Thermal suit in preventing unintentional intraoperative hypothermia during general anaesthesia: a randomized controlled trial.

BACKGROUND: Unintentional perioperative hypothermia causes serious adverse effects to surgical patients. Thermal suit (T-Balance® ) is an option for passive warming perioperatively. We hypothesized that the thermal suit will not maintain normothermia more efficiently than conventional cotton clothes when also other preventive procedures against unintentional hypothermia are used. METHODS: One hundred patients were recruited to this prospective, randomized trial. They were allocated to the Thermal Suit group or a Control group wearing conventional hospital cotton clothes. All patients received our institution's standard treatment against unintentional hypothermia including a warming mattress, a forced-air upper body warming blanket and a warming device for intravenous fluids. Eardrum temperature was measured pre-operatively. In the operating room and post-anaesthesia care unit temperatures were measured from four locations: oesophagus, left axilla, dorsal surface of the left middle finger and dorsum of the left foot. The primary outcome measure was temperature change during robotic-assisted laparoscopic radical prostatectomy. RESULTS: The temperatures of 96 patients were analysed. There was no difference in mean core temperatures, axillary temperatures or skin temperatures on the finger between the groups. Only foot dorsum temperatures were significantly lower in the Thermal Suit group. Intraoperative temperature changes were similar in both groups. In the post-anaesthesia care unit temperature changes were minimal and they did not differ between the groups. CONCLUSION: Provided that standard preventive procedures in maintaining normothermia are effective the thermal suit does not provide any additional benefit over conventional cotton clothes during robotic-assisted laparoscopic radical prostatectomy.

Comparison of Bispectral Index and Entropy values with electroencephalogram during surgical anaesthesia with sevoflurane.

BACKGROUND: Concomitantly recorded Bispectral Index® (BIS) and Entropy™ values sometimes show discordant trends during general anaesthesia. Previously, no attempt had been made to discover which EEG characteristics cause discrepancies between BIS and Entropy. We compared BIS and Entropy values, and analysed the changes in the raw EEG signal during surgical anaesthesia with sevoflurane. METHODS: In this prospective, open-label study, 65 patients receiving general anaesthesia with sevoflurane were enrolled. BIS, Entropy and multichannel digital EEG were recorded. Concurrent BIS and State Entropy (SE) values were selected. Whenever BIS and SE values showed ≥10-unit disagreement for ≥60 s, the raw EEG signal was analysed both in time and frequency domain. RESULTS: A ≥10-unit disagreement ≥60 s was detected 428 times in 51 patients. These 428 episodes accounted for 5158 (11%) out of 45 918 analysed index pairs. During EEG burst suppression, SE was higher than BIS in 35 out of 49 episodes. During delta-theta dominance, BIS was higher than SE in 141 out of 157 episodes. During alpha or beta activity, SE was higher than BIS in all 49 episodes. During electrocautery, both BIS and SE changed, sometimes in the opposite direction, but returned to baseline values after electrocautery. Electromyography caused index disagreement four times (BIS > SE). CONCLUSIONS: Certain specific EEG patterns, and artifacts, are associated with discrepancies between BIS and SE. Time and frequency domain analyses of the original EEG improve the interpretation of studies involving BIS, Entropy and other EEG-based indices. CLINICAL TRIAL REGISTRATIONCLINICALTRIALSGOVIDENTIFIER: NCT01077674.

Effect of heat treatment of wood on the morphology, surface roughness and penetration of simulated and human blood.

BACKGROUND: Wood has been used as a model material for the development of novel fiber-reinforced composite bone substitute biomaterials. In previous studies heat treatment of wood was perceived to significantly increase the osteoconductivity of implanted wood material. AIM: The objective of this study was to examine some of the changing attributes of wood materials that may contribute to improved biological responses gained with heat treatment. METHODS: Untreated and 140°C and 200°C heat-treated downy birch (Betula pubescens Ehrh.) were used as the wood materials. Surface roughness and the effect of pre-measurement grinding were measured with contact and non-contact profilometry. Liquid interaction was assessed with a dipping test using two manufactured liquids (simulated blood) as well as human blood. SEM was used to visualize possible heat treatment-induced changes in the hierarchical structure of wood. RESULTS: The surface roughness was observed to significantly decrease with heat treatment. Grinding methods had more influence on the surface contour and roughness than heat treatment. The penetration of the human blood in the 200°C heat-treated exceeded that in the untreated and 140°C heat-treated materials. SEM showed no significant change due to heat treatment in the dry-state morphology of the wood. DISCUSSION: The results of the liquid penetration test support previous findings in literature concerning the effects of heat treatment on the biological response to implanted wood. Heat-treatment has only a marginal effect on the surface contour of wood. The highly specialized liquid conveyance system of wood may serve as a biomimetic model for the further development of tailored fiber-composite materials.

Surface modification of fiber reinforced polymer composites and their attachment to bone simulating material.

The purpose of this study was to investigate the effect of fiber orientation of a fiber-reinforced composite (FRC) made of poly-methyl-methacrylate (PMMA) and E-glass to the surface fabrication process by solvent dissolution. Intention of the dissolution process was to expose the fibers and create a macroporous surface onto the FRC to enhance bone bonding of the material. The effect of dissolution and fiber direction to the bone bonding capability of the FRC material was also tested. Three groups of FRC specimens (n = 18/group) were made of PMMA and E-glass fiber reinforcement: (a) group with continuous fibers parallel to the surface of the specimen, (b) continuous fibers oriented perpendicularly to the surface, (c) randomly oriented short (discontinuous) fibers. Fourth specimen group (n = 18) made of plain PMMA served as controls. The specimens were subjected to a solvent treatment by tetrahydrofuran (THF) of either 5, 15 or 30 min of time (n = 6/time point), and the advancement of the dissolution (front) was measured. The solvent treatment also exposed the fibers and created a surface roughness on to the specimens. The solvent treated specimens were embedded into plaster of Paris to simulate bone bonding by mechanical locking and a pull-out test was undertaken to determine the strength of the attachment. All the FRC specimens dissolved as function of time, as the control group showed no marked dissolution during the study period. The specimens with fibers along the direction of long axis of specimen began to dissolve significantly faster than specimens in other groups, but the test specimens with randomly oriented short fibers showed the greatest depth of dissolution after 30 min. The pull-out test showed that the PMMA specimens with fibers were retained better by the plaster of Paris than specimens without fibers. However, direction of the fibers considerably influenced the force of attachment. The fiber reinforcement increases significantly the dissolution speed, and the orientation of the glass fibers has great effect on the dissolving depth of the polymer matrix of the composite, and thus on the exposure of fibers. The glass fibers exposed by the solvent treatment enhanced effectively the attachment of the specimen to the bone modeling material.

Can electromyographic arousal be detected visually on the Datex-Ohmeda S/5™ anesthesia monitor?

BACKGROUND: Electroencephalogram (EEG)-based depth of anaesthesia monitoring is susceptible to contaminating electromyographic (EMG) activity. Many authorities have suggested that anaesthesiologists using these monitors should interpret the raw EEG waveform seen on the anaesthesia monitor. METHODS: In 34 patients anaesthetized with propofol using two doses of rocuronium (0.6 and 1.2 mg/kg), we studied whether the EMG arousal can be detected visually on the anaesthesia monitor. The Bispectral Index (BIS) and Entropy biosignals on the monitor were recorded with a video camera, and the one-channel EEG recorded by the Entropy strip was collected on a laptop computer. The recordings and the one-channel EEG were analyzed offline by two experts (anaesthesiologist and neurophysiologist), both with a long experience on anaesthesia-related EEG. RESULTS: EMG arousal existed in 14/34 and 13/33 patients in the BIS and Entropy biosignals, respectively. The anaesthesiologist detected EMG on the monitor in 7/14 patients with BIS (sensitivity 50%) and in 4/13 patients with Entropy (31%). The clinical neurophysiologist detected EMG in 6/14 (43%) patients with BIS and in 5/13 (38%) with Entropy. The specificity of the EMG analyses was 55 and 65% with BIS, and 85 and 90% with Entropy. EMG arousal was detected in BIS biosignal in 10/17 and 4/17 patients with 0.6 and 1.2 mg/kg doses of rocuronium (P = 0.04). CONCLUSIONS: In contrast to many EEG phenomena, EMG activity cannot be accurately detected visually from the raw EEG on the anaesthesia monitor. Further development in the quality of the anaesthesia monitors is warranted.

Elevated BIS and Entropy values after sugammadex or neostigmine: an electroencephalographic or electromyographic phenomenon?

BACKGROUND: Sugammadex is designed to antagonize neuromuscular blockade (NMB) induced by rocuronium or vecuronium. In clinical practice, we have noticed a rise in the numerical values of bispectral index (BIS) and Entropy, two electroencephalogram (EEG) - based depth of anesthesia monitors, during the reversal of the NMB with sugammadex. The aim of this prospective, randomized, double-blind study was to test this impression and to compare the effects of sugammadex and neostigmine on the BIS and Entropy values during the reversal of the NMB. METHODS: Thirty patients undergoing gynecological operations were studied. Patients were anesthetized with target-controlled infusions of propofol and remifentanil, and rocuronium was used to induce NMB. After operation, during light propofol-remifentanil anesthesia, NMB was antagonized with sugammadex or neostigmine. During the following 5 min, the numerical values of BIS, BIS electromyographic (BIS EMG) and Entropy were recorded on a laptop computer, as well as the biosignal recorded by the Entropy strip. The Entropy biosignal was studied off-line both in time and frequency domain to see if NMB reversal causes changes in EEG. RESULTS: In some patients, administration of sugammadex or neostigmine caused a significant rise in the numerical values of BIS, BIS EMG and Entropy. This phenomenon was most likely caused by increased electromyographic (EMG) activity. The administration of sugammadex or neostigmine appeared to have only minimal effect on EEG. CONCLUSION: The EMG contamination of EEG causes BIS and Entropy values to rise during reversal of rocuronium-induced NMB in light propofol-remifentanil anesthesia.

Explaining Entropy responses after a noxious stimulus, with or without neuromuscular blocking agents, by means of the raw electroencephalographic and electromyographic characteristics.

BACKGROUND: Entropy™, an anaesthetic EEG monitoring method, yields two parameters: State Entropy (SE) and Response Entropy (RE). SE reflects the hypnotic level of the patient. RE covers also the EMG-dominant part of the frequency spectrum, reflecting the upper facial EMG response to noxious stimulation. We studied the EEG, EMG, and Entropy values before and after skin incision, and the effect of rocuronium on Entropy and EMG at skin incision during sevoflurane-nitrous oxide (N2O) anaesthesia. METHODS: Thirty-eight patients were anaesthetized with sevoflurane-N2O or sevoflurane-N2O-rocuronium. The biosignal was stored and analysed off-line to detect EEG patterns, EMG, and artifacts. The signal, its power spectrum, SE, RE, and RE-SE values were analysed before and after skin incision. The EEG arousal was classified as ß (increase in over 8 Hz activity and decrease in under 4 Hz activity with a typical ß pattern) or δ (increase in under 4 Hz activity with the characteristic rhythmic δ pattern and a decrease in over 8 Hz activity). RESULTS: The EEG arousal appeared in 17 of 19 and 15 of 19 patients (NS), and the EMG arousal in 0 of 19 and 13 of 19 patients (P<0.01) with and without rocuronium, respectively. Both ß (n=30) and EMG arousals increased SE and RE. The δ arousal (n=2) decreased both SE and RE. A significant increase in RE-SE values was only seen in patients without rocuronium. CONCLUSIONS: During sevoflurane-N2O anaesthesia, both EEG and EMG arousals were seen. ß and δ arousals had opposite effects on the Entropy values. The EMG arousal was abolished by rocuronium at the train of four level 0/4.

Effects of heat treatment of wood on hydroxylapatite type mineral precipitation and biomechanical properties in vitro.

Wood is a natural fiber reinforced composite. It structurally resembles bone tissue to some extent. Specially heat-treated birch wood has been used as a model material for further development of synthetic fiber reinforced composites (FRC) for medical and dental use. In previous studies it has been shown, that heat treatment has a positive effect on the osteoconductivity of an implanted wood. In this study the effects of two different heat treatment temperatures (140 and 200 degrees C) on wood were studied in vitro. Untreated wood was used as a control material. Heat treatment induced biomechanical changes were studied with flexural and compressive tests on dry birch wood as well as on wood after 63 days of simulated body fluid (SBF) immersion. Dimensional changes, SBF sorption and hydroxylapatite type mineral formation were also assessed. The results showed that SBF immersion decreases the biomechanical performance of wood and that the heat treatment diminishes the effect of SBF immersion on biomechanical properties. With scanning electron microscopy and energy dispersive X-ray analysis it was shown that hydroxylapatite type mineral precipitation formed on the 200 degrees C heat-treated wood. An increased weight gain of the same material during SBF immersion supported this finding. The results of this study give more detailed insight of the biologically relevant changes that heat treatment induces in wood material. Furthermore the findings in this study are in line with previous in vivo studies.

Osteoblast response to polymethyl methacrylate bioactive glass composite.

Polymethylmethacrylate (PMMA) has been used in many orthopedic and dental applications since the 1960s. Biocompatibility of newly developed surface porous fiber reinforced (SPFR) PMMA based composite has not been previously proven in cell culture environment. Analysis of rat bone marrow stromal cells grown on the different test materials showed only little difference in normalized cell activity or bone sialoprotein (BSP) production between the test materials, but the osteocalcin (OC) levels remained higher (P < 0.015-0.005) through out the test with SPFR-material when compared to tissue culture poly styrene (TCPS). The cells grown on SP-FRC material also showed highest calcium depletion from the culture medium (P < 0.026-0.001) when compared to all other test substrates. SEM images of the cultured samples confirmed that all the materials enabled cell spreading and growth on their surface, but the roughened surface remarkably enhanced this process of cell attachment, division and calcified nodule formation. This study shows that the SP-FRC composite material does not elicit harmful/toxic reactions in cell cultures more than neutral TCPS and can be considered biocompatible. The material possesses good capabilities to form new mineralized tissue onto its surface, and through that a possibility to bond directly to bone. Rough surface seems to enhance osteoblast proliferation and formation of mineralized extracellular matrix.

Bone attachment to glass-fibre-reinforced composite implant with porous surface.

A method has recently been developed for producing fibre-reinforced composites (FRC) with porous surfaces, intended for use as load-bearing orthopaedic implants. This study focuses on evaluation of the bone-bonding behaviour of FRC implants. Three types of cylindrical implants, i.e. FRC implants with a porous surface, solid polymethyl methacrylate (PMMA) implants and titanium (Ti) implants, were inserted in a transverse direction into the intercondular trabeculous bone area of distal femurs and proximal tibias of New Zealand White rabbits. Animals were sacrificed at 3, 6 and 12 weeks post operation, and push-out tests (n=5-6 per implant type per time point) were then carried out. At 12 weeks the shear force at the porous FRC-bone interface was significantly higher (283.3+/-55.3N) than the shear force at interfaces of solid PMMA/bone (14.4+/-11.0 N; p<0.001) and Ti/bone (130.6+/-22.2N; p=0.001). Histological observation revealed new bone growth into the porous surface structure of FRC implants. Solid PMMA and Ti implants were encapsulated mostly with fibrous connective tissue. Finite element analysis (FEA) revealed that porous FRC implants had mechanical properties which could be tailored to smooth the shear stress distribution at the bone-implant interface and reduce the stress-shielding effect.

The effect of heat treatment of wood on osteoconductivity.

Wood is a natural porous fibre composite, which has some structural similarities to bone. Recently, it has been used as a modelling material in developing synthetic fibre-reinforced composite to be used as load-bearing non-metallic artificial bone material. In this study, the behaviour of wood implanted into bone was studied in vivo in the femur bone of the rabbit. Wood was pre-treated by heat, which altered its chemical composition and structure, as well as the biomechanical properties. In the heat treatment, wood's dimensional stability is enhanced, equilibrium moisture content reduces and the biological durability increases. Cone-shaped implants were manufactured from heat-treated (at 200 and 140 degrees C) birch wood (Betula pubescens) and from untreated birch. A total of 62 implants were placed in the distal femur of 50 white New Zealand rabbits. The behaviour of the implants was studied at 4, 8 and 20 weeks with histological and histometrical analysis. Osteoconductive contact line and the presence of fibrous tissue and foreign body reaction were determined. The amount of fibrous tissue diminished with time, and the absence of foreign body reaction was found to be in correlation to the amount of heat treatment. Histologically found contact between the implant and the host bone at the interface was significantly more abundant in the 200 degrees C group (avg. 12.8%) vs. the 140 degrees C (avg. 2.7%) and the untreated groups (avg. 0.6%). It was observed that the heat treatment significantly modified the biological behaviour of the implanted wood. The changes of the wood by heat treatment showed a positive outcome concerning osteoconductivity of the material.

Facial muscle activity, Response Entropy, and State Entropy indices during noxious stimuli in propofol-nitrous oxide or propofol-nitrous oxide-remifentanil anaesthesia without neuromuscular block.

BACKGROUND: Entropy is an anaesthetic EEG monitoring method, calculating two numerical parameters: State Entropy (SE, range 0-91) and Response Entropy (RE, range 0-100). Low Entropy numbers indicate unconsciousness. SE uses the frequency range 0.8-32 Hz, representing predominantly the EEG activity. RE is calculated at 0.8-47 Hz, consisting of both EEG and facial EMG. RE-SE difference (RE-SE) can indicate EMG, reflecting nociception. We studied RE-SE and EMG in patients anaesthetized without neuromuscular blockers. METHODS: Thirty-one women were studied in propofol-nitrous oxide (P) or propofol-nitrous oxide-remifentanil (PR) anaesthesia. Target SE value was 40-60. RE-SE was measured before and after endotracheal intubation, and before and after the commencement of surgery. The spectral content of the signal was analysed off-line. Appearance of EMG on EEG was verified visually. RESULTS: RE, SE, and RE-SE increased during intubation in both groups. Elevated RE was followed by increased SE values in most cases. In these patients, spectral analysis of the signal revealed increased activity starting from low (<20 Hz) frequency area up to the highest measured frequencies. This was associated with appearance of EMG in raw signal. No spectral alterations or EMG were seen in patients with stable Entropy values. CONCLUSIONS: Increased RE is followed by increased SE at nociceptive stimuli in patients not receiving neuromuscular blockers. Owing to their overlapping power spectra, the contribution of EMG and EEG cannot be accurately separated with frequency analysis in the range of 10-40 Hz.

Long-term evaluation of blood silicon and ostecalcin in operatively treated patients with benign bone tumors using bioactive glass and autogenous bone.

In a study on 25 patients with verified benign bone tumors, bioactive glass (BG) and autogenous bone (AB) were used as bone-graft substitutes. The patients were randomized into two groups according to the filling material. Blood samples were taken both preoperatively, at 2 weeks, and 3, 8, 12, 24, and 36 months postoperatively, for evaluation of silicon concentration in blood. In the determination, direct current plasma atomic emission spectroscopy was used. No significant difference in blood silicon concentration between the BG group or the AB group could statistically be observed (p = 0.5400), and neither did the size of the bone tumor (p = 0.4259) nor the follow-up time affect the results (p = 0.2094). Concentration of osteocalcin in blood was significantly higher for large cysts (p < 0.0001). The filler material (BG or AB) did not affect the osteocalcin concentration level in blood.

Surface porous fibre-reinforced composite bulk bone substitute.

The aim of this study was to describe and evaluate the significance of a porous surface with bioactive glass granules (S53P4) covering an artificial bulk material based on polymethylmetacrylate (PMMA) and fibre-reinforced composite (FRC) technology. Effort was focused particularly on characters of the porous surface and biomechanical properties of the material in vitro , and test in vivo the implant in reconstruction in an experimental long bone segment defect model. The defect, 10 mm in length, created in the shaft of rabbit tibia, was reconstructed by the implant and fixed by intramedullary K-wires. The implant was incorporated within 4 weeks by new bone growth from the host bone covering particularly its posterior surface and cortex/implant junctions with bridging trabecular bone. Later, at 8 weeks, new bone was found also at the cortex/implant interface and in the medullary canal of the implant. Histometric measurements revealed direct bone/implant surface contact in 34% at the interface. Bioactive glass granules in the porous surface evoked the most direct contact with bone. The implants manufactured from PMMA only served as a control group, and showed significantly lower osteoconductive properties. Biomechanical measurements in vitro of fibre-reinforced PMMA specimens revealed values for bending strength and the flexural modulus to match them to human bone. This artificial bulk bone material based on PMMA/FRC technology seems to have proposing properties to be used as a bone substitute on load-bearing conditions.

Granule size and composition of bioactive glasses affect osteoconduction in rabbit.

Bioactive glass granules of three different compositions, regarding particularly Si- and Al- content (S53P4, S59.7P2.5, S52P3) and of two different granule sizes (200-250 microm and 630-800 microm) were implanted for 4 and 8 weeks in the distal part of rabbit femur. The effect of glass composition and granule size on bone formation was studied. The results were evaluated using histology, computerized histomorphometry, scanning electron microscopy and energy dispersive X-ray analysis, and used for mathematical description of bone formation. The results showed that both the composition of the glass and the granule size of the granules, have influence on bone growth from the surrounding tissue. Glass S53P4, which from previous observations is known to be an effective bioactive glass and widely used in the Biomaterial Project of Turku, Finland, showed bone bonding and increasing bone growth between the granules. Glass S59.7P2.5 which due to its high Si-content should be inert, showed bone bonding. At 4 weeks the bone growth was significantly more abundant in bone defects filled with large granules (630-800 microm) than in defects filled with small granules (200-250 microm). Glass S52P3 with an alumina content of 3 wt %, showed good bone conduction, possibly even bone bonding for granules of 630-800 microm size. Granules of 200-250 microm with a high alumina content at the surface of the reaction layer, showed hardly any bone contact at all. This data, therefore, gives new information concerning bone bonding and osteoconduction of bioactive glasses with a high silica or alumina content.

Bioactive glass as bone-graft substitute for posterior spinal fusion in rabbit.

Bioactive glass S53P4 and autogenous bone were studied as bone graft materials for spinal fusion in a rabbit model. Sixteen rabbits underwent surgery by a dorsal approach. A bioactive glass, a combination of bioactive glass and autogenous bone (70/30 vol%), and autogenous bone were implanted at two thoracolumbar vertebraes for 4 and 12 weeks. The volume, consolidation to vertebrae, and fusion of the graft material were evaluated with plain-film radiology, computed tomography (CT) and bone-mineral density measurements, and compared with histomorphometrical measurements. Radiological consolidation by CT of bone graft to underlying vertebrae at 12 weeks was observable in all groups. This was histologically confirmed as bone was growing from the vertebrae into the graft material. Radiologic fusion of vertebraes was, at 12 weeks, observable in all groups in 50--75% of the cases. The radiologic fusion seen at the CT scans could, however, not be confirmed by histology in any of the three groups. Significant differences for graft material and observation period with the use of bone-mineral density measurements (Hounsfield units) were also observable, with the highest measured values for the bioactive glass group and the lowest for the autogenous bone group. The results indicate that bioactive glass have potential as bone-graft material in spinal fusion. The reliability of radiologic evaluation methods in spinal surgery using bone substitutes is also questioned and discussed.

Tissue response to bioactive glass and autogenous bone in the rabbit spine.

Bioactive glass S53P4 and autogenous bone were used as bone graft materials in an experimental rabbit model for spinal fusion. The study focused on differences in bone formation using bioactive glass and autogenous bone as bone graft materials. Bioactive glass, a mixture of bioactive glass and autogenous bone or autogenous bone was implanted for 4 and 12 weeks at the thoracolumbar level. Undecalcified sections were prepared for histological and histomorphometric evaluation. New bone formation was seen in all implanted areas, with the bone growing from the surface of the vertebrae enclosing both glass and autogenous bone in the bone fusion mass. During the observation period, the measured amount of bone remained at the same level in the autograft group, while in the glass and the glass/autograft bone groups it increased. By 12 weeks, no significant difference in bone formation between the three groups was observable. The bone formation in two selected standardized areas at 12 weeks was 21 and 24% in the glass group, 23 and 28% in the glass/autograft bone group and 27 and 26% in the autograft bone group. We consider bioactive glass as a potential bone graft material in experimental spinal fusion.

Bone morphogenetic protein in bone neoplasms: comparison of different detection methods.

The presence of bone morphogenetic proteins (BMPs) in 13 primary bone neoplasms was investigated with conventional bioassay method and immunohistochemically using antiserum against highly purified mixture of bovine BMPs as antibody. In conventional bioassay after implantation of lyophilized bone tumor tissues into mouse muscle pouches 9/13 samples turned out positive by radiography and 10/13 histologically. By immunohistochemical staining, using the avidin-biotin-peroxidase method, signs of BMPs could be verified in all cases investigated. Microscopical scoring showed the local concentration of BMPs to be especially high in sections from giant cell tumors when compared to other bone neoplasms.

Immune responses and clinical outcome of massive human osteoarticular allografts.

Cell mediated immune responses as measured by lymphocyte proliferation induced by the mitogens phytohemagglutinin and concanavalin A and antigen extracts of donor derived bone were studied within 2 years after wide resection of bone tumors in 18 patients receiving fresh frozen massive osteoarticular allografts. No uniform changes were seen in mitogen induced responses in 18 patients. However, five of nine patients tested with antigen extracts of donor derived bone showed elevated immune responses, one moderate and four weak. The incorporation of the allograft (evaluated by repeated radiographs; specific isotope techniques; clinical outcome assessed by the functional rating scores of Mankin-Waber and the Musculoskeletal Tumor Society; and histologic biopsy findings on new bone formation) did not differ in these patients from those in patients without any response to donor derived tissue. During a long term followup (mean, 11 years; range, 2-20 years), degenerative joint and sclerotic density bone changes developed after 2 to 4 years without correlation to immune responses. Histologic specimens showed no signs of immunologic reaction, and no clinical rejection episodes were recorded. A slightly variable immune response to allograft bone seems to occur, but its clinical significance for outcome of the grafts remains to be determined. The low immune responses might reflect a low antigen release rate through an indirect pathway or immunologic tolerance to antigens or proteins shed from massive allografts that are nonliving scaffold implants during the creeping substitution process, corresponding to the low immune response and the slow histologic repair.