Biomedical subjects

Frederic Shapiro

Publications and source records attributed to Frederic Shapiro.

13 recordsLinked to original sources

PubMed2007

Early ischemia in growing piglet skeleton: MR diffusion and perfusion imaging.

PURPOSE: To determine whether diffusion changes with ischemia of increasing duration, whether diffusion magnetic resonance (MR) imaging provides different information than does gadolinium-enhanced imaging, and which structural and/or biochemical changes are potentially responsible for any changes in diffusion. MATERIALS AND METHODS: Ischemia was surgically induced in one hip of each piglet (n=8) after approval from the Subcommittee on Research Animal Care; the other hip served as a control. Piglets were imaged at approximately 48 hours and 1, 2, 4, and 8 weeks after surgery at 1.5 T by using line-scan diffusion and dynamic gadolinium-enhanced MR imaging. Apparent diffusion coefficients (ADCs) and enhancement ratios (ERs) were calculated. Significant differences in ADC and ER values over time were evaluated by using the Student t test (P<.05). At 8 weeks, piglets were sacrificed for histologic evaluation. RESULTS: MR images of ischemic hips showed essentially no flow 48 hours after surgery. Spontaneous partial reperfusion was observed 1-4 weeks after surgery (ischemic ER/control ER=66%+/-35 [standard deviation]), and the ER of the ischemic hips was well above that of the control hips at 8 weeks. The ADC of ischemic hips was elevated above that of control hips before reperfusion 1 week after surgery by 47%+/-12 and remained elevated despite flow restoration. Gross structural abnormalities on MR images appeared to coincide with reperfusion. Histologic findings revealed abnormal epiphyseal cartilage thickening, cartilaginous islands within ossified tissue, and less fatty marrow in ischemic hips than in control hips; all of these factors could explain elevated ADC. CONCLUSION: Diffusion is sensitive to early ischemia and follows a different time course than that of changes observed with gadolinium enhancement. ADC remained elevated in this model of severe, prolonged ischemia despite the spontaneous partial restoration of blood flow seen on gadolinium-enhanced images.

Animals↗

PubMed2006

Gadolinium-enhanced MR images of the growing piglet skeleton: ionic versus nonionic contrast agent.

PURPOSE: To determine whether there are differences in the distribution of ionic and nonionic gadolinium-based contrast agents by evaluating contrast enhancement of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis in the knees of normal piglets. MATERIALS AND METHODS: Following approval from the Subcommittee on Research Animal Care, knees of 12 3-week-old piglets were imaged at 3-T magnetic resonance (MR) imaging after intravenous injection of gadoteridol (nonionic contrast agent; n = 6) or gadopentetate dimeglumine (ionic contrast agent; n = 6). Early enhancement evaluation with gradient-echo MR imaging was quantified and compared (Student t test) by means of enhancement ratios. Distribution of contrast material was assessed and compared (Student t test) by means of T1 measurements obtained before and at three 15-minute intervals after contrast agent administration. The relative visibility of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis was qualitatively assessed by two observers and compared (Wilcoxon signed rank test). Differences in matrix content and cellularity that might explain the imaging findings were studied at histologic evaluation. RESULTS: Enhancement ratios were significantly higher for gadoteridol than for gadopentetate dimeglumine in the physis, epiphyseal cartilage, and secondary ossification center (P < .05). After contrast agent administration, T1 values decreased sharply for both agents-but more so for gadoteridol. Additionally, there was less variability in T1 values across structures with this contrast agent. Gadoteridol resulted in greater visibility of the physis, while gadopentetate dimeglumine resulted in greater contrast between the physis and metaphysis (P < .05). CONCLUSION: The results suggest different roles for the two gadolinium-based contrast agents: The nonionic contrast medium is better suited for evaluating perfusion and anatomic definition in the immature skeleton, while the ionic contrast medium is better for evaluating cartilage fixed-charge density.

Animals↗

PubMed2005

Hydrogel-beta-TCP scaffolds and stem cells for tissue engineering bone.

Trabecular bone is a material of choice for reconstruction after trauma and tumor resection and for correction of congenital defects. Autologous bone grafts are available in limited shapes and sizes; significant donor site morbidity is another major disadvantage to this approach. To overcome these limitations, we used a tissue engineering approach to create bone replacements in vitro, combining bone-marrow-derived differentiated mesenchymal stem cells (MSCs) suspended in hydrogels and 3-dimensionally printed (3DP) porous scaffolds made of beta-tricalcium-phosphate (beta-TCP). The scaffolds provided support for the formation of bone tissue in collagen I, fibrin, alginate, and pluronic F127 hydrogels during culturing in oscillating and rotating dynamic conditions. Histological evaluation including toluidine blue, alkaline phosphatase, and von Kossa staining was done at 1, 2, 4, and 6 weeks. Radiographic evaluation and high-resolution volumetric CT (VCT) scanning, expression of bone-specific genes and biomechanical compression testing were performed at 6 weeks. Both culture conditions resulted in similar bone tissue formation. Histologically collagen I and fibrin hydrogels specimens had superior bone tissue, although radiopacities were detected only in collagen I samples. VCT scan revealed density values in all but the Pluronic F127 samples, with Houndsfield unit values comparable to native bone in collagen I and fibrin glue samples. Expression of bone-specific genes was significantly higher in the collagen I samples. Pluronic F127 hydrogel did not support formation of bone tissue. All samples cultured in dynamic oscillating conditions had slightly higher mechanical strength than under rotating conditions. Bone tissue can be successfully formed in vitro using constructs comprised of collagen I hydrogel, MSCs, and porous beta-TCP scaffolds.

Alginates↗

PubMed2005

Tranexamic acid reduces intraoperative blood loss in pediatric patients undergoing scoliosis surgery.

BACKGROUND: Excessive bleeding often occurs during pediatric scoliosis surgery and is attributed to numerous factors, including accelerated fibrinolysis. The authors hypothesized that administration of tranexamic acid would reduce bleeding and transfusion requirements during scoliosis surgery. METHODS: Forty-four patients scheduled to undergo elective spinal fusion were randomly assigned to receive either 100 mg/kg tranexamic acid before incision followed by an infusion of 10 mg . kg . h during surgery (tranexamic acid group) or 0.9% saline (placebo group). General anesthesia was administered according to a standard protocol. Blood loss, transfusion requirements, coagulation parameters, and complications were assessed. RESULTS: In the tranexamic acid group, blood loss was reduced by 41% compared with placebo (1,230 +/- 535 vs. 2,085 +/- 1,188 ml; P < 0.01). The amount of blood transfused did not differ between groups (615 +/- 460 vs. 940 +/- 718 ml; P = 0.08). Administration of tranexamic acid was a multivariate predictor of blood loss, as was American Society of Anesthesiologists physical status and preoperative platelet count. No apparent adverse drug effects occurred in any patient. CONCLUSION: Intraoperative administration of tranexamic acid significantly reduces blood loss during spinal surgery in children with scoliosis.

Adolescent↗

PubMed2005

Association of Duchenne muscular dystrophy with autism spectrum disorder.

We hypothesize that Duchenne muscular dystrophy and autism spectrum disorder/pervasive developmental disorder co-occur with a greater than random frequency. In this study, we set out to reject the hypothesis that Duchenne muscular dystrophy and autism spectrum disorder/pervasive developmental disorder co-occur no more often than expected by chance. Two index cases and six additional boys with concomitant Duchenne muscular dystrophy and autism spectrum disorder were identified in a muscular dystrophy clinic that approximates the total number of Duchenne muscular dystrophy boys (158) in the state of Massachusetts. The rate of prevalence (6 of 158) was compared with the prevalence rate of autism spectrum disorder in boys in the general population (1.6 in 1,000). We rejected the hypothesis that Duchenne muscular dystrophy and autism spectrum disorder co-occurrence was likely to be explained by chance (P = .006). We identify a previously unrecognized association of Duchenne muscular dystrophy with autism spectrum disorder. Further work might elucidate the level of association between these two conditions, either at the genetic or at the protein level, and might clarify, at least partially, the neurobiologic mechanisms associated with autism spectrum disorder.

Autistic Disorder↗

PubMed2005

Scapulothoracic fusion for facioscapulohumeral muscular dystrophy.

BACKGROUND: Facioscapulohumeral muscular dystrophy causes winging of the scapula and weakness and discomfort of the shoulder. Surgical stabilization of the scapula to the posterior part of the chest wall permits shoulder abduction and flexion by the deltoid muscle. In the present retrospective study, we describe our experience with eleven scapulothoracic fusion procedures that were performed for the treatment of the infantile and adolescent forms of the disease. METHODS: Eleven procedures were performed in eight patients, including four male patients (one of whom had bilateral involvement and three of whom had unilateral involvement) and four female patients (two of whom had bilateral involvement and two of whom had unilateral involvement). One of the female patients had the infantile variant, whereas all other patients had the adolescent form of the disease. The mean age at the time of the eleven operations was seventeen years. The scapula was fused to the thorax in 25 degrees of abduction with use of 16-gauge wires, a plate or washers on the posteromedial scapular surface to prevent wire pull-out, and iliac crest autograft. After a mean duration of follow-up of 6.3 years, all patients were assessed clinically and radiographically. RESULTS: In all cases, scapular winging and shoulder fatigue and pain were initially eliminated. In the first year after the operation, active abduction and flexion of the shoulder improved to a mean of 145 degrees (range, 110 degrees to 160 degrees ) and 144 degrees (range, 130 degrees to 160 degrees ), respectively, from a preoperative mean of 75 degrees (range, 70 degrees to 90 degrees ). At the time of the final assessment (mean, 6.3 years postoperatively), abduction and flexion were maintained at a mean of 139 degrees and 134 degrees , respectively, in seven shoulders; however, in the remaining four shoulders, both of these motions had decreased to a mean of 48 degrees because of progressive loss of deltoid muscle strength. In two cases, prominent subcutaneous wires required trimming. There were no other complications. CONCLUSIONS: Scapulothoracic fusion relieves shoulder fatigue and pain, allows for smooth functional abduction and flexion of the upper extremity, and improves the appearance of the neck and shoulder in patients who have symptomatic scapular winging due to facioscapulohumeral muscular dystrophy. The procedure is associated with a low risk of complications. Progression of the disease affecting the deltoid muscle can cause loss of abduction, but the other benefits of stabilization persist. LEVEL OF EVIDENCE: Therapeutic Level IV.

Adolescent↗

PubMed2005

Bone development: interaction of molecular components and biophysical forces.

A deeper understanding of skeletal development comes from knowledge of the molecular components, cell and tissue structure, and biophysical and vascular mechanisms underlying physiologic function. Endochondral and intramembranous bone formation mechanisms are active during long bone synthesis. Most endochondral growth in length occurs at the physes by the coordinated actions of cell proliferation, matrix synthesis, and chondrocyte hypertrophy. Several intrinsic molecules act to modulate physeal structure and function whereas extrinsic molecules, such as hormones, provide systemic regulation of growth. Biophysical forces develop intrinsically within the growing bone, serving to enlarge it in three dimensions, while extrinsic forces resist and channel expansion into normal recognizable and functional forms. Newer imaging modalities, such as magnetic resonance imaging, are highly effective in assessing epiphyseal vascularity and differentiating fibrous, cartilaginous, mineralized and osseous tissues in prenatal and postnatal developing bone. This study illustrates the interplay between the molecular and biophysical aspects of normal bone growth, shows ways in which altered development leads to abnormal structures, and provides examples where biologic and biophysical interventions can affect bone development in favorable ways.

Biomechanical Phenomena↗

PubMed2004

Skeletal development in fetal pig specimens: MR imaging of femur with histologic comparison.

PURPOSE: To evaluate the magnetic resonance (MR) imaging features of the developing femur in fetal pig specimens. MATERIALS AND METHODS: MR images of 15 fetal pig femurs, which were categorized into three groups of specimens representing each third of the gestational period, were used to compare increasing femoral length (as an indication of gestational age) with epiphyseal growth in multiple dimensions by using Pearson product moment correlation. Physeal-epiphyseal demarcation, visibility of the secondary ossification center and its physis, prominence of the perichondrial structures (ie, groove of Ranvier and bone bark), metaphyseal undulation, and corticomedullary differences were evaluated qualitatively. These features were also evaluated on histologic sections. RESULTS: With femoral length measurements used as indications of gestational age, there were three, five, and seven fetal pig specimens in each gestation group. During fetal development, the cartilaginous epiphysis of the distal femur transformed from an oval to a bicondylar structure, with most of the growth occurring sagittally (P < .001). Physeal-epiphyseal demarcation, visibility of the secondary ossification center and its physis, and metaphyseal undulation increased later in gestation. Detection of perichondrial structures, however, was greatest during the middle third of gestation and decreased thereafter. During the fetal period, the perichondrial groove of Ranvier and the bone bark were easily identifiable at MR imaging. Marrow cavitation increased with gestation. CONCLUSION: MR imaging depicts fetal pig skeletal features that can be confirmed histologically and that may prove to be useful at human prenatal skeletal imaging.

Animals↗

PubMed2004

Blood loss in pediatric spine surgery.

This article reviews the extent of blood loss in spine surgery for scoliosis corrections in the pediatric age group. An extensive literature review presents blood loss values in surgery for adolescent idiopathic scoliosis, cerebral palsy, Duchenne muscular dystrophy, spinal muscular atrophy, and myelomeningocoele. The underlying disorder plays a major role in determining the extent of blood loss. Blood loss is considerably higher in those patients with a neuromuscular scoliosis compared with adolescent idiopathic scoliosis. Within the neuromuscular group those with Duchenne muscular dystrophy demonstrate the highest mean levels of blood loss. Blood loss is also shown to be progressively greater with increasing numbers of vertebral levels incorporated into the fusion, with posterior fusions compared to anterior fusions, and in those patients having both anterior and posterior fusions.

Adolescent↗

PubMed2004

Age-related vascular changes in the epiphysis, physis, and metaphysis: normal findings on gadolinium-enhanced MRI of piglets.

OBJECTIVE: We sought to study the normal enhancement patterns seen on MRIs of the epiphysis, physis, and metaphysis and age-related vascular changes in piglets using gadoteridol, a nonionic gadolinium chelate. MATERIALS AND METHODS: We quantitatively and qualitatively analyzed the normal changes on sequential T1-weighted images after the IV administration of gadoteridol. In an investigation approved by the research animal care committee at our hospital, we studied the proximal and distal femurs of 26 piglets 1-6 weeks old and correlated the enhanced images with findings on intermediate-weighted, T2-weighted, and gradient-recalled echo images and at histologic examination. RESULTS: We observed early enhancement of the epiphyseal vascular canals, the main physis, the physis of the secondary ossification center, and a metaphyseal band adjacent to the physis. Enhancement of the epiphyseal and metaphyseal marrow and of the epiphyseal cartilage was slower. In the epiphyseal cartilage, we saw three phases of enhancement: vascular, canalicular, and cartilaginous. As the piglets matured, enhancement of the epiphyseal cartilage decreased, and the epiphyseal vascular canals were less conspicuous. Physeal enhancement was greatest during the first week of life, declined at 3 weeks, and subsequently increased again as the physis came to lie adjacent to a larger segment of the epiphyseal ossification center. CONCLUSION: Gadoteridol-enhanced MRIs showed multiple cartilaginous and vascular structures of the growing skeleton. With maturity and progressive epiphyseal ossification, epiphyseal cartilage enhancement decreased, and physeal cartilage enhancement increased.

Aging↗

PubMed2003

Normal and ischemic epiphysis of the femur: diffusion MR imaging study in piglets.

PURPOSE: To evaluate normal diffusion characteristics in the femur in piglets and changes in diffusion with increasing duration of femoral head ischemia. MATERIALS AND METHODS: Normal epiphyses, physes, and metaphyses of piglets were evaluated with line-scan diffusion imaging (n = 12) and diffusion-tensor imaging (n = 4). Apparent diffusion coefficient (ADC) differences between normal proximal and distal femoral structures, epiphyseal and physeal cartilage, and epiphyseal and metaphyseal marrow were compared (Mann-Whitney test). Short-term femoral ischemia was investigated after maximal abduction of the hips for 3 hours (n = 6); ADCs before and after abduction were compared (Wilcoxon signed rank test). Prolonged ischemia was investigated with placement of a ligature around the neck of a femur (n = 7); the ADC of the femur in this condition was compared (Wilcoxon signed rank test) with that of the normal contralateral femur. Changes in ADC ratios at three durations of ischemia (Kruskal-Wallis test) were compared. RESULTS: ADC was greater in epiphyseal cartilage (mean +/- 1 SD, 1.62 x 10(-3) mm2/sec +/- 0.38) than it was in physeal cartilage (1.28 x 10(-3) mm2/sec +/- 0.31) (P <.007) and greater in epiphyseal marrow (1.26 x 10(-3) mm2/sec +/- 0.38) than it was in metaphyseal marrow (0.91 x 10(-3) mm2/sec +/- 0.35) (P <.001). There was columnar arrangement of tensors in the physis. ADC decreased 26% after 3 hours of maximal abduction. After femoral neck ligature, ADC increased a mean of 27% after 6 hours and a mean of 75% after 96 hours. CONCLUSION: Normal line-scan diffusion imaging findings indicate relative restriction of diffusion in the metaphysis and parallel orientation of tensors in the physis. Diffusion is initially restricted with decreased blood flow but increases if ischemia lasts longer.

Animals↗

PubMed2002

Structural stages in the development of the long bones and epiphyses: a study in the New Zealand white rabbit.

BACKGROUND: Histologic delineation of the events involved in the development of long bones and the developmental age at which these events occur is needed to elucidate the genetic and molecular mechanisms associated with these events. This report describes the sequence of histologic events involved in the formation of long bones and their epiphyses in the New Zealand White rabbit. METHODS: Prenatal studies were performed on twelve, fourteen, fifteen, sixteen, eighteen, twenty-one, twenty-four, and twenty-seven-day-old rabbit embryos, and postnatal studies were performed on newborn rabbits and on three-to-four-day-old; one, two, four, and six-week-old; and two, three, four, six, and eight-month-old rabbits. Histologic specimens from embryos were embedded in plastic and stained with toluidine blue or safranin O-fast green, and specimens from postnatal rabbits were embedded in paraffin and stained with hematoxylin and eosin or safranin O-fast green. RESULTS: Studies of twelve-day-old embryos demonstrated upper and lower limb buds filled with undifferentiated mesenchymal cells, and studies of fourteen-day-old embryos showed mesenchymal condensation and beginning cartilage formation outlining major long bones. Long-bone and epiphyseal development progressed through sixteen structural stages, and the developmental age at which these stages occurred was determined. These stages included limb-bud formation with uniform distribution of mesenchymal cells and formation of an apical ectodermal ridge (stage 1); mesenchymal condensation (stage 2); cartilage differentiation (stage 3); formation of a primary center of ossification (stage 4a); epiphyseal cartilage vascularization with formation of cartilage canals (stage 7); vascular invasion of the developing secondary ossification center (stage 9); bone formation and marrow cavitation in the secondary ossification center with formation of hematopoietic marrow (stage 10); fullest relative extent of secondary-ossification-center development in epiphyseal cartilage (stage 14); thinning of the physis (stage 15); and resorption of the physis with establishment of continuity between epiphyseal and metaphyseal circulations (stage 16).

Animals↗

PubMedDate not supplied

Rough endoplasmic reticulum abnormalities in a patient with spondyloepimetaphyseal dysplasia with scoliosis, joint laxity, and finger deformities.

Iliac crest growth cartilage biopsy in spondyloepimetaphyseal dysplasia (SEMD) showed an endoplasmic reticulum storage disorder of epiphyseal and physeal chondrocytes. Biochemical analyses of iliac crest cartilage extracellular matrix showed no signs of deficits in any of the structural collagens types II, IX, or XI. The physis was abnormal by light microscopy with chondrocyte columnation replaced by clone-like cell accumulations surrounded by widened acellular cartilage septae. The rough endoplasmic reticulum (RER) of most chondrocytes was dilated. In some cells the RER contained homogeneous material but in most there were abnormal electron-dense accumulations. In some the material was seen in small amounts adjacent to the edge of the RER. In others, increasingly large amounts were seen that were randomly oriented and diffusely marginated. In many cells, assembly had progressed to well-marginated collections of wavy rod-like structures with a circular orientation parallel to the outer edges of the RER. The electron-dense accumulations measured from 34 to 40 nm in diameter. Mutations have prevented normal processing of collagen such that exit from the RER is abnormally slowed and abnormal self-assembly occurs within the dilated cisternae.

Cartilage↗