[Neurological dysfunction induced by bilirrubin]. / Disfunción neurológica inducida por bilirrubina.

INTRODUCTION: "Kernicterus" is a term currently used to describe bilirrubin induced brain injury in the neuro-pathological studies. This is a confusing term and nowadays we prefer bilirrubin encephalopathy or bilirrubin induced neurological dysfunction. The clinical signs vary and it is clearly decreasing in prevalence in developed countries. MATERIAL AND METHODS: We review a series of 7 patients with bilirrubin encephalopathy and variable neurological manifestations, who were seen in the Neuropaediatric Department in the last 10 years. Only one patient died in the neonatal period with hyperbilirubinaemia, sepsis and multi-organ failure. RESULTS: Diverse aetiological factors were related to hyperbilirubinaemia. All patients had clinical symptoms due to hyperbilirubinaemia. Neuroimaging during the neonatal period showed involvement of the nucleus pallidus, with hyperintensity in T1 in the brain MR scan as the most consistent finding. All the patients who survived developed neurological signs and we try to correlate them with biochemical, clinical, neuroimaging and neurophysiological parameters. CONCLUSIONS: An increase in the number of patients with bilirrubin encephalopathy has been observed over the last few years, and we attempt to find out the causes. The increased survival of the low birth weight newborns, the increase in the immigration population and the use of diagnostic neuroimaging contribute to this increase. It is a great challenge for the neonatologist and for neuropaediatricians to prevent its occurrence and to minimise the effects of bilirrubin encephalopathy.

Molecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III - identification of eight novel mutations.

Mucolipidosis II (ML II) and mucolipidosis III (ML III) are diseases in which the activity of the uridine diphosphate (UDP)-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) is absent or reduced, respectively. In the absence of mannose phosphorylation, trafficking of lysosomal hydrolases to the lysosome is impaired. In these diseases, mistargeted lysosomal hydrolases are secreted into the blood, resulting in lysosomal deficiency of many hydrolases and a storage-disease phenotype. GlcNAc-phosphotransferase is a multimeric transmembrane enzyme composed of three subunits (alpha, beta and gamma) encoded by two genes -GNPTAB and GNPTG. Defects in GNPTAB result in ML II and III whereas mutations in GNPTG were only found in ML III patients. We have performed a molecular analysis of the GNPTAB and GNPTG genes in 13 mucolipidosis II and III patients (10 Portuguese, one Finnish, one Spanish of Arab origin and one Indian). Mutations were identified by the study of both cDNA and gDNA. The GNPTAB and GNPTG mRNA expressions were determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The study led to the identification of 11 different mutations. Eight of these mutations are novel, six in the GNPTAB gene [c.121delG (V41FfsX42), c.440delC (A147AfsX5), c.2249_50insA (N750KfsX8), c.242G>T (W81L), c.1208T>C (I403T) and c.1999G>T (p.E667X)] and two in the GNPTG gene [c.610-1G>T and c.639delT (F213LfsX7)]. With regard to the mRNA expression studies, the values obtained by qRT-PCR indicate the possible existence of feedback regulation mechanisms between alpha/beta and the gamma subunits.

[Postoperative hyperuricemia of cyanotic and acyanotic congenital cardiopathies]. / Hiperuricemia en el post-quirúrgico de cardiopatías congénitas cianóticas y acianóticas.

In a prospective study, 10 children with congenital heart disease were studied before and after surgery (24-48 h). Mean age and weight, type of disease and surgery performed are described in Table 1. Six patients had acyanotic disease and 4 were cyanotic. Before surgery, the acyanotic group (AG) showed hyperuricemia compared to normal children of the same chronological age (mean +/- SE: 5.53 +/- 0.42 vs 4.27 +/- 0.22, p less than 0.02). Initial seric creatinine (sCr), increased in 3 patients of the AC and in the 4 patients of the cyanotic group (CG) compared to normal values of sCr for height (AG: 0.47 +/- 0.05 vs 0.34 +/- 0.03, p less than 0.05; CG: 0.63 +/- 0.05 vs 0.38 +/- 0.05, p less than 0.01). Post-surgery, sCr and serum uric acid (sUA) increased significantly at 24 and 48 h in both groups (Fig 1); at 24 h the increment in sUA in the AG was higher than that in the CG (p less than 0.05). There was a direct and significant correlation between the increment in sUA and sCr in the AG (Fig. 2). The urine excretion of uric acid paralleled the increment of sUA in the CG (Table 2). Fractional excretion of, sodium (FENa) was less than 1% and greater than 1% in the AG and the CG, respectively, being the basal FENa of the AG significantly lower (Table 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory blood pressure monitoring after recovery from hemolytic uremic syndrome.

The outcome of acute renal failure due to diarrhea-associated hemolytic uremic syndrome (D+ HUS) is generally predicted to be good. However, there are only a few long-term observations with detailed reports on long-term sequelae. Specifically, adequate long-term blood pressure (BP) evaluations are scarce. The present study evaluated BP in pediatric patients after childhood D+ HUS. The study group comprised 28 patients (20 males) aged 6-23.5 years (median 10.1 years). All patients had a history of D+ HUS at a median age of 1.1 years (range 0.5-6 years). Based on the duration of oliguria and/or anuria, the primary disease was classified as mild (n=6), moderate (n=6), or severe (n=16). The BP in these patients was studied at a median time of 8.4 years (range 2.3-22.9 years) after manifestation of D+ HUS by means of office BP measurements and 24-h ambulatory BP monitoring (ABPM) using a Spacelabs 90207 oscillometric monitor. Measurements were compared with normal values of published standards for healthy children and adolescents. Conventional office BP measurements were above the 95th percentile in 1 patient. By ABPM, 2 patients were diagnosed to have mean systolic daytime and nighttime values in the hypertensive range, and systolic and diastolic hypertension was confirmed in the first patient. All these patients had a severe form of D+ HUS in the past. By applying ABPM, BP anomalies were detected in 5 additional patients. Elevated systolic BP loads were found in 4 patients, and daytime systolic and diastolic hypertension in the other 1. At the time of the study, 2 of them were classified as "recovered." The late outcome of D+ HUS may be worse than anticipated. BP anomalies as long-term sequelae of D+ HUS could be identified by ABPM but not by office BP measurements. These findings may represent an isolated sign of residual renal disturbance.

An intraspecific linkage map of the chickpea ( Cicer arietinum L.) genome based on sequence tagged microsatellite site and resistance gene analog markers.

An intraspecific linkage map of the chickpea genome based on STMS as anchor markers, was established using an F(2) population of chickpea cultivars with contrasting disease reactions to Ascochyta rabiei (Pass.) Lab. At a LOD-score of 2.0 and a maximum recombination distance of 20 cM, 51 out of 54 chickpea-STMS markers (94.4%), three ISSR markers (100%) and 12 RGA markers (57.1%) were mapped into eight linkage groups. The chickpea-derived STMS markers were distributed throughout the genome, while the RGA markers clustered with the ISSR markers on linkage groups LG I, II and III. The intraspecific linkage map spanned 534.5 cM with an average interval of 8.1 cM between markers. Sixteen markers (19.5%) were unlinked, while l1 chickpea-STMS markers (20.4%) deviated significantly ( P < 0.05) from the expected Mendelian segregation ratio and segregated in favor of the maternal alleles. However, ten of the distorted chickpea-STMS markers were mapped and clustered mostly on LG VII, suggesting the association of these loci in the preferential transmission of the maternal germ line. Preliminary comparative mapping revealed that chickpea may have evolved from Cicer reticulatum, possibly via inversion of DNA sequences and minor chromosomal translocation. At least three linkage groups that spanned a total of approximately 79.2 cM were conserved in the speciation process.

QTL analysis for ascochyta blight resistance in an intraspecific population of chickpea (Cicer arietinum L.).

In both controlled environment and the field, six QTLs for ascochyta blight resistance were identified in three regions of the genome of an intraspecific population of chickpea using the IDS and AUDPC disease scoring systems. One QTL-region was detected from both environments, whereas the other two regions were detected from each environment. All the QTL-regions were significantly associated with ascochyta blight resistance using either of the disease scoring systems. The QTLs were verified by multiple interval mapping, and a two-QTL genetic model with considerable epistasis was established for both environments. The major QTLs generally showed additive gene action, as well as dominance inter-locus interaction in the multiple genetic model. All the QTLs were mapped near a RGA marker. The major QTLs were located on LG III, which was mapped with five different types of RGA markers. A CLRR-RGA marker and a STMS marker flanked QTL 6 for controlled environment resistance at 0.06 and 0.04 cM, respectively. Other STMS markers flanked QTL 1 for field resistance at a 5.6 cM interval. After validation, these flanking markers may be used in marker-assisted selection to breed for elite chickpea cultivars with durable resistance to ascochyta blight. The tight linkage of RGA markers to the major QTL on LG III will allow map-based cloning of the underlying resistance genes.

Neumonía por neumocystis carinii en pacientes con S.I.D.A: diagnóstico y manejo Hospital tipo 2 / Pneumonia by pneumocystis carinii in AIDS patient: diagnosis and manegement

La infección por Neumocystis Carinii es una de las manifestaciones clínicas más frecuentes y precoces en pacientes con SIDA. Se describe caso clínico de paciente VIH (+), ingresada por Neumonitis inespecífica a Hospital tipo 2, logrando diagnosticarse Neumonitis por Neumocystis Carinii, por visualización directa de quistes con tinción de PAP y PAS en expectoración bronquial, obtenida con nebulizaciones con suero hipertónico, mucolíticos y apoyo kinésico. Se trató con trimetropin-sulfametoxazol ev. (100 mg/kp y 20 mg/kp, respectivamente) durante 15 días y profilaxis posterior, asociando céfalosporina de tercera generación por infección pulmonar oportunista (I.I.H.), evolucionando satisfactoriamente y con regresión completa de compromiso respiratorio, tanto clínico, gasométrico, como radiológico. Por estudio inmunológico y clínico se clasificó a dicha paciente como WRG (Walter Reed Army Medical Center, USA. 1986). Se concluye la factibilidad de efectuar diagnóstico y tratamiento, así como manejo de pacientes con SIDA e infección por Neumocystis Carinii, en un Hospital tipo 2, con apoyo de laboratorio de Centro de mayor complejidad

Hiperuricemia en el post-quirurgico de cardiopatias congenitas cianoticas y acianoticas / Postoperative hyperuricemia of cyanotic and acyanotic congenital cardiopathies

En forma prospectiva, se estudiaron 10 niños con cardiopatías congénitas antes de la cirugía y en el post-operatorio inmediato(24-48 h). La edad promedio de los pacientes fue de 2,81 años (0,5-8,75). Seis de los 10 niños eran portadores de una cardiopatía acianótica (CA) y 4 de cardiopatías cianóticas (CC). Antes de la cirugía, el grupo acianótico (GA) presentaba hiperuricemia significativa con respecto a niños sanos de igual edad cronológica. En el mismo perído de estudio 3 de los 6 pacientes del GA y los 4 pacientes de GC, mostraban caída de la filtración glomerular expresada por un aumento de la creatinina suérica (Crs) en relación al valor normal de Crs por talla. En el post-operatorio inmediato, la Crs aumentó en forma significativa con respecto a los valores basales (pre-quirúrgicos), tanto en el GA como en el GC. El ácido úrico suérico (AUs), mostró en los dos grupos de pacientes el mismo comportamiento que la Crs, siendo el aumento del SAUs sa las 24 h significativamente mayor en el GA. Este aumento del AUs en el GA, se correlacionó en forma directa y significativa con el aumento de la Crs. En el GC, el aumento del AUs se acompañó de un aumento tanto en la excreción fraccional de ácido úrico como en la excreción de ácido úrico ajustada a la filtración glomerular; esta respuesta no fue observada en el GA, a pesar de una hiperuricemia significativamente mayor. En el GA, la excreción fraccional de sodio tanto antes de la cirugía como en el post-operatorio fue < de 1% y en el período basal, esta fue significativamente menor que la del GC. A las 24 h de la cirugía, el aumento significativo del U/P de úrea en el GA con respecto al basal y al del GC, se acompaño de un aumento también significativo del U/P de potasio y de la actividad de la aldosterona. Nuestros datos indicarían que la hiperuricemia en el post-quirúrgico de las cardiopatías congénitas no está limitada a las CC y puede estar presente antes de la cirugía. En las CA, además de una disminución de la excreción por caída de la filtración glomerular, existiría una alteración en el transporte tubular bidireccional del ácido úrico. En las CC, los datos sugerirían que la hiperuricemia obedecería a una disminucuón de la excreción como consecuencia de una disminución de la masa funcionante renal. La sobreproducción de ácido úrico, no puede ser descartada en los dos grupos