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Biomedical subjects

E S Garnett

Publications and source records attributed to E S Garnett.

At least 19 recordsLinked to original sources
PubMed1995

Redistribution of myocardial blood flow with topical nitroglycerin in patients with coronary artery disease.

BACKGROUND: Unlike nonselective coronary vasodilators, nitroglycerin (GTN) is said to exert its primary vasodilatory effect on epicardial conductance vessels. Thus, in experimental models of coronary occlusion GTN appears to preferentially direct blood flow to poststenotic zones of ischemia. This phenomenon has, to date, not been tested in humans. Using positron emission tomography we examined the effect of transdermal GTN on global and regional myocardial perfusion in patients with angiographically proven coronary artery disease. METHODS AND RESULTS: Myocardial perfusion with [13N]ammonia was estimated from dynamic time-activity curves at baseline and 3 hours following application of either a 0.4 mg/h GTN skin patch (n = 10) or a placebo patch (n = 10) in a double-blind parallel design. From resliced cross-sectional images, regional flow, expressed as [13N]ammonia retention, was estimated from 216 myocardial sectors. Ischemia was defined as a significant reduction (> 2 SDs from average counts/pixel in maximally perfused zones) in [13N]ammonia retention within 10 contiguous myocardial sectors coupled with an increase or no change in counts derived from [18F]fluorodeoxyglucose. There was no change in global myocardial blood flow as expressed by [13N]ammonia retention following either placebo (0.61 +/- 0.14 to 0.62 +/- 0.12 min-1) or GTN (0.75 +/- 0.22 to 0.74 +/- 0.19 min-1). Conversely, there was a significant increase in the proportion of blood flow to the ischemic zones with GTN (73.9 +/- 12.6% to 94.9 +/- 17.8%; P < .05). No change in the distribution of blood flow to either ischemic or nonischemic zones was observed with placebo. A slight but insignificant decrease in [13N]ammonia retention in nonischemic zones was observed with GTN (1.01 +/- 0.31 to 0.93 +/- 0.26 min-1). CONCLUSIONS: This study suggests that under resting conditions topical GTN alters myocardial perfusion by preferentially increasing flow to areas of reduced perfusion with little or no change in global myocardial perfusion in patients whose angina is responsive to GTN.

Administration, Cutaneous↗
PubMed1995

A probe for intracerebral aromatic amino-acid decarboxylase activity: distribution and kinetics of [18F]6-fluoro-L-m-tyrosine in the human brain.

Positron tomography, using [18F]6-fluoro-L-dopa as a tracer, has been used for the study of Parkinson's disease. Unfortunately, the analysis of data obtained with this agent is bedeviled because it readily forms labeled methylated metabolites that enter the brain. We have evaluated [18F]6-fluoro-L-m-tyrosine (FmT) as an alternative tracer to study intracerebral dopamine metabolism with positron tomography. Imaging studies in humans showed specific accumulation of this tracer in the dopamine-rich striatal regions. Reduced striatal uptake of the tracer was demonstrated in a patient suffering from Parkinson's disease. Increased retention of the tracer was demonstrated in a subject pretreated with the peripheral decarboxylase inhibitor carbidopa. Analysis of plasma samples for labeled metabolites of FmT revealed no methylated metabolites. Results of compartmental analysis showed that a two-compartment three rate constant model described adequately the time course of radioactivity in the striatum after an injection of FmT. The FmT decarboxylation rate constant (k21) was found to be 0.0108 min-1. Because the peripheral metabolism of FmT is simpler than that of [18F]6-fluoro-L-dopa, we propose FmT as a superior agent with which to study intracerebral dopamine metabolism in health and disease in humans.

Adolescent↗
PubMed1995

Electrophilic 18F from a Siemens 11 MeV proton-only cyclotron.

Because more and more PET centres are using small proton cyclotrons there is a renewed interest in methods for the production of electrophilic 18F by proton irradiation of [18O]O2. A method for the routine production of clinically useful quantities of [18F]F2 having a specific activity of 35 Ci/mmol has been developed and implemented using an 11 MeV proton cyclotron and [18O]O2. Based on the yield, purity, reproducibility, and specific activity of [18F]F2 this is the most efficient method reported thus far.

Cyclotrons↗
PubMed1994

The distribution and kinetics of [18F]6-fluoro-3-O-methyl-L-dopa in the human brain.

The analysis of positron tomographic studies of 3,4-dihydroxyphenylethylamine (dopamine) metabolism in which [18F]6-fluoro-L-3,4-dihydroxyphenylalanine (F-dopa) is used as a tracer is confounded by the presence of [18F]6-fluoro-3-O-methyl-L-3,4-dihydroxyphenylalanine (OMFD). This labeled molecule, formed by the action of peripheral catechol-O-methyltransferase on F-dopa, crosses the blood-brain barrier and contributes to the radioactivity measured by the tomograph. Corrections for this radioactivity in the brain have been proposed. They rely upon the assumption that regional variations in the handling of this molecule by the brain are negligible. Although this assumption is pivotal for the proper quantification of dopamine metabolism using F-dopa, the distribution and kinetics of OMFD have never been studied in humans. We present results in humans that show that there is little selective regional 18F accumulation in the brain, that the distribution volume of OMFD is close to unity, and that a single, reversible compartment is adequate to model the measured time course of radioactivity after an OMFD injection. Analysis of plasma samples for labeled metabolites showed that more than 95% of the radioactivity was associated with OMFD at all times. Our results for OMFD kinetics are in accord with published results obtained in nonhuman primates and for the bidirectional transport of large neutral amino acids across the blood-brain barrier measured using a synthetic amino acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Three clinical syndromes of schizophrenia in untreated subjects: relation to brain glucose activity measured by positron emission tomography (PET).

A number of studies of chronically ill, medicated patients have found that the clinical symptoms of schizophrenia segregate into three syndromes which can be labelled poverty, disorganization, and reality distortion. It has been previously found that each of these syndromes is associated with a specific pattern of perfusion (rCBF) in paralimbic and association cortex and in related subcortical nuclei. We replicated the symptom factors in 20 untreated subjects. Utilizing positron emission tomography with 18-F-fluorodeoxyglucose as a tracer for glucose metabolism, we reconstructed a map of the entire cortical activity from 16 to 20 tomographic slices. Each of the three syndromes was associated with a different pattern of regional glucose metabolism. Findings in common with previous studies were an association of poverty with left cortical metabolic activity in prefrontal and superior parietal areas, reality distortion with left temporal activity, and disorganization with left inferior parietal lobule. This is the first report of an association between regional metabolic activity and clinical syndromes in untreated patients, strengthening previous models of distributed neural networks in this disorder.

Adolescent↗
PubMed1992

Fluctuating cognitive abnormalities and cerebral glucose metabolism in neuropsychiatric systemic lupus erythematosus.

Brain imaging techniques such as MRI and PET have the potential for identifying central nervous system involvement in SLE. They may also help elucidate the mechanisms giving rise to the widely diverging manifestations of CNS involvement in SLE. This report documents an intensive longitudinal study of three women with neuropsychiatric SLE. PET and neuropsychological evaluation were both used to examine the co-occurrence of behavioural/cognitive deficits with alterations in regional brain glucose metabolism. In all three patients, FDG uptake indicated abnormalities which were not identified on CT scan, but corresponded well with localisable cognitive deficits. Changes in each patient's cognitive profile on reassessment paralleled changes on PET. These findings support the suggestion that cognitive deficits in SLE patients reflect primary CNS involvement.

Adolescent↗
PubMed1992

Toward a brain map of auditory hallucinations.

OBJECTIVE: This study asks whether auditory hallucinations are reflected in a distinctive metabolic map of the brain. METHOD: Regional brain metabolism was measured by positron emission tomography with [18F]-fluorodeoxyglucose in 12 DSM-III schizophrenic patients who experienced auditory hallucinations during glucose uptake and 10 who did not. All patients were free of neuroleptics and 19 had never been treated with neuroleptics. Nine patients were reexamined after 1 year to assess effects of neuroleptic treatment. RESULTS: Compared with the patients who did not experience hallucinations, the patients who did experience hallucinations had significantly lower relative metabolism in auditory and Wernicke's regions and a trend toward higher metabolism in the right hemisphere homologue of Broca's region. Hallucination scores correlated positively and significantly with relative metabolism in the striatum and anterior cingulate regions. Neuroleptic treatment resulted in a significant increase in striatal metabolism and a reduced frontal-parietal ratio, which was significantly correlated with a decrease in hallucination scores. CONCLUSIONS: Auditory hallucinations involve language regions of the cortex in a pattern similar to that seen in normal subjects listening to their own voices but different in that left prefrontal regions are not activated. The striatum plays a critical role in auditory hallucinations.

Adult↗
PubMed1991

Apomorphine effects on brain metabolism in neuroleptic-naive schizophrenic patients.

Since neuroleptic treatment produces a significant increase in striatal metabolism relative to cortical metabolism, we wished to determine whether the dopamine agonist apomorphine (APO) might have the opposite effect, and whether it would discriminate schizophrenic patients from healthy controls. Eleven neuroleptic-naive schizophrenic patients (diagnosed according to DSM-III) and eight normal subjects were compared with respect to cerebral accumulation of 18F-fluorodeoxyglucose measured by positron emission tomography following APO, 0.75 mg/70 kg (weight adjusted), or saline. Relative striatal glucose metabolism decreased significantly after APO in schizophrenic patients but not in control subjects. Post hoc analysis of data in 12 other regions revealed that relative superior temporal metabolism decreased very slightly, but significantly, in schizophrenic patients but not in control subjects after APO, and that the posterior frontal region increased in control subjects but not in the patient group.

Adolescent↗
PubMed1991

Posterior cortical dementia with alexia: neurobehavioural, MRI, and PET findings.

A progressive disorder of relatively focal but asymmetric biposterior dysfunction is described in a 54 year old right handed male. Initial clinical features included letter-by-letter alexia, visual anomia, acalculia, mild agraphia, constructional apraxia, and visuospatial compromise. Serial testing demonstrated relentless deterioration with additional development of transcortical sensory aphasia, Gerstmann's tetrad, and severe visuoperceptual impairment. Amnesia was not an early clinical feature. Judgment, personality, insight, and awareness remained preserved throughout most of the clinical course. Extinction in the right visual field to bilateral stimulation was the sole neurological abnormality. Early CT was normal and late MRI showed asymmetrical bioccipitoparietal atrophy with greater involvement of the left hemisphere. Results from positron emission tomography (PET) showed bilaterally asymmetric (left greater than right) occipitotemporoparietal hypometabolism. The metabolic decrement was strikingly asymmetric with a 50% reduction in glucose consumption confined to the left occipital cortex. The picture of occipitotemporoparietal compromise verified by MRI, PET, and neurobehavioural testing would be unusual for such degenerative dementias as Alzheimer's (AD) and Pick's disease, although atypical AD with predominant occipital lobe involvement cannot be excluded. This case supports the concepts of posterior cortical dementia (PCD) as a clinically distinct entity and for the first time documents its corresponding metabolic deficit using PET.

Atrophy↗
PubMed1990

Regional brain metabolism during auditory hallucinations in chronic schizophrenia.

Regions of the brain involved in language and attention were studied using [18F]-fluorodeoxy-glucose in PET. In nine chronic DSM-III schizophrenic patients who had persistent auditory hallucinations, ten who had recovered from hallucinations and ten normal controls. In none of the regions examined was metabolic activity significantly different in hallucinating patients compared with that in other groups. However, a pattern of seven significant correlations of metabolic activity between language regions and between frontal and parietal cortex characterised the hallucinating but not the other groups. Three of the seven correlations were significantly greater in hallucinating patients than in the two other groups, and six were greater in hallucinating patients than controls. Metabolism in Broca's region and its right-hemisphere homologue correlated positively and significantly in the hallucinating group, as it did in anterior cingulate and left superior temporal areas, and in right frontal and parietal areas. Hallucination ratings correlated with metabolism in the anterior cingulate region.

Adult↗
PubMed1990

New 18F tracers for the investigation of brain functions.

Advances in the synthetic methodology of radiofluorination have increased the number of clinically useful 18F labeled tracers for positron emission tomography of the brain. It is now possible to measure in vivo with 18F tracers regional cerebral blood flow (18F-fluoromethane), dopamine metabolism (6-18F-fluoro-L-dopa) and dopamine D-2 receptor density (N-18F-fluoroethylspiperone). At present 18F tracers are being developed that will, in the near future, make accessible to investigation cerebral serotonin metabolism, serotonin receptor density, melatonin receptor density, activity of L-aromatic acid decarboxylase, and protein synthesis rate.

Brain↗
PubMed1989

Increased frontal and reduced parietal glucose metabolism in acute untreated schizophrenia.

Frontal and parietal lobe metabolism was measured by [18F] fluorodeoxyglucose positron emission tomography in 8 never-medicated DSM-III schizophrenic patients and in 10 control subjects. Patients were in a psychotic episode at the time of this scan. Seven of eight had been ill less than 2 years and had only mild neurocognitive impairment. Frontal lobe glucose metabolism was significantly greater in schizophrenic patients than in controls. This finding differs from that of hypofrontality reported in chronic patients previously treated with neuroleptics. Relative glucose metabolism in the interior parietal lobe was significantly lower in schizophrenic patients than in controls. The frontal/parietal ratios were significantly greater in patients than in controls.

Acute Disease↗
PubMed1988

Effect of neuroleptics on altered cerebral glucose metabolism in schizophrenia.

This study examines whether the duration of treatment with antipsychotic drugs influences the regional distribution of cerebral [18F]2-fluoro-2-deoxy-D-glucose utilization as measured by positron emission tomography. Two groups of schizophrenic patients are compared with normal volunteers (n = 10). One group (n = 5) consisted of patients treated for one year, and the second (n = 12) of patients medicated for four to 14 years (mean +/- SD duration, 7.4 +/- 3.4 years). The first group was also examined before patients received their first dose ever of antipsychotic medication. One year of medication was not sufficient to alter the schizophrenic profile of cerebral cortical glucose activity but did elevate activity of the corpus striatum. Medication for 7.4 years also did not alter the schizophrenic pattern of frontal hyperactivity and posterior hypoactivity, although deviations from control values appeared less marked than after one year. On the other hand, in patients medicated for 7.4 years, there was perhaps an even greater increase in the activity of the corpus striatum and of the thalamus. Thus, duration of exposure to antipsychotic medication may affect the pattern of cerebral glucose activity; possibly, even longer exposure may contribute to the hypofrontality noted by others, although this can be confounded with the duration of illness as a factor. In considering the biological significance of the observed profile of cortical glucose activity, we introduce the concept of cerebral metabolic tone. We suggest that a disturbance of this tonus may account for some symptoms of schizophrenia and could be consistent with the hypothesis of abnormal developmental changes in the brains of schizophrenics.

Acute Disease↗
PubMed1988

Nigrostriatal dopaminergic activity is increased during exhaustive exercise stress in rats.

Exercise capacity is influenced by both increases and decreases in central dopaminergic activity. To investigate the effects of exercise stress on intracerebral dopamine metabolism, rats were run on a motor driven treadmill at 37 m/min for varying times up to exhaustion at 19.6 +/- 0.6 min. Dopamine, DOPAC, and HVA concentrations in striatum, brain stem, and hypothalamus increased towards exhaustion. 5-HIAA concentrations increased in striatum whereas norepinephrine concentrations decreased in hypothalamus. The results indicate that delayed increases in dopaminergic activity occurs during exercise. These, and other observations indicate that central dopaminergic activity modulates exercise performance.

3,4-Dihydroxyphenylacetic Acid↗