Biomedical subjects

J Bergman

Publications and source records attributed to J Bergman.

At least 73 records · Page 4Linked to original sources

PubMed1999

Apparent pA2 values of benzodiazepine antagonists and partial agonists in monkeys.

Drugs that bind to benzodiazepine recognition sites of gamma-aminobutyric acid type A receptor complexes may function as agonists in some behavioral assays and as antagonists in other behavioral assays. The present studies compared the effects of the benzodiazepines midazolam, flumazenil, bretazenil, Ro 41-7812, and Ro 42-8773 and the beta-carboline, beta-carboline-3-carboxylate-t-butyl ester (beta-CCt) under two different types of schedule-controlled responding in squirrel monkeys. One group of monkeys responded under a fixed-ratio schedule of stimulus-shock termination, and a second group of monkeys responded under a multiple fixed-ratio schedule of food presentation involving suppressed and nonsuppressed behavior. Under the schedule of stimulus-shock termination, midazolam produced dose-related decreases in response rate, and these effects were surmountably antagonized by flumazenil, bretazenil, Ro 41-7812, Ro 42-8773, and beta-CCt. Schild plot analysis of these data revealed the following mean pA(2) values: flumazenil, 7.18; bretazenil, 7.62; Ro 41-7812, 7. 06; Ro 42-8773, 6.95. Apparent pA(2) values were not calculated for beta-CCt because the CL of the slope of the Schild plot included positive values. Under the multiple schedule, midazolam, bretazenil, and Ro 42-8773 dose-dependently increased rates of suppressed responding, whereas flumazenil, Ro 41-7812, and beta-CCt had no significant rate-altering effects. Flumazenil antagonized the antisuppressant effects of midazolam and bretazenil; however, individual variability in these effects prohibited the determination of apparent pA(2) values. These results indicate that in vivo pA(2) values may be determined for benzodiazepine-site ligands. These results further demonstrate that some benzodiazepine-site ligands, e. g., bretazenil and Ro 42-8773, may function as both agonists and as competitive antagonists in vivo.

Animals↗

PubMed1999

Effects of dopamine D(1-like) and D(2-like) agonists in rats that self-administer cocaine.

The reinforcing effects of D(1-like) and D(2-like) agonists, and their capacity to modify cocaine self-administration, were compared in rats with extensive cocaine self-administration experience. Cocaine (0.01-1.0 mg i.v.) dose-dependently maintained responding under a fixed ratio (FR) 5 schedule of reinforcement, and an inverted U-shaped function characterized the relationship between unit dose and self-administration behavior. When substituted for cocaine, the D(1-like) agonists SKF 82958 (0.001-0.032 mg i.v.) and SKF 77434 (0.001-0.1 mg i.v.) did not maintain responding above levels observed during saline substitution. In contrast, the D(2-like) agonists quinelorane (0.001-0.1 mg i.v.) and 7-hydroxy-dipropylaminotetralin (7-OH-DPAT; 0.01-0.32 mg i.v.) reliably maintained i.v. self-administration behavior that was characterized by inverted U-shaped dose-effect functions. Pretreatment with the D(1-like) agonists SKF 82958 and SKF 77434 (0.1-1.0 mg/kg i.p.) shifted the dose-effect function for cocaine self-administration downward, whereas pretreatment with the D(2-like) agonists quinelorane (0.01 mg/kg i.p.) and 7-OH-DPAT (0.32-1.0 mg/kg i.p.) shifted the cocaine dose-effect function to the left. Effects of D(1-like) and D(2-like) agonists on patterns of responding maintained by cocaine (0.32 mg i.v.) also differed: D(1-like) agonists increased the latency to the first response but did not otherwise alter patterns of cocaine self-administration, whereas D(2-like) agonists increased the intervals between self-administered cocaine injections. The results suggest that D(2-like) agonists, but not D(1-like) agonists, have prominent reinforcing effects and enhance the effects of self-administered cocaine in rats with extensive cocaine self-administration experience. Consequently, D(2) receptor-related neuronal mechanisms may be especially important in mediating the abuse-related effects of cocaine.

Animals↗

PubMed1999

Increased brain glucose utilization in Salla disease (free sialic acid storage disorder).

UNLABELLED: Salla disease is an autosomal recessive lysosomal free sialic acid storage disorder characterized by psychomotor retardation and ataxia. MRI studies have revealed evidence of dysmyelination, but the biological mechanism of the brain dysfunction is unknown. METHODS: Nine patients with Salla disease (age 2.5 mo-42 y) presenting the disease in varying degrees of severity were studied by PET using 2-fluoro-2-deoxy-D-glucose (FDG) as a tracer. Local cerebral metabolic rates for glucose (LCMRGlc) in individual brain regions were compared with controls. RESULTS: The FDG PET results showed significantly increased LCMRGlc values in the frontal and sensorimotor cortex and especially in the basal ganglia of the patients. Cerebellar hypometabolism was present in all seven patients with marked ataxia, whereas the less severely affected patients without obvious ataxia had normal or even high glucose uptake in the cerebellum. CONCLUSION: The increased cerebral glucose utilization is a constant finding in Salla disease and may reflect the basic defect of the sialic acid metabolism in this disorder. The FDG PET findings in the cerebellum suggest a correlation between glucose uptake and the severity of the clinical symptoms.

Adolescent↗

PubMed1998

Promethazine overdose: is it a "Goodnight" after all?

AIMS: To evaluate and describe the perceived increase in number of promethazine overdoses presenting to Auckland Hospital Emergency Department since Goodnight became available in New Zealand. METHOD: Emergency Department records were reviewed for 19.5 months from 19 December 1994 (when Goodnight became available on the New Zealand market) until 31 July 1996. The Emergency Department database for the preceding years dating back to 1 January 1984 was reviewed. RESULTS: There were a total of 25 patients (18 female; 7 male) with 17 patients being between the ages of 15-25. The first cases presented in April 1995 and 15 cases (60%) presented during the 1996 period of the study. Fifteen patients (60%) ingested one or more full boxes of Goodnight. Twelve patients (48%) were admitted to intensive care, eight of whom were intubated. Fifteen patients were discharged from hospital in under 24 hours, but five (20%) stayed 2-3 days. Records dating back to 1 January 1984 revealed a total of 31 cases of promethazine overdose in just under 11 years, nine being accidental ingestion in children less than 5 years of age. CONCLUSIONS: This review highlights the high morbidity and cost of having promethazine available as an unrestricted, pharmacy--only medication. It suggests that marketing laws should be reviewed and the availability of promethazine be curtailed.

Adolescent↗

PubMed1998

Interactions of the antiviral quinoxaline derivative 9-OH-B220 [2, 3-dimethyl-6-(dimethylaminoethyl)- 9-hydroxy-6H-indolo-[2, 3-b]quinoxaline] with duplex and triplex forms of synthetic DNA and RNA.

The binding of an antiviral quinoxaline derivative, 2,3-dimethyl- 6 - (dimethylaminoethyl) - 9 - hydroxy - 6H - indolo - [2,3 - b]quinoxaline (9-OH-B220), to synthetic double and triple helical DNA (poly(dA).poly(dT) and poly(dA).2poly(dT)) and RNA (poly(rA). poly(rU) and poly (rA).2poly(rU)) has been characterized using flow linear dichroism (LD), circular dichroism (CD), fluorescence spectroscopy, and thermal denaturation. When either of the DNA structures or the RNA duplex serve as host polymers a strongly negative LD is displayed, consistent with intercalation of the chromophoric ring system between the base-pairs/triplets of the nucleic acid structures. Evidence for this geometry also includes weak induced CD signals and strong increments of the fluorescence emission intensities upon binding of the drug to each of these polymer structures. In agreement with intercalative binding, 9-OH-B220 is found to effectively enhance the thermal stability of both the double and triple helical states of DNA as well as the RNA duplex. In the case of poly(dA).2poly(dT), the drug provides an unusually large stabilization of its triple helical state; upon binding of 9-OH-B220 the triplex-to-duplex equilibrium is shifted towards higher temperature by 52.5 deg. C in a 10 mM sodium cacodylate buffer (pH 7.0) containing 100 mM NaCl and 1 mM EDTA. When triplex RNA serves as host structure, LD indicates that the average orientation angle between the drug chromophore plane and the helix axis of the triple helical RNA is only about 60 to 65 degrees. Moreover, the thermal stabilizing capability, as well as the fluorescence increment, CD inducing power and perturbations of the absorption envelope, of 9-OH-B220 in complex with the RNA triplex are all less pronounced than those observed for the complexes with DNA and duplex RNA. These features indicate binding of 9-OH-B220 in the wide and shallow minor groove of poly(rA).2poly(rU). Based on the present results, some implications for the applications of this low-toxic, antiviral and easily administered drug in an antigene strategy, as well as its potential use as an antiretroviral agent, are discussed.

Antiviral Agents↗

PubMed1998

[18F]CFT [(18F)WIN 35,428], a radioligand to study the dopamine transporter with PET: characterization in human subjects.

We have characterized the usage of [18F]CFT (also known as [18F]WIN 35,428) as a radioligand for in vivo studies of human dopamine transporter by PET. CFT was labeled with 18F to a high specific activity, and dynamic PET scans were conducted in healthy volunteers at various time points up to 5 h from [18F]CFT injection. The regional distribution of [18F]CFT uptake correlated well with the known distribution of dopaminergic nerve terminals in the human brain and also with that of other dopamine transporter radioligands. Striatal binding peaked at 225 min after injection and declined thereafter, demonstrating the reversible nature of the binding to the dopamine transporter. Therefore, due to the relatively long half-life of 18F (109.8 min), PET scans with [18F]CFT could easily be conducted during the binding equilibrium, allowing estimation of Bmax/Kd values (i.e., binding potential). Binding potentials for putamen and caudate measured at equilibrium were 4.79+/-0.11 and 4.50+/-0.23, respectively. We were able to also visualize midbrain dopaminergic neurons (substantia nigra) with [18F]CFT in some subjects. In conclusion, the labeling of CFT with 18F allows PET scans to be conducted at binding equilibrium, and therefore a high signal-to-noise ratio and reliable quantification of binding potential can be achieved. With a high resolution 3D PET scanner, the quantification of extrastriatal dopamine transporters should become possible.

Adult↗

PubMed1998

Long-term outcome of autoimmune disease following allogeneic bone marrow transplantation.

OBJECTIVE: To investigate the long-term outcome of autoimmune disease following allogeneic bone marrow transplantation (BMT), and its relationship to hemopoietic chimerism. METHODS: Three previously described patients with rheumatoid arthritis (RA) who underwent allogeneic BMT for therapy-related severe aplastic anemia and 1 new patient with psoriasis who received BMT for chronic myeloid leukemia (CML) were followed up. Molecular studies were performed to assess hemopoietic and immune reconstitution in 3 cases. RESULTS: In 2 of the RA patients, the RA remained in remission without treatment, with nonprogressive disease, 11 and 13 years after BMT. The third patient with RA had a relapse 2 years after BMT, although the previously aggressive disease subsequently ran an attenuated course with treatment-free remission for the last 11 years. Comparison with other cases of RA suggests that graft-versus-host disease may influence the long-term outcome, perhaps through ongoing inhibition of the immune system. In the patient with psoriasis, BMT was followed by remission, but the psoriatic rash recurred and arthropathy developed 12 months later. The psoriasis and arthropathy remained active 4.5 years post-BMT, although the CML remained in remission. Molecular studies in the 2 patients whose RA remained in continued remission and in the patient with psoriasis that relapsed confirmed complete donor hemopoietic reconstitution. CONCLUSION: Long-term followup of autoimmune disease after allogeneic transplantation confirmed cure of the autoimmune disease in some, but eventual relapse in others. The occurrence of relapse despite complete donor hemopoietic reconstitution is evidence for the development of de novo, as opposed to persistent, disease, and is possibly related to intrinsic susceptibility of the transplanted stem cells or to host factors. There may be a relationship between remission of autoimmune disease and graft-versus-host reaction. These findings have relevance for the evolving application of stem cell transplantation as a therapy for autoimmune diseases.

Adult↗

PubMed1998

Striatal presynaptic dopamine function in type 1 alcoholics measured with positron emission tomography.

Recent in vivo studies have shown low dopamine D2 receptor and dopamine transporter densities among late onset (type 1) alcoholics. We have now studied 6-[18F]-FDOPA (FDOPA) uptake in 10 type 1 alcoholics and eight matched controls to test the hypothesis that striatal presynaptic dopamine function is lower among alcoholics. Markedly low FDOPA uptake (Ki) was observed in the left caudate of two alcoholic patients, but the mean striatal uptake values of the patient group were higher than those of the control group. The greatest difference was observed in the mean FDOPA intake in the left putamen, which was 28% higher in the patient group (t = 3.00, P = 0.008, d.f. = 16, independent samples t-test), and in the right caudate (difference 36%, t = 2.87, P = 0.01). The elevated FDOPA uptake in putamen and caudate correlated with poor Wisconsin Card Sorting Test (WCST) performance (error %) among alcoholics (correlation coefficients from 0.49 to 0.56), which suggests that the magnitude of presynaptic dopamine function alteration correlates with the degree of disability to modify one's behavior. The results do not give support to the hypothesis of generally decreased striatal dopamine turnover in type 1 alcoholism, but on the contrary indicate an increased presynaptic dopamine function. This may represent a compensatory mechanism to low postsynaptic DA function. The low presynaptic DA function observed in the left caudate of two patients suggests that type 1 alcoholism may be a heterogeneous disorder.

Adult↗

PubMed1998

Drug discrimination in methamphetamine-trained monkeys: agonist and antagonist effects of dopaminergic drugs.

The involvement of D1 and D2 subtypes of dopamine receptors in behavioral effects of methamphetamine was studied in squirrel monkeys using a two-lever drug discrimination procedure. In monkeys that discriminated i.m. injections of 0.3 mg/kg methamphetamine from saline, methamphetamine (0.03-0.3 mg/kg), cocaine (0.1-1.0 mg/kg) and the selective dopamine uptake inhibitor, GBR 12909 (3.0-17.8 mg/kg) produced dose-related increases in responding on the methamphetamine-associated lever and, at the highest doses, full substitution. In contrast, the norepinephrine and serotonin uptake inhibitors, tomoxetine (1.0-17.8 mg/kg) and fluoxetine (0.3-10.0 mg/kg), respectively, did not substitute appreciably for methamphetamine. Substitution for methamphetamine also was observed with the D1 receptor agonists, SKF 81297, SKF 82958 and dihydrexidine, and the D2 receptor agonist, (+)-PHNO in the majority of monkeys. Lower-efficacy D1 or D2 agonists substituted for methamphetamine either partially (SDZ 208-911) or not at all (SKF 77434, SDZ 208-912). Pretreatment with dopamine receptor blockers [D1 (SCH 39166, 0.1 mg/kg) or D2 (remoxipride, 3.0 mg/kg and nemonapride, 0.003 mg/kg)] and low-efficacy agonists [D1 (SKF 77434; 3.0 mg/kg) or D2 (SDZ 208-911 and SDZ 208-912; 0.01-0.03 mg/kg)] antagonized the discriminative-stimulus effects of methamphetamine. In separate studies, comparable doses of each of these drugs, except SKF 77434, induced significant levels of catalepsy-associated behavior. These results support the view that both dopaminergic D1 and D2 mechanisms mediate the discriminative-stimulus effects of methamphetamine; further, they indicate that selected dopamine D1 partial agonists may have antagonist actions at doses that do not produce undesirable effects associated with dopamine receptor blockade.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1997

Cerebral metabolic rate for glucose after neonatal hypoglycaemia.

OBJECTIVE: We studied the effect of neonatal hypoglycaemia on the local cerebral metabolic rate for glucose (LCMRglc). MATERIALS AND METHODS: Eight newborn infants with neonatal hypoglycaemia were studied. The LCMRglc in the whole brain, in five cerebral regions and in skeletal muscles were quantitated using positron emission tomography (PET) and 2-[18F]Fluoro-2-deoxy-D-glucose (FDG). The PET studies were performed at the age of 5.3 +/- 6.2 days during normoglycaemia. The LCMRglc of these infants were compared to the age-adjusted LCMRglc of eight infants with suspected hypoxic-ischaemic brain injury but with normal neurological development. RESULTS: After neonatal hypoglycaemia the age-adjusted LCMRglc in the whole brain was not lower than LCMRglc of the control infants (5.33 +/- 0.60 mumol/100 g/min vs. 6.71 +/- 0.60 mumol/100 g/min). Also the metabolic rate for glucose (MRglc) in the skeletal muscles was similar in hypoglycaemic and control infants (5.56 +/- 2.48 mumol/100 g/min vs. 6.99 +/- 2.41 mumol/100 g/min). CONCLUSION: MRglc in brain and in skeletal muscle seems to be normal after neonatal hypoglycaemia, although larger group of patients with more severe hypoglycaemia are needed to confirm this finding.

Animals↗

PubMed1997

Regulation of dioxin receptor function by omeprazole.

The intracellular dioxin (aryl hydrocarbon) receptor mediates signal transduction by dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) and related environmental pollutants and functions as a ligand-activated transcription factor. In this study we have examined the effects on dioxin receptor function of a potentially novel ligand, omeprazole, which is widely clinically used as a gastric anti-ulcer drug. In primary human hepatocytes omeprazole potently induced cytochrome P4501A1 mRNA expression, whereas this effect was not detected in mouse primary hepatocytes. In human hepatoma cells omeprazole was found to induce transcription of reporter genes via the xenobiotic response element that is recognized by the ligand-activated dioxin receptor. In contrast, the human dioxin receptor was not activated by omeprazole upon expression in a receptor-deficient mouse hepatoma cell line. In a reconstituted yeast (Saccharomyces cerevisiae) model system, however, both the mouse and human dioxin receptors were potently activated by omeprazole. Although omeprazole failed to displace dioxin in in vitro ligand binding assays, a residue within the ligand binding domain that is critical for dioxin binding in vitro was also critical for omeprazole responsiveness in vivo. Consistent with this observation, both omeprazole and dioxin responsiveness of the dioxin receptor was inhibited in mutant yeast cells expressing low levels of the molecular chaperone hsp90 that is critical for ligand binding activity. The sulfoxide group that is essential for formation of a planar conversion product of omeprazole was found to be critical for dioxin receptor activation. Taken together, these data suggest that omeprazole represents a precursor for a novel class of dioxin receptor agonists that are bona fide dioxin receptor ligands but generated in a strictly species-specific manner.

Animals↗

PubMed1997

JL13, a pyridobenzoxazepine compound with potential atypical antipsychotic activity: a review of its behavioural properties.

The search for an improved clozapine-like compound has resulted in the selection of a new molecule: JL13 (5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5] benzoxazepine fumarate). Like clozapine, JL13 did not antagonize apomorphine-induced stereotypy and did not produce catalepsy but antagonized apomorphine-induced climbing in rodents (ID50 = 3.9 mg kg-1 s.c.). It was inactive against d-amphetamine-induced stereotypy but antagonized d-amphetamine-induced hyperactivity in the mouse (ID50 = 4.4 mg kg-1 i.p.). JL13, like clozapine, was able to antagonize (+/-)-DOI-induced head-twitches in the mouse (ID50 = 2.0 mg kg-1 i.p.). In the open-field test in the rat and forced swimming test in the mouse a high similarity was noted between the two drugs in the same range of doses. In a complex temporal regulation schedule in the dog, JL13 showed a high resemblance with clozapine without inducing sialorrhea, palpebral ptosis or any significant motor side effects. In rats trained to discriminate clozapine, JL13 (10 mg kg-1 i.p.) induced a high level of generalization (70%) to clozapine. In a drug discrimination procedure in the squirrel monkey, JL13 (3-10 mg kg-1 i.m.) produced a full substitution of clozapine. On the basis of these preclinical data, it is thus predicted that JL13 would be a promising atypical antipsychotic drug.

Animals↗

PubMed1997

Discriminative-stimulus effects of clozapine in squirrel monkeys: comparison with conventional and novel antipsychotic drugs.

The effects of conventional and novel atypical antipsychotic drugs were compared to clozapine in squirrel monkeys that discriminated I.M. injections of clozapine (1.0 mg/kg) from saline in a two-lever drug discrimination procedure. Clozapine (0.03-3.0 mg/kg) produced dose-related increases in responding on the clozapine-associated lever with full substitution at the training dose in all monkeys. Dose-related increases in responding on the clozapine-associated lever and full substitution also were observed with structural analogues of clozapine including perlapine and fluperlapine (0.1-3.0 mg/kg), seroquel (0.1-5.6 mg/kg), and JL 5, JL 8 and JL 18 (0.1-3.0 mg/kg). Other clozapine analogues, including olanzapine, amoxapine, loxapine and clothiapine, and conventional antipsychotic drugs, including phenothiazines such as chlorpromazine and thioridazine, produced some clozapine-associated responding up to the highest doses that could be studied, but did not substitute for clozapine. Olanzapine did produce full clozapine-lever responding following pretreatment with the dopamine D2-receptor agonist (+)-PHNO (0.003-0.01 mg/kg). Putatively atypical antipsychotics that are structurally unrelated to clozapine including risperidone (0.003-0.1 mg/kg), sertindole (0.03-1.0 mg/kg) and remoxipride (0.1-5.6 mg/kg) similarly failed to substitute for clozapine up to the highest doses. The present results indicate that some, but not all, structural analogs of clozapine have clozapine-like discriminative-stimulus effects and that novel antipsychotic drugs which purportedly have clozapine-like clinical efficacy may not produce its interoceptive stimulus effects.

Animals↗

PubMed1997

Differential modulation of behavioral effects of cocaine by low- and high-efficacy D1 agonists.

Dopamine D1 agonists differing in efficacy with respect to stimulation of adenylate cyclase activity and other in vitro and in vivo criteria were evaluated for their capacity to modulate the behavioral effects of cocaine in squirrel monkeys. Monkeys were trained either to respond on a fixed-ratio schedule in which lever pressing terminated a stimulus associated with electric shock or to discriminate cocaine from vehicle using a two-lever drug-discrimination procedure. When administered in combination with cocaine, D1 agonists displaying relatively low efficacy (SKF 38393, SKF 75670) attenuated both the rate-altering effects of cocaine on fixed-ratio responding and the discriminative-stimulus effects of cocaine, resulting in overall rightward shifts of the cocaine dose-response functions. Maximal attenuation of the behavioral effects of cocaine by the D1 partial agonists was comparable to that produced by the D1 antagonist SCH 39166. In contrast, D1 agonists displaying relatively high efficacy (SKF 81297, SKF 82958, SKF 83189) either had little effect on or accentuated the rate-altering and discriminative-stimulus effects of cocaine. The results show that D1 partial agonists can act as functional cocaine antagonists and may be viable candidate medications for the management of cocaine addiction.

Animals↗

PubMed1997

Microsatellites of the parasitic nematode Haemonchus contortus: polymorphism and linkage with a direct repeat.

To develop tools to analyse parasitic nematode population structures and the effects of selection pressure on the nematode population, we isolated and characterised 13 microsatellite markers of the nematode Haemonchus contortus. The density of CA/GT microsatellites, once in 575 kb, is lower than in mammals. Although the isolated CA/GT repeats were imperfect, the majority of the microsatellites were polymorphic in one or more populations. An extensive genetic diversity both within and between populations could be established. Two-thirds of the CA/GT microsatellites were followed by a variable number of 128 bp direct repeat elements, HcREP1. HcREP1 is a repetitive element in the H. contortus genome, which is homologous to the repetitive TcREP element in the nematode Trichostrongylus colubriformis.

Animals↗

PubMed1997

Fluorine-18-labeled fluorine gas for synthesis of tracer molecules.

The aim of this work was to develop a method to produce 18F-labeled fluorine gas ([18F]F2) with high specific radioactivity (SA, radioactivity/mass-ratio). 18F-Labeled methyl fluoride ([18F]CH3F) was synthesized from [18F]F-aq and mixed with carrier F2 in an inert neon matrix. The constituents were atomized in an electric discharge, after which a rearrangement and 18F for 19F exchange took place. [18F]F2 with a specific radioactivity of up to 55 GBq/mumol is available for the labeling synthesis of tracers for positron emission tomography (PET).

Chromatography, Gas↗

PubMed1997

[18F]fluorodopa PET shows striatal dopaminergic dysfunction in juvenile neuronal ceroid lipofuscinosis.

OBJECTIVES: To investigate whether nigrostriatal dopaminergic hypofunction is related to the extrapyramidal symptoms in patients with juvenile neuronal ceroid lipofuscinosis (JNCL). METHODS: Nine patients with JNCL and seven healthy controls were studied using [18F]fluorodopa PET. RESULTS: In the patients with JNCL [18F]fluorodopa uptake (K[i][occ]) in the putamen was 60% of the control mean and the corresponding figure in the caudate nucleus was 79%. There was a weak correlation between putamen K(i)(occ) values and extrapyramidal symptoms of the patients evaluated by the motor part of the unified Parkinson's disease rating scale (r = -0.57, P < 0.05). The overall severity of the disease also displayed a negative correlation with the K(i)(occ) values in the putamen (r = -0.71, P < 0.05). CONCLUSION: In patients with JNCL there was reduced striatal [18F]fluorodopa uptake, which had a modest correlation with extrapyramidal symptoms. Dysfunction of nigrostriatal dopaminergic neurons is therefore not the only cause of the patients' extrapyramidal symptoms, but degenerative changes in other brain areas are also contributory.

Adolescent↗

PubMed1997

Comparison of [18F]FDG-PET, [99mTc]-HMPAO-SPECT, and [123I]-iomazenil-SPECT in localising the epileptogenic cortex.

OBJECTIVES: Firstly, to compare the findings of interictal 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and of single photon emission computed tomography (SPECT) using 99mTc-hexamethyl propylene-amine-oxime (HMPAO) and 123I-iomazenil in localising the epileptogenic cortex in patients who were candidates for epilepsy surgery, but in whom clinical findings, video EEG monitoring (V-EEG), MRI, and neuropsychological evaluations did not give any definite localisation of the seizure onset. Secondly, to assess the ability of these functional methods to help in the decision about the epilepsy surgery. METHODS: Eighteen epileptic patients were studied with FDG-PET and iomazenil-SPECT. HMPAO-SPECT was performed in 11 of these 18 patients. Two references for localisation was used--ictal subdural EEG recordings (S-EEG) and the operated region. RESULTS: Fifteen of 18 patients had localising findings in S-EEG. FDG-PET findings were in accordance with the references in 13 patients and iomazenil-SPECT in nine patients. HMPAO-SPECT visualised the focus less accurately than the two other methods. In three patients S-EEG showed independent bitemporal seizure onset. In these patients FDG-PET showed no lateralisation. However, iomazenil-SPECT showed temporal lobe lateralisation in two of them. CONCLUSION: FDG-PET seemed to localise the epileptogenic cortex more accurately than interictal iomazenil-SPECT in patients with complicated focal epilepsy.

Adolescent↗