Mescaline-induced psychopathological, neuropsychological, and neurometabolic effects in normal subjects: experimental psychosis as a tool for psychiatric research.

The psychological, neuropsychological, and neurometabolic effects of the hallucinogenic agent mescaline were investigated in 12 normal men who were volunteers. Mescaline produced an acute psychotic state 3 1/2-4 hr after drug intake, as measured by the Brief Psychiatric Rating Scale (BPRS) and Paranoid Depression Scale (PDS). The Assessment of Altered States of Consciousness (APZ) questionnaire revealed specific effects of mescaline in the visual system. Neuropsychological effects were studied with a face/nonface decision task with known right-hemisphere advantage, in which mescaline induced a decrease of functioning of the right hemisphere. In functional brain imaging using single photon emission computed tomography (SPECT), mescaline produced a "hyperfrontal" pattern with an emphasis on the right hemisphere, which was correlated with mescaline-induced psychotic psychopathology. Our findings question the validity of the concept of hypofrontality as an explanation for schizophrenic symptomatology. The study of psychoactive substances under controlled laboratory conditions has the methodological advantage of intraindividual control, and hence, minimal variability of data.     

Dependence of presaccadic cortical potentials on the type of saccadic eye movement.

Premovement cortical potentials were studied with 4 types of saccadic eye movement: (a) visually triggered saccades of normal reaction time (RT; regular saccades); (b) visually triggered saccades of extremely short RT (express saccades); (c) saccades towards predicted target locations (anticipatory saccades); (d) saccades back towards predicted location of fixation point (refixation saccades). With all 4 saccade types a "presaccadic negativity" with the maximum at the vertex (Cz) was observed. A bilaterally symmetrical component contained in this potential (being smallest with almost unconsciously performed refixation saccades and smaller in trained than in naive subjects) appeared to be related mainly to the subjects' volitional effort. In addition, anticipatory and refixation saccades were preceded by an early, widespread contralateral negativity, which we relate to cortical activities that prepare, in general terms, action within or towards the hemifield containing the saccade goal. During the 60 msec before anticipatory saccades, a negativity occurred over the contralateral central lead, which may reflect neural activation in the frontal eye field (FEF) and premotor cortex. In contrast, regular saccades were preceded 30 msec before onset by a negativity over the contralateral parietal cortex, which probably reflects an activation of parietal visuo-motor neurons. No lateralization of the cortical potentials was observed before express saccades, which suggests that these saccades are generated in a reflex-like way mainly by subcortical mechanisms.     

Thalamic connections of the vestibular cortical fields in the squirrel monkey (Saimiri sciureus).

The afferent thalamic connections to cortical fields important for control of head movement in space were analysed by intracortical retrograde tracer injections. The proprioceptive/vestibular area 3aV, the neck-trunk region of area 3a, receives two thirds of its thalamic projections from the oral and superior ventroposterior nucleus (VPO/VPS), which is considered as the proprioceptive relay of the ventroposterior complex (Kaas et al., J. Comp. Neurol. 226:211-240, 1984). The parieto-insular vestibular cortex (PIVC, area retroinsularis, Ri) receives its main thalamic input from posterior parts of the ventroposterior complex and from the medial pulvinar. Anatomical evidence is presented that the posterior region of the ventroposterior complex is a special compartment within this principal somatosensory relay complex. The parietotemporal association area T3, mainly involved in visual-optokinetic signal processing, receives a substantial input from the medial, the lateral, and the inferior pulvinar. Dual tracer experiments revealed that about 5% of the thalamic neurons projecting to 3aV were spatially intermingled with neurons projecting to areas PIVC or T3. This spatial intermingling was distributed over small but numerous, circumscribed thalamic regions, called "common patches," which were found mainly in the intralaminar nuclei, the posterior group of thalamic nuclei, and the caudal parts of the ventroposterior complex. The "common patches" may indicate a functional coupling of area 3aV with the PIVC or area T3 on the thalamic level. In control experiments thalamic projections to the granular insula Ig and the anterior part of area 7, two cerebral structures connected with the vestibular cortical areas, were studied. Some overlap in the thalamic relay structures projecting to these areas with those projecting to the vestibular cortices was found. A quantitative evaluation of thalamic regions projecting to different cortical structures was performed by constructing so-called "thalamograms." A scheme was developed that describes the afferent thalamic connections by which vestibular, visual-optokinetic, and proprioceptive signals reach the vestibular cortical areas PIVC and 3aV.     

Assessment of intracranial hemodynamics in sleep apnea syndrome.

BACKGROUND AND PURPOSE: Sleep apnea syndrome may lead to changes in cerebral hemodynamics due to altered alveolar ventilation. We investigated the dynamics of CO2- and blood pressure-regulated alterations of cerebral blood flow velocities during apneic episodes and evaluated CO2 reactivity during different sleep stages. METHODS: A computer-assisted pulsed Doppler system (2 MHz) was used for continuous overnight recordings of middle cerebral artery flow patterns together with simultaneous polysomnography, continuous blood pressure recordings, and measurements of end-expiratory CO2 in six patients with sleep apnea syndrome. RESULTS: Increases in mean flow velocity of 19-219% and in blood pressure of 12.5-83.1% could be observed during the apneic episodes, with maximum increases during rapid eye movement (REM) sleep. CO2 reactivity was in the normal range (4.4 +/- 1.2%) in the waking state and was markedly increased during sleep stages 1 and 2 (p less than 0.005 compared with awake). The greatest increase was found during REM sleep, with a rise of up to three times the waking value (p less than 0.0001 compared with sleep stage 2). CONCLUSIONS: The changes of mean flow velocity could be interpreted as reactive adaptation processes because of CO2 and blood pressure increases corresponding to apnea. The increased CO2 reactivity during sleep may indicate a "hypersensitivity" of intracranial vascular CO2 or pH receptors and a disturbance of central catecholaminergic and cholinergic systems. The pronounced velocity changes during apneic episodes and the concomitant alterations of vessel wall tension might lead to microangiopathies and macroangiopathies due to chronic strain on the brain vessels.     

Dose finding study of telenzepine (1.5 vs. 3 vs 5 mg once daily) in acute treatment of duodenal ulcer. A double-blind, randomized, multicenter parallel group comparison

Three different doses of the M1-selective antimuscarinic compound telenzepine were investigated in the treatment of acute duodenal ulcer in a randomized, double-blind dose-range finding study. In four investigating centers, 120 patients with endoscopically proven, florid duodenal ulcer were treated with either 1.5 mg, 3 mg or 5 mg telenzepine once daily at bedtime (40 patients per dose group). After two weeks of treatment differences in the healing rates were statistically not significant. After four weeks the ulcers of 26 (65%) patients in the 1.5 mg group and 34 (85%) and 31 (78%) in the 3 mg and 5 mg groups, respectively, were completely healed. Only the difference in the healing rates between the 1.5 and 3 mg groups was significant at p less than 0.05. Mean reductions in ulcer area were 90% (1.5 mg), 97% (3 mg) and 93% (5 mg) after four weeks; 1.5 vs. 3 mg, p less than 0.025. These results show that telenzepine dose-dependently accelerates ulcer healing and that maximal effect is obtained with the 3-mg dose. The ulcer symptoms were dose-dependently alleviated. Dry mouth of moderate or severe intensity was stated more frequently under 5 mg telenzepine (by 14% of patients) than under 1.5 and 3 mg (5% each). The antimuscarinic side effect "disturbed accommodation" was rarely found. It is concluded that once daily administration of 3 mg in the evening must be regarded as the optimal dosage regimen of telenzepine.     

Trommsdorff and his relations to dentistry

In the mirror of the publication "Kallopistria oder die Kunst der Toilette für die elegante Welt" (1805) the scarcely noticed relations to dentistry in the total work of the Erfurter university professor and dispensing chemist J. B. Trommsdorff (1770-1837) are represented. Thw new details og the correlation pharmacy-dentistry at the beginning 19th century are presented.     

Low T3 syndrome and chronic inflammatory rheumatism

For the clarification of pathogenesis and clinical relevance of decreases of the triiodothyronine (T3) level in patients with chronic inflammatory rheumatism in a group of 63 patients with clinically, paraclinically and roentgenologically diagnosed rheumatoid arthritis (59 times) and with SLE (4 times), respectively, parallel were determined parameters of the thyroid gland function and of the rheumatic activity as well as a subtile drug anamnesis for the medication of antirheumatic drugs was established. In 33 of the 63 patients who were included into the study decreases and low normal values, respectively, for the total T3 (TT3 less than 1.5 nmol/l) were found. In comparison to the remaining 30 patients with normal TT3 a typical constellation of paraclinical parameters of the thyroid gland with distinct reduction of TT3 and free T3 (FT3), low normal total T4 (TT4), slight increase of the reverse T3 (rT3), moderate decrease of the basal and stimulated TSH and an only very small restriction of the binding capacity of the thyroid hormone (TBG) were found. A clinically relevant hypothyroidism is thus to be excluded with certainty. Antirheumatic drugs, in particular steroidal ones (glucocorticoids) may on principle also induce such paraclinical constellations, related to the thyroid gland. In our investigations a therapy with antirheumatic drugs is causally scarcely considered, since both in the group of patients with decrease of T3 and without decrease comparable quantities of antirheumatic drugs including glucocorticoids were administered and the cortisol values in the plasma do not differ. The investigations confirm our already formerly expressed supposition that also in rheumatics a "low-T3-syndrome" is existing as it is otherwise described in consumptive extrathyroidal diseases (NTI).(ABSTRACT TRUNCATED AT 250 WORDS)     

Histologic features in autoimmune hepatitis

In order to see if the term of "plasma cell hepatitis", dating back to the early sixties, is still valid as a morphological diagnosis for autoimmune chronic hepatitis (AICH), and to find out if the existence of several subgroups is reflected by histopathology, we investigated 26 patients with chronic hepatitis, who met the criteria of autoimmune hepatitis based on tests for antinuclear, anti-smooth muscle antibodies (SMA) and on immunoassays for liver-kidney-microsomal (LKM) antigen, liver membrane antigen (LMA), and soluble liver antigen (SLA). In our material autoimmune hepatitis represent the entire spectrum of chronic hepatitis with variable inflammatory activity ranging from chronic persistent hepatitis to severe inflammatory lesions in chronic active hepatitis with transition to cirrhosis. When compared to viral chronic hepatitis A and non-A, non-B, however, characteristic features can be evaluated consisting in broad hypocellular areas of collapse and microacinar transformation of hepatocytes with hydropic swelling being the predominant type of cell lesion. Eosinophilic clumping and acidophilic necrosis were insignificant. Plasma cells were not a constituent feature of AICH. From this histopathologic pattern it may be concluded that the disease seems to run a sluggish course in most patients, however, in few cases a dramatic development may determine the disease with fatal acute episodes which are terminated by death or fade into slow progression. The different subgroups could not be distinguished by histopathology.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Role of Horizontal Connections in Generating Long Receptive Fields in the Cat Visual Cortex

The cells in the primary visual cortex possess numerous functional properties that are more complex and varied than those seen in the cortical input. These properties result from the network of intrinsic cortical connections running across the cortical layers and between cortical columns. In the current study we relate the long receptive fields that are characteristic of layer 6 cells to the input that these cells receive from layer 5. The axons of layer 5 pyramidal cells project over long distances within layer 6, enabling layer 6 cells to collect input from regions of cortex representing large parts of the visual field. When layer 5 was locally inactivated by injection of the inhibitory transmitter GABA, layer 6 cells lost sensitivity over the portion of their receptive fields corresponding to the inactivated region of layer 5. This suggests that the extensive convergence in the projection from layer 5 to layer 6 is responsible for generating the long receptive fields characteristic of the layer 6 cells.     

Measured attenuation correction methods

Accurate attenuation correction is a prerequisite for the determination of exact local radioactivity concentrations in positron emission tomography. Attenuation correction factors range from 4–5 in brain studies to 50–100 in whole body measurements. This report gives an overview of the different methods of determining the attenuation correction factors by transmission measurements using an external positron emitting source. The long-lived generator nuclide⁶⁸Ge/⁶⁸Ga is commonly used for this purpose. The additional patient dose from the transmission source is usually a small fraction of the dose due to the subsequent emission measurement. Ring-shaped transmission sources as well as rotating point or line sources are employed in modern positron tomographs. By masking a rotating line or point source, random and scattered events in the transmission scans can be effectively suppressed. The problems of measured attenuation correction are discussed: transmission/emission mismatch, random and scattered event contamination, counting statistics, transmission/emission scatter compensation, transmission scan after administration of activity to the patient. By using a double masking technique simultaneous emission and transmission scans become feasible.This article was presented at the 1st EEC workshop on accuracy determination in PET, January 19–20th. 1989 Pisa, Italy (COMAC-BME Concerted Project Characterization and Standardization of PET Instrumentation)