CSF/serum quotient graphs for the evaluation of intrathecal C4 synthesis.

BACKGROUND: Cerebrospinal fluid (CSF)/serum quotient graphs have been used previously to determine local synthesis in brain of immunoglobulins and C3 complement component. The aim of this study was to use the same technique to construct quotient graphs, or Reibergrams, for the beta globulin C4 and to evaluate the method for assessing intrathecal synthesis in neurological disease. METHODS: The constants in the previously-defined Reibergram for immunoglobulin IgA were used to calculate the CSF/serum quotient for C4. CSF and serum were analyzed for C4, IgA and albumin from a total of 12 patients with meningoencephalitis caused by encapsulated microorganisms and 10 subjects without infections or inflammatory neurological disease, some of which had dysfunction of the blood-CSF barrier, RESULTS: The formula and C4 Reibergram with the constants previously found for IgA, determined the intrathecal C4 synthesis in CSF. The intrathecal C4 fraction in CSF (C4 loc in mg/l) was compared to the C4-Index (fraction of CSF: serum for C 4/fraction of CSF: serum for albumin). There was a significant correlation between the two formulae. The CSF/Serum quotient graph was superior for detecting intrathecal synthesis of C4 under variable conditions of blood-CSF barrier permeability. CONCLUSION: The C4 Reibergram can be used to quantify the intrathecal synthesis of this component of the complement system in different infectious diseases of the central nervous system and is especially useful for patients with blood-brain barrier dysfunction.

Molecular diagnosis of Toxoplasma gondii infection in cerebrospinal fluid from AIDS patients.

BACKGROUND: Toxoplasmic encephalitis (TE) is one of the most common opportunistic infections in immunocompromised patients. In Cuba, despite the highly active antiretroviral therapy, TE is still the most important cause of cerebral mass lesions in patients infected with the human immunodeficiency virus (HIV). The detection of Toxoplasma gondii by PCR may facilitate the diagnosis and follow-up of TE in acquired immunodeficiency syndrome (AIDS) patients by direct identification of parasite DNA in clinical samples. The aim of the present study was to evaluate a rapid PCR method using the B1 gene to detect T. gondii in cerebrospinal fluid (CSF) samples from patients with suspected TE. METHODS: CSF samples from AIDS and HIV-negative patients were analyzed. Patients were divided into two groups according to the Centre for Disease Control and Prevention (CDC) criteria for AIDS-related TE: AIDS patients with suspected neurotoxoplasmosis and AIDS and HIV-negative patients with other confirmed neurological diseases but no suspicions of TE. Predictive values, diagnostic accuracy, sensitivity and specificity of the PCR B1 method were calculated. RESULTS: The results obtained from 190 patients showed that this assay has a good sensitivity and specificity (83.3% and 95.7%, respectively) for the diagnosis of TE in AIDS patients. CONCLUSION: PCR using the B1 gene and B22/B23 set of primers is a single, rapid and reliable method that may be valuable for discrimination between toxoplasmosis and other central nervous system (CNS) diseases.

Detection of Toxoplasma gondii in cerebrospinal fluid from AIDS patients by nested PCR and rapid identification of type I allele at B1 gene by RFLP analysis.

Highly active antiretroviral therapy (HAART) has decreased the incidence of opportunistic infections in the central nervous system (CNS) in AIDS patients. However, toxoplasmic encephalitis (TE) still represents the most common cerebral mass lesion in patients infected with human immunodeficiency virus (HIV). The aim of this study was to evaluate nested PCR-B1 using cerebrospinal fluid (CSF) to detect Toxoplasma gondii DNA for the diagnosis of TE. A total of 114 samples were evaluated, and 33/44 samples from patients with TE were positive by PCR (sensitivity 75%), demonstrating the diagnostic usefulness of PCR technique. PCR-B1 products were analyzed by restriction fragment length polymorphism (RFLP) in 30 samples. Only type I allele at B1 was identified in these samples according banding patterns. This is the first report of evaluation of S1-AS1/S2-AS2 set of primers in more than 100 clinical samples as well as the first genotyping study of T. gondii in Cuba.

Cuban Scientific Production on Diabetes, 2000-2017: Peer-reviewed Publications, Collaboration and Impact.

INTRODUCTION The steadily increasing prevalence of diabetes globally has captured researchers' attention. Cuban production of scientific articles on diabetes has not been studied from a bibliometric perspective. OBJECTIVE Characterize the production and impact of research and review articles on diabetes by Cuban authors in journals listed in the Scopus bibliographic database, as well as related collaboration among Cuban institutions and between Cuban and non-Cuban institutions. METHODS A bibliometric analysis was conducted using 2000-2017 data from the Scopus database. The following search strategy was used: descriptor (diabetes), country (Cuba), publication source (journal), article type (original research, review article). Bibliographic indicators of production, visibility, impact and collaboration were examined. RESULTS Cuba contributed 3.2% of Latin American production and 0.1% of global production related to diabetes. Within Cuba's scientific production (610 articles, 538 original research and 72 review), 85.9% had a Cuban corresponding author (Cuban leadership). In articles with international collaboration (22.9%), however, most (67.9%) had non-Cuban corresponding authors. A total of 47% (287) were articles involving a single institution. Only 11.1% were published in top-ranked journals, and 14.4% were cited >10 times. Cubans were lead authors on 0.3% of the most frequently cited (top 10%) articles on diabetes in Scopus. A total of 38.4% of this production appeared in low-impact journals and 57.9% in Cuban journals. Articles published in English accounted for 30% of total and obtained higher impact in terms of citations than articles in Spanish. The strongest networks for scientific collaboration were those that connected Cuban and US researchers. CONCLUSIONS Cuban scientists conduct research on diabetes, but their work is not highly visible in the peer-reviewed literature, particularly in top-ranked journals. The problem is not simply one of publishing more, but of knowing how and where to publish. It is urgent that Cuban universities training health professionals at all levels include instruction on scientific writing.

Intrathecal synthesis of IgE in children with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis.

BACKGROUND: Eosinophilic meningoencephalitis caused by the helminth Angiostrongylus cantonensis, is an emerging infectious disease in America. The objective of this paper was to determine if the intrathecal synthesis of immunoglobulin E is produced during the acute phase of the disease. METHODS: Thirteen patients, mean age 4.5 years were studied; a diagnostic lumbar puncture was performed and serum samples taken. Immunoglobulin E (IgE) in serum and in cerebrospinal fluid (CSF) was quantified by nephelometry. Control patients had other infections or other neurological diseases. RESULTS: The mean cell count in the CSF was 500 x 10-6 cells/L and of these 23% were eosinophils. In blood the eosinophils were 13%. The chief symptoms of the patients were migraine, vomiting and fever and 50% presented some meningeal signs. IgE intrathecal synthesis analyzed by the corresponding quotient diagram (Reibergram) was observed in all patients. No intrathecal IgE synthesis was seen in control patients. CONCLUSION: Intrathecal synthesis of IgE demonstrates the participation of this immunoglobulin in the destruction of the third stage larvae of the parasite in the CSF. The test should be considered in our environment as a tool to aid diagnosis.

sICAM-1 intrathecal synthesis and release during the acute phase in children suffering from Coxsackie A9 and S. pneumoniae meningoencephalitis.

The intercellular adhesion molecule is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Serum and cerebrospinal fluid (CSF) soluble intercellular adhesion molecule 1 (sICAM-1) from normal control children as well as from children with Guillain-Barré syndrome (GBS), with Coxsackie A9 virus meningoencephalitis and with Streptococcus pneumoniae meningoencephalitis were studied. sICAM-1 was quantified using an immunoenzimatic assay and albumin using the immunodiffusion technique in both biological fluids. Increased sICAM-1 values in CSF in patients with GBS correspond to an increase of the albumin CSF/serum quotient. In contrast, in inflammatory diseases like S. pneumoniae and Coxsackie A9 virus meningoencephalitis an increased brain-derived fraction was observed. In particular cases these values are 60-65% and 70-75% respectively. The results indicate an additional synthesis of sICAM-1 in subarachnoidal space during central nervous system (CNS) inflammatory process. An important role of sICAM-1 in the transmigration of different cell types into CSF during CNS inflammation in children with S. pneumoniae and Coxsackie A9 meningoencephalitis may be suggested.

C3c intrathecal synthesis evaluation in patients with multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a chronic, inflammatory and progressive disease of the central nervous system in which local inflammatory injuries of the brain white matter appears, being the most outstanding feature the myeline loss (demyelination). OBJECTIVE: To determine if the complement system might be involved in the MS immunopathogeny favouring the mechanism intervening in the myelin destruction. METHOD: Samples of sera and CSF from twelve patients with a diagnosis of MS obtained at the moment of the admission to the hospital at the beginning of the break out, were collected. Levels of C3c and albumin in sera and in CSF were quantified using radial immunodiffusion plates. RESULTS: High values over 80% of intrathecal synthesis were obtained except in one of the patients. CONCLUSION: Intrathecal synthesis of C3c and its liberation to the CSF means that the activation of the complement system in any of the two ways has taken place, and that once performed its biological functions, has suffered a degradation process.

Conventional polymerase chain reaction for the diagnosis of neurotoxoplasmosis: comparison of three sets of primers for the B1 gene using CSF samples.

Polymerase chain reaction (PCR) has made a significant improvement in the diagnosis of toxoplasmic encephalitis (TE). Nevertheless, a wide variety of targets and primers has been used in different assays, and few comparative studies had been carried out. The aim of the present study was to compare the efficiency of 3 conventional PCR methods by using 3 sets of primers targeting the repetitive B1 gene in the diagnosis of TE. Diagnostic sensitivity and specificity of PCR and nested-PCR protocols were assessed for 207 (nested-PCR/T1-T4), 200 (nested-PCR/S1-AS1), and 206 (PCR/B22-B23) cerebrospinal fluid (CSF) samples, including AIDS and HIV-negative patients. The diagnostic sensitivity of PCR and nested-PCR assays was 50.85%, 68.97%, and 72.41% for T1-T4, S1-AS1, and B22-B23, respectively. The diagnostic specificity was high for all the assays showing values between 95% and 97%. In general, the best results were obtained for the B22-B23 set of primers, suggesting their usefulness compared with 2 nested-PCR protocols and showing that this simple and rapid strategy may be the preferred one for the diagnosis of TE in AIDS patients.

Algunos comentarios sobre los métodos alternativos métricos / Some comments on the metric alternative methods

Una parte importante e imprescindible de la actividad de los científicos y docentes de universidades e institutos de investigación es la divulgación de sus resultados a través de la publicación en revistas especializadas y sobre la base de estas descansa su evaluación. En Cuba la medición de los resultados científicos se realiza por el conteo simple de los artículos que publican los profesionales: Un científico tiene un mayor mérito si publica más artículos, un docente para pasar de una categoría a otra superior tiene que tener en su aval un número determinado de publicaciones; o sea, esta es la etapa cuantitativa por la que aun transitan muchos países. Luego surgieron los métodos para combinar la cantidad con la calidad y entonces se pasa una escala superior que ocurre cuando los trabajos publicados son leídos y son citados en otros artículos, esto ya es una métrica que mide calidad porque significa que la ciencia se ha “consumido.”

An important and indispensable part of the activity of the scientists and teachers of universities and investigation institutes it is the popularization of their results through the publication in specialized magazines and on the base of these rests their evaluation. In Cuba the mensuration of the scientific results is carried out by the simple count of the articles that professionals publish: A scientist has a bigger merit if he publishes more articles, a teacher one to pass from a category to another superior has to have in his reference a certain number of publishing; that is to say, this is the quantitative stage to which still traffic many countries. Then the methods arose to combine the quantity with the quality and then to pass to a superior scale that happens when the published works are read and quoted in other articles, this is already a metric that measures quality because it means that the science has been "consumed."

Comparison of major immunoglobulins intrathecal synthesis patterns in Ecuadorian and Cuban patients with angiostrongyliasis.

Angiostrongylus cantonensis meningitis was first reported in Cuba in 1981, and it was recently reported in South America. The aim of this paper is to evaluate the intrathecal immunoglobulin synthesis patterns from Cuba's and Ecuador's patients with angiostrongyliasis; 8 Ecuadorian patients from two different outbreaks and 28 Cuban patients were studied. Simultaneous blood and cerebrospinal fluid samples were taken. Immunoglobulin (Ig) A, IgM, IgG, and albumin were quantified by radial immunodiffusion. Corresponding Reibergrams were applied. A three-Ig pattern was the most frequent in the two groups, but IgM was presented in all Ecuadorian young mature patients; however, in the Cuban children, only 12 of 28 patients had intrathecal IgM, but about 90% had an IgA and IgG synthesis at time of later puncture. This indicates that, with a larger amount of parasites ingested, clinical symptoms are more severe, and a higher frequency of intrathecal IgM synthesis could be observed. This is discussed as a similarity with the intrathecal IgM synthesis in African trypanosomiasis.

Neuroimmunological findings of Angiostrongylus cantonensis meningitis in Ecuadorian patients.

UNLABELLED: Meningitis caused by Angiostrongylus cantonensis has recently been reported in patients resulting from the first outbreaks in subtropical regions of Ecuador. METHOD: Eight young adult patients from the two outbreaks were studied. IgA, IgM, IgG and albumin in cerebrospinal fluid and serum were quantified and plotted in cerebrospinal fluid/serum quotient diagrams (Reibergrams). The anamnesis on the patients included asking about any consumption of raw snails, symptoms and harm caused. RESULTS: Mean eosinophilia of 7.5% and 26% in serum and cerebrospinal fluid respectively was observed, as well as a moderate increase in total proteins. The most frequent pattern of intrathecal synthesis was observed in three classes of immunoglobulins. Intrathecal synthesis of IgM was observed in all cases two weeks after the first symptoms appeared. CONCLUSION: The intrathecal synthesis patterns of eosinophilic meningitis due to Angiostrongylus cantonensis, facilitated by cerebrospinal fluid analysis, were similar to those of previous cases from abroad.

Mannose-binding lectin deficiency with eosinophilic meningoencephalitis due to Angiostrongylus cantonensis in children: a case series.

INTRODUCTION: Eosinophilic meningitis, a potentially fatal disease caused by Angiostrongylus cantonensis, is considered an emerging infectious disease. CASE PRESENTATION: Three Caucasian boys (aged five-years-old, 10-years-old and six-years-old) with a diagnosis of eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis were studied. Serum immunoglobulin A (IgA), IgM, IgG, and complements C3c and C4 levels were quantified by using an immunodiffusion technique. Immunoglobulin E in serum was quantified by nephelometry and mannose-binding lectin by time-resolved fluorometry. Mannose-binding lectin deficiency was observed in the three patients. The first patient showed a reduction in the levels of IgA and IgM and an increase in the values of IgE and C4. The second patient showed a reduction in mannose-binding lectin level with increased IgG, C4 and IgE levels, and the third patient showed a decrease in mannose-binding lectin level and increased levels of IgM and complement C3c as well as a low level of C4. CONCLUSIONS: To the best of our knowledge, this is the first report of mannose-binding lectin deficiency associated with Angiostrongylus cantonensis meningoencephalitis in children, and it may contribute to the understanding of the participation of this component of the lectin pathway in the development of the disease.

[Towards a scientific synergy: Cuba and the United States of America]. / Hacia una sinergia científica: Cuba y Estados Unidos.

TITLE: Hacia una sinergia cientifica: Cuba y Estados Unidos.

[Collaborative networks between Spain and Latin America regarding multiple sclerosis]. / Redes de colaboración entre España y Latinoamérica sobre esclerosis múltiple.

TITLE: Redes de colaboracion entre España y Latinoamerica sobre esclerosis multiple.

Clinical behavior of Streptococcus pneumoniae meningoencephalitis.

OBJECTIVE: There was an increased number of cases of meningoencephalitis caused by Streptococcus pneumoniae, after the successful vaccination campaigns against Neisseria meningitidis and Haemophilus influenzae. This paper aims at describing the clinical characteristics, the laboratory findings, the complications, and the therapeutic management of these patients, who have been suffering from this disease since 1993 to 2006. METHOD: Twelve children with Streptococcus pneumoniae meningoencephalitis admitted to the pediatric hospital of San Miguel del Padron, City of Havana in this period were assessed. RESULTS: Children under one year are the most frequently affected. Septic shock and brain edema were the most severe complications. Three patients died, implying that this disease has a serious course. Early treatment of brain edema is very important to reduce mortality. The elective drugs for treatment of these cases of Streptococcus pneumoniae meningoencephalitis were vancomycin combined with cephalosporin, cefotaxime or ceftriaxone type. CONCLUSION: Patients with Streptococcus pneumoniae meningoencephalitis show clinical characteristics, complications, and sequels that are different to other bacterial meningoencephalitis, meaning that they could be helpful for physicians considering the differential diagnosis of meningoencephalitis.

Reibergrama para evaluar la síntesis intratecal de Lectina de unión a Manosa / Reibergram to evaluate the Mannan binding Lectin intrathecal synthesis

INTRODUCCIÓN: la dinámica particular de las proteínas derivadas del cerebro en el líquido cefalorraquídeo es diferente a la dinámica de las proteínas derivadas de la sangre. OBJETIVO: describir los datos empíricos de la lectina de unión a manosa y brindar una interpretación teórica de la dinámica de esta proteína a través de la confección un nuevo reibergrama. MÉTODOS: la lectina de unión a manosa en suero y líquido cfalorraquídeo, fue medida en 40 adultos normales a través de un ensayo inmunofluorométrico. El criterio diagnóstico estuvo basado en; muestras controles (pacientes normales) y muestras de pacientes con enfermedades que cursaron con disfunción de barrera sangre-líquido cefalorraquídeo. RESULTADOS: el coeficiente de correlación entre la lectina de unión a manosa en el líquido cefalorraquídeo y en el suero, fue muy bajo. El reibergrama de la lectina de unión a manosa se diseñó de acuerdo con procedimientos previos. CONCLUSIONES: bajo cualquier condición de barrera sangre-líquido cefalorraquídeo, el reibergrama puede identificar la ocurrencia de síntesis intratecal de lectina de unión a manosa.

BACKGROUND: The dynamics of brain derived proteins in cerebrospinal fluid is different from the dynamics of blood-derived proteins. Aim: To describe the empirical data for mannan binding lectin and gives a theoretical interpretation of the dynamics of this protein in cerebrospinal fluid through a new reibergram. METHODS: Serum and cerebrospinal fluid mannan binding lectin were measured in 40 normal adults by immunofluorometric assays. The diagnostic criteria were based in; normal control samples defined clinically and diseases with blood-cerebrospinal fluid barrier dysfunction. RESULTS: Correlation coefficient between cerebrospinal fluid MBL and serum MBL was very low. Mannan binding lectin reibergram was designed according with previous procedures. CONCLUSION: Under all conditions of the blood-cerebrospinal fluid barrier, the reibergram can identify the occurrence of intrathecal mannan binding lectin synthesis.