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Biomedical subjects

J Marienhagen

Publications and source records attributed to J Marienhagen.

At least 19 recordsLinked to original sources

Mechanisms of regional wall motion abnormalities in contrast-enhanced dobutamine stress echocardiography.

BACKGROUND: In the diagnosis of coronary artery disease (CAD) with Dobutamine Stress Echocardiography (DSE), regional wall motion abnormalities (RWMA) are assumed to indicate a perfusion deficit. METHODS AND RESULTS: For a more particular examination of RWMAs, we compared simultaneous echo-contrast (Optisone)-enhanced DSE (0-40 microg/kg Dobutamine, 16-segment- model) and MiBi-SPECT in a prospective double-blinded study design in 69 non-selected consecutive patients (44 male, 25 female, age 64+/-12 years). Additionally, all patients were examined by coronary-angiography. The prevalence of significant CAD (stenosis >50% lumen diameter) was 52%. DSE had a sensitivity of 78% and a specificity of 66% for the detection of significant CAD with a positive and negative predictive value of 72 and 73%, respectively. Among 28 patients with significant CAD and positive DSE study (true positive), 78% displayed a corresponding perfusion deficit in MiBi-SPECT. Among 11 patients with a positive DSE study but no current significant coronary stenosis (false positive), 82% showed stress-induced RWMAs in the inferior/posterior region, 73% displayed left ventricular hypertrophy, 54% resting-ECG abnormalities and 45% resting-RWMA (3 previous MI, 2 previous CABG surgery). Among 8 patients with negative DSE study but significant coronary stenosis (false negative), 75% had a stenosis of the LCX, 63% displayed resting- WMA, 63% displayed left bundle branch block or ST-segment depression, 50% displayed only peripheral coronary stenosis, and DSE visualization was suboptimal in 38%. CONCLUSION: This prospective study in non-selected patients shows that the majority of RWMAs in DSE are matched to a perfusion deficit detectable by nuclear imaging. Nevertheless, pre-existing cardiac abnormalities may also lead to stress-induced RWMA not associated with a perfusion deficit or mask a perfusion deficit upon DSE. Particularly in patients with LV hypertrophy, resting-RWMA, bundle branch block or ST segment depression, the predictive value of DSE may, therefore, be limited.

Cardiotonic Agents↗

[Treatment of chronic tinnitus with neuronavigated repetitive Transcranial Magnetic Stimulation (rTMS)].

BACKGROUND AND OBJECTIVE: Idiopathic tinnitus is a frequent and debilitating disorder of largely unknown pathophysiology. Focal brain activation in the auditory cortex has recently been demonstrated in chronic tinnitus. Low-frequency rTMS can reduce cortical hyperexcitability. PATIENTS AND METHODS: In 12 patients with chronic tinnitus, fusion of [18F]deoxyglucose-PET and structural MRI (T1, MPRAGE) scans allowed the area of increased metabolic activity in the auditory cortex to be exactly identified; this area was selected as the target for rTMS. A neuronavigational system adapted for TMS positioning enabled the relative positions of the figure-8 coil and the target area to be monitored. Repetitive TMS (110% motor threshold; 1 Hz; 2000 stimuli per day over 5 days) was performed using a placebo-controlled crossover design. A sham coil system was used for the placebo stimulation. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller). RESULTS: In all 12 patients an asymmetrically increased metabolic activation of the gyrus of Heschl was detected. The tinnitus score was significantly improved after 5 days of active rTMS, an effect not seen after placebo stimulation. CONCLUSION: These preliminary results show that neuronavigated rTMS may improve our understanding and treatment of chronic tinnitus.

Adult↗

[Integration of PACS and HIS into the workflow of a nuclear medicine department. Experience in Regensburg].

AIM: The development of new diagnostic techniques and the implementation of a modern quality control management system requires the continuous adaptation of existing data processing tools to the nuclear medicine diagnostic workflow. Furthermore, PACS connected to HIS facilitates and enhances the transfer of data and pictures, and satisfies the legal requirements for data retention as regulated by law. Therefore, the aim of this work is to present the architecture, structure and results of such a system newly installed in a department of nuclear medicine. METHODS: Initially, the nuclear medicine workflow was carefully analyzed and each step was correlated to the corresponding module. The standard SAP R/3 and IS-H/IS-H(*)med based software used for patient administration at the University of Regensburg Hospital was adapted to the needs of the Nuclear Medicine Department. The networking of the imaging systems was done by integration of a PACS. Finally, the PACS was connected to the HIS to allow the attachment of images to the medical report. RESULTS, CONCLUSION: By connecting the HIS to the nuclear medicine PACS, the workflow was significantly improved. The data management sequence starting at the reception desk, continuing through the nuclear medical examination, to the physician's final written and image report is clearly structured. Although high demands exist on technical support and administration the integration of PACS and HIS into the nuclear medicine workflow leads to enhanced efficiency and reduction in hospital costs. Patient and data management are considerably improved in this way.

Documentation↗

The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2.

BACKGROUND: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), or Nasu-Hakola disease, is a presenile dementia associated with loss of myelin, basal ganglia calcification, and bone cysts. It is caused by recessively inherited mutations in two genes encoding subunits of a cell membrane-associated receptor complex: TREM2 and DAP12. The clinical course of PLOSL has not been characterized in a series of patients with TREM2 mutations. METHODS: The authors compare neurologic and neuroradiologic follow-up data of six patients carrying TREM2 mutations with PLOSL due to defective DAP12 genes. The authors review the known mutations in these two genes. RESULTS: Mutations in DAP12 and TREM2 result in a uniform disease phenotype. In Finnish and Japanese patients with PLOSL, DAP12 mutations predominate, whereas TREM2 is mutated more frequently elsewhere. CONCLUSIONS: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy should be considered in adult patients under age 50 years with dementia and basal ganglia calcification. Radiographs of ankles and wrists, and DNA test in uncertain cases, confirm the diagnosis.

Adaptor Proteins, Signal Transducing↗

Cardiovascular risk estimates and risk factors in renal transplant recipients.

Cardiovascular morbidity, including coronary artery disease and left ventricular hypertrophy, and mortality are high in patients following renal transplantation. Cardiovascular disease is thought to be due to traditional (hypertension, hyperlipidemia, diabetes mellitus and smoking) as well as nontraditional cardiovascular risk factors (microinflammation). Furthermore, immunosuppressive drugs, namely, calcineurin inhibitors, sirolimus, and steroids, have been reported to adversely affect cardiovascular risk factors (e.g., hypertension, hyperlipidemia, hyperglycemia). Evidence from comparative trials and from conversion studies suggest that blood pressure, hyperlipidemia, and hyperglycemia after renal transplantation may be differentially affected by the calcineurin inhibitors cyclosporine and tacrolimus. In the European Tacrolimus versus Cyclosporin A Microemulsion Renal Transplantation Study, 557 patients were randomly allocated to therapy with tacrolimus (n = 286) versus cyclosporine (n = 271). In addition, to blood pressure, serum cholesterol, HDL cholesterol, triglycerides, and blood glucose, we estimated the 10-year risk of coronary heart disease (Framingham risk score). Tacrolimus resulted in a significantly lower time-weighted average of serum cholesterol (P < .001), and mean arterial blood pressure (P < .05), but a higher time-weighted average of blood glucose (P < .01) than cyclosporine. Mean 10-year coronary artery disease risk estimate was significantly lower in men treated with tacrolimus, (10.0% versus 13.2%; P < .01) but was unchanged in women (4.7% versus 7.0%). Tacrolimus and cyclosporine microemulsion have compound-specific effects on cardiovascular risk factors that differentially affect the predicted rate of coronary artery disease.

Cardiovascular Diseases↗

Dual function of membrane-bound heat shock protein 70 (Hsp70), Bag-4, and Hsp40: protection against radiation-induced effects and target structure for natural killer cells.

CX+/CX- and Colo+/Colo- tumor sublines with stable heat shock protein 70 (Hsp70) high and low membrane expression were generated by fluorescence activated cell sorting of the parental human colon (CX2) and pancreas (Colo357) carcinoma cell lines, using an Hsp70-specific antibody. Two-parameter flow cytometry revealed that Hsp70 colocalizes with Bag-4, also termed silencer of death domain, not only in the cytosol but also on the plasma membrane. After nonlethal gamma-irradiation, the percentage of membrane-positive cells and the protein density of Hsp70 and Bag-4 were found to be strongly upregulated in carcinoma sublines with initially low expression levels (CX-, Colo-). Membrane expression of Hsp70 was also elevated in Bag-4 overexpressing HeLa cervix carcinoma cells when compared to neo-transfected cells. In response to gamma-irradiation, neo-transfected HeLa cells behaved like Hsp70/Bag-4 low-expressing CX- and Colo-, and Bag-4-transfected HeLa cells like Hsp70/Bag-4 high-expressing carcinoma sublines CX+ and Colo+. Immunoprecipitation studies further confirmed colocalization of Hsp70 and Bag-4 but also point to an association of Hsp70 and Hsp40 on the plasma membrane of CX+ and Colo+ cells; on CX- and Colo- tumor sublines, Hsp40 was detectable in the absence of Hsp70 and Bag-4. Other co-chaperones including Hsp60 and Hsp90 were neither found on the cell surface of CX+/CX-, Colo+/Colo- nor on HeLa neo-/HeLa Bag-4-transfected tumor cells. Functionally, Hsp70/Bag-4 and Hsp70/Hsp40 membrane-positive tumor cells appeared to be better protected against radiation-induced effects, including G2/M arrest and growth inhibition, on the one hand. On the other hand, membrane-bound Hsp70, but neither Bag-4 nor Hsp40, served as a recognition site for the cytolytic attack mediated by natural killer cells.

Adaptor Proteins, Signal Transducing↗

Clioquinol treatment in familiar early onset of Alzheimer's disease: a case report.

Recently the metal chelator clioquinol (CQ) has been suggested as a possible option for treatment of Alzheimer's disease (AD). We report two patients with early onset of AD [one with a mutant amyloid-precursor-protein (APP) gene] who received long-term treatment with CQ. In both cases focally augmented cerebral glucose metabolism and stabilization but no amelioration of the clinical impression were observed without signs of neurotoxicity. In one case CSF-tau and beta-Amyloid (42/40) concentrations changed during CQ treatment.

Alzheimer Disease↗

[The therapeutic impact of (18)F-FDG whole body PET. A radiooncologist's view].

AIMS: An explorative analysis of the diagnostic as well as therapeutic impact of (18)F-FDG whole body PET on patients with various tumours in the setting of an university hospital radiation therapy was performed. PATIENTS AND METHODS: 222 FDG PET investigations (148 initial stagings, 74 restagings) in 176 patients with diverse tumour entities (37 lung carcinoma, 15 gastrointestinal tumours, 38 head and neck cancer, 30 lymphoma, 37 breast cancer, 19 sarcoma and 16 other carcinomas) were done. All PET scans were evaluated in an interdisciplinary approach and consecutively confirmed by other imaging modalities or biopsy. Unconfirmed PET findings were ignored. Proportions of verified PET findings, additional diagnostic information (diagnostic impact) and changes of the therapeutic concept intended and documented before PET with special emphasis on radiooncological decisions (therapeutic impact) were analysed. RESULTS: 195/222 (88%) FDG-PET findings were verified, 104/222 (47%) FDG-PET scans yielded additional diagnostic information (38 distant, 30 additional metastasis, 11 local recurrencies, 10 primary tumours and 15 residual tumours after chemoptherapy). The results of 75/222 (34%) scans induced changes in cancer therapy and those of 58/222 (26%) scans induced modifications of radiotherapeutic treatment plan (esp. target volumes). CONCLUSION: (18)F-FDG whole body PET is a valuable diagnostic tool for therapy planning in radiooncology with a high impact on therapeutic decisions in initial staging as well as in restaging. Especially in a curative setting it should be used for definition of target volumes.

Biopsy↗

Vocal stability in functional dysphonic versus healthy voices at different times of voice loading.

Functional (nonorganic) dysphonia is often characterized by vocal instability. The purpose of the prospective study was to examine whether there is a difference in vocal instability of functional dysphonic voices compared with healthy ones, this means whether electroglottographic perturbation values differ (1) between healthy and dysphonic voices and (2) between two subgroups of the dysphponic voices (hypertonic and hypotonic dysphonic voices). Twenty-three patients with hypertonic functional dysphonia, 9 with hypotonic functional dysphonia and 31 healthy nonsmokers, were each examined electroglottographically before (Ex 1), immediately after (Ex 2), and 1 hour after (Ex 3) voice loading. Perturbations of frequency, amplitude, quasi-open-quotient, and contact-index were calculated from the EGG signal. At all three times of examination, hypertonic dysphonic voices showed higher perturbations than healthy voices, and they had higher perturbations than hypotonic dysphonic voices before and 1 hour after voice loading. Hypotonic dysphonic voices showed higher perturbations than healthy voices only 1 hour after voice loading. Voice loading induced different reactions in dysphonic voices: Some voices showed increased perturbations, and others exhibited normal or even decreased perturbation immediately after voice loading. Examination of electroglottographic-derived perturbations immediately after voice loading seems not to be useful. Differentiation of hypertonic and hypotonic dysphonic voices was possible with an estimated sensitivity of 88.9% and a specificity of 87.0% by using the sum of the amplitude-perturbation and the quasi-open-quotient-perturbation measured before voice loading.

Adult↗

Contrasting metabolic impairment in frontotemporal degeneration and early onset Alzheimer's disease.

[18F]FDG positron emission tomography (PET) scans of 14 patients comprising the clinical prototypes of dementias that are considered to be associated with frontotemporal lobar degeneration (FTLD) were compared to a population of 15 patients with early onset Alzheimer's disease (EOAD). The FTLD group included patients with frontotemporal dementia (FTD), semantic dementia (SD), and primary progressive aphasia (PPA). A voxel to voxel group comparison identified metabolic impairment in the bilateral ventromedial frontal area, the left anterior insula, and inferior frontal cortex, and indicated the right middle temporal gyrus to exhibit increased activity in FTLD compared to EOAD patients. All identified cortical structures are considered to be critically involved in neuropsychological features associated with FTLD (altered social behavior, aphasia) and EOAD (impaired linguistic and visuo-constructive abilities). In conjunction with recent insights from neuropathologic investigations, these results implicate that the a priori heterogeneous prototypes of FTLD (FTD, SD, PPA) may share more common ground than previously assumed, and therefore would become distinguishable as an entire group from EOAD.

Age of Onset↗

High-frequency repetitive transcranial magnetic stimulation in schizophrenia: a combined treatment and neuroimaging study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of frontal brain regions is under study as a non-invasive method in the treatment of affective disorders. Recent publications provide increasing evidence that rTMS may be useful in treating schizophrenia. Results are most intriguing, demonstrating a reduction of negative symptoms following high-frequency rTMS. In this context, disentangling of negative and depressive symptoms is of the utmost importance when understanding specific rTMS effects on schizophrenic symptoms. METHOD: Using a sham-controlled parallel design, 20 patients with schizophrenia were included in the study. Patients were treated with high-frequency 10 Hz rTMS over 10 days. Besides clinical ratings, ECD-SPECT (technetium-99 bicisate single photon emission computed tomography) imaging was performed before and after termination of rTMS treatment. RESULTS: High-frequency rTMS leads to a significant reduction of negative symptoms combined with a trend for non-significant improvement of depressive symptoms in the active stimulated group as compared with the sham stimulated group. Additionally, a trend for worsening of positive symptoms was observed in the actively treated schizophrenic patients. In both groups no changes in regional cerebral blood flow could be detected by ECD-SPECT. CONCLUSIONS: Beneficial effects of high-frequency rTMS on negative and depressive symptoms were found, together with a trend for worsening positive symptoms in schizophrenic patients.

Adult↗

Intraventricular cytarabine in a case of idiopathic hypertrophic pachymeningitis.

Idiopathic hypertrophic chronic pachymeningitis (IHCP) is characterised by inflammatory fibrotic thickening of the dura mater. Long term management is controversial. A 28 year old man with craniospinal IHCP and prominent lymphocytic meningitis is reported. Cerebrospinal fluid and histological examination suggested a CD4+ T cell driven process and B cell stimulation. After surgical, tuberculostatic, and immunosuppressive treatment failed to control the progressive meningeal hypertrophy, causing severe headache and neurological disability, the disease process eventually abated with intraventricular cytarabine treatment.

Adult↗

[Critical appraisal of diagnostic studies in nuclear medicine].

The conceptual ideas of evidence based critical appraisal of diagnostic studies are described in this survey. In this context special attention is given to biases in study design such as verification- as well as information-bias limiting the validity of diagnostic studies. The practice of critical appraisal is demonstrated in an application to an example of a nuclear medicine scenario. The impact of evidence based medicine on nuclear medicine as a diagnostic discipline is discussed in detail.

Diagnosis↗

Sonographic parenchymal and brain perfusion imaging: preliminary results in four patients following decompressive surgery for malignant middle cerebral artery infarct.

To investigate new methods of diagnostic transcranial sonography for brain parenchymal, vascular and perfusion imaging, we performed 3-D native tissue harmonic transcranial sonography (3D-nthTCS), 3-D transcranial color-coded duplex sonography (3D-TCCS), and "loss-of-correlation" imaging (LOC-TCCS) in four patients following early hemicraniectomy due to space-occupying "malignant" middle cerebral artery infarction (MMCAI). Three-dimensional datasets, utilizing 3D-nthTCS and 3D-TCCS, were created and up to 10 axial 2-D B-mode image planes, similar to CCT, reconstructed in each patient. Three-dimensional reconstructions of the circle of Willis documented one persistent carotid-T occlusion and three recanalizations of the MCA. LOC-TCCS, based on stimulated acoustic emission from an ultrasound (US) contrast agent, demonstrated a perfusion deficit in 2 of 3 patients, with regard to their infarcts. Concluding, 3D-nthTCS, 3D-TCCS and LOC-TCCS are promising tools for bedside monitoring, early prognosis and treatment evaluation for MMCAI in the postoperative period. Further studies should be performed to standardize these new methods and evaluate their applications through the intact calvarina.

Adult↗

[Aphasia and dementia].

Primary progressive aphasia (PPA) is an uncommon neurodegenerative syndrome characterized by a relatively isolated dissolution of language function at the beginning, followed by deterioration of general cognitive function and of activities of daily living after 2 or more years. On account of neuropathological and clinical findings, PPA is supposed to form part of the spectrum of frontotemporal lobar degeneration. We present a case study of a 66-year-old woman with a probable fluent progressive aphasia. She initially experienced word amnesia and developed after 2 - 3 years gradual regression of word comprehension, over-fluent speech with semantic paraphasias, and at last generalized dementia. In addition to minor bilateral cortical volume reduction on CCT, MRI showed left temporal lobe atrophy involving hippocampus, SPECT revealed reduced uptake left frontal and temporal.

Aged↗

Stochastic model of central synapses: slow diffusion of transmitter interacting with spatially distributed receptors and transporters.

A detailed mathematical analysis of the diffusion process of neurotransmitter inside the synaptic cleft is presented and the spatio-temporal concentration profile is calculated. Using information about the experimentally observed time course of glutamate in the cleft the effective diffusion coefficient Dnet is estimated as Dnet approximately 20-50 nm(2) microseconds(-1), implying a strong reduction compared with free diffusion in aqueous solution. The tortuosity of the cleft and interactions with transporter molecules are assumed to affect the transmitter motion. We estimate the transporter density to be 5170 to 8900 micrometer(-2) in the synaptic cleft and its vicinity, using the experimentally observed time constant of glutamate. Furthermore a theoretical model of synaptic transmission is presented, taking the spatial distribution of post-synaptic (AMPA-) receptors into account. The transmitter diffusion and receptor dynamics are modeled by Monte Carlo simulations preserving the typically observed noisy character of post-synaptic responses. Distributions of amplitudes, rise and decay times are calculated and shown to agree well with experiments. Average open probabilities are computed from a novel kinetic model and are shown to agree with averages over many Monte Carlo runs. Our results suggest that post-synaptic currents are only weakly potentiated by clustering of post-synaptic receptors, but increase linearly with the total number of receptors. Distributions of amplitudes and rise times are used to discriminate between different morphologies, e.g. simple and perforated synapses. A skew in the miniature amplitude distribution can be caused by multiple release of pre-synaptic vesicles at perforated synapses.

Animals↗