贵州省2003～2004年麻疹疫苗强化免疫效果评价

目的总结贵州省实施麻疹疫苗(MV)强化免疫的效果。方法综合分析强化免疫期间的现场调查、项目年度评估报告和强化免疫后1年的麻疹监测系统和法定传染病报告系统的疫情资料。结果本次强化免疫共计接种目标儿童8 611 528人,报告接种率和调查接种率均>95%;共报告预防接种异常反应354例,发生率4.11/10万;接种后经过1个最长潜伏期,麻疹发病数明显减少,每周报告疑似麻疹2~34例,且近1/3为风疹;目前78.3%的麻疹病例发生在8月龄~14岁,病例71.1%无免疫史或免疫史不详。结论高质量MV强化免疫能够迅速降低麻疹发病,实施该项工作的关键环节包括广泛的社会动员、细致的培训和清晰的物流是前提保障;目标人群的确定必须结合当地流行病学监测的资料;尽可能在较大范围内开展,以形成有效的人群免疫屏障阻断麻疹病毒传播;接种时间选择在麻疹低发季节,且尽可能在15d内完成;保证>95%接种率是活动的前提目标;必须针对可能发生的预防接种后异常反应做好充分准备;如果该地区常规免疫服务质量在1~2年内不能明显加强,需要同时考虑4~5年后的后续免疫。     

A Folate Receptor–Targeted Lipid Nanoparticle Formulation for a Lipophilic Paclitaxel Prodrug

No HeadingPurpose. The anticancer drug paclitaxel has poor aqueous solubility and is difficult to formulate in a lipid-based formulation due to its limited lipid solubility. Paclitaxel-7-carbonyl-cholesterol (Tax-Chol), a prodrug of paclitaxel with increased lipophilicity, was therefore synthesized and evaluated for incorporation into a lipid nanoparticle (LN) formulation, which also contained folate-polyethylene glycol-cholesterol (f-PEG-Chol) as a ligand that targets the tumor marker folate receptor (FR). This novel formulation was designed for prolonged systemic circulation and selective targeting of tumor cells with amplified FR expression.Methods. Tax-Chol was synthesized. FR-targeted LNs, composed of distearoyl phosphatidylcholine (DSPC)/triolein/Chol oleate/PEG-Chol/f-PEG-Chol (40:40:18:2.0:0.5, mole/mole), were then prepared by solvent dilution followed by diafiltration. FR-targeted LNs containing Tax-Chol were then evaluated for cytotoxicity in KB, a human oral carcinoma cell line, and M109, a murine lung carcinoma cell line, both of which are FR(+) and in FR(–) Chinese hamster ovary (CHO) cells. Furthermore, tumor growth inhibition and animal survival in response to treatment with FR-targeted LNs and control formulations were evaluated in BALB/c mice bearing subcutaneously engrafted M109 tumors.Results. The LNs had a mean diameter of 130 nm and Tax-Chol incoporation efficiency of greater than 90% and exhibited excellent colloidal stability. FR-targeted LNs showed greater uptake and cytotoxicity in FR(+) KB and M109 cells than nontargeted LNs. Furthermore, treatment of mice bearing M109 tumors with FR-targeted LNs resulted in significantly greater tumor growth inhibition and animal survival compared to treatment with nontargeted LNs or paclitaxel formulated in Cremophor EL.Conclusions. FR-targeted LNs containing Tax-Chol are a promising novel formulation for the treatment of FR(+) tumors and further preclinical studies are warranted.     

Liquid-Crystal Display Monitors and Cathode-Ray Tube Monitors: A Comparison of Observer Performance in the Detection of Small Solitary Pulmonary Nodules

Objective

To compare observer performance using liquid-crystal display (LCD) and cathode-ray tube (CRT) monitors in the interpretation of soft-copy chest radiographs for the detection of small solitary pulmonary nodules.

Materials and Methods

By reviewing our Medical Center''s radiologic information system, the eight radiologists participating in this study (three board-certified and five resident) retrospectively collected 40 chest radiographs showing a solitary noncalcified pulmonary nodule approximately 1 cm in diameter, and 40 normal chest radiographs. All were obtained using a storage-phosphor system, and CT scans of the same patients served as the gold standard for the presence of a pulmonary nodule. Digital images were displayed on both high-resolution LCD and CRT monitors. The readers were requested to rank each image using a five-point scale (1 = definitely negative, 3 = equivocal or indeterminate, 5 = definitely positive), and the data were interpreted using receiver operating characteristic (ROC) analysis.

Results

The mean area under the ROC curve was 0.8901±0.0259 for the LCD session, and 0.8716±0.0266 for the CRT session (p > 0.05). The reading time for the LCD session was not significantly different from that for the CRT session (37.12 and 41.46 minutes, respectively; p = 0.889).

Conclusion

For detecting small solitary pulmonary nodules, an LCD monitor and a CRT monitor are comparable.     

5-hydroxyindalpine, an agonist at the putative 5-HT1P receptor, has no activity on human recombinant monoamine receptors but accelerates distension-induced peristalsis in mouse isolated colon

Abstract Although the putative 5‐HT_1P receptor has been implicated to have a role in peristalsis, experiments which suggest this function are preliminary or have measured only components of the reflex. We have, therefore, further characterized a reported agonist at this receptor (5‐hydroxyindalpine; 5‐OHIP) and investigated the effects of 5‐OHIP and 5‐hydroxytrytophan‐dipeptide (5‐HTP‐DP), a reported 5‐HT_1P receptor antagonist, on distension‐induced peristalsis in mouse colon. The effects of 5‐OHIP on intracellular calcium, cyclic adenosine monophosphate concentrations or GTPγS binding were measured in cell lines expressing human recombinant 5‐HT_{1A, 1B, 1D, 2A, 2B, 2C, 3, 4, 6, 7} and α_1A, α_1B, D₁, D₂, D₃, H₁, H₃ receptors. The effects of 5‐OHIP and 5‐HTP‐DP on peristalsis were assessed by measuring changes in frequency and times to reach threshold of peristaltic contractions, as well as the threshold and maximum pressures of each peristaltic stroke. 5‐hydroxyindalpine (1 nmol L^?1–10 μmol L^?1) had no significant activity at any of the receptors studied. However, 5‐OHIP (0.1 nmol L^?1–1 μmol L^?1) concentration‐dependently increased the frequency of peristalsis (EC₅₀ = 4.4 nmol L^?1) and reduced the time taken to reach threshold and threshold pressure, without altering maximum pressures. The maximum effect of 5‐OHIP was at 1 μmol L^?1 (68.0 ± 14.5% increase in frequency); 10 μmol L^?1 decreased peristalsis. 5‐hydroxytrytophan‐dipeptide (1–300 nmol L^?1) also increased the frequency of peristalsis and prevented the actions of 5‐OHIP. The higher concentration (1 μmol L^?1) transiently inhibited peristalsis and after recovery, prevented the actions of 5‐OHIP but not the excitatory activity of the cholinesterase inhibitor neostigmine. In summary, the present data demonstrate an interaction of ‘5‐HT_1P‐ligands’ with the peristaltic reflex. However, the absence of an effect of 5‐OHIP on a range of different monoamine receptors continues to highlight the need to investigate the identity of the putative 5‐HT_1P receptor.     

Differential expression of P2X-purinoceptor subtypes in circular and longitudinal muscle of canine colon

Adenosine triphosphate (ATP) mediates excitatory junction potentials through P2X receptors in many smooth muscles. However, relatively little is known about postjunctional intestinal P2X receptors. We examined the effect of exogenous ATP on circular and longitudinal myocytes of canine colon using the patch clamp technique at 32 degrees C. In both cell types, ATP induced inward currents (I(ATP)) at -70 mV in a concentration-dependent manner. The potency profile of ATP analogues in circular myocytes was: ATP approximately 2-methylthio-ATP > alpha,beta-methylene ATP, and that in longitudinal myocytes was: alpha,beta-methylene ATP approximately ATP > 2-methylthio-ATP. Pretreatment of circular myocytes with alpha,beta-methylene ATP inhibited the response to subsequent ATP, suggesting receptor desensitization. I-V relationships of I(ATP) were linear with inward rectification and E(rev) of -13 mV. I(ATP) at -70 mV was carried predominantly by Na+ as determined by shifts in E(rev) when extracellular Na+ was lowered. In RT-PCR, circular myocytes expressed mRNAs encoding P2X2, 3 and 4, while longitudinal myocytes expressed mRNAs for P2X3 and 5. P2X7 was absent in both cells. Fragments of each subtype were cloned and sequenced. We failed to clone P2X1 and P2X6 genes. Overall, different P2X receptor subtypes are expressed in circular and longitudinal canine colonic myocytes. Their activation produces non-selective cation currents that can depolarize and excite muscles of both layers.     

Association between interleukin-1β-511C/T polymorphism and reflux esophagitis in Japan

Background Interleukin-1β (IL-1β) gene polymorphisms are related to hypochlorhydria and increase the risk of gastric cancer in the presence of Helicobacter pylori infection. However, little information is available about the genetic risk factors of reflux esophagitis. In this study we investigated its association with the IL-1β polymorphisms. Methods We examined 48 patients with reflux esophagitis and 96 control subjects, 89 with gastric cancer. IL-1β-511C/T genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results The frequency of IL-1β-511T alleles was significantly higher in reflux esophagitis patients (57.3%) than in controls (41.1%) (P = 0.0215, χ² = 5.289). The frequency of IL-1β-511T/T genotypes was also significantly higher in reflux esophagitis patients (31.3%) than in controls (15.6%). The odds ratio and the 95% confidence interval were 4.000 and 1.393–11.486, respectively. The frequency of IL-1β-511T/T genotypes was significantly higher in reflux esophagitis patients (31.3%) than in gastric cancer patients (21.4%). The odds ratio and the 95% confidence interval were 2.961 and 1.054–8.316, respectively. Conclusions IL-1β-511T was associated with reflux esophagitis having hyperacidity. Differences of genetic background regarding gastric acid secretion may exist between Japanese and Caucasians.     

Doubling time of thymic epithelial tumours on CT: correlation with histological subtype

Objectives

We retrospectively evaluated the doubling time (DT) of thymic epithelial tumours (TET) according to the histological subtype on CT.

Methods

From January 2005 to June 2016, we enrolled 53 patients who had pathologically confirmed TET and at least two CT scans. Tumour size was measured using a two-dimensional method, and the DT was calculated. DTs were compared among histological subtypes, and factors associated with rapid tumour growth (DT <180 days) were assessed.

Results

In 42 of the 53 patients (79.2%) the tumours showed interval growth (>2 mm) during follow-up. The median DT for all tumours was 400 days (range 48–1,964 days). There were no significant differences in DT in relation to histological subtype (p?=?0.177). When TETs were recategorized into three groups, i.e. low-risk thymomas (types A, AB, B1), high-risk thymomas (types B2, B3), and thymic carcinoma, DT was significantly different among the groups (median DT 436, 381 and 189 days, respectively; p?=?0.031). Histological subtype (type B3 and thymic carcinoma) was the single independent predictor of rapid tumour growth.

Conclusions

The majority of TETs grew during follow-up with variable and relatively slow growth rates. Histological features of aggressive behaviour significantly correlated with a decreased DT and rapid growth.

Key points

? The majority of thymic epithelial tumours grew during follow-up (79.2%, 42/53).? Doubling times of thymic epithelial tumours were highly variable (median 400 days).? Histological features of aggressive behaviour significantly correlated with a decreased doubling time.

     

“人鱼小姐”素肌手记（二）

在生活中，我们都像安徒生童话中的美人鱼，为了换取梦中最绮丽的那一束焰火，甘愿让自己成为刀尖上最寂寞的舞者……[编者按]