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PubMed1996

Role of donor-specific cytotoxic T cells in rejection of corneal allografts in normal and high-risk eyes.

Clinical ophthalmologists are highly successful in grafting allogeneic corneas onto healthy eye graft beds--only a small percentage are rejected. By contrast, a high percentage of allografts are rejected when grafted into vascularized or '"high-risk' recipient eyes. The following experiments test the hypothesis that donor-specific cytotoxic T cells mediate graft rejection in high-risk, but not normal, eyes. MHC plus minor histoincompatible C57BL/6 corneas were grafted orthotopically onto BALB/c mice. Healthy recipient eyes were trephined and served as normal graft beds; corneal vascularization was induced by penetrating sutures and these eyes served as 'high-risk' graft beds. Cytotoxic T cells were assayed at 2 and 8 weeks postgrafting using either draining cervical lymph nodes or spleen cells restimulated for 3 days with irradiated allogeneic splenic stimulator cells. As a positive control, donor-specific cytotoxic T cells were induced in mice immunized by subcutaneous injection of allogeneic spleen cells. A low percentage (only 50%) of corneal allografts were rejected when placed orthotopically onto normal healthy eyes. Donor-specific cytotoxic cells were not detected in the draining lymph nodes or spleens of mice that either accepted, or rejected their corneal graft. The failure to detect cytotoxic T cells was not due to anergy or the deletion of allospecific precursors of cytotoxic T cells. By contrast, 97% of corneal allografts were rejected from high-risk recipient eyes (no immune privilege). Donor-specific cytotoxic T cells were routinely detected in the draining lymph nodes of these mice and their appearance coincided with graft rejection. We conclude that allografts placed onto normal healthy eyes fail to induce donor-specific cytotoxic T cells. In the absence of specific cytotoxic T cells, other alloimmune effectors are less successful at mediating rejection. By contrast, allografts placed onto high-risk eyes induce donor-specific cytotoxic T cells, and all grafts are universally rejected. These results imply that immune privilege can protect corneal allografts from most effector mechanisms, except cytotoxic T cells.

Animals↗
PubMed1990

Regeneration of cranial suture and bone plate lesions in rabbits. Implications for positioning of osteotomies.

The positioning of osteotomies in intramembranous cranial bone was studied by exploring the pattern of bone regeneration in growth areas (the sutural region) as compared to that of the bone plate proper. Trephine defects in the left coronal suture area and the right parietal bone were produced in fifty-nine young rabbits. A pilot study to refine operative and analytical methods comprised 22 animals. The experiments were terminated at one, three, and six weeks after surgery. The bone regenerative response was assessed by x-ray planimetry, plain microscopy, enzyme histochemistry, and fluorescent labelling. Only minor divergences in healing capacity between the two defects were found. No adverse effects on the growth process were indicated. As to clinical management, the findings suggest that osteotomies designed to traverse sutural areas will, under normal circumstances, regenerate in a similar manner and rate to adjoining bone plates.

Acid Phosphatase↗
PubMedDate not supplied

Guided bone regeneration of cranial defects, using biodegradable barriers: an experimental pilot study in the rabbit.

The aim of this study was to test if a biodegradable barrier could be used to achieve proper bone healing of full-thickness trephine skull defects, applying the biological principle of guided tissue regeneration (GTR). Two New Zealand white rabbits were used. In each animal, 2 circular through-and-through bone defects with a diameter of 8 mm were created in the midline of the frontal and parietal bones of the calvarium. One defect was covered with the mucoperiosteal flaps without placement of an intervening membrane barrier (control). One test defect (test 1) was covered by a biodegradable, non-porous polylactic acid membrane on the outer (supra-calvarial) side of the defect, and 2 test defects (tests 2 and 3) were covered by similar membranes on both the outer and the inner aspects of the defects, prior to flap closure. 6 weeks postsurgically, the animals were sacrificed and the defect areas including surrounding tissues were harvested for histological preparation. The control defect was essentially occupied by supra-calvarial soft tissue, located in direct contact with the dural tissue. In the test cavities, there was a continuous bridge of regenerated bone extending from one edge of the defect to the other, although in test 1 not attaining the same thickness as the bone bordering the defect. In the 2 other test defects, the regenerated bone had reached a thickness almost corresponding to that of the surrounding bone. The bone regeneration was achieved without recourse to adjunctive bone graft materials.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Comparison of regenerative capacity elicited by demineralized bone matrix of different embryonic origins.

In the cranio-maxillo-facial field, extensive research has been conducted to find substitutes for autogeneic bone as a grafting material. The present study examined the effect of demineralized allogeneic bone material of membranous and enchondral origin compared with autogenous bone chips on the healing response in rabbit skull defects. The demineralized bone matrix (DBM) was bioassayed in a critical-size defect rat model. Four trephined calvarial defects were created in each of 14 adult rabbits and the experimental materials implanted into three defects leaving the fourth defect empty for control purposes. The results were assessed by light microscopy and contact radiography after periods of 4 and 15 weeks. The DBM of both origins displayed extensive osteoinductive capacity and early bone production significantly exceeded that of the two control groups. The embryological origin implied minor effects on the initial regenerative response and bone marrow redevelopment. The clinical significance of these findings is discussed.

Animals↗
PubMed2003

Primary extramedullary plasmacytoma of the esophagus.

An uncommon manifestation of plasma cell neoplasia occurs outside the bone marrow and is designated "extramedullary plasmacytoma." These are usually encountered in mucosal sites of the head and neck region. The gastrointestinal tract may be secondarily involved in multiple myeloma or be the site of primary extramedullary plasmacytomas (PEMPs). The esophagus is the least common site of gastrointestinal PEMP. A 58-year-old man presented with dysphagia for solids over a period of 2 months. Otherwise, he was well and systemic examination did not reveal anything of note. After a nondiagnostic biopsy, the patient was subjected to esophago-gastrectomy. Gross examination of the esophagus revealed a large polypoid tumor. Histologically, it was composed of mature plasma cells, plasmablasts (some of which appeared anaplastic), and a minor admixture of lymphoid cells. Focally, the infiltrate permeated the squamous epithelium simulating lymphoepithelial lesions. The neoplastic cells were positive for epithelial membrane antigen, CD79a, IgG, and kappa, while the lymphoid cells were predominantly B cells. The patient did not have a monoclonal gammopathy. Skeletal x-rays and bone trephine examination were both normal. PEMP is biologically and prognostically different to other plasma cell neoplasms. Although rare, esophageal PEMP should be considered in the differential diagnosis of so-called undifferentiated malignant tumors of the esophagus.

Biomarkers, Tumor↗
PubMed2006

Metastatic meningioma to the eleventh dorsal vertebral body: total en bloc spondylectomy. Case report and review of the literature.

INTRODUCTION: One in every thousand intracranial meningiomas metastatize extracranially. Lung and intraabdominal organs are most frequently affected. Only 7% involve vertebrae and just a dozen cases have been reported in the literature. To our knowledge, this is the first description of a total en bloc spondylectomy through a posterior approach for the treatment of an intraosseous metastatic meningioma to the eleventh dorsal vertebra. CASE REPORT: In March 1996, a 37 year-old male underwent surgical resection for a left occipital intraventricular benign meningioma (WHO I). He was reoperated in February 2002 due to local recurrence. By the end on 2003 he developed progressively invalidating dorsolumbar pain. MRI studies revealed a T11 intraosseous mass. In March 2004, a percutaneous biopsy and vertebroplasty were performed. The pathological specimen was identified as adenocarcinoma and he initiated chemotherapy. Advice from a second pathologist was seeked, who suggested the diagnosis of intraosseous meningioma. Workup studies failed to reveal any primary tumor. In May 2004 the patient was admitted to our department and a new transpedicular biopsy confirmed the diagnosis. In June 2004 he underwent T11 total en bloc spondylectomy (Tomita's procedure), fusion with bone and calcium substitute-filled stackable carbon-fiber cages, and T9 to L1 transpedicular screw fixation. No postoperative complications ocurred and he is, so far, free from primary and secondary disease. Definite pathology: benign meningioma (WHO I). DISCUSSION: Distant metastases from intracranial meningiomas are rare entities, arising from benign lesions in, at least, 60% of cases. Enam et al proposed a specific pathological score to differentiate benign, atypic and malignant meningiomas. Such score correlates with the chance of metastatizing: more than 40% in malignant meningiomas compared to 3.8% of brain tumors overall. The ability to metastatize seems to be linked to vascular or lifatic invasiveness. Metastases ocurr more frequently in angioblastic, papillary and meningothelial variants. Hematogenous (especially venous; Batson's perivertebral plexus), linfatic and cerebrospinal fluid are the main routes involved in the spreading of the tumor. Craniotomy itself may also play a role, for the majority of patients have been previously operated on repeatedly. The interval between the onset of the intracranial disease and the appearance of the metastasis varies from months to many years. The value of transpedicular biopsy is widely recognized (efficacy over 80%) and the suitability of the specimen for pathological examination improves when wide inner caliber trephines are used. In the case presented we applied the oncologic concept of vertebral en bloc resection. We believe this case represents a paradigmatic indication of this technique because it respects the concepts of radical resection and spinal stability, and offers an opportunity for the curation of the disease.

Adult↗
PubMed1989

Diagnosis of frontal sinusitis: one-dimensional ultrasonography versus radiography.

In a series of 407 patients suffering from acute frontal sinusitis, 159 sinuses of 134 patients were trephined. Initial radiography of the operated sinuses pointed out a slight tendency to overdiagnosis; 19 (12 per cent) of the 157 sinuses with positive radiographic signs did not yield secretion. Radiography missed only two true cases of fluid retention. Accuracy of diagnosis by radiography was 87 per cent. Initial ultrasonography gave a sign of retained secretion in 127 cases, of which 122 (96 per cent) were true positive. However, 18 (13 per cent) tracings of the 140 sinuses with secretion gave wrong negative findings. Accuracy of diagnosis by ultrasonography was 86 per cent. It seems evident, that ultrasonography measures better retained secretion (excluding very small amounts) and radiography shows better mucosal swellings.

Adult↗
PubMedDate not supplied

Calbindin D-28K immunoreactivity of human cone cells varies with retinal position.

Calbindin D-28K is a calcium-binding protein found in the cone but not rod photoreceptor cells in the retinas of a variety of species. Recent studies of the monkey retina indicated that calbindin D-28K may be expressed preferentially in non-foveal regions of the retina. In the current studies of human retinas, immunohistochemical experiments demonstrated that calbindin D-28K is reduced or absent in the fovea and parafovea, but prevalent in the perifovea and periphery. These findings were supported by the quantification of calbindin D-28K in 1-mm trephine punches obtained from different regions of the human retina. The specificity of the anti-calbindin D-28K antibodies used in these studies was confirmed by Western blot analysis using purified calbindin D-28K. The protein was purified from retinal tissue and its identity confirmed by partial amino-acid sequence analysis. The expression of calbindin D-28K did not correlate with the spectral properties of the cones, rather to their position in the retina. The study of spatially expressed genes, like the one encoding calbindin D-28K, may help explain the patterns of retinal degeneration seen in some human cone-rod dystrophies.

Aged↗
PubMed2001

Demineralized Bone Matrix-stimulated Bone Regeneration in Rats Enhanced by an Angiogenic Dipeptide Derivate.

A lysyl-proline derivate (LP) known to stimulate angiogenesis and formation of granulation tissue was tested as a local additive to allogeneic demineralized bone matrix (DBM) using a rat craniotomy model. Peracetic-acid sterilized DBM (10 mg/defect) was implanted into three groups of 45 animals each with 0, 6 and 20 microg LP. Subsequent evaluation was done by descriptive histology, histomorphometry, and determination of the calcium content of the explants 7, 14, 28, 42 and 84 days post-implantation. Grafting with DBM alone resulted in defect bridging by newly formed bone with incorporated DBM residues on day 84. Addition of LP to the implants caused an enhanced capillarization on day 14 and 28 as well as an enhanced mineralization on day 14, 28, 42 and 84. Both effects were dose-dependent. These data suggest that the local application of a synthetic angiogenic factor significantly improve bone regeneration in DBM-grafted trephine defects in rats. Thereby, they reinforce the opinion that early angiogenesis is crucial for a number of subsequent events in the bone regeneration process.

Journal Article↗
PubMed1997

Biomechanical assessment of bone ingrowth in porous hydroxyapatite.

Porous hydroxyapatite (Endobon) specimens were implanted into the femoral condyle of New Zealand White rabbits for up to 6 months. After sacrifice, specimens were sectioned for histology and mechanical testing, where the extent of reinforcement by bony ingrowth was assessed by compression testing and fixation was assessed by push-out testing. From histological observations, it was established that the majority of bone ingrowth occurred between 10 day and 5 weeks after implantation and proceeded predominantly from the deep end of the trephined defect, with some integration from the circumferential sides. At 3 months, the implants were fully integrated, exhibiting bony ingrowth, vascularization and bone marrow stroma within the internal macropores. After 5 weeks, the mean ultimate compressive strength of retrieved implants (6.9 MPa) was found to be greater than that of the original implant (2.2 MPa), and by 3 months the fully integrated implants attained a compressive strength of approximately 20 MPa. Push-out testing demonstrated that after 5 weeks in vivo, the interfacial shear strength reached 3.2 MPa, increasing to 7.3 MPa at 3 and 6 months.

Journal Article↗
PubMed1998

The healing effect of all-trans retinoic acid on epithelial corneal abrasions in rabbits.

PURPOSE: The aim of the study was to investigate the possible healing effect of the vitamin A analogue all-trans retinoic acid 0.05% (RA) in vaseline on epithelial corneal abrasions in 13 ocularly healthy Copenhagen white rabbits. METHODS: A corneal abrasion with a diameter of 6 mm was created centrally in both eyes with a trephine and subsequent rubbing off of the corneal epithelium with an n-heptanol soaked swab The corneal abrasions were treated twice daily with topical applications (50 microl); RA was placed in the right inferior fornix and its vaseline vehicle in the left inferior fornix. Photographic documentation of fluorescein stained, non-healed areas, was performed at time points 0, 12, 24, 36, 48 and 72 h. The rabbits were sacrificed by an overdose of pentobarbital and enucleated. Planimetry was performed from corneal photographs. RESULTS: Healed epithelial mean area at time point 36 h was significantly higher after RA compared to vehicle (p=0.036, paired t-test). Median time to 75% and 85% healing was significantly shorter for RA compared to vehicle (p= 0.03 and 0.02, log rank-test). No morphological difference, evaluated by light microscopy (hematoxylin-eosin) or scanning electron microscopy, was noted between the two treatments. CONCLUSION: It is concluded that RA 0.05% applied twice daily increases the healing rate compared to vaseline vehicle.

Administration, Topical↗
PubMed1999

Homologous penetrating central limbo-keratoplasty (HPCLK) in bilateral limbal stem cell insufficiency.

PURPOSE: Bilateral stem cell deficiency can be overcome only by keratoplasty plus additional homologous limbal transplantation. We have four years' experience with a new surgical one-stage procedure, homologous penetrating central limbo-keratoplasty (HPCLK). METHODS: A clinical trial was performed in order to evaluate the effectiveness of this new method. The first 25 eyes after HPCLK for limbal stem cell deficiency have been followed for more than 12 months. The eccentrically trephined unmatched grafts contained 40% limbus and were transplanted centrally in the host. Systemic cyclosporin A (CSA) was administered for at least one year. Central clear graft survival was the main outcome criterion. RESULTS: 18 grafts failed, mostly because of postoperative surface disorders. Seven grafts have remained centrally clear 12-41 months after HPCLK. CONCLUSIONS: In the majority of the grafts the transplanted limbal stem cells underwent immune destruction. The survival of seven grafts, however, shows that HPCLK is principally a promising new procedure. Further progress can be expected from the use of well HLA-matched grafts instead of unmatched grafts and from further improved systemic immune modulation.

Adolescent↗
PubMed1994

Healing of implant dehiscence defects with and without expanded polytetrafluoroethylene membranes: a controlled clinical and histological study.

Bone augmentation around implant fixtures using the technique of guided tissue regeneration has been described in a number of reports. The aim of this study was to evaluate bone fill around dehiscence defects at matched defects randomly allocated to test (expanded polytetrafluoroethylene; Gore-Tex) or control treatments within the same patient. Six edentulous subjects were treated with overdentures supported by 2 fixtures ad modum Bränemark. In addition, 2 experimental 7-mm fixtures with nearly identical dehiscence defects on the labial aspect were placed in the anterior part of the mandible. Baseline defect heights ranged from 2.5 to 4.0 mm with 2 to 4 threads exposed. The test fixture dehiscence was covered with a Gore-Tex membrane secured with a cover screw. The experimental fixtures were exposed after 5 months at stage 2 surgery and measurements and photographs repeated. The fixtures were then removed with a trephine and processed for histological evaluation. Regeneration of a hard tissue resembling bone was observed in 4 of 6 cases treated with Gore-Tex, amounting to between 95 and 100% elimination of the dehiscence and total coverage of the threads. However, in one of these cases, histological evaluation showed that it was soft tissue and not bone, and in a further case soft tissue regeneration was apparent both clinically and histologically. In another case there was no significant regeneration at either test or control defects. Although there was a trend for the Gore-Tex-treated dehiscences to respond more favourably, the differences in clinical and histological measurements between test and control failed to reach statistical significance.

Adult↗
PubMed1995

Augmentation of intramembraneous bone beyond the skeletal envelope using an occlusive titanium barrier. An experimental study in the rabbit.

The aim of this investigation was to evaluate whether augmentation of intramembraneous bone beyond the skeletal envelope can be predictably achieved by placing a completely occlusive barrier on the skull bone of rabbits, hereby creating a secluded space with bone tissue being the only adjoining tissue. The experiment was carried out in 3 New Zealand white rabbits. In each animal, a midline incision was made down to the bone surface of the skull and a skin-periosteal flap was raised to expose the skull bone on both sides of the midline. Two prefabricated titanium domes with an inner diameter of 4.5 mm and an inner height of 3.0 mm were installed on each side. The domes were supplied with a horizontal, peripheral flange and a vertical edge, fitting tightly into a circular slit, prepared by a trephine into the skull bone. This arrangement ensured a stable anchorage of the dome and a reliable peripheral sealing of the space. The skin-periosteal flaps were relocated to cover the domes and sutured. After a healing period of 3 months, the animals were killed and the experimental areas excised and prepared for histological transversal ground sections with each dome in situ. The results demonstrated complete bone fill of all domes, with no signs of ingrowth of other types of tissues, indicating that the use of a barrier with total occlusiveness, sufficient stiffness and stability and reliable peripheral sealing will result in predictable bone augmentation of spaces also beyond the skeletal envelope.

Animals↗
PubMed1996

Surgical correction of malpositioned implants. A case report.

A new technique for surgical correction of malpositioned implants is described. A 64-year-old female got her first fixed prosthesis anchored to 6 Brånemark implants in her upper jaw, in April 1993. The implants were poorly positioned and despite great efforts to make the construction aesthetically acceptable, the patient did not approve. In order to obtain better aesthetics, it was decided to move some of the osseointegrated implants to other positions. With a trephine drill, fixtures were removed including the surrounding bone, and 2 of them were placed in new sites made with the same drill. After a healing period of 6 months, abutments were connected and a new fixed prosthesis was made. After 1 year of loading, all implants were still stable. A marginal bone resorption to the 3rd thread was found around one of the implants.

Dental Implantation, Endosseous↗
PubMed1998

Effect of loading on bone regenerated at implant dehiscence sites in humans.

Few investigations have studied the long-term fate of bone formed following the technique of guided tissue regeneration. The aim of the present study was to evaluate bone fill around implant fixtures with dehiscence defects and to study its response to loading. Ten patients were treated with overdentures supported by 2 fixtures ad modum Brånemark. A third 7 mm x 3.75 mm diameter fixture was placed for the purposes of the study in the most anterior part of the mandible with a dehiscence defect of 4 to 5 mm on the buccal aspect (and 3 to 4 threads exposed) which was covered with a Gore-Tex membrane and buried beneath the mucosa. Fixtures were exposed after 5 months (stage 2), ball abutments connected and loaded through an overdenture for 1 year. Nine fixtures were functioning well after 1 year of loading, 6 of which were retrieved with a trephine for histological examination and compared with 6 unloaded fixtures retrieved in our previously reported study. The bone area filling the thread profiles (BA%) and the bone to metal contact (BMC%) were measured in the 3 most apical and 3 most coronal thread profiles on the buccal and lingual surfaces. Statistically significant higher BMC% (P < 0.01) were observed in loaded fixtures in the apical regions (buccal: loaded 51%, unloaded 25%; lingual: loaded 49%, unloaded 24%). Differences approached significance for the regeneration site (loaded 22%, unloaded 6%) but were no different for the coronal lingual region (loaded 28%, unloaded 20%). There were no differences for BA%. This study confirms that there is an increase in bone to metal contact with time and following fixture loading and that this may also occur with bone regenerated under Gore-Tex membranes.

Adult↗
PubMed2000

Maxillary sinus augmentation using xenogenic bone substitute material Bio-Oss in combination with venous blood. A histologic and histomorphometric study in humans.

The aim of the present study was to evaluate bone formation following maxillary sinus augmentation using bovine bone substitute material Bio-Oss in combination with venous blood by means of histologic and histomorphometric examination of human biopsies. This involved a total of 15 sinus floor elevation procedures being carried out on 11 patients (average age of 49.6 years) according to the technique described by Tatum (1986). The subantral sinus cavity was augmented using bovine apatite combined with venous blood. After an average healing phase of 6.8 months, trephine burrs were used to take 22 bone biopsies from the augmented sinus region. Then 38 Brånemark implants were inserted in both the osteotomies resulting from bone sampling and in regular sites in the augmented posterior maxilla. Histomorphometric analysis of ground sections from the bone biopsies prepared according to the standard method of Donath & Breuner (1982) produced an average percentage of newly-formed bone of 14.7% (+/- 5.0%) and a proportion of residual xenogenic bone substitute material of 29.7% (+/- 7.8%). Some 29.1% (+/- 8.1%) of the surface of the Bio-Oss granulate was in direct contact with newly-formed bone. Histologically, newly-developed bone became evident, partly invaginating the particles of apatite and forming bridges in the form of trabeculae between the individual Bio-Oss particles. Despite the absence of osteoclastic activity, the inward growth of bone indicates slow resorption of the xenogenic bone graft material. When the implants were uncovered, after an average healing phase of 6 months, 4 of the 38 implants had become loose. Of these 4 implants, 1 had to be subsequently explanted, while the others remained as "sleeping implants" and were not included in the implants superstructure. Thus, the resulting clinical survival rate, prior to prosthetic loading, was 89.5%.

Adult↗
PubMed2001

Histologic evaluation of the bone integration of TiO(2) blasted and turned titanium microimplants in humans.

Twenty-seven patients received 2 microimplants each during implant surgery. One microimplant was blasted with 25 microm sized particles of TiO(2); the other was left as machined i.e. a turned surface. Before insertion the surface topography was characterized with an optical confocal laser profilometer. The surface roughness was greater than standard implants, and was similar for both surface modifications averaging over all parts of the implant i.e. tops, valley and flanks. The mean surface roughness from flank measurements only replicated previously reported findings: i.e. significantly rougher surfaces on blasted implants. After a mean healing period of 6.3 months in the maxillae and 3.9 months in the mandible, the microimplants and surrounding tissue were removed with a trephine burr. The histomorphometrical evaluation demonstrated significantly higher bone-to-implant contact for the blasted implants, inserted in the maxilla or in the mandible. Significantly more bone was found inside the threaded area for the blasted implants in the mandible, but there was no difference for implants positioned in maxillae.

Aged↗