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Biomedical subjects

R M Kessler

Publications and source records attributed to R M Kessler.

At least 19 recordsLinked to original sources
PubMed1999

Retrospective intermodality registration techniques for images of the head: surface-based versus volume-based.

The primary objective of this study is to perform a blinded evaluation of two groups of retrospective image registration techniques, using as a gold standard a prospective marker-based registration method, and to compare the performance of one group with the other. These techniques have already been evaluated individually [27]. In this paper, however, we find that by grouping the techniques as volume based or surface based, we can make some interesting conclusions which were not visible in the earlier study. In order to ensure blindness, all retrospective registrations were performed by participants who had no knowledge of the gold-standard results until after their results had been submitted. Image volumes of three modalities: X-ray computed tomography (CT), magnetic resonance (MR), and positron emission tomography (PET) were obtained from patients undergoing neurosurgery at Vanderbilt University Medical Center on whom bone-implanted fiducial markers were mounted. These volumes had all traces of the markers removed and were provided via the Internet to project collaborators outside Vanderbilt, who then performed retrospective registrations on the volumes, calculating transformations from CT to MR and/or from PET to MR. These investigators communicated their transformations, again via the Internet, to Vanderbilt, where the accuracy of each registration was evaluated. In this evaluation, the accuracy is measured at multiple volumes of interest (VOI's). Our results indicate that the volume-based techniques in this study tended to give substantially more accurate and reliable results than the surface-based ones for the CT-to-MR registration tasks, and slightly more accurate results for the PET-to-MR tasks. Analysis of these results revealed that the rotational component of error was more pronounced for the surface-based group. It was also apparent that all of the registration techniques we examined have the potential to produce satisfactory results much of the time, but that visual inspection is necessary to guard against large errors.

Algorithms↗
PubMed1996

Multiple polyposis and adenocarcinoma arising in Barrett's esophagus.

Adenomatous polyps of the esophagus are rare in comparison with those of the lower gastrointestinal tract. Like adenomatous colon polyps, they have been associated with malignancy. We describe a case of early adenocarcinoma and multiple polyposis of the esophagus arising in a Barrett's epithelium, treated with surgical resection.

Adenocarcinoma↗
PubMed1996

Postsurgical outcome of patients with uncontrolled complex partial seizures and temporal lobe hypometabolism on 18FDG-positron emission tomography.

RATIONAL AND OBJECTIVE: The purpose of this study is to evaluate the relation between a focus of temporal lobe hypometabolism, including comparison between mesial and lateral asymmetry on fluorine-18-labeled-deoxyglucose-positron emission tomography (18FDG-PET) and surgical outcome in patients with uncontrolled partial seizures. METHODS: Case histories, electroencephalogram (EEG) findings, radiographic findings, and surgical outcome (36 +/- 11 months of follow-up) were reviewed in 38 consecutive patients who had a interictal 18FDG-PET scan and subsequent temporal resection. RESULTS: Among the 36 patients who had a temporal lobe focus of hypometabolism (more than 15% asymmetry to contralateral side), 61% (22 of 36) became seizure-free, 33% (12 of 36) markedly improved and 6% (2 of 36) did not improve. The focus of hypometabolism on PET was in agreement with the epileptic focus on the noninvasive EEG in 30 of 36 patients and in 19 of the 22 patients who underwent an invasive EEG. The asymmetry index for the mesial temporal lobe was significantly higher in the group of patients who became seizure-free compared with the other patients. CONCLUSION: This study confirms that a focus of interictal temporal hypometabolism on PET is associated with marked improvement of seizure control after surgery in 94% (34 of 36) of the patients. Hypometabolism in the mesial temporal lobe appears to be associated with a seizure-free outcome.

Adolescent↗
PubMed1996

Intrapleural fibrinolytics in management of empyema thoracis.

STUDY OBJECTIVE: To determine the success and complication rates of fibrinolytic therapy (FL) in the treatment of thoracic empyema. DESIGN AND PATIENTS: Between December 1992 and November 1994, all patients referred with empyema thoracis (ET) were offered FL. FL consisted of streptokinase (275,000 +/- 170,000 IU) or urokinase (121,000 +/- 57,000 IU) daily for a mean of 6.2 +/- 2.1 days. SETTING: The University of New Mexico Health Sciences Center and the Albuquerque Veterans Affairs Medical Center. RESULTS: Twenty-six patients were treated. Sixty-two percent (16/26) had complete resolution (CR) of symptoms, near or complete normalization of chest radiographic findings, and required no surgery or empyema tubes. Eight percent (2/26) had relief of symptoms and partial resolution (PR) of radiographic abnormalities and were discharged from the hospital with empyema tubes in place. All patients with PR had empyema tubes removed within 30 days of hospital discharge. Thirty-one percent (8/26) of patients failed to completely improve clinically or radiographically (nonresponse) and were treated with decortication or empyema tubes for greater than 30 days. Bleeding occurred in a single patient (4%). There was no mortality associated with FL use. CONCLUSIONS: The use of FL is associated with resolution of ET in 69% (18/26) of patients. This modality is safe, effective, and spares most patients with empyema the morbidity and mortality of thoracotomy.

Adult↗
PubMed1995

Evaluating contrast-enhancing brain lesions in patients with AIDS by using positron emission tomography.

OBJECTIVE: To determine whether a noninvasive method for evaluating contrast-enhancing brain lesions in patients with the acquired immunodeficiency syndrome (AIDS) can accurately differentiate between lymphoma and nonlymphoma diagnoses. This method is based on Toxoplasma serologic testing and positron emission tomography. DESIGN: Prospective, nonrandomized, criterion-standard clinical study. SETTING: An academic center in the mid-southeastern United States. PATIENTS: 20 patients with AIDS and contrast-enhancing brain lesions. INTERVENTIONS: Positron emission tomographic scanning and Toxoplasma serologic testing. MAIN OUTCOME MEASURE: Diagnoses were confirmed by clinical response, autopsy, or brain biopsy. RESULTS: Eight patients had a confirmed diagnosis of toxoplasmosis, six had lymphoma, four had other diagnoses, and two were not evaluable. Seven of eight patients with toxoplasmosis had positron emission tomographic scans; all of these scans showed hypometabolic lesions consistent with a nonlymphoma diagnosis. The six patients with lymphoma all had hypermetabolic lesions on positron emission tomographic scans. The difference between these two sets of results was statistically significant (P < 0.001, Fisher exact test, two-tailed). The anti-Toxoplasma titer was greater than or equal to 1:4 in all patients with confirmed toxoplasmosis who had serologic testing and in three of six patients with lymphoma. CONCLUSIONS: Evaluating contrast-enhancing brain lesions in patients with AIDS by using Toxoplasma serologic testing and positron emission tomography can accurately guide therapy and obviate the need for most brain biopsies in these patients. A larger, national, multicenter study is needed to confirm our findings and to determine the effect of earlier diagnosis and treatment on morbidity and mortality in patients with AIDS and primary central nervous system lymphoma.

AIDS-Related Opportunistic Infections↗
PubMed1995

Esophago-airway fistula in AIDS.

Fistula formation between the esophagus and airway in acquired immunodeficiency syndrome is extremely unusual. We report 2 cases, the first in a patient who did not undergo definitive surgical management and died shortly after diagnosis. The second patient was managed successfully for 5 months by insertion of a Celestin endoesophageal prosthesis. This procedure can be performed with low morbidity and mortality, and may become the treatment of choice for this complex problem.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Inhibitory motor seizures: correlation with centroparietal structural and functional abnormalities.

Six adults and 2 children with focal inhibitory motor seizures (ictal paralysis) were evaluated during a 4-year period. Paresthesias at seizure onset occurred during some seizures in all patients, and focal clonic activity followed paralysis in 4. EEG-CCTV recordings of the seizures in 2 patients showed that ictal paralysis coincided with an ictal discharge starting in one centroparietal area. MRI showed centroparietal structural lesions in six patients. One patient with a normal MRI scan had right centroparietal hypometabolism on PET. Inhibitory motor seizures must be differentiated from transient ischemic attacks and migraine. In our patients a centroparietal epileptogenic focus was suggested by neuroimaging studies, and in 2 instances by ictal EEG.

Adolescent↗
PubMed1995

Optimal cutoff levels of F-18 fluorodeoxyglucose uptake in the differentiation of low-grade from high-grade brain tumors with PET.

PURPOSE: To determine the optimal cutoff level of fluorine-18-labeled fluorodeoxyglucose (FDG) uptake in the differentiation of low-grade from high-grade cerebral tumors at position emission tomography (PET). MATERIALS AND METHODS: The authors retrospectively reviewed images from PET, magnetic resonance imaging, and computed tomography performed in 58 consecutive patients with histologically proved brain tumors. There were 32 high-grade tumors (20 gliomas) and 26 low-grade tumors (18 gliomas). RESULTS: The best cutoff level of FDG uptake ratios in the differentiation of high-grade from low-grade tumors was 1.5 for tumor-to-white matter (T/WM) ratios and 0.6 for tumor-to-cortex (T/C) ratios. These levels were the same when only gliomas were analyzed and when all tumors were analyzed. When a T/WM ratio of more than 1.5 was considered indicative of a high-grade tumor, the sensitivity and specificity were 94% and 77%, respectively. The results were similar for the T/C ratio. CONCLUSION: Cutoff levels of 1.5 for the T/WM FDG uptake ratio and 0.6 for the T/C ratio are useful in the differentiation of low-grade from high-grade gliomas with PET.

Adult↗
PubMed1995

FDG-SPECT: correlation with FDG-PET.

UNLABELLED: The clinical utility of FDG-PET imaging in the evaluation of patients with cardiac, oncologic and neurologic diseases is well documented. The major disadvantages of PET continue to be its high cost and limited availability. METHODS: With the goal of providing equivalent diagnostic information using a widely available, less expensive modality, we evaluated the clinical utility of FDG-SPECT imaging with a conventional dual-headed camera as compared to PET in 21 patients. RESULTS: To compare the image quality of the two modalities, major physical parameters and phantom determinations were obtained. By using the 511-keV collimators, we achieved resolution and system volume sensitivity that were less than those for PET by factors of 2.6 and 8, respectively. The SPECT system, on the other hand, could easily resolve 2 x 0.5-cm cold defects in the heart phantom and 2-cm hot lesions in a 22-cm cylindrical phantom with a target-to-background ratio of 5:1. FDG-SPECT imaging of nine patients with heart disease yielded similar diagnostic information of the amount of viable myocardium present when compared to PET. In seven of eight patients, malignant tissue visualized with FDG-PET was seen equally well with SPECT. The lesions not visualized with FDG-SPECT were either small (< or = 1.5 cm) or benign. SPECT imaging of four patients with cerebral lesions was inconclusive due to the small sample size but seemed promising. CONCLUSION: FDG-SPECT with 511-keV collimation is less expensive, more available and technically simpler than PET. We believe that FDG-SPECT has achieved sufficient sensitivity and resolution to detect myocardial viability and diagnose malignant tumors > or = 2 cm in diameter.

Adult↗
PubMed1995

Dosimetry of iodine-123-epidepride: a dopamine D2 receptor ligand.

UNLABELLED: Substituted benzamides have been shown to have very high affinity and specificity for the dopamine D2 receptor. One of these is radiolabeled epidepride, an iodine-substituted benzamide currently under evaluation as a SPECT imaging agent. Detailed estimates of the radiation absorbed dose to 26 organs and the whole body from [123I]epidepride have been calculated. METHODS: The dosimetry calculations use a combination of in vivo uptake and biodistribution data from one rhesus monkey and seven humans to estimate residence times in eight organs. The computer program MIRDOSE2 was used to calculate the dosimetry. RESULTS: Results indicate that 75% of the radioactivity is cleared through the urinary tract while the remaining radioactivity clears through the gallbladder and intestinal tract. The radiation absorbed dose can be minimized by administering a high lipid content meal 1.5 hr postinjection to empty the gallbladder and by giving large volumes of fluids throughout the study to induce increased urinary output. CONCLUSION: By emptying the gallbladder and urinary bladder, the lower large intestine becomes the critical organ, 0.102 mGy/MBq (0.38 rad/mCi) followed by the upper large intestine, 0.092 mGy/MBq (0.34 rad/mCi). The effective dose equivalent is 0.025 mSv/MBq (0.092 rem/mCi).

Animals↗
PubMed1994

Aromatic and amine substituent effects on the apparent lipophilicities of N-[(2-pyrrolidinyl)methyl]-substituted benzamides.

Lipophilic properties of 92 dopamine D-2 receptor antagonists belonging to the substituted benzamide class of compounds (orthopramides and methoxysalicylamides) were determined by octadecylsilane reversed-phase HPLC. The apparent lipophilicity at pH 7.5 (log kw) was obtained from the chromatographic capacity factors in 0.02 M3-(morpholino)propanesulfonic acid (MOPS) buffer at various concentrations of methanol. The experimental log kw values were validated by comparison with the apparent octanol-water partitioning (log Papp) of 15 compounds of low to medium lipophilicity. The global lipophilicity of the neutral molecule (log kwo) was obtained by correcting for ionization of the amine and the phenol, using known relationships for the effects on the pKa (where Ka is the dissociation constant) of aromatic and aliphatic substituents. Multiple regression analysis showed that log kwo can be expressed as the sum of pi contributions and a cross correlation term (sigma rho sigma) for interactions between the aromatic substituents. Comparison between the methoxysalicylamide (raclopride) series and the orthopramide (sulpiride) series demonstrated that an aromatic 6-hydroxy group increased log kw by 0.4 in the 5-halogen series and by 0.8 in the 5-alkyl series, and that a 6-methoxy group decreased log kw by 0.5. These paradoxical effects can be explained by the masking of the polarity of the amide caused by the 6-hydroxy group forming an intramolecular hydrogen bond with the amide carbonyl group. Introduction of an additional ortho-methoxy substituent had the opposite effect because the resulting steric hindrance prevents the amide moiety from adopting a coplanar conformation with the benzene ring. The presence of a substituent in the aromatic 3-position lowered log kw by 0.3 via a combination of steric and electronic influences on the adjacent 2-methoxy group, causing a weakening of the hydrogen bond between the amide and the oxygen atom of the 2-methoxy group. As a result, halogen and alkyl substituents in the 3-position increase the apparent lipophilicity only half that of similar substituents in the 5-position. Substitution with omega-fluoroalkoxyl groups in the aromatic 2- and 3-positions and with omega-fluoroalkyl groups in the 5-position reduced lipophilicities by 0.5 as compared with the corresponding desfluoro derivatives, thereby making them equivalent to an alkyl derivative with one less carbon atom in the chain. In contrast, substitution on the pyrrolidine nitrogen atom with a 2-fluoroethyl or a 3-fluoropropyl group produced compounds with apparent lipophilicities approximately 1.5 and approximately 0.5 higher, respectively, than those of the corresponding N-ethyl derivatives.(ABSTRACT TRUNCATED AT 400 WORDS)

Amines↗
PubMed1994

Comparison of three high affinity SPECT radiotracers for the dopamine D2 receptor.

The regional brain distribution and pharmacological specificity of three high affinity tracers for the dopamine (DA) D2 receptor: [123I]IBF, [123I]epidepride, and [123I]2'-ISP were assessed by SPECT imaging of non-human primates. The ratios of striatal-to-occipital activities at the time of peak striatal uptake were 2.2, 6.3 and 1.7, respectively. From the peak striatal activities, washout rates were 33, 4 and 16%/h for [123I]IBF, [123I]epidepride and [123I]2'-ISP, respectively. The reversibility of the striatal uptake of all three agents was demonstrated by the rapid displacement induced by the dopamine D2 selective antipsychotic agent raclopride, which increased washout rates to 96, 58 and 43%/h. The administration of d-amphetamine, which induces release of dopamine, had no noticeable effect on [123I]epidepride but increased the washout rate of [123I]IBF. These results suggest that, among these three agents, [123I]epidepride is the superior tracer for in vivo displacement studies because of its slow washout and high target-to-background ratios. However, for tracer kinetic modeling, [123I]IBF may be the superior agent because of its early time of peak uptake and its higher target-to-background ratios than [123I]2'-ISP.

Animals↗
PubMed1994

Ascending aorta to right pulmonary artery interposition shunt in critically ill infants.

In spite of a trend toward earlier complete repair, some neonates and infants with complex cyanotic heart disease continue to require interim palliation with systemic-to-pulmonary artery shunts. A variety of shunt procedures have been proposed, each with inherent advantages and disadvantages. We have found a prosthetic interposition shunt between the ascending aorta and right pulmonary artery (AA-RPA) to be effective in very young infants with small vessels. Over a 15-year period, 51 patients, mean weight 3.33 kg and mean age 59 days, underwent this procedure with a 13% perioperative mortality and a 78% 2-year overall shunt patency rate. We conclude that the AA-RPA interposition shunt is a safe, effective procedure in these infants.

Aorta↗
PubMed1993

Identification of extrastriatal dopamine D2 receptors in post mortem human brain with [125I]epidepride.

The regional distribution of striatal and extrastriatal dopamine D2 receptors in human brain was studied in vitro with (S)-N-[(1-ethyl-2- pyrrolidinyl)methyl]-5-[125I]iodo-2,3-dimethoxybenzamide, [125I]epidepride, using post mortem brain specimens from six subjects. Scatchard analysis of the saturation equilibrium binding in twenty-three regions of post mortem brain revealed highest levels of binding in the caudate (16.5 pmol/g tissue) and putamen (16.6 pmol/g tissue) with lower levels seen in the globus pallidus (7.0 pmol/g tissue), nucleus accumbens (7.2 pmol/g tissue), hypothalamus (1.8 pmol/g tissue), pituitary (1.3 pmol/g tissue), substantia innominata (1.0 pmol/g tissue), and amygdala (0.87 pmol/g tissue). Of note was the presence of dopamine D2 receptors in the four thalamic nuclei studied, i.e. anterior nucleus (1.0 pmol/g tissue), dorsomedial nucleus (0.96 pmol/g tissue), ventral nuclei (0.72 pmol/g tissue), and pulvinar (0.86 pmol/g tissue), at levels comparable to the amygdala (0.87 pmol/g tissue) and considerably higher than levels seen in anterior cingulate (0.26 pmol/g tissue) or anterior hippocampus (0.36 pmol/g tissue). The frontal cortex had very low levels of dopamine D2 receptors (0.17-0.20 pmol/g tissue) while the inferior and medial temporal cortex had relatively higher levels (0.31-0.46 pmol/g tissue). Inhibition of [125I]epidepride binding by a variety of neurotransmitter ligands to striatal, ventral thalamic and inferior temporal cortical homogenates demonstrated that [125I]epidepride binding was potently inhibited only by dopamine D2 ligands. The present study demonstrates that dopamine D2 receptors are present in basal ganglia, many limbic regions, cortex and in the thalamus. The density of thalamic D2 receptors is comparable to many limbic regions and is considerably higher than in cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1993

Evaluation of 5-[18F]fluoropropylepidepride as a potential PET radioligand for imaging dopamine D2 receptors.

This study evaluated the utility of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2,3 - dimethoxybenzamide ([18F]fluorpropylepidepride), [18F]5-FPrEpid, as a ligand for PET studies of cerebral dopamine D2 receptors. The in vitro affinity for the rat striatal dopamine D2 receptor, KD 138 pM, was determined by Scatchard analysis of in vitro binding to rat striatal homogenate. The apparent lipophilicity, log kw 1.6, was measured with reverse phase HPLC at pH 7.5. The receptor specificity was determined by competitive displacement of [18F]5-FPrEpid by a variety of neurotransmitter ligands. Only dopamine D2 ligands displaced [18F]5-FPrEpid with high affinity. Positron tomographic imaging studies in primates of [18F]5-FPrEpid demonstrated a stable striatal uptake of 0.02% injected dose/ml for up to 5 h after injection. The striatal: cerebellar ratio increased from 2 at 15 min, to 7 at 200 min, and to 10 at 300 min. Striatal uptake was displaceable by haloperidol (1 mg/kg) or raclopride (2.5 mg/kg) to cerebellar levels with a t1/2 of washout of 9 or 15 min. Striatal uptake was mildly susceptible to displacement by d-amphetamine (1-2 mg/kg) released endogenous dopamine; d-amphetamine administration produced a 10% h increase in the rate of striatal washout. Although uptake in the striatum is reversible, an equilibrium between receptor bound [18F]5-FPrEpid in striatum and [18F]5-FPrEpid in plasma is not reached within 5 h postinjection.

Animals↗
PubMed1993

Failure of the three compartment model to describe the pharmacokinetics in brain of a high affinity substituted benzamide.

The applicability of using the standard 3-compartment model to describe the neuropharmacokinetics of a high affinity substituted benzamide was investigated. We performed the following experiments using the [18F]-5-(3-fluoropropyl) analog of epidepride ([18F]5-FPrEpid), a potent dopamine D2 receptor antagonist: constant left ventricular infusion, first-pass clearance, varying ligand specific activity, and displacing bound ligand with varying amounts of unlabelled ligand. Taken together, the information from these experiments rigorously tests the standard 3-compartment model. The obtained data and predictions from the model of the kinetic behavior of the ligand are inconsistent. The measured and model predicted dissociation rate (measured koff = 0.065 min-1, model prediction koff = 0.007 min-1) and the equilibrium dissociation constant (measured KD = 0.14 nM, model prediction KD = 2.2 nM) differ by an order of magnitude. Furthermore, the model cannot be used to accurately estimate the receptor density. We postulate that the synapse geometry and physical relationship between receptors are necessary components of a model that describes the pharmacokinetics of [18F]5-FPrEpid.

Animals↗