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Biomedical subjects

R Lisbona

Publications and source records attributed to R Lisbona.

At least 19 recordsLinked to original sources

Alpha-[11C] methyl-L-tryptophan and glucose metabolism in patients with temporal lobe epilepsy.

OBJECTIVE: To determine whether metabolism in the brain serotonergic system, including the kynurenine pathway, is involved in temporal lobe epilepsy (TLE). METHODS: The authors studied 14 patients with intractable TLE by PET using alpha-[11C] methyl-L-tryptophan (alpha-MTrp) and 2-[18F]-fluoro-deoxy-glucose (FDG) and compared results with 21 healthy control subjects who had alpha-MTrp PET studies. Seven patients had unilateral hippocampal atrophy (HA), and seven had normal hippocampal volumes (NV). The regional uptake constant (K*) for alpha-MTrp and regional FDG uptake were calculated in regions with high serotonergic innervation, including the hippocampus, amygdala, lateral temporal lobe, frontal lobe, thalamus, lenticular nucleus, and cingulate cortex. RESULTS: A significant increase of alpha-MTrp uptake was observed in the hippocampus ipsilateral to the seizure focus in seven TLE patients with NV compared to seven patients with HA as well as to healthy controls. In patients with TLE, glucose utilization in the lateral temporal lobe ipsilateral to the seizure focus was correlated negatively with K* for alpha-MTrp in the ipsilateral hippocampus and positively with K* in the ipsilateral lenticular nucleus and cingulate cortex. Glucose utilization in the frontal lobe ipsilateral to the seizure shows a reduction in the glucose utilization which relates to the increase in the alpha-MTrp uptake in the ipsilateral lateral temporal lobe. CONCLUSION: This study demonstrates dysfunction of the serotonergic system, which could include metabolism through the kynurenine pathway in TLE patients with normal hippocampal volumes. alpha-MTrp PET studies might be useful for lateralizing the epileptic focus in TLE patients with normal hippocampal volumes.

Adolescent↗

Positron emission mammographic instrument: initial results.

Performance characteristics of a positron emission mammographic (PEM) instrument were studied. This dedicated metabolic breast imaging system has spatial resolution of 2.8-mm full width at half maximum (FWHM), coincidence resolving time of 12-nsec FWHM, and absolute efficiency of 3%. Hot spots with diameter of 16 mm in a phantom with signal-to-background activity ratio of 6:1 were distinguishable with a scanning time of 5 minutes.

Adult↗

Results of preliminary clinical trials of the positron emission mammography system PEM-I: a dedicated breast imaging system producing glucose metabolic images using FDG.

UNLABELLED: Early detection of breast cancer is crucial for efficient and effective treatment. We have developed an instrument for positron emission mammography (PEM) called PEM-I that performs high-resolution metabolic imaging of breast cancer. Images of glucose metabolism are obtained after injection of 75 MBq FDG. The PEM detectors are integrated into a conventional mammography system, allowing acquisition of the emission images immediately after the mammogram, without subject repositioning, and accurate coregistration of images from the 2 modalities. In this article, we present the results of the first clinical pilot study with the instrument. METHODS: Sixteen subjects (age range, 34-76 y) were studied. All subjects were nondiabetic, nonpregnant, and without a history of cancer. They had recently been found to have suggestive mammography findings or a palpable breast mass and underwent lumpectomy or mastectomy within 2 wk of the study. Results from the PEM study were compared with those from mammography and pathology. A PEM test was classified positive (indicating the presence of cancer) if significant focal uptake was seen in the image or if the counting rate in the breast with suggestive findings was significantly higher than in the contralateral breast. RESULTS: Of the 16 subjects studied, 14 were evaluable. Ten cancerous tumors and 4 benign tumors were confirmed by pathologic examination after complete removal of the tumor. PEM correctly detected the presence of disease in 8 of 10 subjects. Findings were false-negative in 2 instances and false-positive in none, giving the instrument 80% sensitivity, 100% specificity, and 86% accuracy. CONCLUSION: Our preliminary results suggest that PEM can offer a noninvasive method for the diagnosis of breast cancer. Metabolic images from PEM contain unique information not available from conventional morphologic imaging techniques and aid in expeditiously establishing the diagnosis of cancer. In all subjects, the PEM images were of diagnostic quality, with an imaging time of 2-5 min.

Adult↗

Scintigraphic diagnosis of polysplenia in the adult.

PURPOSE: The authors describe an adult patient with low index of suspicion for polysplenia. The diagnostic contribution of various investigative modalities is considered, and the key role of scintigraphy is specifically highlighted. RESULTS: CT scan findings revealed multiple abdominal and retroperitoneal masses. Needle biopsy of a flank mass was nonspecific. Tc-99m sulfur colloid liver spleen scintigraphy and Tc-99m heat-denatured RBC scans showed the presence of polysplenia. CONCLUSIONS: Multiple spleens can be mistaken for abdominal neoplasms on CT. Biopsy results may not always be helpful. In patients in whom there is such a diagnostic dilemma, Tc-99m heat-denatured RBC scans can successfully establish the definitive diagnosis of polysplenia.

Abdominal Neoplasms↗

Regional cerebral blood flow and language dominance: SPECT during intracarotid amobarbital testing.

We examined the relation between language dominance and regional cerebral blood flow (rCBF) during the intracarotid amobarbital procedure (IAP). A previous report limited to three patients suggested that dominant rather than nondominant hemisphere IAP may have a differential effect on rCBF. Behavioral assessment during the IAP also suggests that dominant hemisphere injection results in a differential effect on memory and affective symptoms rather than nondominant injection. Thirteen patients were assessed using single-photon emission CT (SPECT) brain imaging during both left and right IAP. The SPECTs were coregistered with the individual's MRI. Changes in rCBF during each IAP were compared with the patient's baseline SPECT. Nine patients had left hemisphere dominance, two were right dominant, and two had bilateral speech representation. In the left dominant subjects, left-hemisphere injection had a consistently greater effect on rCBF than right-hemisphere injection in the anterior (p < 0.005) and posterior (p < 0.01) temporal neocortex. There was also a trend for greater hypoperfusion in the frontal lobe of the left hemisphere. rCBF in the ipsilateral hippocampus was not significantly different after each injection (p > 0.05). In the two patients with right hemisphere speech, the reverse pattern was seen, with greater hypoperfusion after right (dominant) hemisphere injection. There was no consistent asymmetry in the two patients with bilateral speech. Dominant hemisphere IAP results in significantly greater hypoperfusion than does nondominant injection. These data provide a physiologic basis for behavioral differences noted after dominant versus nondominant IAP.

Adolescent↗

Assessment of the functional effect of the intracarotid sodium amobarbital procedure using co-registered MRI/HMPAO-SPECT and SEEG.

We studied the functional effect of injection of sodium amobarbital (SA) in 10 patients with intractable epilepsy. During the intracarotid amobarbital procedure, we measured delta activity in EEG recording from implanted electrodes and regional cerebral blood flow (rCBF) using HMPAO-SPECT co-registered with MRI. SA injection resulted in an increase in delta activity and a decrease in rCBF in all areas examined. Direct functional changes were observed in structures perfused by the carotid artery injected. In addition, we observed indirect effects, probably owing to deafferentation of neuronal pathways connecting these structures to ipsilateral and contralateral regions, including middle and posterior hippocampus.

Amobarbital↗

Small molecule nerve growth factor analogs image receptors in vivo.

The in vivo targeting efficacy of small molecule analogs of nerve growth factor (NGF) that bind the NGF receptor p140 TrkA was evaluated and compared with that of a high-affinity anti-TrkA monoclonal antibody (Mab 5C3). Nuclear imaging studies were done after the injection of 99mTc-labeled compounds in nude mice bearing tumors. Kinetics of tumor targetting, blood clearance, and bioavailability of NGF mimics were equivalent or better than Mab 5C3. Tumors that do not express TrkA were not targeted, demonstrating the specificity of NGF mimics in vivo. This comparative biodistribution study demonstrates that receptor-specific small molecule analogs designed from large polypeptides may be more useful than antibodies and may be effective agents for the detection, diagnosis, and possible treatment of neoplasias involving overexpressed oncogenic receptors such as TrkA.

3T3 Cells↗

Supine and prone SPECT Tc-99m MIBI myocardial perfusion imaging for dipyridamole studies.

Aartifactual inferior wall defects of perfusion are a source of frequent concern during TI-201 exercise stress redistribution SPECT imaging in the supine position. These artifactual changes also affect Tc-99m sestamibi dipyridamole myocardial perfusion studies with supine SPECT yielding a specificity of only 58% for right coronary artery (RCA) disease. Complementary SPECT prone imaging will enhance this specificity for inferior wall abnormalities to 79% (P < 0.05) and is recommended for more accurate assessment of RCA stenosis, whether the patient challenge is pharmacological or by exercise.

Adult↗

Report of a patient with syndrome X due to excessive adenosine effect: myocardial migraine without myocardial ischemia.

A 53-year-old female presented with disabling chest pain. The pain had most of the characteristics of ischemic pain; however, the results of the initial clinical investigation were consistent with the diagnosis of syndrome X. That is, her treadmill exercise test was positive but her coronary angiogram was normal. A dipyridamole-thallium test resulted in severe chest pain, marked ST abnormalities, but no evidence of any focal reduction in flow. A dipyridamole stress echocardiogram revealed that left ventricular function was entirely normal during the dipyridamole-induced pain and ST segment abnormalities, making ischemia an unlikely cause for either. To attempt to account for this paradox, the hypothesis was generated that both the pain and ST segment abnormalities were due to a primary abnormality of adenosine metabolism rather than secondary to ischemia. Accordingly, adenosine-MIBI scans were done with and without pretreatment with aminophylline. Infusion of adenosine virtually immediately resulted in crushing chest pain and profound ST abnormalities again without any evidence of focal abnormalities of MIBI estimated flow. By contrast, administration of adenosine after pretreatment with aminophylline failed to produce either chest pain or ST abnormalities. Moreover, long term therapy with aminophylline almost entirely relieved the symptoms which had been so distressing. This case indicates that there is a subset of patients with syndrome X--in which faults in adenosine metabolism result in excessive adenosine accumulation or effect and this results, in turn, in adenosine-induced ischemic-like chest pain and adenosine-induced ST abnormalities. There is, however, no actual ischemia of the myocardium. Given the known effects of adenosine on coronary flow, the problem in this subset of patients appears to be equivalent to an attack of myocardial migraine and blockers of adenosine action might be of help to other patients with a similar pathophysiology for their chest pain.

Adenosine↗

Role of vasoconstriction in gravity-nondependent central-peripheral gradient in pulmonary blood flow.

To examine the effect of vasoconstriction on the gravity-nondependent distribution of pulmonary blood flow, albumin macroaggregates labeled with either 99mTc or 111In were injected at end expiration into dogs (anesthetized, supine, and breathing room air spontaneously). The first dose of macroaggregates was injected during baseline conditions and the second during infusion of serotonin or histamine. Five minutes after the second injection, the chest was opened and the lungs were removed, drained of blood, and dried while fully inflated. Single photon emission computed tomography was performed on the dry lungs to map the three-dimensional distribution of activity of the two isotopes. Images of coronal and sagittal slices were displayed. The results showed that changes in vascular muscle tone did not alter pulmonary blood flow distribution. The absolute flow in a central and peripheral region changed in proportion to cardiac output changes, indicating that during vasoconstriction, as during baseline conditions, there was a preferential perfusion to the interior of the lung. Examination of the average flow in the individual coronal slices showed that during serotonin or histamine infusion, the average flow in each slice changed in proportion to change in cardiac output but that the vertical average flow was not affected significantly. These findings are consistent with the notion that resistive properties (length, diameter, branching pattern) of the pulmonary vascular tree are responsible for the central-peripheral gradient.

Animals↗

Enhanced revascularization of the ischemic limb by angiogenic therapy.

BACKGROUND: This study tests the efficacy of an angiogenic growth factor, endothelial cell growth factor, in a rabbit model of persistent hindlimb ischemia. METHODS AND RESULTS: Ischemia was induced in the left hindlimb of 22 New Zealand White rabbits by ligation of the distal external iliac artery and complete excision of the common and superficial femoral arteries. Two groups of animals were studied: Group 1 consisted of 11 animals who for 10 days received daily intramuscular injections of 4 mg of endothelial cell growth factor beginning on postoperative day 11, and group 2 consisted of 11 animals who underwent the same surgical ischemic procedure but received only injections of saline daily for the same postoperative period. Perfusion of the ischemic left limb was compared with the normal right limb in each animal on postoperative days 10, 20, 30, and 40 using the calf blood pressure ratio, 99mTc macroaggregate radioisotopic perfusion scans, and serial angiography. Neovascularization in the left thigh at day 40 was quantified from the angiograms. Each technique documented that animals in group 1 had significantly better perfusion than animals in group 2; that is, the calf pressure ratio was higher in group 1 than in group 2 (0.56 versus 0.32 at day 20, 0.64 versus 0.44 at day 30, and 0.70 versus 0.50, P < .0001), and the calf radioisotopic perfusion ratio was also higher in group 1 than in group 2 (0.88 versus 0.74 at day 20, P < .02; 0.93 versus 0.76 at day 30, and 0.96 versus 0.79 at day 40, P < .008). Angiographic studies correlated well with these results demonstrating much earlier distal arterial reconstitution and enhanced neovascularization (23.8 versus 9.0 vessels, P < .007). CONCLUSIONS: The data clearly indicate that an angiogenic growth factor, endothelial cell growth factor, promotes revascularization in this experimental ischemic hindlimb model, raising the possibility that in the future such agents might be of value in humans.

Angiography↗

Gallium-67 scintigraphy in tuberculous and nontuberculous infectious spondylitis.

Vertebral osteomyelitis is a difficult condition to diagnose clinically. A retrospective review of 21 cases of infectious spondylitis (6 tuberculous, 15 nontuberculous) confirmed the utility of 67Ga scintigraphy in imaging this process. Gallium-67 scans were positive at all sites of disease in this patient population. They anticipated the presence of spondylar infection in 23% of regions where radiographic abnormalities were originally lacking, while confirming a current and ongoing septic process at the other sites where vertebral destruction was already present on x-ray. Gallium-67 studies, as compared to the 99mTc-MDP bone scans, also provided important information as to the extent of disease by documenting the presence of eight paraspinal abscesses and the location of remote extraspinal foci of infection both in soft tissues and in bone. The relative merits of all radiologic imaging procedures are discussed. A diagnostic algorithm is also suggested.

Adolescent↗