Efeito da desmineralização ácida da interface enxerto-leito na consolidação de enxertos ósseos autógenos em bloco / Influence of acid demineralization of contacting osseous surfaces on the consolidation of autogenous onlay bone grafts

Para testar a hipótese de que a desmineralização in situ das superfícies de contato enxerto-leito, e a forma como o enxerto é estabilizado ao leito, podem influenciar os mecanismos envolvidos na consolidação do enxerto, fragmentos ósseos de 10 mm de diâmetro foram removidos das metáfises proximais tibiais de 36 coelhos (Oryctolagus Cuniculus) e transplantados para uma área adjacente. Na tíbia esquerda dos animais, as superfícies de contato do enxerto e do leito hospedeiro foram desmineralizadas com ácido cítrico pH 1,0 por 3 minutos antes dos enxertos serem fixados ao leito. Na tíbia direita, o transplante do bloco ósseo não foi precedido de desmineralização. Metade dos enxertos foi imobilizada sobre o leito pela superposição de uma membrana não reabsorvível de politetrafluoretileno colada com cianoacrilato ao leito à distância da interface enxerto-leito. A outra metade dos enxertos foi fixada por um parafuso de titânio no centro do enxerto. Assim, foram formados 4 grupos de estudo: membrana (M), membrana + ácido (MA), parafuso (P) e parafuso + ácido (PA). Três animais de cada grupo forneceram espécimes para análise microscópica quantitativa e qualitativa aos 15, 30 e 45 dias de pós-operatório. A análise qualitativa demonstrou que não houve formação óssea na interface em nenhum espécime aos 15 dias e que nos demais períodos, em todos os grupos, a quantidade de tecido ósseo neoformado na interface e seu estágio de maturação aumentaram com o tempo. Ambos os métodos de fixação empregados foram eficientes em manter os enxertos em posição, porém a membrana promoveu menor reabsorção da estrutura do enxerto. A análise quantitativa computadorizada revelou que, aos 30 dias, os grupos MA e PA apresentaram maior área de formação óssea na interface (71,34 ± 12,03%; 56,74 ± 2,15% respectivamente) em relação aos grupos M e P (51,75 ± 11,02%; 43,95 ± 4,05% respectivamente) e superfícies de consolidação óssea mais extensas (93,41 ± 5,95%; 93,73 ± 4,96%...

In order to test the hypothesis that the demineralization "in situ" of contacting surfaces of bone graft/bone bed and the fixation method used for graft stabilization can influence the mechanisms involved in the consolidation of the graft, bone fragments of 10 mm in diameter were removed from the proximal tibial metaphysis of thirty-six male rabbits (Oryctolagus Cuniculus) and transplanted to an adjacent area. In the left tibia of the animals, the contacting surfaces of the graft and host bed were demineralized with citric acid pH 1.0 for 3 minutes before the grafts were fixed to the receptor bed. In the right tibia, the bone block transplantation was not preceded by demineralization. Half of the grafts were immobilized on the bone bed by a nonresorbable polytetrafluoroethylene membrane glued with cyanoacrylate adhesive to the host bed distant from the bone graft-bone bed interface. The other half of the grafts were fixed by a titanium screw in the center of the graft. Thus, four groups were formed: membrane (M), membrane + acid (MA), screw (P) and screw + acid (PA). Three animals from each group provided specimens for quantitative and qualitative microscopic analysis at 15, 30 and 45 days postoperatively. Qualitative analysis showed no significant bone formation at the interface in any specimen of the groups at 15 days and on the other periods in all groups, the amount of newly formed bone at the interface as well as the stage of bone maturation increased with time. Both fixation methods were effective in maintaining the graft in position, but the membrane resulted in less resorption of the graft. Quantitative analysis, performed by means of a computer program for image analysis, showed that at day 30, groups MA and PA, showed greater area of bone formation at the interface (71.34 ± 12.03%; 56.74 ± 2 15%) than groups M and P (51.75 ± 11.02%, 43.95 ± 4.05%) and more osseointegrated bone surfaces (93.41 ± 5.95%, 93.73 ± 4.96%) than those...

Autologous olfactory mucosal cell transplants in clinical spinal cord injury: a randomized double-blinded trial in a canine translational model.

This study was designed to determine whether an intervention proven effective in the laboratory to ameliorate the effects of experimental spinal cord injury could provide sufficient benefit to be of value to clinical cases. Intraspinal olfactory ensheathing cell transplantation improves locomotor outcome after spinal cord injury in 'proof of principle' experiments in rodents, suggesting the possibility of efficacy in human patients. However, laboratory animal spinal cord injury cannot accurately model the inherent heterogeneity of clinical patient cohorts, nor are all aspects of their spinal cord function readily amenable to objective evaluation. Here, we measured the effects of intraspinal transplantation of cells derived from olfactory mucosal cultures (containing a mean of ~50% olfactory ensheathing cells) in a population of spinal cord-injured companion dogs that accurately model many of the potential obstacles involved in transition from laboratory to clinic. Dogs with severe chronic thoracolumbar spinal cord injuries (equivalent to ASIA grade 'A' human patients at ~12 months after injury) were entered into a randomized double-blinded clinical trial in which they were allocated to receive either intraspinal autologous cells derived from olfactory mucosal cultures or injection of cell transport medium alone. Recipients of olfactory mucosal cell transplants gained significantly better fore-hind coordination than those dogs receiving cell transport medium alone. There were no significant differences in outcome between treatment groups in measures of long tract functionality. We conclude that intraspinal olfactory mucosal cell transplantation improves communication across the damaged region of the injured spinal cord, even in chronically injured individuals. However, we find no evidence for concomitant improvement in long tract function.

Porcine alanine transaminase after liver allo-and xenotransplantation.

Aspartate transaminase (AST) and alanine transaminase (ALT) are measured following liver transplantation as indicators of hepatocellular injury. During a series of orthotopic liver allo-and xenotransplants, we observed that there was an increase in AST in all cases. The anticipated concomitant rise in ALT did not occur when a wild-type (WT) pig was the source of the liver graft, but did occur when a baboon or a genetically engineered (α1,3-galactosyltransferase gene-knockout [GTKO]) pig was the source of the graft. We hypothesized that the cience of Galα1,3Gal in GTKO pig livers may render pig hepatocytes similar to human and baboon hepatocytes in their response to hepatocellular injury. Reviewing the literature, after WT pig liver allotransplantation or xenotransplantation, in the majority of reports, although changes in AST were reported, no mention was made of changes in ALT, suggesting that there was no change in ALT. However, Ramirez et al. reported two cases of liver xenotransplants from hCD55 pigs, following which there were increases in both AST and ALT, suggesting that it is not simply the cience of expression of Galα1,3Gal that is the cause. We acknowledge that our observation is based on a small number of experiments, but we believe it is worth recording.

Emerging restorative treatments for Parkinson's disease: manipulation and inducement of dopaminergic neurons from adult stem cells.

Parkinson's disease (PD) is a common neurodegenerative disease, characterized by a selective loss of midbrain Dopaminergic (DA) neurons. To address this problem, various types of stem cells that have potential to differentiate into DA neurons are being investigated as cellular therapies for PD, including cells derived from embryonic or adult donor tissue, and embryonic stem cells. These cell sources, however, have raised certain questions with regard to ethical and rejection issues. Recent progress in adult stems has further proved that the cells derived from adult tissue could be expanded and differentiated into DA precursor cells in vitro, and cell therapy with adult stem cells could produce a clear improvement for PD models. Using adult stem cells for clinic application may not only overcome the ethical problem inherent in using human fetal tissue or embryonic stem cells, but also open the possibility for autologous transplantation. The patient-specific adult stem cell is therefore a potential and prospective candidate for PD treatment.

Histological examination of frozen autograft treated by liquid nitrogen removed after implantation.

BACKGROUND: Several oncological sterilization methods involving autoclaving, irradiation, or pasteurization have been developed for limb reconstruction of large bone defects following tumor excision. Studies involving histological examinations of these autografts have all found that osteogenesis occurs slowly. We have used frozen autografts treated by liquid nitrogen for limb reconstruction and have achieved excellent results for bone union. To determine if frozen autografts exhibit early bone remodeling, we investigated the repair processes of the frozen bones. METHODS: We analyzed frozen autografts treated by liquid nitrogen, retrieved at a mean of 19.1 months (2-75 months) after implantation because of complications or local tumor recurrence. The specimens were obtained from six patients with a mean age of 36.2 years (8-68 years). The six grafts comprised three osteoarticular grafts, two intercalary grafts, and one joint graft. We histologically reviewed the autograft-containing sections for tumor cell necrosis, evidence of cortical repair, the cortical junction, and joint cartilage. RESULTS: Tumor cells were completely eradicated from the frozen bone in all cases. In a specimen retrieved 5 months after implantation, a small area of the bone showed active osteocytes and osteoblasts. In three cases retrieved more than 1 year after implantation, osteocytes and osteoblasts were observed in broad portions of the frozen bones, indicating the onset of osteogenesis in the frozen bone at an early stage. The cortical host-graft junction showed incorporation along with continuity of bone trabeculae. In addition, we were able to fi nd normal chondrocytes on the articular surface. CONCLUSIONS: The frozen bone specimens in this study thus showed evidence of newly formed bone and earlier osteogenesis than has been previously reported. Our results suggest that frozen autografts may be considered one of the most useful recycled materials for biological reconstruction.

Evaluation of pulsatile perfusion machine RM3 for kidney preservation in a swine model of renal autotransplantation.

AIM: Transplantations of kidneys from non-heart-beating donors (NHBD) are intended to increase the donor pool by 20% to 30%. Nevertheless the rate of primary nonfunction and delayed graft function is generally higher among this group of donors. The goal of this study was to assess whether kidney preservation by a pulsatile perfusion machine was able to limit the renal lesions due to ischemia reperfusion injuries as compared with static incubation. We have used a model of an autotransplanted kidney exposed to controlled warm ischemia in the pig to mimic the clinical conditions of NHBD. MATERIAL AND METHODS: Left kidneys from 11 large white pigs aged 4 weeks were harvested after vascular clamping of the renal vessels for 1 hour. Kidneys were preserved for 22 hours. Two groups were studied: the MPS static group (static incubation with Belzer MPS; n = 6) versus the MPS RM group (renal perfusion with Belzer MPS; n = 5). Kidneys were then autotransplanted into pigs after a right nephrectomy. The primary end point was animal survival rate at 1 month. Secondary endpoints were evolution of the plasma creatinine values, proteinuria, tubular sodium reabsorption, and histological features at 1 month. RESULTS: For all biological parameters, the differences between the perfusion and the static incubation groups were significant, except creatinine, with favorable effects for the perfusion machine group. The histological data at 1 month showed recovery of the normal kidney architecture in the MPS RM group. CONCLUSION: In our pig experimental model that reproduced the clinical conditions of a NHBD, we demonstrated better kidney preservation when the pulsatile perfusion machine was used as compared with static conservation.

Poor functional recovery after transplantation of diabetic bone marrow stem cells in ischemic myocardium.

BACKGROUND: Autologous bone marrow mononuclear cell (BMMC) therapy has shown promise for improving cardiac function after myocardial infarction. The efficiency of such therapy for diabetic patients remains unknown. METHODS: BMMCs were harvested from type 2 diabetic male BKS.Cg-m+/+Lepr(db)/J mice or C57BLKS/J (non-diabetic control) mice and were isolated using Ficoll-based separation. Cell characterization was performed by flow cytometry. Cell viability was determined by apoptosis and proliferation assays. Female BKS.Cg-m+/+Lepr(db)/J mice underwent left anterior descending artery ligation and were randomized into 3 groups receiving 2.5 x 10(6) diabetic BMMCs (n = 8), 2.5 x 10(6) control BMMCs (n = 8), or phosphate-buffered saline (n = 6). At Week 5, cardiac function was assessed with echocardiography and invasive hemodynamic measurements. Post-mortem cell survival was quantified by TaqMan real-time transcription polymerase chain reaction (RT-PCR) for the male Sry gene. RESULTS: BKS.Cg-m+/+Lepr(db)/J BMMCs showed a significantly lower mononuclear fraction and a significantly lower proliferation rate compared with C57BLKS/J BMMCs. Fractional shorting (40.1% +/- 1.2% vs 30.3% +/- 1.9%; p = 0.001) and cardiac output (4,166 +/- 393 vs 2,246 +/- 462 microl/min; p = 0.016) significantly improved for mice treated with control BMMCs injection compared with those treated with diabetic BMMCs, respectively. This difference could not be attributed to difference in cell engraftment because TaqMan RT-PCR showed no significant difference in cell survival in infarcted hearts between the 2 groups. CONCLUSIONS: Diabetic BMMCs are significantly impaired in their ability to improve cardiac function after myocardial infarction compared with control BMMCs. These findings could have significant clinical implication regarding autologous BMMC therapy in diabetic patients.

Direct thrombin inhibitor prevents delayed graft function in a porcine model of renal transplantation.

BACKGROUND: Kidney transplantations from donors after cardiac arrest (DCA) are characterized by an increase in the occurrence of delayed graft function and primary nonfunction. In this study, Melagatran, a selective reversible direct thrombin inhibitor was used to limit renal injury in a DCA pig kidney transplantation model. METHODS: We used a porcine model of DCA to study the effects of treatment with Melagatran in the peri-conservation period. Thromboelastography was used to check Melagatran antithrombin effect on in vitro clot formation. Reverse-transcriptase polymerase chain reaction was used to analyze the peripheral immune cells activation status. Renal function and morphologic study were performed at days 1 and 7. Finally, we analyzed the mechanisms of Melagatran protection on kidney microvasculature primary endothelial cells. RESULTS: Prolongation of coagulation time (Ex-Tem) was observed 10 min after injection; however, Melagatran did not modulate increases of thrombin-antithrombin complexes following reperfusion. Melagatran significant treatment lowered the proinflammatory status of circulating immune cells. Animal's survival was increased in Melagatran-treated groups (9 of 10 in Melagatran groups vs. 4 of 10 in controls at day 7). Renal injury and inflammation were also significantly reduced in treated groups. We also demonstrated a direct protective effect of Melagatran against endothelial cell activation and inflammation in vitro. CONCLUSION: Direct thrombin inhibitor administration in the periconservation period improved graft outcome and reduced renal injury in a model of DCA.

Experience with the longer (8.5 mm) abutment for Bone-Anchored Hearing Aid.

BACKGROUND: Use of the longer (8.5 mm) abutment for a Bone-Anchored Hearing Aid has been helpful for a certain group of patients. The most common reason for its use is soft tissue problems with tissue overgrowth interfering with device function. The longer abutment has been used in our institution, a tertiary referral center, on a named patient basis since 2002, and more than 100 patients have received it. OBJECTIVES: This paper will review this subgroup of patients and describe their demographics. Comorbidity, smoking history, graft failure, infection, and index of deprivation will be looked at as contributing factors for this group with soft tissue problems. PATIENTS: We identified 111 patients who had longer abutments ordered for them, and a retrospective case review was performed. RESULTS: Eighty-one patients required soft tissue reduction surgery because of overgrowth, and all but one (80/81 [98.8%]) of these patients required no further surgery after having their 5.5-mm abutment changed to the 8.5-mm version. One patient underwent further surgery 10 months after the longer abutment was inserted but has been problem-free for 16 months since then. Length of follow-up ranged from 6 months to 5 years after converting to the longer abutment. CONCLUSION: We have found the longer abutment to be very successful for the small proportion of patients with troublesome soft tissue overgrowth. We would advocate its use when topical management and surgical intervention have failed to control the skin reaction.

Islet autotransplant outcomes after total pancreatectomy: a contrast to islet allograft outcomes.

INTRODUCTION: Islet allografts are currently associated with a high rate of early insulin independence, but after 1 year insulin-independence rates rapidly decline for unclear reasons. In contrast, as shown here, islet autotransplants (IATs) show durable function and extended insulin-independence rates, despite a lower beta-cell mass. METHODS: IAT function was determined in 173 patients after total pancreatectomy at our center. Islet function was considered full in insulin-independent patients, partial when euglycemic on once-daily long-acting insulin (all tested were C-peptide positive), and failed if on a standard diabetic regimen. Outcomes for autoislet recipients by Kaplan-Meier survival analysis were compared with those of alloislet recipients in the Collaborative Islet Transplant Registry. RESULTS: IAT function (full/partial combined) and insulin independence correlated with islet yield. Overall only 65% functioned within the first year, and only 32% were insulin independent, but of IATs that functioned initially (n=112), 85% remained so 2-years later, in contrast to 66% of allografts (n=262). Of IAT recipients who became insulin independent (n=55), 74% remained so 2-years later versus 45% of initially insulin-independent allograft recipients (n=154). Of IATs that functioned or induced insulin independence, the rates at 5 years were 69% and 47%, respectively. CONCLUSION: Islet function is more resilient in autografts than allografts. Indeed, the 5-year insulin-independence persistence rate for IATs is similar to the 2-year rate for allografts. Several factors unique to allocases are likely responsible for the differences, including donor brain death, longer cold ischemia time, diabetogenic immunosuppression, and auto- and alloimmunity. IAT outcomes provide a minimum theoretical standard to work toward in allotransplantation.

Comparação entre enxerto ósseo autólogo, homólogo congelado e homólogo liofilizado em modelo experimental de cranioplastia / Comparison between autogenous, deep-frozen homologous, and lyophilized homologous bone grafts in an experimental model of cranioplasty

Objetivo: O objetivo deste experimento é comparar, em um modelo experimental de cirurgia craniomaxilofacial, o comportamento de ossos processados e armazenados pelos métodos de liofilização e a congelação profunda, com o enxerto autólogo. Método: Trinta ratos Wistar adultos foram divididos em três grupos submetidos a cranioplastia com reconstrução com enxerto ósseo. O grupo 1 recebeu homoenxertos congelados, o grupo 2 recebeu homoenxertos liofilizados e o grupo 3 foi reconstruído com enxertos autólogos frescos. Os animais foram sacrificados na 6ª e na 15ª semana. Os resultados foram avaliados por parâmetros macroscópicos e histopatológicos. Resultados: Na primeira avaliação, os grupos 1 e 3 apresentavam resultados semelhantes, enquanto o grupo 2 mostrava resultados significativamente piores em vários parâmetros avaliados. Na avaliação tardia, enquanto o grupo 1 mostrou uma diminuição na neoformação óssea e na atividade osteoblástica, o grupo 2 apresentou índices significativamente maiores para estes parâmetros. O grupo 3 manteve sua proporção de osso neoformado inalterada, com uma diminuição da atividade dos osteoblastos. Conclusão: Conclui-se que o enxerto autólogo fresco permanece como primeira opção na reparação do esqueleto facial. Embora os enxertos homólogos tenham apresentado resultados satisfatórios, com capacidade de osteoindução e osteocondução, os enxertos homólogos liofilizados parecem ter um melhor comportamento em longo prazo.

Objective: This experiment was designed to compare, in an experimental model of craniomaxillofacial surgery, the behavior of processed and banked bones through lyophilization with autoclave or deep-freezing with autogeneic grafts. Method: Thirty Wistar rats were divided in three groups and submitted to cranioplasty with reconstruction using bone graft. Group 1 received deepfrozen allografts, group 2 received lyophilized allografts, and group 3 was reconstructed with fresh autografts. Four animals of each group were sacrificed at week 6. The remaining 6 were sacrificed at week 15. Results: Results were evaluated by macroscopic and histopathologic parameters. In the first evaluation, groups 1 and 3 showed similar results, while group 2 showed significantly worse results in several parameters. In the late evaluation, group 1 showed diminished bone neoformation and osteoblastic activity, whereas group 2 showed significantly higher indexes in these parameters. Group 3 kept its proportion of neoformed bone unchanged, with a decrease in osteoblastic activity. Conclusion: It is concluded that fresh autografts remain as the first choice in repairing the facial skeleton. Although allografts presented satisfactory results, with osteoinductive and osteoconductive properties, lyophilized allografts appear to show a better behavior in the follow up.

Trasplante autólogo de progenitores hematopoyéticos seguido de bexaroteno oral en paciente con micosis fungoide avanzada / Autologous hematopoietic stem cell transplantation folowed by oral bexarotene in a patient with advanced mycosis fungoides

Exponemos el caso de una paciente de 17 años que presentó una micosis fungoide de evolución rápida y agresiva, con múltiples tumores cutáneos y transformación fenotípica celular a linfoma de células grandes. Fue tratada inicialmente con 3 ciclos de quimioterapia en dosis altas (MEGA-CHOP) sin respuesta, por lo que se decidió realizar un trasplante autólogo de progenitores hematopoyéticos. Este tratamiento consiguió una remisión parcial de la enfermedad, y con la posterior introducción del bexaroteno oral se logró la remisión completa, que se ha mantenido durante más de 3 años con muy buena tolerancia al bexaroteno oral. Analizamos las ventajas y desventajas de la utilización del trasplante autólogo de progenitores hematopoyéticos y del uso de bexaroteno oral (AU)

We describe the case of a 17-year-old patient with rapidly progressing and aggressive mycosis fungoides, with multiple cutaneous tumors and large cell transformation. She was initially treated with 3 cycles of high-dose chemotherapy with mega-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) without response, leading to the decision to undertake autologous hematopoietic stem cell transplantation. Partial remission of the disease was achieved with this treatment and subsequent introduction of oral bexarotene led to complete remission, which has been maintained for more than 3 years with good tolerance of oral therapy. We discuss the advantages and disadvantages of autologous hematopoietic stem cell transplantation and the use of oral bexarotene (AU)

Bone regeneration after topical BMP-2-gene delivery in circumferential peri-implant bone defects.

OBJECTIVES: The aims of this study were to evaluate the rate of bone formation and osseointegration after topical gene delivery with a liposomal vector system carrying bone morphogenetic protein (BMP)-2 cDNA in combination with a collagen carrier and autologous bone as a carrier in freshly created peri-implant bone defects. MATERIALS AND METHODS: Eight domestic pigs received nine calvariae defects each (10 x 7 mm). A dental implant was inserted into the centre of each defect. In the test groups, the remaining space was filled with the liposomal vector/BMP-2 complex combined with a collagen carrier (n=18) or an autologous bone graft (n=18). Control groups were collagen only (n=18) and autologous bone graft only (n=18). RESULTS: There was a significant difference in mineralisation rate in the BMP-2/bone graft (29.9%+/- 4.8 and 68.3%+/- 7.2) and bone graft only (22.6%+/- 2.6 and 49.4%+/- 13.9) groups after 7 and 28 days. Mineralisation values were also significantly higher in the BMP-2/collagen group (21.2%+/- 16.2 and 53.1%+/- 12.5) compared with the collagen-only group (8.2%+/- 7 and 41%+/- 8.1) in two different regions after 28 days. Also the bone-to-implant contact was significantly increased in the BMP-2/bone graft group after 28 days and in the BMP-2/collagen group after 7 and 28 days compared with their control groups. CONCLUSIONS: The results of this study show a significantly positive effect of liposomal vector/BMP-2 on bone regeneration and osseointegration in bony circumferential peri-implant defects.

Implantation of autologous bone marrow mononuclear cells into ischemic myocardium enhances coronary capillaries and systolic function in miniswine.

OBJECTIVE: To investigate the therapeutic effectiveness of intracoronary implantation of autologous bone marrow mononuclear cells (BM-MNC) in miniswine model of reperfused myocardial infarction. METHODS: Sixteen miniswine myocardial ischemic reperfusion injury models made by ligation of the distal one third segment of left anterior descending artery for 90 minutes were randomized into 2 groups. In BM-MNC group (n = 9), (3.54 +/- 0.90) X 10(8) BM-MNC were intracoronary injected, and in the control group (n = 7), phosphate buffered saline was injected by the same way. Echocardiographic and hemodynamic results, vessel density, and myocardial infarction size were evaluated and compared before and 4 weeks after cell transplantation. RESULTS: In BM-MNC group, there were no differences between before and 4 weeks after transplantation in aspects of left ventricular ejection fraction (LVEF), interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, or +dp/dtmax. In control group, LVEF, interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, and +dp/dtmax decreased significantly 4 weeks after transplantation (P < 0.05). Left ventricular end-diastolic pressure and -dp/dtmax, did not change significantly before and after cell transplantation in both groups. Capillary density in BM-MNC group was greater than that in control group [(13.39 +/- 6.96)/high power field vs. (3.50 +/- 1.90)/high power field, P < 0.05]. Infarction area assessed by tetrazolium red staining and the infarction percentage decreased in BM-MNC group compared with those in control group (P < 0.05). CONCLUSIONS: Transplantation of BM-MNC into myocardium with ischemic reperfusion injury increases capillary density and decreases infarction area. It has significantly beneficial effect on cardiac systolic function rather than on diastolic function.

Beta-2-microglobulin level predicts outcome following autologous hematopoietic stem cell transplantation in patients with multiple myeloma.

Despite the widespread use of high-dose therapy combined with autologous hematopoietic stem cell transplantation (autoHSCT), the outcomes of multiple myeloma (MM) treatment remain variable. The aim of this study was to define pretransplantation factors that influence outcomes following autoHSCT in patients with MM. Eighty-one MM patients, aged 51 years (range 31-70 years), undergoing first autoHSCT were included in the analysis. Thirty patients were in complete remission and 51 were in partial remission. The conditioning regimen was based mainly on melphalan (200 mg/m(2) intravenous [iv]). The following factors were tested for their prognostic significance: beta-2-microglobulin (B2M), lactate dehydrogenase, monoclonal protein level, bone marrow plasma cell percentage (PL), hemoglobin level, age, interval from diagnosis to autoHSCT, and number of transplanted CD34-positive cells. The transplant-related mortality at day 100 was 3.7% (3/81). The incidence of progression at 9.2 years was 71% for patients with elevated B2M, and 32% for those where B2M was within normal limits (P = .02.) The probability of PFS was decreased for patients with B2M > or = versus < normal limits (29% vs 68%; P = .02) and PL > or = versus < 5% (0% vs 45%; P = 0.03). In a multivariate analysis B2M remained the only factor associated with increased risk of progression (relative risk [RR] = 3.3; P = .03) and reduced probability of PFS (RR = 3.3; P = .03). We concluded that B2M level measured at first autoHSCT was a useful predictor for progression and PFS in MM patients.

Which parameters of nutritional status should we choose for nutritional assessment during hematopoietic stem cell transplantation?

Since changes in nutritional indices after hematopoietic stem cell transplantation (HSCT) have not been well studied, there is no definition of risk factors for the development of malnutrition, and the inception of total parenteral nutrition (TPN). We sought to analyze changes in nutritional status parameters and acute phase protein levels as qualifications for TPN. Nutritional status was assessed in 54 patients during autologous (n = 30) on allogeneic (n = 24) transplantations. Eight of 15 patients who had to be treated with TPN, needed prolonged hospitalization (>5 weeks). We assessed biochemical and anthropometric indices of nutritional status, body fat and resting energy expenditure, and acute phase protein levels on the day before starting a conditioning regimen, after chemotherapy completion, and every 7 days until engraftment, which was at least three times after stem cell infusion. Wilcoxon test and canonical analysis were used for statistical analyses. The measurement of body weight and retinol binding protein or transferrin may be useful for nutritional assessment during autologous or allogeneic HSCT, respectively. Prealbumin level, measured 8 days after the end of the conditioning regimen was helpful to make a decision about starting TPN.

A cytotoxic analysis of antiseptic medication on skin substitutes and autograft.

BACKGROUND: There is an increasing demand for the clinical application of human skin substitutes (HSSs) for treating ulcers, burns and surgical wounds. Due to this increasing demand and due to the simultaneous requirement for the administration of topical antiseptic medications, there is a need to determine potential cytotoxic effects of these medications on HSSs compared with autograft skin. OBJECTIVES: To perform such an evaluation. METHODS: Two different HSSs were used (autologous reconstructed epidermis on fibroblast-populated human dermis and allogeneic reconstructed epidermis on a fibroblast-populated rat collagen gel) and were compared with conventional full-thickness autograft. Twelve different antiseptics were applied topically to the stratum corneum in vitro for 24 h. The degree of cytotoxicity was analysed as detrimental changes in histology, metabolic activity (MTT assay) and RNA staining of tissue sections. RESULTS: The antiseptic medications tested showed different degrees of cytotoxicity. Acticoat, Aquacel Ag, Dermacyn, Fucidin, 0.5% silver nitrate solution and chlorhexidine digluconate were not cytotoxic for either HSS or autograft, and can therefore be used as required. Flamazine and zinc oxide cream resulted in moderate cytotoxicity. However, application of Betadine((R)), cerium-silver sulfadiazine cream, silver sulfadiazine cream with 1% acetic acid and Furacine resulted in a substantial decrease in cell viability and a detrimental effect on tissue histology when applied to autograft and especially to HSS. CONCLUSIONS: Due to the potential cytotoxic effect of some antiseptics on HSS, it is advised that clinicians balance the cytotoxicity of the medication, its antiseptic properties and the severity of colonization in choosing which one to apply.

Spleen autotransplantation. Morphological and functional follow-up after spleen autotransplantation in mice: a research summary.

In 1986, we started the research on spleen surgery aimed at saving the splenic mass after its traumatic injury, with elaboration of special resection and autotransplantation techniques. The researches started on mongrel dogs and were continued on inbred mice and beagle dogs with complex histological, imaging, and laboratory investigations, following-up the function and the regeneration of autotransplanted spleen chips. Performing research on mice provided more immunological methods, such as lymphocyte subsets, immunoglobulin levels, and monitoring the phagocytic functions. Researches showed evidence also on the presence of apoptosis, furthermore, stem cell studies on regeneration and functional restoration of the spleen chips are in progress. Our results contributed to two multidisciplinary guidelines in Hungary: (1) One of them is under preparation and underlines the importance of spleen saving methods after traumatic splenic injury; (2) The second guideline shows that hemorheological changes can be early indicators of the increased sensitivity to postsplenectomy infections.