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Biomedical subjects

R W Seiler

Publications and source records attributed to R W Seiler.

At least 55 records · Page 3Linked to original sources

Noninvasive differentiation of meningiomas from other brain tumours using combined 111Indium-octreotide/99mtechnetium-DTPA brain scintigraphy.

We have studied prospectively 47 patients with CNS tumours including 16 meningiomas and 33 other tumours using combined 111In-octreotide and 99mTc-DTPA brain scintigraphy. 111In-octreotide scintigraphy was used to image somatostatin receptors (SSR) and 99mTc-DTPA scintigraphy was used to assess the integrity of the blood-brain barrier (BBB). A total of 32 tumours (65%) were detected. All SSR positive tumours also had positive 99mTc-DTPA scans and all SSR negative tumours were negative on 99mTc-DTPA scans. Among the tumours located outside the BBB, all meningiomas and two out of six schwannomas were positive on combined SSR/99mTc-DTPA scintigraphy. Among the tumours located inside the BBB, seven out of nine gliomas grade I-III were negative, whereas all glioblastomas were positive. Other positive tumours included one malignant non-Hodgkin lymphoma and two cerebral metastases. SSR scintigraphy alone was non-specific in the diagnosis of meningiomas, as 16 non-meningiomatous tumours also had positive SSR scans probably due to a breakdown of the BBB (excluding the malignant lymphoma). Measuring the tumour-to-background ratio on SSR scans improved specificity, but sensitivity was decreased below 70% because some meningiomas were only slightly positive. Only the ratio of SSR scintigraphy to conventional 99mTc-DTPA brain scintigraphy (SSR-to-BS index) allowed a reliable differentiation of meningiomas from other CNS tumours, most notable from schwannomas (sensitivity: 94%; specificity: 100%). Our results support the usefulness of combined SSR and conventional brain scintigraphy in the noninvasive pre-operative diagnosis of meningiomas.

Adolescent↗

Noninvasive dopamine determination by reversed phase HPLC in the medium of free-floating roller tube cultures of rat fetal ventral mesencephalon: a tool to assess dopaminergic tissue prior to grafting.

The low availability of dopamine containing neurons for grafting in Parkinson's disease is a general problem. Free-floating roller tube (FFRT) cultures allow storage of fetal mesencephalic tissue prior to transplantation. Preoperative functional testing permits to select an optimized set of individual cultures for transplantation. Rat fetal ventral mesencephali (E13) were dissected out and divided into four equally sized pieces each and individually prepared as FFRT cultures. After 4, 8, 12, and 16 days in vitro (DIV) the medium of each culture was collected during routine medium change and immediately stabilized. Dopamine was extracted and probes were determined with reversed phase HPLC using electro-chemical detection. After 16 DIV cultures were fixed and cell counts performed in tyrosine hydroxylase (TH)-immunostained serial sections. The mean dopamine content +/- SEM In culture conditioned media was at 4 DIV: 21 +/- 2 pg, n = 38; at 8 DIV: 37 +/- 4 pg, n = 40; at 12 DIV: 52 +/- 7 pg, n = 38; and at 16 DIV: 39 +/- 5 pg, n = 38. In all cultures devoid of dopamine after 4 and 8 DIV (12.5%) levels remained below detectability at 12 and 16 DIV. Cultures derived from the rostral mesencephalon showed significantly higher dopamine values than those from the caudal mesencephalon at 12 DIV. The mean number of TH-immunoreactive (-ir) cells/culture +/- SEM after 16 DIV was 556 +/- 51, n = 40. The correlation between TH-ir cell number (CN) and dopamine content of rostrally derived cultures at 16 DIV was: CN = 7.4 (dopamine [pg]) + 248; R = 0.75; n = 19; p < 0.001. No dopamine was present in cultures without TH-ir cells. These results demonstrate that sequential noninvasive screening of dopamine in single cultures is feasible and that the dopamine content is correlated to the number of surviving TH-ir cells. This permits to select cultures rich in dopaminergic neurons for transplantation.

Animals↗

Identification of posttraumatic ischemia and hyperperfusion by determination of the effect of induced arterial hypertension on carbon dioxide reactivity.

BACKGROUND AND PURPOSE: Both ischemia and hyperperfusion are known phenomena that follow traumatic brain injury. Cerebral carbon dioxide reactivity is diminished in both conditions. Differentiation is important because ischemia is thought to be a major factor of secondary neuronal loss and is potentially amenable to therapy by manipulation of cerebral perfusion pressure. METHODS: The response of transcranial Doppler-based carbon dioxide reactivity to pharmacologically induced hypertension was studied sequentially in 29 patients with severe to moderate head injury to identify ischemia and luxury perfusion. After simultaneous baseline registration of the carbon dioxide reactivity of both middle cerebral arteries by two-channel transcranial Doppler, systolic arterial pressure was raised approximately 20 mm Hg by means of phenylephrine (Neosynephrine) infusion, and the carbon dioxide reactivity test was repeated. RESULTS: A significant improvement of impaired (< 2%/mm Hg) carbon dioxide reactivity after arterial pressure was raised by 20 mm Hg (signaling ischemia) was found in 32 of 124 evaluated middle cerebral arteries. Further deterioration of impaired reactivity occurred in only four tested hemispheres. While ischemic conditions were identified during the entire study period, hyperperfusion was encountered only after day 3. CONCLUSIONS: Ischemia after traumatic brain injury is a frequent phenomenon, whereas hyperperfusion is rare. Whether therapeutic optimization of carbon dioxide reactivity can improve the outcome of head-injury patients needs to be evaluated in further studies.

Blood Pressure↗

[Subarachnoid hemorrhage].

The rupture of a cerebral aneurysm is the main cause of a spontaneous subarachnoid hemorrhage. Complications after the initial hemorrhage are recurrent bleeds, hydrocephalus and ischemia. Main symptom of a subarachnoid hemorrhage is the sudden, intense headache, often followed by loss of consciousness. The diagnosis is made by CT. If the CT is negative, lumbar puncture has to be performed, because in 5% of patients the blood may not be seen on the CT. If the diagnosis is confirmed, the patients has to be transferred as an emergency to a neurosurgical center. If his condition is satisfactory, the aim of the treatment is to occlude the ruptured aneurysm by microsurgical technique within the first three days after the hemorrhage. In patients with high surgical risk or bad general condition, the aneurysm can also be treated by the interventional neuroradiologist with endovascular techniques.

Embolization, Therapeutic↗

Comparison of the effects of the neurotrophins on the morphological structure of dopaminergic neurons in cultures of rat substantia nigra.

The effect of the various neurotrophin family members on the morphological structure of dopaminergic neurons was compared in dissociated cultures of embryonic rat ventral mesencephalon. Cultures were maintained in vitro in the presence of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrohin-4/5 (NT-4/5), nerve growth factor (NGF) or no added growth factors. Three-dimensional reconstructions of 48 neurons were made in each of the experimental groups following immunocytochemical staining for tyrosine hydroxylase to detect dopaminergic neurons. In addition [3H]mazindol binding analyses were carried out in replicate cultures in order to quantify the effects of the neurotrophins on the number of dopamine uptake sites. Among the neurotrophins tested, NT-4/5 influenced the proximal morphological parameters most, as determined by a 36% increase in the soma profile area and 35% in the number of stem neurites. Analysis of neuritic size and complexity in these cultures revealed that combined neuritic length and number of segments/cell were increased by 45 and 40% respectively. A change in neurite complexity in the NT-4/5 treated cultures was further confirmed using Scholl's concentric sphere analysis. In addition, relative to the control, NT-4/5 increased the neuronal differentiation as evidenced by increases in varicosity density and [3H]mazindol binding by 114 and 101% respectively. BDNF and, to a lesser extent, NT-3 also increased both proximal parameters and parameters of differentiation, but were without effect on parameters of neuritic size and complexity. No effects on neuronal structure were observed in NGF treated cultures. These findings demonstrate that BDNF, NT-3 and NT-4/5 influence the morphological differentiation of dopaminergic neurons in vitro, suggesting they may play a role in the structural development and plasticity of these neurons in the mesencephalon.

Animals↗

Effects of BDNF on dopaminergic, serotonergic, and GABAergic neurons in cultures of human fetal ventral mesencephalon.

The neurotrophin brain-derived neurotrophic factor (BDNF) was tested for its ability to promote the survival and regulation of expression of phenotypic markers of dopaminergic, serotonergic, and GABAergic neurons in free-floating roller tube cultures of human fetal ventral mesencephalon. This culture system contains neurons of the anlage of the substantia nigra as well as that of the rostral raphe nucleus. Dopaminergic neuron number and tyrosine hydroxylase (TH) fiber density was monitored by TH immunocytochemistry. Measurement of dopamine (DA) content, TH enzymatic activity, serotonin (5-HT) content, and glutamic acid decarboxylase (GAD) activity were used as indices of their respective neurotransmitter function. The presence of GABAergic and serotonergic neurons in this culture system was confirmed by GABA and 5-HT immunocytochemistry. In cultures maintained in the presence of BDNF (10 ng/ml), the density of TH-positive cells was increased by 2.5-fold (P F 0.05), and the TH-positive fiber density was increased by 3.5-fold (P F 0.01), relative to control cultures. Similarly, the relative increases in DA content and TH activity were 2.6- and 2.3-fold, respectively, in the BDNF-treated cultures (P F 0.01 and P F 0.01). On a per neuron basis, DA content and TH activity were not markedly changed by BDNF treatment, suggesting that the increases in DA content and TH activity are due to more DA neurons surviving. Relative elevations were also observed in serotonin content (2.0-fold, P F 0.01) and GAD enzymatic activity (1.4-fold, P F 0.01). Future studies will need to determine whether these changes result from the direct action of BDNF on these neurons or through some indirect mechanism. The results demonstrate that BDNF has beneficial effects on cultured human fetal tissue, which may be relevant in optimizing neuronal transplantation techniques, and that multiple systems are simultaneously influenced by BDNF.

Abortion, Induced↗

Severe symptomatic vasospasm after rupture of an arteriovenous malformation.

A 31-year-old woman had intracerebral and intraventricular hemorrhage from an arteriovenous malformation. Vasospasm of the internal carotid arteries developed and was treated with angioplasty. On initial CT scans, only traces of blood were seen in the basal cisterns; thus, the development of symptomatic vasospasm was an unexpected complication.

Adult↗

Somatostatin receptor scintigraphy in central nervous system tumors: role of blood-brain barrier permeability.

UNLABELLED: Somatostatin receptors are expressed in meningiomas and low-grade gliomas, raising the hope that scintigraphy with 111In-DTPA-D-Phe1-octreotide might be helpful in the in vivo localization, differential diagnosis and postoperative/postradiotherapy brain tumor follow-up. METHODS: Indium-111-DTPA-D-Phe1-octreotide scintigraphy and brain scintigraphy using 99mTc-DTPA as a nonspecific tracer for blood-brain barrier integrity were simultaneously performed in 60 patients with CNS tumors using dual-isotope acquisition mode SPECT. For 23 patients, the scintigraphic findings were also compared with in vitro somatostatin receptor autoradiography of surgical biopsy specimens. RESULTS: In meningiomas (located outside the blood-brain barrier), the somatostatin receptor scan showed all tumors and scintigraphic signal intensity correlating with in vitro SSR density positive in all meningiomas. Less contrast was seen on 99mTc-DTPA scans. In all tumors inside the blood-brain barrier, the 111In-DTPA-D-Phe1-octreotide scan visualized the tumors with a disrupted blood-brain barrier, as seen by 99mTc-DTPA scintigraphy. Discrepancies, however, were observed between somatostatin receptor scintigraphy and in vitro receptor autoradiography. CONCLUSION: Combined somatostatin receptor and 99mTc-DTPA scintigraphy may be helpful for noninvasive differentiation between meningiomas and other CNS tumors. False-negative scans were observed as a result of shielding by the intact blood-brain barrier. Interpretation of negative and positive somatostatin receptor scans in CNS tumors must therefore be done with caution.

Adolescent↗

NGF increases neuritic complexity of cholinergic interneurons in organotypic cultures of neonatal rat striatum.

The influence of NGF on cholinergic interneurons in organotypic roller tube cultures of 4 day postnatal rat striatum was examined after 13 to 16 days in vitro. Cultures were divided into four groups. The medium of the NGF treated group was supplemented with 5 ng/ml NGF, whereas control groups were cultured either without NGF, by adding 20 ng/ml neutralising anti-NGF antibody, or by adding both NGF and anti-NGF antibody to the medium. Two different cell populations were identified by an image analysis system which measured acetylcholinesterase staining intensity. It was demonstrated that NGF promotes survival of the large, intensely stained population. Eighty computer-assisted reconstructions of intensely stained cells, 20 for each treatment group, were performed in a random order by means of a neuron tracing system. Axons and dendrites were analysed separately. NGF enhanced complexity of neuritic, predominantly axonal trees by increasing the number of axonal segments by 91% to 100% (P < 0.01), the number of dendritic segments by 33% to 63% (P = 0.09 to P < 0.01), maximal axonal branch order by 37% to 50% (P < 0.05), and maximal dendritic branch order by 22% to 37% (P < 0.05). Further evidence of more complex neuritic trees was given by Sholl concentric sphere analysis. Anti-NGF antibody could block all these effects. General rules of branching architecture were not affected by NGF treatment as shown by analysing mean segment length in relation to the branch order, branch point exit angles, total tortuosity, Rall's ratio, and tapering of neuritic trees.

Acetylcholine↗

Current pattern of in-hospital aneurysmal rebleeds. Analysis of a series treated with individually timed surgery and intravenous nimodipine.

The management of aneurysmal subarachnoid haemorrhage has recently changed considerably. Emergency admission to specialized centres and early surgery have become common practice. In addition, the use of nimodipine has gained widespread acceptance. Little data are available concerning the frequency and temporal profile of reruptures under the current policies. The case histories of 387 patients treated for aneurysmal subarachnoid haemorrhage between January 1984 and March 1992 were reviewed with regard to the incidence of in-hospital reruptures. All patients were managed according to the same protocol including a policy of individually timed early surgery and intravenous nimodipine. A total of 44 first in-hospital rebleeds were observed during the waiting period. Two percent of the patients admitted on the day of haemorrhage had a rebleed on the same day after admission to the hospital. No rebleeds were observed on the day after subarachnoid haemorrhage. Rebleed rates on day 2 and 3 were also low with 0.6 and 0.8% of the population with an unclipped aneurysm. For the following 10 days, the daily rate of rerupture increased. A further peak was observed during the 4th week. Using life-table methods, the cumulative rate of rebleeds was calculated as 23% within 2 weeks and 42% within 4 weeks. Although patients suffering rebleeds differed in several respects from patients without rebleeds, most of the differences could be identified to be a consequence of a selection bias resulting in a longer period of exposure to the risk of rerupture for certain subgroups. Only patients suffering a loss of consciousness after the initial subarachnoid haemorrhage were definitively exposed to a higher daily risk of rerupture.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Long-term survival of dopaminergic neurones in free-floating roller tube cultures of human fetal ventral mesencephalon.

Transplantation of human fetal ventral mesencephalon (VM) to Parkinsonian patients has shown beneficial effects in several clinical trials. However, further improvements in the transplantation technique are needed. Delayed surgery, i.e., the in vitro maintenance of the tissue prior to transplantation would present several advantages. The roller tube technique as initially described by Gähwiler (1981) was modified in several aspects for the long-term maintenance of dopaminergic neurones of human fetal VM. Tissue cultures were maintained free-floating in the medium for up to 42 days. The human fetal material was obtained from legal induced suction abortions. The embryonic age ranged from 5 to 12 weeks post-conception. Identification of VM was possible in 43% of the cases. Neurones in cultures were demonstrated by means of immunohistochemistry for tyrosine hydroxylase (TH) and gamma-amino butyric acid (GABA), by electron microscopy and by hybridisation histochemistry using a TH-mRNA-sensitive probe. A high variability in the number of TH-positive cells in individual cultures derived from the same embryo was observed. In 20 microns frozen sections of such tissue cultures the mean +/- SEM of TH-positive cells was 6.5 +/- 1.2/0.1 mm2 (n = 79; range: 0-73). The technique described insures the growth of long-term cultures of human fetal VM.

Cell Survival↗

Intraoperative motor and sensory monitoring of the cauda equina.

A set of standard techniques to monitor the motor and sensory function of the cauda equina is proposed for surgery in the lumbosacral spinal canal for the release of a tethered cord or the removal of a neoplasm. Continuous loudspeaker-controlled recording of electromyographic activity in four leg muscles of both sides supplied the surgeon with immediate feedback on injury to any of the motor roots from the second lumbar to the fourth sacral segment. Continuous recording of tibial nerve somatosensory evoked potentials yielded information about the functional state of parts of the lumbosacral sensory pathways. Motor roots could be identified by electrical stimulation in the operating field with bipolar stimulation forceps and recording of compound muscle action potentials from the leg muscles. Sensory nerve roots could be identified by nerve root somatosensory evoked potentials recorded from the scalp after the electrical stimulation of the exposed nerve. This set-up is a combination of previously developed monitoring techniques and provides the surgeon with functional information: 1) continuous feedback on the state of the endangered motor and sensory function of the cauda equina; and 2) rapid anatomical identification of nerve roots and their distinction from fibrous or neoplastic structures.

Adolescent↗

Transcranial Doppler monitoring in head injury: relations between type of injury, flow velocities, vasoreactivity, and outcome.

Eighty-six patients with head injuries with an admission Glasgow Coma Scale score between 3 and 12 were studied sequentially by transcranial and cervical Doppler sonography. On a subset of 26 patients, sequential autoregulation and CO2 reactivity testing was also performed. Patient characteristics and hemodynamic data were correlated and analyzed with respect to the final outcome. The internal carotid artery (ICA) and middle cerebral artery flow velocities followed a typical pattern. Both were depressed during the first 3 days after the trauma and then increased to a maximum between Days 5 and 7. The increase of the middle cerebral artery flow velocities was more pronounced than the increase of the ICA flow velocities, thus indicating some degree of vasospasm. The amount of subarachnoid hemorrhage on the initial computed tomography correlated with the average middle cerebral artery/ICA flow velocity ratio (r = 0.5). Subarachnoid hemorrhages on computed tomography and, to a lesser degree, subdural and intracerebral hematomas were correlated with an unfavorable outcome. Vasospasm remained subcritical, and no negative relationship to outcome could be identified. Hyperperfusion, as based on ICA flow velocities, and vasospasm were correlated with diminished vasoreactivity. However, disturbed vasoreactivities, particularly during the first days, were common and did not necessarily predict an unfavorable outcome.

Adolescent↗

Early prognosis of supratentorial grade 2 astrocytomas in adult patients after resection or stereotactic biopsy. An analysis of 50 cases operated on between 1984 and 1988.

50 adult supratentorial low-grade astrocytomas operated upon between 1984 and 1988 were analysed retrospectively with respect to postoperative condition and progression-free survival. Pilocytic lesions were excluded. In 32 instances the tumour was macroscopically completely removed and partially in 4. In 14 cases a stereotactic biopsy was performed only. 10 patients received postoperative radiotherapy with 55 to 65 Gy. 1 patient died perioperatively from pulmonary embolism. 39 patients could resume their previous activities after discharge from the hospital, 10 were significantly disabled by neurological deficit, reduced neuropsychological performance or medically intractable epilepsy. Postoperatively, most patients required continuous anti-epileptic medication, 10 recurrences or tumour progressions of incompletely removed or merely biopsied lesions were observed within the mean follow-up period of 22 months. All recurrences after gross total removal, that were reoperated, had progressed to a malignant glioma. Of the prognostic tumour characteristics analysed, a histologically well-delineated tumour demarcation was most clearly associated with a favourable prognosis. Concerning treatment modalities, gross total resection was associated with a favourable prognosis. Radiotherapy was associated with an unfavourable outcome but this is probably due to selection of otherwise unfavourable cases.

Adolescent↗

Evaluation of posttraumatic cerebral blood flow velocities by transcranial Doppler ultrasonography.

Thirty-five patients were admitted to the hospital with Glasgow coma scale scores of 4 to 7 after severe, blunt head injury. Blood flow velocities of the middle cerebral artery (MCA) and the ipsilateral internal carotid artery (ICA), high in the neck, were recorded noninvasively by Doppler ultrasonography. Serial examinations were begun within 48 hours of trauma and continued until the patient either died or was discharged. Spasm of the MCA was assumed if the ratio of the velocity of blood flow in the MCA (VMCA) to the velocity of blood flow in the ICA (VICA) exceeded 3 (normal value, 1.7 +/- 0.4). In cases of severe MCA spasm, this ratio is higher because of increased flow velocity in the MCA and reduced flow in the ICA due to increased cerebrovascular resistance. Higher MCA velocities with VMCA/VICA above 3, consistent with MCA spasm, were found in 14 of the 35 patients (40%). The increase began as early as 48 hours after injury, reached a maximum between Days 5 and 7, and lasted until 2 weeks after injury. There was a significant correlation between the occurrence of vasospasm and the quantity of cisternal or intracerebral blood seen on a computed tomographic scan. No correlation was found with the age of the patients, the Glasgow coma scale score at admission, the intracranial pressure, or the functional outcome 6 months after injury. The occurrence of a secondary infarction in a patient with severe MCA spasm suggests that, at least in some cases, spasm may influence the prognosis.

Adolescent↗

Effect of nimodipine on cerebrovascular response to CO2 in asymptomatic individuals and patients with subarachnoid hemorrhage: a transcranial Doppler ultrasound study.

The cerebrovascular response to CO2 was evaluated by measuring relative changes in blood flow velocity within the middle cerebral artery by transcranial Doppler ultrasonography during normo-, hypo-, and hypercapnia. In seven patients without subarachnoid hemorrhage (five with unruptured arteriovenous malformations and two with aneurysms), the CO2 vasoreactivity was tested on the side of the middle cerebral artery with normal flow velocities opposite the lesion. A baseline CO2 reactivity test was obtained in each patient and then repeated under constant intravenous infusion of nimodipine, 2 mg/hr. Nine patients with ruptured aneurysms who were rated at Hunt and Hess Grades 1 or 2 were operated on within 1 to 3 days after the hemorrhage and treated with nimodipine, 2 mg/hr, given intravenously. In these patients, CO2 vasoreactivity was tested during the second week after the hemorrhage, when the middle cerebral artery velocity was increased by at least 50% of the initial value or more. Nimodipine was then discontinued and, 48 hours later, when the middle cerebral artery velocity was still in the same range, CO2 vasoreactivity was tested again. Two months later, after full recovery from the subarachnoid hemorrhage and normalization of the velocities, a third measurement of CO2 reactivity was obtained as a baseline control. No significant effect of nimodipine on CO2 vasoreactivity could be demonstrated in any of the test periods. In the second week after a subarachnoid hemorrhage, a significant reduction of the cerebrovascular response to CO2 was found (P less than 0.005).

Adolescent↗

[Stereotaxic brain puncture. Indications and results].

228 stereotactic biopsies for the diagnosis of brain lesions were evaluated. In 98.2% a diagnosis could be established. The diagnosis was made of brain tumor in 79.3%, of brain abscess in 7.5% and of encephalitis in 3.5% of cases. In 2.2% of the patients a pathological finding was obtained without a clear histological definition. No histological diagnosis could be made in 1.8% of the patients. A severe complication of brain biopsy occurred in 2.2% of the patients (1 death, 1 abscess, 3 increased impairments). The stereotactic procedure appears to have a low mortality and morbidity, and to be highly accurate.

AIDS Dementia Complex↗