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Biomedical subjects

L Junck

Publications and source records attributed to L Junck.

66 records · Page 4Linked to original sources

Intra-arterial bromodeoxyuridine radiosensitization and radiation in treatment of malignant astrocytomas.

Bromodeoxyuridine (BUdR), a nonhypoxic radiosensitizing drug, is a halogenated pyrimidine analog that is incorporated into the deoxyribonucleic acid of dividing cells in a competitive process with thymidine; BUdR also sensitizes these cells to radiation therapy. Neurons and glial cells have a very low mitotic rate. They will not incorporate BUdR and will not be sensitized. Bromodeoxyuridine is best delivered intra-arterially because of its regional advantage, calculated to be between 6 and 16. An 8-week BUdR infusion is delivered before and during radiation therapy through a permanently implanted pump with a catheter placed retrograde into the external carotid artery. Eighteen patients with malignant glioma (15 grade IV, and three grade III) were entered into a Phase I dose-escalation protocol with BUdR dosages ranging from 400 to 600 mg/sq m/day. The maximum dose that can be tolerated appears to be 400 mg/sq m/day for 8 weeks. The 18 patients entered in this study have a median Kaplan-Meier estimated survival time (+/- standard error of the mean) of 22 +/- 5 months with 11 patients still alive. Three patients are alive at 30, 29, and 21 months after diagnosis with no evidence of tumor on computerized tomography. There have been no vascular complications. Side effects in all patients have included anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, iritis, and nail ridging. Myelosuppression requiring dose reduction occurred in one patient. One patient had a Stevens-Johnson syndrome requiring termination of BUdR. It is concluded that intra-arterial BUdR may improve survival times in patients with malignant gliomas.

Adult↗

In vivo measurement of brain tumor pH using [11C]DMO and positron emission tomography.

In vivo measurements of regional brain tissue/tumor pH (rpH) have been accomplished in 9 patients with primary or metastatic brain tumors using [11C]dimethyloxazolidinedione [( 11C]DMO) and positron emission tomography. Tumor rpH values ranged from 6.88 to 7.26, whereas gray matter and white matter rpH values ranged from 6.74 to 7.09 and from 6.77 to 7.03, respectively. Our results, which are consistent with reported [14C]DMO autoradiographic measurements of brain and tumor pH, suggest that the pH microenvironment of brain tumors is not more "acidic" than that of normal gray or white matter.

Adult↗

Effects of xenon and krypton on regional cerebral blood flow in the rat.

The effects of high inspired concentrations of xenon and krypton on regional CBF (rCBF) were assessed in the rat using [14C]iodoantipyrine and quantitative autoradiography. Inhalation of 80% xenon for 1 or 2 min and inhalation of 40% xenon for 2 min were found to have significant effects on rCBF, including average increases of 75-96% in cerebral neocortical regions. Inhalation of 40% xenon for 1 min and of 80% krypton for 2 min had no significant effect on rCBF in most brain regions studied. If xenon inhalation produces effects on rCBF in humans similar to those observed in the rat, such effects could be an important source of error in xenon computed tomography rCBF studies.

Animals↗

In vivo measurement of regional brain and tumor pH using [14C]dimethyloxazolidinedione and quantitative autoradiography.

Using [14C]dimethyloxazolidinedione ([14C]-DMO) and quantitative autoradiography, we estimated tissue pH (pHt) and intracellular pH (pHi) in nine regions of the normal rat brain and in intracerebrally implanted RG-2 gliomas. Calculations of regional pHt, based on equilibrium tissue and arterial plasma [14C]DMO concentration, ranged from 6.83 to 6.94; pHi, calculated assuming an extracellular water volume of 0.15 ml/g for gray matter and 0.11 ml/g for white matter, ranged from 6.61 to 6.78. No consistent difference was found in pHt or pHi between white and gray matter regions. Tumor tissue water content was determined by drying to constant weight, and extracellular space water volume (Ve) was estimated with [14C]sucrose in nephrectomized rats using quantitative autoradiography. Tumor pHt ranged from 7.08 to 7.18. For Ve = 0.17 (measured), pHi was 6.94-7.06; for Ve = 0.30 (assumed), the corresponding range for pHi was 6.63-6.90. Thus, the RG-2 glioma is not more "acidic" than adjacent brain tissue and its "alkaline" pHt probably reflects a large extracellular water content and plasma-like extracellular pH.

Animals↗

In vivo measurement of regional brain tissue pH using positron emission tomography.

Carbon-11-labeled dimethyloxazolidinedione ([11C]DMO) was injected intravenously into human subjects, and serial positron emission tomographic (PET) scans were obtained until brain-blood equilibration was achieved or could be accurately predicted from dynamic PET and 11C blood data. Knowledge of regional brain-blood partition coefficients for DMO, together with measurements of arterial blood hematocrit and pH, permitted the calculation of regional brain tissue and tumor pH (rpH). [11C]DMO PET rpH values were similar to rpH values derived from quantitative autoradiographic measurements of [14C]DMO concentrations in rat brain slices.

Brain↗

Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system.

Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.

Adult↗

Neurotoxicity of radiological contrast agents.

The most important complications of intravascular administration of contrast agents include idiosyncratic (anaphylactoid) reactions, shock, congestive heart failure, cardiac arrhythmias, acute renal failure, and neurotoxic effects. The incidence of serious neurotoxic effects is low. Entry of contrast agents into the central nervous system normally is limited but may be increased by osmotic opening of the blood-brain barrier with cerebral arteriography or arch aortography. Most neurotoxic effects are thought to represent direct effects of the contrast agent on brain or spinal cord. Adverse effects with arteriography include seizures, transient cortical blindness, brain edema, and spinal cord injury. Most cases of focal brain deficit (other than cortical blindness) are attributed to embolism secondary to the catheter. Seizures may occur with intravenous administration, especially in patients with brain tumors or other processes disrupting the blood-brain barrier. The most important adverse effects observed with myelographic agents include acute and chronic meningeal reactions with iophendylate, and seizures and transient encephalopathy with metrizamide.

Animals↗

C-11 dimethyloxazolidinedione (DMO): biodistribution, radiation absorbed dose, and potential for PET measurement of regional brain pH: concise communication.

An improved radiochemical synthesis for C-11 dimethyloxazolidinedione (C-11 DMO) makes this agent attractive for the measurement of regional brain tissue pH (rpH) using positron emission tomography (PET). Toward this end, biodistribution data for C-14 DMO in rats at various times after an intravenous bolus injection are reported, together with estimates of radiation absorbed dose for C-11 DMO in man. An error analysis of C-11 DMO PET measurement of rpH indicates that rpH can be determined to within +/- 0.1 pH unit for pH greater than 6.5 with a 20-mCi injected bolus of C-11 DMO, a 30- 45-min equilibration time, and a 15-min PET imaging period.

Animals↗

Prolonged brain retention of contrast agent in neonatal herpes simplex encephalitis.

A neonate with herpes simplex encephalitis type 2 manifested progressively increasing density of the gray matter on serial computed tomographic scans. Postmortem examination of the brain proved the cause of the increased density to be a high concentration of iodine that had been retained following the intravenous administration of sodium diatrizoate 25 and 16 days previously. This demonstrates that a water-soluble iodinated contrast agent or its iodine component may be retained in the brain for a prolonged period of time. It is recommended that such agents be avoided when possible in neonates with herpes simplex encephalitis.

Brain↗

Cerebral distribution of contrast medium during slow intracarotid infusion.

A prospective study was performed to evaluate in vivo the uniformity of cerebral distribution of iodinated contrast medium during slow intraarterial injection at rates used for chemotherapy installation in the internal carotid artery. We evaluated seven patients with primary intracranial neoplasms with routine film-screen angiography and with digital angiography during slow infusion. In six internal carotid artery injections the distribution of contrast material was identical during the late arterial phase of routine angiography and the digital study. In three vertebral artery injections the opacification during the slow infusion was inadequate to make meaningful comparison. Our results indicate that solutions infused into the internal carotid artery at rates as low as 0.25 ml/sec are distributed well throughout the carotid territory opacified during the late arterial phase of film-screen angiography.

Angiography↗