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Biomedical subjects

R M Kessler

Publications and source records attributed to R M Kessler.

At least 55 records · Page 3Linked to original sources
PubMed1990

Gadolinium-enhanced MR angiography.

Experience in three patients (one each with meningioma, pineal tumor, and prominent jugular bulb) illustrates that magnetic resonance (MR) angiography can benefit from the administration of gadolinium diethylenetriaminepentaacetic acid. Data were acquired with a three-dimensional velocity-compensated (fast imaging with steady-state precession) sequence. MR angiograms were obtained with a ray projection algorithm by using maximum intensity values. Portions of the vascular anatomy--particularly venous structures and smaller arteries--were better portrayed on the postcontrast than on the precontrast angiograms. Enhancing lesions were also seen on the projection images. Enhancement of dura and extracranial tissues (sinus and nasal mucosa) can obscure vascular detail.

Adult↗
PubMed1990

Sodium-dependent isomerization of dopamine D-2 receptors characterized using [125I]epidepride, a high-affinity substituted benzamide ligand.

We have characterized the in vitro binding of a new ligand, [125I]epidepride, and used this substituted benzamide to assess the sensitivity of dopamine D-2 receptors to sodium. Both direct and indirect binding studies with [125I]epidepride and unlabeled epidepride, respectively, demonstrated that the affinity of D-2 receptors for the ligand was decreased from 20 to 30 pM in the presence of sodium to 350 to 500 pM in the absence of sodium. The density of binding sites for [125I]epidepride was identical in the presence and absence of NaCl. The time courses for association of [125I]epidepride to and dissociation from D-2 receptors in the presence of sodium were not consistent with simple bimolecular reactions, suggesting the possibility of a sodium-dependent ligand-induced receptor isomerization. Thus, dissociation of [125I]epidepride was biphasic in the presence of sodium, but monophasic in the absence of sodium. The rank order of potency for inhibition of [125I]epidepride binding by drugs was identical in rat striatum and cells expressing a D-2 receptor cDNA, and similar to the previously described pharmacological profile of D-2 receptors labeled by [3H]spiperone. [125I]Epidepride bound to two classes of binding sites in rat medial prefrontal cortex. One class, present at a density of 10 fmol/mg of protein and with a Kd value of approximately 40 pM, was pharmacologically indistinguishable from D-2 receptors in striatum and transfected cells. The pharmacological profile of the second class of sites was similar to that of alpha-2 adrenergic receptors. [125I]Epidepride had 50- to 100-fold lower affinity (approximately 2 nM) for alpha-2 receptors than for D-2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

(S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-[125I]iodo- 2-methoxybenzamide hydrochloride, a new selective radioligand for dopamine D-2 receptors.

From salicyclic acid, the two enantiomers of N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2-methoxybenzamide (6b) were prepared in a five-step synthesis. With use of Heindel's triazene method for introduction of the radionuclide, the iodine-125-labeled substituted benzamide was obtained with a calculated specific activity of 136 Ci/mmol and 14% radiochemical yield. For the preparation of the iodine-125-labeled benzamide with higher specific activity, this method was unsuccessful and utilization of the corresponding tri-n-butyltin derivative was required. Treatment of the latter in dilute hydrochloric acid with sodium iodide-125 and chloramine-T gave [125I](S)-6b in 56% radiochemical yield and at least 97% radiochemical purity. The displacement of [125I](S)-6b and [3H](S)-sulpiride from their respective binding sites in striatal rat brain homogenates using various neuroleptic agents showed that (S)-6b has the same binding profile but more potent binding for dopamine D-2 receptors than has sulpiride. These experiments also indicate that the S enantiomer of 6b is a specific ligand (KD = 1.2 nM) for the D-2 receptor. Further, the octanol-water partition coefficient of (S)-6b as determined by reverse-phase high-performance liquid chromatography was found to be 40 times greater than that for sulpiride. Thus (S)-6b has a lipophilicity that will allow a relatively higher uptake into the brain compared to sulpiride. In vivo experiments with rats show that [125I](S)-6b penetrates readily into the brain and is preferentially localized in the striatum as compared to the cerebellum, the ratio of uptake being 7.2 to 1, 60 min after injection. These observations of good brain penetration and high affinity and selectivity for D-2 receptors indicate that the corresponding iodine-123-labeled benzamide may be a useful ligand for the noninvasive visualization study of dopamine D-2 receptor sites in vivo by single photon emission computed tomography.

Animals↗
PubMed1988

Central nervous system lesions in pediatric patients: Gd-DTPA-enhanced MR imaging.

Twenty pediatric patients, aged 2-18 years, with known or suspected masses in the brain and/or spinal cord were studied with magnetic resonance imaging at 0.6T with and without use of 0.1 mmol/kg gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). The multisection, multiecho imaging mode was utilized. Surgically proved mass lesions included astrocytoma (n = 6), medulloblastoma (n = 2), ependymoma (n = 1), craniopharyngioma (n = 1), oligodendroglioma (n = 1), germinoma (n = 1) and fibrosarcoma (n = 1). Presumptive diagnoses included astrocytoma (n = 3), arachnoid cyst (n = 1), tuberous sclerosis (n = 1), cryptic vascular malformation (n = 1), and normal (n = 1). There was dramatic enhancement in 11 of 20 patients, with improved definition of the presence and extent of lesions in six patients. No adverse effects were noted in any of the 20 patients. It is concluded that Gd-DTPA is useful in delineating the presence, extent, and number of certain lesions of the central nervous system in children.

Adolescent↗
PubMed1987

MRI of mumps encephalitis: comparison with CT evaluation.

The evaluation of a patient with mumps encephalitis by computed tomography (CT) and magnetic resonance (MR) imaging is reported. Correlation of findings on MR and CT in relation to clinical symptoms is presented. MR was found to be more sensitive in the number of lesions detected (11) as compared to CT (3). Thus, it seems that MR imaging may be a sensitive diagnostic adjunct in cases of suspected viral encephalitis.

Child, Preschool↗
PubMed1987

Magnetic resonance brain tumor imaging in canine glioma.

This study investigates a canine model of experimental brain tumor. Particularly addressed was the usefulness of gadolinium contrast-enhanced MRI for differentiating brain tumor tissue from cerebral edema. Cultured canine glioma cells were injected into the left hemispheres of six adult mongrel dogs. All dogs developed brain tumors. Serum samples drawn prior to and serially after tumor inoculation showed development of antibodies reactive to the tumor. All tumors were visualized with MRI. Contrast-enhanced T1-weighted imaging was the most sensitive with gadolinium producing tumor enhancement due to blood-brain barrier breakdown. Gross and microscopic autopsy findings correlated well with MRIs.

Animals↗
PubMed1985

Clinical history, brain metabolism, and neuropsychological function in Alzheimer's disease.

Data concerning 7 patients with a diagnosis of presumptive Alzheimer's disease (mean age, 65.6 years) are presented in detail in relation to the patients' regional cerebral metabolic rates for glucose. Rates were measured by positron emission tomography with fluorine 18-labeled fluoro-2-deoxy-D-glucose under conditions of reduced visual and auditory stimulation. A relationship was found between severity of dementia and brain metabolism. In patients with mild to moderate Alzheimer's disease, memory and intellectual deficits were evident without major reductions in absolute metabolic rates, while ratios of regional to whole brain metabolism revealed reductions in regions of the parietal lobes. In the late, severe form of the disease, brain metabolic rates were consistently and significantly reduced. The findings suggest that memory and intellectual deficits are reflected in reductions of brain metabolism in some brain regions in mild to moderate forms of Alzheimer's disease and that, in the late, severe form of the disease, reductions occur consistently throughout the brain.

Aged↗
PubMed1985

Functional brain imaging.

Recent advances in brain imaging have allowed a regional examination of brain function using multiple-probe inert gas studies of cerebral blood flow, positron or single photon tomography. Inert gas blood flow methods using inhalation or injection of 133xenon have been used with multiple-probe systems to measure blood flow in 1 to 2 cm regions of lateral cortex. The sensitivity of these systems to neurophysiological stimuli and neurological diseases have been demonstrated in numerous studies of the normal resting state, memory and learning, motor activity and sensory input, dementia, and aphasia, to name some. Positron tomography utilizes cyclotron-produced, short-lived positron-emitting isotopes to label biologically active radiopharmaceuticals. Using positron tomographs capable of quantitative three-dimensional imaging and appropriate tracer-kinetic models, regional metabolic function, including glucose, oxygen, amino acid metabolism, and receptor-binding can be regionally studied throughout the brain. Clinical studies have been performed in dementia, schizophrenia, affective disorders, resting states, and sensory stimulation. Positron tomography offers potentially the greatest variety of studies and highest temporal and spatial resolution of any of the presently available functional brain-imaging modalities. Its principal drawback is the very high cost. Single photon tomography uses gamma-emitting isotopes such as 123iodine and 133xenon to image regional cerebral blood flow and recently receptor function. Although at present it does not have the variety of studies or the technical capabilities of positron tomography, it does provide three-dimensional studies with 1 to 2 cm resolutions throughout the brain at a considerably lower cost than positron tomography. In the future, magnetic resonance studies of blood flow or phosphorus metabolism may add a fourth modality.

Brain↗
PubMed1984

Measurement of blood-brain barrier permeability with positron emission tomography and [68Ga]EDTA.

Positron emission tomography (PET) was employed to examine time-dependent changes in blood-brain barrier (BBB) permeability to [68Ga]ethylenediaminetetraacetate (EDTA) in the rhesus monkey, following reversible barrier opening by intracarotid infusion of a hypertonic mannitol solution. The PET technique, when combined with measurements of plasma radioactivity, provided a quantitative measure of the cerebrovascular permeability-area product (PA) at different times following mannitol infusion. Hypertonic mannitol treatment reversibly increased PA to [68Ga]EDTA more than 10-fold; much of the barrier effect was over by 10 min after mannitol treatment. The results show that PET can be used to measure transient changes in BBB integrity in specific brain regions, under in vivo, noninvasive conditions.

Animals↗
PubMed1984

Analysis of emission tomographic scan data: limitations imposed by resolution and background.

The proper analysis of positron emission tomographic scan data requires a careful knowledge of the limitations of the tomographic system used so that scan data can be collected and sampled in a manner consistent with those limitations. The present investigation was undertaken to clarify some of the limitations imposed by resolution. The usual imaging situation, e.g., 218FDG , C15O2, or 15O2 , involves imaging structures of limited size in all three dimensions which may appear either warm or cool in relation to some background level of activity. In emission tomography the importance of adequate data sampling within a given plane has been frequently emphasized. Little attention, however, has been given to proper z axis sampling for clinical scanning. The actual selection of regions of interest from scans can have a significant impact on the subsequent statistical analysis. Previous work on this subject has experimentally examined the relationship of object size to quantitative estimation in the hot spot-cold background situation for the one- and two-dimensional cases. Approximate three-dimensional recovery coefficients for the hot spot-cold background situation have been calculated. An examination of the factors discussed above, three-dimensional objects with varying contrast, z axis sampling, and selection of regions of interest, has not yet been addressed in the literature. The purpose of the present investigation is to examine these factors.

Background Radiation↗
PubMed1983

Down's syndrome in adults: brain metabolism.

The cerebral metabolic rate for glucose, as measured with positron emission tomography and fluorine-18-labeled 2-deoxy-D-glucose, was significantly higher in four healthy young subjects with trisomy 21 syndrome (Down's syndrome) than the mean rate in healthy young controls. The rate of cerebral glucose utilization in the frontal lobe of a 51-year-old subject with Down's syndrome was significantly lower than the rate in the young subjects with this syndrome, but approximated the rate in middle-aged controls. Thus glucose utilization by the brain appears to be excessive in young adults with Down's syndrome but may decline with age in some brain regions.

Adult↗
PubMed1983

[18F]fluorodeoxyglucose positron emission tomography in refractory complex partial seizures.

Positron emission tomography with simultaneous electroencephalographic monitoring was performed with [18F]fluorodeoxyglucose in 20 patients with complex partial seizures who had normal computed tomographic scans. Seven patients had only unilateral epileptiform discharges on the electroencephalogram, 3 had predominantly unilateral discharges, and 10 had nonlocalized epileptiform abnormalities. Positron emission tomography showed a hypometabolic lesion in 16 of the 20 patients. Pathological changes in the hypometabolic region were found in postoperative specimens in 4 of 5 patients studied. Positron emission tomography was unaffected by the seizure frequency, state of alertness, or number of spike discharges during the scan. There was a tendency for patients to have higher overall metabolic rates when taking less medication. Seizures occurring during [18F]fluorodeoxyglucose uptake in 3 patients produced a hypermetabolic area at the interictal hypometabolic focus. Positron emission tomography sometimes showed more widespread hypometabolism than suspected on the basis of the scalp-recorded electroencephalogram. The frontal lobe showed a greater degree of hypometabolism than the temporal lobe in 3 patients. Focal lesions may be identified by positron emission tomography even if the electroencephalographic abnormality is not well localized.

Adult↗
PubMed1983

Localization of 111In- and 125I-labeled monoclonal antibody in guinea pigs bearing line 10 hepatocarcinoma tumors.

A murine monoclonal antibody (D3) with demonstrated specificity for the guinea pig line 10 hepatocarcinoma (L10) was radiolabeled with either 125I or 111In and used to image dermal tumors in vivo. In one set of experiments, L10 tumors were established middorsally in one group of animals, and the similarly derived, antigenically distinct line 1 tumor was established in another group of animals. In spite of background imaging of liver, kidney, and spleen, L10 tumors were visualized clearly. Incorporation of radiolabel was demonstrated to predominate in the L10 tumor. In a separate set of experiments, L10 and line 1 tumors were established in contralateral thighs in the same animals. L10 tumors were visualized clearly, and tissue uptake of radiolabel was demonstrated to reside predominantly in the L10 tumor.

Animals↗
PubMed1982

Handgrip exercise in normal young women: a noninvasive cardiovascular assessment.

Blood pressure, heart rate, and echocardiographic parameters of left ventricular size and shortening were measured both under baseline conditions and during handgrip exercise (50% maximum handgrip effort held to fatigue) in 20 normal women (20 through 29 years of age). As a group, there was a significant increase in heart rate (72 +/- 10 vs 83 +/- 12; P less than .001), systolic blood pressure (111 +/- 8 vs 133 +/- 14 mm Hg; P less than .001), diastolic blood pressure (67 +/- 8 vs 89 +/- 12 mm Hg; P less than .001), and calculated cardiac output (4.3 +/- 1.5 vs 5.2 +/- 1.7 liters/minute; P less than .005). There was no significant change in left ventricular internal dimension in diastole or systole, shortening fraction, or calculated stroke volume. The average group response of an increase in cardiac output secondary to an increase in heart rate is similar to that of male subjects in their second decade. Individual variability in responses was of specific interest since only three of the 20 women demonstrated a totally characteristic response to handgrip exercise. Handgrip exercise in young women may not provide a uniformly characteristic response from which to predict hemodynamic changes in a given individual and may lead to clinical misinterpretation if appropriate caution is not used.

Adult↗
PubMed1982

Work in progress: [18F] fluorodeoxyglucose and positron emission tomography in the evaluation of radiation necrosis of the brain.

Five patients who had undergone radiation therapy for cerebral tumors and whose conditions were deteriorating were examined by means of positron emission tomography (PET) with [18F] fluorodeoxyglucose. All five cases had similar clinical and computed tomographic findings. Using the PET technique the two cases of radiation necrosis were distinguished from the three recurrent tumors. In the two cases of radiation necrosis the rate of glucose utilization in the lesion was markedly reduced compared with the normal brain parenchyma. In the recurrent gliomas, however, the glucose metabolic rate was elevated. All five diagnoses were confirmed by biopsy or autopsy.

Astrocytoma↗