Evaluation of the predisposition and clinical impact of BK virus replication in kidney transplant patients

ABSTRACT The BK virus (BKV) produces a subclinical kidney infection in immunocompetent individuals. However, viremia may occur in kidney transplant patients with ongoing immunosuppression. BKV-associated nephropathy (BKVN) has no specific treatment and is a leading cause of organ transplant loss. In this study, we evaluated the predisposition and the clinical impact of BKV replication in kidney transplant patients during post-transplant monitoring in a reference institution in Brazil. Demographic, clinical and laboratory data generated during routine outpatient follow-up were retrospectively collected. BK viremia was investigated using real-time polymerase chain reaction. Of the 553 participants, 7.4% (n = 41) presented BKV replication. Of these, 16 (39%) lost their kidney graft and interstitial nephritis was identified on kidney biopsy in 50% of the cases. Among the evaluated variables, only the use of the immunosuppressant mycophenolate sodium was identified as a risk factor for viremia (OR 7.96; 95% CI 2.35 to 26.98). The graft survival estimate in BKV-positive patients was significantly reduced (24.8% vs. 85.6%) after 10 years of transplantation. We concluded that defining predisposing factors remains an important challenge for the prevention and control of BKV activity following kidney transplantation, especially considering the development of BKVN and its strong effect on graft maintenance.

JC polyomavirus infection in candidates for kidney transplantation living in the Brazilian Amazon Region

This study evaluated the relative occurrences of BK virus (BKV) and JC virus (JCV) infections in patients with chronic kidney disease (CKD). Urine samples were analysed from CKD patients and from 99 patients without CKD as a control. A total of 100 urine samples were analysed from the experimental (CKD patients) group and 99 from the control group. Following DNA extraction, polymerase chain reaction (PCR) was used to amplify a 173 bp region of the gene encoding the T antigen of the BKV and JCV. JCV and BKV infections were differentiated based on the enzymatic digestion of the amplified products using BamHI endonuclease. The results indicated that none of the patients in either group was infected with the BKV, whereas 11.1% (11/99) of the control group subjects and 4% (4/100) of the kidney patients were infected with the JCV. High levels of urea in the excreted urine, low urinary cellularity, reduced bladder washout and a delay in analysing the samples may have contributed to the low prevalence of infection. The results indicate that there is a need to increase the sensitivity of assays used to detect viruses in patients with CDK, especially given that polyomavirus infections, especially BKV, can lead to a loss of kidney function following transplantation.

Papilomavírus humano e neoplasia cervical: [revisão] / Human papillomavirus and cervical neoplasia: [revision]

Human papillomavirus (HPV) has been established as an important etiological factor for the development of cervical cancer. This DNA virus primarily infects the epithelium and can induce benign and malignant lesions of the mucous membranes and skin. Some HPVs are considered high risk due to their role in malignant progression of cervical tumors. Genital HPV infections are common and usually transient among young sexually active women. Only a small fraction of infected women develop cervical cancer, implying the involvement of environmental and genetic cofactors in cervical carcinogenesis. Classification, virology, pathology, natural history, epidemiological features of genital HPV infection, and future prospects for cervical cancer prevention with HPV vaccines will be reviewed here.

O papilomavírus humano (HPV) é um fator etiológico bem estabelecido para o câncer cervical. Esse vírus de DNA infecta primariamente o epitélio e pode induzir lesões benignas ou malignas na pele e na mucosa. Alguns HPVs são considerados de alto risco, responsáveis pela progressão das lesões precursoras até câncer cervical. A infecção genital pelo HPV é comum em mulheres jovens e geralmente é transitória. Uma pequena proporção de mulheres infectadas desenvolve câncer cervical, implicando o envolvimento de fatores ambientais e fatores genéticos na carcinogênese. Essa revisão aborda a estrutura viral, classificação e patologia do HPV, história natural e fatores de risco para neoplasia cervical e perspectivas futuras com a vacina anti-HPV.

Atrofia cerebelosa por el virus JC en un paciente con SIDA / Cerebellar atrophy by the JC virus in a patient with AIDS

The progressive multifocal leukoencephalopathy (PML) is a demyelinating CNS disease, characterized by lysis of injected oligodendrocytes by JC virus (JCV). Immunodeficiency is a predisposing factor for acquiring the disease and at least 5 percent of AIDS patients may develop PML. Among patients infected with HIV has also been described the lysis of the granullar cells of the cerebellum and cerebellar atrophy, attributed to a variant of the JCV. We present 37 years old HIV infected men, with postural dizziness, followed by gait disturbances, and a cerebellar syndrome, scanned speech, hyperreflexia, pendular reflexes, Babinski sign and mild cognitive impairment were present. Brain MRI showed hyperintense areas of the white matter in the cerebral hemispheres, thalamus and brainstem, associated with incipient atrophy of the cerebellum. The CSF was normal except for the PCR positive for the JCV. The patient received antiretroviral therapy. A second MRI, eight months later, showed a slightly increase in lesions of the cerebral hemispheres, and the left cerebellar hemisphere, but had developed a marked cerebellar atrophy. After two years, the patient remained with a serious cerebellar syndrome. That in association with the slow course of the disease and the particular cerebellar lesions, are suggestive of a mixed JCV infection of both, the typical and mutant type, in this patient. This is the first case of cerebellar atrophy by the JCV reported in the Chilean literature.

La leucoencefalopatía multifocal progresiva es un proceso desmielinizante del SNC, que se caracteriza por la lisis de los oligodendrocitos infectados por el virus JC. La inmunodeficiencia es un factor predisponente para adquirir la enfermedad y al menos el 5 por ciento de los pacientes con SIDA pueden desarrollar una LMP. Entre pacientes infectados con VIH también se ha descrito una lisis de las células granulosas del cerebelo y atrofia cerebelosa, atribuida a una variante del virus JC. Se presenta un hombre de 37 años portador de VIH, que consulta por vértigos posturales, seguidos de alteraciones de la marcha y un síndrome cerebeloso, palabra escandida, hiperreflexia, reflejos pendulares, Babinski y un leve deterioro cognitivo. La RM cerebral mostró áreas de hiperintensidad en T2 de la substancia blanca en los hemisferios cerebrales, en los tálamos y en estructuras bulbo-protuberanciales, asociadas a una atrofia incipiente del cerebelo. El LCR era normal, salvo la PCR positiva para el VJC. El paciente estaba con terapia antiretroviral que se mantuvo. Una segunda RM, ocho meses después, mostró leve aumento de las lesiones de los hemisferios cerebrales, de la protuberancia y del hemisferio cerebeloso izquierdo, pero se había incrementado la atrofia de la corteza cerebelosa. Después de dos años, el paciente ha mantenido el síndrome cerebeloso, que unido a la detención clínica de la enfermedad y a la atrofia del cerebelo, sugieren que este paciente pudiera tener una doble infección por VJC tanto de la variedad típica como de la mutante. Este sería el primer caso de atrofia cerebelosa por el VJC pesquisado en Chile.

Importância do tabagismo na carcinogênese do colo uterino / Significance of smoking in cervical carcinogenesis

A associação entre a infecção pelo papilomavirus humano (HPV) e o desenvolvimento das neoplasias intra-epiteliais cervicais (NIC) e do carcinoma cervical atualmente está bem estabelecida. Entretanto, existe discrepância entre a freqüência de mulheres infectadas e aquelas que desenvolvem as referidas lesões, sendo que a maioria das infecções causadas por esse vírus é transitória. Acredita-se, assim, que co-fatores devem ser considerados, além do HPV, na gênese dessas anormalidades cervicais. Entre eles, destacam-se principalmente: fatores genéticos, alimentares e ambientais, uso de contraceptivos hormonais, tabagismo e estado imunológico. Estudos atuais têm demonstrado forte associação entre consumo de cigarros e desenvolvimento das NICs e do câncer cervical. Diversos são os mecanismos postulados na origem dessa associação. Embora haja diferenças individuais no metabolismo das substâncias químicas da fumaça do cigarro, além da suscetibilidade genética individual, o efeito deletério do tabagismo sobre o tecido cervical estaria relacionado a: elevada concentração de substâncias carcinógenas no muco cervical com dano direto às moléculas de DNA; modificações da flora vaginal com risco mais alto de infecções; aumento do índice de proliferação celular na zona de transformação; diminuição de ambas as respostas imunes celular e humoral, ocasionando dificuldades no reconhecimento do HPV, bem como na persistência de sua infecção.

Polyomavirus (BK Virus) Nephropathy in Kidney Transplant Patients: A Pathologic Perspective

Reactivation of polyoma virus (BK virus) is a significant cause of morbidity in kidney transplant patients. This seemingly insignificant viral infection that affects the majority of population at a young age, once reactivated by immunosuppression, is a major factor contributing to graft loss. Screening techniques have been developed for early prediction of BK virus reactivation. These include plasma and urine assays for detection of BK virus DNA by PCR, urine cytology for detection of "decoy cells" and electron microscopy. Combining urine cytology and serology screening can be more effective for early detection of BK virus reactivation. Immunohistochemistry can be utilized as an additional tool to support the diagnosis. Once screening tests reveal a suspicious BK virus reactivation, tissue biopsy should be performed to confirm the diagnosis, rule out acute cellular rejection and plan treatment approaches. Treatment normally includes decreasing immunosuppression and the use of antiviral drug therapy. Unfortunately, disease outcome is often unfavorable and can culminate with eventual graft loss. Renal retransplantation has been performed with mixed results. As new data emerges, we will gain a better understanding of the disease caused by BK virus and respond with improved early diagnosis and treatment to preserve graft function.

Associação de CD23 sérico sCD23 e linfoma não Hodgkin em pacientes com AIDS / Association of CD23 serum (sCD23) and non Hodgkin's lymphoma in patients with AIDS

Há evidências de que níveis elevados de sCD23 poderiam ser um marcador sorológico para linfoma não-Hodgkin (LNH) em pacientes com infecção pelo HIV. Realizamos um estudo transversal para medir os níveis séricos de sCD23 em 5 grupos de pacientes: LNH HIV positivos, pacientes com LNH HIV negativos, com AIDS sem LNH, e doadores de sangue HIV positivos e negativos. O nível sérico médio de sCD23 foi .de 7,178,42 g/L nos patients com AIDS e LNH, 4,18 4,99g/L nos patients com AIDS sem LNH, 7,322,09 g/L nos doadores de sangue HIV positivo, 4,701,75 g/L nos doadores de sangue HIV negativo e 15,0220,96 nos pacientes com LNH HIV negativos (P=0,001) / There are evidences that elevated serum levels of sCD23 could be used as a marker to non-Hodgkin’s Lymphoma (NHL) in patients with HIV infection. In order to verify this hipotheses, we carried out a transversal study to measure levels of sCD23 in 5 groups of patients: HIV positive with NHL, HIV negative with NHL, AIDS without NHL, and HIV positive and negative blood donors. The mean levels of sCD23 were 7.178.42g/L in AIDS with NHL, 4.18 4.99g/L in AIDS without NHL, 7.322.09 g/L in the HIV positive blood donors, 4.701.75 g/L in the HIV negative blood donors, and 15.0220.96 in the HIV negative patients with NHL (P=0.001)...

Human papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women

HIV-infected women from S o Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN) prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD(4)(+) cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5). Twenty (7.5) women were infected by one or more low-risk viruses, 89 (33) by one or more high-risk viruses, and 64 (24) harbored at least one HPV type from each risk group. Abnormal smears were observed in 19 of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD(4)/microL <100) were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

Etiopatogenia do câncer vulvar / Etiopathogenesis of vulvar cancer

Existem poucos trabalhos na literatura a respeito dos mecanismos moleculares envolvidos na patogênese do carcinoma vulvar. Estudos que servem como base para a compreensão destes mecanismos são discutidos de forma compreensiva neste artigo de revisão. As alterações genéticas, a associação com o papilomavírus humano (HPV) e outros possíveis fatores envolvidos na carcinogênese dos tumores vulvares são abordados

Infección por virus del papiloma humano de alto y bajo riesgo en mujeres con NIC. Características diferenciales / High and low risk human papilloma virus infection in women with CIN. Differential characteristics

The objective of this study was to determine high risk human papillomavirus infection (HPV-RH) and factors with cervical intraepithelial neoplasia appears (CIN). MATERIAL AND METHOD: From October 1998 to January 2000, a case-control study, was made; women with benefit package from Mexican Institute of Social Security. The cases were of the colposcopic clinic of the department of the Hospital Obstetrics and Gynecology Luis Castelazo Ayala, women histologically diagnosed with colposcopy and CIN cervical biopsy, and controls patients with negative cervical uterine cytologic study of the Preventive Medicine Department, Unit of Familiar Medicine No. 8, of Mexico City. Trained personnel obtained information about socioeconomic and reproductive factors did the interview. A cytobrush was used to take the cervical sample for HPV-RH to determine HPV-RH utilizing Hybrid Capture II test. Both bivariate analysis and logistic regression analysis were used for the adjustment of variables. RESULTS: We analyzed 102 cases and 192 controls, 79 (44/56) of the cases with CIN I and 89 (37/42) of CIN II-III as 21 of controls, respectively, were positive for HPV-RH. Global risk for HPV-RH association to CIN was OR = 40.6 (95 CI, = 17-96.8). Women age was determinative for HPV-RH association to CIN. We observed a high correlation between HPV positive magnitude and CIN degree. CONCLUSIONS: Frequency of RH-HPV in controls and CIN I is higher than other reports in the literature. HPV was identified as the most important agent associated with this neoplasia, other factors involved and age is an important modifier in HPV-RH and CIN.

Analysis of the p53 gene and papillomavirus detection in smears from cervical lesions

CONTEXT: Alterations of the p53 tumor suppressor gene are correlated with a critical step in the development of many human cancers.The tumor suppressor gene functions include regulation of the cell cycle and the cellular response to DNA damage, initiation of DNA repair and replication, induction of apoptosis and promotion of cell differentiation. CASE REPORT: Smears from ten cases of cervical lesions were analyzed for status of exons 5-8 of the p53 gene using PCR/SSCP. HPV infection was also screened by the PCR method using two PCR primer sets. Changes in the p53 gene were observed in a case of squamous carcinoma and a case of asymptomatic cervical intraepithelial neoplasia grade III (CIN III). High-risk HPV was detected in both cases showing that HPV infection and p53 mutation are not exclusive events

The Application of Human Papillomavirus Testing to Cervical Cancer Screening

Although cytologic screening has considerably reduced the incidence of cervical cancer, there are some problems which remain to be solved, such as the low sensitivity of this procedure. HPV testing is fundamentally different from conventional cytologic testing, because it evaluates the HPV infection itself, the most important causative factor for cervical cancer. In this study, the roles and clinical applications of HPV testing in cervical cancer screening are examined from 3 standpoints: in primary screening, in the management of women with low-grade cytologic abnormalities, and in the follow-up after treatment of pre-invasive or early invasive lesions.

Incidence of Gardnerella vaginalis, Candida sp and human papilloma virus in cytological smears

CONTEXT: In spite of the wide-ranging literature on the microbiology of normal and abnormal flora of the vagina, there are few studies on the relationship between human papilloma virus (HPV) and other vaginal microorganisms. OBJECTIVE: To analyze the frequency of infection by human papilloma virus (HPV) and other agents like Candida sp., Gardnerella vaginalis and Trichomonas vaginalis in cytological smears. DESIGN STUDY: Retrospective study SETTING: A public tertiary referral center. SAMPLE: An analysis of 17,391 cytologies from outpatients seen between January 1997 and August 1998. The control group was made up of patients in the same age group and same period with no cytological evidence of HPV infection. Patients with a diagnosis of cervical intraepithelial neoplasia (CIN) II or III were excluded from this analysis. MAIN MEASUREMENTS: The diagnosis of HPV infection was made in accordance with the criteria of Schneider et al. and the diagnosis of Gardnerella vaginalis was made with a finding of clue cells. RESULTS: 390 (2.24 per cent) had alterations consistent with infection by HPV, sometimes associated with CIN I. The results showed that Gardnerella vaginalis was the most frequent agent in women with HPV infection (23.6 per cent versus 17.4 per cent; P <0.05), while in the control group the most frequent agent was Candida sp. (23.9 per cent versus 13.8 per cent; p <0.001). CONCLUSION: In spite of this study being based solely on cytological criteria, in which specific HPV and Gardnerella diagnostic tests were not used, the cytological smear is widely used in clinical practice and the data presented in this investigation show that there is an association between Gardnerella vaginalis and HPV infection. It remains to be established whether the microorganisms favor each other

p53 status and human papillomavirus infection in Thai women with cervical carcinoma.

Loss of p53 function has been implicated in a wide variety of human malignacies. Many studies suggest that in cervical carcinoma p53 function is inactivated either by gene mutation or by complex formation with E6 oncoprotein product of high-risk human papillomavirus (HPV). The aim of this study was to determine the status of HPV infection and p53 gene mutation as well as their correlation in cervical carcinomas. Formalin-fixed paraffin-embedded tissues of 12 cervicitis, 21 cervical intraepithelial neoplasia grade 3 (CIN 3) and 17 squamous cell carcinomas were determined for the presence of HPV using polymerase chain reaction (PCR) amplification and dot blot hybridization. The status of p53 mutations in exons 5-8 was evaluated by polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) and confirmed by direct nucleotide sequencing. HPV infections were detected in all CIN 3 and squamous cell carcinomas (100%). Mutations of p53 were present in 3 of 38 HPV-positive samples: one with an ATG-->TTG transversion (Met-->Leu) in codon 237 of exon 7; and the others with a TGC-->TGG transversion (Cys-->Trp) in codon 242 of exon 7, and a CGT-->CCT transversion (Arg-->Pro) in codon 273 of exon 8, respectively. Our findings show that the frequency of p53 mutation is low in primary cervical carcinoma and that the p53 gene mutation and HPV infection are not mutually exclusive events in the development of cervical cancer. Thus, other genetic events independent of p53 inactivation may also significantly contribute to the carcinogenesis of the uterine cervix.

Infecçäo por papilomavírus humano (HPV) e neoplasias do colo uterino / Human papillomavirus (HPV) infection and uterine cervice neoplasms

Este trabalho compreende um estudo clínico e morfológico do colo uterino de 262 pacientes com lesöes pré-malignas e malignas, relacionadas com o papilomavírus humano (HPV). Foram analisados dados epidemiológicos, tais como idade, cor e parturiçäo das pacientes. A idade média geral encontrada foi 41.42 anos; os casos com HPV apresentaram idade média menor (35.47 anos) que aqueles sem HPV (48.03 anos). Houve predomínio de mulheres brancas (78.62 por cento) e maior prevalência de multiparidade (74.33 po cento) nos casos estudados. Os aspectos clínicos foram analisados pela relaçäo da citologia, colposcopia e histopatologia, onde o índice de acerto da colposcopia (93.10 por cento) foi superio ao da citologia (59.97 por cento) na comparaçäo com a histopatologia. O aspecto colposcópico mais freqüente foi o epitélio aceto-branco (23.94 por cento); porém, este näo apresentou diferença significativa entre os casos com e sem HPV. O pontilhado e o mosaico foram significativamente mais freqüentes nas portadoras de HPV. Foi realizada, também, a relaçäo entre os resultados histopatológicos de biopsias e peças operatórias, sendo que 14.62 por cento dos casos apresentaram, nas peças operatórias, grau de comprometimento histológico maior; 35.38 por cento, menor; e 50 por cento, igual ao das biopsias. Todos os casos do estudo foram submetidos a uma revisäo histopatológica objetivando o HPV. A coilocitose foi encontrada em 52.67 por cento dos casos. Outras alteraçöes, como paraceratose (41.60 por cento), e binucleaçäo e/ou multinucleaçäo (81.68 por cento), também foram consideradas.

EBV-elicited familial hemophagocytic lymphohistiocytosis

Familial hemophagocytic lymphohistiocytosis (FHL) is a rapidly fatal illness, usually encountered in infancy, characterized by fever, hepatosplenomegaly, pancytopenia, and central nervous system involvement. Microscopic examination of tissue shows a non-malignant lymphohistiocytic infiltrate, with prominent erythrophagocytosis. FHL is an autosomal recessive hereditary disorder but may develop secondarily to other conditions such as immunosuppression, malignancies, fat overload and certain infections. We recently experienced a case of siblings developing FHL, which may be associated with EBV infection.

Detection and typing of human papillomavirus in cervical cancer in the Thai.

One hundred formalin-fixed paraffin embedded tissues with histopathologic diagnosed invasive cervical cancer (squamous cell carcinoma) were examined for the presence of HPV-DNA by polymerase chain reaction (PCR) using L1-consensus primers. The results indicated that 82 out of 100 (82%) samples were positive for HPV-DNA. Among the positive samples, 50 samples (61%) were typed by dot hybridization technique (DH). HPV-16 was the dominant type (42.68%), followed by HPV-18 (20.73%) and HPV-33 (3.66%). There were double infection of HPV-16 and 18 in 5 (6.1%) samples. None of HPV-6 and 11 were detected in this study. This finding suggests that HPV infection is an important etiologic factor for the development of cervical cancer especially the infection with high risk types, i.e., HPV-16 and 18.