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Biomedical subjects

E Arbit

Publications and source records attributed to E Arbit.

At least 55 records · Page 3Linked to original sources

Characterization of neuroblastoma xenograft in rat flank. I. Growth, interstitial fluid pressure, and interstitial fluid velocity distribution profiles.

The growth, interstitial fluid pressure (IFP) and interstitial fluid velocity (IFV) profiles of a human neuroblastoma propagated in the flank of an immune suppressed rat were characterized. IFP was measured in the tumor center as a function of size, while radial distributions of IFP and IFV were measured in 2-cm tumors. IFP and IFV were measured using the wick-in-needle and clearance of locally generated hydrogen techniques, respectively. These techniques have a high spatial resolution, permit repetitive measurements, and are minimally invasive. We observed that IFP in the neuroblastoma increased as the tumor grew. Furthermore, IFP increased and its IFV decreased from the periphery toward the center of the tumor. Measured IFP and IFV values were compared to theoretical expectations calculated from the Baxter and Jain mathematical model. The predictions were highly correlated to the measured IFP and IFV profiles with the transport impedence parameter alpha 2 = 24.4. From our measurement data and the Baxter-Jain equations, we computed the interstitium hydraulic conductivity for neuroblastoma to be 7.11 x 10(-6) cm2/mm Hg-sec.

Animals↗

Development of a method to measure kinetics of radiolabelled monoclonal antibody in human tumour with applications to microdosimetry: positron emission tomography studies of iodine-124 labelled 3F8 monoclonal antibody in glioma.

We present a method to assess quantitatively the immunological characteristics of tumours using radiolabelled monoclonal antibody and positron emission tomography (PET) to improve dosimetry for radioimmunotherapy. This method is illustrated with a glioma patient who was injected with 96.2 MBq of iodine-124 labelled 3F8, a murine antibody (IgG3) specific against the ganglioside GD2. Serial PET scans and plasma samples were taken over 11 days. A three-compartment model was used to estimate the plasma to tumour transfer constant (K1), the tumour to plasma transfer constant k2, the association and dissociation constants (k3, k4) of antibody binding, and the binding potential. Tumour radioactivity peaked at 18 h at 0.0045% ID/g. The kinetic parameters were estimated to be: K1 = 0.048 ml h-1 g-1, k2 = 0.16 h-1, k3 = 0.03 h-1, k4 = 0.015 h-1 and BP = 2.25. Based on these kinetic parameters, the amount of tumour-bound radiolabelled monoclonal antibody was calculated. This method permits estimates of both macrodosimetry and microdosimetry at the cellular level based on in vivo non-invasive measurement.

Brain↗

Treatment of spinal epidural neuroblastoma xenografts in rats using anti-GD2 monoclonal antibody 3F8.

Epidural neuroblastoma xenografts in nude rats causing paraparesis were treated with intravenous injection of an anti-GD2 monoclonal antibody 3F8. Metastatic or primary epidural tumors in humans cause rapid neurologic compromise. Treatment is often unsatisfactory. An animal model was established to study antibody targeted therapy of epidural tumor. Human neuroblastoma was xenotransplanted into the thoracic epidural space of nude rats. When paraparesis developed, animals were treated intravenously with an anti-GD2 monoclonal antibody, 3F8, either alone or radiolabeled with 131Iodine. Improvement in neurologic function occurred in 2 of 20 (10%) animals receiving no treatment or control antibody, 14 of 17 (82%) animals receiving 3F8 alone and all 9 animals receiving 131I-3F8 (p < 0.0001 for 3F8 or 131I-3F8 vs. control). Six animals treated with 3F8 alone recovered normal neurologic function and remained well until sacrifice 10 days later. Four animals treated with 3F8 alone had no tumor evident on pathologic examination. The percent injected dose of 131I-3F8/g tumor in 5 samples ranged from 0.73% to 3.8%. These observations demonstrate that neoplastic epidural compression of the spinal cord in the rat can be treated successfully with intravenous unmodified monoclonal antibody and that signs of neurologic dysfunction can be reversed. The potential of this approach in treating patients with epidural tumors and other neoplasms, especially those that are not sensitive to chemotherapy or radiotherapy, deserves to be explored.

Animals↗

Endometrial cancer metastasis to brain: report of two cases and a review of the literature.

Two cases of brain metastases from endometrial adenocarcinoma are reported. A 70-year-old female presented with lung metastases 14 months after hysterectomy and adjuvant treatment. At 6 months later, a cerebellar metastasis was resected and followed by radiation therapy. The patient died 5.5 months later. In the second case, a 60-year-old patient developed a lung endometrial metastasis 6 years after initial treatment. At 1 year later she was diagnosed with bilateral hydrocephalus caused by a left temporal and posterior fossa tumor. A ventriculoperitoneal shunt was inserted and she received brain radiation. Two weeks later she gradually became comatose, with right hemiparesis. A metastatic, hemorrhagic temporal tumor was resected but the patient never regained consciousness and died after 7 weeks. The existing literature on brain metastases from endometrial adenocarcinoma is reviewed.

Adenocarcinoma↗

Reversible diencephalic dysfunction: episodic hyperhidrosis due to a trapped third ventricle.

We present a patient with episodic hyperhidrosis (EH) who had 15 attacks per day for 3 years following placement of a lateral ventricular shunt. MRI revealed that she had an isolated third ventricle. Stereotactic shunting of the third ventricle resulted in immediate and complete resolution of her symptoms. We suggest that this patient had periodic rises in third ventricular pressure resulting in episodic diencephalic dysfunction and EH.

Aged↗

The significance of morphologically viable glioma cells found at the time of operation after interstitial brachytherapy.

The significance of finding morphologically intact viable glioma cells in tumors treated with high-dose irradiation delivered by interstitial brachytherapy was examined. Freshly resected tissue was taken from 12 patients after (n = 8) or both before and after (n = 4) interstitial brachytherapy. All posttreatment tissue was taken from regions within a radius of 2.0 to 4.0 cm of the radioactive source. From each sample, monolayer cell culture was established. All untreated samples from primary tumors grew well and became established as cell lines within 1 to 3 weeks. In contrast, cells from treated tumors only formed small colonies of 50 to 100 cells each. These cells grew slowly and, within 14 to 21 days, degenerated. Neither the use of conditioned medium or cell extract from established glioma cell lines nor the application of growth factors (platelet-derived growth factor and/or epidermal growth factor) stimulated growth or lengthened survival. The only exception was tumor resected from approximately 4 cm from the nearest radioactive source and from which a viable cell line could be established (IRR). Cytogenetic analysis of tissue from one sample (IR) before source implantation and from another (IRR) after source implantation, both from the same patient, showed that cells IR and IRR were derived from the same stem cell. To establish the reason why cell IRR remained clonogenic despite high-dose irradiation, IRR cells were irradiated with gamma irradiation with a dose rate of approximately 1 Gy/min for 24 hours. This colony-forming assay showed that IRR cells were radiosensitive.(ABSTRACT TRUNCATED AT 250 WORDS)

Astrocytoma↗

Percutaneous lateral cervical cordotomy: target localization with water-soluble contrast medium.

Water-soluble intrathecal contrast material was used for radiographic identification of the cord target in 13 patients undergoing percutaneous lateral cervical cordotomy. Adequate visualization of the dentate ligament, considered essential for successful placement of the electrode, was achieved in seven cases. In the remaining six patients, four with suboptimal definition and two with nonvisualization of the ligament, an additional injection of contrast medium using a modified coaxial needle system outlined the entire thickness of the cervical cord. This technique improved needle-tip positioning in relation to the cord and resulted in successful surgery in all six patients.

Contrast Media↗

Craniofacial resection for tumors involving the anterior skull base.

A consecutive series of 71 patients who underwent craniofacial resection between 1974 and 1990 for tumors that involved the anterior cranial base was reviewed. A variety of histologic diagnoses was present in this series. The most prevalent sites of origin included the nasal cavity, ethmoid sinus, and frontal sinus. Gross tumor removal was achieved in all patients, with 29 requiring orbital exenteration. Adjuvant radiation therapy was used in 25 patients. Two patients died of postoperative complications and 26 had complications that increased morbidity and length of the hospitalization. Five-year overall survival was 56%, with a median survival of 4.2 years. Local control was observed in 40 of 56 patients with negative margins and 9 of 15 patients with positive margins. There was no difference in survival between previously treated and untreated patients. Survival varied considerably among the various pathologic diagnoses. Survival was related to the extent of disease. Patients with either dural or brain invasion had significantly decreased survival compared to those with no dural invasion. The operative procedure is safe, with acceptable morbidity and mortality, and offers respectable survival in properly selected patients.

Adolescent↗

Resection of brain metastases from non-small-cell lung carcinoma. Results of therapy. Memorial Sloan-Kettering Cancer Center Thoracic Surgical Staff.

The treatment of patients with a solitary brain metastasis has been evolving, with most centers recommending resection in patients with good performance status. To evaluate the results of resection of brain metastases from non-small-cell lung cancer, we reviewed our 16-year experience with 185 consecutive patients undergoing resection of brain metastases from 1974 to 1989, inclusive. There were 89 men and 96 women; ages ranged from 34 to 75 years (median 54). Sixty-five (35%) had synchronous and 120 (65%) metachronous brain metastases. Discounting the brain metastasis, 68 patients (37%) had stage I, 13 (7%) stage II, 62 (33%) stage IIIA, 30 (16%) stage IIIB, and 12 (6%) stage IV carcinoma. There was no significant difference in age, locoregional stage (TN), or histologic features in patients with synchronous versus metachronous lesions. The overall survival rates (n = 185) were as follows: 1 year, 55%; 2 years, 27%; 3 years, 18%; 5 years, 13%; and 10 years, 7% (median 14 months). There was no significant difference in survival between patients with synchronous and metachronous lesions. To evaluate the impact of locoregional stage and treatment of the primary site, we analyzed only those patients with synchronous brain metastases. Multivariate analysis demonstrated that locoregional stage had no significant effect on survival (p = 0.97), but complete resection of the primary disease significantly prolonged survival (p = 0.002). Therefore complete resection, and not stage, of the locoregional primary lesion is the primary determinant of survival in patients undergoing resection of brain metastases from non-small-cell lung cancer.

Actuarial Analysis↗

Measurement of brain tissue specific gravity using pycnometry.

In this paper we introduce and characterize pycnometry, a method used to measure fluid density, for determining a tissue's specific gravity. It uses a 2-ml glass pycnometer filled with distilled water to determine a tissue sample's displacement volume. The tissue's density is determined when it's weight is divided by this volume and specific gravity is computed by dividing the tissue density by the density of water. Pycnometry was validated using pre-calibrated glass, specific gravity standards over the range 1.03-1.26, and compared to the density gradient method using rat brain tissue. We observed that the specific gravity values obtained using pycnometry were highly correlated with the specific gravity standards (slope = 1.0107, r = 0.996) and with the density gradient column when tissue volumes larger than 0.120 ml were used with the pycnometer (slope = 1.0707, r = 0.9826). Good correlation was also observed between percent water content values computed using the Nelson equation with pycnometry or density gradient specific gravity values versus the measured percent water content values obtained with the wet weight/dry weight method. Pycnometry is an accurate, reproducible technique to measure tissue specific gravity and brain edema and is best suited for use in a laboratory that engages sporadically in brain edema measurement.

Animals↗

Paraspinal tumors: techniques and results of brachytherapy.

Because of their proximity to nerve roots and the spinal cord, it is frequently difficult to achieve complete resection of paraspinal tumors. We have used brachytherapy in an attempt to prevent local recurrence and its associated neurological sequelae. This report analyzes our experience with 35 patients to determine the feasibility, optimal techniques, and efficacy of this approach. The tumor types were non small-cell lung cancer (18), sarcomas (9), and other tumor types (8). Temporary, single plane implants using Ir-192 (median minimum peripheral dose 3000 cGy) were used in 21 patients, and permanent I-125 implants were used in 14 cases (median matched peripheral dose 12,500 cGy). Local control was achieved in 51% (18/35). However, local control was poor when lung cancers were implanted and in cases where the dura was exposed. Radiation myelitis did not occur despite the combined effects of previous external beam radiotherapy (N = 21) and brachytherapy. Our experience demonstrates that combined surgery and paraspinal brachytherapy can be performed with acceptable toxicity and is reasonably effective in preventing local relapse and its neurologic sequelae, particularly for tumors other than lung cancers.

Brachytherapy↗

Percutaneous radiofrequency neurolysis guided by computed tomography for the treatment of glossopharyngeal neuralgia.

The technique of radiofrequency neurolysis guided by computed tomography for the treatment of glossopharyngeal neuralgia is described. This technique has the advantage of being performed in a neutral head position, affording excellent visualization of the jugular foramen, and also of simulating radiographically the precise trajectory of the electrode. This procedure is of particular value in treating patients with neoplastic disease and those in whom the outlines of the jugular foramen are poorly visualized on fluoroscopy or plain radiography.

Aged↗

Tension pneumocephalus: treatment with controlled decompression via a closed water-seal drainage system. Case report.

The successful treatment of a patient with tension pneumocephalus by controlled decompression via external drainage is described. The advantage of the technique includes the immediate release of high pressure and the capability of maintaining constant low pressure to enable and facilitate sealing of dural tears. The method has been used in three other patients, leading to resolution of the tension pneumocephalus without recurrence or other complications.

Cerebrospinal Fluid Shunts↗

Measurement of brain tissue density using pycnometry.

A novel method to measure specific gravity (SG) of tissues, pycnometry (PYC), is described. This method utilizes a 2ml glass pycnometer filled with distilled H2O to determine the displacement volume of a tissue sample and an equation to compute SG from the sample's weight and the pycnometer's weight before and after adding the sample. The PYC method was validated using glass SG standards over the range 1.02-1.26, and against the column density gradient (DG) method using brain tissue from 250-300 g male rats. Factors which affect PYC accuracy, i.e. sample size, were also evaluated. Our results indicate that PYC SG values are highly correlated with the glass SG standards (slope = 1.0107, r = 0.9955, p less than 0.001), and highly correlated with DG when approximately 0.120 ml tissue samples are used in the pycnometer. The DG method was preferable to the PYC method, however, when small tissue samples, i.e. 0.60 ml or less, were used.

Animals↗

The effect of the aminosteroid U-78517G on peritumoural brain oedema.

U-78517G belongs to a novel group of compounds-aminosteroids (AS) which are potent inhibitors of central nervous system tissue lipid peroxidation and are devoid of classical glucocorticoid and mineralocorticoid activities. The AS have been found to possess cerebral protective properties against ischaemia, ischaemic oedema, trauma to the cerebrum and spinal cord and in sub-arachnoid hemorrhage. The possible efficacy of U-78517G in attenuating peritumoural oedema was examined in rats harbouring cerebral 9L gliosarcomas. 19 Sprague-Dawley rats were implanted intracranially with 9L gliosarcoma cells. On day 14 post implantation rats were randomized to control (no treatment n = 10) and AS treated animals (n = 9). On day 20 animals were sacrificed and six brain samples per rat were examined for the percentage of water content. Oedema was assessed with the wet/dry weight technique. The AS treated animals were found to have a significant increase in peritumoural oedema (+1.38%, P less than 0.001) possibly related to an increase in cerebral blood flow associated with AS treatment. Further studies are, however, underway to precisely clarify this unexpected observation.

Animals↗

Spinal cord blood flow in the rat under normal physiological conditions.

Regional spinal cord blood flow (SCBF) was measured in a group of rats under conditions of normothermia, normocarbia, normoxia, and normal blood pressure, using the hydrogen clearance technique. Regional SCBF in the cervical white matter was 26.8 +/- 1 (SE) ml/100 g/min and in the cervical gray matter 53.6 +/- 2.5; in the thoracic white matter it was 22.2 +/- 2.4 ml/100 g/min and in the thoracic gray matter 41.2 +/- 12/6 ml/100 g/min; and in the lumbar gray matter it was 52.3 +/- 1.9 ml/100 g/min. The effect of changes in blood pressure on SCBF (autoregulation) was investigated in nine rats. We have observed that SCBF remains relatively constant in the blood pressure range of 45 to 165 mm Hg and assumes a passive flow below or above this range.

Animals↗

Cerebrovasculr response to CO2 in edematous brain during either fentanyl or isoflurane anesthesia.

Cerebral blood flow response to changes in PaCO2 was studied in the edematous cerebral cortex of 19 patients with malignant supratentorial tumors using laser Doppler flowmetry technology. General anesthesia for craniotomy was induced with thiopental, 3-5 mg/kg i.v., and N2O, 60% in O2. In random sequence, 8 patients were assigned to receive fentanyl, 6 +/- 1.6 (SEM). mug/kg i.v.; the other 11 received isoflurane, 0.56% end-tidal + 0.07 (SEM). After a craniotomy bone flap was turned and the dura was opened, laser flowmetry probes were placed over surgically undisturbed cortex that was known to be edematous from preoperative CT and MRI scans. Flow index measurements were first made at hypocarbia (PaCO2 = 24.2 +/- 0.9 and 21.5 +/- 2.1 mm Hg for the fentanyl and isoflurane groups, respectively). Minute ventilation was then decreased and cortical flow index was remeasured with PaCO2 = 34.2 +/- 0.6 and 33.0 +/- 0.8 mm Hg for the fentanyl and isoflurane groups, respectively. Hypocarbia during fentanyl-supplemented N2O-O2 anesthesia resulted in a cortical flow index that was 70 +/- 8% of the flow index at near normocarbia (p <0.05). During isoflurane N2O-O2 anesthesia, however, there was a wide variety of responses to hypocarbia, including three patients whose flow indices increased markedly. The mean flow index during hypocarbia was significantly (p <0.05) lower during fentanyl-N2O anesthesia than it was during isoflurane-N2O anesthesia. There was no predictable relationship between the type of brain tumor and the CBF response to hypocapnia during isoflurane-N2O anesthesia. It is concluded that, in edematous brain, cerebral cortical blood flow response to hypocarbia is more likely to be preserved during fentanyl-supplemented N2O-O2 anesthesia than it is during isoflurane-supplemented N2O-O2 anesthesia. In neuropathologic states where hyperventilation is thought to be necessary to reduce cerebral blood flow and decrease brain bulk, isoflurane may be less satisfactory than fentanyl as a supplement to N2O-O2 anesthesia.

Journal Article↗