Expression of fatty acid synthase (FASN) in oral nevi and melanoma

Oral Diseases (2011) 17 , 808–812 Objective: The aim of this study was to determine the expression of fatty acid synthase (FASN) in oral nevi and melanomas, comparing the results with correspondent cutaneous lesions. Materials and Methods: Expression of FASN was evaluated by immunohistochemistry in 51 oral melanocytic lesions, including 38 intramucosal nevi and 13 primary oral melanomas, in 10 cutaneous nevi and in 14 melanomas. Results: Fatty acid synthase was strongly expressed only in melanomas, either of the oral mucosa or cutaneous. On the other hand, most oral and cutaneous nevi were negative, with a few oral cases showing focal and weak expression. Conclusion: Fatty acid synthase is expressed in malignant melanocytes, and it can be a helpful marker to distinguish oral melanomas from oral melanocytic nevi.     

Intracranial Pressure Monitoring: Fundamental Considerations and Rationale for Monitoring

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. In large part critical care for TBI is focused on the identification and management of secondary brain injury. This requires effective neuromonitoring that traditionally has centered on intracranial pressure (ICP). The purpose of this paper is to review the fundamental literature relative to the clinical application of ICP monitoring in TBI critical care and to provide recommendations on how the technique maybe applied to help patient management and enhance outcome. A PubMed search between 1980 and September 2013 identified 2,253 articles; 244 of which were reviewed in detail to prepare this report and the evidentiary tables. Several important concepts emerge from this review. ICP monitoring is safe and is best performed using a parenchymal monitor or ventricular catheter. While the indications for ICP monitoring are well established, there remains great variability in its use. Increased ICP, particularly the pattern of the increase and ICP refractory to treatment is associated with increased mortality. Class I evidence is lacking on how monitoring and management of ICP influences outcome. However, a large body of observational data suggests that ICP management has the potential to influence outcome, particularly when care is targeted and individualized and supplemented with data from other monitors including the clinical examination and imaging.     

乡土特色的少年宫活动对中小学生积极心理品质的提升作用

目的探究乡土特色少年宫活动对学生积极心理品质的提升作用。方法采用实验组、对照组前后测实验设计,选取绵阳市某学校三年级到八年级学生共530名,随机分为实验组(n=265)和对照组(n=265)。实验组学生参与12次为期90天的乡土特色的少年宫活动,对照组处于常态。活动前后采用中国中小学生积极心理品质量表进行测量。结果①实验组和对照组在六个维度上的前测分数差异均无统计学意义(P均0.05)。②实验组在人际维度、公正维度、节制维度、超越维度上,后测分数均高于前测,差异有统计学意义(P0.05);而在认知维度和情感维度上,前、后测分数差异无统计学意义(P均0.05)。③对照组在六个维度上的前后测分数差异均无统计学意义(P均0.05)。④后测分数中,实验组在人际维度、公正维度、节制维度、超越维度上的得分均高于对照组,差异有统计学意义(P0.05);而两组在认知维度和情感维度上分数差异无统计学意义(P均0.05)。结论乡土特色的少年宫活动可能有利于提升中小学生人际、公正、节制和超越等积极心理品质。     

Esophageal Dysmotility After Laparoscopic Gastric Band Surgery

Background

The effect of the laparoscopic adjustable gastric band (LAGB) on the esophagus has been the subject of few studies despite recognition of its clinical importance. The aim of this study was to investigate the frequency and clinical effect of esophageal dysmotility and dilatation after LAGB.

Methods

We undertook a retrospective analysis of 50 consecutive patients with no dysmotility on perioperative video contrast swallow who underwent primary LAGB operation. All patients had serial focused postoperative contrast studies for band adjustments at least 6 months post-LAGB. Clinical and radiological outcomes were assessed.

Results

Median follow-up time was 18 months (range 7–39 months), and the median number of contrast swallows per patient was 5. The mean excess weight loss (EWL) overall was 47 % (standard deviation (SD) 22.3). Radiological abnormalities were recorded in 17 patients (34 %, 95 % confidence interval (CI) 21–49 %), of whom 15 had radiological dysmotility and 7 had esophageal dilatation (five patients had both dysmotility and dilatation). Of these 17 patients, six (35 %) developed significant symptoms of dysphagia, gastroesophageal reflux disease (GERD) or regurgitation requiring fluid removal. In comparison, 12 of 33 (36 %) patients without radiological abnormalities developed symptoms requiring fluid removal (p?=?1.00). Patients with radiological abnormalities were significantly older than those without these abnormalities. Symptoms were alleviated by removing fluid in most patients.

Conclusions

The LAGB operation results in the development of radiological esophageal dysmotility in a significant proportion of patients. It is not clear if these changes are associated with an increased risk of significant symptoms. Fluid removal can reverse these abnormalities and their associated symptoms.     

Glucuronidation of monohydroxylated warfarin metabolites by human liver microsomes and human recombinant UDP-glucuronosyltransferases

Our understanding of human phase II metabolic pathways which facilitate detoxification and excretion of warfarin (Coumadin) is limited. The goal of this study was to test the hypothesis that there are specific human hepatic and extrahepatic UDP-glucuronosyltransferase (UGT) isozymes, which are responsible for conjugating warfarin and hydroxylated metabolites of warfarin. Glucuronidation activity of human liver microsomes (HLMs) and eight human recombinant UGTs toward (R)- and (S)-warfarin, racemic warfarin, and major cytochrome P450 metabolites of warfarin (4'-, 6-, 7-, 8-, and 10-hydroxywarfarin) has been assessed. HLMs, UGT1A1, 1A8, 1A9, and 1A10 showed glucuronidation activity toward 4'-, 6-, 7-, and/or 8-hydroxywarfarin with K(m) values ranging from 59 to 480 microM and V(max) values ranging from 0.03 to 0.78 microM/min/mg protein. Tandem mass spectrometry studies and structure comparisons suggested glucuronidation was occurring at the C4'-, C6-, C7-, and C8-positions. Of the hepatic UGT isozymes tested, UGT1A9 exclusively metabolized 8-hydroxywarfarin, whereas UGT1A1 metabolized 6-, 7-, and 8-hydroxywarfarin. Studies with extrahepatic UGT isoforms showed that UGT1A8 metabolized 7- and 8-hydroxywarfarin and that UGT1A10 glucuronidated 4'-, 6-, 7-, and 8-hydroxywarfarin. UGT1A4, 1A6, 1A7, and 2B7 did not have activity with any substrate, and none of the UGT isozymes evaluated catalyzed reactions with (R)- and (S)-warfarin, racemic warfarin, or 10-hydroxywarfarin. This is the first study identifying and characterizing specific human UGT isozymes, which glucuronidate major cytochrome P450 metabolites of warfarin with similar metabolic rates known to be associated with warfarin metabolism. Continued characterization of these pathways may enhance our ability to reduce life-threatening and costly complications associated with warfarin therapy.     

Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial

It is believed that glycogen synthase kinase‐3 hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) trial assessed the glycogen synthase kinase‐3 inhibitor tideglusib as potential treatment. For the magnetic resonance imaging (MRI) substudy reported here, we assessed the progression of brain atrophy. TAUROS was a multinational, phase 2, double‐blind, placebo‐controlled trial in patients with mild‐to‐moderate PSP who were treated with oral tideglusib (600 mg or 800 mg daily) or with placebo for 1 year. A subset of patients underwent baseline and 52‐week MRI. Automated, observer‐independent, atlas‐based, and mask‐based volumetry was done on high‐resolution, T1‐weighted, three‐dimensional data. For primary outcomes, progression of atrophy was compared both globally (brain, cerebrum) and regionally (third ventricle, midbrain, pons) between the active and placebo groups (Bonferroni correction). For secondary outcomes, 15 additional brain structures were explored (Benjamini & Yekutieli correction). In total, MRIs from 37 patient were studied (placebo group, N = 9; tideglusib 600 mg group, N = 19; tideglusib 800 mg group, N = 9). The groups compared well in their demographic characteristics. Clinical results showed no effect of tideglusib over placebo. Progression of atrophy was significantly lower in the active group than in the placebo group for the brain (mean ± standard error of the mean: ?1.3% ± 1.4% vs. ?3.1% ± 2.3%, respectively), cerebrum (?1.3% ± 1.5% vs. ?3.2% ± 2.1%, respectively), parietal lobe (?1.6% ± 1.9% vs. ?4.1% ± 3.0%, respectively), and occipital lobe (?0.3% ± 1.8% vs. ?2.7% ± 3.2%, respectively). A trend toward reduced atrophy also was observed in the frontal lobe, hippocampus, caudate nucleus, midbrain, and brainstem. In patients with PSP, tideglusib reduced the progression of atrophy in the whole brain, particularly in the parietal and occipital lobes. © 2014 International Parkinson and Movement Disorder Society     

Douleur chronique : la place du psychiatre

Objectives

Chronic pain affects nineteen percent of the European adult population and its impact on morbidity is major. Considering psychosocial factors allows improving functional re-establishment. Psychiatric comorbidities are under-diagnosed and worsen the prognosis. The psychiatrist has an important role to play in the assessment and treatment of these subjects.

Methods

We will detail the relationship between chronic pain and some psychiatric diseases as well as their psychological and biological correlation. Then, we will discuss the therapeutic implements available to the psychiatrist.

Results

We have to distinguish the psychosomatic disorders, which is a somatic disorder closely intertwined with a psychic disorder, from the somatoform disorder which is a body complaint to indicate a psychosocial distress. These disorders induce huge medico-economic costs: high prevalence and wrong care pathways, rarely using the psychiatrist expertise. The subjects with post-traumatic disorder combined with chronic pain have more severe post-traumatic symptoms with greater functional impairment. Twenty to fifty percent of subjects suffering of chronic pain have a depressive syndrome and fifty percent of the depressed subjects complain about chronic pain. Their symptoms are more numerous, more intense and longer lasting. Regardless of the used assessment tools, there are more pathological personality traits in chronic pain subjects with heterogeneous profiles than in general population which is useful for offering more targeted therapeutic strategies. Neurobiological integration of painful experience is based on two components : A somatosensory component (S1 and S2 areas) and an affective component with a central role of the anterior cingulate cortex. Functional dysfunctions involved in chronic pain affects the affective component of the pain experience and this component can be modulated. The psychiatrist should definitely avoid psychological explanation for the pain. He should focus on a multidisciplinary approach with partnership and complementarity. Its assessment identifies involved psychosocial factors, not for disqualifying the complaint but for considering all its aspects. Among drug treatments, antidepressants have a specific analgesic action particularly for IRS and MAOIs. Among non-drug treatments, reconditioning through physical activity combined or not with behavioral experiments can be associated with psycho education. Mindfulness, therapy of acceptance and commitment are used to promote voluntary consciousness of the body, of the pain and of thoughts. In some situations, transcranial magnetic stimulation can provide a useful aid. Analytical inspired therapies allow the subjects who are questioning about the meaning of the pain, better understanding a broader suffering.

Conclusion

Chronic pain is closely linked to some psychiatric disorders. We should propose specific therapeutic strategies to each patient and the psychiatrist should be involved in assessment and treatment of chronic pain. In particular, the fear related to pain should be always assessed and supported. There are drug and non-drug strategies available for the psychiatrist to help taking care of these patients.