RESUMO
INTRODUCTION: Ibrutinib is a selective oral inhibitor of Bruton's tyrosine kinase. It is used in haematology to treat lymphoid B disorders. Haemorrhagic complications in dermatological surgery are occasionally associated with the use of anti-platelet and/or anticoagulant medication. Herein, we report a case of haemorrhage under ibrutinib following skin surgery. PATIENTS AND METHODS: A 70-year-old male patient began treatment with ibrutinib for chronic lymphocytic leukaemia had 2 basal cell carcinomas of the face. The next day he had a persistent haemorrhage lasting more than 48h, with no effects on the final scarring result. DISCUSSION: Ibrutinib is a tyrosine kinase inhibitor whose mechanism of action plays a role in platelet adhesion. It is known to cause haemorrhaging, either spontaneously or following invasive procedures, especially at the beginning of treatment. In the case of low-risk haemorrhagic procedures in which bleeding may be controlled by mechanical haemostasis, ibrutinib should be discontinued 3 days before and after surgery. In the event of recent initiation of ibrutinib and in the absence of urgent dermatological management, it is preferable to schedule any surgical procedures 3 months after the start of ibrutinib.
Assuntos
Leucemia Linfocítica Crônica de Células B , Adenina/análogos & derivados , Tirosina Quinase da Agamaglobulinemia , Idoso , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Piperidinas , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversosRESUMO
BACKGROUND: Drug addiction causes chronic wounds (CW) responsible for severe complications. Very few studies are available on this topic. The aim of our study was to describe the demographic, clinical and etiological characteristics as well as the course of CW in drug addicts. PATIENTS AND METHODS: This was a retrospective and prospective multicenter study including all drug addicts with CW. RESULTS: We included 58 patients (17 prospectively), 84.5% of whom were male, of median age 43 years, presenting multiple CW as a result of intravenous (78.2%), inhaled (41.1%) and/or snorted (20%) drug abuse. Addiction to opioids (68.4%), cocaine (47.4%) and/or cannabis (40.4%) was ended and/or treated through substitution in 79.3% of patients. CW were fibrinous and necrotic (42.9 to 53.6%), recurrent (54.2%), and in some cases had been present for more than 1 year (61.5%). Intravenous drug addiction was associated with large, fibrinous, ulcers in a setting of venous and lymphatic insufficiency (74%). Only 23% of these wounds involved the upper limbs. Necrotic ulcers associated with clinical arteriopathy were described mainly with inhaled addiction. Abscesses (50%) and erysipelas (29.3%) were the most common cutaneous complications. After 3 months, 50% of CW were improved and 29.2% of patients were lost to follow-up. DISCUSSION: Drug abuse-related CW occurred preferentially in young men with history of intravenous abuse. For the most part, CW were seen on the legs and were associated with venous and lymphatic insufficiency, and the resulting major risk for cutaneous infection increased morbidity and mortality in this population in whom medical follow-up is inherently complicated.
Assuntos
Abscesso/etiologia , Erisipela/etiologia , Úlcera Cutânea/etiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Insuficiência Venosa/etiologiaRESUMO
We expressed peptides from the HIV-1 envelope protein at the surface of Escherichia coli by genetic insertions into an exposed loop of the outer membrane protein LamB. Recombinant bacteria expressing eight peptides from gp110 (pep1-pep8), conserved between HIV-1 and HIV-2, were used as live immunogens in rabbits by the intravenous route. The eight constructions elicited anti-LamB antibodies, showing that the hybrid proteins were immunogenic. One of them, LamB-pep8, gave rise to antibodies able to react with gp160 and to neutralize HIV-1 in vitro. We also show that this type of recombinant E. coli can provide a convenient reagent to monitor and characterize specific antibodies. Recombinant clones were used to test sera of seropositive individuals, as well as to narrow down the monoclonal antibody 110-1 recognition site to a cluster of eight residues at the carboxy-terminal end of gp110.
Assuntos
Escherichia coli/genética , Antígenos HIV/imunologia , HIV-1/imunologia , Proteínas do Envelope Viral/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Proteínas da Membrana Bacteriana Externa , Western Blotting , Produtos do Gene env/genética , Produtos do Gene env/imunologia , Antígenos HIV/genética , Proteína gp160 do Envelope de HIV , Dados de Sequência Molecular , Testes de Neutralização , Porinas , Precursores de Proteínas/genética , Precursores de Proteínas/imunologia , Coelhos , Receptores Virais/imunologia , Recombinação Genética , Proteínas do Envelope Viral/genéticaRESUMO
BACKGROUND: We have previously demonstrated that induction of mixed lymphohematopoietic chimerism resulted in donor specific renal allograft tolerance without the need for chronic immunosuppression in nonhuman primates. Here we have tested whether tolerance can be similarly induced for baboon to cynomolgus renal xenografts. METHODS: After preconditioning with anti-thymocyte globulin (ATG), nonlethal total body irradiation, and thymic irradiation, cynomolgus monkeys underwent splenectomy, native nephrectomies, and baboon marrow and renal transplants. Postoperative cyclosporine was given for 28 days. RESULTS: In Group 1 (n=2, survival= 13, 14 days), both animals developed anti-donor immunoglobulin G, had biopsy findings consistent with humoral rejection, and showed rapidly progressive xenograft failure. In Group 2 (n=5, survival=1, 16, 33, 112, 190 days), 15-deoxyspergualine was added to the regimen (Day 0-13). In one long-term survivor, donor specific hyporesponsiveness was first observed (mixed lymphocyte culture [(MLR]) on Day 48. MLR reactivity returned on Day 64 together with the development of anti-donor antibody and subsequent xenograft failure on Day 112. Donor specific T-cell hyporesponsiveness was detected in the other long-term survivor for the first 133 days, after which a donor-specific skin xenograft was placed, (survival 24 days). Following the skin graft rejection, a rise in the MLR, development of anti-donor antibody and progressive rejection of the renal xenograft were observed. CONCLUSIONS: Antibody-mediated rejection seems to constitute the major difference between concordant xenografts and allografts. Addition of 15-deoxyspergualine for 2 weeks posttransplant extended concordant primate xenograft survival to 6 months without chronic immunosuppression. In contrast to the allogeneic model, renal transplant acceptance in this xenogeneic system was interrupted by placement of a donor-specific skin graft.
Assuntos
Transplante de Medula Óssea/imunologia , Tolerância Imunológica/fisiologia , Transplante de Rim/imunologia , Transplante Heterólogo/imunologia , Animais , Anticorpos Heterófilos/análise , Anticorpos Monoclonais/farmacologia , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Guanidinas/farmacologia , Imunossupressores/farmacologia , Macaca fascicularis , Masculino , Camundongos , Papio , Transplante de Pele/imunologia , Linfócitos T/fisiologia , Fatores de TempoRESUMO
Antibody-mediated rejection appears to constitute the major difference between concordant xenografts and allografts in nonhuman primates. Consistent with its known effect on antibody responses, 5-7 addition of DSG to the conditioning regimen has extended concordant primate xenograft survival for up to 6 months after discontinuation of conventional immunosuppression. In contrast to our observations in recipients of renal allografts, donor-specific skin graft rejection can occur and even in long-term recipients may induce rejection of a previously accepted renal xenograft.
Assuntos
Transplante de Medula Óssea/imunologia , Rejeição de Enxerto/imunologia , Transplante de Rim/imunologia , Transplante Heterólogo/imunologia , Animais , Anticorpos Heterófilos/sangue , Formação de Anticorpos , Soro Antilinfocitário/uso terapêutico , Ciclosporina/farmacologia , Sobrevivência de Enxerto , Guanidinas/farmacologia , Imunidade Celular , Imunoglobulina G/sangue , Terapia de Imunossupressão/métodos , Imunossupressores/farmacologia , Macaca fascicularis , Papio , Esplenectomia , Timo/efeitos da radiação , Transplante Heterólogo/patologia , Irradiação Corporal TotalAssuntos
Anticorpos Monoclonais/farmacologia , Antígenos CD2/imunologia , Imunossupressores/farmacologia , Isoantígenos/imunologia , Linfócitos T/imunologia , Sequência de Aminoácidos , Animais , Citotoxicidade Celular Dependente de Anticorpos , Citocinas/biossíntese , Humanos , Imunoglobulina G/farmacologia , Células Matadoras Naturais/imunologia , Camundongos , Dados de Sequência Molecular , RatosRESUMO
Primary cultures of porcine endothelial cells (EC) can only be maintained for a limited number of passages. To facilitate studies of xenogeneic human anti-pig immune responses in vitro, pig microvascular bone-marrow (BM) and macrovascular aortic EC were obtained from our herd of partially inbred miniature swine, homozygous for the major histocompatibility locus, and immortalized with a modified SV40 large T vector. The resulting BM-derived (2A2) and aortic (PEDSV.15) immortalized EC lines showed unlimited growth and EC phenotype as indicated by expression of von Willebrand Factor (vWF) and low density lipoprotein (LDL) receptors as well as by formation of typical cobblestone monolayers. Ultrastructural studies revealed morphological similarities in primary and immortalized EC. Flow cytometry analysis demonstrated constitutive SLA class I expression by all lines whereas SLA class II was only expressed after stimulation with porcine IFNgamma. Furthermore, pig CD34 mRNA was detected by Northern blot analysis in primary and immortalized aortic EC but not in 2A2. Both EC lines expressed a number of myeloid markers, adhesion molecules and xenoantigens, the latter being determined by binding of human natural antibodies. Gene transfer into the porcine EC lines was successfully performed by electroporation or calcium-phosphate transfection, as well as by adenoviral infection. Finally, the functional similarity between primary and immortalized EC was demonstrated in adhesion and cytotoxicity assays. Together, these results suggest that 2A2 and PEDSV. 15 represent valuable tools to study both human cellular and humoral immune responses in vitro against pig EC derived from microvascular and large vessels.
Assuntos
Células da Medula Óssea , Transformação Celular Viral , Endotélio Vascular , Transplante Heterólogo , Animais , Antígenos Transformantes de Poliomavirus , Linhagem Celular Transformada , Eletroporação , Humanos , SuínosRESUMO
Prior studies from our laboratory have demonstrated that a nonmyeloablative conditioning regimen can induce transient mixed chimerism and renal allograft tolerance between MHC disparate cynomolgus monkeys. We have also shown that this preparative regimen can be extended to a concordant baboon to cynomolgus xenograft model by adding, to the post transplant protocol, therapy designed to prevent antibody production. Here we examine the use of brequinar (BQR) for this purpose and the efficacy of two new reagents developed to demonstrate the establishment of chimerism in the xenograft recipients. The cynomolgus recipients were conditioned with WBI (300 cGy), TI (700 cGy), ATG, cyclosporine, and brequinar sodium. To detect engraftment of the donor marrow, we prepared a polyclonal cynomolgus anti-baboon antibody (CABA) and a monoclonal antibody (215.1), which distinguish baboon and cynomolgus lymphocytes and granulocytes. We employed flow cytometry analysis to detect multilineage chimerism in the xenograft recipients. Five of the six recipients monitored using our new reagents (CABA and 215.1) developed detectable chimerism and only one of these animals lost its kidney to rejection. However, other complications have not permitted assessment of long-term outcome. The features of the multilineage chimerism included the detection of donor granulocytes (1.8-77.4%) and lymphocytes (2.4-22.2%) for 9 to 37 days. Our new reagents permit the detection of multilineage mixed chimerism, which may be a predictor of xenograft tolerance. We also conclude that brequinar may be effective in preventing antibody formation, but because of its toxicity, it is probably not the drug of choice for extension of the mixed chimerism protocol to concordant xenografts.