Neurovascular contact of cranial nerve IX and X root-entry zone in hypertensive patients.
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Biomedical subjects
Publications and source records attributed to C Menzel.
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The dependence of the signal intensity of analyte and matrix ions on laser fluence was investigated for infrared matrix-assisted laser desorption/ionization (IR-MALDI) mass spectrometry using a flat-top laser beam profile. The beam of an Er : YAG laser (wavelength, 2.94 microm; pulse width, 90 ns) was coupled into a sapphire fiber and the homogeneously illuminated end surface of the fiber imaged on to the sample by a telescope. Three different laser spot sizes of 175, 350 and 700 microm diameter were realized. Threshold fluences of common IR matrices were determined to range from about 1000 to a few thousand J m(-2), depending on the matrix and the size of the irradiated area. In the MALDI-typical fluence range, above the detection threshold ion signals increase strongly with fluence for all matrices, with a dependence similar to that for UV-MALDI. Despite the strongly different absorption coefficients of the tested matrices, varying by more than an order of magnitude at the excitation laser wavelength, threshold fluences for equal spot sizes were found to be comparable within a factor of two. With the additional dependence of fluence on spot size, the deposited energy per volume of matrix at threshold fluence ranged from about 1 kJ mol(-1) for succinic acid to about 100 kJ mol(-1) for glycerol.
Mental retardation is a very common and extremely heterogeneous disorder that affects about 3% of the human population. Its molecular basis is largely unknown, but many loci have been mapped to the X chromosome. We report on two mentally retarded females with X;autosome translocations and breakpoints in Xp11, viz., t(X;17)(p11;p13) and t(X;20)(p11;q13). (Fiber-) FISH analysis assigned the breakpoints to different subbands, Xp11.4 and Xp11.23, separated by approximately 8 Mb. High-resolution mapping of the X- chromosome breakpoints using Southern blot hybridization resulted in the isolation of breakpoint-spanning genomic subclones of 3 kb and 0. 5 kb. The Xp11.4 breakpoint is contained within a single copy sequence, whereas the Xp11.23 breakpoint sequence resembles an L1 repetitive element. Several expressed sequences map close to the breakpoints, but none was found to be inactivated. Therefore, mechanisms other than disruption of X-chromosome genes likely cause the phenotypes.
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UNLABELLED: AIM of this study was to determine whether the sentinel lymph nodes (SLNs) can be accurately identified in breast cancer patients with intradermal injection of the radiotracer above the primary tumour in comparison to peritumoural injection. METHODS: In 45 women with breast cancer we performed lymphoscintigraphy on two separate days. We injected Tc-99m nanocolloid on the first day peritumourally, and on a separate day intradermally. The results of both investigations using different injection sites were compared in order to determine the number and location of SLNs. RESULTS: The SLN identification rate using peritumoural injection was 71% (32 of 45 patients) and 96% (43 out of 45 patients) using intradermal injection. In 62% (28 of 45 patients) the number and location of the SLNs were identical. In 97% (31 of 32 patients) in whom a SLN was detected using peritumoural injection, the same SLNs reappeared with intradermal injection. There were no false negative findings with the peritumoural administration of tracer whereas the intradermal administration approach resulted in a false negative rate of 13%. CONCLUSION: In women with breast cancer the reproducibility of lymphoscintigraphy using peritumoural and intradermal injection sites was 62%. The intradermal injection modality enables the detection of a SLN in patients where the peritumoural injection failed but it has the disadvantage of a higher false negative rate in comparison to the peritumoural injection technique.
BACKGROUND: Bacteriorhodopsin (bR) from Halobacterium salinarum is a proton pump that converts the energy of light into a proton gradient that drives ATP synthesis. The protein comprises seven transmembrane helices and in vivo is organized into purple patches, in which bR and lipids form a crystalline two-dimensional array. Upon absorption of a photon, retinal, which is covalently bound to Lys216 via a Schiff base, is isomerized to a 13-cis,15-anti configuration. This initiates a sequence of events - the photocycle - during which a proton is transferred from the Schiff base to Asp85, followed by proton release into the extracellular medium and reprotonation from the cytoplasmic side. RESULTS: The structure of bR in the ground state was solved to 1.9 A resolution from non-twinned crystals grown in a lipidic cubic phase. The structure reveals eight well-ordered water molecules in the extracellular half of the putative proton translocation pathway. The water molecules form a continuous hydrogen-bond network from the Schiff-base nitrogen (Lys216) to Glu194 and Glu204 and includes residues Asp85, Asp212 and Arg82. This network is involved both in proton translocation occurring during the photocycle, as well as in stabilizing the structure of the ground state. Nine lipid phytanyl moieties could be modeled into the electron-density maps. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis of single crystals demonstrated the presence of four different charged lipid species. CONCLUSIONS: The structure of protein, lipid and water molecules in the crystals represents the functional entity of bR in the purple membrane of the bacteria at atomic resolution. Proton translocation from the Schiff base to the extracellular medium is mediated by a hydrogen-bond network that involves charged residues and water molecules.
Magnetic resonance imaging (MRI) was performed on an infant with typical complex partial seizures. Visual analysis revealed MRI signs of left hippocampal sclerosis (HS) at an age of 9 months. Morphometric data including volumetry and relaxometry confirming the diagnosis are shown. This is the first report of an infant younger than 2 years with typical MRI findings including morphometric data on HS.
The diagnostic potential of technetium-99m hexamethylpropylene amine oxime (HMPAO) following systemic administration of the cerebral vasodilator acetazolamide (acetazolamide test) was evaluated by regional cerebral blood flow (rCBF) single-photon emission tomography (SPET) in patients with Alzheimer's disease (AD) or vascular dementia (VD). An initial, high-resolution SPET study was performed with 99mTc-HMPAO, and after 2 days the patients were re-evaluated with 99mTc-HMPAO following systemic administration of acetazolamide. Reconstructed SPET slices were evaluated visually and semiquantitatively by a semi-automatic rCBF map method. When 99mTc-HMPAO alone was used, bilateral hypoperfusion was found in the temporal and/or parietal regions in 33% (6/18) of the VD patients and in 70% (23/33) of the AD patients. The corresponding data obtained by quantitative evaluation were 41% (7/17) and 71% (15/21), respectively. The vascular reserve capacity, as determined with the acetazolamide test, was preserved visually in 22% (4/18) and quantitatively in 29% (5/17) of the VD patients, but in 73% (24/33) and 76% (16/21) of the AD patients. The differences in the perfusion patterns between the VD and AD patients were statistically significant (P<0.01, Fischer's exact test). Of the VD patients with hypoperfusion (bilateral temporal and/or parietal), 4/6 (67%, visual evaluation) and 4/7 (57%, quantitative evaluation) had a decreased vascular reserve capacity as determined with the acetazolamide test. In the AD group of patients the corresponding results were 3/23 (13%) and 4/15 (27%). It is concluded that the acetazolamide test is promising in rCBF SPET to differentiate VD from AD.
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Disease associated balanced chromosome rearrangements (DBCRs) have been instrumental in the isolation of many disease genes. To facilitate the molecular cytogenetic characterisation of DBCRs, we have generated a set of >1200 non-chimeric, cytogenetically and genetically anchored CEPH YACs, on average one per 3 cM, spaced over the entire human genome. By fluorescence in situ hybridisation (FISH), we have performed a systematic search for YACs spanning translocation breakpoints. Patients with DBCRs and either syndromic or non-syndromic mental retardation (MR) were ascertained through the Mendelian Cytogenetics Network (MCN), a collaborative effort of, at present, 270 cytogenetic laboratories throughout the world. In this pilot study, we have characterised 10 different MR associated chromosome regions delineating candidate regions for MR. Five of these regions are narrowed to breakpoint spanning YACs, three of which are located on chromosomes 13q21, 13q22, and 13q32, respectively, one on chromosome 4p14, and one on 6q25. In two out of six DBCRs, we found cytogenetically cryptic deletions of 3-5 Mb on one or both translocation chromosomes. Thus, cryptic deletions may be an important cause of disease in seemingly balanced chromosome rearrangements that are associated with a disease phenotype. Our region specific FISH probes, which are available to MCN members, can be a powerful tool in clinical cytogenetics and positional cloning.
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AIMS: One-hundred and eighty-eight cases of human mammary carcinoma were examined immunohistochemically for their expression of Ki67, p34cdc2 and c-erbB-2. DNA image cytometry was performed to evaluate DNA ploidy, Auer type, S-phase fraction (SPF), 5c exceeding rate (5cER) and 2c deviation index (2cDI). METHODS AND RESULTS: One-hundred and sixty-eight cases were invasive ductal carcinomas, 20 were of invasive lobular type. Routinely assessed oestrogen and progesterone receptor scores were available. The results were analysed statistically in comparison to tumour type, histopathological grade, lymph node status, menopausal status, patient age and overall survival. Ki67 (P < 0.002) and c-erbB-2 (P < 0.0001) correlated well with overall survival (P < 0.0008) and grade (P < 0.038) but not with lymph node status and tumour type. p34cdc2 showed a trend towards a positive correlation with Ki67 (P < 0.058) and a significant negative correlation with receptor status (P < 0.008) but with none of the other parameters examined. CONCLUSIONS: No association between the DNA measured parameters (Auer type, SPF, 5cER and 2cDI) and survival was found. Our results suggest that c-erbB-2 and Ki67 are parameters which might, in combination with receptor status, help to define subgroups with different outcomes.
BACKGROUND: The diagnostic potential of 99mTc-HMPAO following systemic administration of the cerebral vasodilator acetazolamide (acetazolamide test) was evaluated using regional-cerebral-blood-flow (rCBF) SPECT in patients with Alzheimer's disease (AD) or with vascular-type of dementia (VD). METHODS: An initial, high-resolution SPELT study was performed with 99mTc-HMPAO, and after 2 days patients were re-evaluated with 99mTc-HMPAO following systemic administration of acetazolamide. Reconstructed SPELT slices were evaluated visually and semiquantitatively by a semiautomatic rCBF map method. RESULTS: Using 99mTc-HMPAO alone, a bilateral hypoperfusion was found in the temporal and/or parietal regions in 33% (6/18) of VD patients and in 70% (23/33) of AD patients. The vascular reserve capacity, as determined with the acetazolamide test, was not impaired in 22% of the VD patients but in 76% of the AD patients. The differences in the perfusion patterns between VD and AD patients were statistically different (p < 0.01, Fischer's exact test). Of the 6 VD patients with hypoperfusion (bilateral temporal and/or parietal), 4 had a decreased vascular reserve capacity as determined in the acetazolamide test. Decreased reserve capacity was found in only 4 out of 25 patients with AD. CONCLUSIONS: The acetazolamide test is helpful in rCBF SPECT to differentiate VD from AD.
We report on a patient with a follicular Hurthle cell carcinoma in whom distant metastases were initially radioiodine negative or only weakly positive. Redifferentiation therapy with 13-cis retinoic acid induced a significant radioiodine uptake in metastatic tissue. Thyroglobulin (Tg) immunostaining and autoradiography of a bone metastasis in the right femur, which was initially radioiodine negative, proved Tg synthesis, combined with iodine incorporation into tumor cells. Glucose metabolism in metastases was partially increased and partially unchanged after redifferentiation therapy. The distinct increase of serum Tg after retinoic acid treatment was interpreted as a functional sign of redifferentiation.
UNLABELLED: Due to a dedifferentiation of tumor cells, some thyroid carcinomas lose their capability for radioiodine (RI) concentration. This phenomenon is associated with a worse prognosis and prevents effective treatment. Retinoic acid (RA) is known to induce redifferentiation in various kinds of tumors and has been used recently in thyroid cancer. METHODS: Twelve patients (9 women, 3 men) with 6 papillary, 4 follicular and 2 mixed-cell type tumors (including 4 Hurthle cell carcinomas) were treated orally with RA (dose: 1.18 +/- 0.37 mg/kg body weight) for at least 2 mo before RI therapy. None of the patients could be treated with any other modality (RI, surgery, external radiation) when RA administration was started. Initially, clinically important tumor sites did not take up significant amounts of RI. Changes of RI uptake and thyroglobulin (Tg) serum values were determined. Glucose metabolism was followed with fluorodeoxyglucose (FDG) PET imaging in 10 patients before and in 5 patients after RA treatment. RESULTS: In 2 patients, a significant RI uptake was induced by RA, and in another 3 patients a faint RI uptake was achieved (responder group). In 7 patients, no change of RI uptake was observed (nonresponder group). Median Tg was increased from 105-840 microg/liter during RA therapy in the responder group, which was significantly higher than the nonresponder group (173-134 microg/liter). FDG PET was positive in all 10 patients before RA therapy. PET showed variable patterns of changes (increase/decrease/disappearance) in glucose consumption related to RA response. CONCLUSION: RA can induce RI uptake in some patients with RI negative thyroid carcinoma tumor sites. Response to RA is associated with a significantly higher increase of Tg, suggesting that a restoration of Tg synthesis can be addressed as a redifferentiation parameter in these patients.
PURPOSE: A retrospective evaluation of the ictal temporal tracer uptake and the perfusion pattern in other neo- and subcortical structures was performed to define typical extratemporal changes of rCBF that might further aid the differentiation of temporal and extratemporal seizures. METHOD: Ictal and interictal rCBF brain SPECT studies were done in 17 patients with seizures of mesial temporal onset according to scalp electroencephalography (EEG) and electrocorticography (ECoG) using 99mTc-ECD. Except for hippocampal sclerosis/atrophy, which was found in 11/17 patients, no morphologic anomalies were detected by MRI. Ictal tracer injections were given immediately after the onset of the seizure according to continuous video-EEG monitoring. The injection latency was two to twenty seconds. The data acquisition was done 45 minutes after the tracer injection using an annular crystal system (Ceraspect, DSI). In 15 patients a semiquantitative ROI-analysis of the tracer uptake in temporal and frontal regions could be obtained. RESULTS: All ictal studies correctly localised the affected temporal lobe. A detection of the epileptogenic focus itself was successful in 59% of patients while in the remaining patients the maximum of tracer uptake was not found to be located in the mesial temporal lobe only. In contrast to all other cerebral structures, only within the ipsilateral basal frontal cortex a frequent reaction to the temporal seizure was found. The basal frontal cortex ipsilateral to the affected temporal lobe showed a reduction of tracer uptake between the ictal and interictal study in 82% of patients which was semiquantitatively significant using a paired t-test (p < 0.05). Other neo- or subcortical structures showed inconsistent results. CONCLUSION: Secondary involvement of neocortical temporal structures in ictal rCBF-SPECT with 99mTc-ECD occurs early and focal maxima of tracer uptake within the temporal lobe do not necessarily represent the epileptogenic focus itself. Seizures of mesial temporal origin did not activate but frequently depressed the ipsilateral basal frontal tracer uptake during the early ictal phase. This phenomenon may account for some aspects of the clinical appearance of mesial temporal seizures.
18Fluorine-fluorodeoxyglucose (FDG) positron-emission tomography (PET) has emerged as a useful method in various fields of oncology. The aim of the present study was to evaluate the clinical significance of this technique in differentiated thyroid carcinoma and to compare the results with other imaging modalities, particularly with whole-body 131iodine scintigraphy (WBS) and hexakis (2-methoxyisobutylisonitrile) (99m)technetium (I) scintigraphy (MIBI). Whole-body PET imaging using FDG was performed in 54 patients. There were 39 patients with papillary tumors and 15 patients with follicular tumors (including 3 Hürthle-cell carcinomas). Primary tumor stage (pT) was pT1 in 5 cases, pT2 in 19 cases, pT3 in 2 cases, pT4 in 24 cases, and unknown in 4 cases, respectively. Finally, for each case an overall clinical evaluation was done including histology, cytology, thyroglobulin level, sonography, computed tomography, magnetic resonance imaging, and subsequent clinical course, to allow a comparison with functional imaging results. Compared with WBS, FDG-PET gave different results in the majority of cases with recurrence/metastases (11 FDG-true-positive/WBS-negative tumor sites and 8 WBS-true-positive/FDG-negative tumor sites). In 7 patients with recurrence/metastases, FDG-PET and WBS gave corresponding results (10 sites). In 28 patients, FDG-PET and WBS were normal (including 2 false-negative cases). MIBI was performed in 44 cases. FDG-PET was better correlated to MIBI (congruent positive results in 13 tumor sites) than to WBS. Compared with MIBI, FDG-PET was superior in 5 cases (including 3 patients with distant metastases). Two FDG-negative/MIBI-positive tumors were observed. Different tracer uptake mechanisms have to be considered regarding "nonspecific" tumor imaging with FDG-PET or MIBI. Nevertheless, since spatial resolution with respect to tomographic imaging is inferior with single photon emission computer tomography (SPECT) using MIBI, the observed higher sensitivity of PET might be due to the higher spatial resolution of this method. As far as grading could be obtained, FDG-PET seemed to be more sensitive than WBS in high-grade tumors, whereas WBS was positive predominantly in low-grade carcinomas, although statistical significance could not be reached. The results prove the clinical usefulness of FDG-PET and MIBI for detection of 131iodine-negative tumor tissue in differentiated thyroid cancer.