Hormonal imbalance in two types of endometrial cancer and genetic polymorphism of steroidogenic enzymes

OBJECTIVES: Modern data on endometrial cancer (EC) incidence demonstrate that it is one of the most prevalent gynecologic malignancies. It is possible that some allelic polymorphisms of the genes involved in steroidogenesis or steroid metabolism differently contribute into susceptibility to described types of this disease, namely to type I (which is considered to be hormone dependent) and type II. METHODS: Distribution of allelic polymorphisms of CYP17 (17alpha-hydroxylase/17,20-lyase), CYP19 (aromatase), catechol-O-methyltransferase (COMT) and CYP1B1 (primarily, estrogen 4-hydroxylase) genes was compared totally in 156 endometrial cancer patients, approximately two-third of who belonged (on the basis of case history and some characteristics of host and tumor) to type I of the disease, and one-third to type II. Blood leukocytes were used as source of normal DNA for PCR-genotyping. RESULTS: No differences were found in distribution of CYP17 and CYP1B1 genotypes between patients belonging to type I or II of the disease. On the other side, in case of CYP19, the ratio of incidence of A6A6 genotype to the frequency of A1A6 and A3A6 genotypes was higher in type II patients (1.0) than in type I patients (0.3). Besides, incidence of high activity (HH) COMT genotype was higher among patients with type I of disease than in patients with type II of it (33.3% versus 14.7%, OR=2.9, z=1.96, p=0.05) revealing tendency to the lower inactivation of catecholestrogens in the latter group. CONCLUSION: It may be suggested that more aggressive clinically and frequently receptor-negative type II of endometrial cancer is associated with indirect signs of mainly intratumoral hyperproduction of estrogens (excess of CYP19 A6A6 genotype) without their sufficient inactivation into methoxyderivatives that warrants further study.     

HL-A Antigens in a Chinese Population

The HL-A antigens of a Chinese population now living on the island of Taiwan have been investigated with reagents obtained from and characterized in Caucasian populations and with antisera obtained from Chinese multiparous women. Both HL-A2, the most frequent specificity found, and HL-A9 appear highly heterogeneous in this Chinese population since groups of antisera used to define HL-A2 or 9 in Caucasians gave discordant reactions. Moreover, new associations were found using chi-square and cluster analyses, further demonstrating the complexity of HL-A in this Taiwanese population. Fourteen % of 1183 Chinese multipara sera and 237 sera from multiple tranfused individuals were lymphocytotoxic and could be placed by cluster analysis into three major groups.     

Modulation of systolic and diastolic function by endothelin-1: relation to coronary flow

Different conclusions have been reached with regard to the effect of endothelin (ET-1) on cardiac contractility. We examined systolic and diastolic function in response to constant known concentrations of ET-1 with or without ET-1 induced reductions in coronary flow (CF). Rat hearts (n= 21) were buffer-perfused using constant coronary flow (cCF) or constant perfusion pressure (cPP). Left ventricular function was assessed isovolumically. Addition of ET-1 (10^-9 M) in the cCF group caused a gradual increase in PP from 61 ± 2 to 165±6mmHg (mean±SE) (P < 0.01). Within 10 min left ventricular systolic pressure (LVSP) increased from 111 ± 2 to a maximum of 134±4mmHg (P < 0.01) and [L\dP/dt] increased from 1640 ± 81 to a maximum of 2020 ± 92 mmHg s“¹ (P < 0.01). After 15 min left ventricular end diastolic pressure (LVEDP), a measure of diastolic stiffness (DS), also increased. With ET-1 (10 ⁸ M), similar haemodynamic alterations appeared more rapidly. In the cPP group, ET-1 (10”⁹ M) caused a sharp decrease in CF and LVSP fell from 115 ± 8 to 62±12 mmHg at 10 min (P < 0.001). Systolic function remained stable at a reduced level for 1 h. DS did not change. Thus, ET-1 possesses positive inotropic effects and increases diastolic stiffness. Both effects may be masked by vasoconstriction-induced ischaemia.     

腓骨高位截骨在膝关节骨性关节炎的应用

目的:探讨腓骨高位截骨术对膝关节骨性关节炎的短中期疗效。方法:2014年10月至2016年7月,采用腓骨高位截骨治疗膝关节骨性关节炎76例,男22例,女54例;年龄47~82岁,平均61.62岁。术前查体膝关节内侧压痛,内侧麦氏征阳性,摄膝关节负重正侧位X线片显示内侧间隙变窄,术后行膝内侧间隙、股骨胫骨角、VAS疼痛评分及AKS评分进行评价。结果:术后随访10~18个月,平均8.9个月。与术前相比,术后膝内侧间隙明显变宽,股骨胫骨角度变大。术前VAS疼痛评分5.70±1.56,术后1周3.70±1.03,1个月3.20±0.95,3个月2.35±0.99,1年2.10±0.97。膝关节功能AKS评分术前疼痛14.45±1.76,活动度12.60±1.98,稳定性12.15±1.72;末次随访疼痛42.60±2.28,活动度21.80±2.14,稳定性20.85±2.16。VAS评分术前与术后各时间段相比差异有统计学意义,AKS评分术前与术后差异均有统计学意义。结论:腓骨高位截骨操作简单,并发症少,能有效减轻膝关节疼痛,改善膝关节功能,临床效果满意。     

原发性十二指肠恶性肿瘤的X 线诊断

目的　探讨X线诊断原发性十二指肠恶性肿瘤的价值。方法　回顾性分析 2 1例原发性十二指肠恶性肿瘤的X线所见并与手术病理对照。结果　X线表现包括充盈缺损、黏膜改变、肠腔狭窄和龛影。结论　根据临床及X线表现 ,术前可以正确诊断原发性十二指肠恶性肿瘤。     

Fatty acid-binding protein-4 as a biomarker predicting acromegaly-associated diabetes mellitus

Background/aimThe known pathogenesis of diabetes mellitus (DM) in acromegaly is mainly based on growth hormone (GH) and insulin-like growth factor-1 (IGF-1) excess. Fatty acid-binding protein 4 (FABP-4), a novel adipokine, is found to induce insulin resistance and type 2 DM. We aimed to investigate the possible effect of FABP-4 on glucose metabolism in patients with acromegaly.Materials and methodsThis case-control study included 28 patients newly diagnosed with acromegaly and 57 healthy volunteers. The patients with acromegaly were classified according to their glycemic status as with DM, prediabetes, and normal glucose tolerance. Anthropometric measurements, laboratory test results, and FABP-4 levels of the subjects were evaluated.ResultsAlthough no difference was observed in FABP-4 levels between acromegaly and control groups, the FABP-4 level was higher in the patients with acromegaly having DM compared to the patients with acromegaly having prediabetes and NGT, and the control group (p = 0.004, p = 0.001, p = 0.004, respectively). Logistic regression analysis suggested that the FABP-4 is an independent predictor of DM in acromegaly (β = 7.382, OR = 38.96, 95% CI: 1.52-5.76, p = 0.018).Conclusion The FABP-4 may be a helpful predictor of acromegaly-associated DM.     

On the origin and diffusion of BRCA1 c.5266dupC (5382insC) in European populations

The BRCA1 mutation c.5266dupC was originally described as a founder mutation in the Ashkenazi Jewish (AJ) population. However, this mutation is also present at appreciable frequency in several European countries, which raises intriguing questions about the origins of the mutation. We genotyped 245 carrier families from 14 different population groups (Russian, Latvian, Ukrainian, Czech, Slovak, Polish, Danish, Dutch, French, German, Italian, Greek, Brazilian and AJ) for seven microsatellite markers and confirmed that all mutation carriers share a common haplotype from a single founder individual. Using a maximum likelihood method that allows for both recombination and mutational events of marker loci, we estimated that the mutation arose some 1800 years ago in either Scandinavia or what is now northern Russia and subsequently spread to the various populations we genotyped during the following centuries, including the AJ population. Age estimates and the molecular evolution profile of the most common linked haplotype in the carrier populations studied further suggest that c.5266dupC likely entered the AJ gene pool in Poland approximately 400-500 years ago. Our results illustrate that (1) BRCA1 c.5266dupC originated from a single common ancestor and was a common European mutation long before becoming an AJ founder mutation and (2) the mutation is likely present in many additional European countries where genetic screening of BRCA1 may not yet be common practice.     

口服氨基葡萄糖联合关节腔内注射治疗膝骨性关节炎

目的 探讨口服氨基葡萄糖联合关节腔内注射治疗膝骨性关节炎的疗效.方法 门诊选取膝骨性关节炎患者402例,将患者按第1次关节腔内注射药物的不同分为透明质酸钠关节腔内注射组(214例)和三联针(透明质酸钠、醋酸曲安奈德、盐酸利多卡因)关节腔内注射组(188例),并在治疗后1、2、3、5周对患者按预先设定的疗效评价标准进行随访.结果 治疗后两组患者西安大略麦马斯特大学骨性关节炎指标可视化量表 (WOMAC) 疼痛指标和机体功能指标均明显下降,而且随观察时间延长,呈逐渐下降趋势,组间比较差异无统计学意义(P>0.05),但治疗后第1周随访,三联针关节腔内注射组疼痛指标下降趋势更明显,两组治疗期间塞来昔布用量比?差异有统计学意义(P<0.05).两组的不良反应发生率分别为8.9%(19/214)和8.5%(16/188),主要表现为轻中度的胃肠道不适和便秘.结论 口服氨基葡萄糖联合关节腔内注射在短期内能有效减轻膝骨性关节炎患者疼痛,改善关节功能,第1次关节腔内注射三联针能更快、更有效地缓解疼痛,减少了塞来昔布的用量.     

CHEK2 variants predispose to benign, borderline and low-grade invasive ovarian tumors

OBJECTIVE: Three founder alleles of the CHEK2 gene have been associated with predisposition to a range of cancer types in Poland. Two founder alleles (1100delC and IVS2 + 1G >A) result in a truncated CHEK2 protein and the other is a missense substitution, leading to the replacement of a threonine with an isoleucine (I157T). METHODS: To establish if these variants play a role in the etiology of ovarian tumors, we genotyped 1108 Polish women with various types of ovarian tumors and 4000 controls for the three CHEK2 variants. We included 539 Polish women with benign ovarian cystadenomas, 122 women with borderline ovarian malignancies and 447 women with invasive ovarian cancer. RESULTS: Positive associations were seen with the CHEK2 I157T missense variant and ovarian cystadenomas (OR = 1.7; P = 0.005), with borderline ovarian cancers (OR = 2.6; P = 0.002) and with low-grade invasive cancers (OR = 2.1; P = 0.04). There was no association with ovarian cancer of high grade (OR = 1.0). The association between the I157T missense variant was then confirmed in a second sample of Russian patients with borderline ovarian cancers (OR = 2.7; P = 0.06). CONCLUSION: These data indicate that CHEK2 variants may predispose to a range of ovarian tumor types of low malignant potential, but not to aggressive cancers.