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Islet allotransplantation can achieve insulin independence in patients with type I diabetes. Recent reports show that the two‐layer method (TLM), which employs oxygenated perfluorochemical (PFC) and UW solution, is superior to simple cold storage in UW for pancreas preservation in islet transplantation. However, UW solution has several disadvantages, including the inhibition of Liberase activity. In this study, we investigated the features of a new solution, designated M‐Kyoto solution. M‐Kyoto solution contains trehalose and ulinastatin as distinct components. Trehalose has a cytoprotective effect against stress, and ulinastatin inhibits trypsin. In porcine islet isolation, islet yield was significantly higher in the M‐Kyoto/PFC group compared with the UW/PFC group. There was no significant difference in ATP content in the pancreas between the two groups, suggesting that different islet yields are not due to their differences as energy sources. Compared with UW solution, M‐Kyoto solution significantly inhibited trypsin activity in the digestion step; moreover, M‐Kyoto solution inhibited collagenase digestion less than UW solution. In conclusion, the advantages of M‐Kyoto solution are trypsin inhibition and less collagenase inhibition. Based on these data, we now use M‐Kyoto solution for clinical islet transplantation from nonheart‐beating donor pancreata.

A process for the synthesis of ONO-2506, an agent that suppresses astrocyte activation, has been developed. Significant improvement of the level of impurities in the final product has been achieved compared with the laboratory-scale procedure. Kilogram quantities of the compound have been supplied for preclinical studies by this improved process, with both a high quality (99.8%) and a high optical purity (99.6% ee). This was achieved by formation of a crystalline salt of an intermediate which could be recrystallized to give high purity. Toward the future launch of this product, residual problems such as byproduct formation during stereoselective allylation and removal of chiral auxiliary steps were also solved by further investigation.

We studied the impact of emergency neurosurgery and intensive care on the outcome for patients with severe intracerebral haemorrhage after endovascular treatment of brain arteriovenous malformations (AVMs). We reviewed the case notes of 18  patients with severe haemorrhage after embolisation of a brain AVM between 1986 and 2001. During this period the treatment changed: before 1993, these patients were not surgically treated, and they died, while after 1994, all patients underwent emergency surgery. We established a standardised protocol for emergency treatment and intensive care in May 1998, and emergency surgery was performed as soon as possible after the onset of symptoms of haemorrhage. Postoperative intensive care was according to a standardised regime. During these 15 years, 24 out of 605 patients undergoing 1066 interventions had a haemorrhage during or after the procedure, of which 18 were severe (3% of patients, 1.7% of interventions). All patients had a severe clinical deficit (mean Glasgow coma scale 4.2); eight had uni- or bilateral mydriasis. From 1989 to April 1998 four (31%) of 13 patients died, one (7.5%) remained in a vegetative state and eight (61.5%) made a good recovery. All five patients treated between 1998 and 2001 had a favourable outcome. The mean time from onset of the symptoms of haemorrhage to reaching the operation room was 129 min between 1989 and 1998 and 24 min between 1998 and 2001. Standardised emergency treatment and intensive care with early resuscitation, minimal radiological exploration before rapid surgery improved the outcome. A short time between the onset of the symptoms of haemorrhage and evacuation of the haematoma may be the most important factor for a favourable outcome.

We demonstrate the usefulness of "near real-time" neuro-navigation by open MRI systems for guidance of stereotactic evacuation of intracranial abscesses. A 70-year-old patient was referred to our institution with an intracranial left temporal abscess. He presented with headache, senso-motor aphasia and mild right hemiparesis. The abscess (35×25 mm) was stereotactically evacuated under MRI guidance, and a recurrence of a daughter abscess was again evacuated on the 9th postoperative day. "Near real-time" imaging showed an indentation of the abscess wall of 11 mm along the trajectory. A thermosensitive MRI protocol demonstrated a higher temperature around the abscess capsule than in the brain tissue more distant to the capsule, demonstrating the inflammatory process. The patient had 6 weeks of antibiotic therapy for gram-negative bacteria and was discharged with improved clinical symptoms 5 weeks after admission. Follow-up CT 2 months postoperatively showed a complete resolution of the abscess. Open MRI-guided interventions with "near real-time" imaging demonstrate the anatomical changes during an ongoing procedure and can be accommodated for enhancing the overall precision of stereotactic procedures. Thermosensitive MRI protocols are capable of revealing temperature gradients around inflammatory processes.

O(6)-Methylguanine-DNA methyltransferase (MGMT) is a repair protein that specifically removes promutagenic alkyl groups from the O(6) position of guanine in DNA. Repair of O(6)-alkylguanine adducts by tumour cells has been implicated in drug resistance since it reduces the cytotoxicity of alkylating chemotherapeutic agents. We assessed promoter methylation of the MGMT gene in astrocytic brain tumours by methylation-specific PCR. MGMT promoter methylation was detected in 26 of 54 (48%) low-grade diffuse astrocytomas (WHO grade II) and in 12 of 16 (75%) of secondary glioblastomas (WHO grade IV) that had progressed from low-grade astrocytomas. The frequency of MGMT methylation was significantly lower in primary (de novo) glioblastomas (13 of 36, 36%, P = 0.0155). The majority of low-grade astrocytomas with MGMT methylation (24/26, 92%) contained a TP53 mutation, whereas only 11 out of 28 (39%) cases without MGMT methylation carried a TP53 mutation (P < 0.0001). Furthermore, G:C --> A:T transition mutations at CpG sites were significantly more frequent in low-grade astrocytomas with MGMT methylation (15/26, 58%) than in those without (3/28, 11%, P = 0.0004). These results suggest that loss of MGMT expression as a result of promoter methylation, which frequently occurs at an early stage in the pathway leading to secondary glioblastomas, appears to be associated with increased frequency of TP53 mutations, in particular G:C --> A:T transitions.

It should never be forgotten that there is far more to microsurgery than the mere possession of a highly perfected optical instrument. Without bipolar coagulation, specialized instruments, and, above all, knowledge and skill in atraumatic microtechniques, the microscope alone is of little value. Perfection of atraumatic microsurgical technique is best acquired by operating on small-diameter blood vessels (0.8 mm to 1.5 mm) in animals.

Abstract: We investigated the haemodynamics in the parent artery of 17 small (< 9 mm) and 17 large (L 9.5 mm) saccular aneurysms by transcranial colour-coded Doppler sonography (TCCD) and related the findings to digital subtraction angiography (DSA). We measured flow velocity within the parent artery and, by positioning the Doppler gate within the colour flow image close to the ostium of the aneurysm, obtained a superselective Doppler spectral waveform. The parameters measured included the time-averaged maximal velocity (TAMX), peak systolic, and end-diastolic velocity and pulsatility index (PI). The values were compared to the contralateral side and between small and large aneurysms. DSA was analysed for parent artery stenosis. Mean systolic velocities in the parent arteries of large aneurysms were significantly higher than in the contralateral normal artery (1.08 ± 0.23 vs 0.80 ± 0.23 m/s; P = 0.0003) and higher than in the parent artery of small aneurysms (0.89 ± 0.18 m/s; P = 0.01). Increased systolic velocity accounted for a higher PI in the parent artery of large aneurysms (mean 1.48 ± 0.42) than on the other side (0.87 ± 0.12; P = 0.0001) and in the parent artery of small aneurysms (0.85 ± 0.14; P = 0.0001). PI proximal to seven thrombosed large aneurysms was higher (mean 1.85 ± 0.38) than close to unthrombosed large aneurysms (1.23 ± 0.22; P = 0.0005). Increased PI and systolic velocities could not be shown within branches of 5 large aneurysms and were reversible in the parent artery of four patients examined again after occlusion of the aneurysm. Systolic velocities and PI did not differ significantly (P = 0.41 and P = 0.25, respectively) in ruptured and unruptured aneurysms. Stenosis of the parent artery was not shown by DSA in any case.

Abstract: In a retrospective study of 30 consecutive patients with symptomatic vasospasm the mean degree of narrowing as compared to the initial angiogram was 35 % (± 24 %) in 12 intradural internal carotid arteries (ICA), 42 % (± 17 %) in 42 proximal middle cerebral (MCA) and 38 % (± 19 %) in 27 anterior cerebral arteries (ACA). The corresponding increase in mean flow velocities from baseline values obtained by transcranial colour Doppler sonography (TCD) within 12 h of the first angiogram to the time of clinical vasospasm was considerably higher, with 49 % (± 34 %) in the ICA, 119 % (± 92 %) in the MCA and 147 % (± 170 %) in the ACA. Following superselective intra-arterial papaverine application in 66 arteries and balloon angioplasty of 15 arteries, 78 (96.3 %) of 81 dilated. Sustained clinical improvement was achieved in 22 patients (73.3 %). The mean reversal of angiographic vasospasm was 71 % for the ICA (range 10–100 %), 81 % for the MCA (range 9–100 %) and 82 % (range 0–100 %) for the A1 segment. The mean reduction of flow velocities after treatment was much less with 23 % (± 21 %) in the ICA, 32 % (± 24 %) in the MCA and 25 % (± 22 %) in the A1 segment.

Summary:  Objective. To report the early clinical results, quantitative angiographic and sonographic findings, and final outcome in patients with symptomatic vasospasm who had undergone surgical occlusion of the aneurysm and a structured protocol including aggressive intensive care management, endovascular procedures (EP), and barbiturate coma (BC).  Results. Thirty consecutive patients (19 women, 11 men, age: 51±8 years) underwent 38 EP for the treatment of 81 vascular territories (15 balloon dilatations and 66 papaverine infusions). Overall angiographic vasospasm in the intradural ICA improved significantly from 44. 7±19.8% to 16.5±16%, in the MCA from 44.2±14.7% to 14.4±14%, and in the ACA from 38.7±18.6% to 13.3±12%. Mean flow velocities (Vm) in the MCA and ACA decreased significantly from 135±48 cm/sec to 87±32 cm/sec and from 110±36 cm/sec to 84±30 cm/sec, respectively. No significant Vm improvement in the ICA could be demonstrated. Six patients (20%) developed intractable vasospasm after repeated EP and five patients underwent BC. The correlation coefficient between percentage of angiographic vasospasm and Vm increase was −0.19 (p=NS) for the ICA, 0.2 (p<0.001) for the MCA, and 0.3 (p<0.05) for the ACA. Correlation coefficient between percentages of angiographic and sonographic improvement was −0.12 (p=NS) for the ICA, 0.42 (p<0.001), and 0.1 (p<0.05) for the ACA. Early clinical improvement after EP was observed in 73% of patients and was significantly associated with favourable outcome (GOS 4–5). Sixteen patients (53%) had a GOS 5, six patients (20%) a GOS 4, six patients (20%) a GOS 3, and two patients (6.6%) died as consequence of devastating vasospasm.  Conclusions. Changes in vessel diameter and increases of Vm during vasospasm correlate weakly. In spite of the fact that significant differences in vessel diameter and Vm were demonstrated after treatment, a moderately good correlation between percentages of angiographic and Vm improvement was observed only in the M1 segments. In our experience, a reduction of mortality and disabilities can be achieved with a maximal structured treatment of vasospasm. Early clinical improvement after endovascular treatment is strongly associated with favourable outcome, nevertheless, cost-benefit and controlled trials are necessary to evaluate these techniques.

Sixteen patients with symptomatic dural caroticocavernous fistulae were treated by transvenous embolization, via the jugular vein and inferior petrosal sinus. The fistula was occuladed by thrombogenic coils. Complete resolution of symptoms and signs was achieved in 14 patients, and complete angiographic resolution was also obtained in 14 patients. Failures to achieve angiographic cure were attributed to failure to reach the fistula within the cavernous sinus precisely. Factors which make placement of the catheter at the fistula difficult are trabeculae within the cavernous sinus, a specific configuration of the superior ophthalmic vein and venous thrombosis. To improve the efficacy of tranvenous embolization, every possible venous route to the cavernous sinus therefore should be tried, to facilitate reaching the fistula and the possibility of transvenous embolization should not be thwarted by venous thrombosis.

Summary We investigated the haemodynamic dysfunction and secondary thalamic and brainstem atrophy in 24 patients with angiographically proven cerebral arteriovenous malformations (AVM) and no clinical history of cerebral haemorrhage. Cerebral blood flow (CBF) was measured by the method using either stable Xenon or single photon emission computerized tomography (SPECT). Morphological changes in the thalamus and brainstem were evaluated by magnetic resonance imaging (MRI). Two factors are considered to influence hypoperfusion in the ipsilateral cerebral and contralateral cerebellar hemisphere and secondary atrophy of the thalamus and brainstem. One is the size of the nidus and the other is the involvement of the basal ganglia. It is presumed that continuous haemodynamic stress over a long period of time may cause irreversible histological changes in areas remote from the lesion, especially in the AVM which demonstrates involvement of the basal ganglia or a large nidus.

Summary We investigated the protective action of nerve growth factor (NGF) on delayed neuronal death, and we also studied the involvement of the 200 kDa neurofilament (NF 200) cytoskeletal proteins.

Summary The neuroprotective effect of neurotrophic factors has been demonstrated in experimental cerebral ischaemia recently. These include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (basic FGF). The neuroprotective effect of ciliary neurotrophic factor (CNTF), however, has not been studied so far.

Summary Cortical blood flow (CoBF) monitoring with a thermal diffusion flow probe was performed during the clipping of aneurysms of the ICA and MCA regions, on a series of patients during the acute stage of subarachnoid haemorrhage. Emphasis was placed on the CoBF recovery after temporary clip release. Since the absolute value in this technique is unreliable, recovery of blood flow after temporary clipping is represented as %CoBF according to the following equation: %CoBF recovery = (CoBFpost-CoBFintra)/(CoBFpre-CoBFintra)

We aimed to develop a pre-procedural imaging protocol which provides functional and anatomic information for lesion characterisation and procedural planning and to determine appropriate sequence parameters for “real-time” intra-procedural tracking of interventional devices. 34 patients underwent MRI guided procedures using a 0.5 T open-bore magnet. Interactive “real time” imaging was accomplished with a 3D optical tracking system and specialised image guidance software implemented on an interactive workstation. Pre-procedural planning in a 1.5 T magnet included standard T1- and T2-weighted images, 3D target volume determination and segmentation analysis, 3D time-of-flight MRA, cerebral blood volume mapping, and functional cortical mapping. Intra-procedure imaging included baseline and final T1- and T2-weighted imaging and interactive T1-weighted RF-spoiled GE images acquired every 4 sec for contrast enhancing lesions; or T2-weighted SSFSE images acquired every 3 sec, for nonenhancing lesions. Pre-procedural imaging offered precise anatomic, functional and volumetric definition of the target, eloquent brain, skull surface and surrounding vessels for appropriate burr hole placement and trajectory planning. MR perfusion offered tissue characterisation and margin definition not evident with conventional MRI. Real time imaging helped avoid vascular structures and eloquent brain without complications, always yielded diagnostic biopsy tissue and showed progressive collapse of necrotic tumors, abscesses, and hematomas with relief from mass effect. On-line imaging during excision of an infiltrating glioma allowed more confident tumor margin estimation. Improved pre-procedural image acquisition and processing and on-line imaging in an accessible MR system allows real time procedural monitoring increasing its accuracy, safety and diagnostic and therapeutic yield.