Interleukin-11 stimulates multilineage progenitors, but not stem cells, in murine and human long-term marrow cultures

Interleukin-11 (IL-11) is a bone marrow microenvironment-derived growth factor with pleiotropic effects on a variety of hematopoietic cells. To more accurately assess the effects of IL-11 on stem and progenitor compartments within the hematopoietic microenvironment (HM), we added recombinant human (rh) IL-11 to human and murine long-term bone marrow cultures (LTMC) and analyzed primitive (high proliferative potential- colony forming cells [HPP-CFC], long-term culture-initiating cells [LTC- IC], and long-term reconstituting stem cells) and progenitor (day 12 colony forming unit-spleen [CFU-S12], colony forming unit-megakaryocyte [CFU-Mk] and colony forming unit-granulocyte/macrophage [CFU-GM]) compartments throughout the duration of the cultures. rhIL-11 (100 ng/mL) added twice weekly resulted in significantly increased nonadherent (NA) cellularity, CFU-GM, and CFU-Mk production in human LTMC. Addition of rhIL-11 to murine LTMC was associated with a 5- to 40- fold increase in CFU-GM and a four- to 20-fold increase in day 12 CFU-S in NA cells. However, IL-11 had no significant effect on total HPP-CFC concentration and decreased the size of the more primitive stem/progenitor compartment as evidenced by both decreased LTC-IC frequency in human LTMC and decreased frequency of long-term reconstituting stem cells in murine LTMC. These data suggest that IL-11 may increase commitment of stem cells into a multipotential progenitor compartment.     

Acquired immune hemolytic anemia associated with IgA erythrocyte coating: investigation of hemolytic mechanisms

We have investigated the hemolytic mechanisms in a patient with acquired immune hemolytic anemia whose red cells appeared to be coated with IgA alone. The clinical course was similar to that of patients with hemolytic anemia mediated by warm-reacting IgG antibody. Splenic sequestration of red cells was demonstrated, and marked reduction of hemolysis occurred after corticosteroid therapy. Antibody was eluted from the patient's red cells and used to sensitize normal red cells in vitro. These sensitized red cells were not lysed by fresh autologous serum, nor did they fix detectable amounts of C3. However, red cells sensitized by eluted antibody were lysed by normal human peripheral blood monocytes in a system designed to demonstrate antibody-dependent cell-mediated cytotoxicity. Monocyte-mediated hemolysis of sensitized red cells was inhibited by the addition of low concentrations of normal serum IgA to the system, but not by IgG. The ability of the eluate to induce monocyte-mediated hemolysis was abolished by its adsorption on Sepharose-bound anti-IgA, but not by preincubation with Sepharose-bound anti-IgG. In addition, normal human monocytes were demonstrated to ingest eluate-sensitized red cells. These data demonstrate an in vitro interaction of IgA-sensitized red cells with leukocytes and suggest a possible mechanism for the patient's hemolysis.     

高黏度与低黏度骨水泥在经皮椎体后凸成形术中的应用比较

目的对比高黏度与低黏度骨水泥经皮椎体后凸成形术(PKP)治疗骨质疏松性椎体压缩性骨折(OVCF)的疗效差异。方法将2013年3月至2014年9月高要市人民医院收治的60例OVCF患者采用随机抽签法分为低黏度组(低黏度骨水泥PKP治疗)和高黏度组(高黏度骨水泥PKP治疗),每组各30例。对比两组手术前后伤椎椎体高度和后凸Cobb角;采用视觉模拟量表(VAS)评分、Oswestry功能障碍指数(ODI)、36项健康调查简表(SF-36)评分对患者疼痛程度、功能障碍和生活质量等主观感受进行评价;统计骨水泥渗漏、近期肺栓塞等并发症发生情况。结果低黏度组和高黏度组骨水泥注入量分别为(3.1±0.6)m L和(3.6±0.8)m L,两组比较,差异有统计学意义(P0.05)。术后随访3~6个月(平均4个月),两组术后1 d、3个月VAS评分、ODI、SF-36评分、伤椎椎体高度和后凸Cobb角均优于术前(P0.05),其中高黏度组术后1 d、3个月上述指标均优于低黏度组(P0.05)。低黏度组和高黏度组术后发生骨水泥渗漏、近期肺栓塞分别为6、2例和1、0例,两组并发症发生率比较,差异有统计学意义(P0.05)。结论与低黏度骨水泥比较,高黏度骨水泥PKP治疗OVCF近期疗效更为理想,骨水泥渗漏、近期肺栓塞等并发症发生率相对较低,值得临床推广应用。     

改良颈腮腺入路切除咽旁间隙高位良性肿瘤

目的 探讨改良颈腮腺入路在高位咽旁间隙良性肿瘤手术中的应用疗效。 方法 7例咽旁间隙良性肿瘤患者,术前影像学检查提示为高位、肿瘤巨大、哑铃型且边界欠清,采用改良颈腮腺入路术式,解剖辨认面神经总干及颞面干后,于外耳道软骨前方、腮腺的后缘以及颞面干的上方间隙向深部分离至肿瘤上极,剥离子分离并下压肿瘤与下方常规颈部自下而上肿瘤游离会师后,从颌下区取出肿瘤。腮腺浅叶不切除,面神经分支不做过多解剖。 结果 所有患者均一次性完整切除肿瘤;术后病理示多形性腺瘤6例,神经鞘瘤1例;术中出血均少于300 mL;1例患者出现术后同侧眼睑轻度闭合障碍,两周后完全正常;所有患者面容美学保存理想。 结论 对于高位咽旁间隙良性肿瘤采用改良颈腮腺入路术式,不仅可以安全完整地切除肿瘤,同时由于减少了面神经及腮腺浅叶的处置,术后相关神经并发症及腮腺区凹陷性改变的发生率下降。     

Incretin,insulinotropic and glucose-lowering effects of whey protein pre-load in type 2 diabetes: a randomised clinical trial

Aims/hypothesis

Since protein ingestion is known to stimulate the secretion of glucagon-like peptide-1 (GLP-1), we hypothesised that enhancing GLP-1 secretion to harness its insulinotropic/beta cell-stimulating activity with whey protein pre-load may have beneficial glucose-lowering effects in type 2 diabetes.

Methods

In a randomised, open-label crossover clinical trial, we studied 15 individuals with well-controlled type 2 diabetes who were not taking any medications except for sulfonylurea or metformin. These participants consumed, on two separate days, 50 g whey in 250 ml water or placebo (250 ml water) followed by a standardised high-glycaemic-index breakfast in a hospital setting. Participants were randomised using a coin flip. The primary endpoints of the study were plasma concentrations of glucose, intact GLP-1 and insulin during the 30 min following meal ingestion.

Results

In each group, 15 patients were analysed. The results showed that over the whole 180 min post-meal period, glucose levels were reduced by 28% after whey pre-load with a uniform reduction during both early and late phases. Insulin and C-peptide responses were both significantly higher (by 105% and 43%, respectively) with whey pre-load. Notably, the early insulin response was 96% higher after whey. Similarly, both total GLP-1 (tGLP-1) and intact GLP-1 (iGLP-1) levels were significantly higher (by 141% and 298%, respectively) with whey pre-load. Dipeptidyl peptidase 4 plasma activity did not display any significant difference after breakfast between the groups.

Conclusions/interpretation

In summary, consumption of whey protein shortly before a high-glycaemic-index breakfast increased the early prandial and late insulin secretion, augmented tGLP-1 and iGLP-1 responses and reduced postprandial glycaemia in type 2 diabetic patients. Whey protein may therefore represent a novel approach for enhancing glucose-lowering strategies in type 2 diabetes. Trial registration ClinicalTrials.gov NCT01571622 Funding The Israeli Ministry of Health and Milk Council funded the research.     

The spatial relationship between neurons and astrocytes in HIV-associated dementia

Specific neuronal spatial distributional patterns have previously been correlated with increasing severity of HIV-associated dementia (HAD). As astrocytes are also a putative site of neurotoxicity, we investigated the spatial relationships of astrocytes with pyramidal and interneurons in the superior frontal gyrus from 29 patients who died from acquired immunodeficiency syndrome. Frontal cortical brain tissue was taken from diseased HIV patients who had been assessed for the presence and severity of HAD using the Memorial Sloan-Kettering Scale. No correlation was found between neuronal density and severity of dementia. However, the pattern of astrocytes became more clustered as dementia progressed. Bivariate spatial pattern analysis of neuronal populations with astrocytes revealed that, with increasing dementia severity, astrocytes and large pyramidal neurons increasingly “repelled” each other, while astrocytes and interneurons evidenced increasing “attraction.” This implies that astrocytes may be more likely to be situated in the vicinity of surviving interneurons but less likely to be situated near surviving large pyramidal neurons in the setting of progressing HAD.     

Low rate of active treatment of patients with hilar cholangiocarcinoma

Introduction

The results of surgical resection and palliative chemotherapy use in hilar cholangiocarcinoma (HC) have been well publicised but the proportion of patients able to undergo these treatments and the comparative outcomes in a population of patients with HC are less well known.

Methods

Patients with HC were identified by review of all patients undergoing percutaneous cholangiography over a nine-year period (2002–2010) in a tertiary facility. The treatment undertaken and outcomes were recorded.

Results

Overall, 68 patients were identified (37 female) with a median age of 70 years. Forty-five (66%) were treated solely by insertion of a metal stent (median survival 4.73 months) and nine (13%) also received palliative chemotherapy (median survival 13.7 months). Persisting jaundice after stent insertion was noted in 18 of 35 patients (51%) tested within one month of death. Fourteen patients (21%) underwent surgical resection (median survival 20.2 months).

Conclusions

Patients undergoing surgical resection had significantly longer survival than those receiving only a palliative stent but not compared with those also receiving palliative chemotherapy, with short-term follow-up. Only a third of patients, however, receive active treatment (surgery or chemotherapy) and improvements in long-term biliary palliation are needed.