RESUMO
Modern and effective patient care requires specialist healthcare professionals working together. Interprofessional learning (IPL) seeks to provide opportunities for different healthcare disciplines to learn with, from and about each other. This study focused on the delivery and evaluation of a cytomegalovirus (CMV) case study workshop to facilitate IPL between two Health and Care Professions Council (HCPC) regulated courses: Biomedical Science and Audiology. The 2 h online workshop consisted of 1) defining the roles, responsibilities and skills of the two healthcare professions, 2) the structure of the Biomedical Science and Audiology departments, 3) routes to HCPC registration, 4) core curriculum of both degree programmes and 5) interpreting interdisciplinary data related to a CMV patient case. The workshop was interactive, with the virtual learning environment promoting peer discussions and the use of online polling. Student responses were collected through an online questionnaire. A total of 108 respondents completed a post-event survey and Mann-Whitney U tests revealed there were no significant differences in the responses between the two student cohorts in response to each of the survey statements (p > 0.05). A total of 82.4% of students agreed that they need to know the role of other healthcare professionals for their future practice, whilst 84.2% agreed that the CMV case study was a good format to facilitate effective IPL. A total of 93.5% of respondents recognised the importance of both professions in diagnosing a patient with CMV. Thematic analysis identified four common themes, including appreciation of shared roles, recognition of similarities in registration pathways, working together to provide holistic patient care and the role of clinicians in the patient journey. This novel collaboration between Biomedical Science and Audiology facilitated effective IPL whilst meeting the interprofessional education HCPC requirements. Collaborative working is an essential component of delivering effective patient care and allied healthcare degrees need to provide opportunities within their curriculum to foster this. We hope this study encourages other higher education institutes to expand and develop their current IPL activities to include a broader spectrum of healthcare courses.
Assuntos
Audiologia , Infecções por Citomegalovirus , Humanos , Citomegalovirus , Relações Interprofissionais , Estudantes , Infecções por Citomegalovirus/diagnósticoRESUMO
OBJECTIVE: To assess the cost-effectiveness of prenatal detection of congenital cytomegalovirus (cCMV) following maternal primary infection in the first trimester within standard pregnancy follow-up or involving population-based screening (serological testing at 7 and 12 weeks of gestation), with or without secondary prevention (valaciclovir) in maternal CMV primary infection. DESIGN: Cost-effectiveness study from the perspective of the French national health insurance system. SETTING: Cost-effectiveness based on previously published probability estimates and associated plausible ranges hypothetical population of 1,000,000 pregnant women. POPULATION: Hypothetical population of 1,000,000 pregnant women. METHODS: Cost-effectiveness of detecting fetal cCMV in terms of the total direct medical costs involved and associated expected outcomes. MAIN OUTCOME MEASURES: Detection rates and clinical outcomes at birth. RESULTS: Moving to a population-based approach for targeting fetal CMV infections would generate high monetary and organizational costs while increasing detection rates from 15% to 94%. This resource allocation would help implementing horizontal equity according to which individuals with similar medical needs should be treated equally. Secondary prevention with valaciclovir had a significant effect on maternal-fetal CMV transmission and clinical outcomes in newborns, with a 58% decrease of severely infected newborns for a 3.5% additional total costs. Accounting for women decision-making (amniocentesis uptake and termination of pregnancy in severe cases) did not impact the cost-effectiveness results. CONCLUSIONS: These findings could fuel thinking on the opportunity of developing clinical guidelines to rule identification of cCMV infection and administration of in-utero treatment. These findings could fuel the development of clinical guidelines on the identification of congenital CMV infection and the administration of treatment in utero. TWEETABLE ABSTRACT: CMV serological screening followed by valaciclovir prevention may prevent 58% to 71% of severe cCMV cases for 38 per pregnancy.
Assuntos
Infecções por Citomegalovirus/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Diagnóstico Pré-Natal , Análise Custo-Benefício , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/economia , Feminino , França , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Programas Nacionais de Saúde , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/economia , Primeiro Trimestre da GravidezRESUMO
Nucleobase and nucleoside analogs (NNA) are widely used as anti-viral and anti-cancer agents, and NNA phosphorylation is essential for the activity of this class of drugs. Recently, diphosphatase NUDT15 was linked to thiopurine metabolism with NUDT15 polymorphism associated with drug toxicity in patients. Profiling NNA drugs, we identify acyclovir (ACV) and ganciclovir (GCV) as two new NNAs metabolized by NUDT15. NUDT15 hydrolyzes ACV and GCV triphosphate metabolites, reducing their effects against cytomegalovirus (CMV) in vitro. Loss of NUDT15 potentiates cytotoxicity of ACV and GCV in host cells. In hematopoietic stem cell transplant patients, the risk of CMV viremia following ACV prophylaxis is associated with NUDT15 genotype (P = 0.015). Donor NUDT15 deficiency is linked to graft failure in patients receiving CMV-seropositive stem cells (P = 0.047). In conclusion, NUDT15 is an important metabolizing enzyme for ACV and GCV, and NUDT15 variation contributes to inter-patient variability in their therapeutic effects.
Assuntos
Aciclovir/farmacologia , Antivirais/farmacologia , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/análogos & derivados , Pirofosfatases/genética , Aciclovir/uso terapêutico , Adolescente , Adulto , Idoso , Animais , Antibioticoprofilaxia , Antivirais/uso terapêutico , Variação Biológica da População/genética , Linhagem Celular , Criança , Pré-Escolar , Cristalografia por Raios X , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/virologia , DNA Viral/sangue , DNA Viral/isolamento & purificação , Modelos Animais de Doenças , Farmacorresistência Viral , Feminino , Ganciclovir/farmacologia , Ganciclovir/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Interações entre Hospedeiro e Microrganismos/genética , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Muromegalovirus/isolamento & purificação , Muromegalovirus/patogenicidade , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Pirofosfatases/metabolismo , Pirofosfatases/ultraestrutura , Resultado do Tratamento , Adulto JovemRESUMO
Early treatment of single sided deafness in children has been recommended to protect from neurodevelopmental preference for the better hearing ear and from social and educational deficits. A fairly homogeneous group of five young children (≤3.6 years of age) with normal right sided hearing who received a cochlear implant to treat deafness in their left ears were studied. Etiology of deafness was largely cytomegalovirus (n = 4); one child had an enlarged vestibular aqueduct. Multi-channel electroencephalography of cortical evoked activity was measured repeatedly over time at: 1) acute (0.5 ± 0.7 weeks); 2) early chronic (1.1 ± 0.2 months); and 3) chronic (5.8 ± 3.4 months) cochlear implant stimulation. Results indicated consistent responses from the normal right ear with marked changes in activity from the implanted left ear. Atypical distribution of peak amplitude activity from the implanted ear at acute stimulation marked abnormal lateralization of activity to the ipsilateral left auditory cortex and recruitment of extra-temporal areas including left frontal cortex. These abnormalities resolved with chronic implant use and contralateral aural preference emerged in both auditory cortices. These findings indicate that early implantation in young children with single sided deafness can rapidly restore bilateral auditory input to the cortex needed to improve binaural hearing.
Assuntos
Implante Coclear , Surdez/cirurgia , Estimulação Acústica , Córtex Auditivo/fisiologia , Mapeamento Encefálico , Pré-Escolar , Infecções por Citomegalovirus/diagnóstico , Surdez/patologia , Eletroencefalografia , Potenciais Evocados Auditivos , Feminino , Lateralidade Funcional , Humanos , Estudos Longitudinais , MasculinoRESUMO
BACKGROUND: Cytomegalovirus (CMV) disease represents a major cause of post-transplantation morbidity and mortality. To estimate the risk of infection and monitor response to antiviral therapy, current guidelines suggest combination of viral load monitoring with direct assessment of CMV-specific immune response. We used enzyme-linked immunospot (ELISpot) for the evaluation of CMV-specific T-cell response in kidney transplant recipients with CMV viremia and investigated how information gained could help manage CMV infection. METHODS: Seventeen patients on pre-emptive antiviral therapy and CMV quantitative polymerase chain reaction (qPCR) ≥500 copies/mL (first episode after transplantation) were assessed using ELISpot and divided into Weak (9 patients with baseline ELISpot <25 spot-forming colonies [SFCs]/200,000 peripheral blood mononuclear cells [PBMCs]) and Strong Responders (8 patients with baseline ELISpot ≥25 SFCs/200,000 PBMCs). CMV-specific T-cell response, infection severity, viral load, and antiviral therapy were prospectively recorded and compared between groups at 1, 2, and 24 months of follow-up. RESULTS: Demographic and transplant characteristics of Weak and Strong Responders were similar. No episodes of CMV disease were observed. Weak Responders were more likely to experience CMV syndrome (56% vs 36.5%) and late virus reactivation (56% vs 25%) than Strong Responders. Weak Responders showed higher baseline median viral loads (19,700 vs 9265 copies/mL) and needed antiviral therapy for longer (179 vs 59.5 days). T-cell response showed 2 main patterns: early and delayed. CONCLUSIONS: ELISpot provides prognostic information about infection severity, risk of late reactivation, and response to therapy. Randomized trials, evaluating the need for antiviral therapy in kidney transplant recipients with asymptomatic infection and effective virus-specific T-cell immune response, are warranted.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , ELISPOT , Transplante de Rim , Adulto , Anticorpos Antivirais/sangue , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Humanos , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Linfócitos T/imunologia , Carga Viral , Viremia/tratamento farmacológicoRESUMO
Crohn's disease and ulcerative colitis are the two major types of inflammatory bowel disease, and affect mainly the gastrointestinal tract but also have extraintestinal sequelae, such as arterial and venous thromboembolism. Thromboembolic complications, particularly pulmonary thromboembolism, can be life threatening and require prompt management with anticoagulants. Conventional vitamin K antagonists have been used for the treatment of thromboembolic complications, but the development of novel oral anticoagulants has shifted the paradigm. We report a case of a 42-year-old female with ulcerative colitis who experienced an acute flare-up due to cytomegalovirus superinfection with pulmonary thromboembolism. She was treated with oral mesalamine, intravenous steroid and ganciclovir and low-molecular-weight heparin, followed by rivaroxaban, a novel oral anticoagulant. Her symptoms resolved after treatment, and no recurrence was noted during a 6-month post-treatment follow-up.
Assuntos
Anticoagulantes/uso terapêutico , Colite Ulcerativa/diagnóstico , Infecções por Citomegalovirus/diagnóstico , Embolia Pulmonar/diagnóstico , Administração Oral , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colonoscopia , Infecções por Citomegalovirus/complicações , Feminino , Ganciclovir/uso terapêutico , Humanos , Mucosa Intestinal/patologia , Mesalamina/uso terapêutico , Embolia Pulmonar/complicações , Embolia Pulmonar/tratamento farmacológico , Rivaroxabana/uso terapêutico , Tomografia Computadorizada por Raios XRESUMO
When we examine a patient with symptoms of acute enteritis in the course of chemotherapy with oral fluoropyrimidines such as uracil-tegafur (often referred to as UFT), we usually suspect 5-fluorouracil-induced enterocolitis. In case of persistent clinical symptoms despite discontinuation of chemotherapy, cytomegalovirus colitis should be considered in the differential diagnosis of chemotherapy-induced enterocolitis. We herein report the case of a patient who underwent surgery for lung adenocarcinoma followed by postoperative adjuvant chemotherapy with uracil-tegafur and was diagnosed as having cytomegalovirus colitis during the therapy. In the course of chemotherapy, cytomegalovirus colitis occasionally occurs even though the patient does not experience severe myelosuppression; thus, it is necessary that we recognize its potential occurrence.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colite/diagnóstico , Colite/virologia , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma de Pulmão , Idoso , Quimioterapia Adjuvante/métodos , Infecções por Citomegalovirus/virologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Cuidados Pós-Operatórios , Tegafur/administração & dosagemRESUMO
OBJECTIVE: This study had three main goals: (1) to determine the hearing configuration in hearing-impaired children born with a congenital CMV (cCMV) infection, (2) to see whether auditory neuropathy spectrum disorder (ANSD) was present, and (3) to propose a flow chart for the follow-up of hearing in children with cCMV. DESIGN: Hearing configuration and the presence of ANSD in cCMV infected children was analysed. Selection criteria were: hearing-impaired children with a regular audiometric follow-up for at least 36 months, no other major risk factors for hearing loss, a normal middle-ear status, and an appropriate behavioral response to the given pure-tone stimuli. STUDY SAMPLE: Out of a cohort of 206 cCMV infected children, 18 hearing-impaired children were selected. RESULTS: Audiograms of all children showed a flat configuration of SNHL: the slope between octave bands was never greater than 10 decibels. None of the 18 children were found to have ANSD. CONCLUSIONS: Hearing impairment in cCMV infants affected all frequencies equally and ANSD does not appear to be a feature of cCMV infection. A flow chart for hearing follow-up in children with cCMV infection was suggested in order to provide guidance, improve uniformity in follow-up, and to make results easier to compare.
Assuntos
Percepção Auditiva , Procedimentos Clínicos , Infecções por Citomegalovirus/congênito , Perda Auditiva/diagnóstico , Testes Auditivos/métodos , Audição , Estimulação Acústica , Adolescente , Comportamento do Adolescente , Desenvolvimento do Adolescente , Fatores Etários , Audiometria de Tons Puros , Vias Auditivas/fisiopatologia , Criança , Desenvolvimento Infantil , Pré-Escolar , Procedimentos Clínicos/normas , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Perda Auditiva/etiologia , Perda Auditiva/fisiopatologia , Testes Auditivos/normas , Humanos , Lactente , Comportamento do Lactente , Recém-Nascido , Masculino , Triagem Neonatal , Emissões Otoacústicas Espontâneas , Valor Preditivo dos Testes , Prognóstico , Psicoacústica , Fatores de TempoRESUMO
BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major cause of long-term morbidity and mortality after heart transplantation (HTx), whose relationship with CMV infection is uncertain. This study evaluated the influence of CMV infection in the development of CAV. METHODS: We enrolled 166 consecutive HTx recipients who underwent their first transplant from January 1995 to July 2002. All patients received 14 days of intravenous ganciclovir and were prospectively monitored for CMV infection during the first year after HTx. CAV was diagnosed by coronary angiography performed at 1, 5, and 10 years after HTx, following the new criteria of the International Society for Heart and Lung Transplantation. We collected all variables potentially related with the development of CAV. Risk factors were studied using a complementary log-log model. RESULTS: After a median follow-up of 11 years (range, 1-17 years), 72 patients (43%) developed CAV (63.8% CAV(1), 15.2% CAV(2), 20.8% CAV(3)). Symptoms secondary to CAV were present in 32% of these patients, and 8% died because of it. In the regression multivariate analysis, independent variables associated with the development of CAV were donor age (hazard ratio [HR], 1.028; 95% confidence interval [CI], 1.002-1.053; p < 0.028), presence of cellular acute rejection ≥ 2R (HR, 1.764; 95% CI, 1.011-3.078; p < 0.0414), CMV infection (HR, 2.334; 95% CI, 1.043-5.225; p < 0.0354), and not having been treated with a calcium channel blocker (HR, 0.472; 95% CI, 0.275-0.811; p < 0.0055). CONCLUSIONS: Standardized angiographic criteria show CMV infection is associated with the development of CAV.
Assuntos
Infecções por Citomegalovirus/etiologia , Rejeição de Enxerto/virologia , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/virologia , Transplante de Coração/efeitos adversos , Adulto , Idoso , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/mortalidade , Intervalo Livre de Doença , Feminino , Rejeição de Enxerto/epidemiologia , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
La infección por citomegalovirus es frecuente en pacientes trasplantados cardiacos. Foscarnet se utiliza, con evidencia limitada, como tratamiento de segunda línea tras el fracaso de ganciclovir en estos pacientes. Presentamos un caso de alteraciones electrolíticas por foscarnet administrado para el tratamiento de infección por citomegalovirus en un paciente pediátrico trasplantado cardiaco. La infección se resolvió tras 6 semanas de tratamiento, apareciendo niveles de calcio iónico bajos durante la infusión del fármaco e hipomagnesemia mantenida tratada con suplementos, que revirtieron al retirar el fármaco
Cytomegalovirus infection is common in cardiac transplant patients. Foscarnet is used, with limited evidence, as second-line treatment after ganciclovir failure in these patients. We describe the case of a paediatric cardiac transplant patient who developed electrolyte disturbances during foscarnet treatment for cytomegalovirus infection. The infection resolved after 6 weeks of treatment. Low ionized calcium and magnesium levels were observed during the drug infusion, which were treated with supplements. The serum levels reverted to normal after drug withdrawal
Assuntos
Humanos , Masculino , Feminino , Criança , Infecções/complicações , Infecções/diagnóstico , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Reação em Cadeia da Polimerase/ética , Reação em Cadeia da Polimerase/instrumentação , Infecções/metabolismo , Infecções/mortalidade , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/virologia , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da PolimeraseRESUMO
Dejerine-Roussy syndrome, also known as the thalamic pain syndrome is a condition in which the body becomes hypersensitive to pain as a result of damage to the thalamus, a part of the brain that affects sensation. Association of this syndrome with HIV is rare with few case reports described in adults. We report a 10 year old male child who was HIV positive and had developed this syndrome due to cytomegalovirus vasculitis.
Assuntos
Infecções por Citomegalovirus/complicações , Infecções por HIV/complicações , Doenças Talâmicas , Vasculite/complicações , Criança , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Ganciclovir/uso terapêutico , Cefaleia/fisiopatologia , Cefaleia/virologia , Humanos , Masculino , Doenças Talâmicas/diagnóstico , Doenças Talâmicas/etiologia , Tálamo/fisiopatologia , Vasculite/diagnóstico , Vasculite/tratamento farmacológico , Vasculite/virologiaRESUMO
Congenital cytomegalovirus (CMV) infection is the most common infection in newborns worldwide and causes hearing loss and other neurological disability in 15-20% of infected infants. Only about half of the hearing loss resulting from congenital CMV infection is currently detected by universal newborn hearing screening because of late-onset hearing loss. Thus, much of the hearing loss and the majority of other CMV-associated disabilities remain undetected for years after birth and are never connected to CMV infection. Congenital CMV may be appropriate to include in national newborn screening (NBS) programs because it is more common than other disorders tested for by NBS programs and is a major cause of disability. Significant obstacles to the implementation of screening for congenital CMV include the lack of a standardized, high-throughput screening test and a protocol for follow-up of CMV-infected children. Nonetheless, screening newborns for congenital CMV infection merits further consideration.
Assuntos
Técnicas de Laboratório Clínico , Infecções por Citomegalovirus/diagnóstico , Triagem Neonatal , Saúde Pública , Infecções por Citomegalovirus/congênito , Política de Saúde , Perda Auditiva Neurossensorial/virologia , Humanos , Recém-Nascido , Programas Nacionais de Saúde , Triagem Neonatal/legislação & jurisprudência , Triagem Neonatal/métodos , Prognóstico , Saúde Pública/legislação & jurisprudênciaRESUMO
Esophageal ulcer (EU) represents an important comorbidity in AIDS. We evaluated the prevalence of EU, the accuracy of the endoscopic and histologic methods used to investigate viral EU in HIV-positive Brazilian patients and the numerical relevance of tissue sampling. A total of 399 HIV-positive patients underwent upper gastrointestinal (UGI) endoscopy. HIV-positive patients with EU determined by UGI endoscopy followed by biopsies were analyzed by the hematoxylin-eosin (HE) and immunohistochemical (IH) methods. EU was detected in 41 patients (mean age, 39.2 years; 23 males), with a prevalence of 10.27%. The median CD4 count was 49 cells/mm(3) (range, 1-361 cells/mm(3)) and the viral load was 58,869 copies per milliliter (range, 50-77,3290 copies per milliliter). UGI endoscopy detected 29 of 41 EU suggestive of cytomegalovirus (CMV) infection and 7 of 41 indicating herpes simplex virus (HSV) infection. HE histology confirmed 4 of 29 ulcers induced by CMV, 2 of 7 induced by HSV, and 1 of 7 induced by HSV plus CMV. IH for CMV and HSV confirmed the HE findings and detected one additional CMV-induced case. UGI endoscopy showed 100% sensitivity and 15% specificity for the diagnosis of EU due to CMV or HSV compared to HE and IH. HE proved to be an adequate method for etiologic evaluation, with 87% sensitivity and 100% specificity compared to IH. The number of samples did not influence the etiologic evaluation. The data support the importance of IH as a complementary method for HE in the diagnosis of EU of viral etiology.
Assuntos
Doenças do Esôfago/diagnóstico , Doenças do Esôfago/epidemiologia , Infecções por HIV/complicações , Úlcera/diagnóstico , Úlcera/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Brasil/epidemiologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , Endoscopia Gastrointestinal , Amarelo de Eosina-(YS) , Doenças do Esôfago/complicações , Doenças do Esôfago/virologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hematoxilina , Herpes Simples/complicações , Herpes Simples/diagnóstico , Herpes Simples/epidemiologia , Herpes Simples/virologia , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Prevalência , Sensibilidade e Especificidade , Simplexvirus/isolamento & purificação , Úlcera/complicações , Úlcera/virologiaRESUMO
Cytomegaloviral hepatitis is an infantile liver disease commonly encountered in China, which could be differentiated into 4 patterns with different clinical conditions. Along with the progress of laboratory diagnostic techniques, multiple diagnostic approaches are available for this disease, but accurate diagnosis can only be made when individual patients' realities are taken into consideration. Clinical treatments are various, and the Western medicine used is mainly anti-viral agents such as Ganciclovir, and so far no unified therapeutic program has been formed. More and more ways of regarding Chinese medicine treatment of cytomegaloviral hepatitis have been published increasingly in recent years, though further research to seek preferable treatment programs is still expected.
Assuntos
Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/terapia , Técnicas e Procedimentos Diagnósticos/tendências , Hepatite Viral Humana/diagnóstico , Hepatite Viral Humana/terapia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/imunologia , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite Viral Humana/etiologia , Hepatite Viral Humana/imunologia , Humanos , Sistema Imunitário/fisiologia , Sistema Imunitário/fisiopatologia , Lactente , Medicina Tradicional Chinesa/métodos , Medicina Tradicional Chinesa/tendências , Prática Profissional , OcidenteAssuntos
Colite Ulcerativa/virologia , Bolsas Cólicas/virologia , Infecções por Citomegalovirus/diagnóstico , Ganciclovir/análogos & derivados , Pouchite/virologia , Ciprofloxacina/uso terapêutico , Colite Ulcerativa/patologia , Colite Ulcerativa/cirurgia , Bolsas Cólicas/patologia , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/patologia , Suplementos Nutricionais , Ganciclovir/uso terapêutico , Humanos , Ferro da Dieta , Masculino , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Omeprazol/uso terapêutico , Complicações Pós-Operatórias/virologia , Pouchite/tratamento farmacológico , Pouchite/patologia , Proctocolectomia Restauradora/efeitos adversos , Recidiva , ValganciclovirRESUMO
Human cytomegalovirus (HCMV) remains a cause of serious infectious complications after allogeneic transplantation of hematopoietic stem cells, especially in recipients of T-cell-depleted grafts. Here we investigated the antiviral activity of natural killer (NK) cells from healthy donors (n = 8) as well as of mononuclear cells (MNC) from transplanted pediatric patients (n = 11) who had received CD34(+) selected (and thus T-cell-depleted) stem cells from unrelated and mismatched related donors. Allogeneic human fibroblasts infected with HCMV laboratory strain AD169 for 5 days were used as targets in a 2-h cytotoxicity assay. Downregulation of human leukocyte antigen class I and upregulation of the adhesion molecules CD54 (ICAM-1) and CD58 (LFA-3) were observed after infection. In this experimental setting, NK cells from healthy donors exerted no specific lysis. However, antibody-dependent cellular cytotoxicity (ADCC) mediated by human anti-CMV IgG (cytoglobin) as well as stimulation with low-dose interleukin-(IL)-2 or IL-15 enhanced lysis markedly. MNC from two thirds of the patients (7/11) were capable of lysing infected targets without stimulation. Here also, lytic activity was significantly increased by IL-2 or IL-15, used in combination with ADCC. In contrast, 4/11 patients exerted no lysis. The observed antiviral activity may contribute to the low incidence of CMV DNAemia (29% at day 100, detected by polymerase chain reaction) in the whole group of our patients who have been transplanted with CD34(+)-selected allografts since 1995. Furthermore, our data suggest a potential benefit of using low-dose IL-2 or IL-15, also combined with anti-CMV immunoglobulinG, for immune modulation in CMV disease.
Assuntos
Antígenos CD34/imunologia , Citomegalovirus/imunologia , Citotoxicidade Imunológica/imunologia , Fibroblastos/virologia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Antígenos CD/análise , Antígeno CD56/análise , Antígenos CD58/metabolismo , Criança , Infecções por Citomegalovirus/diagnóstico , Testes Imunológicos de Citotoxicidade , DNA Viral/análise , Fibroblastos/química , Fibroblastos/imunologia , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-15/farmacologia , Interleucina-2/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Doadores de Tecidos , Transplante HomólogoRESUMO
The incidence of human cytomegalovirus (HCMV) disease in AIDS patients decreased dramatically after the introduction, a few years ago, of highly active antiretroviral combination therapy. As a consequence, the emergence of drug-resistant HCMV strains is no longer a major problem in HIV-infected individuals. However, HCMV resistance to antiviral drugs is presently recognized as an emerging problem in transplantation settings. The mechanisms of HCMV drug resistance will be analysed along with the clinical features relevant to the emergence of drug-resistant HCMV strains during antiviral treatment of patients receiving either solid organ or haematopoietic stem cell transplantation.
Assuntos
Antivirais/farmacologia , Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Citomegalovirus/efeitos dos fármacos , Farmacorresistência Viral , Citomegalovirus/genética , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/fisiopatologia , Genótipo , Infecções por HIV/complicações , Humanos , Testes de Sensibilidade Microbiana , FenótipoRESUMO
BACKGROUND: Post-transplantation lymphoproliferative disease (PTLD) is an important source of morbidity and mortality in transplant recipients, with a reported incidence of 0.8% to 20%. Risk factors are thought to include immunosuppressive agents and viral infection. This study attempts to evaluate the impact of different immunosuppressive regimens, ganciclovir prophylaxis and other potential risk factors in the development of PTLD. METHODS: We reviewed the records of 1026 (874 heart, 152 heart-lung) patients who underwent transplantation at Stanford between 1968 and 1997. Of these, 57 heart and 8 heart-lung recipients developed PTLD. During this interval, 4 different immunosuppressive regimens were utilized sequentially. In January 1987, ganciclovir prophylaxis for cytomegalovirus serologic-positive patients was introduced. Other potential risk factors evaluated included age, gender, prior cardiac diagnoses, HLA match, rejection frequency and calcium-channel blockade. RESULTS: No correlation of development of PTLD was found with different immunosuppression regimens consisting of azathioprine, prednisone, cyclosporine, OKT3 induction, tacrolimus and mycophenolate mofetil. A trend suggesting an influence of ganciclovir on the prevention of PTLD was not statistically significant (p = 0.12). Recipient age and rejection frequency, as well as high-dose cyclosporine immunosuppression, were significantly (p < 0.02) associated with PTLD development. The prevalence of PTLD at 13.3 years was 15%. CONCLUSIONS: The overall incidence of PTLD was 6.3%. It was not altered by sequential modifications in treatment regimens. Younger recipient age and higher rejection frequency were associated with increased PTLD occurrence. The 15% prevalence of PTLD in 58 long-term survivors was unexpectedly high.
Assuntos
Ciclosporina/administração & dosagem , Transplante de Coração/efeitos adversos , Imunossupressores/administração & dosagem , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/etiologia , Adolescente , Adulto , Antivirais/uso terapêutico , Criança , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/terapia , Relação Dose-Resposta a Droga , Feminino , Ganciclovir/uso terapêutico , Transplante de Coração-Pulmão/efeitos adversos , Humanos , Incidência , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
BACKGROUND: Since ganciclovir-resistant cytomegalovirus (CMV) disease was initially described in a patient with acquired immunodeficiency syndrome (AIDS) in 1986, the incidence of ganciclovir-resistant CMV disease appears to be increasing in immunocompromised patients. More recently, there have been sporadic reports of ganciclovir-resistant CMV disease in solid organ transplantation. METHODS: We retrospectively assessed the incidence of ganciclovir-resistant CMV disease in all lung transplant recipients transplanted between 6/93 and 6/01 at Loyola University Medical Center. All patients underwent routine CMV blood culture, shell vial assay as well as phenotypic and genotypic anti-viral susceptibility testing according to a pre-determined schedule. The number of CMV episodes, intravenous ganciclovir use, acute and chronic rejection and survival data were documented for all patients. RESULTS: Twelve of 212 (6%) transplant recipients developed ganciclovir-resistant CMV disease. Ganciclovir resistance was associated with a higher number of CMV episodes (3.4 +/- 2.3 episodes/patient vs 1.7 +/- 0.7 episodes/patient [p < 0.05]) and an increased exposure to cumulative intravenous ganciclovir in the primary CMV-mismatched (D(+)R(-)) population (22 +/- 10 vs 13 +/- 7 days [p < 0.05]) compared with patients who did not develop ganciclovir resistance. In addition, the use of daclizumab therapy was associated with a 7-fold greater likelihood of developing ganciclovir resistance (p < 0.0001). The presence of ganciclovir-resistant CMV disease in our population was associated with a decreased survival that could be attributed to CMV disease itself (p < 0.05). CONCLUSIONS: By screening all lung transplant recipients with CMV disease for ganciclovir resistance, we were able to detect a higher incidence of ganciclovir-resistant CMV disease (6%) than previously seen in solid organ transplantation. High-risk patients (D(+)R(-) CMV serostatus) who receive anti-lymphocytic therapy should be monitored aggressively and treated to prevent the development of ganciclovir resistance and avert a negative outcome.
Assuntos
Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/efeitos dos fármacos , Ganciclovir/uso terapêutico , Transplante de Pulmão/efeitos adversos , Infecções Oportunistas/diagnóstico , Complicações Pós-Operatórias/virologia , Adulto , Estudos de Casos e Controles , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/tratamento farmacológico , DNA Viral/análise , Resistência Microbiana a Medicamentos , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Transplante de Pulmão/imunologia , Transplante de Pulmão/mortalidade , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Reação em Cadeia da Polimerase , Complicações Pós-Operatórias/epidemiologia , Probabilidade , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Estatísticas não Paramétricas , Taxa de Sobrevida , Imunologia de Transplantes/fisiologiaRESUMO
BACKGROUND: Febrile ulceronecrotic Mucha-Habermann's disease (FUMHD) is a severe and very rare variant of pityriasis lichenoides et varilioformis acuta, which is characterized by large coalescing, and ulceronecrotic maculopapules or plaques. Morphological changes of the skin accompanied by persistent high fever and several constitutional symptoms have suggested virus infection in patients with FUMHD. However, the available information of viral origin is limited. In this study we investigated the relationship of cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), type I human T-cell lymphotropic virus (HTLV-I), and parvovirus B19 (PVB19) with FUMHD in a Taiwanese patient. METHODS: The existence of CMV, EBV, HHV8, HTLV-I, and PVB19 was determined by polymerase chain reaction (PCR). The presence of CMV in the endothelial cells was characterized by in situ hybridization (ISH) and immunohistochemistry (IHC). RESULTS: Serologic immunoglobulin to CMV and IHC identification of CMV late gene in the biopsy specimen indicated that the patient was infected with CMV. Detection of CMV was confirmed by PCR and ISH. CONCLUSIONS: These results indicate that FUMHD is associated with dermal CMV manifestation. Nonetheless, the induction mechanism of FUMHD with CMV infection has yet to be determined.