Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

Depression in a Patient With Alzheimer Disease

This is a case study of a 73-year-old woman recently diagnosed with Alzheimer disease living in an assisted living facility who presented to an outpatient behavioral health clinic with her son for evaluation and treatment of depression. This article highlights the presentation of depression (a diagnosis) versus apathy (a symptom of Alzheimer disease) and the need to assess for co-occurring mood disorders that warrant pharmacologic intervention as well as treatment for cognitive decline in Alzheimer disease.     

Spread of an Enterococcus faecalis sequence type 6 (CC2) clone in patients undergoing selective decontamination of the digestive tract

Enterococcus faecalis (E. faecalis) is a common cause of nosocomial infection in immunocompromised patients. The presence and dissemination of high‐risk clonal complexes, such as CC2, is an ongoing problem in hospitals. The aim of this work was to characterize 24 E. faecalis isolates from ICU patients undergoing selective decontamination of the digestive tract (SDD) by phenotypical (antimicrobial susceptibility) and genotypical (presence of virulence genes, RAPD‐PCR and MLST) methods. Our results showed high prevalence of the ST6 E. faecalis clone (91.6%), especially adapted to the hospital environment, with a multidrug resistance pattern and a multitude of putative virulence genes. In addition, ST179 (4.2%) and ST191 (4.2%) were detected. By RAPD–PCR analysis, the 22 isolates identified as ST6 showed six different DNA patterns, while the two remaining isolates, ST179 and ST191, showed two additional profiles. CC2 is a known clonal complex with high adaptability to hospital environment and worldwide distribution. The high prevalence of the ST6 clone in the studied population could be related to the presence of gentamicin in the SDD mixture since most strains were gentamicin resistant. Consequently, strict surveillance should be applied for rapid detection and control of this clone to prevent future spread outside the ICU.     

The detection and management of complications following the treatment of liver metastases

While once considered as incurable systemic disease, treatment options for liver metastases have increased over the last 30 years and safety has improved dramatically, such that for a selected group of patients the hope of cure can now be offered with radical treatment, and low morbidity interventions can be offered which prolong survival, even in patients with more widely disseminated disease. Advances have been made in selection and surgical technique for liver resection and several adjuncts to resection now exist in the form of portal vein embolization, thermal ablation and targeted drug or radiotherapy delivery options. A natural consequence of these developments has been the delivery of services within fewer specialist units, with the result that later complications of therapy may present to local hospitals, rather than directly to the specialist centres. This article will describe the current common liver-directed therapies and outline the presentation and management of their complications.     

Cutaneous afferent activity in the median nerve during grasping in the primate

Neural activity was recorded from the median nerve of a monkey during grasping and lifting, using a chronically implanted cuff electrode. At the onset of lifting, there was an initial dynamic response during which the intensity of the neural signal increased rapidly. This neural response attained its peak value well before the displacement, the load force or the grip force. The time course and peak of the rectified, integrated neurogram were best correlated with the rate of change of grip force. The neural activity declined exponentially to a steady value following the initial peak. During steady holding the mean amplitude of the neurogram was best correlated with the mean grip force. At the end of the holding phase there was a short burst of neural activity as the monkey relaxed the grip force and released the object. During some blocks of trials pulse perturbations were applied to the object. When the monkey did not increase the grip force in advance of the perturbation, the perturbation produced a relatively large displacement of the object and a burst of neural activity whose onset coincided with the onset of displacement. When the monkey anticipated the perturbation by increasing the grip force during the holding period preceding the perturbation, the perturbation produced a relatively small displacement and relatively little increase in neural activity.     

使用新型倒刺电极的骶神经调节治疗神经源性膀胱的初步临床结果

目的探讨应用新型倒刺电极（Tined-lead）对神经源性膀胱患者行S骶神经调节（SNM）的初步疗效。方法对5例神经源性膀胱患者采用新型倒刺电极，在X线监测下将电极植入S3骶神经孔，进行SNM。术前、术后详细记录排尿日记，用影像尿动力学方法评估患者的膀胱尿道功能。结果患者1（隐性骶裂）术后排尿次数和排尿量分别改善22％和49％；患者2（隐性骶裂）术后排尿次数、排尿量和残余尿量分别改善0．7％、11％和46％；患者3（隐性骶裂）术后排尿次数、排尿量和残余尿量分别改善0．4％、18％和44％。患者4（脑外伤）术后漏尿次数和漏尿量分别改善36％和54％。患者5（高位截瘫）术后间歇导尿次数和导尿量分别改善42％和54％，尿动力学参数改善37％～45％。结论用新型倒刺电极进行SNM为神经源性膀胱的治疗提供了一条新的可供选择的微创方法。     

Implantable Transvenous Pacing Leads:

With the dawn of a new millennium, physicians' demands for very thin transvenous leads able to be positioned in nontraditional sites like the Bachmann's bundle, the high and mid-right ventricular septum, and the His bundle have created new and exciting challenges for lead engineers. Bipolar leads can now be as thin and reliable as unipolar leads. Cathode electrodes are very small, porous, and demonstrate high impedance. To optimize stimulation thresholds, steroid-eluting passive- and active-fixation electrodes have become popular for use in the atrium and ventricle. To create thin lead body diameters, new insulation and conductor materials and lead body designs are necessary. Hybrid medical materials having the best features of silicone rubber and polyurethane will allow for reliable insulation. Conductor cables instead of helical coils permit strong thin diameter leads to be designed. Transvenous lead implantation using the traditional stylet may not be possible with thin diameter leads, necessitating the use of sophisticated workstations using steerable catheters to guide these new active-fixation leads to selective sites in the right heart. The pacing lead of the future may be very different from the one used today. Ironically, it will have features and implantation techniques similar to the transvenous leads designed prior to the use of the stylet. We are now approaching full circle in lead development, retracing the footprints of the early implanters of three and a half decades ago. (PACE 2004; 27[Pt. II]:887–893)     

Toxic epidermal necrolysis; 15 years'' experience in a Dutch burns centre

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe and potentially fatal drug reaction characterized by an extensive skin rash with blisters and exfoliation, frequently accompanied by mucositis. The wounds caused by TEN are similar to second-degree burns and severe cases may involve large areas of skin loss. OBJECTIVES: Analysis of our results in patients with TEN and evaluation of the variety of therapeutic interventions that has been studied and suggested in TEN. PATIENTS/METHODS: Retrospective analysis of 19 consecutive patients with TEN treated in our burns centre between 1989 and 2004. RESULTS: Immediate withdrawal of any potentially fatal drug, maximum supportive care, and a restricted and tailored antibiotic, medical and surgical treatment regimen confined mortality to 21%, whereas prognosis scores like APACHE II and SCORTEN predicted mortality of 22 and 30%, respectively. A positive contribution of selective digestive decontamination is suggested but has yet to be established. CONCLUSIONS: Because of a potentially fatal outcome, fast referral of a patient suspected of TEN to a specialized centre (mostly a burns unit or specialized dermatology centre) for expert wound management and tailored comprehensive care is strongly advised and contributes to survival.