Hipoglicemia infantil / Hypoglycemia of infancy

Hypoglycemia of infancy is a common metabolic disorder that can have serious neurological consequences. Therefore, its early diagnosis and treatment are crucial prognostic factors. Hypoglycemia has a variety of causes and a good clinical history, physical examination and laboratory determination will orient the correct diagnosis. Occasionally a molecular study will be required.

Síndrome metabólico en niñas púberes con hiperplasia suprarrenal congénita clásica / Metabolic syndrome among puberal girls with classic congenital adrenal hyperplasia

Background: Adult women with adrenal congenital hyperplasia (AH) have a higher risk for insulin resistance, dyslipidemia, hypertension, high body mass index (BMI) and increased body fat. All these factors are associated with cardiovascular risk and metabolic syndrome (MS). Aim: To evaluate the presence of MS in pubertal classic AH girls (CAH) and a control group (C). Material and Methods: We studied 15 pubertal AH patients (12.0 +/- 1.9 years) and 26 controls (11.7+/- 0.3 years) matched by age and tanner stage. Weight, height, BMI, waist/hip ratio, blood pressure and serum lipids were measured. An oral glucose tolerance test (OGTT) and insulin curve was performed in CAH girls whereas in controls basal insulin and glucose were determined. The homeostasis model assessment for insulin resistance (HOMAIR) was calculated. Cook, Ferranti and international diabetes federation (IDF) criteria were used to determine the presence of MS. Results: CAH and C girls had similar BMI (22.0 +/- 5.1 and 20.1 +/- 3.6 kg/m2 respectively; p = 0,11). CAH girls had higher basal blood glucose (80.8 +/- 7.7 and 60.6 +/- 10.6 mg/dl respectively, p < 0.01) and controls had higher triglyceride levels (147.0 +/- 69.3 and 79.7 +/-16.3 mg/dl respectively, p < 0.01) and lower HDL cholesterol levels (45.8 +/- 12.8 and 56.9 +/- 17.5 mg/dl respectively, p = 0.02). According to cook criteria 4 percent of CAH girls and 23 percent of controls has MS. These figures were 14 and 32 percent respectively according to Ferranti criteria and 0 and 5 percent respectively according to IDF criteria. Conclusions: CAH puberal patients do not have a higher prevalence of metabolic syndrome, compared with controls with similar Tanner stage and BMI.

Síndrome hemolítico urémico en Chile: presentación clínica, evolución y factores pronósticos / Hemolytic-uremic syndrome in Chile: clinical features, evolution and prognostic factors

Background: Hemolytic-uremic syndrome (HUS) is characterized by acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. Aim: To describe the characteñstics ofpatients with the diagnosis ofHUS in Chile, and to identify the most reliable early predictors oímorbidity and moñality. Material and methods: The clinical records ofpatients with HUS aged less than 15 years, attended between January 1990 and December 2003 in 15 hospitals, were reviewed. Demographic, clinical, biochemical, hematological parameters, morbidity and mortality were analyzed. Results: A cohort of 587 patients aged 2 to 8 years, 48 percent males, was analyzed. Ninety two percent had diarrhea. At the moment of diagnosis, anuria was observed in 39 percent of the patients, hypertension in 45 percent and seizures in 17 percent. Forty two percent required renal replacement therapy (RRT) and perítoneal dialysis was used in the majoríty of cases (78 percent). The most frequently isolated etiological agentwas Escherichia coli. Mortality rate was 2.9 percent in the acute phase of the disease and there was a positive correlation between mortality and anuria, seizures, white blood cell count (WCC) >20.000/mm³ and requirements of renal replacement therapy (p <0.05). Twelve percent of patients evolved to chronic renal failure and the risk factors during the acute phase were the need for renal replacement therapy, anuria, WCC >20.000/mm³, seizures and hypertension. Conclusions: The present study emphasizes important clinical and epidemiological aspeets ofHUSin a Chilean pediatricpopulation.

[Hemolytic-uremic syndrome in Chile: clinical features, evolution and prognostic factors]. / Síndrome hemolítico urémico en Chile: presentación clínica, evolución y factores pronósticos.

BACKGROUND: Hemolytic-uremic syndrome (HUS) is characterized by acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. AIM: To describe the characteristics of patients with the diagnosis of HUS in Chile, and to identify the most reliable early predictors of morbidity and mortality. MATERIAL AND METHODS: The clinical records of patients with HUS aged less than 15 years, attended between January 1990 and December 2003 in 15 hospitals, were reviewed. Demographic, clinical, biochemical, hematological parameters, morbidity and mortality were analyzed. RESULTS: A cohort of 587 patients aged 2 to 8 years, 48% males, was analyzed. Ninety two percent had diarrhea. At the moment of diagnosis, anuria was observed in 39% of the patients, hypertension in 45% and seizures in 17%. Forty two percent required renal replacement therapy (RRT) and peritoneal dialysis was used in the majority of cases (78%). The most frequently isolated etiological agent was Escherichia coli. Mortality rate was 2.9% in the acute phase of the disease and there was a positive correlation between mortality and anuria, seizures, white blood cell count (WCC)>20.000/mm3 and requirements of renal replacement therapy (p<0.05). Twelve percent of patients evolved to chronic renal failure and the risk factors during the acute phase were the need for renal replacement therapy, anuria, WCC>20.000/mm3, seizures and hypertension. CONCLUSIONS: The present study emphasizes important clinical and epidemiological aspects of HUS in a Chilean pediatric population.

Pesquisa precoz de nefropatía diabética en niños y adolescentes portadores de diabetes mellitus tipo 1 / Early detection of diabetic nephropathy in children and adolescents with type 1 diabetes mellitus

La nefropatía diabética es la principal causa de insuficiencia renal crónica terminal (IRCT) en adultos a nivel mundial, a la vez que la IRCT es la principal causa de mortalidad de los pacientes con diabetes mellitus (DM) tanto tipo 1 como tipo 2.

[Fasting glucose versus oral glucose tolerance test for detection of glucose intolerance in obese children]. / Glicemia de ayuno versus prueba de tolerancia oral a la glucosa en la detección de intolerancia a la glucosa en niños y adolescentes obesos.

BACKGROUND: Recently, the cut-off point for normal fasting glucose (FG) level, was decreased to 100 mg/dl. AIM: To determine the frequency of abnormal carbohydrate abnormalities in children with obesity and evaluate if the fasting glucose level is a useful tool for the screening of glucose intolerance (GI). PATIENTS AND METHODS: Children and adolescents, referred for evaluation of obesity were evaluated with an oral glucose tolerance test (OGTT) and FG. The sensitivity of FG for detection of GI, using the 100 and 110 mg/dl cut-off point, was evaluated. RESULTS: We studied 186 patients (125 females) aged 12.1 (range: 5.4-19.3) years with a body mass index (BMI) of 29.9 (18.3-44.6) kg/mt2 and a BMI Z score of 2.1 (1.7-3.2). Seven patients (3.8%) had abnormalities in the carbohydrate metabolism. The sensitivity of FG for the detection of GI using the 100 and 110 mg/dl cut-off values was 42.9 and 14.3%, respectively. Receiver operating characteristic (ROC) curves showed that the optimal diagnostic level for FG corresponds to 80 mg/dl (sensitivity: 85.7% and specificity of 74.9%). CONCLUSIONS: An abnormal carbohydrate metabolism was detected in 3.8% of the obese children and adolescents in this sample. FG of 100 mg/dl does not detect 57.1% of the patients with glucose intolerance. These data suggest that FG is not a useful screening tool for glucose intolerance in young patients.

Glicemia de ayuno versus prueba de tolerancia oral a la glucosa en la detección de intolerancia a la glucosa en niños y adolescentes obesos / Fasting glucose versus oral glucose tolerance test for detection of glucose intolerance in obese children

Background: Recently, the cut-off point for normal fasting glucose (FG) level, was decreased to 100 mg/dl. Aim: To determine the frequency of abnormal carbohydrate abnormalities in children with obesity and evaluate if the fasting glucose level is a useful tool for the screening of glucose intolerance (GI). Patients and methods: Children and adolescents, referred for evaluation of obesity were evaluated with an oral glucose tolerance test (OGTT) and FG. The sensitivity of FG for detection of GI, using the 100 and 110 mg/dl cut-off point, was evaluated. Results: We studied 186 patients (125 females) aged 12.1 (range: 5.4-19.3) years with a body mass index (BMI) of 29.9 (18.3-44.6) kg/mt² and a BMI Z score of 2.1 (1.7-3.2). Seven patients (3.8 percent) had abnormalities in the carbohydrate metabolism. The sensitivity of FG for the detection of GI using the 100 and 110 mg/dl cut-off values was 42.9 and 14.3 percent, respectively. Receiver operating characteristic (ROC) curves showed that the optimal diagnostic level for FG corresponds to 80 mg/dl (sensitivity: 85.7 percent and specificity of 74.9 percent). Conclusions: An abnormal carbohydrate metabolism was detected in 3.8 percent of the obese children and adolescents in this sample. FG of 100 mg/dl does not detect 57.1 percent of the patients with glucose intolerance. These data suggest that FG is not a useful screening tool for glucose intolerance in young patients.

Pesquiza precoz de nefropatía diabética en niños y adolescentes portadores de diabetes mellitus tipo 1 / Early detection of diabetic nephropathy in children and adolescents with type 1 diabetes mellitus

Introducción: La nefropatía diabética se iniciaría precozmente, luego del debut de DM-1 y se han descrito factores de riesgo asociados a su progresión como años de evolución, mal control metabólico, pubertad e hipertensión arterial. Objetivo: Evaluar parámetros de compromiso renal precoz en pacientes con DM-1 y asociarlos con los factores de riesgo mencionados. Método: Se estudiaron prospectivamente pacientes con DM-1, con microalbuminura y creatininuria aislada matinal (índice microalbuminuria/creatininuria ACR), creatinina plasmática, clearance de creatinina, ecografía renal, hemoglobina glicosilada A1c (HbA1c) actual y promedio de años anteriores, microalbuminurias previas, edad al debut, años de evolución, estadío puberal y presión arterial. Resultados: Se evaluaron 44 DM-1 20 varones, edad promedio 11,68 ± 3,01 años, y 3,8 ± 2,84 años de evolución. Al analizar el control metabólico mediante HbA1c, el promedio fue de 9,1 ± 1,9 por ciento. La hiperfiltración se observó en 7 pacientes (15,9 por ciento) y nefromegalia en 25 por ciento de los pacientes que se les realizó ecografía renal. Ocho pacientes (18,2 por ciento) tuvieron ACR elevado y los prepúberes que presentan ACR elevado (25 por ciento) tienen su debut a menor edad. No existió correlación entre las variables control metabólico, hiperfiltración y nefromegalia con las demás variables estudiadas. Conclusiones: La microalbuminuria determinada por ACR está presente en el 18,2 por ciento de los pacientes, siendo más frecuente en los prepúberes y la menor edad al debut sería un factor de riesgo para desarrollarla.

Síndrome hemolítico urémico en Santiago de Chile: evolución de la función renal y factores pronósticos / Hemolytic uremic syndrome (HUS), prognostic factors and follow up of renal function, in Santiago, Chile

Introducción: El Síndrome Hemolítico Urémico (SHU) se caracteriza por falla renal aguda, anemia hemolítica microangiopática y trombocitopenia; es la causa más frecuente de insuficiencia renal aguda en la infancia. Objetivo: a) Describir las características actuales del cuadro inicial de SHU en nuestro medio y comparar con lo descrito anteriormente; b) Describir la evolución a 1 año plazo y evaluar posibles factores pronósticos de función renal. Sujetos y Métodos: Se estudiaron variables demográficas, presentación clínica, exámenes bioquímicos y hematológicos, en 374 pacientes con SHU diagnosticados entre Enero 1990 a Diciempe 2002 en 9 hospitales de la Región Metropolitana; se evaluó además función renal al año de seguimiento en una muestra de 213 pacientes y se identificaron factores pronósticos de insuficiencia renal crónica y mortalidad utilizando el análisis de regresión logística. Resultados: Se analizaron 374 pacientes, 50,5 por ciento mujeres, 65,5 por ciento de la Región Metropolitana, edad promedio 1,5 ± 1,4 años (0,2 a 8); 91 por ciento presentó diarrea, 31 por ciento ocurrió en verano, al ingreso 57 por ciento presentó anuria, 43,3 por ciento hipertensión arterial y convulsiones 23 por ciento. Al alta 28 por ciento persistía hipertenso. Las terapias de sustitución renal utilizadas fueron: diálisis peritoneal (50 por ciento), hemodiafiltración (6 por ciento) y hemodiálisis (3 por ciento); recibió plasmaféresis 1 por ciento. Se aisló agente etiológico en 17 por ciento, siendo en 69 por ciento E. coli enterohemorrágica. La mortalidad fue de 2,7 por ciento, siendo la causa principal la falla orgánica múltiple. En el seguimiento al año: 80 por ciento mantuvo función renal normal, 14 por ciento presento deterioro de la función renal, 6 por ciento proteinuria y 4 por ciento hipertensión. Se encontró significativo como factor pronóstico de daño renal: hipertensión arterial (p < 0,0001), necesidad de peritoneodiálisis y hemodiálisis (p: 0,001, p: 0,0015 respectivamente), anuria (p: 0,005) y convulsiones (p: 0,01). Se correlacionó con mortalidad en la etapa aguda: convulsiones, requerimiento de hemodiafiltración y plasmaféresis, (p < 0,0001, p: 0,0001 y p < 0,0001 respectivamente).

MarC-V: a spreadsheet-based tool for analysis, normalization, and visualization of single cDNA microarray experiments.

The comprehensive analysis and visualization of data extracted from cDNA microarrays can be a time-consuming and error-prone process that becomes increasingly tedious with increased number of gene elements on a particular microarray. With the increasingly large number of gene elements on today's microarrays, analysis tools must be developed to meet this challenge. Here, we present MarC-V, a Microsoft Excel spreadsheet tool with Visual Basic macros to automate much of the visualization and calculation involved in the analysis process while providing the familiarity and flexibility of Excel. Automated features of this tool include (i) lower-bound thresholding, (ii) data normalization, (iii) generation of ratio frequency distribution plots, (iv) generation of scatter plots color-coded by expression level, (v) ratio scoring based on intensity measurements, (vi) filtering of data based on expression level or specific gene interests, and (vii) exporting data for subsequent multi-array analysis. MarC-V also has an importing function included for GenePix results (GPR) raw data files.

Indoor respirable particulate matter concentrations from an open fire, improved cookstove, and LPG/open fire combination in a rural Guatemalan community.

Improved biomass cookstoves have the potential to reduce pollutant emissions and thereby reduce pollution exposure among populations in developing countries who cook daily with biomass fuels. However, evaluation of such interventions has been very limited. This article presents results from a study carried out in 30 households in rural Guatemala. Twenty-four hour PM3.5 concentrations were compared over 8 months for three fuel/cookstove conditions (n = 10 households for each condition): a traditional open fire cookstove, an improved cookstove called the plancha mejorada, and a liquefied petroleum gas (LPG) stove/open fire combination. Twenty-four hour geometric mean PM3.5 concentrations were 1560 micrograms/m3 (n = 58; 95% C.I. 1310, 1850), 280 micrograms/m3 (n = 59; 95% C.I. 240-320), and 850 micrograms/m3 (n = 60; 95% C.I. 680-1050) for the open fire, plancha, and LPG/open fire combination, respectively. A generalized estimating equation model showed a 45% reduction in PM3.5 concentrations for the LPG/open fire combination as compared to the open fire alone. The difference approached significance (p < 0.0737). The plancha showed an 85% reduction in PM3.5 concentrations as compared to the open fire (p < 0.0001). An analysis of the interaction of time with stove type showed that the temporal trend in pollution did not significantly differ among the three stove types. The reduced PM3.5 concentrations were maintained over time. Season did not affect pollutant concentrations. Of the two interventions, the plancha appears to offer the best prospects for achieving substantial reductions in indoor air pollution levels, although issues of cost and stove maintenance remain to be addressed.

Gamma-lactone-Functionalized antitumoral acetogenins are the most potent inhibitors of mitochondrial complex I.

To study the relevance of the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety of the antitumoral acetogenins of Annonaceae for potent mitochondrial complex I inhibition, we have prepared a series of semisynthetic acetogenins with modifications only in this part of the molecule, from the natural rolliniastatin-1 (1) and cherimolin-1 (2). Some of the hydroxylated derivatives (1b, 1d and 1e) in addition to two infrequent natural beta-hydroxy gamma-methyl gamma-lactone acetogenins, laherradurin (3) and itrabin (4), are more potent complex I inhibitors than any other known compounds.

Semisynthesis of antitumoral acetogenins: SAR of functionalized alkyl-chain bis-tetrahydrofuranic acetogenins, specific inhibitors of mitochondrial complex I.

The acetogenins of Annonaceae are known by their potent cytotoxic activity. In fact, they are promising candidates as a new future generation of antitumoral drugs to fight against the current chemiotherapic resistant tumors. The main target enzyme of these compounds is complex I (NADH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain, a key enzymatic complex of energy metabolism. In an attempt to characterize the relevant structural factor of the acetogenins that determines the inhibitory potency against this enzyme, we have prepared a series of bis-tetrahydrofuranic acetogenins with different functional groups along the alkyl chain. They comprise several oxo, hydroxylimino, mesylated, triazido, and acetylated derivatives from the head series compounds rolliniastatin-1, guanacone, and squamocin. Our results suggest a double binding point of acetogenins to the enzyme involving the alpha,alpha'-dihydroxylated tetrahydrofuranic system as well as the alkyl chain that links the terminal alpha, beta-unsaturated-gamma-methyl-gamma-lactone. The former mimics and competes with the ubiquinone substrate. The latter modulates the inhibitory potency following a complex outline in which multiple structural factors probably contribute to an appropriate conformation of the compound to penetrate inside complex I.

Repeat polymorphisms within gene regions: phenotypic and evolutionary implications.

We have developed an algorithm that predicted 11,265 potentially polymorphic tandem repeats within transcribed sequences. We estimate that 22% (2,207/9,717) of the annotated clusters within UniGene contain at least one potentially polymorphic locus. Our predictions were tested by allelotyping a panel of approximately 30 individuals for 5% of these regions, confirming polymorphism for more than half the loci tested. Our study indicates that tandem-repeat polymorphisms in genes are more common than is generally believed. Approximately 8% of these loci are within coding sequences and, if polymorphic, would result in frameshifts. Our catalogue of putative polymorphic repeats within transcribed sequences comprises a large set of potentially phenotypic or disease-causing loci. In addition, from the anomalous character of the repetitive sequences within unannotated clusters, we also conclude that the UniGene cluster count substantially overestimates the number of genes in the human genome. We hypothesize that polymorphisms in repeated sequences occur with some baseline distribution, on the basis of repeat homogeneity, size, and sequence composition, and that deviations from that distribution are indicative of the nature of selection pressure at that locus. We find evidence of selective maintenance of the ability of some genes to respond very rapidly, perhaps even on intragenerational timescales, to fluctuating selective pressures.

[Calcified bladder squamous carcinoma: radiologic considerations]. / Carcinoma escamoso vesical calcificado: consideraciones radiológicas.

OBJECTIVE: To report a case of squamous cell carcinoma of the bladder, an uncommon tumor type, that presented with wide calcified areas. The literature on calcified bladder tumors is reviewed with special reference to the diagnostic aspects. METHODS/RESULTS: The plain film, US and CT findings are presented. All the diagnostic imaging techniques demonstrated calcifications on the tumor surface and the characteristic curvilinear shape of this lesion. CONCLUSIONS: Calcified bladder carcinoma is rare and occurs in only 0.5% of the cases evaluated by conventional radiology. All calcifications probably arising in the bladder detected on conventional radiological evaluation should be studied further with other imaging techniques. If its etiology is unclear, cystoscopy with biopsy and/or a microbiological study should be performed.

Physical map and characterization of transcripts in the candidate interval for familial chondrocalcinosis at chromosome 5p15.1.

The gene for familial chondrocalcinosis (MIM 118600; gene symbol CCAL2) has been localized to a 0.8-cM interval on the short arm of chromosome 5, between the polymorphic microsatellite markers D5S416 and D5S2114. We have undertaken the physical and transcript mapping of this interval, as well as regions telomeric to the interval, in an attempt to define ultimately the gene for this disorder. The physical map is composed of YAC, BAC, PAC, and cosmid resources and spans a physical distance of approximately 0.3 Mb. Using cDNA selection, we have identified eight novel transcripts in and around the interval; two of the selected transcripts reside in the candidate interval. We have also more precisely placed several expressed sequence tags (ESTs) that were previously mapped by radiation hybrid analysis and were reported to reside in or near the candidate interval. Two of the ESTs analyzed overlap with the selected cDNAs that reside in the candidate interval. All of the selected cDNAs are expressed partial transcripts, as determined by Northern blot analysis, and using RT-PCR analysis, we have determined that the cDNAs that reside in the candidate interval are expressed in cartilage and synovium, tissues that are presumably relevant to the chondrocalcinosis phenotype.

Specific interactions of monotetrahydrofuranic annonaceous acetogenins as inhibitors of mitochondrial complex I.

Annonaceous acetogenins (ACG) are a wide group of cytotoxic compounds isolated from plants of the Annonaceae family. Some of them are promising candidates to be a future new generation of antitumor drugs due to the ability to inhibit the NADH:ubiquinone oxidoreductase of the respiratory chain (mitochondrial complex I), main gate of the energy production in the cell. ACG are currently being tested on standard antitumor trials although little is known about the structure activity relationship at the molecular level. On recent studies, the relevance of several parts of the molecule for the inhibitory potency has been evaluated. Due to the great diversity of skeletons included in this family of natural products, previous studies on the presence and distribution of oxygenated groups along the alkyl chain only covered the compounds with different bis-tetrahydrofuranic (bis-THF) relative configurations. Therefore, we have investigated the inhibitory action of all the mono-tetrahydrofuranic (mono-THF) acetogenins available, which differ in the oxygenated arrangements along the molecule. Our results show that the hydroxyl and carbonyl groups, placed in the aliphatic chain that links the initial gamma-lactone moiety with the dihydroxylated tetrahydrofuranic ring system, significantly contribute for modulating the inhibitory potency of the ACG through specific effects.

10-Oximeguanacone, the first nitrogenated acetogenin derivative found to be a potent inhibitor of mitochondrial complex I.

A new 10-keto bis-tetrahydrofuran acetogenin, guanacone (1), has been isolated from a cytotoxic extract of Annona aff. spraguei seeds. The 10-oximeguanacone derivative 1f is the first bioactive nitrogenated acetogenin found to be a very potent inhibitor of complex I. In addition, a SAR study of guanacone analogues is reported based on the titration of the NADH oxidase and NADH:ubiquinone oxidoreductase activities.

Cosmid contig and transcriptional map of three regions of human chromosome 21q22: identification of 37 novel transcripts by direct selection.

Human chromosome 21 is associated with many disorders, including Down syndrome (DS). In an effort to identify genes involved in brain development or function and therefore implicated in the mental retardation associated with DS, we chose YACs from three regions of chromosome 21: a region within the so-called "Down syndrome critical region," a region proximal to it, and one distal to it. We made cosmid libraries from these YACs and generated high-resolution physical maps by constructing cosmid contigs. These are the first cosmid contigs on chromosome 21 outside the critical region. The cosmids were used for direct selection of cDNAs to isolate chromosome 21 expressed sequences. We have isolated 45 nonredundant partial cDNAs and mapped these back to the cosmid contigs. We isolated 3 nonoverlapping portions of DSCR1 and a part of GIRK2 and identified 3 nonoverlapping partial cDNAs with similarity to the rat Dyrk gene, which turned out to be the human homologue (MNB) of the Drosophila minibrain gene. Twelve sequences had matches with either STS or EST entries in the databases, including a chromosome 21 EST, a chromosome 21 STS, and 6 unmapped expressed sequence entries. Only 1 sequence resulted in a match with a protein entry. The remaining 25 sequences revealed no similarity to any database entry. All of these partial cDNAs are expressed as determined by Northern blotting or by RT-PCR.