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1.
BMC Genomics ; 25(1): 217, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413905

RESUMO

BACKGROUND: The genomic region that lies between the telomere and chromosome body, termed the subtelomere, is heterochromatic, repeat-rich, and frequently undergoes rearrangement. Within this region, large-scale structural changes enable gene diversification, and, as such, large multicopy gene families are often found at the subtelomere. In some parasites, genes associated with proliferation, invasion, and survival are often found in these regions, where they benefit from the subtelomere's highly plastic, rapidly changing nature. The increasing availability of complete (or near complete) parasite genomes provides an opportunity to investigate these typically poorly defined and overlooked genomic regions and potentially reveal relevant gene families necessary for the parasite's lifestyle. RESULTS: Using the latest chromosome-scale genome assembly and hallmark repeat richness observed at chromosome termini, we have identified and characterised the subtelomeres of Schistosoma mansoni, a metazoan parasitic flatworm that infects over 250 million people worldwide. Approximately 12% of the S. mansoni genome is classified as subtelomeric, and, in line with other organisms, we find these regions to be gene-poor but rich in transposable elements. We find that S. mansoni subtelomeres have undergone extensive interchromosomal recombination and that these sites disproportionately contribute to the 2.3% of the genome derived from segmental duplications. This recombination has led to the expansion of subtelomeric gene clusters containing 103 genes, including the immunomodulatory annexins and other gene families with unknown roles. The largest of these is a 49-copy plexin domain-containing protein cluster, exclusively expressed in the tegument-the tissue located at the host-parasite physical interface-of intramolluscan life stages. CONCLUSIONS: We propose that subtelomeric regions act as a genomic playground for trial-and-error of gene duplication and subsequent divergence. Owing to the importance of subtelomeric genes in other parasites, gene families implicated in this subtelomeric expansion within S. mansoni warrant further characterisation for a potential role in parasitism.


Assuntos
Schistosoma mansoni , Telômero , Humanos , Animais , Schistosoma mansoni/genética , Telômero/genética , Genômica , Duplicação Gênica , Família Multigênica
2.
J Environ Manage ; 259: 110044, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31929029

RESUMO

Graphene oxide (GO) is a single-atom-thick sheet of carbon with oxygen-containing functional groups decorating its basal plane and edge sites. Most of its high surface area can be lost due to restacking of individual layers during the synthesis and drying of GO-based bulk sorbents. There is great interest to increase the specific surface area of graphene-based sorbents by introducing organic molecules as "pillaring agents" between GO sheets to hinder the stacking process and create sorbents with elevated surface area. This work synthesizes pillared GO by introducing chitosan (CS), a linear polysaccharide with various molecular weights. A composite of low molecular weight CS at a CS/GO ratio of 0.1 is shown to have the highest specific surface area (up to 70.5 m2/g) in comparison to the medium and high CS molecular weight, pristine GO, and the CS/GO composite materials. The affinity of the optimized GO/CS composites towards benzene, toluene, and naphthalene was evaluated at 19.3 mg/L of organic matter content while altering pH. Sips and Langmuir adsorption isotherm models well described the adsorption behavior, and benzene adsorption performance was reduced at low pH. Related to the presence of dissolved organic matter (DOM) in solution, lower diffusivity constants (k1) in hydrocarbon systems were recorded. Our results demonstrate the feasibility of CS as a potential pillaring agent in CS/GO composites to increase specific surface area and enhance the capture of soluble hydrocarbons from aqueous solutions.


Assuntos
Grafite , Adsorção , Concentração de Íons de Hidrogênio , Óxidos , Água
3.
Am J Transplant ; 17(4): 1129-1131, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27873483

RESUMO

Lung transplantation using RNA+ hepatitis C (HCV+) donors to seronegative recipients is not currently performed due to the very high risk of transmission. Previous reports have shown poor survival when this practice was applied. The emergence of new direct-acting antiviral drugs (DAA) suggests a high chance of sustained virologic response in immunocompetent patients. We report here successful transplantation of lungs from HCV+ donor to HCV- recipient. The recipient was an HCV- patient with chronic lung allograft dysfunction. Viral transmission occurred early posttransplant but excellent clinical outcomes were observed including elimination of HCV after 12 weeks of treatment using DAAs.


Assuntos
Sobrevivência de Enxerto , Hepatite C/prevenção & controle , Transplante de Pulmão/métodos , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Transplantados , Adulto , Hepacivirus/fisiologia , Hepatite C/transmissão , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade
4.
Actas Dermosifiliogr ; 108(7): e49-e52, 2017 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28407871

RESUMO

Darier disease is an autosomal-dominant inherited condition caused by mutation of a gene, which produces a protein involved in calcium channel regulation. The disease has a variety of manifestations and lacks consistent genotype-phenotype correlations. Acral hemorrhagic Darier disease causes macules, papules, vesicles and/or hemorrhagic blisters on the extremities. Other classic signs of the disease may be present in the same patient or relatives. Histopathology reveals dyskeratosis and suprabasal acantholysis with hemorrhagic lacunae. We report 3 new cases of this type of Darier disease triggered by injuries. Response to retinoid therapy was good.


Assuntos
Doença de Darier/etiologia , Traumatismos da Mão/complicações , Acitretina/uso terapêutico , Adulto , Doença de Darier/tratamento farmacológico , Doença de Darier/genética , Doença de Darier/patologia , Fármacos Dermatológicos/uso terapêutico , Feminino , Humanos , Isotretinoína/uso terapêutico , Masculino , Pessoa de Meia-Idade , Unhas Malformadas/etiologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Estações do Ano , Tretinoína/uso terapêutico
5.
Am J Transplant ; 15(2): 417-26, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25612494

RESUMO

Donor-specific HLA antibodies (DSA) have an adverse effect on short-term and long-term lung transplant outcomes. We implemented a perioperative strategy to treat DSA-positive recipients, leading to equivalent rejection and graft survival outcomes. Pretransplant DSA were identified to HLA-A, B, C, DR and DQ antigens. DSA-positive patients were transplanted if panel reactive antibody (PRA) ≥30% or medically urgent and desensitized with perioperative plasma exchange, intravenous immune globulin, antithymocyte globulin (ATG), and mycophenolic acid (MPA). PRA-positive/DSA-negative recipients received MPA. Unsensitized patients received routine cyclosporine, azathioprine and prednisone without ATG. From 2008-2011, 340 lung-only first transplants were performed: 53 DSA-positive, 93 PRA-positive/DSA-negative and 194 unsensitized. Thirty-day survival was 96 %/99%/96% in the three groups, respectively. One-year graft survival was 89%/88%/86% (p = 0.47). DSA-positive and PRA-positive/DSA-negative patients were less likely to experience any ≥ grade 2 acute rejection (9% and 9% vs. 18% unsensitized p = 0.04). Maximum predicted forced expiratory volume (1 s) (81%/74%/76%, p = NS) and predicted forced vital capacity (81%/77%/78%, respectively, p = NS) were equivalent between groups. With the application of this perioperative treatment protocol, lung transplantation can be safely performed in DSA/PRA-positive patients, with similar outcomes to unsensitized recipients.


Assuntos
Dessensibilização Imunológica/métodos , Sobrevivência de Enxerto/fisiologia , Transplante de Pulmão/mortalidade , Pulmão/fisiologia , Assistência Perioperatória/métodos , Transplantados , Adulto , Idoso , Soro Antilinfocitário/uso terapêutico , Canadá , Estudos de Coortes , Feminino , Seguimentos , Volume Expiratório Forçado/fisiologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Troca Plasmática , Estudos Retrospectivos , Resultado do Tratamento , Capacidade Vital/fisiologia
6.
J Antimicrob Chemother ; 70(4): 1064-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25604745

RESUMO

OBJECTIVES: The most common mechanism of azole (itraconazole and voriconazole) resistance in Aspergillus fumigatus is a mutation at the cyp51A locus. The aim of our study was to determine the rate of cyp51A mutations in lung transplant recipients (LTR) undergoing targeted antifungal prophylaxis with 12 weeks of voriconazole. METHODS: We conducted a prospective study that included 22 LTR with A. fumigatus between October 2008 and November 2011. Of those, 10 LTR were colonized with A. fumigatus and 12 had invasive pulmonary aspergillosis. RESULTS: Four patients were found to have A. fumigatus isolates with a cyp51A mutation, two had colonization and two had invasive pulmonary aspergillosis. The remaining 18 LTR had WT cyp51A A. fumigatus isolates. All A. fumigatus isolates (except one due to mixed growth) were tested for antifungal susceptibility. A total of nine LTR were exposed to azoles prior to A. fumigatus isolation for a median duration of 249 (IQR 99-524) days. Azole exposure preceded the isolation of two mutant isolates and seven WT isolates. None of the cyp51A mutant isolates conferred phenotypic resistance to azoles. CONCLUSIONS: Targeted antifungal prophylaxis in LTR did not lead to cyp51A resistance mutations in this cohort. Data on larger cohorts who receive universal antifungal prophylaxis are needed.


Assuntos
Antifúngicos/uso terapêutico , Aspergillus fumigatus/enzimologia , Sistema Enzimático do Citocromo P-450/genética , Proteínas Fúngicas/genética , Transplante de Pulmão , Taxa de Mutação , Aspergilose Pulmonar/microbiologia , Voriconazol/uso terapêutico , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , Quimioprevenção/métodos , Humanos , Estudos Prospectivos , Transplantados
7.
Am J Transplant ; 13(10): 2722-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24007361

RESUMO

Primary graft failure and chronic lung allograft dysfunction (CLAD) limit lung transplant long-term outcomes. Various lung diseases have been correlated with surfactant protein (SP) expression and polymorphisms. We sought to investigate the role of SP expression in lung allografts prior to implantation, in relation to posttransplant outcomes. The expression of SP-(A, B, C, D) mRNA was assayed in 42 allografts. Posttransplant assessments include pulmonary function tests, bronchoscopy, broncho-alveolar lavage fluid (BALF) and biopsies to determine allograft rejection. BALF was assayed for SP-A, SP-D in addition to cytokines IL-8, IL-12 and IL-2. The diagnosis of CLAD was evaluated 6 months after transplantation. Lung allografts with low SP-A mRNA expression prior to implantation reduced survival (Log-rank p < 0.0001). No association was noted for the other SPs. Allografts with low SP-A mRNA had greater IL-2 (p = 0.03) and IL-12 (p < 0.0001) in the BALF and a greater incidence of rejection episodes (p = 0.003). Levels of SP-A mRNA expression were associated with the SP-A2 polymorphisms (p = 0.015). Specifically, genotype 1A1A(0) was associated with lower SP-A mRNA expression (p < 0.05). Lung allografts with low levels of SP-A mRNA expression are associated with reduced survival. Lung allograft SP-A mRNA expression appears to be associated with SP-A gene polymorphisms.


Assuntos
Rejeição de Enxerto/genética , Pneumopatias/cirurgia , Transplante de Pulmão , Polimorfismo Genético/genética , Proteína A Associada a Surfactante Pulmonar/genética , Adulto , Idoso , Aloenxertos , Líquido da Lavagem Broncoalveolar , Citocinas/genética , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prognóstico , Estudos Prospectivos , Proteína D Associada a Surfactante Pulmonar/genética , RNA Mensageiro/genética , Estudos Retrospectivos , Taxa de Sobrevida
8.
Mol Biol Evol ; 28(11): 3139-50, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21616911

RESUMO

Whole genome duplication (WGD) and subsequent evolution of gene pairs have been shown to have shaped the present day genomes of most, if not all, plants and to have played an essential role in the evolution of many eukaryotic genomes. Analysis of the rice (Oryza sativa ssp. japonica) genome sequence suggested an ancestral WGD ∼50-70 Ma common to all cereals and a segmental duplication between chromosomes 11 and 12 as recently as 5 Ma. More recent studies based on coding sequences have demonstrated that gene conversion is responsible for the high sequence conservation which suggested such a recent duplication. We previously showed that gene conversion has been a recurrent process throughout the Oryza genus and in closely related species and that orthologous duplicated regions are also highly conserved in other cereal genomes. We have extended these studies to compare megabase regions of genomic (coding and noncoding) sequences between two cultivated (O. sativa, Oryza glaberrima) and one wild (Oryza brachyantha) rice species using a novel approach of topological incongruency. The high levels of intraspecies conservation of both gene and nongene sequences, particularly in O. brachyantha, indicate long-range conversion events less than 4 Ma in all three species. These observations demonstrate megabase-scale conversion initiated within a highly rearranged region located at ∼2.1 Mb from the chromosome termini and emphasize the importance of gene conversion in cereal genome evolution.


Assuntos
Cromossomos de Plantas/genética , Evolução Molecular , Conversão Gênica/genética , Oryza/genética , Recombinação Genética/genética , Sequência de Bases , Cromossomos Artificiais Bacterianos/genética , Mapeamento de Sequências Contíguas , Genômica , Funções Verossimilhança , Modelos Genéticos , Dados de Sequência Molecular , Análise de Sequência de DNA , Especificidade da Espécie
9.
Am J Transplant ; 12(7): 1929-35, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22486950

RESUMO

Voriconazole is commonly used for prophylaxis and treatment of invasive aspergillosis in lung transplant recipients. However, the use of voriconazole may at times be limited by the development of hepatotoxicity. Our goal is to determine predictors of voriconazole-associated hepatotoxicity in lung transplant recipients. We conducted a single center retrospective cohort study of lung transplant recipients from 2006 to 2010 who received voriconazole therapy. We compared characteristics of patients who developed hepatotoxicity and those who did not. One hundred five lung transplant recipients received voriconazole. Hepatotoxicity occurred in 51% (54/105) of patients and lead to discontinuation in 34% (36/105). In univariate analysis, age less than 40 years, cystic fibrosis, use of azathioprine, history of liver disease and early initiation of voriconazole were associated with hepatotoxicity. In multivariable logistic regression analysis, perioperative initiation of voriconazole (within 30 days of transplantation) was independently associated with hepatotoxicity (OR 4.37, 95% CI: 1.53-12.43, p = 0.006). The five risk factors identified in the univariate analysis were used to build a K-nearest neighbor algorithm predictive model for hepatotoxicity. This model predicted hepatotoxicity with an accuracy of 70%. Voriconazole therapy initiated within the first 30 days of transplantation is associated with a greater risk of developing hepatotoxicity.


Assuntos
Antifúngicos/efeitos adversos , Fígado/efeitos dos fármacos , Transplante de Pulmão , Pirimidinas/efeitos adversos , Triazóis/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Voriconazol , Adulto Jovem
10.
Clin Transplant ; 26(1): 34-41, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21272072

RESUMO

People with severe cystic fibrosis (CF) lung disease with co-existent CF-associated liver disease (CFLD) are often excluded from consideration of sole lung transplantation, largely because of the concerns that they will subsequently develop hepatic decompensation. This retrospective cohort study aimed at determining whether patients with severe cirrhosis caused by CFLD have any differences in perioperative and relevant post-transplant outcomes compared to CF patients without CFLD when undergoing sole lung transplantation. Six patients with CFLD were matched with 18 CF patients without CFLD undergoing sole lung transplant at the same institution. There were no differences in total operative time or intra-operative requirements for cardiopulmonary bypass or blood products. Over a period of five yr post-transplant, no differences were observed between the two groups in body mass index, six-min walk, lung function, and survival. None of the CFLD subjects developed variceal bleeding; however, one developed hepatocellular and renal failure at four yr post-transplant and is being assessed for liver-kidney transplant. One additional patient with CFLD required repeat lung transplantation for bronchiolitis obliterans syndrome. This study provides evidence that CF patients with liver cirrhosis caused by CFLD can safely be considered for sole lung transplantation provided there is no evidence of significant hepatocellular dysfunction with decompensated cirrhosis or hepatic synthetic failure.


Assuntos
Fibrose Cística/mortalidade , Fibrose Cística/terapia , Cirrose Hepática/mortalidade , Transplante de Pulmão/mortalidade , Adolescente , Adulto , Criança , Fibrose Cística/complicações , Feminino , Volume Expiratório Forçado , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
12.
Clin Nutr ; 40(3): 895-900, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33097307

RESUMO

There are reports of children COVID-19 or COVID-19 like symptoms with hyperinflammatory multisystem syndrome, ARDS, gastrointestinal and atypical Kawasaki disease presenting to PICU worldwide temporally associated with COVID-19, for which there are important nutrition support considerations. As a result, the European Society of Pediatric and Neonatal Intensive Care - Metabolism, Endocrine and Nutrition group (ESPNIC-MEN) and paediatric nutritionists working in PICUs are being consulted regarding nutrition management of critically ill children with COVID-19 or COVID-19 like symptoms. Therefore, the aim of this short report is to provide a summary of nutrition support recommendations for critically ill children with COVID-19. They are based on the ESPNIC-MEN section recommendations published in January 2020 and surviving sepsis recommendations from February 2020.


Assuntos
COVID-19/terapia , Apoio Nutricional/métodos , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica/terapia , Criança , Cuidados Críticos/métodos , Estado Terminal , Nutrição Enteral/métodos , Humanos , Unidades de Terapia Intensiva Pediátrica , Estado Nutricional
13.
Transpl Infect Dis ; 12(6): 551-4, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20553438

RESUMO

Cystic fibrosis (CF) lung transplant recipients infected with Burkholderia cenocepacia have a worse survival rate after lung transplantation than those who are not infected with this organism. The decreased survival is predominantly due to recurrent B. cenocepacia infection, with the majority of affected recipients succumbing within 3 months after transplant. B. cepacia complex (BCC) sepsis is one of the defining criteria for cepacia syndrome, an almost universally fatal necrotizing pneumonic illness. We report 2 CF patients who were long-term survivors of B. cenocepacia sepsis after lung transplantation. The aim of this report is to demonstrate that, although survival of B. cenocepacia sepsis after lung transplantation is extremely uncommon, with aggressive multidisciplinary management, long-term survival remains a realistic objective.


Assuntos
Infecções por Burkholderia/mortalidade , Complexo Burkholderia cepacia/isolamento & purificação , Fibrose Cística/complicações , Fibrose Cística/mortalidade , Transplante de Pulmão/efeitos adversos , Sepse/mortalidade , Adulto , Antibacterianos/uso terapêutico , Infecções por Burkholderia/microbiologia , Infecções por Burkholderia/cirurgia , Complexo Burkholderia cepacia/classificação , Complexo Burkholderia cepacia/efeitos dos fármacos , Fibrose Cística/tratamento farmacológico , Fibrose Cística/cirurgia , Empiema Pleural/microbiologia , Empiema Pleural/cirurgia , Feminino , Humanos , Pulmão/cirurgia , Abscesso Pulmonar/microbiologia , Abscesso Pulmonar/cirurgia , Transplante de Pulmão/mortalidade , Masculino , Sepse/tratamento farmacológico , Sepse/microbiologia , Sepse/cirurgia , Taxa de Sobrevida , Sobreviventes , Adulto Jovem
14.
J Cyst Fibros ; 17(1): e1-e4, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28549610

RESUMO

Cystic fibrosis (CF) affects multiple organs including the lung, liver, and pancreas. Lung transplant, liver transplant, and combined lung-liver transplant have become well-established therapies for CF patients with end-stage organ failure. Thus far, however, there has been limited experience with pancreas transplantation in CF. In this report, we detail the clinical history, transplant procedure, and post-operative recovery of a patient who underwent combined lung-liver-pancreas transplant for advanced CF.


Assuntos
Fibrose Cística , Transplante de Fígado/métodos , Transplante de Pulmão/métodos , Transplante de Pâncreas/métodos , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Fibrose Cística/fisiopatologia , Fibrose Cística/cirurgia , Progressão da Doença , Humanos , Fígado/fisiopatologia , Fígado/cirurgia , Pulmão/fisiopatologia , Pulmão/cirurgia , Masculino , Pâncreas/fisiopatologia , Pâncreas/cirurgia , Assistência Perioperatória/métodos , Resultado do Tratamento , Adulto Jovem
15.
Transplantation ; 72(11): 1783-6, 2001 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-11740388

RESUMO

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is now a widely recognized complication of lung transplantation. In the current study, we present our experience with PTLD over a 15-year period, which includes the incidence rates in 242 lung allografts and the relative risk of developing PTLD in 146 patients with known pretransplantation Epstein-Barr virus (EBV) status. METHODS: Inpatient and outpatient charts of 300 consecutive lung transplant recipients between 1984 and 1999 were retrospectively reviewed. RESULTS: Twelve cases of PTLD were observed for a total incidence rate of 5.0%. Ten of these patients had pretransplantation EBV testing, and the consequent increase in relative risk for patients who were EBV negative was 6.8-fold. The mean time between organ transplantation and tissue diagnosis of PTLD was 17.6 months. Total 1-year survival rate from the time of diagnosis for the cohort was 58%, whereas 2-year survival rate was 50%. Median survival for the six patients who died was 4.5 months. CONCLUSIONS: These data suggest that although EBV seronegativity does carry a 6.8-fold increase in the relative risk of developing PTLD, long-term survival despite the development of PTLD can be achieved, and thus EBV seronegativity by itself should not be considered a contraindication to lung transplantation.


Assuntos
Reações Antígeno-Anticorpo , Herpesvirus Humano 4/imunologia , Transplante de Pulmão/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Incidência , Transtornos Linfoproliferativos/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo
16.
Chest ; 115(3): 741-5, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10084486

RESUMO

BACKGROUND: Immunosuppression and chronic lung disease are known risk factors for mycobacterial infection and might be expected to develop with an increased frequency in lung transplant recipients. We therefore sought to document the incidence and type of mycobacterial infections in a large lung transplant program. METHODS: A retrospective review of 219 transplant procedures (60 single lung transplants and 159 double lung transplants) in 210 patients was conducted. All patients had scheduled surveillance bronchoscopies at 3, 6, 9, 12, 18, and 24 months, and yearly thereafter. BAL samples were processed routinely for mycobacterium. RESULTS: Eight patients (3.8%) had evidence of infection (5 men, 3 women; age range, 26 to 63 years). The reasons for transplant were obstructive lung disease (six), cystic fibrosis (one), and pulmonary fibrosis (one). Five recipients had infection in their native lungs; two of five cultured mycobacterium from BAL following transplantation. At least four of five patients had nontuberculous mycobacterium (one showed acid fast bacilli and granuloma on a biopsy specimen that was not sent for culture). None of the five developed disease (mean follow-up = 22 months; range, 3 to 30 months). The organisms were Mycobacterium avium complex (three), Mycobacterium xenopi (one), and unidentified (one). Of the three remaining patients who developed infection after transplantation, one grew Mycobacterium chelonae and the others grew Mycobacterium tuberculosis (both received double lung transplants and had no evidence of mycobacterium in their native lungs). The only definite symptomatic disease occurred in the patients with M tuberculosis, one of whom had evidence of dissemination. The patients with M tuberculosis responded to standard treatment. There have been no deaths due to mycobacterium. CONCLUSION: Mycobacterial disease rarely occurs following lung transplantation. Cultures for mycobacterium in surveillance BALs in the absence of symptoms are likely unnecessary.


Assuntos
Hospedeiro Imunocomprometido , Transplante de Pulmão , Infecções por Mycobacterium , Complicações Pós-Operatórias , Adulto , Anti-Infecciosos/uso terapêutico , Feminino , Humanos , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium/tratamento farmacológico , Infecções por Mycobacterium/imunologia , Complicações Pós-Operatórias/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
17.
Chest ; 113(4): 924-32, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9554627

RESUMO

BACKGROUND: Cytomegalovirus (CMV) disease is an important cause of organ transplant-related morbidity and mortality. During the last 5 years at our institution, prophylactic ganciclovir and hyperimmune globulin have been routinely administered to lung transplant recipients whenever the donor or the recipient was CMV antibody-positive. We sought to assess the efficacy of prophylaxis on viremia, CMV disease, and bronchiolitis obliterans syndrome (BOS). METHODS: A retrospective chart review of 61 consecutive lung transplants performed between recipients between January 1993 and August 1995 was performed. Fifty-six patients who survived at least 1 month were analyzed. Patients were considered at risk for CMV disease whenever pretransplant donor or recipient serology was positive. RESULTS: Fourteen of the 39 patients at risk (36%) had viremia while on prophylaxis. The rate of CMV disease was 13% during the first 6 months following transplantation. A donor whose CMV serology was positive appeared to increase the risk of BOS in a Cox regression model (relative risk=2.4; 95% confidence interval=0.86-6.74; p=0.0957). Neither age, CMV infection (viremia or a positive specimen from BAL), recipient's serology at the time of transplantation, or CMV disease was associated with BOS. None of these variables was associated with mortality on Cox regression analysis or univariate analysis. CONCLUSIONS: Administration of combination ganciclovir and hyperimmune globulin prophylactic therapy to lung transplant recipients at risk for CMV infection and disease is associated with a relatively low incidence of disease, which appears only after prophylaxis treatment with ganciclovir is completed. Ganciclovir prophylaxis does not prevent CMV viremia; however, viremia while on prophylaxis is not predictive of disease.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Transplante de Pulmão , Complicações Pós-Operatórias/prevenção & controle , Viremia/prevenção & controle , Adulto , Idoso , Bronquiolite Obliterante/complicações , Líquido da Lavagem Broncoalveolar/virologia , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos
18.
Chest ; 110(5): 1150-4, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8915212

RESUMO

We reviewed all tissue specimens from 163 transplant patients (108 double lung transplant [DLT], 55 single lung transplant [SLT]) between November 1983 and January 1994 for abnormalities indicating bronchiolitis obliterans organizing pneumonia (BOOP) and found 17 cases (14 DLT and 3 SLT). Of the three SLTs, BOOP was diagnosed by open lung biopsy (OLB) in two and one was found at autopsy. Of the 14 DLTs, BOOP was diagnosed by transbronchial biopsy (TBB) specimens (9), OLB specimens (2), autopsy (1), TBB and OLB specimens (1), and OLB specimens and autopsy (1). BOOP was found between 1 and 43 months posttransplantation; time of survival from diagnosis was between 2 and 36 months with 9 patients presently alive. Concurrent pathologic diagnosis at the time of BOOP findings were as follows: acute rejection (7) (grade 1 [4] and grade 2 [3]), BO and grade 1 rejection (2), BO and grade 2 rejection (2), BO and Aspergillus infection (1), acute alveolar injury (1), acute alveolar injury and pulmonary embolus (1), acute rejection (grade 1) and Burkholderia cepacia pneumonia (1). No other pathologic diagnosis was found in 1 patient. In total, 11 of 17 patients (65%) had associated acute rejection. Of the 17 patients, 7 subsequently developed BO and 3 had BO before the finding of BOOP. Death occurred in 8 patients (5 DLT and the 3 SLT) between 2 and 6 months after the diagnosis. We conclude that BOOP is an important complication after lung transplantation; it was present in 13% of DLTs and 5% of SLTs. BOOP was most often associated with acute rejection.


Assuntos
Pneumonia em Organização Criptogênica/etiologia , Transplante de Pulmão , Doença Aguda , Adolescente , Adulto , Aspergilose/etiologia , Aspergilose/patologia , Autopsia , Biópsia , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/patologia , Infecções por Burkholderia/etiologia , Infecções por Burkholderia/patologia , Burkholderia cepacia , Pneumonia em Organização Criptogênica/patologia , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Pneumopatias Fúngicas/etiologia , Pneumopatias Fúngicas/patologia , Transplante de Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/etiologia , Pneumonia Bacteriana/patologia , Embolia Pulmonar/etiologia , Embolia Pulmonar/patologia , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/patologia , Estudos Retrospectivos , Taxa de Sobrevida
19.
Chest ; 117(2): 476-81, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10669693

RESUMO

STUDY OBJECTIVE: Osteoporosis is a well-recognized complication of lung transplantation that may significantly impair the quality of life of transplant recipients. We performed a prospective study of bone mineral density (BMD) before and after transplantation to determine the degree of bone mass loss associated with lung transplantation Patients and design: We conducted a prospective study of BMD in 28 patients with various end-stage respiratory diseases pretransplantation and 6 to 12 months posttransplantation. The BMD of the lumbar spine (LS) and femoral neck (FN) were measured. All 28 patients were treated only with vitamin D and calcium supplementation posttransplant. The primary endpoint was the percentage change in BMD. The secondary endpoint was the incidence of fractures posttransplant. A univariate analysis was conducted to determine the various risk factors associated with bone mass loss pretransplant and posttransplant. RESULTS: Prior to transplantation, moderate to severe bone disease was evident. The mean (+/- SD) pretransplant T score (the number of SDs from the peak bone mass) and Z score (the number of SDs from the age-matched mean) for the LS were -1.72 +/- 1.37 and -1.44 +/- 1.31, respectively. The mean pretransplant T score and Z score for the FN were -2.65 +/- 1.01 and -1.5 +/- 1.43, respectively. Within 6 to 12 months posttransplant, the mean BMD for the LS decreased by 4.76% (p < 0.001), while the mean BMD for the FN decreased by 5.3% (p < 0.001). Five of the 28 patients (18%) suffered osteoporotic fractures posttransplant, while no fractures were documented pretransplant. The cumulative steroid dose posttransplant was associated with a drop in BMD for the LS and FN (r = 0.39, p = 0.039 and r = 0.63, p < 0.001, respectively), while a negative association was found between cumulative steroid use pretransplant and baseline LS and FN T scores (r = -0.4, p = 0. 02 and r = -0.43, p = 0.023, respectively). CONCLUSION: Within 6 to 12 months after lung transplantation, there is a significant decrease in BMD at both the LS and FN levels (approximately 5%) despite vitamin D and calcium supplementation. This drop in BMD is associated with a relatively high incidence of osteoporotic fractures posttransplant.


Assuntos
Densidade Óssea/fisiologia , Transplante de Pulmão/fisiologia , Osteoporose/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Absorciometria de Fóton , Adulto , Idoso , Osso e Ossos/fisiopatologia , Feminino , Seguimentos , Fraturas Espontâneas/diagnóstico , Fraturas Espontâneas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Estudos Prospectivos , Fatores de Risco
20.
J Thorac Cardiovasc Surg ; 110(1): 22-6, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7541881

RESUMO

Pleural complications occurred in 30 (22%) of 138 patients after 53 single and 91 double lung transplants between September 1986 and February 1993. These were defined for the purpose of this study as pneumothorax persisting beyond the first 14 postoperative days, recurrent pneumothorax, or any other pleural process that necessitated diagnostic or therapeutic intervention. Overall, a higher pleural complication rate was seen in double lung transplantation (25 of 30) than in single lung transplantation (5 of 30) with no differences noted in the frequency among preoperative diagnostic groups (p > 0.05). Pneumothorax was the most frequent complication, affecting 14 of 30 patients, with 6 of 14 cases occurring after transbronchial biopsy. All pneumothoraces in single (n = 4) and double lung transplantation (n = 10) resolved spontaneously or with chest tube thoracostomy. One patient required placement of a Clagett window after open lung biopsy and another required thoracotomy and pleural abrasion after transbronchial biopsy. Parapneumonic effusion was observed in 4 of 30 double lung transplantations with spontaneous resolution in all cases. Empyema affected 7 of 30 patients and occurred exclusively in the double lung transplant group. Sepsis developed in three of the patients with this complication and they subsequently died. The risk of empyema was independent of preoperative diagnosis (p > 0.05). Of interest, all patients with cystic fibrosis (n = 3) with complicating empyema had Pseudomonas cepacia in the pleural fluid. Other miscellaneous complications included subpleural hematoma, chylothorax, and hemothorax. The latter two necessitated thoracic duct and bronchial artery ligation, respectively. In summary, a significant proportion of lung transplant recipients will have pleural space complications. The vast majority of these will resolve spontaneously or with conservative procedures. These complications were not related to preoperative diagnosis nor associated with a significant prolongation of hospital stay (p > 0.05). Empyema is the only pleural space complication associated with increased patient mortality and, as such, is an important clinical marker for those at risk for sepsis and death.


Assuntos
Transplante de Pulmão/efeitos adversos , Doenças Pleurais/etiologia , Pneumotórax/etiologia , Adulto , Burkholderia cepacia/isolamento & purificação , Distribuição de Qui-Quadrado , Fibrose Cística/complicações , Empiema/etiologia , Empiema/mortalidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Derrame Pleural/microbiologia , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosa/isolamento & purificação , Recidiva , Fatores de Risco , Análise de Sobrevida
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