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Biomedical subjects

U Jürgens

Publications and source records attributed to U Jürgens.

At least 19 recordsLinked to original sources

Lack of cortico-striatal projections from the primary auditory cortex in the squirrel monkey.

The projections of the superior temporal gyrus to the caudate nucleus were studied in 10 squirrel monkeys (Saimiri sciureus). It was found that the primary auditory cortex lacks direct connections with the caudate nucleus as well as the putamen. Areas RL and T1 of Burton and Jones, bordering the primary auditory cortex laterally, show a moderate projection to the body and tail of the caudate nucleus; area T2, bordering areas RL and T1, shows an extensive projection into the head, body and tail. A comparison of the temporo-caudate projections of the monkey with those of rodents and carnivores suggests that primary and secondary auditory cortices differ in their connections in primates more than in other mammals, pointing to a greater functional differentiation of these areas in primates.

Animals

Photometric determination of human serum bromide levels--a convenient biomonitoring parameter for methyl bromide exposure.

Methyl bromide is one of the most important pesticides for the control of insects, fungi and nematodes. Serum bromide has been proposed as a biomonitor for occupational exposure to methyl bromide. Therefore, a novel, sensitive photometric method was developed for the determination of serum bromide at concentrations relevant for such exposure. Further possible applications are monitoring of intoxication victims and halothane narcosis. Using the method we have established a mean serum bromide level of 4.13 +/- S.D. 1.05 mg/l (n/64) in a group of healthy female and male volunteers not knowingly exposed to bromide or bromine containing organics. Serum of a subject accidently exposed to methyl bromide revealed a bromide level of 11.5 mg/l serum, while two individuals exposed to methyl iodide had no elevated levels. A group of 30 agricultural workers showed a mean serum bromide level of 15.33 +/- S.D. 1.90 mg/l at the end of the methyl bromide application season.

Bromides

Comparison between premortem and postmortem serum concentrations of phenobarbital, phenytoin, carbamazepine and its 10,11-epoxide metabolite in institutionalized patients with epilepsy.

The last premortem serum concentrations of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ) and its CBZ-10,11-epoxide metabolite (CE) were compared with the corresponding postmortem serum concentrations in 16 adult patients of an epilepsy centre. Based on complete postmortem examinations, 12 individuals showed a known cause of death (KCD) and four patients succumbed from sudden unexplained death (SUD). The last premortem and the postmortem serum levels of PB (r = 0.991), PHT (r = 0.986), CBZ (r = 0.985) and CE (r = 0.936) were highly correlated. However, the regression analysis indicated that, except for CE, the premortem concentrations were significantly higher than the postmortem concentrations, i.e. 65% for PB, 34% for PHT, and 16% for CBZ. Varying time lapses (4-62 h) between death and serum sampling during autopsy did not significantly influence the ratio of premortem to postmortem serum levels for PB, PHT, CBZ, and CE (p > 0.1). Furthermore we found no significant differences between the premortem and the postmortem serum concentration ratios CE/CBZ. Considering the above variables, the data of SUD and KCD patients were comparable. Postmortem decrease in anticonvulsant serum concentrations, especially for PB and PHT, should be considered in order to avoid misinterpretation in respect to so-called 'subtherapeutic' serum levels and noncompliance in context with SUD or fatal intoxication.

Adult

Influence of oxcarbazepine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication: results of a retrospective study.

The aim of this retrospective study was to investigate the influence of oxcarbazepine (OCBZ) and methsuximide (MSM) on lamotrigine (LTG) serum concentrations. The effect of OCBZ compared to carbamazepine (CBZ) and the effect of MSM on LTG serum concentrations were examined in patients with and without valproic acid (VPA) comedication. Altogether, 376 samples from 222 patients were analyzed in routine drug monitoring. Two or more serum samples from the same patient were considered only if the comedication had been changed. For statistical evaluation, regression analytical methods and an analysis of variance were performed. For the analysis of variance, the LTG serum concentration in relation to LTG dose/ body weight--level-to-dose ratio (LDR), in (microg/mL)/(mg/kg)--was calculated and compared for different drug combinations. The nonlinear regression analysis including the LTG dose per body weight, age, gender, and the different kinds of comedication revealed that these variables have a significant influence on LTG serum concentration (r2 = 0.724). The relationship between LTG dose/body weight and serum concentration deviates only slightly from linearity, the LTG concentration was about 18% lower in women than in men, and age had a significant influence. The data indicate that children have significantly lower LTG concentrations than adults on a comparable LTG dose per body weight and that children may be more prone to enzyme induction by comedicated drugs. Methsuximide has a strong inducing effect on the LTG metabolism and decreases the LTG concentrations markedly (about 70% compared to LTG monotherapy). Carbamazepine also reduces the LTG concentrations considerably (by 54%). The inducing effect of OCBZ (29%) was less pronounced but also significant. The inducing effect of MSM, CBZ, and OCBZ was also seen in combination with VPA: VPA alone increases the LTG concentration approximately 211%, whereas in addition to MSM (8%), CBZ (21%), or OCBZ (111%), the increase of LTG was significantly smaller. The analysis of variance confirmed the results of the regression analysis. The effect of MSM on the LTG concentration should be considered if MSM is added or withdrawn in patients treated with LTG. Oxcarbazepine had a less pronounced inducing effect on LTG metabolism compared to CBZ. If CBZ is replaced by OCBZ as comedication, an increase in LTG serum concentrations should be expected.

Adolescent

Neuronal control of mammalian vocalization, with special reference to the squirrel monkey.

Squirrel monkey vocalization can be considered as a suitable model for the study in humans of the neurobiological basis of nonverbal emotional vocal utterances, such as laughing, crying, and groaning. Evaluation of electrical and chemical brain stimulation data, lesioning studies, single-neurone recordings, and neuroanatomical tracing work leads to the following conclusions: The periaqueductal gray and laterally bordering tegmentum of the midbrain represent a crucial area for the production of vocalization. This area collects the various vocalization-triggering stimuli, such as auditory, visual, and somatosensory input from diverse sensory-processing structures, motivation-controlling input from some limbic structures, and volitional impulses from the anterior cingulate cortex. Destruction of this area causes mutism. It is still under dispute whether the periaqueductal region harbors the vocal pattern generator or merely couples vocalization-triggering information to motor-coordinating structures further downward in the brainstem. The periaqueductal region is connected with the phonatory motoneuron pools indirectly via one or several interneurons. The nucleus retroambiguus represents a crucial relay station for the laryngeal and expiratory component of vocalization. The articulatory component reaches the orofacial motoneuron pools via the parvocellular reticular formation. Essential proprioceptive feedback from the larynx and lungs enter the vocal-controlling network via the solitary tract nucleus.

Animals

Comparison of total and free phenytoin serum concentrations measured by high-performance liquid chromatography and standard TDx assay: implications for the prediction of free phenytoin serum concentrations.

The free fraction of phenytoin (PHT) in serum increases considerably in combination with valproic acid (VPA), depending on the VPA concentration. Equations to predict the free PHT concentration (PHTf) from the total PHT concentration (PHTt) and from the VPA concentration were developed by Haidukewych and colleagues. (equation 1: PHTf = 0.095 x PHTt + 0.001 x VPA x PHTt) and May and colleagues (equation 2: PHTf = 0.0792 x PHTt + 0.000636 x VPA x PHTt]; in both equations, PHTf, PHTt, and VPA are given in microg/ml. Obviously, the equations give different predictions. The aim of this study was to investigate whether different methods for the determination of PHTt and PHTf were responsible for the differences; equation 1 was calculated from standard TDx measurements and equation 2 from high-performance liquid chromatography (HPLC) values. A total of 52 samples from patients with VPA (n=26) or without VPA (n=26) were analyzed using HPLC and TDx. The concentrations measured by HPLC and TDx were highly correlated but TDx yields significantly higher PHTt (Y = 0.98 x X + 2.46; X = HPLC, Y = TDx, r2 = 0.957) and, in particular, higher PHTf concentrations (Y = 1.03 x X + 0.30; X = HPLC, Y = TDx, r2 = 0.919), compared with our HPLC method. The accuracy of the predictive equations depends on the method used for the determination of PHTt and PHTf. The best predictions of PHTf were obtained if equation 2 and HPLC measurements were used. However, the differences in the predicted PHTf could only partly be explained by the different methods of determination.

Chromatography, High Pressure Liquid

Dual-channel telemetry system for recording vocalization-correlated neuronal activity in freely moving squirrel monkeys.

A miniature telemetric system is described which allows simultaneous measurements of neural activity and vocalization in freely moving monkeys within their social group. Single and multi-unit activities were detected with medium impedance electrodes that were fixed to self-made microdrives allowing accurate vertical positioning over a range of 8 mm. Vocalizations were registered by means of a piezo-ceramic device sensing the vocalization-induced skull vibrations. This allowed identification of the vocalizing animal in a larger group and eliminated environmental noise. Neuronal activity and vocalization were transmitted via separate channels of a FM transmitter using different carrier frequencies. The signals were decoded in two conventional FM receivers equipped with an automatic frequency control. The signals were stored for off-line analysis on a HiFi videotape recorder.

Amplifiers, Electronic

Concentrations of lamotrigine in a mother on lamotrigine treatment and her newborn child.

OBJECTIVE: To investigate the transfer of lamotrigine in pregnancy and during lactation from a mother on lamotrigine treatment to her child. METHODS: Concentrations of lamotrigine were measured by high-pressure liquid chromatography in umbilical cord serum and in serum samples of the mother and her child as well as in the mother's milk during the first five postpartum months. RESULTS: In the child lamotrigine serum concentrations (up to 2.8 micrograms ml-1) comparable to those usually achieved in active treatment with lamotrigine were found not only after birth, but also during lactation. A considerable amount of lamotrigine (2-5 mg per day) was excreted in breast milk. No adverse effects were seen in the child. CONCLUSION: The transfer of lamotrigine taking place during pregnancy and lactation should not be neglected. In this case the child should be thoroughly observed for potential adverse effects.

Adult

Anterograde projections of the cortical tongue area of the tree shrew (Tupaia belangeri).

In altogether seven tree shrews, Tupaia belangeri, the anterograde projections of the motorcortical tongue area were investigated as part of a larger comparative study. Identification of the tongue area was carried out by electrical brain stimulation. Three different tracers were used: biotin-conjugated dextranamine (BDA), Phaseolus vulgaris leucoagglutinin (PHA-L) and 3H-leucine. Intracortical projections were found to the motor cortex around the injection site, the premotor cortex, supplementary motor area, the homologues of the primate frontoparietal operculum and insula, the anterior cingulate and agrannular retrosplenial cortex, the somatosensory and bordering inferior parietal cortex as well as to the perirhinal cortex. Except the very weak projections into the retrosplenial, posterior parietal and perirhinal region which were ipsilateral, all other projections were bilateral. Subcortically, there was a projection into the ventral putamen, rostrodorsal claustrum and, very sparsely, into the caudate nucleus. In the thalamus, terminal labeling was found in the nuclei reticularis, anteroventralis, anteromedialis, ventralis lateralis, ventralis posterior medialis, ventralis posterior inferior, medialis dorsalis, in the intralaminar nuclei paracentralis, centralis lateralis, centrum medianum and parafascicularis, in the midline thalamus and in the nuclei posterior and pulvinaris. Further diencephalic projections, however all of them wak, could be traced into the zona incerta, dorsolateral subthalamus, dorsomedial, lateral and supraoptic hypothalamus. In the midbrain, labeling was found in the deep layers of the lateral superior colliculus, in the bordering reticular formation and, very sparsely, in the periaqueductal grey. In the lower brain-stem, fibres ended in the griseum pontis, dorsolateral reticular formation, principal and spinal trigeminal nucleus and, sparsely, in the lateral parabrachial region, solitary tract nucleus, inferior olive and magnocellular reticular formation. No terminals were found in the hypoglossal nucleus. The projection system revealed with PHA-L was less extensive than that demonstrated with BDA and 3H-leucine, both of which were similar.

Animals

The role of the periaqueductal grey in limbic and neocortical vocal fold control.

The effects of a pharmacological blockade of the periaqueductal grey of the midbrain (PAG) on the elicitability of vocal fold movements from the facial motor cortex on the one hand and the anterior cingulate cortex and dorsomedial hypothalamus on the other were studied in the squirrel monkey. PAG blockade abolished vocal fold activity induced by the cingulate cortex and hypothalamus, but not that induced by the neocortex. These results point to the existence of two separate vocal fold control pathways at midbrain level: one limbic, responsible for non-verbal emotional vocal utterances, and one neocortical, responsible for the production of learned vocal patterns. The PAG represents a crucial relay station of the limbic but not the neocortical vocal control pathway.

Animals

Lack of influence of histopathological changes on carbamazepine and carbamazepine-10, 11-epoxide concentrations in the brain cortex of epileptic patients.

Post-mortem concentrations of carbamazepine (CBZ) and its anticonvulsive metabolite carbamazepine-10,11-epoxide (CE) were determined in different lesions of the cerebral cortex and in the serum (total and free) from 13 epileptic patients. Twenty cortical specimens were obtained from the superior frontal gyrus, the temporopolar region and the neocerebellum. The cortical samples showed various pathological changes characterized by augmented glial cells, fibre gliosis or ulegyria as well as abundant corpora amylacea or encephalitic signs of viral type besides neuronal depletion. The CBZ and CE concentrations in the 20 cortical lesions were not significantly decreased when compared to the control specimens of 32 epileptic patients without essential histopathological alterations of the specified cortical areas (p < 0.05). A comparable result had been found in our former study on phenytoin (PHT) and phenobarbital (PB). Six patients with cortical lesions of the present series had already been included in this PHT/PB study. Five of these patients revealed unchanged CBZ and CE as well as PHT and PB concentrations. Only in one neocerebellar specimen the CE concentration was just above the upper 95% confidence limit of the control group. But, most probably this finding has no further relevance. The results greatly favour the nonspecific binding of CBZ and CE to cerebral tissue constituents.

Adult

Relationship between ischemic damage and concentrations of phenytoin and phenobarbital in the brain cortex of epileptic patients in vegetative state at death.

Post-mortem concentrations of phenytoin (PHT) and phenobarbital (PB) were determined by high-performance liquid chromatography in the cortical matter of specified brain regions and in the serum (total and free) from 3 epileptic males in vegetative state and compared to the data of 45 deceased epileptic control patients. The duration of the vegetative state was 12 days, 15 days or about 4 months until death and was associated with corresponding stages of generalized ischemic brain damage. The histological examination was completed by immunohistochemical and morphometric methods. According to other investigators nerve cells are the major binding sites for PHT and PB in the cerebral cortex of rodents. But, in the 3 comatose patients the PHT and PB concentrations of the isocortex and neocerebellum were not significantly decreased in comparison with the control patients despite necrosis and loss of neurons as well as other distinct tissue alterations. The results strongly favor the non-specific binding of PHT and PB to cells and subcellular structures of the brain-mainly based on simple physico-chemical principles.

Adult

Serum concentrations of lamotrigine in epileptic patients: the influence of dose and comedication.

Lamotrigine (LTG) is a new antiepileptic drug (AED), chemically unrelated to the drugs in current use. Previous studies have shown that LTG has only a limited effect on other AEDs, but its own metabolism can be strongly induced or inhibited by the comedication. We investigated the influences of carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), valproic acid (VPA), and combinations of these drugs on the serum concentration of LTG. A total of 588 blood samples from 302 patients were analyzed. The mean duration of LTG therapy was 141 +/- 137 days (mean +/- SD). A patient was only considered twice in this study if his or her comedication had been changed. The LTG serum concentration in relation to LTG dose/body weight (level-to-dose ratio, LDR, microgram/ml/mg/kg) was calculated and compared for different drug combinations. The results showed that comedication had a highly significant (p < 0.001) influence on the LTG serum concentrations. The mean LDR for LTG was 0.32 (LTG + PHT) < 0.52 (LTG + PB) approximately equal to 0.57 (LTG + CBZ) < 0.98 (LTG mono) approximately equal to 0.99 (LTG + VPA + PHT) < 1.67 (LTG + VPA + CBZ) approximately equal to 1.80 (LTG + VPA + PB) < 3.57 (LTG + VPA (<, p < 0.05; approximately equal to, p > 0.05, multiple comparisons). The mean LTG concentrations in patients on comedication with VPA were about two times higher than on patients on LTG monotherapy or on comedication without VPA (5.0 vs. 2.6 micrograms/ml), despite the LTG doses being half as high (3.0 vs. 5.9 mg/kg). The correlations of the serum concentrations and doses of CBZ, PB, PHT, and VPA with the LDR of LTG were only weak or not significant. Furthermore, the distribution of LTG serum concentrations and dosages was compared with the tentative therapeutic range for the LTG concentration (1-4 micrograms/ml), proposed by some investigators, and the recommendations for the LTG dosage. Remarkable discrepancies were observed. The comedication has an important influence on the LTG concentration and should be considered in LTG dosage.

Adult

C-fos expression during vocal mobbing in the new world monkey Saguinus fuscicollis.

In order to find brain areas involved in the vocal expression of emotion, we compared c-fos expression in three groups of saddle-back tamarins (Saguinus fuscicollis). One group, consisting of three animals, was made to utter more than 800 mobbing calls by electrical stimulation of the periaqueductal grey of the midbrain (PAG). A second group, consisting of two animals, was stimulated in the PAG with the same intensity and for the same duration as the first group but at sites that did not produce vocalization. These sites lay somewhat medial to the vocalization-eliciting sites. A third group, consisting of two animals, was stimulated at vocalization-eliciting sites in the PAG but with an intensity below vocalization threshold. Fos-like immunoreactivity that was found in the vocalizing but not in the non-vocalizing animals was located in the dorsomedial and ventrolateral prefrontal cortex, anterior cingulate cortex, ventrolateral premotor cortex, sensorimotor face cortex, insula, inferior parietal cortex, superior temporal cortex, claustrum, entorhinal and parahippocampal cortex, basal amygdaloid nucleus, anterior and dorsomedial hypothalamus, nucleus reuniens, lateral habenula, Edinger-Westphal nucleus, ventral and dorsolateral midbrain tegmentum, nucleus cuneiformis, sagulum, pedunculopontine and laterodorsal tegmental nuclei, ventral raphe, periambigual reticular formation and solitary tract nucleus. For some of these structures (e.g. anterior cingulate cortex and periambigual reticular formation), there is evidence also from electrical stimulation, lesioning and single-unit recording studies that they are involved in vocal control. For other structures (e.g. lateral habenula, Edinger-Westphal nucleus), the available evidence speaks against such a role. Fos activation in these cases is probably related to non-vocal reactions accompanying the electrically elicited vocalizations. A third group of structures consists of areas for which a role in vocal control cannot be excluded but for which the present study presents the first evidence for such a role (e.g. claustrum and sagulum). These structures deserve further studies using more specific methods.

Animals

Lack of effect of histological lesions on the phenytoin and phenobarbital concentrations in the brain cortex of epileptic patients.

Postmortem concentrations of phenytoin (PHT) and phenobarbital (PB) were determined in 24 specimens of the frontal, temporal, occipital or neocerebellar cortex with different pathological changes and in the serum (total and free) from 11 epileptic patients. The cortical lesions were characterized by various degrees of neuronal loss or necrosis associated with other changes such as proliferated gliocytes, fibre gliosis, Rosenthal fibres or numerous corpora amylacea. According to other investigators neurons are the main binding sites of PHT and PB in rodent brains. The PHT and PB concentrations in 20 cortical lesions from nine patients were not significantly reduced as compared to the data of 46 deceased epileptic control patients. A significantly decreased PB value could only be demonstrated in the temporal specimen of an old scarred infarction with complete demyelination. On the other hand a slight but significant increase of PB was observed in three neocortical samples from a child exhibiting severe brain oedema and thrombosis of the sinuses. The results favour the unspecific binding of PHT and PB to cerebral tissue constituents and do not support the hypothesis of major binding to specific receptors.

Aged

The role of the periaqueductal grey in vocal behaviour.

This is a review of our current knowledge about the role of the periaqueductal grey (PAG) in vocal control. It shows that electrical stimulation of the PAG can evoke species-specific calls with short latency and low habituation in many mammals. The vocalization-eliciting region contains neurones the activity of which is correlated with the activity of specific laryngeal muscles. Lesioning studies show that destruction of the PAG and laterally bordering tegmentum can cause mutism without akinesia. Neuroanatomical studies reveal that the PAG lacks direct connections with the majority of phonatory motoneurone pools but is connected with the periambigual reticular formation, an area which does have direct connections with all phonatory motor nuclei. The PAG receives a glutamatergic input from several sensory areas, such as the superior and inferior colliculi, solitary tract nucleus and spinal trigeminal nucleus. Glutamatergic input, in addition, reaches it from numerous limbic structures the stimulation of which also produces vocalization, such as the anterior cingulate cortex, septum, amygdala, hypothalamus and midline thalamus. Pharmacological blocking of this glutamatergic input causes mutism. The glutamatceptive vocalization-controlling neurones are under a tonic inhibitory control from GABAergic neurones. Removal of this inhibitory input lowers the threshold for the elicitation of vocalization by external stimuli. A modulatory control on vocalization threshold is also exerted by glycinergic, opioidergic, cholinergic, histaminergic and, possibly, noradrenergic and dopaminergic afferents. It is proposed that the PAG serves as a link between sensory and motivation-controlling structures on the one hand and the periambigual reticular formation coordinating the activity of the different phonatory muscles on the other.

Animals

Role of extralaryngeal muscles in phonation of subhuman primates.

1. The electromyographic activity of eight external laryngeal and hyoid muscles was recorded during vocalization in the squirrel monkey (Saimiri sciureus). Calls of different types were elicited by electrical stimulation of the central grey of the midbrain in narcotized animals. 2. Peeping, a short, high-pitched call with minor frequency modulations, is associated with a marked activity in the cricothyroid, a moderate activity in the thyrohyoid, a weak activity in the sternohyoid and no activity in the sternothyroid, omohyoid, mylohyoid and anterior digastric muscles. 3. Chuck, a short, plosive call with a steep frequency descent over several kHz, is associated with a marked activity in the cricothyroid, a moderate activity in the thyrohyoid, sternothyroid and mylohyoid, a weak activity in the sternohyoid and omohyoid, and no or rare activity in the anterior digastric and inferior pharyngeal constrictor, respectively. 4. Cackling, a long and loud call consisting of alternating high- and low-pitched elements which follow each other repetitively in a 12-14 Hz rhythm, is associated with a similar muscular activity pattern as chuck except that the sternohyoid activity is relatively stronger. 5. Cawing, a short low-pitched call with a fundamental frequency of 200-700 Hz, shows a moderate activity in the sternothyroid, an occasional activity in the thyrohyoid and no activity in the cricothyroid, sternohyoid, omohyoid, anterior digastric and inferior pharyngeal constrictor.

Animals