RESUMEN
BACKGROUND: Ring chromosome 20 (R20) syndrome is a chromosomal disorder characterized mainly by drug-resistant frontal lobe seizures, recurrent nonconvulsive status epilepticus (NCSE), and typical EEG features. The aim of this study was to investigate if this triad is common and specific to all patients with R20. METHODS: In this cross-sectional study (from 2000 to 2011), we selected patients who fulfilled at least two out of three criteria: drug-resistant frontal lobe seizures, recurrent NCSE, and characteristic electroencephalography (EEG) features. In all patients, diagnosis was based on karyotype analysis of at least 100 metaphases. RESULTS: We identified 36 patients who met at least two of the selected criteria: six patients (16.7%) with R20 and 30 (83.3%) without R20 (non-R20). All patients with R20 met all three criteria. Eleven (36.7%) patients without R20, however, also displayed the full triad. In 19 patients without R20 (63.3%), one of the three clinical features was missing: frontal lobe seizures were not resistant to antiepileptic drugs (AED) in four (13.3%), recurrent NCSE was missing in six (20%), and nine (30%) patients did not have typical EEG features. Based on this data, specificity was 63.3%, positive predictive value was 35.3%, and sensitivity and negative predictive values were 100%. Additionally, a review of all publications describing the R20 phenotype revealed that 81.98% of patients with R20 display the full electroclinical triad. CONCLUSIONS: In our study, all patients with R20 displayed the three electroclinical characteristics. This is in line with previous reports (presenting high sensitivity and negative predictive value). However, these features can also be observed in other epilepsies and are not specific to R20. Our findings suggest that in the presence of the full triad of symptoms, karyotype analysis focused on chromosome 20 should be conducted.
Asunto(s)
Trastornos de los Cromosomas/genética , Cromosomas Humanos Par 20/genética , Electroencefalografía , Cromosomas en Anillo , Convulsiones/diagnóstico , Estado Epiléptico/diagnóstico , Adolescente , Adulto , Niño , Trastornos de los Cromosomas/fisiopatología , Estudios Transversales , Citogenética , Epilepsia/diagnóstico , Epilepsia/genética , Femenino , Lóbulo Frontal , Humanos , Cariotipificación , Masculino , Valor Predictivo de las Pruebas , Convulsiones/genética , Sensibilidad y Especificidad , Estado Epiléptico/genéticaRESUMEN
PURPOSE: Obesity is a risk factor for developing abdominal wall hernias and is associated with major postoperative complications, such as surgical site infection, delayed wound healing and recurrent hernia. Therefore, treating incisional hernia in this patient subgroup is a challenge. METHODS: We conducted a comparative, prospective study on patients who underwent primary ventral hernia surgery or incisional hernia surgery through the extended totally extraperitoneal pathway, with body mass indices (BMIs) ≤ 30 (no obesity) and BMI > 30 (with obesity). We collected demographic data, preoperative and intraoperative variables, complication and recurrence rate, hospital stay and follow-up as postoperative data. RESULTS: From May 2018 to December 2020, 74 patients underwent this surgery, 38 patients without obesity and 36 with obesity. The median area of the hernia defect measured by CT was 57 cm2 and 93 cm2 in patients without and with obesity, respectively (p = 0.012). The median follow-up was 16 months. One patient without obesity experienced some postoperative complication compared with four patients with obesity (p > 0.05). No patient without obesity had recurrent hernia compared with two patients with obesity (p > 0.05). CONCLUSIONS: There were statistically significant differences between patients with and without obesity in the size of the hernia defect. However, there were no significant differences in terms of complications, hospital stay, postoperative pain or relapses. Therefore, the minimally invasive completely extraperitoneal approach for patients with obesity appears to be a safe procedure despite our study limitations. Studies with longer follow-ups and a greater number of patients are needed.
Asunto(s)
Hernia Ventral , Hernia Incisional , Laparoscopía , Humanos , Herniorrafia/efectos adversos , Herniorrafia/métodos , Hernia Incisional/cirugía , Hernia Incisional/etiología , Índice de Masa Corporal , Estudios Prospectivos , Mallas Quirúrgicas , Hernia Ventral/complicaciones , Hernia Ventral/cirugía , Recurrencia , Obesidad/complicaciones , Laparoscopía/métodos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugíaRESUMEN
Plasma and urine free and acyl carnitine were measured in 19 children with nephropathic cystinosis and renal Fanconi syndrome. Each patient exhibited a deficiency of plasma free carnitine (mean 11.7 +/- 4.0 [SD] nmol/ml) compared with normal control values (42.0 +/- 9.0 nmol/ml) (P less than 0.001). Mean plasma acyl carnitine in the cystinotic subjects was normal. Four subjects with Fanconi syndrome but not cystinosis displayed the same abnormal pattern of plasma carnitine levels; controls with acidosis or a lysosomal storage disorder (Fabry disease), but not Fanconi syndrome, had entirely normal plasma carnitine levels. Two postrenal transplant subjects with cystinosis but without Fanconi syndrome also had normal plasma carnitine levels. Absolute amounts of urinary free carnitine were elevated in cystinotic individuals with Fanconi syndrome. In all 21 subjects with several different etiologies for the Fanconi syndrome, the mean fractional excretion of free carnitine (33%) as well as acyl carnitine (26%) greatly exceeded normal values (3 and 5%, respectively). Total free carnitine excretion in Fanconi syndrome patients correlated with total amino acid excretion (r = 0.76). Two cystinotic patients fasted for 24 h and one idiopathic Fanconi syndrome patient fasted for 5 h showed normal increases in plasma beta-hydroxybutyrate and acetoacetate, which suggested that hepatic fatty acid oxidation was intact despite very low plasma free carnitine levels. Muscle biopsies from two cystinotic subjects with Fanconi syndrome and plasma carnitine deficiency had 8.5 and 13.1 nmol free carnitine per milligram of noncollagen protein, respectively (normal controls, 22.3 and 17.1); total carnitines were 11.8 and 13.3 nmol/mg noncollagen protein (controls 33.5, 20.0). One biopsy revealed a mild increase in lipid droplets. The other showed mild myopathic features with variation in muscle fiber size, small vacuoles, and an increase in lipid droplets. In renal Fanconi syndrome, failure to reabsorb free and acyl carnitine results in a secondary plasma and muscle free carnitine deficiency.
Asunto(s)
Carnitina/deficiencia , Síndrome de Fanconi/metabolismo , Músculos/análisis , Carnitina/sangre , Carnitina/metabolismo , Niño , Preescolar , Cistinosis/metabolismo , Humanos , Lactante , Riñón/metabolismoRESUMEN
11 children with either cystinosis or Lowe's syndrome had a reduced content of plasma and muscle carnitine due to renal Fanconi syndrome. After treatment with oral L-carnitine, 100 mg/kg per d divided every 6 h, plasma carnitine concentrations became normal in all subjects within 2 d. Initial plasma free fatty acid concentrations, inversely related to free carnitine concentrations, were reduced after 7-20 mo of carnitine therapy. Muscle lipid accumulation, which varied directly with duration of carnitine deficiency (r = 0.73), improved significantly in three of seven rebiopsied patients after carnitine therapy. One Lowe's syndrome patient achieved a normal muscle carnitine level after therapy. Muscle carnitine levels remained low in all cystinosis patients, even though cystinotic muscle cells in culture took up L-[3H]carnitine normally. The half-life of plasma carnitine for cystinotic children given a single oral dose approximated 6.3 h; 14% of ingested L-carnitine was excreted within 24 h. Studies in a uremic patient with cystinosis showed that her plasma carnitine was in equilibrium with some larger compartment and may have been maintained by release of carnitine from the muscle during dialysis. Because oral L-carnitine corrects plasma carnitine deficiency, lowers plasma free fatty acid concentrations, and reverses muscle lipid accumulation in some patients, its use as therapy in renal Fanconi syndrome should be considered. However, its efficacy in restoring muscle carnitine to normal, and the optimal dosage regimen, have yet to be determined.
Asunto(s)
Carnitina/administración & dosificación , Cistinosis/tratamiento farmacológico , Síndrome de Fanconi/tratamiento farmacológico , Síndrome Oculocerebrorrenal/tratamiento farmacológico , Defectos Congénitos del Transporte Tubular Renal/tratamiento farmacológico , Administración Oral , Transporte Biológico , Carnitina/deficiencia , Carnitina/farmacocinética , Células Cultivadas , Niño , Preescolar , Colesterol/sangre , Cisteamina/farmacología , Ácidos Grasos no Esterificados/sangre , Humanos , Lactante , Trasplante de Riñón , Metabolismo de los Lípidos , Tasa de Depuración Metabólica , Músculos/metabolismo , Triglicéridos/sangreRESUMEN
A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI <0, 20.6; 83 deaths) and ill-defined and secondary cancers (ERR/Sv 1.96, 90% CI -0.26, 5.90; 328 deaths). Stratification on duration of employment had a large effect on the ERR/Sv, reflecting a strong healthy worker survivor effect in these cohorts. This is the largest analytical epidemiological study of the effects of low-dose protracted exposures to ionizing radiation to date. Further studies will be important to better assess the role of tobacco and other occupational exposures in our risk estimates.
Asunto(s)
Industrias/estadística & datos numéricos , Neoplasias Inducidas por Radiación/mortalidad , Reactores Nucleares/estadística & datos numéricos , Enfermedades Profesionales/mortalidad , Exposición Profesional/estadística & datos numéricos , Medición de Riesgo/métodos , Recuento Corporal Total/estadística & datos numéricos , Adulto , Estudios de Cohortes , Empleo/estadística & datos numéricos , Femenino , Humanos , Cooperación Internacional , Masculino , Dosis de Radiación , Factores de Riesgo , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
Interstitial deletions of the long arm of chromosome 2, involving band 2q24, have been described on three occasions. We report our findings in a further case, in which we mapped the deletion to band 2q24.3.
Asunto(s)
Cromosomas Humanos 1-3 , Bandeo Cromosómico , Deleción Cromosómica , Humanos , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Masculino , Trastornos Psicomotores/genéticaRESUMEN
Tyrosine countertransport was used to demonstrate the hormonal stimulation of neutral amino acid transport across the lysosomal membrane of FRTL-5 cells. Cells grown with thyrotropin (1 X 10(-10) M) had 7-fold (+/- S.E.) higher tyrosine countertransport activity in their lysosomes than cells grown without thyrotropin. Thyrotropin also stimulated the uptake into tyrosine-loaded lysosomes of other neutral amino acids recognized by the tyrosine carrier, namely, phenylalanine (3-fold) and leucine (6-fold). In contrast lysosomal cystine countertransport was not affected by thyrotropin. Addition of thyrotropin to cells grown without thyrotropin showed that the stimulation of tyrosine counter-transport (a) required at least 48 h to reach the level of the thyrotropin-supplemented cells, (b) depended upon protein synthesis, since cycloheximide (20 microM) was inhibitory, and (c) depended upon RNA synthesis, since actinomycin D (1 nM) was inhibitory. Cells grown without thyrotropin but with dibutyryl cyclic AMP (1 mM) or cholera toxin (1 nM) exhibited enhanced lysosomal countertransport of tyrosine, suggesting that cyclic AMP may act as a messenger. This represents the first demonstration of hormonal responsiveness in a lysosomal transport system and may reflect the importance of salvage and reutilization of lysosomal degradation products for the thyroid epithelial cell.
Asunto(s)
Lisosomas/metabolismo , Tirotropina/farmacología , Tirosina/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Bucladesina/farmacología , Línea Celular , Toxina del Cólera/farmacología , AMP Cíclico/metabolismo , Cicloheximida/farmacología , Cistina/metabolismo , Dactinomicina/farmacología , Cinética , Leucina/metabolismo , Lisosomas/efectos de los fármacos , Fenilalanina/metabolismo , Ratas , Glándula TiroidesRESUMEN
Two persons within the same family were discovered to be trisomic for the segment 7qter. However, several features differed from those described in other patients with this syndrome, for example, normal birth weight and neck size, cleft palate, and beaked nose. In addition to the phenotypic variation, there were three independently segregating autosomal translocations in the pedigree: t(1;7)(q43;q32), t(1;6) (p22.3;q14.1), and t(3;10)(q26.1;p11.21). This is a finding that, to our knowledge, has not been previously reported.
Asunto(s)
Cromosomas Humanos 1-3 , Cromosomas Humanos 6-12 y X , Fisura del Paladar/genética , Nariz/anomalías , Translocación Genética , Trisomía , Adulto , Peso al Nacer , Bandeo Cromosómico , Femenino , Humanos , Recién Nacido , Discapacidad Intelectual/genética , Cariotipificación , Masculino , Linaje , Fenotipo , SíndromeRESUMEN
Congenital heart disease occurred in 62% of the reported cases of supernumerary der(22) syndrome. These were most commonly acyanotic lesions such as atrial septal defect, ventricular septal defect or patent ductus arteriosus. Heart disease did not, however, appear to be a major determinant of survival.
Asunto(s)
Cromosomas Humanos 21-22 e Y , Cromosomas Humanos 6-12 y X , Cardiopatías Congénitas/genética , Translocación Genética , Trisomía , Niño , Preescolar , Conducto Arterioso Permeable/genética , Femenino , Defectos del Tabique Interatrial/genética , Defectos del Tabique Interventricular/genética , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
Tyrosine countertransport was used to demonstrate the existence of a carrier system for neutral amino acids in the lysosomal membrane of FRTL-5 thyroid cells. In addition to tyrosine, the carrier system recognized the neutral amino acids leucine, histidine, phenylalanine, and tryptophan. Cystine and lysine, amino acids for which a lysosomal carrier system has been demonstrated, showed no competition with tyrosine for countertransport. The tyrosine system showed stereospecificity and cation independence. It did not require an acidic lysosome or the availability of free thiols. The apparent Km for tyrosine was approximately 100 microM; the energy of activation of the system was approximately 9.7 kcal/mol. This new lysosomal membrane carrier system for neutral amino acids resembles the plasma membrane L system in 3T3 Chinese hamster ovary cells and melanoma B-16 cells.
Asunto(s)
Aminoácidos/metabolismo , Proteínas Portadoras/metabolismo , Membranas Intracelulares/metabolismo , Lisosomas/metabolismo , Glándula Tiroides/metabolismo , Tirosina/metabolismo , Animales , Transporte Biológico Activo , Línea Celular , Cinética , Lisosomas/ultraestructura , Microscopía Electrónica , Ratas , TermodinámicaRESUMEN
Neurologic features of oculocerebrorenal (Lowe) syndrome include mental retardation, hypotonia, and areflexia. We performed a sural nerve biopsy, computerized tomography (CT) scan, and magnetic resonance imaging (MRI) scan on a 14-year-old boy with oculocerebrorenal syndrome with very mild renal disease. The nerve biopsy exhibited decreased number of myelinated fibers, normal myelination on remaining axons without redundant basal lamina, and no evidence of active degeneration or regeneration. MRI scan revealed diffuse and irregular foci of increased T2 signal with sparing of commissural fibers, pyramidal tracts, and cerebellar white matter. We conclude that both a peripheral axonopathy and a central demyelinating or gliotic process occurs in oculocerebrorenal syndrome in the absence of the severe renal disease that often complicates this disorder.
Asunto(s)
Imagen por Resonancia Magnética , Síndrome Oculocerebrorrenal/diagnóstico , Enfermedades del Sistema Nervioso Periférico/complicaciones , Defectos Congénitos del Transporte Tubular Renal/diagnóstico , Adolescente , Humanos , Masculino , Síndrome Oculocerebrorrenal/complicaciones , Síndrome Oculocerebrorrenal/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Adenylosuccinate lyase deficiency is an autosomal recessive defect of purine metabolism. Succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide riboside (SAICAr) are the disease marker metabolites in physiological fluids. The Bratton-Marshall test for detection of SAICAr in urine has been added to the selective screening for inborn errors of metabolism that is carried out in our lab. During the last three years, around 2,000 patients have been screened by this method, resulting in the detection of four new cases with this disease. They all presented with severe psychomotor delay, hypotonia and refractory epilepsy since the neonatal period. The S-Ado/SAICAr ratio in cerebrospinal fluid was below 2, indicating that they correspond to the most severe form of the disease. New missense mutations were found in a heterozygous fashion in three patients. The study of purines in all patients with neurological disease of unknown etiology is highly recommended.