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Biomedical subjects

D J Burn

Publications and source records attributed to D J Burn.

64 records · Page 4Linked to original sources
PubMed1994

The effect of entacapone (OR-611) on brain [18F]-6-L-fluorodopa metabolism: implications for levodopa therapy of Parkinson's disease.

We used PET and [18F]-6-L-fluorodopa ([18F]dopa) to measure the effect of a peripheral COMT inhibitor, entacapone, on the extracerebral metabolism and subsequent striatal uptake of [18F]dopa. Four parkinsonian patients and six age-matched normal controls were each scanned twice, once after carbidopa (150 mg) plus placebo and once after carbidopa (150 mg) plus entacapone (400 mg or 800 mg). Without entacapone premedication, by 90 minutes from injection, only 22% of the [18F] signal in plasma represented unmetabolized [18F]dopa (the balance being 3-O-methyl[18F]dopa). After entacapone medication, this fraction increased to 56% of the [18F] signal (p < 0.0001). We did not find any significant differences between the changes observed in patients versus controls or between those subjects who received 400 mg entacapone versus 800 mg in either this or any of the other reported measures. PET image contrast increased in all cases, reflecting an increase in the specific striatal signal ([striatum-occipital]:occipital ratio increased 38% [p < 0.0001]). Entacapone did not alter the rate of striatal uptake and decarboxylation of [18F]dopa as estimated using a graphic approach with metabolite-corrected plasma as input function to calculate the influx constant, Ki(p) (p = NS). This confirms that such an analytic approach adequately corrects for the effect of extracerebral [18F]dopa methylation. In contrast, the influx constant Ki(o) (calculated using occipital counts as the input function) increased 45% after entacapone (p < 0.0001). This demonstrates the sensitivity of this analytic approach to the presence of peripheral 3-O-methyl[18F]dopa and provides an estimate of the percentage increase in brain free [18F]dopa resulting from entacapone premedication.

Aged↗
PubMed1993

Nigral dysfunction in drug-induced parkinsonism: an 18F-dopa PET study.

We studied 13 patients with severe drug-induced parkinsonism (DIP) using L-6-[18F]fluorodopa positron emission tomography (18F-dopa PET) to investigate the integrity of their dopaminergic nigrostriatal projections. Twelve of these patients were subsequently followed clinically for a median of 23.5 months (range, 6 to 49). Nine patients had normal putamen 18F-dopa uptake. In eight of these nine patients where follow-up was available, a normal 18F-dopa PET study was predictive of subsequent improvement of parkinsonism. Four of 13 DIP patients (31%) had significantly reduced putamen 18F-dopa uptake, within the Parkinson's disease range, and in three of these four (75%), this reduction was associated with continued, or worsening, parkinsonism. There were no clinical features at the time of PET that distinguished those who recovered and those who did not. We conclude that a normal 18F-dopa PET study correlates well with improvement from DIP, but an abnormal study does not necessarily indicate a poor prognosis.

Adult↗
PubMed1993

Comparison of striatal 18F-dopa uptake in adult-onset dystonia-parkinsonism, Parkinson's disease, and dopa-responsive dystonia.

We studied six patients with adult-onset dystonia-parkinsonism (DYS-P) with 18F-6-fluoro-dopa (18F-dopa) positron emission tomography and compared their influx constants (Ki values) with those of six patients with classical childhood-onset dopa-responsive dystonia (DRD), 12 age-matched Parkinson's disease (PD) patients without dystonia, and 21 normal controls. The DYS-P group had significantly reduced mean caudate (67% of normal) and putamen (45% of normal) 18F-dopa uptake. These Ki values were similar to mean caudate and putamen Ki values obtained for the PD group. In contrast, the DRD group showed minor reductions in mean caudate (9%) and putamen (18%) 18F-dopa uptake when compared with normals. The mean caudate:putamen Ki ratio was 1.7 in the DYS-P group and 2.1 in the PD group. In the DRD and normal groups, the caudate:putamen ratios were close to unity. The findings of this study are that adult-onset DYS-P targets the nigrostriatal dopaminergic projections in a pattern similar to PD, with the putamen being more affected. This provides support for the hypothesis that DYS-P may be a phenotypic variant of Lewy body disease. DYS-P seems distinct from childhood-onset DRD, in which striatal 18F-dopa uptake is either normal or only mildly reduced.

Adult↗
PubMed1992

Langerhans' cell histiocytosis and the nervous system.

We report two cases of Langerhans' cell histiocytosis with unusual central nervous system (CNS) involvement. The first patient had behavioural disturbances, memory loss and diabetes insipidus. His response to a range of treatments was poor. The second patient presented with seizures and headaches suggestive of raised intracranial pressure. Etoposide (VP16) chemotherapy led to a dramatic clinical and radiological improvement. The various CNS manifestations of Langerhans' cell histiocytosis and their management are discussed.

Adult↗
PubMed1992

Is bed rest useful after diagnostic lumbar puncture?

A randomized study of 110 patients undergoing their first diagnostic lumbar puncture was performed to compare the effect of immediate mobilization with 4 hours bed rest on the incidence of post lumbar puncture headache. There was no difference between the mobile (n = 54) and bed rest (n = 56) groups in the incidence of post lumbar puncture headache (32% versus 31%, respectively). We conclude that bed rest following lumbar puncture may be an unnecessary imposition on the patient, as well as on nursing staff.

Adult↗
PubMed1992

Parkinson's disease in twins studied with 18F-dopa and positron emission tomography.

We used 18F-dopa PET to examine concordance for dysfunction of the nigrostriatal dopaminergic system in 18 co-twins of patients with Parkinson's disease (PD) and scanned one clinically concordant monozygotic (MZ) twin pair, 17 asymptomatic co-twins (10 MZ, 7 dizygotic [DZ]), and 13 twins with PD (8 MZ, 5 DZ). Mean 18F-dopa uptake of the twins with PD was significantly reduced in putamen to 38% and in caudate to 66% of normal. Mean putamen 18F-dopa uptake for the 17 asymptomatic co-twins was also significantly reduced (86% of normal), as was putamen tracer uptake for the 10 MZ (87% of normal) and seven DZ (83% of normal) asymptomatic co-twin subgroups. Four of 10 MZ and two of seven DZ asymptomatic co-twins had putamen 18F-dopa uptake reduced more than 2 SDs below the normal mean. Three of these four asymptomatic MZ co-twins had tremor on examination at the time of PET and one has now developed PD 2 years later. Our PET findings give concordances for nigral dysfunction of 45% in the MZ pairs and 29% in the DZ pairs at a 2-SD threshold, and 18% in MZ and 0% in DZ pairs at a 3-SD threshold of significance. These data suggest that the concordance for nigral pathology in PD twins may be higher than previously realized and that the presence of an isolated postural or rest tremor may be a phenotypic expression of PD.

Adult↗
PubMed1991

A case of progressive encephalomyelitis with rigidity and positive antiglutamic acid decarboxylase antibodies [corrected].

A 50 year old woman developed progressive encephalomyelitis with rigidity over a three year period. Her CSF contained oligoclonal bands and both her serum and CSF contained antibodies directed against GABA-ergic synapses (antiglutamic acid decarboxylase [corrected] antibodies). These antibodies have recently been described in cases of stiff man syndrome. Both disorders may be part of a clinical spectrum that has an underlying autoimmune basis.

Autoantibodies↗
PubMed1991

Subarachnoid haemorrhage in Wegener's granulomatosis, with negative four vessel angiography.

Two patients with Wegener's granulomatosis and spontaneous subarachnoid haemorrhage are presented in whom four vessel angiograms were normal. The diagnosis of Wegener's granulomatosis should be considered in patients with subarachnoid haemorrhage and negative four vessel angiography. The presence of antibodies to a neutrophil cytoplasmic antigen may be of diagnostic value.

Adult↗
PubMed1989

Strychnine poisoning as an unusual cause of convulsions.

A fatal case of strychnine poisoning is presented. The patient vomited then suffered a series of tonic convulsions which were triggered by tactile stimulation. In between paroxysms he was initially alert. Eventually the patient became comatosed due to anoxia and had a cardiac arrest. He presented with a marked metabolic acidosis and rapidly developed renal failure caused by acute rhabdomyolysis. This clinical picture is classical for strychnine poisoning and the complications which the intoxication produces. Attention is drawn to the fact that survival can even follow the ingestion of very large doses of strychnine providing there is no delay in diagnosis and treatment.

Adult↗