Small cell carcinomas of the large intestine.

The authors studied the clinical and pathologic features of 38 small cell carcinomas of the large intestine. Most were located in the right colon. Overlying adenomas were present in 45% and squamous differentiation in 21% of tumors. Endocrine differentiation was present in all tumors by at least one method; neuron-specific enolase, dense-core granules, and synaptophysin were present in most cases. Seventy-one percent of tumors metastasized to the liver; 64% of patients were dead at five months follow-up. Twenty-one poorly differentiated adenocarcinomas and undifferentiated carcinomas of the large intestine accessioned during the same period showed less endocrine (7 of 21) and squamous differentiation (1 of 15) and fewer liver metastases (4 of 15) than did small cell carcinomas. Among all 59 tumors studied, small cell histologic characteristics correlated better with liver involvement than did endocrine markers or other histologic features. Small cell carcinomas of the large intestine are aggressive tumors with a propensity for early liver involvement. Although there is a spectrum of squamous, endocrine, and glandular features in large bowel tumors of low degrees of differentiation, the identification of a small cell component appears to be most clinically relevant.     

Phenotypic characteristics of Obsessive-Compulsive Disorder ascertained in adulthood.

Over the past decade, the increased awareness and knowledge of Obsessive-Compulsive Disorder (OCD) has allowed the in-depth study of its phenotypic characteristics. The largest studies to date have described the symptom and syndrome characteristics of treatment-seeking patients. While usefully homogeneous with regard to their current state, the clinical characteristics of patients seeking treatment may only partially represent the OCD population. We report findings from 100 self-selected volunteers at various stages of their OCD illness who were participating in a genetic study. Many similarities with past reports were found, including high rates of mood disorder, significantly more mood disorder in females as compared with males, and increased social impairment among males despite an equal amount of time in episodes of disorder. On the other hand, mean age of onset in this nontreatment seeking population was younger. Lifetime rates of obsessions and compulsions in this population were substantially higher than previous reports, suggesting that the content of obsessions and compulsions shifted over time, and evolved into a lifetime repertoire. Furthermore, a separate analysis of the age of clinically significant O-C symptom onset without impairment revealed that males and females did not differ, suggesting that previous reports of earlier onset age in males may actually reflect earlier onset of impairment. Future genetic studies may benefit from the analysis of both significant O-C symptom onset, as well as the onset of full-syndromal OCD. These findings may suggest phenotypic characteristics that define homogeneous subgroups of patients with OCD.     

Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction

Following traumatic brain injury (TBI), raised cerebral lactate/pyruvate ratio (LPR) reflects impaired energy metabolism. Raised LPR correlates with poor outcome and mortality following TBI. We prospectively recruited patients with TBI requiring neurocritical care and multimodal monitoring, and utilised a tiered management protocol targeting LPR. We identified patients with persistent raised LPR despite adequate cerebral glucose and oxygen provision, which we clinically classified as cerebral ‘mitochondrial dysfunction’ (MD). In patients with TBI and MD, we administered disodium 2,3-¹³C₂ succinate (12 mmol/L) by retrodialysis into the monitored region of the brain. We recovered ¹³C-labelled metabolites by microdialysis and utilised nuclear magnetic resonance spectroscopy (NMR) for identification and quantification.Of 33 patients with complete monitoring, 73% had MD at some point during monitoring. In 5 patients with multimodality-defined MD, succinate administration resulted in reduced LPR(−12%) and raised brain glucose(+17%). NMR of microdialysates demonstrated that the exogenous ¹³C-labelled succinate was metabolised intracellularly via the tricarboxylic acid cycle. By targeting LPR using a tiered clinical algorithm incorporating intracranial pressure, brain tissue oxygenation and microdialysis parameters, we identified MD in TBI patients requiring neurointensive care. In these, focal succinate administration improved energy metabolism, evidenced by reduction in LPR. Succinate merits further investigation for TBI therapy.     

Consensus on core phenomena and statements describing Basic Body Awareness Therapy within the movement awareness domain in physiotherapy

Physiotherapists are facing complex health challenges in the treatment of persons suffering from long-lasting musculoskeletal disorders and mental health problems. Basic Body Awareness Therapy (BBAT) is a physiotherapy approach within the movement awareness domain developed to bridge physical, mental, and relational health challenges. The purpose of this study was to reach a consensus on core phenomena and statements describing BBAT. A consensus-building process was conducted using the nominal group technique (NGT). Twenty-one BBAT experts from 10 European countries participated in a concentrated weekend workshop of 20 hours. All participants signed informed consent. Participants reached a consensus on 138 core phenomena, clustered in three overarching categories: clinical core, historical roots, and research and evaluation phenomena. Of the 106 clinical core phenomena, the participants agreed on three categories of phenomena: movement quality, movement awareness practice, and movement awareness therapy and pedagogy. Furthermore, the participants reached 100 percent consensus on 16 of 30 statements describing BBAT. This study provides a consensus on core phenomena and statements describing BBAT. The data reveal phenomena implemented when promoting movement quality through movement awareness. Data provide clarity in some aspects of the vocabulary as fundamental theory. Further reearch will be developed.     

Characterization of mice expressing Ins1 gene promoter driven CreERT recombinase for conditional gene deletion in pancreatic β-cells

Gene manipulation using Cre-loxP recombination has proven to be an important approach for studying the impact of gene expression on pancreatic β-cell biology. We report the generation of a transgenic mouse line that enables a highly specific system for conditional gene manipulation within β-cells and achieve tissue specific and temporally regulated deletion of the Ctnnb1 (β-catenin) gene in pancreatic β-cells. cDNA encoding Cre recombinase fused to modified estrogen receptor (CreERT) under control of mouse insulin 1 gene promoter (Ins1) was used to construct the mouse line Tg(Ins1-Cre/ERT)1Lphi, also termed MIP1-CreERT. In a cross of MIP1-CreERT with a ROSA26/LacZ reporter strain, tamoxifen [Tmx] - dependent β-galactosidase expression occurred within pancreatic β-cells but not in other organ systems. Intraperitoneal glucose tolerance tests and glucose-stimulated changes in β-cell cytoplasmic calcium concentration were not adversely affected in adult MIP1-CreERT. A mouse line with floxed Ctnnb1 gene (Ctnnb1f/f) was crossed with the MIP1-CreERT line to generate a mouse model for inducible β-cell specific deletion of β-catenin gene (Ctnnb1f/f:MIP1-CreERT). Ctnnb1f/f:MIP1-CreERT mice and Ctnnb1f/f littermate controls, were injected with Tmx as adults to knock down β-catenin production in the majority of pancreatic β-cells. These mice showed normal glucose tolerance, islet cyto-architecture and insulin secretion. A novel protein fraction of 50Kd, immunoreactive with anti-β-catenin was observed in islet extracts from Ctnnb1f/f:MIP1-CreERT[Tmx] mice but not MIP1-CreERT-negative Ctnnb1f/f[Tmx] controls, indicating possible presence of a cryptic protein product of recombined Ctnnb1 gene. The MIP1-CreERT mouse line is a powerful tool for conditional manipulation of gene expression in β-cells.     

应用两层法保存和运输成人胰腺的实验

目的:提高胰岛的分离纯化率是胰岛移植成功的关键,其中胰腺的冷缺血时间是主要影响因素之一。探讨并建立供体胰腺长时间(>8h)保存和运送方法。方法:实验于2006-06/2007-02在解放军南京军区福州总医院全军器官移植中心完成,得到医院伦理道德委员会批准。①实验方法:应用两层保存法(University of Wisconsin液/全氟化碳),将25例成人胰腺置于广口瓶中,充氧并盖紧,放入冰筒中送达实验室,按冷缺血时间的长短,分为>8h组(n=17)和≤8h组(n=8)。参照改良后Ricordi方法分离胰岛,将胰腺切片置入消化罐中循环消化。应用连续密度梯度离心法在COBE2991离心机中纯化胰岛组织,并用双硫腙、吖啶橙、碘化丙啶染色。②实验评估:分别进行纯化后胰岛计数、纯度和活率检测,同时检测胰岛对高、低糖的反应性。结果:①冷缺血时间>8h组胰腺的冷缺血时间显著长于≤8h组(P<0.01)。②经双硫腙染色后,两组分离纯化的总胰岛当量、胰岛收获量差异无显著性意义(P>0.05);两组胰岛纯度和活率差异也无显著性意义(P>0.05)。③经低糖、高糖分别刺激后,两组胰岛素释放量及其刺激指数差异均无显著性意义(P>0.05)。结论:应用两层保存法保存和运送供体胰腺,可明显延长保存时间,但对胰岛的分离纯化数量和功能没有明显影响,为胰岛移植远距离保存和运送腺体提供了有利条件。     

Cardiopulmonary exercise testing as a predictor of complications in oesophagogastric cancer surgery

Introduction

An anaerobic threshold (AT) of <11ml/min/kg can identify patients at high risk of cardiopulmonary complications after major surgery. The aim of this study was to assess the value of cardiopulmonary exercise testing (CPET) in predicting cardiopulmonary complications in high risk patients undergoing oesophagogastric cancer resection.

Methods

Between March 2008 and October 2010, 108 patients (83 men, 25 women) with a median age of 66 years (range: 38–84 years) underwent CPET before potentially curative resections for oesophagogastric cancers. Measured CPET variables included AT and maximum oxygen uptake at peak exercise (VO₂ peak). Outcome measures were length of high dependency unit stay, length of hospital stay, unplanned intensive care unit (ICU) admission, and postoperative morbidity and mortality.

Results

The mean AT and VO₂ peak were 10.8ml/min/kg (standard deviation [SD]: 2.8ml/min/kg, range: 4.6–19.3ml/min/kg) and 15.2ml/min/kg (SD: 5.3ml/min/kg, range: 5.4–33.3ml/min/kg) respectively; 57 patients (55%) had an AT of <11ml/min/ kg and 26 (12%) had an AT of <9ml/min/kg. Postoperative complications occurred in 57 patients (29 cardiopulmonary [28%] and 28 non-cardiopulmonary [27%]). Four patients (4%) died in hospital and 21 (20%) required an unplanned ICU admission. Cardiopulmonary complications occurred in 42% of patients with an AT of <9ml/min/kg compared with 29% of patients with an AT of ≥9ml/min/kg but <11ml/min/kg and 20% of patients with an AT of ≥11ml/min/kg (p=0.04). There was a trend that those with an AT of <11ml/min/kg and a low VO₂ peak had a higher rate of unplanned ICU admission.

Conclusions

This study has shown a correlation between AT and the development of cardiopulmonary complications although the discriminatory ability was low.