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Biomedical subjects

J Weis

Publications and source records attributed to J Weis.

At least 19 recordsLinked to original sources

Phrenic nerves and diaphragms in sudden infant death syndrome.

Disturbances of the respiratory system may be an important factor in the cascade of events leading to sudden infant death syndrome (SIDS). Even though the diaphragm is the major respiratory muscle in infants, little is known about alterations of this muscle and of the phrenic nerve in SIDS. In the present study, diaphragms and phrenic nerves of 24 SIDS infants and seven controls were analyzed. Morphometric analysis revealed only slightly larger cross sectional areas of phrenic nerve axons but no increase in myelin sheath thickness in SIDS cases. However, in one SIDS case, myelinated nerve fibre density was severely reduced. Using electron microscopy, several nerve fibres of SIDS infants showed focal accumulations of neurofilaments. Muscle fibre diameters in SIDS diaphragms were significantly larger compared to controls (P < 0.0001). However, in almost all SIDS and control cases, axons and myelin sheaths were artificially swollen, and acute segmental muscle fibre ruptures and contracture bands were found. These prominent nonspecific ultrastructural alterations should advise caution in the interpretation of morphometric data. Thus, in some cases exemplified by one case of the present series, decreased density of phrenic nerve myelinated axons might contribute to SIDS. Still, the present results indicate that development of phrenic nerves and diaphragms is not delayed in most SIDS infants.

Autopsy

Distribution of B-50(GAP-43) mRNA and protein in the normal adult human spinal cord.

B-50(GAP-43) is a phosphoprotein mainly found in the nervous system which plays a major role in neurite growth during development and regeneration as well as in synaptic remodelling. In the mature intact central nervous system, intense B-50 immunoreactivity (B-50-IR) can still be detected in regions which maintain residual capacity for structural re-organization. B-50 expression has been studied extensively in laboratory animals; however, its distribution and regulation in the human spinal cord is largely unknown. As a first step to analyze lesion-induced structural alterations, we investigated the distribution of B-50 protein and mRNA in the normal adult human spinal cord and dorsal root ganglia. Intense B-50-IR was localized to the superficial laminae of the dorsal horn at all segmental levels, the intermediolateral nucleus at thoracic levels and Onuf's nucleus at sacral levels. Scattered neurons, particularly in the ventral horn of lumbar and sacral segmental levels (and occasionally also in Clarke's nucleus) displayed intense B-50-IR in close apposition to the perikaryal and proximal dendritic surfaces. Nonradioactive in situ hybridization indicated that B-50 mRNA could also be detected in neurons of the ventral horn and also in the intermediolateral nucleus. The distribution of B-50 mRNA and protein in the normal human spinal cord shows a marked similarity to that reported in experimental animals, including the selective labelling of Onuf's nucleus. However, the strong B-50-IR on the surface of some large anterior horn motor neurons has not been observed in other mammals. This finding might reflect a particular state of readiness for synaptic plasticity.

Aged

Endovascular coil embolization of microsurgically produced experimental bifurcation aneurysms in rabbits.

BACKGROUND: Endovascular treatment of cerebral aneurysms is a relatively new method, since only a few animal models and data are available. The present experimental study was performed in order to establish an appropriate aneurysm animal model, to determine the rate of permanent occlusion, and to correlate radiologic and morphologic findings. METHODS: End-to-side anastomoses of both common carotid arteries were performed microsurgically in 53 chinchilla rabbits. Venous pouches were adapted into the newly created bifurcation, resulting in berry-shaped aneurysms comparable to those in humans with regard to size and hemodynamics. Platinum and tungsten coils were used for endovascular embolization. The embolized aneurysms were investigated radiologically and morphologically. RESULTS: Twenty-three carotid bifurcation aneurysms remained for testing endovascular therapeutic approaches. The morphologic examinations of 13 embolized aneurysms revealed in no instance a complete obliteration, even in the three cases that were considered completely embolized according to angiographic criteria. CONCLUSIONS: The present animal model is an optimal tool for endovascular research. Analysis of the results of coil obliteration revealed a considerable discrepancy between radiologic and pathologic findings. The radiologic degree of aneurysm occlusion was overestimated.

Animals

A case of primary progressive aphasia. A 14-year follow-up study with neuropathological findings.

Primary progressive aphasia has been clinically defined as a progressive language deficit leading to the dissolution of almost all language functions with relative preservation of other cognitive functions until late in the course of the disease. Two types of language impairment have been described for primary progressive aphasia, which differ with respect to the degree of fluency of spontaneous speech. Whereas some authors have emphasized non-fluency as a defining characteristic of primary progressive aphasia, others have proposed that phonemic rather than semantic paraphasias in naming, both in the fluent and the non-fluent subtype, should be used as a criterion to distinguish primary progressive aphasia from slowly progressive aphasia in other forms of degenerative brain disease. Patients with fluent speech and semantic dementia, as typically seen in Alzheimer's disease, produce semantic paraphasias and circumlocutions rather than phonemic errors in naming. This paper reports the long-term follow-up of a patient with fluent aphasic speech, whose language profile over a decade was similar to that of patients with semantic dementia. Neuropathological examination revealed no evidence of Alzheimer's disease. Pick's disease or Pick variant, but showed spongiform changes of cortical layers (II and III) in temporal and, less severely, in frontal gyri. The present case indicates that semantic dementia is not a reliable indicator of probable Alzheimer's disease and supports the notion that there are different subtypes of primary progressive aphasia which cannot be defined by fluency or by the presence of phonemic paraphasia. Progress in identifying the neuropathological correlates of these subtypes in cases with lobar atrophy and spongiform changes should be expected from hereditary variants of progressive disorder.

Aphasia, Primary Progressive

Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta.

Expression of AP-2 transcription factors has been detected previously in embryonic renal tissues. We show here that AP-2beta -/- mice complete embryonic development and die at postnatal days 1 and 2 because of polycystic kidney disease. Analyses of kidney development revealed that induction of epithelial conversion, mesenchyme condensation, and further glomerular and tubular differentiation occur normally in AP-2beta-deficient mice. At the end of embryonic development expression of bcl-X(L), bcl-w, and bcl-2 is down-regulated in parallel to massive apoptotic death of collecting duct and distal tubular epithelia. Addressing the molecular mechanism we show that transfection of AP-2 into cell lines in vitro strongly suppresses c-myc-induced apoptosis pointing to a function of AP-2 in programming cell survival during embryogenesis. The position of the human AP-2beta gene was identified at chromosome 6p12-p21.1, within a region that has been mapped for autosomal recessive polycystic kidney disease (ARPKD). Sequence analyses of ARPKD patients and linkage analyses using intragenic polymorphic markers indicate that the AP-2beta gene is located in close proximity to but distinct from the ARPKD gene.

Animals

Cytogenetic analysis of gliomas by in situ hybridization of stereotactic biopsy material.

Chromosome analysis of brain tumours can provide important pathobiological data; however, cytogenetic tools are so far not routinely applied for diagnosis. In the present study 25 paraffin embedded stereotactic biopsies from 19 glioma patients were studied using in situ hybridization of chromosome #10 and #15 using biotinylated pericentromeric probes. Numerical changes of chromosome #10 are frequent alterations in glioblastoma. Quantification of chromosome #15 served as a control in order to exclude artificial monosomies or nonspecific changes. The number of chromosomes in at least 200 cells were counted for each specimen. 18 of 25 biopsies could be evaluated quantitatively. The small volume of probes was not a limiting factor for analysis. Quantification of "nonspecific" chromosome #15 revealed single spots in 22-41% of all cells in the 18 biopsies. Chromosome #10 showed single spots in a range between 34 and 44% of counted nuclei in 13/18 biopsies. In 5 out of 18 biopsies 51-60% monosomies were found: in this subgroup were 4 high grade gliomas. These cases were interpreted as monosomy of chromosome #10. The results demonstrate feasibility and quantitative evaluability of cytogenetic analysis in stereotactic biopsy material using in situ hybridization.

Adolescent

1H-spectroscopic imaging with read gradient during acquisition in inhomogeneous fields: analysis, measurement strategy, and data processing.

The proton magnetic resonance spectroscopic imaging techniques that use read gradient during acquisition produce proton spectra with high spatial and moderately high spectroscopic resolution in a reasonable time for in vivo applications. These techniques suffer mainly from the spatial and spectral distortions caused by the convolution of spectral/spatial information (chemical-shift artifacts) and from the spectral shifts caused by static magnetic field inhomogeneities. The investigators analyze the chemical-shift artifacts in the presence of nonnegligible static magnetic field inhomogeneities and propose a postdetection processing scheme to correct for such effects. Spectral artifacts caused by chemical shifts, spectral line overlapping, streak broadening, and magnetic field inhomogeneities are discussed. The postdetection data processing scheme is demonstrated on measurements of a phantom as well as a human leg.

Artifacts

29Si chemical shift tensors of silyl silicate cages.

Static and 29Si CP MAS spectra (spinning rates of 2000 and 500 Hz) of six silyl silicate cages are analyzed by deconvolution and simulation. The principal values of the various 29Si chemical shift tensors provide information about the point symmetry of the Si sites. The intensities of the signals correspond sufficiently well with the stoichiometries.

Isotopes

Endovascular occlusion of experimental aneurysms with detachable coils: influence of packing density and perioperative anticoagulation.

OBJECTIVE: This study was designed to assess the intraluminal biological changes after endovascular coil occlusion of arterial aneurysms with detachable coils, to analyze the relationship between histological occlusion and mechanical packing density, and to evaluate the influence of perioperative anticoagulation on the occlusion rate. METHODS: In rabbits, 30 microsurgically produced arterial bifurcation aneurysms were occluded with coils (18 with platinum coils, electrically detached; 12 with tungsten coils, mechanically detached). Coils were placed until no further coils fit into the aneurysmal lumen and it was no longer filled with radiographic contrast material. The individual degree of occlusion was then determined by the "packing density" on the angiograms. Complete occlusion was considered only if no neck remnant was visible on the films. Anticoagulation during and 2 days after the treatment was performed in 11 cases. After an observation period ranging from 3 to 6 months, angiographic and histological analyses were performed to obtain control data. RESULTS: Complete occlusion was achieved in 9 cases, subtotal occlusion (i.e., > 95% occlusion, residual filling at the neck of the aneurysm) in 10 cases, and partial occlusion in 11 cases. Angiographically documented recanalization was detected in 14 aneurysms. In the remaining 16 aneurysms, the initially documented angiographic results were unchanged. A discrepancy between angiographic and pathological findings was frequently observed. Five of nine angiographically completely occluded aneurysms were recanalized. Endothelial-like tissue at the orifice of the aneurysm was able to be observed in only four of the nine initially completely occluded aneurysms. CONCLUSION: The results suggest that even dense packing does not always guarantee permanent occlusion, although there was a positive relationship between packing density and occlusion rate. Anticoagulation did not have any negative effect on the results.

Animals

Ventricular dilatation in experimental intraventricular hemorrhage in pigs. Characterization of cerebrospinal fluid dynamics and the effects of fibrinolytic treatment.

BACKGROUND AND PURPOSE: Hemorrhagic ventricular dilatation (HVD) is a prominent feature of human intraventricular hemorrhage (IVH) and a strong indicator for poor outcome. We developed an IVH model to define the mechanisms responsible for HVD and to test the efficacy of intraventricular administration of tissue plasminogen activator (TPA) in the treatment of HVD. METHODS: Isolated IVH was produced in pigs by injecting 10 mL of blood simultaneously with thrombin into the right lateral ventricle. The treatment group received 1.5 mg of TPA after induction of IVH. Intraventricular blood volume and the volume of the lateral ventricles were assessed by CT after 90 minutes, 7 days, and 42 days. Intracranial pressure, the pressure-volume index, and the resistance to outflow of cerebrospinal fluid (R(out)) were measured 30 minutes and 7 days after IVH. RESULTS: After IVH, the volume of the lateral ventricles increased from 1.98 +/- 0.69 to 6.43 +/- 1.23 mL (P < .001). There was a linear relationship between ventricular and clot volume (P = .014). Initially, R(out) increased from 24.34 +/- 7.13 to 63.56 +/- 64.91 mm Hg/mL per minute (P < .001). After 7 days, restoration of normal cerebrospinal fluid circulation occurred, but the ventricles were still significantly enlarged (5.24 +/- 1.76 mL, P < .001) and filled with blood. Within 6 weeks, ventricular volume had returned to normal values, paralleled by complete clot resolution. Intraventricular administration of TPA significantly accelerated clot clearance and restoration of normal ventricle volume. CONCLUSIONS: These results suggest that intraventricular bleeding may cause impairment of cerebrospinal fluid circulation but that the mass effect of clots distending the ventricle walls is the most important mechanism responsible for HVD. This model closely imitates several prominent features of human IVH and may therefore be a useful tool for preclinical assessment of the efficacy and safety of treatment with TPA.

Animals

Fasting improves discrimination of grade 1 and atypical or malignant meningioma in FDG-PET.

UNLABELLED: We investigated the use of PET with 2[18F]fluoro-2-deoxy-D-glucose (FDG) to discriminate between atypical or malignant and grade 1 meningiomas. The influence of fasting state and high-dose corticosteroid medication was analyzed retrospectively. METHODS: Preoperative PET scans of 75 patients with suspected diagnosis of intracranial meningioma were evaluated using standardized uptake values (SUV) and tumor-to-contralateral gray matter ratios (TGR) of FDG uptake. Fifty-one of 75 patients fasted before the PET scan, and 27 of 75 patients were studied under high-dose corticosteroid medication. Eighteen tumors had recurred. PET results were compared to histopathological grading. RESULTS: PET correctly identified 8/9 atypical or malignant meningiomas and 58/66 grade 1 meningiomas using TGR and a threshold of 1.05 in primary meningioma and 0.85 in tumor recurrence. This corresponds to a specificity of 0.88 for the detection of higher tumor grading. Specificity was significantly higher in fasting compared to nonfasting subjects (0.96 versus 0.73; p < 0.025). SUV quantification lead to a reduced specificity of 0.77 at the same level of sensitivity. The only false-negative PET finding occurred in a recurrent meningioma, which had been operated on four times before. CONCLUSION: Overnight fasting before injection is needed to improve the diagnostic accuracy of FDG-PET for noninvasive metabolic grading of meningioma. Hyperglycemia in nonfasting patients and in diabetic patients may lead to overestimation of meningioma grading.

Adolescent

Long-term angiographic and histopathologic findings in experimental aneurysms of the carotid bifurcation embolized with platinum and tungsten coils.

PURPOSE: To evaluate the long-term outcome of endovascular occlusion of arterial aneurysms effected with metal coils. METHODS: Microsurgical methods were used to produce carotid bifurcation aneurysms in 20 rabbits and the radiologic and histologic changes were examined. Eight of these aneurysms were occluded with electrically detachable platinum coils (Guglielmi detachable coils [GDCs] and nine were treated with mechanically detachable tungsten coils (mechanical detachable system [MDS]). Three aneurysms remained untreated and served as controls. One animal died of embolic complications 12 hours after endovascular treatment. After observation periods of 3 to 6 months, the remaining animals were examined by intraarterial digital subtraction angiography and subsequent fixation and light and electron microscopy. RESULTS: Large open spaces without signs of thrombosis were found between the loops of the coil baskets in 12 aneurysms (six treated with GDCs and six treated with MDS) regardless of the observation period. In very densely packed aneurysms (four cases with complete occlusion as determined by angiographic criteria), the coil surfaces were for the most part covered by thin cell layers; however, complete endothelialization was never seen. In aneurysms with an initial partial occlusion of 70% to 90%, coil compaction and/or recanalization was a consistent finding. A comparison of the radiologic findings with the histologic aspect revealed that the degree of occlusion was often overrated on the radiographs (in eight of 17 cases). In general, the fibrous tissue reaction appeared to be slightly more pronounced in aneurysms occluded with tungsten coils. CONCLUSIONS: Platinum and tungsten coils were not always effective in causing endoluminal thrombosis leading to long-term occlusion by organized thrombus.

Angiography, Digital Subtraction

Isolated cerebral aspergilloma--long-term survival of a renal transplant recipient.

A renal transplant recipient with isolated cerebral aspergilloma 4 months after allograft transplantation is reported. On admission cerebral computed tomography showed a ring-enhancing mass in the left frontal hemisphere and aspirated purulent material revealed A. fumigatus hyphae. He was cured by short-term antifungal therapy and neurosurgical removal of the well demarcated lesion. He is still alive more than two years later and the renal transplant is well functioning. This is the first report of a renal transplant recipient with isolated cerebral aspergillosis without any relapse and only the third patient who has survived longer than 3 months. Early diagnostic procedures with rapid confirmation of aspergillus infection are pivotal for a benign clinical course.

Amphotericin B

Detection of Anisotropic Pulsating Flow and Its Velocity-Fluctuation Rate in Fertilized Bird Eggs by NMR Microimaging

Coherent and incoherent flows in fertilized quail and bantam eggs have been studied with the aid of NMR microimaging techniques in the course of incubation until the end of the sixth day. The methods employed were multiplane tagging NMR imaging and a NMR gradient-echo imaging pulse sequence supplemented by bipolar gradient pulses in the coherence-evolution interval. The latter technique is suited for recording of velocity maps as well as for localizing of regions with enhanced echo attenuation by incoherent motions. Slight coherent displacements in the middle of the upper part of the egg white were found after the fourth day of incubation with the aid of both pulse schemes. The maximum velocity was estimated to be 1 mmsoliduss. More pronounced effects revealed themselves in the examination of incoherent motions. After the same time of incubation and in a somewhat more restricted area of the upper part of the egg white, distinct motions could be localized consistently with either technique. It is shown that these motions are directed to and from the yolk. Furthermore, the analysis of the time fluctuations of the local signals with the aid of a Fourier transformation showed that the flow is largely of a pulsating nature. The pulsation frequency was found to be 0.4 Hz.

Journal Article

PET-study of intracranial meningiomas: correlation with histopathology, cellularity and proliferation rate.

The glucose metabolism of 62 meningiomas was measured by fluorine -18-2-fluorodeoxyglucose (FDG) PET and correlated with proliferation rate (Ki-67 index) and tumor cellularity. The mean metabolic rate (MRGlu) for meningiomas was 0.26 +/- 0.13 mikromol/g/min (range 0.08-0.62 mikromol/g/min). The relative tumor FDG-uptake (Q-MRGlu) (tumor/contralateral cortex) of all meningiomas was calculated with 0.73 +/- 0.37 (0.24-1.79). Differences of Q-MRGlu were significant between the groups with high vs. low cellularity (p < 0.01), increased vs. normal proliferation rate (p < 0.025) and low (WHO grade I) vs. higher (WHO grades II, III) graded tumors. In recurrent meningiomas (14 tumors) the glucose metabolism was not increased. The data show that 18 FDG-PET is suitable to serve as non-invasive predictor of tumor growth characteristics in meningiomas.

Adult