Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial

BackgroundThis study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli.MethodsThis randomized, double-blinded, controlled phase 2 trial enrolled women aged 18–25 years in China. Totally 1600 eligible participants were randomized to receive 90 μg, 60 μg, or 30 μg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed.ResultsAll but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60 μg (GMT = 10,548) and 90 μg (GMT = 12,505) HPV vaccine groups and were significantly higher than those in the 30 μg (GMT = 7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified.ConclusionThe prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18–25 years. The 60 μg dosage formulation was selected for further investigation for efficacy.Clinical trials registration: NCT01356823.     

ENDOSCOPIC DIAGNOSIS OF INTRADUCTAL PAPILLARY‐MUCINOUS NEOPLASM OF THE PANCREAS BY MEANS OF PERORAL PANCREATOSCOPY USING A SMALL‐DIAMETER VIDEOSCOPE AND NARROW‐BAND IMAGING

Background: Intraductal papillary‐mucinous neoplasm (IPMN) is an intraductal tumor in which the mucin‐producing epithelium shows proliferated papillary and a wide variety of pathological changes ranging from hyperplasia to adenocarcinoma. Therefore, it is important to determine whether an IPMN is benign or malignant. In the present study of patients with IPMN, the protrusion was observed by a peroral pancreatoscopy (PPS) using a small‐diameter videoscope and narrow‐band imaging (NBI). We carried out the differential diagnosis of benign lesion to malignant lesion. Methods: Between April 2003 and May 2009, PPS using a small‐diameter videoscope by means of NBI was carried out on 21 hospitalized patients with IPMN (10 cases of adenocarcinoma, 11 cases of adenoma or hyperplasia; 14 males and seven females, with a mean age of 69.4 years). Results: Fifteen focal lesions of the 16 cases in the head of the pancreas (93.7%) and four focal lesions of the five cases in the pancreatic body (80%) were observable, whereas two lesions (adenocarcinoma in the pancreatic body, and adenoma in the uncus of pancreas) were not observable. Endoscopically, seven cases were classified as villous type and two cases as vegetative type, and nine cases were diagnosed as adenocarcinoma. Ten cases with sessile type or semipedunculated type were diagnosed as adenoma or hyperplasia. Vascular patterns and protrusions were detected more clearly in the NBI images than under white light observation. Conclusions: When combined with a videoscope and NBI, pancreatoscopy provided a clear image and was useful for evaluating whether the IPMN was benign or malignant.     

Calcium pentosan polysulfate and sodium pentosan polysulfate may be used to treat intervertebral disc degeneration

Intervertebral disc degeneration (IDD) is a major health problem world-wide, and several spinal disorders are closely associated with it. Although people have invested a great deal of time and effort, how to prevent and reverse the IDD for the researchers is still a difficult and hot issue. Intervertebral disc belongs to cartilage tissue, and IDD also is the cartilage degeneration disease. A large quantity of studies have shown that Calcium pentosan polysulfate (CaPPS) and sodium pentosan polysulfate (NaPPS) possess chondroprotective activities and play an important role in maintaining cartilage integrity. We reasonably hypothesize that NaPPS and CaPPS may be used to treat IDD. The possible mechanism may include that: (1) the significant effects of NaPPS and CaPPS in improving capillary blood flow could maintain nutritional supply to intervertebral disc, and preserve intervertebral disc tissue against degeneration; (2) CaPPS and NaPPS preserve cartilage integrity, proteoglycan synthesis, and improve cartilage biomechanical properties; (3) as the multifaceted exosite inhibitors of proteinases NaPPS and CaPPS strongly impede the activity and production of proteinases; (4) promotion of the balance between proteinases and TIMPs also may be involved in treating IDD; (5) NaPPS and CaPPS exhibit potent anti-inflammatory effects, and then reduce inflammation-induced IDD. If the hypothesis were conformed, the symptoms caused by IDD and its related diseases would be a corresponding alleviation or even disappearance, which could greatly alleviate the suffering of patients from disc degeneration diseases. Certainly, many roles of CaPPS and NaPPS, such as effectiveness, safety and side effects, need to be tested, and further works such as animal model and clinical trial, need to be done to prove this hypothesis.     

猪苓及猪苓多糖对膀胱癌模型大鼠腹腔巨噬细胞吞噬和表面免疫相关分子表达的影响

目的:观察猪苓及猪苓多糖(PPS)对BBN加糖精诱导的膀胱癌大鼠腹腔巨噬细胞的吞噬功能、体外NO释放及共刺激分子和表面分子表达的影响。方法:实验分为空白对照组、模型组、PPS组和猪苓高中低剂量共6组。用流式细胞术检测膀胱癌大鼠腹腔巨噬细胞的荧光微球吞噬率、TLR4/CD14、CD86、CD40的表达。Griess试剂盒检测并分析猪苓及PPS对腹腔巨噬细胞体外NO释放的影响。结果:PPS组与模型组比较,PPS显著促进巨噬细胞吞噬率的增加、NO释放的比值均降低、巨噬细胞表面分子TLR4/CD14、CD86、CD40的表达均显著升高(P<0.05)。不同浓度猪苓组与模型组比较巨噬细胞吞噬率增加、NO释放的比值均降低(P<0.05),巨噬细胞表面分子CD86表达增加。低浓度猪苓组巨噬细胞CD40表达百分率显著升高(P<0.05);但TLR4/CD14的表达无明显变化;中、高剂量猪苓组TLR4/CD14的表达百分率与模型组比较则降低(P<0.05),CD40的表达无统计学差异。结论:PPS可显著促进膀胱癌大鼠腹腔巨噬细胞的吞噬功能和表面免疫相关分子的表达,但猪苓组对巨噬细胞功能的影响因剂量不同而表现出不同结果,可能与猪苓诸多成分同时作用或各成分作用的靶点不同有关。     

磁共振选择性激励技术在腰骶脊神经根病变成像中的初步应用

目的应用磁共振选择性激励技术（PROSET）直观地显示腰骶脊神经根。方法对36例腰骶椎检查者在常规脊柱扫描后加扫PROSET序列,在PROSET序列原始图像上用3PPS对所需观察的腰骶脊神经追踪定位后再做一次PROSET序列扫描,通过ViewForum4.1工作站MIP和MPR重建图像来观察腰骶脊神经根的显示情况。结果36例受检者中,腰椎间盘突出15例、神经鞘膜囊肿7例、单纯性神经根变异1例、转移瘤3例,正常腰骶脊神经根10例。本组PROSET原始图像均能清楚地显示腰骶脊神经根的结构,结合3PPS定位后PROSET图像能直观地显示脊神经的硬膜囊、神经根、神经节、神经干;MIP重建后的图像能利用不同层厚从不同角度不同方向来显示脊神经根的形态学改变,而MPR重建可获得选择切面的重建图像,显示病变细节。结论PROSET能清楚地显示腰骶脊神经根的结构,能直观地显示腰骶脊神经根的完整形态,为腰骶脊神经根病变的诊断提供可靠依据。     

2005年河北省碘缺乏病监测结果分析

目的掌握河北省2005年碘缺乏病病情和人群碘营养状况,评价食盐加碘控制碘缺乏病的效果。方法采用人口比例概率抽样方法（PPS）进行抽样。结果采集测定居民户盐样1200份,盐碘中位数为28．6mg／kg,碘盐合格率为90．2％。触诊法和B超法检查8～10岁儿童1200名,肿大率分别为2．75％和2．17％。采集测定8～10岁儿童1次即时尿样362份,尿碘中位数为212．35μg／L。测试8～10岁儿童1200名智商,平均智商为105．3。结论河北省碘缺乏病得到有效控制,但由于受非碘盐的影响,居民碘盐合格率较低;8～10岁儿童的碘营养状况总体上良好。     

A permeation enhancer for increasing transport of therapeutic macromolecules across the intestine

Delivery of therapeutic macromolecules is limited by the physiological limitations of the gastrointestinal tract including poor intestinal permeability, low pH and enzymatic activity. Several permeation enhancers have been proposed to enhance intestinal permeability of macromolecules; however their utility is often hindered by toxicity and limited potency. Here, we report on a novel permeation enhancer, Dimethyl palmitoyl ammonio propanesulfonate (PPS), with excellent enhancement potential and minimal toxicity. PPS was tested for dose- and time-dependent cytotoxicity, delivery of two model fluorescent molecules, sulforhodamine-B and FITC-insulin in vitro, and absorption enhancement of salmon calcitonin (sCT) in vivo. Caco-2 studies revealed that PPS is an effective enhancer of macromolecular transport while being minimally toxic. TEER measurements in Caco-2 monolayers confirmed the reversibility of the effect of PPS. Confocal microscopy studies revealed that molecules permeate via both paracellular and transcellular pathways in the presence of PPS. In vivo studies in rats showed that PPS enhanced relative bioavailability of sCT by 45-fold after intestinal administration. Histological studies showed that PPS does not induce damage to the intestine. PPS is an excellent permeation enhancer which provides new opportunities for developing efficacious oral/intestinal delivery systems for therapeutic macromolecules.     

The proportionator: unbiased stereological estimation using biased automatic image analysis and non-uniform probability proportional to size sampling

The proportionator is a novel and radically different approach to sampling with microscopes based on the well-known statistical theory (probability proportional to size-PPS sampling). It uses automatic image analysis, with a large range of options, to assign to every field of view in the section a weight proportional to some characteristic of the structure under study. A typical and very simple example, examined here, is the amount of color characteristic for the structure, marked with a stain with known properties. The color may be specific or not. In the recorded list of weights in all fields, the desired number of fields is sampled automatically with probability proportional to the weight and presented to the expert observer. Using any known stereological probe and estimator, the correct count in these fields leads to a simple, unbiased estimate of the total amount of structure in the sections examined, which in turn leads to any of the known stereological estimates including size distributions and spatial distributions. The unbiasedness is not a function of the assumed relation between the weight and the structure, which is in practice always a biased relation from a stereological (integral geometric) point of view. The efficiency of the proportionator depends, however, directly on this relation to be positive. The sampling and estimation procedure is simulated in sections with characteristics and various kinds of noises in possibly realistic ranges. In all cases examined, the proportionator is 2-15-fold more efficient than the common systematic, uniformly random sampling. The simulations also indicate that the lack of a simple predictor of the coefficient of error (CE) due to field-to-field variation is a more severe problem for uniform sampling strategies than anticipated. Because of its entirely different sampling strategy, based on known but non-uniform sampling probabilities, the proportionator for the first time allows the real CE at the section level to be automatically estimated (not just predicted), unbiased-for all estimators and at no extra cost to the user.     

Feasibility of using point prevalence surveys to assess antimicrobial utilisation in public hospitals in South Africa: a pilot study and implications

Objectives: There is currently a lack of data regarding antimicrobial use among public hospitals in South Africa. This is a concern given their growing use and increasing antimicrobial resistance rates in South Africa. Consequently, the objectives of this study were to firstly determine the appropriateness of point prevalence survey (PPS) data collection instruments for performing antimicrobial utilization studies among public sector hospitals in South Africa; secondly, to determine current antimicrobial utilization in a public sector hospital, and thirdly evaluate the prescribing of antimicrobials with those contained within the national Essential Medicines List and Standard Treatment Guidelines (EML/STGs). The findings will be used to guide future activities in South Africa.

Methods: A PPS was conducted in Dr George Mukhari Academic Hospital. For each in-patient ward, all patients’ files were completely surveyed on a single day. The number of patients who were on antimicrobials served as the numerator and the denominator comprised the total number of patients in the ward.

Results: 39 wards and 512 patient files were surveyed. The overall prevalence of antimicrobial use was 37.7%, highest in the ICUs. Beta lactamase inhibitors and antimicrobials for tuberculosis were the most prevalent antimicrobials. More than two thirds (83%) of antimicrobial treatment was modified following culture sensitivity test results when requested, and 98% of antimicrobials prescribed were contained within the current EML/STGs. In 10.8% of occasions, antimicrobials appear to have been prescribed other than for treatment, i.e. no systemic infection. There were concerns though with the lack of IV to oral switching.

Conclusion: The PPS method offers a standardized tool that can be used to identify targets for quality improvement. However, there were concerns with the time taken to conduct PPS studies, which is an issue in resource limited settings. This is being addressed alongside concerns with the lack of IV to oral switching.