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Biomedical subjects

W Feindel

Publications and source records attributed to W Feindel.

At least 55 records · Page 3Linked to original sources
PubMed1988

The cytolytic effect of L-2,4 diaminobutyric acid with malignant glioma cells and fibroblasts.

L-2,4-Diaminobutyric acid (DABA), an amino acid analogue, produced a cytolytic effect with a human glioma cell line, SKMG-1, and normal human fibroblasts. The concentrations of DABA necessary to reduce the cell count to 50% of control (LD50) following a 24-h incubation at 37 degrees C were 12.5 mM for the human fibroblasts and 20 mM for the glioma cell line. The concentrations of DABA necessary to produce an LD50 after a 48-h incubation at 37 degrees C were 10 mM for the human fibroblasts and 14 mM for the human glioma cell line. The cytolytic effect of DABA was similar in the absence or the presence of serum with the human glioma cell line. The cytolytic effect of 20 mM DABA was partially prevented by the presence of 5 mM methyl-AIB. DABA was not preferentially toxic to this human glioma cell line compared with normal fibroblasts.

Aminobutyrates↗
PubMed1988

Excitatory amino acids are elevated in human epileptic cerebral cortex.

We used intraoperative electrocorticography to identify and compare specimens from two groups of patients undergoing temporal lobectomy: (1) spiking cortex (12 patients)--epileptic activity recorded over much of the temporal convexity; and (2) nonspiking cortex (9 patients)--temporal convexity free of interictal spiking, epileptic activity confined to the hippocampus and/or amygdala. Comparative amino acid levels were (mumol/g protein, mean +/- SEM): glutamate--spiking 109.8 +/- 1.8, nonspiking 87.4 +/- 2.0 (p less than 0.001); aspartate--spiking 15.2 +/- 0.9, nonspiking 12.2 +/- 0.5 (p less than 0.05); GABA--spiking 15.0 +/- 1.0, nonspiking 13.9 +/- 1.4 (NS); taurine--spiking 14.5 +/- 0.8, nonspiking 12.2 +/- 0.8 (NS); and glycine--spiking 11.5 +/- 0.8, nonspiking 7.4 +/- 0.6 (p less than 0.01). Cortical epileptic activity appears to be associated with elevated concentrations of glutamate, aspartate, and glycine, but not GABA and taurine, perhaps indicating a relative imbalance between putative excitatory and inhibitory amino acid neurotransmitters.

Adolescent↗
PubMed1987

Magnetic resonance imaging in temporal lobe epilepsy: pathological correlations.

A retrospective single-blind study assessing the value of magnetic resonance imaging (MRI) in 48 patients treated surgically for temporal lobe epilepsy was carried out. The imaging findings were correlated with the surgical findings in all cases. Abnormal MRI signals were detected in 34 of 48 (71%) epileptic patients and in 3 of 48 (6.2%) normal or disease control subjects. Twelve patients had structural foreign-tissue lesions, all detected by MRI. Of 14 patients with severe gliosis of the neocortex and/or mesial temporal structures, 11 had abnormal MRI scans. In patients with mild or moderate gliosis of mesial temporal structures, 6 of 12 had abnormal MRI scans. These results indicate that MRI is a sensitive technique for localizing foreign-tissue lesions, mesial temporal sclerosis, and gliosis in patients with intractable temporal lobe seizures.

Adolescent↗
PubMed1987

Diagnostic potential of magnetic resonance in cases of foramen magnum meningiomas.

Meningioma is a histologically benign tumor that is second in frequency only to gliomas among primary intracranial tumors. Its extracerebral development and generally clear demarcation from the brain does not make it easier to detect on magnetic resonance (MR) scanning. Only 2 to 3% of meningiomas occur in the foramen magnum, and these tumors are often clinically misdiagnosed. We discuss four cases of foramen magnum meningioma, with emphasis on MR scanning.

Adult↗
PubMed1987

Radiation dose to upper airways from inhaled oxygen-15 carbon dioxide.

According to Powell et al., significant retention of 15O in the tracheal mucosa results in a radiation absorbed dose of 75 to 200 rad upon breathing of 15O-CO2 for one hour at 1 mCi/liter. Such a high dose would seriously compromise the 15O-CO2 inhalation method for positron emission tomographic (PET) measurement of cerebral blood flow (CBF). In order to verify these results, we have assayed 15O activity in the tracheal region of three volunteers by PET during inhalation of 15O-CO2 and 15O-O2. Using methods similar to those of the above authors for estimating absorbed dose in the tracheal mucosa, we have obtained a value of 14-38 rad, which is more in keeping with 3-5 rad found by Bigler et al. from direct assay of mucus and saliva. We conclude that the 15O-CO2 inhalation method is a safe and practical means of measuring CBF by PET.

Carbon Dioxide↗
PubMed1987

Metabolic and hemodynamic evaluation of gliomas using positron emission tomography.

Positron emission tomography (PET) was used on 16 patients with untreated cerebral gliomas to measure cerebral glucose and oxygen metabolism, oxygen extraction, blood flow, and blood volume. In addition, pH values were obtained for seven cases. Gliomas were later proven by biopsy; two patients had tumors with degrees of malignancy of grade II, two patients had grade III, and 12 patients had grade IV tumors. Compared with homologous gray matter regions in the opposite hemisphere, tumor tissue showed increased blood volume, but decreased oxygen extraction and oxygen metabolism. Compared with grade II tumors, grade IV tumors demonstrated higher blood volumes, but lower relative oxygen extraction and utilization. Tumor blood flow was variable, but was lower in the higher grade tumors. Rates of glucose utilization in tumor, calculated by using individually determined rate constants, were variable, and did not correlate with tumor size or tumor grade. Parietal tumors (n = 6) tended to have higher relative glucose utilization and blood flow, and lower relative oxygen extraction, when compared with frontal tumors (n = 4). Tumor pH differed significantly from the pH in contralateral brain (p less than 0.005); alkalotic pH values were consistently seen. These findings in and around cerebral gliomas studied before intervention differ from the results found in gliomas after exposure to radiation or chemotherapy.

Blood Volume↗
PubMed1987

Metabolic changes in cerebral gliomas within hours of treatment with intra-arterial BCNU demonstrated by phosphorus magnetic resonance spectroscopy.

A 40-year-old female with a recurrent mixed astrocytoma/oligodendroglioma was treated with intra-arterial BCNU at six week intervals. Phosphorus magnetic resonance spectroscopy was performed before, and on two occasions after her third treatment. Before treatment, phosphodiesters were 25% less than normal and intracellular pH was 7.14 (normal 6.97 +/- 0.02). Eight hours following treatment phosphocreatine and phosphodiesters were reduced by approximately 40% and pHi increased to 7.24. Thirty-two hours after treatment, phosphocreatine and phosphodiesters had reversed their decline, but pHi had increased further to 7.35. MRI and x-ray CT scans did not show any change during this period. This study demonstrates that chemical changes can be observed in a glioma by magnetic resonance spectroscopy shortly after chemotherapy in a clinical setting and before changes are observable by imaging modalities. This approach evidently offers a possible means of monitoring the acute metabolic response of tumours to chemotherapy or other forms of treatment by a non-invasive repeatable quantitative method.

Adult↗
PubMed1986

Stability of alpha-1 adrenoceptors in surgically excised human brain.

Alpha-1 adrenoceptor sites were measured in membranes prepared from nonepileptic superficial cortex following temporal lobectomy for lesions in deep medial structures. There was no significant change in receptor density (Bmax) or affinity (Kd) when paired samples were either frozen immediately or kept at room temperature for 24 hours before freezing and storage at -70 degrees C. Regional variability in the Bmax or Kd of alpha-1 adrenoceptor binding was not observed in serial samples from lateral temporal cortex. We previously reported a localized decrease in alpha-1 adrenoceptors in epileptic foci when compared to adjacent nonepileptic tissue obtained from the same patient. As nonepileptic control tissue from an adjacent gyrus is frequently not available in the same specimen, the stability of alpha-1 adrenoceptors justifies the use of postmortem brain for comparative studies.

Adolescent↗
PubMed1986

Pharmacokinetics of superselective intra-arterial and intravenous [11C]BCNU evaluated by PET.

The pharmacokinetics of i.v. and superselective intra-arterial carbon-11 1,3-bis-(2-chloroethyl)-1-nitrosourea ([11C]BCNU) were directly compared for the first time in ten patients with recurrent gliomas using positron emission tomography (PET). Intra-arterial administration of [11C]BCNU achieved concentrations of the drug in the tumor that averaged 50 times higher than with a comparable i.v. dose. These preliminary results suggest that the degree of early metabolic trapping of BCNU in tumor correlates with the clinical response to this chemotherapy.

Adult↗
PubMed1985

Pharmacokinetics of 11C-BCNU in experimental brain tumor.

Wistar rats implanted intracerebrally with AA ascites tumor were injected seven or eight days later with 11C-labelled BCNU. Radioactive compounds in samples of plasma, tumor, and contralateral brain were identified after injection at intervals by doing chloroform extraction and thin layer radiochromatography. At 60 min after injection radioactivity levels were 56% higher in the tumor than in contralateral brain. This increase was due mainly to 2-chlorethyl isocyanate, which binds to amino groups and/or nucleic acid. The results demonstrated both a higher concentration and a faster decomposition of BCNU in the tumor.

Animals↗
PubMed1985

Regional glucose utilization and blood flow in experimental brain tumors studied by double tracer autoradiography.

Coupling of regional glucose utilization (GLU) and blood flow (CBF) was examined in rats with implanted brain tumors (AA ascites tumor) by quantitative double tracer autoradiography using 18F-2-fluorodeoxyglucose and 14C-iodoantipyrine. Four to 13 days after implantation, the animals were injected with the two tracers to obtain autoradiograms from the same brain section before and after the decay of 18F. The autoradiograms were then analyzed by an image processor to obtain a metabolic coupling index (MCI = GLU/CBF). In the tumor, high GLU and low CBF were uncoupled to give a high MCI which implied anerobic glycolysis. In large tumors, the CBF was even lower. In the peri-tumoral region, GLU was reduced (especially in gray matter) and reduction was lowest around the larger tumors. CBF in the peri-tumoral region was also reduced, but this reduction became less as the distance from the tumor margin increased. These changes in the peri-tumoral region may be secondary to edema. The GLU and CBF of white matter was little influenced by the presence of tumors except for some reduction in these values in relation to the larger tumors. On a narrow margin of tumor and brain, corresponding to a zone of increased vascularity, CBF was moderately high. The MCI in the tumor was higher than in the cortex of the same as well as the opposite hemisphere. These findings indicate that the metabolism and blood flow of the tumor and surrounding brain are variable and directly related to tumor size.

Animals↗
PubMed1985

Utilization of the HTSCA and CFU-C assay to identify two new 2-chloroethylnitrosourea congeners of amino acid amides with increased in vitro activity against human glioma compared with BCNU.

AspCNU and SarCNU are two amino acid amide congeners (L-asparaginamide and sarcosinamide congeners) of chloroethylnitrosoureas. The in vitro myelotoxicity of these agents compared with BCNU at 1-8 micrograms/ml was determined in bone marrow cells from normal volunteers in the CFU-C assay. AspCNU and SarCNU were significantly (P less than 0.05) less myelotoxic than BCNU at equivalent microgram concentrations. SarCNU or AspCNU at 3 micrograms/ml demonstrate equivalent in vitro myelotoxicity to BCNU 1 microgram/ml. We used the human tumor stem cell assay (HTSCA) to investigate in vitro antitumor activity. We obtained four specimens of malignant glioma and one specimen of meningioma from patients not previously treated with chemotherapy. AspCNU and SarCNU were significantly (P less than 0.05) more active than BCNU at 1-3 micrograms/ml concentrations in the HTSCA in all four malignant glioma specimens. In the one meningioma specimen, BCNU was significantly (P less than 0.05) more active than either AspCNU or SarCNU at all concentrations studied. These results suggest that AspCNU or SarCNU at doses that should produce less myelotoxicity than BCNU may be more active than BCNU against gliomas.

Antineoplastic Agents↗
PubMed1985

Quantification of glucose utilization in an experimental brain tumor model by the deoxyglucose method.

Reevaluation of lumped and rate constants is necessary when Sokoloff's 2-deoxyglucose (DG) method is used to measure glucose utilization in pathological tissue. We describe here a modification of Sokoloff's lumped constant measurement that permits simultaneous estimation of both lumped and rate constants from a single animal experiment. A subcutaneous tumor model (AA ascites tumor) was used for measurement of these constants with a procedure similar to Sokoloff's that kept the plasma tracer concentration constant. Measured constants were as follows: lumped constant, 0.654 +/- 0.081; k1, 0.196 +/- 0.038 min-1; k2, 0.262 +/- 0.067 min-1; k3, 0.117 +/- 0.044 min-1. These constants were used to quantify glucose utilization in the implanted brain tumor. To test the validity of this method, we compared a fraction of the free DG pool calculated using the tumor constants with a fraction measured directly by chromatographic analysis of tissue samples from both subcutaneous tumor and implanted brain tumor. The values derived by chemical analysis agreed well with those predicted by the calculations. The value of k4 varied from 0.0031 +/- 0.0018 min-1 for the tumor tissue to 0.0214 +/- 0.0024 min-1 for tumors with a large necrotic center. This method would be especially useful when applied to xenograft human gliomas in nude mice for quantification of glucose utilization in human gliomas by means of positron emission tomography.

Animals↗
PubMed1984

Improved synthesis and low-temperature autoradiographic evaluation of 18F-n-fluoropropane as a myelin tracer for positron emission tomography.

An improved synthesis of the lipophile 18F-fluoropropane, yielding 30-45 mCi 18F-labelled radiopharmaceutical, is described. The radiochemical yield was 55%-66% determined at the end of a 1-h synthesis. Radiochemical and chemical purity of 18F-fluoropropane was 99% as determined by gas chromatography. Low-temperature autoradiography was used to investigate the lipophile 18F-n-fluoropropane as a myelin tracer for use with positron emission tomography. The white to grey matter ratio based on autoradiograms 12 min after administration of the radiotracer was 2:1, the highest reported to date.

Animals↗
PubMed1984

Reversal of acute experimental cerebral vasospasm by calcium antagonism with verapamil.

Acute vasospasm of the transclivally exposed basilar artery of anesthetised cats was produced by the subarachnoid injection of platelet-rich plasma (PRP) treated with enough adenosine diphosphate (ADP) to induce platelet aggregation and secretion. Vasorelaxation was produced by the topical application of the calcium antagonist verapamil. Changes in the internal diameter of the basilar artery were determined by measuring the blood column diameter from photomicrographs taken sequentially, at 5 minute intervals, through the operating microscope. Changes in blood vessel diameter are expressed as a plus or minus percentage of the pretreatment diameter. Arterial blood pressure and blood gas values were kept in the physiological range for the cat. The subarachnoid injection of PRP-ADP produced severe constriction of the basilar artery (mean constriction at 5 minutes after injection: -40.7% +/- 2.8 SEM). Platelet-free plasma, ADP alone and Elliott's A solution had no spasmogenic effect when injected into the subarachnoid space. The topical application of the calcium channel blocker verapamil (0.1 mg per kg) 30 minutes after the injection of PRP-ADP, with the basilar artery still in spasm (mean constriction: -23% +/- 3.5 SEM), produced prompt and dramatic vasodilation (mean dilation at 5 minutes after application: +52.7% +/- 18.1 SEM). This spasmolytic effect persisted in a decremental fashion for the 60 minute period of observation, by which time the previously constricted vessel had returned to its normal size. These observations indicate that the platelet fraction of whole blood may be involved in the genesis of acute vasospasm following subarachnoid hemmorrhage and that this phenomenon can be readily reversed by calcium antagonism.

Acute Disease↗