Respiratory Disease Occupational Biomonitoring Collaborative Project (ROBoCoP): A longitudinal pilot study and implementation research in the Parisian transport company.

The ROBoCoP project is launched within the EU COST Action CA16113 "CliniMARK" aiming to increase the number of clinically validated biomarkers and focused on chronic obstructive pulmonary disease (COPD) biomarker development and validation. ROBoCoP encompasses two consecutive studies consisting of a pilot study followed by a field study. The pilot study is a longitudinal exposure assessment and biomarker study aiming at: 1-understanding the suitability of the candidate biomarkers in surveying populations at risk such as workers exposed to COPD causing agents; 2-determining the best sampling plan with respect to the half-life of the candidate biomarkers; 3-implementing and validating the sampling procedures and analytical methods; 4-selecting the best suitable biomarkers to be measured in the field. Each study participant is surveyed every day during the 6-8 h work-shifts for two consecutive weeks. The field study has an implementation research designe that enabled us to demonstrate the applicability of the standardized protocol for biomarker measurements in occupational settings while also assessing the biomarkers' validity. ROBoCoP will focus on particulate matter (PM) exposure measurements, exposure biomarkers and a series of effect biomarkers, including markers of lipoperoxidation: 8-isoprostane, malondialdehyd in exhaled breath condensate (EBC) and urine, potential markers of nitrosative stress: NO2-, NO3- and formate anion in EBC; markers of DNA oxidation: 8-hydroxy-2'deoxyguanosine in EBC and urine, marker of genotoxicity: micronuclei in buccal cells, and oxidative potential in exhaled air (OPEA). OPEA appears particularly promising as a clinical biomarker for detecting COPD, and will be tested independently and as part of a biomarker panel. COPD diagnosis will be performed by an experienced occupational physician according to international diagnostic standards and confirmed by a pulmonologist.This research will include approximatively 300 underground subway workers randomly selected from the personnel registry of a large Parisian transport company. Underground subways are suggested as the most PM polluted urban transport environment. We believe this occupational exposure is relevant for biomonitoring of workers and early detection of respiratory diseases.

Diagnóstico de la dinámica cardiaca durante 16 horas desde los sistemas dinámicos aplicable en UCI / Diagnosis of cardiac dynamics for 17 hours from dynamical systems applicable to ICU

RESUMEN Introducción: El comportamiento caótico de la dinámica cardiaca normal y aguda ha sido caracterizado en el contexto de la teoría de los sistemas dinámicos y la geometría fractal. Objetivo: Desarrollar una nueva metodología diagnóstica para la evaluación de la dinámica cardiaca en pacientes de UCI, durante 16 horas. Metodología: Este es un estudio en pacientes ingresados a Cuidados Intensivos posquirúrgicos (UCI) y sujetos sanos, tomando un total de 47 registros electrocardiográficos continuos y/o Holter, normales y con patología aguda, evaluados en 16 horas. Se desarrolló una inducción con dos dinámicas normales y tres de UCI; a partir de los valores máximos y mínimos de la frecuencia cardiaca/hora y total de latidos/hora, registrados durante 16 horas se construyeron atractores para evaluar sus espacios de ocupación y dimensión fractal, con el fin de establecer diferencias e igualdades respecto a estados normales y patológicos. Se realizaron medidas de sensibilidad y especificidad con las dinámicas restantes para comparar el diagnostico matemático con el diagnóstico clínico. Resultados: Los espacios de ocupación de los atractores cardiacos diferencian dinámicas cardiacas normales de dinámicas con enfermedad crónica y aguda, detectando además dinámicas patológicas con valores superiores a los límites de normalidad, logrando valores de sensibilidad de 0,937 y especificidad del 1. Conclusión: se estableció una nueva metodología de evaluación de la dinámica cardiaca de utilidad para el seguimiento clínico en pacientes de UCI.

ABSTRACT Introduction: The chaotic behavior of normal and acute cardiac dynamics has been characterized in the context of theory of dynamical systems and fractal geometry. Objective: to establish a new diagnostic method for assessing cardiac dynamics in ICU patients, for 16 hours. Methodology: This is a study in post-surgical patients admitted to intensive care (ICU) and in healthy subjects, taking a total of 47 continuous electrocardiographic recordings and/ or Holter, normal and acute pathology, evaluated in 16 hours. Induction with two normal and three UCI dynamics was developed; from the maximum and minimum values of the heart/time and total frequency of beats/minute for 16 hours recorded attractors they were constructed to assess their areas of occupation and fractal dimension, in order to establish differences and equalities regarding normal states and pathological. Sensitivity and specificity measurements were performed with the remaining dynamic to compare mathematical diagnosis with clinical diagnosis. Results: Space occupancy heart attractors differ dynamic normal cardiac dynamics with chronic and acute illness, in addition detecting dynamic pathological with above normal limits values, achieving sensitivity values of 0.937 and specificity of 1. Conclusion: a new methodology for evaluating cardiac dynamics useful for clinical monitoring in ICU patients was established.

Method validation of nanoparticle tracking analysis to measure pulmonary nanoparticle content: the size distribution in exhaled breath condensate depends on occupational exposure.

A particle exposure assessment based on the dose deposited in the lungs would be the gold standard for the evaluation of any resulting health effects. Measuring particles in exhaled breath condensate (EBC)-a matrix containing water and airway lining fluid-could help to evaluate particle retention in the lungs. This study aimed to (1) validate a nanoparticle tracking analysis (NTA) method for determining the particle number concentration and their hydrodynamic size distribution in EBC, and (2) apply this method to EBC collected from workers exposed to soapstone (n = 55) or quartz dust (n = 12) and controls (n = 11). A standard latex bead solution was used to determine the linear range, limit of detection (LOD), repeatability (coefficient of variation, CV), and bias in spiked EBC. An LM10 NanoSight instrument with NTA version 3.1 software was used for measurement. RTubes® were used for field collection of EBC. The repeatability obtained for a D50 size distribution in EBC showed less than 8% variability, with a bias <7%. The particle concentration was linear in the range ≤2.5 × 108 particles ml-1 with a LOD of 4 × 106 particles ml-1. A recovery of 117 ± 20% at 6.2 × 107 particles ml-1 was obtained with a CV <10% and a bias <20%. EBC from workers exposed to quartz, who experienced the largest exposure to silica particles, consistently exhibited a statistically significant (p < 0.01) higher concentration of particles in their EBC, with a size distribution shift towards larger values than the other groups. Results showed that the NTA technique performed well for characterizing the size distribution and concentrations of particles in EBC. The technique needs to be corroborated with a larger population of workers.

Urinary Clara Cell Protein in Kidney Transplant Patients: A Preliminary Study.

OBJECTIVE: The aim of this exploratory study was to analyze the urinary excretion of Clara cell protein (CC16), a new marker of proximal tubular dysfunction (PTD), in kidney transplantation (KT). MATERIALS AND METHODS: Urinary concentrations of CC16, ß2-microglobulin (ß2m), and N-acetyl-glucosaminidase (NAG) were measured in 50 KT patients (72% men; mean age 50.4 ± 12.4 years; diabetes in 24%; duration of KT 4.3 ± 3.1 years) and 10 healthy controls (6 men; mean age 33.6 ± 13.4 years). RESULTS: Urinary levels of ß2m, NAG, and CC16 were significantly higher in KT patients than in controls: ß2m: 0.77 (interquartile range [IQ] 0.22 to 4.62) g/g vs 0.069 (IQ 0.05 to 0.10) g/g; NAG: 3.16 (IQ 2.09 to 5.33) U/g vs 1.73 (IQ 1.25 to 2.07) U/g; CC16: 26.01 (IQ 8.62 to 123.3) g/g vs 2.51 (IQ 0.83 to 7.18) g/g (P < .001). Elevated levels of ß2m, NAG, and CC16 were found in 81%, 28%, and 71% of KT patients, respectively. Urinary levels of ß2m, NAG, and CC16 significantly increase as glomerular filtration rate (GFR) decreases. Interestingly, in patients with GFR >60 mL/min, we still found high levels of ß2m, NAG, and CC16 in 77%, 13%, and 52%, respectively. Diabetic subjects had significant higher levels of the 3 markers compared with nondiabetic subjects, without differences in albumin excretion or GFR. CC16 showed a positive correlation with urinary albumin (r = 0.42, P < .001), NAG (r = 0.352, P < .05), and ß2m (r = 0.75, P < .001). CONCLUSION: PTD is highly prevalent in KT patients. This is the first study that analyzes CC16 in KT patients, showing that the urinary excretion of this protein is significantly increased in this population. Further studies are needed to examine the clinical value of CC16 in KT patients.

Pathogenic Helicobacter pylori strains translocate DNA and activate TLR9 via the cancer-associated cag type IV secretion system.

Helicobacter pylori (H. pylori) is the strongest identified risk factor for gastric cancer, the third most common cause of cancer-related death worldwide. An H. pylori constituent that augments cancer risk is the strain-specific cag pathogenicity island, which encodes a type IV secretion system (T4SS) that translocates a pro-inflammatory and oncogenic protein, CagA, into epithelial cells. However, the majority of persons colonized with CagA+ H. pylori strains do not develop cancer, suggesting that other microbial effectors also have a role in carcinogenesis. Toll-like receptor 9 (TLR9) is an endosome bound, innate immune receptor that detects and responds to hypo-methylated CpG DNA motifs that are most commonly found in microbial genomes. High-expression tlr9 polymorphisms have been linked to the development of premalignant lesions in the stomach. We now demonstrate that levels of H. pylori-mediated TLR9 activation and expression are directly related to gastric cancer risk in human populations. Mechanistically, we show for the first time that the H. pylori cancer-associated cag T4SS is required for TLR9 activation and that H. pylori DNA is actively translocated by the cag T4SS to engage this host receptor. Activation of TLR9 occurs through a contact-dependent mechanism between pathogen and host, and involves transfer of microbial DNA that is both protected as well as exposed during transport. These results indicate that TLR9 activation via the cag island may modify the risk for malignancy within the context of H. pylori infection and provide an important framework for future studies investigating the microbial-epithelial interface in gastric carcinogenesis.

Nefrocalcinosis como complicación de hipercalcemia por ingesta excesiva de calcio en el embarazo

Antecedentes: La hipercalcemia durante el embarazo es un hallazgo raro. La exposición prolongada a los altos niveles de calcio puede llevar a calcificaciones en distintos órganos maternos y en el feto puede llevar a abortos espontáneos y mortinatos. Caso clínico: Paciente primípara, con gestación de 20+4 semanas, remitida por falla renal aguda e hipertensión arterial. Ella reportó ingesta excesiva de queso, leche y multivitamínicos. Con calcio de 9,2 mg/dL y relación BUN/Creatinina de 6,8 se diagnostica intoxicación alimentaria y nefrocalcinosis medular por alta ingesta de calcio. Al cuarto día de hospitalización presenta sangrado vaginal y debido a las condiciones de la madre se termina el embarazo. Posteriormente presenta una mejoría clínica significativa y se da de alta. Discusión: La relevancia de este caso es que la presencia de hipercalcemia en el embarazo y su no identificación, aumenta el riesgo de aborto, y de hipocalcemia neonatal, que a su vez puede causar muerte materna. En este cuadro se pueden presentar varias complicaciones, siendo una de las más frecuentes la nefrocalcinosis, identificada en este reporte. Conclusión: La ingesta de calcio excesiva en gestantes puede causar nefrocalcinosis. Es importante la educación para evitar ésta y otras complicaciones.

Background: Hypercalcemia during pregnancy is a strange finding. The long exposure to high calcium levels can take to calcifications in different maternal organs and it can lead to miscarriage and stillborn. Case presentation: A woman with 20+4 weeks' gestation, who was remitted because of an acute renal failure and hypertension. She reported excessive intake of cheese, milk and multivitaminics. With a calcium level of 9.2 mg/dL and BUN/Creatinine of 6.8, diagnosed with food poisoning and medullary nephrocalcinosis as a result of the high calcium intake. At the fourth day at the hospital she presented vaginal bleeding and due to the conditions of the mother the pregnancy was ended. Afterwards she presented a significant clinical improvement and she was discharged from the hospital. Discussion: The relevance of this case is that the presence of hypercalcemia during pregnancy and not identifying it elevates the risk of miscarriage and neonatal hypocalcemia, which can cause maternal death. In this aspect, many complications can develop, being one of the most important the nephrocalcinosis, identified in this report. Conclusion: The excessive calcium intake in pregnant women can cause nephrocalcinosis. It is important to educate them to avoid this and other complications.

Management of congenital midline nasofrontal masses: case report and review of literature.

Epidermoid cysts, dermoids, gliomas, and meningo-/encephaloceles are the most important differential diagnoses in congenital nasofrontal masses. Since they arise from an abnormal fusion during fetal development, intracranial extension of the lesion has to be ruled out radiologically before therapy. Dermoids are the most common entity. We report about a congenital epidermoid cyst of the glabella and nasion that had been growing over the last two years before presentation in a 24-year-old patient. We discuss radiological imaging and the different surgical approaches described in literature.

Is "intra-operating room" thromboelastometry useful in liver transplantation? A case-control study in 303 patients.

Coagulation monitoring during liver transplantation (LT) is, even today, fundamental to reduce blood loss during surgery. Thromboelastometry (TEM) is a proven technique for controlling the various parameters that influence coagulation. However, there are no studies linking "intra-operating room" TEM (orTEM) with LT outcomes. We describe a case-control study in 303 liver graft recipients analyzing variables associated with operative complications and long-term LT outcomes. The results showed that orTEM reduced the use of blood products in patients with Model for End-Stage Liver Disease scores of ≥ 21, retransplantation, and high surgical difficulty and important intraoperative bleeding. In addition, results in survival and postoperative complications were better when orTEM was used. In conclusion, we confirm that use of orTEM is associated with less use of blood products and a lower rate of complications after LT.

Donor characteristics that are associated with survival in liver transplant recipients older than 70 years with grafts.

INTRODUCTION: The use of grafts from donors older than 70 years of age is increasing due to the decrease in the number of donors and the increase in waiting list patients. MATERIAL AND METHODS: We undertook a univariate and multivariate analysis of 980 adult recipients of whole liver grafts, 129 of them from donors aged 70 years or older. RESULTS: No differences were found in patient survival compared with recipients of younger grafts. There were no higher rates of rejection, vascular or biliary complications, postoperative bleeding, or infections, but older grafts were associated with graft dysfunction (P = .01) and a higher frequency of postoperative refractory ascites (P = .007), but without a greater need for retransplantation. As graft-associated factors, the joint presence in the donor of diabetes (P = .00; confidence interval [CI] = 0.04-0.117), hypertension (P = .00; CI = 0.22-0.39), and weight of more than 90 kg (P = .031; CI = 0.05-0.104) were suggestive of poor prognostic factors in recipient survival. Survival in hepatitis C virus (HCV) recipients or recipients aged older than 60 years was worse with donors aged older than 70 years, although not significantly so. With grafts from donors aged older than 80 years (n = 15), although patient survival rate was good (70% at 10 years), there was a higher rate of retransplantation (20%) and the early mortality rate was 13.3%. CONCLUSIONS: Use of grafts from donors aged older than 70 years is safe, with similar survival to patients with younger grafts. The appearance of initial dysfunction with prolonged ascites may be due to a delay in reaching a correct functionality, but was not associated with increased mortality, complications, or need for retransplantation. It should also be avoided in recipients older than 60 years or with HCV. Grafts older than 80 years were associated with a good long-term patient survival but at the expense of a higher rate of retransplantation. However, it helps to reduce the time on the waiting list and, thus, mortality. We noted decreased survival associated with donor hypertension, diabetes, and obesity, so these donors should be selected more rigorously.

Human papillomavirus genotypes in genital warts in Latin America: a cross-sectional study in Bogota, Colombia.

Epidemiological studies on benign lesions related to human papillomavirus (HPV) infection are scarce in Latin America. We enrolled 342 consecutive patients with lesions suspected of being genital warts (GW). All patients underwent confirmatory biopsy and GP5+/GP6+/- Reverse Line Blot HPV testing on frozen tissue. In 261 (81%) cases, the diagnosis was confirmed by histopathology and HPV was detected in 90.6% of men and 87.7% of women. HPV 6 was by far the most common type in both women (62%) and men (56%), followed by HPV 11 (∼20%). Co-infection with these two types occurred in 7% and 12% of women and men, respectively. HPV16 ranked third in prevalence, with 16% of patients testing positive. Twenty-five percent of cases tested positive for multiple HPV genotypes. Although HPV 6 and HPV 11 were the main types detected and no differences between men and women were observed, we found HPV 11 contributed more to GW aetiology compared with previous reports, showing a variability of HPV type distribution in GW across populations. This information is valuable baseline data in Latin America for future estimations of the burden of GW in men and women and shows the potential benefit obtainable by prophylactic vaccination against HPV types 6 and 11.

Risk factors for wheezing in infants born in Cuba.

BACKGROUND: Cuba is a unique country, and despite limited economic development, has an excellent health system. However, the prevalence of asthma symptoms in children in Havana, Cuba, is unusually high. AIM: As early life exposures are critical to the aetiology of asthma, we have studied environmental influences on the risk of wheezing in Cuban infants. DESIGN: Cross-sectional study. METHODS: A random sample of 2032 children aged 12-15 months living in Havana was selected for inclusion in the cohort. Data were collected using questionnaires administered by researchers. RESULTS: Of 2032 infants invited to participate, 1956 (96%) infants provided data. The prevalence of any wheeze was 45%, severe wheeze requiring use of emergency services was 30% and recurrent wheeze on three or more occasions was 20%. The largest adjusted risk factors for any wheeze were presence of eczema [odds ratio (OR) 2.09; 95% confidence interval (CI) 1.48-2.94], family history of asthma (OR 2.05; 95% CI 1.60-2.62), poor ventilation in the house (OR 1.99; 95% CI 1.48-2.67), attendance at nursery (OR 1.78; 95% CI 1.24-2.57), male sex (OR1.52; 95% CI 1.19-1.96) and the number of smokers in the house (P < 0.03 for trend), OR 1.64 (95% CI 1.17-2.31) for three or more smokers in the house compared to no smokers in the household. CONCLUSION: We have identified several risk factors for any wheeze in young infants living in modern day Cuba. As the prevalence of smoking in the house is high (51%), intervention studies are required to determine effective strategies to improve infant health.

The utility of serologic tests as biomarkers for Helicobacter pylori-associated precancerous lesions and gastric cancer varies between Latin American countries.

PURPOSE: Currently, studies on serologic diagnosis of Helicobacter pylori-associated gastric cancer (GC) in Latin America are scarce. The aim of the present study was to evaluate the association between H. pylori serology tests in patients with early precancerous lesions or GC, when compared with non-atrophic gastritis in Colombia, Paraguay, and Mexico, three countries in Latin America with a high prevalence of H. pylori infection but contrasting rates of GC mortality. METHODS: Gastric biopsies and blood samples were obtained from patients attending the gastroenterology or oncology services of hospitals in the three participating countries. IgG antibodies against H. pylori whole-cell antigens and CagA were tested in 1,117 sera using an enzyme-linked immunoabsorbent assay. RESULTS: Positive and significant associations were shown for H. pylori seropositivity and preneoplastic lesions in Mexico (OR 2.0; 95 % CI 1.1-3.4) but not in Colombia (OR 1.2; 95 % CI 0.6-2.1) or Paraguay (OR 1.5; 95 % CI 0.6-3.2); no significant associations were shown for GC in any country. CagA seropositivity was associated with preneoplasic lesions in all three countries (ORs = 2.1, 3.0, and 3.1 for Mexico, Colombia, and Paraguay, respectively), and with GC only in Colombia (OR 4.3; 95 % CI 2.1-9.2). CONCLUSIONS: In countries of Latin America, the IgG CagA test might be a useful biomarker for patients with gastric preneoplastic lesions and for those at risk of developing gastric cancer.

El ejercicio en el tratamiento de la diabetes mellitus tipo 2 / Exercise in the treatment of type 2 diabetes mellitus

La Diabetes Mellitus Tipo 2 (DMT2) es una patología que se reporta en todo el mundo y genera una considerable morbilidad y mortalidad. Sus medidas epidemiológicas de frecuencia han aumentado globalmente en las últimas décadas y si no se toman medidas urgentes el problema crecerá con consecuencias relevantes. La prescripción adecuada del ejercicio aeróbico y de fuerza en el diabético es un pilar fundamental en su manejo, tratamiento, control y pronóstico y tiene múltiples beneficios, no solo en el control glicémico, sino también en parámetros cardiovasculares, metabólicos, antropométricos, psicosociales, e incluso mortalidad. Por lo mencionado, esta revisión comprende en general, el rol del ejercicio en el tratamiento de la DMT2, la prescripción especial del ejercicio, los mecanismos para la mejoría del control glicémico, los beneficios del ejercicio en el diabético y relata algunas recomendaciones basadas en la evidencia para el tratamiento de la DMT2 con el ejercicio aeróbico y el de fuerza. Los autores declaran no poseer conflictos de interés.

Type 2 Diabetes Mellitus (T2DM) is a condition that is reported worldwide and that generates a considerable morbidity and mortality. The epidemiological measures of frequency of this disease have globally increased in recent decades, and unless urgent action is taken, the problem will grow with relevant consequences. The appropriate prescription of aerobic exercise and strength training in diabetic patients is a fundamental pillar in the management, treatment, control and prognosis of this condition and it has many benefits, not only in glycemic control but also on cardiovascular, hemodynamic, metabolic, anthropometric and psychosocial parameters, and even mortality. Therefore, this review addresses in general the role of exercise in the treatment of T2DM, the specific prescription of exercise, the mechanisms for improving glycemic control, the benefits of exercise in diabetic patients, and it provides some evidence-based recommendations for the treatment of T2DM with aerobic exercise and strength training. No financial conflicts of interest exist.

Antitumor efficacy of mammalian target of rapamycin inhibitor therapy in liver transplant recipients with oncological disease: a case-control study.

INTRODUCTION: The reported incidences of de novo malignancy following orthotopic liver transplantation (OLT) are significantly greater than those in the general population. We have analyzed the efficacy of mammalian target of rapamycin inhibitor (mTORi) as immunosuppressant therapy in patients with de novo malignancies or those engrafted because of a primary liver cancer. METHODS: We performed a case-control study of patients with hepatocellular carcinoma (HCC; n = 119), cholangiocarcinoma (n = 1) or de novo malignancies (n = 73). Thirty-seven patients with these tumors were treated with mTORi, and 167, with calcineurin inhibitors (CNI). Switching to mTORi was performed progressively, withdrawing the CNI over 15 days, until obtaining levels of 5-10 ng/dL. RESULTS: No incidence of rejection, serious adverse events, or death was observed with an overall actuarial survival of 68.5% in the mTORi group versus 45.7% among the CNI group. Overall rates of tumor recurrence were 15.2% and 36.8%, respectively (P < .05). Among patients with HCC, survival was 100% of mTORi with and 61.5% among CNI patients, with tumor recurrence rates of 6.2% and 19.1%, respectively (P < .05). DISCUSSION: Surprising differences in survival and tumor recurrence rates were observed among the mTORi-treated group compared with controls. Switching from CNI to mTORi immunosuppressant therapy appeared to be safe. It seems to be reasonable to employ this strategy in liver transplant patients with primary hepatic or "de novo" neoplasms.

Liver transplantation in patients with cryptogenic cirrhosis: long-term follow-up.

OBJECTIVE: The objective of this study was to evaluate long-term survival, histological diagnoses, and mobility of patients with cryptogenic cirrhosis (CC) treated with orthotopic liver transplantation (OLT). PATIENTS AND METHODS: We performed a retrospective analysis of 35 patients who underwent transplantation with CC among 800 OLT patients. There were no differences in gender, mean age of 47 years, average MELD (Model for End-stage Liver Disease) of 16, and hepatocellular carcinoma incidence (8%). RESULTS: In 28.6% of patients, the diagnosis of CC was wrong. There was no incidence of an acute rejection episode and a low incidence of complications, although the postoperative mortality rate was 20%, of chronic rejection was 25%, and recurrence of disease was 4%. Cumulative at 3-, 5-, and 10-year survivals were lower than the other OLT. Survival was lower in patients receiving suboptimal grafts. CONCLUSIONS: One of 3 patients who underwent transplantation for CC had a specific etiologic diagnosis. The chronic rejection rate and postoperative mortality rate were higher than other etiologies, and survivals at 5, 10, and 15 years were lower than other OLT.

MFI ratio estimation of ZAP-70 in B-CLL by flow cytometry can be improved by considering the isotype-matched antibody signal.

INTRODUCTION: The IgV(H) mutational status of B-cell chronic lymphocytic leukemia (B-CLL) is of prognostic value. Expression of ZAP-70 in B-CLL is a surrogate marker for IgV(H) unmutated (UM). As determination of IgV(H) mutational status involves a methodology currently unavailable for most clinical laboratories, it is important to have available a reliable technique for ZAP-70 estimation in B-CLL. Flow cytometry (FC) is a convenient technique for this purpose. However, there is still no adequate way for data analysis, which would prevent the assignment of false positive or negative expression. METHODS: We have modified the currently most accepted technique, which uses the ratio of the mean fluorescent index (MFI) of B-CLL to T cells. The MFI for parallel antibody isotype staining is subtracted from the ZAP-70 MFI of both B-CLL and T cells. We validated this technique comparing the results obtained for ZAP-70 expression by FC with those obtained with quantitative PCR for the same patients. RESULTS: We applied the technique in a series of 53 patients. With this modification, a better correlation between ZAP-70 expression and IgV(H) UM was obtained. CONCLUSIONS: Thus, the MFI ratio B-CLL/T cell corrected by isotype is a reliable analysis technique to estimate ZAP-70 expression in B-CLL.

Infección del torrente circulatorio en una unidad de neonatología de Medellín-Colombia, 2008-2009 / Bloodstream infection in a neonatology unit of Medellín-Colombia, 2008-2009

Bloodstream infection (BSI) is one of the main causes of sepsis and death in newborns. The relative importance of nosocomial and non-nosocomial agents in developing countries is not clear. We conducted a prospective study of newborns hospitalized with a first episode of BSI in order to classify it as early, late or nosocomial, describe the clinical and microbiological charateristics, and explore risk factors between hospital-acquired vs commu-nity-acquiered BSI (HA-BSI vs CA-BSI). Twenty-seven newborns with a first episode of BSI were identified. Streptococcus agalactiae and coagulase negative Staphylococcus were the main agents in CA-BSI and HA-BSI, respectively. The only significant intrinsic risk factor between HA-BSI and CA-BSI was gestational age. The frequent finding of S. agalactiae warrants routine screening and prophylaxis in pregnant women. The risk factors for HA-BSI were mostly extrinsic, and thus, susceptible of being modified.

La infección del torrente circulatorio (ITC) es una de las principales causas de sepsis y muerte neonatal. Su etiología en países en vía de desarrollo, entre agentes no nosocomiales vs nosocomiales no está suficientemente esclarecida. Estudio prospectivo que incluyó neonatos hospitalizados que presentaron un primer hemocultivo positivo, con el propósito de describir características clínicas, microbiológicas, clasificar la ITC en temprana, tardía y nosocomial, y explorar factores de riesgo entre ITC adquirida en la comunidad vs ITC adquirida en el hospital (ITC-AC vs ITC-AH). Se identificaron 27 neonatos con un primer episodio de ITC. Streptococcus agalactiae y Staphylococcus coagulasa negativa fueron los principales agentes en ITC-AC e ITC-AH, respectivamente. El factor de riesgo intrínseco que mostró una diferencia significativa entre ITC-AC vs. ITC-AH fue la edad gestacional. La presencia de S. agalactiae permite plantear el tamizaje y profilaxis a la gestante. Los factores de riesgo para ITC-AH fueron en su mayoría extrínsecos, es decir, susceptibles de ser modificados.

[Goodpasture's syndrome with neurologic involvement and negative ANCA]. / Síndrome de Goodpasture asociado con vasculitiscerebral ANCA negativa.

Goodpasture's syndrome is a rare autoimmune disorder characterized by rapidly progressive glomerulonephritis (RPGN) and alveolar hemorrhage in the presence of antiglomerular basement membrane (anti-GBM) antibodies. Central nervous system involvement is highly unusual in the absence of anti-neutrophil cytoplasmic antibodies. We report the case of a 20-year-old man with RPGN accompanied by bloody sputum, tonic-clonic seizure and high titers of anti-GBM antibody. After treatment with immunosuppressants and plasmapheresis, the patient showed reduced anti-GBM antibody titers and improved neurologic and respiratory symptoms, but renal failure persisted, requiring hemodialysis. Twenty months later, with the disease in remission, he underwent deceased-donor renal transplantation.

Efficacy, tolerance, and safety of mammalian target of rapamycin inhibitors as rescue immunosuppressants in liver transplantation.

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors behave as potent immunosuppressants which have the advantages, with respect to calcineurin inhibitors (CNI: cyclosporine or tacrolimus), of no nephrotoxicity and inhibition of cell proliferation. They are particularly suitable for patients with renal insufficiency or neoplasias. MATERIALS AND METHODS: Twenty-two liver transplant patients were immunosuppressed with everolimus or sirolimus as rescue therapy after CNI treatment: 7 hepatocellular carcinomas; 5 de novo malignancies; 4 renal insufficiencies; 4 chronic rejections; and 2 acute rejection episodes. RESULTS: There were 16.7% tumor recurrences, and 25% improvements in renal function, 75% in chronic rejection, and 50% in acute rejection. There was no incidence of rejection, kidney failure, gastrointestinal intolerance, hydrocarbon intolerance, hypertension, or arterial or venous thrombosis. We observed incidences of 50% for hypercholesterolemia, 31.8% for hypertriglyceridemia, 22.7% for thrombocytopenia, 18.2% for leukopenia, and 9.1% for anemia. The intercurrent infection rate was 13.6%, including oral thrush in 13.6%. Lower limb edema occurred in 13.6%, with 1 case of facial edema and 1 of alopecia. CONCLUSIONS: mTOR inhibitors were safe immunosuppressive drugs whose side effects were controlled and easily managed. They have advantages with respect to CNI due to their slight effects on kidney function and lack of promotion of diabetes mellitus. Although their long-term effectiveness for control of neoplastic diseases is yet to be seen, they can be used safely in these patients with no incidence of rejection. Their effectiveness to control chronic rejection seems significant, but it is doubtful for steroid-resistant acute rejection episodes.

Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women.

Little is known about the dynamics of human papillomavirus (HPV) infection and subsequent development of high-grade cervical intraepithelial neoplasia (CIN2/3), particularly in women >30 years of age. This information is needed to assess the impact of HPV vaccines and consider new screening strategies. A cohort of 1728 women 15-85 years old with normal cytology at baseline was followed every 6 months for an average of 9 years. Women with squamous intraepithelial lesions were referred for biopsy and treatment. The Kaplan-Meier method was used to estimate the median duration of infection and Cox regression analysis was undertaken to assess determinants of clearance and risk of CIN2/3 associated with HPV persistence. No difference in the likelihood of clearance was observed by HPV type or woman's age, with the exception of lower clearance for HPV16 infection in women under 30 years of age. Viral load was inversely associated with clearance. In conclusion, viral load is the main determinant of persistence, and persistence of HPV16 infections carry a higher risk of CIN2/3.