Mosaic trisomy 16 ascertained through amniocentesis: Evaluation of 11 new cases

Trisomy 16, once thought to result uniformly in early pregnancy loss, has been detected in chorionic villus samples (CVS) from on-going pregnancies and was initially ascribed to a second, nonviable pregnancy. Prenatally detected trisomy 16 in CVS and its resolution to disomy has led to the re-examination of the viability of trisomy 16. This study evaluates 11 cases of mosaic trisomy 16 detected through second trimester amniocentesis. In 9 of the 11 cases, amniocenteses were performed in women under the age of 35 because of abnormal levels of maternal serum alpha-fetoprotein (MSAFP) or maternal serum human chorionic gonadotropin (MShCG). The other two amniocenteses were performed for advanced maternal age. Five of the 11 pregnancies resulted in liveborn infants, and six pregnancies were electively terminated. The liveborn infants all had some combination of intrauterine growth retardation (IUGR), congenital heart defects (CHD), or minor anomalies. Two of them died neonatally because of complications of severe congenital heart defects. The three surviving children have variable growth retardation, developmental delay, congenital anomalies, and/or minor anomalies. In the terminated pregnancies, the four fetuses evaluated by ultrasound or autopsy demonstrated various congenital anomalies and/or IUGR. Cytogenetic and fluorescent in situ hybridization studies identified true mosaicism in 5 of 10 cases examined, although the abnormal cell line was never seen in more than 1% of cultured lymphocytes. Placental mosaicism was seen in all placentas examined and was associated with IUGR in four of seven cases. Maternal uniparental disomy was identified in three cases. Mosaic trisomy 16 detected through amniocentesis is not a benign finding but associated with a high risk of abnormal outcome, most commonly IUGR, CHD, developmental delay, and minor anomalies. The various outcomes may reflect the diversity of mechanisms involved in the resolution of this abnormality. As 80% of these patients were ascertained because of the presence of abnormal levels of MSAFP or MShCG, the increased use of maternal serum screening should bring more such cases to clinical attention. Am. J. Med. Genet. 80:473–480, 1998. © 1998 Wiley-Liss, Inc.     

A Clinical and Molecular Analysis of Branchio‐Oculo‐Facial Syndrome Patients in Russia Revealed New Mutations in TFAP2A

Branchio‐oculo‐facial syndrome (BOFS, OMIM# 113620) is a rare autosomal dominant disorder characterised by branchial cleft sinus defects, ocular anomalies and facial dysmorphisms, including lip or palate cleft or pseudocleft, and is associated with mutations in the TFAP2A gene. Here, we performed clinical analysis and mutation diagnostics in seven BOFS patients in Russia. The phenotypic presentation of BOFS observed in three patients showed high heterogeneity, including variation in its main clinical manifestations (linear loci of cervical cutaneous aplasia, ocular anomalies and orofacial cleft). In certain other cases, isolated ocular anomalies, or an orofacial cleft with accessory BOFS symptoms, were observed. In five BOFS patients, conductive hearing loss was diagnosed. Direct sequencing of the coding region of the TFAP2A gene revealed missense mutations in four BOFS patients. One patient was observed to have a previously described mutation (p.Arg251Gly), while three patients from two families were found to have novel mutations: p.Arg213Ser and p.Val210Asp. These novel mutations were not present in healthy members of the same family and therefore should be classified as de novo.     

冠心病合并糖尿病多支血管病变介入治疗与外科旁路移植术比较的Meta分析

目的 评价冠心病合并糖尿病多支血管病变介入治疗与外科旁路移植术治疗效果.方法 计算机检索Cochrane图书馆、MedLine、EMbase(1974-2014.11)、中国生物医学文献数据库、中国期刊全文数据库和万方数据库,收集冠心病合并糖尿病多支血管病变介入治疗与外科旁路移植术治疗的随机对照研究(RCT).有两名评价员按照纳入与排除标准选择文献,评价质量与提取资料,对符合纳入标准的研究以RevMan5.2软件进行Meta分析.结果 共纳入5个随机对照研究,共2288例患者.Meta分析结果显示,介入治疗与外科旁路移植比较,随访30 d患者全因病死率与MACE事件发生率差异无统计学意义,RR=0.42,95％CI(0.05～3.44),P=0.42.对随访1年以上的长期随访结果分析:全因病死率差异无统计学意义,RR=0.14,95％CI(0.47～2.78),P=0.77.MACE事件发生率,两组差异有统计学意义RR=1.65,95％CI(1.29～2.11),P＜0.0001.说明从远期MACE事件发生率而言外科旁路移植术对于治疗冠心病合并糖尿病伴多支血管病变患者更占优势.对于长期靶血管重建率Meta分析结果显示两组差异有统计学意义RR=3.08,95％CI(2.28～4.17),P＜0.00001.此结果说明外科旁路移植术更优于介入治疗,靶血管重建较介入治疗低.CCSⅡ级人数Meta分析结果显示,两组差异有统计学意义,RR=2.07,95％CI(1.50～2.87),P＜0.0001.外科旁路移植术随访1年后远期轻度心绞痛情况更少见.结论 冠心病伴糖尿病多支血管病变患者治疗上对于MACE事件发生率,长期靶血管重建,CCSⅡ级事件发生的情况看,外科旁路移植术疗效更优于介入治疗术.     

多器官功能障碍综合征并发急性肾损伤的相关因素分析

目的:探讨多器官功能障碍综合征(MODS)并发急性肾损伤(AKI)的相关因素.方法:重症监护病房收治的MODS患者41例,根据是否发生AKI分为AKI组(n=16)及非AKI组(n=25),比较两组患者年龄、性别、基线血肌酐及死亡率等临床资料.结果:AKI组死亡率(50％)明显高于非AKI组(20％),差异有统计学意义(P ＜0.05);AKI组患者较非AKI组患者年龄大、基线血肌酐水平高、消化道出血及脓毒症发生率高、机械通气时间长,差异有统计学意义(P＜0.05).结论:AKI可明显增加MODS患者的死亡率,其发生与高龄、基线血肌酐高、消化道出血、机械通气及脓毒症有关.     

新疆鼠尾草茎化学成分的研究

目的 :研究新疆鼠尾草茎的化学成分。 方法 :采用色谱法分离化合物 ,用波谱和化学方法鉴定结构。结果 :从新疆鼠尾草茎中分离得到 5个化合物 :β 谷甾醇 (Ⅰ )、齐墩果酸 (Ⅱ )、7 O acetyl horminone(Ⅲ )、β 谷甾醇葡萄糖苷 (Ⅳ )、丹酚酸K(Ⅴ )。 结论 :除 β 谷甾醇、齐墩果酸、丹酚酸K外 ,其余均为从本属植物的地上部分中首次得到。     

Medical triggers are associated with better short- and long-term weight loss outcomes

BACKGROUND: Medical events are often reported as triggers for weight loss, but it is unknown whether medical triggers result in better short- and long-term weight control. METHODS: The relationship between medical triggers and weight loss was examined in the National Weight Control Registry (NWCR), a database of individuals who have lost > or =30 lbs and kept it off for > or =1 year. Recall of weight loss triggers may become difficult over time, thus participants were limited to those reporting weight loss <5 years ago. Three groups were examined: (1) participants with medical triggers (N = 207), (2) participants with nonmedical triggers (N = 539), and (3) participants with no trigger (N = 171). RESULTS: Participants with medical triggers were older than those with nonmedical triggers or no trigger (50.5 +/- 11.7, 44.9 +/- 11.8, 46.7 +/- 13.3 years; P = 0.0001), had a higher initial BMI at entry into the NWCR (26.1 +/- 5.0, 25.0 +/- 4.3, 24.8 +/- 4.4 kg/m2; P = 0.004), and were more likely to be male (37.1%, 18%, 17.2%; P = 0.0001). Participants with medical triggers reported greater initial weight loss than those with nonmedical triggers or no trigger (36.5 +/- 25.0, 31.8 +/- 16.6, 31.8 +/- 17.1 kg; P = 0.01). Participants with medical triggers also gained less weight over 2 years of follow-up than those with nonmedical triggers or no trigger (P = 0.003). CONCLUSIONS: Medical triggers may produce a teachable moment for weight control, resulting in better initial weight loss and long-term maintenance.     

Informal interpreting in general practice: the migrant patient’s voice

Objective: To explore the perspective of Turkish-Dutch general practitioner (GP) patients on informal interpreting from an integrated theory base, focusing on interpreters’ roles, trust and power.

Design: Semi-structured in depth interviews were conducted with 21 first-generation Turkish-Dutch migrant patients who made use of informal interpreters to communicate with their GPs. An interview guide was designed based on the theoretical framework of interpreter’s roles, trust and power, covering questions about interpreters’ role, trust in informal/professional interpreters and power division in the medical consultation. The interviews were transcribed verbatim and analyzed according to the constant comparative method.

Results: Besides providing linguistic translation, informal interpreters were expected to perform the roles of advocates and caregivers of the patients. Informal interpreters were trusted more than professional interpreters, mainly for fidelity reasons, that is, because the patients assumed that informal interpreters would act in their best interests. Although informal interpreters were often perceived as the primary interlocutor, the patients did not feel dominated by them, but rather empowered by their presence.

Conclusion: Our findings indicate a connection between the role of the advocate, the fidelity dimension of trust and the perceived empowerment of the patients. By linking interpreters’ role to trust and power, this study contributes to theory building in the field of informal interpreting, which is needed to design evidence-based interventions to improve health care delivery to patients with insufficient language ability and thus to advance health care delivery to migrant patients, which is currently lagging behind.     

Pharmacometric dose optimization of buprenorphine in neonatal opioid withdrawal syndrome

Results from Blinded Buprenorphine OR Neonatal morphine solution (BBORN), a previous phase III trial in infants with neonatal opioid withdrawal syndrome (NOWS), demonstrated that sublingual buprenorphine resulted in a shorter duration of treatment and shorter length of hospital stay than the comparator, oral morphine. Objectives of Buprenorphine Pharmacometric Open Label Research study of Drug Exposure (BPHORE), a new trial with buprenorphine in a similar population, were to (1) optimize initial dose, up‐titration to achieve symptom control and weaning steps of pharmacologic treatment and (2) investigate safety of the revised regimen. A pharmacodynamic model linked buprenorphine exposure to NOWS symptom scores. Adaptive dose regimens were simulated using BBORN results to compare dosing regimens for times to stabilization, weaning, and cessation. A clinical trial using model informed doses (BPHORE), was conducted. Simulations indicated benefits in time to stabilization and weaning when up‐titration rates increased to 30%. Stabilization time was not greatly impacted by the starting dose. Time to wean and time to cessation were dose dependent. A weaning rate of 25% shortened time to cessation. Ten infants were enrolled in BPHORE using buprenorphine starting dose of 24 µg/kg/day, 33% titration, and 15% wean rate. Five subjects required adjuvant therapy. Half‐maximal effective concentration (EC₅₀) values indicated maximum buprenorphine doses did not generate maximal effect size, suggesting potential efficacy of a further increased dose if a goal was to reduce the use of adjunct agents. Simulations indicated that further benefits can be gained by increasing starting doses of buprenorphine and increasing wean rates. Use of a model‐based analysis to provide focused guidelines for care can be used with goals of reducing treatment time and hospital stays in infants with NOWS.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Buprenorphine has demonstrated efficacy for the pharmacologic treatment of neonatal opioid withdrawal syndrome (NOWS).

• WHAT QUESTION DID THIS STUDY ADDRESS?

The study sought to explore a variety of buprenorphine dose regimens using modeling and simulation. A revised dose approach was explored in an open label clinical trial.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

The study explored the exposure response of buprenorphine in controlling the symptoms of NOWS. The exposure response relationship was described.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

The model of buprenorphine response will allow the optimization of dose regimens that may reduce the length of pharmacologic treatment and length of stay for infants treated for NOWS.