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1.
BMC Musculoskelet Disord ; 25(1): 784, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39367372

RESUMO

BACKGROUND: Lengthening of the extensor hallucis longus (EHL) is performed to address various forefoot pathologies. The retraction of this tendon is strongly associated with the Hallux Abductus Valgus (HAV) deformity. Minimally Invasive Surgery (MIS) lengthening of the EHL is carried out in combination with other surgical techniques for HAV bone realignment. It is performed without ischemia, using local anesthesia and sedation if required by the patient. One of the advantages of this technique is immediate ambulation with a postoperative shoe without the need for a cast. The objective of the research was to demonstrate the efficacy and safety of the minimally invasive technique for lengthening the tendon in patients with HAV. MATERIALS AND METHODS: The procedures were performed on 11 fresh cryopreserved cadaveric feet. HAV surgery was performed through dorsomedial and dorsolateral portals for Reverdin-Isham, Akin and adductor tenotomy. In addition, EHL tendon elongation was performed using the Beaver 67 MIS scalpel through an incomplete zigzag tenotomy. The specimens used did not present any type of disease nor had they undergone previous surgeries that could affect the technique. First, the plantar flexion of the metatarsophalangeal joint was measured with a goniometer to establish the degrees of this joint before proceeding with the technique, the tenotomy was performed and remeasured and finally the osteotomy was performed. In addition, an anatomical dissection of cadaveric specimens was performed and various anatomical and surgical relationships were analyzed and measured. RESULTS: The data indicate that, after performing zigzag tenotomy, there is an average improvement of 13.91 degrees in plantar flexion. CONCLUSIONS: The study confirms the effectiveness and safety of elongating the extensor hallucis longus tendon of the hallux using minimally invasive surgery. The zigzag technique for tendon elongation may be considered a viable minimally invasive treatment option for addressing tendon hyperextension in patients with HAV.


Assuntos
Cadáver , Procedimentos Cirúrgicos Minimamente Invasivos , Tenotomia , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Tenotomia/métodos , Tendões/cirurgia , Hallux Valgus/cirurgia , Masculino , Feminino , Idoso
2.
Ann Hematol ; 101(10): 2263-2270, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35997804

RESUMO

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Piridazinas , Antineoplásicos/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Proteínas de Fusão bcr-abl/genética , Humanos , Imidazóis , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Niacinamida/análogos & derivados , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis , Piridazinas/efeitos adversos , Estudos Retrospectivos
3.
Phys Rev Lett ; 124(24): 244801, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32639812

RESUMO

Continuous-wave photoinjectors operating at high accelerating gradients promise to revolutionize many areas of science and applications. They can establish the basis for a new generation of monochromatic x-ray free electron lasers, high-brightness hadron beams, or a new generation of microchip production. In this Letter we report on the record-performing superconducting rf electron gun with CsK_{2}Sb photocathode. The gun is generating high charge electron bunches (up to 10 nC/bunch) and low transverse emittances, while operating for months with a single photocathode. This achievement opens a new era in generating high-power beams with a very high average brightness.

4.
J Environ Manage ; 213: 159-167, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29494932

RESUMO

The anaerobic biodegradation of ethanol-glycol ether mixtures as 1-ethoxy-2-propanol (E2P) and 1-methoxy-2-propanol (M2P), widely used in printing facilities, was investigated by means of two laboratory-scale anaerobic bioreactors at 25oC: an expanded granular sludge bed (EGSB) reactor and an anaerobic hybrid reactor (AHR), which incorporated a packed bed to improve biomass retention. Despite AHR showed almost half of solid leakages compared to EGSB, both reactors obtained practically the same performance for the operating conditions studied with global removal efficiencies (REs) higher than 92% for organic loading rates (OLRs) as high as 54 kg of chemical oxygen demand (COD) m-3 d-1 (REs of 70% and 100% for OLRs of 10.6 and 8.3 kg COD m-3 d-1 for E2P and M2P, respectively). Identified byproducts allowed clarifying the anaerobic degradation pathways of these glycol ethers. Thus, this study shows that anaerobic scrubber can be a feasible treatment for printing emissions.


Assuntos
Etanol , Éter , Eliminação de Resíduos Líquidos , Anaerobiose , Reatores Biológicos , Éteres , Esgotos
5.
Actas Dermosifiliogr ; 106(7): 569-77, 2015 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-25935194

RESUMO

INTRODUCTION: In biologic therapy, dose modification in carefully selected patients when psoriasis is in remission could reduce treatment costs and the risks associated with drug exposure. MATERIAL AND METHODS: Observational, descriptive, crosssectional study, performed in January 2014, of 112 patients with moderate to severe psoriasis who had been on biologic therapy for at least 6 months. The therapeutic objective in all cases was to achieve and maintain a 75% reduction in Psoriasis Area and Severity Index (PASI 75). All the patients had started treatment with the standard regimen. During treatment, the dose had been reduced in patients who achieved the therapeutic objective and escalated in those who failed to respond adequately to standard doses. RESULTS: At the time of the study, 42.9% of the patients were receiving the standard dose, 50% were on a reduced dose, and 7.1% were on an escalated regimen. The agent with which the dose was most often reduced was adalimumab (57.7%), and the agents with which therapy was most often escalated were ustekinumab (17.9%) and infliximab (12.5%). Patients who received reduced doses had significantly longer-standing disease (P=.049) and longer treatment duration with the same biologic agent (P=.009). In the group that did not fulfill the criteria for dose reduction, the proportion of patients with psoriatic arthritis was significantly higher (P=.023). Cost savings were as follows: 21.5% with adalimumab, 13.8% with etanercept, .9% with ustekinumab, and .55% with infliximab. CONCLUSIONS: Patients with longer-standing disease and longer treatment duration with the same biologic agent were significantly more likely to be candidates for dose reduction. The proportion of patients with psoriatic arthritis was greater in the group of patients who did not fulfill the conditions for dose reduction. The overall cost saving achieved using the dose modification algorithm described in this study was 13%. Controlled studies are needed to define the profile of the patients best suited for dose reduction strategies without loss of treatment efficacy.


Assuntos
Adalimumab/uso terapêutico , Terapia Biológica/métodos , Fármacos Dermatológicos/uso terapêutico , Etanercepte/uso terapêutico , Infliximab/uso terapêutico , Psoríase/tratamento farmacológico , Ustekinumab/uso terapêutico , Adalimumab/administração & dosagem , Adalimumab/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Terapia Biológica/economia , Redução de Custos , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/economia , Relação Dose-Resposta a Droga , Esquema de Medicação , Custos de Medicamentos , Etanercepte/administração & dosagem , Etanercepte/economia , Feminino , Humanos , Infliximab/administração & dosagem , Infliximab/economia , Masculino , Pessoa de Meia-Idade , Psoríase/economia , Resultado do Tratamento , Ustekinumab/administração & dosagem , Ustekinumab/economia , Adulto Jovem
6.
J Affect Disord ; 333: 365-376, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37094658

RESUMO

BACKGROUND: The study of Obsessive-Compulsive Disorder (OCD) genomics has primarily been tackled by Genome-wide association studies (GWAS), which have encountered troubles in identifying replicable single nucleotide polymorphisms (SNPs). Endophenotypes have emerged as a promising avenue of study in trying to elucidate the genomic bases of complex traits such as OCD. METHODS: We analyzed the association of SNPs across the whole genome with the construction of visuospatial information and executive performance through four neurocognitive variables assessed by the Rey-Osterrieth Complex Figure Test (ROCFT) in a sample of 133 OCD probands. Analyses were performed at SNP- and gene-level. RESULTS: No SNP reached genome-wide significance, although there was one SNP almost reaching significant association with copy organization (rs60360940; P = 9.98E-08). Suggestive signals were found for the four variables at both SNP- (P < 1E-05) and gene-levels (P < 1E-04). Most of the suggestive signals pointed to genes and genomic regions previously associated with neurological function and neuropsychological traits. LIMITATIONS: Our main limitations were the sample size, which was limited to identify associated signals at a genome-wide level, and the composition of the sample, more representative of rather severe OCD cases than a population-based OCD sample with a broad severity spectrum. CONCLUSIONS: Our results suggest that studying neurocognitive variables in GWAS would be more informative on the genetic basis of OCD than the classical case/control GWAS, facilitating the genetic characterization of OCD and its different clinical profiles, the development of individualized treatment approaches, and the improvement of prognosis and treatment response.


Assuntos
Estudo de Associação Genômica Ampla , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno Obsessivo-Compulsivo/genética , Transtorno Obsessivo-Compulsivo/psicologia , Polimorfismo de Nucleotídeo Único/genética , Endofenótipos , Genômica
7.
Water Sci Technol ; 65(1): 177-82, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22173423

RESUMO

The study of an industrial unit of biotrickling filter for the treatment of the exhaust gases of a flexographic facility was investigated over a 2-year period with the objective to meet the volatile organic compound (VOC) regulatory emission limits. Increasing the water flow rate from 2 to 40 m(3) h(-1) improved the performance of the process, meeting the VOC regulation when 40 m(3) h(-1) were used. An empty bed residence time (EBRT) of 36 s was used when the inlet air temperature was 18.7 °C, and an EBRT as low as 26 s was set when the inlet temperature was 26.8 °C. During this long-term operation, the pressure drop over the column of the bioreactor was completely controlled avoiding clogging problems and the system could perfectly handle the non-working periods without VOC emission, demonstrating its robustness and feasibility to treat the emission of the flexographic sector.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/prevenção & controle , Reatores Biológicos , Filtração/instrumentação , Impressão , Compostos Orgânicos Voláteis/análise , Pressão , Esgotos
8.
J Environ Manage ; 92(8): 1978-85, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21531069

RESUMO

The effect of using ground tire rubber (GTR) as an adsorptive material in the removal of a 2:1:1 weight mixture of n-butyl acetate, toluene and m-xylene by using a peat biofilter under different intermittent conditions was investigated. The performance of two identical size biofilters, one packed with fibrous peat alone and the other with a 3:1 (vol) fibrous peat and GTR mixture, was examined for a period of four months. Partition coefficients of both materials were measured. Values of 53, 118 and 402 L kg(-1) were determined for n-butyl acetate, toluene and m-xylene in peat, respectively; and values of 40, 609 and 3035 L kg(-1) were measured for the same compounds in GTR. Intermittent load feeding of 16 h per day, 5 days per week working at an EBRT of 60 s and an inlet VOC concentration of 0.3 g C m(-1), resulted in removal efficiencies higher than 90% for both biofilters, indicating that the addition of GTR did not adversely affect the behavior of the bioreactor. Full removal of n-butyl acetate was obtained for both biofilters. GTR improved the removal of the aromatics in the first part of the biofilter, facilitating lower penetration of the toluene and m-xylene into the bed. A 31-day starvation period was applied and intermittent operation subsequently restarted. In both biofilters, high removal efficiencies after a re-acclimation period of two days were achieved. A shock loading test related to 1-h peaks of three- and four-fold increases in its baseline concentration (0.30 g C m(-3)) was applied in both biofilters. For the biofilter packed with the peat and GTR mixture, attenuation greater than 60% was observed in the maximum outlet concentration when compared to the biofilter packed with peat alone.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/prevenção & controle , Filtração/métodos , Borracha/química , Solo/química , Compostos Orgânicos Voláteis/análise , Acetatos/análise , Adsorção , Cromatografia Gasosa , Tolueno/análise , Xilenos/análise
10.
Pharmacogenomics J ; 8(2): 101-12, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17505499

RESUMO

Brain-derived neurotrophic factor (BDNF) has been studied extensively in relation to the susceptibility to mood disorders (MD), although it remains to be clarified whether BDNF is a susceptibility locus for MD phenotypes, including therapeutic response to antidepressants. We have performed a single-marker and haplotype association study of eight TagSNPs polymorphisms in the genomic region containing the BDNF gene in 342 control subjects and 374 patients with MD, and have tested the association with antidepressant treatment outcome. None of the eight single nucleotide polymorphisms (TagSNPs) was significantly associated with MD phenotype after Bonferroni correction. In the single-marker analysis, a SNP was found to be associated with the patient's state of 'remitter' after adequate trial with a single antidepressant phenotype (odds ratio (OR)=2.95; P=0.0025). We also identified a haplotype associated with this phenotype. This study supports the implication of BDNF in antidepressant treatment outcome in MD, with specific association with 5' upstream region of BDNF gene.


Assuntos
Antidepressivos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/genética , Haplótipos , Transtornos do Humor/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Regiões 5' não Traduzidas , Adulto , Idoso , Estudos de Casos e Controles , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/genética , Razão de Chances , Fenótipo , Fatores de Risco , Espanha , Resultado do Tratamento
11.
Bioresour Technol ; 99(2): 269-76, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17317157

RESUMO

In order to investigate suitable packing materials, a soil amendment composed of granular high mineralized peat (35% organic content) locally available has been evaluated as carrier material for biofiltration of volatile organic compounds in air by comparison with a fibrous peat (95% organic content). Both supports were tested to eliminate ethylbenzene from air streams in laboratory-scale reactors inoculated with a two-month conditioned culture. In pseudo-steady state operation, experiments at various ethylbenzene inlet loads (ILs) were carried out. Maximum elimination capacity of about 120 g m(-3) h(-1) for an IL of 135 g m(-3) h(-1) was obtained for the fibrous peat. The soil amendment reactor achieved a maximum elimination capacity of about 45 g m(-3) h(-1) for an inlet load of 55 g m(-3) h(-1). Ottengraf-van den Oever model was applied to the prediction of the performance of both biofilters. The influence of gas flow rate was also studied: the fibrous peat reactor kept near complete removal efficiency for empty bed residence times greater than 1 min. For the soil amendment reactor, an empty bed residence time greater than 2 min was needed to achieve adequate removal efficiency. Concentration profiles along the biofilter were also compared: elimination occurred in the whole fibrous peat biofilter, while in the soil amendment reactor the biodegradation only occurred in the first 65% part of the biofilter. Results indicated that soil amendment material, previously selected to increase the organic content, would have potential application as biofilter carrier to treat moderate VOC inlet loads.


Assuntos
Derivados de Benzeno/isolamento & purificação , Filtração/métodos , Solo/análise , Filtração/instrumentação , Modelos Teóricos , Espanha
12.
Bone Marrow Transplant ; 52(5): 745-752, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28112745

RESUMO

The pathogenesis of GvHD involves migration of donor T-cells into the secondary lymphoid organs in the recipient, which is steered by two homing molecules, CD62L and CCR7. Therefore, we investigated whether the migratory capacity of donor T-cells is associated with GvHD. This single center prospective study included 85 donor-recipient pairs. In vitro chemotaxis assays of the lymphocytes of the apheresis product were performed in parallel to the analysis of CD62L and CCR7 by flow cytometry. The migratory index to the CCR7 ligands, CCL19 and CCL21, was higher in T-cells from donors whose recipients will develop GvHD. Similarly, the acute GvHD (aGvHD) group received higher percentage of CD4+CCR7+ T-cells, whereas chronic GvHD (cGvHD) patients were transplanted with higher percentages of CD8+CCR7+ T-cells compared with the non-GvHD group. These results were confirmed when patients were subdivided according to degrees of severity. Further, multivariate analysis confirmed that the proportions of CCR7+ CD4+ and CCR7+ CD8+ T-cells are risk factors for the development and severity of aGvHD and cGvHD, respectively. Functional experiments demonstrated that CCR7+ T-cells exhibited higher potential for activation than CCR7- T-cells did. We therefore propose that the selective depletion of CCR7-expressing T-cells may be an effective preventive therapy for GvHD.


Assuntos
Linfócitos T CD4-Positivos/citologia , Quimiotaxia , Doença Enxerto-Hospedeiro/patologia , Receptores CCR7/análise , Adolescente , Adulto , Idoso , Relação CD4-CD8 , Linfócitos T CD4-Positivos/transplante , Quimiocina CCL19/análise , Quimiocina CCL21/análise , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Incidência , Selectina L/análise , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores CCR7/imunologia , Receptores de Retorno de Linfócitos/fisiologia , Índice de Gravidade de Doença , Doadores de Tecidos , Transplante Homólogo/efeitos adversos , Adulto Jovem
13.
Int J Oncol ; 28(1): 143-8, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16327990

RESUMO

Invasiveness and metastatic potential are the two most important properties defining malignancy. The adeno-virus E1A (Ad-E1A) gene has a dual effect as a proliferative gene and as a tumor-suppressor gene, decreasing tumor growth and the metastatic potential of malignant cells. In order to study genes related with the antimetastatic effect of Ad-E1A in human cells, we performed a microarray analysis using OncoChiptrade mark. In three independent experiments, NIH3T3, IMR90 and MDA MB 435 cells were infected with pLPC retroviruses carrying the adenovirus 12S E1A gene or the GFP gene. We analyzed cDNA expression by using the CNIO OncoChipTM, a cDNA microarray containing a total of 6386 genes represented by 7237 clones. uPA, uPAr, tPA, PAI-1 and PAI-2 were also studied at RNA and protein levels. Microarrays of cDNA expression, RT-PCR and Western blot performed in IMR90 E1A-expressing cells showed downregulation of uPA, uPAr, tPA, PAI-1 and upregulation of PAI-2. These results were confirmed in NIH3T3 and MDA MB 435 breast carcinoma cells, with PAI-2 upregulation by RT-PCR and Western blot. In addition, zymographic analysis demonstrated that E1A expression greatly reduced the gelatinase activity of the pro-MMP2 and -MMP9 proteins. We propose that adenovirus E1A may orchestrate the expression of most members of the urokinase-plasminogen activation system, downregulating potentially invasive genes and upregulating PAI-2, which is associated with a better prognosis in human tumors.


Assuntos
Adenoviridae/genética , Proteínas Precoces de Adenovirus/fisiologia , Neoplasias da Mama/patologia , Carcinoma/patologia , Regulação Neoplásica da Expressão Gênica , Inibidor 1 de Ativador de Plasminogênio/biossíntese , Adenoviridae/fisiologia , Western Blotting , Feminino , Perfilação da Expressão Gênica , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Regulação para Cima
14.
Neurocirugia (Astur) ; 16(5): 441-6, 2005 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-16276452

RESUMO

BACKGROUND: In the surgical approaches to the posterior fossa, the accurate location of the transverse-sigmoid sinus (TS-SS) complex is of great importance. The asterion is a referral landmark to the transverse sinus location. METHOD: Twenty-five skulls of adult cadavers were studied. We seek for the relationships of the asterion with: TS location, mastoid emissary vein, suprametal crest and inion. RESULTS: The asterion was found in 49 cases. In the great majority of cases (87.8%) the asterion was over the TS (72.2% over the sinus proper, 27.8% over the TS-SS transition). The mastoid emissary vein was present in 46 cases, and in 36% we found two veins. DISCUSSION AND CONCLUSIONS: The burr hole for posterolateral approaches to the posterior fossa must be located below and behind the asterion.


Assuntos
Fossa Craniana Posterior/anatomia & histologia , Cavidades Cranianas/anatomia & histologia , Adulto , Cadáver , Fossa Craniana Posterior/cirurgia , Humanos , Procedimentos Neurocirúrgicos , Crânio/anatomia & histologia , Propriedades de Superfície
15.
Thromb Haemost ; 81(6): 887-90, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10404762

RESUMO

We present the case of a full-term newborn in whom purpura fulminans developed shortly after birth. A diagnosis of homozygous protein C deficiency was established based upon undetectable plasma protein C activity and antigenemia in the newborn infant, and was later confirmed by protein C gene analysis. Specific replacement therapy with intravenous protein C concentrate was started 9 days after birth. This rapidly led to the complete regression of cutaneous lesions and consumption coagulopathy. After stabilization, oral anticoagulation was initiated in association with prophylactic treatment with intravenous protein C concentrate. However, oral anticoagulation was finally abandoned as the patient presented several thrombotic and hemorrhagic episodes clearly related to difficulties with anticoagulation. Due to the hazards related to prolonged venous access, we are currently using subcutaneous infusion of protein C concentrate for the long-term management of this condition, with satisfactory results.


Assuntos
Deficiência de Proteína C/tratamento farmacológico , Proteína C/administração & dosagem , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Feminino , Homozigoto , Humanos , Recém-Nascido , Injeções Subcutâneas , Deficiência de Proteína C/genética
16.
Bone Marrow Transplant ; 26(11): 1199-204, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11149731

RESUMO

Acute renal failure and veno-occlusive disease of the liver are serious complications following stem cell transplantation (SCT) and contribute to the non-relapse mortality associated with this procedure. Endothelins, a family of vasoconstrictor peptides, may be involved in the pathogenesis of a variety of renal and hepatic diseases, including CsA-associated hypertension and the hepatorenal syndrome. In order to study the relevance of endothelins to SCT-related liver and kidney dysfunction, we determined endothelin-1 (ET-1) levels in plasma samples obtained from 65 patients (38 autologous, 27 allogeneic) 7 days before and 7, 14 and 28 days after SCT. A steady increase in plasma ET-1 was observed after SCT (5.36 pg/ml, 95% CI 4.30-6.43 on day +28 vs 3.82 pg/ml, 95% CI 3.21-4.43 on day -7; P = 0.020). No differences in ET-1 levels existed between autologous and allogeneic SCT recipients at any of the time points studied (P = 0.561). In addition, no significant differences were observed among patients with renal dysfunction vs those without (P = 0.187), nor in patient groups with or without hepatic dysfunction (P = 0.075). In conclusion, even though plasma ET-1 levels showed a steady increase following SCT, no correlation could be found with development of SCT-related kidney or liver dysfunction.


Assuntos
Endotelina-1/sangue , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Adolescente , Adulto , Ciclosporina/sangue , Ciclosporina/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Hepatopatia Veno-Oclusiva/sangue , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade
17.
Bone Marrow Transplant ; 17(6): 979-84, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8807103

RESUMO

Between May 1983 and March 1994, 31 patients with AML in second CR underwent BMT. Fifteen underwent allogeneic BMT from an HLA-identical sibling donor and 16 without a donor, unpurged ABMT. Two different preparative regimens were used: CY (120 mg/kg) and 12 Gy of fractioned TBI (19 patients), and Bu (16 mg/kg) and Cy (120 mg/kg) (BuCy2) in 12 patients. Main clinical characteristics including age, sex, length of first remission, FAB type, and number of leukocytes at diagnosis were similar in both groups. A combination of MTX and CsA was used in 13 cases whereas either CsA or MTX alone was employed in the other two patients. With a median follow-up of 5 years the actuarial 5 year probability of disease-free survival (DFS) for the whole group was 39.8% (95% CI: 29.5-50.1%). The 5 year DFS was equivalent for those who received either ABMT (41.6 +/- 14.2%) or allogeneic BMT (40 +/- 15%). Probabilities of relapse and non-relapse mortality for ABMT and allo BMT patients were 48.7 +/- 16.1 and 18.7 +/- 14.3, and 30.1 +/- 19.2 and 40.7 +/- 16.9, respectively. DFS was better in those patients with a longer duration of first CR (> 18 months) 62.5 +/- 14.4 vs 30.4 +/- 17.9%, attributable to a significantly lower relapse rate in this group of patients 16.6 +/- 12.8 vs 57.8 +/- 22.7 (P 0.05). In conclusion, similar results were observed when ABMT and allo BMT were compared for AML in CR2. A higher antileukemic effect associated with the allo BMT is balanced by an increase in transplant-related mortality. Duration of first remission was the most important factor affecting DFS and better outcome was observed for patients with longer CR1.


Assuntos
Transplante de Medula Óssea , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Transplante de Medula Óssea/efeitos adversos , Criança , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Tempo , Transplante Autólogo , Transplante Homólogo
18.
Med Clin (Barc) ; 109(1): 12-5, 1997 May 31.
Artigo em Espanhol | MEDLINE | ID: mdl-9303971

RESUMO

BACKGROUND: A single-center experience review about accessibility to bone marrow transplantation (BMT) as postremission therapy for acute myeloid leukemia (AML) is analyzed. PATIENTS AND METHODS: From January 1988 to December 1994, 86 patients were diagnosed from de novo AML in our institution. A BMT was the treatment of choice for all patients younger than 55 years. An allogenic BMT (Allo-BMT) was offered for all patients younger than 35 years with a compatible sibling donor or those older patients, 35-55 years, with bad prognosis features. An autologus BMT (ABMT) was offered to those patients older than 35 years or those younger than 35 without an histocompatible donor. RESULTS: 52 out of 86 diagnosed patients were younger than 50 years (60%). 29 of them were candidates to Allo-BMT (24 patients younger than 35 years and 5 patients older than 35 with refractory disease) and the rest 23 to ABMT. 22 out of the 24 candidates to Allo-BMT entered complete remission (CR) and 12 of them had an HLA-identical donor. The Allo-BMT was performed in CR1 in 7 patients in CR2 in three patients and with refractory disease in two cases. An ABMT was finally planned in 30 patients, 18 patients older than 35 who entered CR and the rest 12 patients younger than 35 years in CR without a sibling donor. Only 11 out of this 30 patients underwent an ABMT in first CR. Reasons for this low number were: early relapse (B), toxicity (6), refuse (2), lost of follow-up (2) and suicide (1). Five out of this early relapse patients underwent an ABMT in CR2. Disease-free survival (DFS) at three years was 23 +/- 10% for the 52 patients included in the study. DFS obtained with Allo-BMT and AMBT were 39 +/- 16% and 63 +/- 22% respectively. CONCLUSIONS: In spite of the new postremission treatment modalities available for AML the rate of longer survivals are still low. When data from BMT is analyzed we must be awared because only a small fraction of patients assigned to BMT will finally access to this treatment.


Assuntos
Transplante de Medula Óssea/estatística & dados numéricos , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
19.
Med Clin (Barc) ; 108(6): 201-6, 1997 Feb 15.
Artigo em Espanhol | MEDLINE | ID: mdl-9102484

RESUMO

BACKGROUND: A single-center experience using autologous bone marrow transplantation (ABMT) as postremission therapy for acute myeloid leukemia (AML) in first complete remission (CR1) in 41 patients is analyzed. PATIENTS AND METHODS: From July 1986 to March 1994, 41 patients with AML in CR1 underwent an ABMT. Source of hematopoietic stem cells was bone marrow in all cases. In eleven patients the marrow was purged with mafosfamide (ASTA-Z 7654). Median age was 31 years (17-59) and median time from CR to ABMT was 7 months (3-27). Busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) was employed as conditioning regimen in 36 patients. The rest 5 patients were prepared with cyclophosphamide (120 mg/kg) and fractioned total body irradiation (12 Gy). Eleven patients received G-CSF after AMBT because of an absolute neutrophil count lower than 0.5 x 10(9) on day +30. Survival analysis was performed according to the methods of Kaplan and Meier and comparison between groups used the log-rank test. RESULTS: With a median follow-up of 26 months (12-75) 21 patients remain alive in CR. Disease-free survival (DFS) at five years was 40% (95% CI: 25-55%). Transplant-related mortality, mainly for infection and hemorrhage, occurred in 6/41 patients (16%). Leukemia relapse was the main cause of treatment failure: 14/35 (40%). Probability of DFS and relapse was similar for those patients with purged ABMT on unpurged ABMT 45 +/- 23% vs 38 +/- 16% and 37 +/- 14% vs 54 +/- 22% respectively. A significantly longer engraftment time for neutrophils (> 0.5 x 10(9)) and platelets (> 20 x 10(9)) was observed in those patients who received a bone marrow treated with mafosfamide compared with the unpurged group (54 vs 29 days for neutrophils and 102 vs 58 for platelets respectively) (p < 0.05). CONCLUSIONS: ABMT is a feasible treatment for AML in CR1. Using bone marrow as hematopoietic stem cell support we observed that delayed engraftment was a common finding among AML patients, specially when the marrow was treatment with mafosfamide. Leukemia relapse remains as the main cause of treatment failure for ABMT.


Assuntos
Transplante de Medula Óssea , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Transplante de Medula Óssea/métodos , Terapia Combinada , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Espanha/epidemiologia , Análise de Sobrevida , Fatores de Tempo , Transplante Autólogo
20.
Med Clin (Barc) ; 105(16): 605-11, 1995 Nov 11.
Artigo em Espanhol | MEDLINE | ID: mdl-8523939

RESUMO

BACKGROUND: The 10 year experience of a single center performing allogeneic bone marrow transplantation in 70 patients with chronic myeloid leukemia (CML) is analyzed. METHODS: Seventy patients transplanted for CML between November 1982 and October 1992 were evaluated. Fifty-two patients were in the first chronic phase (FC), 10 in an accelerated phase, 4 in blast crisis and 4 in the second chronic phase. The combination of cyclosporin and methotrexate was the most commonly used prophylactic schedule for graft versus host disease (GVHD) (60 cases) and T depletion was not performed in any case. The combination of cyclophosphamide (120 mg/kg) and total body irradiation was used in 48 patients with the remaining patients received busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). The estimation of survival was performed using the Kaplan-Meier limit product method. The prognostic factors influencing survival, disease free period and relapse were evaluated by Cox multivariate models of proportional risk. RESULTS: Actuarial survival at four years was 40% (95% Cl: 26-58%). Multivariate analysis selected variables associated with lower survival, the presence of acute GVHD (relative risk-RR-4.75), advanced disease phase (RR: 3.26) and age over 30 years (RR: 3.57). Eleven patients had relapsed. Multivariate analysis found the absence of chronic GVHD (RR: 5.3) and advanced phase (RR: 1.91) to be associated to a higher probability of relapse. In a separate analysis of the 48 patients transplanted in chronic phase who received cyclosporin and methotrexate, the disease free survival was longer for those under the age of 30 years (71.4% vs. 36%) without acute GVHD (68.8% vs. 39.6%) and those transplanted from a male donor (64.6% vs. 30%). CONCLUSIONS: Advanced phase of the disease, the presence of acute graft versus host disease and the age and female sex of the donor are the main factors associated to shorter survival in allogeneic bone marrow transplant for chronic myeloid leukemia. In contrast, the presence of chronic graft versus host disease decreases the possibilities of relapse.


Assuntos
Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adolescente , Adulto , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Transplante de Medula Óssea/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Indução de Remissão , Fatores de Risco , Espanha/epidemiologia , Transplante Homólogo , Resultado do Tratamento
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