Studies in neural tube defects I. Epidemiologic and etiologic aspects

In the NIH Collaborative Perinatal Project, a prospective study of over 53,000 pregnant women and their offspring, 71 single-born children (13.33/10,000) were found to have a non-syndromal neural tube defect (NTD). A family history was present in only one case. The group of individuals with NTD was compared to a group of 400 randomly selected non-malformed control infants. Of over 50 maternal factors studied the following showed significant association with NTD in the offspring: diabetes mellitus; organic heart disease; lung disease; and diuretic, antihistamine, and sulfonamide use. The interval between the termination of the immediately previous pregnancy and the start of the proband pregnancy was significantly shorter in mothers of NTD children than in mothers of control infants. The risk for NTD was also significantly increased if the immediately previous pregnancy was a spontaneous abortion. There was no increased risk for NTDs among sibs of children with major malformations such as tracheo-esopha-geal “dysraphism,” cleft lip/palate, or renal agenesis. NTDs are apparently etiologically heterogeneous.     

Effect of Intra-Scrotal Implants of Prostaglandin E2 or F2α on Blood Steroids in the Adult Male Rats

The effects of the insertion of Silastic-PVP tubes containing either 3 mg PGF_2α or 3 mg PGE₂ per tube into each of the scrotal sacs on steroid concentration were studied in the mature male rat. Seven days after the insertion a more pronounced reduction in the weights of the testes, ventral prostate and seminal vesicles was recorded in the PGE₂- than in the PGF_2α-treated males. Further, it was observed that 3 and 7 days after the initiation of treatment the serum testosterone concentration significantly decreased ( P < 0.01). Likewise, serum 5α-dihydrotestosterone, androstenedione and progesterone were also reduced significantly. This suggests that a decrease in progesterone synthesis impairs androgen production, which in turn leads to a reduction in the weights of testes, epididymides and accessory glands.     

Theoretical consideration of drug distribution kinetics in a noneliminating organ: Comparison between a “homogeneous (well-stirred)” model and “nonhomogeneous (tube)” model

Drug distribution kinetics in a noneliminating organ or tissue has been mathematically examined. The homogeneous (well-stirred) model regards the noneliminating organ or tissue as a homogeneous compartment in which the drug is equilibrated with that in the blood leaving the organ or tissue. The nonhomogeneous (tube) model views the noneliminating organ or tissue as comprising a number of parallel cylindrical tubes containing binding sites distributed homogeneously along these tubes. These two models are examined, considering the pseudo-distribution equilibrium phase after bolus injection and a linear binding condition. Although both models predict a similar tissue distribution under a variety of conditions, significant differences exist in the predictions of various pharmacokinetic parameters as a function of the drug distribution, such as blood flow, organ volume, slope of the terminal phase, and the tissue-to-blood partition coefficients. The predictability and limitations of these two models are explored. Distribution characteristics of the two models are also examined for adriamycin, actinomycin D, tetrachlorobiphenyl, hexachlorobiphenyl, digoxin, and ethoxybenzamide; no difference is observed. It is concluded that the assumption of a homogeneous (well-stirred) compartment is suitable for describing the drug distribution kinetics of these drugs.Abstracted in part from a dissertation submitted by T.T. to the Graduate School, Division of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan, in partial fulfillment of the Doctor of Philosophy degree requirements.     

The influence of excess vitamin A on neural tube closure in the mouse embryo

Summary The effect of excess vitamin A on the closure of the neural tube in mouse embryos was examined with light microscopy, transmission and scanning electronmicroscopy. The embryos were treated with the vitamin just before closure of the brain vesicles and examined during the following 24 h, a period during which under normal conditions the brain completely closes.At 18–24 h after treatment the external features of the treated specimens began to differ from those of the controls. In the treated embryos the neural walls folded laterally and became widely separated, whereas those of the controls folded dorsomedially and fused in the midline. Histologically, the first difference between treated and control embryos was noted at two hours after treatment, when large intercellular spaces appeared between the neuroepithelial cells of the treated embryos. These spaces were mainly present between the apical ends of the wedge-shaped neuroepithelial cells. This accumulation of intercellular spaces interfered with the normal morphogenetic movement of the neural walls, which remained convex instead of becoming concave. This convex bending resulted in non-closure of the neural tube.In addition to the appearance of large intercellular spaces some neuroepithelial cells as well as some mesenchymal, endothelial, and surface ectoderm cells showed swelling and degeneration as a result of the vitamin A treatment. This cell degeneration probably contributes to failure of the neural tube to close due to loss of cohesion at the luminal surface and the lack of mesenchymal support needed for the elevation of the neural walls. However, the increase of intercellular spaces at the apical side of the neuroepithelium is in all probability the major cause for the failure of the neural tube to close.     

定性分析羊水乙酰胆硷酯酶在早期诊断开放性神经管缺陷胎儿中的应用

分析羊水乙酰胆硷酯酶是早期诊断开放性神经管缺陷胎儿(NTDs)的一种新的、可靠的检测方法。鉴于目前所用的定量法测定羊水胆硷酯酶的可靠性差,本文介绍了一种分辨率高的定性分析法,即垂直平板聚丙烯酰胺凝胶电泳法。其优点是操作方便、判断结果容易、可靠;设备简单;国内可供应各类必需试剂,便于推广应用。结合9例NTDs 结果的初步分析,提示妊娠期越早的羊水标本,其诊断的正确率越高。     

Immunologic-mediated eustachian tube obstruction: a double-blind crossover study

Eight subjects with seasonal allergic rhinitis confirmed by positive skin tests and serum radioallergosorbent test to ragweed or timothy grass pollen were identified. A double-blind provocative antigen challenge was performed with intranasal insufflation of 50 mg of dry pollen to which the subject was either sensitive (ragweed or timothy) or not sensitive (pine). Before and after pollen insufflation, measurements of nasal function by nasal rhinomanometry and eustachian tube (ET) function by the nine-step tympanometry test were performed for up to 14 days. The ability to dilate the ET was documented in 14 of the 16 ears of the eight subjects before challenge. Within 30 min after antigen challenge transient obstruction of the ET associated with inability to dilate upon swallowing was observed in all 14 ears. Clinical symptoms of allergic rhinitis, including rhinorrhea and nasal obstruction, were produced in all subjects. ET function changes were reversible in three of 14 ears within 2 hr but persisted for more than 3 days in six of the ears. As a control, insufflation of pine pollen did not alter ET function or rhinomanometric values or produce clinical symptoms in the eight subjects. These findings suggest an allergic basis for ET obstruction and possibly for the development of otitis media with effusion.     

Balloon tamponade to control haemorrhage following transanal rectal surgery

Background Bleeding following transanal rectal surgery can be difficult to manage. Case We report a case where a Minnesota tube was used to achieve haemostasis in a patient with severe bleeding after transanal excision of a large dysplastic polyp.     

Water sources are associated with childhood diarrhoea prevalence in rural east-central Mali

BACKGROUND: Water supply improvements generally reduce the incidence of diarrhoea. However, populations with limited access to a safe water supply may continue to draw water from unimproved sources, thereby increasing their risk of diarrhoea. Furthermore, young children who are not breastfed may be even more susceptible to water-borne diarrhoeal pathogens. Our study explored the interactive protective effects against diarrhoea of exclusively using improved water sources and breastfeeding among children in rural Mali. METHODS: Interviews were conducted with parents or guardians of children under 7 years of age in seven villages with access to a variety of water supplies. Water sources used, breastfeeding status, demographics and recent diarrhoea symptoms were determined for 1117 children. The cross-sectional findings were used to compare diarrhoea prevalence among exclusive and non-exclusive users of improved water sources. Variation in prevalence by age and exclusive breastfeeding status was evaluated using chi-square and multivariate analyses. RESULTS: Children whose water was drawn exclusively from wells had a significantly lower prevalence of diarrhoea as compared with children whose water was drawn from a spring or stream (5.9% vs. 8.7%; P=0.04). The exclusive use of improved water sources had no impact on diarrhoea prevalence among children who were exclusively breastfed. Similarly, the strongest protective effect was observed among children who were not exclusively breastfed. CONCLUSIONS: Our results indicate that using surface water as a primary or secondary water source exposes children to greater risk of diarrhoeal disease than using only improved sources such as wells. It is particularly beneficial for young children who are not exclusively breastfed to be supplied with water drawn from improved sources.     

Novel association of VACTERL,neural tube defect and crossed renal ectopia – Sonic hedgehog signaling: A point of coherence?

The present case report describes two patients with a novel combination of VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb), neural tube defect and crossed renal ectopia. Though cases of VACTERL associated with crossed renal ectopia have been described, the present case report is the first to describe its combination with neural tube defect. The cases reported here are significant because central nervous system manifestations are scarce in VACTERL syndrome. The role of sonic hedgehog pathway has been proposed in VACTERL association and neural tube defects. Axial Sonic hedgehog signaling has also been implicated in the mediolateral positioning of the renal parenchyma. With this knowledge, the etiopathogenesis of this novel combination is discussed to highlight the role of sonic hedgehog signaling as a point of coherence.