Biomedical subjects

L Junck

Publications and source records attributed to L Junck.

At least 55 records · Page 3Linked to original sources

PubMed1990

Cerebral glucose hypermetabolism in Friedreich's ataxia detected with positron emission tomography.

Local cerebral metabolic rate for glucose was studied with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 22 patients with Friedreich's ataxia and 23 age-matched normal control subjects. The diagnosis of Friedreich's ataxia was established by the history and physical findings and by excluding other diseases through laboratory investigations. PET studies revealed a statistically significant widespread increase of local cerebral metabolic rate for glucose in the brains of patients with Friedreich's ataxia who were still ambulatory, in comparison with normal control subjects. Nonambulatory patients with Friedreich's ataxia, in comparison with normal control subjects, had significantly increased local cerebral metabolic rates for glucose in the caudate and lenticular nuclei, but not in the other structures studied. The rate was significantly greater in ambulatory patients with Friedreich's ataxia than in nonambulatory patients in all structures studied except the caudate and lenticular nuclei. The data suggest that early in the course of Friedreich's ataxia, the local cerebral metabolic rate for glucose is increased extensively in the central nervous system, and as the disease progresses, it decreases in a regionally specific manner.

Adolescent↗

PubMed1990

Random sampling by glitter drop method.

In the course of a study on glioblastoma tissue and cultured cell lines, a glitter drop technique for random sampling was introduced (1). Here, we report the initial description of the details of this procedure and its application to cell counts from explant slides and to determining bromodeoxyuridine (BUdR) labeling indices (LI) in tissues. The method is without bias, easy to perform and takes only a short time. It compares well with three other generally used random sampling procedures.

Bromodeoxyuridine↗

PubMed1990

Intra-arterial bromodeoxyuridine radiosensitization of malignant gliomas.

In the 1950's it was first observed that mammalian cells exposed to the halogenated deoxyuridines were more sensitive to ultraviolet light and radiation than untreated cells. This prompted early clinical trials with bromodeoxyuridine (BUdR) which showed mixed results. More recently, several Phase I studies, while establishing the feasibility of continuous intravenous (IV) infusion of BUdR, have reported significant dose limiting skin and bone marrow toxicities and have questioned the optimal method of BUdR delivery. To exploit the high mitotic activity of malignant gliomas relative to surrounding normal brain tissue, we have developed a permanently implantable infusion pump system for safe, continuous intraarterial (IA) internal carotid BUdR delivery. Since July 1985, 23 patients with malignant brain tumors (18 grade 4, 5 grade 3) have been treated in a Phase I clinical trial using IA BUdR (400-600 mg/m2/day X 8 1/2 weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy/day in 6 1/2 weeks). Following initial biopsy/surgery the infusion pump system was implanted; BUdR infusion began 2 weeks prior to and continued throughout the 6 1/2 week course of radiotherapy. There have been no vascular complications. Side-effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. Myelosuppression requiring dose reduction occurred in one patient. An overall Kaplan-Meier estimated median survival of 20 months has been achieved. As in larger controlled series, histologic grade and age are prognostically significant. We have shown in a Phase I study that IA BUdR radiosensitization is safe, tolerable, may lead to improved survival, and appears to be an efficacious primary treatment of malignant gliomas.

Adult↗

PubMed1990

The ocular effects of intracarotid bromodeoxyuridine and radiation therapy in the treatment of malignant glioma.

Since July 1985, 23 patients have been entered into a phase I/II clinical trial using intraarterial 5-bromodeoxyuridine (BUdR) (400-600 mg/m2 daily for 8.5 weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy daily in 6.5 weeks) in the treatment of malignant gliomas (Kernohan grades 3 and 4). The side effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. Mucopurulent conjunctivitis and exposure keratitis developed in several patients and spontaneous corneal perforation developed in one. Eyes from two individuals examined at autopsy showed significant changes. Animal studies that predated clinical trials using rhesus monkeys did not predict the ophthalmologic complications seen in human subjects.

Adult↗

PubMed1990

Nuclear parameters as prognostic indicators in glioblastoma patients.

The objective of this study was to determine whether nuclear parameters were associated with prognosis in glioblastoma multiforme. DNA indices, cell cycle parameters, and nuclear population densities were compared with patient survival. Selection criteria included the pathologic diagnosis of a cerebral glioblastoma multiforme, absence of therapy before surgery, and adequate tissue to measure each nuclear parameter studied. Nine cases accrued over a two year period. The amount of DNA per nucleus was quantified in fresh tissue specimens by nuclear-isolation flow cytometry in Vindelov's solution. One particular association was significant when tested by Cox models: The percentage of nuclei with S-phase amounts of nuclear DNA was a significant predictor of decreased survival (regression coefficient = 0.20, p = 0.04). The percentage of nuclei in the G0/G1 peak was marginally associated with longer survival. These data are evidence of an association between nuclei in certain phases of the DNA cell cycle and postoperative survival.

Adolescent↗

PubMed1990

Procarbazine chemotherapy in the treatment of recurrent malignant astrocytomas after radiation and nitrosourea failure.

The Brain Tumor Study Group has shown procarbazine (PCB) to be as effective an adjuvant treatment as 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). We treated 35 patients with recurrent malignant astrocytomas after radiation and nitrosourea failure with successive courses of PCB 150 mg/m2/d for 28 days every 8 weeks. After 2 courses, 2 patients had complete responses, 7 had partial responses, 11 had stable disease, and 15 had progression. Significantly more patients receiving PCB had complete or partial responses or stable disease than a similar group of patients in a previous trial who received intra-arterial (IA) cisplatin (DDP). There is a significant advantage in time to disease progression for those receiving PCB compared with those receiving IA diaziquone (AZQ). Our results suggest that PCB is a more effective 2nd agent than IA DDP or AZQ following radiation and nitrosourea failure.

Adult↗

PubMed1990

Correlation methods for the centering, rotation, and alignment of functional brain images.

Simple methods are described using correlation analysis to rotate functional brain images to a standard vertical orientation, identify the antero-posterior centerline, and align multiple images from the same brain level. Image rotation and centering are performed by determining the angle of rotation and centerline coordinate that result in maximal left-right correlation. Testing of this method on sets of multiple images acquired simultaneously through different brain levels suggests that the optimal rotation can be determined within 1 degree and the centerline within 0.3 mm. Spatial alignment of two or more images from the same brain level of a single subject is accomplished by finding the translation and rotation that yield the highest correlation between the images. Testing of the alignment method on sets of simultaneously acquired images at multiple brain levels suggests that the optimal translation can be determined within 0.45-0.69 mm and the optimal rotation within 0.8 degrees. These methods are completely objective and can easily be automated.

Aged↗

PubMed1989

PET imaging of human gliomas with ligands for the peripheral benzodiazepine binding site.

Human gliomas were imaged in vivo using ligands for the peripheral-type benzodiazepine binding site (or omega 3 binding site) and positron emission tomography (PET). Although gliomas have a high density of the peripheral-type benzodiazepine binding site, PET scans with a selective ligand for this site, [11C] Ro5-4864, failed to demonstrate higher radioactivity levels in human gliomas than in brain. In vitro studies of surgically removed specimens of human glioma demonstrated little binding of Ro5-4864 but high levels of binding of another selective ligand, PK 11195. Scans with [11C]PK 11195 demonstrated increased radioactivity in glioma compared to brain in 8 of 10 patients. Radioactivity in tumor and the ratios of radioactivity in tumor to that in remote gray and in white matter correlated significantly with the specific activity of [11C]PK 11195, suggesting that accumulation represents saturable high-affinity binding. We conclude that the PK 11195 manifests greater binding than Ro5-4864 to the peripheral-type benzodiazepine binding site on human gliomas and that human gliomas can be successfully imaged using [11C]PK 11195 and PET.

Benzodiazepinones↗

PubMed1989

Intra-arterial cisplatin for the treatment of malignant gliomas.

Cisplatin (DDP) is a chemotherapeutic agent that has shown efficacy against primary CNS malignancies. Intra-arterial (IA) administration of DDP to patients with brain tumors should produce higher peak levels of drug than intravenous (IV) administration of an identical dose and reduce systemic toxicity. Twelve patients with malignant glioma were entered into the study. All had failed irradiation, 11 had failed IA BCNU. Each patient received IA DDP, 58-100 mg/m2, into the internal carotid artery at four to six week intervals. One of 12 patients had a partial response of 6 months. The remaining 11 patients had progressive disease or severe complications. Toxicity included seizures in four patients, weakness and/or aphasia in four patients, coma in two patients, and visual deterioration in two patients. IA DDP has very limited efficacy in patients with malignant gliomas after failure of nitrosoureas and is associated with an unacceptable level of toxicity. IA DDP may be more effective when used as initial chemotherapy of malignant gliomas.

Adolescent↗

PubMed1989

Mixing in the human carotid artery during carotid drug infusion studied with PET.

The safety and efficacy of drug infusion into the carotid artery require adequate mixing of the infused solution with carotid blood. Using positron emission tomography (PET), we studied the mixing of solutions infused into the human carotid artery in seven patients by analyzing the distribution of [15O]H2O infused into the carotid artery and by vein. At four infusion rates ranging from 0.5 to 10 ml/min, the variability in distribution averaged 16.5-17.8% among the pixels in a large volume of interest, without dependence on the infusion rate. The overall correlation between [15O]H2O influx with arterial infusion and [15O]H2O influx with venous injection was 0.78-0.82 at the four infusion rates, with no trend toward higher correlations at the faster infusion rates. The distribution into the anterior, middle, and posterior cerebral artery territories differed from distribution throughout the entire carotid territory by an average of 6.2-9.6% at the four infusion rates, with no trend toward smaller differences at the faster infusion rates. Infusions performed into a vinyl tube simulating the carotid artery indicated that at 0.5 ml/min, the velocity of fluid exiting the catheter makes no apparent contribution to mixing. We conclude that with infusions at the carotid bifurcation, mixing in the human carotid artery is complete or nearly complete over a wide range of infusion rates. The mixing appears to result from the patterns of blood flow within the artery, and not from jet effects at the catheter tip.

Adult↗

PubMed1989

Progression of hydrocephalus during corticosteroid therapy for neurosarcoidosis.

We describe a patient with sarcoid meningitis and hydrocephalus who improved rapidly after initiation of oral prednisone therapy, but who later decompensated acutely and required an emergency ventriculoperitoneal shunt. Hydrocephalus associated with neurosarcoidosis may progress despite steroid treatment, even when symptoms have improved. If hydrocephalus associated with neurosarcoidosis is treated with corticosteroids and without a shunt procedure we suggest that the corticosteroids should be continued at high doses for a prolonged period.

Adult↗

PubMed1989

Idiopathic intracranial hypertension (pseudotumor cerebri): MR imaging.

Magnetic resonance (MR) imaging was performed on six patients with idiopathic intracranial hypertension (IIH). The patients were all women with a mean age of 27 years (range, 17-41 years). Six healthy women volunteers with a mean age of 33 years (range, 25-46 years) were studied for comparison. All six patients had elevated opening pressures at lumbar puncture. MR imaging demonstrated a partially empty sella in two patients, and one patient had signal aberration in the dural venous sinuses suggestive of slow flow. There were no white matter signal abnormalities, even in the periependymal space. Volumetric pixel analysis revealed significantly larger subarachnoid space volumes in patients than in control subjects, without a significant difference in ventricular volumes. No other intracranial abnormalities were found in any IIH patient or control subject. The results suggest that, in IIH, (a) although the subarachnoid spaces are enlarged, the wide range of normal values would limit the clinical use of these measurements and (b) the role of MR imaging, as with CT, is primarily in the exclusion of other diseases with clinical presentations similar to that of IIH.

Adolescent↗

PubMed1988

Isoquinoline and peripheral-type benzodiazepine binding in gliomas: implications for diagnostic imaging.

Binding of the isoquinoline PK 11195 and of the benzodiazepines Ro5-4864 and flunitrazepam was compared in glioma cells and tissues. In human and rat glioma cell cultures [3H]PK 11195 bound with higher affinity (Kd = 14.01 and 15.76 nM, respectively) than either Ro5-4864 (Ki = 1200 and 84.9 nM, respectively) or flunitrazepam (Ki greater than 10,000 and = 848 nM, respectively). Autoradiograms of postmortem human brain sections containing glioma revealed that [3H]PK 11195 bound specifically to intact tumor cells and not to cells of normal cerebral cortex or necrotic areas of the tumor. Total [3H]Ro5-4864 or [3H]flunitrazepam binding to these sections was indistinguishable from nonspecific binding, and regions of tumor and normal brain could not be delineated. These results support the use of radiolabeled PK 11195 for clinical trials of imaging human gliomas by positron emission tomography.

Benzodiazepines↗

PubMed1988

Cerebellar and brainstem hypometabolism in olivopontocerebellar atrophy detected with positron emission tomography.

We studied local cerebral metabolic rates for glucose (1CMRglc) with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 30 patients with olivopontocerebellar atrophy (OPCA) and 30 age-matched control subjects without neurological disease. The diagnosis of OPCA was based on the history and physical findings and on the exclusion of other causes of cerebellar ataxia by means of laboratory investigations. Computed tomographic scans revealed some degree of atrophy of the cerebellum in most patients with OPCA, and many also had atrophy of the brainstem. PET studies in these patients revealed significant hypometabolism in the cerebellar hemispheres, cerebellar vermis, and brainstem in comparison with the normal control subjects. A significant relationship was found between the degree of atrophy and the level of 1CMRglc in the cerebellum and brainstem. Nevertheless, several patients had minimal atrophy and substantially reduced 1CMRglc, suggesting that atrophy does not fully account for the finding of hypometabolism. 1CMRglc was within normal limits for the thalamus and cerebral cortex. The data suggest that PET/1CMRglc may be useful as a diagnostic test in patients with the adult onset of cerebellar ataxia.

Adult↗

PubMed1988

Speech disorders in olivopontocerebellar atrophy correlate with positron emission tomography findings.

We compared the severity of ataxic and spastic dysarthria with local cerebral metabolic rates for glucose (lCMRGlc) in 30 patients with olivopontocerebellar atrophy (OPCA). Perceptual analysis was used to examine the speech disorders, and rating scales were devised to quantitate the degree of ataxia and spasticity in the speech of each patient. lCMRGlc was measured with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET). PET studies revealed marked hypometabolism in the cerebellar hemispheres, cerebellar vermis, and brainstem of OPCA patients compared with 30 control subjects. With data normalized to the cerebral cortex, a significant inverse correlation was found between the severity of ataxia in speech and the lCMRGlc within the cerebellar vermis, cerebellar hemispheres, and brainstem, but not within the thalamus. No significant correlation was found between the severity of spasticity in speech and lCMRGlc in any of these structures. The findings support the view that the severity of ataxia in speech in OPCA is related to the functional activity of the cerebellum and its connections in the brainstem.

Adult↗

PubMed1988

Motor dysfunction in olivopontocerebellar atrophy is related to cerebral metabolic rate studied with positron emission tomography.

We compared the severity of motor dysfunction with local cerebral metabolic rates for glucose (lCMRGlc) and the degree of tissue atrophy in 30 patients with olivopontocerebellar atrophy (OPCA). We devised a scale to quantitate the degree of ataxia in the neurological examinations. lCMRGlc was measured with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET). Tissue atrophy was assessed by visual rating of computed tomographic scans. PET studies revealed marked hypometabolism in the cerebellar vermis, cerebellar hemispheres, and brainstem of OPCA patients compared with 30 control subjects. A significant correlation was found between severity of motor impairment and lCMRGlc within the cerebellar vermis, both cerebellar hemispheres, and the brainstem. A significant but weaker relationship was noted between the degree of tissue atrophy in these regions and clinical severity. Partial correlation analysis revealed that motor dysfunction in OPCA correlated more strongly with lCMRGlc than with the amount of tissue atrophy. These results suggest that the clinical manifestations of OPCA are more closely related to the metabolic state of the tissue than to the structural changes in the cerebellum.

Adult↗

PubMed1988

Radioiodinated benzodiazepines: agents for mapping glial tumors.

Two isomeric iodinated analogues of the peripheral benzodiazepine binding site (PBS) ligand Ro5-4864 have been synthesized and labeled in high specific activity with iodine-125. Competitive binding assays conducted with the unlabeled analogues indicate high affinity for PBS. Tissue biodistribution studies in rats with these 125I-labeled ligands indicate high uptake of radioactivity in the adrenals, heart, and kidney--tissues known to have high concentrations of PBS. Preadministration of the potent PBS antagonist PK 11195 blocked in vivo uptake in adrenal tissue by over 75%, but to a lesser degree in other normal tissues. In vivo binding autoradiography in brain conducted in C6 glioma bearing rats showed dense, PBS-mediated accumulation of radioactivity in the tumor. Ligand 6 labeled with 123I may have potential for scintigraphic localization of intracranial glioma.

Animals↗

PubMed1988

A relationship between metabolism in frontal lobes and cerebellum in normal subjects studied with PET.

Lesions of one cerebral hemisphere are associated with decreased glucose metabolism, oxygen metabolism, and blood flow in the contralateral cerebellar hemisphere. We used positron emission tomography to look for a functional relationship in cerebral metabolism between the cerebral cortex and the contralateral cerebellum in normal human subjects. Twenty-four normal subjects were scanned with [18F]fluoro-2-deoxy-D-glucose while in a resting state. Asymmetry in local CMRglu (LCMRglu) in the frontal cortex was strongly correlated with asymmetry in LCMRglu in the opposite direction in the cerebellar hemispheres (r = -0.60, p less than 0.001). Widespread subregions of the frontal cortex were found to contribute to this relationship. Considering these results together with previous studies demonstrating that frontal lesions are associated with decreased metabolism in the contralateral cerebellum, we conclude that the frontal cortex exerts a strong modulating influence on metabolism in the contralateral cerebellum in normal subjects, and that this influence may be asymmetrical.

Adolescent↗