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1.
Cell Transplant ; 27(6): 937-947, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29860900

RESUMO

Ten mongrel dogs were used in this study. Diabetes was chemically induced in 7 dogs, and 3 dogs served as normal controls. For each diabetic dog, 5 million human bone marrow-derived mesenchymal stem cells/kg were differentiated to form insulin-producing cells using a trichostatin-based protocol. Cells were then loaded in 2 TheraCyte capsules which were transplanted under the rectus sheath. One dog died 4 d postoperatively from pneumonia. Six dogs were followed up with for 6 to 18 mo. Euglycemia was achieved in 4 dogs. Their glucose tolerance curves exhibited a normal pattern demonstrating that the encapsulated cells were glucose sensitive and insulin responsive. In the remaining 2 dogs, the fasting blood sugar levels were reduced but did not reach normal values. The sera of all transplanted dogs contained human insulin and C-peptide with a negligible amount of canine insulin. Removal of the transplanted capsules was followed by prompt return of diabetes. Intracytoplasmic insulin granules were seen by immunofluorescence in cells from the harvested capsules. Furthermore, all pancreatic endocrine genes were expressed. This study demonstrated that the TheraCyte capsule or a similar device can provide adequate immunoisolation, an important issue when stem cells are considered for the treatment of type 1 diabetes mellitus.

2.
Stem Cell Res Ther ; 8(1): 254, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29115987

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) play different roles in modulating tumor progression, growth, and metastasis. MSCs are recruited to the tumor site in large numbers and subsequently have an important microenvironmental role in modulating tumor progression and drug sensitivity. However, the effect of the tumor microenvironment on MSC plasticity remains poorly understood. Herein, we report a paracrine effect of cancer cells, in which they secrete soluble factors that promote a more stem-like state in bone marrow mesenchymal stem cells (BM-MSCs). METHODS: The effect of soluble factors secreted from MCF7, Hela, and HepG2 cancer cell lines on BM-MSCs was assessed using a Transwell indirect coculture system. After 5 days of coculture, BM-MSCs were characterized by flow cytometry for surface marker expression, by qPCR for gene expression profile, and by confocal immunofluorescence for marker expression. We then measured the sensitivity of cocultured BM-MSCs to chemotherapeutic agents, their cell cycle profile, and their response to DNA damage. The sphere formation, invasive properties, and in-vivo performance of BM-MSCs after coculture with cancer cells were also measured. RESULTS: Indirect coculture of cancer cells and BM-MSCs, without direct cell contact, generated slow cycling, chemoresistant spheroid stem cells that highly expressed markers of pluripotency, cancer cells, and cancer stem cells (CSCs). They also displayed properties of a side population and enhanced sphere formation in culture. Accordingly, these cells were termed cancer-induced stem cells (CiSCs). CiSCs showed a more mesenchymal phenotype that was further augmented upon TGF-ß stimulation and demonstrated a high expression of the ß-catenin pathway and ALDH1A1. CONCLUSIONS: These findings demonstrate that MSCs, recruited to the tumor microenvironment in large numbers, may display cellular plasticity, acquire a more stem-like state, and acquire some properties of CSCs upon exposure to cancer cell-secreted factors. These acquired characteristics may contribute to tumor progression, survival, and metastasis. Our findings provide new insights into the interactions between MSCs and cancer cells, with the potential to identify novel molecular targets for cancer therapy.


Assuntos
Células-Tronco Mesenquimais/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Microambiente Tumoral
3.
Biomed Res Int ; 2017: 3854232, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28584815

RESUMO

The aim of this study is to compare human bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs), for their differentiation potentials to form insulin-producing cells. BM-MSCs were obtained during elective orthotopic surgery and AT-MSCs from fatty aspirates during elective cosmetics procedures. Following their expansion, cells were characterized by phenotyping, trilineage differentiation ability, and basal gene expression of pluripotency genes and for their metabolic characteristics. Cells were differentiated according to a Trichostatin-A based protocol. The differentiated cells were evaluated by immunocytochemistry staining for insulin and c-peptide. In addition the expression of relevant pancreatic endocrine genes was determined. The release of insulin and c-peptide in response to a glucose challenge was also quantitated. There were some differences in basal gene expression and metabolic characteristics. After differentiation the proportion of the resulting insulin-producing cells (IPCs), was comparable among both cell sources. Again, there were no differences neither in the levels of gene expression nor in the amounts of insulin and c-peptide release as a function of glucose challenge. The properties, availability, and abundance of AT-MSCs render them well-suited for applications in regenerative medicine. Conclusion. BM-MSCs and AT-MSCs are comparable regarding their differential potential to form IPCs. The availability and properties of AT-MSCs render them well-suited for applications in regenerative medicine.


Assuntos
Tecido Adiposo/metabolismo , Células da Medula Óssea/metabolismo , Peptídeo C/metabolismo , Diferenciação Celular , Insulina/metabolismo , Células-Tronco Mesenquimais/metabolismo , Tecido Adiposo/citologia , Células da Medula Óssea/citologia , Humanos , Células-Tronco Mesenquimais/citologia
4.
Appl Radiat Isot ; 118: 131-135, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27640173

RESUMO

A point source is used to investigate the effect of water phantom thickness and source-to-detector distance (SDD) on the sensitivity and counting efficiency of a rectangular detector gamma camera. The increase in water thickness resulted in an increase in scatter fraction, a decrease in sensitivity, and counting efficiency. The increase in SDD resulted in a decrease in sensitivity and an increase in counting efficiency. An SDD of 0.79±0.02m is found to provide a good compromise for acceptable sensitivity and reasonable counting efficiency.

5.
Neurourol Urodyn ; 35(4): 497-502, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25663249

RESUMO

AIMS: Post-exstrophy incontinence is a challenge because continence is difficult to achieve and more difficult to maintain. Feasibility and outcomes of a bulbourethral sling to treat post-exstrophy incontinence is shown in this report. METHODS: A retropubic bulbourethral sling was applied to male patients with incontinence post-exstrophy-epispadius repair. The study included children with total (continuous) incontinence who underwent multiple previous anti-incontinence procedures, ranging from bladder neck injection to bladder neck reconstruction. Preoperative assessment includes urinalysis, renal US, VCUG, 1-hr pad test and urodynamics. The bulbourethral sling applied is made of polypropylene and is suspended by 4 pairs of nylon sutures, to support the bulbar urethra within its covering muscles with the sutures tied on the rectus muscles. Continence was evaluated as well as adverse events. RESULTS: Seventeen children, (median age 8.7 years) completed 24-month of follow up. All had CPRE. Five children (29.27%) were dry. Four micturated through the urethra and one by catheterizing his cutaneous stoma every 3-4 hr. In none, PVR exceeded 10% of expected capacity. Four children underwent re-tightening 1-4 weeks after removal of urethral catheter. Perineal wound dehiscence occurred in one, perineal/suprapubic pain in seven and epididymo-orchitis in one child. CONCLUSION: The current technique is promising for difficult cases of incontinence after CPRE. It is safe, as no serious adverse events occurred during follow up period. It is economic and re-tightening is easy to perform. Neurourol. Urodynam. 35:497-502, 2016. © 2015 Wiley Periodicals, Inc.


Assuntos
Complicações Pós-Operatórias/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Slings Suburetrais , Uretra/cirurgia , Incontinência Urinária/cirurgia , Adolescente , Criança , Pré-Escolar , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Bexiga Urinária/cirurgia , Incontinência Urinária/etiologia , Urodinâmica
6.
Biomed Res Int ; 2015: 575837, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26064925

RESUMO

The aim of this study was to provide evidence for further in vivo maturation of insulin-producing cells (IPCs) derived from human bone marrow-derived mesenchymal stem cells (HBM-MSCs). HBM-MSCs were obtained from three insulin-dependent type 2 diabetic volunteers. Following expansion, cells were differentiated according to a trichostatin-A/GLP protocol. One million cells were transplanted under the renal capsule of 29 diabetic nude mice. Blood glucose, serum human insulin and c-peptide levels, and glucose tolerance curves were determined. Mice were euthanized 1, 2, 4, or 12 weeks after transplantation. IPC-bearing kidneys were immunolabeled, number of IPCs was counted, and expression of relevant genes was determined. At the end of in vitro differentiation, all pancreatic endocrine genes were expressed, albeit at very low values. The percentage of IPCs among transplanted cells was small (≤3%). Diabetic animals became euglycemic 8 ± 3 days after transplantation. Thereafter, the percentage of IPCs reached a mean of ~18% at 4 weeks. Relative gene expression of insulin, glucagon, and somatostatin showed a parallel increase. The ability of the transplanted cells to induce euglycemia was due to their further maturation in the favorable in vivo microenvironment. Elucidation of the exact mechanism(s) involved requires further investigation.


Assuntos
Diferenciação Celular/genética , Diabetes Mellitus Experimental/terapia , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Transplante de Células-Tronco Mesenquimais , Animais , Glicemia , Células da Medula Óssea/citologia , Diabetes Mellitus Experimental/patologia , Glucagon/metabolismo , Humanos , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Transplante das Ilhotas Pancreáticas , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos NOD
7.
Saudi J Kidney Dis Transpl ; 25(4): 733-40, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24969181

RESUMO

To evaluate the role of power Doppler in the identification and differentiation between acute renal transplant rejection and acute tubular necrosis (ATN), we studied 67 live donor renal transplant recipients. All patients were examined by spectral and power Doppler sonography. Assessment of cortical perfusion (CP) by power Doppler was subjective, using our grading score system: P0 (normal CP); homogenous cortical blush extending to the capsule, P1 (reduced CP); cortical vascular cut-off at interlobular level, P2 (markedly reduced CP); scattered cortical color flow at the interlobar level. Renal biopsies were performed during acute graft dysfunction. Pathological diagnoses were based on Banff classification 1997. The Mann- Whitney test was used to test the difference between CP grades with respect to serum creatinine (SCr), and resistive index (RI). For 38 episodes of acute graft rejection grade I, power Doppler showed that CP was P1 and RI ranging from 0.78 to 0.89. For 21 episodes of acute graft rejection grade II, power Doppler showed that CP was P1, with RI ranging from 0.88 to >1. Only one case of grade III rejection had a CP of P2. Twelve biopsies of ATN had CP of P0 and RI ranging from 0.80 to 0.89 There was a statistically significant correlation between CP grading and SCr (P <0.01) as well as between CP grading and RI (P <0.05). CP grading had a higher sensitivity in the detection of early acute rejection compared with RI and cross-sectional area measurements. We conclude that power Doppler is a non-invasive sensitive technique that may help in the detection and differentiation between acute renal transplant rejection and ATN, particularly in the early post-transplantation period.


Assuntos
Rejeição de Enxerto/diagnóstico por imagem , Transplante de Rim/efeitos adversos , Necrose Tubular Aguda/diagnóstico por imagem , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Imagem de Perfusão/métodos , Circulação Renal , Ultrassonografia Doppler , Adolescente , Adulto , Biópsia , Diagnóstico Diferencial , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/fisiopatologia , Humanos , Necrose Tubular Aguda/etiologia , Necrose Tubular Aguda/fisiopatologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Biomed Res Int ; 2014: 832736, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24818157

RESUMO

INTRODUCTION: Many protocols were utilized for directed differentiation of mesenchymal stem cells (MSCs) to form insulin-producing cells (IPCs). We compared the relative efficiency of three differentiation protocols. METHODS: Human bone marrow-derived MSCs (HBM-MSCs) were obtained from three insulin-dependent type 2 diabetic patients. Differentiation into IPCs was carried out by three protocols: conophylline-based (one-step protocol), trichostatin-A-based (two-step protocol), and ß -mercaptoethanol-based (three-step protocol). At the end of differentiation, cells were evaluated by immunolabeling for insulin production, expression of pancreatic endocrine genes, and release of insulin and c-peptide in response to increasing glucose concentrations. RESULTS: By immunolabeling, the proportion of generated IPCs was modest ( ≃ 3%) in all the three protocols. All relevant pancreatic endocrine genes, insulin, glucagon, and somatostatin, were expressed. There was a stepwise increase in insulin and c-peptide release in response to glucose challenge, but the released amounts were low when compared with those of pancreatic islets. CONCLUSION: The yield of functional IPCs following directed differentiation of HBM-MSCs was modest and was comparable among the three tested protocols. Protocols for directed differentiation of MSCs need further optimization in order to be clinically meaningful. To this end, addition of an extracellular matrix and/or a suitable template should be attempted.


Assuntos
Células da Medula Óssea/citologia , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Insulina/biossíntese , Células-Tronco Mesenquimais/citologia , Adulto , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Peptídeo C/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Citometria de Fluxo , Imunofluorescência , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Fenótipo
9.
Biomed Res Int ; 2013: 912413, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23878820

RESUMO

INTRODUCTION: The aim of this report is to study the graft and patient survival in a large cohort of recipients with an analysis of factors that may affect the final outcomes. METHODS: Between March 1976 and March 2008, 1967 consecutive live-donor renal transplants were carried out. Various variables that may have an impact on patients and/or graft survival were studied in two steps. Initially, a univariate analysis was carried out. Thereafter, significant variables were embedded in a stepwise regression analysis. RESULTS: The overall graft survival was 86.7% and 65.5%, at 5 and 10 years, respectively. The projected half-life for grafts was 17.5 years and for patients was 22 years. Five factors had an independent negative impact on graft survival: donor's age, genetic considerations, the type of primary immunosuppression, number of acute rejection episodes, and total steroid dose during the first 3 months after transplantation. CONCLUSIONS: Despite refinements in tissue matching techniques and improvements in immunosuppression protocols, an important proportion of grafts is still lost following living donor kidney transplantation, presumably due to chronic allograft nephropathy.


Assuntos
Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Transplante de Rim/mortalidade , Doadores Vivos/estatística & dados numéricos , Complicações Pós-Operatórias/mortalidade , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Egito/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
10.
J Nucleic Acids ; 2013: 194858, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23762531

RESUMO

Advanced type 2 diabetes mellitus is associated with significant morbidity and mortality due to cardiovascular, nervous, and renal complications. Attempts to cure diabetes mellitus using islet transplantation have been successful in providing a source for insulin secreting cells. However, limited donors, graft rejection, the need for continued immune suppression, and exhaustion of the donor cell pool prompted the search for a more sustained source of insulin secreting cells. Stem cell therapy is a promising alternative for islet transplantation in type 2 diabetic patients who fail to control hyperglycemia even with insulin injection. Autologous stem cell transplantation may provide the best outcome for those patients, since autologous cells are readily available and do not entail prolonged hospital stays or sustained immunotoxic therapy. Among autologous adult stem cells, mesenchymal stem cells (MSCs) therapy has been applied with varying degrees of success in both animal models and in clinical trials. This review will focus on the advantages of MSCs over other types of stem cells and the possible mechanisms by which MSCs transplant restores normoglycemia in type 2 diabetic patients. Sources of MSCs including autologous cells from diabetic patients and the use of various differentiation protocols in relation to best transplant outcome will be discussed.

11.
Appl Radiat Isot ; 77: 18-22, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23500653

RESUMO

An evaluation of the effect of scattered radiation on the performance of a gamma camera is carried out using a specially designed home-made homogeneous circular planar flood source filled with 0.2±0.01 GBq of (99m)Tc solution as a scattering medium. The scatter effects are assessed by analyzing the energy spectrum of (99m)Tc for the scatter fraction and calculating the camera's extrinsic counting efficiency and sensitivity, for five flood source thicknesses (12, 50, 100, 150 and 200 mm ) and three source-to-detector distances (0.7, 0.9 and 1.1 m). Results showed an increase in the scatter fraction from 0.29 to 22.96 as the source thickness increased. This increase was associated with a decrease in the extrinsic sensitivity from 121.36 to 49.58 counts/s GBq, and a decrease in counting efficiency as from 3.78 to 1.55%. With the increase in source-to-detector distance, the extrinsic sensitivity decreases from 121.36 to 118.77 counts/s GBq, while the counting efficiency increases from 3.78 to 11.66%. It was found that a source-to-detector distance of 0.96±9×10(-3) m is a good compromise for an acceptable extrinsic sensitivity and a reasonable counting efficiency.


Assuntos
Artefatos , Câmaras gama , Tecnécio/análise , Tecnécio/química , Desenho de Equipamento , Análise de Falha de Equipamento , Raios gama , Reprodutibilidade dos Testes , Espalhamento de Radiação , Sensibilidade e Especificidade
12.
Clin Transpl ; : 111-2, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-25095498

RESUMO

Gene and stem cell therapy has been on the scientific agenda in many laboratories for more than 20 years. The literature is enormous, but practical applications have been few. Recently advances in stem cell biology and gene therapy are clarifying some of the issues. I have made a few observations concerning our own studies on bone marrow mesenchymal stem cells cultured to produce a small percentage of insulin-producing cells and human insulin gene engineered into Lenti and AA viruses. The aim of clinical application would still seem to be several years away, if all goes well. The first step will be to produce enough insulin-secreting cells to be of potential value to patients. The next crucial question will be how to persuade the cells to respond to blood glucose levels swiftly and appropriately. With both stem cell and gene therapy, another important factor will be to ensure that any positive results will continue long enough to be preferable to insulin injections.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Terapia Genética/tendências , Transplante das Ilhotas Pancreáticas/tendências , Transplante de Células-Tronco/tendências , Humanos
13.
Cell Transplant ; 22(1): 133-45, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22710060

RESUMO

Harvesting, expansion, and directed differentiation of human bone marrow-derived mesenchymal stem cells (BM-MSCs) could provide an autologous source of surrogate ß-cells that would alleviate the limitations of availability and/or allogenic rejection following pancreatic or islet transplantation. Bone marrow cells were obtained from three adult type 2 diabetic volunteers and three nondiabetic donors. After 3 days in culture, adherent MSCs were expanded for two passages. At passage 3, differentiation was carried out in a three-staged procedure. Cells were cultured in a glucose-rich medium containing several activation and growth factors. Cells were evaluated in vitro by flow cytometry, immunolabeling, RT-PCR, and human insulin and c-peptide release in responses to increasing glucose concentrations. One thousand cell clusters were inserted under the renal capsule of diabetic nude mice followed by monitoring of their diabetic status. At the end of differentiation, ∼5-10% of cells were immunofluorescent for insulin, c-peptide or glucagon; insulin, and c-peptide were coexpressed. Nanogold immunolabeling for electron microscopy demonstrated the presence of c-peptide in the rough endoplasmic reticulum. Insulin-producing cells (IPCs) expressed transcription factors and genes of pancreatic hormones similar to those expressed by pancreatic islets. There was a stepwise increase in human insulin and c-peptide release by IPCs in response to increasing glucose concentrations. Transplantation of IPCs into nude diabetic mice resulted in control of their diabetic status for 3 months. The sera of IPC-transplanted mice contained human insulin and c-peptide but negligible levels of mouse insulin. When the IPC-bearing kidneys were removed, rapid return of diabetic state was noted. BM-MSCs from diabetic and nondiabetic human subjects could be differentiated without genetic manipulation to form IPCs that, when transplanted, could maintain euglycemia in diabetic mice for 3 months. Optimization of the culture conditions are required to improve the yield of IPCs and their functional performance.


Assuntos
Células da Medula Óssea/metabolismo , Diabetes Mellitus Experimental/cirurgia , Células Secretoras de Insulina/transplante , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Adulto , Animais , Células da Medula Óssea/citologia , Diferenciação Celular , Feminino , Expressão Gênica , Humanos , Insulina/biossíntese , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade
14.
Urology ; 80(2): 452-8, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22676948

RESUMO

OBJECTIVE: To assess the long-term outcome of using the serous-lined extramural tunnel technique for construction of continent-cutaneous urinary reservoir in an objective way. METHODS: Cases that were operated until the end of 2003 and were eligible for evaluation at the time of the study were included. Continence, upper tract status, and complications were the targets of evaluation. Clear definition of continence was used, and biochemical kidney function profile was assessed with calculation of estimated glomerular filtration rate (eGFR) as a measure of the overall renal function in addition to the standard radiological assessment tools. A modified Clavien scale was followed for grading of complications. RESULTS: After a median of 121.3 months, the final continence rate was 91.1%. Maintained upper tract status was in almost 96.6% of cases and stricture of ureterointestinal anastomosis (UIA) was diagnosed in 3 renal units, and ureteral reflux was diagnosed in 24 renal units. Biochemical kidney function profile showed mean percent reduction of total eGFR to be 14.2%, and 3 patients had ≥50% reduction of total eGFR. On the Clavien scale, low-grade complications (GI-II) occurred in 30 patients (33%) and high-grade complications (≥GIII) occurred in 36 patients (40%). Stoma complications were the most frequent complications. At last follow-up, 42 patients (47%) were free of complications. CONCLUSION: The serous-lined extramural valve is an efficient technique for maintaining unidirectional flow. Over a decade, good functional outcome of the cutaneous reservoir has been evident. However, with a clear definition of continence and objective assessment of the outcome, at least one third of patients will have high-grade complications, with excellent reintervention outcome maintaining efficacy of the technique.


Assuntos
Procedimentos Cirúrgicos Dermatológicos , Derivação Urinária/métodos , Coletores de Urina , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
J Urol ; 187(3): 1041-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22264457

RESUMO

PURPOSE: There is a lack of a standardized reporting methodology for surgical complications of pediatric renal transplantation. We applied Martin criteria and the modified Clavien-Dindo classification in pediatric renal transplantation. MATERIALS AND METHODS: We retrospectively reviewed the charts of 447 patients 20 years or younger who underwent renal transplantation between March 1976 and January 2011. Martin criteria were fulfilled and complications were graded according to the modified Clavien-Dindo classification. For early complications grades I and II were considered low grade and III to V high grade. A similar grading system was adopted for late complications. RESULTS: A total of 84 early complications (18.5%) occurred in 77 transplant recipients (17%). Of grade I complications 37 (8.1%) were asymptomatic lymphoceles. Grade II complications were observed in 2 patients (0.4%). Grade IIIa complications included aspiration of hematoma (1 case), percutaneous nephrostomy fixed for ureteral obstruction (3), percutaneous tube drain for symptomatic lymphoceles (7) and antegrade ureteral stenting for ureteral leakage (6). Grade IIIb complications included exploration for wound dehiscence (1 case), revision of ureterovesical anastomosis (8), marsupialization of lymphoceles (4), hemorrhage (3) and vascular thrombotic accidents (6). Graft nephrectomy (grade IVa) complications occurred in 2 transplant recipients. Among 4 mortalities (grade V) only 1 patient died due to surgical complications. On multivariate analysis delayed graft function was the only predicator of high grade surgical complications (p = 0.005). High grade surgical complications affected recipient but not graft survival. CONCLUSIONS: Using a standardized, high quality reporting methodology is feasible in pediatric renal transplantation. However, consensus should be sought regarding medical complications and a grading system should be developed for reporting of late complications.


Assuntos
Transplante de Rim , Doadores Vivos , Complicações Pós-Operatórias/classificação , Adolescente , Criança , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Análise de Sobrevida
16.
Arab J Urol ; 10(2): 155-61, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26558019

RESUMO

OBJECTIVES: To compare the haemorrhagic and vascular complications between paediatric and adult renal transplant recipients with a long-term follow-up. PATIENTS AND METHODS: Between March 1976 and December 2006, in all, 1865 live-donor renal transplants were carried out. Patients were stratified according to their ages into two groups; paediatric (⩽18 years; 259) and adult (>18 years; 1606). Variables assessed included incidence, risk factors, management and sequelae of vascular and haemorrhagic complications. The effect of these complications on patient and graft survival was compared. RESULTS: Haemorrhage requiring active intervention (percutaneous drainage or surgical exploration) was reported in seven children (2.7%) and 29 adults (1.8%), while thrombotic or stenotic complications were recorded in two children (0.77%) and 19 adults (1.18%; P < 0.05). Female gender, delayed onset of diuresis and acute tubular necrosis were significant predictors of vascular complications on univariate analysis, but none remained significant on multivariate analysis. In adults, vascular complications had a significant negative effect on mean (SD) 10-year graft survival compared to patients with no complications, at 19.8 (7.63)% vs. 55.7 (1.66)% (P = 0.01). Children who developed vascular complications had a significantly higher 5- and 10-year graft survival rate than adults (P = 0.01). CONCLUSION: The incidence of vascular complications is comparable in paediatric and adult transplants. Vascular complications had a significant negative influence on graft survival in adult recipients. Children who developed vascular complications appear to tolerate its effects and have a better graft survival than have adults.

17.
Exp Clin Transplant ; 9(5): 295-301, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21967254

RESUMO

OBJECTIVES: This prospective study was designed to develop a steroid and calcineurin inhibitor-free regimen for kidney transplants using alemtuzumab. MATERIALS AND METHODS: A single dose of alemtuzumab (30 mg) was given preoperatively. Phase 1: Twenty-one patients were randomized into 2 groups; the tacrolimus (n=11) and the sirolimus groups (n=10). Steroids were given for 5 days. Azathioprine (1 mg/kg) was added when white blood cells ≥ 4000 cells/cm(3). Mean follow-up was 48 ± 2.8 and 48.2 ± 1.6 months for the tacrolimus and sirolimus groups. Phase 2: Twenty patients were included and the study design was modified. Tacrolimus was given for 2 months, and was replaced by sirolimus thereafter. The mean follow-up was 28.3 ± 2.1 months. RESULTS: Phase 1: Acute rejection episodes were encountered in 5 patients of the tacrolimus versus 2 cases in the sirolimus group (P = .44). Antibody-mediated rejection was diagnosed in 2 recipients in each group. Four patients were switched from sirolimus to tacrolimus owing to resistant rejection, significant proteinuria, persistent thrombocytopenia, lymphocele, and urinary leakage. One patient was shifted from tacrolimus to sirolimus owing to Kaposi sarcoma. Glomerular filtration rate was significantly higher in the sirolimus group. Currently, 14 patients (8 tacrolimus, and 6 sirolimus) are steroid-free. One patient died from the tacrolimus group owing to fulminant hepatitis. Two grafts were lost in the sirolimus group versus 1 graft in the tacrolimus group. Phase 2: Five patients developed successfully treated borderline changes with no antibody-mediated rejection. Mean serum creatinine was 114.9 ± 17.7 µmol/L. Currently, 17 patients are steroid free and 15 of them are calcineurin inhibitor-free as well. In this phase, only 1 patient died with a functioning graft. CONCLUSIONS: This clinical trial provides a good insight into a potentially effective steroid and calcineurin inhibitor-free protocol with the use of alemtuzumab induction in combination with sirolimus.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Antineoplásicos/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Transplante de Rim , Doadores Vivos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Alemtuzumab , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Antineoplásicos/efeitos adversos , Azatioprina/administração & dosagem , Inibidores de Calcineurina , Esquema de Medicação , Substituição de Medicamentos , Quimioterapia Combinada , Egito , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/imunologia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Estudos Prospectivos , Sirolimo/administração & dosagem , Esteroides/administração & dosagem , Tacrolimo/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
Exp Clin Transplant ; 9(4): 247-51, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21819369

RESUMO

OBJECTIVES: The effect of basiliximab induction therapy on long-term patient and graft survival is not clear. We sought to evaluate if there is any advantage to routine basiliximab induction on the long-term outcome of living-related donor kidney transplants. MATERIALS AND METHODS: One hundred adult recipients with their first kidney allograft were randomized into 2 treatment groups; 1 group received basiliximab, and the second served as a control. All patients received a maintenance triple immunosuppressive therapy (steroids, cyclosporine, microemulsion, and azathioprine). We followed them for 10 years. RESULTS: Basiliximab reduced the proportion of patients who experienced an acute rejection in the first year (18/50) when compared with the control group (31/50) (P = .009), and in 10 years (28/50) when compared with controls (37/50) (P = .059). The cumulative steroid dosage used throughout the study was significantly lower in the basiliximab group. The overall incidence of posttransplant complications was comparable among the 2 groups. There was no significant difference in patient and graft survival; 10-year patient and graft survival were 92% and 76% for basiliximab and 90% and 68% for the control group. CONCLUSIONS: Routine basiliximab induction significantly reduces the incidence of acute rejection without any noticeable effects on the long-term renal transplant outcome.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Rim , Doadores Vivos , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Basiliximab , Distribuição de Qui-Quadrado , Quimioterapia Combinada , Egito , Feminino , Rejeição de Enxerto/imunologia , Humanos , Estimativa de Kaplan-Meier , Transplante de Rim/imunologia , Masculino , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Eur Urol ; 60(3): 572-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21684070

RESUMO

BACKGROUND: Controversy exists regarding the optimal extent of lymphadenectomy and the number of lymph nodes to be retrieved at radical cystectomy (RC). OBJECTIVE: To compare the disease-free survival of patients with standard lymphadenectomy (endopelvic region composed of the internal, external iliac, and obturator groups of lymph nodes) versus extended lymphadenectomy (up to the level of origin of the inferior mesenteric artery) at RC in a prospective cohort of patients at a single, high-volume center. DESIGN, SETTING, AND PARTICIPANTS: Prospective data were collected from 400 consecutive patients treated with RC for bladder cancer by two high-volume surgeons at Mansoura Urology and Nephrology Center. Of the 400 patients, 200 (50%) received extended lymphadenectomy and the other 200 (50%) underwent standard lymphadenectomy at RC. The patients did not receive any neoadjuvant or adjuvant therapy. MEASUREMENTS: Patient characteristics and outcomes are evaluated. RESULTS AND LIMITATIONS: Median patient age for the entire group was 53.0 yr. Ninety-six patients (24.0%) had lymph node metastases. Median follow-up was 50.2 mo. Estimates of 5-yr disease-free survival in the extended lymphadenectomy group were 66.6% compared with 54.7% for patients with standard lymphadenectomy (p = 0.043). Extended lymphadenectomy was associated with better disease-free survival after adjusting for the effects of standard pathologic features (p = 0.02). When restricting the analyses to lymph node-positive patients, patients with extended lymphadenectomy had much better 5-yr disease-free survival compared with patients with standard lymphadenectomy (48.0% vs 28.2%; p = 0.029). The study was nonrandomized. CONCLUSIONS: Extended lymphadenectomy is associated with better disease-free survival for bladder cancer patients with endopelvic lymph node involvement and should be considered in these patients.


Assuntos
Cistectomia , Excisão de Linfonodo/métodos , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Distribuição de Qui-Quadrado , Cistectomia/efeitos adversos , Cistectomia/mortalidade , Intervalo Livre de Doença , Egito , Feminino , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Regressão , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/secundário
20.
Exp Clin Transplant ; 9(1): 14-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21605018

RESUMO

OBJECTIVES: Renal transplant from living donors is widely accepted as a highly effective treatment for end-stage renal disease. Donors undergo a major operation with considerable perioperative risks of morbidity and mortality. Living with a single kidney also confers long-term risks. This study sought the incidence and causes of end-stage renal disease among living kidney donors. MATERIALS AND METHODS: This study included all donors who had reached end-stage renal disease among 2000 consecutive living-kidney donors. All operations and follow-up were performed in a single center. We studied the onset of renal disease, cause of end-stage renal disease, date of replacement therapy, and outcome. We also revised the donor's medical records related to their corresponding recipients. RESULTS: Of 2000 living donors, 8 developed end-stage renal disease; 6 were men (mean age, 30.87 ± 5.84 years. Renal failure occurred 5 to 27 years after donation. Renal transplant was done in 1 donor. Medical complications were proteinuria (6 patients), hypertension (7 patients), diabetes (3 patients), gout (3 patients), ischemic heart disease (5 patients), and hepatitis viral infection (4 patients). The causes of end-stage renal disease were diabetic nephropathy in 3 patients. Other possible causes included toxic nephropathy, chronic pyelonephritis, and preeclampsia. CONCLUSIONS: Living kidney donation is safe, and development of renal failure after donation is caused by the same causes as in the general population.


Assuntos
Falência Renal Crônica/epidemiologia , Transplante de Rim/efeitos adversos , Doadores Vivos/estatística & dados numéricos , Nefrectomia/efeitos adversos , Adulto , Comorbidade , Egito/epidemiologia , Feminino , Humanos , Incidência , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Terapia de Substituição Renal , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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