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  • 2000-2004  (711)
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  • 101
    ISSN: 1432-1920
    Keywords: Key words Morphine sulphate intoxication ; Leukoencephalopathy ; Neurotoxicity ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a 14-year-old girl with an unusual pattern of leukoencephalopathy after intentional intoxication with morphine sulphate tablets. Toxicological analysis showed exceedingly high levels of morphine and its metabolites. MRI disclosed a leukoencephalopathy with high signal from the centrum semiovale, corpus callosum and cerebellar white matter on T2-weighted images. These findings could be only partially explained by a hypoxic-ischaemic event; neurotoxic effects must be considered in this atypical leukoencephalopathy.
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  • 102
    Electronic Resource
    Electronic Resource
    Springer
    Neuroradiology 42 (2000), S. 881-884 
    ISSN: 1432-1920
    Keywords: Key words Virchow-Robin spaces ; Midbrain ; Hydrocephalus ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe two patients with mild ventricular dilatation, shown to have cystic spaces in the midbrain, which we interpreted as greatly enlarged Virchow-Robin spaces. We discuss the pathophysiology and the possible relations to the mild hydrocephalus.
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  • 103
    ISSN: 1432-1920
    Keywords: Key words Multiple sclerosis ; Magnetic resonance imaging ; Immunoglobulin G
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We conducted a double-blind, placebo-controlled study in 13 patients (aged 22 to 54 years) with relapsing-remitting multiple sclerosis (MS). They were randomly assigned to receive a loading dose of immunoglobulin IgG, 0.4 g/kg body weight/day for 5 consecutive days, followed by single booster doses of 0.4 g/kg/day, or placebo, once a month for 9 months. MRI was obtained before and during the 3rd and 6th months of treatment; examinations in the 9th and 12th months were planned. Qualitative and quantitative blinded assessments were performed. There were seven patients who received active treatment and six who received placebo. Statistical analysis was performed by the Wilcoxon test. A decrease in the size and number of lesions was observed on MRI in five patients (71 %) in the treatment group, and in two (33 %) of the placebo group at 3-month follow-up. At 6 months follow-up MRI, a decrease in the amount of lesions was observed in all patients treated with IV IgG, and in two (33 %) of the placebo group; four patients (66 %) receiving placebo showed an increase. Quantitative analysis showed a statistically significant decrease in the volume of lesions in treatment group at both 3 and 6 month follow-up. There was no statistically significant change in the placebo group.
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  • 104
    Electronic Resource
    Electronic Resource
    Springer
    Neuroradiology 42 (2000), S. 99-103 
    ISSN: 1432-1920
    Keywords: Key words Hypertension arterial ; Medulla oblongata ; Compression ; Neurovascular ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neurovascular compression (NVC) of the left ventrolateral medulla (VLM) has been implicated as a cause of essential hypertension. We investigated whether high-resolution MRI of the posterior cranial fossa could identify patients with essential hypertension who may benefit from surgery. A retrospective analysis of imaging and clinical records from 162 patients was performed. There were 38 patients with essential hypertension and 124 who were normotensive. Contact or compression of the VLM was present in 42.1 % (16/38) of the hypertensive group on the left and 47.3 % (18/38) on the right. In the normotensive group it was seen in 32.2 % (40/124) on the left and 26.6 % (33/124) on the right. There was no significant difference between the hypertensive and control groups with regard to contact or compression of the left VLM. The results support the contention that neurovascular compression (NVC) of the left or right VLM is a common finding on MRI in normotensive individuals. We therefore believe that high-resolution MRI cannot be used as a screening tool to identify patients who may benefit from surgery.
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  • 105
    ISSN: 1432-1920
    Keywords: Key words Magnetisation transfer ; Normal-pressure hydrocephalus ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We measured the magnetisation transfer ratios (MTR) of normal-appearing rostral (PR) and caudal (PC) periventricular white matter, the genu (CG) and the splenium (CS) of the corpus callosum and the thalamus (TH) in 12 patients with normal-pressure hydrocephalus (NPH) and compared them with 16 healthy control subjects. We found a significantly lower MTR in the NPH group than in the normal group for PR, PC, CG, and CS but not for TH. MT measurements give additional information which cannot be gained by conventional MRI, suggesting that NPH is associated with diffuse white matter damage, even in normal-appearing cerebral white matter.
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  • 106
    Electronic Resource
    Electronic Resource
    Springer
    Neuroradiology 42 (2000), S. 199-202 
    ISSN: 1432-1920
    Keywords: Key words Dural tail sign ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report two cases in which the MRI appearances mimicked the dural tail sign; a glioma extending into the subarachnoid space, and a meningioma extending to the subdural space. They indicate that tumour invasion into the subarachnoid or subdural space, should be considered when prominent linear enhancement is observed along the dura mater adjacent to tumours.
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  • 107
    ISSN: 1432-1920
    Keywords: Key words Aqueduct ; stenosis ; Fistula ; arteriovenous ; dural ; Magnetic resonance imaging ; Embolisation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report aqueduct compression by venous ectasia in a 65-year-old man with a dural arterio-venous fistula in the posterior cranial fossa draining into a superior vermian vein. Conventional and phase-contrast MRI showed the aqueduct stenosis and the causative dilated vein.
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  • 108
    Electronic Resource
    Electronic Resource
    Springer
    Neuroradiology 42 (2000), S. 280-284 
    ISSN: 1432-1920
    Keywords: Key words Oedema ; intramedullary ; Spinal cord ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transient but very intense oedema of the cervical spinal cord was observed in two patients with obstruction of the cerebrospinal fluid (CSF) pathways. Both presented with hydrocephalus, one due to an infratentorial obstructing mass and the other due to postmeningitic adhesive obstruction of the outlet foramina of the fourth ventricle. In animal experiments with obstruction of CSF pathways (due to outlet foramina obstruction or to downward tentorial herniation) flattening and stretching of the ependymal cells along the central canal is observed, followed by disruption and splitting of the ependymal lining and then by extracellular oedema of the subependymal tissue. Without treatment, frank cavity formation develops in a fourth stage. In our two patients, however, most probably because of appropriate decompressive therapy, the oedema disappeared completely without a residual spinal cord lesion.
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  • 109
    ISSN: 1432-1920
    Keywords: Key words Optic glioma ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serial MRI over 60 months demonstrated regression after biopsy of a pilocytic opticochiasmatic astrocytoma in a 20-year-old woman with no signs of neurofibromatosis, together with improvement in vision. The patient did not receive radio- or chemotherapy. Close MRI follow-up of optic gliomas is recommended. Aggressive treatment should be limited to cases with clear clinical and radiological progression.
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  • 110
    ISSN: 1432-1920
    Keywords: Key words Tumour malignant rhabdoid ; Computed tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a mass in the left cerebral hemisphere of a 20-year-old man. Histological, ultrastructural and immunohistochemical features of the tumour were consistent with primary malignant rhabdoid tumour. The age of presentation, imaging features prior to histological examination, and prognosis in this case were unusual.
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  • 111
    ISSN: 1432-1920
    Keywords: Key words Nasu-Hakola disease ; Membranous lipodystrophy ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report radiological features of a biopsy-proven early infantile form of Nasu-Hakola disease in two Tunisian sisters with new bony and cerebral findings.
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  • 112
    ISSN: 1432-1920
    Keywords: Key words Pineal region ; Cysts pineal ; Pineocytomas ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pineal lesions are rare. Tumours in this location comprise 0.4–1 % of intracranial tumours. They grow mainly as solid-mass lesions, and cystic tumours are not common. On MRI, a cystic configuration is associated usually with non-neoplastic pineal lesions rather than with a tumour, but analysis does not allow cystic pineal tumours to be distinguished from glial cysts with certainty. We compared neuroradiological and pathological data from 13 cystic pineal lesions, analysing preoperative MRI. Formalin-fixed, paraffin-embedded surgical specimens were stained routinely and immunocytochemically, using the streptavidin-biotin-complex method. Histology revealed six pineocytomas, four glial cysts, an arachnoid cyst, a low-grade astrocytoma and a teratoma. Signal characteristics of pineocytomas were similar in many respects to those of glial pineal cysts. Histomorphological analysis allowed unambiguous discrimination between pineocytomas and glial pineal cysts.
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  • 113
    Electronic Resource
    Electronic Resource
    Springer
    Neuroradiology 42 (2000), S. 368-370 
    ISSN: 1432-1920
    Keywords: Key words Decompression illness ; Caisson disease ; Spinal cord ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a case of decompression illness in which the patient developed paraparesis during scuba diving after rapid ascent. MRI of the spine revealed a focal intramedullary lesion consistent with the symptoms. The pathophysiological and radiological aspects of spinal decompression illness are discussed.
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  • 114
    Electronic Resource
    Electronic Resource
    Springer
    Neuroradiology 42 (2000), S. 357-359 
    ISSN: 1432-1920
    Keywords: Key words Stalk, pituitary ; Cyst, infundibular ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 74-year-old man reported headaches and blurring of vision for 1 month. MRI showed a nonenhancing infundibular cyst. Neurologic findings, blood and cerebrospinal fluid examinations, and chest and abdominal CT were all normal. MRI 4 months later showed no change. The patient was without any medication other than simple analgesics. One year later, the stalk had returned to its normal size and configuration on MRI.
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  • 115
    ISSN: 1432-1920
    Keywords: Key words Lymphomatosis intravascular ; Infarcts, brain haemorrhagic ; Venous occlusion ; Magnetic resonance imaging ; Magnetic resonance angiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a case of intravascular lymphomatosis of the brain with 8 months' follow-up and fatal outcome. Several MRI investigations revealed variegated, rapidly changing infarct-like lesions and invasion of the walls of the superior sagittal sinus and deep veins. When disturbances of the venous outflow are detected with multifocal infarct-like lesions, intravascular lymphomatosis should be considered in the differential diagnosis. Brain biopsy may ensure the proper diagnosis ante mortem, but failure of biopsy is frequent, as in our case.
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  • 116
    Electronic Resource
    Electronic Resource
    Springer
    Neuroradiology 42 (2000), S. 529-531 
    ISSN: 1432-1920
    Keywords: Key words Meninges ; Hypotension ; spontaneous intracranial ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a case of spontaneous intracranial hypotension diagnosed with unenhanced cranial MRI, showing laminar subdural fluid and engorgement of the hypophysis and perisellar sinuses. Cerebrospinal fluid pressure was low. MRI was normal after resolution of symptoms. Prior reports emphasise the enhancing pachymeninges seen in this syndrome. We maintain that, when subdural collections and perisellar engorgement are detected on unenhanced MRI in the proper clinical setting, contrast enhancement may not be necessary for the diagnosis.
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  • 117
    ISSN: 1432-1920
    Keywords: Key words Spine ; surgery ; Infection ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the role of MRI in the diagnosis of postoperative spondylodiscitis. Spondylodiscitis is a serious complication of surgery, and the diagnosis frequently depends on a combination of clinical, laboratory and imaging findings. We compared the MRI findings in six patients with biopsy- or surgery-proven spondylodiscitis with those in 38 asymptomatic postoperative patients. Contrast enhancement and signal changes in the intervertebral disc or the vertebral endplates are not specific for spondylodiscitis, being also seen in the asymptomatic patients. However, absence of Modic type 1 changes, of contrast enhancement of the disc or of enhancing paravertebral soft tissues suggests that the patient does not have spondylodiscitis. MRI appears more useful for exclusion than for confirmation of postoperative spondylodiscitis.
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  • 118
    Electronic Resource
    Electronic Resource
    Springer
    Neuroradiology 42 (2000), S. 612-615 
    ISSN: 1432-1920
    Keywords: Key words Gliomatosis cerebri ; Magnetic resonance imaging ; Magnetic resonance spectroscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two cases of gliomatosis cerebri are presented in which there was markedly decreased N-acetyl aspartate and an elevated lactate-lipid area in the MR proton spectra.
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  • 119
    Electronic Resource
    Electronic Resource
    Springer
    Neuroradiology 42 (2000), S. 586-590 
    ISSN: 1432-1920
    Keywords: Key words Spine ; Subdural haematoma ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We present MRI findings in three patients with acute spontaneous subdural haematomas of the spine. Acute haematomas (1–3 days) were isointense or gave slightly high signal on T1- and heterogeneous signal on T2-weighted images. MRI precisely defined the level and extent of the haematoma preoperatively. The MRI was prospectively correctly interpreted as acute subdural haematomas in all patients. As a specific, noninvasive modality, MRI is the preferred imaging technique in this rare clinical entity.
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  • 120
    Electronic Resource
    Electronic Resource
    Springer
    Neuroradiology 42 (2000), S. 9-13 
    ISSN: 1432-1920
    Keywords: Key words Haemochromatosis ; Magnetic resonance imaging ; Computed tomography ; Transcranial ultrasound ; Nucleus, lentiformis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Haemochromatosis is characterised by deposition of iron-containing pigment in various organs, but little is known about possible deposition in the brain and its clinical impact. We therefore investigated 14 patients with hereditary haemochromatosis with MRI, CT and transcranial ultrasound (TCS) and examined them neurologically. In six of the patients dense lesions were found within the lentiform nucleus on CT, all of whom displayed hyperechogenic lesions in the same area on TCS, as did one other patient. In these patients the relative signal intensities of the lentiform nucleus measured by MRI relaxometry were higher. No patient had clinical signs of basal ganglia disorders.
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  • 121
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    Springer
    Neuroradiology 42 (2000), S. 48-50 
    ISSN: 1432-1920
    Keywords: Key words Gaucher's disease ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We present the cranial MRI findings in a 6-month-old girl with biopsy-proven acute neuropathic Gaucher's disease, which include unilateral cerebral atrophy and dural thickening with contrast enhancement.
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  • 122
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    Springer
    Neuroradiology 42 (2000), S. 54-55 
    ISSN: 1432-1920
    Keywords: Key words Brain, hypoxia ; Blood-aqueous barrier ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The MRI findings of a patient with diffuse cortical hypoxic brain damage (Adams pattern III) are presented. Besides intense cortical contrast enhancement, a peculiar leakage of contrast medium at the anterior chambers of the eye was observed. The pathogenetic mechanism of this enhancement is discussed.
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  • 123
    Electronic Resource
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    Neuroradiology 42 (2000), S. 746-748 
    ISSN: 1432-1920
    Keywords: Key words Granulation, arachnoid ; Sinuses, venous ; Computed tomography ; Magnetic resonance imaging ; Magnetic resonance venography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report CT, MRI and angiographic findings of an arachnoid granulation in the straight sinus in a young man. Its density and signal intensity were isodense and isointense with cerebrospinal fluid on CT and MRI, respectively. The lesion appeared as a filling defect on MR venography and conventional angiography.
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  • 124
    ISSN: 1432-1920
    Keywords: Key words Spinal cord, central canal ; Syringomyelia ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The central canal of the spinal cord is present at birth and becomes progressively obliterated. Cadaver studies have shown that it may persiste partially or completely. To our knowledge, this entity has not been described on MRI. We reviewed 794 MRI studies of the spinal cord, and found 12 patients (aged 14 to 65 years) who had an intramedullary cavity. The cavity was at the junction of the ventral 1/3 and dorsal 2/3 of the spinal cord, except at the level of the lumbar enlargement, where it was central. It was filiform in most cases, although sometimes fusiform (3 to 4 mm in diameter), and had regular contours. The cavity were thoracic in 69 % of cases. The clinical features were totally unrelated to the image, and there were no anatomical factors (Chiari malformation, dysraphism) predisposing to syringomyelia. The images were perfectly compatible with a persistent central canal, which we interpret as a variant of normal anatomy. Therefore it is important to regard these findings as normal, to avoid unnecessary treatment and follow-up.
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  • 125
    ISSN: 1432-1920
    Keywords: Key words Hemimegalencephaly ; Positron emission tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report hemimegalencephaly in a 44-year-old woman with mental retardation, epilepsy and a mild hemiparesis. In addition to typical findings on MRI, 2-deoxy-2[18F]fluorodeoxyglucose positron-emission tomography (PET) demonstrated glucose hypometabolism of the affected hemisphere. The results of PET have been coregistered with morphological information from the MRI studies by image fusion.
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  • 126
    ISSN: 1432-1920
    Keywords: Key words Cerebral palsy ; Birth asphyxia ; Magnetic resonance imaging ; Single-photon emission computed tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe the findings on single-photon emission computed tomography (SPECT) in patients with perinatal asphyxia at term, with perirolandic cortico-subcortical changes on MRI, and to correlate them with clinical features. SPECT of 7 patients was obtained after injection of 185–370 MBq of Tc-99m-ECD (ethyl cysteinate dimer). The patients had spastic quadriplegia (7/7) with perinatal asphyxia (6/7) at term (7/7). The results were correlated with the MRI findings. Hypoperfusion of the perirolandic cortex was clearly seen on SPECT in all patients, even in two with subtle changes on MRI. SPECT demonstrated a more extensive area of involvement than MRI, notably in the cerebellum (in 4), the thalamus (in 7) and basal ganglia (in 5), where MRI failed to show any abnormalities.
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  • 127
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    Neuroradiology 42 (2000), S. 917-922 
    ISSN: 1432-1920
    Keywords: Key words Mouth, cysts ; Neck, cysts ; Glands, salivary ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We reviewed the MRI of 20 patients with a ranula (8 simple and 12 plunging) and ten with other cystic masses in the floor of the mouth and/ or suprahyoid portion of the neck (three haemangiomas, two neuromas, one monomorphic adenoma, one lipoma, two lateral cervical cysts and one dermoid cyst). Histological diagnoses were obtained in all cases with the exception of one presumed haemangioma. Ranulas were all well-defined, homogeneous masses giving low signal on T1-and markedly high signal on T2-weighted images. While simple ranulas were all confined to the sublingual space, plunging ranulas were centered on the submandibular space and tended to spill into one or more adjacent spaces. They extended into the sublingual space anteriorly (producung a so-called tail sign) in eight of 12 cases and into the parapharyngeal space superiorly in five. Although they sometimes filled a considerable part of the parapharyngeal space, displacement of surrounding muscles or vessels was usually slight, which was thought to reflect the nature of extravasation pseudocysts. All other cystic masses in our study had one or more MRI finding different from those of ranulas and could be easily differentiated from them.
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  • 128
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    Springer
    Neuroradiology 42 (2000), S. 112-114 
    ISSN: 1432-1920
    Keywords: Key words Hypophosphataemia ; Brain ; Myelinolysis, extrapontine ; Computed tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a 38-year-old woman with extreme hypophosphataemia in whom CT and MRI disclosed bilateral lesions within the basal ganglia, thalamus and occipital lobes. After adequate substitution of phosphate the lesions grossly resolved and the patient recovered. This case is the first to demonstrate that profound changes of serum phosphate may be associated with reversible brain lesions.
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  • 129
    ISSN: 1432-1920
    Keywords: Key words Carcinoma nasopharyngeal ; Radionecrosis ; Magnetic resonance imaging ; Pulse sequences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined nine patients with histologically proven nasopharyngeal carcinoma (NPC), treated with radiotherapy, using dynamic susceptibility contrast MRI (DSC-MRI). In eight there was clinical evidence of radionecrosis of the temporal lobe, and one was examined for local recurrence in the nasopharynx. All patients had either high-signal finger-like or cystic lesions in the temporal lobes on T2-weighted images. Heterogeneous contrast enhancement occurred in all patients. Relative regional cerebral blood volume (rrCBV) mapping revealed marked hypoperfusion in all patients. One underwent bilateral temporal lobectomy and radionecrosis was confirmed histologically.
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  • 130
    ISSN: 1432-1920
    Keywords: Key words Dysplasia, focal cortical ; Hamartomas ; Epilepsy ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Focal cortical dysplasia (FCD) is a pathological entity first described in 1971. Other more subtle cortical malformations found in patients with epilepsy include microdysgenesis (MD), and glioneuronal hamartias. Although these glial and neuronoglial malformations have distinct histological features, there is terminological confusion in the radiological literature. Few cases have been reported in adults with both imaging and histology. We address these issues, giving a radiological-pathological correlation of histologically proven cortical malformations in adults. We describe clinical, radiological and histological features of 12 cases (five FCD, five MD with glioneuronal hamartias, and two hamartomas), unassociated with other conditions, and discuss them in the light of the literature. FCD is usually seen on MRI as cortical thickening, with or without signal change, which may extend into the adjacent white matter. On histology, abnormal neurons and/or glial cells, blurring of the grey-white matter interface, myelin pallor, demyelination, and gliosis may be found. Glioneuronal hamartias and hamartomas usually appear as complex masses on MRI. FCD and hamartias may be associated, and a combination of imaging findings may be seen on MRI. Atrophy of the ipsilateral hippocampus may be present on MRI in patients with hamartias, and minor cell loss on histology, but not definitive hippocampal sclerosis. Although the imaging findings of cortical malformations are protean, some characteristic MRI features, with histological correlates, may be found. The relevance of most of these observations remains unclear.
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  • 131
    ISSN: 1432-1920
    Keywords: Key words Acquired immunodeficiency syndrome ; Magnetic resonance imaging ; Contrast-enhancement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Our purpose was to determine whether triple-dose delayed contrast-enhanced images would improve lesion detection in patients with symptomatic human immunodeficiency virus (HIV) infection. We reviewed 33 MRI studies on 29 patients. Single-dose immediate T 1-weighted spin-echo (1x-T 1) images were compared with delayed triple-dose images (D3x-T 1). Two neuroradiologists decided which technique showed more lesions, increased lesion conspicuity and/or altered the radiologic diagnosis. The D3x-T 1 technique improved lesion detection in 14 of 29 patients (48 %). In two patients (7 %), the improvement changed the radiologic diagnosis by showing new meningeal lesions.
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  • 132
    ISSN: 1432-1920
    Keywords: Key words Cerebral autosomal dominant arteriopathy ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clinical data and MRI findings are presented on 18 subjects from two families with neuropathologically confirmed CADASIL. DNA analysis revealed mutations in exon 4 of Notch 3 gene in both families. All family members with mutations in Notch 3 gene had extensive abnormalities on MRI, principally lesions in the white matter of the frontal lobes and in the external capsules. Of several family members in whom a diagnosis of CADASIL was suspected on the basis of minor symptoms, one had MRI changes consistent with CADASIL; none of these cases carried a mutation in the Notch 3 gene. MRI and clinical features that may alert the radiologist to the diagnosis of CADASIL are reviewed. However, a wide differential diagnosis exists for the MRI appearances of CADASIL, including multiple sclerosis and small-vessel disease secondary to hypertension. The definitive diagnosis cannot be made on MRI alone and requires additional evidence, where available, from a positive family history and by screening DNA for mutations of Notch 3 gene.
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  • 133
    ISSN: 1432-1920
    Keywords: Key words Rhombencephalosynapsis ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rhombencephalosynapsis is an unusual disorder characterised by maldevelopment of the rhombencephalon, sometimes with supratentorial midline anomalies. We report MRI findings in a 39-year-old woman, the oldest in the literature. MRI demonstrated hypoplasia of the cerebellar vermis, with fusion of the cerebellar hemispheres and abnormally oriented folia. Supratentorial anomalies were also seen.
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  • 134
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    Neuroradiology 42 (2000), S. 360-362 
    ISSN: 1432-1920
    Keywords: Key words Cyst, cavum septi pellucidi ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 20-year-old woman with secondary amenorrhoea and an empty sella turcica was found to have a cyst of the cavum septi pellucidi (CSP) on MRI. The cyst had regressed spontaneously on follow-up MRI.
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  • 135
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    Neuroradiology 42 (2000), S. 406-412 
    ISSN: 1432-1920
    Keywords: Key words Lymphoma, primary central nervous system ; Chemotherapy ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract On MRI, primary brain tumors are commonly seen as contrast-enhancing masses surrounded by areas of abnormal signal on T2-weighted images. Following successful treatment tumors may no longer show contrast enhancement. The residual abnormalities are assumed to be represent “edema” and infiltrating tumor cells. We report nine patients with primary lymphoma of the central nervous system who had complete responses to intravenous methotrexate, but did not receive intrathecal chemotherapy or cranial irradiation. After complete resolution of contrast-enhancing lesions, persistent abnormalities on T2-weighted images in the region of prior tumor were initially assumed to reflect residual viable tumor. As they remained unchanged for years, however, this may not hold true in the cases in which primary central nervous system lymphoma responds to chemotherapy alone.
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  • 136
    ISSN: 1432-1920
    Keywords: Key words Corpus callosum ; White matter lesions ; Cerebral ischaemia ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Many studies of white matter high signal (WMHS) on T2-weighted MRI have disclosed that it is related to cerebral ischaemia and to brain atrophy. Atrophy of the corpus callosum (CC) has also been studied in relation to ischaemia. Our objective was to test the hypothesis that CC atrophy could be due to ischaemia. We therefore assessed CC, WMHS and brain atrophy in patients with risk factors without strokes (the risk factor group) and in those with infarcts (the infarct group), to investigate the relationships between these factors. We studied 30 patients in the infarct group, 14 in the risk factor group, and 29 normal subjects. Using axial T1-weighted MRI, cortical atrophy and ventricular enlargement (brain atrophy) were visually rated. Using axial T2-weighted MRI, WMHS was assessed in three categories: periventricular symmetrical, periventricular asymmetrical and subcortical. Using the mid-sagittal T1-weighted image, the CC was measured in its anterior, posterior, midanterior and midposterior portions. In the normal group, no correlations were noted between parameters. In the infarct group, there were significant correlations between CC and brain atrophy, and between CC atrophy and WMHS. After removing the effects of age, gender and brain atrophy, significant correlations were noted between some CC measures and subcortical WMHS. In the risk factor group, there were significant correlations between CC and brain atrophy and between CC atrophy and WMHS. After allowance for age, gender and brain atrophy, significant correlations between some CC measures and periventricular WMHS remained. The hypothesis that CC atrophy could be due to cerebral ischaemia was supported by other analyses. Namely, for correlations between the extent of infarcts and partial CC atrophy in patients with anterior middle cerebral artery (MCA) and with posterior MCA infarcts, there were significant correlations between the extent of infarct and midanterior CC atrophy in the former, and posterior CC atrophy in the latter. Our findings could indicate that CC atrophy is associated with cerebral ischaemia.
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  • 137
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    Neuroradiology 42 (2000), S. 551-563 
    ISSN: 1432-1920
    Keywords: Key words Acquired immune deficiency syndrome ; Spine ; infections ; Spine ; neoplasms ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Our purpose was to describe the range of MRI findings in infectious and neoplastic involvement of the spine and spinal cord in symptomatic patients with the acquired immunodeficiency syndrome (AIDS). MRI studies in 55 patients with AIDS and neurological signs and symptoms thought to be related to the spine or spinal cord were reviewed. We categorized the findings according to the spinal compartment involved. There were 29 patients with extradural, 11 with intradural-extramedullary and 9 with intramedullary disease. In 6 patients more than one compartment was involved simultaneously, and patients presented with multiple lesions in the same compartment. The most common causes of extradural disease were bone lesions (28); an epidural mass was seen in 14 and spondylodiscitis in 4 patients. Cytomegalovirus polyradiculitis was the most common cause of intradural-extramedullary disease (in 10 cases); herpes radiculitis was seen in two, and tuberculous infection in another two. In three cases leptomeningeal contrast enhancement was due to lymphoma. Human immunodeficiency virus (HIV) myelitis was seen in two patients, presumed vacuolar myelopathy in two, toxoplasma myelitis in four, intramedullary lymphoma in one, and herpes myelitis in one. Familiarity with the various potential pathological entities that can affect the spine and spinal cord in the AIDS population and their imaging characteristics is crucial for initiation of further diagnostic tests and appropriate medical or surgical treatment.
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  • 138
    ISSN: 1432-1920
    Keywords: Key words Progressive supranuclear palsy ; Magnetic resonance imaging ; Diffusion-weighted imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We measured the apparent diffusion coefficient (ADC), using diffusion-weighted imaging (DWI) and signal intensity on T2-weighted MRI in the cerebral white matter of patients with progressive supranuclear palsy (PSP) and age-matched normal subjects. In PSP, ADC in the prefrontal and precentral white matter was significantly higher than in controls. There was no significant difference in signal intensity on T2-weighted images. The ADC did correlate with signal intensity. The distribution of the elevation of ADC may be the consequence of underlying pathological changes, such as neurofibrillary tangles or glial fibrillary tangles in the cortex. Our findings suggest that ADC measurement might be useful for demonstrating subtle neuropathological changes.
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  • 139
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    Neuroradiology 42 (2000), S. 676-678 
    ISSN: 1432-1920
    Keywords: Key words. Syringomyelia, spontaneous drainage ; Cerebrospinal fluid, hydrodynamics ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. We present five cases of syringomyelia associated with Chiari I or other causes of partial obstructions at the cervicomedullary junction, with spontaneous disruption of the wall of a cervical syrinx and formation of a communication between the cavity and the subarachnoid space, shown on axial MRI. MRI can be used to investigate the hydrodynamics, showing the liquid inside the disrupted syrinx wall and the pathway of drainage. The finding of spontaneous drainage may be important for understanding the pathogenesis of syringomyelia and may be helpful for choosing a surgical approach.
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  • 140
    ISSN: 1432-198X
    Keywords: Key words Henoch-Schönlein purpura ; Methylprednisolone ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Neurological complications are rare during the course of Henoch-Schönlein purpura (HSP). We report a 7-year-old girl with HSP who presented with seizures, loss of vision and disturbance of consciousness. Magnetic resonance imaging (MRI) showed high signal intensity in the gray and white matter over the left parietal and both occipital lobes, compatible with MRI findings of cerebral vasculitis. The eye fundi revealed multiple branches of retinal artery occlusion. Intravenous pulse methylprednisolone (MTP) followed by oral steroid therapy was initially administered for HSP nephritis. Cerebral vasculitis developed 10 days post-MTP treatment, with progressive worsening of consciousness. Oral steroid was discontinued and plasmapheresis was performed alone. Her level of consciousness dramatically improved after plasmapheresis. The brain MRI and eye fundi findings were consistent with her clinical improvement. To the best of our knowledge, this is the first description of MRI abnormalities and multiple retinal artery branch occlusion of cerebral vasculitis in a patient with HSP that was successfully treated by plasmapheresis alone. In conclusion, we propose that plasmapheresis may be used as a first-line therapy or rescue therapy for cerebral vasculitis in HSP.
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  • 141
    ISSN: 1432-198X
    Keywords: Key words Metabolic acidosis ; Growth ; Growth hormone ; Insulin-like growth factor-I ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Growth impairment induced by chronic metabolic acidosis is associated with an abnormal growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. To examine the potentially beneficial effects of IGF-I on acidosis-induced growth impairment and the influence of GH and IGF-I treatment on the GH/IGF-I axis, three groups of acidotic young rats (untreated, AC, n=12; treated with recombinant human GH, GH, n=8; treated with recombinant human IGF-I, IGF-I, n=8) were studied, and compared with nonacidotic rats fed ad libitum (C, n=9)) or pair-fed with the AC group (PF, n=12). After 14 days of acidosis and 7 days of treatment, growth rate, hepatic abundance of 4.7-kilobase (kb) and 1.2-kb GH receptor transcripts and 7.5-kb and 1.8- to 0.8-kb IGF-I transcripts, serum GH-binding protein (GHBP), and IGF-I concentrations (mean±SEM) were analyzed. Significant decreases of 4.7-kb GH receptor [26±2 vs. 49±6 arbitrary densitometry units (ADU)] and 7.5 kb IGF-I (41±3 vs. 104±10 ADU) transcripts and low serum GHBP (25±1 vs. 32±1 ng/ml) and IGF-I (279±50 vs. 366±6 nmol/l) levels were found in the AC compared with the C rats. The majority of these alterations were also observed in PF rats. Compared with acidotic untreated rats, GH and IGF-I therapy produced no improvement in growth rate. GH treatment normalized the levels of IGF-I mRNA, aggravated the acidosis-related inhibition of the GH receptor gene, and did not modify the serum levels of GHBP and IGF-I. In contrast, IGF-I administration depressed the hepatic expression of all GH and IGF-I transcripts and normalized serum IGF-I concentrations. Our results confirm that sustained metabolic acidosis alters the GH/IGF-I axis, in part because of associated malnutrition, and induced growth retardation that is resistant to GH therapy. Our study also shows that administration of IGF-I does not accelerate the growth of acidotic rats, suggesting a peripheral mechanism, at the level of target tissues, is responsible for the resistance to the growth-promoting actions of GH and IGF-I.
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  • 142
    ISSN: 1432-198X
    Keywords: Key words Hemolytic uremic syndrome ; Cerebral hypoxia ; Magnetic resonance imaging ; Central nervous system lesions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report a 20-month-old girl with post- diarrheal (Shiga toxin) hemolytic uremic syndrome and severe encephalopathy. Magnetic resonance (MR) images were obtained in the acute phase of the disease and after 10 months. The first MR images showed widespread high signal intensity on T2-weighted and low signal intensity on T1-weighted images, in deep and subcortical white matter; the splenium of the corpus callosum was also involved, as well as cerebellar hemispheres. Neurological symptoms and signs gradually disappeared within 35 days. Follow-up MR imaging showed almost complete resolution of the previous findings, and the patient recovered without central nervous system impairment. The neurological lesions were probably due to hypoxia, although several other mechanisms could be involved, such as metabolic derangements and the action of Shiga toxin. In spite of the dramatic clinical manifestations, we observed a good outcome, indicating that patients with similar lesions do not necessarily have a poor prognosis.
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  • 143
    ISSN: 1432-198X
    Keywords: Key words Apoptosis ; Ceramide ; Development ; Kidney ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Ceramide is emerging as an important hydrophobic sphingolipid involved in cell differentiation and apoptosis. Since apoptosis plays a significant role in cellular remodeling during renal morphogenesis, we measured ceramide content and apoptosis in the fetal (18 days gestation), neonatal (3, 7, and 14 days postnatal), and adult rat kidney. In addition, to determine whether developmental changes in ceramide content are tissue-specific, we compared renal ceramide content with that in lung and liver. Ceramide was measured by the diacylglycerol kinase assay, and apoptosis was determined by the TUNEL technique. Renal ceramide content fell over 100-fold from the fetus to the 7th postnatal day. Renal apoptosis paralleled ceramide content, with a greater than 300-fold decrease in apoptosis from fetal to adult life. Ceramide content of the lung and liver was significantly less than that of the kidney, and changed less with maturation. We conclude that maturational changes in ceramide content are tissue-specific, and that the high rate of apoptosis in the developing kidney may be related to the elevated ceramide content.
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  • 144
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    Der Radiologe 40 (2000), S. 904-915 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Leber ; Sonographie ; Computertomographie ; Magnetresonanztomographie ; Szintigraphie ; Positronenemissionstomographie ; Keywords Liver ; Ultrasonography ; Computed tomography ; Magnetic resonance imaging ; Radionuclide imaging ; Positron emission tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Highly specific methods are required for the diagnostic workup of focal hepatic lesions, since benign circumscribed liver changes are very common. Although cross-sectional imaging techniques have a high diagnostic accuracy, radionuclide imaging techniques such as colloid, red blood cell, or hepatobiliary scan are commonly performed when a benign lesion is assumed since these permit a definite diagnosis with high specificity. The diagnosis of a primary or secondary malignant liver tumor, however, usually relies on radiological imaging techniques alone, supported by needle biopsy. Whether positron emission tomography as a primary or supplementary diagnostic tool will have a role in the routine staging of malignant tumors remains to be determined.
    Notes: Zusammenfassung Die Abklärung umschriebener Leberveränderungen erfordert den Einsatz von Methoden hoher Spezifität, da die Prävalenz benigner, fokaler Läsionen sehr hoch ist. Hierfür sind radiologische Schnittbildtechniken grundsätzlich gut geeignet. Wenn aufgrund der sonographischen, computertomographischen oder magnetresonanztomographischen Befunde eine gutartige Läsion anzunehmen ist, werden jedoch häufig ergänzend die Kolloiderythrozyten- oder hepatobiliäre Szintigraphie – ggf. in Kombination – eingesetzt, da hiermit rasch eine abschließende Diagnose mit hoher Spezifität gestellt werden kann. Bei malignen primären oder sekundären Lebertumoren hingegen werden nuklearmedizinische Zusatzuntersuchungen seltener angefordert, da der radiologische Befund, ggf. gestützt durch eine Ultraschall- oder CT-gezielte Biopsie, eine Diagnose in den meisten Fällen erlaubt. Inwieweit sich der primäre oder ergänzende Einsatz der Positronenemissionstomographie im Vergleich zu radiologischen Schnittbildtechniken beim Staging bösartiger Tumoren bewährt, ist noch nicht abschließend geklärt.
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    Der Radiologe 40 (2000), S. 1064-1076 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Sarkoidose ; Neurosarkoidose ; Granulom ; MRT ; Keywords Sarcoidosis ; Sarcoidosis complications ; Neurosarcoidosis ; Granuloma ; Brain diseases complications ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The central nervous system is frequently affected during the course of sarcoidosis. Many of these lesions remain without clinical correlates. Unenhanced and contrast enhanced CT and MRI play an important role during the diagnostic work-up of patients with sarcoidosis and suspected or proved CNS involvement. This article summarizes the most frequent manifestations of neurosarcoidosis and provides illustrative examples of MRI findings.
    Notes: Zusammenfassung Das Nervensystem ist bei der Sarkoidose häufiger mitbeteiligt als nach klinischen Gesichtspunkten zu vermuten wäre. Den bildgebenden Untersuchungsverfahren kommt eine große Bedeutung beim Nachweis der pathologischen Veränderungen zu. Insbesondere die Kernspintomographie sichert die Diagnosestellung und dient der Verlaufsbeurteilung. In dieser Übersichtsarbeit werden die typischen klinischen und bildgebenden Befunde bei der Neurosarkoidose vorgestellt.
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    Der Radiologe 40 (2000), S. 870-877 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Lunge ; Perfusion ; Ventilation ; Computertomographie (CT) ; Magnetresonanztomographie (MRT) ; Keywords Lung ; Perfusion ; Ventilation ; Computed tomography ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Radiological cross-sectional imaging modalities, particularly computed tomography (CT) have become the mainstays for diagnosing lung disease in recent years. These enable morphological visualization of pathological processes with the greatest possible spatial resolution. Modern technical developments and complementary strategies have led to new applications and new functional assessments which need to be reviewed together with state-of-the-art techniques in nuclear imaging. The diagnosis of pulmonary embolism using spiral CT angiography and magnetic resonance (MR) angiography certainly belongs in this category. CT has become the an alternative modality of first choice, and it is also challenging pulmonary angiography as the gold standard. Direct visualization of patent pulmonary arteries and thromboembolic material is complemented by that of effects on the pulmonary parenchyma and right heart function; it also provides perfusion studies and MR-based flow measurement to assess hemodynamic compromise. Ventilation studies have long been a domain of nuclear imaging, and new techniques for the direct visualization of ventilation are emerging from recent developments in the field of MR imaging, for example, using hyperpolarized inert gases. New functional parameters of ventilation can be derived from these studies. For the diagnosis of metabolically active disease, such as tumor and pneumonia, CT offers very high sensitivity, for example, in screening for intrapulmonary nodules using low-dose CT and in the early detection of pulmonary infiltrates in high-risk patients. Especially for characterizing pulmonary nodules there is a need to combine nuclear medicine techniques, such as in positron-emission tomography.
    Notes: Zusammenfassung Die radiologischen Schnittbildverfahren, insbesondere die CT, haben sich innerhalb kurzer Zeit einen herausragenden Stellenwert in der Diagnostik von Lungenerkrankungen erworben. Dies umfasst in erster Linie die morphologische Darstellung pathologischer Prozesse mit hoher räumlicher Auflösung. Moderne technische Entwicklungen und kombinierte Untersuchungsstrategien eröffnen neue Einsatzgebiete und auch funktionelle Aussagen, die nach einer aktuellen Standortbestimmung gemeinsam mit den nuklearmedizinischen Verfahren verlangen. Dazu gehört die Diagnostik der Lungenembolie mittels Spiral-CT-Angiographie und MR-Angiographie der Pulmonalarterien. Hier hat sich mittlerweile die CT als alternatives Verfahren der Wahl etabliert und die Rolle der Pulmonalisangiographie als Goldstandard infrage gestellt. Die reine direkte Darstellung der durchströmten Pulmonalarterien und des thromboembolischen Materials wird durch Diagnostik intrapulmonaler und kardialer Veränderungen, Perfusionsuntersuchungen sowie MR-basierte Flussmessungen zur hämodynamischen Beurteilung erweitert. Nachdem Untersuchungen der Ventilation lange Zeit eine Domäne der Nuklearmedizin waren, eröffnen aktuelle Entwicklungen in der MRT neue Verfahren zur direkten Visualisierung der Lungenbelüftung, z. B. mittels polarisierter Edelgase. Aus diesen Verfahren lassen sich auch neue funktionelle Parameter der Ventilation ableiten. In der Diagnostik von Tumoren und Entzündungen überzeugt die CT insbesondere durch ihre hohe Sensitivität, z. B. beim Screening auf intrapulmonale Rundherde mittels Niedrigdosis-CT oder bei der Früherkennung pneumonischer Infiltrate bei Risikopatienten. Insbesondere bei der Charakterisierung intrapulmonaler Rundherde ist eine Kombination mit nuklearmedizinischen Verfahren (PET) grundsätzlich anzustreben.
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  • 147
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Koronare Herzkrankheit ; Magnetresonanztomographie ; Myokardperfusion ; SPECT ; Key words ; Coronary artery disease ; Magnetic resonance imaging ; Myocardial perfusion ; SPECT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Aim: Performance of combined rest/stress MR perfusion studies and the analysis of qualitative signal intensity parameters in comparison with 99mTc-SestaMIBI SPECT in patients with known coronary artery disease (CAD). Methods: Sixteen patients with CAD underwent MR myocardial perfusion assessment at rest and after dipyridamole-induced hyperemia. Qualitative parameters (SI increase, SI upslope) of the SI time-curves were evaluated and characteristics of normal, reversible and persistent hypoperfused myocardium as assessed by 99mTc-SestaMIBI SPECT were compared. Results: Compared with the rest values, normal myocardium showed a significant increase of the SI upslope during hyperemia (P〈0.001), whereas persistent (P=0.07) and reversible (P=0.15) hypoperfusions showed only minor changes. SI increase over baseline also showed a significant increase only in normal myocardium (P〈0.001). At rest, reversible ischemic areas showed no significant differences from normal myocardium, whereas during hyperemia SI increase was significantly lower (P=0.02). Conclusions: Qualitative SI parameters of a combined rest/stress MR myocardial perfusion study allow to differentiate normal from reversibly or persistently hypoperfused myocardium.
    Notes: Zusammenfassung Fragestellung: Die kombinierte Ruhe- und Belastungsuntersuchung der myokardialen Durchblutung in der MRT sowie die Analyse qualitativer SI-Parameter der MR-Myokardperfusion bei Patienten mit koronarer Herzkrankheit wurden mit der 99mTc-SestaMIBI SPECT verglichen. Methode: Bei 16 Patienten mit koronarer Herzkrankheit (KHK) wurde in der MRT mit einer Mehrschichtgradientenechotechnik die Myokardperfusion unter Ruhe- und Belastungsbedingungen untersucht. Qualitative Signalintensitätsparameter der Kontrastmittelanflutung wurden berechnet und die Parameter in normalen, reversibel und persistierend minderperfundierten Myokardarealen miteinander verglichen. Ergebnisse: Normales Myokard zeigte im Gegensatz zu reversiblen (P=0,15) und persistierenden (P=0,07) Ischämien eine signifikante Zunahme der SI-Anstiegssteilheit unter Belastung (P〈0,001). Die SI-Zunahme zeigte ebenfalls nur in normal perfundierten Arealen eine signifikante Zunahme (P〈0,001) nach Belastung. Unter Belastung zeigte sich bei reversiblen Ischämien eine signifikant niedrigere SI-Zunahme als in normalem Myokard (P=0,02), während sich in Ruhe kein Unterschied zeigte. Schlussfolgerung: Qualitative SI-Parameter der kombinierten MR-Perfusionsuntersuchung des Myokards in Ruhe und unter Belastung erlauben die Differenzierung zwischen normalem sowie reversibel oder persistierend minderperfundiertem Myokard.
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    Der Radiologe 40 (2000), S. 465-468 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Fäkale Inkontinenz ; Magnetresonanztomographie ; Endoanalspule ; Key words Faecal incontinence ; Magnetic resonance imaging ; Endoanal coil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Purpose. Within the recent years several studies have been performed to determine the value of endoanal magnetic resonance imaging (MRI) in faecal incontinence. Methods. MRI is performed using a 0.5 – 1.5T unit. A surface coil with a maximum diameter of 19 mm is placed in the anal canal. T2* 3D gradient-echo-sequences and T2-weighted turbo-spin-echo-sequences in coronal, axial und sagittal orientation are acquired. Results. Compared to endoanal ultrasound (EUS), which is the gold standard for diagnosis in faecal incontinence, endoanal MRI is better in visualization of the external sphincter. The accurate delineation of the external sphincter has led to the possibility to evaluate sphincter atrophy. Preliminary results have shown, that endoanal MRI has an accuracy of 90–95% in the demonstration of lesions in the external sphincter. In detection of lesions of the internal sphincter EUS is still superior to endoanal MRI. Conclusion. EUS and endoanal MRI are currently the optimal imaging techniques for faecal incontinenc, with the advantage of detecting external sphincter atrophy with endoanal MRI.
    Notes: Zusammenfassung Zielsetzung. In den letzten Jahren wurden mehrere Studien durchgeführt, deren Ziel es war, den Stellenwert von Endoanalspulen in der Magnetresonanztomographie (MRT) zur Abklärung von Sphinkterdefekten bei fäkaler Inkontinenz (FI) zu bestimmen. Methode. Die endoanale MRT wird an 0,5–1,5-Tesla-Geräten durchgeführt. Zur Darstellung der Sphinkteren werden Oberflächenspulen mit einem maximalen Querdurchmesser von 19 mm endoanal appliziert. T2*-gewichtet 3D-Gradientenechosequenzen und T2-gewichtete Turbospinechosequenzen in koronaler, axialer und sagittaler Schnittführung werden zur Darstellung des Analkanals angefertigt. Ergebnisse. Im Vergleich zum endoanalen Ultraschall (EUS), der den Goldstandard bei der Abklärung einer FI darstellt, kann mit der endoanalen MRT v. a. der M. sphincter externus besser abgegrenzt werden. Die exakte Differenzierung des M. sphincter externus vom ischiorektalem Fettgewebe ermöglicht die Diagnose einer Atrophie des äußeren Schließmuskels. Erste Studienergebnisse haben gezeigt, daß die endoanale MRT eine Treffsicherheit von 90–95% bei der Detektion von Defekten im M. sphincter externus erreicht. Die Abklärung einer Kontinuitätsunterbrechung im M. sphincter internus ist nach wie vor eine Domäne des EUS. Schlussfolgerung. Die endoanale MRT stellt eine ergänzende Methode zum EUS dar und ist diesem in der Beurteilung der Morphologie des M. sphincter externus überlegen.
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    Der Radiologe 40 (2000), S. 625-631 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Computertomographie ; Magnetresonanztomographie ; Pharynx ; Tumoren ; Key words Computed tomography ; Magnetic resonance imaging ; Pharynx ; Tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background. Malignant tumors of the head and neck region are amongst the six most often occurring tumors of the body. They can be associated with the different anatomical compartments as well as different histologic types. The way of tumor spread of these malignancies depends on their histologic type and on the region. These compartments can be separated into the nasopharynx, the oropharynx, and the hypopharynx. Most of the malignant tumors belong to the squamous cell carcinomas, other histologic types are depicted less frequently. The histologic types of the other groups which are seen more often comprise of lymphomas and adenoidcystic carcinomas. The undifferentiated carcinoma of the nasopharynx is supposed to be a special type of tumor. The malignant tumors of the pharynx can also involve all three compartments. Beside these tumors, malignancies of mesenchymal origin can also be delineated. Imaging modalities. The imaging modalities most frequently used to detect these tumors and to clarify their extension are contrast enhanced computed tomography, magnetic resonance imaging, nuclearmedicine imaging modalities such as positron emission tomography. Other scintigraphic imaging methods play a less important role. Conclusion. The different imaging modalities of malignant pharyngeal tumors and of potentially infiltrated lymphnodes with the weightness on computed tomography and magnetic resonance imaging and their appearance in these imaging techniques shall be enhanced in this paper.
    Notes: Zusammenfassung Hintergrund. Der Kopf-Hals-Bereich zählt weltweit zu den 6 am häufigsten von malignen Tumoren befallenen Körperregionen. Maligne Tumoren des Pharynx können dabei entsprechend der anatomischen Unterteilung – d. h. Nasopharynx, Oropharynx und Hypopharynx – diesen Regionen zugeordnet werden. Neben der grundsätzlich heterogenen Wachstumstendenz weisen diese Tumoren je nach histologischer Herkunft ein recht unterschiedliches Ausbreitungsmuster auf. Bei der überwiegenden Mehrzahl handelt es sich um Plattenepithelkarzinome, die anderen histologischen Typen – wie adenoidzystische Karzinome oder Lymphome – sind weitaus seltener vertreten. Daneben kommen sehr selten auch noch maligne Tumoren mesenchymalen Ursprungs wie z. B. die Rhabdomyosarkome vor. Bildgebung. Die bildgebende Abklärung erfolgt mit der kontrastmittelverstärkten CT, der MRT und in jüngster Zeit mit nuklearmedizinischen Methoden, z. B. PET. Andere szintigraphische Untersuchungsmethoden spielen eine untergeordnete Rolle. Resümee. Verschiedene bildgebende Methoden (schwerpunktmäßig CT und MRT) und die entsprechenden Erscheinungsbilder sowie Lokalisations- bzw. Ausbreitungsdiagnostik der malignen Tumoren und evtl. befallener Lymphknoten dieser Regionen werden vorgestellt.
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  • 150
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Zerebrovaskuläre Erkrankung ; Arteriosklerose ; Magnetresonanztomographie ; Magnetresonanzangiographie ; Digitale Subtraktionsangiographie ; A. carotis ; Keywords Cerebrovascular disease ; Arteriosclerosis ; Magnetic resonance imaging ; Magnetic resonance angiography ; Digital subtraction angiography ; Carotid artery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Purpose. To compare high resolution contrast-enhanced MR angiography (MRA) and digital subtraction angiography (DSA) in the assessment of supraaortic vessel stenosis. Methods. 14 patients with suspicion of cerebrovascular disease or upper limb ischemia underwent selective DSA and high resolution contrast enhanced MRA employing a new Panoramic-Array coil. Stenosis assessment in comparison to DSA followed NASCET criteria. Additionally signal-/noise ratios (SNR) were evaluated to assess contrast enhancement. Results. Diagnostic image quality was achieved in all patients. Sensitivity and specificity for assessing high-grade stenosis of the supraaortic vessels were 100% and 96% respectively. In the assessment of high-grade common or internal carotid artery stenosis sensitivity and specificity was 100%. Conclusion. High resolution contrast enhanced supraaortic MRA combined with new coil sytems allow for a reliable assessment of stenoses along the whole vessel course including the aortic arch. Previous stent procedures limit its use in post-interventional follow-up.
    Notes: Zusammenfassung Fragestellung. Ziel der Studie war ein Vergleich zwischen hochauflösender kontrastverstärkter MR-Angiographie (MRA) und digitaler Subtraktionsangiographie (DSA) in der Diagnostik von Stenosen der supraaortalen Gefäße. Methoden. 14 Patienten mit Verdacht auf eine zerebrovaskuläre Erkrankung oder Durchblutungsstörung der oberen Extremität wurden mit DSA und hochaufgelöster, kontrastverstärkter MR-Angiographie mit Verwendung einer Panoramic-Array-Spule untersucht. Neben der Beurteilung der Kontrastierung erfolgte die Bestimmung der Stenosegrade im Vergleich zur selektiven DSA nach den NASCET-Kriterien. Ergebnisse. Bei allen Patienten konnte mit der MRA eine diagnostisch ausreichende Bildqualität erzielt werden. In der Diagnostik hochgradiger Stenosen der supraaortalen Gefäße ergab sich eine Sensitivität von 100% und eine Spezifität von 96%. In der Erkennung hochgradiger Stenosen der A. carotis communis oder interna lagen Sensitivität und Spezifität bei 100%. Schlussfolgerung. Die ultraschnelle MRA der supraaortalen Gefäße in Kombination mit einer geeigneten Spulenkombination ermöglicht die zuverlässige Erkennung stenotischer Veränderungen im gesamten Gefäßverlauf einschließlich des Aortenbogens. Stentimplanationen limitieren derzeit den Einsatz in der postinterventionellen Kontrolle.
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  • 151
    ISSN: 1432-2072
    Keywords: Keywords Novelty ; Context ; Environment ; Stress ; 6-OHDA ; Rotational behavior ; Striatum ; Nucleus accumbens shell ; Caudate ; Amphetamine ; Dopamine ; Glutamate ; Aspartate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: We have previously shown that environmental novelty enhances the behavioral activating effects of amphetamine and amphetamine-induced expression of the immediate early gene c-fos in the striatal complex, particularly in the most caudal portion of the caudate. In contrast, we found no effect of novelty on the ability of amphetamine to induce dopamine (DA) overflow in the rostral caudate or in the core of the nucleus accumbens. Objectives: The twofold aim of the present study was to determine the effect of environmental novelty on (1) amphetamine-induced DA overflow in the shell of the nucleus accumbens and in the caudal portions of the caudate, and (2) glutamate and aspartate overflow in the caudal portions of the caudate. Methods: Two groups of rats with a unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system received amphetamine (0.5 mg/kg, i.v.) in physically identical cages. For one group, the cages were also the home environment, whereas, for the other group, they were a completely novel environment. In vivo microdialysis was used to estimate DA, glutamate, and aspartate concentrations. Results: Environmental novelty enhanced amphetamine-induced rotational behavior (experiments 1–3) but did not alter amphetamine-induced DA overflow in either the shell of the nucleus accumbens (experiment 1) or the caudate (experiment 2). In addition, the ability of environmental novelty to enhance amphetamine-induced behavioral activation was not associated with changes in glutamate or aspartate efflux in the caudate (experiment 3). Conclusions: The present data indicate that the psychomotor activating effects of amphetamine can be modulated by environmental context independent of its primary neuropharmacological actions in the striatal complex.
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  • 152
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    Psychopharmacology 148 (2000), S. 106-110 
    ISSN: 1432-2072
    Keywords: Key words Interferon ; Depression ; Forced swimming test ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objectives: We examined the immobility of the forced swimming test induced in an animal model by human interferon (IFN), which has often been reported to induce depression in clinical use. Methods: In the present study, we examined the effects of human IFNs on results of the forced swimming test in rats. Results: Single intravenous (IV) administration of human IFN-α (6×104 IU/kg), but not of human IFN-β or -γ, significantly increased immobility time in the forced swimming test in rats. Repeated administration of human IFN-α (6×103 IU/kg) also significantly increased the immobility time. On the other hand, none of the rat IFNs (rat IFN-α, -β and -γ, 6×104 IU/kg, IV) changed the immobility time. Neither human IFNs nor rat IFNs changed the locomotor activity of rats. Conclusions: These findings suggest that human IFN-α has a greater potential for inducing increase of the immobility in the rat forced swimming test than human IFN-β and -γ, and that the effect of human IFN-α might not be mediated through IFN-α/β receptors.
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  • 153
    ISSN: 1432-2072
    Keywords: Key words Opiate receptor ; Antinociception ; Habituation ; Novelty ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: There is now extensive evidence demonstrating that exposure to novel stimuli induces hypoalgesia and that this effect habituates over repeated exposure to the stimuli. Moreover, it has been shown that administration of the nonselective opiate receptor antagonist naloxone can attenuate the rate of habituation of novelty-induced hypoalgesia. Objectives: The present experiments were conducted to determine the relative influence of different opiate receptor subtypes in the attenuation of the habituation of novelty-induced hypoalgesia. Methods: In experiments 1–3, different groups of male, Wistar rats (275–300 g) were administered vehicle, 0.5, 1.0 or 2.0-nmol doses of the µ-selective antagonist Cys2-Tyr3-Orn5-Pen7-amide (CTOP), the δ-receptor selective antagonist naltrindole, or the κ-selective antagonist nor-binaltorphimine (nor-BNI). In experiment 4, animals were administered vehicle, 5, 25 or 75-nmol doses of nor-BNI. All injections were delivered to the right lateral ventricle 30 min prior to exposure to a novel hot-plate apparatus (48.5°C), once a day for eight consecutive days. Results: Paw-lick latencies in vehicle-treated animals were long during the initial exposures and declined over repeated tests, suggesting the habituation of novelty-induced hypoalgesia. The rate of habituation was significantly attenuated by administration of 1.0-nmol and 2.0-nmol doses of CTOP, by a 2.0-nmol dose of naltrindole, but was unaffected by all doses of nor-BNI. Conclusions: These results support the involvement of the µ and δ, but not the κ, opiate receptor subtypes in the habituation of novelty-induced hypoalgesia.
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  • 154
    ISSN: 1432-2072
    Keywords: Key words Morphine ; Opioid receptor ; NMDA ; Tolerance ; Rat ; Tail flick
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Pairings of a sweet taste and injection of morphine result in a learned avoidance of that taste and learned analgesic tolerance. This avoidance is mediated by the drug’s peripheral effect, while learned tolerance involves activation of N-methyl-d-aspartate (NMDA) receptors. Exposure to a sweet taste also reduces morphine analgesia. We studied whether this taste-mediated reduction was reversed by an NMDA or peripheral opioid receptor antagonist. Objectives: To determine whether an intraoral infusion of saccharin would modulate morphine analgesia in rats, and to study the contribution of NMDA as well as peripheral opioid receptors to this modulation. Methods: Six experiments used the rat’s tail-flick response to study the effect of an intraoral infusion of a sodium saccharin solution on morphine analgesia, and the effects of the quaternary opioid receptor antagonist methylnaltrexone as well as the non-competitive NMDA receptor antagonist MK-801 on this modulation of analgesia. Results: An intraoral infusion of saccharin reduced the analgesic effects of an intraperitoneal (i.p.) injection of morphine across a range of doses (experiment 1a), which was not attributable to an influence on tail-skin temperature (experiment 1b). This reduction was mediated by opioid receptors in the periphery and activation of NMDA receptors because morphine analgesia was reinstated by an i.p. injection of either methylnaltrexone (experiment 2a) or MK-801 (experiment 3a), which was not due to the effect of methylnaltrexone (experiment 2b) or MK-801 (experiment 3b) on morphine analgesia in the absence of saccharin. Conclusions: These results document evidence for an antagonism of morphine analgesia by actions of the drug at peripheral opioid receptors and excitatory amino-acid activity at NMDA receptors. They are discussed with reference to the aversive motivational effects of peripheral opioid receptors and pain facilitatory circuits.
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  • 155
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    Psychopharmacology 149 (2000), S. 115-120 
    ISSN: 1432-2072
    Keywords: Key words Opiate ; Withdrawal ; Place aversion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Administration of low doses of opiate antagonists to morphine-dependent rats produces an aversive response as measured by a conditioned place aversion, but the time course of such a learned aversion is largely unknown. Objectives: The purpose of this experiment was to examine the time course for the expression of a place aversion to opiate withdrawal. Methods: Morphine-dependent rats were tested in a three-chamber place- aversion apparatus. The conditioning phase consisted of three pairings of either naloxone (15 µg/kg s.c.) or vehicle with two compartments, with the most similar time allotments during the preconditioning test. During the testing phase, rats were again allowed to explore the entire apparatus. Different groups were tested at 24 h, 1 week, 2 weeks, 4 weeks, 8 weeks, and 16 weeks post-conditioning (morphine-free tests). Results: A robust place aversion was recorded at every time point tested, including at 16 weeks. In previously published work, placebo-pelleted rats tested with naloxone at the same dose failed to show a place aversion and nondependent rats showed a stable lack of aversion at tests up to 56 days. Dependent animals without naloxone also failed to show a place aversion at any of those time points. Conclusions: In the absence of any active intervention, the place aversion produced by opiate withdrawal is very long lasting and provides a model for protracted abstinence that may be useful for delineating the neurobiological substrate for vulnerability to relapse.
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  • 156
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    Psychopharmacology 149 (2000), S. 181-188 
    ISSN: 1432-2072
    Keywords: Key words Acoustic startle response ; Prepulse inhibition ; Sensorimotor gating ; Schizophrenia ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Prepulse inhibition of acoustic startle is the reduction in startle response to an intense auditory stimulus when this stimulus is immediately preceded by a weaker prestimulus. Prepulse inhibition occurs normally in humans and experimental animals, but schizophrenic persons often exhibit a marked impairment in this measure. Previous studies have shown that dopamine (DA)-dependent neuronal mechanisms are involved in the modulation of prepulse inhibition. Objective: Experiments were conducted in rats to elucidate further the involvement of DA-ergic mechanisms in prepulse inhibition. Results: In line with previous studies, the indirect DA agonist, amphetamine, was shown to decrease prepulse inhibition. A close reverse relationship over time between DA overflow in the nucleus accumbens and prepulse inhibition was obtained using a technique allowing concomitant measurement of these parameters in awake, freely moving rats. This effect was more pronounced in amphetamine-treated rats compared to rats treated with equimolar doses of cocaine, which increased DA overflow without affecting prepulse inhibition. In other experiments, the combined treatment with subthreshold doses of the selective DA D1 agonist, SKF 38393, and the selective DA D2 agonist, quinpirole, was also shown to decrease prepulse inhibition. Finally, the selective DA D2 antagonist, raclopride, was shown to enhance prepulse inhibition. Conclusions: In line with previous studies, it is concluded that DA neurotransmission is involved in the modulation of prepulse inhibition and that the ventral part of the mesostriatal DA system may serve an important role in this modulation. Furthermore, the possibility is discussed that the discrepant results on prepulse inhibition obtained with amphetamine and cocaine may disclose functionally relevant differences in their mechanisms of action, and that the enhancement of prepulse inhibition induced by some antipsychotics in rats may reflect their propensity to induce adverse mental effects in humans.
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  • 157
    ISSN: 1432-2072
    Keywords: Key words Prefrontal cortex ; Dopamine ; Anxiety ; Drug discrimination ; Pentylenetetrazol ; Chlordiazepoxide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The prefrontal cortical (PFC) dopamine (DA) system has been implicated in anxiety-related behavioral changes, but direct, unequivocal support for this idea is sparse. Objectives: The present aim was to study the functional significance of prefrontal DA using the pentylenetetrazol (PTZ) discrimination model of anxiety. A comparison was made with its role in the cue of the anxiolytic drug chlordiazepoxide (CDP). Methods: Two groups of rats were trained to discriminate either PTZ (20 mg/kg, s.c.) or CDP (10 mg/kg, i.p.) from saline using an operant drug discrimination procedure. After prolonged training, half of each group was used to assess biochemical changes induced by both drugs in different sub areas of the PFC. For the remaining rats, discrimination training continued and generalization tests with PTZ and CDP were performed. Rats were then provided with bilateral guide cannulae aimed at the ventromedial (vm) PFC, and the effects of local infusions of DAergic drugs on discriminative performance were evaluated. Results: CDP did not affect PFC DA activity, but PTZ increased the DOPAC/DA ratio in the vmPFC selectively. Generalization tests showed that the cues of PTZ and CDP were dose dependent. In PTZ-trained rats, infusions of the DA receptor antagonist cis-flupenthixol into the vmPFC blocked the PTZ cue dose dependently, whereas the agonist apomorphine partially generalized to this cue. In CDP-trained rats, neither drug antagonized or generalized to the CDP cue, showing that PFC DA is not critically involved in the CDP cue and that local pharmacological manipulations of PFC DA do not affect discriminative abilities per se. Conclusions: The DAergic innervation of the PFC is directly involved in the behavioral effects of PTZ, suggesting a role for it in anxiety.
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  • 158
    ISSN: 1432-2072
    Keywords: Key words 5-HT1A agonist ; Intrinsic activity ; Efficacy ; Irreversible antagonism ; Lower-lip retraction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Maximal responses are often used as a measure of intrinsic activity or efficacy, but cannot be directly equated to efficacy. Using irreversible antagonists, estimates of efficacy can be obtained that may be less dependent on specific conditions. Objectives: To characterize the intrinsic activity of serotonin (5-HT)1A agonists by examining the effects of an irreversible antagonist on their ability to produce 5-HT1A receptor-mediated responses. Methods: The effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on the ability of 5-HT1A agonists to produce lower-lip retraction (LLR) in rats were studied. Results: In the absence of EEDQ, each 5-HT1A agonist produced full effects, the rank order of potency being: S 14506 〉 8-OH-DPAT 〉 buspirone 〉 ipsapirone. EEDQ decreased the number of 5-HT1A binding sites and shifted the dose–response curves (DRCs) of each agonist either to the right or, at higher EEDQ doses, to the right and downward. The manner in which these shifts occurred, however, differed among the compounds. For each agonist, all DRCs obtained after different doses of EEDQ were fitted to models proposed by Furchgott and Black and Leff, and the results indicated the following rank order of efficacy: ipsapirone 〈 buspirone ≈ 8-OH-DPAT 〈 S 14506. 5-HT1A agonist-induced LLR appears to be mediated by 5-HT1A receptors, because the 5-HT1A antagonist, WAY 100635, shifted the agonist DRCs to the right in a parallel and dose-related manner, with pA2 values ranging from 7.8 to 8.1. Moreover, pretreatment with WAY 100635 protected against the antagonist activity of EEDQ. Conclusions: The results suggest that the effects of EEDQ on the ability of 5-HT1A agonists to produce LLR in rats may be useful to obtain estimates of their apparent efficacy at 5-HT1A receptors.
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  • 159
    ISSN: 1432-0738
    Keywords: Key words Flutamide ; Androgen antagonist ; Rat ; Enhanced OECD Test Guideline 407 ; Endocrine disrupters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In association with the international validation project to establish a test protocol for the `Enhanced OECD Test Guideline 407', we performed a preliminary 28-day, repeated-dose toxicity study of flutamide, a non-steroidal androgen antagonist, and assessed the sensitivity of a list of parameters for detecting endocrine-related effects of endocrine-disrupting chemicals (EDCs). Seven-week-old CD(SD)IGS rats were divided into four groups, each consisting of 10 males and 10 females, and administered flutamide once daily by oral gavage at doses of 0 (control), 0.25, 1 and 4 mg/kg body weight/day. Male rats were killed 1 day after the 28th administration. Female rats were killed on the day they entered the diestrus stage in the estrous cycle following the last treatment. Male rats receiving flutamide at dose levels of 1 and 4 mg/kg showed lobular atrophy of the mammary gland and a decrease in epididymal weight. In addition, 4 mg/kg flutamide-treated males exhibited raised serum testosterone and estradiol levels and decreased weight of the accessory sex glands. In females, a slight prolongation of the estrous cycle was also observed in the 4 mg/kg flutamide-treated group. No dose-related changes could be detected by haematology, serum biochemistry and sperm analysis. Thus, among the parameters tested in the present experimental system, the weight of endocrine-linked organs and their histopathological assessment, serum hormone levels, and estrous cycle stage allowed the detection of endocrine-related effects of flutamide.
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  • 160
    ISSN: 1432-0738
    Keywords: Key wordsα2u-Globulin ; Diethylstilbestrol ; Endocrine disrupter ; Rat ; Screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract α2u-Globulin (AUG) is a major rat urinary protein, which has a molecular weight of 16 kDa (kidney type) or 19 kDa (native type). The biosynthesis of this protein is under multi-hormonal regulation. In this study, we investigated changes in serum AUG level and their association with changes in the reproductive organs of male rats after the administration of the estrogenic chemical, diethylstilbestrol (DES) at doses ranging from 0.01 mg/kg per day to 100 mg/kg per day by gavage for 14 days. Our aim was to establish basic data for the development of a new screening method for endocrine disrupting chemicals based on serum AUG levels. DES treatment decreased the weight of testes in a dose-dependent manner; and was accompanied by atrophic histopathological changes in testes. Testis weights were significantly decreased by the group given 1 mg/kg per day DES; however, histopathological abnormalities were found in the group given 0.1 mg/kg per day DES. In four of five animals in the group given 1 mg/kg per day there was no significant decrease in testis weight and only a slight or moderate degeneration of the pachytene spermatocytes. Despite these findings, serum AUG levels in this group decreased markedly, while the serum AUG level markedly decreased even in the animals with no histopathological change in the 1 mg/kg per day or 0.1 mg/kg per day groups with no histopathological change also showed decreased serum AUG level. These results suggest that the serum AUG level may be a sensitive parameter for detecting the activity of estrogenic chemicals in intact male rats. Although a uterotropic assay has been proposed for immature female or ovariectomized female rats and is currently undergoing validation studies internationally, there is no screening method for estrogenic chemicals in intact male animals. More data on AUG changes by treatment with other estrogenic chemicals are needed in order to determine the sensitivity and specificity of this response to estrogens. Nonetheless, an AUG-based screening test for estrogenic chemicals may be useful owing to its applicability to conventional toxicity studies and an apparently higher sensitivity of this parameter compared to organ weight change or histology of testis in intact male rats and applicability to conventional toxicity studies.
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  • 161
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    Journal of neurology 247 (2000), S. 943-948 
    ISSN: 1432-1459
    Keywords: Key words Transverse myelitis ; Motor evoked potentials ; Somatosensory evoked potentials ; Electromyography ; Prognosis ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A systematic evaluation of anterior horn cell, motor and sensory pathways is possible by electromyography (EMG), motor (MEPs) and somatosensory (SEPs) evoked potentials, respectively, which may provide valuable information on acute transverse myelitis (ATM). In a prospective hospital-based study, EMG, MEP and SEP studies were carried out on admission and after 3 months in 39 patients with ATM. All the patients also underwent detailed clinical evaluation, and spinal magnetic resonance imaging (MRI) was performed in 28. Outcome was defined at the end of 3 months as poor, partial or complete recovery on the basis of functional status. Spinal MRI revealed hyperintense signal changes in T2 extending for two segments to the entire spinal cord. Central motor conduction time to tibialis anterior (CMCT-TA) was more frequently abnormal (90%), followed by tibial SEP (77%). CMCT to abductor digiti minimi (ADM) was abnormal in 30% and median SEP in 15% of patients. Evidence of denervation on EMG was present in 51% of patients. The CMCT-TA improved in 48% patients and tibial SEP in 32%. Median SEP improved in all patients, and CMCT-ADM remained prolonged in two. At 3 months 2 patients had died, and 18 had poor, 10 partial and 9 complete recovery. CMCT was correlated with miscle power, tone, reflec and MRI changes. Patients' outcome of was correlated with CMCT, SEP and EMG. These results are consistent with pronounced involvement of dorsal region of spinal cord in ATM. MEP is more frequently abnormal than SEP.
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  • 162
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    Journal of neurology 247 (2000), S. 252-258 
    ISSN: 1432-1459
    Keywords: Key words Cerebral venous ¶thrombosis ; Dural sinuses ; Magnetic resonance imaging ; Heparin ; Thrombolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In contrast to arterial stroke, cerebral venous thrombosis (CVT) is an infrequent condition which presents with a wide spectrum of signs and with a highly variable mode of onset. The clinician must therefore consider it systematically in all brain syndromes and perform the appropriate neuroimaging investigations: computed tomography (CT) with computed tomography angiography and/or magnetic resonance imaging with magnetic resonance angiography and, if necessary intra-arterial angiography. Once the diagnosis is established, a wide investigation for should be carried out in search of the cause, and treatment started as soon as possible. Treatment is based on the combination of intravenous heparin (followed by oral anticoagulants for 3–6 months), symptomatic treatment (anticonvulsants, analgesics, treatment of increased intracranial pressure) and treatment of the cause. Local thrombolysis is indicated if there is deterioration due to thrombosis extension despite adequate anticoagulation. Diagnosis and treatment of CVT should be considered as an emergency because of the considerable potential for full recovery in this condition.
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  • 163
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Neuropsychological ; Cognitive ; Magnetic resonance imaging ; Lesion load
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuropsychological deficits and the relationship to brain pathology were examined in 13 primary progressive (PP) and 12 secondary progressive (SP) multiple sclerosis patients with a similar duration of the progressive phase and comparable physical disability. A battery of neuropsychological tests to assess attention, short-term and working memory was administered to the patients, and their performance was compared to that of 20 healthy controls matched for age and premorbid IQ. Total cerebral lesion load on T2-weighted magnetic resonance imaging was measured in the patients. Both PP and SP patients performed significantly worse than controls in most of the neuropsychological tests. There were only subtle differences between SP and PP on the working memory task although magnetic resonance imaging lesion load was significantly higher in SP than in PP patients. In this exploratory study only subtle differences in cognitive impairment were detected between SP and PP patients matched for physical disability and relevant illness features. The results also suggest that the severity of cognitive impairment cannot be fully explained by the extent of abnormalities detected on conventional T2-weighted magnetic resonance images, and that other pathological abnormalities such as in normal-appearing white matter are likely to be involved.
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  • 164
    ISSN: 1432-1459
    Keywords: Key words Leukoaraiosis ; Aged ; Atherosclerosis ; Magnetic resonance imaging ; Carotid artery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cerebral white matter lesions are frequently observed on magnetic resonance imaging of elderly, nondemented persons. There is evidence that white matter lesions are involved in the pathophysiology of cognitive decline and dementia. White matter lesions can be divided into those in the periventricular and those in the subcortical region. Pathological and epidemiological studies suggest that atherosclerosis is involved in the pathogenesis of these lesions. Our study reports on the association between atherosclerosis in the carotid arteries and white matter lesions in a population-based study among 1077 elderly subjects. We randomly sampled 1077 subjects aged between 60–90 years from two prospective population-based studies. All subjects underwent ultrasonography of the carotid artery. In addition, 1.5 T magnetic resonance imaging was performed; white matter lesions in the subcortical and periventricular regions were rated separately. With increasing number of plaques in the carotid artery the severity of periventricular white matter lesions increased (P trend = 0.03), but not the severity of subcortical white matter lesions (P trend = 0.19). In addition, an increase in intima media thickness was borderline significantly associated with an increased severity of periventricular white matter lesions (P trend = 0.09), but not of subcortical white matter lesions (P trend = 0.68). These findings suggest that partly dissimilar pathogenetic mechanisms are involved in the etiology of periventricular and subcortical white matter lesions.
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  • 165
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Fatigue ; Magnetic resonance imaging ; Motor evoked potentials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fatique is a common symptom of multiple sclerosis (MS) even in the early phases of the disease, when neurological disability is usually still not present. To investigate the pathophysiology of fatigue we compared neurophysiological (motor evoked potentials of the four limbs, MEPs) and brain magnetic resonance imaging (MRI) findings in two groups of nondisabled MS patients, those with (n=15) and those without (n=15) fatigue. Fatigue was assessed by an interview and scored by the Fatigue Severity Scale. The two groups were matched for sex, age, disease duration, Expanded Disability Status Scale score, pyramidal Functional System (FS) score, and depression score. MEPs were abnormal in five patients with fatigue and in one patient without fatigue. A significant association was found between the patient scores on the Fatigue Severity Scale, and the burden of MRI lesions (r=0.5; P〈0.005). Significantly higher parietal lobe (P〈0.05), internal capsule (P〈0.05), and periventricular trigone (P〈0.05) lesion loads were found in patients with fatigue than in those without. Our results agree with a central nervous system origin of fatigue in MS patients. This symptom might be a consequence either of a functional deafferentation of the cortex due to cortico-subcortical interconnection damage or of a demyelination in critical sites of the CNS, such as the cortico-spinal tract.
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  • 166
    ISSN: 1432-1459
    Keywords: Key words Small subcortical ¶infarction ; Large-vessel disease ; Magnetic resonance imaging ; Silent white-matter hyperintensity ; Lacunar infarction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Small subcortical infarctions resulting from large-vessel disease are often observed. It is important to distinguish these from pure lacunar infarction resulting from small-vessel disease because the investigations and examinations differ. We investigated the differences on brain magnetic resonance imaging (MRI) between small subcortical ¶“lacunar-like” infarcts resulting from large-vessel disease and pure lacunar infarcts. Thirteen subjects with small lacunar-like infarcts (size 〈 2 cm), resulting from large-vessel disease, ¶and 30 subjects with lacunar infarcts (〈 2 cm), without large-vessel disease were studied. We measured infarction size using a 1.5-T MRI device and evaluated silent subcortical hyperintensity lesions using the modified Scheltens’ score. Large-vessel lesion was confirmed by conventional angiography, duplex carotid scan, and magnetic resonance angiography. There was no difference in the mean age of the two groups. Cerebrovascular risk factors and atherosclerotic complications were also comparable for the two groups. Progressive stroke was more common ¶in the lacunar-like infarction group than in the lacunar infarction group ¶(P = 0.004). Scores for periventricular hyperintensity, white matter hyperintensity, basal ganglia hyperintensity, and total subcortical hyperintensity scores were significantly higher in the lacunar infarction group than in the lacunar-like infarction group. The difference in basal ganglia hyperintensity scores was remarkable (P = 0.001). The enlargement of the perivascular space was also significantly greater in the lacunar infarction group than in the lacunar-like infarction group. These findings seem to reflect differences in the pathogenesis of infarction between the two groups. Silent subcortical hyperintensity lesions and enlargement of perivascular space are useful for between distinguishing small lacunar-like infarct resulting from large-vessel disease and pure lacunar infarction. This may have significant implications for the management of patients with lacunar-sized infarctions. It suggests that the pathogenesis of lacunar-sized infarction is variable.
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  • 167
    ISSN: 1432-1459
    Keywords: Key words Sarcoidosis ; Spinal cord ; Magnetic resonance imaging ; Corticosteroid therapy ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Spinal cord sarcoidosis is a rare disorder whose natural history and therapeutic outcome are not fully known. We examined four patients with spinal cord sarcoidosis both clinically and radiologically, particularly in relation to corticosteroid treatment. The initial manifestation was cervical myelopathy in three and uveitis in one. All four patients progressed slowly until corticosteroid therapy was initiated. The cervial spine was involved in all patients. Magnetic resonance imaging (MRI) showed spinal cord swelling with T2-weighted high intensity and linear leptomeningeal and patchy or diffuse intramedullary enhancement with gadolinium diethylene triaminepentaacetic acid. With corticosteroid therapy, dramatic improvement was seen on MRI, including disappearance or marked reduction of swelling and enhancement. Plasma levels of angiotensin-converting enzyme (ACE) were also markedly improved. In contrast, the clinical symptoms were little improved in one patient, unchanged in two, and rather worsened in one patient. Recurrence was seen on MRI at the maintenance dose in all four patients, without any dramatic change in clinical manifestation. MRI findings and plasma ACE are well correlated with active leasion of the spinal cord sarcoidosis, providing a useful marker for recurrence, but do not parallel the clinical manifestations.
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  • 168
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    Skeletal radiology 29 (2000), S. 726-728 
    ISSN: 1432-2161
    Keywords: Keywords Developmental dysplasia ; Hip ; Membrane ; Interposition ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Intra-articular membranous interposition was detected by MRI in the hip joint with residual subluxation of a girl aged 5 years 10 months. This structure, which had low signal intensity on both T1- and T2-weighted images, separated the femoral head from the acetabulum. Histological examination revealed chondrometaplasia, which suggested that this interposition might be transformed to a surface cartilaginous tissue of the secondary acetabulum often observed in residual subluxation of the hip.
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  • 169
    ISSN: 1432-2161
    Keywords: Key words Rheumatoid arthritis ; Cervical spine ; Magnetic resonance imaging ; Dynamic imaging ; Flexion views
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To determine whether MR imaging in flexion adds value relative to imaging in the neutral position with respect to displaying involvement of the subarachnoid space, brainstem and spinal cord. Design and patients. T1-weighted MR images of the cervical spine in 42 rheumatoid arthritis patients with cervical spine involvement were obtained and analyzed prospectively. We assessed changes between images obtained in the neutral position and following active flexion, especially horizontal atlantoaxial and subaxial motion, presence or absence of brainstem compression, subarachnoid space involvement at the atlantoaxial and subaxial level and the cervicomedullary angle. Vertical atlantoaxial subluxation and the amount of pannus were correlated with motion and change in subarachnoid space. Results. The flexion images showed horizontal atlantoaxial motion in 21 patients and subaxial motion in one patient. The flexion view displayed brainstem compression in only one patient. Involvement of the subarachnoid space increased at the atlantoaxial level in eight (19%) patients (P=0.004) and at the level below C2 in five (12%) patients (P=0.03). There were no patients with a normal subarachnoid space in neutral position and compression in the flexed position. The cervicomedullary angle changed significantly with flexion. Vertical atlantoaxial subluxation and the amount of pannus did not show a significant correlation with motion or subarachnoid space involvement. Conclusion. MR imaging in the flexed position shows a statistically significant narrowing of the subarachnoid space at the atlantoaxial level and below C2. Cord compression is only observed on flexion views if the subarachnoid space in neutral position is already decreased. MR imaging in the flexed position might be useful, since subarachnoid space involvement may be an indicator for the development of neurologic dysfunction.
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  • 170
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    Skeletal radiology 29 (2000), S. 104-108 
    ISSN: 1432-2161
    Keywords: Key words Adult teratoma ; Dumb-bell type tumor ; Lumbar spine ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report a case of a lumbar teratoma in a 50-year-old woman. The teratoma showed a dumb-bell-type expansion at the level of the left L3/4 foramen with massive erosion of the L3 vertebral body. MRI revealed inhomogeneous signal changes in the tumor, which were histologically compatible with a mixture of bone, muscle, fat, and cyst containing sebaceous material. Complete resection of the tumor and spinal arthrodesis with pedicle screw fixation was necessary to obtain stability of the affected spinal segment.
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  • 171
    ISSN: 1432-2307
    Keywords: Key words T-type calcium channel blockade ; Mibefradil ; Myocardial infarction ; Cardiac remodeling ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Fibrillar collagen accumulates within the interstitium and around coronary arteries following cardiac failure and is responsible for abnormal myocardial stiffness and reduced coronary performance associated with impaired cardiac function. The aim of the study was to determine the effects of long-term treatment with the T-type calcium channel antagonist mibefradil on myocardial remodeling and cardiac function after chronic myocardial infarction (MI). MI was induced by permanent ligation of the left coronary artery in male Wistar rats. Animals were assigned to sham-operated, placebo-treated or mibefradil-treated (10 mg/kg per day p.o.) MI groups. Treatment with mibefradil was started either 7 days before, 24 h after, or 7 days after ligation and continued for 6 weeks after MI. At this time point, mean arterial blood pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP) and cardiac contractility (dP/dtmax) were measured in conscious rats. Morphometric parameters were determined in picrosirius red-stained hearts: total heart weight (THW), interstitial and perivascular collagen volume fraction (ICVF, PCVF), myocardial infarct size (IS), vascular perimeter (VP), inner vascular diameter (IVD) and media thickness (MT). Six weeks after MI, MAP and dP/dtmax were decreased, and LVEDP was increased in placebo-treated animals. In mibefradil-treated animals whose treatment started 7 days before or 24 h after MI, MAP and dP/dtmax were higher, and LVEDP was lower than in placebo-treated controls. THW, ICVF, PCVF and MT were higher in placebo-treated animals. Mibefradil treatment resulted in higher ICVF and IS, higher VP and IVD (when started 7 days before MI) and lower PCVF and MT (when started 7 days before or 24 h after MI) than were observed in placebo-treated controls. Chronic treatment with mibefradil reduced interstitial and perivascular fibrosis and improved cardiac function in MI-induced heart failure in rats. Cardiac remodeling was best prevented when treatment was begun before the ischemic event.
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  • 172
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    Child's nervous system 16 (2000), S. 138-142 
    ISSN: 1433-0350
    Keywords: Key words Craniopharyngioma ; Posterior fossa tumors ; Microsurgery ; Magnetic resonance imaging ; Computerized tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Between 1991 and 1998, 24 patients underwent surgery for a craniopharyngioma in our department. This group included two patients who had tumors with extensive growth along the midline, and along the posterior fossa in particular. In both cases suprasellar calcifications were typical features on magnetic resonance imaging (MRI) and computed tomography (CT). A 7-year-old boy presented with a 6-month history of headache, nausea, and progressive unilateral hearing loss. With a suboccipital approach it was possible to remove the main part of the tumor. In a 13-year-old boy headache and visual deterioration led to the diagnosis of a craniopharyngioma, which was removed with a pterional approach. For the neuroimaging work-up in such cases of atypically growing craniopharyngiomas MRI is the method of choice. Additional CT scanning is recommended, which provides valuable information about bony changes at the skull base due to space-occupying growth. CT substantiates the differential diagnosis if typical calcifications are seen.
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  • 173
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    Child's nervous system 16 (2000), S. 398-401 
    ISSN: 1433-0350
    Keywords: Keywords Primitive neuroectodermal tumor ; Diffuse leptomeningeal neoplasia ; Magnetic resonance imaging ; Pseudotumor cerebri ; Sinus thrombosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Primitive neuroectodermal tumors are easily detected by neuroradiologic imaging, as a rule. We report on two patients with early diffuse leptomeningeal primitive neuroectodermal tumors which escaped detection by contrast-enhanced magnetic resonance imaging.
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  • 174
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    Child's nervous system 16 (2000), S. 551-554 
    ISSN: 1433-0350
    Keywords: Keywords Acute myelitis of childhood ; Fibrocartilaginous embolism ; Magnetic resonance imaging ; Spinal cord infarction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Fibrocartilaginous embolus causing acute spinal cord infarction is a rare cause of acute-onset paraplegia or quadriplegia. Few cases of survivors have been reported in the neurosurgical literature, with most reports involving post-mortem or biopsy findings. There is little information on MRI findings in such patients. We present the youngest patient ever reported, and discuss the important differences between fibrocartilaginous embolus and acute myelitis of childhood. A 6-year-old girl with a history of back pain presented with sudden-onset nontraumatic paraplegia, with a clinical anterior spinal artery syndrome. Initial MRI scan revealed intervertebral disc disease at L1–2 and an incidental thoracic syrinx, but no cause for her acute-onset paraplegia was identified. Cerebrospinal fluid and other investigations were all negative. Sequential MRI scans revealed development of spinal cord expansion from T10 to the conus medullaris, with increased cord signal in the anterior aspect of the spinal cord. The intervertebral disc disease was unchanged. The imaging and clinical findings were caused by fibrocartilaginous embolus, which meant there was no need for spinal cord biopsy. The report describes the clinical and imaging criteria for diagnosis of fibrocartilaginous embolus, highlighting the case for avoiding an unnecessary biopsy. The clinical pattern in the paediatric group is discussed, with features differentiating it from acute myelitis of childhood.
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  • 175
    ISSN: 1433-0350
    Keywords: Keywords Cavernous angioma ; Cerebral angiography ; Dynamic scan ; Magnetic resonance imaging ; Sinus pericranii
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objects: Sinus pericranii is only a symptom complex, and it can have a variety of etiologies. Therefore, it is important to differentiate these etiologies preoperatively by means of radiological examinations. A 5-year-old boy was admitted with a soft and fluctuant tumor in the right parietal region near the midline. The tumor appeared when the child was in a recumbent position, distending noticeably with the Valsalva maneuver and disappearing completely when the patient was in the sitting position. Methods: Magnetic resonance imaging showed the lesion with honeycomb-like heterogeneous iso- and low-intensity signals on the T1-weighted image and with heterogeneous high- and iso- intensity signal on the T2-weighted image. Dynamic study with an injection of gadolinium diethylene-triaminopentaacetic acid demonstrated and nodular peripheral enhancement at early phase and subsequent progressive enhancement towards the center of tumor. The internal carotid angiogram was normal. The external carotid angiogram, however, showed a tumor stain fed by the superficial temporal arteries. The stain was retained until the late phase and drained into the scalp veins and into the superior sagittal sinus. Following direct injection of contrast medium into the tumor there was prolonged retention of the medium in the tumor and leakage into scalp veins and the superior sagittal sinus. The mass under the periosteum was totally removed and proved to be a cavernous angioma. Conclusions: Scalp cavernous angioma is one of the etiologies of sinus pericranii and may be diagnosed preoperatively by cerebral angiography or magnetic resonance imaging. Serial dynamic magnetic resonance imaging will be particularly helpful for this diagnosis.
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  • 176
    ISSN: 1432-2072
    Keywords: Key words  m-Chlorophenylpiperazine ; Drug discrimination ; Ethanol withdrawal ; Anxiety ; 17β-estradiol ; Sex difference ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The serotonergic system plays a role in regulation of anxiety and ethanol withdrawal (EW). Nevertheless, few studies have assessed sex differences in serotonergic effects on EW. Objectives: This study examined sex differences in the anxiogenic stimu-li induced by a serotonin (5-HT)1b/2 agonist, meta- chlorophenylpiperazine (mCPP), prior to ethanol and during EW. Methods: Gonadectomized or sham-operated adult male and female rats and 17β-estradiol (2.5 mg, 21-day release, s.c.) -replaced ovariectomized (OVX) rats were trained to discriminate mCPP (1.2 mg/kg, i.p.) from saline in a two-lever choice task for food. Latency to the first lever press and mCPP lever selection were measured following mCPP (0–1.2 mg/kg). Rats then received chronic ethanol-containing liquid diet (6.5%) for 10 days and were tested for mCPP lever selection 12 h and 36 h after removal of ethanol. Results: Fewer sham female and β-estradiol-replaced OVX rats selected the mCPP lever than male or OVX rats, and showed an increased initiation latency after mCPP injection. During EW (12 h and 36 h), fewer sham female and β-estradiol-replaced OVX rats responded on the mCPP-lever after saline injection as well as after mCPP challenge than male or OVX rats. Castration did not alter any response of male rats to mCPP. Conclusions: (1) mCPP discrimination is a useful measure of EW in male and female rats; and (2) sham female and β-estradiol-replaced OVX rats are less sensitive to the discriminative stimulus prior to and during EW, but more sensitive to impaired behavioral initiation induced by mCPP than male or OVX rats.
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  • 177
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Diffusionsgewichtete Kernspintomographie ; Wirbelkörpermetastasen ; Diffusionskoeffizient ; Keywords Diffusion weighted imaging (DWI) ; Magnetic resonance imaging ; Vertebral metastases ; Diffusion coefficient ; ADC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Aim of the study. The aim of the study was the evaluation of the diffusion coefficient (ADC) of vertebral metastasis and regular vertebral bodies with diffusion weighted MRI (DWI). DWI evaluates the tissue-specific molecular diffusion of protons. In tissues with high cell densities (neoplasm) a decreased ADC can be expected due to restricted diffusion according to an exaggerated amount of intra- and intercellular membranes (i. e. diffusion barriers). Methods. In 5 breast cancer patients the ADC of both known vertebral metastases and of adjacent regular vertebral bodies were measured with DWI (1.0 T; Phased-Array-Body-Coil; b: 880 and 440 s/mm2). Results. The ADC of regular vertebral bodies (1.3±0.23×10–,3s/mm2) was significantly (p≤0.0002) higher than in vertebral metastases (0.39±0.11×10–3s/mm2). Conclusions. These data demonstrate that the ADC can be reliably measured in vertebral bodies. The quantitative evaluation of the ADC in vertebral bodies seems to be an objective and comparable parameter for differentiating malign from benign vertebral tissue.
    Notes: Zusammenfassung Ziel. Ziel der Arbeit war die Messung des Diffusionskoeffizienten (ADC) mittels diffusionsgewichteter (DW) MRT in Wirbelkörpermetastasen und in MR-morphologisch unauffälligen Wirbelkörpern. Die DW-MRT misst den für ein Gewebe spezifischen ADC, welcher der Eigendiffusion von Wasserstoffmolekülen entspricht. In zellreichem Tumorgewebe mit zahlreichen intra- und interzellulären Membranen (d. h. Diffusionsbarrieren) ist ein niedriger, in zellarmen oder nekrotischem Gewebe, ein hoher ADC zu erwarten. Methode. Bei 5 Patientinnen mit Mammakarzinom wurde der ADC von Lendenwirbelkörpermetastasen sowie von angrenzenden, MR-morphologisch unauffälligen Wirbelkörpern ermittelt (1,0 T; Phased-Array-Body-Coil; b: 880 und 440 s/mm2). Ergebnisse. Der ADC in MR-morphologisch unauffälligen Wirbelkörpern (1,3±0,23×10–3s/mm2) war signifikant (p≤0,0002) höher als in Wirbelkörpermetastasen (0,39±0,11×10–3s/mm2). Schlussfolgerung. Anhand dieser Daten konnte gezeigt werden, dass der ADC von Wirbelkörpern verlässlich gemessen werden kann, und dass durch die quantitative Bestimmung des ADC ein objektiv vergleichbarer Parameter zur Verfügung steht, der zur Differenzierung von malignem und benignem Gewebe gut geeignet erscheint.
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  • 178
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Diffusion ; Magnetresonanztomographie ; Encephalitis disseminata ; Keywords Diffusion ; Magnetic resonance imaging ; Multiple sclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Magnetic resonance (MR) imaging is one of the best methods in diagnosis of multiple sclerosis, particularly in disclosure of active demyelinating lesions. Aim of this study was to compare diffusion weighted imaging and contrast enhancement in the detection of active lesions. A MR study with a contrast enhanced T1-weighted pulse sequence with magnetization transfer presaturation and a diffusion weighted echoplanar pulse sequence (b=1000 s/mm2) was performed in 17 patients (11 women, 6 men) with multiple sclerosis. 29 of 239 lesions showed an increased signal intensity in diffusion weighted imaging, 24 lesions a contrast enhancement, but only 16 lesions were visible in both pulse sequences. In patients with short clinical symptomatology significant more lesions could be detected with diffusion-weighted pulse sequence in comparison to patients with long standing symptomatology showing more lesions with contrast enhancement. Hence it is likely, that both pulse sequences detect different histopathologic changes. The early detection of demyelinating lesions in diffusion weighted imaging is attributed to the extracellular edema, however the contrast enhancement is caused by a blood brain barrier abnormality. It can be expected that diffusion weighted imaging will have a high impact on imaging of multiple sclerosis not only in therapeutic trials, but also in clinical routine.
    Notes: Zusammenfassung Die Magnetresonanztomograpie ist eine der wichtigsten Untersuchungsmethoden in der Diagnostik der Encephalitis disseminata, insbesondere im Nachweis aktiver Entmarkungsherde. Ziel der Untersuchung war es, diffusionsgewichtete und kontrastverstärkte Untersuchungen bezüglich der Erkennung aktiver Läsionen zu vergleichen. Bei 17 Patienten (11 Frauen, 6 Männer) mit bekannter Encephalitis disseminata wurden sowohl eine kontrastverstärkte T1-gewichtete Sequenz mit Magnetization-Transfer-Sättigung als auch eine diffusionsgewichtete Echoplanar-Sequenz (b=1000 s/mm2) durchgeführt. 29 der 239 Läsionen zeigten eine Signalsteigerung in der diffusionsgewichteten Sequenz, 24 eine Kontrastmittelaufnahme, jedoch waren nur 16 Läsionen in beiden Techniken nachweisbar. Bei Patienten mit kurzzeitig bestehender Symptomatik zeigten sich signifikant mehr Entmarkungsherde mit Signalsteigerung in der Diffusionswichtung im Vergleich zu Patienten mit länger bestehender neurologischer Symptomatik, die mehr kontrastmittelaffine Läsionen aufwiesen. Dies lässt darauf schließen, dass mit beiden Verfahren unterschiedliche histopathologische Veränderungen beobachtet werden. Das sehr frühe Auftreten der Diffusionsänderung in den Entmarkungsherden wird auf das Ödem zurückgeführt, während die Kontrastmittelaufnahme durch eine Blut-Hirnschranken-Störung verursacht wird. Es ist zu erwarten, dass die diffusionsgewichtete Magnetresonanztomographie einen hohen Stellenwert in der Bildgebung der Encephalitis disseminata nicht nur in Therapiestudien, sondern auch in der klinischen Routinediagnostik erlangen wird.
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  • 179
    ISSN: 1433-7347
    Keywords: Key words Osteonecrosis ; Bone marrow edema ; Knee ; High tibial osteotomy ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Sports Science
    Notes: Abstract Symptoms in patients suffering from spontaneous osteonecrosis of the knee (SONK) may be reduced by high tibial osteotomy (HTO). However, the fate of the necrotic lesion is unknown and needs further investigation. We conducted a prospective study to evaluate magnetic resonance imaging (MRI) changes after operative and nonoperative treatment. Ten consecutive patients suffering from SONK of the medial compartment were given two treatment options: either HTO (n = 6) or conservative treatment with partial weight bearing for 3 months (n = 4). We measured the greatest extent of well-defined subchondral low signal intensity abnormality, considered to represent necrosis, and the surrounding area of intermediate signal intensity, considered to represent perifocal bone marrow edema, on T1-weighted coronal MRI images before and after treatment. The MRI follow-up period was 17.5 months (range 12–¶27) in the HTO group and 14.5 months (range 8–25) in the nonoperative group. At follow-up the MRI evaluation revealed a decrease in the low signal intense areas (necrosis) in five of the six patients in the HTO group. Only one of the four nonoperative patients showed a decrease in the low signal intense area. The intermediate intense areas (edema) decreased in all patients in the HTO group and in three of four in the nonoperative group. The mean decrease in the area of perifocal edema was significantly greater in the HTO group than in the nonoperative group (P = 0.019). No statistically significant difference was found for the area of necrosis between the two groups (P = 0.171). A clinical improvement was observed in all patients of the HTO group but in only two of the four patients of the nonoperative group. We conclude that the decrease in perifocal bone marrow edema seems to be associated with improved patient comfort. The MRI appearance of the necrotic lesion does not alter with either treatment mode.
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  • 180
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    Child's nervous system 16 (2000), S. 829-831 
    ISSN: 1433-0350
    Keywords: Keywords Intraoperative imaging ; Magnetic resonance imaging ; Anatomical and functional neuronavigation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The Erlangen-concept of image-guided-surgery is based on the installation of an open magnetic resonance (MR) scanner (Magnetom Open, 0.2 T, Siemens AG) in a twin operating room in combination with two neuronavigation systems (Stealth NeuroStation, Sofamor Danek, MKM Zeiss). Since March 1996 this method has been used for a total of 402 patients, among them 44 children. In 214 patients, mainly with gliomas or pituitary adenomas or who needed surgery for epilepsy, we performed intraoperative MR imaging to monitor the extent of resection, allowing a second look for possible tumor remnants and also compensating for brain shift by an intraoperative update of neuronavigation. Functional neuronavigation, i.e. the combination of anatomical neuronavigation with functional imaging [e.g. magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI)] was used in patients with lesions in brain areas such as the motor and speech areas. For MEG we used a MAGNES II biomagnetometer (Biomagnetic Technologies, San Diego, Calif.) and for fMRI a 1.5 T Siemens Symphony MR scanner. So far we have treated 89 patients with functional neuronavigation. Our preliminary experience indicates that intraoperative MR imaging, especially in combination with functional neuronavigation, allows more radical resections with lower morbidity.
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  • 181
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    Child's nervous system 16 (2000), S. 451-456 
    ISSN: 1433-0350
    Keywords: Keywords Intracranial pressure ; CSF dynamics ; Infusion test ; Rat ; H-Tx rat ; Outflow resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Although the hydrocephalic H-Tx rat is a widely used model, data on the cerebrospinal fluid (CSF) dynamics in hydrocephalic rats are rare or – as the pressure volume index (PVI) – not available. We used hydrocephalic and nonhydrocephalic H-Tx rats, a stock with a high percentage of inherited hydrocephalus, for the evaluation of such data. In addition, a new, simple mathematical algorithm (”dynamic infusion test”), which has not formerly been used in animal experiments, was used as a pathophysiological model of CSF dynamics. Compared with classical methods for evaluation of these data, the dynamic infusion test gives a deeper insight into the relation between ICP and CSF dynamics. It was found that the resistance to outflow (ROF) in hydrocephalic rats was at least twice that in nonhydrocephalic rats. The PVI measured was similar in hydrocephalic and nonhydrocephalic animals, but clearly higher than the values reported in the literature. This may be attributable to the fact that the classically used bolus test, in contrast to the ”dynamic infusion test”, is representative only for the CSF compartment which is directly exposed to the bolus application.
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  • 182
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    European archives of psychiatry and clinical neuroscience 250 (2000), S. 76-78 
    ISSN: 1433-8491
    Keywords: Key words Septum pellucidum ; Developmental ¶disorder ; Schizophrenia ; Magnetic resonance imaging ; Cavum veli interpositi ; Cavum septi pellucidi
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The case of monocygotic twins discordant for a psychotic disorder is presented. An anomaly of the septum pellucidum, a so-called cavum veli interpositi was found in the psychotic twin while his brother showed no such anomaly. Previous studies have shown a higher prevalence of septum pellucidum anomalies in schizophrenic patients. Abnormalities of the septum pellucidum may be associated with disturbed neuronal development in distinct limbic brain areas which cannot yet be visualized yet by brain imaging techniques. The finding of the cavum veli interpositi in the psychotic twin could be incidental; however, it may indicate a dysgenic process in early brain development and, thus, play a significant role in the etiology of psychosis.
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  • 183
    ISSN: 1432-2013
    Keywords: Key words vitamin C (L-ascorbic acid) ; apoptosis ; human articular chondrocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chondrocytes present in articular cartilage survive as a resident cell population throughout the lifespan of the individual organism. However, articular chondrocytes as other cells also undergo apoptosis and there is an ever increasing list of diverse stimuli that can induce this phenomenon in vitro. Our main interest was to investigate potential cytotoxic effects of vitamin C (L-ascorbic acid) on human articular chondrocytes. The present study suggests that vitamin C can induce apoptosis in a cell culture of chondrocytes after 18 h of cultivation. Apoptosis-inducing activity of L-ascorbic acid is dose dependent and significantly affected by the presence of serum. The increased number of vitamin C induced apoptotic cells was associated with DNA fragmentation and morphological changes of the cells.
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  • 184
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; antifolates ; apoptosis ; DNA repair ; p53 ; thymidylate synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thymidylate synthase (TS) is an essential enzyme for the de novo synthesis of thymidylate and subsequently DNA synthesis. TS has been usedas a target for cancer chemotherapy in the development of fluoropyrimidinessuch as 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine and of novelfolate-based TS inhibitors such as ZD1694 (Tomudex, Raltitrexed), ZD9331,LY231514 (ALIMTA, Pemetrexed), AG337 (Thymitaq, Nolatrexed) and AG331.Although TS has been considered as a target for chemotherapy, the precisemechanism by which TS inhibition leads to cell death is still not completelyresolved. TS inhibition results in depletion of dTTP, an essential precursorfor DNA, and an increase in dUTP. This results in the so-called thymine-lessdeath due to misincorporation of dUTP into DNA; its excision, catalysed byuracil-DNA glycosylase, results in DNA damage. Both this imbalance indTTP/dUTP and DNA damage can result in induction of downstream events, leadingto apoptosis. On the other hand a specific interaction exists betweenoncogenes and TS, by binding of TS protein to the p53and c-mycRNA, while wt p53can also inhibit TS promotor activity. TSinhibition by either 5-FU or antifolates can also result in a depression ofTS protein mediated inhibition of TS mRNA translation leading to induction ofmore TS protein synthesis, and p53protein may further deregulatethis process. These complex indirect and direct interactions between oncogenesand TS may have as yet unclear clinical implications, since most data arebased on in vitroor in vivo studies and some results arecontradictive. In some preliminary clinical studies evidence was postulatedfor a combined prognostic role for TS and p53.This knowledge shouldbe used to design clinical studies with the aim to deliver effective treatmentto potentially sensitive patients both in the adjuvant setting and in advancedstage disease.
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  • 185
    ISSN: 1573-4919
    Keywords: endosulfan ; cytotoxicity ; mitochondria ; apoptosis ; Jurkat cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Several organochlorinated pesticides including DDT, PCBs and dieldrin have been reported to cause immune suppression and increase susceptibility to infection in animals. Often this manifestation is accompanied by atrophy of major lymphoid organs. It has been suggested that increased apoptotic cell death leading to altered T-B cell ratios, and loss of regulatory cells in critical numbers leads to perturbations in immune function. The major objective of our study was to define the mechanism by which endosulfan, an organochlorinated pesticide, induces human T-cell death using Jurkat, a human T-cell leukemic cell line, as an in vitro model. We exposed Jurkat cells to varying concentrations of endosulfan for 0-48 h and analyzed biochemical and molecular features characteristic of T-cell apoptosis. Endosulfan lowered cell viability and inhibited cell growth in a dose- and time-dependent manner. DAPI staining was used to enumerate apoptotic cells and we observed that endosulfan at 10-200 μM induced a significant percentage of cells to undergo apoptotic cell death. At 48 h, more than 90% cells were apoptotic with 50 μM of endosulfan. We confirmed these observations using both DNA fragmentation and annexin-V binding assays. It is now widely being accepted that mitochondria undergo major changes early during the apoptotic process. We examined mitochondrial transmembrane potential (ΔΨm) in endosulfan treated cells to understand the role of the mitochondria in T-cell apoptosis. Within 30 min of chemical exposure, a significant percentage of cells exhibited a decreased incorporation of DiOC6(3), a cationic lipophilic dye into mitochondria indicating the disruption of ΔΨm. This drop in ΔΨm was both dose- and time-dependent and correlated well with other parameters of apoptosis. We also examined whether this occurred by the down regulation of bcl-2 protein expression that is likely to increase the susceptibility of Jurkat cells to endosulfan toxicity. Paradoxically, the intracellular expression of bcl-2 protein was elevated in a dose dependent manner suggesting endosulfan-induced apoptosis occurred by a non-bcl-2 pathway. Based on these data, as well as those reported elsewhere, we propose the following sequence of events to account for T-cell apoptosis induced by endosulfan: uncoupling of oxidative phosphorylation → excess ROS production → GSH depletion → oxidative stress → disruption of ΔΨm → release of cytochrome C and other apoptosis related proteins to cytosol → apoptosis. This study reports for the first time that endosulfan can induce apoptosis in a human T-cell leukemic cell line which may have direct relevance to loss of T cells and thymocytes in vivo. Furthermore, our data strongly support a role of mitochondrial dysfunction and oxidative stress in endosulfan toxicity.
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  • 186
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    Molecular and cellular biochemistry 204 (2000), S. 83-88 
    ISSN: 1573-4919
    Keywords: FHIT ; cell cycle ; ecdysone ; tumor suppressor ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The mechanism of tumor suppressor action of the fragile histidine triad (FHIT) gene is unknown. Disruption of cell cycle regulation leads to the tumor formation and many tumor suppressor genes suppress tumorigenesis through their effect on cell cycle regulation. We examined the expression of FHIT during the cell cycle, and determined whether overexpression of FHIT affects cell cycle kinetics and apoptosis. The FHIT cDNA was cloned into the ecdysone-inducible expression vector in both the sense and antisense orientations. Overexpression of the sense or antisense construct did not affect cell proliferation, cell cycle distribution or apoptosis in human 293T cells. Analysis of the FHIT expression in 293T cells collected at various cell cycle phases showed that the expression of FHIT is not under cell cycle regulation. These results indicate that the tumor suppressor activity of the FHIT gene may be independent of an effect on the cell cycle and apoptosis mechanisms.
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  • 187
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    Molecular and cellular biochemistry 212 (2000), S. 19-28 
    ISSN: 1573-4919
    Keywords: melanoma ; transcription factors ; CREB ; invasion ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The purpose of this study was to determine the role of CREB and its associated proteins in melanoma progression. We used MeWo human melanoma cells transfected with a dominant negative construct of CREB, KCREB. KCREB has a mutation in its DNA-binding domain and can not bind the CRE element. Expression of KCREB yields proper heterodimerization with CREB and its associated proteins, but the proteins associated with KCREB do not confer the same degree of transcriptional activity as they would in the case of wild-type CREB. Here, we demonstrate that expression of KCREB in MeWo melanoma cells leads to a decrease in their tumorigenicity and metastatic potential in nude mice. We identified two mechanisms that explain at least partially this effect of KCREB. The first, is one in which CREB and its associated proteins play an essential role in invasion. We showed that the invasive properties of KCREB-transfected MeWo cells were reduced due to the downregulation of the CRE-dependent expression of the type IV collagenase MMP-2 and the adhesion molecule MCAM/MUC18. In the second mechanism, CREB and its associated proteins act as survival factors for human melanoma cells. Here we demonstrated that expression of KCREB in MeWo cells rendered them susceptible to apoptosis induced by thapsigargin, which in turn increased the intracellular level of Ca2+. Thapsigargin induced CREB and ATF-1 phosphorylation and activated CRE-dependent transcription in MeWo cells. Collectively, our data demonstrate that CREB and its associated proteins play an important role in tumor growth and metastasis of human melanoma.
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  • 188
    ISSN: 1573-4919
    Keywords: T-type Ca2+ channel ; polyglutamine-expanded androgen receptor ; CAG trinucleotide repeats ; spinobulbar muscular atrophy ; apoptosis ; motorneuron ; cell lines ; neuroblastoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract We have analyzed Ca2+ currents in two neuroblastoma-motor neuron hybrid cell lines that expressed normal or glutamine-expanded human androgen receptors (polyGln-expanded AR) either transiently or stably. The cell lines express a unique, low-threshold, transient type of Ca2+ current that is not affected by L-type Ca2+ channel blocker (PN 200-110), N-type Ca2+ channel blocker (ω-conotoxin GVIA) or P-type Ca2+ channel blocker (Agatoxin IVA) but is blocked by either Cd2+ or Ni2+. This pharmacological profile most closely resembles that of T-type Ca2+ channels [1-3]. Exposure to androgen had no effect on control cell lines or cells transfected with normal AR but significantly changed the steady-state activation in cells transfected with expanded AR. The observed negative shift in steady-state activation results in a large increase in the T-type Ca2+ channel window current. We suggest that Ca2+ overload due to abnormal voltage-dependence of transient Ca2+ channel activation may contribute to motor neuron toxicity in spinobulbar muscular atrophy (SBMA). This hypothesis is supported by the additional finding that, at concentrations that selectively block T-type Ca2+ channel currents, Ni2+ significantly reduced cell death in cell lines transfected with polyGln-expanded AR.
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  • 189
    ISSN: 1573-4919
    Keywords: retinoic acid ; RARβ ; protein kinase A ; apoptosis ; caspase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Both cAMP and retinoids play a role in cell differentiation and the control of cell growth. A site-selective cAMP analog, 8-Cl-cAMP and retinoic acid synergistically inhibit growth and induce apoptosis in certain cancer cells. In advanced or recurrent malignant diseases, retinoic acid (RA) is not effective even at doses that are toxic to the host. The objective of our present study was to examine the mechanism(s) of synergistic effects of retinoic acid (9-cis, 13-cis or all-trans RA) and 8-Cl-cAMP on apoptosis in human ovarian cancer NIH: OVCAR-3 and OVCAR-8 cells. RA induced growth inhibition and apoptosis in OVCAR-3 and OVCAR-8 cells. 8-Cl-cAMP acted synergistically with RA in inducing and activating retinoic acid receptor β (RARβ) which correlates with growth inhibition and apoptosis in both cell types. In addition, induction of apoptosis by RA plus 8-Cl-cAMP requires caspase-3 activation followed by cleavage of anti-poly(ADP-ribose) polymerase. Furthermore, mutations in CRE-related motif within the RARβ promoter resulted in loss of both transcriptional activation of RARβ and synergy between RA and 8-Cl-cAMP. RARβ expression appears to be associated with induction of apoptosis. Introduction of the RARβ gene into OVCAR-3 cells resulted in gain of RA sensitivity. Loss of RARβ expression, therefore, may contribute to the tumorigenicity of human ovarian cancer cells. Thus, combined treatment with RA and 8-Cl-cAMP may provide an effective means for inducing RARβ expression leading to apoptosis in ovarian cancer cells.
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  • 190
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    Molecular and cellular biochemistry 203 (2000), S. 59-71 
    ISSN: 1573-4919
    Keywords: PTEN tumor suppressor ; cyclin-dependent kinase inhibitors ; apoptosis ; chemosensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The recently discovered tumor suppressor gene PTEN has been found mutated in many types of advanced tumors. When introduced into tumor cells that lack the wild-type allele of the gene, PTEN was able to suppress the growth of these cells. Here, we have analyzed how PTEN might alter cell cycle-regulatory controls to achieve this growth-inhibitory effect. We found that overexpression of PTEN stimulates the synthesis of three inhibitors of cyclin-dependent kinases, p21WAF1, p27KIP1, and p57,KIP2. This effect is very specific, as the expression of other components of the cell cycle engine, various cyclins and cyclin-dependent kinases, is not affected. For p21WAF1 we show that this induction is due to the p53-independent transcriptional activation of its promoter. In addition, increased expression of PTEN rendered the cells more sensitive to apoptotic cell death. Therefore, our data suggest a two-fold mechanism of growth inhibition by PTEN: one that acts via the increased expression of CKIs such as p21WAF1, and another that augments the cellular propensity for apoptotic cell death.
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  • 191
    ISSN: 1573-4919
    Keywords: tumour necrosis factor ; receptors ; subtypes ; calcium ; apoptosis ; cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Tumour necrosis factor-α (TNF) receptors mediate a variety of effects dependent on cell type. A role for Ca2+ in TNF-induced death remains uncertain. Here we investigated restricting intracellular/extracellular Ca2+ in HeLa epithelial carcinoma cells expressing low and high levels of p75TNFR receptor subtype and KYM-1 rhabdomyosarcoma cells, models of rapid TNF-induced apoptosis. Ca2+-chelators EGTA and BAPTA-AM as well as microsomal Ca2+-ATPase inhibitor thapsigargin, did not alter TNF-induced death. TNF was also unable to alter resting [Ca2+]i levels which remained 〈 200 nM even during times when these cells were undergoing apoptotic cell death. These findings indicate no role for modulated Ca2+ concentrations in TNF-induced apoptotic cell death.
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  • 192
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    Journal of clinical immunology 20 (2000), S. 229-239 
    ISSN: 1573-2592
    Keywords: Aging ; apoptosis ; TNF receptor ; Fas ; Fas ligand ; mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cellular and molecular basis of immune senescence is unclear. A number of mechanisms have been proposed. In this issue of the Journal of Clinical Immunology, some of the mechanisms for various immunologic abnormalities in aging are presented. In this article, various molecular steps of both death receptor and mitochondrial pathways of apoptosis in general are reviewed. In particular, the role of apoptosis in T-cell immune senescence is discussed.
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  • 193
    ISSN: 1573-4919
    Keywords: etoposide ; Bcl-XL ; Bax ; apoptosis ; K562 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Etoposide is a potent anticancer agent that is used to treat various tumors. We have investigated the dose-dependent effect of etoposide on apoptosis using chronic myeloid leukemia K562 cells treated with low (5 μM) or high (100 μM) concentrations of the drug. At a low concentration, etoposide induced little apoptosis at 24 h, while about 20% of the cells showed apoptosis morphologically at a high concentration. Processing of caspase-3 was slightly detected from 12 h and became obvious at 24 h with 100 μM etoposide. Caspase-3-like protease activity was detected at 24 h with a high concentration. Moreover, these changes were accompanied by cleavage of poly ADP ribose polymerase (PARP). Changes of the mRNA levels of most apoptosis-regulating genes were not prominent at both concentrations, except for the rapid induction of c-IAP-2/HIAP-1 and the down-regulation of Bcl-XL by 100 μM etoposide. The downregulation of Bcl-XL protein occurred from 6 h, while Bax protein conversely showed a slight increase from 6 h. Taken together, the present findings show that the dose-dependent apoptotic effect of etoposide is based on a change in the balance between Bcl-XL and Bax, which precedes the activation of caspase-3.
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  • 194
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    Molecular and cellular biochemistry 207 (2000), S. 19-27 
    ISSN: 1573-4919
    Keywords: PKC ; apoptosis ; bile acid ; hepatocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of GCDC-induced apoptosis on PKC activity and PKC's role in GCDC-induced hepatocyte apoptosis is unclear. The specific aims of this study were to determine if GCDC-induced apoptosis changed intracellular PKC activity and if modulation of PKC activity affected GCDC-induced hepatocyte apoptosis. Apoptosis was induced in isolated hepatocytes using GCDC. PKC activity was measured and specific PKC and calpain inhibitors were used to study the effects of PKC and calpain modulation on GCDC-induced apoptosis. After 4 h exposure, 50 μM GCDC induced apoptosis in 42% of hepatocytes. Intracellular PKC activity decreased to 44% of controls 2 h after exposure of hepatocytes to GCDC (p 〈 0.001). Pre-incubation of hepatocytes with the calpain protease inhibitor restored PKC activity in GCDC exposed hepatocytes to 91± 5% of control cells. Pre-incubation of hepatocytes with a calpain inhibitor decreased GCDC-induced apoptosis as did pre-incubation with the PKC activating phorbol ester, PMA. The combination of calpain inhibition and PMA further reduced GCDC-induced apoptosis but caused low level hepatic apoptosis. Inhibition of PKC with chelerythrine also substantially reduced GCDC-induced hepatocyte apoptosis. GCDC-induced apoptosis is associated with decreases in total cellular PKC activity, which appear to be dependent on intracellular calpain-like protease activity. The combination of protease inhibition and phorbol ester pretreatment preserved total cellular PKC activity and decreased GCDC-induced apoptosis but induced low level apoptosis in the absence of GCDC exposure. PKC inhibition also decreased GCDC-induced hepatocyte apoptosis highlighting the complex interactions of PKC and proteases during GCDC-induced apoptosis.
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  • 195
    ISSN: 1573-4919
    Keywords: phosphatidylserine ; base exchange ; apoptosis ; thymocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The exposure of phosphatidylserine toward the external surface of the membrane is a well-established event of programmed cell death. The possibility that an apoptotic stimulus influences the metabolism of this phospholipid could be relevant not only in relation to the previously mentioned event but also in relation to the capability of membrane phosphatidylserine to influence PKC activity. The present investigation demonstrates that treatment of mouse thymocytes with the apoptotic stimulus dexamethasone, enhances the incorporation of [3H]serine into phosphatidylserine. Cell treatment with dexamethasone also enhanced the activity of serine base exchange enzyme, assayed in thymocyte lysate. Both the effects were observed at periods of treatment preceding DNA fragmentation. The addition of unlabelled ethanolamine, together with [3H]serine to the medium containing dexamethasone-treated thymocytes lowered the radioactivity into phosphatidylserine. Serine base exchange enzyme activity was influenced by the procedure used to prepare thymocyte lysate and was lowered by the addition of fluoroaluminate, that is widely used as a G-protein activator. The increase of serine base exchange enzyme activity induced by dexamethasone treatment was observed independently by the procedure used to prepare cell lysate and by the presence or absence of fluoroaluminate.
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  • 196
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    Molecular and cellular biochemistry 212 (2000), S. 35-43 
    ISSN: 1573-4919
    Keywords: cAMP ; CRE ; Cox-2 ; NO ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Previous studies revealed that expression and activation of cyclooxygenase-2 (Cox-2) conveyed a protective principle in murine macrophages, thus attenuating pro-apoptotic actions of chemotherapeutic agents or programmed cell death as a result of massive nitric oxide (NO) generation. Expression of Cox-2 was achieved by treatment of cells with lipopolysaccharide/interferon-γ or nontoxic doses of NO releasing agents. We reasoned E-type prostanoid formation, and in turn an intracellular cAMP increase as the underlying protective mechanism. To prove our hypothesis, we analyzed the effects of lipophilic cAMP-analogs on NO, cisplatin, or etoposide induced apoptosis in RAW 264.7 macrophages. Selected apoptotic parameters comprised DNA fragmentation (diphenylamine assay), annexin V staining of phosphatidylserine, caspase activity (quantitated by the cleavage of a fluorogenic caspase-3-like substrate Ac-DEVD-AMC), and mitochondrial membrane depolarisation (ΔΨ). Western blots detected accumulation of the tumor suppressor protein p53, relocation of cytochrome c to the cytosol, and expression of the anti-apoptotic protein Bcl-xL. Prestimulation with lipophilic cAMP-analogs attenuated apoptosis with the notion that cell death parameters were basically absent. To verify gene induction by cAMP in association with protection we established activation of cAMP response element binding protein (CREB) by gel-shift analysis and moreover, treated macrophages with oligonucleotides containing a cAMP-responsive element (CRE) in order to scavenge CREB. Decoy oligonucleotides, but not control oligonucleotides, attenuated cAMP-evoked protection and reestablished pro-apoptotic parameters. We conclude that gene induction by cAMP protects macrophages towards apoptosis that occurs as a result of excessive NO formation or addition of chemotherapeutica. Attenuating programmed cell death by the cAMP-signaling system may be found in association with Cox-2 expression and tumor formation.
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  • 197
    ISSN: 1573-4978
    Keywords: apoptosis ; CD95 ; human hepatoma cell ; hydrogen peroxide ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Reactive oxygen species (ROS) play an important role in cell death induced by many different stimuli. Direct exposure of human hepatoma cell line SMMC-7221 to hydrogen peroxide (H2O2) can induce apoptosis characterized by morphological evidence and fragmentation of DNA assayed by terminal deoxynucleotidyl transferase assay (TUNEL assay). Analysis of flow cytometry indicated that H2O2 can decrease the level of CD95(APO-1/Fas), and it is confirmed that H2O2 can also activate the differential expression of some specific gene such as p53 by means of RT-PCR technique. The results indicated that CD95 signal transduction system may be involved in the H2O2-induced apoptosis, and can regulate some specific genes associated with apoptosis in transcription and translation levels such as p53.
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  • 198
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    Psychopharmacology 151 (2000), S. 219-225 
    ISSN: 1432-2072
    Keywords: Keywords Amphetamine ; Wheel running ; Behavioral sensitization ; Pharmacological sensitization ; Novelty ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: This study explored whether repeated injections of amphetamine (AMP), which increase general locomotion, also increase acute wheel running, a highly structured, rewarding, motor behavior not correlated with other locomotor activities. Objectives: The experiments determine how 1–5 mg/kg d-AMP affects wheel running and see if, over repeated injections, the AMP effects show context specific sensitization. Methods: In experiment 1, 2 mg/kg AMP or saline (SAL) was injected on days 1, 3, 6, 8, and 10 to male Sprague-Dawley rats with either limited or no wheel experience. 20 min after the injection animals were tested in an open field for 5 min and then in a running wheel for 1 h. Rats were injected with SAL or AMP on the days following testing. On days 13 and 15, animals were tested for conditioning (following SAL) and sensitization (following AMP). In experiment 2, the effects on wheel running of repeated 1, 2, or 5 mg/kg AMP were tested. Results: In experiment 1, AMP (2 mg/kg) elevated open field ambulation but suppressed wheel running. Limited wheel experience potentiated the AMP-induced suppression. At test, the suppression of running was found to be context specific. In experiment 2, 1 mg/kg did not affect running, while 2 and 5 mg/kg resulted in dose-dependent running suppression. Acquisition and test AMP dose both influenced the running suppression at test; context had a marginal influence. Conclusions: The degree of running suppression induced by repeated AMP is determined by both psychological (the injection context) and pharmacological (the acquisition dose) factors. This AMP-induced running suppression is consistent with the sensitization of stereotyped behavior.
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  • 199
    ISSN: 1432-2072
    Keywords: Key words Fentanyl ; mu opioids ; Drug discrimination ; Training dose ; pA2 analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Discriminative stimulus effects of mu opioids vary systematically as a function of training dose. Differences among training doses may arise from multiple mechanisms. Objectives: In vivo apparent pA2 analyses were used to examine the contributions of opioid mechanisms to stimulus control by low and high training doses of the mu opioid fentanyl. Methods: Saline and one of two doses of fentanyl, administered s.c., were established as discriminative stimuli in two groups of rats (low training dose group: 0.01 mg/kg; high training dose group: 0.04 mg/kg). Generalization tests and in vivo apparent pA2 analyses were used to evaluate receptor mechanisms of stimulus control. Results: Fentanyl, etonitazene, methadone, and morphine evoked full fentanyl generalization in both groups but were more potent in the low-dose group. Spiradoline and d-amphetamine did not evoke generalization in either group. Naltrexone antagonized stimulus and rate-altering effects of fentanyl in both groups, with apparent pA2 values of 7.6 in the low-dose group and 7.5 in the high-dose group. Nalbuphine and nalorphine evoked full generalization in the low-dose group but less than 40% generalization in the high-dose group. In the high-dose group, nalbuphine and nalorphine antagonized the stimulus and rate-altering effects of fentanyl with apparent pA2 values of 5.3 and 6.1, respectively, demonstrating lower efficacy mu actions. Conclusions: Changes in fentanyl training dose preserved the mu opioid selectivity of stimulus control but altered the intensity of the transduced mu opioid stimulus required for generalization. These differences in intensity of the fentanyl stimulus determined whether low efficacy mu opioids would evoke or antagonize fentanyl generalization.
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  • 200
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    Psychopharmacology 148 (2000), S. 146-152 
    ISSN: 1432-2072
    Keywords: Key words Alprazolam ; Drug discrimination ; Benzodiazepines ; Antidepressant ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The triazolobenzodiazepine alprazolam has a unique clinical profile compared to most other benzodiazepines (e.g. diazepam, chlordiazepoxide), in that it is used to treat panic disorder and is effective in depression, two disorders that are usually treated with anti-depressants. Previous drug discrimination studies suggested that alprazolam has stimulus properties in common with antidepressants. Objective: In the present study, the discriminative stimulus properties of alprazolam were investigated to test more conclusively the role of benzodiazepine receptors and whether alprazolam has stimulus properties in common with antidepressants. Methods: Male Wistar rats (n=12) were trained to discriminate between alprazolam (2.0 mg/kg, PO) and vehicle in an operant two-lever drug discrimination procedure under a tandem VI40”-FR10 schedule of reinforcement. Generalization and antagonism tests were carried out under 2 min extinction. Results: In generalization tests, a number of benzodiazepines (alprazolam, chlordiazepoxide, midazolam, lorazepam) and the barbiturate pentobarbital substituted completely, while zolpidem and abecarnil substituted partially for alprazolam. In contrast, no significant degree of generalization to the antidepressants imipramine and fluvoxamine and the putative antidepressants buspirone and flesinoxan was found. In antagonism studies alprazolam could be antagonized (almost) completely by flumazenil, partially by pentylenetetrazole, but not by methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), N-methyl-β-carboline-3-carboxamide (FG-7142) and picrotoxin. Conclusions: These results show that the discriminative stimulus properties of alprazolam are mediated by benzodiazepine receptors and that the finding that antidepressants share discriminative stimulus effects with alprazolam may have limited generality.
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