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PubMed1993

A new look at intraoperative completion arteriography: classification and management strategies for intraluminal defects.

Completion arteriography is widely regarded as an essential component of infrainguinal bypasses. However, the significance of various intraluminal filling defects is poorly defined, and strategies for managing these defects are unclear. Completion arteriography was performed by a standard technique in 78 infrapopliteal bypasses and were evaluated prospectively for the presence of angiographic defects. Thirty-nine arteriograms (50%) had no visible abnormality (grade O). Six arteriograms (8%) had minimal (grade I) defects, i.e., round lucencies (bubbles) or valve leaflets. Eighteen arteriograms (23%) had moderate (grade II) defects, i.e., uniform smooth tapering (up to 90% of luminal diameter) of the graft or outflow artery, irregular intraluminal filling defect (less than 60% of luminal diameter) within the distal graft or its adjacent outflow artery, or incomplete or faint graft opacification. Fifteen arteriograms (19%) had severe (grade III) defects, i.e., total cutoff of graft or outflow artery opacification or irregular intraluminal filling defect (greater than 60%) in the distal graft or adjacent outflow artery. Completion arteriograms were further stratified for type of bypass and outflow characteristics. All 24 bypasses with grade I or grade II defects on completion arteriography had no further surgical treatment. However, the 18 bypasses with grade II defects on completion arteriography had minimal nonsurgical manipulations consisting of repeat arteriography without or with papaverine infusion or urokinase instillation. In all 18, repeat arteriography showed improvement in the defect. The 15 bypasses with grade III defects had further surgical intervention (graftotomy, thrombectomy, vein patching, interposition graft, or graft extension). One-month and 1-year patency rates for grafts with grade I and grade II defects (87% and 79%, respectively) were not significantly worse than those for the 39 grafts with no arteriographic abnormalities (87% and 82%, respectively). In contrast, grafts with grade III defects had significantly worse (p < 0.01) 1-month and 1-year patency rates (33% and 20%, respectively) despite aggressive surgical correction of the arteriographic defects. These results emphasize the value of repeat completion arteriography and minimal interventional strategies when grade I or II defects are seen on arteriography. The poor outcome with surgical correction of grade III defects suggests that completion arteriography may not always define the full extent of the problem or that the corrective surgical maneuvers were either incomplete or detrimental.

Aged↗
PubMed1996

Defects of the respiratory chain in oxyphil and chief cells of the normal parathyroid and in hyperfunction.

Immunohistochemical detection of complex HIII (ubiquinone- cytochrome-c-oxidoreductase) and complex IV (cytochrome-c-oxidase) of the respiratory chain was performed in parathyroids of 164 humans with normal renal function (group I) and in 55 patients with chronic renal insufficiency (group II) obtained at autopsy. In group I, 33 of the 164 cases showed defects of the respiratory chain (20%). Eighty-five percent of the defects occurred in advanced age (> 50 years). In group II, 39 of 55 cases (70%) had defects, and about 70% of the defects occurred after age 50. In both groups, more than 80% of the defects were localized in oxyphil cell nodules. However, not every oxyphil nodule was involved. In group I, selective defects of complex IV predominated and were found in 47 of 86 defects (55%). Combined defects of complexes III and IV were present in 25 of 86 defects (29%). In contrast, in group II combined defects predominated and were found in 45% (107 of 240 defects), whereas single defects of complex IV existed in 38% (93 of 240 defects). The frequency of selective defects of complex III was about 16% to 17% in both groups. In situ hybridization and PCR studies for the detection of the common deletion (4.977 base pairs) and of various point mutations of mitochondrial of (m)DNA revealed no consistent molecular genetic abnormalities. A point mutation in the tRNALeu(UUR) at nucleotide (nt) 3.260 was found in only one probe. The results show that defects of the respiratory chain occur already in normal parathyroids, most probably during cell aging, especially in oxyphil cells and at a higher rate in hyperfunction. The high predominance of respiratory chain defects in oxyphil cells and their random distribution favors mutations of mtDNA as a possible cause of oxyphilic cell transformation and of the respiratory chain defects. However, the mutations of mtDNA in the parathyroids are apparently different from those in other ageing tissues.

Adult↗
PubMedDate not supplied

Regeneration of segmental diaphyseal defects in sheep tibiae using resorbable polymeric membranes: a preliminary study.

OBJECTIVE: To investigate whether a long bone cortex of well-defined thickness can be regenerated by using an anatomically designed membranous resorbable "tube-in-tube" implant and to establish the functions of membranes in the healing of segmental diaphyseal bone defects larger than the "critical size." DESIGN: Bone healing in segmental diaphyseal defects larger than the critical size in the sheep tibiae covered with a single porous tubular membrane or implanted with anatomically shaped porous double tube-in-tube membranes was evaluated. Membranes with different pore structures were applied alone and/or in combination with autogenous bone graft. BACKGROUND: Healing of segmental diaphyseal bone defects in animals can be enhanced by covering the defects with resorbable polylactide membranes. Based on the results of bone healing in defects ten millimeters long in the rabbit radii, it was suggested that the membrane prevents muscle and soft tissue from invading the defect and maintains osteogenic cells and osteogenic substances within the space covered with membrane, thus promoting new bone formation. The functions of membranes may differ, however, depending on the size and the location of the defect and on the experimental species used. Bone defects larger than the critical size may not heal at all, even if membranes are used. The critical-size defect is defined as the smallest bone defect that does not heal spontaneously when covered with polymeric membranes. To heal such defects, it is mandatory that membranes are used in combination with autogenic bone graft and/or a suitable bone substitute. If bone graft is used to fill the defect, the structure and geometry of the covering membrane will determine whether the graft will be vascularized and/or nourished from the surrounding soft tissue and, in consequence, survive. It can be appreciated that bone healing in areas of good vascularity should be more efficient than bone healing in poorly vascularized areas. The influence of all these factors on healing of bone in segmental diaphyseal defects covered with membranes is not known. METHODS: Four-centimeter-long diaphyseal segmental defects in the tibiae of six- to seven-year-old Swiss mountain sheep were covered with resorbable membranes from poly(LDL-lactide). In Group 1, a single microporous external membrane was used. In Group 2, one microporous membrane was inserted into the medullary cavity at the cut ends of the tibiae (internal membrane), and the other microporous membrane was placed on the outer surface of the cortex (external membrane). In Group 3, a single microporous external membrane was also laser-perforated to produce openings with a diameter in the range of 800 to 900 micrometers. In Group 4, the defect was filled with autogenous cancellous bone graft and covered with a single perforated membrane. In Group 5, one perforated internal membrane was inserted into the medullary cavity at the cut ends of the tibiae, and the other perforated membrane was placed on the outer surface of the cortex. Group 6 was identical to Group 5, except that cancellous bone graft was placed in the space between these two membranes. RESULTS: There was no bone healing in Groups 1, 2, 3, and 5. Only in Groups 4 and 6 did the defects heal. In Group 4, new bone was dispersed across the "medullary canal" formed by the membrane. In Group 6, the new bone had grown into the space between the outer and inner membranes, forming the "neocortex." CONCLUSIONS: The resorbable polymeric implant consisting of two concentric perforated membranes (the tube-in-tube implant) used in combination with cancellous bone graft to treat segmental diaphyseal defects in sheep tibiae allows for the reconstitution of the "neocortex" with well-defined thickness. (ABSTRACT TRUNCATED)

Absorbable Implants↗
PubMed2004

Effect of GBR in combination with deproteinized bovine bone mineral and/or enamel matrix proteins on the healing of critical-size defects.

OBJECTIVES: To evaluate the effect of guided bone regeneration (GBR) in combination with or without deproteinized bovine bone mineral (DBBM) and/or an enamel matrix derivative (EMD) on the healing of critical-size calvarial defects. MATERIAL AND METHODS: Forty rats were used. In all animals, a standardized critical-size calvarial defect was created surgically. The animals were randomly allocated into 4 groups of 10 animals each. Group A: One calvarial defect was left untreated, while the galeal and the cerebral aspect of the contralateral defect were covered with a bioresorbable membrane (GBR). Group B: One calvarial defect was filled with EMD, while the contralateral defect was treated with GBR and EMD. Group C: One defect was filled with DBBM, while the contralateral defect was treated with combination of GBR and DBBM. Group D: One defect was filled with DBBM combined with EMD, while the contralateral defect was treated with combination of GBR, DBBM and EMD. The healing period was 4 months. Five specimens from each group were macerated and the length, the width and the vertical dimension (thickness) of the remaining defect were evaluated by a stereomicroscope. The remaining specimens in each group were analyzed histologically. RESULTS: The defects of the macerated specimens that were left untreated or were treated only by EMD, DBBM and combination of EMD and DBBM did not present predictably complete healing of the defects. All the defects where GBR was applied alone or combined with DBBM and/or EMD presented always complete healing (P<0.05). The combined use of GBR with EMD and/or DBBM did not offer any significant advantage above GBR alone in terms of healing of the length and the width of the defect. However, the vertical dimension of the defect was significantly higher (P<0.05) in the GBR-treated specimens of Groups C and D. The histological analysis supported these findings. CONCLUSION: The predictability of bone formation in critical-size defects depends mainly on the presence or absence of barrier membranes (GBR). The combined use with deproteinized bovine bone mineral and/or enamel matrix proteins did not significantly enhance the potential for complete healing provided by the GBR procedure.

Animals↗
PubMed2005

Healing of extraction sockets and surgically produced - augmented and non-augmented - defects in the alveolar ridge. An experimental study in the dog.

OBJECTIVES: The current experiments had three aims (i) to determine whether the absence of the periodontal ligament (PDL) may alter features of the healing of an extraction socket, (ii) to examine if there were differences in the proportion of different tissues in resolved extraction sockets and surgically produced defects after 3 months of healing, (iii) to study the influence of different biomaterials on the healing of surgically produced bone defects. MATERIAL AND METHODS: Extraction sites: In five dogs, the 4th mandibular pre-molars were hemi-sected and the distal roots were removed. The extraction socket of one of the pre-molars was instrumented to eliminate all remnants of the PDL tissue. The socket of the contra-lateral pre-molar was left without instrumentation. The dogs were sacrificed after 3 months of healing. Defect sites: In five dogs, the pre-molars and 1st molars on both sides of the mandible were first removed and 3 months of healing allowed. After this interval three standardized cylindrical defects were prepared in each side of the mandible. The defects were 3.5 mm in diameter and 8 mm deep. In each quadrant one defect was grafted with Bio-Oss Collagen, one with Collagen Sponge and one defect was left non-grafted. The dogs were sacrificed 3 months after the grafting procedure. RESULTS: Extraction sites: The two categories of extraction sockets did not differ with respect to gross morphological features. The tissue of the extraction sites, apical of a newly formed bone bridge, was dominated by bone marrow. Few trabeculae of lamellar bone were also present. Defect sites: The non-augmented defect was sealed by a hard-tissue bridge. In the central and apical portions of the defect bone marrow made up about 61%, and mineralized bone 39% of the tissues. The invagination of the surface of this crestal bone was 0.8+/-0.3 mm. The defect augmented with Collagen Sponge was covered by a hard-tissue bridge 38% of the tissue within the defect was made up of bone marrow while the remaining 62% was occupied by mineralized bone. The invagination of the hard-tissue bridge was on the average 0.6+/-0.1 mm. In defects augmented with Bio-Oss Collagen the biomaterial occupied a substantial portion of the tissue volume. Eighty-five percent of the periphery of the Bio-Oss particles were found to be in direct contact with newly formed mineralized bone. Woven bone and bone marrow made up 47% and 26% of the newly formed tissue. The invagination of the most coronal part of the bone defect was 0.1+/-0.1 mm. CONCLUSION: Sockets that following tooth removal had their PDL tissue removed exhibited similar features of healing after 3 months as sockets which had the PDL retained. The tissues present in an extraction site appeared to be more mature than those present in a surgically produced defect of similar dimension. The Bio-Oss Collagen augmented defect exhibited less wound shrinkage than the non-augmented defect.

Alveolar Process↗
PubMed2000

Repair of articular cartilage defects one year after treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2).

BACKGROUND: Damaged articular cartilage has a limited ability to repair. Operative removal of damaged cartilage and penetration into the subchondral bone to allow population of the defect with progenitor cells can result in filling of the defect with repair tissue. However, this repair tissue often degenerates over time because of its inability to withstand the mechanical forces to which it is subjected. We previously reported that recombinant human bone morphogenetic protein-2 (rhBMP-2) improves the repair of full-thickness defects of cartilage as long as six months postoperatively. We have now extended that study to examine the quality of the repair tissue at one year. METHODS: Full-thickness defects of cartilage were created in the trochlear groove of twenty-five adult New Zealand White rabbits. Eight defects were left empty, eight were filled with a collagen sponge, and nine were filled with a collagen sponge impregnated with five micrograms of rhBMP-2. The animals were killed at fifty-two weeks postoperatively, and the gross appearance of the healed defect was assessed. The repair tissue was examined histologically and was evaluated, according to a grading scale, by four individuals who were blinded with respect to the treatment. The tissue sections were immunostained with antibodies against type-I collagen, type-II collagen, aggrecan, and link protein. The residence time of the rhBMP-2 in the cartilage defect was evaluated in vivo with use of scintigraphic imaging of radiolabeled protein. RESULTS: One year after a single implantation of a collagen sponge containing five micrograms of rhBMP-2, the defects had a significantly better histological appearance than the untreated defects (those left empty or filled with a collagen sponge). The histological features that showed improvement were integration at the margin, cellular morphology, architecture within the defect, and reformation of the tidemark. The total scores were also better for the defects treated with rhBMP-2 than for the untreated defects, but in no instance was the repair tissue identical to normal articular cartilage. The thickness of the cartilage in the defects treated with rhBMP-2 was 70 percent that of the normal cartilage, an observation that was identical to that at twenty-four weeks postoperatively. Immunostaining demonstrated significantly less type-I collagen in the defects treated with rhBMP-2 than in the untreated defects. Immunostaining for other matrix components showed no difference among the treatment groups. The mean residence time of rhBMP-2 in the cartilage defects was eight days with an elimination half-life of 5.6 days. Detectable amounts of rhBMP-2 were present as long as fourteen days after implantation. CONCLUSIONS: The problems associated with operative repair of cartilage include the formation of fibrocartilage rather than normal articular cartilage and the degeneration of that repair tissue over time. Our results demonstrate that the addition of rhBMP-2 to the operative site after creation of a full-thickness defect results in an improvement in the histological appearance and composition of the extracellular matrix at one year postoperatively. If these experimental results translate directly to the clinical situation, it is possible that the addition of rhBMP-2 to existing operative treatments for the repair of cartilage may improve the repair process and may help to maintain the integrity of the repair tissue.

Animals↗
PubMed1989

[Correlation of various types of perfusion defects with supraventricular and ventricular arrhythmias in hypertrophic cardiomyopathy].

To ascertain the relationship between the types of myocardial perfusion defects and supraventricular and ventricular tachyarrhythmias in hypertrophic cardiomyopathy (HCM), 26 patients were studied with dipyridamole-loading thallium-201 scintigraphy and the results were correlated with 24-hour ambulatory ECG, echocardiograms and hemodynamic data. Myocardial perfusion defects were detected in 10 of the 26 patients (38%); three with large defects (LD) and seven with multiple small defects (SD). The patients with defects had greater degree of asymmetric septal hypertrophy (1.82 +/- 0.49 vs 1.27 +/- 0.38, p less than 0.01) and lower cardiac indices (2.35 +/- 0.31 vs 2.70 +/- 0.43, p less than 0.05) than did the patients without defects. Paroxysmal atrial fibrillation (PAf) and/or paroxysmal supraventricular tachycardia (PSVT) were observed in six of the 10 patients with defects (60%) and in four of the 16 patients without defects (25%). Ventricular tachycardia (VT) was identified in six of the 10 patients with defects (60%) but in only three of the 16 patients without defects (19%) (p less than 0.05). Among 10 patients with defects, PAf and/or PSVT were present in six of the seven patients with SD, but not in any of the patients with LD (p less than 0.05). VT was present in five of the seven patients with SD and in one of the three patients with LD. In conclusion, 1) perfusion defects in HCM are associated with greater degree of asymmetric septal hypertrophy, the lower cardiac indices, and higher prevalences of PAf, PSVT and VT; 2) Perfusion defects can be classified in two types; ie., multiple small defects and large defects; 3) Patients with multiple small defects commonly have PAf, PSVT as well as VT. This correlation may be of clinical importance, particularly in evaluating the causes of the defects and mechanisms of these arrhythmias.

Adolescent↗
PubMed1993

Predictive factors for spontaneous closure of atrial septal defects diagnosed in the first 3 months of life.

OBJECTIVES: To establish the rate of spontaneous closure of atrial septal defects diagnosed before age 3 months, 101 infants (mean age 26 days) with an interatrial shunt confirmed by Doppler echocardiography were followed up for an average of 265 +/- 190 days. BACKGROUND: Even if interatrial shunts in the newborn are frequently encountered, little is known about their natural history. METHODS: Defect diameter on two-dimensional echocardiography and width of color flow jet were measured in the subcostal view. Right and left ventricular diameters and atrial septal curvature were also studied. Kaplan-Meier curves were obtained to predict age of spontaneous closure in relation to initial defect diameter. RESULTS: There was no significant correlation between the diameter of the atrial septal defect and right ventricular/left ventricular ratio or type of septal curvature (vertical or concave toward the left atrium). The classic predominance of girls over boys was observed only for defects > 5 mm. An overall rate of spontaneous closure of 87% was observed. Frequency and timing of closure were inversely correlated to atrial septal defect diameter: closure occurred in 100% (32 of 32) of defects in group 1 (diameter < 3 mm), 87% of defects (39 of 45) in group 2 (diameter 3 to 5 mm), 80% of defects (16 of 20) in group 3 (diameter 5 to 8 mm). Spontaneous closure did not occur in four patients of group 4 (defect > or = 8 mm) during an average follow-up interval of 417 days (range 294 to 597 days). CONCLUSIONS: These results suggest that infants with an atrial septal defect < 3 mm need not be followed up as 100% of these defects will be closed by age 18 months; those with a defect 3 to 5 or 5 to 8 mm should be evaluated by the end of the 12th and the 15th month, respectively, when > 80% of these defects will be closed. An atrial septal defect with a diameter > or = 8 mm may have little chance of closing spontaneously and the possibility of surgical correction should be considered. Defects < 3 mm probably do not constitute a cardiac malformation in light of their natural evolution and gender distribution.

Age Factors↗
PubMed1992

The changing epidemiology of neural tube defects. United States, 1968-1989.

OBJECTIVE: To describe the recent trends and epidemiologic characteristics of neural tube defects in the United States. RESEARCH DESIGN: Ongoing surveillance data. SETTING: Two birth defect surveillance systems: the nationwide Birth Defects Monitoring Program and the Metropolitan Atlanta (Ga) Congenital Defects Program for 1970 through 1989 and 1968 through 1989, respectively. PARTICIPANTS: Between 1970 and 1989, using discharge diagnoses of approximately 1 million live-born and stillborn infants per year, the Birth Defects Monitoring Program identified 15,503 cases of spina bifida and anencephaly. Between 1968 and 1989, using discharge diagnoses and clinical records until age 1 year of 38,000 infants per year, the Metropolitan Atlanta Congenital Defects Program identified 800 cases of spina bifida and anencephaly. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Nationwide, neural tube defect rates have declined from 1.3 per 1000 births in 1970 to 0.6 per 1000 births in 1989. In Atlanta, neural tube defect rates have declined from 2.0 per 1000 births in 1968 to 0.6 per 1000 births in 1989. Several changes in the epidemiologic characteristics of neural tube defects were observed: (1) the proportion of spina bifida cases has increased; (2) the proportion of neural tube defect cases compared with the proportion of other unrelated defects has increased; (3) the race ratio of whites to other races for isolated neural tube defect cases has declined in Atlanta; and (4) the rate of isolated neural tube defects in females has also decreased. CONCLUSIONS: The declining rates of neural tube defects can be partially explained by increased widespread prenatal diagnostic techniques, strongly suggesting the role of environmental factors in neural tube defects. In particular, the use of multivitamins and folic acid to prevent the occurrence of neural tube defects needs further evaluation. Nevertheless, the changing clinical and epidemiologic characteristics of cases over time points to the etiologic heterogeneity of these conditions.

Anencephaly↗
PubMed1992

Trends in rates of multiple vascular disruption defects, Atlanta, 1968-1989: is there evidence of a cocaine teratogenic epidemic?

Research suggests that, perhaps through mechanisms initiated by vasoconstriction and leading to vessel thrombosis or embolism, cocaine causes vascular disruption defects, and that frequent cocaine use during early pregnancy could disrupt multiple organ systems in the fetus. We hypothesized that if cocaine is an important cause of multiple vascular disruption defects, a rising prevalence of cocaine use by mothers during pregnancy should be accompanied by rising rates of these defects in their offspring. Using data from the Metropolitan Atlanta Congenital Defects Program, we identified all infants born in Atlanta from 1968 through 1989 who had nonsyndromic, provisional vascular disruption defects affecting more than one organ system: 61 infants (78%) had gastrointestinal and genitourinary defects, 7 (9%) had gastrointestinal and abdominal wall defects, 2 (3%) had gastrointestinal and limb reduction defects, 2 (3%) had limb reduction and abdominal wall defects, 2 (3%) had central nervous system and gastrointestinal defects, 2 (3%) had genitourinary and limb reduction defects, 1 (1%) had genitourinary and abdominal wall defects, and 1 (1%) had central nervous system and genitourinary defects. The prevalence of Atlanta infants with more than one vascular disruption defect is 0.13 per 1,000 live births. Chi-square analysis for trends showed no increase in prevalence during the study period. Our data are from one of the first population-based studies in which trends for defects potentially caused by maternal cocaine use are examined; the results of our study show no significant change in the prevalence of multiple vascular disruption defects over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed2002

Contribution of birth defects to infant mortality in the United States.

BACKGROUND: While overall infant mortality rates (IMR) have declined over the past several decades, birth defects have remained the leading cause of infant death in the United States. To illustrate how this leading cause of infant mortality impacts subgroups within the US population a descriptive analysis of the contribution of birth defects to infant mortality at the national and state level was conducted. METHODS: Descriptive analyses of birth defects-specific IMRs and proportionate infant mortality due to birth defects were conducted for the US using 1999 mortality data from the National Center for Health Statistics. In 1999, the change to ICD-10 impacted how cause-specific mortality rates were coded. Aggregated 1995-1998 state- birth defects infant death statistics were used for state comparisons. RESULTS: In 1999, birth defects accounted for nearly 1 in 5 infant deaths in the US. Variation in birth defects-specific IMRs were observed by maternal race with black infants having the highest rates when compared with other race groups. However, among black infants prematurity/low birthweight was the leading cause of death, followed by birth defects. There is substantial variation in state-specific birth defects IMRs and the state-specific proportion of infant deaths due to birth defects. CONCLUSIONS: Birth defects remain the leading cause of infant death in the United States, despite the changes that resulted in 1999 from an update in the coding of cause of death from ICD-9 to ICD-10. While birth defects-specific IMRs provide an overall picture of fatal birth defects and a gauge of the impact of life-threatening anomalies, they represent only a fraction of the impact of birth defects, missing those who survive past infancy and those birth defects related losses in the antepartum period. Expansion and support of effective birth defects monitoring systems in each state that include the full spectrum of perinatal outcomes must be a priority. However, paralleling these efforts, analyses of this leading cause of infant mortality provide critical insight into perinatal health and should continue, with appropriate adjustments for the 1999 classification changes.

Black or African American↗
PubMedDate not supplied

Frequency of prenatal diagnosis of birth defects in Houston, Galveston and the Lower Rio Grande Valley, Texas 1995.

BACKGROUND: Estimates of the proportion of birth defects diagnosed before birth exist for only a few types of birth defects and for a few geographic regions in the United States. This population-based study examines rates of prenatal diagnosis for previously unstudied birth defects in a new geographic region. METHODS: Active surveillance of 23 categories of birth defects among 111,902 infants born in 77 birthing hospitals in Texas in 1995 identified 852 infants or fetuses with major birth defects. Surveillance was conducted by the Texas Birth Defects Monitoring Program of the Texas Department of Health. Two regions were covered, the Houston/Galveston metropolitan area as well as the Lower Rio Grande Valley of Texas. Rates of prenatal diagnosis were evaluated for 23 different types of birth defects, using proportions and 95% confidence intervals. RESULTS: One third of the 852 infants or fetuses with birth defects were prenatally diagnosed. Diagnosis rates varied greatly depending on the type of birth defects and were lower among infants born to Black and Hispanic women. More than 60% of anencephaly, encephalocele, gastroschisis and trisomies 13 and 18 were diagnosed antenatally. Many of the fetuses that were electively terminated had birth defects or combinations of birth defects that were potentially lethal. Prevalence rates for birth defects generally do not include fetuses that die or are electively terminated before 20 weeks of gestation. Thus, 36% of anencephaly, 21% of omphalocele, 15% of encephalocele and between 7 and 10% of spina bifida, hydrocephaly, renal agenesis, and trisomies 13, 18, and 21 were not included in our published rates. CONCLUSIONS: Published rates for specific types of birth defects are spuriously low. This should be considered when investigating alleged clusters and comparing rates of birth defects across geographic areas. Since many elective abortions are for lethal or potentially lethal birth defects, a major effect of prenatal diagnosis is the resultant decrease in infant mortality attributable to birth defects.

Abortion, Induced↗
PubMed2001

Application of bone morphogenetic proteins in the treatment of clinical oral and maxillofacial osseous defects.

BACKGROUND: Commonly occurring extensive osseous defects in the oral and maxillofacial area are seen following complete or partial resection of the mandible and other facial bones in oncologic surgery or following traumatic injury. Autogenous osseous grafts have been used to restore these defects. Additionally, bone graft substitute materials and autogenous osseous grafts are applied to congenital defects such as cleft palate, facial clefts, and facial asymmetry. We have simulated these types of defects in appropriately aged Macaca fascicularis and Macaca mulatta monkeys to study the efficacy of using bone morphogenetic protein (BMP) as an osseous inductor. The objective of these studies was to obtain information on the feasibility of employing bone inductors to regenerate large continuity critical-sized maxillofacial defects without using bone grafts. METHODS AND RESULTS: In one study, involving eight animals, the body of the mandible was removed, simulating hemi-mandibulectomy defects following traumatic bone loss or oncologic surgery. Recombinant human (rh) BMP-2 (Genetics Institute, Cambridge, Massachusetts) in a collagen carrier (Colla-Tec Inc., Plainsboro, New Jersey) then was placed in the hemi-mandibulectomy defect with use of titanium orthopaedic mesh fixation (Sofamor Danek-Medtronic, Memphis, Tennessee). Entire bone regeneration of the defect was observed 5 and 6 months postoperatively. In another group of subhuman primates, the restored area was functionally stimulated at the 5-month post-BMP implantation level by placement of intraoral titanium implants. The animals were allowed to function for 8 months with these titanium implants. Microscopic results showed increased density, bone volume, and thickness of the trabecular bone pattern. The bone cortex in the restored defect also increased in thickness compared with the nonsurgical areas. To evaluate the effect of rhBMP-2 in aging individuals, a group of six Macaca animals over 20 years of age received the same type of mandibular resection followed by BMP grafting with functional stimulation by mastication on root form implants placed at 5 months after BMP implantation. The entire mandible regenerated as in the younger group of animals; therefore, age did not appear to be a factor in the reparative process. Thus, the number of stem cells supposedly reduced with increasing age did not appear to affect the overall result of BMP-induced bone regeneration. Additionally, in applying the inductor material to younger monkeys (1-1 1/2 years of age), the rhBMP-2 was placed in simulated bilateral cleft palate defects. On one side, the rhBMP-2 was placed with use of the collagen sponge carrier. The autogenous graft most frequently used at present for regeneration of the osseous defects of maxillary clefts is iliac crest particulate cancellous bone. As a control graft on the contralateral side, therefore, autogenous particulate bone and marrow was placed. At the end of 3 months, the cleft side receiving the BMP-2 showed complete osseous restoration of the simulated cleft. The autogenously grafted side exhibited bone repair but incomplete regeneration of the bone defect at the early (3-months postoperative) stage of healing. CONCLUSIONS AND CLINICAL RELEVANCE: The results of these three subhuman primate defect studies--(a) mandibular resection defects in middle-aged Macaca fascicularis animals, (b) mandibular resection defects in Macaca fascicularis animals over 20 years of age, and (c) simulated bilateral clefts in Macaca mulatta animals 1 1/2 years of age (comparable with a 5-year-old child)--were very encouraging. Histomorphometric analysis in all of these investigations indicated that the use of rhBMP-2 in bone repair without the use of bone grafting materials will offer a new method of osseous reconstruction in clinical facial bone defects.

Aging↗
PubMed1992

A long-term study on defect filling and bone ingrowth using a canine fiber metal total hip model.

When performing primary and revision total hip arthroplasty (THA), bone defects are often encountered. At present, grafting osseous defects with autogeneic bone is a common means of treatment. In this study, defects in bone were created in the femora and acetabula of dogs being treated with cementless THA with a fiber metal implant (Group A) or a hydroxyapatite tricalcium phosphate (HA/TCP) sprayed implant (Group B). The following methods of defect filling were compared: (1) leaving defects unfilled, (2) filling with autogeneic bone graft, (3) filling with a 50:50 mixture of autograft and a biphasic ceramic composed of HA/TCP, and (4) filling with a collagen-HA/TCP-bone marrow mixture. Analysis of defect healing and the extent of ingrowth into the overlying fiber metal, at defect sites and sites distant from defects, was made at six, 12, and 24 weeks postimplantation. Defect healing was enhanced at six and 12 weeks in all grafted groups when compared with ungrafted controls. Bone ingrowth into the porous fiber metal overlying the defects was not significantly affected by grafting the defects, compared with the ungrafted defects. The extent of bone ingrowth into the fiber metal acetabular implant at sites away from the defects increased during the entire study. In contrast, the extent of bone ingrowth on the femoral side was maximal at 12 weeks. The HA/TCP coating enhanced ingrowth into the acetabular component at 12 weeks, compared with the uncoated prosthesis, but did not enhance ingrowth on the femoral side. The data from this study demonstrate that defect healing is enhanced with graft materials. However, this does not necessarily result in increased ingrowth into porous surfaces overlying osseous defects. General bone ingrowth and ingrowth at defect sites at 12 weeks postimplantation can be enhanced on the acetabular side with the use of HA/TCP-sprayed implants. However, no positive effect is seen with the use of an HA/TCP-sprayed femoral implant.

Acetabulum↗
PubMed1991

Ingrowth and formation of bone in defects in an uncemented fiber-metal total hip-replacement model in dogs.

An osseous defect was created in the acetabulum and femur of twenty dogs, and then a fiber-metal total hip prosthesis was inserted. A comparison was made between the effects of leaving the defects unfilled, filling the defects with an autogenous bone graft, and filling them with a 50:50 mixture of autogenous bone graft and a biphasic ceramic composed of hydroxyapatite and tricalcium phosphate. The characteristics of formation of bone within the sites of the defects and the extent of the ingrowth of bone into the underlying porous surface were analyzed. At six and twelve weeks after implantation, the dogs in the control group (unfilled defects) had the least amount of bone in the sites of the defects. In the dogs that had had an autogenous bone graft and those in which the defects had been filled with a mixture of autogenous bone graft and biphasic ceramic, there were excellent osteoconductive properties in the filling of the sites of the defects with new bone. A comparison was made between the amount of bone that formed in the osseous defects and the amount that formed in the spaces of the porous-surfaced fiber-metal components of the prostheses, directly underlying and adjacent to the defects. At six weeks, the greatest amount of ingrowth of bone into the spaces of the underlying titanium fiber-metal acetabular components was seen in the control group (22 per cent of the porous surface), followed by the group in which the defects had been filled with a mixture of autogenous bone graft and biphasic ceramic (19 per cent). The defects that had been filled only with autogenous bone graft had poor ingrowth of bone into the porous surface (4 per cent) and predominantly fibrous ingrowth. At twelve weeks, these defects again showed the least amount of ingrowth of bone (15 per cent) compared with the defects in the control group (24 per cent) and those that had been filled with a mixture of autogenous bone graft and biphasic ceramic (24 per cent). No statistically significant differences were found in the amount of ingrowth of bone into the defects that had been created in the femur in the three groups of dogs at either six or twelve weeks. However, the trends appeared to correlate with the data for the acetabular defects.

Acetabulum↗
PubMed1982

How accurate is the ultrasonic estimation of ventricular septal defect size?

The relationship between the size of ventricular septal defects estimated from ultrasonic images and the actual size of the ventricular septal defects is currently unknown. Our goal was to image simulated defects of known size under conditions as physiological as possible with several two-dimensional ultrasonic instruments. The study was not viewed as a contest between instruments. A static heart model we tested consisted of a simulated chest wall-right ventricular anterior wall, a human septum or muscular septal equivalent, and a simulated left ventricular posterior wall. Model tissues were placed in holders in a water bath for imaging at 90 degrees and 180 degrees with respect to the ventricular septal defect. These angles tested the lateral and axial resolution necessary for imaging simulated ventricular septal defects. Actual ventricular septal defect sizes ranged from 5 to 17.5 mm. Images were obtained with a 30 degrees, 3.5-MHz, mechanical sector scanner, a 2.4-MHz range focused phased array, and a prototype transmit and dynamically focused, 3.5-MHz phased array. Image quality of the defect varied at 90 degrees but was generally poor at 180 degrees. For studies conducted at 180 degrees, phased arrays imaged sharp defect edges for larger holes, but the mechanical sector scanner did not. Signal attenuation appeared to be the major limiting factor for axial resolution. For imaging at 90 degrees, the mechanical sector scanner approximated the actual defect size less 4 mm. The prototype phased array scanner approximated the defect size less 4 to 6 mm. With the range focused, phased array, imaged size was always less than one half actual size. The smallest defect imaged with our simulation with any instrument was 7 mm. These data or their regression equation should not be used to compute the actual size of a clinical ventricular septal defect, since different machines, transducers, and situations might alter the exact relationship between imaged and actual defect size. However, the data led to the conclusion that imaged size of a defect is instrument and transducer dependent and is always smaller than actual defect size.

Animals↗
PubMed2003

Defective influenza A virus generated entirely from plasmids: its RNA is expressed in infected mouse lung and modulates disease.

Naturally produced defective influenza virus has antiviral activity and, in sufficient amount, can protect mice from lethal influenza, irrespective of the virus subtype causing the disease. However, such defective virus preparations contain many undefined defective RNA sequences, and it is thus not possible to establish dose-response relationships. To address this situation, we have transfected DNA encoding a cloned defective RNA into Vero cells along with the 17 A/WSN (H1N1) plasmids required for infectious helper virus, and produced molecularly cloned defective virus. Here we used POLI-220 that expresses a 445 nt defective RNA isolated from a mouse-protective defective equine H3N8 virus, and POLI-317 that expresses a 585 nt defective RNA from an avian H7N7 virus. Both originate from genomic segment 1. Virus preparations were UV-irradiated selectively to destroy virus infectivity but not the activity of the defective RNAs, and adult mice were inoculated intranasally with defective virus and WSN (H1N1) challenge virus (10 LD(50)). Defective POLI-220 and POLI-317 RNAs were detected readily in infected lung tissue by RT-PCR, but these Vero cell preparations did not modulate disease. However, after a single passage in embryonated eggs, defective POLI-220 and POLI-317 viruses significantly delayed the onset of disease and death in WSN-infected mice, although did not affect final mortality. Direct PCR sequencing confirmed the identity of mouse-passaged defective RNAs and showed that none had undergone any sequence changes. With this advance it will now be possible to study the interference phenomenon in vivo with defective viruses carrying a defined defective RNA.

Animals↗
PubMed2004

Visual field defects after intravitreous administration of indocyanine green in macular hole surgery.

OBJECTIVES: To report the findings on a patient cohort with visual field defects after macular hole surgery with indocyanine green (ICG)-assisted internal limiting membrane peeling and to investigate the correlation between the defects and the use of ICG. DESIGN: Retrospective, noncomparative interventional case series. PARTICIPANTS: Thirty-nine eyes of 38 patients having the clinical diagnosis of a macular hole who underwent pars plana vitrectomy between January 1, 2001, and December 31, 2002, were enrolled in this study. INTERVENTION: Indocyanine green-assisted internal limiting membrane peeling was performed on a series of 22 eyes: 12 eyes using a 0.5% ICG solution and 3-minute exposure to the retina (group 1), 4 eyes using a 0.5% ICG solution and immediate washout (group 2), and 6 eyes using a 0.25% ICG solution and immediate washout (group 3). The remaining 17 eyes underwent vitrectomy without ICG-assisted internal limiting membrane peeling (group 4). MAIN OUTCOME MEASURES: Visual field, best-corrected visual acuity, and fundus photography were evaluated. RESULTS: Postoperatively, all patients (100%) in group 1 and 1 (25%) of 4 eyes in group 2 had visual field defects. None of the patients in group 3 had a visual field defect. The visual field defects included 10 eyes (84%) with nasal defects, 1 eye (8%) with an inferotemporal defect, and 1 eye (8%) with an extensive visual field defect. Ophthalmoscopy revealed mild to moderate optic disc pallor in 8 (62%) of 13 eyes with postoperative visual field defects. Only 1 patient in group 4 had an inferotemporal defect; none of the other patients in group 4 had visual field defects. There was no statistically significant difference in postoperative visual acuity between patients with and without postoperative visual field defects. CONCLUSIONS: Although this study was limited by the few patients enrolled, our experience indicates that visual field defects, specifically nasal defects, can occur after macular hole surgery with ICG-assisted internal limiting membrane peeling, and that the incidence depends on the concentration of the ICG solution and/or the exposure time to the retina. Further studies are needed to clarify the pathomechanism of visual field defects.

Coloring Agents↗