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Tissue-engineered repair of osteochondral defects: effects of the age of donor cells and host tissue.

Transplantation of a tissue-engineered construct containing cells of a chondrocytic phenotype into an osteochondral defect provides a biological solution to this type of injury. Among the factors that affect cell proliferation and phenotypic expression, age is one that has not been well characterized. In this study adult and aged male donor cells, derived from perichondrium, were cultured and adsorbed into a polylactic acid (PLA) scaffold and transplanted into osteochondral defects created in adult (8- to 10-month-old) and aged (4- to 5-year-old) female rabbits. Three groups were investigated: (1) adult cells transplanted into aged defects, (2) aged cells transplanted into aged defects, and (3) aged cells transplanted into adult defects. In vitro characterization of adult and aged cells and in vivo assessment of osteochondral repair tissue at 12 weeks posttransplantation were carried out. The in vitro studies demonstrated that the proliferation rate of aged cells was less than that of mature cells during the earliest stage of culture. Also, the chondrocytic phenotype was reduced in aged cells compared with mature cells. The in vivo results showed that donor (SRY-positive) cell survival differed among the three groups: survival of adult cells into aged defect > survival of aged cells into aged defect > survival of aged cells into adult defect. The biological acceptability of the repair, defined as smooth firm cartilaginous tissue filling the defect, was < 25% of the operated specimens in each of the three groups. This repair tissue contained only 20-25% of the amounts of type II collagen and glycosaminoglycans found in normal articular cartilage. These data suggest that the outcome of tissue-engineered repair of osteochondral defects is affected by both the age of donor cells and the age of the host.

Age Factors↗

Use of muscle cells to mediate gene transfer to the bone defect.

Segmental bone defects and nonunions are relatively common problems facing all orthopaedic surgeons. Osteogenic proteins, i.e., BMP-2, can promote bone healing in segmental bone defects. However, a large quantity of the human recombinant protein is needed to enhance the bone healing potential. Cell mediated gene therapy in the bone defect can allow a sustained expression of the osteogenic proteins and further enhance bone healing. Muscle cells can be easily isolated and cultivated, and they are known to be an efficient gene delivery vehicle to muscle and nonmuscle tissues. Furthermore, they are capable of transforming into osteoblasts when stimulated by BMP-2. Thus, the utilization of muscle cells as the gene delivery vehicle to a bone defect would be an important step in establishing a less invasive treatment for non-unions and segmental bone defects. Muscle cells were transduced when the adenoviral-lacZ vector and injected into the bone defect and the muscles surrounding the defect. Expression of the marker gene was visualized 7 days after the injection, both macroscopically and microscopically, using lacZ histochemistry. The lacZ expressing cells in the defect tissue were also stained for desmin, a muscle specific marker, indicating the presence of muscle cells that have fused into myofibers in this nonmuscle bone defect area. With successful myoblast mediated gene delivery into the segmental bone defect, future experiments would focus on delivering viral vectors expressing osteogenic proteins to eventually improve bone healing postinjury.

Animals↗

Paternal age and birth defects: how strong is the association?

BACKGROUND: Although the association between maternal age and the risks of birth defects has been well studied, the evidence from population data linking paternal age with birth defects was limited and inconsistent. METHODS: We conducted a population-based retrospective cohort study of 5,213,248 subjects from the 1999-2000 birth registration data of the USA. Multiple logistic regressions were used to estimate the independent effect of paternal age on all birth defects and 21 specific defects groups after adjusting for potential confounding of maternal age, race, education, marital status, parity, prenatal care initiation, maternal smoking and alcohol drinking during pregnancy. RESULTS: A total of 77,514 (1.5%) birth defects were recorded in the study cohort. The adjusted odds ratios were 1.04 (1.01, 1.06), 1.08 (1.04, 1.12), 1.08 (1.02, 1.14) and 1.15 (1.06, 1.24), respectively, for infants born to fathers 30-35, 40-44, 45-49 and over 50 years (test for trend, P = 0.0155), when compared with those infants born to fathers aged 25-29 for any birth defect. Advanced paternal age was associated with increased risks of heart defects, tracheo-oesophageal fistulaoesophageal atresia, other musculoskeletal/integumental anomalies, Down's syndrome and other chromosomal anomalies. Fathers under 25 years of age were also at increased risks of spina bifida/meningocele, microcephalus, omphalocele/gastroschisis and other musculoskeletal/integumental anomalies. CONCLUSIONS: Infants born to older fathers have a slightly increased risk of birth defects. Young paternal age is also associated with slightly increased risk of several selected birth defects in their offspring. However, given the weak association, paternal age appears to play a small role in the aetiology of birth defects.

Adult↗

Completeness of the discharge diagnoses as a measure of birth defects recorded in the hospital birth record.

Licensed hospitals usually maintain a discharge diagnoses index, which provides an inexpensive tool for the surveillance of birth defects diagnosed shortly after birth. Government agencies in several states routinely use discharge diagnoses for this purpose. To evaluate the completeness of the discharge diagnoses, the authors compared birth defects noted in the discharge diagnoses with those noted anywhere in the hospital birth record in a cohort of 3,421 infants born to US Army veterans from 1966 to 1986. In this cohort, 237 birth defect cases were documented in hospital birth records, and 49% of those cases were missed in the discharge diagnoses (28% of major defect cases and 66% of minor defect cases). The extent of missed defects varied greatly by organ system and by specific defect. Significant predictors of a missed defect were the presence of multiple defects, female sex, and western region of birth. The underascertainment of defects in the discharge diagnoses should be considered in the development and operation of surveillance systems using this source of data.

Abnormalities, Multiple↗

Anal sphincter defects. Correlation between endoanal ultrasound and surgery.

OBJECTIVE: This study was performed to (1) correlate and sphincter defects, identified by endoanal ultrasound with operative findings, and (2) define the appearance of such sphincter defects as seen at operation. SUMMARY BACKGROUND DATA: Endoanal ultrasonography is a minimally invasive method of imaging the anal sphincter complex and enables identification of anal sphincter defects. Little is known about the accuracy and limitations of endoanal ultrasound in identifying such defects. Furthermore, there are no data about the appearances of these endosonic sphincter defects as seen at operation. METHODS: Forty-four patients (40 women; age range, 26 to 80 years; mean age, 56 years) with fecal incontinence, undergoing pelvic floor repair, were investigated by endoanal ultrasound before operation. Endosonic findings were correlated with the appearances of external anal sphincter, internal anal sphincter, and intersphincteric space, at operation. Diagnosis of the site and type of defect was made by macroscopic appearances. Uncertainty about the type of sphincter defect was resolved by obtaining muscle biopsies for histology. RESULTS: All external sphincter defects seen by endoanal ultrasound (n = 23) were confirmed at operation. Twenty-one of 22 internal sphincter defects identified by endosonography also were confirmed at operation. In ten patients with a neuropathic anal sphincter complex, the morphology was normal on endosonography, and this was confirmed at operation. (Sensitivity and specificity of 100% for external anal sphincter; 100% and 95.5%, respectively, for internal and sphincter) CONCLUSIONS: These data show that endoanal ultrasound is an accurate method of identifying anal sphincter defects.

Adult↗

A prospective study of the risk of congenital defects associated with maternal obesity and diabetes mellitus.

This study was designed to evaluate the effects of maternal obesity and diabetes mellitus on the risk of nonchromosomal congenital defects. We used data from 22,951 pregnant women enrolled in a prospective cohort study of early prenatal exposures and pregnancy outcome. The relative risks [prevalence ratios (PRs)] of major nonchromosomal congenital defects associated with obesity and diabetes, alone or in combination, were calculated using multiple logistic regression analysis. In this study, in the absence of diabetes, obese women (body mass index > or =28) had no higher risk, overall, of having an offspring with a major defect [PR = 0.95; 95% confidence interval (CI) = 0.62-1.5]. Their offspring, however, did have a higher prevalence of certain types of defects, including orofacial clefts; club foot; cardiac septal defects; and, to a lesser extent, hydrocephaly and abdominal wall defects. Women with pre-existing or gestational diabetes who were not obese also had no excess risk overall of having offspring affected by a major defect (PR = 0.98; 95% CI = 0.43-2.2), although they did have a higher prevalence of musculoskeletal defects. The pregnancies of women who were both obese and diabetic were 3.1 times as likely (95% CI = 1.2-7.6) to result in an offspring with a defect than were those of nonobese, nondiabetic women, which suggests that obesity and diabetes mellitus may act synergistically in the pathogenesis of congenital anomalies. The defects were largely craniofacial or musculoskeletal.

Adult↗

Closure of critical sized defects with allogenic and alloplastic bone substitutes.

PURPOSE: This study evaluates bone regeneration of critical sized cranial vault defects in New Zealand white rabbits using four commercially available bone substitutes: OsteoSet (calcium sulphate pellets), DynaGraft Putty (demineralized bone matrix delivered in a poloxmer excipient), Norian CRS, and Bone Source (two commercially available calcium phosphate cements). MATERIALS AND METHODS: Critical sized defects 15 mm in diameter were created bilaterally in the parietal bones of 30 adult male New Zealand White rabbits. They were divided into three groups with ten animals in each. Bone healing was assessed clinically, radiographically, and histomorphometrically. Group 1 had calcium sulfate bioimplant on one side of the calvarium and an unfilled defect on the contralateral side. Group 2 had DBM putty on one side and Poloxamer gel on the contralateral side. Group 3, the Calcium phosphate cements (CPC), had Norian CRS on one side and Bone Source on the contralateral side. Five animals in each group were killed at 6 weeks and 12 weeks post operatively. RESULTS: All unfilled defects healed with fibrous scar, as did the Plaster of Paris and the poloxamer gel defects. Defects reconstructed with the demineralized bone matrix putty healed with bone throughout the entire defect. This was obvious clinically and radiographically where the defects appeared completely filled with a dense radiopaque tissue. The six-week group displayed new bone formation (87.1%) surrounding the remaining allogeneic particles. Resorption was evidenced by the presence of osteoclastic activity and by the significant decrease in the size of the demineralized bone particles. By 12 weeks, the demineralized bone putty bioimplant was almost completely replaced by new bone (95.5%). Both calcium phosphate cement groups (Norian CRS and Bone Source) had identical patterns of healing. They clinically were visible and firm and uniformly radiopaque with little evidence of new bone formation. Histologically the cement remained unresorbed with little new bone with in the defect at 12 weeks. CONCLUSIONS: The utilization of a demineralized bone matrix putty appeared to allow for complete closure of critical sized calvarial defects in New Zealand white rabbits with viable new bone at 12 weeks.

Analysis of Variance↗

Clinical features of thrombophilia in families with gene defects in protein C or protein S combined with factor V Leiden.

Twenty-nine clinically well-characterized, symptomatic index patients, 15 with protein C and 14 with protein S deficiency, in whom the genetic defect had been identified, were investigated for the presence of factor V Leiden. In six of 15 (40%) propositi with protein C and four of 14 (29%) with protein S deficiency, factor V Leiden was present. The age at first thrombosis was significantly lower (P < 0.001) in the ten propositi with a combined genetic defect (mean age 18.4 +/- 6.6 years) than in those with a single defect (mean age 32.6 +/- 10.4 years). Spontaneous occurrence, recurrence and site of thrombosis were similar in propositi with the single and the combined defect. Family studies led to the identification of a combined defect in 18 individuals from 11 families (11 propositi and 29 relatives), seven subjects had no abnormality, and in 15 a single defect was found. In individuals with a combined defect, thrombosis-free survival time was significantly shorter than in individuals with a single defect, even after exclusion of index patients. None of the seven individuals without genetic abnormality had experienced thrombosis. Our findings indicate a higher risk for development of thrombosis in individuals with a combined defect compared with those with a single defect.

Adolescent↗

Comparison of planar and SPECT 99Tcm-DMSA scintigraphy for the detection of renal cortical defects in children.

Renal cortical scintigraphy with 99Tcm-dimercaptosuccinic acid is an excellent imaging modality for the detection of renal cortical defects in children presenting with vesicoureteric reflux and urinary tract infections. Single photon emission computed tomography (SPECT) has proven increased sensitivity over planar scintigraphy for lesion detection in the heart, liver and brain. However, its role in the evaluation of renal cortical defects compared to planar scintigraphy has not been fully assessed. We wished to determine whether SPECT increases the sensitivity for detecting renal cortical defects in children compared to high-resolution planar scintigraphy. Forty-one children (90 renal units) with underlying vesicoureteric reflux and/or recently treated urinary tract infection (UTI) were evaluated. There was no statistically significant difference in the number of defects detected between a single-head SPECT system and high-resolution planar scintigraphy, 24 and 20, respectively (P = 0.54). There were four defects detected by SPECT not reported by planar scintigraphy; two of these were only seen retrospectively on planar scintigraphy. There were two children with renal cortical defects detected by SPECT and not by planar scintigraphy. All defects defected by planar scintigraphy were detected by SPECT. It is concluded that although the risk of missing renal cortical defects is low when using high-resolution, three-view planar scintigraphy, SPECT should be employed whenever feasible. Single photon emission computed tomography detected renal cortical defects in children not diagnosed by planar scintigraphy and hence patient management may be altered.

Child↗

Tissue engineered bone repair of calvarial defects using cultured periosteal cells.

Periosteum has been demonstrated to have cell populations, including chondroprogenitor and osteoprogenitor cells, that can form both cartilage and bone under appropriate conditions. In the present study, periosteum was harvested, expanded in cell culture, and used to repair critical size calvarial defects in a rabbit model. Periosteum was isolated from New Zealand White rabbits, grown in cell culture, labeled with the thymidine analog bromodeoxyuridine for later localization, and seeded into resorbable polyglycolic acid scaffold matrices. Thirty adult New Zealand White rabbits were divided into groups, and a single 15-mm diameter full-thickness calvarial defect was made in each animal. In group I, defects were repaired using resorbable polyglycolic acid implants seeded with periosteal cells. In group II, defects were repaired using untreated polyglycolic acid implants. In group III, the defects were left unrepaired. Rabbits were killed at 4 and 12 weeks postoperatively. Defect sites were then studied histologically, biochemically, and radiographically. In vitro analysis of the cultured periosteal cells indicated an osteoblastic phenotype, with production of osteocalcin upon 1,25(OH)2 vitamin D3 induction. In vivo results at 4 weeks showed islands of bone in the defects repaired with polyglycolic acid implants with periosteal cells (group I), whereas the defects repaired with untreated polyglycolic acid implants (group II) were filled with fibrous tissue. Collagen content was significantly increased in group I compared with group II (2.90 +/- 0.80 microg/mg dry weight versus 0.08 +/- 0.11 microg/mg dry weight, p < 0.006), as was the ash weight (0.58 +/- 0.11 mg/mg dry weight versus 0.35 +/- 0.06 mg/mg dry weight, p < 0.015). At 12 weeks there were large amounts of bone in group I, whereas there were scattered islands of bone in groups II and III. Radiodensitometry demonstrated significantly increased radiodensity of the defect sites in group I, compared with groups II and III (0.740 +/- 0.250 OD/mm2 versus 0.404 +/- 0.100 OD/mm2 and 0.266 +/- 0.150 OD/mm2, respectively, p < 0.05). Bromodeoxyuridine label, as detected by immunofluorescence, was identified in the newly formed bone in group I at both 4 and 12 weeks, confirming the contribution of the cultured periosteal cells to this bone formation. This study thus demonstrates a tissue-engineering approach to the repair of bone defects, which may have clinical applications in craniofacial and orthopedic surgery.

Absorptiometry, Photon↗

Corneal epithelial defects following vitrectomy surgery using hand-held, sew-on, and noncontact viewing lenses.

PURPOSE: To compare the incidence of corneal epithelial defects following vitrectomy surgery with Charles hand-held infusion lenses, Landers sew-on lenses, and the Oculus BIOM noncontact lens system. METHODS: We performed a retrospective chart review of 234 patients who underwent initial vitrectomy surgery by one surgeon. We determined the presence and duration of postoperative epithelial defects and identified predisposing factors. RESULTS: There were more corneal epithelial defects noted postoperatively in eyes with hand-held infusion lenses (23.8%) compared with eyes with sew-on lenses (8.6%; P = 0.010) and eyes with noncontact lenses (0%; P < 0.001). There were also more defects in sew-on versus noncontact lenses (P = 0.014). Diabetic patients had more postoperative epithelial defects with hand-held infusion lenses (32.1 %) than with sew-on lenses (8.8%; P = 0.011) or with noncontact lenses (0%; P < 0.001). The average operative time for patients with epithelial defects (169 minutes) was longer than for patients without defects (117 minutes) (P < 0.001). The risk of these defects remained significant after controlling for both length of surgery and diabetes status. CONCLUSIONS: Corneal epithelial defects were more common after vitrectomy surgery using hand-held infusion lenses than after surgery using sew-on lenses and did not occur with the noncontact lens system. In addition, reducing the operative time may independently reduce the risk of epithelial defects, regardless of lens type.

Corneal Diseases↗

Evaluation of a two-stage neural model of glaucomatous defect: an approach to reduce test-retest variability.

PURPOSE: The purpose of this study is to model perimetric defect and variability and identify stimulus conditions that can reduce variability while retaining good ability to detect glaucomatous defects. METHODS: The two-stage neural model of Swanson et al. was extended to explore relations among perimetric defect, response variability, and heterogeneous glaucomatous ganglion cell damage. Predictions of the model were evaluated by testing patients with glaucoma using a standard luminance increment 0.43 degrees in diameter and two innovative stimuli designed to tap cortical mechanisms tuned to low spatial frequencies. The innovative stimuli were a luminance-modulated Gabor stimulus (0.5 c/deg) and circular equiluminant red-green chromatic stimuli whose sizes were close to normal Ricco's areas for the chromatic mechanism. Seventeen patients with glaucoma were each tested twice within a 2-week period. Sensitivities were measured at eight locations at eccentricities from 10 degrees to 21 degrees selected in terms of the retinal nerve fiber bundle patterns. Defect depth and response (test-retest) variability were compared for the innovative stimuli and the standard stimulus. RESULTS: The model predicted that response variability in defective areas would be lower for our innovative stimuli than for the conventional perimetric stimulus with similar defect depths if detection of the chromatic and Gabor stimuli was mediated by spatial mechanisms tuned to low spatial frequencies. Experimental data were consistent with these predictions. Depth of defect was similar for all three stimuli (F = 1.67, p > 0.19). Mean response variability was lower for the chromatic stimulus than for the other stimuli (F = 5.58, p < 0.005) and was lower for the Gabor stimulus than for the standard stimulus in areas with more severe defects (t = 2.68, p < 0.005). Variability increased with defect depth for the standard and Gabor stimuli (p < 0.005) but not for the chromatic stimulus (slope less than zero). CONCLUSIONS: Use of large perimetric stimuli detected by cortical mechanisms tuned to low spatial frequencies can make it possible to lower response variability without comprising the ability to detect glaucomatous defect.

Color Perception↗

Effects of defect configuration, size, and remaining teeth on masticatory function in post-maxillectomy patients.

The aim of this study was to investigate the correlation between the masticatory function and the maxillary defect configuration, size, and remaining teeth in post-maxillectomy patients restored with an obturator prosthesis. Fifty consecutive post-maxillectomy patients (mean age 67.0) participated in this study. The subjects consisted of 26 dentate and 24 edentulous patients. Data were collected from the patients' clinical records, diagnostic casts, and a questionnaire on masticatory function to evaluate the defect configuration, size, and the masticatory function scores associated with wearing obturator prostheses. The defect size was evaluated by the ratio of defect area to the horizontal impression area. The defect configuration was assessed according to Aramany's classification and separated into unilateral and bilateral defects. The multiple regression analysis and the Mann-Whitney U-test (P<0.05) were used to assess statistical significance. The Spearman's correlation coefficient by rank test was also used to detect correlation. The following conclusions were made: (i) The presence of teeth in the maxillary dentition and the different type of the defect configuration had significant correlation with the masticatory function score (r=0.616). (ii) The masticatory function scores of the subjects differed significantly with the presence of teeth in the maxillary dentition and the different types of defect configurations (P=0.005, P=0.002, respectively). (iii) There was significant correlation between the masticatory function score and the size of the defect area in the edentulous group (r=-0.648, P=0.001). The presence of teeth, the size and configuration of the defect influenced the masticatory function of post-maxillectomy patients with obturator prostheses.

Adult↗

Recurrent pregnancy loss as an indicator for increased risk of birth defects: a population-based case-control study.

Stillbirths and spontaneous abortuses have higher rates of birth defects than liveborn infants. The relationship between a woman's previous pregnancy loss and the risk of birth defects in the offspring has not been adequately examined, however. Using data from a population-based case-control study, we assessed whether one or more previous pregnancy loss was associated with increased birth defect risks. Case subjects were 4918 infants with serious births defects diagnosed in the first year of life and ascertained by the Metropolitan Atlanta Congenital Defects Program from 1968 to 1980. Control subjects were 3028 normal liveborn infants frequency-matched to case infants by race, hospital and period of birth. Among case and control infants whose mothers had already had at least one previous pregnancy, reported pregnancy losses (stillbirths and miscarriages) were associated with elevated risks of birth defects (odds ratios for one pregnancy loss of 1.24, two pregnancy losses of 1.49, and three or more pregnancy losses of 1.62, P < 0.0001 for trend). This association held after considering several potential confounders using logistic regression analysis. When specific defects were examined, many exhibited this association, notably hydrocephalus, and some cardiovascular, genital and limb defects. We estimate that the risk of serious birth defects increases from 2.5% for infants of women with no prior pregnancy loss to 4.2% for infants of women with three or more pregnancy losses. This finding has both clinical implications for pregnancy counselling and pathogenetic implications related to birth defect aetiology.

Abortion, Habitual↗

Guided tissue regeneration/deproteinized bovine bone mineral or papilla preservation flaps alone for treatment of intrabony defects. II: radiographic predictors and outcomes.

OBJECTIVES: This study reports the secondary analysis of a randomized-controlled clinical trial designed to assess the efficacy of deproteinized bovine mineral and a collagen membrane in the treatment of intrabony defects. The specific aims of this report are (1) to analyse the radiographic bone changes 1 year after therapy and (2) to assess the association between radiographic defect angle and treatment outcomes. MATERIALS AND METHODS: Baseline and 12-month radiographs were collected from 120 patients with advanced chronic periodontitis from 10 centres in seven countries as part of a multi-centre clinical trial. All patients had at least one intrabony defect > or =3 mm in depth. The treatment consisted of simplified or modified papilla preservation flaps to access the defect. After debridement of the area, a deproteinized bovine mineral and a collagen membrane were applied in the test subjects, and omitted in the controls. Main outcome measures were radiographic bone fill and defect resolution 1 year after surgery. RESULTS: One hundred and twenty pairs of radiographs were obtained, of which 110 pairs were measurable (57 tests and 53 controls). One year after treatment, radiographic resolution of the intrabony component was significantly higher in the test group (3.2+/-1.7 mm) when compared with the controls (1.7+/-1.9 mm). Multivariate analysis indicated that the treatment and the baseline radiographic depth of the intrabony defect significantly influenced the radiographic bone fill of the intrabony defect 1 year following treatment. The percentage of resolution of the defect was influenced by the treatment provided and the baseline plaque score. The baseline radiographic defect angle did not show a significant impact on the clinical and radiographic outcomes. CONCLUSIONS: Regenerative periodontal surgery with a deproteinized bovine bone mineral and a collagen membrane offered additional benefits in terms of radiographic resolution of the intrabony defect and predictability of outcomes with respect to papilla preservation flaps alone.

Alveolar Bone Loss↗

Late defect on delayed contrast-enhanced multi-detector row CT scans in the prediction of SPECT infarct size after reperfused acute myocardial infarction: initial experience.

PURPOSE: To prospectively assess the accuracy of multi-detector row computed tomography (CT) in the prediction of infarct size after successful reperfusion of acute myocardial infarction (MI) by using single photon emission computed tomography (SPECT) images obtained 6 weeks later as the reference standard. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. A total of 34 patients (29 men and five women; mean age, 56 years +/- 13) underwent dual-phase 16-detector row CT within 3 days +/- 3 after successful reperfusion of acute MI. Iodinated contrast medium (1.5 mL per kilogram of body weight) was injected at a flow rate of 3.5 mL/sec. A first arterial phase acquisition was followed 5 minutes later by a late acquisition, without reinjection of contrast medium. A radiologist and a cardiologist used a 17-segment model in a blind analysis of images obtained during late acquisition. For each segment, presence of late defect or late enhancement was recorded. Findings were compared with SPECT studies analyzed by a nuclear medicine physician and a cardiologist 6 weeks after the acute event. CT defects were compared with SPECT defects on a segmental and per-patient basis. Mean number of segments with late defects on multi-detector row CT scans was compared with infarct size on SPECT images by using the t test. RESULTS: All patients had late enhancement in the infarcted myocardium. In 27 of 34 patients, a late defect surrounded by a subepicardial late enhancement was detected. Segments with late defect on CT scans were predictive of residual perfusion defects at 6-week follow-up, with sensitivity of 78%, specificity of 91%, and accuracy of 90%. On a per-patient basis, sensitivity was 93%, specificity was 100%, and accuracy was 94%. Mean number of segments with late defects on multi-detector row CT scans (ie, 3.1 segments) was not significantly different from infarct size on SPECT images (eg, 2.5 segments) (P = .2). CONCLUSION: Late defect on multi-detector row CT scans indicates residual perfusion SPECT defect and infarct size after successfully reperfused MI, with sensitivity of 93%, specificity of 100%, and accuracy of 94%.

Adult↗

Hepatic parenchymal perfusion defects detected with CTAP: imaging-pathologic correlation.

To determine whether characteristics of focal hepatic parenchymal perfusion defects detected with computed tomographic arterial portography (CTAP) correlate with underlying pathologic processes, 245 perfusion defects detected with CTAP in 60 patients who subsequently underwent definitive hepatic surgery were characterized by shape, location within the liver, and relative attenuation value and were prospectively correlated with sectioned pathologic specimens. Of 177 round perfusion defects, 102 (58%) were malignant and 75 (42%) were benign. Only one (2%) of 53 peripheral wedge-shaped defects was malignant. All 15 peripheral flat defects were benign. Defects in characteristic locations anterior to the porta hepatis (n = 15) and adjacent to the intersegmental fissure (n = 7) were uniformly benign. While 83 (56%) of 147 soft-tissue attenuation defects were malignant, only four (6%) of 68 intermediate-attenuation defects were malignant. Although these characteristics of parenchymal perfusion defects aid in differentiation of benign from malignant processes, all other types of perfusion defects are nonspecific and may require biopsy.

Adenoma, Bile Duct↗

A single low dose of RGTA, a new healing agent, hastens wound maturation and enhances bone deposition in rat craniotomy defects.

RGTA, a new family of dextran-derived healing agents, promotes the repair of various tissues, including bone. In this study, we examined whether a dose of RGTA lower than in our previous studies could still modify the healing pattern in craniotomy defects. In 24 rats, two defects (3 mm diameter) were drilled on either side of the calvaria sagittal suture. The right defect was filled with a piece of collagen soaked with RGTA in phosphate-buffered saline (PBS; 4 microg/ml), and the left one with collagen soaked in PBS only. After 7, 14 and 21 days, the calvaria were removed and processed for histometry. On day 7, in contrast with the control defects, the treated sites were inflammation-free and centripetal bone plates had started to grow. By day 14, the bone filling was significantly enhanced in the treated defects (+290%, p<0.05), and isolated bone nodules had formed within the fibrous connective tissue (= fibrous hammock) joining the defect edges. The hammock had already differentiated by day 7 in all the RGTA-treated defects, and it was significantly thicker on days 14 (+190%, p<0.05) and 21 (+139%, p<0.05). The colonization of the hammock by mast cells was increased in the treated sites (+320%, p<0.05 on day 21). On day 7, most of the bony edges of the treated defects had been resorbed by osteoclasts, while the process only started in the controls. These data indicate that a low dose of RGTA modified the cascade of events occurring at the initial stages of repair, so that the tissular maturation of the treated defects was more rapid. In fact the use of RGTA in the wounds provoked a shift from a fibrous repair as seen in the controls, to a bone reconstruction favoring defect closure.

Animals↗