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OBJECTIVE: Single-level selective dorsal rhizotomy (SDR), typically indicated for ambulatory patients, is a controversial topic for severe spastic cerebral palsy (CP) with Gross Motor Function Classification System (GMFCS) level IV or V. The objective of this case series and systematic literature review was to outline the indication and outcome of palliative SDR for nonambulatory patients with CP and GMFCS level IV and V, focusing on improvement of spasticity and of patient and caregiver reported quality of life assessment. METHODS: A retrospective case series of patients with CP and GMFCS level IV or V who underwent single-level SDR at the authors' institution is presented. Furthermore, two databases (PubMed and Embase) were searched and a systematic review with a search string based on the terms "selective dorsal rhizotomy," "cerebral palsy," and "outcome" was conducted. The primary outcome was the reduction of spasticity based on the modified Ashworth scale (MAS). Secondary outcomes were change on the Gross Motor Function Measure-66 (GMFM-66), evaluation of patient-reported outcome measures (PROMs), surgical morbidity, and mortality. RESULTS: Eleven consecutive children under the age of 25 years undergoing palliative single-level SDR were included. All patients showed a reduction in MAS score (mean 1.09 ± 0.66 points) and no surgical morbidity and mortality occurred. For the systematic review results from our case series, in addition to 4 reports, 274 total patients were included. Reduction of spasticity based on MAS score was noted in all studies (mean range 1.09-3.2 points). Furthermore, in 2 studies spasticity of the upper extremities showed a MAS score reduction as well (range 1.7-2.8 points). The GMFM-66 score improved in 72% of the patients, while bladder function improved in 78% of the patients. Based on the PROMs, 92% of the patients/caregivers were satisfied with the outcome and their quality of life after the procedure. Two wound infections (2.7%) and one CSF leak (1.3%) occurred, while no surgery-related deaths were described. CONCLUSIONS: This analysis showed an improvement in spasticity, daily care, and comfort for patients with CP and GMFCS levels IV and V. Larger cohorts analyzing the outcome of palliative single-level SDR, based on the MAS, GMFM-66, and PROMs, are still needed and should be the focus of future studies. Systematic review registration no.: CRD42024495762 (https://www.crd.york.ac.uk/prospero/).
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Parálisis Cerebral , Espasticidad Muscular , Cuidados Paliativos , Rizotomía , Humanos , Parálisis Cerebral/cirugía , Parálisis Cerebral/complicaciones , Rizotomía/métodos , Niño , Masculino , Femenino , Preescolar , Estudios Retrospectivos , Adolescente , Espasticidad Muscular/cirugía , Espasticidad Muscular/etiología , Cuidados Paliativos/métodos , Calidad de Vida , Resultado del TratamientoRESUMEN
INTRODUCTION: The aim of this cohort study was to assess the outcome of single-level selective dorsal rhizotomy (SDR) in children and young adults with spastic cerebral palsy (CP) treated at our institution, focusing on patient-reported outcome measures (PROMs) and quality of life (QoL) of patients and their caregivers. METHODS: We included consecutive patients undergoing SDR from 2018 to 2020 at our institution. Subjective outcome was measured through PROMs, while functional outcome was measured through baseline characteristics, operative outcome, as well as short- and long-term follow-up. Furthermore, the effect of age at the time of surgery on patient/caregiver satisfaction was analyzed. RESULTS: Seven patients (3 female, 43%) with a median age at surgery of 11.9 years (IQR 8.7-15.5) were included. All patients had a Gross Motor Function Classification (GMFCS) score of at least IV before surgery. Five surgeries were palliative and two non-palliative. Based on PROMs, SDR showed very good QoL and health-related outcome measures for both palliative and non-palliative patients. Patient/caregiver satisfaction was higher for the early subgroup (age ≤11) than the late subgroup (age >11). Functional outcome showed reduced spasticity in both groups. Blood transfusions were never needed, while no cerebrospinal fluid leak, infection, or permanent morbidity was seen. CONCLUSION: Based on PROMs, SDR leads to high satisfaction and improved QoL, especially if done at an early age. Further studies with larger cohorts are necessary to underline and confirm our observations.
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Parálisis Cerebral , Rizotomía , Niño , Humanos , Femenino , Adulto Joven , Adolescente , Calidad de Vida , Cuidadores , Estudios de Cohortes , Parálisis Cerebral/cirugía , Resultado del Tratamiento , Medición de Resultados Informados por el PacienteRESUMEN
INTRODUCTION: Drug-resistant epilepsy occurs in up to 30% of children suffering from seizures and about 10% qualify for surgical treatment. The aim of this systematic review and meta-analysis is to analyze the potential benefit of early epilepsy surgery in children concerning primarily seizure and developmental outcome. METHODS: PubMed and Embase databases were searched using a systematic search strategy to identify studies on pediatric epilepsy surgery under 3 years from their inception up to 2022. Outcome measures were seizure outcome, postoperative complications, seizure onset, and reduction rate of antiepileptic drugs. A meta-analysis was thereafter performed for all included cohort studies. A p-value of < 0.05 was considered as statistically significant. RESULTS: A total of 532 patients were analyzed with 401 patients (75%) receiving resective or disconnective surgery under the age of 3 years and 80 patients (15%) receiving surgery older than 3 years. The remaining 51 patients (9%) underwent VNS implantation. Pooled outcome analysis for resective/disconnective surgery showed favorable outcome in 68% (95% CI [0.63; 0.73]), while comparative analysis between the age groups showed no significant difference (77% early group and 75% late group; RR 1.03, 95% CI [0.73; 1.46] p = 0.75). Favorable outcome for the VNS cohort was seen in 52%, 65% in the early and 45.1% in the late group (RR 1.4393, 95% CI [0.87; 2.4] z = 1.42, p = 0.16). Developmental outcome was improved in 26%. Morbidity rate was moderate and showed no significant difference comparing the age groups, and overall surgical mortality rate was very low (0.1%). CONCLUSION: Epilepsy surgery in pediatric age, especially under the age of 3 years, is a feasible and safe way to treat intractable epilepsy. Further comparative studies of prospective nature, analyzing not only seizure but also developmental outcome, should be the focus of future studies.
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Epilepsia Refractaria , Epilepsia , Niño , Humanos , Preescolar , Estudios Prospectivos , Epilepsia/cirugía , Epilepsia/tratamiento farmacológico , Convulsiones/cirugía , Epilepsia Refractaria/cirugía , Epilepsia Refractaria/tratamiento farmacológico , Anticonvulsivantes/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Pediatric brain tumors are the most common solid tumor in children. Traditionally, tumor diagnosis and molecular analysis were carried out on tumor tissue harvested either via biopsy or resection. However, liquid biopsy allows analysis of circulating tumor DNA in corporeal fluids such as cerebrospinal fluid or blood. METHODS: We performed a systematic review in Pubmed and Embase regarding the role of liquid biopsy in pediatric brain tumors. RESULTS: Nine studies with a total of 570 patients were included. The preferred corporeal fluid for analysis with a relatively high yield of ct-DNA was cerebrospinal fluid (CSF). For high-grade glioma, liquid biopsy can successfully characterize H3K27mutations and predict tumor progression before it is radiographically detected. Moreover, liquid biopsy has the potential to distinguish between pseudo-progression and actual progression. In medulloblastoma, ct-DNA in the CSF can be used as a surrogate marker of measurable residual disease and correlates with response to therapy and progression of the tumor up to three months before radiographic detection. CONCLUSION: Liquid biopsy is primarily useful in high-grade pediatric brain tumors such as diffuse midline glioma or medulloblastoma. Disease detection and monitoring is feasible for both tumor entities. More trials to standardize its use for pediatric brain tumors are necessary.
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BACKGROUND: Pediatric glioblastoma (GBM) is an aggressive central nervous system tumor in children that has dismal prognosis. Standard of care is surgery with subsequent irradiation and temozolomide. We aimed to outline currently available data on novel pharmacological treatments for pediatric GBM. METHODS: We conducted a systematic literature search in PubMed and Embase, including reports published in English from 2010 to 2021. We included randomized trials, cohort studies and case series. Phase I trials were not analyzed. We followed PRISMA guidelines, assessed the quality of the eligible reports using the Newcastle-Ottawa scale (NOS) and the RoB-2 tool and registered the protocol on PROSPERO. RESULTS: We included 6 out of 1122 screened reports. All six selected reports were prospective, multicenter phase II trials (five single-arm and one randomized controlled trial). None of the investigated novel treatment modalities showed any benefit regarding overall or progression free survival. CONCLUSIONS: To date, the role of pharmacological approaches regarding pediatric GBM remains unclear, since no novel treatment approach could provide a significant impact on overall or progression free survival. Further research should aim to combine different treatment strategies in large international multicenter trials with central comprehensive diagnostics regarding subgrouping. These novel treatment approaches should include targeted and immunotherapeutic treatments, potentially leading to a more successful outcome.
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OBJECTIVE: Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder presenting mostly with a facial port-wine stain and leptomeningeal angiomatosis. More than 85% of the patients are affected by epilepsy by the age of 2 years. Seizure and symptom control is the focus of SWS treatment, since no causal therapy exists yet. For pharmacologically intractable epilepsy, surgery is a treatment option. The aim of this systematic review and meta-analysis was to provide an overview of the literature regarding lesionectomy in SWS with a focus on seizure outcome, complications, and motor and cognitive development. METHODS: The PubMed and Embase databases were searched using a systematic search strategy to identify studies on SWS from their inception until 2021. Two independent researchers assessed the studies for inclusion and quality. Outcome measures were seizure outcome, postoperative complications, and motor and cognitive development. Thereafter, a systematic review was conducted, and a meta-analysis was performed for all included cohort studies. Risk of bias was assessed using the Newcastle-Ottawa Scale. Forest plots have been generated for all outcomes; risk ratio was used for pooled outcomes. A p value < 0.05 was considered as statistically significant. RESULTS: After removal of duplicates, the authors screened 439 articles, of which 9 articles with 150 patients were included. Our case and 5 case reports and 4 retrospective cohort studies were included for systematic review. The latter 4 studies qualified for the meta-analysis. In these 4 articles, 144 patients received surgical treatment: 81 (56%) underwent focal lesionectomy and 63 (44%) hemispherectomy. Pooled outcome analysis for postoperative favorable seizure outcome showed a nonsignificant difference between lesionectomy and hemispherectomy (69.2% vs 87.3%; RR 0.73, 95% CI 0.50-1.08; t = -2.56, p = 0.08). Lesionectomy showed a significantly lower rate for developmental delay and postoperative hemiparesis in comparison with hemispherectomy (29.8% vs 76.3%; RR 0.41, 95% CI 0.28-0.59; z = -4.77, p < 0.0001 and 18.1% vs 100%; RR 0.11, 95% CI 0.06-0.21; z = -6.58, p < 0.0001, respectively). CONCLUSIONS: Based on the limited literature available, lesionectomy leads to a nonsignificant lower seizure control rate, while postoperative developmental or motor deficits are significantly lower compared with hemispherectomy. Therefore, focal lesionectomy remains a valid alternative to hemispherectomy in SWS with a clearly localized epileptogenic area; however, individual case-based decisions in a specialized multidisciplinary team are of paramount importance.
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Epilepsia , Hemisferectomía , Síndrome de Sturge-Weber , Preescolar , Epilepsia/etiología , Epilepsia/cirugía , Humanos , Estudios Retrospectivos , Convulsiones/etiología , Convulsiones/cirugía , Síndrome de Sturge-Weber/complicaciones , Síndrome de Sturge-Weber/diagnóstico , Síndrome de Sturge-Weber/cirugíaRESUMEN
OBJECTIVE: The main indication for craniofacial remodeling of craniosynostosis is to correct the deformity, but potential increased intracranial pressure resulting in neurocognitive damage and neuropsychological disadvantages cannot be neglected. The relapse rate after fronto-orbital advancement (FOA) seems to be high; however, to date, objective measurement techniques do not exist. The aim of this study was to quantify the outcome of FOA using computer-assisted design (CAD) and computer-assisted manufacturing (CAM) to create individualized 3D-printed templates for correction of craniosynostosis, using postoperative 3D photographic head and face surface scans during follow-up. METHODS: The authors included all patients who underwent FOA between 2014 and 2020 with individualized, CAD/CAM-based, 3D-printed templates and received postoperative 3D photographic face and head scans at follow-up. Since 2016, the authors have routinely planned an additional "overcorrection" of 3 mm to the CAD-based FOA correction of the affected side(s). The virtually planned supraorbital angle for FOA correction was compared with the postoperative supraorbital angle measured on postoperative 3D photographic head and face surface scans. The primary outcome was the delta between the planned CAD/CAM FOA correction and that achieved based on 3D photographs. Secondary outcomes included outcomes with and those without "overcorrection," time of surgery, blood loss, and morbidity. RESULTS: Short-term follow-up (mean 9 months after surgery; 14 patients) showed a delta of 12° between the planned and achieved supraorbital angle. Long-term follow-up (mean 23 months; 8 patients) showed stagnant supraorbital angles without a significant increase in relapse. Postsurgical supraorbital angles after an additionally planned overcorrection (of 3 mm) of the affected side showed a mean delta of 11° versus 14° without overcorrection. The perioperative and postoperative complication rates of the whole cohort (n = 36) were very low, and the mean (SD) intraoperative blood loss was 128 (60) ml with a mean (SD) transfused red blood cell volume of 133 (67) ml. CONCLUSIONS: Postoperative measurement of the applied FOA on 3D photographs is a feasible and objective method for assessment of surgical results. The delta between the FOA correction planned with CAD/CAM and the achieved correction can be analyzed on postoperative 3D photographs. In the future, calculation of the amount of "overcorrection" needed to avoid relapse of the affected side(s) after FOA may be possible with the aid of these techniques.
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Craneosinostosis , Fotograbar , Procedimientos de Cirugía Plástica , Cirugía Asistida por Computador , Diseño Asistido por Computadora , Computadores , Craneosinostosis/diagnóstico por imagen , Craneosinostosis/cirugía , Humanos , Lactante , Recurrencia Local de NeoplasiaRESUMEN
AIMS/HYPOTHESIS: We aimed to investigate the association between maternal consumption of gluten-containing foods and other selected foods during late pregnancy and offspring risk of islet autoimmunity (IA) and type 1 diabetes in The Environmental Determinants of Diabetes in the Young (TEDDY) study. METHODS: The TEDDY study recruited children at high genetic risk for type 1 diabetes at birth, and prospectively follows them for the development of IA and type 1 diabetes (n = 8556). A questionnaire on the mother's diet in late pregnancy was completed by 3-4 months postpartum. The maternal daily intake was estimated from a food frequency questionnaire for eight food groups: gluten-containing foods, non-gluten cereals, fresh milk, sour milk, cheese products, soy products, lean/medium-fat fish and fatty fish. For each food, we described the distribution of maternal intake among the four participating countries in the TEDDY study and tested the association of tertile of maternal food consumption with risk of IA and type 1 diabetes using forward selection time-to-event Cox regression. RESULTS: By 28 February 2019, 791 cases of IA and 328 cases of type 1 diabetes developed in TEDDY. There was no association between maternal late-pregnancy consumption of gluten-containing foods or any of the other selected foods and risk of IA, type 1 diabetes, insulin autoantibody-first IA or GAD autoantibody-first IA (all p ≥ 0.01). Maternal gluten-containing food consumption in late pregnancy was higher in Sweden (242 g/day), Germany (247 g/day) and Finland (221 g/day) than in the USA (199 g/day) (pairwise p < 0.05). CONCLUSIONS/INTERPRETATION: Maternal food consumption during late pregnancy was not associated with offspring risk for IA or type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00279318.
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Autoinmunidad , Diabetes Mellitus Tipo 1/etiología , Islotes Pancreáticos/inmunología , Fenómenos Fisiologicos Nutricionales Maternos/fisiología , Adulto , Autoanticuerpos/análisis , Autoanticuerpos/sangre , Autoinmunidad/fisiología , Lactancia Materna , Dieta , Encuestas sobre Dietas , Ingestión de Alimentos/fisiología , Femenino , Glútenes/administración & dosificación , Glútenes/efectos adversos , Humanos , Recién Nacido , Masculino , Periodo Posparto , Embarazo , Tercer Trimestre del Embarazo/sangre , Tercer Trimestre del Embarazo/fisiología , Factores de RiesgoRESUMEN
Primary focal hyperhidrosis (PFH, OMIM %144110) is a genetically influenced condition characterised by excessive sweating. Prevalence varies between 1.0-6.1% in the general population, dependent on ethnicity. The aetiology of PFH remains unclear but an autosomal dominant mode of inheritance, incomplete penetrance and variable phenotypes have been reported. In our study, nine pedigrees (50 affected, 53 non-affected individuals) were included. Clinical characterisation was performed at the German Hyperhidrosis Centre, Munich, by using physiological and psychological questionnaires. Genome-wide parametric linkage analysis with GeneHunter was performed based on the Illumina genome-wide SNP arrays. Haplotypes were constructed using easyLINKAGE and visualised via HaploPainter. Whole-exome sequencing (WES) with 100x coverage in 31 selected members (24 affected, 7 non-affected) from our pedigrees was achieved by next generation sequencing. We identified four genome-wide significant loci, 1q41-1q42.3, 2p14-2p13.3, 2q21.2-2q23.3 and 15q26.3-15q26.3 for PFH. Three pedigrees map to a shared locus at 2q21.2-2q23.3, with a genome-wide significant LOD score of 3.45. The chromosomal region identified here overlaps with a locus at chromosome 2q22.1-2q31.1 reported previously. Three families support 1q41-1q42.3 (LOD = 3.69), two families share a region identical by descent at 2p14-2p13.3 (LOD = 3.15) and another two families at 15q26.3 (LOD = 3.01). Thus, our results point to considerable genetic heterogeneity. WES did not reveal any causative variants, suggesting that variants or mutations located outside the coding regions might be involved in the molecular pathogenesis of PFH. We suggest a strategy based on whole-genome or targeted next generation sequencing to identify causative genes or variants for PFH.
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Mapeo Cromosómico/métodos , Estudio de Asociación del Genoma Completo/métodos , Hiperhidrosis/genética , Polimorfismo de Nucleótido Simple , Femenino , Ligamiento Genético , Predisposición Genética a la Enfermedad , Alemania , Haplotipos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Linaje , Secuenciación del ExomaRESUMEN
BACKGROUND: Although breastfeeding is touted as providing many health benefits to infants, some aspects of this relationship remain poorly understood. METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective longitudinal study that follows children from birth through childhood, and collects data on illness events, breastfeeding duration, and time to introduction of formula or foods at 3 month intervals up until 4 years of age and at 6 months intervals thereafter. Exclusive and non-exclusive breastfeeding is examined in relation to the 3-month odds of a respiratory or gastrointestinal infection for 6861 children between the ages of 3-18 months, and 5666 children up to the age of 4 years. Analysis was performed using logistic regression models with generalized estimating equation methodology. All models were adjusted for potential confounding variables. RESULTS: At 3-6 months of age, breastfeeding was found to be inversely associated with the odds of respiratory infections with fever (OR = 0.82, 95% CI = 0.70-0.95), otitis media (OR = 0.76, 95% CI = 0.62-0.94), and infective gastroenteritis (OR = 0.55, 95% CI = 0.46-0.70), although the inverse association with respiratory illnesses was observed only for girls during the winter months. Between 6 and 18 months of age, breastfeeding within any 3 month period continued to be inversely associated with the odds of ear infection and infective gastroenteritis, and additionally with the odds of conjunctivitis, and laryngitis and tracheitis, over the same 3 month period within this age range. However, breastfeeding in this group was associated with increased reports of common cold. Duration of exclusive breastfeeding was inversely associated with the odds of otitis media up to 48 months of age (OR = 0.97, 95% CI = 0.95-0.99) after breastfeeding had stopped. CONCLUSIONS: This study demonstrates that breastfeeding can be protective against multiple respiratory and gastrointestinal acute illnesses in some children up to at least 6 months of age, with duration of exclusive breastfeeding being somewhat protective of otitis media even after breastfeeding has stopped. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00279318 . Date of registration: January 17, 2006 (proactively registered). First Posted: January 19, 2006.
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Lactancia Materna/efectos adversos , Gastroenteritis/etiología , Infecciones del Sistema Respiratorio/etiología , Enfermedad Aguda , Lactancia Materna/estadística & datos numéricos , Preescolar , Conjuntivitis/epidemiología , Conjuntivitis/etiología , Recolección de Datos/métodos , Diabetes Mellitus Tipo 1/etiología , Europa (Continente)/epidemiología , Femenino , Fiebre/epidemiología , Fiebre/etiología , Predicción , Gastroenteritis/epidemiología , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/etiología , Humanos , Lactante , Islotes Pancreáticos/inmunología , Laringitis/epidemiología , Laringitis/etiología , Modelos Logísticos , Estudios Longitudinales , Masculino , Oportunidad Relativa , Otitis Media/epidemiología , Otitis Media/etiología , Estudios Prospectivos , Características de la Residencia , Infecciones del Sistema Respiratorio/epidemiología , Estaciones del Año , Factores Sexuales , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: 13-Deoxy, 5-iminodoxorubicin (GPX-150) is a doxorubicin (DOX) analog synthesized to reduce the formation of reactive oxygen species and the cardiotoxic metabolite, doxorubiciniol, the two pathways that are linked to the irreversible, cumulative dose-dependent cardiotoxicity of DOX. In a preclinical chronic models and a phase I clinical study of GPX-150, no irreversible, cumulative dose-dependent cardiotoxicity was demonstrated. Recent studies suggest that DOX cardiotoxicity may be mediated, at least in part, by the poisoning of topoisomerase IIß. PATIENTS AND METHODS: An open-label, single-arm phase II clinical study in metastatic and unresectable soft tissue sarcoma (STS) patients was initiated to further evaluate the efficacy and safety of GPX-150, including cardiac function, specifically left ventricular ejection fraction (LVEF). RESULTS: GPX-150 was administered at 265 mg/m2 every 3 weeks for up to 16 doses with prophylactic G-CSF until progression, death, or patient withdrawal from the study. GPX-150 exhibited efficacy assessed as progression-free survival (PFS) rates of 38% and 12% at 6 and 12 months and an overall survival rate of 74% and 45% at 6 and 12 months. GPX-150-treated patients did not develop any evidence of irreversible, cumulative dose-dependent chronic cardiotoxicity. Toxicities included grade 3 anemia, neutropenia, and one grade 4 leukopenia. Correlative analysis demonstrated that GPX-150 was more selective than DOX for the inhibition of topoisomerase IIα over IIß in vitro. CONCLUSION: These results suggest future studies are warranted to further evaluate the clinical efficacy of GPX-150 in STS, perhaps at doses higher than 265 mg/m2 .
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Doxorrubicina/análogos & derivados , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Sarcoma/mortalidad , Neoplasias de los Tejidos Blandos/mortalidadRESUMEN
Purpose A novel doxorubicin (DOX) analog, 13-deoxy, 5-iminodoxorubicin (DIDOX), was synthesized to prevent quinone redox cycling and alcohol metabolite formation, two prevailing hypotheses of anthracycline cardiotoxicity. The chronic cardiotoxicity of DOX and DIDOX was compared. Since a recent hypothesis posits that DOX-induced chronic cardiotoxicity may be mediated by inhibition of the topoisomerase IIß/DNA reaction, we also compared potency of DOX and DIDOX to inhibit topoisomerase IIß decatenation of kinetoplast DNA (kDNA) (a series or interlocking small rings of DNA). Methods We compared DIDOX with DOX to alter cardiac function in a chronic rabbit model. We also compared potency to inhibit decatenation of kDNA by purified topoisomerase IIß in vitro. Results DOX and DIDOX caused similar decreases in white and red blood cell counts indicating similar positions on the dose-response curve for cytotoxic efficacy. However, DOX but not DIDOX elicited a decrease in left ventricular fractional shortening and contractility of isolated left atrial preparations obtained at sacrifice. Histological scoring of apex and left ventricular free wall samples showed that DOX-treated rabbits had significantly more cardiac injury than samples from DIDOX or saline-treated rabbits. DOX inhibited decatenation of DNA by topoisomerase IIß with an EC50 of 40.1 µM while DIDOX did not have any apparent effect on topoisomerase IIß at the concentrations used in the study (0.1-100 µM). Conclusions Unlike DOX, DIDOX did not cause chronic cardiotoxicity and did not appear to interact with topoisomerase IIß in decatenation assays consistent with the hypothesis that inhibition of the topoisomerase IIß/DNA reaction may be a contributor of the mechanism of chronic DOX cardiotoxicity.
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Función del Atrio Izquierdo/efectos de los fármacos , ADN-Topoisomerasas de Tipo II/metabolismo , Modelos Animales de Enfermedad , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacología , Atrios Cardíacos/metabolismo , Inhibidores de Topoisomerasa II/farmacología , Animales , ADN-Topoisomerasas de Tipo II/química , Femenino , Atrios Cardíacos/efectos de los fármacos , Humanos , ConejosRESUMEN
OBJECTIVE: To assess the association between diabetes family history and infant feeding patterns. DESIGN: Data on breast-feeding duration and age at first introduction of cow's milk and gluten-containing cereals were collected in 3-month intervals during the first 24 months of life. SETTING: Data from the multicentre TEDDY (The Environmental Determinants of Diabetes in the Young) study, including centres in the USA, Sweden, Finland and Germany. SUBJECTS: A total of 7026 children, including children with a mother with type 1 diabetes (T1D; n 292), gestational diabetes mellitus (GDM; n 404) or without diabetes but with a father and/or sibling with T1D (n 464) and children without diabetes family history (n 5866). RESULTS: While exclusive breast-feeding ended earlier and cow's milk was introduced earlier in offspring of mothers with T1D and GDM, offspring of non-diabetic mothers but a father and/or sibling with T1D were exclusively breast-fed longer and introduced to cow's milk later compared with infants without diabetes family history. The association between maternal diabetes and shorter exclusive breast-feeding duration was attenuated after adjusting for clinical variables (delivery mode, gestational age, Apgar score and birth weight). Country-specific analyses revealed differences in these associations, with Sweden showing the strongest and Finland showing no association between maternal diabetes and breast-feeding duration. CONCLUSIONS: Family history of diabetes is associated with infant feeding patterns; however, the associations clearly differ by country, indicating that cultural differences are important determinants of infant feeding behaviour. These findings need to be considered when developing strategies to improve feeding patterns in infants with a diabetes family history.
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Diabetes Mellitus Tipo 1 , Diabetes Gestacional , Dieta , Familia , Conducta Alimentaria , Fenómenos Fisiológicos Nutricionales del Lactante , Leche , Adulto , Animales , Lactancia Materna , Estudios de Cohortes , Cultura , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Gestacional/epidemiología , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Embarazo , Estados Unidos/epidemiologíaRESUMEN
The subjects of the article are investigations concerning the ability of both Rhodococcus opacus 1CP and mixed bacterial cultures to use selected surfactants as sole carbon and energy source. In a comparative manner the biosurfactants rhamnolipid, sophorolipid and trehalose tetraester, and the synthetic surfactant Tween 80 were examined. Particular emphasis was put on a combinatorial approach to determine quantitatively the degree of surfactant degradation by applying calorimetry, thermodynamic calculations and mass spectrometry, HPLC as well as determination of biomass. The pure bacterial strain R. opacus was only able to metabolize a part of the synthetic surfactant Tween 80, whereas the mixed bacterial cultures degraded all of the applied surfactants. Exclusive for the biosurfactant rhamnolipid a complete microbial degradation could be demonstrated. In the case of the other surfactants only primary degradation was observed.
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Calorimetría/métodos , Rhodococcus/metabolismo , Tensoactivos/metabolismo , Glucolípidos/química , Glucolípidos/metabolismo , Polisorbatos/química , Polisorbatos/metabolismo , Rhodococcus/química , Rhodococcus/crecimiento & desarrollo , Tensoactivos/química , Trehalosa/química , Trehalosa/metabolismoRESUMEN
AIMS: To investigate the stress response during nutrient deprivation, particularly with regard to the application of phenol as growth substrate of Pseudomonas putida with calorimetric measurements as a new method. METHODS AND RESULTS: The online and noninvasive measurement of the thermal power P(0) permits the detection of microbial activity during the starvation period. While the results of the investigations with phenol reveal a significant loss of activity as a function of the temporal nutrient dosage, only a small loss of activity was detected by using glucose. Microbiological methods (colony forming units (CFU) and activity of catechol-2,3-dioxygenase) showed a loss of the enzyme activity at a constant CFU. The introduction of a simple decay parameter k(D) in the kinetic description of the growth process on phenol was sufficient for the successful kinetic modelling. CONCLUSIONS: The combination of calorimetric measurements and the determination of the enzymatic activity proved the loss of activity of Ps. putida during the deprivation of the substrate phenol. SIGNIFICANCE AND IMPACT OF THE STUDY: The initial heat power (P(0)) proves to be a suitable parameter for the characterization of the physiological state of the culture and can be used for the regulation of nutrient supply in biotechnological process development.
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Glucosa/metabolismo , Fenol/metabolismo , Pseudomonas putida/crecimiento & desarrollo , Pseudomonas putida/metabolismo , Calorimetría , Catecol 2,3-Dioxigenasa/metabolismo , Cinética , Pseudomonas putida/enzimologíaRESUMEN
OBJECTIVE: To evaluate the efficacy of an inactivated bovine herpesvirus-1 (BHV-1) vaccine to protect against BHV-1 challenge-induced abortion and stillbirth. DESIGN: Prospective study. ANIMALS: 35 beef heifers. PROCEDURES: Before breeding, heifers were vaccinated with a commercially available BHV-1 inactivated vaccine SC or IM. The estrous cycle was then synchronized, and heifers were artificially inseminated 30 to 60 days after vaccination. Heifers (n = 21) were challenge inoculated IV at approximately 180 days of gestation with virulent BHV-1. Fourteen control heifers were not vaccinated. Clinical signs of BHV-1 infection were monitored for 10 days following challenge; serologic status and occurrence of abortion or stillbirth were evaluated until time of calving. RESULTS: 18 of 21 (85.7%) heifers that received vaccine were protected from abortion following challenge, whereas all 14 control heifers aborted. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that an inactivated BHV-1 vaccine can protect against abortion resulting from a substantial challenge infection, with efficacy similar to that of modified-live BHV-1 vaccines.
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Aborto Veterinario/prevención & control , Muerte Fetal/veterinaria , Herpesvirus Bovino 1/inmunología , Rinotraqueítis Infecciosa Bovina/prevención & control , Complicaciones Infecciosas del Embarazo/veterinaria , Vacunas Virales , Animales , Bovinos , Femenino , Muerte Fetal/prevención & control , Embarazo , Complicaciones Infecciosas del Embarazo/prevención & control , Estudios Prospectivos , Vacunación/veterinaria , Vacunas Atenuadas , Vacunas de Productos InactivadosRESUMEN
AIM: This study explored the lived experience of phenylketonuria (PKU) for the New Zealand adult and its relevance for issues of treatment adherence. METHOD: In-depth qualitative interviews were conducted with eight New Zealand adults with early-treated PKU regarding their experiences of living with PKU. The interviews were transcribed, and then analysed using grounded theory. A review of relevant medical, scientific and social science literature placed this analysis in a broader context. RESULTS: A number of consistent themes emerged as characteristic of the participants' life experiences, including a chronic uncertainty existing on several levels, the challenges posed by the maintenance of interpersonal relationships with respect to the PKU diet, and a basic incompatibility between the PKU diet and many lifestyle demands. Social science commentary on the topics of risk management, stigma, and other types of "dieting" experiences further elucidates these themes. CONCLUSION: Based on the findings of this research, medical practitioners may be able to better tailor their services for, and interactions with, the adult PKU community, for example, by facilitating self-management, conveying realistic expectations of metabolic control, and increasing the volume of information directed to PKU adults.