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The effect of regional gene therapy with bone morphogenetic protein-2-producing bone-marrow cells on the repair of segmental femoral defects in rats.

BACKGROUND: Recombinant human bone morphogenetic proteins (rhBMPs) can induce bone formation, but the inability to identify an ideal delivery system limits their clinical application. We used ex vivo adenoviral gene transfer to create BMP-2-producing bone-marrow cells, which allow delivery of the BMP-2 to a specific anatomical site. The autologous BMP-2-producing bone-marrow cells then were used to heal a critical-sized femoral segmental defect in syngeneic rats. METHODS: Femoral defects in five groups of rats were filled with 5 x 10(6) BMP-2-producing bone-marrow cells, created through adenoviral gene transfer (twenty-four femora, Group I); twenty micrograms of rhBMP-2 (sixteen femora, Group II); 5 x 10(6) beta-galactosidase-producing rat-bone-marrow cells, created through adenoviral gene transfer of the lacZ gene (twelve femora, Group III); 5 x 10(6) uninfected rat-bone-marrow cells (ten femora, Group IV); or guanidine hydrochloride-extracted demineralized bone matrix only (ten femora, Group V). Guanidine hydrochloride-extracted demineralized bone matrix served as a substrate in all experimental groups. Specimens that were removed two months postoperatively underwent histological and histomorphometric analysis as well as biomechanical testing. RESULTS: Twenty-two of the twenty-four defects in Group I (BMP-2-producing bone-marrow cells) and all sixteen defects in Group II (rhBMP-2) had healed radiographically at two months postoperatively compared with only one of the thirty-two defects in the three control groups (beta-galactosidase-producing rat-bone-marrow cells, uninfected rat-bone-marrow cells, and guanidine hydrochloride-extracted demineralized bone matrix alone). Histological analysis of the specimens revealed that defects that had received BMP-2-producing bone-marrow cells (Group I) were filled with coarse trabecular bone at two months postoperatively, whereas in those that had received rhBMP-2 (Group II) the bone was thin and lace-like. Defects that had been treated with bone-marrow cells producing beta-galactosidase (Group III), uninfected bone-marrow cells (Group IV), or guanidine hydrochloride-extracted demineralized bone matrix only (Group V) demonstrated little or no bone formation. Histomorphometric analysis revealed a significantly greater total area of bone formation in the defects treated with the BMP-2-producing bone-marrow cells than in those treated with the rhBMP-2 (p = 0.036). Biomechanical testing demonstrated no significant differences, with the numbers available, between the healed femora that had received BMP-2-producing bone-marrow cells and the untreated (control) femora with respect to ultimate torque to failure or energy to failure. CONCLUSIONS: This study demonstrated that BMP-2-producing bone-marrow cells created by means of adenoviral gene transfer produce sufficient protein to heal a segmental femoral defect. We also established the feasibility of ex vivo gene transfer with the use of biologically acute autologous short-term cultures of bone-marrow cells.

Animals↗

The effect of osteogenic protein-1 on the healing of segmental bone defects treated with autograft or allograft bone.

BACKGROUND: Large amounts of bone graft are frequently used to elicit the healing of bone defects resulting from reconstructive procedures. Autograft and allograft bone are often used, but each has its limitations. Bone morphogenetic proteins (BMPs) improve the healing of segmental bone defects treated with autograft or allograft. The objective of the present study was to determine the effect of implantation of a recombinant osteogenic protein-1 (OP-1) in combination with bone graft on the healing of a critical-sized (2.5-cm) segmental defect in canine ulnae. METHODS: Either autograft bone, allograft bone, osteogenic protein-1 (OP-1) mixed with type-1 bovine collagen, or various combinations of OP-1 and collagen (OP-1 device) mixed with allograft or autograft were implanted in the segmental bone defects. The combinations included 67% bone graft with 33% OP-1 device and 33% bone graft with 67% OP-1 device. The healing of the defects was assessed with radiographic, biomechanical, and histological studies. The animals were killed at twelve weeks postoperatively. RESULTS: The use of the OP-1 device alone or any combination of autograft or allograft bone and the OP-1 device demonstrated improved healing on radiographic, mechanical, and histological studies compared with that demonstrated after use of autograft or allograft bone alone. The highest radiographic and histological grades and the greatest mechanical strength were achieved with the use of 33% allograft and 67% OP-1 device, although no significant differences were observed among the different groups containing the OP-1 device. At twelve weeks postoperatively, the defects treated with any amount of the OP-1 device obtained greater mechanical strength than that obtained by autograft bone alone. CONCLUSIONS: Major bone defects may be treated with allograft bone combined with the OP-1 device, instead of autograft alone, to avoid complications associated with the use of autograft. The combination of allograft bone and the OP-1 device resulted in optimum healing of the defect, according to the radiographic, mechanical, and histological parameters measured in this study. CLINICAL RELEVANCE: The combination of freeze-dried allograft bone with the OP-1 device is an attractive graft material for the treatment of large bone defects. Although similar results were observed when autogenous bone graft was used in combination with the OP-1 device, the results of the present study suggest that allograft, because of its relatively unlimited supply, can be substituted without reduced efficacy. In addition, avoiding the need to harvest autogenous bone eliminates the additional operative time and risk associated with a second surgical procedure.

Animals↗

rhBMP-2 delivered in a calcium phosphate cement accelerates bridging of critical-sized defects in rabbit radii.

BACKGROUND: Treatment of segmental bone loss remains a challenge in skeletal repairs. This study was performed to evaluate the efficacy of the use of recombinant bone morphogenetic protein-2 (rhBMP-2) delivered in an injectable calcium phosphate cement (alpha bone substitute material [alpha-BSM]) to bridge critical-sized defects in the rabbit radius. METHODS: Unilateral 20-mm mid-diaphyseal defects were created in the radii of thirty-six skeletally mature New Zealand White rabbits. The defects in twelve rabbits each were filled with 0.166 mg/mL rhBMP-2/alpha-BSM cement, 0.033 mg/mL rhBMP-2/alpha-BSM cement, or buffer/alpha-BSM cement. Six rabbits from each group were killed at four weeks, and six were killed at eight weeks. Serial radiographs were made to monitor defect-bridging and residual alpha-BSM carrier. A semiquantitative histological scoring system was used to evaluate defect-bridging. Histomorphometry was used to quantify residual alpha-BSM; trabecular bone area; trabecular bone volume fraction; and cortical length, width, and area. RESULTS: At four weeks, there had been more rapid resorption of alpha-BSM and filling of the defects with trabecular bone in the group treated with 0.166 mg/mL rhBMP-2/alpha-BSM than in the other two groups. Histomorphometry confirmed an increased trabecular area and volume fraction in this group compared with the other two groups. In both rhBMP-2/alpha-BSM-treated groups, the majority of the trabecular bone was formed by a direct process adjacent to the resorbing alpha-BSM. At eight weeks, complete cortical bridging and regeneration of the marrow space were present in all of the defects treated with 0.166 mg/mL rhBMP-2/alpha-BSM. That group also had reduced residual alpha-BSM and trabecular area and volume, compared with the other two groups, at eight weeks as a result of a rapid remodeling process. CONCLUSIONS: Treatment of a critical-sized defect in a rabbit radius with 0.166 mg/mL rhBMP-2/alpha-BSM injectable cement can result in bridging with cortical bone and a regenerated bone-marrow space by eight weeks. Site-specific remodeling appears to be responsible for corticalization and marrow regeneration. CLINICAL RELEVANCE: RhBMP-2 delivered in a calcium phosphate cement may be useful to achieve bridging of critical-sized defects in patients. Its injectable properties may allow minimally invasive use. Delayed percutaneous administration would also be possible when augmentation is desired following an initial surgical procedure or when soft-tissue injuries preclude adequate initial treatment.

Animals↗

Risk factors in the development of early renal cortical defects in children with urinary tract infection.

OBJECTIVE: Defects seen on early cortical scintigrams of the renal cortex in children with urinary tract infection may represent acute inflammatory change or established scar. The purpose of this study was to determine the relationship between these defects and age, sex, the presence and grade of vesicoureteral reflux, and infective organism in a cohort of children examined after their first proved urinary tract infection. SUBJECTS AND METHODS: We prospectively examined 193 consecutive patients less than 5 years old who were seen at the ambulatory pediatric department during a 3-year period and had a first proved urinary tract infection. Children with obstructed or solitary kidneys were excluded. All patients were imaged with scintigraphy of the renal cortex and radiographic voiding cystourethrography within 15 days of diagnosis. The association of age, sex, the presence and grade of vesicoureteral reflux, and infective organism with a defect (acute pyelonephritis or a renal scar) seen on a cortical renal scan was studied. RESULTS: The prevalence of cortical defects was greater in the kidneys of patients less than 2 years old (96/290, 33%) than in older children (16/96, 17%) and greater in those with vesicoureteral reflux (41/92, 45%) than in those without it (71/294, 24%). Vesicoureteral reflux was absent in 63% (71/112) of kidneys with a cortical defect. No association with sex or infective organism was established. As well as having a greater prevalence of cortical defects, 145 (75%) of the 193 urinary tract infections included in the study were in children less than 2 years old. The kidneys of these younger patients also had a greater severity and prevalence of vesicoureteral reflux (74/290, 26%) than did those of older children (18/96, 19%). CONCLUSION: Early cortical defects are associated with an age less than 2 years and vesicoureteral reflux. However, the association of early defects with the presence and grade of vesicoureteral reflux is confounded by the declining prevalence and severity of reflux with age. A significant proportion of cortical defects occur in the absence of vesicoureteral reflux, and the contribution of reflux to scar formation might be less than previously considered.

Age Distribution↗

Nondiseased portal perfusion defects adjacent to the right ribs shown on helical CT during arterial portography.

OBJECTIVE: The purpose of our study was to assess the frequency and imaging characteristics of nonpathologic portal perfusion defects in subcapsular liver parenchyma adjacent to the right ribs as seen on CT hepatic arteriography combined with helical CT during arterial portography (CTAP). MATERIALS AND METHODS: From January 1994 to June 1997, helical CTAP and CT hepatic arteriography were performed in 94 patients with suspected malignant hepatic tumors. The patient group comprised 66 men and 28 women ranging from 37 to 83 years old (mean, 64 years old). Three radiologists retrospectively reviewed the images obtained by CTAP to evaluate portal perfusion defects adjacent to the right ribs for location, shape, size, and correlation with findings seen on CT hepatic arteriography. RESULTS: We identified 16 nonpathologic portal perfusion defects adjacent to the right eighth (n = 1), ninth (n = 12), and tenth (n = 3) ribs in 12 (13%) of 94 patients. The shapes of the 16 defects were circular (n = 1), oval (n = 7), wedge (n = 3), and irregular (n = 5). The defects were 10-30 mm in diameter (mean, 16.9 mm). In four (25%) of 16 locations, CT hepatic arteriography showed poorly identified, homogeneous, irregularly shaped areas of contrast enhancement corresponding to the defects seen on CTAP. The portal perfusion defects were proven to be nonpathologic on definitive surgery in four patients and on follow-up radiography in eight patients. CONCLUSION: Helical CTAP may show nonpathologic portal perfusion defects adjacent to the right ribs. Most defects did not appear circular but rather were oval, irregular, or wedge-shaped. CT hepatic arteriography infrequently showed corresponding findings. Radiologists should recognize this potential pitfall when interpreting images obtained by helical CTAP.

Adult↗

Alpha 1 antitrypsin defective Lewis rats injected with heparin: comparison of the glomerular changes with those of Lewis rats produced anti BSA antibody.

Heparin effects were studied on Lewis rats with alpha 1 antitrypsin (AT) defect. Among 8 rats that were born at the same birth, three rats were shown to have mild defect of alpha 1 AT. Heparin was injected repeatedly into all the 8 rats. Interstitial pneumonia and localized periodic acid-Schiff (PAS) stain of hepatocytes were found in alpha 1 AT defective male. One of the three alpha 1 AT defective rats had about a half of normal alpha 1 AT level. Antithrombin (AT) III level was slightly low in the alpha 1 AT defective female with splenomegaly. Lung electron micrograph of the other alpha 1 AT defective female showed edematous changes of capillaries and alveolar basement membranes and also proliferated collagen fibers. In the lung of alpha 1 AT defective male, many thrombocytes adhered to alveolar degenerated smooth muscles that were recognized as Masson bodies. Extracted platelet-activating factor (PAF) in the plasma of the alpha 1 AT defective male was shown to trigger T lymphocyte chemotaxis. Five normal Lewis rats were immunized with bovine serum albumin (BSA). IgG1 antibody to BSA was produced in all the rats. The rats with high titers of IgG1 anti BSA antibody showed more strongly atrophic changes of glomerulus than those of the mild alpha 1 AT defective rats treated with heparin.

Animals↗

Biocompatibility of three-dimensional chondrocyte grafts in large tibial defects of rabbits.

OBJECTIVE: To evaluate biocompatibility and effects of implantation of 3-dimensional chondrocyte-agarose autografts in tibial defects in rabbits and to compare in vitro and in vivo chondrocyte-agarose constructs with respect to cell viability, differentiation, and matrix production. ANIMALS: 24 adult New Zealand White rabbits. PROCEDURE: Three-dimensional constructs with (grafted group) or without (control group) autogenous chondrocytes were implanted into tibial defects of rabbits and cultured in vitro. During an 8-week period, defects were evaluated radiographically, grossly, histologically, biochemically, and immunohistochemically. In vitro constructs were evaluated histologically, biochemically, and immunohistochemically. RESULTS: Tibial defects had significantly higher radiographic densitometry values at 4 and 6 weeks after implantation in grafted group rabbits, compared with control group rabbits. Number of observed centers of endochondral ossification was significantly greater in defects of grafted group rabbits, compared with control group rabbits. On day 14, glycosaminoglycan concentration was significantly higher in tibial defects of grafted group rabbits, compared to defects of control group rabbits or in vitro constructs. At weeks 2, 4, and 8, glycosaminoglycan concentrations were significantly lower in the in vitro control constructs, compared with other groups. Collagen type I was present in bone and bony callous in defects of grafted and control group rabbits. Collagen type II was identified in cartilaginous tissues of grafted and control group rabbits. Collagen type X was associated with hypertrophic chondrocytes. Only type II collagen was found in the in vitro chondrocyte constructs. CONCLUSIONS AND CLINICAL RELEVANCE: Chondrocyte-agarose grafts are biocompatible in large tibial defects and appear to provide a cell source for augmenting endochondral ossification.

Animals↗

Response of induced bone defects in horses to collagen matrix containing the human parathyroid hormone gene.

OBJECTIVE: To determine whether human parathyroid hormone (hPTH) gene in collagen matrix could safely promote bone formation in diaphyseal or subchondral bones of horses. ANIMALS: 8 clinically normal adult horses. PROCEDURE: Amount, rate, and quality of bone healing for 13 weeks were determined by use of radiography, quantitative computed tomography, and histomorphometric analysis. Diaphyseal cortex and subchondral bone defects of metacarpi were filled with hPTH(1-34) gene-activated matrix (GAM) or remained untreated. Joints were assessed on the basis of circumference, synovial fluid analysis, pain on flexion, lameness, and gross and histologic examination. RESULTS: Bone volume index was greater for cortical defects treated with hPTH(1-34) GAM, compared with untreated defects. Bone production in cortical defects treated with hPTH(1-34) GAM positively correlated with native bone formation in untreated defects. In contrast, less bone was detected in hPTH(1-34) GAM-treated subchondral bone defects, compared with untreated defects, and histology confirmed poorer healing and residual collagen sponge. CONCLUSIONS AND CLINICAL RELEVANCE: Use of hPTH(1-34) GAM induced greater total bone, specifically periosteal bone, after 13 weeks of healing in cortical defects of horses. The hPTH(1-34) GAM impeded healing of subchondral bone but was biocompatible with joint tissues. Promotion of periosteal bone formation may be beneficial for healing of cortical fractures in horses, but the delay in onset of bone formation may negate benefits. The hPTH(1-34) GAM used in this study should not be placed in articular subchondral bone defects, but contact with articular surfaces is unlikely to cause short-term adverse effects.

Analysis of Variance↗

A multi-center study for birth defect monitoring systems in Korea.

The aim of this study was to establish a multi-center birth defects monitoring system to evaluate the prevalence and the serial occurrence of birth defects in Korea. Ten medical centers participated in this program. A trained nurse collected relevant records from delivery units and pediatric clinics in participating hospitals on a monthly basis. We observed 1,537 cases of birth defects among 86,622 deliveries, which included live births and stillbirths. The prevalence of birth defects was 1.8%, and the sex distribution of the birth defect cases was 55.2% male and 41.6% female. The highest proportion of birth defects was in the cardiovascular system (17.5%), followed by birth defects involving in the genitourinary system (15.6%). Chromosomal anomalies were detected 30.0 per 10,000 births. Of these chromosomal anomalies, Down syndrome was most frequently observed. This study led to an establishment of a multi-center active monitoring system for birth defects. To better understand the serial occurrence of birth defects in Korea, it is necessary to increase the number of participating hospitals and to launch on a nation-wide multi-center study.

Child↗

Long-term refractive results of myopic LASIK complicated with intraoperative epithelial defects.

PURPOSE: To evaluate the long-term refractive results of LASIK for myopia complicated with intraoperative epithelial defects. METHODS: Twenty-six eyes with epithelial defects on the LASIK flap were compared with the contralateral eye that had no intraoperative complications. Pre- and postoperative data were compared between the two groups including 3-, 6- and 12-month postoperative spherical equivalent refraction, amount of undercorrection, and complications. RESULTS: Eyes with intraoperative epithelial defects showed more undercorrection at 3 and 6 months postoperatively (P < .05). No statistically significant difference was noted at 12 months. Twenty (76%) eyes in the epithelial defect group lost best spectacle-corrected visual acuity (BSCVA) at 3 months postoperatively compared with 2 (7%) eyes in the control group. By 1 year, however, only 2 (7%) eyes in the epithelial defect group and no eyes in the control group lost > 1 line of BSCVA. Diffuse lamellar keratitis was observed in 15 (58%) of 26 eyes with epithelial defects and these eyes had more undercorrections at 6 and 12 months (P < .05) and higher corneal irregularity index at 6 and 12 months compared with controls (P < .05). Eyes with small epithelial defects (> 1 mm2 to < 3 mm2) had more undercorrections at 6 months (-1.08 +/- 0.76 diopters [D]) compared with the control group (-0.46 +/- 0.87 D). Eyes with centrally located epithelial defects had more undercorrections and increased corneal irregularity index compared with controls (P < .05). CONCLUSIONS: Intraoperative epithelial defects after LASIK should be considered a severe complication that may result in diffuse lamellar keratitis, induce loss of BSCVA, prolong recovery of visual acuity, and induce undercorrection.

Adult↗

Potential parental exposure to pesticides and limb reduction defects.

OBJECTIVES: The goal of the study was to examine the effects of the potential pesticide exposure of parents on the risk of limb reduction defects in their offspring. METHODS: A case-referent study was conducted utilizing New York State Congenital Malformation Register data. Persons with limb reduction defects and referents were compared in terms of parental occupations and residence counties. Parental occupations and industries reported on birth certificates were qualitatively rated by industrial hygienists to estimate potential pesticide (list four groups) exposures. Residential exposures were estimated from agricultural census data according to county of residence. RESULTS: Neither parental exposure to pesticides [odds ratio (OR) 0.9, 95% confidence interval (95% CI) 0.6-1.4] nor farming occupation (OR 1.1, 95% CI 0.5-2.7) had an effect on the risk of total limb reduction defects. Those persons with limb reduction defects who had additional defects showed weak but consistent elevated risks in relation to parental occupational pesticide exposure. However, isolated cases of limb reduction defects were negatively related to these exposures. Residence in a farming or high pesticide use county was not associated with any type of limb reduction defect. CONCLUSIONS: Cases of limb reduction defect with additional malformations appear to be associated with parental occupational pesticide exposure. Improving exposure classifications and subdividing the limb reduction defects by types in the analyses are suggested for future research.

Adolescent↗

Imaging ultrasound in the intraoperative diagnosis of vascular defects.

High-resolution real-time ultrasonography was employed during 267 vascular operations in order to diagnose vascular defects such as intimal flaps, strictures, and thrombi. These defects occur at operative areas (e.g., anastomoses, endarterectomized segments, and sites of placement of occlusive clamps) and can lead to serious thrombotic complications in the early post-operative period. Ultrasound detected vascular defects in 83 patients (31.1 per cent). The defects in 59 patients were considered clinically insignificant because of their sizes and locations, and were not re-explored. Early post-operative results of these patients were comparable to those of the patients without demonstrated defects. In 24 patients (9.0 per cent of all patients examined), ultrasonography revealed clinically significant defects which prompted re-exploration. In 20 of these 24 patients, these vascular defects were confirmed and corrected. No defect was found at re-exploration in four patients, but two of them developed early postoperative thrombosis. Ultrasonography and arteriography were compared at 100 operative sites. The two imaging methods were equal in terms of sensitivity, specificity, efficiency, and predictability of a negative test. Predictability of a positive test was 77.8 per cent for ultrasonography and 59.1 per cent for arteriography. This indicates that fewer needless re-explorations would occur following a decision based on ultrasonography. Operative ultrasonography is a simple, safe and accurate technique that should be applied to reconstructive vascular surgery for diagnosis of vascular defects.

Diagnostic Techniques, Surgical↗

Combined use of pectoralis major myocutaneous and free radial forearm flaps for reconstruction of through-and-through defects from excision of head and neck cancers.

OBJECTIVES: The aim of this study was to examine the outcome and complication in patients who underwent reconstruction with combined use of pectoralis major myocutaneous flap (PMMCF) and free radial forearm flap (FRFF) for the through-and-through defect after surgical resection for head and neck cancer. METHOD: Twelve patients underwent primary reconstruction with the combined use of PMMCF and FRFF for through-and-through defect of facial or cervical skin and oral or pharyngeal mucosa resulting from treatment of head and neck cancer. Free radial forearm flap was used for three patients with oral mucosal defect, two patients with oropharyngeal mucosal defect, and two patients with defect from total laryngopharyngectomy. The osteocutaneous FRFF was used for five patients with defect of oral mucosa and mandible. Pectoralis major myocutaneous flap was used for seven patients with facial skin defect and five patients with cervical skin defect. RESULTS: All PMMCFs and FRFFs were successful. Early complications were minor and occurred in 4 (33%) of 12 patients. No delayed complication was observed. During the follow-up period, 5 patients died of disease between 10 and 52 months. Currently, 6 patients are alive with no evidence of disease and 1 patient developed a distant metastasis to the lung. The follow-up period ranged from 12 to 54 months. CONCLUSION: For patients with through-and-through defect after resection of mucosa of upper aerodigestive tract and skin, the combination of PMMF and FRFF reconstruction achieved optimal long-term results.

Aged↗

Tissue regeneration in bone defects adjacent to endosseous implants: an experimental pilot study.

Extraction socket defects or alveolar ridge defects may limit or restrict placement of implants. The present study assessed the efficacy of inducing bone formation with demineralized freeze-dried bone (DFDB), osteoinduction with hydroxyapatite (HA), and guided bone regeneration with expanded polytetrafluoroethylene (e-PTFE) in bone defects adjacent to endosseous implants in an animal model. Twenty-four implants were placed in the long bones of 3 pigs. After preparation of 24 cylindric acute defects adjacent to the coronal 5 mm of each implant, 18 of the defects were treated by DFDB, HA, or e-PTFE. The 6 remaining defects healed spontaneously with no treatment (controls). In each pig, one tibia received 4 commercially pure titanium screw implants (3.75 mm x 15 mm), while the contralateral tibia received 4 HA-coated cylindric implants (3.25 mm x 15 mm). Bone formation in response to the 3 treatments and control cases was evaluated using computer-assisted densitometric image analysis. The results showed that a higher density of tissue formed under e-PTFE membranes. A significantly greater increase in bone density was noticed in bone defects treated with an e-PTFE membrane vs DFDB (P = 0.04), in e-PTFE vs control sites (P = 0.04), and in defects treated with HA vs DFDB (P = 0.04) in HA-coated implants. In titanium implants the differences observed were not significant. It was also observed that bone regeneration in defects treated with HA differs with the type of implant used (titanium vs HA-coated implants), but such differences were not significant.

Analysis of Variance↗

Implantation of octacalcium phosphate nucleates isolated bone formation in rat skull defects.

OBJECTIVE: Our previous radiographic examinations have indicated that the synthetic octacalcium phosphate (OCP) may provide the core for nucleating multiple osteogenic sites in the experimentally created cranial defect. DESIGN: The present study was designed to confirm the possibility that the implanted OCP causes the osteoinduction as well as the osteoconduction in the rat cranial defect. MATERIALS AND METHODS: Standardized defects were created in male Wistar rat calvaria, and the OCP granules were implanted into the defect. The sham operated rats were processed in the same way except that nothing was implanted. The rats were fixed at 4 weeks after implantation of OCP or the sham operation. We examined bone formed on the implanted OCP, analyzing serial sections histologically combined with immunohistochemistry for the bone specific protein, osteocalcin. RESULTS: In the defects treated with OCP, the radiopacity was scattered throughout the defect besides being observed along the defect margin of the parietal bone. Examination of the serial sections showed that some of new bones on the implanted OCP were formed away from the defect margin of the parietal bone with regard to both histological identification and specific molecular marker. CONCLUSIONS: The present study suggested that the implanted OCP can serve as a core for initiating bone formation and cause the osteoinduction as well as the osteoconduction in the defect.

Animals↗

[Percutaneous autogenous bone marrow grafting for repairing bone defect: an experimental study in rabbits].

OBJECTIVE: To observe osteogenesis of percutaneous autogenous bone marrow into cicatrix of bone defect. METHODS: 18 rabbits were used to observe the osteogenesis of percutaneous autogenous bone marrow into cicatrix of bone defect. A 1 cm bone defect model was made in each side of the radius. And 2 ml autogenous bone marrow was injected in the right radial bone defect after 6 weeks, and 2 ml peripheral blood in the left side. The animals were sacrificed in 1, 2, 3, 4, 12 weeks after injection. Bone formation was studied with histologic technique, X-ray examination and Ca-P quantitative estimates. RESULTS: After 1 week of injection, a big shadow of softtissue was found around the bone defect in the right side(bone marrow). Histologically a lot of new cartilage like tissues were found. In the left side(peripheral blood), no change was seen. After 4 weeks of injection, many of new bone-like shadows were observed around the defect by X-ray examination in the right side. The defect was smaller(average 1.5 mm) and bone formation was found. But in the left side, no signs for osteogenesis were noted. In 12 weeks defect was smaller(average 1 mm). Histologic sections proved well-developed bone tissue. In the left side, no bone formation found. CONCLUSION: Autogenous bone marrow can induce osteogenesis in cicatric bone defect, whereas no osteogenesis is found in the peripheral blood injection side.

Animals↗

Changes of blood circulation of the extremity after external fixation for tibia shaft defect: an experimental study.

OBJECTIVE: To assess and compare two approaches, end to end compression with lengthening (EECL) and segmental bone transport by lengthening (STBL), for long tubular bone defect and nonunion. METHODS: Ten goats were used to establish the bone defect model of the mid-tibia. The bone defect ends were shortened step by step with a sulcated half-ring external fixator. Changes of the blood flow of the distal extremity were measured with pulse-Doppler monitor and angiography. RESULTS: The blood flow in the distal extremity was not affected when bone defect was less than 15% of the original length. Blood circulatory disorder would appear in the distal extremity when bone defect ranged 15%-20% of the original length. The necrosis would appear in the extremity because of the blood circulatory obstacle when bone defect was more than 20% of the original length. CONCLUSIONS: EECL is an appropriate alternative of treatments if bone defect is less than 15%; while SBTL may be feasible if bone defect is over 20% of the original length. When bone defect ranges between 15% and 20%, EECL should be applied with great care on condition of keeping watch on the extremity circulation with pulse-Doppler monitor.

Angiography↗

[A population-based surveillance system on birth defects and its application].

OBJECTIVE: To describe a unique surveillance system on birth defects in the People's Republic of China. METHODS: The system was instituted in 1992 as a component for the evaluation on the effectiveness of a community intervention program using periconceptional folic acid supplementation to prevent neural tube defects and currently carries out surveys on a birth cohort of approximately 150 000 infants per year. Information was collected in the form of detailed written descriptions by local health care providers and photographs of affected infants. The system allowed for detection of birth defects at the local level with later definitive classification and coding; however, information was limited to those structural anomalies which were visible on physical examination. RESULTS: This surveillance system on birth defects provides an extensive database of infants with major and minor external structural anomalies. From 1993 to 1996, more than one million births were monitored, with more than 10 000 birth defects and 30 000 photos submitted. Among them 5 000 were identified with major birth defects. Neural tube defects, oral clefts and extremity abnormalities were the first few defects with most cases. Data were used in birth defect surveillance reports and scientific papers. CONCLUSIONS: This system can be utilized for studies on etiology, descriptive epidemiology, and identification of unusual trends which is unique with multiple advantages in the People's Republic of China.

Congenital Abnormalities↗