Maternoembryonic transfusion and congenital malformations: an experimental study using rat embryos

In an experimental study, using an in vitro whole rat embryo culture, the effects of a maternoembryonic transfusion and immunologic interaction on the development of ten-day-old rat embryos (stages 8 to 10 somites) has been studied. Transplacental transfusion has been simulated by embryonic intracardiac microinjection of 0.1 to 0.5 microL immunologically active rat serum. After an incubation of 24 and 48 hours, respectively, the embryos were killed. All tested embryos have survived the incubation period. On microscopic examination of the tested embryos those that were taken from the incubator after 24 hours showed no signs of pathogenic cell degeneration, while the embryos that were taken from the incubator after 48 hours all had localized lesions with pathogenic cell degeneration in one or multiple major structures. The neurectoderm and endoderm seem to be the most sensitive tissues in this period of organogenesis. The results suggest that immunologic reaction to transplacental transfusion of maternal serum may lead to congenital malformations.     

Effects of hypoxia on the embryogenesis of congenital vertebral malformations in the mouse

With use of the mouse as the experimental animal and hypoxia as the teratogenic agent, the author produced congenital vertebral malformations identical in form to those found in man. Induced malformations were present in the cartilaginous stage of spine development. During the mesenchymal (prechondral) stage, two different phases of interaction occur between the matrix macromolecules (hyaluronate, glycosaminoglycans) secreted by the notochord and the sclerotomic cells. During the first phase, when the matrix is rich in hyaluronate, sclerotomic cells proliferate and migrate around the notochord in the control embryo. At the same time, in hypoxia-treated embryos, the author observed an inhibition of cell proliferation that was concomitant with a delay in reaching the normal concentration of hyaluronate. During the second phase, after the degradation of the hyaluronate complex, when the matrix is rich in free sulfated GAG, cell differentiation occurred around the notochord in control embryos. At this time, in the hypoxia-treated embryos the author found a delay in the liberation of sulfated GAG from the hyaluronate complex, which markedly changed the normal ratio between the sulfated GAG and nonsulfated GAG. He postulates that this delay in liberation of free sulfated GAG produces the asymmetrical (malformed) cartilage primum by asymmetrical cell differentiation.     

Congenital malformations of the external, middle, and inner ear produced by isotretinoin exposure in mouse embryos

Isotretinoin (Accutane), a widely used dermatologic drug, produces severe congenital malformations when used during pregnancy. The isotretinoin teratogen syndrome consists of multiple cardiovascular and craniofacial anomalies, most commonly involving the external ear. This study examined the pathogenesis of isotretinoin teratogenicity in a mouse model, using microdissection and histologic examination of fetal mouse ears after treatment with the drug at various stages of embryonic development. In this study, earlier treatment times frequently produced microtia similar to that seen in affected infants, as well as recognizable patterns of temporal bone and ossicular abnormalities; exposure at a later developmental stage resulted in facial tags with less severely affected ears. Possible teratogenic mechanisms of isotretinoin are discussed. Suitability of the mouse model for studying human congenital craniofacial malformations, such as Goldenhar's and Treacher Collins Syndrome, is also explored.     

Pattern of congenital malformations in Nigerian children

A series of 252 abortuses, stillbirths and neonates at the University of Ilorin Teaching Hospital and ECWA Hospital, Egbe, in Nigeria, were examined by autopsy dissection between 1983 and 1985. Their clinical cohorts in the nurseries, pediatric wards and those subjected to operations were also reviewed. Primary school children volunteers in two Ilorin schools were also examined in 1987 for cardiopulmonary malformations and umbilical hernia. Incident rates for congenital malformations ranged from 0.08 to 38.27% for congenital groin hernia, 2.39 to 8.73% for umbilical hernia, and 0.21 to 21.05% for the entire gastrointestinal tract. Other incident rates are 0.10 to 7.14% for genitourinary tract, 0.33 to 6.69% for CNS, 0.16 to 5.55% for musculoskeletal system, 0.26 to 4.76% for cardiovascular and 0.06 to 3.9% for bronchopulmonary malformations. The scope of the study is expected to make it adaptable in other developing countries.     

Comparison of high- and low-diabetes-incidence NOD mouse strains

The nonobese diabetic (NOD) mouse is a model of insulin-dependent diabetes mellitus. These mice develop insulinopenia and hyperglycemia secondary to beta-cell destruction, which is associated with insulitis and autoantibody production. We have two strains of NOD mice: a low-incidence strain (NOD/Wehi), in which less than 10% females and less than 1% males develop diabetes by 150 days despite intense insulitis, and a high-incidence strain (NOD/Lt), in which most females and many males develop diabetes by 150 days. This phenotypic difference has been maintained for 24 mo despite identical housing in our specific pathogen-free unit. Reciprocal skin grafting and allozyme electrophoresis have not identified a difference between the strains. Mixed-lymphocyte cultures were performed with splenic T-lymphocytes cultured with equal numbers of irradiated stimulator splenocytes for 3-6 days. NOD/Wehi mice demonstrated a heightened syngeneic mixed-lymphocyte response (SMLR), averaging 19% of the allogeneic response to CBA/CaHWehi cells. The response to NOD/Lt stimulator cells was not significantly different from the syngeneic response. In contrast, NOD/Lt mice had an SMLR similar to that of BALB/cAnBradleyWehi control mice, averaging 5% of the allogeneic response. NOD/Lt cells also responded similarly to NOD/Wehi stimulator cells and briskly to allogeneic cells. The heightened SMLR in NOD/Wehi mice may reflect active generation of suppressor function, and this may account for the low incidence of diabetes.     

Megabladder mouse model of congenital obstructive nephropathy: genetic etiology and renal adaptation

Congenital obstructive nephropathy remains one of the leading causes of chronic renal failure in children. The direct link between obstructed urine flow and abnormal renal development and subsequent dysfunction represents a central paradigm of urogenital pathogenesis that has far-reaching clinical implications. Even so, a number of diagnostic, prognostic, and therapeutic quandaries still exist in the management of congenital obstructive nephropathy. Studies in our laboratory have characterized a unique mutant mouse line that develops in utero megabladder, variable hydronephrosis, and progressive renal failure. Megabladder mice represent a valuable functional model for the study of congenital obstructive nephropathy. Recent studies have begun to shed light on the genetic etiology of mgb ^?/? mice as well as the molecular pathways controlling disease progression in these animals.     

ICSI导致小鼠胚胎雄原核H3K9甲基化异常以及胚胎发育迟缓

目的:以小鼠为模型,评估卵细胞胞质内单精子注射(ICSI)技术的安全性。方法:模拟临床ICSI技术,通过孤雌激活、免疫荧光、胚胎移植、早期植入点检测、中期顶臀径检测等实验方法综合评估该技术。结果:ICSI导致小鼠植入前胚胎发育能力显著下降,尤其是8细胞之后的胚胎发育率下降极显著(P<0.01),而且在ICSI胚胎的雄原核上检测到异常的H3K9双甲基化荧光。进一步检测移植后的ICSI胚胎发育情况,结果显示,与对照(正常受精)相比,E5.5 d早期植入率无显著差异(P=0.6),但是E9.5 d的正常胚胎百分率却显著降低(P<0.01),即使在这些正常的ICSI胚胎中也出现了高比例的发育滞后现象。结论:ICSI有可能通过对雄原核H3K9双甲基化的影响进而影响胚胎生长发育。     

先天性血管畸形治疗中的问题与对策

血管畸形是由于胚胎肢芽内原始血管的发育障碍或发育异常所致,是一组先天性血管畸形病变,其临床表现不一,病理组合多样,治疗棘手,一直是医学领域难题之一。尽管近年出现了一些新的诊治手段,其中多已取得肯定效果,但临床上依然存在许多尚未解决的难题。诸如血管畸形的分类问题及如何治疗弥漫性海绵状血管瘤而保留神经肌肉等组织功能、如何选择先天性动静脉畸形栓塞的材料、如何选择先天性静脉畸形骨肥大综合征的处理时机等问题,是影响血管畸形疗效提高的关键环节,近年我科积极采取了一些针对性的处理方法,积累了比较丰富的经验和体会。关于生…     

Fundamental concepts in the management of congenital anorectal malformations

Congenital anorectal deformities present a therapeutic challenge to the paediatric surgeon. The anomalies encountered range in complexity from the most simple to the most intricate. It is for this reason that three clear phases in management are defined and applied in every instance, i.e. absolute clarification of the anatomy of the defect, its appropriate operative correction, and, finally, a protracted postoperative period of care during which time voluntary stool control is acquired. Anal continence is the ultimate functional objective. The meticulous treatment required by the unfortunate baby born with this correctable abnormality is emphasized.     

Associated malformations in delayed presentation of congenital diaphragmatic hernia

Background/Purpose

Delayed presentation of congenital diaphragmatic hernia (CDH) has been considered rare, and clinical manifestations differ from the more common newborn entity. Associated malformations in late-appearing CDH have been reported in a few patients. The authors reviewed their clinical experience to catalogue the frequency and clinical importance of associated malformations in patients with late-presenting CDH.

Methods

The records of patients greater than 1 month of age with Bochdalek type CDH treated in the authors’ clinic, from 1991 to 2001, were retrospectively reviewed. Twenty patients (age range, 1 month to 10 years) were included in the study.

Results

Associated malformations were documented in 16 of the patients (80%) and included malrotation in 12 patients, umbilical hernia in 2, pulmonary hypoplasia in 4, pulmonary sequestration in 1, gastroesophageal duplication cyst coexisting with polysplenia in 1, atrial septal defect and ventricular septal defect in 1, hydronephrosis in 1, wandering spleen in 1, talipes equinovarus in 1, and type I diabetes mellitus in 1.

Conclusions

The results of this study show a significant incidence and a wide spectrum of associated malformations. These findings suggest that patients with late CDH should be evaluated carefully for additional anomalies that may help to establish correct diagnosis and treatment.     

伊立替康药物基因组学研究进展

伊立替康自20世纪90年代问世以来,已广泛应用于结肠直肠癌、肺癌等实体瘤治疗,可明显提高病人的总生存期,但因其毒性较大(Ⅲ～Ⅳ度腹泻和粒细胞缺乏),应用受到限制.伊立替康毒性与其主要的药物代谢酶UGT1A1有关,而其酶活性高低又受UGT1A1基因多态性的影响.     

Progress in the treatment of congenital malformations of the hand

Treatment of congenital malformations of the hand and forearm has progressed not only from new procedures, but especially due to a new technique, namely microsurgery. Microsurgery enables skilled hand surgeons to operate on the tiny hands of babies without damaging the anatomical structures. The optimal time for the correction of many deformities is during the first 2 years of life. This gives excellent adaptation of the corrected structures to their altered function, especially in combination with a long period of further growth. Several new procedures are described which have been made possible only since the introduction of microsurgery, either by microvascular anastomoses or by meticulous dissection technique (toe transplantation, proximal toe phalanx transplantation, nail wall formation in complex syndactyly, transposition of digital parts in polydactyly and radial club hand).

---

Resumen El tratamiento de las malformaciones congénitas de la mano y el antebrazo ha progresado no sólo en términos de nuevos procedimientos, sino, especialmente, en razón de una nueva técnica, la microcirugía. La microcirugía permite que los cirujanos de mano idoneos puedan operar sobre las pequeñas manos de bebés sin causar daño a las estructuras anatómicas. La época óptima para la corrección de muchas deformaciones es durante los 2 primeros años de vida. Esto hace posible una excelente adaptatión, de las estructuras que han sido corregidas a la función alterada, especialnmente durante períodos prolongados del crecimiento. Se describen algunos nuevos procedimientos que han sido factibles sólo desde la introducción de la microcirugía, bien sea por anastomosis microvascular o por una meticulosa técnica de disecci [trasplante de un artejo, transplante de la falange proximal, formación de la uña en sindatilia compleja, transposición de partes de dígitos en polidactilia y en mano zamba radial (club hand)].

---

Résumé Le traitement des malformations congénitales de la main et de l'avant-bras a progressé non seulement grâce à de nouveaux procédés mais surtout grâce à l'apparition de toute une technique nouvelle: la microchirurgie. Celle-ci permet à des chirurgiens de la main expérimentés d'opérer les toutes petites mains des jeunes enfants sans compromettre la fonction des structures anatomiques. Les 2 premières années de la vie sont la meilleure période pour corriger la plupart des malformations: elles permettent une adaptation excellente des structures de fonction auparavant altérée, en se combinant avec la longue période de croissance à venir. Plusieurs procédés nouveaux sont répertoriés. Ils sont devenus possibles seulement depuis l'introduction de la microchirurgie: il s'agit notamment des anastomoses microvasculaires ou des techniques méticuleuses de dissection comme le transfert d'orteil ou de la phalange proximale de l'orteil, la création du mur latéral d'ongle dans un cas de syndactylie complexe ou la transposition de segments des doigts pour polydactylie ou main bote radiale.

     

小鼠着床前胚胎miRNA表达的实验研究

目的研究微小RNA(miRNA)在小鼠着床前胚胎各发育阶段的表达谱,探讨miRNA在着床前胚胎发育中的作用和意义。方法建立小鼠超排卵、交配和胚胎收集系统,采用miRNA扩增、miRNA芯片和荧光实时定量逆转录聚合酶链反应(RT-PCR)的方法研究小鼠着床前胚胎miRNA表达。结果小鼠卵母细胞、2细胞胚胎、4~8细胞胚胎和囊胚分别表达55、53、62和72个miRNA;四个发育阶段共筛查到表达94个miRNA,32个在各发育阶段均表达,62个在不同发育阶段特异性表达。实时荧光定量PCR方法验证mmu-miR-721在小鼠着床前胚胎中表达。结论小鼠着床前胚胎表达大量的miRNA,其可能对胚胎发育和胚胎细胞的分化起重要调控作用。