Impact of BK Polyomavirus Plasma Viral Load in Kidney Transplant Outcomes.

BACKGROUND: BK polyomavirus infection (BKVi) is an important cause of kidney transplant (KT) loss, but there is scarce evidence on the impact of BK plasma viral load on graft function and long-term KT survival. METHODS: A retrospective cohort study including all KT recipients with BKVi (BK viremia identified in ≥3 consecutive samples by polymerase chain reaction) in our center from January 2010 to December 2020 was performed. A case-control study (1:2) was performed. We grouped the cases according to their highest peak viral load: low-level viremia (<10,000 copies/mL) and high-level viremia (≥10,000 copies/mL). To identify risk factors for BKVi, a logistic regression analysis was achieved, and a multivariable Cox regression was used to describe risk factors for graft loss. RESULTS: A total of 849 KTs were performed, and 67 presented BKVi (low-level viremia, n = 35 and high-level viremia, n = 26). In logistic regression analysis male sex (odds ratio [OR], 4.226; 95% CI, 1.660-10.758, P = .002), age (OR, 1.047; 95% CI, 1.008-1.088; P = .018), and retransplant (OR, 4.162; 95% CI, 1.018-17.015; P = .047) were predictors of BKVi. Acute rejection was more frequent in the BKVi group (18% vs 4.9%, P = .004), and graft survival was lower in patients with BKVi and high-level viremia (P = .027). In Cox regression analysis, BKVi (hazard ratio, 3.657; 95% CI, 1.146-11.670; P = .029) and specific BKV (BK polyomavirus) high-level viremia (hazard ratio, 1.988; 95% CI, 1.012-3.907; P = .046) were predictors of shorter graft survival. CONCLUSIONS: BKV high-level viremia was associated with BKV nephropathy and poorer graft survival. Additionally, acute rejection is more frequent after BKVi. It is necessary to develop strategies safe and effective for these patients.

Convolutional Neural Networks for Chagas' Parasite Detection in Histopathological Images.

Chagas disease is a widely spreaded illness caused by the parasite Trypanosoma cruzi (T. cruzi). Most cases go unnoticed until the accumulated myocardial damage affect the patient. The endomyocardium biopsy is a tool to evaluate sustained myocardial damage, but analyzing histopathological images takes a lot of time and its prone to human error, given its subjective nature. The following work presents a deep learning method to detect T. cruzi amastigotes on histopathological images taken from a endomyocardium biopsy during an experimental murine model. A U-Net convolutional neural network architecture was implemented and trained from the ground up. An accuracy of 99.19% and Jaccard index of 49.43% were achieved. The obtained results suggest that the proposed approach can be useful for amastigotes detection in histopathological images.Clinical relevance- The proposed method can be incorporated as automatic detection tool of amastigotes nests, it can be useful for the Chagas disease analysis and diagnosis.

Machine Learning based Classification of Local Robotic Surgical Skills in a Training Tasks Set.

During surgical training, it is important for the surgeon develops good motor skills throughout his training. For this reason, various surgical training systems have been developed to enhance these skills. However, one of the great challenges in these training systems is being able to objectively measure the ability and performance of the main surgical tasks, where currently only a global measurement is obtained once the task is completed. In this work, a temporal evaluation scheme is proposed, that is, an evaluation of local surgical performance at different time intervals during the training of typical tasks (knot-tying, needle-passing and suturing). The goal is to automatically classify expert (experience >100 hrs) and non-expert (experience <10 hrs) surgeons according to their performance during training, based on three classifiers: K-Nearest Neighborhood, Random Forest, and Support Vector Machine Unlike other previously reported methods, this work proposes a new evaluation scheme based on segments or time intervals, which can be an indicator of the surgeon's local performance during a robotic surgical task, without the need for direct labeling of the data at the segment level. The classification performance from obtained results was in accuracy 83% to 100%, 88% to 100% of AUC-ROC, and 88% to 100% of F1-Score in the final test between experts and non-experts surgeons, where the Support Vector Machine classifier presented the best performance. These results suggest that this proposed method by time intervals could be used in various surgical trainers to evaluate the local performance of a surgeon during trainingand thus be able to provide a tool for the quantitative visualization of opportunities to improve surgical skills.Clinical relevance- We consider that the proposed method to carry out a local performance evaluation during surgical training can provide useful information in the learning and improvement of surgical skills.

Unlocking the full power of electrochemical fingerprinting for on-site sensing applications.

Electrochemical sensing for the semi-quantitative detection of biomarkers, drugs, environmental contaminants, food additives, etc. shows promising results in point-of-care diagnostics and on-site monitoring. More specifically, electrochemical fingerprint (EF)-based sensing strategies are considered an inviting approach for the on-site detection of low molecular weight molecules. The fast growth of electrochemical sensors requires defining the concept of direct electrochemical fingerprinting in sensing. The EF can be defined as the unique electrochemical signal or pattern, mostly recorded by voltammetric techniques, specific for a certain molecule that can be used for its quantitative or semi-quantitative identification in a given analytical context with specified circumstances. The performance of EF-based sensors can be enhanced by considering multiple features of the signal (i.e., oxidation or reduction patterns), in combination with statistical data analysis or sample pretreatments or by including electrode surface modifiers to enrich the EF. In this manuscript, some examples of EF-based sensors, strategies to improve their performances, and open challenges are discussed to unlock the full power of electrochemical fingerprinting for on-site sensing applications. Graphical abstract Electrochemical fingerprint-based sensing strategies can be used for the detection of electroactive analytes, such as antibiotics, phenolic compounds, and drugs of abuse. These strategies show selective and sensitive responses and are easily combined with portable devices.

An improved simple method for the identification of Mycobacteria by MALDI-TOF MS (Matrix-Assisted Laser Desorption- Ionization mass spectrometry).

The aim of this study was to establish a simple method for the rapid identification of Mycobacteria species by MALDI-TOF (Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass spectrometry) using the Bruker MALDI-TOF Biotyper system (Bruker Daltonik, Bremen, Germany). A multicentre, prospective, and single blind study was performed in three European Hospitals, two Spanish and one UK hospital from May to August 2018. The BD BACTEC MGIT (Becton Dickinson, Berks, UK) liquid culture system was used in all three centres for the growth of Mycobacteria. When signal positive, tubes were removed from the analyser and in addition to standard laboratory procedures were subcultured on blood agar plates for MALDI-TOF analysis. Plates were incubated aerobically for 1 to 7 days at 37 °C and inspected every day. Once any growth was visible, it was transferred to the steel target plate, overlaid with 1 µl of neat formic acid and 1 µl HCCA matrix (alpha hydroxyl 4 cinnamic acid), and analysed in a Bruker Biotyper MALDI-TOF. Results given by MALDI-TOF were compared with the reference methods used for identification in the different centres. At two Spanish hospitals, identification by MALDI-TOF was only attempted on presumptive non-tuberculosis mycobacteria (NTM) and the results were initially compared with the results obtained by a commercial reverse hybridisation assay, GenoType CM/AS (Hain Lifescience, Tübingen, Germany). At the UK Hospital, identification of any presumptive mycobacteria was attempted and compared with the results obtained by whole genome sequencing (WGS). Overall in 142/167 (85%) of cases the identifications obtained were concordant; all Mycobacterium tuberculosis (MTB) isolates 43/43 (100%), 57/76 (75%) of the rapid growing nontuberculous mycobacteria (NTM), and 42/48 (85%) slow growing NTM tested were identified correctly. We report a new, easy, cheap and quick method for isolation and identification of Mycobacterium spp. without the need for additional steps or equipment and this method is in routine used in all three centres.

Tortuosidad discreta como medida morfométrica en tumores cerebrales / Discrete tortuosity as a morphometric measure in brain tumors

Resumen: Los tumores cerebrales pueden presentar cambios morfológicos dependiendo de su grado de malignidad. El objetivo de este trabajo es poder detectar y cuantificar estos cambios morfológicos a partir imágenes de resonancia magnética, ya que puede representar una ventaja importante para el diagnóstico no invasivo de los pacientes. Una forma de identificar dichos cambios morfológicos es a través de la medición de su tortuosidad. La tortuosidad discreta es un descriptor que caracteriza curvas bidimensionales, como el contorno de una región. En este trabajo se propone una variante para calcular la tortuosidad de superficies volumétricas. Esta técnica se basa en el uso del código cadena de cambios de pendientes del contorno superficial de un volumen y la denominamos como tortuosidad discreta tridimensional. Este descriptor se utiliza como un índice morfométrico para estudiar la tortuosidad de tumores cerebrales. Para ello se analizan imágenes de resonancia magnética de 20 pacientes con presencia de gliomas de bajo y alto grado de malignidad, considerando cuatro regiones de interés: edema, tumor entero, región activa y necrosis. Como resultado, se muestran los distintos grados de tortuosidad de las diversas regiones, encontrándose solo en algunas de ellas diferencias significativas. Cabe señalar que una desventaja que se tiene presente, es la dependencia de la medición a la utilización de un método robusto de segmentación de las regiones, sin embargo la propuesta de la tortuosidad discreta para superficies volumétricas es satisfactoria.

Abstract: A decision tree based system with heuristic weight factors oriented to diagnosis by Morphological changes in brain tumors may be related to their malignancy. The objective of this work is to be able to detect and quantify these changes in a magnetic resonance imaging, since it can represent an important advantage for the noninvasive diagnosis in patients. One way to identify such morphological changes can be through the measurement of their tortuosity. The discrete tortuosity is a descriptor that characterizes bi-dimensional curves, as the contour of a region. In this work an alternative procedure for calculating the volumetric tortuosity of a surface is proposed. This technique is based in the slope chain code of the surface contour of a volume, and here we call it tridimensional discrete tortuosity. This descriptor is used as a morphometric index to study the tortuosity of brain tumors. For this, magnetic resonance images from 20 patients with low and high malignancy levels were analyzed, considering four regions: edema, whole tumor, enhancing region, and necrotic region. As a result, the tortuosities of the different regions are presented, with significant differences only in some of them. It should be noted that a disadvantage that is present, is the dependence of the measurement to the use of a robust method of segmentation, nevertheless the proposal of the discrete tortuosity for volumetric surfaces is satisfactory.

Prevalence and distribution of hepatitis C virus genotypes in Spain during the 2000-2015 period (the GEHEP 005 study).

We report the largest study on the prevalence and distribution of HCV genotypes in Spain (2000-2015), and we relate them with clinical, epidemiological and virological factors. Patients from 29 hospitals in 10 autonomous communities (Andalusia, Aragon, Castilla-Leon, Catalonia, Galicia, Canary Islands, Madrid Community, Valencian Community, Murcia Region and Basque Country) have been studied. Annual distribution of HCV genotypes and subtypes, as well as gender, age, transmission route, HIV and/or HBV coinfection, and treatment details were recorded. We included 48595 chronically HCV-infected patients with the following characteristics: median age 51 years (IQR, 44-58), 67.9% male, 19.1% HIV-coinfected, 23.5% HBV-coinfected. Parenteral transmission route was the most frequent (58.7%). Genotype distribution was 66.9% GT1 (24.9% subtype 1a and 37.9% subtype 1b), 2.8% GT2, 17.3% GT3, 11.4% GT4 and 0.1% GT5 and 0.02% GT6. LiPA was the most widely HCV genotyping test used (52.4%). HCV subtype 1a and genotypes 3 and 4 were closely associated with male gender, parenteral route of infection and HIV and HBV coinfection; in contrast, subtype 1b and genotype 2 were associated with female gender, nonparenteral route and mono-infection. Age was related to genotype distribution, and different patterns of distribution and biodiversity index were observed between different geographical areas. Finally, we describe how treatment and changes in transmission routes may have affected HCV genotype prevalence and distribution patterns. We present the most recent data on molecular epidemiology of hepatitis C virus in Spain. This study confirms that genotype distributions vary with age, sex, HIV and HBV coinfection and within geographical areas and epidemiological groups.

The impact of an antimicrobial stewardship programme on the use of antimicrobials and the evolution of drug resistance.

Misuse of antibiotics can provoke increased bacterial resistance. There are no immediate prospects of any new broad-spectrum antibiotics, especially any with activity against enterobacteria, coming onto the market. Therefore, programmes should be implemented to optimise antimicrobial therapy. In a quasi-experimental study, the results for the pre-intervention year were compared with those for the 3 years following the application of an antimicrobial stewardship programme. We describe 862 interventions carried out as part of the stewardship programme at the Hospital Costa del Sol from 2009 to 2011. We examined the compliance of the empirical antimicrobial treatment with the programme recommendations and the treatment optimisation achieved by reducing the antibiotic spectrum and adjusting the dose, dosing interval and duration of treatment. In addition, we analysed the evolution of the sensitivity profile of the principal microorganisms and the financial savings achieved. 93 % of the treatment recommendations were accepted. The treatment actions taken were to corroborate the empirical treatment (46 % in 2009 and 31 % in 2011) and to reduce the antimicrobial spectrum taking into account the antibiogram results (37 % in 2009 and 58 % in 2011). The main drugs assessed were imipenem/meropenem, used in 38.6 % of the cases, and cefepime (20.1 %). The sensitivity profile of imipenem against Pseudomonas aeruginosa increased by 10 % in 2011. Savings in annual drug spending (direct costs) of 30,000 Euros were obtained. Stewardship programmes are useful tools for optimising antimicrobial therapy. They may contribute to preventing increased bacterial resistance and to reducing the long-term financial cost of antibiotic treatment.

Time-dependent biodistribution and transgene expression of a recombinant human adenovirus serotype 5-luciferase vector as a surrogate for rAd5-FMDV vaccines in cattle.

Replication-defective recombinant adenovirus 5 (rAd5) vectors carrying foot-and-mouth disease virus (FMDV) transgenes elicit a robust immune response to FMDV challenge in cattle; however mechanistic functions of vaccine function are incompletely understood. Recent efforts addressing critical interactions of rAd5 vectors with components of the bovine immune system have elucidated important aspects of induction of protective immunity against FMDV. In the current study, a rAd5-Luciferase (rAd5-Luc) surrogate vector was utilized for indirect assessment of rAd5-FMDV distribution during the first 48 hours post inoculation (hpi). To compare vector distribution dynamics and time-dependent transgene expression, bovine cells were inoculated in vitro with rAd5-FMDV and rAd5-Luc vectors. Superior transgene expression was detected in cells infected with rAd5-Luc compared to rAd5-FMDV. However, both vectors behaved remarkably similar in demonstrating elevated mRNA transcription at 24 and 48 hpi with peak occurrence of transgene expression at 48 hpi. Injection sites of cattle inoculated with rAd5-Luc contained mononuclear inflammatory infiltrates with hexon and transgene proteins associated with antigen-presenting cells. Luciferase activity, as well as microscopic detection of luciferase antigens, peaked at 24 hpi. Presence of viral mRNA also peaked at 24 hpi but unlike luciferase, remained strongly detected at 48 hpi. Cell-associated luciferase antigens were detected as early as 6 hpi at the cortical interfolicullar areas of local LN, indicating rapid trafficking of antigen-presenting cells to lymphoid tissues. This work provides mechanistic insights on rAd5-mediated immunity in cattle and will contribute to ongoing efforts to enhance rAd5-FMDV vaccine efficacy.

Hyperglycemia and the fate of apparent diffusion coefficient-defined ischemic penumbra.

BACKGROUND AND PURPOSE: Previous data have shown the feasibility of identifying ischemic penumbra in patients with acute stroke by using a semiautomated analysis of ADC maps. Here, we investigated whether the fate of ADC-defined penumbra was altered by HG. We also examined the interaction between HG and arterial recanalization on infarct growth. MATERIALS AND METHODS: We examined 94 patients by using MR imaging within 6 hours of stroke onset and a follow-up MR imaging within 7 days. The ADC-defined tissue-at-risk was calculated from the early MR imaging. Patients were classified according to high (>7 mmol/L; n = 34/94, HG) or normal (n = 60/94) baseline SGL. The impact of HG status on infarct growth was assessed by using multiple regression models and analysis of the slopes of regression lines for each group. Interaction between HG status and arterial recanalization on infarct growth was investigated by using multiple regression analysis. RESULTS: The slope of the predicted versus observed infarct growth regression line was steeper in HG than non-HG patients (P = .0008), suggesting that infarct growth within ADC-defined tissue-at-risk was increased in HG patients. The effect was 2.8 times more severe in nonrecanalized patients (P = .01) than in patients with recanalization (P = .001). CONCLUSIONS: ADC-defined tissue-at-risk may represent ischemic penumbra because part of this area may be salvaged in normal SGL patients. The toxicity in HG patients seems to be more related to penumbra-infarction transition than reperfusion injury in humans because the effect was larger in nonrecanalized than in recanalized patients.

An updated review of simian betaretrovirus (SRV) in macaque hosts.

This review is an updated summary of nearly 30 years of SRV history and provides new and critical findings of original research accomplished in the last 5 years including, but not limited to, the pathogenetic mechanisms underlying the origin of hematopoietic abnormalities observed in infected hosts and proposed new SRV serotypes. Despite major advances in the understanding and control of SRV disease, much more remains to be learned and SRV continues to be an exciting and attractive primate model for comparative studies of the mechanisms of retroviral immunosuppression.

Infecciones por neumococo: ¿debemos conocer el perfil de sensibilidad local? / Pneumococcal infections: do we have to know the local antibiotic sensibility?

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Insulinorresistencia en mujeres obesas afrovenezolanas / Insulin resistance in women obesas afrovenezuelan

Se ha demostrado que los factores genéticos se ven influenciados por la raza, donde las de origen africano presentan tendencia a poseer índice de masa corporal (IMC) elevado con perfil lipídico normal (HDL-c elevado y triglicéridos bajos). El objetivo de este estudio fue analizar el grado de insulino-resistencia utilizando para ello el modelo matemático Homeostasis Model Assessment (HOMA) en 2 pobalciones venezolanas de origen africano. La muestra estuvo conformada por 72 mujeres afrovenezolanas de las poblaciones de Santa María (SM) y San José (SJ), Venezuela, con edades comprendidas entre 36 y 48 años, a las cuales se les realizó historia médica y se les calculó IMC para dividirlas en grupos de mujeres obesas y mujeres no obesas; se determinó glicemia, perfil lipídico y HOMA-IR. Al comparar el grupo de mujeres obesas de las dos poblaciones con las no obesas, no se observó diferencia estadísticamente significativa en la Glicemia (obesas 85,1 ± 3,5 SM y 83 ± 2,9 SJ; no obesas 77,3 ± 2,2 SM y 190,1 ± 9,1 SJ; no obesas 184,4 ± 8.8 SM y 193,4 ± 7,4 mg/dl), Triacilglicéridos (obesas 109,8 ± 16,3 SM y 114,8 ± 21,9 SJ; no obesas 64,9 ± 7,6 SM y 77,5 ± 10,8 SJ mg/dl), LDL-c (obesas 126,6 ± 14,8 SM y 126,9 ± 8,6 Sj; no obesas 115,5 ± 133,6 ± 11,4 SJ mg/dl) y HDL-c séricos (obesas 46,3 ± 4,0 SM y 40,2 ± 3,4 SJ; no obesas 55,5 ± 2,8 SM y 44,1 ± 2,3 SJ mg/dl). Igualmente no hubo diferencia significativa entre el HOMA IR del grupo de mujeres obesas de ambas poblaciones (3,3 ± 0,2 SM y 3,2 ± 0,1 SJ) y el del grupo de no obesas (2,8 ± 0,1 SM y 3,1 ± 0,1 SJ). En conclusión, los grupos de mujeres obesas de las poblaciones de Santa María y San José presentaron HDL-c deprimidas y HOMA IR sobre los límites normales

[Imbalance of plasma amino acids in patients with autism and subjects with attention deficit/hyperactivity disorder]. / Desequilibrio de aminoácidos plasmáticos en pacientes autistas y en sujetos con trastorno de déficit de atención o hiperactividad.

INTRODUCTION: Plasma and brain amino acids are influenced by dietary intake. Alterations of plasma amino acid concentrations have been reported in neuropsychiatric disorders. OBJECTIVE: To analyse the plasma amino acid values in subject diagnosed with autism, with attention deficit/hyperactivity disorder (ADHD), and healthy subjects as controls. PATIENTS AND METHODS: Forty subjects affected by autism, 11 with ADHD and 41 healthy subjects (age range 3 18 years old) were included in this study. Peripheral venous blood was obtained in fasting condition, collected in EDTA tubes and centrifuged. Plasma was de proteinised with sulfosalicylic acid. Amino acids were analysed by ion exchange liquid chromatography with an LKB amino acid analyser with sodium citrate elution system and ninhydrin reaction. Results were expressed as mmol/L. RESULTS AND CONCLUSIONS: In both disorders a diminution of phenylalanine and glutamine plasma concentrations was observed beside an increase of glycine. Lysine appeared increased only in autistic subjects. These alterations produce an imbalance with the rest of plasma amino acids competing at the brain blood barrier by the same transport system thus causing alterations in the metabolism and/or transport of amino acids to the brain, altering CNS functions. The phenylalanine decreasing, beside glycine increasing appear to support the hypothesis of a disorder in the inhibitory neurotransmission system, especially in ADHD. The diminution of phenylalanine and the increasing of lysine in autism are suggestive that these two amino acids are metabolically related.

Desequilibrio de aminoácidos plasmáticos en pacientes autistas y en sujetos con trastorno de déficit de atencióno hiperactividad / Imbalance of plasma amino acids in patients with autism and subjects with attention deficit/hyperactivity disorder

Introducción. Los aminoácidos en la dieta influyen en su concentración en el plasma y en el cerebro. En pacientes neuropsiquiátricos se ha descrito alteración en la concentración de aminoácidos plasmáticos. Objetivos. Analizar el perfil de aminoácidos plasmáticos en pacientes con autismo, con trastorno de déficit de atención con hiperactividad (TDAH) y sujetos sanos (control). Pacientes y métodos. Se analizaron 40 pacientes autistas, 11 con TDAH y 41 sujetos sanos con edades comprendidas entre 3 y 18 años. La sangre, obtenida en ayunas por punción venosa, se recogió en tubos con EDTA; se centrifugó y el plasma se desproteinizó con ácido sulfosalicílico. El análisis de aminoácidos se realizó por cromatografía líquida de intercambio iónico, en un analizador de aminoácidos LKB, sistema de elución de citrato de sodio y reacción de ninhidrina. Los resultados se expresaron en mmol/l. Resultados y conclusiones. En ambos trastornos se apreció disminución de las concentraciones plasmáticas de glutamina y fenilalanina, así como aumento de la glicina. La lisina sólo apareció aumentada en los casos de autismo. Estas alteraciones producen un desequilibrio con el resto de los aminoácidos que compiten en la barrera hematoencefálica por el mismo sistema de transporte, afectándose el metabolismo y transporte de estos aminoácidos hacia el cerebro y, por consiguiente, la función del SNC. La disminución de fenilalanina y el aumento de glicina parecen apoyar la hipótesis del trastorno de la neurotransmisión inhibitoria en ambos trastornos, aunque principalmente en el TDAH. La disminución de fenilalanina y el aumento de lisina en autistas sugiere que estos dos aminoácidos están relacionados metabólicamente (AU)

Quality assurance of point-of-care testing in the Costa del Sol Healthcare Area (Marbella, Spain).

Traditionally, point-of-care testing (POCT) has been used throughout the healthcare system without the involvement of the central laboratory. After an exhaustive study of the situation of these laboratories in the Costa del Sol Healthcare Area, we designed a quality control program for the POCT. This program targeted the tests done at the points of care throughout the hospital and the Primary Healthcare Area (PHA), using the Joint Commission on Accreditation of Healthcare Organisations (JCAHO) standards for waived testing. We developed two programs: hospital-based tests and ambulatory POCT for outpatients in PHA. The hospital-based POCT apparatus was used for gases, glucose, qualitative urinalysis, Helicobacter pylori detection in gastrointestinal biopsies and coagulation tests. Ambulatory POCT was used to detect glucose, qualitative urinalysis and pregnancy tests. The personnel responsible are nursing staff with no continuing training program. There was no explicit quality control program and most of the results were used as screening except for glucose in the neonatal department. Criteria for selection of kits and devices were basically based on ergonomic and economic evaluation. Therefore, we performed an evaluation of precision and accuracy of two glucose meter devices. We implemented the internal and external quality programs (IQC and EQC) for glucose testing. We elaborated a guide of standard proceedings for quantitative and qualitative POCT and created an annual course for nursing staff. The annual evaluation of the indicators showed 96% for degree of compliance with IQC; 54% of nursing staff participated in the training program; 98% of the glucometers were operating; and 88% agreement between central laboratory and POCT. As there is no previous experience in our healthcare system, this represents a promising new area of working with nurses, who show great interest in participating in these new programs.

Disseminated histoplasmosis successfully treated with liposomal amphotericin B following azathioprine therapy in a patient from a nonendemic area.

Histoplasma infections in Europe are rare, and acute disseminated histoplasmosis has been observed only in immunocompromised persons. An unusual case of autochthonous disseminated histoplasmosis in a 22-year-old Spanish man who had been treated with azathioprine and prednisone for 4 weeks before admission is reported. The development of an acute form of the disease may represent an endogenous reactivation of a latent infection as a complication of immunosuppression resulting from the use of these drugs. This case illustrates the potential risk of this opportunistic fungal infection in patients receiving azathioprine therapy, an association that has been rarely described before.

[Immunologic characteristics of undernutrition. I. The undernourished patient in nutritional recovery]. / Aspectos inmunológicos del desnutrido. I. El desnutrido en recuperación nutricional.

Malnutrition in children is a well known critical factor that determines immunocompetence changes with altered immune response and higher risk to many diseases, especially in developing countries. Moreover, it is related to increased morbi-mortality rates mainly due to infections. For those reasons, 12 undernourished children, age 5 to 24 months were studied along 8 weeks at the Nutritional Recovery Center of Chiquinquira Hospital in Maracaibo, Venezuela. There were 5 cases of kwashiorkor, 5 marasmatics, 1 mixed marasmus/kwashiorkor and 1 case with moderate malnutrition. After a control blood sample was taken and cutaneous tests were done, a nutritional recovery program was began. At regular time intervals and at the end of the study, tests were done again by measuring seric immunoglobulins (IgG, IgA, IgM), secretory IgA (IgAs), C3 and C4 complement, lymphocytic sub-populations, and auto antibodies; cutaneous hipersensitivity tests were also done. As a control group, 10 apparently healthy children of matching age and sex were also studied with the same parameters. Results show that basal seric Igs did not differ significantly from the control group and did not change along the recovery program period, but there was a significant decrease in IgAs at all times of the study. C4 did not change and C3 was lower than control (p < 0.05) but returned to normal value at the end of the recovery period. CD3 and CD4 lymphocytes showed the same pattern. Only two patients showed positive skin tests and auto antibodies were not detected. It is concluded that there is indeed an altered immune competence with low levels of C3, IgAs, and CD3-CD4 lymphocytes that is reversible after nutritional recovery.

Hepatitis C virus RNA in patients with anti-HCV on hemodialysis. Relationship to transaminase levels.

This study was performed in patients with hepatitis C virus (HCV) who were treated with hemodialysis to determine the relationships among alanine amino-transferase (ALT) levels, immunoglobulin (Ig) G anti-HCV, IgM anti-HCV core, and HCV RNA. Of 107 patients on hemodialysis, 27 had positive IgG anti-HCV. Eight of the patients who had HCV were evaluated every 8 months during a period of 2 years, using the following selection criteria: positive IgG against c-22, c33-c, 5-1-1, and c100-3 viral peptides; absence of infection by hepatitis A virus, hepatitis B virus, cytomegalo-virus, Epstein-Barr virus, herpes simplex virus, and human immunodeficiency virus, as well as absence of hepatotoxic drugs or cholelithiasis. We considered elevated ALT values as those more than 150% of the upper limit of normal. Three of the patients had persistent elevation of ALT levels, two had alternating elevation of ALT levels, and three had normal ALT levels in all blood samples. Of the 24 blood samples, 11 had elevation of ALT (45.8%) levels that showed positive IgM anti-HCV, but only 7 of these 11 had positive HCV RNA (63.6%). None of the 13 blood samples without elevation of ALT had positive IgM anti-HCV, but 5 had positive HCV RNA (38.5%). We found an excellent correlation between IgM anti-HCV and ALT levels (r = 0.81). There was no statistically significant difference between the mean ALT values on the 12 blood samples that had positive HCV RNA and the mean ALT values of the negative HCV RNA samples (53.5 +/- 28.0 IU/l vs. 37.4 +/- 17.5 IU/l, respectively). IgM anti-HCV is related to the elevation of ALT levels and can be used as a serologic marker to indicate the presence of active HCV induced liver damage. Serum ALT levels do not correlate with the detection of viral genome in sera. IgG anti-HCV is not necessarily associated with HCV RNA or IgM anti-HCV. The absence of IgM and HCV RNA in patients with IgG anti-HCV and normal ALT levels does not necessarily suggest the absence of active HCV infection.