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PubMed2001

Major birth defects in very low birth weight infants in the Vermont Oxford Network.

OBJECTIVE: To study the frequency and types of major birth defects in very low birth weight (VLBW) infants and their impact on mortality and resource use. STUDY DESIGN: Analysis of data from the Vermont Oxford Network Database from 1994 and 1995 on infants with birth weights of 501 to 1500 g. Major birth defects were reported from a list of 40 defined major defects or if they were considered lethal or life-threatening. Mortality and length of stay were determined. RESULTS: Major birth defects were present in 823 (4.3%) of 19,228 VLBW infants from 147 hospitals. The most common categories were chromosomal anomalies (20%); named syndromes, sequences, and associations (19%); and gastrointestinal (14%), cardiovascular (11%), and nervous system (10%) anomalies. Infants with major birth defects had a higher mortality rate (58% vs 13%, P <.001) and a higher rate of major surgery (29% vs 5%, P <.001) than infants without such defects. Infants with major birth defects accounted for 16.3% of deaths and 18.9% of major surgical procedures but only for 2.9% of total hospital days. CONCLUSIONS: Major birth defects accounted for 16% of all deaths in VLBW infants. However, they accounted for a low proportion of total hospital days.

Birth Weight↗
PubMed2005

Distinct DNA-damage-dependent and -independent responses drive the loss of oocytes in recombination-defective mouse mutants.

Defects in meiotic recombination in many organisms result in arrest because of activation of a meiotic checkpoint(s). The proximal defect that triggers this checkpoint in mammalian germ cells is not understood, but it has been suggested to involve either the presence of DNA damage in the form of unrepaired recombination intermediates or defects in homologous chromosome pairing and synapsis independent of DNA damage per se. To distinguish between these possibilities in the female germ line, we compared mouse oocyte development in a mutant that fails to form the double-strand breaks (DSBs) that initiate meiotic recombination (Spo11-/-) to mutants with defects in processing DSBs when they are formed (Dmc1-/- and Msh5-/-), and we examined the epistasis relationships between these mutations. Absence of DSB formation caused a partial defect in follicle formation, whereas defects in DSB repair caused earlier and more severe meiotic arrest, which could be suppressed by eliminating DSB formation. Therefore, our analysis reveals that there are both DNA-damage-dependent and -independent responses to recombination errors in mammalian oocytes. By using these findings as a paradigm, we also examined oocyte loss in mutants lacking the DNA-damage checkpoint kinase ATM. The absence of ATM caused defects in folliculogenesis that were similar to those in Dmc1 mutants and that could be suppressed by Spo11 mutation, implying that oocyte death in Atm-deficient animals is a response to defective DSB repair.

Animals↗
PubMed1995

An incomplete program of cellular tyrosine phosphorylations induced by kinase-defective epidermal growth factor receptors.

Although signaling by the epidermal growth factor (EGF) receptor is thought to be dependent on receptor tyrosine kinase activity, it is clear that mitogen-activated protein (MAP) kinase can be activated by receptors lacking kinase activity. Since analysis of the signaling pathways used by kinase-defective receptors could reveal otherwise masked capabilities, we examined in detail the tyrosine phosphorylations and enzymes of the MAP kinase pathway induced by kinase-defective EGF receptors. Following EGF stimulation of B82L cells expressing a kinase-defective EGF receptor mutant (K721M), we found that ERK2 and ERK1 MAP kinases, as well as MEK1 and MEK2 were all activated, and SHC became prominently tyrosine-phosphorylated. By contrast, kinase-defective receptors failed to induce detectable phosphorylations of GAP (GTPase-activating protein), p62, JAK1, or p91STAT1, all of which were robustly phosphorylated by wild-type receptors. These data demonstrate that kinase-defective receptors induce several protein tyrosine phosphorylations, but that these represent only a subset of those seen with wild-type receptors. This suggests that kinase-defective receptors activate a heterologous tyrosine kinase with a specificity different from the EGF receptor. We found that kinase-defective receptors induced ErbB2/c-Neu enzymatic activation and ErbB2/c-Neu binding to SHC at a level even greater than that induced by wild-type receptors. Thus, heterodimerization with and activation of endogenous ErbB2/c-Neu is a possible mechanism by which kinase-defective receptors stimulate the MAP kinase pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1989

Increased radiosensitivity and the basic defect in ataxia telangiectasia.

Various cellular defects have been found in ataxia telangiectasia (A-T) cells including increased radiosensitivity, increased sensitivity to various chemical agents, a probable DNA repair defect and a defect in DNA synthesis. How these different features are related to each other is at present unknown. It has been suggested that there is a defect in A-T that acts in tissue differentiation as well as during growth and in the mature adult. This hypothesis is supported by the observations, for example, of an immature thymus present in patients, the production of alpha-fetoprotein, which results in a high serum level, and ovarian dysgenesis. A gene for A-T has recently been localized to chromosome region 11q22-23, a site involved in chromosomes translocations in some non-lymphoid leukaemias. At the chromosomal level the spontaneous abnormalities in A-T include, first, an increased frequency of cells showing chromosome translocations involving immune system genes that normally undergo rearrangement to form a functional product; secondly, the formation of telometric dicentrics in both lymphocytes and fibroblasts; and thirdly formation of long-lived chromosome damage following exposure to ionizing radiation and radiomimetic drugs. The gene defect underlying this disorder is unknown and distinguishing between primary and secondary effects of the mutant gene is difficult. We consider alternative models for retention of translocation T cells. First, it is possible that there is a defect in recognition of site-specific damage leading to retention of translocation cells that might otherwise be removed. Secondly, a feature common to the production of illegitimate T-cell receptor gene rearrangements and to formation of telomeric dicentric chromosomes in A-T cells is an increased period of time available for chromosome interchange, possibly due to a site-specific defect in strand break repair. It is possible that this defect may also prevent chromosome restitution following exposure of cells to ionizing radiation.

Ataxia Telangiectasia↗
PubMed2006

Visual field defects in epidemic dropsy.

UNLABELLED: Epidemic dropsy is a multi-system disease involving the cardiovascular, hepatic, renal, ocular and other systems. It is a toxic disease caused by the unintentional ingestion of Argemone mexicana (prickly yellow poppy) seeds as an adulterant of wheat flour or more commonly of cooking oil such as mustard oil. PURPOSE: To investigate the occurrence of visual field defects in patients suffering from epidemic dropsy glaucoma. METHODS: Visual field analysis was performed to ascertain the field defects, in patients suffering from epidemic dropsy. Group I consisted of 35 patients (69 eyes) whose intraocular pressure (IOP) was > or = 22 mmHg. Ten dropsy patients (20 eyes) with normal IOP (<22 mm Hg) formed Group II. Ten healthy unexposed volunteers (20 eyes) constituted Group III. All the patients were tested using the Armaly full field glaucoma screening test on the Humphrey field analyzer. RESULTS: Forty seven of the 69 eyes (68%) suffering from epidemic dropsy glaucoma, and 18 out of 20 (90%) eyes in dropsy patients with normal IOP, showed field defects. In the control group, 15% eyes had only nasal field defects. The difference between Group I and II was not significant (p = 0.054), though the field defects were significantly more frequent in dropsy patients as compared to the controls (p < 0.01 in either case). The results suggest that visual field defects in epidemic dropsy occur independently of the rise in intraocular pressure. Field defects were detected more frequently in patients who underwent visual field analysis early in the course of disease, as compared to those who underwent screening later on in the disease course. CONCLUSIONS: In epidemic dropsy, acute visual field defects occur independent of rise of intraocular pressure and more frequently in the early stage of the disease.

Adolescent↗
PubMed1994

Endocytosis is required for the growth of vacuolar H(+)-ATPase-defective yeast: identification of six new END genes.

Yeast mutants that are defective in acidification of the lysosome-like vacuole are able to grow at pH 5.5, but not at pH 7. Here, we present evidence that endocytosis is required for this low pH-dependent growth and use this observation to develop a screen for mutants defective in endocytosis. By isolating mutants that cannot grow when they lack the 60-kD vacuolar ATPase subunit (encoded by the VAT2 gene), we isolated a number of vat2-synthetic lethal (Vsl-) mutant strains. Seven of the Vsl- mutants are defective in endocytosis. Four of these mutant strains (end8-1, end9-1, end10-1, and end11-1) show altered uptake of the endocytosed ligand, alpha-factor, and three (end12-1, end12-2, and end13-1) are probably defective in transfer of internalized material to the vacuole. Most of the mutations also confer a strong Ts- growth defect. The mutants defective in uptake of alpha-factor sort newly synthesized vacuolar proteins correctly, while those which may be defective in subsequent transport steps secrete at least a fraction of the newly synthesized soluble vacuolar proteins. The mutations that result in a defect in alpha-factor uptake are not allelic to any of the genes previously shown to encode endocytic functions.

Carboxypeptidases↗
PubMed2001

The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas.

A comprehensive analysis of somatic and germline mutations related to DNA mismatch-repair (MMR) genes can clarify the prevalence and mechanism of inactivation in colorectal carcinoma (CRC). In the present study, 257 unselected patients referred for CRC resection were examined for evidence of defective DNA MMR. In particular, we sought to determine the frequency of hereditary defects in DNA MMR in this cohort of patients. MMR status was assessed by testing of tumors for the presence or absence of hMLH1, hMSH2, and hMSH6 protein expression and for microsatellite instability (MSI). Of the 257 patients, 51 (20%) had evidence of defective MMR, demonstrating high levels of MSI (MSI-H) and an absence of either hMLH1 (n=48) or hMSH2 (n=3). All three patients lacking hMSH2, as well as one patient lacking hMLH1, also demonstrated an absence of hMSH6. DNA sequence analysis of the 51 patients with defective MMR revealed seven germline mutations-four in hMLH1 (two truncating and two missense) and three in hMSH2 (all truncating). A detailed family history was available for 225 of the 257 patients. Of the seven patients with germline mutations, only three had family histories consistent with hereditary nonpolyposis colorectal cancer. Of the remaining patients who had tumors with defective MMR, eight had somatic mutations in hMLH1. In addition, hypermethylation of the hMLH1 gene promoter was present in 37 (88%) of the 42 hMLH1-negative cases available for study and in all MSI-H tumors that showed loss of hMLH1 expression but no detectable hMLH1 mutations. Our results suggest that, although defective DNA MMR occurs in approximately 20% of unselected patients presenting for CRC resection, hereditary CRC due to mutations in the MMR pathway account for only a small proportion of patients. Of the 257 patients, only 5 (1.9%) appear to have unequivocal evidence of hereditary defects in MMR. The epigenetic (nonhereditary) mechanism of hMLH1 promoter hypermethylation appears to be responsible for the majority of the remaining patients whose tumors are characterized by defective DNA MMR.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Vector-specific complementation profiles of two independent primary defects in cystic fibrosis airways.

Cystic fibrosis (CF) lung disease has been linked to multiple primary defects in airway epithelia caused by a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) gene. These defects include altered Cl- and Na+ permeability as well as intracellular defects in glycoprotein processing. This apparent diversity in CFTR function is reflected in the complex patterning of CFTR expression in airway epithelia. Such complexities present challenges in the design of CF gene therapies that are capable of reconstituting the endogenous patterns of CFTR gene expression in appropriate target cells. Using a human bronchial xenograft model of the CF airway, we have evaluated the efficacy of recombinant adenoviral and cationic liposome-mediated gene transfer to correct Cl- permeability and mucous sulfation defects found in CF lung disease. Results from these studies demonstrated a clear vector-specific complementation profile for these two defects that was dependent on the type of cell transduced and the level of transgene expression. Single-dose administration of recombinant adenovirus effectively transduced high levels of CFTR transgene expression in 11 +/- 1% of epithelial cells and was capable of correcting cAMP-induced changes in Cl- permeability to 91 +/- 14% that seen in non-CF airways. However, this level of transgene expression was incapable of reversing defects in mucous sulfation due to the lack of efficient targeting to goblet cells. In contrast, cationic liposome-mediated delivery of CFTR encoding plasmids to CF airways achieved extremely low levels of transgene expression with insignificant correction (7.4 +/- 2.4%) of cAMP-induced Cl- permeability. This low level of transgene expression, however, efficiently reduced mucous sulfation to levels seen in non-CF airways. Differences in the complementation profiles of these two vectors in correcting Cl- permeability and mucous sulfation defects mirror the ability of recombinant adenovirus and liposomes to reconstitute only certain features of the endogenous distribution and abundance of CFTR protein expression. Such findings suggest that the level of intracellular CFTR required to facilitate proper glycoprotein processing may be much lower than that needed to mediate bulk Cl- flow across the airway epithelium. In summary, these data present the first example by which two different vector systems can efficiently complement independent primary defects associated with a single dysfunctional gene.

Adenoviridae↗
PubMedDate not supplied

Repair of osteochondral defects in rabbits with ectopically produced cartilage.

Cartilage has poor regenerative capacity. Donor site morbidity and interference with joint homeostasis should be considered when applying the autologous chondrocyte transplantation technique. The use of ectopically produced cartilage, derived from periosteum, might be a novel method to heal cartilage defects. Ectopic cartilage was produced by dissecting a piece of periosteum from the tibia of rabbits. After 14 days the reactive tissue at the dissection site was harvested and a graft was cored out and press-fit implanted in an osteochondral defect in the medial condyle of the femur with or without addition of hyaluronan. After 3 weeks and 3 months the repair reaction was evaluated by histology. Thionine- and collagen type II-stained sections were evaluated for graft viability, ingrowth of the graft, and joint surface repair. Empty defects remained empty 3 weeks after implantation, ectopic cartilage filled the defect to the level of the surrounding cartilage. Histologically, the grafts were viable, consisting mainly of cartilage, and showed a variable pattern of ingrowth. Three months after implantation empty defects with or without hyaluronan were filled primarily with fibrocartilaginous tissue. Defects treated with ectopic cartilage contained mixtures of fibrocartilaginous and hyaline cartilage. Sometimes a tidemark was observed in the new articular cartilage and the orientation of the cells resembled that of healthy articular cartilage. Subchondral bone repair was excellent. The modified O'Driscoll scores for empty defects without and with hyaluronan were 12.7 +/- 6.4 and 15.3 +/- 3.2; for treated defects scores were better (15.4 +/- 3.9 and 18.2 +/- 2.9). In this conceptual study the use of ectopic cartilage derived from periosteum appears to be a promising novel method for joint surface repair in rabbits.

Animals↗
PubMed1991

The site of the molecular defect in the thyroid gland of the hyt/hyt mouse: abnormalities in the TSH receptor-G protein complex.

The hyt/hyt mouse has a severe and pervasive primary inherited hypothyroidism with significantly depressed serum T4, elevated serum and pituitary TSH, and reduced thyroid gland iodide uptake. Previous ultrastructural and histologic analysis of the hyt/hyt thyroid gland along with these biochemical abnormalities support an inherited defect in TSH responsiveness of the hyt/hyt thyroid gland. In order to evaluate the potential site of the defect in the hyt/hyt mouse, we have studied the hyt/hyt gland and hyt/hyt TSH from a biochemical and molecular standpoint. Based on demonstrated bioactivity of hyt/hyt serum in the McKenzie bioassay, this reduced responsiveness to TSH in the hyt/hyt mouse is not due to reduced bioactivity of hyt/hyt TSH or a major structural abnormality in the hyt/hyt TSH molecule. In comparison to hyt/ + euthyroid littermates and +/+ BALB/cBY progenitor strain mice, the hyt/hyt mouse demonstrates a twofold reduction in thyroid gland basal cAMP and a markedly diminished response of adenylyl cyclase to exogenous TSH. However, hyt/hyt cAMP production is equivalent to the euthyroid mice after stimulation of thyroid glands by forskolin, cholera toxin, PGE1, and isoproterenol. These results support a defect in the TSH-G protein-adenylyl cyclase system in the hyt/hyt thyroid gland. Specifically, these findings suggest that the hyt/hyt mouse has a defect in TSH responsivity due to an inherited defect in the thyroid gland TSH receptor molecule. Since the hyt/hyt gland makes T3 and T4 but at diminished levels, the proposed defect in the TSH receptor would still impart partial function. Both hyt/hyt and euthyroid hyt/ + littermates make TSH receptor mRNAs of 5500 and 2400 base pairs. This suggests that the receptor defect does not represent a major structural abnormality of the gene. The receptor defect could represent a reduction in receptor number, receptor-TSH affinity, or TSH receptor-G protein coupling. The specificity of this effect on adenylyl cyclase-cAMP is shown by the reduction of TSH-cAMP regulated thyroid peroxidase (TPO) and thyroglobulin mRNAs in the hyt/hyt thyroid gland. Given the importance of TPO and thyroglobulin in normal thyroid hormone synthesis, the reductions in TPO and thyroglobulin mRNAs in the hyt/hyt thyroid gland may underlie the significant decrease in thyroid hormone production by the hyt/hyt mouse.

Adenylyl Cyclases↗
PubMed1993

Genetic heterogeneity of the excision repair defect associated with trichothiodystrophy.

Trichothiodystrophy (TTD) is a rare autosomal recessive disease characterized by brittle hair with reduced sulfur content, mental and physical retardation, a peculiar face and ichthyosis. Photosensitivity has been reported in approximately 20% of the cases in the literature. DNA repair investigations demonstrated that clinical photosensitivity is usually associated with an enhancement of the cellular UV-sensitivity and that the repair defect is in the same gene as in patients from group D of xeroderma pigmentosum (XP). In this paper we describe the characterization of 13 further TTD patients; a defect in the nucleotide-excision repair was observed in fibroblast strains from 10 patients, confirming that TTD is frequently associated with DNA repair defects. Genetic analysis based on complementation studies demonstrated the presence of the XP-D defect in seven repair-defective TTD cases, indicating definitively that the concurrence of TTD with XP-D is not a sporadic or casual event. However, three further cell strains (TTD4VI and TTD6VI from two French siblings and TTD1BR from an English patient) showed restoration of normal UV-induced DNA repair synthesis after fusion with XP or TTD cells belonging to XP group D. These observations, which give the first indication that TTD is associated with repair defects behaving differently in the functional test of complementation, suggest some kind of causal connection between defective excision-repair factors and clinical features diagnostic for TTD. A peculiar aspect of TTD in which repair deficiencies are not related to an increased susceptibility to cancer is confirmed also in all the repair-defective TTD patients investigated in this paper.

Abnormalities, Multiple↗
PubMed2001

Growth hormone treatment promotes guided bone regeneration in rat calvarial defects.

This study evaluated the biomechanical strength and bone formation in calvarial critical size bone defects covered with expanded polytetrafluoroethylene (e-PTFE) membranes in rats treated systemically with recombinant human growth hormone (rhGH). A full-thickness bone defect, 5 mm in diameter, was trephined in the central part of each parietal bone in 40 one-year-old female Wistar rats, which were randomly assigned to two groups of 20 animals each. The bone defects were covered with an exocranial and an endocranial e-PTFE membrane. From the day of operation, the rhGH-treated animals were given 2.7 mg rhGH/kg/day and the placebo-injected rats were given isotonic sodium chloride. The animals were killed 28 days after operation. The biomechanical test was performed by a punch out test procedure placing a 3.5-mm diameter steel punch in the centre of the right healed defect. After mechanical testing, the newly formed tissue inside the defect was removed and the dry and ash weights were measured. The left healed defects were used for three-dimensional (3D) reconstruction by means of micro-computer tomography (micro-CT). Ultimate load, ultimate stiffness, and energy absorption at ultimate load were significantly increased in the rhGH-treated group (P < 0.003). Also, tissue dry and ash weights were significantly augmented in the rhGH-treated group (P < 0.001). The 3D reconstruction of newly formed bone showed that there was almost twice as much bone volume present in the rhGH-treated defects compared with the placebo group. The experiment demonstrated that rhGH administration enhances bone deposition and mechanical strength of healing rat calvarial defects, covered with e-PTFE membranes.

Animals↗
PubMed2003

Embryoscopic and cytogenetic analysis of 233 missed abortions: factors involved in the pathogenesis of developmental defects of early failed pregnancies.

BACKGROUND: While chromosomal abnormalities are often the cause of missed abortions, other defects could be involved, which might be screened for by transcervical embryoscopy. METHODS: A total of 272 patients with missed abortion underwent transcervical embryoscopy prior to dilatation and curettage, together with cytogenetic analysis of chorionic villi, using either standard G-banding cytogenetic techniques or comparative genomic hybridization in combination with flow cytometry analysis. RESULTS: Visualization of the embryo or early fetus (12 cases) was successful in 233 patients, and karyotyping in 221. Among 233 examined cases, 33 had normal external features, 71 were classified as growth-disorganized and 129 had either isolated or multiple defects, including holoprosencephaly, anencephaly, encephalocele, spina bifida, microcephaly, facial dysplasia, limb reduction defect, cleft hand, syndactyly, pseudosyndactly, polydactyly, various forms of cleft lip and an amniotic adhesion. Of the 165 cases with an abnormal karyotype, there were 46 grossly disorganized embryos, 98 multiple defects, six single defects and 15 morphologically normal cases. Of the 56 cases with a normal karyotype, there were 20 grossly disorganized embryos, 16 multiple defects, four single defects and 16 morphologically normal cases. CONCLUSIONS: A total of 75% of the cases with missed abortion had an abnormal karyotype, 18% had a morphological defect with a normal karyotype, while no embryonic or chromosomal abnormality could be diagnosed in 7% of the cases. Correlation of morphological and cytogenetic findings in spontaneous abortion specimens could provide valuable information for genetic counselling and prenatal care in future pregnancies in couples with a history of repeated pregnancy loss.

Abnormalities, Multiple↗
PubMed1990

Birth defects among offspring of firemen.

The authors conducted an exploratory case-control study of paternal employment as a fire fighter and the risk of birth defects among offspring. By means of a population-based registry in British Columbia, 22,192 liveborn children with birth defects were identified for the period, 1952-1973. Two comparisons were made to evaluate the risk among offspring of firemen: 1) comparison with the risk among offspring of fathers employed in other occupations using a matched (two per case) control group, and 2) comparison with the risk among offspring of policemen. Among the 20 birth defect groups studied, an association was found for paternal employment as a fire fighter (relative to all other occupations) and increased risks were observed for ventricular septal defects (odds ratio (OR) = 2.70, 95% confidence interval (Cl) 1.02-7.18) and atrial septal defects (OR = 5.91, 95% Cl 1.60-21.83) among offspring. When compared with policemen, firemen had increased risks of having a child with a ventricular septal defect (OR = 4.68, 95% Cl 1.66-13.17) and atrial septal defect (OR = 3.76, 95% Cl 1.40-10.07). Analyses using a pathogenetic classification for these heart defects yielded similar increased odds ratios for firemen.

Case-Control Studies↗
PubMed2001

The National Birth Defects Prevention Study.

The National Birth Defects Prevention Study was designed to identify infants with major birth defects and evaluate genetic and environmental factors associated with the occurrence of birth defects. The ongoing case-control study covers an annual birth population of 482,000 and includes cases identified from birth defect surveillance registries in eight states. Infants used as controls are randomly selected from birth certificates or birth hospital records. Mothers of case and control infants are interviewed and parents are asked to collect buccal cells from themselves and their infants for DNA testing. Information gathered from the interviews and the DNA specimens will be used to study independent genetic and environmental factors and gene-environment interactions for a broad range of birth defects. As of December 2000, 7,470 cases and 3,821 controls had been ascertained in the eight states. Interviews had been completed with 70% of the eligible case and control mothers, buccal cell collection had begun in all of the study sites, and researchers were developing analysis plans for the compiled data. This study is the largest and broadest collaborative effort ever conducted among the nation's leading birth defect researchers. The unprecedented statistical power that will result from this study will enable scientists to study the epidemiology of some rare birth defects for the first time. The compiled interview data and banked DNA of approximately 35 categories of birth defects will facilitate future research as new hypotheses and improved technologies emerge.

Case-Control Studies↗
PubMed1982

Detection of vascular defects during operation by imaging ultrasound.

Real-time high resolution ultrasound imaging was employed during reconstructive vascular operation in 165 patients. The purpose of this diagnostic procedure was to detect unrecognized strictures, thrombi, and intimal flaps in order to permit their surgical correction at the primary operation. Defects were discovered in 48 patients (29%). In 34 patients (21%), because of size and location, defects were not considered sufficiently significant to warrant re-exploration. In 14 patients (8%), ultrasound revealed defects that prompted immediate re-exploration. Patients with ultrasound defects considered to be insignificant did as well as patients with no demonstrable defects. In the 14 patients who were re-explored, 12 had major defects that were corrected. These 12 patients also did well after operation. In two of the 14 patients, defects could not be found at re-exploration. Both these patients experienced early thrombosis of bypass grafts. In 56 patients, ultrasound was compared with arteriography at the same operation. The accuracy of operative ultrasound and operative arteriography was 96% and 85%, respectively. Operative ultrasound is more accurate, simpler and safer than arteriography and may be the preferred method for detection of vascular defects at reconstructive surgery.

Humans↗
PubMed1996

Use of a fibrillar polylactic acid homopolymer in sheep cranial defects.

Guided tissue regeneration has been shown to permit osteoconduction in otherwise nonhealing cranial defects. The relative importance of preventing the prolapse of soft tissue versus the infiltration of individual connective tissue cells has not been determined. A fibrillar form of polylactic acid (PLA) was tested in 13-mm-diameter defects in the parietal bones of 12 sheep. The polymer was hypothesized to prevent the prolapse of dura and periosteum but allow entrance of individual cells. Control defects in the same sheep were either filled with autogenous bone shavings or left unfilled. The animals were killed at times ranging from 6 to 25 weeks and the defects examined grossly, radiologically, and histologically. The autogenous bone-filled defects were spanned by trabeculated bone by 6 weeks. The unfilled defects demonstrated prolapse of soft tissues into the defect; however, progressive centripetal bone growth was evident. The fibrillar PLA-filled defects were occupied by a full-thickness mixture of fibrous tissue interspersed with PLA. After 19 weeks, small "fingers" of bone were seen to minimally infiltrate the fibrous tissue. Although separation of the dura and periosteum was maintained by the fibrillar PLA, invasion of fibrous tissue restricted osteoconduction.

Animals↗
PubMed2004

Intermittent parathyroid hormone treatment enhances guided bone regeneration in rat calvarial bone defects.

This study investigates the effects of intermittent parathyroid hormone (PTH(1-34)) treatment on bone regeneration and mechanical strength of critically sized rat calvarial bone defects covered with expanded membranes. A full-thickness bone defect (diameter 5 mm) was trephined in the central part of the parietal bones in 20-month-old female Wistar rats. The bone defects were covered with an exocranial and an endocranial expanded polytetrafluoroethylene membrane. The animals were killed 35 days after operation. 60 microg PTH(1-34)/kg was administered daily during the healing period, and control animals with calvarial bone defects were given vehicle. Mechanical testing was performed by a punch out testing procedure by placing a steel punch (diameter 3.5 mm) in the center of the healed defect. After mechanical testing, the newly formed tissue inside the defect was removed and the dry weight and ash weight were measured. PTH(1-34) increased dry weight by 48%, ash weight by 51%, and ash concentration by 26%. PTH(1-34) also augmented the mechanical strength of the new bone formed inside the defect by increasing ultimate stiffness by 87%. No differences in body weight were found between the vehicle-injected and the PTH-treated animals during the experiment. The experiment demonstrates that intermittent PTH(1-34) treatment increases bone deposition and enhances mechanical strength of healing rat calvarial defects covered with expanded polytetrafluoroethylene membranes.

Animals↗