Estimated fetal weight in the detection of the small-for-menstrual-age fetus

The purpose of this study was to assess the value of calculated fetal weight in the detection of the small-for-menstrual-age fetus. An ultrasound screening scan was performed on 1624 singleton pregnancies at 30 weeks to 36 weeks, menstrual age. Head, abdomen, and femur diaphysis measurements were recorded and used to estimate fetal weight. These and other more widely used parameters were used to predict birth weight below the 10th percentile for menstrual age. Estimated fetal weight at 34 weeks achieved sensitivity of 100% and specificity of 70%, the best result for any parameter. Specificity is improved using growth measurements.     

Insulin detemir reduces weight gain as a result of reduced food intake in patients with type 1 diabetes

OBJECTIVE

Insulin detemir lacks the usual propensity for insulin to cause weight gain. We investigated whether this effect was a result of reduced energy intake and/or increased energy expenditure.

RESEARCH DESIGN AND METHODS

A 32-week, randomized crossover design trial was undertaken in 23 patients with type 1 diabetes. Patients on a basal-bolus regimen (with insulin aspart as the bolus insulin) were randomly assigned to insulin detemir or NPH insulin as a basal insulin for 16 weeks, followed by the other basal insulin for 16 weeks. At the end of each 16-week period, total energy expenditure, resting energy expenditure, diet-induced thermogenesis, activity energy expenditure, energy intake, weight change, glycemic control, hypoglycemic episodes, and hormones that affect satiety and fuel partitioning were measured.

RESULTS

After 16 weeks, weight change was −0.69 ± 1.85 kg with insulin detemir and +1.7 ± 2.46 kg with NPH insulin (P < 0.001). Total energy intake was significantly less with insulin detemir (2,016 ± 501 kcal/day) than with NPH insulin (2,181 ± 559 kcal/day) (P = 0.026). There was no significant difference in any measure of energy expenditure, HbA_1c percentage, or number of hypoglycemic episodes. Leptin was lower and resistin was higher with insulin detemir compared with NPH insulin (P = 0.039, P = 0.047). After the meal, ghrelin and pancreatic polypeptide levels (P = 0.002, P = 0.001) were higher with insulin detemir.

CONCLUSIONS

The reduced weight gain with insulin detemir compared with NPH insulin is attributed to reduced energy intake rather than increased energy expenditure. This may be mediated by a direct or indirect effect of insulin detemir on the hormones that control satiety.Exogenous insulin-replacement therapy remains the most effective treatment for hyperglycemia in type 1 diabetic and poorly controlled type 2 diabetic patients, but it regularly results in excessive weight gain. The Diabetes Control and Complications Trial showed that insulin-associated weight gain (1) was greater in patients receiving intensified intervention than in those receiving conventional intervention (5.1 vs. 3.7 kg, P < 0.0001, during first 12 months of therapy).In type 1 diabetes, adherence to prescribed insulin regimens may be compromised by a desire to avoid weight gain. The problem of insulin omission was confirmed in a U.K. study (2) of 65 young subjects with type 1 diabetes. A total of 30% of the women admitted to having underdosed insulin to manipulate their weight, whereas 45% of women who developed microvascular complications had intentionally misused insulin to prevent weight gain.Not all types of insulin treatment are equally prone to causing weight gain. Treatment with insulin detemir, a novel basal insulin analog, has been consistently shown to cause no weight gain in patients with type 1 diabetes, compared with NPH insulin (3), and lower weight gain in patients with type 2 diabetes. A myristic fatty-acid chain attached to the B-terminal of the insulin molecule allows reversible albumin binding and prolonged residence time in the subcutaneous depot and in the circulation (4).The mechanism(s) underlying the apparent weight advantage of insulin detemir has not been identified. Elucidation of this mechanism(s) could provide valuable insights into the ways in which insulin treatment causes weight gain in diabetes. Such knowledge also might enable the future development of insulin analogs with even greater metabolic advantages.     

非同位素银染单链构象多态性技术筛查葡萄糖激酶基因突变

目的建立银染单链构象多态性（ＳＳＣＰ）技术筛查葡萄糖激酶基因点突变。方法收集１０个ＮＩＤＤＭ家系的１１２例基因组（ＤＮＡ），经多聚合酶链反应（ＰＣＲ）扩增葡萄糖激酶基因第２～１０号外显子，ＳＳＣＰ电泳，硝酸银染色筛查点突变。结果发现３个家系，９例受试者第５，６号外显子出现异常ＤＮＡ片段条带，经顺序分析证实为第５号内含子１２位碱基Ｃ→Ｇ突变。结论非同位素ＳＳＣＰ技术是一种简便、经济、快速、准确和有效的筛查基因点突变的方法。     

临床干预减少胎粪吸入综合征的效果观察

目的 降低胎粪吸入综合征(MAS)的发生率.方法 对实验组胎粪污染羊水的498例新生儿采用彻底清除呼吸道羊水、粘液及洗胃、吸氧等综合性干预措施.结果 实验组MAS发生率明显低于对照组,与对照组比较有统计学差异(P＜0.01).结论 采用综合性措施可明显降低MAS发生率,保障婴儿安全.     

Mutations of the dystrophin gene in dilated cardiomyopathy

X-linked dilated cardiomyopathy(XLDCM) is caused by mutations of the dystrophin gene, which was originally cloned as the responsible gene for Duchenne muscular dystrophy and Becker muscular dystrophy. Mutations due to XLDCM are centered on 5' end of the gene, especially M-promoter and the adjacent region. However, other mutations are dispersed and cannot be characterized. Three mechanisms have been proposed by which the involvement of cardiac muscle is so severe in spite of the lack of skeletal muscle symptoms; 1) up-regulation of B- and P-dystrophin in merely skeletal muscle compensating for the defect of M-dystrophin, 2) dysfunction of some parts of dystrophin specifically essential to cardiac muscle, 3) different expression patterns of mutant mRNA between cardiac and skeletal muscle.     

Mutations of the Igbeta gene cause agammaglobulinemia in man

Agammaglobulinemia is a rare primary immunodeficiency characterized by an early block of B cell development in the bone marrow, resulting in the absence of peripheral B cells and low/absent immunoglobulin serum levels. So far, mutations in Btk, mu heavy chain, surrogate light chain, Igalpha, and B cell linker have been found in 85-90% of patients with agammaglobulinemia. We report on the first patient with agammaglobulinemia caused by a homozygous nonsense mutation in Igbeta, which is a transmembrane protein that associates with Igalpha as part of the preBCR complex. Transfection experiments using Drosophila melanogaster S2 Schneider cells showed that the mutant Igbeta is no longer able to associate with Igalpha, and that assembly of the BCR complex on the cell surface is abrogated. The essential role of Igbeta for human B cell development was further demonstrated by immunofluorescence analysis of the patient's bone marrow, which showed a complete block of B cell development at the pro-B to preB transition. These results indicate that mutations in Igbeta can cause agammaglobulinemia in man.     

内源性胰岛素替代疗法中葡萄糖激酶基因逆转录病毒表达载体的构建

背景由于胰岛细胞分离技术难度较大,目前糖尿病细胞移植治疗尚缺乏理想的细胞来源。目的构建葡萄糖激酶(Glucokinase,GK)基因逆转录病毒表达载体及稳定的产毒细胞系,为构建具有葡萄糖反应性胰岛素分泌能力的胰岛代理细胞打下基础,可望为糖尿病提供一种更符合生理要求的内源性胰岛素替代疗法。设计非随机非对照的实验研究。地点、材料和干预本研究在解放军第三军医大学附属新桥医院中心实验室进行。将GK质粒(pCMV4-GKZ1)经EcoR1/BamH1双酶切后亚克隆至逆转录病毒载体PLXSN,构建逆转录病毒表达载体PLX-GK,用酶切法和测序法对重组体进行鉴定。然后脂质体介导逆转录病毒表达载体PLX-GK转入包装细胞PA317,筛选病毒滴度较高的稳定产毒细胞系,PCR鉴定。主要观察指标①重组逆转录病毒载体构建与鉴定结果。②病毒滴度鉴定及PCR结果。结果成功构建GK基因逆转录病毒表达载体,经酶切及测序证明目的基因插入位点和读码框架正确、无突变;产毒细胞系的平均病毒滴度为6.8×108CFU/L,筛选出一株病毒滴度为1.8×109CFU/L稳定产毒细胞系PA317/GK,PCR证实GK基因整合入细胞基因组。结论成功构建了携GK基因的逆转录病毒表达载体及高滴度的产毒细胞系。     

Mutations in 2 distinct genetic pathways result in cerebral cavernous malformations in mice

Cerebral cavernous malformations (CCMs) are a common type of vascular malformation in the brain that are a major cause of hemorrhagic stroke. This condition has been independently linked to 3 separate genes: Krev1 interaction trapped (KRIT1), Cerebral cavernous malformation 2 (CCM2), and Programmed cell death 10 (PDCD10). Despite the commonality in disease pathology caused by mutations in these 3 genes, we found that the loss of Pdcd10 results in significantly different developmental, cell biological, and signaling phenotypes from those seen in the absence of Ccm2 and Krit1. PDCD10 bound to germinal center kinase III (GCKIII) family members, a subset of serine-threonine kinases, and facilitated lumen formation by endothelial cells both in vivo and in vitro. These findings suggest that CCM may be a common tissue manifestation of distinct mechanistic pathways. Nevertheless, loss of heterozygosity (LOH) for either Pdcd10 or Ccm2 resulted in CCMs in mice. The murine phenotype induced by loss of either protein reproduced all of the key clinical features observed in human patients with CCM, as determined by direct comparison with genotype-specific human surgical specimens. These results suggest that CCM may be more effectively treated by directing therapies based on the underlying genetic mutation rather than treating the condition as a single clinical entity.     

Mutations in insulin-receptor gene in insulin-resistant patients

Defects in insulin-receptor function have been associated with insulin-resistant states such as obesity and non-insulin-dependent diabetes mellitus (NIDDM). Several types of mutations in the insulin-receptor gene have been identified in patients with genetic syndromes of extreme insulin resistance. In some patients, insulin resistance results from a decrease in the number of insulin receptors on the cell surface. In one patient with leprechaunism (leprechaun/Minn-1), there is greater than 90% decrease in the levels of insulin-receptor mRNA. This patient is a compound heterozygote for two mutations in the insulin-receptor gene, both of which act in a cis-dominant fashion to decrease levels of mRNA transcribed from that allele. In one allele, there is a nonsense mutation at codon 897. All 22 exons of the other allele have a normal sequence, so that the mutation in this allele appears to map outside the coding sequence of the gene. Impaired insertion in the plasma membrane also causes insulin resistance. In two sisters (patients A-5 and A-8) with type A extreme insulin resistance, there is an 80-90% decrease in the number of insulin receptors expressed on the surface of their cells. Both sisters, whose parents are first cousins, are homozygous for a point mutation in which valine is substituted for phenylalanine at position 382 in the alpha-subunit of the insulin receptor. This mutation retards the posttranslational processing of the receptor and impairs the transport of receptors to the cell surface. Another patient with leprechaunism (leprechaun/Ark-1) is a compound heterozygote with two different mutant alleles of the insulin-receptor gene. In the allele derived from the father, there is a nonsense mutation at codon 672 that truncates the insulin receptor by deleting the COOH-terminal of the alpha-subunit and the entire beta-subunit. This truncated receptor, lacking a transmembrane domain, appears not to be expressed at the plasma membrane. In leprechaun/Ark-1, there is a missense mutation in the allele of the insulin-receptor gene derived from the mother. This point mutation results in substitution of glutamic acid for lysine at position 460 in the COOH-terminal half of the alpha-subunit. This mutation increases receptor affinity and impairs the ability of acid pH to dissociate insulin from the receptor within the endosome. There is a defect in recycling the receptor back to the plasma membrane associated with this defect. This results in an accelerated rate of receptor degradation and a consequent decrease in the number of receptors on the cell surface in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mutations of the p53 gene in hematologic neoplasms]

The p53 gene encodes a nuclear phosphoprotein and is now considered as a tumor suppressor gene. Mutations of the p53 gene have frequently been observed in several types of solid tumors and are believed to be implicated in the development of these tumors. Recent studies have shown that the p53 gene is altered in chronic myelogenous leukemia (CML) in blast crisis. In CML, alterations of the p53 gene may play an important role in the development of blast crisis. More recently, p53 mutations have been reported in other types of hematologic neoplasms, such as acute leukemia, adult T-cell leukemia, and malignant lymphoma. These observations suggest that inactivation of the p53 gene is involved in the tumorigenesis of various types of hematologic neoplasms.     

Mutations in the gene encoding cytosolic beta-glucosidase in Gaucher disease

Patients with Gaucher disease have a deficiency of the lysosomal acid beta-glucosidase. The phenotypes of genotypically identical patients with Gaucher disease may differ markedly. We have examined the possibility that polymorphisms in another beta-glucosidase are responsible for this variability in the phenotype. Sequence analysis of the gene encoding cytosolic beta-glucosidase (GBA3) from 4 chromosomes revealed the presence of 4 single-nucleotide substitutions: c.316 G -->A (D106N), c.1353A-->G (Y451Y), c.1368T-->A (Y456X), and c.1540 to 1541AG -->T in the 3' untranslated region. We examined the DNA from 62 patients with Gaucher disease who were homozygous for the 1226A-->G (N370S) mutation and from 542 control subjects from various populations for these polymorphisms. Six of the possible 16 haplotypes were found, and none was over- or underrepresented among patients with the severe Gaucher disease phenotypes compared with those from patients with mild phenotypes.     

测量估算胎儿体重对诊断巨大儿的临床意义

[目的]评价测量估算胎儿体重对诊断巨大儿的临床价值.[方法]以回顾性诊断试验评价为研究方式,采用产前胎儿体重估算和新生儿出生后测重,对120例疑似巨大儿者以出生后测重做为金标准,统计数据列入四格表计算.[结果]在107例巨大儿中,103例与产前测量估算相符合,灵敏度96.1%、特异度92.2%、准确度95.8%、阳性预告值99.0%.[结论]测量估算胎儿体重诊断巨大儿的方法简单、经济、快速、可靠.     

测量估算胎儿体重对诊断巨大儿的临床意义

[目的] 评价测量估算胎儿体重对诊断巨大儿的临床价值。[方法] 以回顾性诊断试验评价为研究方式，采用产前胎儿体重估算和新生儿出生后测重，对120例疑似巨大儿者以出生后测重做为金标准，统计数据列入四格表计算。[结果] 在107例巨大儿中，103例与产前测量估算相符合，灵敏度96．1％、特异度92．2％、准确度95．8％、阳性预告值99．0％。[结论] 测量估算胎儿体重诊断巨大儿的方法简单、经济、快速、可靠。