[Neurologic presentation in haemolytic-uraemic syndrome]. / Manifestaciones neurológicas en el síndrome hemolítico urémico.

INTRODUCTION: Haemolytic-uraemic syndrome (HUS) is characterized by microangiopathic hemolytic anaemia, thrombopenia and multiorganic aggression, specially renal, gastrointestinal and central nervous system disturbances. Sporadic in Spain (2/1,500,000 inhabitants), its clinical onset includes acute renal failure, hypertension and central nervous system symptoms (irritability, drowsiness, convulsions, cortical blindness, hemiparesia or coma), due to metabolic distress, hypertension or central nervous system microangiopathy. Few long-term outcome studies have been published. PATIENTS AND METHODS: A retrospective analysis of a series of 58 patients with HUS between 1981 and 2006, is reported. Clinical onset, laboratory, electrophysiology, neuroimaging tests, and prognosis factors are reviewed, together with long-term clinical outcome. RESULTS: 22 children presented neurologic symptoms, seven had some neurological test; one patient died; in five some neurological sequelae persisted (hemiparesia, cognitive deficit, visual-perception deficit), the other 16 remaining asymptomatic. CONCLUSIONS: Neurological morbility is high in HUS (27% of the children with neurological symptoms), with a 1.7% mortality. Seizure at onset was not a poor prognosis factor in our group. No positive correlation can be established between neuroimaging and long-term outcome.

Manifestaciones neurológicas en el síndrome hemolítico urémico / Neurologic presentation in haemolytic uraemic syndrome

Introducción. El síndrome hemolítico urémico (SHU) se define como anemia hemolítica microangiopática, trombopenia y daño multiparenquimatoso fundamentalmente renal, con frecuente afectación digestiva y del sistema nervioso central. En España es esporádico (incidencia 2/1.500.000 habitantes). Las manifestaciones iniciales incluyen insuficiencia renal aguda, hipertensión arterial y sintomatología neurológica (irritabilidad, somnolencia, convulsiones, ceguera cortical, hemiparesiao coma), que puede deberse a una alteración metabólica, hipertensión arterial o microangiopatía del sistema nervioso central. Además del tratamiento específico del SHU, es fundamental la valoración y seguimiento del estado neurológico para prevenir secuelas. Existen pocas referencias bibliográficas acerca de la evolución neurológica a largo plazo. Pacientes y métodos. Estudio retrospectivo de algunos factores relacionados con el pronóstico y análisis de la evolución neurológica a largo plazo de pacientes con SHU mediante una revisión de los pacientes con SHU con manifestaciones neurológicas en fase aguda tratados en nuestro centro entre 1981 y 2006. Se analizan la clínica, analítica, estudios electrofi-siológicos y neuroimagen, y su correlación con la evolución a medio y largo plazo. Resultados. De los 58 niños con SHU, 22 presentaron síntomas neurológicos en fase aguda: en siete se realizó alguna exploración complementaria neurológica; un paciente falleció, en cinco persistió algún déficit neurológico (hemiparesia, déficit cognitivo o déficit visuoperceptivo) y 16 permanecieron asintomáticos.Conclusiones. El SHU con clínica neurológica inicial asocia una alta morbilidad (un 27% de los niños con clínica neurológica), con mortalidad del 1,7%. Las convulsiones en la fase aguda no supusieron un factor de mal pronóstico en nuestro grupo. No se puede establecer una correlación entre los hallazgos de neuroimagen y la evolución a largo plazo

Introduction. Haemolytic-uraemic syndrome (HUS) is characterized by microangiopathic hemolytic anaemia,thrombopenia and multiorganic aggression, specially renal, gastrointestinal and central nervous system disturbances. Sporadic in Spain (2/1,500,000 inhabitants), its clinical onset includes acute renal failure, hypertension and central nervous systemsymptoms (irritability, drowsiness, convulsions, cortical blindness, hemiparesia or coma), due to metabolic distress, hypertension or central nervous system microangiopathy. Few long-term outcome studies have been published. Patients and methods. A retrospective analysis of a series of 58 patients with HUS between 1981 and 2006, is reported. Clinical onset, laboratory, electrophysiology, neuroimaging tests, and prognosis factors are reviewed, together with long-term clinical outcome. Results. 22 children presented neurologic symptoms, seven had some neurological test; one patient died; in five some neurological sequelae persisted (hemiparesia, cognitive deficit, visual-perception deficit), the other 16 remaining asymptomatic.Conclusions. Neurological morbility is high in HUS (27% of the children with neurological symptoms), with a 1.7% mortality. Seizure at onset was not a poor prognosis factor in our group. No positive correlation can be established between neuroimaging and long-term outcome

Ictus y trombolisis en un hospital básico. Un deber posible / Stroke and thrombolysis in a basic hospital. A possible duty

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New approach to osteopenia in phenylketonuric patients.

AIM: To study bone mineralization in a group of phenylketonuric patients and to search for a possible relationship between bone mineral density, dietary control, serum minerals and nutrition intake. The response to treatment with low-dose 1.25-(OH)2 vitamin D in patients with osteopenia was evaluated. METHODS: Twenty-eight phenylketonuric patients (age range: 10-33 y) on dietary treatment were investigated. Bone density at the lumbar spine (Dual Energy X-ray Absorptiometry), bone formation markers (osteocalcin and bone alkaline phosphatase), serum minerals, index of dietary control and protein, vitamin D and mineral intakes were determined. RESULTS: Of the patients studied, 78.6% had good dietary compliance (462 +/- 89 micromol/L). Mean protein, vitamin D and mineral intakes met the recommended dietary allowances (RDAs). Nevertheless, 8 patients had calcium intakes lower than 1000 g/d, and a positive correlation between Z-score and calcium (r = 0.585; p = 0.002) or phosphorus intake (r = 0.546; p = 0.005) was observed. Osteopenia was detected in 14 patients (50%). Moreover, bone alkaline phosphatase in phenylketonuric patients older than 18 y of age was significantly lower than that in controls (p < 0.0001). No correlation was found between bone mineral density, age, serum minerals, bone formation markers or index of dietary control. Treatment with 0.25 microg/d calcitriol significantly increased bone density in 6 patients. CONCLUSION: A defect in bone mineralization was detected in 50% of patients in our series. The correct amount of formula intake seems to be necessary for bone mineralization in phenylketonuric patients. Calcitriol can be a useful treatment for these patients, although more studies are needed to confirm these results. Hypercalcaemia and hypercalciuria need to be carefully monitored.

Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter.

Neurospora crassa ARG13 and Saccharomyces cerevisiae ARG11 encode mitochondrial carrier family (MCF) proteins that transport ornithine across the mitochondrial inner membrane. We used their sequences to identify EST candidates that partially encode orthologous mammalian transporters. We thereby identified such a gene (ORNT1) that maps to 13q14 and whose expression, similar to that of other urea cycle (UC) components, was high in liver and varied with changes in dietary protein. ORNT1 expression restores ornithine metabolism in fibroblasts from patients with hyperammonaemia-hyperornithinaemia-homocitrullinuria (HHH) syndrome. In a survey of 11 HHH probands, we identified 3 ORNT1 mutant alleles that account for 21 of 22 possible mutant ORNT1 genes in our patients: F188delta, which is common in French-Canadian HHH patients and encodes an unstable protein; E180K, which encodes a stable, properly targeted protein that is inactive; and a 13q14 microdeletion. Our results show that ORNT1 encodes the mitochondrial ornithine transporter involved in UC function and is defective in HHH syndrome.

Facilitated diagnosis of the contiguous gene syndrome: tuberous sclerosis and polycystic kidneys by means of haplotype studies.

Tuberous sclerosis (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are genetically heterogeneous diseases. The major gene for ADPKD (PKD1) lies adjacent to the TSC2 gene on chromosome 16p13. Some reports in the literature referred to an unusual presentation of TSC with enlarged cystic kidneys at birth, but it was not until the localization of the TSC2 and PKD1 genes that it was possible to analyze the interaction between both genes. We describe a case of a child with TSC and enlarged cystic kidneys. The study of genetic marker segregation in the family pointed to the presence of a deletion involving the 3' region of PKD1. A further study of the region showed a deletion of 40 kb involving both PKD1 and TSC2. We suggest that an additive or synergistic effect between PKD1 and TSC2 may cause this renal phenotype. A contiguous gene syndrome involving PKD1 and TSC2 should be suspected in children with TSC and enlarged polycystic kidneys at birth. The first approach to identify a deletion of both genes could be the analysis of the segregation of PKD1 and TSC2 markers in the family.

[Severe-grade tetanus in a multipurpose ICU: review of 13 cases]. / Tétanos de grado grave en una UCI polivalente: revisión de 13 casos.

BACKGROUND: The mortality of severe tetanus (grades II-III) remains high today, being greater than 20% with a large number of complications, due to the lengthy stay of these patients in the ICU. METHODS: A review of 13 cases of severe tetanus over the last 5 years was performed analyzing age, entrance, previous immunization, ICU stay, grade of severity, complications and mortality. RESULTS: The ages ranged between 35 to 79 years (mean 54 years). No patient had been previously immunized. Entrance was determined in 11 patients (84.6%). The mean ICU stay was 27.3 days. Complications were presented in 76.8% of the patients, with the most frequent being vegetative alterations (38%). The global mortality was 30.7% (4 patient), 3 secondary to sepsis of pulmonary origin and one from a cardiac arrest of vegetative etiology. CONCLUSIONS: The authors believe that prophylaxis is fundamental in prevention of the disease but an important sector of the population remains unvaccinated. On appearance of severe tetanus, admission to the ICU is essential since many complications may appear requiring specialized techniques and personnel.

[Restrictive myocardiopathy in children. A study of 4 patients]. / Miocardiopatía restrictiva en el niño. Estudio de cuatro pacientes.

Restrictive cardiomyopathy is an unusual form of cardiomyopathy during childhood. Only occasional cases or reduced populations have been reported in international journals. The purpose of this report is to document the clinical, echocardiographic and hemodynamic profile and outcome of restrictive cardiomyopathy in a group of four children (two boys and two girls). The mean age at admission was 3.5 +/- 2.7 years (range 1(3/12) to 7(10/12) years). The diagnosis was made by clinical, echocardiographic and hemodynamic criteria. The main symptoms were bronchial disease (two patients), hepatomegaly and a cardiac murmur. All of the patients had impaired growth and physical development, normal or near-normal Rx cardiothoracic ratio, evidence of congestive heart failure and only one of them showed a cardiac murmur. The most common ECG finding was biatrial enlargement and incomplete right-bundle branch block. The echocardiographic feature was severe biatrial dilatation in the presence of normal ventricular cavity size. Left ventricular shortening was normal and there was diastolic dysfunction. Doppler mitral flow was restrictive, with an E/A ration > 1.5. Marked elevation of left ventricular end-diastolic pressure was noted in cardiac catheterization (x = 32 +/- 7 mmHg). Right ventricular end-diastolic pressure was elevated, but less than the left side (x = 19 +/- 12 mmHg). The outcome was very poor. Two patients died, one remains with heart failure NYHA II and the other with heart failure NYHA IV. We conclude that restrictive cardiomyopathy during childhood may simulate a bronchial or liver disease, so we must bear this in mind in order to make the differential diagnosis. Because of the poor prognosis and lack of specific treatment, the best therapeutic option may be heart transplantation.

Characterization of the alpha-1 adrenoceptor subtype mediating [3H]-arachidonic acid release and calcium mobilization in Madin-Darby canine kidney cells.

The authors characterized the alpha-1 adrenoceptor subtype located on Madin-Darby canine kidney (MDCK) cells by measuring norepinephrine-mediated [3H]-arachidonic acid release and Ca++ mobilization in fura 2-loaded cells. In both assays, prazosin and chloroethylclonidine acted as unsurmountable antagonists, whereas 5-methyl-urapidil acted as a competitive antagonist with pA2 estimates of 7.3 (arachidonic acid assay) and 7.7 (Ca++ assay). Competitive antagonism toward arachidonic acid release was also obtained with the following alpha-1 adrenoceptor antagonists (pA2): (+)-niguldipine (7.6), 2-(2,6-dimethoxy-phenoxy-yethyl)aminomethyl-1,4-benzodioxane hydrochloride (WB 4101; 8.3), phentolamine (7.6) and oxymetazoline (6.4). Arachidonic acid release by norepinephrine was abolished in the absence of extracellular Ca++ and was antagonized by 1-[beta-[3-(4-methoxy-phenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride (SK&F 96365) but was insensitive to antagonism by L-type Ca++ channel antagonists and La . Norepinephrine-mediated increases in intracellular Ca++ consisted of two distinct phases: a transient phase followed by a sustained plateau. The transient phase was resistant to EGTA, whereas the plateau phase was abolished by EGTA. Potassium chloride did not evoke a response in either assay. Northern blot analysis demonstrated that MDCK cells express alpha-1B adrenoceptor messenger RNA. It was concluded that typical alpha-1B adrenoceptors mediate responses to norepinephrine in MDCK cells and that these receptors couple to both intracellular Ca++ release and Ca++ influx by a voltage-independent mechanism. This influx pathway is insensitive to L-type Ca++ channel antagonists but is antagonized by the receptor-operated Ca++ channel antagonist SK&F 96365.

Opposing influences of dexamethasone and retinoic acid on adenylate cyclase activity in ROS 17/2.8 cells.

Exposure of ROS 17/2.8 cells to dexamethasone (DEX) or retinoic acid (RA) increases and decreases, respectively, adenylate cyclase activity (ACA) in response to isoproterenol, forskolin, guanylylimidodiphosphate, or NaFl. Despite dramatic changes in ACA, there were no significant changes in levels of cholera toxin- or pertussis toxin (PT)-dependent ADP-ribosylation of membranes prepared from cells after DEX or RA exposure as compared to controls. Similarly, immunochemical detection of alpha S, alpha i1-3, and alpha O, as well as Northern blot analysis of messenger RNA for each of the respective GTP binding proteins, also failed to demonstrate an influence of DEX or RA when contrasted with controls. In a novel use of the cyc- reconstitution assay, wherein the influence of inhibitory guanine nucleotide binding proteins in the extracts of control, DEX-, and RA-treated membranes is removed by a previous 24-h incubation with PT in the intact cell, we demonstrate that this PT treatment markedly enhances ACA in the cyc- reconstitution assay for all three preparations, but that the fold-increase due to PT-treatment is greatest in RA-treated cells. The greater magnitude of the effect of PT on RA-treated ROS 17/2.8 cells, in the absence of any obvious quantitative changes in the levels of the PT substrates, suggests that the effect of RA on ROS 17/2.8 cells appears to be an augmentation of the influence of inhibitory guanine nucleotide binding proteins, ultimately leading to reduced ACA.

Accelerated ribosome formation and growth in neonatal pig hearts.

Rapid growth (5 mg dry heart/h) of the left ventricular free wall (LVFW) in the newborn pig heart accompanied by lack of growth of the right ventricular free wall (RVFW) represents a unique natural model of cardiac enlargement that is free of pathophysiological influences. By 3 days of life, LVFW was 71% larger than at 4 h of age. Rates of protein synthesis were measured during perfusion of isolated pig hearts with bicarbonate buffer containing glucose, lactate, insulin, and plasma concentrations of amino acids of an aortic pressure of 60 mmHg. In hearts from pigs that were 18 h of age, rates of protein synthesis were the same in RVFW and LVFW, but in 2-day-old pigs the rate was 52% greater in LVFW than RVFW. During the first 3 days of life, RNA content (mg/g) increased 3.4-fold faster in LVFW than RVFW. When RNA content was expressed per total heart portion, the increase was 7.9-fold greater. Because approximately 85% of total RNA is rRNA, these values indicated much more rapid formation of ribosomes in the LVFW than RVFW. When ribosome formation was measured in vitro in hearts from 48-h-old pigs, rates of formation were 39% greater in LVFW than RVFW, and at 18 h of age, ribosome formation was 40% faster in LVFW than RVFW. These findings indicated that formation of new ribosome preceded accelerated synthesis of total heart proteins. These findings indicated that rapid growth of LVFW compared with no growth of RVFW was associated with a 67% faster rate of ribosome formation and a 32% greater rate of protein synthesis.

[Severe aortic stenosis in the neonate and infant under 6 months old]. / Estenosis aórtica severa en el recién nacido y lactante menor de seis meses.

24 patients with diagnosed aortic stenosis are reported. Clinical symptoms started before 6 months of age (between 24 hours and 6 months, average 87 days). In all cases aortic stenosis was the only existing malformation, except in one patient who had a small muscular ventricular septal defect and in another case who had a patent ductus arteriosus. Clinical symptoms were early and notable. In nineteen there was congestive heart failure whose appearance in the first week of like was a bad prognosis. Relationship between severity of aortic stenosis and electrocardiographic findings was closer than in older patients. Death rate was very high in children who had not been operated (5 out of 12). Of children who received surgery only one died out of 12. Treatment, therefore, in this pathology must be aggressive.

[Aortic coarctation in children. Analysis of 100 cases]. / Coartación de aorta en el niño. Análisis de 100 casos.

One hundred clinical records of coarctation of aorta are presented with 78% catheterization and 31% postmortem examination. Surgical treatment was performed in 46%, 8, in the first month of life, 13 from 1 to 6 month, 5, from 6 to 12 month, 9 from 12 to 24 month and 11 older than 2 years. The surgical mortality was 13%. There was recoarctation in 7.5%. The mortality in the patients not operated on was 31%. This mortality was influenced by the severity of associated malformations. The most frequent associated cardiac malformations were left to right shunts followed by left heart pathology. The association with complex cardiopathies was frequent.

Growth of the pulmonary arteries following Blalock-Taussig shunt.

The Blalock-Taussig (BT) shunt remains the standard systemic-to-pulmonary artery shunt. We reviewed our experience with the classic BT shunt in terms of mortality, patency, duration of palliation, and growth of the pulmonary artery. Records were reviewed in 49 consecutive patients, 25 of whom were less than one month old at the time of operation. They underwent a total of 53 BT shunts. Also, the pulmonary artery index (PAI), or the sum of the cross-sectional areas of the right and left pulmonary arteries standardized by the body surface area (BSA), was calculated. There were 4 operative deaths (7.5%) and 1 late death (2.0%). Early shunt thrombosis (within 72 hours postoperatively) occurred in 3 patients. Four patients required a second BT shunt, 5 underwent a palliative outflow tract reconstruction, and 5 required a polytetrafluoroethylene graft. Twenty-one patients underwent a corrective procedure, and 26 underwent a second cardiac catheterization. Of these 26 patients, 24 represent the subgroup used to assess the growth of the pulmonary arteries. The mean duration of palliation was 25.15 months. Mean PAI increased significantly from 127 +/- 40 mm2/BSA pre-shunt to 286.1 +/- 144 mm2/BSA post-shunt (p less than .004). This series demonstrates that the pulmonary arteries do grow after BT shunt. Pulmonary artery growth in patients with tetralogy of Fallot was greater than that in patients with single ventricle, and the duration of palliation was acceptable in most patients. Calculation of PAI may aid in the decision whether to perform a corrective surgical procedure or a second palliative shunt procedure.