Effect of electroconvulsive therapy on neural response to affective pictures: A randomized,sham-controlled fMRI study

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression but its neurocognitive mechanisms are unclear. This randomized, sham-controlled functional magnetic resonance imaging (fMRI) study explored the effects of a single ECT on neural response to affective pictures. Twenty-seven patients with major depressive disorder were randomized to a single active ECT (N?=?15) or sham (N?=?12) session in a double-blind, parallel-group design. On the following day, patients underwent fMRI during which they viewed pleasant, unpleasant and neutral pictures and performed a free recall test after the scan. Mood symptoms were assessed before ECT/sham and at the time of fMRI. Subsequently, all patients continued active ECT as usual. Mood symptoms were reassessed after six active ECT sessions. A single ECT vs. sham session reduced neural response to unpleasant vs. pleasant pictures in the medial prefrontal cortex, a region showing greater response in the more depressed patients. This effect occurred in the absence of between-group differences in picture recall, mood symptoms or concomitant medication. In conclusion, modulation of medial prefrontal hyper-activity during encoding of negative affective information may be a common mechanism of distinct biological depression treatments.     

生物膜与膨体聚四氟乙烯包裹治疗动脉瘤的效果对照

目的:比较生物膜与膨体聚四氟乙烯在动脉瘤包裹的远期治疗效果。方法:实验于2004-12/2006-10年在南方医院神经外科实验室与广东冠昊动物实验中心进行。取成年健康杂种犬10只,采用显微外科技术,将双侧的颈外静脉1.5cm嫁接双侧颈总动脉缺损1.5cm制作梭形动脉瘤模型20枚。左侧10枚应用生物膜(广东冠昊生物科技有限公司产品)包裹治疗,右侧10枚应用膨体聚四氟乙烯(美国戈尔公司周围血管补片)包裹治疗。术后第1,3,6,9,12个月行彩色多普勒超声血动态观察血流动力学变化,第12个月进行数字减影血管造影检测及解剖组织学观察。结果:10只犬全部进入结果分析。①血流动力学观察:生物膜包裹侧瘤腔消失、形态上趋于正常的颈总动脉,管腔均通畅,造影剂快速通过无滞留;血流恢复为层流,频谱特征与颈总动脉一致;1个月时生物膜与瘤壁存在微小间隙,3个月后间隙完全消失,12个月时血管顺应性、弹性与颈总动脉基本相匹配。膨体聚四氟乙烯包裹侧瘤腔消失、管腔通畅6枚,腔内为层流,频谱特征与颈总动脉相似,但速度明显高于远近端颈总动脉;瘤腔轻度缩窄,内壁出现轻度波状充盈缺损,包裹片长度轻度缩短;1个月和3个月各出现2枚血栓性闭塞,经主动脉弓照影不显像。6个月内膨体聚四氟乙烯与瘤壁存在清晰微小间隙,6个月后间隙消失。②组织学观察:生物膜包裹侧外表柔软类似颈总动脉,有较多毛细血管长入但维持原形,瘤腔内膜光滑无增厚,内皮细胞无增生、脱落,未见附壁血栓;生物膜与瘤壁融合、多层次降解,降解间隙内较多新生血管、组织长入,未见炎症细胞。膨体聚四氟乙烯外表僵硬、未见周围组织长入;内膜增厚、不光滑,内皮细胞核密集、部分脱落,薄层血栓附壁;4例见胶冻状长圆柱形杂色血栓。膨体聚四氟乙烯与瘤壁嵌入无降解,未看到明显的毛细血管长入;有极少的成纤维细胞伸入,散在的淋巴细胞浸润及少量巨噬细胞。结论:生物膜具有良好的理化性能与生物相容性,其效果优于膨体聚四氟乙烯,是动脉瘤包裹治疗的理想再生医学工程材料。     

Pharmacological Risk Factors for Delirium after Cardiac Surgery: A Review

Purpose:

The objective of this review is to evaluate the literature on medications associated with delirium after cardiac surgery and potential prophylactic agents for preventing it.

Source:

Articles were searched in MEDLINE, Cumulative Index to Nursing and Allied Health, and EMBASE with the MeSH headings: delirium, cardiac surgical procedures, and risk factors, and the keywords: delirium, cardiac surgery, risk factors, and drugs. Principle inclusion criteria include having patient samples receiving cardiac procedures on cardiopulmonary bypass, and using DSM-IV-TR criteria or a standardized tool for the diagnosis of delirium.

Principal Findings:

Fifteen studies were reviewed. Two single drugs (intraoperative fentanyl and ketamine), and two classes of drugs (preoperative antipsychotics and postoperative inotropes) were identified in the literature as being independently associated with delirium after cardiac surgery. Another seven classes of drugs (preoperative antihypertensives, anticholinergics, antidepressants, benzodiazepines, opioids, and statins, and postoperative opioids) and three single drugs (intraoperative diazepam, and postoperative dexmedetomidine and rivastigmine) have mixed findings. One drug (risperidone) has been shown to prevent delirium when taken immediately upon awakening from cardiac surgery. None of these findings was replicated in the studies reviewed.

Conclusion:

These studies have shown that drugs taken perioperatively by cardiac surgery patients need to be considered in delirium risk management strategies. While medications with direct neurological actions are clearly important, this review has shown that specific cardiovascular drugs may also require attention. Future studies that are methodologically consistent are required to further validate these findings and improve their utility.     

A diagnostic microdosing approach to investigate platinum sensitivity in non‐small cell lung cancer

The platinum‐based drugs cisplatin, carboplatin and oxaliplatin are often used for chemotherapy, but drug resistance is common. The prediction of resistance to these drugs via genomics is a challenging problem since hundreds of genes are involved. A possible alternative is to use mass spectrometry to determine the propensity for cells to form drug‐DNA adducts—the pharmacodynamic drug‐target complex for this class of drugs. The feasibility of predictive diagnostic microdosing was assessed in non‐small cell lung cancer (NSCLC) cell culture and a pilot clinical trial. Accelerator mass spectrometry (AMS) was used to quantify [¹⁴C]carboplatin‐DNA monoadduct levels in the cell lines induced by microdoses and therapeutic doses of carboplatin, followed by correlation with carboplatin IC₅₀ values for each cell line. The adduct levels in cell culture experiments were linearly proportional to dose (R² = 0.95, p < 0.0001) and correlated with IC₅₀ across all cell lines for microdose and therapeutically relevant carboplatin concentrations (p = 0.02 and p = 0.01, respectively). A pilot microdosing clinical trial was conducted to define protocols and gather preliminary data. Plasma pharmacokinetics (PK) and [¹⁴C]carboplatin‐DNA adducts in white blood cells and tumor tissues from six NSCLC patients were quantified via AMS. The blood plasma half‐life of [¹⁴C]carboplatin administered as a microdose was consistent with the known PK of therapeutic dosing. The optimal [¹⁴C]carboplatin formulation for the microdose was 10⁷ dpm/kg of body weight and 1% of the therapeutic dose for the total mass of carboplatin. No microdose‐associated toxicity was observed in the patients. Additional accruals are required to significantly correlate adduct levels with response.     

Vitamin D status and hyperparathyroisism in postmenopausal osteoporotic patients in Cipto Mangunkusumo hospital Jakarta

Aim: to determine the profile of vitamin D and parathyroid hormone (PTH) and the proportion of vitamin D inadequacy in a population of postmenopausal osteoporotic patients from a rheumatologic outpatient clinic. Methods: a cross sectional study was conducted between October and December 2006 in the Rheumatology Clinic, Cipto Mangunkusumo Hospital with osteoporosis confirmed by bone mineral densitometry (T score less than -2.5 at the lumbar spine or hip). Patients were excluded if there was a history of oral glucocorticoid treatment within 30 days, vitamin D supplementation, and have renal and/or liver function impairments. Forty-two postmenopausal osteoporotic patients aged 51-77 years old who had been postmenopausal for 5-28 years were included in this study. Vitamin D inadequacy was defined as the plasma levels of 25(OH)D less than 50 nmol/L whereas hyperparathyroidism was defined as the PTH level more than 69 pg/dL. Results: vitamin D inadequacy was found in 61.9% of patients and 34.6% of them or 23.8% of total patients were also having high PTH level. There was an inverse correlation between 25(OH)D with PTH levels and positive correlation between duration of menopause and PTH level. Vitamin D inadequacy is common (61.9%) in postmenopausal osteoporotic patients who visited Rheumatology outpatient clinic of Cipto Mangunkusumo Hospital Jakarta. Conclusion: the low concentration of 25(OH)D was correlated with PTH level and duration of menopause. This finding should be confirmed in a larger epidemiological study, either hospital-or community-based to assess vitamin D status among postmenopausal women in Indonesia.