Biomedical subjects

W Hermann

Publications and source records attributed to W Hermann.

At least 19 recordsLinked to original sources

PubMed2007

[Wilson's disease].

Wilson's disease is a rare autosomal recessive disorder of hepatic copper transport leading to a biliary excretion inhibition of copper. Overload of the metal mainly in liver and basal ganglia leads to hepatic but also to extrapyramidal motor as well as psychiatric clinical symptoms. Diagnosis is based on clinical suspicion, parameters of copper metabolism, ophthalmic examination and a liver biopsy. A radiocopper test is able to identify patients even with inconsistent laboratory results. For initial assessment and follow-up neurophysiological investigation and MRI are recommended additionally. Genetic analysis can be helpful to detect asymptomatic relatives of the index patient. Dependent on the stage of the disease for therapy chelating drugs and zinc are possible but must be given lifelong without longer interruptions. With early diagnosis and consequent treatment the prognosis of Wilson's disease is excellent and usually the need for liver transplantation can be prevented.

Adolescent↗

PubMed2006

Profound midbrain atrophy in patients with Wilson's disease and neurological symptoms?

Wilson's disease (WD) is characterized by impaired hepatic copper secretion and subsequent copper accumulation in many organs predominantly liver and brain, secondary to loss of function mutations in the copper transport protein ATP7B. If the disease is recognized too late or treatment is not adequate, brain copper accumulation leads to progressive neurodegeneration with a variety of clinical symptoms. The nigrostriatal dopaminergic system seems rather vulnerable. Midbrain atrophy, however, has not been recognized as one of the prime features of patients with WD. Here we report quantification of midbrain diameter in 41 patients with WD. Data were correlated to the severity of neurological symptoms and the integrity of dopaminergic neurons measured via dopamine transporter binding. For control, we measured midbrain diameter in 18 patients with no evidence for brainstem dysfunction and 5 patients with progressive supranuclear palsy (PSP). Patients with WD had a reduced midbrain diameter (15.5 +/- 0.4 mm) compared to controls (18.5 +/- 0.2 mm). WD patients without neurological symptoms had midbrain diameter that were not different from controls (18.0 +/- 0.3 mm), while patients with neurological symptoms showed midbrain atrophy similar to patients with PSP (14.4 +/- 0.3 mm versus 14.1 +/- 0.3). There was a strong and significant correlation between midbrain atrophy and the severity of neurological symptoms (r= -0.68, p < 0.001) while midbrain atrophy and dopamine transporter binding correlated significantly but was less pronounced (r=0.46, p < 0.001). In summary, we were able to show, that midbrain diameter is an easy to perform quantification of neurodegeneration induced by brain copper accumulation and that other structures than substantia nigra dopaminergic neurons seem to contribute to midbrain atrophy in WD.

Adult↗

PubMed2006

[Correlation of clinical aspects as well as genotype and phenotype in Wilson's disease on the basis of epidemiologic, clinical and cranial MRI findings].

Wilson's disease, a rare autosomal recessive disorder of hepatic copper transport, is characterized by a varying pattern of hepatic, neurologic and psychiatric symptoms. Currently, about 250 causative mutations of the ATP 7B gene are known. However, a correlation between genotype and phenotype according to these mutations is not yet clear. To elucidate a possible correlation in this study 39 patients with Wilson's disease were subdivided into three groups according to the underlying mutation in group I for homocygote respectively group II for compound heterocygote mutation in H1069Q and group III for other mutations. Clinical subtype and extent of neurologic disturbance as well as epidemiologic aspects, presence of psychiatric symptoms, results of acustically evoked potentials (Wave III, interpeak latency III-V) and findings of cranial MRI were considered. While psychopathological symptoms, the results of acustically evoked potentials and cranial MRI show a correlation to the clinical subtype of Wilson's disease there was no genotype-phenotype correlation on the basis of the mutation in H1069Q. The qualitative and quantitative pattern of results do not show any significant differences in the three groups of genotype. Thus, the time of treatment onset still has most influence on the extent of clinical manifestation and reversibility of the toxic copper accumulation.

Adenosine Triphosphatases↗

PubMed2006

Connective tissue diseases and pregnancy.

Connective tissue diseases (CTD) such as systemic lupus erythematosus diffuse or limited systemic sclerosis and numerous others affect women frequently during the childbearing period. Every pregnancy in a patient with CTD should be regarded as high-risk pregnancy, and requires intensive monitoring and immediate treatment of clinical problems. For these reasons, for women suffering from CTD, who are pregnant or who intend to become pregnant, an interdisciplinary setting addressing all aspects of rheumatology, ob-gyn and neonatalogy needs to be provided. This setting includes particular diagnostic tools and laboratory parameters prior to and during pregnancy as well as in the post-partal period. Aside overt organ dysfunction, key problems in pregnant CTD patients consist mainly of haemostaseological problems such as antiphospholipid antibodies, neonatal lupus erythematosus, congenital heart block and drug therapy of the underlying disease, which will be outlined in this review.

Connective Tissue Diseases↗

PubMed2005

[Neurosyphilis and neuroborreliosis. Retrospective evaluation of 22 cases].

We present laboratory data from 22 patients suspected of having neurosyphilis. In two cases the suspicion could not be confirmed, and in 20 cases neurosyphilis was detected. The sera from 17 patients were also assayed for Borrelia-specific antibodies. Suspicious immunoglobulin G antibody indices were detected in nine cases and a suspicious immunoglobulin M antibody index in one. In six of these, stored CSF/serum pairs were available to specify the antibodies by immunoblotting. This allowed for the identification of one patient apparently infected by both Borrelia spp. and Treponema pallidum. In all cases of newly suspected neurosyphilis, we recommend considering neuroborreliosis at the same time.

Adult↗

PubMed2005

[Classification of Wilson's disease based on neurophysiological parameters].

In addition to hepatolenticular degeneration in Wilson's disease, sensory and extrapyramidal motoric systems are also disturbed. In this study a classification on the basis of neurophysiological parameters (EAEP, VEP, MSEP, TSEP and MEP) was established according to subclinical disturbances of these pathways in patients with Wilson's disease on long-term treatment. A cluster analysis of latencies of these evoked potentials was performed. The results of cluster analysis revealed three types of electrophysiological profiles: type I with normal latencies and types II and III showing different patterns of prolonged latencies. However, there was no correlation between clinical classification and the results of cluster analysis based on the electrophysiological data. The neurophysiological based classification provides additional information about central manifestations and aids in characterizing the progress of the disease.

Adult↗

PubMed2005

[Tumour necrosis factor receptor-associated periodic syndrome. A rare differential diagnosis of multiple sclerosis].

Tumour necrosis factor receptor-associated periodic syndrome (TRAPS), a rare autosomal dominant disorder, is characterised by recurrent attacks of fever, myalgias, and abdominal pain. However, manifestations in the central nervous system are hardly known. We describe a family in which one of three affected members developed central nervous system symptoms. First diagnosed as multiple sclerosis (MS), the demyelinisation seems to be a feature of TRAPS rather than MS. The syndrome is discussed as a rare differential diagnosis of MS.

Adult↗

PubMed2005

Classification of fine-motoric disturbances in Wilson's disease using artificial neural networks.

Patients suffering from Wilson's disease are divided into several types according clinical symptoms only at time of manifestation. Thereby two main subgroups exist: neurologic and non-neurologic types. After long-term therapy the neurological symptoms occurring in hepatolenticular degeneration may be improved but frequently with remaining fine-motoric disturbances which should be used for evaluation of the actual patient state. These disturbances are difficult to assess in an exact and objective manner by clinical examination. Therefore we measured fine-motoric passive and active abilities based on a standardized test set using the VSCOPE-system. The parallel evaluation of all fine-motoric data using an artificial neural network leads to a reclassification of these patients based on actual fine-motoric abilities but not reflecting the clinical classification at time of manifestation.

Adult↗

PubMed2003

[Primary nasal epithelial cells and fibroblasts have inflammation-inducing functions].

BACKGROUND: The appearance of neutrophils in rhinitis and sinusitis led to the working hypothesis that neutrophil-specific attractants commonly called chemokines are generated by stimulation with proinflammatory cytokines and bacteria. The receptor mechanism of chemokine synthesis by bacterial products is under discussion and still has to be elucidated. PATIENTS AND METHODS: The primary nasal cultures of epithelial cells and fibroblasts ( n=4) were incubated with TNF-alpha (tumor necrosis factor) for 24 and 72 h. Bacterial stimulation of the cell cultures was performed by adding supernatants from the mucoid phenotype of Pseudomonas aeruginosa (PA01) in dilution 1:5 for 24 and 72 h. Supernatants were collected and the concentration of the chemokines interleukin-8 (IL-8), GRO-alpha (growth-related oncogene-alpha), and ENA-78 (epithelial neutrophil-activating peptide) were determined by ELISA technique. Our results revealed that the protein concentration of the chemokines GRO-alpha and IL-8 was upregulated by TNF-alpha as well as by bacterial supernatants in epithelial cells. CONCLUSION: We conclude that GRO-alpha and IL-8 were inducible by bacterial supernatants in nasal epithelial cells and fibroblasts.

Chemokine CXCL1↗

PubMed2003

[Therapeutic management of necrotizing neck infections].

BACKGROUND: Necrotizing neck infections are uncommon soft-tissue infections, usually caused by virulent, toxin producing bacteria. Necrotizing fasciitis represents a special form of necrotizing soft tissue infection with a mortality rate of up to 76% even though aggressive therapy is recommended. PATIENTS AND METHODS: In the last 2 years we treated four patients with severe necrotizing neck infections and five suffering from necrotizing fasciitis. RESULTS: Microbiological analysis revealed mixed infections with Candida albicans, Streptococcus pyogenes, Fusobacterium, Proprioni bacteria and Staphylococcus. The surgical management was not only restricted to drainage, but also included functional neck dissection in order minimize the spread of the disease. Eight of our patients recovered completely, but one died due to toxic shock as consequence of a delayed in therapy. CONCLUSION: Complete recovery of patients suffering from necrotizing fasciitis depends on early and aggressive surgical therapy including neck dissection and drainage as well as an interdisciplinary strategy of conservative therapy. Hyperbaric oxygen should be considered as a treatment adjunct in patients with necrotizing fasciitis if surgery and antibiotic treatment fail.

Adult↗

PubMed2003

[Electrophysiological impairment profile of patients with Wilson's disease].

In addition to hepatic and extrapyramidal motor clinical symptoms, Wilson's disease patients also exhibit subclinical disorders of other central nervous pathways. In this study, an impairment profile is described by means of eight electrophysiological tests (EAEP, MSEP, TSEP, T-VEP, MEP, EEG, heart frequency variability, and SSR) for 37 patients (28 with neurological, nine with tnon-neurological form) undergoing long-term drug therapy. The occurrence in 64.3% of a delayed wave III and/or IPL III-V prolongation in patients with the neurological form makes pathological FAEP the most common form of the disorder, followed by disorders in MSEP, TSEP, MEP, and T-VEP. Patients with the non-neurological form usually have normal values, although latency prolongations occur in isolated cases. The range of evoked potential findings is characterised primarily by latency prolongations, i.e. a demyelinising impairment type, and significant losses of potential hardly occur (except in the MEP). The electrophysiological impairment profile does not include EEG changes or vegetative disorders.

Autonomic Nervous System Diseases↗

PubMed2003

The degree of depression in Hamilton rating scale is correlated with the density of presynaptic serotonin transporters in 23 patients with Wilson's disease.

OBJECTIVE: One of the most frequent psychiatric symptoms in patients with Wilson's disease (WD) is depression. It has been suggested that depression is associated with deficits in serotonergic neurotransmission, but, hitherto, no measurements have been performed in WD. METHODS: We prospectively examined 23 adult patients (12 women, 11 men, mean age 40 years) with WD for symptoms of depression using the Hamilton rating scale for depression (HAMD). We correlated the data with the presynaptic serotonin transporter density (SERT density) in the thalamus-hypothalamus and the midbrain-pons regions measured with high resolution single-photon emission computed tomography (SPECT) 24 hours after the application of 180 MBq 2beta-carbomethoxy-3beta-(4 [(123)I]iodophenyl)tropane ( [(123)I]b-CIT). The regions of interest were determined by coregistration with a standard MRI dataset. RESULTS: A significant negative correlation was found between HAMD and SERT density in the thalamus-hypothalamus region (r = -0.49, p = 0.02), but not in the midbrain-pons (r = -0.31, p = 0.15). CONCLUSIONS: We conclude that depression in patients with Wilson's disease is correlated with alterations of serotonergic neurotransmission in the thalamus-hypothalamus region.

Adult↗

PubMed2003

Regional serotonin transporter availability and depression are correlated in Wilson's disease.

In patients with Wilson's disease (WD), depression is a frequent psychiatric symptom. In vivo neuroimaging studies suggest that depression and other neuropsychiatric disorders are associated with central serotonergic deficits. However, in vivo measurements of serotonergic neurotransmission have not until now been performed in patients with this copper deposition disorder. The present prospective study revealed that depressive symptomatology is related to an alteration of presynaptic serotonin transporters (SERT) availability as measured by [123I]-2beta-carbomethoxy-3beta-(iodophenyl)tropane ([123I]beta-CIT) and high-resolution single-photon emission computed tomography (SPECT). SERT imaging with [123I]beta-CIT-SPECT could therefore become a useful tool for diagnosis and therapy monitoring in depressed WD patients.

Adult↗

PubMed2003

Investigation of fine-motor disturbances in Wilson's disease.

Patients suffering from Wilson's disease (WD) can be divided into two main subgroups: neurologic and nonneurologic WD. We measured passive and active fine-motor abilities of 37 WD patients and 24 randomly selected volunteers. The measurement was based on a standardized test set in a defined environment for detection of disturbed finemotor control. The set contains 5 tests comprising rest tremor, postural tremor, target tapping, forefinger tapping and spiral painting, reflecting different aspects of movement disorders. The tests showed significant differences between neurologic WD and volunteers, especially for tasks defining active control. In neurologic WD we found no differences between subgroups whereas for non-neurologic WD we often detected slight movement disorders. The detected movement disorders cam be interpreted as persistent disorders after long-term therapy.

Adult↗

PubMed2002

[Cerebral MRI and evoked potentials in Wilson disease. Comparison of findings in patients with neurological follow-up].

Wilson's disease is caused by toxic copper accumulation, which leads predominantly to hepatic and basal ganglia damage. Characteristic findings in MRI and electrophysiologic examinations are described according to the occurrence of neurological symptoms. In the present study, 28 patients suffering from Wilson's disease (neurological type) were investigated. The results of MRI are compared with abnormalities of evoked potentials (BAEP, MSEP, T-VEP, MEP). All patients show hypodensities in the basal ganglial area (putamen and GI. pallidus) regularly combined with atrophy of the cerebrum and cerebellum in MRI. Signal abnormalities in the mesencephalic region (46% occurrence) and Nc. dentatus (36% occurrence) are combined with the other findings in variable patterns. Only slight changes are found in the pontine region. BAEP are disturbed in 71% of all cases and MSEP in 46%. Combined abnormalities of BAEP and MSEP were found in 39%. Pathological values occurred with a lower frequency in T-VEP (36%) and MEP (39%). The comparison of MRI findings with electrophysiological data done separately for each patient reveals no strong correlation between both methods. Individual MRI findings do not correspond with the patterns of disturbed evoked potentials and vice versa. Therefore we conclude that these methods, MRI and electrophysiological evaluation, supplement each other. Magnetic resonance imaging and electrophysiological evaluation should be performed simultaneously for therapy monitoring.

Adult↗

PubMed2002

[Levodopa dependency in Parkinson's disease: case report and review].

Only a few patients with Parkinson's disease and levodopa dependency or abuse have been reported. We present a 35-year-old patient with young-onset Parkinson's disease who developed motor complications, levodopa dependency, and drug-induced psychosis after primary treatment with levodopa. Diagnostic criteria and treatment guidelines for this neuropsychiatric disorder are presented as well as a tentative neurobiological answer to the question of why levodopa dependency is observed only in a minority of patients with Parkinson's disease.

Adult↗

PubMed2002

Comparison of clinical types of Wilson's disease and glucose metabolism in extrapyramidal motor brain regions.

In Wilson's disease a disturbed glucose metabolism especially in striatal and cerebellar areas has been reported. This is correlated with the severity of extrapyramidal motor symptoms (EPS). These findings are only based on a small number of patients. Up to now it is unknown whether EPS are caused by various patterns of disturbed basal ganglia glucose metabolism. We investigated 37 patients and 9 normal volunteers to characterize the disturbed glucose metabolism in Wilson's disease more precisely. The glucose metabolism was determined in 5 cerebellar and cerebral areas (putamen, caput nuclei caudati, cerebellum, midbrain and thalamic area) by using (18)F-Fluorodesoxyglucose-Positron-Emission-Tomography ( [(18)F]FDG-PET). The database was evaluated by a cluster analysis. Additionally, the severity extrapyramidal motor symptoms were judged by a clinical score system. Three characteristic patterns of glucose metabolism in basal ganglia were obtained. Two of them may be assigned to patients with neurological symptoms whereas the third cluster corresponds to most patients without EPS or normal volunteers. The clusters can be identified by characteristic consumption rates in this 5 brain areas. The severity of EPS can not clearly be assigned to one of the clusters with disturbed glucose metabolism. However, the most severe cases are characterized by the lowest consumption in the striatal area. When there is marked improvement of EPS impaired glucose consumption reveals a persistent brain lesion. Finally, the neurological symptoms in Wilson's disease are caused by (at least) two different patterns of disturbed glucose metabolism in basal ganglia and cerebellum. The severity of EPS seems to be determined by a disturbed consumption in the striatal area.

Adult↗

PubMed2002

Neutrophil chemokines in cultured nasal fibroblasts.

BACKGROUND: To gain insight into the mechanisms responsible for tissue neutrophil immigration in sinusitis, primary nasal fibroblasts are analyzed for synthesizing and delivering neutrophil chemokines. METHODS: Primary nasal fibroblast cell culture was treated with tumor necrosis factor (TNF)-alpha concentrations of 20 and 200 ng/ml for 2, 8, 24 and 72 h. Chemokine concentrations in supernatants were determined by enzyme-linked immunoassay (ELISA) and chemokine mRNA expression in fibroblasts was measured by reverse transcriptase polymerase chain reaction (RT-PCR). Biological chemotactic activity was identified by three-step high-performance liquid chromatography (HPLC) and by bioassay measuring neutrophil chemotaxis in a single Boyden chamber system. RESULTS: Interleukin (IL)-8 and growth-related oncogene (GRO)-alpha were induced in nasal fibroblast culture by proinflammatory stimulus. After 24 h of stimulation neutrophil chemotactic activity only was detected for IL-8. Granulocyte chemotactic protein (GCP)-2 mRNA was already significantly up-regulated after 2 h of stimulation. CONCLUSION: Induction of IL-8 protein dominates chemokine synthesis 24 and 72 h after stimulation, whereas induction of GCP-2 mRNA seems to have a role in the early phase after 2 h of exposition with TNF-alpha.

Antimicrobial Cationic Peptides↗