Second trimester total human chorionic gonadotropin,alpha-fetoprotein and unconjugated estriol in predicting pregnancy complications other than fetal aneuploidy

OBJECTIVE: To assess the value of alpha-fetoprotein (AFP), total human chorionic gonadotropin (ThCG) and unconjugated estriol in predicting certain complications of pregnancy other than fetal aneuploidy. STUDY DESIGN: Among 2384 women that underwent biochemical screening between 15 and 22 weeks of gestation, pregnancy outcome was evaluated in 677 women under 35 years of age according to serum marker levels by using cut-off points discriminative for Down syndrome or neural tube defect (NTD). RESULTS: High alpha-fetoprotein levels (MoM>/=2.0) were found to be significantly more frequent (P<0.05) in cases of fetal growth restriction (odds ratio=2.7), miscarriage (odds ratio=4.4) and intrauterine fetal death (odds ratio=5.8). High chorionic gonadotropin levels (MoM>/=2.02) were associated with intrauterine growth restriction (odds ratio=2.1; P<0.05), miscarriage (odds ratio=4; P<0.01), preterm birth (odds ratio=2.5; P<0.05), and intrauterine fetal death (odds ratio=4.2; P<0.01). Among pregnancies with intrauterine growth restriction and threatening preterm delivery, low unconjugated estriol levels (MoM相似文献   

A novel homozygous disruptive mutation in the SRD5A2-gene in a partially virilized patient with 5alpha-reductase deficiency

Steroid 5alpha-reductase deficiency is a rare autosomal recessive disorder caused by mutations in the SRD5A2-gene, resulting in diminished dihydrotestosterone (DHT) formation and, hence, in a severe virilization deficit of the external genitalia in patients with 46,XY karyotype. The phenotype of affected individuals is variable and has been reported to range from completely female over genital ambiguity to normal male, depending on the type of mutation and its effect on enzyme activity. Here we report an adolescent 46,XY patient with predominantly female appearance, who had been gonadectomized in early infancy. Genital status revealed a urogenital sinus equivalent to Prader stage III. Molecular genetic analysis demonstrated a homozygous point mutation in exon 2 of the SRD5A2-gene, leading to a premature termination in codon position 111 of the 5alpha-reductase 2 enzyme, and not allowing formation of a functional 5alpha-reductase type 2 enzyme. This case demonstrates that even despite a complete loss of function of 5alpha-reductase type 2, marked virilization is possible, most likely the result of a testosterone (T) effect during foetal life.     

Developmentally regulated interactions of human thymocytes with different laminin isoforms

The gene family of heterotrimeric laminin molecules consists of at least 15 naturally occurring isoforms which are formed by five different alpha, three beta and three gamma subunits. The expression pattern of the individual laminin chains in the human thymus was comprehensively analysed in the present study. Whereas laminin isoforms containing the laminin alpha1 chain (e.g. LN-1) were not present in the human thymus, laminin isoforms containing the alpha2 chain (LN-2/4) or the alpha5 chain (LN-10/11) were expressed in the subcapsular epithelium and in thymic blood vessels. Expression of the laminin alpha4 chain seemed to be restricted to endothelial cells of the thymus, whereas the LN-5 isoform containing the alpha3 chain could be detected on medullary thymic epithelial cells and weakly in the subcapsular epithelium. As revealed by cell attachment assays, early CD4- CD8- thymocytes which are localized in the thymus beneath the subcapsular epithelium adhered strongly to LN-10/11, but not to LN-1, LN-2/4 or LN-5. Adhesion of these thymocytes to LN-10/11 was mediated by the integrin alpha6beta1. During further development, the cortically localized CD4+ CD8+ thymocytes have lost the capacity to adhere to laminin-10/11. Neither do these cells adhere to any other laminin isoform tested. However, the more differentiated single positive CD8+ thymocytes which were mainly found in the medulla were able to bind to LN-5 which is expressed by medullary epithelial cells. Interactions of CD8+ thymocytes with LN-5 were integrin alpha6beta4-dependent. These results show that interactions of developing human thymocytes with different laminin isoforms are spatially and developmentally regulated.     

Primary cytomegalovirus infection after combined cadaveric transplantation of the liver and kidney

Seronegative transplant recipients are at a high risk of developing primary cytomegalovirus (CMV) infection. The D+/R--constellation produces a 60%-80% probability of CMV disease. In such cases CMV prophylaxis is justified. Presentation of a 12-year old boy who developed a primary CMV infection following A combined liver-kidney transplantation; evaluation of prophylactic options and review of some difficulties in the diagnosis of CMV infection. A cadaveric liver-kidney transplantation (Tx) was done in a 12-year old boy with ESRD due to type I primary hyperoxaluria. CMV status: D+, R-; number of mismatches: 5. PRA 0; kidney cold ischemia time (CIT): 13.54 h; liver CIT: 10.10 h; immediate diuresis; Immunosuppression protocol: anti IL-2 receptor antibodies, steroids, mycophenolate mofetil (MMF); cyclosporine introduced on day 6. Over the first week, daily hemodialyses were done in order to remove oxalate deposits. Kidney and liver biopsies: no ACR, no oxalate deposits. CMV prophylaxis with ganciclovir started on day 0. Routine serology and PCR for CMV follow-up showed: pp 65, IgM and IgG, CMV. DNA (Murex CMV. DNA Hybrid Capture test 2.0): negative over the first 3 months. Day 98: CMV pp 65 positive, IgM neg, DNA neg. Day 108: pp 65 neg, IgM positive, IgG neg. CMV. DNA positive (15 x 105 copies/ml). Clinical status: except for mild Cushing, liver tests and kidney function were normal. Ganciclovir was administered intravenously (i.v.) and after 14 days continued perorally. A few days later, leukopenia with severe neutropenia (neutrophil count: 400) and right otitis media developed. MMF and ganciclovir were withdrawn for a few days and reintroduced after WBC count reconstitution. We had no possibility to monitor MMF. Day 150 pp 65 neg, IgM still positive, IgG neg. No clinical signs of infection. Liver and kidney functions normal. After liver-kidney transplantation in a CMV high-risk pediatric patient (D+/R-), asymptomatic CMV primary infection developed. Although ganciclovir prophylaxis could not prevent the infection, it was mild and delayed. Due to bone marrow suppression, discontinuation of MMF and ganciclovir was necessary. Antigenemia assay pp 65 did not correlate very well with CMV viremia so it could not be recommended as a routine test. It should be used in combination with other CMV tests.     

Neuronal oxidative damage and dendritic degeneration following activation of CD14-dependent innate immune response <Emphasis Type="Italic">in vivo</Emphasis>

The cause-and-effect relationship between innate immune activation and neurodegeneration has been difficult to prove in complex animal models and patients. Here we review findings from a model of direct innate immune activation via CD14 stimulation using intracerebroventricular injection of lipopolysaccharide. These data show that CD14-dependent innate immune activation in cerebrum leads to the closely linked outcomes of neuronal membrane oxidative damage and dendritic degeneration. Both forms of neuronal damage could be blocked by ibuprofen and alpha-tocopherol, but not naproxen or gamma-tocopherol, at pharmacologically relevant concentrations. This model provides a convenient method to determine effective agents and their appropriate dose ranges for protecting neurons from CD14-activated innate immunity-mediated damage, and can guide drug development for diseases, such as Alzheimer disease, that are thought to derive in part from CD14-activated innate immune response.     

Apolipoprotein E isoform-dependent dendritic recovery of hippocampal neurons following activation of innate immunity

Background  

Innate immune activation, including a role for cluster of differentiation 14/toll-like receptor 4 co-receptors (CD14/TLR-4) co-receptors, has been implicated in paracrine damage to neurons in several neurodegenerative diseases that also display stratification of risk or clinical outcome with the common alleles of the apolipoprotein E gene (APOE): APOE2, APOE3, and APOE4. Previously, we have shown that specific stimulation of CD14/TLR-4 with lipopolysaccharide (LPS) leads to greatest innate immune response by primary microglial cultures from targeted replacement (TR) APOE4 mice and greatest p38MAPK-dependent paracrine damage to neurons in mixed primary cultures and hippocampal slice cultures derived from TR APOE4 mice. In contrast, TR APOE2 astrocytes had the highest NF-kappaB activity and no neurotoxicity. Here we tested the hypothesis that direct activation of CD14/TLR-4 in vivo would yield different amounts of paracrine damage to hippocampal sector CA1 pyramidal neurons in TR APOE mice.     

Tissue microarrays for routine diagnostic assessment of HER2 status in breast carcinoma.

The use of tissue microarray (TMA) technology may substantially reduce the costs of routine testing of breast carcinomas for human epidermal growth factor receptor 2 (HER2) status. After a preliminary pilot study comparing the TMA results with those obtained on whole section, which showed an excellent agreement (with kappa values >0.90) for both immunohistochemical and fluorescent in situ hybridization (FISH) method, we introduced the TMA technique in our routine work. A total of 1158 invasive breast carcinomas were submitted for the determination of HER2 status, which was assessed in 74 weekly runs. One hundred twenty-five of 1084 surgical specimens (11.5%) were judged as unsuitable for inclusion into TMAs. In 32 of 959 tumors included in TMAs (3.3%), the respective cores were uninformative, and HER2 status was determined on whole sections. Thus, HER2 status was finally determined on TMA in 927 cases (81.1%). A typical weekly run comprised 1 TMA (consisting, on average, of 13 tumors), 2 whole sections of surgical specimens and 1 whole section of core needle biopsy, and the number of processed slides for each method decreased from 16 to 4 per week. In all, 14.7% of tumors were HER2 positive by FISH. In both TMAs and whole sections, immunohistochemical results were in good agreement with FISH for cases scored as 0/1+ (98% and 97%) and for those scored as 3+ (96% and 87%), whereas concordance was poor in cases scored as 2+ (30% and 13%, respectively).     

Long-term neurodevelopmental outcome of triplets

OBJECTIVE: To analyze the incidence of neurodevelopmental disabilities in triplets and to find out possible connection between the outcome and perinatal events. DESIGN: Retrospective cohort study of 94 triplets and their outcome at 24-144 months of age correlated with gestational age, birth weight, pregnancy complications, early neonatal period, neonatal cranial ultrasound, period of birth (1985-1995, 1996-2000) and type of antenatal care. RESULTS: Sixty-two triplets are healthy, 15 suffer cerebral palsy (CP) and 17 minimal cerebral dysfunction (MCD). Adverse outcome correlates significantly with prematurity, low birth weight and maternal age. In multivariate analysis, both cerebral palsy and minor disabilities correlate significantly with early neonatal complications, neonatal cranial ultrasound with later CP (p<0.01), and MCD with preterm rupture of membranes (p=0.047). Children conceived spontaneously do worse than those born after assisted reproduction (p=0.004), those born in the time period 1996-2000 do better than those born before (p=0.021). Seventy-seven percent (77%) of newborns delivered in the time period 1996-2000 and after level 1 antenatal care was introduced, compared with 54% being delivered in the time period before 1996 and with less meticulous types of antenatal care, remain healthy (p=0.015). CONCLUSION: Triplets are still at high risk for long-term neurodevelopmental complications. Stringent perinatal care might appear important determinant of their long-term outcome.     

Maternal plasma interleukin-6, interleukin-1beta and C-reactive protein as indicators of tocolysis failure and neonatal outcome after preterm delivery.

OBJECTIVE: To investigate whether maternal serum interleukin-6 (IL-6), interleukin-1beta (IL-1beta) and high sensitive C-reactive protein (CRP) could be used as markers of tocolysis failure and adverse neonatal outcome in pregnancies with preterm labor (PL). METHODS: Forty-seven maternal blood samples taken because of PL at admission and delivery were analyzed. Control samples were taken from 20 gravidas with normal pregnancies. Differences in interleukins and CRP levels with or without chorioamnionitis, connatal infection or periventricular leukomalacia (PVL) were analyzed. Cut-off values were estimated for prediction of tocolysis failure and adverse neonatal outcome. RESULTS: All three parameters were significantly higher in patients delivering prematurely than in patients delivering at term. All three parameters were significantly higher with than without histologic chorioamnionitis (p < 0.001), with than without connatal infection (p < 0.01), with than without PVL (p < 0.01 for IL-6 and IL-1beta, p < 0.05 for CRP), and in pregnancies with preterm premature rupture of membranes (PPROM) delivered within 48 hours compared to those more prolonged (p < 0.01). Choosing 50.9 pg/mL of IL-6 and a CRP of 19.7 as cut-offs in maternal blood admission concentrations for neonatal PVL, resulted in sensitivity of 81% and specificity of 91% and sensitivity of 91% and specificity of 81%, respectively. At respective maternal blood admission cut-off levels of 27.8 pg/mL of IL-6 and 8.9 of CRP, both parameters were effective predictors of connatal infection. CONCLUSIONS: Maternal blood IL-6 and CRP could become useful in predicting tocolysis failure and intrauterine treat for the fetus.