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PubMed1997

Simulation model of defective insulin receptors as byproducts of receptor recycling.

Our simulation model assumes that the defective insulin-binding receptors in non-insulin-dependent diabetes (NIDDM) patients result from functional receptor recycling. The model is a short program written in MS DOS 5.0 Qbasic. MODEL DESIGN: Receptors with intracellular portions damaged in the process of recycling are considered defective since they bind insulin but do mediate insulin effects, or recycle. Their occurrence depends on the average activation rate of functional receptors. The insulin-binding receptors (defective and functional) are objects of slow and time-dependent turnover defined by the turnover rate. Recycled receptors rejoin functional receptors or enter the pool of defective receptors. The waste in the functional receptors' pool is covered by a limited amount of newly synthesized receptors. The defective receptors often accumulate in cases of increased activation of functional receptors. SIMULATION RESULTS: The insulin-binding receptor quantity is determined, in the model, only by the number of newly synthesized receptors, reflecting the intensity of insulin stimulation. Synthesis is increased following variable insulin stimulations and decreased after sustained, intensive insulin stimulation. The number of functional receptors inversely reflects the average activation rate of functional receptors compared with the insulin-binding receptors turnover rate. High activation rates can diminish the proportion of functional receptors to less than 5% of that of all insulin-binding receptors. The model predicts that cells bearing only functional receptors show progressively shortened half-lives of receptors, reflecting the receptor activation intensity. On the other hand, cells bearing both defective and functional receptors show stable receptors' half-lives (20-36% of the defective receptors' half-life). Simulation results suggest that reduced functional receptor proportions in NIDDM patients might reflect the imbalance between the activation of functional receptors and the slow catabolism of defective receptors.

Animals↗

PubMed2002

Osteogenic protein-1 induced bone formation in an infected segmental defect in the rat femur.

The goal of this study was to use a segmental defect model in the rat femur to determine if osteogenic protein-1 (OP-1) is capable of inducing bone formation in the presence of bacterial contamination. A 6 mm segmental defect was surgically created and stabilized with a polyacetyl plate and Kirschner wires in one femur in each of 126 Sprague-Dawley rats. The animals were divided into eight groups in which the defect was either left untreated, or subjected to various combinations of OP-1 (11 or 50 microg), lyophilized bovine type I collagen (carrier for the OP-1), and 10(5) colony-forming units of Staphylococcus aureus. The animals were euthanized at either 2, 4, or 9 weeks. Quantitative radiographic and histologic analyses were performed on the harvested tissue. The initial contamination progressed to infection in all animals receiving bacteria, as determined by qualitative bacteriology. There was very little, if any, bone formation in the untreated defects, and in the contaminated defects with or without collagen carrier. Bone formation was significantly greater in contaminated defects with either dose of OP-1, compared with contaminated defects without OP-1. The 50 microg dose of OP-1 induced significantly more bone formation than the 11 microg dose, both with and without bacteria. This investigation has demonstrated that OP-1 maintains its osteoinductive capability in a contaminated segmental defect. OP-1 may potentially be used in the clinical management of contaminated fractures.

Animals↗

PubMedDate not supplied

Patellar tendon defect during the first year after anterior cruciate ligament reconstruction: appearance on serial magnetic resonance imaging.

The purpose of this study was to use magnetic resonance imaging to evaluate various parameters of the patellar tendon during the first year after harvest for anterior cruciate ligament (ACL) reconstruction. Twelve consecutive patients were serially imaged on a 1.5 Tesla GE magnet (GE Medical Systems, Milwaukee, WI) with a dedicated knee coil at 3 weeks, 3 months, 6 months, and 1 year after undergoing ACL reconstruction using a central one-third patellar tendon autograft. The tendon defect was not closed primarily, but the paratenon was approximated. The following measurements were performed: tendon width, defect width, cross-sectional area of the tendon, and tendon length. In addition, the patellar bone harvest site was evaluated for healing. The width of the tendon defect decreased by 62% over 12 months (P < .05). Only two patients showed complete closure of the defect. Tendon width was noted to decrease by 6.5% (P=.017). The ratio of defect width to overall tendon width (designated R) decreased by 58% (P < .05). Tendon length was noted to decrease during this by 8% (P=.037). The tendon cross-sectional area was noted to increase by 9% at 1 year, but this was not found to be statistically significant (P=.39). One year after ACL reconstruction using a central one-third patellar tendon, the tendon defect has begun to reconstitute itself but there is still a significant gap. This persistent defect must be taken into consideration when planning revision ACL surgery using reharvest of the central one third of the patellar tendon. The entire tendon also exhibits a reduction in width and length, while cross-sectional area increases slightly. Complete healing of the graft defect can not be assumed at 12 months post-ACL reconstruction.

Adolescent↗

PubMed2004

Intraindividual comparison of epithelial defects during laser in situ keratomileusis using standard and zero-compression Hansatome microkeratome heads.

PURPOSE: To determine the difference between the standard and a modified (zero-compression) Hansatome microkeratome head (Bausch & Lomb) in the incidence of epithelial defects. SETTING: Department of Ophthalmology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. METHODS: Ninety-three patients (186 eyes) with a mean age of 39.1 years +/- 9.5 (SD) having laser in situ keratomileusis (LASIK) in both eyes were enrolled in a prospective randomized study using intraindividual comparison. In 1 eye, the flaps were created with the Hansatome microkeratome using the standard Hansatome head and in the other eye, the flaps were created with a microkeratome head with a modified design (zero-compression head). Intraoperative evaluation of epithelial defects was done using a standardized protocol. Statistical evaluation was performed with McNemar and Bowker tests. RESULTS: Epithelial defects occurred in 21 eyes (22.6%) in which the standard head was used and in 2 eyes (2.1%) in which the zero-compression head was used. In the former group, 15 (16.1%) of the epithelial defects were larger than 1.5 mm(2); the remaining 6 (6.4%) were smaller than 1.5 mm(2). In the latter group, both epithelial defects were smaller than 1.5 mm(2); both patients also had an epithelial defect in the eye in which the standard Hansatome head was used. The difference between the 2 Hansatome heads in the incidence (P<.001, McNemar) and size (P<.001, Bowker) of the epithelial defects was statistically significant. CONCLUSIONS: The Hansatome microkeratome with a zero-compression head significantly reduced the occurrence of intraoperative epithelial defects. The change in the construction of the Hansatome head is a useful improvement in LASIK technology.

Adolescent↗

PubMed2001

Immunologic defects and vaccination in patients with chronic renal failure.

Patients with chronic renal failure suffer from defective host defenses which are directly the result of the renal impairment, in addition to those dependent on the primary illness leading to the renal failure. The mechanisms underlying the defective responses in phagocytic cells, lymphocytes and antigen processing are likely due to either failure to adequately eliminate suppressive compounds by the defective kidneys or to improper metabolic processing of the factors by the damaged renal parynchema. That some of the defects are reversed by transplantation and not dialysis suggests that renal parenchymal metabolic activities may be involved, although it is also possible that functioning glomerular cells are capable of filtering substances that membranes are not currently capable of eliminating. The current strategy for dealing with the immunodeficiency appears to be totally based on developing means to circumvent the defective function. The other approach, correction of the impaired function, cannot be even considered until the mechanisms underlying the defective function of the cells involved in defenses are better delineated. It seems possible that one or a few compounds are pivotal in altering the function of all the affected cell lines, since, with only a small amount of effort, it is possible to relate the dysfunction to abnormal cell membrane functions in phagocytic cells, dendritic cells and lymphocytes. Until the biochemical basis of the dysfunction of all the cell types affected are better defined, such exercises cannot be translated into better management of patients with chronic renal failure. Proper function of host defenses requires that appropriate cells can properly respond to threats to host viability. For the cells of the immune system (phagocytes and lymphocytes) this means that their response to regulatory molecules be appropriate, that their mobility be normal, that their adherence to substrates be preserved, and that they can generate the appropriate response to the challenge. For neutrophils, for example, it is necessary that they recognize and mobilize appropriately to chemotactic stimuli, that they be able to adhere to and migrate through endothelial lining, that their phagocytic activity be sufficient, and that they can kill and degrade endocytosed particles and generate appropriate secretions. Similar lists of requirements for good function can be generated for any cell type in the immune defense system. Uremia, as well as currently available treatments for uremia, directly or indirectly alters the function of all phases of appropriate immune cell function. Defective host responses in uremia have been recognized for decades and there has been considerable effort in the past decade to better define the extent and mechanisms of impaired defenses. Despite the multitude of major defects in humoral, cellular, and inflammatory processes, uremic patients who are cared for today, although they remain at higher risk of serious infectious complications, can and do maintain a good quality of life, with most remaining free of major infections for years and decades.

Hepatitis B↗

PubMed1994

The role of autogeneic bone marrow in the repair of a skull trephine defect filled with hydroxyapatite granules in the rabbit.

For study of the effect of autogeneic bone marrow on the repair of skull defects filled with hydroxyapatite (HA) granules, 20 trephine defects 11 mm in diameter in 10 New Zealand rabbit skulls were made. Three defects were implanted with HA granules (HAg), and seven defects were implanted with HA granules mixed with autogeneic bone marrow (HAg/BM) from the femoral medullary canal. Autogeneic bone marrow (BM) was implanted in three defects, and seven defects were left unfilled. Histomorphometric quantitation of bone and connective-tissue ingrowth into defects showed that the area of new bone ingrowth in BM (70.3 +/- 8.4%) was significantly larger than that in HAg (34.4 +/- 3.9%) and in HAg/BM (24.0 +/- 5.1%) (P < 0.01 and P < 0.01, respectively). Immunohistologic staining detected fibronectin and collagen type III as the main components in the defects filled with HAg and HAg/BM. The osteoconductive capacity of HA granules was not stimulated by adding fresh autogeneic bone-marrow cells.

Analysis of Variance↗

PubMed2003

Distribution of MR-detected cartilage defects of the patellofemoral joint in chronic knee pain.

OBJECTIVES: The aim of the study was to detect cartilage defects and determine the center of these defects in MR imaging of the patellofemoral joint (PFJ) in middle-aged people with chronic knee pain. DESIGN: In the format of a prospective study of early osteoarthritis (OA), this cross-sectional study of the signal knee (the most painful one at inclusion in the study in 1990) in 59 individuals, 30 women and 29 men (aged 41-58 years, mean 50 years) with chronic knee pain, with or without radiographically determined knee OA, was examined using MR imaging on a 1.0 T imager. Cartilage defects and the center of these defects in the PFJ were recorded. RESULTS: Cartilage defects were found more often in the patella (40 knees) than in the femoral trochlea (23 knees) (P<0.001) and were unevenly distributed in the patella (P<0.001), with most cartilage defects in the mid-patella. CONCLUSIONS: Since cartilage defects occur more commonly in the mid-patella, radiographs obtained with a knee flexion of approximately 45 degrees may be more accurate to show cartilage defects of early OA of the PFJ than views with another knee flexion.

Adult↗

PubMed1996

Observer differentiation of proximal enamel mechanical defects versus natural proximal dental caries with computed dental radiography.

OBJECTIVES: Various models have been used to study the accuracy of imaging systems for detection of dental caries. This study compares the ability of dentists to detect mechanically created defects versus natural dental caries cavitations on the proximal surfaces of extracted teeth with Computed Dental Radiography (Schick Industries, Long Island City, N.Y.). Detection rates are investigated according to lesion depth to permit comparisons to be made between studies in the literature with other mechanical defects or natural caries models. Discrimination of natural caries versus artificial defects with Computed Dental Radiography is also compared with a previous report that used standard dental film. STUDY DESIGN: Fifty-two extracted molar and premolar teeth were mounted into representative sets of maxillary and mandibular posterior arches for bite-wing radiography. There were 16 proximal surfaces with natural caries and 28 proximal surfaces with mechanical defects. An optical bench was used to ensure constant beam geometry. A 1.8 cm acrylic soft tissue equivalent attenuator was placed in front of the receptor. Thirty dentists acted independently as observers to differentiate between sound proximal tooth surfaces, natural dental caries, and mechanical defects. Evaluation of intra- and interobserver variability was made with use of the kappa statistic. The Zelen test of odds ratios was used to test for homogeneity, and the Mantel-Haenszel analysis plus stratified logistic regression were used for inference about the common odds ratio. Significance was set at p < 0.05. RESULTS AND CONCLUSIONS: Ignoring stipulation of cavity type, detection was 74% for mechanical defects and 67% for natural caries. The odds of detecting a mechanical defect were 1.40 times the odds of finding natural dental caries cavitation of the same depth. Lesion depth did influence the probability of correctly identifying the presence of a lesion; the odds of identifying cavitation increased 1.41 times with every 0.1 mm increase in lesion depth. Correct designation of lesion type was 1.42 times more likely with mechanical defects than with natural caries (p = 0.003). Intraobserver (kappa = 0.65) and interobserver (kappa = 0.43) agreements were fair to good. Discrimination between natural and artificial lesions was less with the Computed Dental Radiography than that found in our previous study with standard direct emulsion x-ray film.

Bicuspid↗

PubMed1997

Dental enamel defects in celiac patients.

OBJECTIVE: The incidence and distribution of enamel defects among patients with celiac disease were examined. STUDY DESIGN: The oral cavity was explored in 137 patients with celiac disease (mean age 16.2 years; age range 5 to 68 years) and in 52 control patients (mean age 19.8 years; age range 5 to 64 years). Permanent dentition enamel defects were recorded, along with their number and locations. The decayed, missing, and filled teeth index rates were also established, and an investigation was made of the human leukocyte antigens among the patients with celiac disease. The results obtained were analyzed with the chi-squared test, statistical significance being regarded for p < or = 0.05. RESULTS: Enamel defects were observed in 72 (52.5%) of the patients with celiac disease (52 patients had systematic defects) and in 22 (42.3%) of the control patients (9 patients had systematic defects). Systematic defects were significantly more common in the celiac disease group. In the patients with celiac disease, 72.2% were symmetrical, compared with 40.9% of the defects in the control patients. The incisors were the most frequently affected teeth, the extent of involvement being significantly greater in the celiac disease group. In patients with celiac disease, DR7, DR3, and DQ2 were the most commonly observed human leukocyte antigens. The mean decayed, missing, and filled teeth index rates were 4.8 and 6.2 in the celiac disease group and the control group, respectively. CONCLUSIONS: Enamel defects are common among patients with celiac disease. They tend to be bilateral and symmetrical, and they are chronologically distributed. The lesions affect mainly the incisors and the molars. Patients with such characteristics should be evaluated for possible celiac disease.

Adolescent↗

PubMed2006

Gate effect of vacancy-type defect of fullerene cages on metal-atom migrations in metallofullerenes.

Metal-atom migration outside from a defective fullerene cage of a metallofullerene Gd@C(82) (Ca@C(82)), where the Gd(3+) (Ca(2+)) ion is incorporated inside the C(2)(v)()-C(82) cage, is discussed in detail at the B3LYP DFT level of theory. The metal-atom migrations are initiated by the formation of vacancy-type defects involving two coordinatively unsaturated C atoms. This step, which is assumed to proceed due to energy-particle irradiation, leads to the formation of antibonding orbitals between the two C atoms. Since the antibonding orbitals can interact with vacant d-orbitals of the Gd(3)(+)() ion in an in-phase fashion, the attractive interactions allow the Gd ion to insert into the two C atoms in the defect. As a result, the metal ion passes through the defect under energy-particle irradiation. In contrast, the Ca(2+) ion with the vacant s-orbitals does not have such orbital interactions, and thus, a C-C bond is reformed between the two C atoms, which prohibits the Ca ion from penetrating the defected C(82) cage. DFT calculations nicely demonstrate that the orbital interactions control metal-atom migration around the defect site using their orbital symmetries, and therefore, the vacancy-type defect acts as a "gate" that permits a specific atom to go out from a defected fullerene cage.

Calcium↗

PubMed2001

Transforming growth factor-beta1 incorporated in calcium phosphate cement stimulates osteotransductivity in rat calvarial bone defects.

Bone regeneration of the alveolar crest around dental implants is an important factor in the success of implant use. Calcium phosphate cement can be used as a bone substitute and applied clinically as a paste to fill micro- and macroscopic bone defects. We have shown earlier that the intermixing of the recombinant human transforming growth factor-beta1 (rhTGF-beta1) in hardening calcium phosphate cement stimulated osteoblastic differentiation of rat primary bone cells in vitro. The aim of the present study was to examine whether the similar enrichment with rhTGF-beta1 affects the replacement of calcium phosphate cement by bone (osteotransduction) in calvarial critical size defects (csd) of adult rats. Two bone defects of 5 mm diameter were created bilaterally in each skull of 10 adult male rats. Both defects were filled with 53 mg of calcium phosphate cement without rhTGF-beta1 (control) at one side, and with 10 or 20 ng rhTGF-beta1 at the other side. After 8 weeks, defects with surrounding skull were analysed histologically and histomorphometrically. The addition of rhTGF-beta1 in the cement increased the amount of bone in rat skull defects. This finding coincidences with our in vitro observations, that intermixing of rhTGF-beta1 in calcium phosphate cement stimulates bone cell differentiation. Addition of rhTGF-beta1 stimulated bone formation as indicated by an increased bone volume of 50% and an increased bone/cement contact of 65%, in comparison to control defects with cement without rhTGF-beta1. In addition, rhTGF-beta1 reduced the remaining volume of cement, by 11% at 10 ng rhTGF-beta1, and by 20% at 20 ng rhTGF-beta1 in the cement. Defect closure was not affected. We conclude that the intermixing of rhTGF-beta1 in a fast-setting calcium phosphate cement stimulates bone growth and the osteotransduction of the cement. For bone regeneration procedures around endosseous implants, calcium phosphate cement with rhTGF-beta1 might be an appropriate combination for early osseointegration and implant use.

Animals↗

PubMed1999

Prevalence and distribution of bone defects in moderate and advanced adult periodontitis.

The purpose of the present investigation was to evaluate the prevalence and distribution of different forms of bone defects using direct observation during periodontal surgery. 286 patients with moderate or advanced adult periodontitis diagnosed during clinical and radiographic examination provided a sample of 5476 teeth. After full thickness mucoperiosteal flaps were raised, osseous defects were explored and classified according to their morphology as interdental craters, hemisepta and infrabony defects with 1, 2, 3 or 4 osseous walls. 981 defects were detected; 533 were in the maxilla and 448 in the mandible (15.4% and 22.4%, respectively, of the teeth examined). The posterior mandibular segment had the highest % of teeth with defects (33.8%) followed by the posterior maxillary segment (19.9%). The proportions of teeth with defects in the anterior segments of both arches were similar. The comparison between maxilla and mandible showed a highly significant difference for the posterior segments (p= 0.00001) but no difference for the anterior segments (p=0.88). The distribution of defects differed between the maxilla and the mandible, both for the posterior and anterior segments. Craters accounted for almost half the defects, being more prevalent in posterior segments, while hemisepta formed the lowest proportion. Anatomical variations in shape and the original morphology of the alveolar bone between the maxilla and the mandible and the anterior and posterior regions might have been the reason for the differences observed.

Adult↗

PubMed2001

Evaluation of the effect of tooth vitality on regenerative outcomes in infrabony defects.

BACKGROUND, AIMS: This investigation was designed to evaluate the null hypothesis of no differences in GTR outcomes in intrabony defects at vital and successfully root-canal-treated teeth. METHOD: 208 consecutive patients with one intrabony defect each were enrolled. Based on tooth vitality, the treated population was divided at baseline into 2 groups: one with 41 non-vital teeth and the other with 167 vital teeth. The 2 groups were similar in terms of patient and defect characteristics. RESULTS: A slight unbalance in terms of depth of the intrabony component was observed in the non-vital group compared to the vital group (6.9+/-2.1 mm versus 6.2+/-2.3 mm, p=0.08). All defects were treated with GTR therapy. At 1 year, the non-vital and the vital groups showed a clinical attachment level (CAL) gain of 4.9+/-2.2 mm and of 4.2+/-2 mm, respectively. The difference was statistically significant (p=0.03). To correct for the baseline unbalance in defect depth, data were expressed as a % of clinical attachment level gains with respect to the original intrabony depth of the defect. % CAL gains were 72.8+/-42.2% and 73+/-26.4% for vital and non-vital teeth, respectively: the difference was not statistically significant (p=0.48). Average residual pocket depths were 2.8+/-1 mm in the vital and 2.8+/-0.9 mm in the non-vital group. Tooth vitality was assessed at baseline, at 1-year and at follow-up (5.4+/-2.8 years after surgery): all teeth vital at baseline were still vital at follow-up with the exception of 2 teeth that received endodontic treatment for reconstructive reasons and for caries. At follow-up visit, the difference in CAL with respect to 1-year measurements was -0.9+/-0.8 mm in the vital group and -0.7+/-0.8 mm in the non-vital group, indicating stability of the regenerated attachment at the majority of sites. CONCLUSIONS: Data from this study demonstrate that root canal treatment does not negatively affect the healing response of deep intrabony defects treated with GTR therapy; furthermore GTR therapy in deep intrabony defects does not negatively influence tooth vitality.

Adolescent↗

PubMed2002

Use of barrier membranes and systemic antibiotics in the treatment of intraosseous defects.

OBJECTIVES: Current literature is ambivalent on the use of barrier membranes for regeneration of intraosseous defects. One of the reasons for unpredictable results may be related to infection before, during and after the surgical procedure. Therefore, the purpose of the present controlled study was to evaluate both the use of membranes (MEM) and antibiotics (AB), separately and in combination. METHODS: In all, 25 patients with two intraosseous periodontal defects each were randomized in two groups: AB+ group receiving systemic antibiotics (n = 13) and AB- group without antibiotics (n = 12). After raising flaps and after debridement, both defects in each patient were covered by a bioresorbable membrane (MEM+). However, just before suturing the flaps in a coronal position, the membrane over one of the two defects was removed at random (MEM-). This protocol resulted in four groups of defects: (i). MEM- AB-; (ii). MEM+ AB-; (iii). MEM- AB+; (iv). MEM+ AB+. Patients were monitored clinically and microbiologically for 1 year. Data were analyzed in repeated measures ancova's and adjusted means for clinical variables were obtained from the final statistical model. RESULTS: Reduction in probing pocket depth (PPD) at 12 months postoperatively varied between 2.54 and 3.06 mm between the four treatment modalities, but overall no main effect of MEM or AB was found. Gains in probing attachment level (PAL) at 12 months postoperatively varied between 0.56 and 1.96 mm for the 4 treatments. In the overall analysis for PAL, no main effect of MEM or AB was found. Gains in probing bone level (PBL) 12 months postoperatively ranged from 1.39 to 2.09 mm between the treatment groups. Again, overall, no main effects of MEM or AB were found for PBL. Explorative statistical analyses indicated that smoking and not MEM or AB is a determining factor for gain in PBL (P = 0.0009). Nonsmokers were estimated to gain 2.04 mm PBL compared to 0.52 mm in smokers. The prevalence of several periodontal pathogens, at the day of surgery or postoperatively, and specific defect characteristics, were not determining factors for gain in PAL and PBL. CONCLUSIONS: Neither the application of barrier membranes nor the use of systemic antibiotics showed an additional effect over control on both soft and hard tissue measurements in the treatment of intraosseous defects. In contrast, smoking was a determining factor severely limiting gain in PBL in surgical procedures aimed at regeneration of intraosseous defects.

Abscess↗

PubMed2005

Identifying and counting point defects in carbon nanotubes.

The prevailing conception of carbon nanotubes and particularly single-walled carbon nanotubes (SWNTs) continues to be one of perfectly crystalline wires. Here, we demonstrate a selective electrochemical method that labels point defects and makes them easily visible for quantitative analysis. High-quality SWNTs are confirmed to contain one defect per 4 microm on average, with a distribution weighted towards areas of SWNT curvature. Although this defect density compares favourably to high-quality, silicon single-crystals, the presence of a single defect can have tremendous electronic effects in one-dimensional conductors such as SWNTs. We demonstrate a one-to-one correspondence between chemically active point defects and sites of local electronic sensitivity in SWNT circuits, confirming the expectation that individual defects may be critical to understanding and controlling variability, noise and chemical sensitivity in SWNT electronic devices. By varying the SWNT synthesis technique, we further show that the defect spacing can be varied over orders of magnitude. The ability to detect and analyse point defects, especially at very low concentrations, indicates the promise of this technique for quantitative process analysis, especially in nanoelectronics development.

Electric Conductivity↗

PubMed2001

Clinical consequences of defects in peroxisomal beta-oxidation.

The disorders of peroxisomal beta-oxidation, which have been well characterised at the molecular level, include defects of acyl-CoA oxidase, defects of the D-bifunctional protein (D-BP) (including specific defects of its enoyl-CoA hydratase and D-3-hydroxyacyl-CoA dehydrogenase components), defects of the very-long-chain fatty acid (VLCFA)-CoA importer [X-linked adrenoleukodystrophy (ALD)] and alpha-methylacyl-CoA racemase deficiency. A survey of the clinical consequences of these defects indicates that defects in the acyl-CoA oxidase and D-BP can produce neonatal hypotonia, seizures in early infancy, retinopathy and progressive neurological dysfunction with leukodystrophy on imaging. Defects in the VLCFA-CoA importer and in the racemase do not produce disease until a long time after the neonatal period. However, again the clinical picture is dominated by neurological disease: impaired cognitive function with leukodystrophy in childhood X-linked ALD and retinopathy and neuropathy in racemase deficiency. It is difficult to escape the conclusion that defective peroxisomal beta-oxidation has effects (such as impaired neuronal migration in the developing brain), which are more serious than those produced by the accumulation of substrates (VLCFAs, pristanic acid) alone.

17-Hydroxysteroid Dehydrogenases↗

PubMed1997

Risk of recurrence of birth defects in Washington State.

A population-based study was conducted using maternally-linked birth certificate records from Washington State for 1980-93 to evaluate the risk of birth defect occurrence among infants with previously affected siblings, relative to infants whose siblings did not have birth defects. The risks of recurrence of similar and dissimilar defects were estimated, and the effects of change in paternity and/or city of residence were evaluated as proxies of genetic and environmental effects. At the first birth on record, 3322 women were identified in the linked certificates as giving birth to a child with a birth defect; 6620 women whose first birth did not result in an infant with a defect were randomly selected for comparison. Women with a malformed infant had an increased risk of having a malformed infant at the subsequent birth (Relative Risk = 1.9, [95% Confidence Interval (CI) = 1.5-2.4]), which did not vary by intervening changes in partner or residence. The risk of recurrence of the same general type of defect [RR = 11.7, 95% CI = 9.7-19.50] was much greater than that of occurrence of a dissimilar defect [RR = 1.5, 95% CI = 1.1-1.9]. This was consistent for all defect categories, and did not vary markedly by changes in partner or residence.

Birth Order↗

PubMed2001

Role of structural birth defects in preterm delivery.

The proportion of preterm births associated with structural birth defects has not been adequately quantified. We explored the proportion of preterm infants with structural birth defects diagnosed in the first year of life, as well as the specific phenotypes of birth defects occurring among preterm infants. The data used were from the California Birth Defects Monitoring Program, a population-based registry, as well as data from California vital records corresponding to births and fetal deaths in the period 1984-96. The prevalence of structural birth defects exceeded 8% among deliveries with gestational ages < or = 30 weeks, and prevalence decreased to 2% as gestational age increased to > or = 37 weeks gestation. The decreasing prevalence pattern with increasing gestational age was observed for a variety of anatomically defined birth defect groups suggesting that certain birth defects were not the sole contributors to the elevated prevalences among preterm births. Decreasing prevalence with increasing gestational age was also observed across strata of maternal race/ethnicities, ages, infant's sex and each year studied. These data indicate that structural birth defects may contribute significantly to the proportion of infants who are delivered before 37 weeks gestation.

Congenital Abnormalities↗