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Normal Karyotype (normal + karyotype)
Selected AbstractsDV-ICE, intensive induction and early transplantation for adult patients with acute lymphoblastic leukemia: a phase II studyEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2009Christine Dudler Abstract Objectives:, Eighty percent of adult patients with acute lymphoblastic leukemia (ALL) achieve a complete remission (CR) but only 30,40% are long term survivors. Best treatment strategies remain to be defined. The role of induction intensity, first remission hematopoietic stem cell transplantation (HSCT) and maintenance chemotherapy continues to be discussed. We tested a strategy of high intensity treatment of short duration followed by HSCT. Patients and methods:, This prospective phase II study used induction with DV-ICE followed by immediate allogeneic or autologous HSCT (depending on donor availability) without additional consolidation or maintenance treatment. DV-ICE consisted of dexamethasone, vincristine, idarubicin, etoposide, and conventional dose cytosine arabinoside; HSCT was planned immediately if CR was achieved or after an additional course of intermediate high dose cytosine arabinoside and etoposide for patients with induction failure. A total of 42 consecutive patients between 17 and 67 yr of age (median 43 yr) were enrolled. Of the 42 patients, 57% were male, 76% had B-lineage ALL, 19% T-lineage ALL and two patients biphenotypic ALL. 29% were Ph+; 7% had 11q23 and 45% had a normal karyotype. CNS involvement was found in three patients. Results:, Thirty-three patients (79%) achieved a CR, 24 patients after induction I or II and nine patients after rescue HSCT. 31 patients received a HSCT (seven autologous and 24 allogeneic). 11 patients did not receive a HSCT because of early death in nine (treatment toxicity in five, refractory disease in four), one patient refused transplantation, one patient was not suitable. Disease-free survival (DFS) of the entire cohort was 46% (95% CI ±16%) at 1 yr and 16% (±13%) at 5 yr. Overall survival (OS) was 63% (±15%) at 1 yr and 23% (±15%) at 5 yr, with a median follow-up of surviving patients of 55 (4,136) months. Neither disease subtype, cytogenetic abnormalities nor patient age or gender was significantly associated with survival. Conclusions:, Intensive induction using DV-ICE followed by early transplantation without treatment beyond 4 months failed to improve outcome compared with standard treatment. [source] Conventional cytogenetics in myelofibrosis: literature review and discussionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2009Kebede Hussein Abstract The clinical phenotype of myelofibrosis (MF) is recognized either de novo (primary) or in the setting of polycythemia vera (post-PV) or essential thrombocythemia (post-ET). Approximately one-third of patients with primary MF (PMF) present with cytogenetic abnormalities; the most frequent are del(20q), del(13q), trisomy 8 and 9, and abnormalities of chromosome 1 including duplication 1q. Other less frequent lesions include ,7/del(7q), del(5q), del(12p), +21 and der(6)t(1;6)(q21;p21.3). In general, cytogenetic abnormalities are qualitatively similar among PMF, post-ET MF and post-PV MF although their individual frequencies may differ. Based on prognostic effect, cytogenetic findings in MF are classified as either ,favorable' or ,unfavorable'. The former include normal karyotype or isolated del(20q) or del(13q) and the latter all other abnormalities. Unfavorable cytogenetic profile in both PMF and post-PV/ET MF confers an independent adverse effect on survival; it is also associated with higher JAK2V617F mutational frequency. In addition to their prognostic value, cytogenetic studies in MF ensure diagnostic exclusion of other myeloid neoplasms that are sometimes associated with bone marrow fibrosis (e.g. BCR-ABL1 -positive or PDGFRB -rearranged) and also assist in specific treatment selection (e.g. lenalidomide therapy is active in MF associated with del(5q). [source] Association of non-alcoholic steatohepatitis (NASH) with chronic neutrophilic leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2004Chikashi Yoshida Abstract: A 54-yr-old female having chronic neutrophilic leukemia (CNL) associated with severe liver injury is presented. Physical examination on admission showed severe jaundice, hepatosplenomegaly, massive ascites, and pretibial edema. Complete blood count showed a hemoglobin level of 9.1 g/dL, platelet count of 25.8 × 104/,L, and white blood cell count of 36.6 × 103/,L with 89.7% neutrophils. Blood chemistry showed hyperbilirubinemia (21.9 mg/dL) with normal transaminase levels. There was no abnormality in serum cholesterol, triglyceride, or glucose levels. Neutrophil alkaline phosphatase activity was significantly elevated. Bone marrow aspiration showed myeloid hyperplasia with normal karyotype. Rearrangement of the bcr/abl was not detected by either polymerase chain reaction or fluorescence in situ hybridization. Human androgen receptor gene assay (HUMARA) of the bone marrow cells showed clonal proliferation of neutrophils. The patient was diagnosed as having CNL. To evaluate the pathogenesis of the liver injury, a needle biopsy was performed, which showed steatohepatitis with infiltration of neutrophils. As the patient had no history of alcohol abuse, a diagnosis of non-alcoholic steatohepatitis (NASH) was made. Assuming that the infiltration of abnormal neutrophils into the liver contributed to the development of NASH, she was treated with cytoreductive chemotherapy (cytosine arabinoside: 100 mg/d, 1,3 doses/wk). With decreases in white blood cell counts, serum bilirubin levels decreased gradually to 1.5 mg/mL. A postchemotherapy liver biopsy specimen showed marked improvement of the fatty degenerative change. To our knowledge, this is the first report describing the development of NASH in a myeloproliferative disorder. We believe that the infiltration of leukemic cells contributed to the development of NASH in this patient. [source] Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemiaGENES, CHROMOSOMES AND CANCER, Issue 3 2003Christine Steudel Partial tandem duplication (PTD) of the MLL gene and internal tandem duplication (ITD) of the juxtamembrane region of the FLT3 receptor tyrosine kinase gene have been described in acute myeloid leukemia (AML) patients, preferentially in those with normal cytogenetics. These alterations have been associated with a poor prognosis. In our study, we analyzed the prevalence and the potential prognostic impact of these aberrations in a large unselected and well-defined cohort of 956 patients with AML. Results were correlated with cytogenetic data and clinical outcome. MLL PTD was detected by RT-PCR, subsequent nucleotide sequencing, and Southern blotting. The overall incidence was found to be 5.0% (48/956), whereas FLT3 ITD was detected in 19.2% (184/956). Sixteen cases were positive for both alterations. The rate of MLL PTD in FLT3 ITD positive patients was significantly higher than that in FLT3 ITD negative patients [16/184 (8.7%); 32/772 (4.1%); P = 0.025]. However, both aberrations were highly increased in patients with normal karyotype (MLL PTD 35/431, P = 0.004; FLT3 ITD 132/334, P < 0.001). When restricted to this subgroup, the rate of MLL PTD in patients with FLT3 mutations was not significantly increased. No statistically significant differences were detected between patients positive for MLL PTD and patients negative for MLL PTD in the rate of complete remissions or the overall survival, although we did see a significantly shorter disease-free survival in patients age 60 or younger. In conclusion, although there is an overlap in the mutational spectrum in AML with FLT3 ITD and MLL PTD mutations, our data do not support a common mechanistic basis. Although associated with inferior disease-free survival, the results of this study do not unequivocally support the notion that MLL PTD mutations represent an independent prognostic factor. © 2003 Wiley-Liss, Inc. [source] Nucleophosmin (NPM1) mutations in adult and childhood acute myeloid leukaemia: towards definition of a new leukaemia entity,HEMATOLOGICAL ONCOLOGY, Issue 4 2009Rachel Rau Abstract Nucleophosmin (NPM) is a ubiquitously expressed chaperone protein that shuttles rapidly between the nucleus and cytoplasm, but predominantly resides in the nucleolus. It plays key roles in ribosome biogenesis, centrosome duplication, genomic stability, cell cycle progression and apoptosis. Somatic mutations in exon 12 of the NPM gene (NPM1) are the most frequent genetic abnormality in adult acute myeloid leukaemia (AML), found in approximately 35% of all cases and up to 60% of patients with normal karyotype (NK) AML. In children, NPM1 mutations are far less frequent, occurring in 8,10% of all AML cases, and in approximately 25% of those with a NK. NPM1 mutations lead to aberrant localization of the NPM protein into the cytoplasm, thus the designation, NPMc+ AML. NPMc+ AML is seen predominantly in patients with a NK and is essentially mutually exclusive of recurrent chromosomal translocations. Patients with NPM1 mutations are twice as likely as those who lack an NPM1 mutation to also have a FMS-like tyrosine kinase (FLT3) internal tandem duplication (ITD) mutation. NPMc+ AML is also characterized by a unique gene expression signature and microRNA signature. NPMc+ AML has important prognostic significance, as NPMc+ AML, in the absence of a coexisting FLT3-ITD mutation, is associated with a favourable outcome. NPM1 mutations have also shown great stability during disease evolution, and therefore represent a possible marker for minimal residual disease detection. Given its distinctive biologic and clinical features and its clear clinical relevance, NPMc+ AML is included as a provisional entity in the 2008 WHO classifications. There is still much to be learned about this genetic alteration, including its exact role in leukaemogenesis, how it interacts with other mutations and why it confers a more favourable prognosis. Further, it represents a potential therapeutic target warranting research aimed at identifying novel small molecules with activity in NPMc+ AML. Copyright © 2009 John Wiley & Sons, Ltd. [source] Detection of pathogenic gene copy number variations in patients with mental retardation by genomewide oligonucleotide array comparative genomic hybridization,,HUMAN MUTATION, Issue 11 2007Yao-Shan Fan Abstract Genomic imbalance is a major cause of developmental disorders. Microarray-based comparative genomic hybridization (aCGH) has revealed frequent imbalances associated with clinical syndromes, but also a large number of copy number variations (CNVs), which have complicated the interpretation of results. We studied 100 consecutive patients with unexplained mental retardation and a normal karyotype using several platforms of CGH arrays. A genomewide array with 44,290 oligonucleotide probes (OaCGH44K) detected imbalances in 15% of cases studied with sizes ranged from 459,kb to 19,Mb while revealing a small number of CNVs (0.72/individual). Another platform with ,240,000 oligonucleotide probes (OaCGH244K) revealed a large number of CNVs (20/individual) in selected cases and their normal parents. We used a comprehensive approach for interpreting the results of aCGH, including consideration of the size, inheritance and gene content of CNVs, and consultation with an online Database of Genomic Variants (DGV) and Online Mendelian Inheritance in Men (OMIM) for information on the genes involved. Our study suggests that genomewide oligonucleotide arrays such as the OaCGH44K platform can be used as a powerful diagnostic tool for detection of genomic imbalances associated with unexplained mental retardation or syndromic autism spectrum disorders. It is interesting to note that a small number of common variants were revealed by OaCGH244K in some study subjects but not in their parents and that some inherited CNVs had altered breakpoints. Further investigations on these alterations may provide useful information for understanding the mechanism of CNVs. Hum Mutat 28(11),1124,1132, 2007. © 2007 Wiley-Liss, Inc. [source] Nonmutilating palmoplantar and periorificial kertoderma: a variant of Olmsted syndrome or a distinct entity?INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2010Ahmad Nofal MD Background, Olmsted syndrome is a rare keratinization disorder characterized by mutilating palmoplantar and periorificial keratoderma as the two major diagnostic features. Some authors believe that atypical cases without this standard combination may not really belong to Olmsted syndrome. Herein, we describe two familial cases with congenital nonmutilating palmoplantar and periorificial keratoderma, and discuss their similarities and differences with Olmsted syndrome. Patients, The study included two sisters who presented with focal and punctate nonmutilating palmoplantar keratoderma (PPK), periorificial hyperkeratotic plaques, and widely distributed keratotic lesions. Fragile denuded areas of the skin were found in sites exposed to trauma. Fingernails showed a characteristic form of leukonychia. Results, Histopathology of plantar keratoderma showed psoriasiform hyperplasia with marked compact hyperkeratosis, while vicinity of denuded skin revealed thin parakeratotic zone and dissolution of the granular cell layer. Immunohistochemistry demonstrated suprabasal staining pattern for acidic keratin (AE1) and uniform positivity, starting four to six layers above the basal layer, for cytokeratin 10. Electron microscopy showed defective keratinization. Cytogenetic studies revealed normal karyotype and no chromosomal breakage. Conclusion, Our cases share Olmsted syndrome in the early onset, and the presence of symmetrical PPK, periorificial keratoderma and keratotic lesions. However, the striking nonmutilating nature of PPK and the presence of unique features in our patients suggest a newly described keratinization disorder. [source] A subpopulation of mesenchymal stromal cells with high osteogenic potentialJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Hua Liu Abstract Current bone disease therapy with bone marrow-derived mesenchymal stromal cells (MSC) is hampered by low efficiency. Advanced allogeneic studies on well-established mouse genetic and disease models are hindered by difficulties in isolating murine MSC (mMSC). And mMSC prepared from different laboratories exhibit significant heterogeneity. Hence, this study aimed to identify and isolate a sub-population of mMSC at an early passage number with high osteogenic potential. Enrichment of mMSC was achieved by 1-hr silica incubation and negative selection. Approximately 96% of these cells synthesized osteocalcin after 28 days of osteogenic induction in vitro, and displayed a complete dynamic alteration of alkaline phosphatase (ALP) activity with increasing osteogenic maturation and strong mineralization. Moreover, the cells displayed uniform and stable surface molecular profile, long-term survival, fast proliferation in vitro with maintenance of normal karyotype and distinct immunological properties. CD73 was found to be expressed exclusively in osteogenesis but not in adipogenesis. These cells also retained high osteogenic potential upon allogeneic transplantation in an ectopic site by the detection of bone-specific ALP, osteopontin, osteocalcin and local mineralization as early as 12 days after implantation. Hence, these cells may provide a useful source for improving current strategies in bone regenerative therapy, and for characterizing markers defining the putative MSC population. [source] Fetal thickened nuchal soft tissues may first appear in the second trimester in Down syndromeJOURNAL OF CLINICAL ULTRASOUND, Issue 2 2010Etan Z. Zimmer MD Abstract Purpose. To describe a series of cases of late-onset fetal nuchal translucency in Down syndrome. Method. In our practice area, most pregnant women usually undergo 3 different sonographic examinations: a fetal nuchal translucency examination in the 1st trimester and 2 detailed surveys of all fetal organs in the early 2nd trimester and in midpregnancy. Result. During the study period (2003,2008), we detected 11 fetuses with new appearance of severe thickened nuchal soft tissues (,6 mm) at 14,16 weeks' gestation after a normal nuchal screening in the 1st trimester. All of these fetuses had trisomy 21. Associated structural anomalies were observed in 10/11 of the cases. In addition, there were 12 fetuses with new appearance of thickened nuchal soft tissues (<4 mm); all these fetuses had a normal karyotype and were normal at delivery. Conclusion. Obstetricians should be aware that a nuchal abnormality may first appear only at 14,16 weeks' gestation. Fetal karyotyping is advocated in these cases because of the high probability of Down syndrome. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2010 [source] Alveolar capillary dysplasia with antenatal anomalies mimicking trisomy 21JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 1 2001J. McGaughran Abstract: Alveolar capillary dysplasia (ACD) has been described in conjunction with a number of congenital abnormalities. The case reported here was noted in utero to have duodenal atresia and a partial atrioventricular canal defect and a provisional diagnosis of trisomy 21 was considered. A fetal blood sample showed a normal karyotype. The diagnosis of ACD was made at post-mortem following a neonatal death on the tenth day. This case further highlights the range of congenital abnormalities that may be present in cases of ACD that may mimic other conditions, including trisomy 21, on antenatal scan. However, the absence of congenital anomalies, even in the same family, would not exclude the diagnosis of ACD. [source] Properties of murine embryonic stem cells maintained on human foreskin fibroblasts without LIF,MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2008G.L. Meng Abstract In embryonic stem (ES) cells, leukemia inhibitory factor (LIF)/STAT3, wnt and nodal/activin signaling are mainly active to control pluripotency during expansion. To maintain pluripotency, ES cells are typically cultured on feeder cells of varying origins. Murine ES cells are commonly cultured on murine embryonic fibroblasts (MEFs), which senesce early and must be frequently prepared. This process is laborious and leads to batch variation presenting a challenge for high-throughput ES cell expansion. Although some cell lines can be sustained by exogenous LIF, this method is costly. We present here a novel and inexpensive culture method for expanding murine ES cells on human foreskin fibroblast (HFF) feeders. After 20 passages on HFFs without LIF, ES cell lines showed normal expression levels of pluripotency markers, maintained a normal karyotype and retained the ability to contribute to the germline. As HFFs do not senesce for at least 62 passages, they present a vast supply of feeders. Mol. Reprod. Dev. 75: 614,622, 2008. © 2007 Wiley-Liss, Inc. [source] Culturing in vitro produced blastocysts in sequential media promotes ES cell derivationMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 8 2006J. Liu Abstract Embryonic stem (ES) cell lines are routinely derived from in vivo produced blastocysts. We investigated the efficiency of ES cells derivation from in vitro produced blastocysts either in monoculture or sequential culture. Zygotes from hybrid F1 B6D2 mice were cultured in vitro to the blastocyst stage in Potassium (K+) simplex optimised medium (KSOM) throughout or in KSOM and switched to COOK blastocyst medium on day 3 (KSOM,CBM). Blastocysts were explanted on a feeder layer of mitomycin C-inactivated murine embryonic fibroblasts (MEF) in TX-WES medium for ES cell derivation. Sequential KSOM,CBM resulted in improved blastocyst formation compared to KSOM monoculture. ES cells were obtained from 32.1% of explanted blastocsyts cultured in KSOM,CBM versus18.4% in KSOM alone. ES cell lines were characterized by morphology, expression of SSEA-1, Oct-4 and alkaline phosphatase activity, and normal karyotype. These results indicate that in vitro culture systems to produce blastocysts can influence the efficiency of ES cell line derivation. Mol. Reprod. Dev. 1017,1021, 2006. © 2006 Wiley-Liss, Inc. [source] Day 15 bone marrow driven double induction in young adult patients with acute myeloid leukemia: Feasibility, toxicity, and therapeutic results,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2010Felicetto Ferrara The strategy named double induction (DI) in acute myeloid leukemia (AML) consists of two courses of chemotherapy irrespective of the degree of cytoreduction in the bone marrow (BM) after the first course, unless severe complications prohibit its application. We describe treatment results from a series of 33 patients in whom DI was adopted only after demonstration of persistence of more than 10% blast cells at day 15 (D15) examination of BM. All patients received as induction idarubicin, cytarabine, and etoposide. As second induction, we administered the combination of fludarabine, intermediate dose cytarabine, and Granulocyte colony stimulating factor (G-CSF). The median blast count at D15 was 30 (15,90). Overall, 30 of 33 patients were judged as eligible to receive DI, reasons for exclusion being in all cases active infection in the context of severe pancytopenia. Nineteen patients (63%) had unfavorable karyotype and 11 (37%) normal karyotype; seven of these had Fms-like tyrosine kinase gene internal tandem duplication (FLT3/ITD) mutation. Overall, complete remission (CR) was achieved in 20/30 patients (67%), while eight patients (27%) were refractory and two died of infectious complications. All refractory patients had unfavorable cytogenetics. All patients achieving CR were programmed to receive allogeneic stem cell transplantation (allo-SCT), which was actually performed in 11 patients. Our study suggest that D15 driven DI represents a feasible and effective therapeutic strategy in young adult AML patients, improving therapeutic results and not compromising feasibility of allo-SCT. When compared with conventional DI, it offers the potential to avoid unnecessary toxicity in a consistent proportion of patients. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] FLT3 mutations have no prognostic impact in elderly patients with acute myeloid leukemia and normal karyotype,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009Felicetto Ferrara No abstract is available for this article. [source] Transcriptosome and serum cytokine profiling of an atypical case of myelodysplastic syndrome with progression to acute myelogenous leukemiaAMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2006Daruka Mahadevan Abstract A Native American-Indian female presenting with anemia and thrombocytosis was diagnosed with myelodysplastic syndrome (MDS, refractory anemia). Over the course of 5 years she developed cytopenias and periods of leukocytosis with normal bone marrow (BM) blast counts, features of an unclassifiable MDS/MPS syndrome. The patient ultimately progressed to acute myelogenous leukemia (AML, FAB M2) and had a normal karyotype throughout her course. The episodes of leukocytosis were associated with infectious complications. Transformation to AML was characterized by a BM blast percentage of 49%. Peripheral blood and BM samples were obtained for serum protein analysis and gene expression profiling (GEP) to elucidate her disease process. An ELISA assay of the serum analyzed ,80 cytokines, which demonstrated that hepatocyte growth factor/scatter factor and insulin-like growth factor binding protein 1 were markedly elevated compared to normal. GEP demonstrated a unique "tumor molecular profile," which included overexpression of oncogenes (HOXA9, N-MYC, KOC1), proliferative genes (PAWR, DLG5, AKR1C3), invasion/metastatic genes (FN1, N-CAM-1, ITGB5), pro-angiogenesis genes (c-Kit), and down regulation of tumor suppressor genes (SUI1, BARD1) and anti-apoptotic genes (PGLYRP, SERPINB2, MPO). Hence, a biomics approach has provided insight into elucidating disease mechanisms, molecular prognostic factors, and discovery of novel targets for therapeutic intervention. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc. [source] Structural heart defects associated with an increased nuchal translucency: 9 years experience in a referral centrePRENATAL DIAGNOSIS, Issue 4 2008S. A. Clur Abstract Objective To investigate the congenital heart disease (CHD) found in association with an increased nuchal translucency (NT) at 11,14 weeks of gestation in chromosomally normal and abnormal fetuses. Methods Patients referred from January 1998 until May 2007 with an increased NT (,95th percentile) where CHD was diagnosed were included. Chromosome analysis, fetal and postnatal echocardiography were performed. A postmortem examination followed pregnancy termination when possible. Results Major CHD was identified in 68 of 967 fetuses with an increased NT (median NT 4.8 mm, range 2.5,22 mm). Major CHD was found in 34 of 693 fetuses (4.9%) with a normal karyotype and increased NT (median 5.2 mm, range 2.5,9.6 mm). CHD frequency increased from 1.9%, with NT between 2.5 and 3.5 mm, to 27.7% when NT was , 6.5 mm. Septal defects predominated (20%) when NT was ,3.5 mm. With NT > 3.5 mm an equal distribution of CHD types was seen. Major CHD was identified in 34 of the 274 fetuses with an abnormal karyotype and increased NT (median 4.2 mm, range 2.5,22 mm). Conclusions A variety of CHD is associated with an increased NT in the first trimester of pregnancy. Conotruncal defects, branchial arch derivative defects, left and right obstructive lesions (inflow and outflow) and shunts were seen. Copyright © 2008 John Wiley & Sons, Ltd. [source] Small intestinal atresia in a defined population: occurrence, prenatal diagnosis and survivalPRENATAL DIAGNOSIS, Issue 13 2007Victoria Hemming Abstract Objective To describe the prevalence, associated anomalies, prenatal diagnosis, and survival of cases of congenital small intestinal atresia (SIA). Method Data were extracted from the Northern Congenital Abnormality Survey (NorCAS) for cases delivered during 1991 to 2001. Results A total of 99 cases of SIA were notified from 372 717 registered births. Twenty-five (25.8%) SIA cases were associated with a chromosomal anomaly. Of the 72 SIA cases with normal karyotype, 18 (25%) were associated with other structural anomalies. The total prevalence for all SIA cases over the 11 years was 2.66 per 10 000 registered births (95% CI 2.13, 3.18), and the livebirth prevalence was 2.37 per 10 000 livebirths (95% CI 1.88, 2.87). For jejunoileal atresia, the total prevalence increased from 0.54 per 10 000 births during 1991,1995 to 1.11 per 10 000 births during 1996,2001, and livebirth prevalence increased from 0.49 to 1.06 per 10 000 livebirths. The more proximal the lesion the prenatal diagnosis sensitivity was slightly better with 19 (44.2%) cases of duodenal atresia and 3 (42.8%) cases of jejunal atresia diagnosed prenatally by routine ultrasonography. Conclusion This population-based study of SIA has confirmed several previous findings but, by considering subtypes separately, it also suggests a trend towards an increase in the prevalence of jejunoileal atresia (JIA). Copyright © 2007 John Wiley & Sons, Ltd. [source] Umbilical artery aneurysm in a severe growth-restricted fetus with normal karyotypePRENATAL DIAGNOSIS, Issue 11 2007Loïc Sentilhes No abstract is available for this article. [source] Prenatal sonographic diagnosis of congenital perineal skin tag: case report and review of the literaturePRENATAL DIAGNOSIS, Issue 11 2006Angelika Bord Abstract Background Skin tags, or acrochordons, are benign, soft, fleshy tumors that are composed of hyperplastic epidermis covering a dermal connective tissue stalk. Methods Case report of a congenital perineal skin tag that presented as a perineal tumor during second-trimester sonographic scan at 23 weeks' gestation. Literature review of the medical literature using Pubmed® and the search terms acrochordon, fibroepithelial polyp (FEP), and skin tag. Results Routine midtrimester targeted organ scanning at 23 weeks' gestation revealed a 5-mm hypoechogenic elongated mass in the perineal area of the fetus. The lesion progressed to twice that size by 36 weeks. Detailed anatomy scan of the fetus was unremarkable, and amniocentesis demonstrated normal karyotype. The mother developed spontaneous labor at 38 weeks' gestation and delivered a phenotypically normal girl with a round smooth mass in the perineal area. The lesion was removed; pathologic examination revealed a lipomatous skin tag. Literature review showed skin tags associated with different medical conditions. Conclusion To the best of our knowledge, no prenatally diagnosed cases of this lesion on the fetal perineum have been published. In the present case, this was an innocuous finding. Copyright © 2006 John Wiley & Sons, Ltd. [source] Complex de novo cryptic subtelomeric rearrangements in a fetus with multiple ultrasonographic abnormalities and a normal karyotype at amniocentesisPRENATAL DIAGNOSIS, Issue 12 2005M. Anwar Iqbal Abstract Objective Prenatal diagnosis is usually offered to the majority of pregnancies with fetal structural abnormalities detected by prenatal ultrasound; however, only a small proportion show an abnormal karyotype. We wanted to detect cryptic subtelomeric rearrangements (CSTR) in a fetus with multiple abnormal ultrasonographic findings that revealed a normal karyotype at amniocentesis. Methods Fetal chromosome analysis was performed from amniotic fluid cells. Parental chromosome analysis was done on PHA stimulated lymphocyte cultures. For fluorescence in situ hybridization (FISH) analysis, ToTelVysion multicolor DNA probe mixture was used to hybridize the p and q telomeres of each chromosome. Results The amniotic fluid chromosome analysis revealed an apparently normal 46,XY karyotype. A follow-up FISH analysis showed three apparently balanced complex translocations involving (1) the chromosome 4p and 22q telomeres (2) 4q and 11q telomeres and (3) 8p, 20p and 20q telomeres. Parental chromosome and subtelomere FISH analysis was found to be normal. Conclusion To our knowledge, this is the first report of complex de novo cryptic translocations in an abnormal fetus. These CSTR identified by FISH with subtelomere-specific probes are not detected by other cytogenetic and/or molecular cytogenetic approaches. However, to confirm the balanced nature of CSTR, array-CGH can be helpful. Further studies are in progress to determine the frequency of CSTR and its significance in the etiology of fetal abnormalities. Copyright © 2005 John Wiley & Sons, Ltd. [source] Trends in elective terminations of pregnancy between 1989 and 2000 in a French county (the Isère)PRENATAL DIAGNOSIS, Issue 11 2003P. Guillem Abstract Objectives This study was performed in order to provide a description of indications for induced elective terminations of pregnancy (ETOP), their characteristics (e.g. gestational age), and their evolution over time. Design of the Study This is an epidemiological study. The geographic area covered is the French county of ,Isère', which represents a mean of 14 000 births per year over the study period. Materials and Methods Data on ETOPs were collected actively from medical records by a register of childhood deficiencies and adverse perinatal events in this county. Between 1989 and 2000, 996 ETOPs were notified. Results Four main grounds for ETOPs were identified: (1) morphological anomalies with normal karyotype (39%), (2) chromosomal anomalies (35%), (3) other fetal grounds (16%), and (4) maternal indications (10%). Prevalence rates for the first two grounds increased significantly over the study period respectively from 2.0 to 2.9 and from 1.4 to 2.7 per 1000. Among the ETOPs carried out because of fetal indications, the percentage of late ETOPs (from 24 weeks of gestation) was 34.6%, and remained stable over the studied period. In some cases, a medical consensus was not reached with respect to indications for termination (sex chromosome anomalies, limb defects). We estimated the percentage of these cases as being 2.7% of the figure for fetal indications, without any variation in prevalence over the whole period (p = 0.59). The increasing number of ETOPs that occurred in the chromosomal aberrations group during the study period is thought to be due to an increase in diagnostic sensitivity. The increase that occurred in the morphological anomalies group is thought to be due both to an increase in sensitivity and to a widening of the field with respect to indications, some of which have an uncertain prognosis (e.g. agenesis of the corpus callosum). Conclusion This study provides useful data for monitoring medical practice consistency within the field of prenatal diagnosis, and for the drive to keep medical practice within ethically acceptable limits. Copyright © 2003 John Wiley & Sons, Ltd. [source] Pregnancy outcome in fetuses with increased nuchal translucency and normal karyotypePRENATAL DIAGNOSIS, Issue 5 2002M. V. Senat Abstract Objective This study was conducted to evaluate pregnancy outcome and mid- and long-term prognosis of cases with nuchal translucency ,4,mm and normal karyotype. Methods Retrospective analysis of 160 cases who presented with a nuchal translucency ,4,mm when the CRL was between 45 and 84,mm was undertaken. Cystic hygromas were excluded. When the karyotype was normal a detailed anomaly scan was performed at 20 to 24 weeks followed by serial ultrasound examination. Clinical examination of the neonates was performed by a paediatrician. Long-term follow-up was completed through a questionnaire filled in by parents, GPs and paediatricians. Results 160 fetuses had an NT ,4,mm. 44.3% had an abnormal karyotype. Of the 55.7% with normal karyotypes, 74 % did not show any abnormalities on follow-up ultrasound scan. Mid- and long-term outcome was known in 91% of the cases. 6.4% had a malformation diagnosed only at birth. Among the normal neonates, 11.1% are considered to have a significant neurological handicap or orthopaedic problems at 12 to 72 months of age. Conclusion In an unselected population, NT ,4,mm is associated with a high incidence of chromosomal and non chromosomal abnormalities. Even when the fetal karyotype and serial ultrasound examinations are considered to be normal, the risk of fetal malformation and developmental delay should not be underestimated. Copyright © 2002 John Wiley & Sons, Ltd. [source] Prenatal findings on ultrasound and X-ray in a case of overgrowth syndrome associated with increased nuchal translucencyPRENATAL DIAGNOSIS, Issue 5 2001P. Schwärzler Abstract A case of prenatal diagnosis of an overgrowth syndrome at 30 weeks of gestation is reported. The diagnosis was suggested on the basis of increased fetal growth from 16 weeks onwards, advanced bone age, and characteristic facial features such as hypertelorism, broad forehead and small chin. The fetus presented at 12 weeks with a markedly increased nuchal translucency thickness and generalized skin edema, but normal karyotype. Serial ultrasound scans revealed brain abnormalities including mild unilateral ventriculomegaly and a cyst in the cavum septi pellucidi. The pregnancy was terminated at the parents' request at 32 weeks of gestation and postmortem examination confirmed the prenatal findings. This case demonstrates the possibility of prenatal diagnosis of early overgrowth syndromes and highlights the dilemma arising from the prenatal diagnosis of a non-lethal condition associated with an uncertain prognosis and poorly documented in utero. Copyright © 2001 John Wiley & Sons, Ltd. [source] ORIGINAL ARTICLE: Peripheral Blood NK Cells Reflect Changes in Decidual NK Cells in Women With Recurrent MiscarriagesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010Dong Wook Park Citation Park DW, Lee HJ, Park CW, Hong SR, Kwak-Kim J, Yang KM. Peripheral blood NK cells reflect changes in decidual NK cells in women with recurrent miscarriages. Am J Reprod Immunol 2010; 63: 173,180 Problem, We aimed to investigate if peripheral blood natural killer (pNK) cell levels are correlated with decidual NK (dNK) cell levels, and if chemokine expression has any role in dNK cell regulation. Method of study, Decidual tissues of women having two or more miscarriages with normal karyotype were collected after miscarriage and an immuno-histochemisty study was made. pNK cells were evaluated using flow cytometric analysis. Results, The %CD3,/56+ and %CD3,/56+/16+ pNK cells showed a significant correlation with mean number of CD56+ dNK cells. The number of decidual CD16+ cells was significantly higher in women with elevated pNK (,15%) than that of normal pNK (<15%). The %CD3,/56+ and %CD3,/56+/16+ pNK cells showed an inverse correlation with duration of gestation. The CCL3+ and CXCL12+ cells were present in the decidua; however, staining intensity was not correlated with number of dNK cells. Conclusion, The pNK cell levels reflect changes in dNK cell levels. This implicates that pNK cell level is a clinically useful marker to predict pregnancy outcome. Further study is needed to examine if elevated pNK cells enhance recruitment of dNK cells in the decidua. [source] Distributions of Endometrial NK Cells, B Cells, T Cells, and Th2/Tc2 Cells Fail to Predict Pregnancy Outcome Following Recurrent AbortionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2002TOSHIHIKO MICHIMATA PROBLEM: To evaluate the ability of immunophenotypes of endometrial leukocytes from patients with histories of recurrent abortion to predict outcome of subsequent pregnancy. METHODS OF STUDY: Seventeen women with two successive spontaneous abortions with normal karyotype in the conceptus and 15 women with male-factor infertility were studied. Subsequent pregnancy outcomes in 17 recurrent abortion patients were noted; 11 had live birth, while six aborted in the first trimester. All of 15 women with male-factor infertility became pregnant after therapy, resulting in live birth in all cases. Endometrium was sampled during the peri-implantation period before subsequent pregnancy. We immunostained paraffin-embedded sections for lymphocyte markers including natural killer (NK) cell markers, CD56 and CD16, a B-cell marker CD20, T-cell markers CD3 and CD8, and a specific T-helper(Th)2 and T-cytotoxic (Tc)2 marker termed `chemoattractant receptor-homologous molecule expressed on Th2 cells' (CRTH2). Immunoreactive cells for these antigens were counted and positivity ratios to CD45- or CD3-positive cells were calculated. These parameter were compared between 17 patients with histories of recurrent abortion and 15 control women and also compared between 11 patients whose subsequent pregnancy was successful and six patients whose subsequent pregnancy was a failure. RESULTS: Numbers of CD45+, CD56+, CD16+, CD20+, CD3+, CD8+, and CRTH2+ cells in recurrent abortion patients resembled those in controls. No significant difference in lymphocyte subset numbers or ratios was noted between patients whose subsequent pregnancy was successful and those who again aborted. CONCLUSION: We could not predict pregnancy outcome by immunophenotypic analysis of endometrium in women with recurrent abortion. [source] Mitochondrial DNA analysis of Nepalese domestic dwarf cattle Lulu,ANIMAL SCIENCE JOURNAL, Issue 2 2004Kumiko TAKEDA ABSTRACT Dwarf Lulu cattle, the only Bos Taurus type of cattle in Nepal, are raised under severe environments in the mountainous zone of that country. In the present study, the body measurement traits, cytogenetic and molecular genetic characteristics of the Lulu cattle are investigated. Blood samples were collected from 31 animals in four villages (altitudes 2590,3550 m) in the southern part of Mustang. The Lulu cattle had a normal karyotype with 2n = 60, XY or XX. Only one male examined had a large submetacentric X-chromosome and a small submetacentric taurine type Y-chromosome. The mitochodrial DNA (mtDNA) genotypes were analyzed by PCR mediated restriction fragment length polymorphisms, displacement (D)-loop region PCR mediated single strand conformation polymorphisms, and D-loop region sequences. Many base substitutions were found in the D-loop region, suggesting that the Lulu cattle originated from at least 10 maternal lines. Three types of mtDNA from these cattle were found, the Bos taurus type (n = 23), the Bos indicus type (n = 6), and the Bos grunniens type (n = 2). In the village at the lowest altitude, four of the five cows were of the Bos indicus type. These results indicated that mtDNA types of the Lulu cattle mostly belong to Bos taurus, but have been hybridized with Bos indicus cattle in lower-elevation regions in their maternal lineage. [source] The outcomes of pregnancies following a prenatal diagnosis of fetal exomphalos in Western AustraliaAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 4 2009Nick CALVERT Aims: To review the perinatal outcomes for prenatally diagnosed exomphalos from a single geographical region. Methods: Retrospective review of cases of prenatally identified exomphalos in the state of Western Australia in the ten-year period 1998,2007 using the medical databases of the sole tertiary obstetric and paediatric hospitals. Results: Ninety-four cases of prenatally identified exomphalos comprise this consecutive case series. Culture-proven karyotypic abnormalities occurred in 40 (42.6%) fetuses. No karyotypically abnormal fetus survived the neonatal period, with 33 of 40 (82.5%) pregnancies interrupted, five of 40 (12.5%) resulting in fetal demise and two (5%) neonatal deaths. For the 49 (52.1%) fetuses with a normal karyotype, 26 (53.1%) had associated abnormalities with termination occurring in 22 (84.6%). Prenatally isolated exomphalos was present in 23 cases (24.5%), with live birth in 15 cases (30.6% of euploid fetuses). Fourteen (93.3%) of the liveborn prenatally isolated exomphalos cases survived with no postoperative deaths, although four (28.5%) had significant abnormalities detected postdelivery and most have experienced childhood morbidity. Conclusions: In the the majority of cases of prenatally detected exomphalos the pregnancy was interrupted secondary to chromosomal or structural abnormalities. In only 10.6% of prenatally recognised fetuses with exomphalos was the disorder truly isolated with neonatal survival occurring. [source] A randomised trial of two methods of issuing prenatal test results: the ARIA (Amniocentesis Results: Investigation of Anxiety) trialBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 4 2007J Hewison Background, Many pregnant women experience anxiety while waiting for the results of diagnostic tests. Policies and practices intended to reduce this anxiety require evaluation. Objectives, To test the following two hypotheses: ,,That giving amniocentesis results out on a fixed date alters maternal anxiety during the waiting period, compared with a policy of telling parents that the result will be issued ,when available' (i.e. variable date). ,,That issuing early results from a rapid molecular test alters maternal anxiety during the waiting period, compared with not receiving any results prior to the karyotype. The effects of the two interventions on anxiety 1 month after receiving karyotype results were also examined. Design, A multicentre, randomised, controlled, open fixed sample, 2 × 2 factorial design trial, with equal randomisation. Setting, The prenatal diagnosis clinics in 12 hospitals in England offering amniocentesis as a diagnostic test for Down's syndrome. Sample, Two hundred and twenty-six women who had had an amniocentesis were randomised between June 2002 and July 2004. Eight women with abnormal results or test failure were excluded postrandomisation. Interventions, Issuing karyotype results on a prespecified fixed date, rather than issuing them as soon as they became available. Issuing karyotype results alone, or subsequent to issuing results from a rapid molecular test for the most common chromosomal abnormalities. Main outcome measures, Average anxiety during the waiting period, calculated using daily scores from the short version of the Spielberger State-Trait Anxiety Inventory (STAI). Anxiety 1 month after receiving karyotype results, measured using the short form STAI. Results, Issuing early results from a partial but rapid test reduced maternal anxiety by a clinically significant amount during the waiting period (mean daily score 12.5 versus 14.8; scale score difference ,2.36, 95% CI ,1.2, ,3.6), compared with receiving only the full karyotype results. There was no evidence that giving out karyotype results on a fixed or on a variable date altered maternal anxiety during the waiting period (mean daily score 13.2 versus 14.2; scale score difference ,1.02, 95% CI ,2.2, 0.2). One month after receiving normal karyotype results, anxiety was low in all groups, but women who had been given rapid test results tended to be more anxious than those who had not (mean single day score 9.2 versus 8.3; mean scale score difference 0.95, 95% CI ,0.03, 1.9). This small to moderate effect did not reach conventional levels of statistical significance. Conclusions, Rapid testing was a beneficial addition to karyotyping, at least in the short term. This does not necessarily imply that early results would be preferred to comprehensive ones if women had to choose between them. Because there are no clear advantages in anxiety terms of issuing karyotype results as soon as they become available, or on a fixed date, women could be given a choice between them. [source] Changes in nuchal translucency thickness in normal and abnormal karyotype fetusesBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 6 2003Maria A. Zoppi Objective To investigate the dynamic trend of the nuchal translucency thickness between fetuses with normal and abnormal karyotype. Design Prospective observational study. Setting Ospedale Microcitemico, Cagliari, Italy. Population A cohort of 305 first trimester fetuses. Methods Fetuses with a nuchal translucency greater than or equal to the 95th centile were invited for a second nuchal translucency measurement. The finding of an ,increased or unchanged' or ,diminished' thickness was compared in fetuses with normal and abnormal karyotype. Main outcome measures Nuchal translucency and karyotype. Results Median maternal age was 35 years (min 17, max 44) and median crown,rump length at first visit was 50 mm (min 38, max 80). A second nuchal translucency measurement was carried out in 292 fetuses, resulting in increased or unchanged values in 95 cases and decreased nuchal translucency in 197 cases. Two hundred and twenty-six (77.4%) fetuses had normal karyotype and 66 (22.6%) had abnormal karyotype (44 trisomies 21, 10 trisomies 18, 5 trisomies 13, 4 cases of 45 X0, 1 case of 47,XXY, 1 case of 47,XXX and 1 translocation). In the 66 chromosomally abnormal fetuses, the second nuchal translucency measurement was enlarged or unchanged in 37 (56%), and diminished in 29 (44%), while in the 226 normal fetuses the second nuchal translucency measurement was enlarged or unchanged in 58 cases (25%) and diminished in 168 (75%) (relative risk 2.6, 95% confidence interval 1.7,4.0). Conclusion In fetuses with abnormal karyotype, the second nuchal translucency measurement tends to be increased or unchanged, while in normal cases the size of nuchal translucency is generally reduced. [source] Total alpha-fetoprotein and Lens culinaris agglutinin-reactive alpha-fetoprotein in fetal chromosomal abnormalitiesBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 11 2001Ritsu Yamamoto Objective To examine the differences in multiples of the median (MoM) of total alpha-fetoprotein, and the proportion of Lens culinaris agglutinin reactive alpha-fetoprotein (% alpha-fetoprotein-L2+L3) in the maternal serum and amniotic fluid of pregnant women whose fetuses were diagnosed with autosomal or sex chromosomal abnormalities. Design Prospective consecutive series. Setting University hospital. Sample Maternal sera and amniotic fluids from 46 pregnant women with trisomy 21 fetuses, 10 pregnant women with trisomy 18 fetuses, one pregnant woman with a trisomy 13 fetus, six pregnant women with fetal sex chromosomal abnormalities, and 100 pregnant women for whom the fetal karyotype was diagnosed as normal following a genetic amniocentesis. Results The proportion of alpha-fetoprotein-L2+L3 in maternal serum for trisomy 21 (40.3%, P<0.0001) and trisomy 18 (39.8%, P<0.05) showed a significantly higher value compared with normal (32.6%). The proportion of alpha-fetoprotein-L2+L3 in amniotic fluid was significantly higher (P<0.0001) for trisomy 21 (46.6%) than for a normal karyotype (41.5%). Only for the trisomy 21 group was there a strong correlation in the % alpha-fetoprotein-L2+L3 between maternal serum and amniotic fluid (r=0.840, P<0.0001). For all groups, there was no correlation between alpha-fetoprotein MoM and % alpha-fetoprotein-L2+L3 in maternal serum and amniotic fluid. Conclusion The proportion of alpha-fetoprotein-L2+L3 in maternal serum is an appropriate choice for a trisomy 21 biochemical marker, and it is possible that combining alpha-fetoprotein-L2+L3 analysis with assays of alpha-fetoprotein in maternal serum could further improve the sensitivity and specificity of multiple marker screening. 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