SrHA/PMMA复合骨水泥的制备、理化性能及细胞相容性研究

目的结合PMMA和锶羟基磷灰石(Sr HA)各自的优势,制备出兼具高的力学强度、合适的固化时间、较低的热释放、生物活性和骨整合性能的Sr HA/PMMA复合骨水泥,并系统性地研究Sr HA的引入对复合骨水泥的体外固化性能、力学强度和生物学性能的影响。方法将水热合成法制备的锶羟基磷灰石引入PMMA基体,制备Sr HA/PMMA复合骨水泥。系统性地对Sr HA/PMMA复合骨水泥的力学强度、固化时间、热释放、生物活性进行研究。将复合骨水泥和细胞共培养,利用MTT法、扫描电镜等研究Sr HA/PMMA复合骨水泥的细胞毒性,粘附和增殖。结果结果表明,与纯的PMMA骨水泥(对照组)相比,Sr HA/PMMA复合骨水泥的固化热释放明显降低(约80~84℃),同时又维持了合适的固化时间(8~11分钟)和较好的力学性能(抗压强度为90MPa左右)。Sr HA的引入,不仅赋予了复合骨水泥生物活性,也显著地改善了其细胞/材料的相互作用。浸泡在SBF后,Sr HA/PMMA复合骨水泥显示出更好的体外矿化性能。与成骨细胞MC3T3-E1共培养后,表面沉积的羟基磷灰石能够更好的促进细胞的粘附和爬行。结论兼具优异的理化性能和生物活性的Sr HA/PMMA复合骨水泥,有着广阔的骨科微创修复应用前景。     

Influence of initial component temperature on the apparent viscosity and handling characteristics of acrylic (PMMA) bone cement

The flow and polymerization characteristics of poly(methylmethacrylate) (PMMA) bone cement can be changed by manipulating the temperature of the bone cement components or the environment that they are prepared in. To quantify the effects of the initial component temperature (T(ic)) of acrylic bone cement on the rheological and handling characteristics, ASTM F451-99a compliant methods and clinically relevant testing methods were utilized. A rheometer was designed and fabricated using the dimensions of a clinical, commercially available, cement gun and nozzle. The influence on the apparent viscosity and handling characteristics (setting time, working time, and peak exotherm temperature) for a high viscosity (HV) commercially-available acrylic bone cement, Palacos R, were determined. The values of T(ic) used were 23 degrees C (room), 6 degrees C (refrigerator), and -14 degrees C (freezer). Using the apparent viscosity of a medium viscosity (MV) bone cement as a benchmark (Simplex P at room temperature), it was found that by adjusting the T(ic) the HV cement was able to mimic the flow characteristics of the MV cement. Lowering the T(ic) lowered the apparent viscosity of the bone cement. The effects of T(ic) on the polymerization of bone cement were studied in dynamic and static conditions. The dynamic test recorded temperature and torque from stirring resistance. Setting times were also determined using the ASTM exotherm mold method. The setting times determined by the dynamic testing conditions were consistently shorter than those determined by the ASTM method. Lowering the T(ic) increased the working and setting times; however, it did not have a significant effect on the peak exotherm temperature.     

A novel and easy-to-prepare strontium(II) modified calcium phosphate bone cement with enhanced mechanical properties

The aim of this study was to evaluate two different approaches to obtaining strontium-modified calcium phosphate bone cements (SrCPCs) without elaborate synthesis of Sr-containing calcium phosphate species as cement precursors that could release biologically effective doses of Sr²⁺ and thus could improve the healing of osteoporotic bone defects. Using strontium carbonate as a strontium(II) source, it was introduced into a hydroxyapatite-forming cement either by the addition of SrCO₃ to an α-tricalcium phosphate-based cement precursor mixture (A-type) or by substitution of CaCO₃ by SrCO₃ during precursor composition (S-type). The cements, obtained after setting in a water-saturated atmosphere, contained up to 2.2 at.% strontium in different distribution patterns as determined by time-of-flight secondary ion mass spectrometry and energy-dispersive X-ray spectroscopy. The setting time of CPC and A-type cements was in the range of 6.5–7.5 min and increased for substitution-type cements (12.5–13.0 min). Set cements had an open porosity between 26 and 42%. Compressive strength was found to increase from 29 MPa up to 90% in substituted S-type cements (58 MPa). SrCPC samples released between 0.45 and 1.53 mg g^?1 Sr²⁺ within 21 days and showed increased radiopacity. Based on these findings, the SrCPC developed in this study could be beneficial for the treatment of defects of systemically impaired (e.g. osteoporotic) bone.     

Fatigue and biocompatibility properties of a poly(methyl methacrylate) bone cement with multi-walled carbon nanotubes

Composites of multi-walled carbon nanotubes (MWCNT) of varied functionality (unfunctionalised and carboxyl and amine functionalised) with polymethyl methacrylate (PMMA) were prepared for use as a bone cement. The MWCNT loadings ranged from 0.1 to 1.0 wt.%. The fatigue properties of these MWCNT-PMMA bone cements were characterised at MWCNT loading levels of 0.1 and 0.25 wt.% with the type and wt.% loading of MWCNT used having a strong influence on the number of cycles to failure. The morphology and degree of dispersion of the MWCNT in the PMMA matrix at different length scales were examined using field emission scanning electron microscopy. Improvements in the fatigue properties were attributed to the MWCNT arresting/retarding crack propagation through the cement through a bridging effect and hindering crack propagation. MWCNT agglomerates were evident within the cement microstructure and the degree of agglomeration was dependent on the level of loading and functionality of the MWCNT. The biocompatibility of the MWCNT-PMMA cements at MWCNT loading levels upto 1.0 wt.% was determined by means of established biological cell culture assays using MG-63 cells. Cell attachment after 4h was determined using the crystal violet staining assay. Cell viability was determined over 7 days in vitro using the standard colorimetric MTT assay. Confocal scanning laser microscopy and SEM analysis was also used to assess cell morphology on the various substrates.     

HA-40vo1％Ti复合材料与动物骨组织相容性体内研究

采用热压烧结法制备HA-40vol％Ti复合材料，并通过体内植入试验，研究了该复合材料的生物相容性。结果表明，HA-40vol.％Ti复合材料具有良好的生物相容性和骨引导性，可以与骨发生骨整合，早期骨整合和骨引导性优于纯Ti。在整个植入时间段内，HA-40vol．％Ti复合材料与周围骨组织的结合强度均比纯钛的高，且增长的快。植入3月后，复合材料与新骨的结合强度已达到4．73MPa。     

Preparation of beta-tricalcium phosphate microsphere-hyaluronic acid-based powder gel composite as a carrier for rhBMP-2 injection and evaluation using long bone segmental defect model

The specific objective of this study was to evaluate whether rhBMP-2-loaded bio-scaffolds can be used as effective rhBMP-2 carriers in the implantation of bone defect sites or poor bone quality in host bone. The rhBMP-2 release pattern test showed slow results in both groups, and a 1:9 ratio composition with a high water-absorption rate was selected for in vivo study. All animals euthanized after 9 weeks. The new bone formation and bone quantity and quality of fibular samples were examined. The results showed that the rhBMP-2 powder gel composite improved the new bone formation in the cortical bone and the marrow space. The length of new bone formation ratio of the rhBMP-2 loaded composite group was significantly higher than the powder gel group. The composite of powder gel seems to be a nice carrier, and slow release of rhBMP-2 can promote new bone formation in a segmental cortical bone defect after implantation.     

Increase of basic fibroblast growth factor (bFGF,FGF-2) messenger RNA and protein following implantation of a microdialysis probe into rat hippocampus

In vivo microdialysis is an established tool for sampling extracellular fluid compartments. However, microdialysis faces the problem that the implantation of the probe damages the microenvironment from which measurements are derived. In this study, we examined the expression of basic fibroblast growth factor mRNA and protein at the cellular level after implantation of a microdialysis probe into the dorsal hippocampus and found that 8 h after inserting the probe bFGF mRNA was markedly increased in a relatively large area centered around the probe, involving both the dorsal hippocampus and the overlying cerebral cortex, as revealed by radioactive in situ hybridization. Using nonradioactive in situ hybridization with digoxigenin-labelled riboprobes, combined with immunohistochemistry for glial fibrillary acidic protein we demonstrated that bFGF mRNA was exclusively increased in astrocytes at the probe insertion site. Using immunohistochemistry we also found that bFGF-like immunoreactivity was increased after implantation of the probe close to the lesion site, as shown by an increased number of bFGF immunoreactive nuclear glial profiles. These results provide evidence that the implantation of a microdialysis probe into the brain induces activation of bFGF gene expression in astrocytes associated with nuclear bFGF-like immunoreactivity. We conclude that lesion-induced effects have to be considered when evaluating microdialysis data, and that mechanical trauma to the brain will activate astroglial trophism, as seen from the increased density of astroglial profiles demonstrating bFGF mRNA and protein levels.     

Crosslinking characteristics of an injectable poly(propylene fumarate)/beta-tricalcium phosphate paste and mechanical properties of the crosslinked composite for use as a biodegradable bone cement.

We investigated the crosslinking characteristics of an injectable composite paste of poly(propylene fumarate) (PPF), N-vinyl pyrrolidinone (N-VP), benzoyl peroxide (BP), sodium chloride (NaCl), and beta-tricalcium phosphate (beta-TCP). We examined the effects of PPF molecular weight, N-VP/PPF ratio, BP/PPF ratio, and NaCl weight percent on the crosslinking temperature, heat release upon crosslinking, gel point, and the composite compressive strength and modulus. The maximum crosslinking temperature did not vary widely among formulations, with the absolute values falling between 38 degrees and 48 degrees C, which was much lower than that of 94 degrees C for poly(methyl methacrylate) bone cement controls tested under the same conditions. The total heat released upon crosslinking was decreased by an increase in PPF molecular weight and a decrease in N-VP/PPF ratio. The gel point was affected strongly by the PPF molecular weight, with a decrease in PPF molecular weight more rapidly leading to a gel point. An increase in initiator concentration had the same effect to a lesser degree. The time frame for curing was varied from 1-121 min, allowing the composite to be tailored to specific applications. The compressive strength and compressive modulus values increased with decreasing N-VP/PPF, increasing NaCl content, and increasing BP/PPF ratio. For all formulations, the compressive strength values fell between 1 and 12 MPa, and the compressive modulus values fell between 23 and 265 MPa. These data suggest that injectable PPF/beta-TCP pastes can be prepared with handling characteristics appropriate for clinical orthopedic applications and that the mechanical properties of the cured composites are suitable for trabecular bone replacement.     

Real-time evaluation of nitric oxide (NO) levels in cortical and hippocampal areas with a nanopore-based electrochemical NO sensor

Nitric oxide (NO) is an important biomolecule for regulating various brain functions, such as the control of neurovascular tone. NO, however, cannot be stored inside cells where NO is produced and immediately diffuses through the cellular membrane and decays rapidly, which makes the detection of NO extremely hard in an in vivo setting. We constructed an amperometric NO nanosensor and utilized it to directly measure NO release in the living brain. The NO nanosensor uses nanopores (pores with an opening radii <500 nm) in which NO is oxidized at the porous platinum surface. The nanopore-based sensor was inserted vertically into the brains of anesthetized mice up to the end of the hippocampal CA 3 region, or to a depth of about 3 mm. The sensor was slowly advanced in the brain in 0.5 μm increments and in 0.05 s temporal steps. Different levels of NO release were monitored by the nanopore NO sensor during the course of the penetration. The hippocampal CA3 region had the highest level of NO release, which was followed by CA2 and CA1 of the hippocampus and the cortex. The levels of NO release were not uniformly distributed within the cortical and hippocampal areas of living brain. In sum, the nanopore-based NO sensor was able to grossly measure NO contents within living brain in real time and with high sensitivity. This study may provide good insights about the relationship between the distributions of NOS-immunoreactive neurons and the directly measured levels of NO release in brain.     

Release of gentamicin sulphate from a modified commercial bone cement. Effect of (2-hydroxyethyl methacrylate) comonomer and poly(N-vinyl-2-pyrrolidone) additive on release mechanism and kinetics

The influence of the (2-hydroxyethyl methacrylate) (HEMA) monomer addition as a comonomer to the cement liquid component and of a polymer, poly(N-vinyl-2-pyrrolidone) (PVP) to the solid component of a standard CMW-1 bone cement on gentamicin sulphate (GS) on its drug release properties have been studied. The addition of HEMA modifies the habit of the delivery curves. The incorporation of PVP into the cement matrix, apparently, did not very much modify the shape of the HEMA modified cement release curves, but led to a remarkable increase of the maximum amount of GS released. This effect was proportional to the PVP concentration incorporated. From the matrix composition and SEM data, a model based on the morphology of the matrix has been proposed. The cumulative amount of GS released by each slab Mt is most adequately fitted and represented by the equation Mt = c + at 1/2 + b[1 - exp(-nt)], which corroborates that the release occurs according to the model proposed. by means of three discrete mechanisms, namely: (i) a short-term initial elution due to the imperfections in the poly(methyl methacrylate) covering of the most external GS beads, burst effect by the buffer solution; (ii) followed by a fracture by stress cracking in an active media of the coated GS beads located on the external surface of the matrix where water molecules enter to dissolve GS molecules releasing them into the buffer solution by a diffusion-controlled process; and (iii) a third process in which the buffer solution penetrates into the internal voids and cracks creating a series of channels in a labyrinthic structure, which may facilitate the access of water molecules to the plastic-coated GS beads within the bulk matrix. This third process is enhanced by the incorporation of PVP beads as dissolved molecules within the matrix. This water-soluble additive is leachable, generating a highly porous structure in the cement. This HEMA and PVP modified cement may be used as a drug delivery system to modulate the GS release rate.     

Influence of a pre-blended antibiotic (gentamicin sulfate powder) on various mechanical, thermal, and physical properties of three acrylic bone cements

The aim of this work was to determine an array of mechanical, physical, and thermal properties of three pairs of commercially available acrylic bone cement brands, with the brands in each pair having the same compositions except that one contains 4.22 wt/wt% gentamicin sulfate blended with the powder by the manufacturer and the other one does not. The difference between the pairs was in the viscosity of the curing cement dough, with one pair of 'low-viscosity', one pair of 'medium-viscosity', and one pair of 'high-viscosity' brands being used. Thus, the brands studied cover the range of those used in anchoring some total joint replacements (TJRs). The properties determined were the strength, modulus, and work-to-fracture (all under four-point bending), plane-strain fracture toughness, Weibull mean fatigue life (fatigue conditions: 15 MPa; 2 Hz), activation energy and frequency factor for the cement polymerization process (both determined, using differential scanning calorimetry, at heating rates of 5, 10, 15, and 20 K min (1)), and the diffusion coefficient for the absorption of phosphate-buffered saline at 37 C by the cured cement. For each property determined, there was no significant difference in the mean values for the brands in each of the pairs. These results indicate that over the range of cement brands that are widely used in the anchoring of cemented TJRs, the addition of gentamicin sulfate powder does not degrade the properties of the cement, and, hence, may not adversely affect the in vivo longevity of the replacement.     

Enhanced pH stability,cell viability and reduced degradation rate of poly(L-lactide)-based composite in vitro: effect of modified magnesium oxide nanoparticles

The modified MgO nanoparticles (m-MgO-NPs) by a copolymer containing the malic acid and low molecular weight poly(L-lactide) (poly(L-lactide-co-malic acid), PLMA) have been successfully prepared. MgO nanoparticles (MgO-NPs) were coated by the PLMA and m-MgO-NPs were uniformly dispersed in the PLLA matrix to a novel biocomposite material (PLLA/m-MgO-NPs) with more excellent interface bonding and uniformer dispersion, compared to the PLLA/MgO-NPs. Compared to neat PLLA and PLLA/MgO-NPs film, the m-MgO-NPs not only shown the obvious neutralization effect on the acidic solution in the degradation of the PLLA and better hydrophilicity, but also exhibited the higher cell viability and decrease the toxicity to the cell in the degradation process of PLLA in vitro. In addition, m-MgO-NPs also reduced the degradation rate of the PLLA. The mechanisms for the excellent dispersion of nanoparticles, enhanced pH stability, reduced degradation rate of the PLLA and the cell viability in vitro in the case of PLLA/m-MgO-NPs have also been proposed and discussed in detail.     

Effect of water storage on fluoride release and mechanical properties of a polyacid-modified composite resin (compomer)

We evaluated the effect of water storage on fluoride release and mechanical properties of compomer restorative material.Fluoride release was recorded using a specific fluoride electrode.Flexural properties and fracture toughness were measured using a universal testing machine.Vickers hardness was measured using a micro-hardness tester.There was initial burst of fluoride release up to 1 w,which was diminished to a low level in 1 mon and remained relatively constant over 6 mon.Flexural strength and hardness were increased up to 1 mon followed by a gradual decrease up to 6 mon.Flexural modulus was decreased gradually up to 6 mon.Fracture toughness was increased during the first week and gradually decreased over the storage period.We concluded that flexural properties,fracture toughness,Vickers hardness and fluoride release of compomer were sensitive to water as well as storage time.There was a significant effect of fluoride release on the studied mechanical properties.     

In vivo dopamine (DA) receptor binding and behavioural effects of the putative DA autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 in rats with a unilateral nigral 6-OH-DA lesion

Summary The in vivo dopamine (DA) receptor binding and behavioural properties of the recently characterised putative preferential DA autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 were studied in rats with a unilateral 6-OH-DA lesion of the substantia nigra. The main findings were a) that (+)-UH 232 and (+)-AJ 76 per se failed to produce significant turning behaviour, b) that both agents antagonised contralateral rotation caused by the DA agonist apomorphine, including a change of the characteristic two-peak apomorphine rotation pattern into a single peak, indicating that the DA antagonist properties of (+)-UH 232 and (+)-AJ 76 are retained also at denervation-sensitised postsynaptic DA receptors and — in support of this notion — c) that (+)-UH 232 and (+)-AJ 76 were able to displace the specific in vivo binding of the DA receptor agonist DP-5,6-ADTN in the denervated as well as in the intact striata of the 6-OH-DA-lesioned animals. Interestingly, in this regard (+)-UH 232 was significantly less efficient on the lesioned as compared to the intact side. The DP-5,6-ADTN-displacing effect of (+)-AJ 76 did not, however, differ between the intact and the denervated striatum. The implications of the present findings are discussed with particular reference to DA receptor sensitivity and adaptational phenomena.     

Ambras syndrome: delineation of a unique hypertrichosis universalis congenita and association with a balanced pericentric inversion (8) (p11.2; q22)

Baumeister FAM, Egger J, Schildhauer MT, Stengel-Rutkowski S. Ambras syndrome: delineation of a unique hypertrichosis universalis congenita and association with a balanced pericentric inversion (8) (p11.2; q22). Clin Genet 1993: 44: 121–128. © Munksgaard, 1993
Congenital hypertrichosis universalis is a rare autosomal dominant disease. We report the further development of a Greek girl, now aged 3 years, the first case associated with a balanced structural chromosomal aberration. She was described as a neonate by Sigalas et al. (1990). Her persistent generalized hypertrichosis is most excessive on the face, ears and shoulders. Her fine silky hair is of the vellus, not the lanugo type. The syndrome features are characterized, referring to nine further published case reports. It is distinguished from other types of congenital hypertrichoses, which have been described in the literature under different synonyms. To avoid confusion in the terminology, we propose to name this type of hypertrichosis Ambras syndrome in reference to the first documented family with congenital hypertrichosis universalis in the 16th century.     

Treatment of stroke with (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate and bone marrow stromal cells upregulates angiopoietin-1/Tie2 and enhances neovascularization

Neovascularization may contribute to functional recovery after neural injury. Combination treatment of stroke with a nitric oxide donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETA-NONOate) and bone marrow stromal cells promotes functional recovery. However, the mechanisms underlying functional improvement have not been elucidated. In this study, we tested the hypothesis that combination treatment upregulates angiopoietin-1 and its receptor Tie2 in the ischemic brain and bone marrow stromal cells, thereby enhancing cerebral neovascularization after stroke. Adult wild type male C57BL/6 mice were i.v. administered PBS, bone marrow stromal cells 5x10(5), DETA-NONOate 0.4 mg/kg or combination DETA-NONOate with bone marrow stromal cells (n=12/group) after middle cerebral artery occlusion. Combination treatment significantly upregulated angiopoietin-1/Tie2 and tight junction protein (occludin) expression, and increased the number, diameter and perimeter of blood vessels in the ischemic brain compared with vehicle control (mean+/-S.E., P<0.05). In vitro, DETA-NONOate significantly increased angiopoietin-1/Tie2 protein (n=6/group) and Tie2 mRNA (n=3/group) expression in bone marrow stromal cells. DETA-NONOate also significantly increased angiopoietin-1 protein (n=6/group) and mRNA (n=3/group) expression in mouse brain endothelial cells (P<0.05). Angiopoietin-1 mRNA (n=3/group) was significantly increased in mouse brain endothelial cells treated with DETA-NONOate in combination with bone marrow stromal cell-conditioned medium compared with cells treated with bone marrow stromal cell-conditioned medium or DETA-NONOate alone. Mouse brain endothelial cell capillary tube-like formation assays (n=6/group) showed that angiopoietin-1 peptide, the supernatant of bone marrow stromal cells and DETA-NONOate significantly increased capillary tube formation compared with vehicle control. Combination treatment significantly increased capillary tube formation compared with DETA-NONOate treatment alone. Inhibition of angiopoietin-1 significantly attenuated combination treatment-induced tube formation. Our data indicated that combination treatment of stroke with DETA-NONOate and bone marrow stromal cells promotes neovascularization, which is at least partially mediated by upregulation of the angiopoietin-1/Tie2 axis.     

Fixation of distal femoral osteotomies with self-reinforced poly(L/DL)lactide 70 : 30 and self-reinforced poly(L/DL)lactide 70 : 30/bioactive glass composite rods. An experimental study on rabbits

Two self-reinforced poly(L/DL)lactide 70 : 30 or self-reinforced poly(L/DL)lactide 70 : 30/bioactive glass (SR-P(L/DL)LA/bioactive glass) composite rods (2 mm × 40 mm) were implanted into the dorsal subcutaneous tissue and osteotomies of the distal femur were fixed with these rods (2 mm × 26 mm) in 36 rabbits. The follow-up times varied from 3 to 100 weeks. After the animals were killed, three-point bending and shear tests and molecular weight measurements were performed for subcutaneously placed rods. Radiological, histological, histomorphometrical, microradiographic and oxytetracycline-fluorescence studies of the osteotomized and intact control femora were performed. After 12 weeks the SR-P(L/DL)LA rods had fragmented into pieces and the mechanical properties could not be measured. The SR-P(L/DL)LA/bioactive glass rods lost their mechanical properties slower, and at 24 weeks the bending strength had decreased by 39% and the shear strength by 50%. After that the mechanical properties of the SR-P(L/DL)LA/bioactive glass rods could not be measured. All osteotomies healed well, and no gross signs of inflammatory reactions were observed. One slight displacement was seen in the three-week follow-up group with SR-P(L/DL)LA rods. Signs of resorption of the implants were seen after 48 weeks in the SR-P(L/DL)LA group and after 24 weeks in the SR-P(L/DL)LA/bioactive glass group. The SR-P(L/DL)LA/bioactive glass rods were almost totally resorbed from the bone at 100 weeks. The present investigation showed that the mechanical strength and fixation properties of the SR-P(L/DL)LA and the SR-P(L/DL)LA/bioactive glass composite rods are suitable for fixation of cancellous bone osteotomies in rabbits.     

In vitro and in vivo evaluation of osteoinductivity and bone fusion ability of an activin a/BMP2 chimera (AB204): a comparison study between AB204 and rhBMP-2

This study compared osteoinductivity and osteogenic capacity between AB204 and rhBMP-2 using hMSCs in vitro and a beagle’s posterolateral spinal fusion model. Cultured hMSCs were treated with AB204 or rhBMP-2 with low to high doses. Three male beagles were performed posterolateral spinal fusion with biphasic calcium phosphate (2?ml)?+?AB204 or rhBMP-2 (20, 50 or 200?µg). They were euthanized after 8?weeks. The fusion rate and bone formation of spine samples were examined. AB204 had higher alkaline phosphatase activity, mineralization and osteogenic-related gene expression than rhBMP-2. Fusion rates in all rhBMP-2 groups were 0. They were 100% for 50?μg and 200?μg AB204 groups. Therefore, AB204 showed higher osteogenicity than rhBMP-2. It could be a better bone graft substitute.     

Myelodysplastic/myeloproliferative disease with erythropoietic hyperplasia (erythroid preleukemia) and the unique translocation (8;9)(p23;p24): first description of a case

We report on a patient fulfilling the diagnostic criteria of unclassifiable myelodysplastic/myeloproliferative diseases with prominent erythropoietic hyperplasia/dysplasia (erythroid preleukemia) and the unique translocation (8;9)(p23;p24). The patient presented with B-symptoms, erythroblastemia, thrombopenia, marked eosinophilia, presence of myeloid precursors in the peripheral blood, and decreased erythropoietin level. Nodular peritrabecular polymorphous blasts, dysplastic megakaryocytes, and a diffuse argyrophilic fibrosis were detected in the trephine bone marrow biopsy. Immunohistochemically, the blasts stained positively for glycophorin C and hemoglobin A; the proliferation fraction was nearly 90% in the Ki-67 stain. Expression of the phosphorylated Janus kinase 2 was detected in almost all megakaryocytes and in isolated erythroblast islets, suggesting a probable activation of Janus kinase 2, the jak-2 gene being mapped on 9p24. Ten months after initial diagnosis, the disease progressed to frank acute erythroid leukemia. We report for the first time a myelodysplastic/myeloproliferative disease (erythroid preleukemia) accompanied by the specific chromosomal aberration t(8;9)(p23;p24), distinct histopathology, and clinical and laboratory symptoms, and progress to acute erythroid leukemia.