Birth defects: clinical and ethical considerations. Annual review of birth defects, 1982.
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The results of investigations by echoCG, ECG, FCG, sphygmography, roentgenography, including cardiac catheterization, of 16 patients with rheumatic mitral-tricuspid disease of the heart were compared. The organic injuries of the tricuspid valves (OITV) were confirmed during operation. With respect to preoperative diagnosis of OITV the sensitivity of echoCG was equal to 94 %, polycardiography--81 %, roentgenography--54 %, cardiac catheterization--94 %. Thus, echoCG proved to be the most accurate method of the primary asanguineous diagnosis of an organic injury of the tricuspid valve. The echocardiographic diagnosis of OITV included the symptoms of constriction of the right atrioventricular orifice and fibrous alterations of the valve cusps. Possible technical errors of the methods in respect to the detection of OITV are discussed.
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To discover if there is difference in central visual field damage between low-tension glaucoma (LTG) and primary open angle glaucoma (POAG) eyes, the data obtained with the 10-2 threshold program of the Humphrey visual field analyzer were analysed using logistic discriminant analysis. One hundred and four LTG eyes from 65 case (maximum IOP < or = 21 mmHg) and 48 POAG eyes from 34 cases (maximum IOP > or = 25 mmHg) with early to moderately advanced visual field damage were included. There was no significant difference in mean deviation (MD, STATPAC), refraction, or age between the 2 groups. The analysis demonstrated that an arcuate area in the upper central 5-10 degrees of the visual field was significantly more depressed in LTG than in POAG eyes.
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Langerhans cells (LC), the APCs in the skin, serve as a model for investigation of dendritic cell (DC) function in tissues. DC play a crucial role in the generation of antitumor immune responses. In this study, we investigated the effect of the presence of tumor in vivo on the ability of LC to take up Ag, migrate to draining lymph nodes, and stimulate primary T cell responses. In two animal models, these functions were substantially inhibited. This effect was not restricted to LC located in the skin near a tumor but was also seen at sites distant from the tumor. The duration of tumor exposure, and not its ultimate size, were found to be important, suggesting that tumors could be inhibiting the maturation of LC rather than directly inhibiting their function. Model experiments with radiation chimeras supported this hypothesis. To investigate the potential role of vascular endothelial growth factor (VEGF) in these effects we used anti-VEGF-neutralizing Ab to treat animals bearing tumors. Treatment with the Ab at a dose of 10 microg i.p. per mouse, twice a week for 4 wk, significantly improved the number and function of LC as measured by their ability to migrate to lymph nodes and stimulate primary T cell responses, even at doses that do not affect the growth of these established poorly immunogenic tumors. Thus, inhibition of VEGF signaling may improve DC function in tumor-bearing hosts and possibly serve to improve the efficacy of cancer immunotherapy.
BACKGROUND: Full-thickness defects measuring 3 mm in diameter have been commonly used in studies of rabbits to evaluate new procedures designed to improve the quality of articular cartilage repair. These defects initially heal spontaneously. However, little information is available on the characteristics of repair of larger defects. The objective of the present study was to define the characteristics of repair of 6-mm full-thickness osteochondral defects in the adult Spanish goat. METHODS: Full-thickness osteochondral defects measuring 6 x 6 mm were created in the medial femoral condyle of the knee joint of adult female Spanish goats. The untreated defects were allowed to heal spontaneously. The knee joints were removed, and the defects were examined at ten time-intervals, ranging from time zero (immediately after creation of the defect) to one year postoperatively. The defects were examined grossly, microradiographically, histologically, and with magnetic resonance imaging and computed tomography. RESULTS: The 6-mm osteochondral defects did not heal. Moreover, heretofore undescribed progressive, deleterious changes occurred in the osseous walls of the defect and the articular cartilage surrounding the defect. These changes resulted in a progressive increase in the size of the defect, the formation of a large cavitary lesion, and the collapse of both the surrounding subchondral bone and the articular cartilage into the periphery of the defect. Resorption of the osseous walls of the defect was first noted by one week, and it was associated with extensive osteoclastic activity in the trabecular bone of the walls of the defect. Flattening and deformation of the articular cartilage at the edges of the defect was also observed at this time. By twelve weeks, bone resorption had transformed the surgically created defect into a larger cavitary lesion, and the articular cartilage and subchondral bone surrounding the defect had collapsed into the periphery of the defect. By twenty-six weeks, bone resorption had ceased and the osseous walls of the lesion had become sclerotic. The cavitary lesion did not become filled in with fibrocartilage. Instead, a cystic lesion was found in the center of most of the cavitary lesions. Only a thin layer of fibrocartilage was present on the sclerotic osseous walls of the defect. Specimens examined at one year postoperatively showed similar characteristics. CONCLUSIONS: Full-thickness osteochondral defects, measuring 6 mm in both diameter and depth, that are created in the medial femoral condyle of the knee joint of adult Spanish goats do not heal spontaneously. Instead, they undergo progressive changes resulting in resorption of the osseous walls of the defect, the formation of a large cavitary lesion, and the collapse of the surrounding articular cartilage and subchondral bone. CLINICAL RELEVANCE: As surgeons apply new reparative procedures to larger areas of full-thickness articular cartilage loss, we believe that it is important to consider the potential deleterious effects of a "zone of influence" secondary to the creation of a large defect in the subchondral bone. When biologic and synthetic matrices with or without cells or bioactive factors are placed into surgically created osseous defects, the osseous walls serve as shoulders to protect and stabilize the preliminary repair process. It is important to protect the repair process until biologic incorporation occurs and the chondrogenic switch turns the cells on to synthesize an articular-cartilage-like matrix. It takes a varying period of time to fill a large, surgically created bone defect underlying a chondral surface. The repair of such a defect requires bone synthesis and the reestablishment of a subchondral plate with a tidemark transition to the new overlying articular surface. The prevention of secondary changes in the surrounding bone and articular cartilage and the durability of the new reparative tissue making up the articulating surface are issues that must be addressed in future studies.
BACKGROUND: Microfracture is a surgical procedure that is used to treat focal articular cartilage defects. Although joint function improves following microfracture, the procedure elicits incomplete repair. As blood clot formation in the microfracture defect is an essential initiating event in microfracture therapy, we hypothesized that the repair would be improved if the microfracture defect were filled with a blood clot that was stabilized by the incorporation of a thrombogenic and adhesive polymer, specifically, chitosan. The objectives of the present study were to evaluate (1) blood clot adhesion in fresh microfracture defects and (2) the quality of the repair, at six months postoperatively, of microfracture defects that had been treated with or without chitosan-glycerol phosphate/blood clot implants, using a sheep model. METHODS: In eighteen sheep, two 1-cm2 full-thickness chondral defects were created in the distal part of the femur and treated with microfracture; one defect was made in the medial femoral condyle, and the other defect was made in the trochlea. In four sheep, microfracture defects were created bilaterally; the microfracture defects in one knee received no further treatment, and the microfracture defects in the contralateral knee were filled with chitosan-glycerol phosphate/autologous whole blood and the implants were allowed to solidify. Fresh defects in these four sheep were collected at one hour postoperatively to compare the retention of the chitosan-glycerol phosphate/blood clot with that of the normal clot and to define the histologic characteristics of these fresh defects. In the other fourteen sheep, microfracture defects were made in only one knee and either were left untreated (control group; six sheep) or were treated with chitosan-glycerol phosphate/blood implant (treatment group; eight sheep), and the quality of repair was assessed histologically, histomorphometrically, and biochemically at six months postoperatively. RESULTS: In the defects that were examined one hour postoperatively, chitosan-glycerol phosphate/blood clots showed increased adhesion to the walls of the defects as compared with the blood clots in the untreated microfracture defects. After histological processing, all blood clots in the control microfracture defects had been lost, whereas chitosanglycerol phosphate/blood clot adhered to and was partly retained on the surfaces of the defect. At six months, defects that had been treated with chitosan-glycerol phosphate/blood were filled with significantly more hyaline repair tissue (p < 0.05) compared with control defects. Repair tissue from medial femoral condyle defects that had been treated with chitosan-glycerol phosphate/blood contained more cells and more collagen compared with control defects and showed complete restoration of glycosaminoglycan levels. CONCLUSIONS: Solidification of a chitosan-glycerol phosphate/blood implant in microfracture defects improved cartilage repair compared with microfracture alone by increasing the amount of tissue and improving its biochemical composition and cellular organization.
Using data from the population-based Metropolitan Atlanta Congenital Defects Program, the association of seven relatively common and easily ascertainable groups of midline defects was studied. These defects were neural tube defects (575 patients), oral clefts (633 patients), omphalocele (141 patients), esophageal atresia/tracheoesophageal fistula (88 patients), imperforate anus (151 patients), conotruncal heart defects (289 patients), and diaphragmatic hernia (75 patients). Known syndromes were excluded from the analysis. Of 1743 infants with at least one midline defect, 86 (4.9%) had at least a second midline defect, and 9 (0.5%) had two additional midline defects. Pairwise analysis of the seven defects shows that, although most midline defects tend to be statistically associated with other midline defects, specific combinations of midline defects are seen. For example, neural tube defects are more strongly associated with cleft lip with or without cleft palate than with cleft palate alone; imperforate anus is more strongly associated with spina bifida than with anencephaly or encephalocele. Moreover, some combinations of defects are not observed (eg, neural tube defect and conotruncal heart defect, clefts and diaphragmatic hernia, omphalocele and esophageal atresia/tracheoesophageal fistula). These data point to the need for further refinement in the study of the association of midline defects in terms of embryologic and pathogenetic mechanisms because most midline defects tend to occur as an isolated defect, some midline defects occur with nonmidline defects (such as limb defects), and specific associations among midline defects are observed.
OBJECTIVE: The purpose of this study was to evaluate the association between the prevalence of birth defects among maternal and paternal occupation groups in Singapore for live births between January 1, 1994, and December 31, 1998, and to determine whether there are certain demographic risk factors and maternal and/or paternal occupation groups that are associated with an increased risk for birth defects versus chromosomal single birth defect, nonchromosomal single birth defect, and multiple birth defects. STUDY DESIGN: This was a retrospective study. Information on live births (Singapore National Registry of Births and Deaths) and birth defect cases (National Birth Defects Register) were studied. Other information included the mother's date of birth, ethnic group, highest educational qualification, and the occupation of the mother and the father. Cox regression analysis was used to determine whether certain demographic and occupational factors were associated with the three groups of birth defects. RESULTS: Of a total of 237,755 live births, there were 3276 birth defect cases (nonchromosomal single birth defect, 1869 cases; chromosomal single birth defect, 197 cases; and multiple birth defects, 1210 cases). Increased risks for all types of birth defects were observed with advancing gestational age. Occurrence of nonchromosomal single birth defect and multiple birth defects were significantly higher for multiple births compared to singleton births. Significant associations were found with the use of "legislators, senior officers, and managers" as reference: Maternal occupation of "cleaners, laborers, and related workers" with chromosomal single birth defect anomalies (adjusted risk ratio, 4.86; 95% CI, 1.07-22.14); paternal occupation of "plant and machine operators and assemblers" (adjusted risk ratio, 1.50; 95% CI, 1.14-1.98) with nonchromosomal single birth defect; "production craftsmen and related workers" and "cleaners and laborers and related workers" with nonchromosomal single birth defect (adjusted risk ratio, 1.42; 95% CI, 1.10-1.82; and adjusted risk ratio, 1.43; 95% CI, 1.07-1.91 respectively); and multiple birth defects (adjusted risk ratio, 1.42; 95% CI, 1.03-1.94; and adjusted risk ratio, 1.47; 95% CI, 1.03-2.09, respectively). CONCLUSION: Maternal delivery age is an important risk factor for all birth defects. Mothers and fathers who work as "cleaners and laborers and related workers" appear to have a higher risk of giving birth to children with chromosomal single birth defect and nonchromosomal single birth defect and multiple birth defects, respectively. Further in-depth study would be needed to confirm these observations.