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Biomedical subjects

H Kolbe

Publications and source records attributed to H Kolbe.

At least 19 recordsLinked to original sources
PubMed2003

[[123I]beta-CIT SPECT imaging of dopamine and serotonin transporters in Parkinson's disease and multiple system atrophy.

AIMS: Definition of the regional pattern of dopamine transporter (DAT) dysfunction in advanced Parkinson's disease (PD) and evaluation of a potential correlation between DAT binding and symptoms; elucidation of the role of DAT imaging in the differential diagnosis of PD and multiple system atrophy (MSA); assessment and comparison of serotonin transporter (SERT) binding in PD and MSA. METHODS: [(123)I]beta-CIT SPECT was performed in 14 patients with advanced PD, 10 with moderate MSA and 20 healthy persons. Specific to nonspecific tracer binding ratios (V(3)") were calculated via ROI analysis of uptake images at 4 h (SERT binding) and 24 h (DAT binding) p. i. RESULTS: In PD bilateral reduction of striatal DAT binding (63-70%) was seen. The caudate ipsilateral to the clinically predominantly affected side showed relatively the least impairment. Significant correlations (r = -0.54 to -0.64) between DAT binding and Hoehn and Yahr stage, UPDRS-scores and duration of disease were found. In MSA DAT binding was less reduced (40-48%) targeting the putamen contralateral to the side of clinical predominance. Significantly lower SERT binding was observed in PD midbrain and MSA hypothalamus compared to controls -- and in MSA relative to PD mesial frontal cortex. CONCLUSIONS: In advanced PD striatal DAT binding is markedly reduced with the least reduction in caudate ipsilateral to the clinically predominantly affected side. In moderate MSA with asymmetrical symptoms DAT dysfunction is predominant in the contralateral putamen, a pattern seen in early PD. The reduction of SERT in the midbrain area of PD patients suggests additional tegmental degeneration while in MSA the serotonergic system seems to be more generally affected.

Brain↗
PubMed2002

Treatment of Tourette's syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial.

Anecdotal reports in Tourette's syndrome (TS) have suggested that marijuana (cannabis sativa) and delta-9-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive ingredient of marijuana, reduce tics and associated behavioral disorders. We performed a randomized double-blind placebo-controlled crossover single-dose trial of Delta(9)-THC (5.0, 7.5 or 10.0 mg) in 12 adult TS patients. Tic severity was assessed using a self-rating scale (Tourette's syndrome Symptom List, TSSL) and examiner ratings (Shapiro Tourette's syndrome Severity Scale, Yale Global Tic Severity Scale, Tourette's syndrome Global Scale). Using the TSSL, patients also rated the severity of associated behavioral disorders. Clinical changes were correlated to maximum plasma levels of THC and its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). Using the TSSL, there was a significant improvement of tics (p=0.015) and obsessive-compulsive behavior (OCB) (p = 0.041) after treatment with Delta(9)-THC compared to placebo. Examiner ratings demonstrated a significant difference for the subscore "complex motor tics" (p = 0.015) and a trend towards a significant improvement for the subscores "motor tics" (p = 0.065), "simple motor tics" (p = 0.093), and "vocal tics" (p = 0.093). No serious adverse reactions occurred. Five patients experienced mild, transient side effects. There was a significant correlation between tic improvement and maximum 11-OH-THC plasma concentration. Results obtained from this pilot study suggest that a single-dose treatment with Delta(9)-THC is effective and safe in treating tics and OCB in TS. It can be speculated that clinical effects may be caused by 11-OH-THC. A more long-term study is required to confirm these results.

Adolescent↗
PubMed2001

Resting regional cerebral glucose metabolism in advanced Parkinson's disease studied in the off and on conditions with [(18)F]FDG-PET.

Studies of resting regional cerebral glucose consumption (rCMRGlc) in nondemented patients with Parkinson's disease (PD) have produced conflicting results, reporting both reduced and normal metabolism in advanced disease and reduced or normal metabolism after dopaminergic therapy. To investigate these issues, [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed in 11 nondemented PD patients with advanced disease and 10 age-matched controls. PD patients were studied after withdrawal of all dopaminergic medication to produce a practically defined off condition, and a second time 1 hour after levodopa, resulting in a clinical on state. Dynamic PET scans and simultaneous arterialised venous blood samples of [(18)F] activity were obtained. A graphical approach was used to generate parametric images of rCMRGlc and statistical parametric mapping to localise significant metabolic changes in PD. Compared with controls, global rCMRGlc was reduced in the on but not in the off condition in PD. In both states, significant regional reductions of glucose uptake were found in the parietal, frontal, temporal cortex, and caudate nucleus. Reductions correlated with the severity of disability in frontal and temporal cortex. Direct comparison between on and off conditions revealed relatively greater reductions of uptake in the ventral/orbital frontal cortex and the thalamus during on. Results suggest that cortical and caudate hypometabolism are common in advanced PD and that caution is mandatory if [(18)F]FDG PET is being used to differentiate advanced PD from dementia and progressive supranuclear palsy where similar reductions are seen. Furthermore, in PD, administration of levodopa is associated with further hypometabolism in orbitofrontal cortex; an area known to be relevant for reversal learning where performance is typically impaired after dopaminergic treatment.

Adult↗
PubMed2001

Influence of treatment of Tourette syndrome with delta9-tetrahydrocannabinol (delta9-THC) on neuropsychological performance.

Previous studies have suggested that marijuana (cannabis sativa) and delta-9-tetrahydrocannabinol (delta9-THC), the major psychoactive ingredient of marijuana, are effective in the therapy of tics and associated behavioral disorders in Tourette Syndrome (TS). Because there is also evidence that cannabis sativa may cause cognitive impairment in healthy users, we performed a randomized double-blind placebo-controlled crossover trial for delta9-THC in 12 adult TS patients to investigate whether treatment of TS with a single dose of delta9-THC at 5.0 to 10.0 mg causes significant side effects on neuropsychological performance. Using a variety of neuropsychological tests, we found no significant differences after treatment with delta9-THC compared to placebo treatment in verbal and visual memory, reaction time, intelligence, sustained attention, divided attention, vigilance, or mood. Only when using the Symptom Checklist 90-R (SCL-90-R) did our data provide evidence for a deterioration of obsessive-compulsive behavior (OCB) and a trend towards an increase in phobic anxiety. However, these results should be interpreted with caution as SCL-90-R has known limitations on measuring OCB. We suggest that the increase in phobic anxiety is mainly due to the fact that a single-dose treatment rules out the possibility of administering the dosage slowly. In contrast to results obtained from healthy marijuana users, a single-dose treatment with delta9-THC in patients suffering from TS does not cause cognitive impairment. We therefore suggest that further investigations should concentrate on the effects of a longer-term therapy of TS with delta9-THC.

Adolescent↗
PubMed2000

Technical validation of radioluminography systems.

More and more laboratories are forced to document evidently that experimental results were achieved compliant with the regulatory of Good Laboratory Pratice (GLP). Thus, also for the imaging plate technique, which is widely used in whole-body autoradiography, it is necessary to provide procedures for formal validation and continuous quality control. Therefore, several European pharmaceutical companies agreed to carry out a project on this subject. This part considers the technical validation. Methods to prove uniform sensitivity and resolution of the technique were developed and are suggested as standard operation procedures and demonstrated, as well, by examples using the isotope (14)C. The high linearity of the detection method is shown by performing a calibration of the image data to the applied radioactivity.

Autoradiography↗
PubMed2000

Dopamine transporter binding in Gilles de la Tourette syndrome.

Preliminary studies in patients with Gilles de la Tourette syndrome (TS) provided evidence of presynaptic dopaminergic dysfunction, demonstrating increased reuptake sites. Therefore we investigated striatal dopamine transporter binding in 12 TS patients and 9 control subjects using single photon emission computed tomography and 123I-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane. In TS patients we found significantly higher relative striatal activity ratios (mean +/- SD 12.33 +/- 3.58) than in controls (9.36 +/- 1.35, P< 0.05). Only five patients, however, showed striatum/occipital cortex ratios more than 2 SD above the normal means. Seven patients had activity ratios within the average ratio of the control group plus 2 SD. Regarding the relationship between clinical parameters and striatum/occipital cortex ratios, we found an association between binding ratios and "self-injurious behavior" and "lack of impulse control." This study corroborates previous data suggesting an involvement of the dopaminergic system in TS pathology. Our results demonstrate that an increase in dopamine transporter capacity is a possible but not a necessary alteration, and which appears more likely when self-injurious behavior and lack of impulse control are associated.

Adult↗
PubMed2000

Dopamine D2 receptor imaging in Gilles de la Tourette syndrome.

OBJECTIVES: To examine postsynaptic dopamine D2 receptors in Tourette syndrome (TS). MATERIAL AND METHODS: Seventeen patients and a control group were investigated using single photon emission computed tomography (SPECT) and iodobenzamide (123I-IBZM). RESULTS: In neuroleptic treated patients (n = 7) 123I-IBZM-binding was significantly reduced compared to both normal controls (P < 0.0001) and unmedicated patients (P < 0.001). In unmedicated patients (n = 10) mean binding ratio did not differ from that of control group. Patients in advanced stages of the disease, however, revealed significantly reduced relative striatal binding compared to patients in the early stages (P<0.005) and normal controls (P<0.0001). CONCLUSION: The results lend further support to the hypothesis that the dopamine receptor is involved in TS pathology. During the natural course of the disease tics often improve in early adulthood. It is suggested that this spontaneous recovery from tics may be associated with reduced receptor binding capacity.

Adolescent↗
PubMed1999

Cannabis in movement disorders.

Central cannabinoid receptors are densely located in the output nuclei of the basal ganglia (globus pallidus, substantia nigra pars reticulata), suggesting their involvement in the regulation of motor activity. Furthermore, there is evidence that endogenous cannabinoid transmission plays a role in the manipulation of other transmitter systems within the basal ganglia by increasing GABAergic transmission, inhibiting glutamate release and affecting dopaminergic uptake. Most hyperkinetic and hypokinetic movement disorders are caused by a dysfunction of basal ganglia-thalamo-cortical loops. It has been suggested that an endogenous cannabinoid tone participates in the control of movements and, therefore, the central cannabinoid system might play a role in the pathophysiology of these diseases. During the last years in humans a limited number of clinical trials demonstrated that cannabinoids might be useful in the treatment of movement disorders. Despite the lack of controlled studies there is evidence that cannabinoids are of therapeutic value in the treatment of tics in Tourette syndrome, the reduction of levodopa-induced dyskinesia in Parkinson s disease and some forms of tremor and dystonia. It can be speculated that cannabinoid antagonists might be useful in the treatment of chorea in Huntington s disease and hypokinetic parkinsonian syndromes.

Basal Ganglia↗
PubMed1998

The basal ganglia and portal-systemic encephalopathy.

Despite decades of research, the pathogenesis of portal-systemic encephalopathy (PSE) remains puzzling. Current hypotheses on the pathophysiology of PSE usually deal with metabolic toxins like ammonia or disturbances in neurotransmitter systems, especially glutamatergic or GABA-ergic neurotransmission. With respect to clinical, neuropathological, MRI and PET findings this review advances the hypothesis that the known alterations of neurotransmission and astrocytic function in PSE might impair basal ganglia function in cirrhotics. The symptoms of PSE - whether cognitive, emotional or motor - are proposed to be a consequence of basal ganglia dysfunction.

Basal Ganglia↗
PubMed1998

Cannabinoids: possible role in patho-physiology and therapy of Gilles de la Tourette syndrome.

High densities of cannabinoid receptors were found in the basal ganglia and hippocampus, indicating a putative functional role of cannabinoids in movement and behaviour. Anecdotal reports suggested beneficial effects of marijuana in Tourette's syndrome (TS). We therefore interviewed 64 TS patients with regard to use of marijuana and its influence on TS symptomatology. Of 17 patients (27%) who reported prior use of marijuana, 14 subjects (82%) experienced a reduction or complete remission of motor and vocal tics and an amelioration of premonitory urges and obsessive-compulsive symptoms. Our results provide more evidence that marijuana improves tics and behavioural disorders in TS. It can be speculated that cannabinoids might act through specific receptors, and that the cannabinoid system might play a major role in TS pathology.

Adolescent↗
PubMed1997

[Gilles de la Tourette syndrome. Effect of nicotine, alcohol and marihuana on clinical symptoms].

Gilles de la Tourette syndrome (TS) is a neuropsychiatric spectrum disorder of unknown etiology. While several studies have provided evidence that nicotine causes an improvement, only anecdotal reports suggest that alcohol and marijuana influence the symptomatology. Using a structured interview, we questioned a larger group of patients with Tourette syndrome (n = 47) about the use of nicotine, alcohol, and marijuana and their subjective experiences. Of 28 smoking patients only 2 (7%) reported a tic reduction when smoking. Of 35 patients drinking alcohol 24 (69%) noted an improvement. Thirteen patients reported the use of marijuana, of whom 11 (85%) noted a marked improvement. Our results provided strong evidence that the use of both alcohol and marijuana causes much more improvement in TS than nicotine smoking. We suggest that marijuana influences an assumed interaction between cannabinoid and dopamine receptors and, by this, influences the dopaminergic processes in basal ganglia and motor activity.

Adolescent↗
PubMed1997

Characterization of a schistosome T cell-stimulating antigen (Sm10) associated with protective immunity in humans.

Parasite antigens that are strong T cell immunogens represent potential candidates for vaccines against pathogens susceptible to T cell-mediated immunity. We have previously shown that chromatographic fractions of schistosomula extracts contain components that are major T cell immunogen(s) in natural schistosome infections in humans and might contribute to the induction of human protective immunity against this parasite. In the present study, we report on the molecular cloning and on the biochemical characterization of the active components of these fractions. The screening of a schistosomula cDNA expression library with antibodies raised against the fractions allowed the cloning of a cDNA that hybridized to a 0.56-kb mRNA of schistosomula and adult worms. This cDNA contains an open reading frame of 267 base pairs (bp) which encodes a 10-kDa polypeptide. The analysis of the cDNA sequence revealed 70% homology with the sequences of previously reported proteins of unknown function. The native molecules in the active fractions were analyzed by mass spectrometry after additional purification by reverse phase high-performance liquid chromatography (HPLC). This procedure revealed two components in the fractions of molecular mass 10383 +/- 2 Da and 10401 +/- 9 Da. Both polypeptides stimulated immune T cells and yielded tryptic peptides whose sequences matched the sequence of the cloned molecule. These two polypeptides probably correspond to different post-translationally modified forms of the polypeptide encoded by the cloned cDNA.

Amino Acid Sequence↗