脾实热证与类风湿关节炎热痹证的关系

类风湿性关节炎属于中医"痹病"范畴。辨证大体分为寒热两类,而类风湿关节炎热痹证临床上较为多见。现代实验研究表明,中医脾气虚时机体免疫系统功能低下。试以探讨脾实热证时机体的免疫功能是否亢进,经研究中医古典医籍,发现脾实热证具有某些热痹证候,而类风湿关节炎热痹证在急性活动期常可见体液免疫亢进,现就脾实热证与类风湿关节炎热痹的关系加以探讨,为清热泻脾法治疗免疫疾病提供理论依据。     

The placenta contributes to activation of the renin angiotensin system in twin-twin transfusion syndrome

The renin-angiotensin system (RAS) in twin-twin transfusion syndrome (TTTS) is up-regulated in the donor fetus's kidneys, but down-regulated in the recipient's. Ultrasonographic and echocardiographic features suggest that the recipient is also exposed to RAS components. In this study we investigated the role and origin of RAS components in the recipient fetus. Monochorionic diamniotic (MCDA) pregnancies were recruited from a tertiary fetal medicine service. Cord blood was collected from MCDA twins (TTTS and control non-TTTS) at delivery for renin and angiotensin II immunoassays. Placental tissue was flash-frozen for mRNA and protein expression or formalin-fixed for immunohistochemistry. Archival placenta and kidney samples were used for immunohistochemistry and in-situ hybridization. Plasma renin levels were elevated (p<0.05) in recipients (median 201pg/ml, range 54-315pg/ml) and donors (125pg/ml, 25-296) with TTTS compared to controls (2.5pg/ml, 1.1-1.5pg/ml). The same was found with angiotensin II with high levels in both recipients (300.5pg/ml, 86.1-488pg/ml) and donors (239pg/ml, 76.6-422) compared to controls (169.5pg/ml, 89-220pg/ml, p<0.05). Renin mRNA expression, and protein appeared qualitatively higher in the placental territory of the recipient compared to that of the donor and non-TTTS controls. We conclude that both fetuses in TTTS are exposed to high levels of RAS components; these appear to be produced from different sites, namely the kidney of the donor, and the placenta of the recipient. Given the markedly different phenotypes in the genetically identical fetuses with TTTS, we suggest that the source of RAS components may influence their clinical manifestations.     

Proliferative responses in the placenta after endotoxin exposure in preterm fetal sheep

OBJECTIVES: Antenatal infections are associated with an increased risk of perinatal morbidity and mortality. Systemic application of endotoxins to the fetus results in an increase in placental vascular resistance and chronic reduction in umbilical blood flow. We studied morphological alterations of the placenta in response to fetal inflammation in the preterm sheep. STUDY DESIGN: Therefore, 14 fetal sheep were chronically instrumented at a mean gestational age of 107+/-1 days (term is 147 days). Four days after surgery fetuses received 100 ng lipopolysaccharide (LPS; n=8) or saline (control; n=6) intravenously. Fetal heart rate and arterial blood pressure were monitored continuously while blood gases and acid-base balance were measured at time points 0, +1, +3, +6, +12, +24, +48 and +72 h. Three days after LPS application placental cotyledons were analyzed by immunohistochemistry and morphometry. Different primary antibodies like AE 1 and AE 3 against cytokeratins were used. Secondary antibodies were visualized with 3-amino-9-ethylcarbazole (AEC) or using the Vectastain kit (Vector Laboratories, Burlingame, CA). Double staining was carried out first by utilizing Vectastain kit (black), followed by AEC staining (red). Counterstaining was performed with haematoxylin. RESULTS: Fetal tachycardia and hypertension were induced transiently during the first 12h after LPS application. Fetuses suffered from mild hypoxaemia while acidemia was absent. Morphometry revealed a non-significant shift in the relation of maternal and fetal placental compartments towards the maternal parts in response to LPS treatment. Endotoxin induced an increased proliferation in both compartments of the placenta with a 3.2-fold increase on the maternal and a 1.8-fold increase on the fetal side. CONCLUSIONS: Systemic endotoxin exposure of the preterm fetal sheep leads to a change in the gross organization of the placenta and changes in the proliferation patterns in both placental compartments. These rearrangements inside the placenta may disturb its organ function and subsequently lead to fetal morbidity associated with the fetal inflammatory response syndrome and chronic placental dysfunction, respectively.     

限制性输液复苏法对失血性休克孕兔血流动力学变化的影响

目的 探讨限制性输液复苏法对失血性休克孕兔血流动力学变化及血清肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)含量变化的影响.方法 将20只妊娠中晚期新西兰大白兔分为2组,分别采用生理盐水传统输液复苏法(PNL组)及限制性输液复苏法(PLH组),每组10只.建立非控制性失血性休克模型,实验设计分为休克期(0～30 min),院前复苏期(30～90 min)及院内复苏期(90～180 min).休克期:两组孕兔均接受颈动脉放血至平均动脉压(MAP)为40～45 mm Hg(1 mm Hg=0.133 kPa).院前复苏期:剪开两组孕兔孕囊血管放血,复制活动性出血模型,然后PNL组和PLH组孕兔分别接受生理盐水及自身血复苏至MAP为80、60 mm Hg.院内复苏期:两组孕兔均接受手术止血及输血、输液治疗.比较两组孕兔各时间点血流动力学、TNF-α及IL-6含量的变化,记录输血、输液量及生存率.结果 (1)120 min时,PLH组孕兔呼吸、心率分别为(66±16)、(235±41)次,PNL组分别为(78±16)、(291±37)次,两组分别比较,差异有统计学意义(P＜0.01);PLH组孕兔MAP和中心静脉压(CVP)分别为(80.4±7.2)mm Hg、(8.0±4.4)cm H2O,PNL组孕兔分别为(72.5±8.2)mm Hg、(5.8±3.1)cm H2O,两组分别比较,差异也有统计学意义(P＜0.01);(2)两组孕兔血清TNF-α、IL-6含量休克后均升高,且在240 min时达高峰,PLH组孕兔血清TNF-α、IL-6含量分别为(105±67)、(118±51)ng/L,PNL组分别为(280±160)、(311±240)ng/L,两组比较,差异有统计学意义(P＜0.01),且PLH组孕兔血清TNF-α、IL-6含量在480 min时已降至正常;(3)PLH组输血、输液量在院前复苏期分别为(16.0±2.2)、(39.0±5.5)ml,在院内复苏期分别为(28.0±6.7)、(90.0±7.1)ml,PNL组在院前复苏期分别为(31.0±8.2)、(85.0±7.9)ml,在院内复苏期分别为(37.5±9.4)、(140.0±24.8)ml,两组比较,差异也有统计学意义(P＜0.05);(4)PLH组孕兔24、72 h的生存率分别为100%、90%;PNL组为80%、60%,两组比较,差异有统计学意义(P＜0.01).结论 限制性输液有利于失血性休克孕兔血流动力学指标的恢复,缓解血清TNF-α、IL-6含量升高的程度,从而提高了动物生存率.     

钙蛋白酶10基因多态性与多囊卵巢综合征患者糖耐量及脂代谢异常的相关性

目的 探讨钙蛋白酶10(CAPN-10)基因56位点单核苷酸多态性(SNP-56)与多囊卵巢综合征(PCOS)患者糖耐量及脂代谢异常的相关性.方法 选取山东地区PCOS患者334例(PCOS组),健康妇女304例(对照组),采用熔解温度不同的基因分型法检测CAPN-10基因SNP-56,并采用免疫化学发光法测定泌乳素、卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇、睾酮水平.PCOS组同时测定血糖、血脂、血清胰岛素水平.结果 (1)基因型及等位基因频率分布两组比较,差异均无统计学意义(P＞0.05).(2)在PCOS组,口服葡萄糖耐量试验(OGTF)180 min血糖水平AA基因型者为(5.7±2.2)mmol/L,GA基因型者为(4.9±1.2)mmol/L,GG基因型者为(4.9±1.4)mmol/L,分别比较,差异均有统计学意义(P均＜0.01);总胆固醇(TC)水平AA基因型者为(4.9±1.0)mmol/L,GA基因型者为(4.5±0.9)mmol/L,两者比较,差异也有统计学意义(P＜0.05).(3)在PCOS组,有糖尿病家族史者共44例,AA基因型频率为22.7%(10/44),GA+GG基因型频率为77.3%(34/44),GG基因型频率为34.1%(15/44);无糖尿病家族史者共290例,AA基因型频率为11.0%(32/290),GA+GG基因型频率为89.0%(258/290),GG基因型频率为47.2%(137/290),有无糖尿病家族史者AA与GA+GG基因型频率比较及AA与GG基因型频率比较,差异均有统计学意义(x2=4.751,x2=5.697;P均＜0.05).在PCOS组,有肿瘤家族史者共21例,AA基因型频率为33.3%(7/21),GA+GG基因型频率为66.7%(14/21),GG基因型频率为19.0%(4/21);无肿瘤家族史者共313例,AA基因型频率为11.2%(35/313),GA+GG基因型频率为88.8%(278/313),GG基因型频率为47.3%(148/313).结论 (1)CAPN-10基因SNP-56与PCOS的遗传易感性无明显相关性,但与PCOS患者糖、脂代谢异常有明显相关性.(2)CAPN-10基因SNP-56与PCOS患者糖尿病家族史及肿瘤家族史相关,应重视对高危PCOS个体的随访.     

Acute promyelocytic leukemia: an unusual cause showing prolonged disseminated intravascular coagulation after placental abruption

Background Disseminated intravascular coagulation (DIC) caused by placental abruption usually improves rapidly after prompt delivery and adequate anti-DIC treatment. Case A 30-year-old nulliparous woman suffered from placental abruption at the 25th week of pregnancy, and emergent cesarean section was done immediately. She exhibited DIC, which continued even after termination of the pregnancy and anti-DIC treatment. She also showed neutropenia. We closely observed her, and at the 58th day postpartum, blast cells appeared in the peripheral blood and she was diagnosed with acute promyelocytic leukemia (APL). Induction chemotherapy was done successfully. The close observation after delivery enabled us to make the prompt diagnosis/treatment, leading to the complete remission. Conclusion APL should be added to the list of differential diagnosis when DIC persists even after prompt delivery and appropriate anti-DIC treatment after placental abruption.     

Genital tuberculosis: an important cause of Asherman’s syndrome in India

Objective To demonstrate the association between genital endometrial tuberculosis and Asherman's syndrome. Materials and methods A total of 28 women who underwent hysteroscopy with or without laparoscopy for suspected Asherman’s syndrome from symptoms (amenorrhoea or oligomenorrhoea, and or primary or secondary infertility) and who were found to have genital tuberculosis on endometrial biopsy (histopathology or culture) or positive polymerase chain reaction (PCR) on endometrial aspirate or positive findings of tuberculosis on laparoscopy or hysteroscopy were enrolled in this retrospective study. Results The mean age and parity were 26.5 years and 0.3, respectively. There was past history of TB in 67.8% women. All women had menstrual dysfunction, with oligomenorrhoea and hypomenorrhoea in 16 (57%) women and amenorrhoea in 12 (42.8%). All women had primary (n = 19, 67.8%) or secondary (n = 9, 32%) infertility. On hysteroscopy, there were various grades of adhesions in all women, with grade I in 17.8%, grade II in 28.5%, grade III in 28.5% and grade IV in 17.5% women. Only four women (14.3%) had open ostia, while others had bilateral (28.5%) or unilateral (21.3%) blocked ostia or inability to see ostia (28.5%). On laparoscopy performed on 18 women, there were varying grades of adhesions in 16 (88.8%) women, with beading (33.3%), tubercles (33.3%), caseation (11.1%) and tubo-ovarian masses (11.1%). The diagnosis of genital TB was made by histopathology (tuberculous granuloma) on endometrial biopsy in 28.6%, positive culture in 3.6%, positive polymerase chain reaction (PCR) in 46.4% and observation of tubercles, beading or caseation on laparoscopy in 17.8% or shaggy cavity with caseation on hysteroscopy in 3.6% women. Conclusion Genital tuberculosis appears to be an important and common cause of Asherman's syndrome in India, causing oligomenorrhoea or amenorrhoea with infertility.     

The correlation of plasma homocysteine with insulin resistance in polycystic ovary syndrome

AIM: This study aims to investigate the existence of any relationship between homocysteine levels and insulin resistance in Turkish women with polycystic ovary syndrome. METHODS: A case-controlled, cross-sectional, observational study was undertaken in a total of 94 infertile Turkish women who required professional help in the Department of Infertility of Dr Zekai Tahir Burak Women's Health Research and Education Hospital. The correlation between serum homocysteine with age, body mass index, hormone profile, fasting insulin and glucose concentrations and insulin resistance were examined in patients with polycystic ovary syndrome and the results were compared to those of women with normal ovaries, who served as a control group. RESULTS: The mean serum fasting glucose and insulin levels, thus insulin resistance index of women with polycystic ovary syndrome, were significantly higher than those of the control subjects. The mean serum homocysteine levels were significantly higher in women with polycystic ovary syndrome than those in the control group. A positive correlation was detected between the mean homocysteine, the insulin resistance index determined by homeostasis model assessment and the fasting insulin levels in polycystic ovary syndrome patients. CONCLUSIONS: Serum homocysteine levels are elevated in women with polycystic ovary syndrome, and this elevation is associated with the serum insulin level rather than androgen excess. The intense treatment of hyperhomocysteinemia in women with polycystic ovary syndrome might improve reproductive outcome and contribute to protection from cardiovascular risks.     

Fetal nasal bone length and Down syndrome during the second trimester in a Chinese population

Objective:  The purpose of the present study was to build a database of reference ranges of fetal nasal bone length (NBL) in a Chinese population. The accuracy rate of detecting Down syndrome was also analyzed using fetal NBL as a marker.
Methods:  The control group of fetuses included 342 normal singleton pregnancies with no chromosomal or congenital anomalies. The present study was a cross-section study and the control group was used to construct percentile values of NBL from 13 to 29 gestational weeks of age. Two-dimensional ultrasonography was used for the nasal bone studies. Measurements of NBL were collected and each fetus contributed a single value to the reference sample. During the study period, 14 fetuses with Down syndrome were examined. Measurement of fetal NBL was made during amniocentesis, with gestational age ranging from 13 to 19 weeks.
Results:  From 342 normal fetuses with gestational age ranging from 13 to 29 weeks, reference ranges of NBL were constructed. The reference ranges were constructed from the 100(1 − p)% reference range:     , where Ŷ  = 25 − exp(3.58 − 0.044 ×  t  + 0.0006 ×  t ²), with Ŷ being the fitted mean of regression model and t being gestational age (weeks). Using fetal NBL, the regression model was Pr (Down syndrome) = exp( W )/[1 + exp( W )], where W  = 0.62–4.80 × NBL (multiples of the median) in predicting Down syndrome. Fetal NBL was found to have a sensitivity and specificity of 0.78 and 0.78, respectively, in predicting Down syndrome in the second trimester of pregnancy.
Conclusions:  Fetal NBL measurement can provide a simple and useful algorithm to predict Down syndrome during the second trimester of pregnancy.     

Outcome of anaemic monochorionic single survivors following early intrauterine rescue transfusion in cases of feto-fetal transfusion syndrome

Objective  To evaluate the outcome of severely anaemic monochorionic (MC) twins surviving the death of their co-twin following early intrauterine rescue transfusion in cases of feto-fetal transfusion syndrome (FFTS).
Study design  We reviewed all MC pregnancies complicated with FFTS following primary management, in which a single intrauterine fetal death (IUFD) was diagnosed with certainty within 24 hours between January 1999 and December 2006. We included MC survivors who presented ultrasound or Doppler features of fetal anaemia following the death of their co-twin. Intrauterine transfusion (IUT) was given to all survivors who were anaemic.
Results  Nineteen MC twin pregnancies presented a single intrauterine death (IUD) associated with an anaemic co-twin. Median gestational age at IUD was 23 [20–28] weeks. The median interval between IUD and IUT was 12 [8–24] hours. There were 58% (11/19) healthy survivors. Perinatal death rate was 26% (5/19) including 16% (3/19) intrauterine and 10% (2/19) neonatal deaths. Abnormal prenatal cerebral findings developed in 21% (4/19) cases, always within 1 month after the death of the co-twin. Considering occlusive techniques and other management separately, there were 64% (7/11) and 50% (4/8) healthy survivors, respectively, and perinatal death occurred in 36% (4/11) and 12.5% (1/8) of fetuses, respectively. Prenatal fetal cerebral lesions developed in 9% (1/11) of cases following occlusive techniques and in 37.5% (3/8) of fetuses when managed differently. The median gestational age at delivery in the survivors was 31 [25–38] weeks.
Conclusion  In cases of FFTS with single anaemic survivors, early IUT could be offered following extensive counselling and close follow up.