First Trimester Aneuploidy Screening Using Nuchal Iranslucency, Free Beta Human Chorionic Gonadotrophin and Maternal Age

Summary: Screening for aneuploidy using maternal age has a low detection rate and high false positive rate. Second trimester maternal serum screening increases trisomy 21 detection and decreases die false positive rate. First trimester screening would enable definitive diagnosis with chorionic villus sampling, and simple surgical termination of affected pregnancies would still be an option. Nuchal translucency (NT), free beta human chorionic gonadotrophin (fβHCG) and maternal age were assessed in 302 patients before chorionic villus sampling. NT positively and fβHCG negatively correlated with gestation, but neither correlated with maternal age nor with each other. Both NT and fβHCG were increased in trisomy 21. NT was increased and fβHCG was decreased in trisomy 18. Multivariate discriminant analysis enabled 87.5% detection of trisomy 21 in this high-risk population, for a 14% false positive rate. In a simulated normal population, using a risk cut-off of 1 in 250, 71% detection was achieved for a 7% false positive rate. The combination of NT, fβHCG and maternal age is a simple, readily available and viable first trimester screening strategy.     

The hospital record of the injured child and the need for external cause-of-injury codes. American Academy of Pediatrics. Committee on Injury and Poison Prevention, 1998-1999

Proper record-keeping of emergency department visits and hospitalizations of injured children is vital for appropriate patient management. Determination and documentation of the circumstances surrounding the injury event are essential. This information not only is the basis for preventive counseling, but also provides clues about how similar injuries in other youth can be avoided. The hospital records have an important secondary purpose; namely, if sufficient information about the cause and mechanism of injury is documented, it can be subsequently coded, electronically compiled, and retrieved later to provide an epidemiologic profile of the injury, the first step in prevention at the population level. To be of greatest use, hospital records should indicate the "who, what, when, where, why, and how" of the injury occurrence and whether protective equipment (eg, a seat belt) was used. The pediatrician has two important roles in this area: to document fully the injury event and to advocate the use of standardized external cause-of-injury codes, which allow such data to be compiled and analyzed.     

Hypoglycemic and anti-lipemic effects of the aqueous extract from Cissus sicyoides

Background

Psoriasis is a chronic inflammatory skin disease that can be successfully treated with a mixture of fumaric acid esters (FAE) formulated as enteric-coated tablets for oral use. These tablets consist of dimethylfumarate (DMF) and salts of monoethylfumarate (MEF) and its main bioactive metabolite is monomethylfumarate (MMF). Little is known about the pharmacokinetics of these FAE. The aim of the present study was to investigate the hydrolysis of DMF to MMF and the stability of MMF, DMF and MEF at in vitro conditions representing different body compartments.

Results

DMF is hydrolyzed to MMF in an alkaline environment (pH 8), but not in an acidic environment (pH 1). In these conditions MMF and MEF remained intact during the period of analysis (6 h). Interestingly, DMF was hardly hydrolyzed to MMF in a buffer of pH 7.4, but was rapidly hydrolyzed in human serum having the same pH. Moreover, in whole blood the half-life of DMF was dramatically reduced as compared to serum. The concentrations of MMF and MEF in serum and whole blood decreased with increasing time. These data indicate that the majority of the FAE in the circulation are metabolized by one or more types of blood cells. Additional experiments with purified blood cell fractions resuspended in phosphate buffered saline (pH 7.4) revealed that at concentrations present in whole blood monocytes/lymphocytes, but not granulocytes and erythrocytes, effectively hydrolyzed DMF to MMF. Furthermore, in agreement with the data obtained with the pure components of the tablet, the enteric-coated tablet remained intact at pH 1, but rapidly dissolved at pH 8.

Conclusion

Together, these in vitro data indicate that hydrolysis of DMF to MMF rapidly occurs at pH 8, resembling that within the small intestines, but not at pH 1 resembling the pH in the stomach. At both pHs MMF and MEF remained intact. These data explain the observation that after oral FAE intake MMF and MEF, but not DMF, can be readily detected in the circulation of human healthy volunteers and psoriasis patients.     

出血热误诊为上呼吸道感染1例

1病例报告患者,男,22岁,因间歇性全身乏力、肌肉酸痛2 wk,发冷1 wk,发热4 d入院.曾在我院查WBC 4.5×109/L,N 0.60,L 0.4,体温波动在38～40℃.初步诊断"上呼吸道感染",用阿莫西林、VC银翘片、清热解毒冲剂等治疗无效.查体:T 38.9℃,BP面性12/8 kPa.全身皮肤无出血点,双眼球结膜轻度充血,咽部充血,软腭未见充血点,心肺腹部未见阳性体征.实验室检查:WBC 7.85 × 109/L,N 0.79,L 0.21,HGB 150g/L,PCL30×109/L,尿蛋白3.2g/L,流行性出血热抗体( ).诊断:流行性出血热.入院后立即按照流行性出血热的治疗原则给予抗病毒、抗渗出、抗出血治疗.具体包括卧床休息,给予高热量,多维生素,易消化饮食;维持水、电解质、酸碱及血浆渗透压平衡;给予大剂量(5 g)Vit.C和Vit.E.同时给予氢化可地松100 mg/d,稀释后缓慢静脉滴注.入院后3 d患者的尿量由450 mL/d增至750 mL/d,肌酐204.6μmol/L,BUN 13.3 mmol/L.5 d尿量增加至4000 mL/d.经综合治疗10 d,肌酐和BUN检查等正常,痊愈出院,随访1 mo未见异常.     

The mutagenic response at the ouabain resistance locus in T cells of mice exposed to N-ethyl-N-nitrosourea parallels the response at the Hprt locus and correlates with mutation target size

The lymphocyte Hprt gene has been used extensively as a reporter locus to monitor the mutational effects of the exposure of animals to genotoxicants. Implicit in this view of the function of a reporter gene is the assumption that its mutagenic response is representative of that of other genes in the organism. As a test of this hypothesis we compared the frequency of 6-thioguanine-resistant (TGr) mutants at the Hprt locus with the mutant frequency (MF) induced at another locus, the ouabain resistance (Oua) locus. The frequency of spontaneous OUA(R) mutants was estimated to be 1.1x10(-7) (MF between <0.3 and 1.1x10(- 7)), which was approximately 30-fold less than the spontaneous TGr MF. Following treatment with N-ethyl-N-nitrosourea (ENU), the induced OUA(R) MF at each of two dose levels (50 and 150 mg/kg ENU) and two time points (3 and 6 weeks post-exposure) was consistently 8- to 9-fold lower than the corresponding TGr MF. Thus the mutagenic response of the Oua locus closely paralleled that of the Hprt locus, indicating a similarity in their response to ENU. In addition, the Oua locus was 3-4 times more sensitive than the Hprt locus to the mutagenic effect of ENU, as measured by the fold increase in MF over the background level. The number of ENU-mutable sites capable of resulting in a TGr or OUA(R) phenotype, otherwise known as the mutation target size, was estimated to differ by an order of magnitude between the two loci. This difference in target size correlates with, and therefore may largely account for, the difference in induced MF between both loci.      

Specificity of mutagenesis by 4-aminobiphenyl: mutations at G residues in bacteriophage M13 DNA and G-->C transversions at a unique dG(8-ABP) lesion in single-stranded DNA

Mutagenesis by the human bladder carcinogen 4-aminobiphenyl (ABP) was studied in single-stranded DNA from a bacteriophage M13 cloning vector. In comparison to ABP lesions in double-stranded DNA, lesions in single- stranded DNA were approximately 70-fold more mutagenic and 50-fold more genotoxic. Sequencing analysis of ABP-induced mutations in the lacZ gene revealed exclusively base-pair substitutions, with over 80% of the mutations occurring at G sites; the G at position 6310 accounted for 25% of the observed mutations. Among the sequence changes at G sites, G- ->T transversions predominated, followed by G-->C transversions and G-- >A transitions. In order to further elucidate the mutagenic mechanism of ABP, an oligonucleotide containing the major DNA adduct, N- (deoxyguanosin-8-yl)-4-aminobiphenyl (dG(8-ABP)), was situated within the PstI site of a single-stranded M13 genome. After in vivo replication of the adduct containing ABP-modified and control (unadducted) genomes, the mutational frequency and mutational specificity of the dG(8-ABP) lesion were determined. The targeted mutational efficiency was approximately 0.01%, and the primary mutation observed was the G-->C transversion. Thus dG(8-ABP), albeit weakly mutagenic at the PstI site, can contribute to the mutational spectrum of ABP lesions.      

The predictive value of the zona-free hamster egg penetration test in relation to in-vitro fertilization at various insemination concentrations

The aim of the study was to evaluate the predictive value of the zona- free hamster egg penetration test (ZHEPT) for success in in-vitro fertilization (IVF) at various insemination concentrations ranging between 0.1 and >0.6 x 10(6)/ml. The ZHEPT was assessed using sperm samples from 87 couples undergoing IVF treatment. A similar test was simultaneously performed on the same semen sample following ionophore induction of the acrosome reaction (ZHEPTii test). Both the tests were poorly correlated with the fertilization rate of IVF at all the insemination concentrations except at >0.6 x 10(6)/ml, when there was good correlation between the ZHEPTii test and the fertilization rate. Following exclusion of two cases with an oocyte problem, further statistical analysis revealed that both the ZHEPT and ZHEPTii tests were poorly correlated with fertilization rate in IVF in this treatment group. This study suggests that the ZHEPT (with and without ionophore induction of the acrosome reaction) has a poor predictive value for the success of fertilization in IVF treatment at any insemination concentration.      

Differential depression at excitatory and inhibitory synapses in visual cortex

The function of cortical circuits depends critically on the balance between excitation and inhibition. This balance reflects not only the relative numbers of excitatory and inhibitory synapses but also their relative strengths. Recent studies of excitatory synapses in visual and somatosensory cortices have emphasized that synaptic strength is not a fixed quantity but is a dynamic variable that reflects recent presynaptic activity. Here, we compare the dynamics of synaptic transmission at excitatory and inhibitory synapses onto visual cortical pyramidal neurons. We find that inhibitory synapses show less overall depression than excitatory synapses and that the kinetics of recovery from depression also differ between the two classes of synapse. When excitatory and inhibitory synapses are stimulated concurrently, this differential depression produces a time- and frequency-dependent shift in the reversal potential of the composite postsynaptic current. These results indicate that the balance between excitation and inhibition can change dynamically as a function of activity.     

樟叶胡椒中新木脂素成分的研究

自胡椒科胡椒属植物樟叶胡椒(Piper polysyphorum C. DC)中分离到六个新木脂素(neolignans)类化合物,经光谱(UV,IR,MS,¹H-NMR,¹³C-NMR,2D-NMR,CD)分析及衍生物制备,确定Ⅱ为新化合物,即threo-△⁷-7-羟基-3,4,5,3′,5′-五甲氧基-8-O-4′-新木脂素,为一对对映体,命名为樟叶素(polysyphorin),Ⅰ,Ⅲ,Ⅳ为新的对映体,分別为(+)-virolongin,(+)-grandisin及(+)-lancifolin D.化合物Ⅴ为南藤素(wallichinine),Ⅵ为山蒟素D(hancinone D)。血小板活化因子(PAF)受体结合实验及PAF引起的血小板聚集实验证明化合物Ⅰ～Ⅴ具有明显的抑制活性。     

025Modulation of Wound Repair in the Obese Diabetic Mouse: a Role for VEGF Gene Transfer

Identifying molecular loci of impaired cutaneous healing in diabetes with an eye towards developing targeted therapy to ameliorate dysrepair continues to evolve as a promising area of study. By using an excisional wound model produced on the dorsum of female diabetic C57BL/KsJ db  + / db + mice as well as their normal (WT) & heterozygous (HZ) littermates, we studied the effects of peri‐wound intradermal injection of adeno‐associated viral vector (AAV) expressing the 165‐amino acid isoform of human vascular endothelial growth factor (VEGF) on the following: kinetics of re‐epithelialization, neoangiogenesis and granulation tissue formation, matrix remodelling, collagen deposition, and maturation. One sq. in. full thickness excisional wound was created in the mid‐upper back, rendering half of the wound as either right or left paravertebral. Animals were randomized to receive 1 of 3 treatments via intradermal injection: 1)VEGF (AAV) vector; 2)Adnull vector; 3)PBS. Postoperatively, wounds were examined & photographed on Days 3, 7, 10, 14, 21 & 28. Also, tissue was harvested for histology & immunohistochemistry (PECAM), and snap frozen for protein & RNA analysis. A scoring system was used to grade re‐epithelialization, granulation tissue thickness, matrix density, inflammation, vascular density, epithelial maturity. AAV‐VEGF exerted minimal effect on repair in WT and HZ mice. However, pronounced neovascularization, thickened granulation tissue & increased matrix deposition was noted after VEGF treatment in the db/db mice compared to those that received PBS or adnull vector at all timepoints. While the induction of angiogenesis in VEGF treated db/db mice lagged behind the unimpaired mice by 5–7 days, a global improvement in wound healng was observed.
R Crystal, Dir Inst Genetic Medicine, Weill Med College‐Cornell Univ