Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DEFECTIVES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,441 records · Page 80Linked to original sources
PubMed1986

The use of demineralized bone matrix in the repair of segmental defects. Augmentation with extracted matrix proteins and a comparison with autologous grafts.

A soluble protein component of bone, bone morphogenetic protein, and decalcified bone matrix have been shown to induce the formation of bone in extraosseous tissue. Clinical and animal studies investigating the use of these materials as bone grafts have shown radiographic and histological evidence of formation of bone, but the clinical usefulness of these grafts remains unknown. This study compared the healing processes when plasma-coated demineralized bone matrix and autologous cancellous bone were used to graft segmental defects of bone. A standard procedure was used to make a two-centimeter defect bilaterally in the ulna of forty-eight skeletally mature New Zealand White rabbits. In each rabbit, one ulnar defect was grafted with autologous citrated plasma-coated demineralized bone matrix while the other defect served as a control and was grafted with either autologous cancellous bone from the iliac crest, demineralized bone matrix, or demineralized bone matrix augmented with bone proteins that had been extracted with guanidinium hydrochloride. The ulnar defect was stabilized by the intact radius, and no supplemental device was necessary for fixation. To examine spontaneous healing in this model, one group of rabbits had a control defect that was not grafted. The grafts were periodically evaluated by radiographs, and twelve weeks after surgery the grafts were harvested and tested to failure in a standard torsion-test machine. The mechanical parameters were calculated, and histological examination of major fragments of the grafts was performed. The results of the radiographic and histological evaluation showed that all of the grafted ulnae healed, with fusion of the graft to the cut ends of the defect and reformation of approximately normal anatomy. No ungrafted ulnar defects healed. The results from the mechanical tests were evaluated by comparing the defect that was grafted with plasma-coated demineralized bone matrix with the control graft in each animal. These data showed that: twelve weeks after grafting, the normal ulnae were significantly stronger than the ulnae that had been grafted with plasma-coated demineralized bone matrix; the ulnae that had been grafted with plasma-coated demineralized bone matrix and those that had been grafted with autologous bone were equivalent in strength; and twelve weeks after grafting, grafts of demineralized bone matrix that were augmented with extracted bone proteins were significantly stronger than those that had not been so augmented.

Amino Acids↗
PubMedDate not supplied

Granular tricalcium phosphate in large cancellous defects.

Tricalcium phosphate (TCP) is a porous ceramic which has biological properties of being non-reactive and resorbable, and acts as a scaffolding for bone ingrowth, undergoing progressive degradation and replacement by bone. Tricalcium phosphate has been shown to be comparable to autogenous bone graft in small periodontal defects. However, orthopedic defects are much larger. This prompted us to review the bone ingrowth potential in large cancellous bone defects (up to 12 cm3) in adult pigs. To quantitate bone ingrowth potential, three skeletally mature pigs had metaphyseal defects created in the tibia and femur of each hind limb, for 12 total sites. Twelve-cc defects in the distal femur and eight cc defects in the proximal tibia were made. Bone curetted was saved to be used as autogenous graft in the control, while the other ipsilateral defect was packed with tricalcium phosphate. Four months following the initial defect, the opposite hind extremity was similarly operated. All animals were sacrificed at nine months. Specimens were imbedded in methyl-methacrylate, cut at 120 microns, and stained. The quantity of regenerated bone was measured by histomorphometric techniques. Qualitative assessment at four months revealed absence of inflammation and TCP surrounded by trabecular bone, which was uniformly viable. There was very little TCP left by nine months. Quantitative analysis revealed the tibias to have a higher percent net bone replacement with TCP as compared to the control (32 percent versus 13 percent). The femoral TCP-filled defects were comparable to autogenous bone (both measured 29 percent).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

The assessment of non-carious defects of enamel.

Developmental defects of dental enamel are very common with at least one in every three individuals having one or more teeth with obvious non-carious defect. The more common defects are opaque areas, hypoplasias (missing enamel) and discoloured enamel; the variety in form, severity and combination of defects is extensive. The lesions are sequelae of systemic, traumatic or genetic events during tooth development. A review of past and current terminologies, and classifications of developmental defects of enamel, reveals ambiguities, deficiencies and lack of uniformity in methods and criteria used in their study. The principal objective for collecting and recording observations on enamel defects is to determine their frequency, severity and distribution for the purpose of assessing the magnitude of the clinical problem they generate and their aetiology. Hence, an internationally recognized classification of developmental enamel defects and recording procedure would increase the value and comparability of future studies. An acceptable uniform terminology and a simple procedure for classifying the more commonly observed defects, defined by their visual characteristics, would achieve these aims. A classification is proposed which identifies and defines the type, number and location of developmental defects affecting tooth enamel on the buccal and lingual surfaces of all teeth. The procedure has been designed for easy interpretation and simple evaluation. It may be modified for use with much less extensive clinical examination.

Adolescent↗
PubMed1995

[Effect of traumatic iris defects on spatial perception].

Perforating injury to the eye often results in iris defects in addition to loss of the lens. To determine whether iris defects can impair stereopsis, we tested the stereoscopic vision of 23 patients treated at the University Eye Clinic in Kiel for perforating eye injuries involving the iris and, in most cases, the lens. The patients were divided into three groups according to the severity of the iris defect and the status of the intraocular lens. Individuals with strabismus or visual acuity < 0.5 (20/40) were excluded. Stereopsis was measured using conventional stereopsis tests (Titmus contour stereopsis, Lang global stereopsis) and by means of the Pulfrich pendulum phenomenon. Patients with traumatic aphakia without an iris defect (n = 33) served as controls. Optical rehabilitation was achieved in the controls lenses (n = 16) or intraocular lens implant (n = 17). In group I (intact lens, iris defect < 135 degrees), two of five patients had attained global stereopsis. In group II (implanted or contact lens, iris defect < 135 degrees), only one of the nine patients exhibited global stereopsis. In group III (no lens, iris defect > 135 degrees), none of the nine patients achieved global stereopsis. In the control group, by contrast, more than half of the patients with an implant (10 of 17) and 3 of 16 patients with a contact lens attained global stereopsis. The results indicate that severe iris defects are especially likely to impair stereoscopic vision, more so than traumatic loss of lens alone without an accompanying iris defect.

Adolescent↗
PubMed1993

The Plunket National Child Health Study: birth defects and sociodemographic factors.

AIMS: The Plunket National Child Health Study was set up to examine the health experience of a representative sample of New Zealand children. This paper examines the association of birth defects with the sociodemographic variables of maternal age and education, parity, socioeconomic group, region of domicile and marital status; infant's ethnic group and sex. The effect of maternal smoking on the prevalence of birth defects was also examined. The paper compares the prevalence of birth defects in infants alive at 6 weeks with the reported prevalence at birth as described in various other publications. METHODS: A cohort of 4286 children born in New Zealand during 1990-1 were enrolled in the study. The presence of birth defects in the study population was determined by clinical examination and review of hospital or midwife referrals. All described defects were reviewed and coded according to the ICD-9. RESULTS: The overall prevalence of birth defects in the study was 4.3%. There was a significant association between socioeconomic status and the incidence of birth defect but no other significant sociodemographic variations. Cigarette smoking had no statistically significant effect on the rate of birth defects. There was a marked difference between the rates for certain defects in the Plunket study when compared to Health Department notifications. CONCLUSIONS: Because of the differences between the current study and official Health Department notifications we suggest that criteria for congenital anomaly notification are clarified, and that a second notification takes place at six weeks of age.

Adult↗
PubMed1994

Fibula osteoseptocutaneous flap for reconstruction of composite mandibular defects.

The fibula osteoseptocutaneous flap is a versatile method for reconstruction of composite-tissue defects of the mandible. The vascularized fibula can be osteotomized to permit contouring of any mandibular defect. The skin flap is reliable and can be used to resurface intraoral, extraoral, or both intraoral and extraoral defects. Twenty-seven fibula osteoseptocutaneous flaps were used for composite mandibular reconstructions in 25 patients. All the defects were reconstructed primarily following resection of oral cancers (23), excision of radiation-induced osteonecrotic lesions (2), excision of a chronic osteomyelitic lesion (1), or postinfective mandibular hypoplasia (1). The mandibular defects were between 6 and 14 cm in length. The number of fibular osteotomy sites ranged from one to three. All patients had associated soft-tissue losses. Six of the reconstructions had only oral lining defects, and 1 had only an external facial defect, while 18 had both lining and skin defects. Five patients used the skin portion of the fibula osteoseptocutaneous flaps for both oral lining and external facial reconstruction, while 13 patients required a second simultaneous free skin or musculocutaneous flap because of the size of the defects. Four of these flaps used the distal runoff of the peroneal pedicles as the recipient vessels. There was one total flap failure (96.3 percent success). There were no instances of isolated partial or complete skin necrosis. All osteotomy sites healed primarily. The contour of the mandibles was good to excellent.

Adult↗
PubMed1993

Prevalence and types of birth defects in Ontario swine determined by mail survey.

Preweaning mortality in piglets constitutes a major loss to the swine industry. Congenital defects account for a small but significant proportion of these losses. To implement appropriate strategies to reduce such losses, it is necessary to identify the specific causes and their relative importance. Consequently, a mail survey of swine production in Ontario was carried out to determine the prevalence and types of birth defects. Statistical comparisons of the prevalence of overall defects were made between accurate and estimate records, breeds (cross vs. purebred), size of operation (number of sows) and geographic location. The mean litter size of 11 pigs born per sow was not significantly different for those with accurate versus estimate records, but the difference in the prevalence of defective pigs (live and dead) was significant (accurate 3.1% vs. estimate 4.1%). Splayleg (spraddleleg) was the most common defect. The next four defects for both groups were belly rupture, other rupture, ridglings and other, but not in the same ranking. Purebred and small farm operations (< 25 sows) had a significantly higher prevalence of birth defects for estimated data only. Geographic location had no effect. Further work is required to determine whether recording prevalence of birth defects in Ontario swine will provide a useful monitor of environmental stress. The study provides a baseline for the prevalence and type of defects in Ontario swine.

Animal Husbandry↗
PubMedDate not supplied

Guided tissue regeneration and local delivery of insulinlike growth factor I by bioerodible polyorthoester membranes in rat calvarial defects.

Thirty 8-week-old male Wistar rats were randomly allocated into three groups of 10 rats each. A 5-mm defect in the left parietal bone was made in each rat. In the defects of the first group of rats, no implant was used (control group). In the second group, polyorthoester membranes were placed in the defects without active substance. In the third group, polyorthoester membranes were placed with insulinlike growth factor I. The rats were sacrificed 6 weeks postoperatively. Bone formation in the defects was quantified by computer-assisted measurements of the area of the residual defect on radiographs. Host-tissue response was evaluated by light microscopy. The area of residual bone defect was greatest in the control group, less for the defects with polyorthoester membrane without active substance, and least for the defects with polyorthoester membranes with the growth factor. During histologic evaluation, no inflammation was seen, and only traces of the polyorthoester were detected in the defects with polyorthoester membrane with or without the growth factor.

Animals↗
PubMed1985

Evaluation of bendectin embryotoxicity in nonhuman primates: I. Ventricular septal defects in prenatal macaques and baboon.

Cynomolgus monkeys, rhesus monkeys and baboons were administered 10 to 40 times the human dose equivalent of Bendectin throughout the major period of organogenesis (22(+/-3)-50 days of gestation). In animals examined prenatally (100 +/- 2 days gestation) the total incidence of ventricular septal defects (VSD) was 40% in cynomolgus monkeys, 18% in rhesus monkeys, and 23% in baboons. The majority of VSD involved the muscular portion of the septum. No dose response was evident and there were no other cardiac or extracardiac defects found except for one baboon fetus with multiple defects. No defects were observed in cynomolgus monkeys administered Bendectin for 4-day periods between 22 and 41 days of gestation. There was no association of Bendectin treatment with any noncardiac defect. In cynomolgus and rhesus monkeys examined at term there was one mitral valve defect and no incidence of VSD. The increased incidence of VSD observed prenatally in all three species and the absence of defects in macaques at term suggests a delay in closure of the ventricular septum in treated animals. The Bendectin-treated monkey may be a suitable model for the study of the pathogenesis of VSD and the mechanism of spontaneous closure of the defect.

Animals↗
PubMed1988

Are routine preoperative cardiac catheterization and angiography necessary before repair of ostium primum atrial septal defect?

Two-dimensional and Doppler echocardiography were compared with cardiac catheterization and angiography in the preoperative evaluation of ostium primum atrial septal defect. Preoperative echocardiographic examinations as well as operative reports of all patients (33 patients aged 2 months to 23 years at surgery) with ostium primum atrial septal defect or transitional atrioventricular (AV) canal defect having had echocardiography and surgical repair at The Children's Hospital, Boston from July 1983 to January 1986 were retrospectively reviewed. Original cardiac catheterization and angiographic reports also were reviewed. Preoperative echocardiography resulted in no false positive or false negative primary diagnoses when compared with the diagnoses obtained at preoperative angiography or surgery. Doppler assessment of mitral regurgitation correlated well with angiographic (93% agreement) and intraoperative (85% agreement) assessments of mitral regurgitation to within two diagnostic categories on the six level scoring system used. There was reasonably good agreement between the two-dimensional echocardiographic estimate of right ventricular systolic pressure and that measured at catheterization when expressed as percent of the simultaneous left ventricular pressure. Seven of nine ventricular septal defects observed intraoperatively were noted on preoperative echocardiography; five of these defects were detected on preoperative angiography. A variety of other surgically confirmed associated cardiovascular defects were observed by both preoperative techniques. However, echocardiography appeared to be superior to angiography for evaluation of AV valve morphology and papillary muscle architecture. This study implies that in children with typical clinical and two-dimensional echocardiographic and Doppler findings for ostium primum atrial septal defect or transitional AV canal defect, routine preoperative cardiac catheterization and angiography are unnecessary.

Adolescent↗
PubMed2000

Transthoracic three-dimensional echocardiography in the preoperative assessment of atrioventricular septal defect morphology.

A prospective study of 3-dimensional (3-D) transthoracic echocardiographic definition of atrioventricular septal defect (AVSD) morphology and its dynamic changes during the cardiac cycle was performed. The information obtained from 2-D and 3-D transthoracic echocardiography (TTE) was compared with intraoperative findings in an unselected group of 15 patients with AVSD (median age 22 months). In all study patients, 3-D reconstructions provided anatomic views of the atrioventricular valve(s) en face from either atrial or ventricular perspectives that allowed comprehensive assessment of dynamic valve morphology and the mechanism of valve reflux. Left-sided valve function was correctly assessed by 2-D TTE in 11 of 15 patients (73%) and in 14 of 15 (93%) by 3-D TTE. In 6 of 15 patients (40%), the severity of right-sided valve reflux was described precisely by 2-D TTE and in 12 of 15 patients (80%) by 3-D TTE. Additionally, 3-D TTE supplemented the diagnostic information to that available from 2-D TTE on atrial and ventricular septal defects. Although primum atrial septal defects were depicted by 2-D and 3-D TTE in all 15 patients, the description of defect size was more precise by the 3-D TTE (80% vs. 100%, respectively). The presence of secundum atrial septal defect was correctly diagnosed by both TTE techniques in 10 of 15 patients. Disagreement regarding the size of the defect was present only in 2 of 10 patients by 2-D TTE. In another 2 patients, 3-D TTE described multiple defect fenestrations that were missed by 2-D TTE. Thus, the agreement score was 73% for 2-D and 100% for 3-D echo. The agreement for the presence and sizing of ventricular septal defects was 67% for 2-D and 93% for 3-D echo. We conclude that 3-D TTE provided accurate anatomic reconstructions of the common atrioventricular junction and that the use of dynamic 3-D TTE enhanced the anatomic diagnostic capability of standard 2-D TTE. Medica, Inc.

Echocardiography↗
PubMed2001

Cardiovascular defects associated with abnormalities in midline development in the Loop-tail mouse mutant.

Loop-tail (Lp) is a naturally occurring mouse mutant that develops severe neural tube defects. In this study, we describe complex cardiovascular defects in Lp homozygotes, which include double-outlet right ventricle, with obligatory perimembranous ventricular septal defects, and double-sided aortic arch, with associated abnormalities in the aortic arch arteries. Outflow tract and aortic arch defects are often related to abnormalities in the cardiac neural crest, but using molecular and anatomic markers, we show that neural crest migration is normal in Lp/Lp embryos. On the other hand, the heart fails to loop normally in Lp/Lp embryos, in association with incomplete axial rotation and reduced cervical flexion. As a consequence, the ventricular loop is shifted posteromedially relative to its position in wild-type embryos. This suggests that the observed cardiac alignment defects in the Lp mutant may be secondary to failure of neural tube closure and incomplete axial rotation. Double-sided aortic arch is a rare finding among mouse models. In humans, it is usually an isolated malformation, only rarely occurring in combination with other cardiac defects. We suggest that the double-sided arch arises as a primary defect in the Lp mutant, unrelated to the alignment defects, perhaps reflecting a role for the (as-yet-unknown) Lp gene in maintenance/regression of the aortic arch system.

Animals↗
PubMed1990

[Pulmonary hypertensive vascular disease in patients with interventricular defect or complete atrioventricular canal].

In 34 patients operated on the morphological and morphometric patterns of the pulmonary vascular bed on lung biopsies, performed during the operation for ventricular septal defect or complete atrio-ventricular septal defect were studied. These patterns were related to the preoperative hemodynamic data. Ages ranged from 2 to 20 months. There were 16 ventricular septal defect (mean age 10 +/- 4 months) and 18 complete atrio-ventricular septal defect (mean age 9.8 +/- 1.2 months). Furthermore, of the latter 15/18 (83%) patients had Down's syndrome. The following hemodynamic data were considered: a) ratio between the pulmonary systolic artery pressure and the systemic systolic artery pressure; b) diastolic pulmonary artery pressure; c) pulmonary vascular resistance; d) ratio between pulmonary and systemic flow. The lung specimens obtained at surgery were routinely processed and embedded in paraffin. Sections measuring 4 microns were stained with hematoxylin-eosin, Masson's thricrome and Miller's elastin. The status of the small pulmonary arteries was assessed according to the Heath-Edwards classification and to the morphometric parameters proposed by Rabinovitch and coll. Ratio between the pulmonary systolic artery pressure and the systemic systolic artery pressure ranged from 0.48 to 1 (mean 0.8 +/- 0.23) in patients with ventricular septal defect, whereas in complete atrio-ventricular septal defects it ranged from 0.42 to 1 (mean 0.86 +/- 0.21). The mean diastolic pulmonary artery pressure was 20 +/- 10 mmHg (range 8-40 mmHg) in ventricular septal defects and 19.5 +/- 2.3 mmHg (range 10-35 mmHg) in complete atrio-ventricular septal defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1985

Further observations on the morphology of atrioventricular septal defects.

Certain morphologic aspects of atrioventricular septal defects ("endocardial cushion defects," "atrioventricular canal malformations") remain controversial. It is still not clear which precise lesions should not be placed in this category. For example, is an "isolated" cleft of the mitral valve or a perimembranous inlet ventricular septal defect to be so described? It is also not fully accepted that the left atrioventricular valve in these lesions bears little resemblance to a morphologically mitral valve. We have investigated these problems by both observation and mensuration. We determined the junctional circumference of the left atrioventricular valve leaflets and the ventricular dimensions in 130 atrioventricular septal defects (95 with common valve orifice and 35 with separate right and left atrioventricular orifices); in 50 hearts with perimembranous ventricular septal defects (20 extending into the inlet septum and 30 with outlet or trabecular extensions); in seven hearts with isolated cleft of the mitral valve, and in 10 normal hearts. All specimens came from the cardiopathological collection of Children's Hospital of Pittsburgh. The measurements showed conclusively that the atrioventricular septal defects were all directly comparable irrespective of the detailed morphology of the atrioventricular valve or valves. The group of atrioventricular septal defects was totally discrete as compared with all the other specimens that had normal atrioventricular septation. The left atrioventricular valve in atrioventricular septal defects is basically a three-leaflet valve which differs from the normal mitral valve in terms of its leaflet, its chordal support, and the arrangement of its papillary muscle. Its only similarity with the normal mitral valve is that it resides in the morphologically left ventricle and guards the left atrioventricular junction.

Child↗
PubMed1982

[Comparison of 2-d-echocardiographic and hemodynamic findings in patients with atrial and ventricular septal defects (author's transl)].

57 patients (age 2 to 79 years) with atrial septal defect and 28 patients (age 1 month to 60 years) with ventricular septal defect were examined to find out whether the 2-d-echo allows to predict the shunt flow and the hemodynamic parameters of the pulmonary system. In 96% of the patients with asd, the defect could be demonstrated in the subcostal view. In 68% of the patients with vsd, the defect was shown in the long axis or the subcostal view. There was a low correlation between the size of the defect and the quotient of pulmonary to systemic flow (for asd: r = 0.73; for vsd: r = 0.62). Also, the quotient of pulmonary to systemic flow related rather poorly to the quotient of pulmonary artery diameter to aortic diameter as determined in th short axis (for asdii: r = 0.75; for vsd: r = 0.73). Nor relation could be found between echocardiographic parameters and pulmonary artery pressure with one exception: if contrast-echocardiography revealed a right-to-left shunt in patients with vsd, the pulmonary pressure exceeded the systemic pressure by 50%. The results show that in patients with asd or vsd the hemodynamic situation cannot be exactly judged from echocardiographic findings alone. The consideration of several echocardiographic parameters, however, seems to allow a distinction between hemodynamically relevant and irrelevant defects, which might be helpful for clinical purposes. For patients with asd, a shunt volume of minor importance (Qp:Qs less than 1.5:1) is found if the defect does not exceed 35% of the atrial septum length and if the quotient of pulmonary to aortic diameter is less than 1. In patients with vsd, the demonstration of the defect itself and a quotient of pulmonary to aortic diameter larger than 1 means that a shunt volume with Qp:Qs greater than 1.5:1 can be expected. Unsatisfactory results concerning the pulmonary pressure are obtained even when applying the contrast-echocardiography.

Adolescent↗
PubMed1997

Diagnosis and surgical repair of partial atrioventricular septal defects in two dogs.

Partial atrioventricular (AV) septal defects consist of an ostium primum defect and malformation of the septal cusp of the mitral valve. A partial AV septal defect was diagnosed by means of echo-cardiography in 2 dogs. Transatrial septal blood flow was high enough in both dogs to warrant surgical correction. Defects were repaired through right fifth intercostal thoracotomies, with the aid of cardiopulmonary bypass. An incision was made in the right atrium to expose the AV septal defect, and the mitral valve was inspected through the septal defect. The cleft in the septal cusp of the mitral valve was repaired with mattress sutures of 6-0 polypropylene. The septal defect was closed with autogenous pericardium harvested from the right aspect of the pericardial sac. Both dogs survived surgery and were alive 15 and 42 months, respectively, after surgery, however, 1 dog developed progressive mitral regurgitation after surgery. Partial AV septal defects can be successfully repaired in dogs. Long-term prognosis probably depends on the adequacy of the mitral valve repair.

Animals↗
PubMed2000

Anal atresia, vertebral, genital, and urinary tract anomalies: a primary polytopic developmental field defect identified through an epidemiological analysis of associations.

Anal atresia (AA) is observed per se or as part of different Mendelian or chromosomal syndromes, and as part of the VACTERL primary developmental field, CHARGE association, cloacal extrophy, in a mitochondrial cytopathy, and other multiple congenital anomaly patterns. There are only a few studies on the defects associated with AA, and in all of them it was observed that genitourinary defects are most frequent in infants with AA. Here we present the analysis of 28,410 malformed infants to study the frequency of 11 selected congenital defects in infants with AA in relation to their frequency in infants with multiple congenital anomaly patterns without AA. We conclude that the association of AA + spine defects + renal/urinary tract defects + genital defects constitutes a group of defects that tends to be present together in the same child because they are pathogenetically related, and since they are of blastogenetic origin they constitute a primary polytopic developmental field defect.

Abnormalities, Multiple↗
PubMed1994

Genetic models of mammalian neural tube defects.

Several mouse mutations disturb the embryonic process of neurulation, yielding neural tube defects. Analysis of the mutations offers the most feasible approach to understanding the aetiology and pathogenesis of human neural tube defects. Interactions between the non-allelic mutant genes and between several of the mutant genes and modifying genes in the genetic background modulate the frequency and severity of the defects that develop. Environmental factors interact with the genetic predisposition either to increase or to decrease the incidence of defects. The gene loci corresponding to two of the mutations, splotch (Sp) and extra toes (Xt), have been identified as those encoding the transcription factors Pax-3 and Gli3, respectively; their human homologues are associated with Waardenburg type I syndrome and Greig's cephalopolysyndactyly. Embryological analysis reveals that several of the mutations disturb the process of neural tube closure at the posterior neuropore (in the lumbosacral region), yielding spina bifida and/or tail defects. The different mutations appear to achieve this developmental end-point by different underlying mechanisms. In curly tail (ct), non-neural tissues proliferate abnormally slowly causing ventral curvature of the neuropore region and inhibiting neural tube closure. Neural tube defects can be prevented in cultured ct/ct embryos by experimentally correcting either the proliferative imbalance or the ventral curvature. In Sp the primary defect appears to reside in the neuroepithelium. A combination of genetic analysis, gene cloning and experimental embryology is revealing that neural tube defects in mice and, by implication, in humans are a developmentally heterogeneous group of malformations.

Animals↗