Neuroimaging in Pineal Tumors

BACKGROUND AND PURPOSE: The authors report radiological findings in 11 tumors in the pineal region, which were histologically diagnosed as germinomas, pineocytomas pineoblastomas, ependymomas, teratomas, and astrocytomas. METHODS: Computed tomography (CT) was performed in seven patients and magnetic resonance imaging (MRI) was performed in all patients. RESULTS: CT showed a solid or solid/cystic mass with variable contrast enhancement. MRI showed a heterogeneous mass, with hypointense signal on T1 and iso/hyperintense signal on T2-weighted images (WI) and gadolinium enhancement. Extension to adjacent structures occurred in five patients and spread through the cerebral spinal fluid (CSF) in two. CONCLUSIONS: Pineal region tumors have no pathognomonic imaging pattern. MRI and CT are complementary in diagnosis and are important to determine localization, extension, and meningeal spread.     

Hyperpipecolic acidaemia: a diagnostic tool for peroxisomal disorders

Peroxisomal disorders include a complex spectrum of diseases, characterized by a high heterogeneity from both the clinical and the biochemical points of view. Specific assays are required for the study of peroxisome metabolism. Among these, pipecolic acid evaluation is considered as a supplementary test. We have established the diagnostic role of pipecolic acid in 30 patients affected by a peroxisomal defect (5 Zellweger syndromes, 10 Infantile Refsum diseases, 1 neonatal adrenoleukodystrophy, 6 patients affected by a peroxisomal biogenesis disorder with unclassified phenotype, 1 case of rhizomelic chondrodysplasia punctata (RCDP), 2 acyl-CoA oxidase deficiencies, 2 bifunctional enzyme deficiencies, 2 Refsum diseases, and 1 beta-oxidation deficiency). Pipecolic acid was increased in all generalized peroxisomal disorders, while normal pipecolic acid with abnormal very long chain fatty acid concentrations was strong evidence for a single peroxisomal enzyme deficiency. Unexpectedly, hyperpipecolic acidaemia was found also in a child affected by RCDP and in two patients with Refsum disease. In six patients the suggestion of a peroxisomal disorder was raised by the fortuitous finding of a pipecolic acid peak in amino acid chromatography, routinely performed as a general metabolic screening. For all patients, pipecolic acid proved to be a useful parameter in the biochemical classification of peroxisomal disorders.     

Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx?

A pilot study was designed to examine whether the outcome of embryo transfer in women with a hydrosalpinx might be improved by surgical drainage of the hydrosalpinx at the time of oocyte collection for in- vitro fertilization treatment. A comparative, controlled but retrospective analysis of the results was performed of all women with infective tubal damage aged <40 years old, who had ovulatory cycles, a normal uterus and a partner with normal spermatozoa. A standardized treatment regimen was used. A maximum of three embryos were transferred. Hydrosalpinx was defined by prior hysterosalpingography and/or laparoscopy with transcervical dye injection. A total of 237 embryo transfer cycles in women with hydrosalpinges (tubal distension not visible in 151, visible but not drained in 30 and drained in 56) were compared with 705 embryo transfer cycles in women with tubal disease but no hydrosalpinx. Results were analysed in the first three cycles but also separately in the first cycle to check for bias. Success rates were higher in the first cycle, but did not significantly influence overall differences. Implantation rates were significantly reduced overall in the hydrosalpinx group (8.0 versus 13.2% for controls; P < 0.001), being 8.3% (P < 0.01) in the subgroup without evident tubal distension and 7.5% (not significant) in the drained hydrosalpinx group. This study shows that tubal damage with distal occlusion is associated with a marked reduction in embryo implantation, even in the absence of obvious fluid distension. Surgical drainage of distended hydrosalpinges appears to offer no benefit.      

住院精神分裂症患者十年前后用药情况对比分析

目的对十年前后精神分裂症患者用药情况的变化进行调查分析.方法对十年前后两个五年段的各500份符合精神分裂症诊断标准的病历进行回顾性调查,并对各项指标进行对比分析.结果两组折算用药剂量经t检验差异无显著性(P>0.05);两组合并用药、合并抗胆碱药及疗效经χ2检验差异有显著性(P<0.01);十年后非典型抗精神病药物氯氮平在临床上的应用比例明显增大并上升为首位.结论十年前后两组抗精神病药的应用发生了明显变化,疗效好、副作用轻的非典型抗精神病药的应用比例明显增加.     

Comparison of manual infusion of propofol and target-controlled infusion: effectiveness, safety and acceptability

BACKGROUND: Diprifusor TCI is a newly developed target-controlled system for the infusion of propofol. Purpose of this study is to evaluate the acceptability, efficacy and safety of Diprifusor TCI in comparison with the manually controlled technique. METHODS: This multicentre, randomised, parallel group study was carried out in 160 patients undergoing surgical procedures of 10 min to 4 h duration in 8 centres. In each centre 20 male or female patients, aged > or = 18 years, ASA I-III were randomised to treatment with either Diprifusor TCI (TCI group--80 patients) or manually controlled infusion (MI group--80 patients). Assessments included hemodynamics; adverse events, including accidents, actual or possible; recovery times; anesthetist ratings of quality of induction and maintenance, and of ease of control and use of technique. Ratings were summed up in a global quality score (study end-point). RESULTS: Induction doses were significantly lower (median values 1.4 vs 1.9 mg/kg) and maintenance infusion rate significantly higher (median values 10.2 vs 8.8 mg/kg/h) in the TCI group; anesthetists ratings obtained maximum scores in most patients of either group, but more frequently in the TCI group, with significant differences for ease of control (good 91.2% TCI vs 74.7% IM; adequate 8.8 vs 21.5%; poor 0 vs 3.8%), and of use of technique (good 91.2% TCI vs 60.8% IM; adequate 8.8 vs 39.2%); the global quality score showed a significant advantage for the TCI system (median value 12 vs 11). CONCLUSIONS: The TCI technique is effective and safe, and has a better acceptability than the manually controlled infusion technique.     

The neural correlates of orienting: an integration of fMRI and skin conductance orienting

In fMRI studies, the averaging of neural activity across multiple trials might obscure important psychophysiological subprocesses. The orienting response (OR) is a distinctive subprocess signalling the active orientation of attention towards potentially significant events. We sought to elucidate fMRI activity associated with visual stimuli that did or did not evoke simultaneously recorded electrodermal ORs (using customised skin conductance recording). 'With-OR' stimuli were associated with significant activity in the hippocampus, anterior cingulate and ventromedial prefrontal cortex. Averaged analysis revealed activity only in the expected visual circuits. Our results suggest that potentially significant stimuli (with-OR) activate different functional networks to familiar (without-OR) stimuli, and that orienting may therefore be an informative subprocess to consider in cognitive fMRI studies.     

A novel MEIS2 mutation explains the complex phenotype in a boy with a typical NF1 microdeletion syndrome

Concurrence of distinct genetic conditions in the same patient is not rare. Several cases involving neurofibromatosis type 1 (NF1) have recently been reported, indicating the need for more extensive molecular analysis when phenotypic features cannot be explained by a single gene mutation. Here, we describe the clinical presentation of a boy with a typical NF1 microdeletion syndrome complicated by cleft palate and other dysmorphic features, hypoplasia of corpus callosum, and partial bicoronal craniosynostosis caused by a novel 2bp deletion in exon 2 of Meis homeobox 2 gene (MEIS2) inherited from the mildly affected father. This is only the second case of an inherited MEIS2 intragenic mutation reported to date. MEIS2 is known to be associated with cleft palate, intellectual disability, heart defects, and dysmorphic features. Our clinical report suggests that this gene may also have a role in cranial morphogenesis in humans, as previously observed in animal models.     

Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder

Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala–calcarine (P=0.01) and amygdala–thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala–ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.     

Hyperhomocysteinemia exacerbates the development of intimal hyperplasia in Sprague-Dawley rats: Alleviation by rosiglitazone

The amino acid intermediate homocysteine (Hcy) is formed during the metabolism of methionine to cysteine. Hyperhomocysteinemia (HHcy) is recognized as an independent risk factor for coronary atherosclerosis. The circulating levels of total Hcy (tHcy) can increase due to intake of foods rich in methionine or deficiencies of vitamins such as folate, pyridoxine and cyanocobalamin, which are required for the metabolism of Hcy. In addition, mutations in the genes coding for Hcy metabolizing enzymes can contribute to an increase in tHcy levels. Clinical and epidemiological studies have shown that an elevated level of tHcy measured in serum or plasma is a strong predictor of cardiovascular disease risk, which appears to be greatest in patients who have HHcy following a methionine load. Intimal hyperplasia (IH) (intima/media [I/M] ratio) is the universal response of a vessel to injury and may result in vasoconstriction when left unattended. The effect of dietary HHcy on balloon catheter-injured carotid artery and its modulation (if any) by the peroxisome proliferator-activated receptor agonist gamma rosiglitazone was evaluated in 12-week-old female Sprague-Dawley rats fed either a control diet or a diet containing 1% L-methionine. Once the rats were established on the diet, the group that was fed 1% L-methionine was further subdivided and either given an aqueous preparation of 3 mg/kg/day rosiglitazone or the vehicle via oral gavage for one week. This was followed by surgically injuring the left carotid artery using a Maverick Over-The-Wire catheter (2.0 mm × 20 mm, 3.2F; Boston Scientific, USA). The rats were continued on their respective diets and drug regimen for 21 days postsurgery. On day 22 of the procedure, the rats were sacrificed for collection of blood, the carotid arteries and liver for biochemical and histological evaluation. Compared with controls there was a significant increase in both tHcy levels and I/M ratio in the rats fed 1% L-methionine (5.4±0.28 μM versus 32.8±3.01 μM, P<0.002; and 0.175±0.05 versus 1.05±0.23, P<0.005, respectively). The effect of rosiglitazone in rats fed the control diet was not prominent. On the other hand, administration of rosiglitazone to the rats on the 1% L-methionine diet significantly reduced the levels of serum tHcy (16.6±2.1 μM versus 32.8±3.01 μM, P<0.001); however, the tHcy levels remained significantly elevated compared with animals on the control diet (P<0.002). The group receiving the L-methionine diet plus rosiglitazone had an inhibition in the development of IH compared with those receiving the L-methionine diet alone (I/M of 0.278±0.041 versus 1.05±0.23, P<0.01). Moreover, the development of IH in the group receiving the L-methionine diet plus rosiglitazone treatment was not significantly different from that observed in the group on the control diet without rosiglitazone (0.278±0.041 versus 0.175±0.05, respectively). These findings may have important implications in deciphering the molecular mechanisms involved in the augmentation of IH in HHcy and modulation of this process by rosiglitazone.