Coupled transcript and metabolite identification: insights on induction and synthesis of resveratrol in peanut, wild relatives and synthetic allotetraploid.

Resveratrol is an antioxidant that is a promising antitumoral, cardioprotective and neuroprotective agent. It has been found in a restricted number of plants including peanut (Arachis hypogaea L.) and its wild relatives. The objective of this study was to understand the relationship between resveratrol content and the expression of putative resveratrol synthase genes in four Arachis genotypes. Two diploids and two tetraploid were analyzed. Contents of resveratrol on non- and UV-treated leaves were estimated using HPLC. Resveratrol synthase (RS) was analyzed using RT-qPCR with primers developed in this study. Sequences of six Arachis species were amplified using two degenerated primer pairs that were designed based on Arachis and general RS available at GenBank. Those sequences were used to qPCR primers design. Test and control leaves were collected from plants cultivated in greenhouse and three biological replicates were evaluated for each genotype. The synthesis of resveratrol in leaves was induced by treatment with UV for 2.5 h. All genotypes studied synthesized resveratrol. Concentrations ranged from 193.66 µg/g in synthetic allotetraploid to 371.97 µg/g in A. duranensis. Natural and induced allotetraoploids showed lower levels of resveratrol than their diploid parents. Untreated samples did not produce significant amounts of resveratrol. The analysis of resveratrol content and levels of RS mRNA allowed the identification of one gene induced by the UV treatment. The data showed different amounts of RS in the different genotypes suggesting early and late response to the UV induction in the different species. The understanding of the variation found among species will help to identify species that have high resveratrol content and their ideal pos-induction times. This also will allow analysis of other tissues where high levels resveratrol would be very important, such as in seeds.

Emission of nanoparticles during friction stir welding (FSW) of aluminium alloys.

Friction stir welding (FSW) is now well established as a welding process capable of joining some different types of metallic materials, as it was (1) found to be a reliable and economical way of producing high quality welds, and (2) considered a "clean" welding process that does not involve fusion of metal, as is the case with other traditional welding processes. The aim of this study was to determine whether the emission of particles during FSW in the nanorange of the most commonly used aluminum (Al) alloys, AA 5083 and AA 6082, originated from the Al alloy itself due to friction of the welding tool against the item that was being welded. Another goal was to measure Al alloys in the alveolar deposited surface area during FSW. Nanoparticles dimensions were predominantly in the 40- and 70-nm range. This study demonstrated that microparticles were also emitted during FSW but due to tool wear. However, the biological relevance and toxic manifestations of these microparticles remain to be determined.

Cytoadherence of erythrocytes invaded by Plasmodium falciparum: quantitative contact-probing of a human malaria receptor.

Cytoadherence of red blood cells (RBCs) invaded by Plasmodium falciparum parasites is an important contributor to the sequestration of RBCs, causing reduced microcirculatory flow associated with fatal malaria syndromes. The phenomenon involves a parasite-derived variant antigen, the P. falciparum erythrocyte membrane protein 1 (PfEMP1), and several human host receptors, such as chondroitin sulfate A (CSA), which has been explicitly implicated in placental malaria. Elucidating the molecular mechanisms of cytoadherence requires quantitative evaluation, under physiologically relevant conditions, of the specific receptor-ligand interactions associated with pathological states of cell-cell adhesion. Such quantitative studies have not been reported thus far for P. falciparum malaria under conditions of febrile temperatures that accompany malarial infections. In this study, single RBCs infected with P. falciparum parasites (CSA binding phenotype) in the trophozoite stage were engaged in mechanical contact with the surface of surrogate cells specifically expressing CSA, so as to quantify cytoadherence to human syncytiotrophoblasts in a controlled manner. From these measurements, a mean rupture force of 43pN was estimated for the CSA-PfEMP1 complex at 37°C. Experiments carried out at febrile temperature showed a noticeable decrease in CSA-PfEMP1 rupture force (by about 23% at 41°C and about 20% after a 40°C heat treatment), in association with an increased binding frequency. The decrease in rupture force points to a weakened receptor-ligand complex after exposure to febrile temperature, while the rise in binding frequency suggests an additional display of nonspecific binding molecules on the RBC surface. The present work establishes a robust experimental method for the quantitative assessment of cytoadherence of diseased cells with specific molecule-mediated binding.

Evaluation of low-level laser therapy in the prevention and treatment of radiation-induced mucositis: a double-blind randomized study in head and neck cancer patients.

The purpose of this prospective study was to determine the effect of the low-level laser in the prevention and treatment of mucositis in head and neck cancer patients. A total of 70 patients with malignant neoplasms in the oral cavity or oropharynx were evaluated. The patients were randomized into two low-level laser therapy groups: Group 1 (660nm/15mW/3.8J/cm(2)/spot size 4mm(2)) or Group 2 (660nm/5mW/1.3J/cm(2)/spot size 4mm(2)) starting on the first day of radiotherapy. Oral mucositis was assessed daily and weekly using the NCI and WHO scales. Oral pain was scored daily with a visual analogue scale before laser application. The patients in Group 1 had a mean time of 13.5days (range 6-26days) to present mucositis grade II, while the patients in Group 2 had a mean time of 9.8days (range 4-14days) (both WHO and NCI p=0.005). In addition, Group 2 also presented a higher mucositis grade than Group 1 with significant differences found in weeks 2 (p=0.019), 3 (p=0.005) and 4 (p=0.003) for WHO scale and weeks 2 (p=0.009) and 4 (p=0.013) for NCI scale. The patients in Group 1 reported lower pain levels (p=0.004). Low-level laser therapy during radiotherapy was found to be effective in controlling the intensity of mucositis and pain.

Efeito da restrição pré e pós-natal sobre o crescimento dos depósitos de gordura de cordeiros Santa Inês / Effects of pre and postnatal nutritional restriction on internal fats growth of Santa Ines lambs

Avaliaram-se os efeitos da restrição pré e pós-natal sobre o tamanho e o crescimento dos depósitos de gordura de cordeiros Santa Inês. Foram utilizados 68 cordeiros, distribuídos em três tratamentos: com restrição pré-natal (RPRE), com restrição pós-natal (RPOS) e sem restrição (controle). Dentro de cada tratamento, os animais foram aleatoriamente sorteados para serem abatidos após o nascimento e com 10, 15, 25, 35 e 45kg de peso vivo. Os depósitos de gordura (omental, mesentérica, perirenal, pélvica e inguinal) foram registrados. Ao nascimento, os depósitos de gordura foram menores nos animais do tratamento RPRE. Entre 15 a 35kg de peso, a quantidade de gordura foi igual nos animais dos três tratamentos e, a partir desse peso (35kg), com exceção da gordura pélvica, os depósitos no animais do tratamento RPRE foram significativamente maiores. A restrição pré-natal elevou consideravelmente as taxas de ganho da gordura omental, mesentérica, perirenal e pélvica, enquanto a restrição pós-natal influenciou somente a taxa de ganho da gordura inguinal. Cordeiros de todos os grupos apresentaram taxas de desenvolvimento tardias (b>1).

Effects of pre and postnatal nutritional restriction on allometric growth of internal fat deposits in Santa Ines lambs were evaluated Sixty eight lambs were randomly alloted to three different nutritional restriction:prenatal nutritional restriction (PRER), postnatal nutritional restriction (POSR), and a control group without nutritional restriction. Lambs of each group were randomly sampled and slaughtered at birth and weighing 10, 15, 25, 35 and 45kg. Fat depositts (omental, mesenteric, perirenal, pelvic and inguinal) of slaughtered lambs were recorded. At birth fat deposits were small for animals from treatment RPRE. From 15 to 35kg of live weight the amount of fat was similar for animals from all groups but lambs from PRER group, with live body weight heavier than 35kg, showed higher fat deposits except for pelvic fat. Prenatal nutritional restriction increased increased the omental, mesenteric, perirenal, and pelvic fat deposits and postnatal restriction decreased the inguinal fat deposits. Lambs from all groups showed a positive heterogenic development (b>1).

Desempenho de novilhos de corte alimentados com dietas contendo quantidades crescentes de concentrado associado à forragem de aveia (Avena strigosa) tratada com uréia / Performance of beef steers fed on diets containing increasing amounts of concentrate associated to oat (Avena strigosa) forage treated with urea

Este trabalho teve por objetivo avaliar o efeito dos níveis 40, 55 e 70 por cento de concentrado associados a um volumoso de baixa qualidade sobre o consumo e ganho de peso de 16 novilhos mestiços, castrados, com 10 meses de idade e peso vivo inicial médio de 312kg, em delineamento inteiramente ao acaso, com três repetiçöes, durante 63 dias. O volumoso usado foi a aveia (Avena strigosa), tratada com uréia e o concentrado era constituído de milho, farelo de arroz, farelo de soja e minerais. Todas as dietas foram ajustadas para conter 12 por cento de proteína bruta. Houve resposta positiva e linear à proporçäo de concentrado na dieta, para as variáveis ganho de peso diário e consumo de matéria seca expresso em kg/animal/dia, em percentagem do peso vivo e em g por kg de peso metabólico em funçäo da proporçäo de concentrado na dieta. Houve resposta linear negativa para conversäo alimentar. O consumo de matéria seca e o ganho de peso diário aumentaram na medida em que se elevou a proporçäo de concentrado na dieta. O volumoso de baixa qualidade empregado possivelmente limitou o consumo e conseqüentemente o aporte de nutrientes

Dual-isotope single-photon emission computerized tomography scanning in patients with glioblastoma multiforme: association with patient survival and histopathological characteristics of tumor after high-dose radiotherapy.

OBJECT: The study was conducted to determine the association between dual-isotope single-photon emission computerized tomography (SPECT) scanning and histopathological findings of tumor recurrence and survival in patients treated with high-dose radiotherapy for glioblastoma multiforme. METHODS: Studies in which SPECT with 201Tl and 99mTc-hexamethypropyleneamine oxime (HMPAO) were used were performed 1 day before reoperation in 47 patients with glioblastoma multiforme who had previously been treated by surgery and high-dose radiotherapy. Maximum uptake of 201Tl in the lesion was expressed as a ratio to that in the contralateral scalp, and uptake of 99mTc-HMPAO was expressed as a ratio to that in the cerebellar cortex. Patients were stratified into groups based on the maximum radioisotope uptake values in their tumor beds. The significance of differences in patient gender, histological characteristics of tissue at reoperation, and SPECT uptake group with respect to 1-year survival was elucidated by using the chi-square statistic. Comparisons of patient ages and time to tumor recurrence as functions of 1-year survival were made using the t-test. Survival data at 1 year were presented according to the Kaplan-Meier method, and the significance of potential differences was evaluated using the log-rank method. The effects of different variables (tumor type, time to recurrence, and SPECT grouping) on long-term survival were evaluated using Cox proportional models that controlled for age and gender. All patients in Group I (201Tl ratio < 2 and 99mTc-HMPAO ratio < 0.5) showed radiation changes in their biopsy specimens: they had an 83.3% 1-year survival rate. Group II patients (201Tl ratio < 2 and 99mTc-HMPAO ratio of > or = 0.5 or 201Tl ratio between 2 and 3.5 regardless of 99mTc-HMPAO ratio) had predominantly infiltrating tumor (66.6%); they had a 29.2% 1-year survival rate. Almost all of the patients in Group III (201Tl ratio > 3.5 and 99mTc-HMPAO ratio > or = 0.5) had solid tumor (88.2%) and they had a 6.7% 1-year survival rate. Histological data were associated with 1-year survival (p < 0.01): however, SPECT grouping was more closely associated with 1-year survival (p < 0.001) and was the only variable significantly associated with long-term survival (p < 0.005). CONCLUSIONS: Dual-isotope SPECT data correlate with histopathological findings made at reoperation and with survival in patients with malignant gliomas after surgical and high-dose radiation therapy.

[Neonatal cholestasis: the delay in referring patients for differential diagnosis]. / Colestase neonatal - atraso no encaminhamento de crianças para diagnóstico diferencial.

OBJECTIVE: An efficient treatment of extrahepatic biliary atresia demands that the diagnostic differentiation between intra- and extrahepatic neonatal cholestasis be performed by the eighth week of life. This study aimed at evaluate the age of the patients admitted to a general hospital for differential diagnosis of cholestatic jaundice. METHODS: Forty nine children from the Pediatric Service at Hospital de Clínicas, in Porto Alegre, have been studied between 1984 and 1991, according to the protocol for diagnostic elucidation followed by this hospital, which includes biliary tract scintigraphy with Tc-99m DISIDA and, depending on its results, an wedge or percutaneous liver biopsy. The ages of the children have been compared on the occasion of the procedures. Twenty six cases have been studied retrospectively and 23, prospectively. RESULTS: Both the patients with intrahepatic and extrahepatic cholestasis underwent scintigraphy, on average at over eight weeks (age 77.94 +/- 42.98 days) and the histopathological study of the liver was performed approximately two weeks after scintigraphy. Only six patients (12.8% of the 47 cases) underwent the liver biopsy before the first eighth week of life. CONCLUSIONS: A delay was observed in referring patients for differential diagnosis of neonatal cholestasis and the performance of tests. The need of hospitalization in order to conduct these procedures delays even further this diagnosis, which should be concluded by the eighth week of life.

Intratumoral administration of 5-[123I]iodo-2'-deoxyuridine in a patient with a brain tumor.

UNLABELLED: We have initiated a study in which patients suspected of having primary gliomas are given a single intracerebral injection of the thymidine analog 5-[123I]iodo-2'-deoxyuridine ([123I]IUdR). The purpose of the study is to determine the biodistribution of the radiopharmaceutical and to calculate dose estimates to the tumor and normal tissues. METHODS: A patient with a cystic glioma was injected with [123I]IUdR. Whole-body scans and brain scans were obtained at various times after injection, and blood, urine and stools were collected and assayed for radioactivity to assess its biodistribution and clearance. RESULTS: Scintigraphic imaging demonstrated that the distribution of radiolabeled IUdR was mainly confined to the tumor (injection site), stomach and bladder. Disappearance from the tumor site and blood clearance were delayed probably due to collection in the cystic lesion. Eighty percent of the injected dose was recovered in the urine. CONCLUSION: The pharmacokinetics of [123I]IUdR locoregionally administered to a human glioma in situ resembled those observed in a rat glioma model where administration of the radiopharmaceutical radiolabeled with the Auger electron emitter 125I was therapeutically effective.

Tc-99m HMPAO brain perfusion SPECT in acute aphasia. Correlation with clinical and structural findings.

Tc-99m hexamethylpropylene amineoxime (HMPAO) brain perfusion SPECT was correlated with CT, MRI, and clinical findings in 17 patients with acute and subacute aphasia to determine its diagnostic potential in the early phases of stroke-associated language dysfunction. SPECT was performed using a dedicated brain imaging system after intravenous injection of 20 mCi (740 MBq) of Tc-99m HMPAO. Transaxial and three-dimensional surface rendered images were evaluated visually, and perfusion defects were correlated with CT, MRI, and a standard battery of clinical tests for aphasia. Clinical examination was insufficient for anatomic localization of aphasia in more than 40% of patients. CT exams were normal in 5 patients, although SPECT demonstrated perfusion defects in all 17. Nonfluent aphasia was present in only 6 of 10 patients with perfusion defects in Broca's area and fluent aphasia was present in only 5 of 10 patients with lesions in Wernicke's area. Auditory comprehension defect was associated with perfusion defects in the inferior parietal region in 9 of 12 patients (P = 0.05); reading and writing abnormalities were associated with perfusion defects in the posterior frontal, superior and inferior parietal cortex, and superior temporal gyri, and repetition deficit was associated with defects involving the inferior parietal cortex, the supramarginal and angular gyri, and the ipsilateral thalamus in 8 of 11 patients (P < 0.05). Brain perfusion SPECT should be included in the initial evaluation of aphasic patients, because clinical tests of aphasia and morphological imaging have limited value for accurately determining the extent and location of functional deficits.

Thallium-201 technetium-99m HMPAO single-photon emission computed tomography (SPECT) imaging for guiding stereotactic craniotomies in heavily irradiated malignant glioma patients.

SPECT scanning with Tl-201 and Tc-99m offers a unique, inexpensive functional imaging modality to combine with CT stereotactic craniotomy for guiding resection of necrosis and/or tumour in patients treated with escalated doses of radiation (> 6000 cGy) by either brachytherapy or radiosurgery. Thirty-two cases were analyzed, with a detailed description of the imaging and operative techniques.

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.

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.

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.

Frontal lobe dysfunction following infarction of the left-sided medial thalamus.

We treated a 62-year-old woman who developed a dramatic change in personality and behavior following a discrete left-sided medial thalamic infarction involving the dorsomedial nucleus. Neuropsychological testing demonstrated severe impairment of complex executive behaviors that are usually associated with frontal lobe function. Electroencephalography and single-photon emission computed tomography strongly implicated dysfunction of the ipsilateral frontal lobe. This case further supports a functional and physiologic thalamofrontal linkage as part of a broader cerebral network modulating complex human behavior.

Radiation necrosis vs high-grade recurrent glioma: differentiation by using dual-isotope SPECT with 201TI and 99mTc-HMPAO.

Conventional imaging techniques are often unreliable in distinguishing between radiation necrosis and recurrent glioma in patients who are symptomatic after high-dose radiotherapy. We performed dual-isotope single-photon emission computed tomography (SPECT) with the use of thallium-201 (201TI) and the perfusion agent 99mTc-hexamethyl-propyleneamine oxime (HMPAO) to aid in this differentiation in 15 patients with glioma prior to biopsy. We found that dual-isotope SPECT scanning correlated with the pathologic findings in 14 of the 15 cases. All patients with high 201TI uptake in their treated tumor beds had local tumor recurrence, and all patients with low 201TI uptake showed only radiation changes without evidence of solid tumor. In patients with an intermediate level of 201TI concentration in their tumor bed, 99mTc-HMPAO uptake differentiated those patients with active tumor from those without; three of four patients with preserved or increased perfusion had pathologic evidence of solid tumor, whereas none of the four patients with decreased perfusion to the tumor bed had evidence of local recurrence. We believe that dual-isotope SPECT with 201TI and 99mTc-HMPAO may be useful in differentiating sites of likely tumor growth from nonspecific radiation changes in patients treated for malignant glioma.

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.

Computer-assisted superimposition of magnetic resonance and high-resolution technetium-99m-HMPAO and thallium-201 SPECT images of the brain.

A method for registering three-dimensional CT, MR, and PET data sets that require no special patient immobilization or other precise positioning measures was adapted to high-resolution SPECT and MRI and was applied in 14 subjects (five normal volunteers, four patients with dementia (Alzheimer's disease), two patients with recurrent glioblastoma, and three patients with focal lesions (stroke, arachnoid cyst and head trauma]. T2-weighted axial magnetic resonance images and transaxial 99mTc-HMPAO and 201Tl images acquired with an annular gamma camera were merged using an objective registration (translation, rotation and rescaling) program. In the normal subjects and patients with dementia and focal lesions, focal areas of high uptake corresponded to gray matter structures. Focal lesions observed on MRI corresponded to perfusion defects on SPECT. In the patients who had undergone surgical resection of glioblastoma followed by interstitial brachytherapy, increased 201Tl corresponding to recurrent tumor could be localized from the superimposed images. The method was evaluated by measuring the residuals in all subjects and translational errors due to superimposition of deep structures in the 12 subjects with normal thalamic anatomy and 99mTc-HMPAO uptake. This method for superimposing magnetic resonance and high-resolution SPECT images of the brain is a useful technique for correlating regional function with brain anatomy.

Brain perfusion is abnormal in cocaine-dependent polydrug users: a study using technetium-99m-HMPAO and ASPECT.

Cocaine abuse is widespread and has been associated with serious neurovascular complications. We studied a group of cocaine-dependent polydrug users with 99mTc-HMPAO and high-resolution SPECT and compared their perfusion pattern to cerebral perfusion in a group of older control subjects. Sixteen of 18 cocaine-dependent polydrug users had abnormal perfusion characterized primarily as small focal defects involving inferoparietal, temporal, and anterofrontal cortex and basal ganglia. Psychometric testing was abnormal in all 18 cocaine-dependent subjects. No relation was found between the severity of SPECT abnormalities and mode of administration or frequency or length of cocaine use. All 15 older normal subjects had normal cerebral perfusion. While the focal perfusion abnormalities to the cortex and basal ganglia could be explained by the profound vasoconstrictor effects of cocaine, the combinational use of multiple substances including cannabis and alcohol may play a contributory role. This study documents the high incidence of functional brain abnormalities in cocaine-dependent chronic polydrug users without corresponding abnormalities on imaging studies of cerebral anatomy and morphology.