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PubMed2002

Thermal changes observed at implant sites during internal and external irrigation.

In the preparation of osseointegrated dental implant sites, the use of bone drilling with conventional external irrigation has been shown to be thermally non-injurious to bovine bone, when employed as a model for dental implantology. The use of internal irrigation drilling systems is promoted on the basis of improved delivery of coolant to the bone/drill interface, which should subsequently improve local debridement and cooling, and therefore reduce thermal insults to the bone. The aim of this bovine model study was to compare the temperatures that were generated with external and internal irrigation systems during bone preparation for dental implants. A constant drill load of 1.7 kg was applied throughout the drilling procedures via a drilling rig. The burs that were used for both irrigation methods were a 2 mm twist drill for cutting the channel and a 3.25 mm drill for trephining this channel. The principal recorded parameter was the change in temperature generated via the drilling procedure. The 2 mm twist drills produced a maximum change in temperature of only 3.0 degrees C and 3.1 degrees C for the internal and external irrigation systems, respectively. Maximum changes for the 3.25 mm drills were 1.34 degrees C and 1.62 degrees C, respectively. Using the t-test, no statistical benefit was observed for one irrigant delivery system over the other. The clinical benefit of using the more expensive internal irrigation systems is therefore deemed unjustifiable, on the grounds that these systems do not appear to reduce the thermal challenge to the bone over and above that of simple flood irrigation.

Animals↗
PubMed2002

Effect of RGD peptide coating of titanium implants on periimplant bone formation in the alveolar crest. An experimental pilot study in dogs.

The aim of the present study was to analyse the effect of organic coating of titanium implants on periimplant bone formation and bone/implant contact. Three types of implants were used: (i) Ti6Al4V implants with polished surface (control 1) (ii) Ti6Al4V implants with collagen coating (control 2) (iii) Ti6Al4V implants with collagen coating and covalently bound RGD peptides. All implants had square cross-sections with an oblique diameter of 4.6 mm and were inserted press fit into trephine burr holes of 4.6 mm in the mandibles of 10 beagle dogs. The implants of five animals each were evaluated after a healing period of 1 month and 3 months, during which sequential fluorochrome labelling of bone formation was performed. Bone formation was evaluated by morphometric measurement of the newly formed bone around the implant and the percentage of implant bone contact. After 1 month there was only little bone/implant contact, varying between 2.6 and 6.7% in the cortical bone and 4.4 and 5.7% in the cancellous bone, with no significant differences between the three types of implants. After 3 months, implants with polished surfaces exhibited 26.5 and 31.2% contact in the cortical and cancellous bone, respectively, while collagen-coated implants had 19.5 and 28.4% bone contact in these areas. Implants with RGD coating showed the highest values with 42.1% and 49.7%, respectively. Differences between the surface types as such were not significant, but the increase in bone/implant contact from 1 to 3 months postoperatively was significant only in the group of RGD-coated implants (P = 0.008 and P = 0.000). The results of this pilot study thus provide only weak evidence that coating of titanium implants with RGD peptides in the present form and dosage may increase periimplant bone formation in the alveolar process. The results therefore require further verification in a modified experimental setting.

Alloys↗
PubMed2002

Vertical distraction of the severely resorbed edentulous mandible: a clinical, histological and electron microscopic study of 10 treated cases.

The aim of this study was to evaluate the clinical and histomorphological results of distraction of the severely resorbed edentulous mandible. In a group of 10 edentulous patients suffering from insufficient retention of their mandibular denture related to a severely resorbed mandible, the anterior segment was augmented as a preimplant surgical procedure using the nonvoluminous Groningen Distraction Device (GDD). Two months after the last day of distraction, a bone biopsy was taken with a trephine, both distraction screws were replaced by endosseous implants and the guide screw was removed. The biopsies were examined by means of light microscopy (LM) and transmission electron microscopy (TEM). Radiographical and histomorphological examination of the biopsies revealed the presence of two cortical zones, one at each end of the biopsies, a poorly mineralized, fibrous interzone in the middle of the distraction gap, and two zones of mineralization between the central fibrous and the peripheral cortical zones. Formation of lamellar bone parallel to the distraction vector was clearly visible in the mineralization zone as well as signs of remodelling at the borderline between the native cortical bone and the generate. Clinical examination showed in all patients that the anterior segment distracted from the mandible body was sufficiently enlarged to enable insertion of endosseous implants with a length of at least 12 mm. One implant was lost during the healing phase, but was successfully replaced thereafter. Implant retained overdentures were fabricated 3 months after implantation. All patients have good function 11.2 +/- 4.3 months after the end of treatment. From this study it is concluded that the GDD has proven to be a reliable tool for augmentation of the anterior segment of a severely resorbed edentulous mandible enabling osseointegration of endosseous load-bearing implants.

Aged↗
PubMed2003

Effects of occlusiveness of a titanium cap on bone generation beyond the skeletal envelope in the rabbit calvarium.

We evaluate the effects of occlusiveness of a titanium cap on bone generation beyond the skeletal envelope. In eight rabbits, the calvarial bone was exposed and a circular groove was prepared with a trephine drill. After marrow penetration, a standardized hemispherical titanium cap, either with or without small holes (1.5 mm in diameter), was then placed into the bone and covered by a cutaneous flap. After 1 month or 3 months of healing, the animals were euthanized and examined histologically. The percentage area of newly generated tissue consisting of mineralized bone and marrow spaces in each section was calculated relative to the area bounded by the hemispherical shape of the titanium cap and the parent bone; this latter volume was taken to be 100%. Furthermore, the cross-sectional areas of generated mineralized bone expressed as percentages of the total tissue area generated within each space were determined. In the 1-month specimens, there was no statistically significant difference between the two caps in the amount of tissue generated, 54.7%+/-12.2% with holes vs. 60.4%+/-8.8% without holes (p=0.225). However, in the 3-month specimens, we observed a significant difference between the caps (55.9%+/-7.4% with holes vs. 89.9%+/-6.5% without holes, P<0.05). Also, there was a statistically significant difference between 1- and 3-month specimens in the amount of tissue generated under the cap without holes (60.4%+/-8.8% vs. 89.9%+/-6.5%, P<0.05). Although there was no significant difference in the relative amount of mineralized bone generated between the caps with holes and those without holes in the 1-month specimens (27.7%+/-4.8% vs. 30.8%+/-6.4%, P=0.225), there was a statistically significant difference between the two caps in the 3-month specimens (24.3%+/-4.1% with holes vs. 34.0%+/-8.6% without holes, P<0.05). A substantial ingrowth of fibrous connective tissue through the holes appeared to prevent further new tissue generation in a defined area adjacent to the bone surface. We concluded that total occlusiveness, sufficient stiffness of the cap, as well as the passage of time will allow predictable mineralized bone augmentation to occur in spaces beyond the skeletal envelope.

Animals↗
PubMed2003

Hard tissue reaction to dual acid-etched titanium implants: influence of plaque accumulation. A histological study in humans.

OBJECTIVES: The aim of this investigation was to evaluate histologically, histometrically, and histomorphometrically the influence of plaque accumulation on the peri-implant hard tissues. MATERIAL AND METHODS: Twelve fully edentulous subjects were selected for this investigation. Four to five standard titanium screw implants were placed interforaminally. Two small custom-made screw implants were incorporated in the region of the former first molar, one in each lower quadrant. One month after abutment connection, plaque control was terminated randomly at one of the custom-made implants and continued at the other implant. The custom-made implants and the surrounding tissue were harvested after different time points of plaque accumulation (7, 21, or 90 days). Thus, according to the plaque control program and implant removal time, there were six groups each with four implants for investigation. After histologic processing of the biopsies, histologic, histometric, and histomorphometric analyses were performed. RESULTS: Four of the 24 implants were unavailable for analysis. One implant was mobile at abutment connection and another implant was mobile 2 weeks after abutment connection; both implants had to be removed. The bone around two implants was destroyed during the removal with the trephine bur; therefore, these two implants could not be evaluated histologically either. No differences in the histologic appearance of the peri-implant bone between the different groups could be observed. Histomorphometrically, the implant surface in contact with mineralized bone as a fraction of the implant surface (measured from the buccal to the lingual implant shoulder) varied between 59% and 73%. The implant surface in contact with mineralized bone from the first bone-to-implant contact buccally to the first bone-to-implant contact lingually varied between 80.6% and 91.5%. The values for the distance from the implant shoulder to the first bone-to-implant contact, i.e. peri-implant bone loss, varied from 1.1 to 2.2 mm. No statistically significant differences could be found between any of the evaluated variables. CONCLUSIONS: This clinical investigation is the first to evaluate the hard tissue reactions to different plaque accumulation periods. Within the limits of this experiment, it can be concluded that the bone reaction toward the different plaque accumulation periods and in the different plaque control/accumulation groups were similar. It can be further concluded that the observed bone loss is rather attributed to the establishment of the biologic width than to plaque accumulation.

Acid Etching, Dental↗
PubMed2003

Effect of rhBMP-2 on guided bone regeneration in humans.

The aim of the present clinical study was to test whether or not the addition of recombinant human bone morphogenetic protein-2 (rhBMP-2) to a xenogenic bone substitute mineral (Bio-Oss) will improve guided bone regeneration therapy regarding bone volume, density and maturation. In 11 partially edentulous patients, 34 Brånemark implants were placed at two different sites in the same jaw (five maxillae, six mandibles) requiring lateral ridge augmentation. The bone defects were randomly assigned to test and control treatments: the test and the control defects were both augmented with the xenogenic bone substitute and a resorbable collagen membrane (Bio-Gide). At the test sites, the xenogenic bone substitute mineral was coated with rhBMP-2 in a lyophilization process. Following implant insertion (baseline), the peri-implant bone defect height was measured from the implant shoulder to the first implant-bone contact. After an average healing period of 6 months (SD 0.17, range 5.7-6.2), the residual defects were again measured and trephine burs were used to take 22 bone biopsies from the augmented regions. The healing period was uneventful except for one implant site that showed a wound dehiscence, which spontaneously closed after 4 weeks. Later at reentry, all implants were stable. At baseline, the mean defect height was 7.0 mm (SD 2.67, range 3-12 mm) at test and 5.8 mm (SD 1.81, range 3-8 mm) at control sites. At reentry, the mean defect height decreased to 0.2 mm (SD 0.35, range 0-1 mm) at test sites (corresponding to 96% vertical defect fill) and to 0.4 mm (SD 0.66, range 0-2 mm) at the control site (vertical defect fill of 91%). Reduction in defect height from baseline to reentry for both test and control sites was statistically significant (Wilcoxon P<0.01). Histomorphometric analysis showed an average area density of 37% (SD 11.2, range 23-51%) newly formed bone at test sites and 30% (SD 8.9, range 18-43%) at control sites. The fraction of mineralized bone identified as mature lamellar bone amounted to 76% (SD 14.4, range 47.8-94%) at test compared to 56% (SD 18.3, range 31.6-91.4%) at control sites (paired t-test P<0.05). At BMP-treated sites 57% (SD 16.2, range 29-81%) and at control sites 30% (SD 22.6, range 0-66%) of the surface of the bone substitute particles were in direct contact with newly formed bone (paired t-test P<0.05). It is concluded that the combination of the xenogenic bone substitute mineral with rhBMP-2 can enhance the maturation process of bone regeneration and can increase the graft to bone contact in humans. rhBMP-2 has the potential to predictably improve and accelerate guided bone regeneration therapy.

Adult↗
PubMed2003

Bilateral simultaneous augmentation of the maxillary sinus floor with particulated mandible. Report of a technique and preliminary results.

This paper describes a surgical technique that permits the achievement of bilateral simultaneous augmentation of the maxillary sinus floor with the use of autologous bone harvested from the mandibular symphysis alone. Out of a group of 26 partially edentulous patients consecutively treated for sinus augmentation in an 18-month period, eight needed a bilateral procedure and were treated with the same surgical protocol. None of the patients had residual molar teeth, crestal bone height was reduced to 4 mm or less. Bone was harvested from the chin in blocks with a trephine bur, 11 or 9 mm in diameter, it was then particulated with a bone mill. Sinus augmentation and implant placement were done simultaneously in both sides of the maxilla. Implant-supported fixed partial dentures were inserted 6 months after the procedure. 44 ITI solid screw implants were placed in the grafted sinuses with a mean of 2.75 implants on each side. Mean follow-up was 19 months. In all patients needing a bilateral sinus lift, the procedure could be successfully completed. All implants were stable at abutment connection. All implants are stable at the latest follow-up, and all prosthesis are still working. In all implants, a clear bone-to-implant contact was visible. No peri-implant radiolucency has been noticed so far. It is concluded that bilateral augmentation of maxillary sinus floor with particulated mandible associated with simultaneous ITI implant insertion is feasible. It is a safe and effective procedure that can be accomplished in an out-patient environment with only minor discomfort for the patient.

Adult↗
PubMed2002

The effect of a fibrin glue on the integration of Bio-Oss with bone tissue. A experimental study in labrador dogs.

BACKGROUND: Bio-Oss is a deproteinized bovine mineral used in bone augmentation procedures. The particles are often mixed with a protein product (Tisseel) to form a mouldable graft material. AIM: The aim of the present experiment was to study the healing of self-contained bone defects after the placement of Bio-Oss particles alone or mixed with Tisseel in cylindrical defects in the edentulous mandibular ridge of dogs. MATERIAL AND METHODS: In 4 labrador dogs, the 2nd, 3rd and 4th mandibular premolars were extracted bilaterally. 3 months later, 3 cylindrical bone defects, 4 mm in diameter and 8 mm in depth, were produced in the right side of the mandible. Following a crestal incision, full thickness flaps were raised and the bone defects were prepared with a trephine drill. The defects were filled with Bio-Oss (Geistlich Biomaterials, Wolhuser, Switzerland) particles alone or mixed with Tisseel (Immuno AG, Vienna, Austria), or left "untreated". A collagen membrane (Bio-Gide, Geistlich Biomaterials, Wolhuser, Switzerland) was placed to cover all defects and the flaps were sutured. 2 months later, the defect preparation and grafting procedures were repeated in the left side of the mandible. After another month, the animals were sacrificed and biopsies obtained from the defect sites. RESULTS: Bio-Oss-treated defects revealed a higher percentage of contact between graft particles and bone tissue than defects treated with Bio-Oss+ Tisseel (15% and 30% at 1 and 3 months versus 0.4% and 8%, respectively). Further, the volume of connective tissue in the Bio-Oss treated defects decreased from the 1 to the 3 month interval (from 44% to 30%). This soft tissue was replaced with newly formed bone. In the Bio-Oss+ Tisseel treated defects, however, the proportion of connective tissue remained unchanged between 1 and 3 months. CONCLUSION: The adjunct of Tisseel may jeopardize the integration of Bio-Oss particles with bone tissue.

Animals↗
PubMed1984

A comparison of the metastatic pattern of infiltrating lobular carcinoma and infiltrating duct carcinoma of the breast.

The metastatic sites of infiltrating duct (IDC) and infiltrating lobular carcinoma (ILC) have been compared using both clinical and autopsy data. The following statistically significant differences were found: Lung parenchymal metastases were more common in IDC. Bone trephine biopsies were more likely to be positive in ILC. Carcinomatous meningitis was associated almost exclusively with ILC. Peritoneal/retroperitoneal metastases of distinctive pattern occurred in ILC. There was often associated linitis plastica-like involvement of the stomach wall and diffuse infiltration of the uterus. Hydronephrosis was a common secondary phenomenon.

Adult↗
PubMed1988

In vitro and in vivo analysis of the effects of recombinant human granulocyte colony-stimulating factor in patients.

Twelve patients with small cell lung cancer were treated with recombinant human granulocyte colony-stimulating factor, rhG-CSF, given by continuous infusion at doses ranging from 1 to 40 micrograms kg-1 day-1. Patients received the rhG-CSF before the start of intensive chemotherapy and after alternate cycles of chemotherapy. Several in vitro assays were performed using peripheral blood neutrophils and marrow progenitor cells collected from patients prior to and after infusion of the growth factor. Peripheral blood neutrophils were tested for mobility and phagocytic activity. In addition, in vitro clonogenic assays of marrow haemopoietic progenitor cells and analysis of bone marrow trephines and aspirates were carried out. We found that rhG-CSF in vivo has at least two main effects: (a) an early fall in peripheral neutrophils, within the first hour, followed by a rapid influx of mature neutrophils into the circulatory pool; (b) stimulation of proliferation and differentiation of neutrophil precursors in the bone marrow. Neutrophils released into the circulation were normal in tests of their mobility and phagocytic activity.

Antineoplastic Agents↗
PubMed1989

Immunological detection of neuroblastoma cells in bone marrow harvested for autologous transplantation.

In about 50% of patients with stage IV neuroblastoma, micrometastases are present in the bone marrow when it is harvested for an autograft to follow induction therapy, and the risk of graft contamination by neuroblastoma cells has been the rationale for the use of a purging procedure. However, bone marrow metastases are detected with trephine biopsies which only explore the sites biopsied and do not reflect potential contamination of the pooled marrow harvested for autograft. A two-colour fluorochrome labelling method is described which permits as few as 1 neuroblastoma cell in 100,000 normal bone marrow cells from the autograft to be detected. Three monoclonal antibodies (UJ13A, H11 and 11.14) which react with neuroblastoma cells are used as single reagent in combination with a fourth anti-panleucocyte antibody. This method requires only 2 h for the analysis of three million marrow cells from the autograft, and is more effective than alkaline phosphatase staining with the same monoclonal antibodies. Results were compared with conventional techniques (four biopsies and four aspirates) carried out at the same time in 34 consecutive patients. Of 18 cases with negative aspirates and biopsies, neuroblastoma cells were detected in two autografts by the immunological method. Of 16 cases with positive aspirates and/or biopsies, 10 autografts were positive by the immunological method and six were negative. Thus, marrow micrometastases were detected in 16 of the 34 patients, but the autograft contained malignant cells in only 12 of these patients and the immunological analysis demonstrated that the use of a purging procedure allowed the elimination of neuroblastoma cells from the autograft before its reinjection to the patients.

Antibodies, Monoclonal↗
PubMed1993

A review of 72 consecutive cases of Acanthamoeba keratitis, 1984-1992.

A review of consecutive cases of Acanthamoeba keratitis presenting since 1984 was undertaken in order to assess prognostic factors, the success of culture procedures and the outcome of medical and surgical management, with reference to current clinical practice. Seventy-two consecutive cases (77 eyes) of Acanthamoeba keratitis have been managed. Sixty-four patients were contact lens wearers, 28 of these wearing disposable lenses. Superficial corneal involvement and perineural infiltrates were common in those diagnosed less than a month after first symptoms, designated 'early' presentation. Ring infiltrates and ulceration with stromal lysis characterised those presenting at 1-2 months ('intermediate') or after 2 months ('late'); these groups also progressed more frequently to hypopyon, scleritis, glaucoma and cataract formation. Positive corneal cultures were obtained in 10 of 14 (71%) intermediate and 17 of 23 (74%) late cases; early cases underwent epithelial biopsy but formal trephine biopsy was not usually justified (1 of 35 cases) and only 19 of 35 (54%) were tissue-positive. Microbial co-isolates were obtained from 20 corneas. Thirty-four penetrating keratoplasties were performed in 23 eyes, 21 whilst inflamed and 13 when quiet. Of 13 failures in inflamed eyes, 9 were due to recurrence of Acanthamoeba infection. Medical cure is known to have been achieved in 64 of 73 (88%) eyes, 4 of the original 77 having been lost to follow-up abroad. Fifty-eight of 73 eyes (79%) achieved a final visual acuity of 6/12, and of the culture-positive cases, 32 of 46 (70%) achieved 6/12.(ABSTRACT TRUNCATED AT 250 WORDS)

Acanthamoeba↗
PubMed1994

An ultrasonic Doppler venous outflow method for the continuous measurement of cerebral blood flow in conscious sheep.

A pulsed ultrasonic Doppler venous outflow method was developed for the continuous measurement of global cerebral blood flow (CBF) in conscious sheep. The sheep were prepared under anesthesia with a "suture down"-style ultrasonic flow probe on the dorsal sagittal sinus placed via a trephine hole. Angiographic and dye studies showed that the dorsal sagittal sinus at the point of placement of the probe collected the majority of the blood from the cerebral hemispheres. Studies of the blood velocity profile across the sinus showed that the dimensions of the dorsal sagittal sinus changed minimally with changes in CBF in vivo. The velocity measurements were calibrated under anesthesia against an in vivo direct venous outflow method. Control CBF values for six sheep ranged from 31 to 53 ml/min for the area of brain described above; for two sheep in which the weight of the brain was determined, this gave total CBF values of approximately 34 and 30 ml min-1 100 g-1. The CBF measured varied in the expected manner with changes in the end-tidal CO2 concentration in expired breath and showed transient reductions with the barbiturate thiopentone and transient increases with the opiate alfentanil. It is concluded that the method is simple and accurate.

Alfentanil↗
PubMed2004

Increased incidence of monoclonal B-cell infiltrate in chronic myeloproliferative disorders.

A total of 106 trephine biopsy specimens with clinical, laboratory and pathology findings corresponding to chronic myeloproliferative disorders (CMPD) were analyzed to reveal the nature of the lymphoid infiltrate in the bone marrow. Histological investigation in 31 chronic myeloid leukemia (CML), 29 CMPDs not otherwise specified (CMPD-NOS), 28 essential thrombocytosis (ET), 15 polycythemia vera (PV) and three chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES) exhibited in 32% various amounts of lymphocytic infiltrate of sparsely to moderately diffuse or nodular types in the bone marrow, but the reactive or coinciding lymphomatous nature could not be revealed by histology alone in the majority of cases. PCR analysis of the immunoglobulin heavy chain (IgH) gene rearrangement was successfully performed in 81 out of the 106 DNA specimens extracted from formol-paraffin blocks. Out of the 81 samples with good-quality DNA, 18 gave a single or double discrete amplification band(s), which was reproducible only in four specimens. Sequencing finally proved monoclonal B-cell population of both pre- and postfollicular origin in all four samples (5%), one CML and three CMPD-NOS. Detailed clinical and pathological investigations indicated overt B-cell malignant lymphoma with clonal relationship to the CMPD in two out of these four patients. We conclude that detailed molecular analysis of IgH gene rearrangement in bone marrow samples of CMPD patients is needed to identify the true monoclonal B-cell infiltration, which-even without overt malignant lymphoma-may occur in this group of disorders. Modern Pathology (2004) 17, 1521-1530, advance online publication, 16 July 2004; doi:10.1038/modpathol.3800225.

B-Lymphocytes↗
PubMed2001

Megakaryopoiesis and myelofibrosis in chronic myeloid leukemia after allogeneic bone marrow transplantation: an immunohistochemical study of 127 patients.

An immunohistochemical and morphometric study was performed on 363 trephine biopsies of the bone marrow derived from 127 patients with chronic myeloid leukemia at standardized end points before and after allogeneic bone marrow transplantation (BMT). The purpose of this investigation was to evaluate features of CD61+ megakaryopoiesis related to successful engraftment. Further, we tried to elucidate possible associations of this lineage, including precursor cells, with the platelet count and reticulin fibrosis during the pretransplant and, specifically, post-transplant periods. A significant correlation was recognizable between the quantity of CD61+ megakaryocytes and the platelet values before BMT and also after completed hematopoietic recovery. In the very early post-transplant period, which is associated with severe thrombocytopenia, patchy regeneration of disarranged hematopoiesis occurred, including dysplastic megakaryocytes. According to planimetric measurements after BMT, the atypical micromegakaryocytes characteristic for chronic myeloid leukemia disappeared, and the engrafted donor bone marrow revealed a prevalence of normal-size cells of this lineage. On the other hand, normalization of megakaryocyte size was absent in sequential examinations of the few patients with a leukemic relapse who had a predominance of atypical dwarf forms comparable with chronic myeloid leukemia. Before BMT occurred, reticulin fiber density was significantly correlated with the number of CD61+ megakaryocytes and its precursor cell population. In 34 patients with myelofibrosis that occurred after myelo-ablative therapy and BMT, an initial regression was followed by an insidious recurrence of fibers concentrated in the areas of regenerating hematopoiesis. This postgraft reappearance of reticulin fibrosis was significantly associated with the quantity of megakaryocytes. Regarding engraftment parameters, pretransplant presence of (reticulin) myelofibrosis exerted a distinctive impact because of a delayed hematopoietic reconstitution according to standard clinical criteria. In line with this finding, slowed engraftment was also significantly related with higher pretransplant megakaryocyte and platelet counts.

Adult↗
PubMed2002

Parathyroid hormone related peptide and receptor expression in paired primary prostate cancer and bone metastases.

Parathyroid hormone-related peptide is a regulatory protein implicated in the pathogenesis of bone metastases, particularly in breast carcinoma. Parathyroid hormone-related peptide is widely expressed in primary prostate cancers but there are few reports of its expression in prostatic metastases. The aim of this study was to examine the expression of parathyroid hormone-related peptide and its receptor in matched primary and in bone metastatic tissue from patients with untreated adenocarcinoma of the prostate. Eight-millimetre trephine iliac crest bone biopsies containing metastatic prostate cancer were obtained from 14 patients from whom matched primary tumour tissue was also available. Histological grading was performed by an independent pathologist. The cellular location of mRNA for parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor was identified using in situ hybridization with (35)S-labelled probe. Expression of parathyroid hormone-related peptide and its receptor was described as uniform, heterogenous or negative within the tumour cell population. Parathyroid hormone-related peptide expression was positive in 13 out of 14 primary tumours and in all 14 metastases. Receptor expression was evident in all 14 primaries and 12 out of 14 metastases. Co-expression of parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor was common (13 primary tumours, 12 metastases). The co-expression of parathyroid hormone-related peptide and its receptor suggest that autocrine parathyroid hormone-related peptide mediated stimulation may be a mechanism of escape from normal growth regulatory pathways. The high frequency of parathyroid hormone-related peptide expression in metastases is consistent with a role in the pathogenesis of bone metastases.

Autoradiography↗
PubMed1999

Angiogenesis in myelodysplastic syndromes.

It is now well established that solid tumour growth depends on angiogenesis. However, less is known about the generation of new vessels in haematological malignancies and, in particular, in preleukaemic-myelodysplastic syndromes (MDS). In this study, bone marrow microvessel density (MVD) was assessed by immunohistochemistry and compared in trephine biopsies from 14 controls, five infectious disease (ID), 82 MDS, 15 acute myeloid leukaemia (AML) and 14 myeloproliferative disorder (MPD) patients. Statistical analysis (P < 0.001) demonstrated that MDS MVD was higher than in controls and ID (21 +/- 9 vs 6 +/- 2 and 10 +/- 8 respectively) but lower than AML (30 +/- 12) and MPD (40 +/- 12). Among MDS-FAB subtypes, MVD was significantly higher in RAEB-t, CMML and fibrosis subsets compared to RA, RARS and RAEB subsets (P= 0.008). To further investigate angiogenesis machinery, the expression of vascular endothelial growth factor (VEGF) was evaluated by means of immunohistochemistry in control, MDS, AML and MPD biopsies. Even though VEGF mRNA expression was reported in the past in AML cell cultures and cell lines, in our samples VEGF expression was found to be particularly strong in most of the megakaryocytes but significantly less prominent in other cell populations including blasts. Since our findings suggest a correlation between angiogenesis and progression to leukaemia, additional work is now warranted to determine what regulates the generation of new vessels in MDS and leukaemia.

Antigens, CD34↗
PubMed1997

Transplantation of cord blood progenitor cells can promote bone resorption in autosomal recessive osteopetrosis.

Allogeneic BMT has been reported to be the only curative therapy for children with juvenile autosomal recessive osteopetrosis. We report the case of a 14-month-old child in whom bone resorption was observed after cord blood transplantation (CBT). The patient was given CBT from an unrelated newborn matched for five of six HLA antigens. At the time of transplantation, the child presented with neurological symptoms, with feeding problems and visual impairment. A successful engraftment of donor hematopoiesis was demonstrated and the child experienced grade I acute GVHD. Progressive bone clearing was achieved and a bone marrow trephine demonstrated signs of osteoclast function. Despite full engraftment and bone resorption, neurologic deterioration did not improve. This experience documents that CBT can promote the correction of juvenile osteopetrosis. The shorter time needed both to identify an unrelated donor and to perform the transplant, as well as the lower incidence of GVHD make this procedure more appealing than BMT in children lacking an HLA-compatible relative.

Bone Resorption↗