PubMed Health⌕ Search

Biomedical subjects

G Stockhammer

Publications and source records attributed to G Stockhammer.

At least 19 recordsLinked to original sources
PubMed2004

Long-term cognitive and MRI findings in a patient with paraneoplastic limbic encephalitis.

This case study describes the long-term course of behavioral alterations and MRI findings in a patient with a combined limbic and cerebellar paraneoplastic syndrome, which was associated with a squamous lung carcinoma. Clinical equivalents were cerebellar ataxia, as well as severe anterograde memory loss, frontal executive dysfunction and behavioral alterations. MRI revealed inflammatory changes followed by progressive atrophy affecting the cerebellum and both temporal lobes. Tumor surgery yielded only a partial and transient recovery of neurological symptoms, and paraneoplastic atrophy continued to progress despite radical excision of the carcinoma. This case of paraneoplastic encephalitis suggests that the related atrophy may present as a chronic, progressive, multifocal encephalopathy and that the associated cognitive impairments may include several cognitive domains.

Cognition↗
PubMed2000

Vascular endothelial growth factor in bacterial meningitis: detection in cerebrospinal fluid and localization in postmortem brain.

Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema. To assess the role of VEGF during bacterial meningitis, VEGF was measured in cerebrospinal fluid (CSF) and blood of 37 patients with bacterial meningitis and 51 control patients, including 16 patients with viral meningitis. Circulating VEGF levels were similar in bacterial meningitis patients and control patients. VEGF(CSF) was detected in 11 (30%) of 37 of bacterial meningitis patients (range, <25-633 pg/mL) but in none of the control patients. The median VEGF index was 6.2 (range, 0.6-42), indicating intrathecal production. Median CSF cell counts, protein levels, and CSF: serum albumin ratios were higher for patients with detectable VEGF(CSF), although the difference was not statistically significant. VEGF immunoreactivity in autopsy brain specimens was found in the inflammatory infiltrate of patients with bacterial meningitis. These results indicate that inflammatory cells secrete VEGF during bacterial meningitis and that VEGF may contribute to blood-brain barrier disruption.

Adolescent↗
PubMed2000

Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells.

BACKGROUND: Vascular endothelial cells lost from the blood-vessel endothelium through necrosis or apoptosis must be replaced. We investigated in a leukaemia model whether bone-marrow-derived endothelial cells contribute to this maintenance angiogenesis. METHODS: We studied six patients with chronic myelogenous leukaemia (CML) carrying the BCR/ABL fusion gene in their bone-marrow-derived cells. We screened endothelial cells generated in vitro from bone-marrow-derived progenitor cells and vascular endothelium in myocardial tissue for the BCR/ABL fusion gene by in-situ hybridisation. For detection of donor-type endothelial cells after transplantation of haemopoietic stem cells, recipient tissue was stained with monoclonal antibodies against donor-type HLA antigens. FINDINGS: We identified the BCR/ABL fusion gene in variable proportions (0-56%) of endothelial cells generated in vitro. Endothelial cells expressing the fusion gene were found in the vascular endothelium of a patient. In a recipient of an allogeneic stem-cell transplant, normal donor-type endothelial cells were detected in the vascular endothelium. INTERPRETATION: These findings suggest that CML is not solely a haematological disease but originates from a bone-marrow-derived haemangioblastic precursor cell that can give rise to both blood cells and endothelial cells. Moreover, normal bone-marrow-derived endothelial cells can contribute to the maintenance of the blood vascular endothelium. The integration of bone-marrow-derived endothelial cells into the vascular endothelium provides a rationale for developing vascular targeting strategies in vasculopathies, inflammatory diseases, and cancer.

Adult↗
PubMed2000

Vascular endothelial growth factor in CSF: a biological marker for carcinomatous meningitis.

OBJECTIVE: To determine the value of vascular endothelial growth factor (VEGF) in CSF as a marker for carcinomatous meningitis (CM). METHODS: The concentration of VEGF was measured by ELISA in matched samples of CSF and serum collected from 162 patients. These included patients with solid tumors with CM (n = 11) or brain metastases without concomitant CM (n = 12), paraneoplastic neurologic syndromes (n = 4), viral (n = 15) and bacterial (n = 20) meningitis, and a variety of non-neoplastic and noninfectious neurologic diseases (n = 100). Using CSF/serum albumin ratios, the VEGF index was calculated to estimate the proportion of intrathecally produced VEGF. Immunohistochemical staining for VEGF was performed in a brain metastasis from a mammary carcinoma associated with CM. RESULTS: High VEGF levels (median 6,794.8 pg/mL) were found in CSF of all patients with CM, whereas VEGF levels in matched sera were comparable to other disease groups. In patients with CM, the concentration of VEGF in CSF decreased significantly following antineoplastic treatment. In CSF samples from patients with brain metastases without concomitant CM, VEGF was not detectable. Median VEGF concentration in CSF from patients with acute bacterial meningitis was 38.6 pg/mL, with only 9 of these 17 patients showing detectable VEGF levels in CSF. The VEGF indices in patients with bacterial meningitis were significantly lower than in tumor patients with CM (<22.8 versus >62.3), suggesting that the proportion of intrathecally produced VEGF is much higher in patients with CM as compared with patients with bacterial meningitis. Patients without neoplastic or infectious neurologic disorders consistently showed VEGF levels in CSF below the assay detection limit of 25 pg/mL. Immunohistochemistry revealed strong cytoplasmic staining for VEGF in a metastatic lesion from breast cancer infiltrating the meninges. CONCLUSION: In patients with carcinomatous meningitis, significant amounts of VEGF are released into CSF. This study yields preliminary evidence that VEGF in CSF may be a useful biologic marker for both the diagnosis and evaluation of treatment response in carcinomatous meningitis.

Adolescent↗
PubMed2000

Progressive multifocal leukoencephalopathy presenting with an isolated focal movement disorder.

Progressive multifocal leukoencephalopathy (PML) is a rare but fatal papovavirus infection of the central nervous system predominantly affecting immunocompromised patients. Although the basal ganglia circuitry may be involved in the pathology of PML, movement disorders are exceedingly rare as presenting symptoms and have not been described as isolated features in such patients. We report a previously healthy, immunocompetent 24-year-old woman with histologically proven PML who presented with a focal movement disorder of the left arm as an isolated symptom for many months before diagnosis.

Adult↗
PubMed2000

Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GFR-alpha 1) are strongly expressed in human gliomas.

Glial cell line-derived neurotrophic factor (GDNF), a sequence-related factor of the transforming growth factor-beta family, has been identified as a potent neurotrophic factor for a variety of neuronal cell populations. At present, it is still unknown whether human gliomas in vivo are also capable of producing GDNF. We studied the expression of GDNF in 14 human glioblastomas, 1 gliosarcoma and 5 astrocytomas. Using an enzyme-linked immunosorbent assay, the amount of GDNF was quantified in human gliomas and compared to GDNF-expression in C6 glioma cells, mouse fibroblasts and normal human and rat brain. Mean concentration of GDNF in gliomas was 937 +/- 140 pg GDNF/g tissue (n = 20). C6 cells revealed the highest expression levels of 2,837 +/- 813 pg/g, whereas mouse 3T3 fibroblasts showed no detectable GDNF protein. Mean GDNF tissue levels in normal human and rat brain were significantly lower. Using reverse transcriptase-polymerase chain reaction, GDNF mRNA was detected in human gliomas and in rat C6 cells. Immunohistochemistry revealed strong GDNF- and GDNF receptor-alpha 1-expressing tumor cells in human glioma tissue. These results show that glial tumors, even in the most dedifferentiated form of glioblastoma, express GDNF at concentrations up to five times higher compared to normal human brain. This overexpression of GDNF may be of biological relevance for proliferation of glial tumors in humans.

Adult↗
PubMed2000

Vascular endothelial growth factor (VEGF) is elevated in brain tumor cysts and correlates with tumor progression.

Vascular endothelial growth factor (VEGF), a key regulatory protein in neoangiogenesis, is strongly expressed in a variety of primary brain tumors, particularly malignant gliomas. In previous studies, high levels of VEGF were also reported in tumor cysts of glioblastomas. Using an ELISA method we measured the concentration of VEGF in matched samples of aspiration fluid from tumor cysts and serum. Samples were collected from 14 patients with primary brain tumors of various histology (six glioblastomas, one protoplasmatic astrocytoma, two pilocytic astrocytomas, one ependymoma, one meningioma, and three craniopharyngiomas) and two patients with solitary cystic brain metastases from adenocarcinomas of the lung. Aspiration fluids of tumor cysts from all patients revealed high VEGF levels ranging between 882 and 1,263,000 pg/ml, which were 2 to more than 2,000 times higher than the corresponding serum levels. Maximum VEGF levels were detectable in cyst fluids from recurrent glioblastoma. Serum VEGF levels ranged between 125 and 716 pg/ml and did not differ from serum levels in 145 healthy volunteers. In a single patient with metastatic lung cancer the concentration of VEGF in serum and cyst fluid was determined during disease progression. During 60 days of follow-up VEGF concentrations in the cyst fluid collected by puncture of an Ommaya reservoir increased 650-fold, while serum levels remained rather constant. These findings indicate that immunoreactive VEGF is produced at the tumor site and abundantly released into the cyst fluid of primary and metastatic brain tumors. Interestingly, this abundant local release is not reflected in serum VEGF levels, even in the case of very high VEGF concentrations in tumor cysts. Thus, VEGF may be biologically relevant for the formation of tumor cysts in brain tumors and correlates with local disease progression.

Adolescent↗
PubMed2000

Thrombocytes are the major source for soluble vascular endothelial growth factor in peripheral blood.

Serum levels of vascular endothelial growth factor (VEGF-S) have been reported to correlate with tumor stage and prognosis in various human malignancies. The source of soluble VEGF in peripheral blood remains obscure. We therefore measured the concentration of immunoreactive VEGF in 241 serum samples and 61 plasma samples (VEGF-P) from 20 subjects undergoing myeloablative chemotherapy and from 3 normal platelet donors. A significant correlation between the peripheral blood platelet count (PC) and VEGF-S (r = 0.86) but not VEGF-P was found. VEGF-S levels were 58.43 +/- 42.50 pg/ml (mean +/- SD) in patients with a PC < 50 x 10(9)/l, 203.29 +/- 176.56 pg/ml for a PC of 50-150 x 10(9)/l, and 457.42 +/- 475.41 pg/ml for a PC > 150 x 10(9)/l. Interestingly, VEGF-P levels were substantially lower than the corresponding VEGF-S values, namely below the detection limit in most cases. Supernatants from platelet-rich plasma contained no VEGF, but after in vitro lysis of the platelets very high VEGF levels were found. The VEGF content per 10(9) platelets was calculated at 2.51 +/- 2.39 pg and was dependent on the mean platelet volume. In summary, VEGF release from platelets during blood clotting was found to be the main source of VEGF in serum samples. Cancer patients in clinical remission have negligible amounts of soluble VEGF in peripheral blood, and myeloablative chemotherapy causes a significant drop in VEGF-S levels corresponding to the decrease in PC. Thus, studies addressing the diagnostic and prognostic value of VEGF-S in cancer patients must be interpreted with caution. Our data provide the basis for predicting VEGF-S in relation to PC in vivo, and for reevaluating former studies of VEGF-S in patients with malignant or nonmalignant disease.

Adult↗
PubMed1998

MRI findings in cerebral fat embolism.

The purpose of this retrospective study was to demonstrate the MRI features of cerebral manifestations in patients with fat embolism syndromes in comparison with cerebral CT (CCT). Magnetic resonance imaging was performed according to standard protocols revealing multiple small non-confluent hyperintense intracerebral lesions larger than 2 mm on proton-density and T2-weighted images to various extents in three of four patients with clinically suspected cerebral fat embolism. Cerebral CT was negative in all patients. Our findings confirm that MRI can detect cerebral fat embolism with a higher sensitivity than CCT. Thus, MRI should be the first choice for imaging of cerebral fat embolism.

Adolescent↗
PubMed1995

Imaging the expression of transfected genes in vivo.

Imaging the expression of successful gene transduction has been demonstrated in vivo for the first time by using an appropriate combination of "marker gene" and "marker substrate" in an experimental animal model. The herpes simplex virus 1 thymidine kinase (HSV1-tk) gene was selected as an example of a marker gene, and the recombinant STK retrovirus containing HSV1-tk was used to transduce RG2 glioma cells in vitro and in vivo. RG2TK+ cell lines expressing the HSV1-tk gene and three potential marker substrates for the HSV1-TK enzyme were evaluated. Radiolabeled 5-iodo-2'-fluoro-2'deoxy-1-beta-D-arabinofuranosyluracil (FIAU) was shown to be a substantially better marker substrate for the HSV1-TK enzyme than 5-iodo-2'-deoxyuridine or ganciclovir. The magnitude of FIAU accumulation in different RG2TK+ clones corresponded to their sensitivity to ganciclovir and to the level of HSV1-tk mRNA expression. Imaging the expression of HSV1-tk in transduced RG2 tumor cells was demonstrated in animals using quantitative autoradiography; 2-[14C]FIAU accumulation was shown to be high in RG2TK+ brain tumors growing in one hemisphere and very low in nontransduced RG2 tumors in the contralateral hemisphere. Transduction of RG2 tumor cells with the HSV-tk gene in vivo resulted in tumors which accumulated FIAU to high levels and produced clearly defined images. Given the level of FIAU accumulation in the transduced tumors, it is likely that a clinically applicable method for imaging HSV1-tk gene expression can be implemented using existing clinical imaging techniques.

Animals↗
PubMed1995

Inhibition of proliferation and induction of differentiation in medulloblastoma- and astrocytoma-derived cell lines with phenylacetate.

The authors investigated the effects of a nontoxic differentiation inducer, phenylacetate (PA), on neuroectodermal tumor-derived cell lines. Treatment of medulloblastoma (Daoy and D283 MED) and glioma (U-251MG, C6, and RG2) cell lines resulted in a dose-dependent decline in DNA synthesis and cell proliferation, associated with accumulation in the G0/G1 phase of the cell cycle. Phenylacetate decreased transforming growth factor (TGF)-beta 2 production by medulloblastoma Daoy cells. Neutralizing antibodies against either TGF beta 2 or TGF beta 1 failed to block the growth arrest observed. This suggests that, unlike other differentiation agents, such as retinoic acid, the effect of PA on medulloblastoma proliferation is not mediated by a TGF beta pathway. In addition to cytostasis, PA induced marked morphological changes in U-251MG and C6 glioma cells associated with increased abundance of glial fibrillary acidic protein-positive processes. Although the morphology of PA-treated medulloblastoma cells was not significantly altered, the D283 MED cells exhibited increased expression of neurofilament proteins and Hu antigen, indicative of differentiation along a neuronal pathway. The effects of PA on the medulloblastoma cell lines were compared to its effects on the human neuroblastoma cell line BE(2)C, which is capable of a bidirectional differentiation toward a neuronal or a glial/schwann cell pathway. In BE(2)C cells, PA induced differentiation toward a schwann/glial cell-like phenotype, suggesting that the choice of differentiation pathway is cell type and agent specific. These in vitro antiproliferative and differentiation inducing effects of PA suggest that this agent warrants further evaluation as a potential therapeutic modality for the treatment of medulloblastoma and malignant glioma in humans.

Animals↗
PubMed1994

Intravascular lymphomatosis: a clinicopathological study of three cases.

In patients with intravascular lymphomatosis (IL) a broad spectrum of neuro-psychiatric disorders including dementia, focal neurological signs and seizures has been reported. Clinical diagnosis is difficult since neuroimaging findings are nonspecific. The clinical histories, biopsy and autopsy findings of three patients with IL, one with brain biopsy, are described. Two of them presented with rapidly progressive, fluctuating dementia. The third patient suffered from seizures followed by aphasia. Histology revealed large-cell lymphoma of the B cell type. The prognosis of IL, in general, is poor.

Aged↗
PubMed1993

Sneddon's syndrome. A long-term follow-up of 21 patients.

BACKGROUND AND DESIGN: Twenty-one patients with histologically proven Sneddon's syndrome were followed up in a retrospective study. We report on their detailed clinical courses and extensive follow-up examinations. RESULTS: Incidence is estimated at four cases per million population per year. Nonspecific prodromal symptoms (headache, dizziness) frequently (80%) precede livedo racemosa for 3.5 and (multi)focal neurological symptoms of fully developed disease for 9 years followed by progressive cognitive impairment (60%) 10 years later. Involvement of fundi, peripheral nerves, heart, and kidneys is frequent (50% to 70%) yet usually asymptomatic. Some symptoms prove irreversible (livedo racemosa, multifocal cerebral lesions on imaging, or creatinine clearance), whereas other symptoms tend to resolve after days to years (many focal neurological symptoms, some electrocardiographic changes, or hypertension). Mortality is calculated at 9.5% within an average observation time of 6.2 years. Laboratory findings, including antiphospholipid antibodies, are normal except for elevated erythrocyte sedimentation rates and complement consumption at times of disease progression and increased cholesterol levels parallel to disease extent. Skin biopsy specimens reveal inflammatory findings ("endothelitis") of small- to medium-sized arteries followed by subendothelial proliferation and fibrosis. Hypertension is the only risk factor significantly associated with a more severe course of the disease; no medication proved effective. CONCLUSIONS: Sneddon's syndrome is an often unrecognized, slowly progressive, systemic disease with evidence of vasculitic origin.

Adult↗
PubMed1993

Sneddon's syndrome: diagnosis by skin biopsy and MRI in 17 patients.

BACKGROUND AND PURPOSE: Sneddon's syndrome, characterized by generalized livedo racemosa and cerebrovascular lesions, is an underdiagnosed disease. We evaluated clinical, laboratory, histological, and neuroradiological findings in a series of 17 patients to improve diagnostic criteria for Sneddon's syndrome. METHODS: Patients with generalized livedo racemosa and cerebrovascular events were included in the study. All underwent neurological and dermatological examination, skin biopsy, computed tomographic scan, magnetic resonance imaging as well as magnetic resonance angiography, sonography of the extracranial arteries, and a comprehensive laboratory protocol. RESULTS: Completed stroke was present in eight patients, and 15 reported transient neurological deficits. Magnetic resonance imaging yielded cerebral abnormalities in 16 of 17, whereas computed tomographic scans were abnormal in only 12 of 16 patients. Magnetic resonance imaging revealed more lesions in individual patients than did computed tomography. Magnetic resonance angiography demonstrated patent intracranial vessels in 16 of 17 patients. Skin biopsy showed distinct histopathological findings in all patients. The involved vessels were small to medium-sized arteries at the border between dermis and subcutis. Early inflammatory reactions were followed by subendothelial proliferation and a late fibrotic stage. Laboratory examinations showed impaired creatinine clearance in eight patients, whereas all other laboratory tests, including antiphospholipid antibodies, were normal. CONCLUSIONS: In this series, magnetic resonance imaging and skin biopsy were useful for confirmation of the diagnosis of Sneddon's syndrome. Magnetic resonance findings were not specific, but the high sensitivity for detection of asymptomatic brain lesions helped to confirm the diagnosis in patients with transient symptoms. Histological features of skin biopsies were characteristic if appropriate techniques were employed.

Adolescent↗
PubMed1993

Early removal of periarticular ossifications in patients with head injury.

Heterotopic ossifications are a well known but serious complication in patients suffering severe head injury. Their prevalence varies between 10% and 20%. The current concept of surgery recommends removal after "maturation" of the new developed bone because of a suspected higher rate of recurrence. The observations of early operations in 6 patients and 9 joints led us to the conclusion that the disadvantages of long lasting joint stiffness and the according complications outweigh the danger of recurrence. In our patients recurrence was observed in one subject and even there recurrence was most probably the result of wound infection and concomitant osteomyelitis.

Adolescent↗