The open section effect in a long bone with a longitudinal defect - a theoretical modeling study

A longitudinal defect dramatically alters the stress distribution within a long bone. The altered stress distribution can influence the structural properties of the bone and the stimulus for repair and remodeling of the defect and the surrounding bone. For applied torsion, the defect interrupts the normal shear flow around the bone. Reversal of the shear flow along the inner cortex of the bone is the primary characteristic of the "open-section" effect. Stress concentration effects also produce large stresses at the defect corners. A finite element model of a femur mid-diaphysis with a rectangular defect in the posterior cortex was developed to quantify the femur stress distribution and torsional stiffness for defect widths ranging from one-tenth of the femur outer diameter (0.1 OD) to 0.3 OD, and defect lengths ranging from 0.5 to 5 OD. Defects with a length of 1 OD or shorter had little influence on the femur torsional stiffness or the femur shear-stress distribution. The torsional stiffness decreased most dramatically as the defect length increased from 2 to 3 OD, but began to approach an asymptote near 5 OD. Shear flow reversal peaked at the center of the defect for defects longer than 1 OD, and the magnitude of the reversal began to approach an asymptote near 5 OD. For each defect, the largest stresses within the bone, developed at the defect corners. The results indicate that the open-section effect decreases the torsional stiffness and stress concentration effects decrease the torsional strength of a long bone with a longitudinal defect.     

A case report of ectopia cordis and omphalocele

A rare congenital defect in fusion of the anterior chest wall resulting in an extrathoracic location of the heart. Cantrell''s pentalogy is a congenital anomaly resulting from embryologic development defect and consists of the following: A deficiency of the anterior diaphragm, a midline supraumbilical abdominal wall defect, a defect in the diaphragmatic pericardium, congenital intracardiac abnormalities, and a defect of the lower sternum. Here we report a rare case of ectopic cordis with omphalocele.     

Ataxia-telangiectasia: an inherited disorder of ionizing-radiation sensitivity in man

Summary This review summarizes the current research on the biochemical defect leading to ataxia-telangiectasia (AT). A DNA repair defect has been linked to AT, although the precise defect has not been found. A critical examination of the evidence for and against a DNA repair defect in AT is presented. Consideration of other recent data on AT raises the possibility that AT may not primarily be the result of a DNA repair defect. Therefore, in this review AT is approached as a syndrome which is defective in the ability to respond to ionizing-radiation-type damage, rather than defective in the ability to repair this damage. However, this does not necessarily exclude the potential involvement of a DNA repair defect in some of the genetically distinct subsets present in AT. Other recent anomalies found in AT, including an altered cell cycle and DNA synthesis profile following ionizing-radiation damage, are also assessed. A suggestion to account for the underlying defect in AT, based on the various research reports, is presented.     

Associated von Willebrand disease as a possible cause of lack of thrombosis in an AT III abnormality (AT III Trento)

In a family with a known antithrombin III abnormality (AT III Trento) an associated von Willebrand defect (Type I) was found. The two defects seem to segregate independently. In fact four types of individuals were present, namely: subjects with isolated AT III abnormality, subjects with isolated von Willebrand defect, patients with double defect and normal subjects. Only one of the two patients with isolated AT III abnormality showed a thrombotic tendency. None of the patients with double defect showed thrombotic disease, indicating a possible protective action of the von Willebrand defect against thrombotic manifestations. Patients with isolated von Willebrand defect showed neither thrombotic nor bleeding manifestations. The study emphasizes the need for a careful evaluation of the hemostatic balance of patients with AT III abnormalities before concluding that they are symptomatic or asymptomatic.     

The osteogenic role of the dura mater in adult rabbits during regeneration of the skull]

It was shown in experiments with adult rabbits that the regeneration of skull vault bones after artificial trauma proceeds, mainly, at the expense of osteogenic activity of dura mater, rather than by means of outgrowth of bone from the defect margins. During regeneration, dura mater connects with the granulation tissue which fills the area of defect. The first bone islets are formed by the surface layer of dura mater near the defect margins and then all over the defect area. During regeneration bone islets merge with each other and with the old bone at the defect margins. In experiments with separation of the defect margins from dura mater by millipore filter, regeneration is insignificant over the filter near the old bone margins (bone trabeculae form which close destructed bone marrow cavities); the bone forms intensively under the filter on dura mater. In experiments with the removal of a piece of skull bone together with the adjacent region of dura mater, no bone regeneration occurs, the defect area is filled by the scar tissue.     

Genetic recombination in Bacillus subtilis 168: contribution of Holliday junction processing functions in chromosome segregation

Bacillus subtilis mutants classified within the epsilon (ruvA, DeltaruvB, DeltarecU, and recD) and eta (DeltarecG) epistatic groups, in an otherwise rec+ background, render cells impaired in chromosomal segregation. A less-pronounced segregation defect in DeltarecA and Deltasms (DeltaradA) cells was observed. The repair deficiency of addAB, DeltarecO, DeltarecR, recH, DeltarecS, and DeltasubA cells did not correlate with a chromosomal segregation defect. The sensitivity of epsilon epistatic group mutants to DNA-damaging agents correlates with ongoing DNA replication at the time of exposure to the agents. The Deltasms (DeltaradA) and DeltasubA mutations partially suppress the DNA repair defect in ruvA and recD cells and the segregation defect in ruvA and DeltarecG cells. The Deltasms (DeltaradA) and DeltasubA mutations partially suppress the DNA repair defect of DeltarecU cells but do not suppress the segregation defect in these cells. The DeltarecA mutation suppresses the segregation defect but does not suppress the DNA repair defect in DeltarecU cells. These results result suggest that (i) the RuvAB and RecG branch migrating DNA helicases, the RecU Holliday junction (HJ) resolvase, and RecD bias HJ resolution towards noncrossovers and that (ii) Sms (RadA) and SubA proteins might play a role in the stabilization and or processing of HJ intermediates.     

Trp64----nonsense mutation in the lipoprotein lipase gene.

A lipoprotein lipase (LpL) gene defect has been identified, a G----A transition at nucleotide position 446 of exon 3, resulting in a premature termination codon (Trp----stop) at amino acid residue 64. This defect was identified in a Type I hyperlipoproteinemic subject with an amino acid residue 194 defect in the other allele. Plasma lipoprotein values as well as LpL mass and activity in postheparin plasma were determined in the subjects with the residue 64 defect and in other LpL-deficient heterozygotes. LpL mass levels in both the Type I and the other subject with a 64 LpL defect were markedly reduced. This may be explained by rapid degradation of LpL protein or decreased secretion from the 64 defective allele. Alternatively, the marked reduction or absence of mass associated with the 64 defect may be due to synthesis of a severely truncated protein which escapes immunologic detection.     

Inheritance of vertical fiber hide defect in cattle

Inheritance of vertical fiber hide defect (VFHD), a structural defect in collagen fiber orientation that causes weakness and reduced value of leather, was examined using histological data on hide biopsies obtained from 465 Hereford cattle by 65 sires. The data set included 44 offspring-dam pairs, for which VFHD phenotypes had been diagnosed on both the offspring and dam. Examination of offspring and parental frequency distributions indicated that inheritance of the condition was likely to be due to an autosomal recessive. In a subsequent experiment, a Hereford bull with a known VFHD phenotype was mated to Hereford cows with known VFHD phenotypes and to Angus cows not showing the defect. Angus were chosen because the defect has never been observed in the breed. All offspring (5) resulting from VFHD X VFHD matings expressed the defect, while no offspring (12) out of VFHD X non-VFHD matings (Angus cows) expressed the defect. It was concluded that VFHD is inherited as an autosomal recessive. The role that selection and alternative crossbreeding systems can play reducing phenotypic frequency of the defect is discussed.     

Indentation of an osteochondral repair: sensitivity to experimental variables and boundary conditions

The sensitivity of the affects of indenter radius, defect depth, cartilage permeability and flow boundary conditions, on the indentation testing of a repairing osteochondral defect was investigated. Since the boundary condition on the flow across the cartilage repair-subchondral bone interface is not known, the effects of two different conditions were investigated: free-flow and no-flow. A poroelastic finite element model of an osteochondral defect at different stages of the repair process was developed using dimensions typical of the rabbit knee. Results showed when the radius of the indenter was much less than the thickness of the cartilage the sensitivity of the indentation displacement to flow boundary conditions decreased. Simulated indentation displacement was insensitive to bone regeneration up to 50% of the initial defect depth, which suggests that only the properties of the material in the upper-half of the defect are being evaluated. Small variations in permeability had little affect on the simulated indentation. In a fully repaired defect, the simulated indentation is independent of the boundary condition. However, while the defect is in the process of repair and the regenerated cartilage is deeper than the host, indentation is sensitive to the flow boundary condition. Based on these results, and feasible experimental conditions, we conclude that the boundary condition on the repair-subchondral bone interface must be known in all cases except when the defect approaches full repair, if accurate estimates of material properties are to be obtained from indentation.     

Manifestation of the fragile site Xq27 in fibroblasts

Summary Fibroblasts from a heterozygous carrier for the Martin-Bell syndrome, who manifests the fragile site Xq27, were cloned to separate the population carrying the primary defect on the active X chromosome from the population with this defect on the inactive X. Clones with this defect on the active X manifest the fra(X)(q27) whereas clones from the other population are fra(X)-negative (Steinbach et al. 1983b). In this project, the replication status of the X chromosome manifesting the fra(X)(q27) was studied in seven clones with this defect on the active X.The results obtained on the clones were very similar to the results obtained from uncloned fibroblasts and lymphocytes. In the clones the fragile site was found manifested on the early replicating X in 73 cells and on the late replicating X in four cells.Since the defect is located on the active X chromosome of these cells the manifestation of the fragile site on the late replicating X suggests that the defect and the fragile site cannot be identical. It is concluded that there is no obligate synteny of this defect and the manifested fragile site.     

Under restrictive conditions,can the widths of linear enamel hypoplasias be used as relative indicators of stress episode duration?

Linear enamel hypoplasia (LEH), a type of enamel defect reflecting nonspecific physiological stress, has traditionally been used by bioarchaeologists to assess human health. Initially, measurements of defect width were used to estimate the duration of stress episodes. More recently, methods of counting within-defect perikymata (enamel growth increments) were developed to more accurately assess duration. Because perikymata are often not continuously visible within defects, while widths can usually be measured, the primary purpose of this article was to determine if, under restrictive conditions, the widths of LEH defects might be used as relative indicators of stress episode duration. Using a set of dental replicas from the prehistoric Irene Mound (1150-1400 A.D.), this study also investigated potential sources of variation in defect widths and how often defect widths could be measured and within-defect perikymata counted. Of 120 defects, only 47 contained both measurable defect widths and total within-defect perikymata, while 79 had measurable defect widths. Regression analysis revealed that, for these 47 defects, defect widths were more strongly related to the total number of within-defect perikymata than they were to crown region or tooth type. Although wide prediction intervals indicated that a defect's width could not be used to predict the number of within-defect perikymata for an individual, narrower confidence intervals associated with hypothetical mean population widths suggested that mean defect widths might be used to rank populations in terms of relative average stress episode duration.     

The Dag defect of the tail of the bull sperm. Studies on the inheritance and pathogenesis

During the period 1963–1979, 15 spontaneous cases of the sterilizing Dag defect of the sperm tail in Danish Jersey bulls have been examined. The pedigree of these bulls could be traced back through both paternal and maternal lines to a common ancestor bull born in 1934. The probable heredity of the defect was tested in a sire-daughter breeding experiment. Six bulls out of 38 sons born produced semen typical of the Dag defect thus confirming that the defect is due to the presence of an autosomal recessive factor. Systematic examination of the epididymal contents from 17 bulls revealed that the defect consistently developed in the distal part of the epididymal caput. Neither biophysical and biochemical qualities of the epididymal contents nor the histological appearance of the duct epithelium differed from the findings in normal bulls.     

Association of cleft lip and atrial septal defect in mice: a preliminary report.

Newborn A/J and CL/Fr mice with congenital cleft lip usually have an atrial septal defect of the secundum type, often associated with cyanosis. Their littermates without cleft lip rarely have a septal defect. The atrial septal defect results from a delay in growth of the atrial septum primum.     

The effect of defect size on the stress concentration and fracture characteristics for a tubular torsional model with a transverse hole

The maximum stress location and crack resistance of a tubular torsional model with varying transverse circular defects were determined by the use of experimental and global-local finite element modeling techniques. The experimental results showed that the reduction in torsional strength was inversely proportional to defect size. In addition, the maximum stress location around the defect was closely related to the normalized defect diameter. By measuring the shifted angle associated with each defect ratio, a linear relationship, delta theta = -6.28 + 0.55*(d/D), was determined. Finite element results indicated that the stress concentration factor, Kg, for a single-cortex defect is similar to that of a double-cortex defect of identical dimension. Application of the strain energy density (SED) theory proposed by Sih and Oliveira Faria (Fracture Mechanics Methodology, Martinus Nijhoff, The Hague, 1984), indicated that the fracture toughness, KIC, for large defects was greater than that for small defects. This implies that tubular structures with large defects have a greater resistance to crack initiation and growth.     

Reconstruction of a soft tissue defect of the back after myelomeningocele closure with modified V-Y plasty

Myelomeningocele is a congenital defect in vertebral arches with cystic dilatation of meninges and structural or functional abnormality of spinal cord or cauda equina. It is a form of spinal dysraphisam with overlying skin defect (spina bifida aperta). That condition is related to other clinical complications such as infection that can produce furthermore complications. To prevent rate of complications surgical treatment in first 24 h is strongly suggested. In this case report we describe a patient (infant) with congenital myelomeningocele who's defect was treated surgically by the neurosurgeon. In operative procedure plastic surgeon was involved to cover the skin defect remaining after neurosurgical closure of spinal canal. Bilateral advancement local skin flaps were used in soft tissue defect closure. Review of the literature that refers to advancement local skin flaps was carried out.     

Mutational evidence for identity of penicillin-binding protein 5 in Escherichia coli with the major D-alanine carboxypeptidase IA activity.

The defect in D-alanine carboxypeptidase IA activity in the dacA11191 mutant of Escherichia coli was correlated with a defect in the release of penicillin G from penicillin-binding protein 5. The results suggest that penicillin-binding protein 5 catalyzes the major D-alanine carboxypeptidase IA activity of the wild type and that the mutation results in a defect in the deacylation step catalyzed by this enzyme.     

Multiple patterns of alloantigen presenting/stimulating cell dysfunction in patients with AIDS.

The APC/stimulating cell (APC/SC) potential of PBMC from Walter Reed stage 1 and 2 patients and patients with AIDS was tested by using these PBMC as stimulators in an allogeneic MLR. The responding cells were PBMC from unrelated, HIV- donors that were either unfractionated or depleted of APC by plastic and nylon wool adherence. Using this approach, we observed no defect in the APC/SC potential of PBMC from Walter Reed stage 1 and 2 patients. However, PBMC from AIDS patients used as allogeneic stimulators exhibited three different patterns of APC/SC function: 1) no defect in alloantigen (ALLO) APC/SC potential; 2) a defect in ALLO APC/SC function that was detected only if the responder cells were depleted of APC (presenting cell defect); and 3) a defect in ALLO APC/SC function, irrespective of whether the responder cells were depleted of APC (stimulating cell defect). These results indicate that in addition to Th cell defects associated with AIDS, the PBMC from AIDS patients can also exhibit a defect in APC/SC function. This study provides an approach that permits the testing of Ag-presenting function in all AIDS patients, and is therefore not limited to testing patients for whom HIV-, HLA-identical T cells and APC are available.     

Brief communication: physiological stress in the Florida Archaic-enamel hypoplasia and patterns of developmental insult in early North American hunter-gatherers

We examined the prevalence and developmental timing of linear enamel hypoplasias (LEHs) in an early Archaic Floridian population from Windover (8,120-6,980 (14)C years B.P. uncorrected). Using digital images, mandibular and maxillary canines were analyzed for defect prevalence and timing of insults. Although overall prevalence was very weakly correlated with earlier defect timing, there were significant differences in defect prevalence that varied by sex and tooth type. The mean LEH count in male mandibular canines was far higher than in male maxillary canines or in female mandibular or maxillary canines. We examined defect timing as a possible predictor of the sex differences in LEH prevalence. There were no significant sex differences in the developmental timing of the earliest defects in either tooth class. Developmental timing is not responsible for the sex differences seen in defect prevalence in mandibular canines.     

Linking teratogen information service and birth defects registry databases to improve knowledge of birth defect status

BACKGROUND: Although teratogen information services (TISs) obtain maternal exposure information from their callers, such services often do not know if the pregnancies were affected by a birth defect. This study attempted to improve the completeness of this information for Texas Teratogen Information Service (TTIS) callers by linking their records with the Texas Birth Defects Registry (TBDR) and Texas birth certificates (TBCs). METHODS: A total of 344 expectant mothers called TTIS with expected dates of delivery between 1 January 2000 and 31 December 2001. These pregnancies were linked with TBDR and TBC data. The percentages of pregnancies with known birth defect information both before and after the linkage were compared. RESULTS: The TTIS originally collected birth defect status information for 101 of the 344 callers (29.4%) and 0.6% of all 344 callers or 2.0% of callers with birth defect status information had a pregnancy affected by a birth defect. Linking TTIS records with TBDR and TBC data helped to raise the percentage of callers with birth defect status information from 29.4% to 71.5%. Among those callers, the percentage known to have birth defects increased from 2.0% to 4.1%. The sensitivity of TTIS follow-up calls in identifying birth defects was 50%, and the specificity was 100%. CONCLUSIONS: Linking TTIS caller records with TBDR and TBC data significantly increased both the percentage of pregnancies with birth defect status information and the percentage of pregnancies identified as affected by birth defects. Such linkage may be a good approach by which TISs can increase the completeness of their birth defect status information.     

The Relationship Between Lesion Size and Load to Failure After Stabilization of Simulated Metastatic Lesions of the Proximal Femur

BackgroundAs overall cancer survival continues to improve, the incidence of metastatic lesions to the bone continues to increase. The subsequent skeletal related events that can occur with osseous metastasis can be debilitating. Complete and impending pathologic femur fractures are common with patients often requiring operative fixation. However, the efficacy of an intramedullary nail construct, on providing stability, continue to be debated. Therefore, the purpose of this study was to utilize a synthetic femur model to determine 1) how proximal femur defect size and cortical breach impact femur load to failure (strength) and stiffness, and 2) and how the utilization of an IMN, in a prophylactic fashion, subsequently alters the overall strength and stiffness of the proximal femur.MethodsA total of 21 synthetic femur models were divided into four groups: 1) intact (no defect), 2) 2 cm defect, 3) 2.5 cm defect, and 4) 4 cm defect. An IMN was inserted in half of the femur specimens that had a defect present. This procedure was performed using standard antegrade technique. Specimens were mechanically tested in offset torsion. Force-displacement curves were utilized to determine each constructs load to failure and overall torsional stiffness. The ultimate load to failure and construct stiffness of the synthetic femurs with defects were compared to the intact synthetic femur, while the femurs with the placement of the IMN were directly compared to the synthetic femurs with matching defect size.ResultsThe size of the defect invertedly correlated with the load the failure and overall stiffness. There was no difference in load to failure or overall stiffness when comparing intact models with no defect and the 2 cm defect group (p=0.98, p=0.43). The 2.5 cm, and 4.5 cm defect groups demonstrated significant difference in both load to failure and overall stiffness when compared to intact models with results demonstrating 1313 N (95% CI: 874-1752 N; p<0.001) and 104 N/mm (95% CI: 98-110 N/mm; p=0.03) in the 2.5 cm defect models, and 512 N (95% CI: 390-634 N, p<0.001) and 21 N/mm (95% CI: 9-33 N/mm, p<0.001) in the models with a 4 cm defect. Compared to the groups with defects, the placement an IMN increased overall stiffness in the 2.5 cm defect group (125 N/mm; 95% CI:114-136 N/mm; p=0.003), but not load to failure (p=0.91). In the 4 cm defect group, there was a significant increase in load to failure (1067 N; 95% CI: 835-1300 N; p=0.002) and overall stiffness (57 N/mm; 95% CI:46-69 N/mm; p=0.001).ConclusionProphylactic IMN fixation significantly improved failure load and overall stiffness in the group with the largest cortical defects, but still demonstrated a failure loads less than 50% of the intact model. This investigation suggests that a cortical breach causes a loss of strength that is not completely restored by intramedullary fixation. Level of Evidence: II