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Maternal obesity and risk for birth defects.

OBJECTIVE: Several studies have shown an increased risk for neural tube defects associated with prepregnancy maternal obesity. Because few recent studies have examined the relation between maternal prepregnancy obesity and overweight and other birth defects, we explored the relation for several birth defects and compared our findings with those of previous studies. METHODS: We conducted a population-based case-control study of several selected major birth defects using data from the Atlanta Birth Defects Risk Factor Surveillance Study. Mothers who delivered an infant with and without selected birth defects in a 5-county metropolitan Atlanta area between January 1993 and August 1997 were interviewed. Maternal body mass index (BMI) was calculated from self-reported maternal prepregnancy weight and height. Women with known preexisting diabetes were excluded. The risks for obese women (BMI > or =30) and overweight women (BMI 25.0-29.9) were compared with those for average-weight women (BMI 18.5-24.9). RESULTS: Obese women were more likely than average-weight women to have an infant with spina bifida (unadjusted odds ratio [OR]: 3.5; 95% confidence interval [CI]: 1.2-10.3), omphalocele (OR: 3.3; 95% CI: 1.0-10.3), heart defects (OR: 2.0; 95% CI: 1.2-3.4), and multiple anomalies (OR: 2.0; 95% CI: 1.0-3.8). Overweight women were more likely than average-weight women to have infants with heart defects (OR: 2.0; 95% CI: 1.2-3.1) and multiple anomalies (OR: 1.9; 95% CI: 1.1-3.4). CONCLUSIONS: Our study confirmed the previously established association between spina bifida and prepregnancy maternal obesity and found an association for omphalocele, heart defects, and multiple anomalies among infants of obese women. We also found an association between heart defects and multiple anomalies and being overweight before pregnancy. A higher risk for some birth defects is yet another adverse pregnancy outcome associated with maternal obesity. Obesity prevention efforts are needed to increase the number of women who are of healthy weight before pregnancy.

Abnormalities, Multiple↗

Morphology of ventricular septal defects in complete transposition. Surgical implications.

Postmortem examination of 62 hearts with complete transposition (concordant atrioventricular and discordant ventriculoarterial connections) and an accompanying ventricular septal defect was performed to determine the morphologic variability of ventricular septal defects and to explore the surgical implications of these defects. Particular attention was directed toward assessing alignment of the outlet septum relative to the muscular septum. Coronary arterial distributions were also evaluated, but specific patterns of distribution did not correlate with morphology of the defect. Of 49 hearts with a normally aligned outlet septum, there were 24 perimembranous, 21 muscular, and 2 doubly committed and juxtaarterial defects. Two hearts had both perimembranous and muscular defects. Twelve of the 21 muscular defects were "central," being surrounded entirely by muscle and located just below the leaflets of the pulmonary valve, and 9 were located in the inlet or apical trabecular septum. There were 13 hearts with malalignment of the outlet septum, anteriorly in 11 and posteriorly in 2. All with anterior malalignment had a subpulmonary defect that was perimembranous in 7 and muscular in 4. Both defects with posterior malalignment had a subaortic perimembranous defect. Because variations in morphology of a ventricular septal defect have a direct impact on selection of the most suitable surgical repair, specific operative approaches are discussed.

Abnormalities, Multiple↗

[Neural tube defects and associated factors in liveborn and stillborn infants].

OBJECTIVES: To evaluate the prevalence and factors associated to neural tube defects in liveborn and stillborn infants delivered at the Hospital das Clínicas, UFMG, from January 8, 1999 to July 31, 2000. METHODS: This is a descriptive study, based on a database, according to the Latin-American Collaborative Study of Congenital Malformation (ECLAMC) rules. Reports on liveborn and stillborn infants with congenital anomalies were prepared including information about morphological description, necropsy results, complementary exams, family, social and pregnancy histories and other clinical data. Each malformed liveborn infant originated a control of the same sex, without malformations. The liveborn and stillborn infants with neural tube defects delivered during that period were classified according to their defect and the presence or absence of associated defects. The liveborn and stillborn infants with neural tube defects were compared to newborns without neural tube defects according to their weight and sex and their mother's age and parity. Epi-Info 6.0 Program was used for the statistical analysis of the results. RESULTS: The prevalence of neural tube defects was 4.73 to 1,000 deliveries (89:18,807); it was significantly higher among stillborn infants (23.7:1,000) than among liveborn infants (4.16:1,000), p < 0.001. Neural tube defects were more often found among low weight liveborn infants (< or = 2,500 g), p < 0.001 and less frequently among women who had had more than three gestations, p = 0.007. No association was found regarding newborn's sex or maternal age. There was no association with newborn's sex and weight, maternal parity or age among stillborn infants. The most common neural tube defects were myelomeningocele (47.2%), anencephaly (26.9%) and encephalocele (16.9%). The defects were found as isolated anomalies in 71.1% of the liveborn and 38.5% of the stillborn infants; they were part of a syndrome in 9.2% (liveborn) and 7.7% (stillborn). CONCLUSION: The neural tube defect prevalence found in this study was higher than the one described in international and Latin-American literature.

Female↗

Assessment of ventricular septal defect by echocardiography.

Both 2-D echocardiography and angiocardiography were performed preoperatively in 40 children with isolated ventricular septal defect (VSD). The diagnosis of VSD was confirmed and the size of VSD was measured during operation within on month of the study. There were 27 males and 13 females (age: 10mos-9 yrs). The VSD was classified into perimembranous type (24), supracristal type (14), and AV canal type (2) by surgery. The maximal VSD areas were calculated by 1/4 pi De2 (De = maximal defect diameter measured by 2D echo). The maximal shunt flow areas were measured by color Doppler echocardiography from frame by frame search of the video tape. The maximal shunt flow area was corrected by the body surface area to be the maximal shunt flow area index. A left ventriculogram (LVG) was performed from 4-chamber and left lateral views to measure the maximal diameter of the defect. The maximal defect area of VSD on angiocardiogram was also calculated by 1/4 pi Da2 (Da = maximal defect diameter measured by angiocardiography). The VSD areas measured by different methods were compared by the linear regression analysis. We found that: (1) there is good correlation of the maximal defect diameter and the area of ventricular septal defect by 2-DE and LVG (r = 0.80, p less than 0.0001 v.s. r = 0.78, p less than 0.0001). (2) the ventricular septal defect area by 2-DE had a better correlation with the surgical measurement than that by LVG (r = 0.93, p less than 0.0001, v.s. r = 0.80, p less than 0.0001). (3) the size of ventricular septal defect measured by two-dimensional echocardiography has a better correlation with the MSFAI than the LVG did (r = 0.81, p less than 0.0001, v.s. r = 0.64, p less than 0.0001). Therefore, by measuring the maximal defect diameter, maximal defect area and maximal shunt flow area index, the echocardiography can provide an accurate and non-invasive assessment of isolated VSD in children.

Child↗

Congenital cardiac defects in calves.

In a 14-year study of calves with cardiac defects, 36 had 78 congenital cardiac defects: ectopia cordia cervicalis (n = 10 defects), common aortic trunk (n = 3 defects), dextraposed aorta (n = 8 defects), duplicated major trunks (n = 1 defect), hypoplastic aorta (n = 2 defects), interventricular septal defect (n = 11), interatrial septal defect (n = 2), left ventricular hypoplasia (n = 10), patent ductus arteriosus (n = 5), patent foramen ovale (n = 5), right ventricular hypoplasia (n = 10), cor triloculare biatriatum (n = 1), endocardial fibroelastosis with calcification (n = 3), and valvular hematomas (n = 7). All septal defects were high in location and ranged from 5 to 35 mm in diameter. One calf with a septal defect also had bilateral microphthalmia.

Animals↗

Antenatal diagnosis of neural tube defects in Canada: extension of a collaborative study.

Experience with the diagnosis of neural tube defects from alpha1-fetoprotein (AFP) concentrations in amniotic fluid is reported from a prospective study of five laboratories testing for 13 Canadian genetic centres. The results of the study indicate that antenatal diagnosis of open neural tube defects is being carried out effectively in Canada (in 99.2% of cases the AFP measurements were interpreted correctly). Amniocentesis should be recommended to women at high risk for having a child with a neural tube defect (i.e., those who have a child, a parent or a sibling with a neural tube defect). The rate of neural tube defects in 182 high-risk pregnancies was 2.2% for an open defect and 1.1% for a closed defect, whereas the rate in 673 pregnancies in which amniocentesis was being performed for other reasons was 0.3%. This suggests that the AFP concentration should be measured in any sample of amniotic fluid collected for other reasons (usually fetal karyotyping). There were three instances of false-negative results, for a rate of 0.4%. Two closed neural tube defects were not detected; this limitation of the test has also been found by others. One of the six fetuses with an open neural tube defect, who died in utero, had a large myelocele in the neck that was not recognized. There were also four instances of false-positive results, for a rate of 0.5%. The findings suggest that AFP values that are more than 2 but less than 7 standard deviations (SDs) above the mean may indicate a neural tube defect, and that values 7 or more SDs above the mean very likely indicate such a defect, although other reasons for such high values (e.g., fetal erythrocytes in the amniotic fluid, intrauterine death and mistaken gestational age) must be ruled out by other methods.

Amniocentesis↗

Trends and patterns of mortality associated with birth defects and genetic diseases in the United States, 1979-1992: an analysis of multiple-cause mortality data.

Contemporary information on the trends and patterns of mortality associated with birth defects and genetic diseases is lacking in the United States. To study these trends and patterns, we used the Multiple-Cause Mortality Files of the National Center for Health Statistics. From 1979 through 1992, 320,208 deaths in the United States were associated with birth defects and genetic diseases. The age-adjusted mortality rates for people with birth defects declined from about 8.2/100,000 in 1979 to about 6.7/100,000 in 1992, and the mortality rates for people with genetic diseases increased from 2.2/100,000 in 1979 to 2.5/100,000 in 1992. The mortality rate was higher among men than among women and higher among blacks than among whites or other races for both birth defect- and genetic disease-associated deaths. The rate among infants with birth defects was more than 25 times higher than that among other age groups. About half of the children whose deaths were associated with birth defects had cardiovascular system defects, 15% had central nervous system defects, and 12% had chromosomal defects. For deaths associated with genetic diseases, hereditary neurologic or storage disorders were the most common genetic diseases (38%), followed by metabolic disorders (21%), sickle cell and thalassemia (12%). The decline in the rate of mortality from birth defects in the United States probably reflects improvements in medical and surgical care and other factors. Most of the mortality associated with birth defects remains in the pediatric age group (less than 15 years old). The upward trend we detected for the deaths with genetic diseases was most likely related to improved recognition and reporting of some genetic diseases rather than to the increased prevalence.

Adolescent↗

Enamel hypoplasia in the deciduous teeth of great apes: variation in prevalence and timing of defects.

The prevalence of enamel hypoplasia in the deciduous teeth of great apes has the potential to reveal episodes of physiological stress in early stages of ontogenetic development. However, little is known about enamel defects of deciduous teeth in great apes. Unresolved questions addressed in this study are: Do hypoplastic enamel defects occur with equal frequency in different groups of great apes? Are enamel hypoplasias more prevalent in the deciduous teeth of male or female apes? During what phase of dental development do enamel defects tend to form? And, what part of the dental crown is most commonly affected? To answer these questions, infant and juvenile skulls of two sympatric genera of great apes (Gorilla and Pan) were examined for dental enamel hypoplasias. Specimens from the Powell-Cotton Museum (Quex Park, UK; n = 107) are reported here, and compared with prior findings based on my examination of juvenile apes at the Cleveland Museum of Natural History (Hamman-Todd Collection; n = 100) and Smithsonian Institution (National Museum of Natural History; n = 36). All deciduous teeth were examined by the author with a x10 hand lens, in oblique incandescent light. Defects were classified using Fédération Dentaire International (FDI)/Defects of Dental Enamel (DDE) standards; defect size and location on the tooth crown were measured and marked on dental outline charts. Enamel defects of ape deciduous teeth are most common on the labial surface of canine teeth. While deciduous incisor and molar teeth consistently exhibit similar defects with prevalences of approximately 10%, canines average between 70-75%. Position of enamel defects on the canine crown was analyzed by dividing it into three zones (apical, middle, and cervical) and calculating defect prevalence by zone. Among gorillas, enamel hypoplasia prevalence increases progressively from the apical zone (low) to the middle zone to the cervical zone (highest), in both maxillary and mandibular canine teeth. Results from all three study collections reveal that among the great apes, gorillas (87-92%) and orangutans (91%) have a significantly higher prevalence of canine enamel defects than chimpanzees (22-48%). Sex differences in canine enamel hypoplasia are small and not statistically significant in any great ape. Factors influencing intergroup variation in prevalence of enamel defects and their distribution on the canine crown, including physiological stress and interspecific dento-gnathic morphological variation, are evaluated.

Age Factors↗

Association of cartilage defects with loss of knee cartilage in healthy, middle-age adults: a prospective study.

OBJECTIVE: The significance of asymptomatic knee cartilage defects in healthy individuals is not known. The aim of this study was to examine the association between cartilage defects in the knee and cartilage volume both cross-sectionally and longitudinally in healthy, middle-age adults. METHODS: Eighty-six healthy men and women (mean +/- SD age 53.8 +/- 8.8 years) underwent T1-weighted fat-suppressed magnetic resonance imaging of their dominant knees at baseline and at the 2-year followup visit. Knee cartilage volume was measured. Cartilage defects were scored according to a grading system (0-4) and as present (a defect score of > or = 2) or absent in the medial and lateral tibiofemoral compartments. RESULTS: Cartilage defects in the medial and lateral tibiofemoral compartments were very common (in 61% and 43% of subjects, respectively). Those with cartilage defects had a 25% reduction in medial tibial cartilage volume, a 15% reduction in lateral tibial cartilage volume, and a 19% reduction in total femoral cartilage volume relative to those with no cartilage defects in cross-sectional analyses (all P < 0.05). In the medial tibiofemoral compartment, the annual loss of tibial cartilage in those with cartilage defects was 2.5% (95% confidence interval [95% CI] 2.2%, 3.1%) compared with an annual loss of tibial cartilage of 1.3% (95% CI 0.5%, 2.0%) in those with no defects (P = 0.028), independent of other known risk factors for osteoarthritis (OA). CONCLUSION: These data suggest that the presence of asymptomatic, non-full-thickness medial tibiofemoral cartilage defects identifies healthy individuals most likely to lose knee cartilage in the absence of radiographic knee OA. Thus, interventions aimed at reducing or reversing cartilage defects may reduce the risk of subsequent knee OA.

Australia↗

Maternal age and non-chromosomal birth defects, Atlanta--1968-2000: teenager or thirty-something, who is at risk?

OBJECTIVE: This investigation explored the association between maternal age and non-chromosomal birth defects to assess any increased risk associated with maternal age. METHODS: Birth defect cases were ascertained by the Metropolitan Atlanta Congenital Defects Program (MACDP), denominator information was obtained using birth certificate data. Infants with any chromosomal diagnosis were excluded. Effect estimates were calculated using 5-year maternal age categories with 25-29 years as the referent. Multiple logistic regression was used to adjust for maternal race, parity, infant sex, and birth year. RESULTS: A total of 1,050,616 singleton infants, born after > or = 20 weeks gestation in the five counties of metropolitan Atlanta from 1968 through 2000 who did not have a chromosomal abnormality and whose mother was 14 to 40 years old, were included in the analyses, 32,816 of them were identified with birth defects by the MACDP. Young maternal age (14-19 years) was associated with anencephaly (OR = 1.81, 95% CI = 1.30-2.52), hydrocephaly without neural tube defect (OR = 1.56, 95% CI = 1.23-1.96), all ear defects (OR = 1.28, 95% CI = 1.10-1.49), cleft lip (OR = 1.88, 95% CI = 1.30-2.73), female genital defects (OR = 1.57, 95% CI = 1.12-2.19), hydronephrosis (OR = 1.42, 95% CI = 1.11-1.82), polydactyly (OR = 1.29, 95% CI = 1.09-1.52), omphalocele (OR = 2.08, 95% CI = 1.39-3.12), and gastroschisis (OR = 7.18, 95% CI = 4.39-11.75). Advanced maternal age (35-40 years) was associated with all heart defects (OR = 1.12, 95% CI = 1.03-1.22), tricuspid atresia (OR = 1.24, 95% CI = 1.02-1.50), right outflow tract defects (OR = 1.28, 95% CI = 1.10-1.49), hypospadias 2nd degree or higher (OR = 1.85, 95% CI = 1.33-2.58), male genital defects excluding hypospadias (OR = 1.25, 95% CI = 1.08-1.45) and craniosynostosis (OR = 1.65, 95% CI = 1.18-2.30). CONCLUSIONS: Young and advanced maternal ages are associated with different types of birth defects. Underlying causes for these associations are not clear.

Adolescent↗

Evaluation of bone regeneration at critical-sized calvarial defect by DBM/AM composite.

This study investigated the bone-regenerative potential of a demineralized bone and acellular matrix (DBM/AM) composite (AlloCraft DBM) in comparison with autologous bone using an in vivo model. Critical-sized calvarial defects (5 mm) were created in athymic rats. The defects were grafted with either the DBM/AM composite or the acellular human dermal matrix (AM), and compared with the defects filled with autologous bone (positive control) and the empty defect (negative control). Histological and radiographic assessments were carried out at 4 and 8 weeks after surgery to determine the biological healing, the amount and type of new bone formation and the percentage of new bone filled in the critical defects. At 4 weeks, DBM/AM composite group had the highest percentage of the defect filled with new bone (84%), which was significantly greater than autologous bone (62%), AM (41%), and untreated control (32%) groups. At 8 weeks, the DBM/AM continued to have the highest percentage of the defect filled with new bone (91%). The autologous bone group increased the percentage of bone fill to 83%. The defects either filled with AM or left untreated still had less of the defect filled with new bone, 57% and 33%, respectively. The total healing of defects grafted with DBM/AM was comparable with autologous bone group at 8 weeks. The results demonstrated that the DBM/AM composite promoted new bone formation more rapidly than autologous bone at calvarial defect in athymic rats. The study supports that DBM/AM is a potential substitute of autologous bone for bone repair.

Animals↗

Torsional strength reduction due to cortical defects in bone.

This study correlated torsional strength reduction with circular defect size in cortical bone, to define the "stress riser" and "open-section" effect of the defects. The experimental model was developed and verified. Circular defects from 10 to 60% of bone diameter were then created in paired sheep femora and the bones loaded to failure. Contrary to theory, this experimental study suggests that small defects (10%) of bone diameter cause no significant torsional strength reduction. A 20% defect caused a 34% decrease in strength, representing the "stress riser" dimension. Defects between 20 and 60% of bone diameter decreased strength linearly as a function of defect size, and thus no discrete "open section" dimension was identified. For circular defects, we were unable to demonstrate a discrete "open-section" effect at which dramatic strength reduction is observed. These data may prove to be helpful when planning surgery that involves placing defects in bone such as for infection, biopsy, and prosthesis removal. The accepted guideline to avoid defects of greater than 50% of the bone diameter may be too great. Our data reveal this 62% reduction in torque strength and 88% energy to failure exist with a 50% circular defect.

Animals↗

The efficacy of cylindrical titanium mesh cage for the reconstruction of a critical-size canine segmental femoral diaphyseal defect.

The authors developed a novel technique for the reconstruction of large segmental long bone defects using a cylindrical titanium mesh cage (CTMC). Although the initial clinical reports have been favorable, the CTMC technique has yet to be validated in a clinically relevant large animal model, which is the purpose of this study. Under general anesthesia, a unilateral, 3-cm mid-diaphyseal segmental defect was created in the femur of an adult canine. The defect reconstruction technique consisted of a CTMC that was packed and surrounded with a standard volume of morselized canine cancellous allograft and canine demineralized bone matrix. The limb was stabilized with a reamed titanium intramedullary nail. Animals were distributed into four experimental groups: in Groups A, B, and C (six dogs each), defects were CTMC reconstructed, and the animals euthanized at 6, 12, and 18 weeks, respectively; in Group D (three dogs), the same defect reconstruction was performed but without a CTMC, and the animals were euthanized at 18 weeks. The femurs were harvested and analyzed by gross inspection, plain radiography, computed tomography (CT), and single photon emission computed tomography (SPECT). The femurs were mechanically tested in axial torsion to failure; two randomly selected defect femurs from each group were analyzed histologically. Groups A, B, and C specimens gross inspection, plain radiography, and CT, demonstrated bony restoration of the defect, and SPECT confirmed sustained biological activity throughout the CTMC. Compared to the contralateral femur, the 6-, 12-, and 18-week mean defect torsional stiffness was 44.4, 45.7, and 72.5%, respectively; the mean torsional strength was 51.0, 73.6, and 83.4%, respectively. Histology documented new bone formation spanning the defect. Conversely, Group D specimens (without CTMC) demonstrated no meaningful bone formation, biologic activity, or mechanical integrity at 18 weeks. The CTMC technique facilitated healing of a canine femur segmental defect model, while the same technique without a cage did not. The CTMC technique may be a viable alternative for the treatment of segmental long bone defects.

Animals↗

Reconstruction of maxillectomy and midfacial defects with free tissue transfer.

The maxillary bones are part of the midfacial skeleton and are closely related to the eyeglobe, nasal airway, and oral cavity. Together with the overlying soft tissues, the two maxillae are responsible to a large extent for facial contour. Maxillectomy defects become more complex when critical structures such as the orbit, globe, and cranial base are resected, and reconstruction with distant tissues become essential. In this article, we describe a classification system and algorithm for reconstruction of these complex defects using various pedicled and free flaps. Most defects that involve resection of the maxilla and adjacent soft tissues may be classified into one of the following four types: Type I defects, Limited maxillectomy; Type II defects, Subtotal maxillectomy; Type III defects, Total maxillectomy; and Type IV defects, Orbitomaxillectomy. Using this classification, reconstruction of maxillectomy and midfacial defects may be approached considering the relationship between volume and surface area requirements, that is, addressing the bony defect first, followed by assessment of the associated soft tissue, skin, palate, and cheek-lining deficits. In our experience, most complex maxillectomy defects are best reconstructed using free tissue transfer. The rectus abdominis and radial forearm free flap in combination with immediate bone grafting or as an osteocutaneous flap reliably provide the best aesthetic and functional results. A temporalis muscle pedicled flap is used for reconstruction of maxillectomy defects only in those patients who are not candidates for a microsurgical procedure.

Adult↗

Limb reduction defects in over one million consecutive livebirths.

Limb reduction defects occurring among 1,213,913 consecutive livebirths in British Columbia during the period 1952-1984 inclusive were reviewed. A total of 659 cases of limb reduction defects were identified, 393 of them involving the long bones and 190 of them more than one limb. The time period 1966-1984, during which ascertainment was consistent, was evaluated, and an incidence of 5.97 per 10,000 livebirths (1 in 1,692 live births) was found. The data were evaluated for trends over time, sex ratio, and regional and ethnic distribution. Associated anomalies of other organ systems in these cases were analyzed, and overall about one-half of the cases have additional defects. The majority of these additional defects affect the musculoskeletal system and include such entities as clubfoot, hip dislocation, and congenital contractures. Defects are also frequent in other organ systems, such as the cardiovascular, gastrointestinal, and genitourinary systems. By far the most common limb defects are terminal longitudinal defects then terminal transverse defects. Of all cases of limb defects, 75% are upper limb and 25% lower limb. We found no evidence that one side is affected more frequently. About 6.5% of cases had another family member registered with a skeletal defect; 12.9% of cases died within the first year of life, the majority (85%) of those dying having additional defects. Etiological considerations are discussed for some subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Multiple↗

Ultrasonography as a screening tool for paravaginal defects in women with stress incontinence: a pilot study.

The aim of the study was to determine whether transabdominal ultrasonography can accurately identify paravaginal defects associated with genuine stress urinary incontinence. Sixteen women were diagnosed with genuine stress urinary incontinence (GSUI) following clinical evaluation, urethroscopy and urodynamic studies. They were then evaluated by transabdominal sonography and a full bladder and immediately following micturition. The ultrasound studies were also carried out in 8 women (5 nulliparous and 3 primiparous) who had no signs or symptoms of urinary incontinence. Paravaginal defects were detected in the 16 women with GSUI: 9 had unilateral defects and 7 had bilateral defects. Only right-sided defects were identified in women with unilateral lesions. Paravaginal defects were confirmed in all symptomatic women at the time of surgery, and corresponded with the defects identified with transabdominal ultrasound. Mild unilateral paravaginal defects were identified in 2 continent parous women. Five nulliparous women and 1 primiparous control had no ultrasound evidence of paravaginal defects. A transabdominal, transverse, suprapubic ultrasound scan with a full bladder is a promising screening technique for the diagnosis of paravaginal defect in women with GSUI. Transabdominal suprapubic longitudinal sections are not useful for the identification of paravaginal defects.

Case-Control Studies↗

Repair of sheep metatarsus defects by using tissue-engineering technique.

Tissue-engineering bone with porous ,betatricalcium phosphate (3-TCP) ceramic and autologous bone marrow mesenchymal stem cells (MSC) was constructed and the effect of this composite on healing of segmental bone defects was investigated. 10-15 ml bone marrow aspirates were harvested from the iliac crest of sheep, and enriched for MSC by density gradient centrifugation over a Percoll cushion (1. 073 g/ml). After cultured and proliferated, tissue-engineering bones were constructed with these,cellS seeded onto porous f-TCP, and then the constructs were implanted in 8 sheep left metatarsus defect (25 mm in length) as experimental group. Porous ,-TCP only were implanted to bridge same size and position defects in 8 sheep as control group, and 25 mm segmental bone defects of left metatarsus were left empty in 4 sheep as blank group. Sheep were sacrificed on the 6th, 12th, and 24th week postoperatively and the implants samples were examined by radiograph, histology, and biomechanical test. The 4 sheep in blank group were sacrificed on the 24th week postoperatively. The results showed that new bone tissues were observed either radiographic or histologically at the defects of experimental group as early as 6th week postoperatively, but not in control group, and osteoid tissue, woven bone and lamellar bone occurred earlier than in control group in which the bone defects were repaired in "creep substitution" way, because of the new bone formed in direct manner without progression through a cartilaginous intermediate. At the 24th week, radiographs and biomechanical test revealed an almost complete repair of the defect of experimental group, only partly in control group. The bone defects in blank group were non-healing at the 24th week. It was concluded that engineering bones constructed with porous -TCP and autologous MSC were capable of repairing segmental bone defects in sheep metatarsus beyond "creep substitution" way and making it healed earlier. Porous ,-TCP being constituted with autologous MSC may be a good option in healing critical segmental bone defects in clinical practice and provide insight for future clinical repair of segmental defect.

Animals↗

Local application of basic fibroblast growth factor minipellet induces the healing of segmental bony defects in rabbits.

Fibroblast growth factor (FGF) has been reported to increase the volume of callus in a fracture model of rats. There are, however, no reports of successful repair of segmental bony defects by application of an FGF solution. In this study, the effects of basic FGF on the repair of segmental bony defects in the rabbit femur were examined. Minipellet, a new drug delivery system using atelocollagen, was employed to ensure effective delivery of FGF. Segmental bony defects (10 mm in length) were created in the right femurs of 19 rabbits. In pilot studies, no defects of this size healed spontaneously within 6 weeks. Bones were stabilized with miniexternal fixators. Minipellets containing basic FGF were implanted between fragments so as to bridge the two fragments. The healing processes were monitored radiographically and studied histologically. In rabbits in which FGF was added to the defect site at doses of 1.4 microgram or higher, approximately 90% of the defects were filled with new bone and cartilage within 6 weeks after minipellet implantation. In rabbits receiving placebo minipellets, however, approximately 15% of the defects were filled by callus within 6 weeks. Furthermore, this callus did not change into mature bone. An injection of 2 microgram of FGF solution to bony defects had no effect on the repair of segmental bony defects. These findings suggest that FGF plays a role in the production of adequate volumes of callus particularly in the initial stages of fracture healing and that sustained local release enables FGF to be effective at a low dose. In summary, large segmental bony defects healed after insertion of low-dose FGF minipellets. An adequate dose of FGF and an appropriate delivery system are required for successful healing of large bony defects. These findings imply the potential value of FGF minipellets in clinical practice.

Animals↗