The beta 1- and beta 2-adrenoceptor affinity and beta 1-blocking potency of S- and R-metoprolol.

1. The beta-adrenoceptor affinity and blocking potency of the two enantiomers and the racemate of metoprolol were investigated in vitro, by use of a receptor-binding technique, and in vivo in the anaesthetized cat. 2. The enantiomeric purity of the S- and R-form was: greater than 99.2% and greater than 99.9%, respectively. 3. The beta 1- and beta 2-adrenoceptor affinity (-log equilibrium dissociation constant) of the enantiomers was determined from competition binding experiments (radioligand: [125I]-(S)-pindolol) performed in membranes prepared from the guinea-pig left ventricular free wall (predominantly beta 1) and soleus muscle (beta 2). The beta 1-adrenoceptor affinity was (means +/- s.d.): 7.73 +/- 0.10 and 5.00 +/- 0.06 for the S- and R-form of metoprolol, respectively. The corresponding values for beta 2-adrenoceptors were 6.28 +/- 0.06 (S) and 4.52 +/- 0.09 (R). Thus, the difference in affinity for the two enantiomers was greater on beta 1- (about 500) than on beta 2-adrenoceptors (about 50). The beta 1-adrenoceptor selectivity of the S-form (about 30) was similar to that of the racemic metoprolol, while the R-form was almost non-selective (3 fold beta 1-selective). 4. In the anaesthetized cat, the (-log) intravenous doses (mumol kg-1) of S- and R-metoprolol causing a 50% reduction (ED50) in the heart rate response to sympathetic nerve stimulation were determined. The doses inducing a 25% depression (DD25) of the basal myocardial contractility were also estimated. For the two enantiomers, the beta 1-blocking potency (-log ED50) was 7.04 +/- 0.16 (S) and 4.65 +/- 0.16 (R).(ABSTRACT TRUNCATED AT 250 WORDS)     

The relationship between head size and intracranial volume in elderly subjects

OBJECTIVE: To study the relationship between parenchymal head volume (PHV) and intracranial volume (ICV), and to compare the ability of these two measurements to reflect the association between maximum mature brain volume and late-life cognition. METHODS: An elderly sample of humans with a range of cognitive functions from normality, via mild cognitive impairment (MCI) to dementia (mean age 78.6, S.D. 2.8; mean MMSE 25.4, S.D. 4.2) was examined. Head-to-head measurements of ICV and parenchymal head volume (PHV) were obtained from three-dimensional T1 weighted magnetic resonance images using automated procedures. Analyses of cognitive functions were based on continuous and categorial variables. RESULTS: PHV explained 55% of the variance in ICV. The ratio between PHV and ICV remained constant with increasing age and cognitive impairment. Measurements of PHV and ICV yielded comparable correlations with global cognitive performance. Group differences over gender and cognitive states were equally present in ICV and PHV. The relative risks of cognitive impairment that were associated with either small ICV or PHV were comparable. CONCLUSIONS: Measures of PHV can be considered as useful estimates of ICV and cerebral volume reserve.     

Neuroimaging tools to rate regional atrophy, subcortical cerebrovascular disease, and regional cerebral blood flow and metabolism: consensus paper of the EADC

Neuroimaging is a mainstay in the differential diagnosis of patients with cognitive impairment. The often equivocal clinical pictures, the prognostic uncertainty of the earliest stages of mild cognitive impairment, and the subtle brain changes mean that neuroimaging techniques are of potentially great incremental diagnostic value. A number of methods, ranging from very simple subjective visual ratings to highly sophisticated computerised tools, have been developed, which allow rating of structural and functional brain changes. The choice of the method is not obvious, and current guidelines provide no indications on which tools should be preferred. In this paper, we give indications for tools with demonstrated accuracy for detecting regional atrophy, cerebrovascular disease, and regional brain function, and discuss these according to increasing technological complexity, ranging from those with high feasibility that can be used at the patient's bedside to highly technological ones that require trained personnel and specific hardware and software.     

Inhibition and executive functioning in Type A and ADHD boys

The present study was aimed at clarifying the standing of Type A behavior, as measured by behavioral observations, relative to Attention Deficit Hyperactivity Disorder (ADHD), using measures of inhibitory control and executive functioning. The study sample included 20 boys exhibiting Type A behavior, 21 boys exhibiting Type B behavior and 14 boys diagnosed with ADHD, ranging in age from 7 to 12 years. The results of the present study showed that the Type A children differed from Type B children on two time-related variables, response latency and reaction time, in accordance with the view of Type As as time-urgent and impatient. Furthermore, in comparisons with the ADHD group, the Type A boys were found to be superior on several performance tasks, such as Go/no-go omissions, time reproduction, story recall and memory for sequences of hand movements, although similarities between Type A and ADHD boys were evidenced in terms of response latency and reaction time. In other words, although Type A boys were similar to ADHD boys in terms of overt displays of time-urgency and impatience, Type As do not display deficits with regard to executive functioning, of the kind often found when ADHD children are compared with normal controls. It may thereby be concluded that Type A behavior and hyperactivity/ADHD appear to be well differentiated except with regard to what may be interpreted as impatience. Speculations concerning differing origins of overtly similar characteristics of Type A behavior and ADHD should be considered in future research.     

Prognostic significance of white matter changes in a memory clinic population

Non-specific white matter changes (WMC) can be seen on neuroimaging of the brain in healthy elderly but are more common in dementia. WMC are correlated to specific cognitive deficits and might also contribute to global cognitive decline. The value of WMC as a predictor of cognitive impairment has been incompletely elucidated. We studied the prognostic significance of extensive WMC in a group of patients with memory disturbances, to evaluate if the presence of such changes predicts a poorer outcome. We retrospectively selected a group of 24 patients with prominent WMC on magnetic resonance imaging (MRI) and with different grades of memory impairment. We matched each patient, with regard to age, education, length of follow-up, initial score on the Mini Mental State Examination (MMSE) and initial diagnosis, to a patient without white matter pathology. The matched pairs were evaluated and the decrease in MMSE score after follow-up (range 2-4 years) was used as the outcome measure. Results showed no difference in the decrease in MMSE score at follow-up between patients with or without WMC. In conclusion, the presence of WMC in cognitively impaired patients had no effect on the progression rate of dementia, as measured by MMSE decline.     

Biochemical markers of cerebrospinal ischemia after repair of aneurysms of the descending and thoracoabdominal aorta

OBJECTIVE: To investigate the clinical potential of several markers of spinal cord ischemia in cerebrospinal fluid (CSF) and serum during aneurysm repair of the descending thoracic or thoracoabdominal aorta. DESIGN: Observational study of consecutive patients. Nonblinded, nonrandomized. SETTING: University hospital thoracic surgical unit. PARTICIPANTS: Eleven consecutive elective patients. INTERVENTIONS: Distal extracorporeal circulation and maintenance of CSF pressure <10 mmHg until intrathecal catheter removal. MEASUREMENTS AND MAIN RESULTS: CSF and serum levels of S100B (and its isoforms S100A1B and S100BB), neuronal-specific enolase (NSE), and the CSF levels of glial fibrillary acidic protein (GFAp) and lactate were determined. Two patients had postoperative neurologic deficit. One with a stroke showed a 540-fold increased GFAp, a 6-fold NSE, and S100B increase in CSF. One with paraplegia had a 270-fold increase in GFAp, a 2-fold increase in NSE, and 5-fold increased S100B in CSF. One patient without deficit increased GFAp 10-fold, NSE 4-fold, and S100B 23-fold in CSF. CSF lactate increased >50% in 6 of 9 patients without neurologic deficit. Serum S100B increased within 1 hour of surgery in all patients without any concomitant increase in CSF. S100A1B was about 70% of total S100B in both serum and CSF in patients with or without neurologic defects. S100B in CSF increased 3-fold in 3 of 9 asymptomatic patients. CONCLUSIONS: In patients with neurologic deficit, GFAp in CSF showed the most pronounced increase. Biochemical markers in CSF may increase without neurologic symptoms. There is a significant increase in serum S100B from surgical trauma alone without any increase in CSF.     

An ultrastructural study of serially sectioned Renshaw cells. II. Synaptic types

Boutons and synaptic contacts on 17 presumed Renshaw cells were studied ultrastructurally. All 17 neurons were postsynaptic to axon collateral boutons of intracellularly HRP-stained triceps surae α-motoneurons and located in lamina VII, ventromedially to the main motor nuclei.The boutons and synaptic contacts could be classified into two main categories on the basis of the synaptic vesicles: S-type boutons with spherical synaptic vesicles and F-type boutons with flattened vesicles, the α-motoraxon collateral boutons falling into the S-category. In addition, some S-type boutons containing neurofilaments and some being apposed by small presynaptic boutons were observed. The results are discussed in relation to earlier observations on the synaptology of central neurons, particularly spinal α-motoneurons.     

Mood effects of diazepam and caffeine

Changes in mood after administration of Diazepam and Caffeine were analyzed. Six aspects were studied: pleasantness, activation, extraversion, calmness, social orientation and control. In addition to this check list, mood ratings using magnitude estimation of selected adjectives were obtained. It was found that Diazepam decreased feelings of activation and extraversion and increased calmness. Caffeine had no clear effects on the check list, but on the magnitude estimation scale some effects opposite to those of Diazepam were observed. Men reported a higher degree of pleasantness than women after administration of Diazepam. No differences in heart rate were found. Few distinct scale values were utilized on the magnitude estimation scale and the discriminative power was found to be larger for the check list than for the magnitude estimation scale.     

Cardiovascular Effects of Zimelidine and Tricyclic Antidepressants in Conscious Rats *

Abstract: Blood pressure, heart rate and electrocardiograms were recorded in conscious rats during intravenous injections of consecutively increasing doses of zimelidine, amitriptyline, clomipramine, desipramine and imipramine. The tricyclic antidepressants (TCA's) increased blood pressure from low doses and induced shortlasting decreases in blood pressure at higher doses. Heart rate was initially increased by amitriptyline while the other TCA's tended to decrease heart rate dose-dependently. The TCA's prolonged the QRS and QT intervals dose-dependently from low doses and the PR interval from intermediate doses. Zimelidine did not affect blood pressure or heart rate until high doses were given. The PR interval was not affected by zimelidine. Moderate to high doses of zimelidine prolonged the QT length and high doses widened the QRS complex. The results indicate a good cardiovascular tolerance for zimelidine.