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INTRODUCTION: Central venous access devices facilitate home treatment in boys with haemophilia. These are usually fully implanted lines, referred to as ports. Caregivers are taught to manage the port using sterile techniques and maintaining patency by flushing with saline or heparin solution. National and international guidelines for the home care of ports are lacking. AIM: To evaluate if infection or occlusion rates differ between home care regimens used for ports in children with haemophilia. METHODS: Children with ports were identified from the PedNet registry. Data on the homecare policy were acquired from each centre. To ensure a complete data set for each port, only ports that had been removed were included in the study. Three care groups were defined: 'aseptic non touch technique', 'sterile technique' and 'fully sterile technique'. Outcomes within and between the groups were analysed. RESULTS: A total of 240 children with 352 ports were studied. Insertion occurred at a median age of 1.32 years. The median port duration was 2.94 years with a total of 215 688 port days in children without and 183 852 in children with inhibitors. Infection was the most common cause of port removal (34%); there was no significant difference with infection as reason for removal between the different care groups. Occlusion was not more frequent in centres that did not use heparin. CONCLUSION: Use of sterile gloves and gowns did not reduce the risk of port infection. Using less stringent sterile techniques for accessing ports is easier for caregivers and in addition may have health economic benefits.
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Cateterismo Venoso Central/instrumentación , Hemofilia A/terapia , Hemofilia B/terapia , Infecciones Relacionadas con Catéteres/etiología , Cateterismo Venoso Central/efectos adversos , Niño , Estudios de Cohortes , Femenino , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
Adults with haemophilia have a higher incidence of chronic kidney disease than general male population. We recently showed that children with haemophilia have higher urinary calcium excretion and lower whole body bone mineral density than controls in spite of prophylaxis with the deficient coagulation factor concentrate, serum vitamin D concentrations comparable to those of healthy children and physically active lifestyle. Persistent hypercalciuria may result in nephrocalcinosis and impact renal function. This study sought to assess persistence of urinary calcium excretion and kidney function in children with haemophilia. We investigated retrospectively urinary calcium excretion in 30 children with haemophilia (mean age 12.5 years) from consecutive urine samples over a 2-year period. Renal evaluation included blood and urine specimen, blood pressure, and renal ultrasound. High number of children with haemophilia had intermittent hypercalciuria. Hypercalciuria was not associated with age, severity of haemophilia or previous hypercalciuria. Kidney function and renal ultrasound were normal with the exception of suspected kidney stone in one patient with haemophilia and transient hypercalciuria. Vitamin D concentrations improved after the families had received information and recommendations concerning vitamin D substitution. Our findings indicate that haemophilia per se predisposes to hypercalciuria which may in turn affect bone mineral content and kidney function. Whether childhood-onset intermittent hypercalciuria contributes to hypertension and renal complications in adulthood remains to be elucidated in future studies.
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Hemofilia A/complicaciones , Hemofilia B/complicaciones , Hipercalciuria/etiología , Adolescente , Presión Sanguínea/fisiología , Calcio/orina , Niño , Femenino , Finlandia , Hemofilia A/fisiopatología , Hemofilia B/fisiopatología , Humanos , Riñón/diagnóstico por imagen , Estudios Longitudinales , Masculino , Estudios Retrospectivos , Factores de Riesgo , UltrasonografíaRESUMEN
Cohen syndrome is an autosomal recessive disorder characterized by mental and motor retardation, short stature, microcephaly, several dysmorphic features, major ocular symptoms and granulocytopenia. Major research challenges are the confusing nosology and the pleiotropy of the gene. We report the mapping of a locus (CHS1) by linkage analysis in as few as four two-generation pedigrees with uniform clinical features. CHS1 was assigned to an interval of approximately 10 cM between D8S270 and D8S521. Our results provide a tool to a more accurate definition of Cohen syndrome(s) and a starting point for the positional cloning of CHS1.
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Anomalías Múltiples/genética , Cromosomas Humanos Par 8 , Discapacidad Intelectual/genética , Mapeo Cromosómico , Femenino , Genes Recesivos , Ligamiento Genético , Marcadores Genéticos , Haplotipos , Humanos , Escala de Lod , Masculino , Linaje , SíndromeRESUMEN
The neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of progressive neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in various tissues. Progressive epilepsy with mental retardation (EPMR, MIM 600143) was recently recognized as a new NCL subtype (CLN8). It is an autosomal recessive disorder characterized by onset of generalized seizures between 5 and 10 years, and subsequent progressive mental retardation. Here we report the positional cloning of a novel gene, CLN8, which is mutated in EPMR. It encodes a putative transmembrane protein. EPMR patients were homozygous for a missense mutation (70C-->G, R24G) that was not found in homozygosity in 433 controls. We also cloned the mouse Cln8 sequence. It displays 82% nucleotide identity with CLN8, conservation of the codon harbouring the human mutation and is localized to the same region as the motor neuron degeneration mouse, mnd, a naturally occurring mouse NCL (ref. 4). In mnd/mnd mice, we identified a homozygous 1-bp insertion (267-268insC, codon 90) predicting a frameshift and a truncated protein. Our data demonstrate that mutations in these orthologous genes underlie NCL phenotypes in human and mouse, and represent the first description of the molecular basis of a naturally occurring animal model for NCL.
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Epilepsia/genética , Discapacidad Intelectual/genética , Proteínas de la Membrana/genética , Lipofuscinosis Ceroideas Neuronales/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Mapeo Cromosómico , Análisis Mutacional de ADN , Epilepsia/complicaciones , Exones , Salud de la Familia , Femenino , Genes/genética , Humanos , Discapacidad Intelectual/complicaciones , Intrones , Ratones , Ratones Mutantes , Datos de Secuencia Molecular , Mutagénesis Insercional , Mutación , Lipofuscinosis Ceroideas Neuronales/complicaciones , Linaje , Mutación Puntual , ARN Mensajero/genética , ARN Mensajero/metabolismo , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Distribución TisularRESUMEN
We report on a 2085 nm holmium-doped silica fiber laser passively mode-locked by semiconductor saturable absorber mirror and carbon nanotube absorber. The laser, pumped by a 1.16 µm semiconductor disk laser, produces 890 femtosecond pulses with the average power of 46 mW and the repetition rate of 15.7 MHz.
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Children with haemophilia are at risk of suboptimal bone mass accrual and low bone mineral density (BMD). We recently demonstrated that although BMD in Finnish children with haemophilia was within the normal range, their whole body BMD was significantly lower and hypercalciuria more prevalent than in controls. This study sought to determine the bone structure and strength in physically active children with haemophilia. To investigate the underlying mechanisms in this group, we conducted a case-control study to assess bone structure and strength by peripheral quantitative computed tomography (pQCT) at the radius. The study group comprised 29 patients (mean age 12.2 years) and 46 age-matched controls. Children with haemophilia had decreased total BMD Z-score at the distal radius (P ≤ 0.001), but increased cortical bone density at the proximal radius (P ≤ 0.001). Total bone area at the proximal radius was significantly lower in children with haemophilia (P = 0.002), whereas there were no differences in cortical bone area or in polar Strength-Strain Index, a parameter of bone strength, between the patients and controls. Patients with mild to moderate haemophilia and on-demand treatment had inferior bone strength compared to those with moderate to severe haemophilia and prophylaxis. Our findings suggest altered skeletal development in patients with haemophilia in the radius, resulting in smaller bone size and higher cortical bone density. Importantly, bone strength at the radius appears equal to healthy children. Prophylactic treatment seems to have a beneficial effect on bone health.
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Huesos/fisiología , Hemofilia A/diagnóstico por imagen , Hemofilia B/diagnóstico por imagen , Adolescente , Factores de Coagulación Sanguínea/uso terapéutico , Densidad Ósea/fisiología , Huesos/anatomía & histología , Estudios de Casos y Controles , Niño , Femenino , Hemofilia A/tratamiento farmacológico , Hemofilia B/tratamiento farmacológico , Humanos , Masculino , Radio (Anatomía)/fisiología , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Central venous access devices (CVADs) are often required in children with haemophilia to secure venous access for prophylactic treatment or immune tolerance therapy. Complications of CVADs include infections, thrombosis and mechanical problems. This study sought to determine the outcome of the vessels by magnetic resonance imaging (MRI) in children with haemophilia and to assess risk factors for development of catheter-related deep venous thrombosis (DVT). After the removal of CVAD an MRI of the chest and neck was performed to 20 boys with haemophilia who each had 1-3 (total number 27) CVADs placed. MRI revealed DVT in five children (25%). As their CVADs were functional at the time of the removal, the DVTs were clinically silent. However, there had been suspicion of DVT leading to replacement of the CVAD in one case. All the children with DVT had their CVADs inserted initially below the age of 1 year. The clinical signs of mild post-thrombotic syndrome (PTS) were common: dilated chest wall veins were observed in 11 (55%) children and were associated with DVT in three cases. Arm circumference discrepancy was observed in one child with DVT. No correlation between the duration or number of CVADs and DVT was detected. None of the patients had subjective symptoms of PTS. Silent DVT is a common complication of CVAD. Catheter insertion at a young age seems to predispose to thrombosis. The long-term consequences of the DVTs remain unknown.
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Cateterismo Venoso Central/efectos adversos , Hemofilia A/terapia , Hemofilia B/terapia , Trombosis de la Vena/diagnóstico , Adolescente , Adulto , Cateterismo Venoso Central/instrumentación , Niño , Coagulantes/administración & dosificación , Remoción de Dispositivos , Femenino , Hemofilia A/complicaciones , Hemofilia B/complicaciones , Humanos , Imagen por Resonancia Magnética , Masculino , Estudios Retrospectivos , Trombosis de la Vena/etiología , Adulto JovenRESUMEN
A 1.6µm mode-locked Raman fiber laser pumped by a 1480nm semiconductor disk laser is demonstrated. Watt-level core pumping of the single-mode fiber Raman lasers with low-noise disk lasers together with semiconductor saturable absorber mirror mode locking represents a highly practical solution for short-pulse operation.
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Today, monitoring of patient complaints in healthcare services is being used as a tool for quality assurance systems and in the future development of services. This nationwide register study describes the number of all complaints processed, number of complaints between different state provinces, healthcare services and healthcare professionals, and outcomes of complaints in Finland during the period 2000-2004. All complaints processed at the State Provincial Offices and the National Authority for Medicolegal Affairs were analysed by statistical methods. Complaints about mental healthcare were explored in greater detail. The analysis showed that the number of patient complaints increased considerably during the study period. There were changes in the number of complaints between study years in different provinces. Out of different healthcare services, an especially marked increase was seen in private healthcare. Nearly all complaints were lodged against physicians, and over half of the complaints were made because of medical error. In mental health care, patients more often complained about unsatisfactory certificates and statements and the use of compulsory hospital care. An analysis of the outcomes revealed that in mental health care complaints more seldom led to consequences. The results need to be utilised when planning interventions for advanced supervision, prevention of adverse events and patient safety in healthcare, and especially in mental health care. From the patients' perspective, it is important to create a culture where most problem situations are handled where the treatment was provided, thus avoiding a complex complaints process.
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Atención a la Salud/normas , Disentimientos y Disputas , Servicios de Salud Mental/normas , Sector Privado/normas , Sector Público/normas , Finlandia , Humanos , Garantía de la Calidad de Atención de Salud , Estudios RetrospectivosAsunto(s)
Inhibidores de Factor de Coagulación Sanguínea/inmunología , Enfermedades en Gemelos/inmunología , Hemofilia B/inmunología , Tolerancia Inmunológica , Coagulantes/uso terapéutico , Enfermedades en Gemelos/tratamiento farmacológico , Factor IX/uso terapéutico , Hemofilia B/tratamiento farmacológico , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Factores Inmunológicos/uso terapéutico , Recién Nacido , Masculino , Gemelos MonocigóticosRESUMEN
INTRODUCTION: Pediatric patients with Hodgkin lymphoma (HL) have several risk factors for venous thromboembolism (VTE). Although these patients are occasionally treated with thromboprophylaxis, no guidelines are implemented in Sweden. Scarce data from adult patients indicate an increased risk of VTE, but pediatric data is largely missing. Given the favorable overall survival of HL, there should reasonably be more focus on preventing complications. MATERIALS AND METHODS: We conducted a retrospective cohort study, including all patients registered in the Childhood Cancer Registry under the age of 18years diagnosed with HL between January 2005 and December 2015 in Sweden. RESULTS: Data was retrieved from the medical records of all 163 patients (100%) at six Swedish pediatric cancer centers. The incidence of VTE was 7.7% (symptomatic VTE 3.9%). The median follow-up was 3.4years (range 0.3-10.5). Only five patients (3.1%) were treated with thromboprophylaxis. All VTE events occurred in the older age category (11-17years) and all but one (92.7%) had a mediastinal mass. While the VTE did not significantly affect the treatment of HL, it caused increased morbidity and 2/12 developed a post-thrombotic syndrome. No significant risk factors for VTE were identified. CONCLUSIONS: VTE is a relatively common complication of HL and its treatment, causing increased acute and long-term morbidity. However, due to limited number of events we could not demonstrate risk-factors for VTE that would identify patients who might benefit from thromboprophylaxis.
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Enfermedad de Hodgkin/complicaciones , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/epidemiología , Adolescente , Anticoagulantes/uso terapéutico , Niño , Femenino , Estudios de Seguimiento , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Incidencia , Estudios Retrospectivos , Suecia/epidemiologíaAsunto(s)
Inhibidores de Factor de Coagulación Sanguínea/análisis , Factor VIII/uso terapéutico , Hemofilia A/inmunología , Tolerancia Inmunológica/efectos de los fármacos , Factores Inmunológicos/uso terapéutico , Adolescente , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Factor VIII/inmunología , Hemofilia A/tratamiento farmacológico , Humanos , Masculino , Proteínas Recombinantes/uso terapéutico , Rituximab , Resultado del TratamientoRESUMEN
UNLABELLED: ESSENTIALS: Children with acute lymphoblastic leukemia (ALL) are at risk of thromboembolism (TE). This is a prospective evaluation of the incidence, risk factors and outcomes of TE in 1038 children with ALL. TE occurred in 6.1% of children, with the highest incidence (20.5%) among those aged 15-17 years. A TE-associated case fatality of 6.4% indicates that TE is a severe complication of ALL treatment. BACKGROUND: Thromboembolism (TE) is a major toxicity in children with acute lymphoblastic leukemia (ALL) and may have a negative impact on ALL treatment. OBJECTIVES: To examine the cumulative incidence, outcomes and risk factors associated with TE in children with leukemia. PATIENTS/METHODS: We prospectively evaluated TE in 1038 Nordic children and adolescents (≥ 1 and < 18 years) diagnosed with ALL during 2008-2013 and treated according to the NOPHO (Nordic Society of Pediatric Hematology and Oncology)-ALL 2008 protocol. The cohort was followed until December 2014. Cox proportional regression was used to compute hazard ratios (HRs). RESULTS: TE events (n = 63) occurred most frequently in conjunction with asparaginase (ASP) administration (52/63). The cumulative incidence of TE was 6.1% (95% confidence interval [CI], 4.8-7.7). Being aged 15-17 years was associated with an increased risk of TE (adjusted HR of 4.0; 95% CI, 2.1-7.7). We found a TE-associated 30-day case fatality of 6.4% (95% CI, 1.8-15.5) and TE-related truncation of ASP therapy in 36.2% (21/58). Major hemorrhage occurred in 3.5% (2/58) of anticoagulated patients. Minor hemorrhage was reported in two out of 58 patients. No major bleeds occurred in children who received low-molecular-weight heparin. CONCLUSIONS: Methods to identify children and adolescents who will benefit from thromboprophylaxis during ALL treatment are called for. The truncation of ASP should be avoided. The long-term survival outcomes for ALL patients with TE require close monitoring in the future.
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Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Tromboembolia/epidemiología , Adolescente , Distribución por Edad , Anticoagulantes/efectos adversos , Antineoplásicos/efectos adversos , Asparaginasa/efectos adversos , Niño , Preescolar , Estonia/epidemiología , Femenino , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Incidencia , Lactante , Lituania/epidemiología , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Países Escandinavos y Nórdicos/epidemiología , Tromboembolia/diagnóstico , Tromboembolia/mortalidad , Tromboembolia/prevención & control , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Recommendations for management of cancer-related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low-quality evidence. This international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagulation strategies. METHODS: Patients with cancer and VTE despite anticoagulant therapy were reported to the registry. Data on treatments, VTE events, major bleeding, residual thrombosis symptoms and death were collected for the following 3 months. Breakthrough VTE and subsequent recurrences were objectively verified. Outcomes with different treatment strategies were compared with Cox proportional hazards regression. RESULTS: We registered 212 patients with breakthrough VTE. Of those, 59% had adenocarcinoma and 73% had known metastases. At the time of the breakthrough event, 70% were on low-molecular-weight heparin (LMWH) and 27% on a vitamin K antagonist (VKA); 70% had a therapeutic or supratherapeutic dose. After breakthrough the regimen was: unchanged therapeutic dose in 33%, dose increased in 31%, switched to another drug in 24%; and other management in 11%. During the following 3 months 11% had another VTE, 8% had major bleeding and 27% died. Of the survivors, 74% had residual thrombosis symptoms. Additional VTE recurrence was less common with LMWH than with a VKA (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.11-0.70) but similar with unchanged or increased anticoagulant intensity (HR, 1.09; 95% CI, 0.45-2.63). The bleeding rate did not increase significantly with dose escalation. CONCLUSION: Morbidity and mortality are high after recurrence of cancer-related VTE despite anticoagulation. Further treatment appears to be more effective with LMWH than with a VKA.
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Anticoagulantes/administración & dosificación , Heparina de Bajo-Peso-Molecular/administración & dosificación , Neoplasias/complicaciones , Tromboembolia Venosa/tratamiento farmacológico , Warfarina/administración & dosificación , Anciano , Anticoagulantes/efectos adversos , Distribución de Chi-Cuadrado , Sustitución de Medicamentos , Femenino , Hemorragia/inducido químicamente , Heparina de Bajo-Peso-Molecular/efectos adversos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/mortalidad , Neoplasias/patología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Recurrencia , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Tromboembolia Venosa/sangre , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/mortalidad , Vitamina K/antagonistas & inhibidores , Warfarina/efectos adversosRESUMEN
Lipolysis and cAMP accumulation were inhibited by low concentrations of adenosine and its analogs in human sc adipocytes stimulated by 2 microM DL-isoproterenol. The order of potency of the adenosine analogs tested was N6-(phenylisopropyl)adenosine greater than 2-chloroadenosine greater than 5'-N-ethylcarboxamidoadenosine greater than adenosine greater than 2',5'-dideoxyadenosine greater than 2'-deoxyadenosine. Inosine was without effect. No stimulation of cAMP accumulation by 5'-N-ethylcarboxamidoadenosine was observed. These results strongly suggest the presence of inhibitory adenosine Ri- and P-sites and the absence of stimulatory Ra-sites in human sc adipocytes.
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Adenosina/análogos & derivados , Tejido Adiposo/efectos de los fármacos , AMP Cíclico/metabolismo , Lipólisis/efectos de los fármacos , Adenosina/farmacología , Tejido Adiposo/metabolismo , Humanos , Técnicas In Vitro , Isoproterenol/farmacología , Relación Estructura-ActividadRESUMEN
In search of the gene for progressive epilepsy with mental retardation (EPMR) we identified DLGAP2, the human homolog of the gene encoding the rat PSD-95/SAP90-associated protein-2 (Dlgap2). We extended the transcript in both the 5' and 3' directions and characterised the genomic structure of the approximately 10 kb gene. Sequence comparisons of human DLGAP2 cDNA sequences obtained from human testis and brain cDNA libraries with homologous rat genes suggest alternative splicing in the 5' end of the gene. The 5' coding sequence of the testis cDNA is complete, whereas based on homology with the rat gene 103 bp of coding sequence may still be missing in the 5' end of the DLGAP2 brain transcript. DLGAP2 was excluded as the gene responsible for EPMR.
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Cromosomas Humanos Par 8 , Epilepsia/genética , Discapacidad Intelectual/genética , Proteínas del Tejido Nervioso/genética , Secuencia de Bases , Mapeo Cromosómico , Clonación Molecular , ADN Complementario/análisis , Genoma Humano , Humanos , Datos de Secuencia Molecular , LinajeRESUMEN
Muscle-Eye-Brain disease (MEB) and Fukuyama type congenital muscular dystrophy (FCMD) are clinically similar autosomal recessive diseases, characterized by congenital muscular dystrophy and severe mental retardation, raising the possibility that they might be caused by mutations of the same gene. Recently FCMD was localized to chromosome 9q31-33 by linkage. We performed a linkage study in seven Finnish MEB families with 12 affected patients using markers D9S53, D9S58, D9S59 and HXB. The MEB phenotype was not linked to any of the markers. A multipoint linkage analysis excluded the entire region harboring FCMD. We thus conclude that MEB and FCMD are not allelic.
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Encéfalo/anomalías , Anomalías del Ojo/genética , Ligamiento Genético , Distrofias Musculares/genética , Adolescente , Adulto , Alelos , Niño , Preescolar , Femenino , Finlandia , Humanos , Escala de Lod , Masculino , Persona de Mediana Edad , Distrofias Musculares/congénito , LinajeRESUMEN
Adenosine is a local hormone or a retaliatory metabolite that executes its effect via a plasma membrane receptor, the R-site. In human adipocytes it inhibits cyclic AMP accumulation and lipolysis. N6-(phenylisopropyl)adenosine is a nonmetabolizable derivative that is an R-site agonist not sharing other effects of the parent nucleoside. In subcutaneous abdominal fat cells from obese subjects (130% to 207% of ideal body weight, N = 8), the antilipolytic effect of N6-(phenylisopropyl) adenosine was markedly attenuated as compared to that in fat cells from normal weight subjects (83% to 121% of ideal body weight, N = 8). There was a negative correlation between the effectiveness of the nucleoside analog and the relative body weight of the donor. The effect of N6-(phenylisopropyl)adenosine on cyclic AMP accumulation was similarly attenuated. These findings may explain some of the metabolic alterations observed in obesity.
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Tejido Adiposo/metabolismo , Obesidad/fisiopatología , Receptores de Superficie Celular/fisiología , Adenosina/metabolismo , Peso Corporal , AMP Cíclico/metabolismo , Humanos , Isoproterenol/farmacología , Lipólisis , Fenilisopropiladenosina/metabolismo , Receptores PurinérgicosRESUMEN
The effects of short-term administration of the antiprogestin and antiglucocorticoid, mifepristone, have been well characterized. However, little is known about the effects of prolonged administration of mifepristone. We analyzed hormonal parameters in four female and three male patients with unresectable meningioma who were treated with mifepristone (200 mg/d) for 20 to 40 months. Serum samples were collected at monthly intervals approximately 24 hours following mifepristone ingestion. Serum thyrotropin (TSH), thyroxine (T4), free T4 (fT4), 3,5,3-triiodothyronine (T3), prolactin, and cortisol were analyzed by fluoroimmunoassay, and androstenedione by radioimmunoassay (RIA). Levels of mifepristone and its three most proximal metabolites were measured by high-performance liquid chromatography. TSH values increased significantly (P < .005, one-way ANOVA), with the most pronounced increase evident during the first 3 months of mifepristone treatment. Despite these changes, concentrations of TSH remained within the normal range throughout the treatment period. There were no significant changes in serum T4, fT4, T3 or prolactin; however, a transient decrease in serum T4 was noted at 2 to 3 months. Cortisol and androstenedione values increased significantly and in parallel (P < .05), suggesting an adrenal origin also for androstenedione. As during short-term administration, levels of mifepristone and its metabolites remained stable in the micromolar range. Individual levels of mifepristone were significantly correlated with those of TSH and cortisol. This suggests that the alterations in the pituitary-thyroid and -adrenal axes occurred in a concentration-dependent manner. It is concluded that long-term mifepristone treatment results in resetting of the pituitary-thyroid balance. As in the case with cortisol and androstenedione, it is likely that the alterations in serum TSH are due to the antiglucocorticoid properties of mifepristone. The clinical significance of these biochemical alterations in thyroid homeostasis remains to be determined. However, monitoring thyroid function during long-term mifepristone treatment appears to be warranted.
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Antagonistas de Hormonas/farmacología , Meningioma/tratamiento farmacológico , Mifepristona/farmacología , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Glándula Tiroides/efectos de los fármacos , Administración Oral , Androstenodiona/sangre , Androstenodiona/metabolismo , Femenino , Antagonistas de Hormonas/administración & dosificación , Antagonistas de Hormonas/química , Antagonistas de Hormonas/farmacocinética , Humanos , Hidrocortisona/sangre , Hidrocortisona/metabolismo , Masculino , Meningioma/sangre , Meningioma/metabolismo , Mifepristona/administración & dosificación , Mifepristona/química , Mifepristona/farmacocinética , Sistema Hipófiso-Suprarrenal/fisiología , Prolactina/sangre , Prolactina/efectos de los fármacos , Prolactina/metabolismo , Glándula Tiroides/fisiología , Tirotropina/sangre , Tirotropina/efectos de los fármacos , Tirotropina/metabolismo , Tiroxina/sangre , Tiroxina/efectos de los fármacos , Tiroxina/metabolismo , Factores de Tiempo , Triyodotironina/sangre , Triyodotironina/efectos de los fármacos , Triyodotironina/metabolismoRESUMEN
BACKGROUND: Because children have less subcutaneous fat, and a higher surface area to body weight ratio than adults, it has been suggested that children cool more rapidly during submersion, and therefore have a better outcome following near-drowning incidents. AIM OF THE STUDY: To study the impact of age, submersion time, water temperature and rectal temperature in the emergency room on outcome in near-drowning. MATERIAL AND METHODS: This retrospective study included all near-drowning victims admitted to the intensive care units of Helsinki University Central Hospital after successful cardiopulmonary resuscitation between 1985 and 1997. RESULTS: There were 61 near-drowning victims (age range: 0.5-60 years, median 29 years). Males were in the majority (40), and 26 were children (<16 years). The median water temperature was 17 degrees C (range: 0-33 degrees C). The median submersion time for the 43 survivors (70%) was 10 min (range: 1-38 min). Intact survivors and those with mild neurological disability (n=26, 43%) had a median submersion time of 5 min (range: 1-21 min). In non-survivors the median submersion time was 16 min (range: 2-75 min). Submersion time was the only independent predictor of survival in linear regression analysis (P<0.01). Patient age, water temperature and rectal temperature in the emergency room were not significant predictors of survival. CONCLUSIONS: Although submersion time is usually an estimate, it is the best prognostic factor after a near drowning incident. Children did not have a better outcome than adults.