Syntheses of the first endothelin-A- and -B-selective radioligands for positron emission tomography.

We have synthesized two potential positron emission tomography (PET) radioligands for the endothelin (ET) receptor. [11C]-PD156707 was produced by O-methylation of PD169390 using [11C]iodomethane. Radiochemical conversions of the order of 74 +/- 3.2% (n = 8) were obtained. The radiochemical purity of the isolated [11C]-PD156707 was 99% and the specific activity was 538 mCi/micromol. [18F]-BQ3020 was produced from [18F]fluoride in a total radiochemical yield of 2.7 +/- 0.4% (n = 10) in 238 +/- 5 min. The radiochemical purity was 95% and specific activities of the order of 670-930 mCi/micromol were obtained.

Potential role of NovoSeven in the prevention of rebleeding following aneurysmal subarachnoid haemorrhage.

Rebleeding following aneurysmal subarachnoid haemorrhage is a major factor contributing to unfavourable outcome. Antifibrinolytic agents reduce the rate of rebleeding but increase the risk of cerebral ischaemia and infarction and hence provide no overall benefit. To address the theoretical concern that recombinant activated factor VII (NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) might increase the risk of cerebral ischaemia while stabilizing the clot at the site of aneurysmal rupture, an open-label, dose-escalation safety study has been developed in collaboration with the UK Spontaneous Intracranial Haemorrhage Group. The trial design includes the recruitment of 15 patients (aged 18 years or over) in good grade with subarachnoid haemorrhage verified by computerized tomography scan or lumbar puncture. Safety evaluation includes clinical observation, monitoring of laboratory variables, positron emission tomography (PET) scanning (rCBF, rOEF, rCMRO2) and transcranial Doppler ultrasound. To date, ten patients have been recruited [NovoSeven 80 microg/kg single bolus (n = 2), NovoSeven 80 microg/kg single bolus followed by continuous infusion at 3.5 microg/kg per h (n = 2) or 7 microg/kg per h (n = 1), or control (n = 5)]. Clinical observation, transcranial Doppler ultrasound and PET studies revealed no evidence of cerebral ischaemia in the first nine patients treated with NovoSeven. The last patient developed middle cerebral artery branch thrombosis contralateral to the aneurysm. The study is currently suspended pending further investigation.

Magnetic resonance imaging compatibility testing of intracranial pressure probes. Technical note.

There is increasing recognition that magnetic resonance (MR) imaging and spectroscopy may provide important information in the assessment of patients with acute brain injury. However, optimum care of the acutely head injured patient requires monitoring of intracranial pressure (ICP). Although many monitoring modalities have been integrated into commercially available MR-compatible systems, there have been no reports of commonly used intraparenchymal ICP sensors in an MR environment. The authors describe the use of an ICP micromanometer probe in an MR environment, with a fiberoptic connection that interfaces the probe with a commercially available MR-compatible monitoring system. Phantom studies were performed to demonstrate the safety and compatibility of the modified MR system at 0.5 tesla. The safety of the device was assessed in relation to its interaction with the static, gradient, and radiofrequency fields used in MR imaging. The MR compatibility was documented by demonstrating that its performance was unaffected by the operation of imaging sequences and by showing that there was no degradation of the diagnostic quality of imaging data obtained during ICP monitoring.

Redefining the functional organization of working memory processes within human lateral prefrontal cortex.

It is widely held that the frontal cortex plays a critical part in certain aspects of spatial and non-spatial working memory. One unresolved issue is whether there are functionally distinct subdivisions of the lateral frontal cortex that subserve different aspects of working memory. The present study used positron emission tomography (PET) to demonstrate that working memory processes within the human mid-dorsolateral and mid-ventrolateral frontal regions are organized according to the type of processing required rather than according to the nature (i.e. spatial or non-spatial), of the information being processed, as has been widely assumed. Two spatial working memory tasks were used which varied in the extent to which they required different executive processes. During a 'spatial span' task that required the subject to hold a sequence of five previously remembered locations in working memory a significant change in blood-flow was observed in the right mid-ventrolateral frontal cortex, but not in the anatomically and cytoarchitectonically distinct mid-dorsolateral frontal-lobe region. By contrast, during a '2-back' task that required the subject to continually update and manipulate an ongoing sequence of locations within working memory, significant blood flow increases were observed in both mid-ventrolateral and mid-dorsolateral frontal regions. When the two working memory tasks were compared directly, the one that emphasized manipulation of information within working memory yielded significantly greater activity in the right mid-dorsolateral frontal cortex only. This dissociation provides unambiguous evidence that the mid-dorsolateral and mid-ventrolateral frontal cortical areas make distinct functional contributions to spatial working memory and corresponds with a fractionation of working memory processes in psychological terms.

Comparison of the mutagenicities of fossil fuels.

Chemical fractions from 4 shale oils including one produced in an above-ground retort (Paraho), 2 produced below ground by in situ method (Occidental and Geokinetics), and 1 produced by a simulated modified in situ process (Livermore), were tested for mutagenicity against Salmonella typhimurium TA98 in the Ames assay system. Their mutagenic activities were compared with 2 other complex materials: a high-boiling coal distillate (The Solvent Refined Coal Process I (SRC II) heavy distillate), and a crude petroleum (Prudhoe Bay). Each material was fractionated by Sephadex LH-20 partition chromatography and by acid-base solvent extraction to provide chemical fractions for bioassay. Mutagenic activity was detected in the coal liquid (and their fractions), but not in the natural crude oil nor in any of its fractions. The basic and tar fractions derived by solvent extraction, and the LH-20 methanol fractions contained most of the mutagenic activity recovered from the unfractionated material. The heavy distillate was approx. 10 times more active in the Ames assay than the most mutagenically active shale oil. The most mutagenically active of the shale oils was about 10 times more active than the least active shale oil.