[Radiologically guided interventional therapies for the treatment of neuroendocrine tumors]. / Radiologisch-interventionelle Möglichkeiten zur Behandlung von neuroendokrinen Tumoren.

BACKGROUND: The majority of patients with neuroendocrine tumors (NET) develop liver metastases during the course of the disease, significantly impacting prognosis and quality of life. CLINICAL ISSUE: Radiologically guided interventional therapies, such as thermal ablation, transarterial embolization (TAE)/chemoembolization (TACE), and selective internal radiotherapy (TARE), can play a crucial role in the treatment of metastatic NET. DATA: Due to the rarity of the disease, the majority of evidence is based on retrospective studies. For thermal ablation, the complete response rates ranging from 31.6 to 95.3% depending on the study. No significant differences in outcomes were found between TAE, TACE, and TARE. In several studies, all intra-arterial procedures led to a reduction of tumor-related symptoms and achieved disease control. CONCLUSION: Thermal ablation can be used as a curative therapy in oligometastatic patients with nonresectable liver metastases from NETs. In cases of disseminated liver metastases, intra-arterial therapy using TAE, TACE, or TARE can be employed.

CT perfusion technique for assessment of early kidney allograft dysfunction: preliminary results.

OBJECTIVES: To assess the benefit of quantitative computed tomography (CT) perfusion for differentiating acute tubular necrosis (ATN) and acute rejection (AR) in kidney allografts. METHODS: Twenty-two patients with acute kidney allograft dysfunction caused by either AR (n = 6) or ATN (n = 16) were retrospectively included in the study. All patients initially underwent a multiphase CT angiography (CTA) protocol (12 phases, one phase every 3.5 s) covering the whole graft to exclude acute postoperative complications. Multiphase CT dataset and dedicated software were used to calculate renal blood flow. Renal biopsy or clinical course of disease served as the standard of reference. Mean effective radiation dose and mean amount of contrast media were calculated. RESULTS: Renal blood flow values were significantly lower (P = 0.001) in allografts undergoing AR (48.3 ± 21 ml/100 ml/min) compared with those with ATN (77.5 ± 21 ml/100 ml/min). No significant difference (P = 0.71) was observed regarding creatinine level with 5.65 ± 3.1 mg/dl in AR and 5.3 ± 1.9 mg/dl in ATN. The mean effective radiation dose of the CT perfusion protocol was 13.6 ± 5.2 mSv; the mean amount of contrast media applied was 34.5 ± 5.1 ml. All examinations were performed without complications. CONCLUSION: CT perfusion of kidney allografts may help to differentiate between ATN and rejection. KEY POINTS: • Quantitative CT perfusion of renal transplants is feasible. • CT perfusion could help to non-invasively differentiate AR from ATN. • CT perfusion might make some renal biopsies unnecessary.

[Lesions of the paravertebral mediastinum]. / Läsionen des paravertebralen Mediastinums.

BACKGROUND: Lesions of the paravertebral mediastinum are rare, and knowledge of possible differential diagnoses is essential for clinical practice. OBJECTIVE/METHODS: To review common lesions of the paravertebral mediastinum. RESULTS: The paravertebral mediastinum mainly includes fatty tissue and neurogenic structures. Imaging is commonly performed using computed tomography (CT) and magnetic resonance imaging (MRI). Neurogenic tumors are the most common lesions of the paravertebral mediastinum. Other pathologies include extramedullary hematopoiesis, lipomatous, lymphogenic, inflammatory, and cystic lesions. Moreover, also diaphragmatic hernias, vascular and esophageal pathologies may be found in the paravertebral mediastinum.

[Covered endovascular reconstruction of aortic bifurcation (CERAB)]. / Gecoverte endovaskuläre Rekonstruktion der Aortenbifurkation (CERAB).

BACKGROUND: Aortoiliac stenosis is common cause of peripheral arterial disease (PAD), which is particularly prevalent in older age (> 60 years) with a prevalence of 20%. In early stages (TASC [Trans-Atlantic Inter-Society Consensus] II A/B), these stenoses can be successfully treated by endovascular procedures. For more complex aortoiliac stenoses (TASC II C/D), open surgical treatment was the primary treatment in the past. CLINICAL ISSUE: Because of the advanced age and multiple comorbidities of PAD patients with complex aortoiliac stenoses, open surgical treatment is usually associated with high risk, and therefore endovascular procedures are an alternative despite their poorer outcome. Covered endovascular reconstruction of the aortic bifurcation (CERAB) aims to improve the primary patency rate compared with the usual endovascular implantation of kissing stents. DATA: With regard to the primary patency rate, open surgical treatment remains superior to both endovascular procedures; however, the CERAB technique shows a better 5­year outcome than the kissing stent technique. No differences are found in the secondary patency rate for any of the three procedures. The morbidity and mortality of the CERAB and kissing stent techniques are comparably low, and both procedures are superior to open surgical treatment. CONCLUSION: Because of the better long-term outcome of the CERAB versus the kissing stent technique, it should be used in patients with complex aortoiliac stenoses with increased risk of complications expected with open surgical treatment.

A direct access to heterobimetallic complexes by roll-over cyclometallation.

Complexes of the type [Cp*Ir(N,N')Cl]+ (N,N' = 2-(2-dialkylaminopyrimidin-4-yl)pyrimidine) can undergo roll-over cyclometallation leading to a novel N,N'-donor site. Following this strategy heterobimetallic complexes including iridium(iii) and a Group X metal centre in the oxidation state +II were achieved.

Is shared learning the way to bring UK neurology and psychiatry closer: what teachers, trainers and trainees think.

BACKGROUND: Rapid advances in brain sciences are challenging the validity of the traditional divide between neurology and psychiatry. The need for closer ties has been widely advocated. OBJECTIVE: To assess attitudes of neurologists and psychiatrists to closer links in general and to joint education in particular. METHODS: Postal questionnaire survey of trainees (SpRs) trainers (Members of Special Advisory Committees in Neurology and General and Old Age Psychiatry) and teachers (Undergraduate coordinators). Analysis based on 55 neurology and 50 psychiatry respondents. RESULTS: 5 general attitude questions on links showed most respondents "keen" on links and "unkeen" on current separation of disciplines. 15 topics possibly suitable for joint teaching were offered. 7 were rated between "keen" and very "keen" with maximum support for somatization, dementia, chronic pain and pharmacology. 7 were rated positively, only eating disorders was felt unsuitable. 6 options were offered for joint training opportunities. Trainees were keen on attending joint education, clinical and patient management sessions and outpatient clinics. Psychiatrists were even keener on links than neurologists with psychiatric SpRs significantly more in favour of certain items. CONCLUSIONS: The survey found widespread support from trainees, trainers and teachers for closer links. Trainees were keen to attend joint clinically focussed sessions. Psychiatrists tended to be keener that neurologists on links. This survey should encourage the establishment of closer educational links at all levels.

Clinical variability of neuroacanthocytosis syndromes-a series of six patients with long follow-up.

OBJECTIVE: To provide clinical clues to differential diagnosis in patients with chorea and other movement disorders with blood acanthocytes. METHODS: We present a long-term video accompanied follow-up of six Caucasian patients with neuroacanthocytosis from several centers, three diagnosed with chorea-acanthocytosis (ChAc): 34-y.o.(no.1), 36-y.o.(no.2), 43-y.o.(no.3), two diagnosed with McLeod Syndrome (MLS): 52-y.o.(no.4), 61-y.o.(no.5) and one 63-y.o.(no.6), a brother of no.5, with clinical suspicion of MLS. Additionally we report pathological findings of the mother of two brothers with MLS reported in our series with acanthocytes on peripheral blood smear RESULTS: The patients had an unremarkable family history and were asymptomatic until adulthood. Patients no. 1,2,4,5,6 developed generalized chorea and patient no. 3 had predominant bradykinesia. Patients no. 1,2,3 had phonic and motor tics, additionally patients no. 1 and 2 exhibited peculiar oromandibular dystonia with tongue thrusting. In patients no. 2 and 3 dystonic supination of feet was observed, patient no. 3 subsequently developed bilateral foot drop. Patients no. 2 and 4 had signs of muscle atrophy. Tendon reflexes were decreased or absent and electroneurography demonstrated sensorimotor neuropathy in patients no. 1,2,3,4,5, except no. 6. Generalized seizures were seen in patients no. 2,3,5,6 and myoclonic jerks in patient no. 1. Cognitive deterioration was reported in patients no. 1,2,3,5,6. Serum creatine kinase levels were elevated in all six patients. CONCLUSION: We highlight the variability of clinical presentation of neuroacanthocytosis syndromes and the long time from the onset to diagnosis with the need to screen the blood smears in uncertain cases, however, as in one of our cases acanthocytes may even be not found. Based on our observations and data from the literature we propose several red flags that should raise the suspicion of an NA syndrome in a patient with a movement disorder: severe orofacial dyskinesia with tongue and lip-biting (typical of ChAc), feeding dystonia, psychiatric and cognitive disturbances, seizures, peripheral neuropathy, elevation of creatine kinase, elevation of transaminases, hepatosplenomegaly, cardiomyopathy and arrhythmias, and an X-linked pattern of inheritance (McLeod Syndrome, MLS).

Candidate tumour suppressor genes at 11q23-q24 in breast cancer: evidence of alterations in PIG8, a gene involved in p53-induced apoptosis.

One of the most consistently deleted chromosomal regions in solid tumours is 11q23-q25, which consequently has been postulated to harbour one or more tumour suppressor loci. Despite large efforts to identify the responsible genes, the goal remains elusive, but as knowledge accumulates new candidates are emerging. The present study was undertaken in an attempt to assess the possible implication of four genes residing at 11q23-q24, in a population of early onset breast cancer (n=41). The coding sequence of PIG8, CHK1, LOH11CR2A and PPP2R1B were screened for mutations using the protein truncation test or single-strand conformational polymorphism, in combination with direct DNA sequencing. Varying proportions of alterations were detected, ranging from 6% in PPP2R1B to 39% in PIG8. Many of these changes were deletions, in some cases corresponding to complete exons, thus likely to represent splice variants, while others were presumed to arise from aberrant splicing, since they occurred at sites with resemblance to exon/intron borders. Considering only bona fide mutations, the highest alteration frequency (17%) was again found in PIG8. Most of these alterations were likely to have an adverse impact on the translated protein as they either altered the reading frame or affected phylogenetically conserved residues. Our data represent the first evidence of alterations in the PIG8 gene in human malignancies, a finding that substantiates its role as a potential tumour suppressor gene as suggested by its involvement in p53-induced apoptosis.

The effect of 6-hydroxydopamine, reserpine and cold stress on the neuropeptide Y content of the rat central nervous system.

Neuropeptide Y has previously been detected in neurons throughout the rat brain and spinal cord. On histochemical grounds, the neuropeptide Y-containing cell bodies have been subdivided into two groups: those in the brain stem in which colocalization with noradrenaline and adrenaline has been demonstrated and those in other brain regions where no catecholamine coexistence is found. In this paper the regional distribution of neuropeptide Y has been investigated in the rat brain by a specific neuropeptide Y radioimmunoassay, before and after the destruction of catecholaminergic nerve terminals by the administration of intraventricular 6-hydroxydopamine. Despite massive reductions in brain catecholamines, the neuropeptide Y level was unchanged in the cerebral cortex, striatum, spinal cord and hippocampus. A minor reduction in neuropeptide Y was found in the hypothalamus. Reserpine treatment, which is known to deplete brain nerve terminal stores of catecholamines, likewise did not result in any loss of neuropeptide Y. Cold stress which increases noradrenergic turnover in the rat brain stem had no effect on neuropeptide Y levels. These results suggest that the bulk of neuropeptide Y in the rat brain and spinal cord may not be stored in catecholaminergic nerve terminals.

Effect of reserpine, phenoxybenzamine and cold stress on the neuropeptide Y content of the rat peripheral nervous system.

The effect of reserpine treatment on the neuropeptide Y content of the rat adrenal gland, heart, kidney and vasculature was studied using a specific radioimmunoassay. One hour after reserpine administration (5 mg/kg) the neuropeptide Y concentration in the adrenal gland was significantly reduced and after 4 h a similar reduction was seen in the heart and kidney. After 48 h, neuropeptide Y concentrations were reduced in all tissues. The greatest reduction occurred in the cardiac septum (77%) and the least in the inferior vena cava (25%). Phenoxybenzamine (2 mg/kg) also caused a reduction in neuropeptide Y concentrations which was less marked than after reserpine, except in the adrenal gland where it was similar. Cold stress caused no change in neuropeptide Y concentrations. The neuropeptide Y depletion induced by reserpine was compared to that following 6-hydroxydopamine. In the heart and pial arteries both drugs caused a similar neuropeptide Y depletion whilst in the pineal gland and renal artery 6-hydroxydopamine had more effect than reserpine. The implications of these results on NPY storage sites are discussed.

Selective uptake of (3H)beta-alanine by glia: association with glial uptake system for GABA.

On the basis of inhibitor studies it has been suggested that the high-affinity GABA uptake system in glial cells differs in its chemical specificity from that present in nerve terminals. In this paper it has been demonstrated that the GABA analogue, beta-alanine, is almost as good a substrate as GABA itself in the glial cell uptake system whilst not being transported at all into nerve terminals. Not only has [3H]beta-alanine been shown autoradiographically to be exclusively accumulated in glial sites in toeh sensory ganglia and slices of cerebral cortex, but in addition a virtually identical high-affinity uptake process for [3H] beta-alanine was demonstrated at both these sites. Furthermore, non-radioactive GABA was shown to be an equipotent inhibitor of [3H]beta-alanine uptake in sensory ganglia as well as in both small slices and synaptosomes prepared from cerebral cortical tissue, Finally, the competitive inhibition kinetics of GABA on [3H]beta-alanine uptake in cortical slices furnishes proof that intact glial sites of GABA uptake were present in such slices in addition to the more prominent and well documented uptake system in nerve terminals. The possible imporatnce of such glial fragments in brain slice and crude synaptosomal preparations is discussed.

On GABA metabolism in the gliocyte cells of the rat pineal gland.

The uptake of the inhibitory transmitter substance gamma-aminobutyric acid (GABA) into the adult rat pineal gland was studied autoradiographically using both light and electron microscopy. The sites of GABA uptake were shown to be exclusively present in the gliocyte cells of the gland following both in vitro incubation with tritiated GABA and after in vivo administration of the amino acid by intra-arterial injection. Both the pinealocyte cells and the numerous sympathetic axons in the gland were devoid of silver grains. Preliminary biochemical studies indicated that the gliocyte uptake process for GABA resembles that in the satellite glia of the sensory ganglia but differed from that in slices of the cerebral cortex. Evidence is also presented which shows the pineal gland to contain endogenous GABA and the enzymes directly associated with its in vivo metabolism, L-glutamate-1-carboxylase (EC 4.1.1.15) (GAD) and GABA-2-oxoglutarate aminotransferase (EC 2.6.1.19) (GABA-T). Furthermore, a 3-fold rise in endogenous GABA occurred in the pineal after inhibition of GABA-catabolism as would be expected if the GABA-shunt pathway was functionally active in the oxidative metabolism of the pineal gland.

The effect of sympathectomy on calcitonin gene-related peptide levels in the rat trigeminovascular system.

The effect of sympathectomy on the calcitonin gene-related peptide (CGRP) level in the rat primary trigeminal sensory neurone was investigated. Six weeks after bilateral removal of the superior cervical ganglion there was a 70% rise in the CGRP content of the iris and the pial arteries, a 34% rise in the concentration in the trigeminal ganglion but no change in the brainstem. The CGRP rise in both end organs suggests that this phenomenon may be common to all peripheral organs receiving combined sensory and sympathetic innervations. The lack of any rise in the brainstem CGRP content raises the possibility that this process spares central terminations. In contrast, the level of neuropeptide Y, a peptide mainly contained in sympathetic terminals, fell to 35% of control values in the iris and pial arteries whilst the trigeminal ganglion and brainstem concentrations remained unchanged. The possible relevance of these observations to the clinical syndrome of postsympathectomy pain (sympathalgia) is discussed. There are similarities between the delayed onset of the human pain state and the delayed rise in sensory peptides after sympathectomy.

Syringomyelia and syringobulbia following tuberculous meningitis.

Tuberculous meningitis may rarely be followed by the development of a syrinx even after apparently successful chemotherapy. There are only six previously reported cases of this unusual complication; these are reviewed. A case is described of syringomyelia which developed 1 year after TBM. One year later magnetic resonance imaging demonstrated not only the spontaneous resolution of the syringomyelia but also the appearance of a new cavity within the brain stem. This surprising sequence of events illustrates the need for extensive studies of the natural history of syrinxes of differing aetiologies.

Optic neuritis following chickenpox in adults.

Three cases of bilateral optic neuritis, one of which also had transverse myelitis, are described in young adults following chickenpox. Severe bilateral loss of vision developed in all cases and was followed by good visual recovery in the two with isolated optic neuritis, but poor recovery in the patient with concomitant transverse myelitis. The interval between the initial rash and subsequent optic neuritis suggests an immunological pathogenesis for this complication.

Neuropeptide Y innervation of the rodent pineal gland and cerebral blood vessels.

Neuropeptide Y (NPY)-immunoreactivity has been shown to be present in sympathetic nerve fibres in the rat pineal gland and a dense network of NPY-containing nerve fibres demonstrated to innervate the rat circle of Willis. The NPY content of the major rabbit intracranial arteries was determined by radioimmunoassay and maximal levels found in the anterior cerebral arteries. After bilateral superior cervical ganglion (SCG) removal, no NPY was detectable in the rat pineal gland; however, significant NPY-immunoreactive nerve fibres remained throughout the rat vertebrobasilar arteries, and 47% of the assayable NPY was still present. Neither intraventricular 6-hydroxydopamine (6-OHDA) nor the combination of 6-OHDA treatment and SCG removal resulted in any further loss of NPY. In conclusion, the NPY innervation of the pineal gland originates exclusively from the peripheral sympathetic nervous system. In contrast the caudal portion of the rat circle of Willis contains NPY fibres which are resistant to sympathectomy.

Tomographic left ventricular volume determination in the presence of aneurysm by three-dimensional echocardiographic imaging. I: Asymmetric model hearts.

To improve the accuracy of measurements of left ventricular volume in the presence of an aneurysm, we used three-dimensional echocardiographic imaging to analyze the shape of left ventricles in 23 asymmetric model hearts with eccentric aneurysms of different sizes, shapes, and localizations. A standard 3.75 MHz ultrasound probe with a rotation motor device was used to obtain a three-dimensional data set. By rotating the probe stepwise 1 degree, 180 radial ultrasound pictures were digitized. On the basis of the three-dimensional data set, the following parameters were determined and compared with the dimensions of the model hearts obtained by direct measurement: total left ventricular volume (LVV), aneurysm volume, area of the aneurysm's base, the longest aneurysm long diameter, and the longest aneurysm cross diameter. In addition, quantification of LVV by three-dimensional echocardiography was compared with biplane two-dimensional echocardiographic measurement according to the disk method. Good agreements were found for LVV measured by both techniques, three-dimensional echocardiographic and direct measurement (mean of differences = 0.91 ml; SD of differences = +/- 6.23 ml; line of regression y = 1.07 x - 14.24 ml; r = 0.968; standard error of the estimate [SEE] = +/- 6.17 ml), aneurysm volume (mean of differences = 0.43 ml; SD of differences = +/- 2.14 ml; line of regression y = 1.05 x - 0.81 ml; r = 0.996; SEE = +/- 1.96 ml), area of the aneurysm's base (mean of differences = 0.24 cm2; SD of differences = +/- 1.72 cm2; line of regression y = 1.02 x - 0.02 cm2; r = 0.981; SEE = +/- 1.75 cm2), the longest aneurysm long diameter (mean of differences = -0.26 mm; SD of differences = +/- 1.60 mm; line of regression y = 0.97 x + 1.34 mm; r = 0.996; SEE = +/- 1.54 mm), and the longest aneurysm cross diameter (mean of differences = 1.35 mm; SD of differences = +/- 3.94 mm; line of regression y = 0.95 x + 3.17 mm; r = 0.941; SEE = +/- 3.99 mm). In contrast, in these extremely asymmetric-shaped model hearts, agreement between biplane two-dimensional echocardiographic and both direct LVV measurement (mean of differences = 7.8 ml; SD of differences = +/- 20.8 ml; line of regression y = 1.48 x - 92.45 ml; r = 0.874; SEE = +/- 18.36 ml) and three-dimensional echocardiographic measurements (mean of differences = -7.6 ml; SD of difference = +/- 18.1 ml; line of regression y = 0.59 x + 80.98 ml; r = 0.908; SEE = +/- 10.36 ml) was poor. Thus tomographic three-dimensional echocardiography allowed accurate volume determination of asymmetric model hearts in the shape of left ventricles with eccentric aneurysms.

Experiments in surgical voice restoration using valve prostheses.

As our experience with 132 laryngectomees shows, the quality of tracheopharyngeal speech differs. Effortless tracheo-pharyngeal speech requires low flow resistance. Testing the individual factors that influence flow resistance and which are due to the prosthesis, we found that prosthesis diameter and slit length were most important. Various types of valve prosthesis differ considerably in their flow resistance. However, a low-flow resistance valve prosthesis is only partly responsible for easy phonation: Contact between the pharyngeal end of the prosthesis and surrounding tissue may influence voice quality considerably. A later paper will describe the extent to which surgery can create a low-resistance vibratile upper digestive tract.

Effect of gingival fluid on marginal adaptation of Class II resin-based composite restorations.

PURPOSE: To evaluate in vitro the marginal quality of Class II composite restorations at the gingival enamel margins as affected by contamination of the cavities with gingival fluid (GF) during different steps of resin bonding procedures. MATERIALS AND METHODS: 70 Class II cavities were prepared in extracted human molars and restored with composite using a multi-component bonding system (OptiBond FL/Herculite XRV; OPTI) or a single-bottle adhesive (Syntac Sprint/Tetric Ceram; SYN). The cavities were contaminated with human GF: C1 after acid etching, C2 after application of the primer (OPTI) or light-curing of the primer-adhesive (SYN), and C3 after light-curing of the resin adhesive (OPTI). Uncontaminated cavities were used as the control (C0). The restored teeth were subjected to thermocycling (TC) and replicated for SEM analysis of marginal gap formation. Microleakage at the gingival margins was determined by dye penetration with basic fuchsin. STATISTICS: non-parametric tests (Kruskal-Wallis test, Mann-Whitney test with Bonferroni correction). RESULTS: In both bonding systems, contamination with GF after acid etching (C1) did not impair the marginal quality; the mean percentages of continuous margin/mean depths of dye penetration were: OPTI: C0: 88.5%/0.10 mm, C1: 95.6%/0.04 mm; SYN: C0: 90.9%/0.08 mm, C1: 97.0%/0.05 mm. Marginal adaptation was adversely affected when GF contamination was performed after

The use of acyclovir in suspected encephalitis.

The early use of intravenous acyclovir in herpes simplex encephalitis (HSE) is essential. However, rapid diagnostic tests are not freely available. Hence, all patients with suspected encephalitis may need to be commenced on acyclovir. In our study, of 34 patients with suspected encephalitis, only two eventually had HSE confirmed, 19 had encephalitis not due to herpes simplex and in 13 a non-encephalitis illness was finally diagnosed. Guidelines for the use of acyclovir in suspected encephalitis are given aimed at minimizing the drug cost whilst still protecting all cases of presumed HSE.