifies a small group of hyperlipidaemic patients, whose lipoprotein profiles improve with drug treatment. Many of those screened, however, do not ultimately require drug treatment using a cut-off of 7.0 mmol/l.     

BLOOD PRESSURE CONTROL AND CARDIOVASCULAR RISK IN PATIENTS OF INDO-ASIAN AND AFRICAN-CARIBBEAN DESCENT

SUMMARY Hypertension is a major risk factor for premature death. Large outcome studies have demonstrated reduced morbidity and mortality associated with antihypertensive therapy in mixed patient populations, but data on morbidity and mortality in defined ethnic groups are lacking. Management of cardiovascular risk factors, which frequently coexist with hypertension, presents a logical management strategy in these patients. Indo-Asian patients are particularly prone to insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM), which are associated in turn with potentially atherogenic lipid profiles and poor cardiovascular outcomes. Diuretics and β-adrenoceptor blockers exert theoretically adverse effects on lipid profiles and should be used with caution in Indo-Asian patients at risk of developing NIDDM. Hypertensive African-Caribbean patients are at increased risk of stroke and tend to suffer greater target organ damage, including renal dysfunction and cardiac hypertrophy. Hypertension in African-Caribbean patients is less sensitive to β-adrenoceptor blockade or ACE inhibition than in white patients. Selective α₁-adrenoceptor antagonists and calcium channel blockers are equally effective antihypertensive agents in all races. While calcium channel blockers are metabolically neutral, α₁-adrenoceptor blockers promote a potentially less atherogenic lipid profile. Further study of the effects of antihypertensive treatment on morbidity and mortality in ethnic groups is required, particularly in Indo-Asian patients.