Fas ligand and tumour counter-attack in colorectal cancer stratified according to microsatellite instability status

Expression of membrane-bound Fas ligand (FasL) by colorectal cancer cells may allow the development of an immune-privileged site by eliminating incoming tumour-infiltrating lymphocytes (TILs) in a Fas-mediated counter-attack. Sporadic colorectal cancer can be subdivided into three groups based on the level of DNA microsatellite instability (NISI). High-level NISI (NISI-High) is characterized by the presence of TILs and a favourable prognosis, while microsatellite-stable (MSS) cancers are TIL-deficient and low-level MSI (MSI-Low) is associated with an intermediate TIL density. The purpose of this study was to establish the relationship between MSI status and FasL expression in primary colorectal adenocarcinoma. Using immunohistochemistry and a selected series of 101 cancers previously classified as 31 MSI-High, 30 NISI-Low, and 40 MISS, the present study sought to confirm the hypothesis that increased TIL density in MSI-High cancers is associated with low or absent membrane-bound FasL expression, while increased FasL in MSS cancers allows the killing of host TILs. TUNEL/CD3 double staining was also used to determine whether MSS cancers contain higher numbers of apoptotic TILs in vivo than MSI-High or MSI-Low cancers. Contrary to the initial hypothesis, it was found that MSI-High cancers were associated with higher FasL expression (p = 0.04) and a stronger intensity of FasL staining (p = 0.007). In addition, mucinous carcinomas were independently characterized by increased FasL expression (p = 0.03) and staining intensity (p = 0.0005). Higher FasL expression and staining intensity did not correlate with reduced TIL density or increased numbers of apoptotic TILs. However, consistent with the hypothesis that curtailment of the host anti-tumour immune response contributes to the poor prognosis in MSS cancers, it was found that apoptotic TILs were most abundant in MSS carcinomas and metastatic Dukes' stage C or D tumours (p = 0.004; p = 0.046 respectively). This study therefore suggests that MSS colorectal cancers are killing incoming TILs in an effective tumour counter-attack, but apparently not via membrane-bound FasL. Copyright (C) 2003 John Wiley Sons, Ltd.

Prevalencia y factores de riesgo asociados a sífilis en mujeres

INTRODUCCIÓN: Se ha demostrado que la sífilis, debido a la ulceración genital que produce, es un cofactor asociado para adquirir otras enfermedades de transmisión sexual (ETS), principalmente de origen viral como herpes tipo-2, hepatitis B, y el VIH. Aunque las mujeres trabajadoras del sexo comercial (MTSC) han adquirido mejores conocimientos para prevenir las ETS, constituyen un grupo que por su heterogenicidad en términos de condición socioeconómica, estado de salud, ambiente y sitio de trabajo, manifiestan diferentes actitudes y conocimientos que hacen latente la posibilidad de adquirir y transmitir ETS incluyendo sífilis, por lo que lo estudio hace un acercamiento hacia los factores asociados a infección por Treponema pallidum en este grupo de mujeres. MÉTODO: Basado en un marco muestral, que identifica sitios donde se practica el comercio sexual femenino en la ciudad de México, se seleccionó una muestra de 807 MTSC, a quienes previo consentimiento informado, se entrevistó para que respondieran un cuestionario estructurado. Se obtuvo una muestra sanguínea para la identificación de diversos marcadores serológicos de ETS de acuerdo al manual de procedimientos para el diagnóstico de ETS. Para el diagnóstico de Treponema pallidum se utilizó una prueba de tamizaje de RPR (Bigaux Diagnóstica), y prueba confirmatoria de FTA-ABS (Pasteur Diagnostics). RESULTADOS: Las prevalencias de sífilis en la muestra de MTSC fue de 6,4% (52/807), siendo mayor en quienes trabajaban en sitios de calle comparadas con aquellas de estéticas. La edad de las mujeres entrevistadas osciló entre 17 y 58 años con una media de 29,2 años (d.s. 7,3 años). La prevalencia de sífilis fue mayor en los grupos etáreos mayores de 30 anos. La edad de inicio de relaciones sexuales varió desde 11 hasta 30 anos con una media de 16 años (d.s. 3,1 años). Los factores predictores de infección por T. pallidum, determinados mediante regresión logística ajustada, fueron: sitio de trabajo (bar y puntos de calle), NSE (medio y bajo), edad (mayores de 30 anos), antiguedad en el trabajo sexual (> 5 años), y número de clientes en una semana (>10). CONCLUSIONES: A pesar de las limitaciones de precisión estadística, queda demostrado que existe una heterogenicidad de MTSC, diferenciado principalmente por el sitio donde se desempeñan. Debe entenderse que más que grupos de riesgo de adquirir y transmitir ETS, existen prácticas sexuales de riesgo en cualquier individuo que tiene relaciones sexuales, que aunadas a infecciones predisponentes como sífilis, facilitan la transmisibilidad de otras ETS. Por lo tanto, las campañas de prevención y fomento de uso de condón, deben orientarse no sólo a las MTSC sino también a sus clientes y parejas, con la finalidad de que todos asuman la responsabilidad del sexo seguro.

HIV infection and related risk behaviors in a community of recyclable waste collectors of Santos, Brazil

OBJECTIVE: To estimate the seroprevalence of HIV, hepatitis B and C and syphilis and to describe risk behaviors associated to their transmission among recyclable waste collectors. METHODS: A seroepidemiological survey was carried out in the city of Santos, Southeastern Brazil, in 2005. A total of 315 individuals were enrolled in the survey, of which 253 subjects underwent serological testing HIV, hepatitis B and C and syphilis. Statistical analysis consisted of univariate and bivariate analyses (cross-tabulation and odds ratio) and multivariate analysis (by logistic regression), relating HIV infection with established risk behaviors and seropositivity. RESULTS: Overall seroprevalences were: HIV, 8.9%; hepatitis B, 34.4%; hepatitis C, 12.4%; and syphilis, 18.4%. Subjects were characterized by a predominance of males with low educational and economic levels, subjected to parenteral and sexual exposures to HIV and other sexually transmitted infections. Multivariate analysis results indicated that risk factors for both sexually and parenterally related exposure were significantly associated with HIV in this community. CONCLUSIONS: Seroprevalences found in the study were approximately 10 to 12 times higher than the national average. These communities are socially marginalized and generally not recognized by national programs as potentially endangered populations.

Seroprevalencia de marcadores de infecciones transmisibles por vía transfusional en banco de sangre de Colombia

OBJETIVO: Determinar la seroprevalencia de marcadores de infecciones transmisibles por vía transfusional. MÉTODOS: Estudio transversal con fuente de información secundaria, basada en los resultados de pruebas biológicas en los donantes de un banco de sangre de Medellín, Colombia, de 2007 a 2010. Se determinó la seroprevalencia de los marcadores de infección y se compararon según sexo y tipo de donante a través de análisis de frecuencias, chi cuadrado, Fisher y razones de prevalencia. RESULTADOS: La población de base estuvo conformada por 65.535 donantes de los cuales, 3,3% presentaran al menos una prueba biológica positiva. El marcador más prevalente en las pruebas del banco de sangre fue sífilis (1,2%), seguido de tripanosomiasis (1,0%), virus de la hepatitis C (VHC) (0,6%), virus de la inmunodeficiencia humana (VIH) (0,5%) y virus de la hepatitis B (VHB) (0,2%). Con base en el laboratorio de referencia se halló una prevalencia de 0,6% para sífilis, 0,1% para VHB y 0% para VHC, VIH y Chagas. Se hallaron diferencias estadísticas en la prevalencia de VHB y sífilis según sexo y tipo de donante. CONCLUSIONES: Los resultados son coherentes con las prevalencias dadas por la Organización Panamericana de la Salud (OPS) y se pueden correlacionar con la prevalencia mundial de las infecciones transmisibles por via transfusional. Los resultados hallados en las pruebas del banco de sangre posibilitan la disminución del riesgo transfusional pero limitan la optimización de recursos al excluir donantes clasificados como falsos positivos.

The frequency of blood-born viral infections in a population of multitransfused Brazilian patients

The frequency of viral markers for hepatitis B (HBV) and C (HCV), human immunodeficiency virus-1 (HIV-1) and human T-lymphotropic virus-1 (HTLV-1) was evaluated in 32 Brazilian ß-thalassemia multitransfused patients. Additionaly the serum concentrations of ferritin and alanine aspartate transaminase (ALAT) were determined. The results show a high prevalence of markers of infection by HBV (25.0%) and HCV (46.8%) and a low prevalence of markers for HIV-1 and HTLV-1. No correlations were demonstrated between the presence of the hepatitis markers and the number of units transfused or the serum concentrations of ferritin and ALAT.

Seroprevalence of HIV, HTLV-I/II and other perinatally-transmitted pathogens in Salvador, Bahia

Generation of epidemiological data on perinatally-transmitted infections is a fundamental tool for the formulation of health policies. In Brazil, this information is scarce, particularly in Northeast, the poorest region of the country. In order to gain some insights of the problem we studied the seroprevalence of some perinatally-transmitted infections in 1,024 low income pregnant women in Salvador, Bahia. The prevalences were as follow: HIV-1 (0.10%), HTLV-I/II (0.88%), T.cruzi (2.34%). T.pallidum (3.91%), rubella virus (77.44%). T.gondii IgM (2.87%) and IgG (69.34%), HBs Ag (0.6%) and anti-HBs (7.62%). Rubella virus and T.gondii IgG antibodies were present in more than two thirds of pregnant women but antibodies against other pathogens were present at much lower rates. We found that the prevalence of HTLV-I/II was nine times higher than that found for HIV-1. In some cases such as T.cruzi and hepatitis B infection there was a decrease in the prevalence over the years. On the other hand, there was an increase in the seroprevalence of T.gondii infection. Our data strongly recommend mandatory screening tests for HTLV-I/II, T.gondii (IgM), T.pallidum and rubella virus in prenatal routine for pregnant women in Salvador. Screening test for T.cruzi, hepatitis and HIV-1 is recommended whenever risk factors associated with these infections are suspected. However in areas with high prevalence for these infections, the mandatory screening test in prenatal care should be considered.

Molecular aspects of hepatic carcinogenesis

Exogenous agents correlated with hepatocellular carcinoma (HCC) have been identified and well characterized. These agents, including the different viruses that cause chronic hepatitis and cirrhosis, can lead to regenerative nodules and dysplastic nodules/adenomatous hyperplasia. These conditions associated with several molecular alterations of hepatocyte ultimately culminate in hepatocellular carcinoma. Recently, there has been a great progress in the identification of somatic and germinative mutations that may be correlated with the development of HCC, justifying a review on the subject. Hence, the factors involved in the process of hepatic carcinogenesis, such as infection by the hepatitis B and C viruses, with a special focus in the molecular alterations described in recent years are discussed herein, pointing out areas potentially relevant for clinical development.

p53 immunostaining pattern in Brazilian patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is an important type of cancer etiologically related to some viruses, chemical carcinogens and other host or environmental factors associated to chronic liver injury in humans. The tumor suppressor gene p53 is mutated in highly variable levels (0-52%) of HCC in different countries. OBJECTIVE: The objective of the present study was to compare the frequency of aberrant immunohistochemical expression of p53 in HCC occurring in cirrhotic or in non-cirrhotic patients as well as in liver cell dysplasia and in adenomatous hyperplasia. We studied 84 patients with HCC or cirrhosis. RESULTS: We detected p53 altered immuno-expression in 58.3% of patients in Grade III-IV contrasting to 22.2% of patients in Grade I-II (p = 0.02). Nontumorous areas either in the vicinity of HCC or in the 30 purely cirrhotic cases showed no nuclear p53 altered expression, even in foci of dysplasia or adenomatous hyperplasia. No significant difference was found among cases related to HBV, HCV or alcohol. CONCLUSION: The high frequency of p53 immunoexpression in this population is closer to those reported in China and Africa, demanding further studies to explain the differences with European and North American reports.

Confirming the presence of HTLV-1 infection and the absence of HTLV-2 in blood donors from Arequipa, Peru

Epidemiological studies conducted in Peru disclosed HTLV-1 to be prevalent in different ethnic groups, and found HTLV-2 in some Amazonian Indians and in men who have sex with men. No data concerning HTLV-1/2 infection in blood donors from Arequipa, a highlands region in southern Peru, is available. We searched for the presence of HTLV-1 and HTLV-2 antibodies in 2,732 serum samples obtained from blood donors from this geographic area. HTLV-1/2-specific antibodies were detected using an enzyme-linked immunosorbent assay (ELISA) and were confirmed by Western blot (WB). Reactive sera had their blood bags discarded from donation, and the demographic characteristics of the donors were analyzed. Thirty-five sera (1.2%) were HTLV seroreactive by ELISA, and 25 were confirmed HTLV-1-positive by WB. One serum disclosed HTLV-positivity, and the remaining nine serum samples showed indeterminate results by WB; three of which had an HTLV-1 indeterminate Gag profile. The median age of HTLV-positive individuals was 34.6 years; 27 were male and eight were female. All individuals were from southern Peru: 27 from Arequipa, five from Puno, and three from Cuzco. HTLV co-positivity with hepatitis B (five sera) and syphilis (one serum) were detected. Previous transfusion and tattooing were observed in two and one individuals, respectively. No serum was positive for HTLV/HIV co-infection. This study confirmed, for the first time, HTLV-1 infection and the absence of HTLV-2 infection in blood donors from Arequipa, Peru and suggests vertical transmission as the major route of HTLV-1 transmission and acquisition in this geographic region.

Impact of Renal Dysfunction on Liver Transplantation: a Retrospective Study in 708 Orthotopic Liver Transplant Recipients

Renal dysfunction often complicates the course of orthotopic liver transplant recipients and is associated with increased morbid -mortality. The aims of this study were to determine the incidence of chronic renal disease and its impact on patient survival. Clinical data included age, gender and weight,aetiology of hepatic failure, presence of diabetes,hypertension, hepatitis B and C infection, renal dysfunction pretransplant and immunosuppression. Laboratory data included serum creatinine at days 1, 7, 21, month 6, 12 and yearly. The glomerular filtration rate was determined by Cockcroft-Gault equation. We studied retrospectively from September 1992 to March 2007 708 orthotopic liver transplant recipients. Mean age 44±12.6 years, 64% males, 17% diabetic, 18.8% hypertensive, 19.9% with hepatitis C and 3.8% hepatitis B. Renal dysfunction pretransplant was known in 21.6%. Mean follow-up was 3.6 years. Mean transplant survival 75% at 12 months. 154 patients died. Univariate and multivariate analyses were performed and a p<0.05 was considered significant. Acute kidney injury occurred in 33.2%. Chronic kidney disease stage 3 was observed in 34.3%,stage 4 in 6.2% and stage 5 in 5.1%. At the time of this study, 46.4% were on Cyclosporine A, 44.7% on tacrolimus and 8.9% on sirolimus. Using multivariate analysis, renal dysfunction was correlated with renal dysfunction pre -orthotopic liver transplant (p<0.001), acute kidney injury (p<0.001), haemodialysis development (p<0.001), and inversely correlated with the use of mycophenolate mophetil (p<0.001); mortality was positively correlated with renal dysfunction pretransplant (p=0.03),chronic kidney disease stage 4 (p=0.001), chronic kidney disease stage 5 (p<0.001) and inversely correlated with the use of tacrolimus (p=0.006). In conclusion orthotopic liver transplant recipients are disposed to renal complications that have a negative impact on survival of these patients.

Demographic and Clinical Characteristics of Human Immunodeficiency Virus-Infected Patients Receiving Dialysis in Portugal: a Nationwide Multicentre Survey

Background: Data on human immunodeficiency virus (HIV) infected patients receiving dialysis in Portugal is scarce. Methods: This nationwide epidemiological survey retrospectively evaluates HIV-infected patients on chronic dialysis in Portugal between 1997 and 2002. Results: Sixty-six patients were evaluated (mean age: 39.1±1.6 years, 47 men, 35 black African). Sixty-two patients started dialysis and 4 patients who were receiving dialysis had HIV seroconversion. Eighty-five percent of patients were treated in Lisbon. The annual incidence of HIV-infected patients on chronic dialysis was 0.5% in 1997 and 0.9% in 2002. Seventy-eight percent of patients were HIV-1 infected , 13% had hepatitis B and 31% hepatitis C. Sexual contact was the mode of transmission of HIV in 53% of cases. Four patients had biopsy-proved HIV-associated nephropathy. Ninety-five percent of patients were on chronic hemodialysis. Fifty percent of patients had acquired immunodeficiency syndrome. At follow-up, 12 patients died. HIV-infected CKD patient survival after starting dialysis was 80% at 3 years. Conclusion: The incidence of HIV-infected patients on chronic dialysis in Portugal has almost doubled. Widespread use of highly active antiretroviral therapy and the increasing number of black Africans from former overseas Portuguese colonies now living in Portugal are possible reasons for this large increase.

Immunization status of residents in pediatrics at the Federal University of São Paulo, Brazil

Vaccination of health care workers is an efficient way to reduce the risk of occupational infection and to prevent nosocomial transmission to vulnerable patients. Despite this, achieving high immunization rates among those professionals is a challenge. We assessed the immunization status of Residents in Pediatrics at the Federal University of São Paulo from June to December 2008. Their immunization records were checked and evaluated according to the Brazilian Immunization Schedule for health care workers. Considering all required vaccines, only 3.1% of the 64 Residents were up-to-date with their immunizations. Influenza was the vaccine with the lowest uptake (3.1%) and measles and rubella were diseases with the highest evidence of immunity (62.5% each). Only 37.5% of Residents had received three hepatitis B vaccine doses with a subsequent serology confirming seroconversion. Moreover, the vast majority of Residents in Pediatrics who were not up-to-date were unaware of the fact. Both medical schools and Pediatric Residence programs should not only offer information but also check vaccination records in an effort to keep their healthcare workers´ vaccinations up-to-date.

HTLV-1/2 seroprevalence and coinfection rate in Brazilian first-time blood donors: an 11-year follow-up

The seroprevalence and geographic distribution of HTLV-1/2 among blood donors are extremely important to transfusion services. We evaluated the seroprevalence of HTLV-1/2 infection among first-time blood donor candidates in Ribeirão Preto city and region. From January 2000 to December 2010, 1,038,489 blood donations were obtained and 301,470 were first-time blood donations. All samples were screened with serological tests for HTLV-1/2 using enzyme immunoassay (EIA). In addition, the frequency of coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), Chagas disease (CD) and syphilis was also determined. In-house PCR was used as confirmatory test for HTLV-1/2. A total of 296 (0.1%) first-time donors were serologically reactive for HTLV-1/2. Confirmatory PCR of 63 samples showed that 28 were HTLV-1 positive, 13 HTLV-2 positive, 19 negative and three indeterminate. Regarding HTLV coinfection rates, the most prevalent was with HBV (51.3%) and HCV (35.9%), but coinfection with HIV, CD and syphilis was also detected. The real number of HTLV-infected individual and coinfection rate in the population is underestimated and epidemiological studies like ours are very informative.

Hepatic Artery Thrombosis in Live Liver Donor Transplantation: How to Solve - a Case Report

The decrease in the number of cadaveric donors has proved a limiting factor in the number of liver transplants, leading to the death of many patients on the waiting list. The living donor liver transplantation is an option that allows, in selected cases, increase the number of donors. One of the most serious complications in liver transplantation is hepatic artery thrombosis, in the past considered potentially fatal without urgent re-transplantation. A white male patient, 48 years old, diagnosed with hepatocellular carcinoma in chronic liver failure caused by hepatitis B virus, underwent living donor liver transplantation (right lobe). Doppler echocardiography performed in the immediate postoperative period did not identify arterial flow in the right branch, having been confirmed thrombosis of the right hepatic artery in CT angiography. Urgent re-laparotomy was performed, which consisted of thrombectomy and re-anastomosis of the hepatic artery with segmental splenic artery allograft interposition. The patient started anticoagulation and antiplatelet therapy with acetylsalicylic acid. Serial evaluation with Doppler echocardiography showed hepatic artery patency. At present, the patient is asymptomatic. One of the most devastating complications in liver transplantation, and particularly in living liver donor, is thrombosis of the hepatic artery; thus, early diagnosis and treatment is vital. The rapid intervention for revascularization of the graft avoids irreversible ischemia of the bile ducts and hepatic parenchyma, thus avoiding the need for re-transplantation.

Lues maligna in an HIV-infected patient

We report such a case of malignant syphilis in a 42-year-old HIV-infected man, co-infected with hepatitis B virus, who presented neurolues and the classical skin lesions of lues maligna. The serum VDRL titer, which was 1:64 at presentation, increased to 1:2,048 three months after successful therapy with penicillin, decreasing 15 months later to 1:8.