Biomedical subjects

Pieter J Emans

Publications and source records attributed to Pieter J Emans.

8 recordsLinked to original sources

PubMed2006

A novel in vivo model to study endochondral bone formation; HIF-1alpha activation and BMP expression.

Numerous growth and transcription factors have been implicated in endochondral bone formation of the growth plate. Many of these factors are up-regulated during hypoxia and downstream of Hypoxia-Inducible Factor (HIF)-1alpha activation. However, the specific function of these factors, in the context of oxygenation and metabolic adaptation during adult periosteal endochondral bone formation, is largely unknown. Here, we studied HIF-1alpha and the possible roles of (HIF-1alpha related) growth and transcription factors in a recently developed in vivo model for adult periosteal endochondral bone formation. At different phases of periosteal endochondral bone formation, mRNA levels of Transforming Growth Factor (TGF)-beta1, Bone Morphogenetic Proteins (BMP)-2, -4, and -7, Indian Hedgehog (Ihh), Parathyroid Hormone-related Protein (PTHrP), Sox9, Runx2, HIF-1alpha, Vascular Endothelial Growth Factor (VEGF), periostin (POSTN), and Glyceraldehyde-3-Phophate Dehydrogenase (GAPDH) were evaluated with RT-real time-PCR. Also protein levels of TGF-beta1, BMP-2, -4, and -7, HIF-1alpha, and POSTN were examined. During the chondrogenic phase, the expression of Sox9, Ihh, and HIF-1alpha was significantly up-regulated. TGF-beta1 mRNA levels were rather constant, and the mRNA levels of BMPs were significantly lower. Immunohistochemical detection of corresponding gene products, however, revealed the presence of the proteins of TGF-beta1, BMP-2, -4, and -7, HIF-1alpha, and POSTN within the chondrocytes during chondrogenesis. This discrepancy in gene expression between mRNA and protein level for TGF-beta1 and the different BMPs is indicative of post-transcriptional regulation of protein synthesis. HIF-1alpha activation and up-regulation of GAPDH support a hypoxia-induced metabolic shift during periosteal chondrogenesis. Our model recapitulates essential steps in osteochondrogenesis and provides a new experimental system to study and ultimately control tissue regeneration in the adult organism.

Animals↗

PubMed2006

Comparison of two hydroxyapatite-coated femoral stems: clinical, functional, and bone densitometry evaluation of patients randomized to a regular or modified hydroxyapatite-coated stem aimed at proximal fixation.

Clinical function, bone mineral density (BMD), and radiographs of 80 randomly allocated, hydroxyapatite-coated femoral stems of two differing lengths were studied for 2 years. The short stem was optimized for proximal fixation. The predictive value of bone densitometry was also studied. After 2 years, significantly more bone apposition and a higher BMD percentage were observed in Gruen zone 7 of the short stem. We conclude that stem design can be enhanced to achieve more proximal fixation. However, we found a higher incidence of pain with the short stem, indicating a trade-off between increased proximal fixation and diminished overall mechanical stability. No strong correlations between clinical function and radiographic evaluation of remodeling were found with BMD, suggesting that dual-energy x-ray absorptiometry has no predictive value for short-term clinical outcome.

Absorptiometry, Photon↗

PubMed2006

Differential cell viability of chondrocytes and progenitor cells in tissue-engineered constructs following implantation into osteochondral defects.

Animal studies in cartilage tissue engineering usually include the transfer of cultured cells into chondral or osteochondral defects. Immediately at implantation, the cells are exposed to a dramatically changed environment. The aim of this study was to determine the viability of two cell types currently considered for cellular therapies of cartilage defects-chondrocytes and progenitor cells-shortly after exposure to an osteochondral defect in rabbit knees. To that end, autogenic chondrocytes and periosteal cells were labeled with CM-DiI fluorochrome, seeded or cultured in PEGT/PBT scaffolds for periods up to 2 weeks, transferred into osteochondral defects, harvested 5 days postimplantation, and analyzed for cell viability. In order to further elucidate factors effecting cell viability within our model system, we investigated the effect of serum, 2) extracellular matrix surrounding implanted cells, 3) scaffold interconnectivity, and 4) hyaluronan, as a known cell protectant. Controls included scaffolds with devitalized cells and scaffolds analyzed at implantation. We found that the viability of periosteum cells (14%), but not of chondrocytes (65-95%), was significantly decreased after implantation. The addition of hyaluronan increased periostium cell viability to 44% (p < 0.05). Surprisingly, cell viability in less interconnected compression-molded scaffolds was higher compared to that of fully interconnected scaffolds produced by rapid prototyping. All other factors tested did not affect viability significantly. Our data suggest chondrocytes as a suitable cell source for cartilage repair in line with clinical data on several chondrocyte-based therapies. Although we did not test progenitor cells other the periosteum cells, tissue-engineering approaches using such cell types should take cell viability aspects into consideration.

Animals↗

PubMed2006

The Currarino triad: neurosurgical considerations.

OBJECTIVES: The Currarino triad, a relatively uncommon hereditary disorder, is often associated with tethered cord and anterior myelomeningocele. Little is known of the implications of these neuroanatomic malformations or of the neurosurgical attitude. The objective of this study is to identify the spinal cord and meningeal malformations associated with the Currarino triad and to discuss the risks and benefits of surgical intervention. METHODS: We analyzed the spinal cord malformations and the neurosurgical involvement with the Currarino triad by retrospective chart review. RESULTS: The Currarino triad neuroanatomic malformations were identified in five patients. The Currarino triad was associated with a tethered cord in three patients, a myelomeningocele in five patients, a syrinx in two patients, a fistula between the colon and spinal canal in two patients, and an Arnold-Chiari Type 1 malformation in one patient. CONCLUSION: Full spine imaging is required for all patients diagnosed with the Currarino triad. Magnetic resonance imaging of the head should be performed in every patient with neuroanatomic anomalies. Surgery of an anterior myelomeningocele is not necessarily indicated, only in the rare case in which the space-occupying aspect is expected to cause constipation or problems during pregnancy or delivery. Constipation directly after birth is seen in virtually all patients with the triad. Therefore, constipation cannot be used to diagnose a tethered cord syndrome nor indicate tethered cord release. Fistulas between the spinal canal and colon have to be operated on directly.

Abnormalities, Multiple↗

PubMed2005

Development of new injectable bulking agents: biocompatibility of radiopaque polymeric microspheres studied in a mouse model.

Radiopaque polymeric microspheres have a potential as new bulking agents for treatment of stress urinary incontinence (SUI). The advantage over existing bulking agents lies in their X-ray visibility in situ; other polymeric bulking agents (e.g., PTFE or silicone rubbers) are practically radiolucent (i.e., incapable of absorbing X-radiation). Radiopacity is useful in practice because of the high spatial accuracy of X-ray imaging. For instance, X-ray fluoroscopy can be used to assess possible migration of the bulking agent over time or to provide guidance in cases in which a second injection of a bulking agent is necessary (repeated treatment of SUI). Biocompatibility of injected radiopaque microspheres was investigated in vivo by using the mouse as a model. Microspheres were injected subcutaneously (9 animals) or intramuscularly (9 animals), and follow-up was 8 days or 3 months. X-ray fluoroscopy gave clear images of the microspheres as an ensemble, and it was found that no migration occurred during 3 months. Histopathology confirmed that all microspheres stayed close to the site of the injection. The microspheres appeared to be well tolerated; only a few giant cells, manifesting a mild inflammatory reaction, were encountered. At 3 months, capillary blood vessels were observed throughout the microsphere beds, and macrophages and fibroblast cells were seen in between the microspheres. This is encouraging with respect to the intended application, although it must be acknowledged that the data refer merely to a mouse model. Further experiments with larger, more representative models (rabbit and goat) are in progress.

Animals↗

PubMed2005

The Currarino triad: the variable expression.

BACKGROUND: The Currarino triad is a relatively unknown hereditary disorder linked to the 7q36 region and characterized by an anorectal malformation, sacrococcygeal defect, and a presacral mass. PURPOSE: The aim of the study was to report the highly variable expression in patients with the Currarino triad and provide a guideline for the clinician if the Currarino triad is suspected. METHODS: We examined the symptoms and associated anomalies in 5 families with the Currarino triad by retrospective chart review. RESULTS: Fifteen patients had Currarino-associated anomalies. This included anorectal malformation in 9, a presacral mass in 9, and a sacral bone defect in 15. Tethered cord was present in 4 patients. There were 12 symptomatic patients. Constipation was diagnosed in all of them. Other symptoms included recurrent urinary tract infections caused by bladder dysfunction in 5, abnormal gait in 1, and another patient who initially presented with meningitis. Two carriers of the genetic defect had no symptoms or anomalies. CONCLUSIONS: The phenotypical expression of the gene mutations causing the Currarino triad can vary from asymptomatic to patients presenting with the complete triad. Presence of a crescent-shaped defect of the sacral bone may be used as initial screening method. As the penetration of the genetic defect is variable, DNA screening is the only method to fully exclude the triad.

Abnormalities, Multiple↗

PubMedDate not supplied

Repair of osteochondral defects in rabbits with ectopically produced cartilage.

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

Animals↗

PubMedDate not supplied

In vivo generation of cartilage from periosteum.

Periosteum has chondrogenic and osteogenic potential and plays an important role in fracture healing. The purpose of this study was to evaluate the reactive tissue formed after damaging the periosteum. Damaging the periosteum may be a way to generate ectopic cartilage or bone, which may be useful for the repair of articular cartilage and bone defects. Periosteum was bilaterally dissected from the proximal medial tibia of New Zealand White rabbits. Reactive periosteal tissue was harvested 10, 20, and 40 days postsurgery and analyzed for expression of collagen types I, II, and X, aggrecan, osteopontin, and osteonectin (by reverse transcription-polymerase chain reaction) and collagen types I and II (by immunohistochemistry). Reactive tissue was present in 93% of cases. Histologically, this tissue consisted of hyaline cartilage at follow-up days 10 and 20. Expression of collagen type II and aggrecan was present at 10 and 20 days postsurgery. Highest expression was at 10 days. Expression of collagen type X increased up to 20 days. No significant changes in the mRNA expression of osteopontin or osteonectin were observed. Immunohistochemistry confirmed the presence of cartilage, which was positive for collagen types I and II at 10 days and only for collagen type II at 20 days. At 20 days postsurgery the onset of bone formation was also observed. At 40 days postsurgery, the reactive tissue had almost completely turned into bone. The quality and amount of cartilage formed 10 days postsurgery make this technique potentially useful to fill large cartilage and bone defects. Also, periosteal callus formation, providing possible useful information for tissue engineering techniques, can be studied with this model.

Animals↗