Search PubMed⌕ Search

Biomedical subjects

H Tost

Publications and source records attributed to H Tost.

At least 19 recordsLinked to original sources
PubMed2005

[One decade of functional imaging in schizophrenia research. From visualisation of basic information processing steps to molecular-genetic oriented imaging].

Modern neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have contributed tremendously to our current understanding of psychiatric disorders in the context of functional, biochemical and microstructural alterations of the brain. Since the mid-nineties, functional MRI has provided major insights into the neurobiological correlates of signs and symptoms in schizophrenia. The current paper reviews important fMRI studies of the past decade in the domains of motor, visual, auditory, attentional and working memory function. Special emphasis is given to new methodological approaches, such as the visualisation of medication effects and the functional characterisation of risk genes.

Biomarkers↗
PubMed2005

[Functional imaging of neurocognitive dysfunction in attention deficit hyperactivity disorder].

Attention Deficit Hyperactivity Disorder (ADHD) is a neurobiological disorder of early childhood onset. Defining symptoms are chronic impairments of attention, impulse control and motor hyperactivity that frequently persist until adulthood. Miscellaneous causes of the disorder have been discussed. Accumulating evidence from imaging- and molecular genetic studies strengthened the theory of ADHS being a predominantly inherited disorder of neurobiological origin. In the last 15 years, non-invasive brain imaging methods were successfully implemented in pediatric research. Functional magnetic resonance imaging studies gave major insight into the neurobiological correlates of executive malfunction, inhibitory deficits and psychomotoric soft signs. These findings are in good accordance with brain morphometric data indicating a significant volumetric decrease of major components of striato-thalamo-cortical feedback loops, primarily influencing prefrontal executive functioning (e.g. basal ganglia). Empirical evidence points to a broad array of associated behavioral disturbances like deficient visuomotor abilities and oculomotor dysfunctions. This paper reviews the current empirical evidence derived from prior imaging studies. Special emphasis is given to the relevance of oculomotor dysfunctions in clinical and research settings, as well as their assessment in the MR environment.

Attention Deficit and Disruptive Behavior Disorder↗
PubMed2004

[Neuropsychiatric aspects of Huntington chorea. Presentation of 2 cases and review of the literature].

Huntington's disease (HD) is an autosomal, dominant, inherited disorder of the central nervous system with characteristic neurodegenerative alterations in the basal ganglia and cortex. Dependent on the individual CAG expansion load, disease onset occurs between the third or fourth decade of life, entailing an invariably lethal progression within 10 to 20 years. Although the clinical picture is characterized equally by cognitive and psychiatric disturbances, the apparent neurodegenerative alterations and presentation as a choreatic movement disorder account for the traditional link of Huntington's disease to the field of neurology. In contrast to the traditionally emphasized core features of chorea and dementia, recent empirical evidence points to the frequent emergence of nonchoreatic motor signs and subtle cognitive and psychiatric complaints, especially in asymptomatic gene carriers and early disease stages. The case studies presented here emphasize the spectrum of neuropsychiatric phenomena associated with HD and illustrate the resulting difficulties of differential diagnosis in clinical settings. Furthermore, current scientific knowledge of HD pleiotrophy is reviewed and the diagnostic power of specific neuropsychological approaches is explained.

Adult↗
PubMed2004

[Depression and modern neuroimaging].

Modern neuroimaging like PET, SPECT, MR-Volumetry, functional MRI and MR-Spectroscopy has effectively advanced research on aetiology, pathogenesis and therapy options of depressive disorders. This review highlights the status of current research on this topic. Consistent with morphological findings, which report alterations in regions of emotionally relevant networks of the brain in depressive disorders, findings of functional studies point to changes in the basal ganglia, the frontal cortex and the limbic system involving the hippocampus and the amygdala. During processing of emotional cues depressive patients show different activation patterns in the regions of the frontal lobe and the amygdala. In our study of a subgroup we were also able to show deficits in processing cues independently from the emotional quality of the stimulus - especially in posterior-parietal and prefrontal areas. In healthy subjects affective modulation correlates with an ordered interaction of ventral-limbic and dorsal-neocortical regions of the brain, which become unbalanced in depressive disorders. In the future, modern neuroimaging will open promising fields of research, which aim at the identification of valid neurofunctional subgroups of the heterogeneous affective disorders and the development of more adjusted and efficient therapy strategies.

Animals↗
PubMed2003

[Functional magnetic resonance imaging of psychopharmacological brain effects: an update].

Functional magnetic resonance imaging (fMRI) is well established for the examination of functional activity in the living brain. The method permits the development of functional activation maps during perceptual, cognitive and emotional efforts with a high temporal and spatial resolution. As of late there has been growing interest in using this technique to investigate regionally specific brain activity following the administration of drugs such as nicotine, cocaine, lorazepam, scopolamine, antipsychotics or antidepressants. Studies in experimental animals investigate signal changes associated with the administration of psychopharmacological substances in different brain areas using a high magnetising field (> 4 Tesla). FMRI-studies in healthy human volunteers and psychiatric patients focus on cerebral activity following acute drug administration (single challenge) and on adaptive effects of the CNS due to long- term medication. Their results provide insights into brain physiology and neuropharmacological mechanisms which are in turn relevant for preclinical pharmacological studies, responder analyses and for the investigation of pathogenetic models in psychiatric diseases. However, with these new opportunities, additional methodological considerations and limitations emerge. Besides the need of controlling motion artefacts, the influence of interfering psychological variables, an exact specification of the experimental design, a standardised analysis for data adjustment and technical limitations have to be considered. This article provides an overview of the underlying model of brain function, present applications, future possibilities and methodological limitations of fMRI for the understanding of human psychopharmacology.

Animals↗
PubMed2002

[Altered perception of temporal relations in schizophrenic psychoses].

Basic perceptual skills involving the central nervous system require the orderly temporal integration of internal as well as external information. Current research in schizophrenia increasingly centers on the accompanying neurocognitive deficits. In association with schizophrenic psychoses, there have been frequent reports of altered temporal processes, but explicit research on the perception of temporal relationship is still rare. Using concrete operationalized neuropsychological procedures, the present pilot study addressed the question whether schizophrenic patients (n = 27) differ from a healthy control group (n = 18) concerning their ability to judge correctly the temporal order of visual stimuli. We found a significant impairment in basal temporal perception among patients. Moderating variables such as antipsychotic medication, attention deficits, or motivation effects did not appear to be essential explanatory factors for this finding. Thus, our findings indicate a fundamental disturbance in the temporal coordination of neuronal network functions in association with schizophrenic psychoses and are in line with neurophysiological, neuroanatomical, and neuropsychological overlappings of schizophrenia and temporal perception.

Adult↗
PubMed2001

[Diffusion tensor imaging (DTI) and functional magnetic resonance tomography (fMRI) expand methodological spectrum in psychiatric research].

In psychiatric research, there is a growing interest in the microstructural and functional characteristics of brain networks, which often form the basis of current etiological concepts. As a result of novel magnetic resonance imaging techniques, the pathogenic characteristics of neuronal activity and connectivity can be examined in a noninvasive, safe, and repeatable manner. Functional magnetic resonance imaging (fMRI) uses blood oxygenation level-dependent (BOLD) measures for identifying the gray matter contribution to cognition. Diffusion tensor imaging (DTI) reveals the course and structural integrity of white matter projections. Because DTI does not require special motivation and performance, group differences in psychiatry are more easily interpreted in terms of underlying pathology. To date few studies have tried to investigate both, i.e. dynamic and microstructural data in the sense of a modern multi-dimensional investigation approach. The combination of both techniques, however, seems to offer a promising vehicle to further extent our current understanding of mental disorders and to identify populations at risk. In addition to addressing findings in psychiatric research, the present article presents a technical overview of DTI and examines the limitations and potential applications of both techniques.

Anisotropy↗
PubMed2001

[Current overview of structural magnetic resonance imaging in schizophrenia].

Non-invasive morphologic imaging (computer tomography, magnetic resonance imaging, MRT) has contributed significantly to our understanding of schizophrenic disorders as diseases of the brain. Improved MRT techniques enable us to analyse anatomical substructures. The present overview evaluates peer-reviewed MRT studies published between 1994 and July 2000 and provides a comparison with our own results. Chronic schizophrenic patients most frequently show an enlargement in the ventricular system along with a reduction in grey matter. A more detailed subdivision into cortical and subcortical regions additionally shows the noted volume reduction to be limited to specific areas within the brain rather than being distributed equally throughout the brain. Within the area of the temporal lobes the two most frequently affected areas are the hippocampus and the gyrus temporalis superior. Alterations within these areas correlate with clinical symptoms such as hallucinations or thought disorders. Within the frontal cortex nearly 70% of all studies show a decrease in overall volume, while 63% note a reduction in size within the thalamus and 60% in the cerebellum. Morphologically speaking these structures therefore play the greatest role in the pathophysiology of schizophrenia and the onset of clinical symptoms. More recent studies also showed a specific progression in subgroups of patients pointing toward a neurodegenerative process. Additionally there are a number of differential antipsychotic effects following longterm treatment with typical neuroleptics as compared to atypical antipsychotics. Based on these findings future longitudinal studies should examine to what extent such a progressive decrease in volume might be influenced by treatment with modern antipsychotics.

Humans↗
PubMed2001

[Homosexual pedophilia and functional networks - An fMRI case report and literature review].

Pedophilia is a complex bio-psycho-social disorder often associated with serious offending. Knowledge about neurobiological correlates that could serve as diagnostic and maybe even as prognostic markers is limited. FMRI examination, which shows neuronal activation in vivo and therefore represents a neurobiological correlate, was not done in pedophilia so far. We report on results of an fMRI examination in a homosexual pedophilic sex offender who differed significantly in neuronal activation during exposure to arousing visual material (young boys in underwear) from normal controls. In self assessment on a visual analogous scale the pedophilic offender scored the pictures of the boys as not being interesting and sexually not stimulating. Nevertheless presentation of the pictures of the boys resulted in the pedophilic offender in a significant activation of the attention network and the right orbitofrontal cortex. In contrast to the controls there was no activation of left hemispheric areas relevant for speech. The study design will be continued in a larger sample to examine whether there is a possible neurobiological correlate of pedophilia which can be changed by therapeutic interventions.

Adult↗
PubMed2001

Intrarenal distribution of blood flow in sodium depleted and sodium loaded rats: role of nitric oxide.

The renal hemodynamic effects of nitric oxide synthase (NOS) inhibition and dietary salt were studied in rats. L-NAME (0.1 mg/ml in the drinking fluid, about 12 mg/kg/day) was given for 4 days to rats receiving low (sodium depletion, SD), normal (N) or high (sodium load, SL) NaCl diet. Intrarenal hemodynamics was studied in anaesthesia. NOS inhibition decreased renal blood flow and increased renal vascular resistance in each group. Cortical and outer medullary but not inner medullary blood flow increased in direct ratio to the sodium intake. NOS inhibition decreased the blood flow and increased the vascular resistance in all layers of the kidney in SD, N, and SL rats as well. In SD and N, but not in SL rats L-NAME induced vasoconstriction was higher in the outer (OM) and inner medulla (IM) than in the cortex (C) [SD: DeltaCVR 43%, DeltaOMVR 54%, DeltaIMVR 84%; N: DeltaCVR 54%, DeltaOMVR 96%, DeltaIMVR 106%; SL: DeltaCVR 50%, DeltaOMVR 64%, DeltaIMVR 35%]; in normal rats blood flow shifts from the medulla toward the cortex. In conclusion, nitric oxide may have a role in the regulation of renal vascular tone not only in the case of regular sodium uptake but in the sodium depleted or loaded organism as well. However, nitric oxide has no role in the dietary salt evoked vascular adaptation in the kidney.

Animals↗
PubMed2000

Effect of nitric oxide synthase inhibition on renal circulation and excretory function in anaesthetized rats.

The effects of nitric oxide synthase (NOS) inhibition (effected using L-NAME, 14 mg (kg body mass (BM))(-1), administered intravenously) on systemic and renal circulation and renal excretory function has been investigated in anaesthetized Wistar rats subjected to one of two different degrees of isotonic extracellular (EC) volume expansion (40 and 60 ml x kg(-1) (240 min)(-1)). The administration of L-NAME resulted in an increase in mean arterial blood pressure and total peripheral vascular resistance (TPR), and a significant reduction in cardiac output (CO) and the kidney fraction of CO in both experimental groups. The total renal blood flow (RBF) dropped from 557 + 43.4 to 149 +/- 13.1 ml x min(-1) (100 g BM)(-1) and from 592 +/- 45.9 to 191 +/- 16.3 ml x min(-1) (100 g BM)(-1) in the 40 and 60 ml x kg(-1) (240 min)(-1) experimental volume expansion groups, respectively. A redistribution of the intrarenal circulation from the medulla of the kidney toward the cortex may have occurred. The NOS inhibition induced a significant decrease in the glomerular filtration rate (GFR; from 1.18 +/- 0.10 to 0.53 +/- 0.08 ml x min(-1) (100 g BM)(-1) and from 1.26 +/- 0.07 to 0.73 +/- 0.08 ml x min(-1) (100 g BM)(-1) in the 40 and 60 ml x kg(-1) (240 min)(-1) experimental volume expansion groups, respectively), and the filtration fraction increased. The urine excretion dropped in parallel with the GFR, while the reduction in sodium and potassium excretion was more marked than that of the GFR, raising the possibility of a direct effect on the kidney tubules. The difference in EC volume expansion (the calculated increases in the EC volume in the last 90 min were 1.30 and 5.44% in the two time control groups and 3.66 and 7.45% in the two L-NAME-treated groups) did not induce any significant modification of the L-NAME effect.

Animals↗
PubMed1998

Blood flow of the submandibular gland in sodium-depleted and -loaded rats: effect of nitric oxide synthase inhibition.

The present investigations were designed to study the hemodynamic effects of different sodium diets in the submandibular gland of rats with or without nitric oxide (NO) synthesis inhibition. Experimental animals were kept on: (1) standard chow and tap water ad libitum (normal group, N), or (2) wheat and distilled water ad libitum for 4 weeks (sodium-depleted animals, SD), or (3) standard chow and saline ad libitum for 4 weeks (sodium-loaded animals, SL). NO synthase was inhibited by N omega-nitro-L-arginine-methyl-ester (L-NAME, 10 mg/kg per day) in the last week. The rats were anesthetized, and blood pressure, cardiac output (Stewart-Hamilton's principle) and blood flow (BF) of the submandibular gland (Sapirstein's technique) were determined. High sodium intake resulted in a 47% increase of glandular BF as compared to BF measured in the control group. In all groups L-NAME decreased BF (ml/min per 100 g gland) as compared to those of rats with no L-NAME treatment (N: 76.4 +/- 15.4 vs. 56.0 +/- 11.6, P < 0.05; SD: 71.0 +/- 17.7 vs. 56.2 +/- 15.1, n.s.; SL: 112 +/- 29.4 vs. 66.9 +/- 18.4, P < 0.001), whereas the vascular resistance (VR, mm Hg x ml-1 x s x kg-1) increased (N: 11.0 +/- 2.3 vs. 17.5 +/- 4.1, P < 0.001; SD: 11.0 +/- 2.7 vs. 17.0 +/- 4.2, P < 0.01; SL: 8.5 +/- 2.4 vs. 14.9 +/- 4.6, P < 0.001). The increase in VR after L-NAME treatment was 64% in normal, 55% in sodium-depleted and 75% in sodium-loaded rats. Our results suggest that NO takes part in the regulation of vascular resistance and BF in the submandibular gland. Sodium load itself increases BF of the submandibular gland and this phenomenon may partly be mediated by NO.

Animals↗
PubMed1995

Conjugate effects of saralasin and indomethacin on kidney function in anesthetized dog.

The intravenous administration of the cyclooxigenase blocking indomethacin results in a very rapid and sharp decrease of renal blood flow (RBF) and in a decrease of water and sodium excretion in anesthetized dogs. The result is very similar to that of the angiotensin II infusion. The present study was undertaken to examine in anesthetized dogs, how the angiotensin II receptor antagonist saralasin can influence the kidney function and the renal effects of the intravenously administered indomethacin. 0.2 micrograms/kg/min saralasin infused directly into the left renal artery induced a slight drop in the arterial blood pressure, and a slight but significant decrease in the renal vascular resistance without affecting other renal parameters. The intrarenal infusion of saralasin, when it preceded the administration of indomethacin, almost completely abolished the renal hemodynamic effects of indomethacin and decreased its effect on the renal water and sodium excretion. It seems therefore probable that in anesthetized dogs the renin-angiotensin system may play a role in the development of the renal effects of indomethacin.

Anesthesia↗
PubMed1995

Effect of volume expansion induced by Ringer's solution or plasma on the natriuretic response of the kidney.

Studies were carried out in anaesthetized dogs, to determine the effects of volume expansion induced by Ringer's solution, plasma taken from non-hydrated or previously volume expanded animals on the natriuretic response of the kidney. When the animals were infused with Ringer's solution (0.25 ml/kg/min iv.) water and sodium excretion increased gradually reaching a peak value at about 70 min. after starting the infusion (3.01 +/- 0.21 ml/min and 329 +/- 23.9 mmol/min, respectively). Infusing the dogs with plasma taken from non-hydrated animals (0.25 ml/kg/min iv.) water and sodium excretion showed a small increase in the first 15 min, but afterwards there was hardly any change in them, and water and sodium excretions were significantly less in the remaining part of the experiment than in with Ringer's solution expanded animals. (Peak values 1.44 +/- 0.53 ml/min and 193 +/- 85.3 mmol/min.) In animals infused with plasma taken from previously hydrated dogs (0.25 ml/kg/min iv.) water and sodium excretion were already after the first 15 min significantly higher than in the two other groups, they increased further in the following 15 to 30 minutes and remained elevated during the time of the study. (Peak values for water and sodium excretion being 3.30 +/- 0.58 ml/min and 344 +/- 73.5 mmol/l.) Blood pressure, CPAH and glomerular filtration rate were the same and did not change in either of the experimental series. We concluded, that besides the physical forces playing certainly a role mainly in the Ringer's solution hydrated dogs, some humoral natriuretic factor liberated in the volume expanded animals plays also a role in the diuretic-natriuretic response. This humoral factor can be released from the atria or other organs, but its production is not primarily regulated by intravasal volume/or pressure changes.

Animals↗
PubMed1994

The renal actions of adenosine.

This study examined the effects of adenosine on the renal function. In ten normal dogs intrarenal adenosine infusion (20 nmol/kg/min) increased the renal blood flow (RBF) from 521 +/- 20 ml/min to 582 +/- 23 ml/min. The extraction of PAH (EPAH) decreased from 0.85 +/- 0.02 to 0.79 +/- 0.02, the Einulin from 0.24 +/- 0.02 to 0.18 +/- 0.02. We conclude that the intrarenal infusion of adenosine modifies the intrarenal redistribution of the blood flow increasing the deep cortical and medullary blood flow. In these experiments the glomerular filtration (GFR) during adenosine infusion calculated from the extraction of the inulin (Einulin) multiplied by the renal plasma flow (RPF) decreased from 79.4 +/- 6.4 ml/min to 62.2 +/- 6.6 ml/min and calculated from the Ecreatinine x RPF from 80.3 +/- 6.3 ml/min to 59.3 +/- 4.9 ml/min. The EPAH x RPF did not change, it was 241 +/- 11 ml/min and 253 +/- 13 ml/min, respectively. While the urinary clearances (the clearance calculated by the classic clearance formula; urinary concentration of the substance multiplied by the urine volume and divided by the plasma concentration) in the control periods did not differ from the direct clearances (Cinulin = 73.3 +/- 3 ml/min, Ccreatinine = 75 +/- 4 ml/min and CPAH = 262 +/- 15 ml/min) during the adenosine infusion there are considerable differences: the Cinulin = 40 +/- 6 ml/min, the Ccreatine = 42 +/- 6 ml/min and the CPAH = 164 +/- 22 ml/min. The differences are mathematically significant (p < 0.01). During the postinfusion periods the urinary clearances did not differ from the direct clearances. These results show that during adenosine infusion there is a definitive loss of the clearance substances somewhere in the nephron between the glomeruli and the pyelon. These observations suggest that during adenosine infusion there is a back-diffusion of the clearance substances because the permeability of the tubuli changes in the medullary part. The rediffused substances will be retransported into the circulation by the renal lymph flow and that is why they do not appear in the renal venous blood. The rediffusion can explain that the intrarenal adenosine infusion decreases considerably the excretion of the sodium and water in the kidney when there is no or only a small reduction of the glomerular filtration rate.

Adenosine↗
PubMed1993

Effects of hypercalcemia on kidney function in anesthetized dogs.

The effects of acute hypercalcemia on renal function were evaluated in anesthetized mongrel dogs. Calcium concentration was increased by infusion of CaCl2 solution into the left renal artery at two different rates. At the lower rate of infusion (0.010 mM/kg/min) the plasma total calcium concentration in the left kidney increased from 2.5 mM/l to 3.76 mM/l and the arterial plasma total calcium concentration to 2.94 mM/l. Renal vascular resistance in the left kidney did not change in association with a small decrement in the renal blood flow (9.5%). The glomerular filtration rate decreased from 82.9 ml/min to 65.9 ml/min in association with a small decrease in the urine output. The calcium excretion increased slightly from 3.3 microM/min to 4.05 microM/min. When this amount of CaCl2 was infused into the left renal artery the parameters of the right intact kidney did not change. During the higher rate of infusion (0.020 mM/kg/min) in the left kidney the plasma total calcium concentration in the left kidney increased from 2.3 mM/l to 6.15 mM/l and in the arterial plasma to 3.4 mM/l. Renal vascular resistance increased considerably from 1.66 to 4.0 and the renal blood flow decreased from 482 ml/min to 311 ml/min. The glomerular filtration rate dropped from 78.7 ml/min to 43 ml/min with a significant decrease in the urine output. The calcium excretion increased from 4.35 microM/min to 7.5 microM/min. In the right kidney during the CaCl2 infusion the CPAH decreased from 304 ml/min to 239 ml/min showing that there was an increase in the vascular resistance in association with decrements in Cinulin from 85 ml/min to 67.2 ml/min. These data prove a direct, but not linear relationship between the total plasma calcium concentration and the renal vascular resistance. We suppose that the distal tubular calcium load participates in the distal tubular feedback regulation, when the calcium ion concentration in the tubular fluid at the macula densa increases. This increment elicits vasoconstriction in the afferent arteriole decreasing the filtered calcium load in the glomeruli.

Acute Disease↗
PubMed1991

Investigations on the circulation of anesthetized dogs.

In the present experiments arterial blood pressure, cardiac output, heart rate, oxygen consumption, AVO2 difference values and their changes were investigated in 64 anesthetized dogs in four periods for altogether 60 min. Blood flows of the renal, commune carotid and femoral arteries were measured in parallel and the changes were recorded throughout the 60 min of the experimental period. Urine was collected separately from both kidneys, in order to determine whether the measurement of the blood flow of the renal artery disturbed renal functions. Total peripheral vascular resistance and the vascular resistance of the territories of the commune carotid and femoral arteries were calculated from the parameters measured. In the present experiments the equation of the regression line between cardiac output and body weight was y = 0.102x + 0.9411. The equation of the regression line between cardiac output an body surface proved to be y = 2.996x + 0.653. The relationship between total oxygen consumption and body weight could be characterized by the y = 5.815x + 24.227 equation. Our data were in accordance with data of the Biology Data Book obtained in dogs anesthetized by pentobarbital. Our present data can be found but partially in the Biology Data Book, so the results obtained in the present study may serve as basis of future comparisons. In this work proper care was taken to maintain the same conditions and, thus ruling out possible artefacts. The experiments were carried out on mongrel dogs of different sexes; nevertheless, the animals were attempted to be kept under the same conditions for the 14 days preceding the experiments.

Anesthesia↗