Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions

We have previously shown that eating disorders are a compulsive behaviour disease, characterized by frequent recall of anorexic thoughts. Evidence suggests that memory is a neocortical neuronal network, excitation of which involves the hippocampus, with recall occurring by re-excitement of the same specific network. Excitement of the hippocampus by glutamate-NMDA receptors, leading to long-term potentiation (LTP), can be blocked by ketamine. Continuous block of LTP prevents new memory formation but does not affect previous memories. Opioid antagonists prevent loss of consciousness with ketamine but do not prevent the block of LTP. We used infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily nalmefene as opioid antagonist to treat 15 patients with a long history of eating disorder, all of whom were chronic and resistant to several other forms of treatment. Nine (responders) showed prolonged remission when treated with two to nine ketamine infusions at intervals of 5 days to 3 weeks. Clinical response was associated with a significant decrease in Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients (non-responders) the score was: before ketamine, 42.8 +/- 3.7; after ketamine, 44.8 +/- 3.1. There was no significant response to at least five ketamine treatments, perhaps because the compulsive drive was re-established too soon after the infusion, or because the dose of opioid antagonist, nalmefene, was too low.      

认知矫正治疗对慢性精神分裂症患者临床症状和社会功能的影响

目的:观察认知矫正治疗对慢性精神分裂症患者临床症状和社会功能的改善作用。方法:选择2003-01/08在北京回龙观医院住院的慢性精神分裂症患者104例。均符合CCMD-Ⅲ及DSM-Ⅳ关于精神分裂症诊断标准;年龄25～55岁;病程≥2年;病情稳定,处于迁延、残留或部分缓解状态;药物治疗状况稳定,近期无换药打算;纳入对象或家属同意入组并签署知情同意书。应用随机数字表法将患者分认知矫正治疗组和对照组,每组52例。在相近药物治疗的基础上,认知矫正治疗组以Ann Delahunty和Rodney Morice等制定的神经认知矫正手册(汉化)为治疗工具,在治疗师的指导下进行认知作业练习,内容包括认知灵活性、工作记忆、计划执行功能3大功能模块。对照组予以相同时间的工娱治疗,主要包括有治疗师指导的操作性音乐治疗和舞蹈治疗。治疗前后两组患者分别进行PANSS、住院精神患者社会功能缺陷量表和护士观察量表的评定。结果:实验共纳入慢性精神分裂症患者104例,认知矫正治疗组44例,对照组46例进入结果分析,14例脱落。①治疗前后两组患者PANSS量表总分以及阴性症状量表、复合量表、一般精神病理量表、反应缺乏量表4个分量表的评分均有下降,组内比较差异有显著性意义(t=2.12～4.59,P<0.05);减分情况在两组间差异不明显(P>0.05)。②两组患者的社会功能缺陷量表总分在治疗后均有下降,与治疗前比较,差异有显著性意义(t=3.89,2.04,P<0.05);两组间比较,差异无显著性意义(P>0.05)。认知矫正治疗组治疗后护士观察量表的总病情以及总消极、迟滞2个分量表评分下降,与治疗前比较差异有显著性意义(t=1.49,1.19,2.81,P<0.05);其中迟滞项的减分在两组间比较,差异具有显著性意义(F=4.97,P<0.05)。③社会功能量表的改善与词语流畅性的改善呈正相关(R2=0.36,P<0.05),护士观察量表中总病情与积极两项评分的改善也与言语流畅性测验的改善正相关(R2=0.37,0.34,P<0.05)。结论:认知矫正治疗能在一定程度上改善精神分裂症患者的社会功能,并与部分认知功能的改善相关,但对临床症状无明显改善作用。     

The systemic inflammatory response syndrome as a predictor of bacteraemia and outcome from sepsis

Criteria defining the <it>systemic inflammatory response syndrome</it> (SIRS) were used to assess prospectively 270 clinical episodes in which blood cultures were taken from patients in general medicine. SIRS, severe sepsis and septic shock occurred in 149 (55%), 13 (5%) and 9 (3%) episodes, respectively. However, evidence of organ hypoperfusion indicating severe sepsis was recorded as sought in only 26% of episodes of SIRS. Crude mortality at 28 days increased sequentially as more SIRS criteria were met, rising from 12% in non-SIRS blood culture episodes, to 36% when all four criteria were met. Mortality from severe sepsis and septic shock was 38% and 56%, respectively. In 61/64 (95%) episodes of clinically important bacteraemia, patients fulfilled SIRS criteria when the blood culture was taken. However, the positive predictive value of SIRS for predicting bacteraemia was only 7%. Patients who did not fulfill SIRS criteria when blood cultures were taken were at low risk of bacteraemia and comprised 45% (121/270) of the study population. Three patients in this low-risk group had bacteraemia. Mortality in bacteraemic patients with severe sepsis or septic shock who were initially treated with ineffective antibiotics for up to 48 h was 80%, compared to 42% in those always treated appropriately.      

Influence of mesh materials on the integrity of the vas deferens following Lichtenstein hernioplasty: an experimental model

Background

The utilization of mesh reinforcement of the inguinal area with polypropylene mesh has increased drastically over the last decade. Infertility due to obstructive azoospermia is a rare but serious complication following inguinal hernia repair, especially in young patients. The aim of this study was to evaluate the effect of different mesh structures on integrity of the vas deferens.

Materials and methods

Twenty male Chinchilla rabbits were used. The spermatic cord was dissected free and a Lichtenstein repair was performed with a low-weight polypropylene mesh (UltraPro^®) and a heavy-weight polypropylene mesh (Prolene^®) on the contralateral side. A vasography was performed after six months in order to investigate obstructions of the vas deferens. Light microscopy of the mesh host tissue interface was also performed and the foreign body reaction analyzed. Spermatogenesis was evaluated using the Johnsen score.

Results

Vasography revealed relevant obstructions (>75% of lumen diameter) located at the mesh margins (50% of Prolene^® and 22.2% of UltraPro^® mesh samples). Microscopic investigation of the mesh–host tissue interface showed typical formation of foreign body granulomas. The diameters of the foreign body granulomas were significantly reduced in the UltraPro^® mesh group (41.7 ± 5.5 μm) compared to the Prolene^® mesh group (48.7 ± 7.7 μm). Upon investigating the percentages of apoptotic (TUNEL) and proliferating (Ki67) cells, no significant differences were found. Following Prolene^® mesh implantation, a mean Johnsen score of 9.1 ± 1.2 was estimated, which was not significantly different from the UltraPro^® mesh samples (8.9 ± 1.4, P > 0.05).

Conclusions

If a mesh material is needed for inguinal hernia repair in young patients, the use of modern low-weight large porous and elastic samples appears to have a beneficial effect on integrity of the vas deferens.

     

Biomechanical analyses of overlap and mesh dislocation in an incisional hernia model in vitro

BACKGROUND: Incisional hernia repair is one of the most common surgical complications. Despite the introduction of mesh techniques of repair, recurrences are still prevalent. The aim of the current study was to evaluate the dependence of mesh dislocation on defect size, facial overlap, mesh-position, and orientation of the mesh in cases of anisotropic stretchability. METHODS: An in vitro incisional hernia model was used, which consisted of a pressure chamber, an elastic silicone pad representing the peritoneal sac, and a silicone mat with bovine muscle tissue representing the abdominal wall. Intrinsic pressure (up to 200 mm Hg) was generated within the pressure chamber by continuous inflation with CO(2). A slit-like or flap-like defect was created in the silicone mat to simulate small or large hernia defects, respectively. The implanted mesh was arranged in both onlay and sublay configurations. A large pore polypropylene mesh with significant anisotropic stretchability was investigated, whereas overlaps of 2, 3, and 4 cm were applied. RESULTS: Despite the application of pressures up to 200 mm Hg, no mesh ruptures occurred. In the slit-like defect model, the minimal overlap required to prevent dislocation at 200 mm Hg was 3 cm using the sublay technique provided that the mesh was positioned with its most stretchable axis parallel to the largest slit dehiscence. Perpendicular rotation of the mesh resulted in dislocation at 160 mm Hg, despite using an overlap of 3 cm. Mesh reinforcement showed less stability in both the onlay position and the flap-like defect. CONCLUSION: An overlap of 3 cm is sufficient to prevent early mesh dislocation. Meshes with anisotropic stretchability should be orientated with the most stretchable axis in the direction of least overlap.     

Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children

CD31(+)CD45RA(+)RO(-) lymphocytes contain high numbers of T cell receptor circle (TREC)-bearing T cells; however, the correlation between CD31(+)CD4(+) lymphocytes and TREC during aging and under lymphopenic conditions has not yet been sufficiently investigated. We analyzed TREC, telomere length and telomerase activity within sorted CD31(+) and CD31(-) CD4(+) lymphocytes in healthy individuals from birth to old age. Sorted CD31(+)CD45RA(+)RO(-) naive CD4(+) lymphocytes contained high TREC numbers, whereas CD31(+)CD45RA(-)RO(+) cells (comprising < or =5% of CD4(+) cells during aging) did not contain TREC. CD31(+) overall CD4(+) cells remained TREC rich despite an age-related tenfold reduction from neonatal (100 : 1000) to old age (10 : 1000). Besides a high TREC content, CD31(+)CD45RA(+)RO(-)CD4(+) cells exhibited significantly longer telomeres and higher telomerase activity than CD31(-)CD45RA(+)RO(-)CD4(+) cells, suggesting that CD31(+)CD45RA(+)RO(-)CD4(+) cells represent a distinct population of naive T cells with particularly low replicative history. To analyze the value of CD31 in lymphopenic conditions, we investigated six children after allogeneic hematopoietic stem cell transplantation (HSCT). Reemerging overall CD4(+) as well as naive CD45RA(+)RO(-)CD4(+) cells predominantly expressed CD31 and correlated well with the recurrence of TREC 5-12 months after HSCT. Irrespective of limitations in the elderly, CD31 is an appropriate marker to monitor TREC-rich lymphocytes essentially in lymphopenic children after HSCT.