Prenatal diagnosis of trisomy 4p: a new locus for holoprosencephaly?

Trisomy of the short arm of chromosome 4 is a well-known syndrome, and several observations have been made in the last 30 years. Herein, we report a new observation of trisomy 4p in a fetus with a semi-lobar holoprosencephaly (HPE), dysmorphic features and multiple malformations. The diagnosis of HPE was made, at 33 weeks' gestation, on the fetus of a healthy G1P0 woman. Amniocentesis was performed for chromosome analysis and additional material was found on a chromosome 22. The couple elected to terminate the pregnancy and fetal examination was realized. Conventional and molecular cytogenetic studies were performed on the fetus and the parents, which showed that the additional material found on one chromosome 22 corresponded to the short arm of chromosome 4 and therefore led us to establish a diagnosis of trisomy 4p inherited from the malsegregation of a paternal translocation t(4;22)(q12;q11.1). The etiology of HPE is very heterogeneous; it includes non-genetic factors such as maternal diabetes and genetic causes. HPE cases have been described in association with many chromosomal anomalies, trisomy 13 being the most frequent. However, to our knowledge, HPE has never been previously reported in association with a trisomy involving solely the short arm of chromosome 4.     

p16INK4a基因与宫颈癌

p16INK4a基因在细胞周期调控RB通路中发挥着负反馈调节作用,决定着细胞周期的正常运转和细胞增殖、分化及凋亡,并与多种人类肿瘤的发生、发展、治疗与预后密切相关.综述p16INK4a基因及其蛋白的表达在宫颈癌中的研究现状,发现p16INK4a基因甲基化是宫颈癌发生的早期事件,p16INK4a在HPV阳性的宫颈上皮内瘤样病变,宫颈腺上皮内病变,宫颈鳞癌及腺癌(ADCA)中呈高表达,且随着病变加重表达增强,而正常宫颈上皮、间质、化生和炎性细胞p16INK4a表达呈阴性,这一特性使得其在检测宫颈癌及其癌前病变、预测病变进展及判断预后等方面有潜在的临床应用价值.     

p16^INK4a基因与宫颈癌

p16^INK4a基因在细胞周期调控RB通路中发挥着负反馈调节作用，决定着细胞周期的正常运转和细胞增殖、分化及凋亡，并与多种人类肿瘤的发生、发展、治疗与预后密切相关。综述p16^INK4a基因及其蛋白的表达在宫颈癌中的研究现状，发现p16^INK4a基因甲基化是宫颈癌发生的早期事件，p16^INK4a在HPV阳性的宫颈上皮内瘤样病变，宫颈腺上皮内病变，宫颈鳞癌及腺癌（ADCA）中呈高表达，且随着病变加重表达增强，而正常宫颈上皮、间质、化生和炎性细胞p16^INK4a表达呈阴性，这一特性使得其在检测宫颈癌及其癌前病变、预测病变进展及判断预后等方面有潜在的临床应用价值。     

Finasteride 5 mg and Sexual Side Effects: How Many of these are Related to a Nocebo Phenomenon?

IntroductionSexual adverse experiences such as erectile dysfunction (ED), loss of libido, and ejaculation disorders have been consistent side effects of finasteride in a maximum percentage of 15% after 1 year of therapy. Such data could be seen as far from reality, if compared to a higher percentage that may be found in any common clinical practice.AimThis study aims to explain the dichotomy between literature's data and clinical practice data.MethodsOne hundred twenty patients with a clinical diagnosis of benign prostatic hyperplasia (BPH), sexually active and with an International Index of Erectile Function-erectile function (IIEF-EF) domain ≥25 were randomized to receive finasteride 5 mg concealed as an “X compound of proven efficacy for the treatment of BPH” for 1 year with (group 2) or without (group 1) counseling on the drug sexual side effect. The phrase used to inform group 2 patients was “. . . it may cause erectile dysfunction, decreased libido, problems of ejaculation but these are uncommon”.Main Outcome MeasuresThe estimation of side effect was conducted at 6 and 12 months using the male sexual function-4 (MSF-4 item) questionnaire and a self-administered questionnaire.ResultsOne hundred seven patients completed the study. Group 2 patients (N = 55) reported a significant higher proportion of one or more sexual side effects as compared to group 1 (N = 52) (43.6% vs. 15.3%) (P = 0.03). The incidence of ED, decreased libido, and ejaculation disorders were 9.6, 7.7, and 5.7% for group 1, and 30.9, 23.6, and 16.3% for group 2, respectively (P = 0.02, P = 0.04, and P = 0.06).ConclusionIn the current study, blinded administration of finasteride was associated with a significantly higher proportion of sexual dysfunction in patients informed on sexual side effects (group 2) as compared to those in which the same information was omitted (group 1) (P = 0.03). A scenario similar to group 2 of the current study is likely to occur in clinical practice, where the patient is counseled by the physician and has access to the drug information sheet. The burden of this nocebo effect (an adverse side effect that is not a direct result of the specific pharmacological action of the drug) has to be taken into account when managing finasteride sexual side effects. Mondaini N, Gontero P, Giubilei G, Lombardi G, Cai T, Gavazzi A, and Bartoletti R. Finasteride 5 mg and sexual side effects: How many of these are related to a nocebo phenomenon? J Sex Med 2007;4:1708–1712.     

De novo unbalanced translocation resulting in monosomy for distal 5p (5p14.1 → pter) and 14q (14q32.31 → qter) associated with fetal nuchal edema,microcephaly, intrauterine growth restriction,and single umbilical artery: Prenatal diagnosis and molecular cytogenetic characterization

ObjectiveTo present prenatal diagnosis of partial monosomy 5p (5p14.1 → pter) and partial monosomy 14q (14q32.31 → qter).Materials and MethodsA 33-year-old woman underwent amniocentesis at 20 weeks of gestation because of abnormal fetal ultrasound. Amniocentesis revealed a dicentric chromosome of dic(5;14). Level II ultrasound at 23 weeks of gestation revealed a fetus with intrauterine growth restriction, microcephaly, nuchal edema, a single umbilical artery, and fetal biometry equivalent to 19 weeks. At 23 weeks of gestation, she requested repeated amniocentesis. Whole-genome array comparative genomic hybridization on uncultured amniocytes was performed. Quantitative fluorescent polymerase chain reaction analysis was performed on uncultured cord blood and parental blood. A fetus was delivered with microcephaly, low-set ears, hypertelorism, depressed nasal bridge, increased nuchal fold, and a single umbilical artery.ResultsThe fetal karyotype was 45,XX,dic(5;14)(p14.1;q32.31)dn. Whole-genome array comparative genomic hybridization analysis on uncultured amniocytes detected arr 5p15.33p14.1 (36,238-28,798,509)×1 and arr 14q32.31q32.33 (101,508,967-107,349,540)×1. Quantitative fluorescent polymerase chain reaction assays showed that the aberrant dic(5;14) was from paternal origin.ConclusionConcomitant occurrence of monosomy for distal 5p and distal 14q my present nuchal edema, microcephaly, IUGR, and single umbilical artery on prenatal ultrasound.     

Ageing and ART: a waste of time and money?

In many societies, more and more young women are delaying childbearing until the fourth decade of life. It is well known that fertility is remarkably reduced with increasing age of women in both natural conceptions and assisted reproductive technology (ART). In this chapter, the effect of ageing on the pregnancy rate in ART, and the options available to improve the reproductive outcomes in women of advanced age will be presented after understanding the mechanism of reproductive ageing and the effects of ageing on the reproductive outcomes in normal women. It is important to identify the predictive factors associated with a better treatment outcome.     

Prenatal diagnosis of partial monosomy 8p (8p23.2→pter) and partial trisomy 15q (15q21.2→qter) and incidental detection of a familial chromosome translocation of paternal origin in a pregnancy associated with increased nuchal translucency and an abnormal maternal serum screening result

ObjectiveWe present partial monosomy 8p (8p23.2→pter) and partial trisomy 15q (15q21.2→qter) and incidental detection of a familial chromosome translocation of paternal origin in a pregnancy associated with increased nuchal translucency (NT) and an abnormal maternal serum screening result.Case ReportA 29-year-old primigravid woman underwent chorionic villus sampling (CVS) at 13 weeks of gestation because of an increased NT thickness of 3.2 mm at 12 weeks of gestation and an abnormal maternal serum screening for Down syndrome result with a calculated risk of 1/29. Her husband was 33 years old, and there was no family history of congenital malformations. CVS revealed a derived chromosome 8 or der(8). Cytogenetic analysis of the parents revealed a karyotype of 46,XY,t(8;15)(p21.3;q13) in the father and a karyotype of 46,XX in the mother. The CVS result was 46,XY,der(8)t(8;15)(p21.3;q13)pat. The woman requested for amniocentesis at 16 weeks of gestation. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed a result of arr 8p23.3p23.2 (191,530–2,625,470) × 1.0, arr 15q21.2q26.3 (50,903,432–102,338,129) × 3.0 with a 2.434-Mb deletion of 8p23.3-p23.2 including DLGAP2, CLN8 and ARHGEF10, and a 51.435-Mb duplication of 15q21.2-q26.3 including CYP19A1 and IGF1R. Conventional cytogenetic analysis of cultured amniocytes revealed the result of 46,XY,der(8) t(8;15)(p23.2;q21.2)pat in the fetus. The pregnancy was subsequently terminated, and a malformed fetus was delivered with characteristic craniofacial dysmorphism.ConclusionMaternal serum screening and NT screening may incidentally detect familial unbalanced reciprocal translocations, and aCGH analysis is useful for a precise determination of the breakpoints of the translocation and the involvement of the related genes under such a circumstance.     

Once a pregnancy, always a cesarean? Rationale and feasibility of a randomized controlled trial

Although vaginal delivery has long been assumed to be the preferred route of delivery in women who have not had a prior cesarean delivery, some have recently advocated that women be offered the option of elective, primary cesarean delivery in all pregnancies. Available outcome data, however, do not permit ready comparison of these alternate plans for delivery. Important maternal outcomes include short-term complications such as death, bleeding, infection, and damage to pelvic organs as well as long-term effects on future pregnancies, fecal and urinary incontinence, and pelvic organ prolapse. Important neonatal outcomes include asphyxic and traumatic birth injury, infection, respiratory complications, and stillbirth. To weigh the relative merits of elective primary cesarean delivery and a trial of labor, a randomized controlled trial is needed. Such a trial would be both ethical and feasible.     

p16^INK4a蛋白检测在宫颈癌及CIN筛查中的作用

p16^INK4a蛋白在宫颈上皮内瘤变（CIN）及宫颈癌中的过表达的意义，已得到许多学者的肯定，并认为可以在组织病理学中用来辅助诊断宫颈癌及其CIN。但在宫颈脱落细胞涂片中检测p16^INK4a蛋白，对于筛查宫颈癌及CIN的研究报道较少。本文对宫颈脱落细胞进行p16^INK4a蛋白检测，探讨其在CIN中的诊断价值对宫颈癌／和CIN的筛查作用。     

Progestogens and risk of breast cancer: a link between bone and breast?

This article reviews the data supporting the role of receptor activator of the nuclear factor kappa (RANK) and its ligand, RANKL, in progestogen-induced breast cancer. Both experimental and clinical studies have been included. The expression of both RANK and RANKL has been described in epithelial cells of both mice and humans. Experiments of gain and loss of function in mice have shown that RANK/RANKL mediate alveologenesis during pregnancy or the estrous cycle. Moreover, the participation of the RANK/RANKL has been detected in models of breast carcinogenesis associated with progestogens-like medroxyprogesterone acetate. Recent clinical studies have found that the expression of RANK is associated with parameters of aggressiveness of the tumor.     

Resumption of ovarian function after 4?years of estro-progestin treatment in a young woman with Crohn’s disease and premature ovarian insufficiency: a case report

Purpose

To report the long-term management of a case of premature ovarian insufficiency of unknown origin in a young woman with Crohn’s disease.

Method

Here is reported the case of a 20 years old woman with Cronh’s disease presenting with two years amenorrhea and FSH and LH levels of 255 mIU/ml and 182 mIU/ml respectively, who received 10 months corticosteroid treatment followed by 7 years of estro-progestin treatment.

Results

Corticosteroid treatment was ineffective in restoring patients gonadotropin levels as well as ovarian volume, while estro-progestins promoted a prompt reduction in gonadotrophin levels, which returned in the normal range after two years of treatment, as well as restoration of ovarian function, which occurred after four years of estrogens administration, as demonstrated by normal ovarian volume and ovulatory follicles at ultrasound, and by the re-establishment of regular menses after estroprogestin discontinuation.

Conclusions

Long-term suppression of the endogenous gonadotropins using estroprogestins may be suggested as a treatment able to restore ovarian responsiveness even in patients with premature ovarian insufficiency showing highly elevated gonadotropin levels.Premature ovarian insufficiency (POI), is defined as secondary amenorrhea with elevated gonadotropin level observed under the age of 40 and affects 1–2 % of women of the general population [7]. POI is highly heterogeneous condition that may have iatrogenic, autoimmune, infective, chromosomal, genetic or idiopathic origin [4]. Post-pubertal onset of ovarian failure represents the large majority of the cases: this is characterized by secondary amenorrhea associated with premature follicular depletion or arrested folliculogenesis [4].Although elevation in gonadotropin serum level may suggest an irreversible impairment of ovarian reserve and function, intermittent follicular function and spontaneous ovulation clearly occur in some POI-affected women [20]. Moreover, POI may either spontaneously resolve or may respond to therapeutic modalities such as glucocorticoids or exogenous estrogen administration, thus indicating that ovarian failure is not always permanent. Immunosuppression with glucocorticoids has been employed for up to 12 months in cases of POI of supposed autoimmune etiology [11], however proof of the efficacy of this treatment has not been forthcoming as the two randomized, placebo-controlled trial using corticosteroid and ovulation induction in POI women demonstrated either no ovulation or a low ovulation rate [2, 21]. On the other hand, either short course or long-term (up to 24 months) estrogen administration have been found to be useful in these patients, as this treatment may overcome ovarian FSH receptor desensitization [18].Here we report the case of a young woman with POI of unknown origin who did not respond to corticosteroid treatment but showed resumption of ovarian function after 4 years of estro-progestin treatment.     

Analysis of correlation factors and pregnancy outcomes of hypertensive disorders of pregnancy – a secondary analysis of a random sampling in Beijing,China

Objective: We aimed to assess the prevalence and risk factors for hypertensive disorders and to study the main pregnancy outcomes in the Beijing area of China.

Study design: This study randomly sampled 15 hospitals in Beijing from Jun 2013 to Nov 2013 and evaluated 15 194 deliveries. Logistic regression analysis was used to study the association between risk factors and hypertensive disorders. Pregnancy outcomes included preterm birth, cesarean delivery and small for gestational age (SGA).

Results: The prevalence of hypertensive disorders, preeclampsia (PE) and severe PE was 4.4, 2.7 and 1.8%, respectively. The risk factors for hypertensive disorders and severe PE were maternal body mass index before pregnancy, gestational weight gain (GWG), gestational diabetes and pre-gestational diabetes, and third trimester cholesterol (CHOL) levels. First trimester high-density lipoprotein was a protective factor for severe PE. The incidence of hypertensive disorders increased with maternal age. Preterm delivery, cesarean delivery and small infant size for gestational age were more prevalent in the severe PE group compared with the non-hypertensive group.

Conclusions: In the Beijing area of China, maternal body mass index before pregnancy, GWG, maternal complications of gestational diabetes and pre-gestational diabetes, and third trimester CHOL levels are risk factors for both hypertensive disorders of pregnancy and severe PE. First trimester high-density lipoprotein is a protective factor for severe PE. Severe preeclampsia leads to a higher incidence of preterm delivery, cesarean delivery and SGA infants.     

Biopsychosocial predictors of preterm labor and preterm delivery? Results of a prospective study

RESEARCH QUESTION: In addition to medical, job related, sociodemographic risk factors, and health related behavior, topics that traditionally have been less in the focus of attention in this context, such as biographic data, coping with stress, personality variables, pregnancy related attitudes, fears, and the social network were examined. PATIENTS AND METHODS: 589 women between 16(th) and 22(nd) week of pregnancy were examined using a questionnaire that was designed for the study. This resulted in 508 women pregnant with a single child, whose pregnancy and delivery were examined based on their medical records. Factor analysis and main component analysis with subsequent varimax rotation resulted in factors that were subject to a proof of reliability. Statistical analysis was based on logistic regression. RESULTS: 129 (27.7%) of women displayed signs/indices of an imminent preterm delivery, 29% (5.8%) of whom later actually had a preterm delivery before the end of the 37(th) week of pregnancy. Pregnant women who were in treatment for an imminent preterm delivery appear to have been subject to higher social stress as compared to those, who later later actually gave birth before completing the 37(th) week of pregnancy. Lack of a female network and lack of emotional understanding from the partner are correlated to both of these complications. Specifically, actual preterm delivery appears to be significantly influenced by partner relationship. Another significant predicting variable for imminent and actual preterm delivery appears to be a history of gynecological problems. A distinct risk factor for delivery before completion of the 37(th) week of pregnancy was a history of colpitis. In addition, pronounced anxieties in respect to the pregnancy, and low general anxiety were significant predicting variables for delivery before completion of the 37(th) week of pregnancy. CONCLUSIONS: Partner relationship, female networks, psychosomatic reactivity in terms of diseases/disorders of the reproductive organs, and anxieties appear to be worthwhile targets in the prevention of preterm delivery.     

p16INK4a免疫细胞化学法对子宫颈癌筛查价值的Meta分析#br#

Objective?To use evidence-based medicine to comprehensively evaluate two methods in cervical cancer screening: Thinprepliquid based cytology test (TCT) and p16INK4a Immunocytochemistry (p16INK4a ICC). Methods?Pubmed, Google scholar, cochrane clinical trial, China National Knowledge Network, Wanfang Medical Network and other databases were searched, and literatures related to p16INK4a ICC and TCT screening for cervical cancer were included.The quality of the included literature was evaluated, and Stata16.0 software was used for meta analysis. Results?Finally, 10 articles were included with a total of 2 694 patients. The combined sensitivity of TCT screening and p16INK4a ICC screening was 86% (95%CI: 77%~92%) and 90% (95%CI: 81%~95%), the combined specificity was 64% (95%CI: 48%~78%) and 79% (95%CI: 69%~86%), and the combined positive likelihood ratio was 2.4 (95%CI: 1.6~3.6) and 4.2 (95%CI: 2.8~6.3), the combined negative likelihood ratio was 0.21 (95%CI: 0.13~0.34) and 0.13 (95%CI: 0.06~0.25), combined diagnostic odds ratio (DOR) was 11 (95%CI: 6~22) and 33 (95%CI: 13~85), and the area under the receiver operating characteristic curve (SROC) (AUC) was 0.85 and 0.91, respectively. Conclusions?The application of p16INK4a ICC test used in cervical cancer screening has higher sensitivity and specificity than TCT, which helps to improve the accuracy of cervical cancer screening and avoid missed diagnosis.