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Biomedical subjects

B L Holman

Publications and source records attributed to B L Holman.

At least 19 recordsLinked to original sources

Traffic volume and collisions involving transit and nontransit vehicles.

This study reports an analysis of collisions occurring between public transit vehicles operated by the San Francisco Municipal Railway System (Muni), the public transit agency for the City of San Francisco, and nontransit vehicles. The analysis, focusing on weekday collisions during 1987, demonstrated a strong association between hourly transit collisions rates and hourly traffic volume. The collision rate varied from 0.01 per 1,000 Muni vehicle-hours of operation during the interval 5 A.M. to 6 A.M., a time of very low traffic volume, to 0.93 (approximately 1 collision per 1,000 Muni vehicle-hours of operation) during the interval 5 P.M. to 6 P.M., a time of very high traffic volume. Using a power function to predict either the total number of collisions, or the rate of collisions per 1,000 Muni vehicle-hours, almost 90% of total variation was accounted for by traffic volume. A very similar pattern was found for collisions judged either avoidable or unavoidable. A peak in the collision rate between 2 A.M. and 3 A.M. could not be accounted for by traffic volume alone. That peak occurred in the one-hour interval following the 2 A.M. closing of bars in San Francisco, and was composed entirely of a sharp increase in unavoidable collisions. Increasing traffic volume appeared to operate through two mechanisms: (i) an increase in the number of opportunities for a collision, defined as a quantity proportional to the product of the number of Muni and non-Muni vehicles; (ii) an increase in the probability of a collision occurring between any given pair of vehicles.

Accidents, Occupational

Comparison of neutral and cationic myocardial perfusion agents: characteristics of accumulation in cultured cells.

Uptake and washout kinetics of two new neutral lipophilic technetium-99m-labeled boronic acid adducts of technetium tris(dioxime) (BATO complexes) were studied in monolayers of contractile chick heart cells and compared to the cationic myocardial perfusion agents, 99mTc(CNCH2C(CH3)2OCH3)6+ (Tc-MIBI) and 201Tl+. 99mTcCl(CDOH)2(CDO)(BCH3), where CDO = cyclohexanedione dioxime (CDO-MeB), had a 7-fold greater net accumulation than Tc-MIBI and the most rapid unidirectional washout with a fast initial phase and a slower secondary component. Incubation with cationic membrane transport inhibitors or metabolic inhibitors had little or modest influence, respectively, on uptake of these BATO complexes. Studies with NIH 3T3 fibroblasts indicated that the neutral complexes did not show myocyte specific accumulation.

3T3 Cells

I-123 iofetamine SPECT scan in systemic lupus erythematosus patients with cognitive and other minor neuropsychiatric symptoms: a pilot study.

Accurate diagnosis of central nervous system (CNS) lupus remains difficult, especially when the manifestations are of subtle cognitive and affective changes. This pilot study reports on the use of I-123 iofetamine single photon emission computerized tomography (SPECT) scans in 18 such patients with documented systemic lupus erythematosus. Eight of the 18 scans were abnormal (44%), four in a diffuse bi-temporo-parietal pattern previously noted only in Alzheimer's disease, and four with large focal deficits. Neither the existence of the abnormal scan nor the particular pattern of abnormality correlated with the results of other diagnostic tests. These preliminary results raise the possibility that SPECT scans may offer an additional valuable diagnostic instrument in CNS lupus, although further studies are necessary to delineate their precise role.

Adolescent

Hypertensive encephalopathy: findings on CT, MR imaging, and SPECT imaging in 14 cases.

Hypertensive encephalopathy is a syndrome consisting of headache, seizures, visual changes, and other neurologic disturbances in patients with elevated systemic blood pressure. The purpose of this study was to analyze the imaging findings in 14 patients with hypertensive encephalopathy. CT (n = 13), MR (n = 12), and single-photon emission computed tomography (n = 2) examinations performed in these patients before and after resolution of symptoms were reviewed. Eight had the preeclampsia-eclampsia syndrome, and six had hypertensive encephalopathy due to other causes. CT and MR findings in all patients having these examinations were indicative of edema in the cortex and subcortical white matter in the occipital lobes. Two of the 14 patients also had similar findings in the cerebellum and frontal lobes. Single-photon emission computed tomography showed increased vascular perfusion adjacent to areas that appeared abnormal on CT and MR. The findings on the imaging studies resolved on follow-up examinations performed after the hypertension was corrected. Our results suggest that the radiologic findings associated with hypertensive encephalopathy may be useful in establishing the diagnosis in the appropriate clinical setting.

Adolescent

Detection of recurrent gliomas with quantitative thallium-201/technetium-99m HMPAO single-photon emission computerized tomography.

Deteriorating clinical status after high-dose radiation therapy for high-grade gliomas may be due to radiation changes or may signal recurrent or residual tumor mass. The two conditions cannot be distinguished reliably by computerized tomography (CT) or magnetic resonance (MR) imaging. The authors assessed the ability of sequential thallium-201 chloride (201Tl) and technetium-99m hexamethylpropylene amine oxime (99mTc HMPAO) single-photon emission CT (SPECT) to distinguish tumor recurrence from radiation changes after high-dose (greater than or equal to 600 cGy) radiation therapy for malignant gliomas. Preoperative tumor/nontumor uptake ratios were analyzed in 32 patients and correlated with the presence of gross tumor at the time of reoperation. In 12 of 13 patients with 201Tl tumor/scalp ratios of 3.5 or greater, recurrent tumor was present. The authors found 99mTc HMPAO SPECT to be useful for identifying the absence of solid tumor recurrence in patients with low to moderate 201Tl uptake (ratio 1.1 to 3.4) and low perfusion to that site. In 11 of 12 patients with 99mTc HMPAO tumor/cerebellum ratios of 0.50 or less, no recurrent tumor mass was present. Three of seven patients with 201Tl ratios of 3.4 or less and 99mTc HMPAO ratios of 0.51 or more had recurrent tumor found at surgery; thus the test was not predictive in this group. It is concluded that the use of sequential 201Tl and 99mTc HMPAO SPECT accurately identifies the presence of tumor recurrence versus radiation changes in most patients with high-grade astrocytomas who have undergone tumor resection and high-dose radiation therapy.

Adult

Human pharmacokinetics and radiopharmacological studies of the myocardial perfusion agent: technetium (2-carbomethoxy-2-isocyano-propane)6+.

The myocardial perfusion agent technetium (2-carbomethoxy-2-isocyano-propane)6+ (99mTc-CPI) is unique from other cationic technetium isonitrile complexes in that it exhibits moderate washout from the heart and rapid hepatobiliary clearance in animal models and human volunteers. Dynamic imaging and HPLC analysis were performed in humans and guinea pigs to outline the pharmacological basis of its pharmacokinetics. Enzymatic hydrolysis of the terminal ester groups in blood was found to occur at a moderate rate producing new species that have been shown not to accumulate in heart tissue. However, after extraction by the heart, liver or kidneys, the 99mTc-CPI complex undergoes metabolism at a much slower rate than observed in the blood. Differences in hydrolysis rate and products obtained indicate separate mechanisms of hydrolysis occurring in blood and other organs. It is proposed that the heart washout occurring after hydrolysis produces a neutral compound which is no longer retained by the negative cytosolic and mitochondrial membrane potentials in myocardial tissue.

Adult

Cerebral perfusion in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder in which structurally preserved cerebral cortex is thought to be functionally disconnected by subcortical lesions. To assess brain functional activity in patients with PSP, we measured regional cerebral perfusion, as estimated by [123I] iofetamine (IMP) and single-photon emission computed tomography (SPECT), in 11 patients with a clinical diagnosis of PSP and 10 healthy control subjects. IMP uptake was measured in 2 basal ganglia and 24 cortical regions. Neuropsychological tests were administered to assess cognitive function. Compared to age-matched normal control subjects, relative IMP uptake was significantly reduced in PSP patients in basal ganglia (21%), superior frontal (25%), anterior parietal (19%), and inferior frontal (18%) regions. Cognitive performance was most abnormal on tests thought to be subserved predominantly by frontal lobes. Our study demonstrates that IMP-SPECT detects physiological abnormalities in the cortex that parallel behavioral impairments in PSP.

Aged

A comparison of brain perfusion SPECT in cocaine abuse and AIDS dementia complex.

Intravenous drug use is a major risk factor for HIV-1 infection. Since both AIDS dementia complex (ADC) and cocaine have been associated with abnormal brain perfusion imaging, we compared the scintigraphic patterns of ADC patients and cocaine polydrug users with normal control subjects using 99mTc-HMPAO SPECT. We found a high incidence of cortical defects in both ADC (100%) and cocaine-dependent (90%) subjects. In the cocaine and ADC patients, cortical defects were most frequent in the frontal, temporal and parietal lobes and occurred with similar frequency in the two populations. In both groups, the number of cortical defects per subject was higher than normal subjects (10.0 +/- 5.0 for ADC, 10.1 +/- 5.2 for cocaine and 0.7 +/- 1.5 for normal), background activity was high (a 65% and 60% incidence for ADC and cocaine, respectively), and basal ganglia involvement was frequent (40% and 65% for ADC and cocaine). We conclude that the brain perfusion pattern, while a sensitive indicator of ADC, cannot be distinguished from chronic cocaine polydrug use and caution should therefore be applied before entertaining a specific diagnosis.

AIDS Dementia Complex

Interspecies variation in biodistribution of technetium (2-carbomethoxy-2-isocyanopropane)6+.

The cationic complex technetium (2-carbomethoxy-2-isocyanopropane)6+ (99mTc-CPI) contains terminal ester groups that were included to provide a pathway for in-vivo metabolism of this compound, thereby enhancing its performance as a myocardial perfusion agent. Biodistribution studies of the compound demonstrated myocardial accumulation in rabbit, guinea pig, and chick, but not in rat and mouse. Radiochemical analysis by HPLC after in-vitro incubation of 99mTc-CPI in blood plasma from the various species confirmed enzymatic hydrolysis to numerous new compounds. Rat and mouse serum produced complete hydrolysis of this agent after incubation for less than 5 sec at 25 degrees C or rates greater than 500 times those observed in human, rabbit, guinea pig and chick serum. Chemical synthesis and isolation of the monohydrolyzed species with subsequent biodistribution studies in guinea pig and rabbit confirmed that this neutral lipophilic complex did not accumulate in heart tissue. It is concluded that varying rates of enzymatic in-vivo hydrolysis produce the interspecies biodistribution differences and may account for the moderate myocardial clearance relative to other isonitrile complexes.

Animals

Subcellular distribution and analysis of technetium-99m-MIBI in isolated perfused rat hearts.

To address the apparent discrepancy between cultured cells and whole heart preparations, Langendorff-perfused rat hearts loaded with hexakis (2-methoxyisobutyl isonitrile) technetium (I) (99mTc-MIBI) were fractionated by a standard differential centrifugation method and fractional contents of 99mTc-MIBI were correlated with the mitochondrial marker, malate dehydrogenase (MDH), and mitochondrial substrates. The "cytosolic" fraction nominally contained 89% +/- 3% of total 99mTc-MIBI, but also contained 91% +/- 1% of total MDH activity by this method. Chromatographic analysis of activity in the "cytosolic" fraction demonstrated greater than 95% of the agent was present as the original free cationic complex; binding to a small molecular weight cytosolic protein was not involved in localization. Addition of the mitochondrial uncoupler CCCP (5 microM) to both "mitochondrial" and "cell fragment" pellets released up to 84% +/- 8% of 99mTc-MIBI content and addition of the mitochondrial substrate succinate (10 microM) in the presence of rotenone (1 microM) enhanced 99mTc-MIBI content by up to 139% +/- 52% over the control. These correlative data from rat hearts indicate that approximately 90% of 99mTc-MIBI activity in vivo is associated with mitochondria in an energy-dependent manner as a free cationic complex, but migrates during fractionation/centrifugation.

Animals

The scintigraphic appearance of Alzheimer's disease: a prospective study using technetium-99m-HMPAO SPECT.

Alzheimer's disease produces regional abnormalities in brain blood flow and metabolism that may result in recognizable scintigraphic patterns. We determined the predictive value of 99mTc-HMPAO SPECT for the presence of Alzheimer's disease based on a prospective study of 132 consecutive patients coming to our nuclear medicine clinical unit for evaluation of their memory loss or cognitive abnormalities. During clinical follow-up averaging 10.1 mo, a final diagnosis was established in 113 patients, 52 of which had Alzheimer's disease. The probability of Alzheimer's disease was determined for seven scintigraphic patterns. The probability was 19% that patients with memory loss and normal perfusion had Alzheimer's disease. For abnormal perfusion patterns, the probability of Alzheimer's disease was 82% with bilateral temporoparietal defects, 77% with bilateral temporoparietal defects with additional defects, 57% with unilateral temporoparietal defects, 43% with frontal defects only, 18% with other large defects and 0% with multiple small cortical defects. We conclude that for 99mTc-HMPAO SPECT the predictive value of bilateral temporoparietal defects for Alzheimer's disease is high, while the perfusion patterns of unilateral temporoparietal perfusion defects and frontal defects only, which occur in 20% of patients with Alzheimer's disease, are not predictive of that disease.

AIDS Dementia Complex

The scintigraphic evaluation of Huntington's disease and other movement disorders using single photon emission computed tomography perfusion brain scans.

The increasing availability of single-photon emission computed tomography (SPECT) perfusion brain scans has led to the investigation of a variety of neuropsychiatric conditions including the movement disorders such as Huntington's and Parkinson's disease. In general, observers have noted that Huntington patients have bilaterally decreased uptake of technetium 99m HM-PAO and iodine 123 IMP in the basal ganglia regions involving the heads of the caudate nucleic and adjacent structure, which reflects decreased neuronal function. These functional changes precede the morphological changes due to caudate nucleus atrophy that are observed on computed tomography and magnetic resonance imaging. Cortical changes occur in severely diseased Huntington's patients but are more nonspecific. Prediction of individuals at risk for Huntington's disease using SPECT scans should be done with caution and in association with other clinical data. In contrast, in Parkinson's disease mild diffusely decreased perfusion is commonly noted throughout the cerebral structures, except for the cerebellum. In Parkinson's disease, there is less agreement among observers as to whether the basal ganglia are abnormal. Some observers report that there are no specific basal ganglia perfusion defects in excess of those changes seen elsewhere in the brain. Others report diminished basal ganglia uptake associated with L-dopa therapy in some Parkinson's patients, and in patients with hemi-parkinsonism there have been perfusion deficits reported in the contralateral basal ganglia. In some Parkinson patients, bilateral Alzheimer's-like posterior temporoparietal cortical perfusion defects have been observed in association with progressive dementia. Basal ganglia and cortical perfusion changes also have been reported in a few patients with a variety of other less common movement disorders.

Brain

Tc-99m MIBI SPECT in the assessment of myocardial reperfusion after percutaneous transluminal coronary angioplasty.

Tc-99m MIBI SPECT was used to assess the early benefits of successful percutaneous transluminal coronary angioplasty (PTCA) in nine consecutive patients. SPECT stress studies were done by artificial cardiac pacing just prior to PTCA and 16-20 hours later, with perfusion images obtained 2-3 hours after pacing stress and Tc-99m MIBI injection. Angiographic restenosis was demonstrated in three patients at a later date, and all of these showed no significant improvement on the perfusion study after PTCA. All four patients asymptomatic at 7 months following PTCA had an average 15% improvement in segmental perfusion after the procedure. In two patients symptomatic after PTCA, one showed angiographic patency and had greater than 15% improvement in perfusion, while the second showed no scintigraphic improvement (no angiographic data obtained). This preliminary study suggests that Tc-99m MIBI is an important adjunct to angiography in estimating the amount of myocardium "at risk" before and after PTCA.

Aged

Embolization of platelets after endothelial injury to the aorta in rabbits. Assessment with 111indium-labeled platelets and angiography.

This study exploits the ability of a collateral arterial network to trap platelet aggregates in order to document the frequency of macroembolization in rabbits after endothelial damage. Two weeks after ligation of the right superficial femoral artery, endothelial injury was induced in the distal aorta; within 3 hours the rabbits were studied using either angiography or 111indium-labeled (111In) platelet scintigraphy. Angiography indicated visible aggregates in the thigh region in eight of 19 and arterial occlusion in three of 19 rabbits. The collateral-dependent thigh also showed more 111In-labeled platelet activity than the contralateral side (P less than .001), whether platelets were injected before or 2 hours after injury. Radioactivity in the limbs of rabbits with no injury was distributed symmetrically. Blood pool volume, assessed with technetium-99m-labeled red blood cells, was the same in both thighs, and could not account for these observations. The findings indicate that platelet activation and aggregation after endothelial injury lead to microembolization much more frequently than it leads to macroaggregate formation and visible artery occlusion.

Animals

Extracranial metastatic glioblastoma: appearance on thallium-201-chloride/technetium-99m-HMPAO SPECT images.

Sequential thallium-201-chloride and technetium-99m-hexamethylpropyleneamine oxime single-photon emission computed tomography (SPECT) images were obtained in a patient with extracranial metastatic glioblastoma multiforme. Thallium-201 uptake was high (three times the scalp background) in all pathologically confirmed extracranial metastases and moderate (1.6 times scalp background) intracranially, where most biopsy specimens showed gliosis with scattered atypical astrocytes. Technetium-99m-HMPAO uptake was decreased intracranially in the right frontal and parietal lobes which had been irradiated. It was also decreased in one well-encapsulated scalp lesion and high in another scalp mass with less defined borders. Possible mechanisms of tumor uptake of these agents are reviewed.

Adult