Surgical management of Crohn’s disease

Introduction

Crohn’s disease is an inflammatory bowel disease that can affect the entire gastrointestinal tract. It is chronic and incurable, and the mainstay of therapy is medical management with surgical intervention as complications arise. Surgery is required in approximately 70% of patients with Crohn’s disease. Because repeat interventions are often needed, these patients may benefit from bowel-sparing techniques and minimally invasive approaches. Various bowel-sparing techniques, including strictureplasty, can be applied to reduce the risk of short-bowel syndrome.

Methods

A review of the available literature using the PubMed search engine was undertaken to compile data on the surgical treatment of Crohn’s disease.

Results and conclusion

Data support the use of laparoscopy in treating Crohn’s disease, although the potential technical challenges in these settings mandate appropriate prerequisite surgical expertise.     

Genetic susceptibility to dental caries on pit and fissure and smooth surfaces

Carious lesions are distributed nonuniformly across tooth surfaces of the complete dentition, suggesting that the effects of risk factors may be surface-specific. Whether genes differentially affect caries risk across tooth surfaces is unknown. We investigated the role of genetics on two classes of tooth surfaces, pit and fissure surfaces (PFS) and smooth surfaces (SMS), in more than 2,600 subjects from 740 families. Participants were examined for surface-level evidence of dental caries, and caries scores for permanent and/or primary teeth were generated separately for PFS and SMS. Heritability estimates (h(2), i.e. the proportion of trait variation due to genes) of PFS and SMS caries scores were obtained using likelihood methods. The genetic correlations between PFS and SMS caries scores were calculated to assess the degree to which traits covary due to common genetic effects. Overall, the heritability of caries scores was similar for PFS (h(2) = 19-53%; p < 0.001) and SMS (h(2) = 17-42%; p < 0.001). Heritability of caries scores for both PFS and SMS in the primary dentition was greater than in the permanent dentition and total dentition. With one exception, the genetic correlation between PFS and SMS caries scores was not significantly different from 100%, indicating that (mostly) common genes are involved in the risk of caries for both surface types. Genetic correlation for the primary dentition dfs (decay + filled surfaces) was significantly less than 100% (p < 0.001), indicating that genetic factors may exert differential effects on caries risk in PFS versus SMS in the primary dentition.     

白花蛇舌草-半枝莲药对组分对结肠腺癌Lovo细胞生物学行为的影响

摘要:目的　探讨白花蛇舌草-半枝莲药对组分对结肠腺癌Lovo细胞增殖、侵袭、迁移和凋亡的影响及作用机制。方法　将白花蛇舌草、半枝莲按质量1∶1进行3次煎煮,获得水提物,后取适量浸膏用石油醚回流脱脂,再以乙酸乙酯进行多次萃取,获得白花蛇舌草-半枝莲药对组分,并计算得率。实验分为对照组（正常培养Lovo细胞）、白花蛇舌草-半枝莲药对组分低剂量组（10 mg/L）、中剂量组（30 mg/L）及高剂量组（50 mg/L）。通过噻唑蓝比色法（MTT）检测各组细胞培养24、48、72 h后的增殖抑制率。各组细胞培养48 h后,流式细胞仪检测细胞周期分布;Transwell实验检测细胞侵袭能力;划痕实验检测细胞迁移能力;TUNEL法检测细胞凋亡情况;Western blot法检测Grb2相关结合蛋白1（Gab1）、血管内皮生长因子受体2（VEGFR-2）、磷脂酰肌醇3-激酶（PI3K）、苏氨酸激酶（Akt）、基质金属蛋白酶-9（MMP-9）、B淋巴细胞瘤-2基因（Bcl-2）、Bcl-2相关X蛋白（Bax）蛋白表达情况。结果　化学萃取后的白花蛇舌草-半枝莲药对中主要含有对羟基苯乙酮、野黄芩苷、木犀草素和芹菜素4种化合物,组分得率为0.61%。与对照组相比,低、中、高剂量组细胞增殖抑制率升高,G1期肿瘤细胞比例增加,细胞凋亡指数增高,侵袭细胞数和划痕闭合率明显减小（均P＜0.05）,细胞中Gab1、VEGFR-2、PI3K、Akt、MMP-9、Bcl-2蛋白表达降低,Bax表达升高（均P＜0.05）,且存在剂量依赖性。结论　白花蛇舌草-半枝莲药对组分可抑制结肠腺癌Lovo细胞的增殖,降低其迁移和侵袭能力,诱导细胞凋亡,其机制可能与抑制Gab1/VEGFR-2/PI3K/Akt信号通路活化有关。     

Association of social support during emergency department evaluation for acute coronary syndrome with subsequent posttraumatic stress symptoms

We examined the associations of different aspects of social support during emergency department (ED) evaluation for an acute cardiac event with perceptions of threat in the ED and subsequent posttraumatic stress symptoms (PSS) in 484 patients. Participants were enrolled in the ED where they reported on their perceptions of threat in the ED. Social support in the ED and PSS were assessed at inpatient bedside or by telephone a median of 3 days later. Positive aspects of social support were not associated with subsequent PSS. Anxiety-provoking social support was significantly associated with increased PSS at follow-up. Greater ED threat perception partially mediated that relationship.     

Prediction of Human Brain Penetration of P-glycoprotein and Breast Cancer Resistance Protein Substrates Using In Vitro Transporter Studies and Animal Models

Four P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrates with human cerebrospinal fluid (CSF) concentrations and preclinical neuropharmacokinetics were used to assess in vitro–in vivo extrapolation of brain penetration in preclinical species and the ability to predict human brain penetration. Unbound brain (C_b,u), unbound plasma (C_p,u), and CSF compound concentrations (C_CSF) were measured in rats and nonhuman primates (NHPs), and the unbound partition coefficients (C_b,u/C_p,u and C_CSF/C_p,u) were used to assess brain penetration. The results indicated that for P-gp and BCRP dual substrates, brain penetration was severally impaired in all species. In comparison, for P-gp substrates that are weak or non-BCRP substrates, improved brain penetration was observed in NHPs and humans than in rats. Overall, NHP appears to be more predictive of human brain penetration for P-gp substrates with weak or no interaction with BCRP than rat. Although C_CSF does not quantitatively correspond to C_b,u for efflux transporter substrates, it is mostly within 3-fold higher of C_b,u in rat and NHP, suggesting that C_CSF can be used as a surrogate for C_b,u. Taken together, a holistic approach including both in vitro transporter and in vivo neuropharmacokinetics data enables a better estimation of human brain penetration of P-gp/BCRP substrates.     

Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor-dependent and T-cell receptor-independent thymocyte proliferation

The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.     

Neonatal chest wall suspension splint: a novel and noninvasive method for support of lung volume

Surfactant and musculoskeletal immaturity results in lower compliance of the lung relative to the chest wall, with clinical manifestations of low lung volume, marked chest wall retractions (CWR), and thoracoabdominal asynchrony. Inspiratory efforts are dissipated on distorting the chest wall inward rather than recruiting lung volumes. The current study tests the hypothesis that a novel neonatal chest wall suspension splint (SP), designed to provide stability to the compliant chest wall, would reduce inspiratory chest wall retractions and improve lung volumes. Nine preterm infants (29 +/- 1 SE weeks of gestation; 1.59 +/- 0.27 SE kg study weight) were studied at 16 +/- 5 SE days of life at baseline (BL) and following application of the front plate (FP) and the full SP (Hug n Snug Neonatal Chest Splint, Respironics, Inc.). Phase angle of thoracoabdominal motion, CWR, functional residual capacity (FRC), and pulmonary function were evaluated during spontaneous breathing. Compared to BL, there was a significant decrease in anterior CWR (2.21 +/- 0.91 SE vs. 0.25 +/- 0.09 SE mm; P < 0.05), an increase in FRC (16.6 +/- 2.8 SE vs. 27.8 +/- 5.5 SE ml/kg; P < 0.05) and tidal volume (4.8 +/- 1.5 SE vs. 7.3 +/- 1.4 SE ml/kg; P < 0.05), minimal effect on pulmonary compliance (1.98 +/- 0.50 SE vs. 1.72 +/- 0.30 SE ml/cmH2O/kg), and a trend for a decrease in phase angle (128.4 +/- 10.9 SE vs. 111.8 +/- 19.3 SE) with the application of the splint. FRC correlated inversely with severity of CWR across all conditions (P < 0.05, r = -0.68). Phase angle was directly correlated to anterior CWR (r = 0.72; P < 0.05) and correlated inversely with FRC (P < 0.005; r = -0.56). We speculate that by improving CW stability, the use of this splint may reduce the energetic requirements of breathing and, potentially, the need for more invasive ventilatory support in the neonate.