Percutaneous gastrostomy for enteral feeding

Over a period of 18 months, percutaneous nonendoscopic gastrostomy using the Seldinger technique was successfully performed in 32 adults for enteral feeding. There were no deaths or major morbidity related to the procedure. Three patients died of existing disease within 30 days; one had peritoneal irritation following dislodgement of the catheter two days after the procedure but responded to conservative treatment with antibiotics alone. The authors conclude that this procedure is simple and safe and represents the preferred method of gastrostomy for enteral feeding.     

The impact of multidrug resistance on the pathogenicity of Escherichia coli: an experimental study

Based on the controversial findings of clinical studies regarding the influence of multidrug resistance on mortality, 10 susceptible and 10 multidrug-resistant (MDR) and extended-spectrum beta-lactamase-producing isolates of Escherichia coli were applied to stimulate monocytes isolated from healthy donors. Immune mediators were estimated in supernatants. Four susceptible isolates (Group A) and four MDR isolates (Group B) were used to initiate acute pyelonephritis in 48 rabbits following inoculation of the pathogen into the right renal pelvis. Survival was recorded and blood monocytes were isolated and incubated to estimate the ex vivo release of tumour necrosis factor-alpha (TNFalpha). Release of TNFalpha, interleukin (IL)-6 and IL-8 was higher after 2 h and 4 h of stimulation by MDR isolates compared with susceptible isolates. The opposite occurred for the release of IL-12. Death occurred in 22 rabbits in Group A (91.7%) compared with 12 in Group B (50.0%) (P=0.003). Monocytes isolated at 24 h from Group A rabbits released significantly higher TNFalpha than monocytes from Group B. Tissue bacterial load after animal death was significantly higher in the kidneys of Group A rabbits. It is concluded that susceptible and MDR E. coli stimulate monocytes resulting in a different pattern of release of pro-inflammatory cytokines, which is accompanied by prolonged survival following experimental sepsis by MDR isolates.     

Colistin Population Pharmacokinetics after Application of a Loading Dose of 9 MU Colistin Methanesulfonate in Critically Ill Patients

Colistin has been revived, in the era of extensively drug-resistant (XDR) Gram-negative infections, as the last-resort treatment in critically ill patients. Recent studies focusing on the optimal dosing strategy of colistin have demonstrated the necessity of a loading dose at treatment initiation (D. Plachouras, M. Karvanen, L. E. Friberg, E. Papadomichelakis, A. Antoniadou, I. Tsangaris, I. Karaiskos, G. Poulakou, F. Kontopidou, A. Armaganidis, O. Cars, and H. Giamarellou, Antimicrob Agents Chemother 53:3430–3436, 2009, http://dx.doi.org/10.1128/AAC.01361-08; A. F. Mohamed, I. Karaiskos, D. Plachouras, M. Karvanen, K. Pontikis, B. Jansson, E. Papadomichelakis, A. Antoniadou, H. Giamarellou, A. Armaganidis, O. Cars, and L. E. Friberg, Antimicrob Agents Chemother 56:4241– 4249, 2012, http://dx.doi.org/10.1128/AAC.06426-11; S. M. Garonzik, J. Li, V. Thamlikitkul, D. L. Paterson, S. Shoham, J. Jacob, F. P. Silveira, A. Forrest, and R. L. Nation, Antimicrob Agents Chemother 55:3284–3294, 2011, http://dx.doi.org/10.1128/AAC.01733-10). In 19 critically ill patients with suspected or microbiologically documented infections caused by XDR Gram-negative strains, a loading dose of 9 MU colistin methanesulfonate (CMS) (∼270 mg colistin base activity) was administered with a maintenance dose of 4.5 MU every 12 h, commenced after 24 h. Patients on renal replacement were excluded. CMS infusion was given over 30 min or 1 h. Repeated blood sampling was performed after the loading dose and after the 5th or 6th dose. Colistin concentrations and measured CMS, determined after hydrolization to colistin and including the partially sulfomethylated derivatives, were determined with a liquid chromatography-tandem mass spectrometry assay. Population pharmacokinetic analysis was conducted in NONMEM with the new data combined with data from previous studies. Measured colistimethate concentrations were described by 4 compartments for distribution and removal of sulfomethyl groups, while colistin disposition followed a 1-compartment model. The average observed maximum colistin A plus B concentration was 2.65 mg/liter after the loading dose (maximum time was 8 h). A significantly higher availability of the measured A and B forms of colistimethate and colistin explained the higher-than-expected concentrations in the present study compared to those in previous studies. Creatinine clearance was a time-varying covariate of colistimethate clearance. The incidence of acute renal injury was 20%.     

HIV／AIDS患者血清自身抗体检测结果分析

目的：了解 HIV /AIDS 患者血清中自身抗体的检出率,探讨自身免疫在 HIV /AIDS 患者中的意义。方法选择2008年1月至2012年10月云南省传染病专科医院门诊和住院就诊,并检测血清抗核抗体（ANA）和抗可提取性核抗原（ENA）等15种抗体的 HIV /AIDS 患者198例为观察组,另选择2012年健康体检者50例为健康对照组。采用间接免疫荧光法检测 HIV/AIDS 患者血清 ANA ;欧蒙印迹法检测自身抗体;流式细胞术检测 CD4＋T 淋巴细胞。比较两组间自身抗体检出率。结果观察组患者自身抗体总阳性率为27．8％,以 Ro-52阳性检出率最高,ANA 和 Ro-52与健康对照组比较差异有统计学意义（P ＜0．05）。 CD4＋ T 淋巴细胞低于200个/μL 的 HIV患者自身抗体检出率为37．1％,与高于200个/μL 的 HIV 患者比较差异有统计学意义（P＜0．01）。结论 HIV 感染能诱导自身免疫反应,使患者出现多种自身抗体,自身抗体的检出率与 CD4＋ T 淋巴细胞密切相关,监测 HIV 患者自身抗体对患者的诊断和治疗有一定的指导意义。     

Validation of Electronic Data Capture of the Irritable Bowel Syndrome—Quality of Life Measure, the Work Productivity and Activity Impairment Questionnaire for Irritable Bowel Syndrome and the EuroQol

OBJECTIVES: To assess the comparability, reliability, and subject acceptability of electronic data capture (EDC) versions of Irritable Bowel Syndrome-Quality of Life (IBS-QOL), EuroQoL (EQ-5D) and Work Productivity and Activity Impairment (WPAI:IBS) instruments. METHODS: Comparability of EDC and paper questionnaires was evaluated in 72 subjects with IBS who completed a baseline EDC or paper questionnaire, a crossover questionnaire 24 hours later, and a retest of the crossover version at 1 week. The EDC version was presented on a hand-held device. Comparability was assessed using paired t-test statistics, intraclass correlation coefficients (ICC) and tests for internal consistency (Cronbach's alpha). RESULTS: No significant differences were found between scores obtained by paper questionnaire and EDC at the baseline and crossover assessments. ICCs between baseline and crossover assessments ranged from 0.83 to 0.96 for the IBS-QOL scores, 0.82 to 0.96 for the WPAI:IBS scores, and 0.77 to 0.82 for the EQ-5D. Internal consistency was comparable for the two data collection methods for the IBS-QOL overall score (0.96) and subscales and the EQ-5D Index (0.70 vs. 0.74). Retest statistics (ICC) were generally comparable between the EDC and paper versions for all scores. Ease of use was comparable for the two modes of administration, but more patients preferred EDC (47.2%) than the paper questionnaire (23.6%). CONCLUSIONS: EDC versions of the IBS-QOL, EQ-5D, and WPAI:IBS are comparable to paper questionnaires in internal consistency and test-retest reliability, and have greater patient acceptability.     

The effect of maternal flora on Candida colonisation in the neonate

Colonisation may be the first step for the development of Candida infection. The source of neonatal colonisation is thought to be the hospital environment or the maternal vaginal tract. This study investigated to what extend Candida isolates in neonates are similar to isolates from their mother's vaginal tract. Vaginal samples were collected from 347 pregnant women within 48 h before delivery. Samples from oral and rectal mucosa of their neonates were collected within 24–72 h after delivery, were cultured and yeast species were identified. Antifungal susceptibility tests against six antifungal agents were performed. All paired isolates from mother and infant were genotyped by pulse field gel electrophoresis. A total of 82 mothers and of 16 infants were found colonised by Candida spp. C. albicans was the most common species in pregnant women (n = 68) followed by C. glabrata (n = 11). Only C. albicans was isolated from infants, mainly (14/16) from rectal site. All colonised neonates were born to mothers colonised by C. albicans. Candida genotyping revealed identical strains in all investigated neonate–mother pairs. All isolates were susceptible to amphotericin B. Our findings strongly suggest that vertical transmission has the principal role in the neonatal colonisation by C. albicans in the very first days of life.     

Regulatory T cells control macrophage accumulation and activation in lymphoma

Strategies of manipulating immunosuppressive regulatory T cells (Treg) in cancer patients are currently evaluated in clinical trials. Treg suppress immune responses of tumor‐specific T cells; yet, relatively little is known about the impact of Treg on innate immune cells in tumor models in vivo. Many tumors lose expression of MHC class I. Therefore, our study aimed at defining strategies to strengthen immune responses against a high tumor burden of the MHC class I‐deficient mouse lymphoma RMA‐S. We demonstrate that Treg depletion in mice led to tumor rejection that was dependent on T cells, NK cells and IFN‐γ. In the absence of Treg elevated levels of IFN‐γ were produced by tumor‐infiltrating T cells and NK cells. Tumor rejection observed in the absence of Treg correlated with a substantial IFN‐γ‐dependent increase in the numbers of tumor‐infiltrating leukocytes. The most abundant cell population in the tumors was macrophages. Tumor‐infiltrating macrophages from Treg‐depleted mice expressed increased amounts of MHC class II, produced highly enhanced levels of pro‐inflammatory cytokines and inhibited tumor cell proliferation. It was reported that tumor‐infiltrating macrophages have multi‐faceted functions promoting or counteracting tumor growth. In our study, high numbers of macrophages infiltrating RMA‐S tumors in the absence of Treg correlated with tumor rejection suggesting that macrophages are additional targets for Treg‐mediated immune suppression in cancer.     

Natural killer cell accumulation in tumors is dependent on IFN-gamma and CXCR3 ligands

Several studies have correlated high numbers of tumor-infiltrating natural killer (NK) cells with a good prognosis for cancer patients. Our study aimed at identifying factors controlling intratumoral NK cell accumulation in s.c. injected NK cell sensitive tumor models and at studying their effect on survival time of recipient mice. We observed that fewer NK cells infiltrated the tumors in IFN-gamma receptor knockout (IFN-gammaR(-/-)) mice compared with wild-type controls that correlated with decreased survival rate. Exogenous application of IFN-gamma in the tumor augmented levels of ligands of the chemokine receptor CXCR3, increased NK cell accumulation, and prolonged survival. Furthermore, our data show that CD27(high) NK cells, which under steady-state conditions express CXCR3, preferentially accumulated in the tumor tissue. Accordingly, significantly lower numbers of tumor-infiltrating NK cells were detected in CXCR3(-/-) mice, and the capacity of adoptively transferred CXCR3(-/-) NK cells to accumulate in the tumor was severely impaired. Finally, exogenous application of the CXCR3 ligand CXCL10 in the tumor or ectopic expression of CXCL10 by tumor cells increased the numbers of NK cells in the tumors and prolonged NK cell-dependent survival. Our results identify IFN-gamma and the expression of CXCR3 on NK cells as prerequisites for NK cell infiltration into tumors. Exploiting strategies to augment NK cell accumulation in the tumor might lead to the development of effective antitumor therapies.