Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 367
Filtrar
1.
BMC Med Inform Decis Mak ; 20(1): 21, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32028934

RESUMO

BACKGROUND: A common problem in machine learning applications is availability of data at the point of decision making. The aim of the present study was to use routine data readily available at admission to predict aspects relevant to the organization of psychiatric hospital care. A further aim was to compare the results of a machine learning approach with those obtained through a traditional method and those obtained through a naive baseline classifier. METHODS: The study included consecutively discharged patients between 1st of January 2017 and 31st of December 2018 from nine psychiatric hospitals in Hesse, Germany. We compared the predictive performance achieved by stochastic gradient boosting (GBM) with multiple logistic regression and a naive baseline classifier. We tested the performance of our final models on unseen patients from another calendar year and from different hospitals. RESULTS: The study included 45,388 inpatient episodes. The models' performance, as measured by the area under the Receiver Operating Characteristic curve, varied strongly between the predicted outcomes, with relatively high performance in the prediction of coercive treatment (area under the curve: 0.83) and 1:1 observations (0.80) and relatively poor performance in the prediction of short length of stay (0.69) and non-response to treatment (0.65). The GBM performed slightly better than logistic regression. Both approaches were substantially better than a naive prediction based solely on basic diagnostic grouping. CONCLUSION: The present study has shown that administrative routine data can be used to predict aspects relevant to the organisation of psychiatric hospital care. Future research should investigate the predictive performance that is necessary to provide effective assistance in clinical practice for the benefit of both staff and patients.


Assuntos
Hospitais Psiquiátricos , Aprendizado de Máquina , Prognóstico , Adulto , Idoso , Bases de Dados Factuais , Técnicas de Apoio para a Decisão , Registros Eletrônicos de Saúde , Feminino , Alemanha , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC
2.
BMC Med Res Methodol ; 17(1): 150, 2017 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29166870

RESUMO

BACKGROUND: There are detailed reviews about different recruitment strategies, but not with regard to differences between recruitment of hospital-based versus office-based physicians. Within this study, the two different recruitment schemes are compared. Advantages and disadvantages of different ways of recruitment in registry-based studies are discussed. METHODS: In a cross-sectional cancer-registry-based study, long-term melanoma patients were contacted by dermatologists rather than directly by the registry on the basis of the legal situation. Logistic regression models and generalized estimating equations were used to assess effects of various patient and physician characteristics on participation and data quality. Especially differences between hospital-based versus office-based dermatologists are evaluated. RESULTS: Seventy two out of 112 contacted dermatologists took part in the study (64.3%). The cooperation proportion was 52.2% (689 participants/1320 contacted patients). Participants and non-participants differed regarding age and sex, but not regarding other social demographic factors and cancer stage. We did not observe a difference in patient participation between hospital-based versus office-based dermatologists (OR 1.08 [CI 0.84-1.39]; p = 0.57). However, medical data provided by the cancer registry were better for participants registered and recruited by hospitals. CONCLUSIONS: In cohort studies with epidemiological cancer registries, recruitment via physicians has potential disadvantages and is more complex. If this indirect way of contact is mandatory, we recommend recruitment procedures including hospital-based rather than office-based physicians. However, physician characteristics were not associated with outcome.


Assuntos
Dermatologistas/estatística & dados numéricos , Melanoma/terapia , Seleção de Pacientes , Sistema de Registros/estatística & dados numéricos , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Hospitais , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Participação do Paciente/métodos , Inquéritos e Questionários
3.
Fiziol Cheloveka ; 43(1): 89-96, 2017 Jan.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-29509367

RESUMO

We investigated changes in the urine protein composition of healthy volunteers in controlled conditions during 105-day isolation (Mars-500 program) at different levels of salt consumption. We used newest proteomic techniques based on chromatography-mass spectrometry and various methods of bioinformatics including opoSOM. The period of observation can be divided into three intervals with different dynamics of protein excretion: early (week 1-6), intermediate (week 7-11) and late interval (week 12-15). We identified about 10 different groups of co-detected proteins, which are directly affected by periods with different-levels of salt consumption. We also determined the biological functions of these proteins, tissue specificity and signaling pathways that involve them.


Assuntos
Proteínas/análise , Cloreto de Sódio na Dieta/administração & dosagem , Urina/química , Adulto , Ambiente Controlado , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Proteômica
4.
Zentralbl Chir ; 141(5): 518-525, 2016 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-26947998

RESUMO

Background: There are not many publications on the long-term results of surgical treatment for abdominal aortic aneurysm (AAA) comparing open repair (OR) and endovascular aneurysm repair (EVAR). Method: Using a propensity score (PS), we matched cohorts which were eligible for both types of treatment and underwent an elective surgical procedure for infrarenal AAA between 2002 and 2008. The endpoint of the study was long-term survival without re-intervention. Results: From a total of 442 patients treated from 2002 to 2008, we identified 140 patients of whom 72 received a tube graft and 68 were treated by EVAR. Median observation time was 5 years (0.04-10.3). Mortality was zero in the EVAR group and 1 % in the OR group, with cumulative survival after 5 and 10 years being 82 (79 %) in the OR group and 80 (58 %) in the EVAR group. Three patients (4 %) out of 72 with open surgery and 23 patients (34 %) from the EVAR group had to undergo a repeat surgery. Conclusion: Both procedures are safe methods to eliminate aneurysms. However, the high rate of re-interventions or conversions in the EVAR group has to be considered in the selection of treatment.


Assuntos
Aneurisma da Aorta Abdominal/mortalidade , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Complicações Pós-Operatórias/mortalidade , Pontuação de Propensão , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Estudos de Coortes , Comorbidade , Feminino , Seguimentos , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Reoperação , Fatores de Risco
5.
J Endocrinol Invest ; 38(7): 769-77, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25736545

RESUMO

PURPOSE: Recognition of dysthyroid optic neuropathy (DON) requires sensitive diagnostic tools. Clinical assessment may fail to reliably evaluate the acuteness of DON especially if signs for inflammation are missing. Aim of this cross-sectional study was to assess the relationship between thyroid-stimulating immunoglobulins (TSI) and onset of DON. METHODS: At a multidisciplinary orbital center, serum TSI levels were measured in 180 consecutive patients with thyroid eye disease (TED) and 302 healthy controls with a FDA-cleared cell-based bioassay using a chimeric TSH receptor and a CRE-dependent luciferase. RESULTS: Thirty of 180 (16.7 %) patients with TED had DON of recent onset or a past history of DON (post-DON). Optic disk swelling was present and visual-evoked potentials were pathologic in all eyes with DON of recent onset, but in one of 13 (7.7 %) with post-DON, only (p = 0.005). 19/20 (96 %) patients with DON of recent onset were TSI-positive. TSI was associated with DON of recent onset (OR: 20.96; 95 % CI 1.064-412.85, p = 0.045). All controls were TSI negative. TSI correlated with the clinical activity score (R = 0.70, p < 0.001) and higher TSI-levels were noted in active vs. inactive TED (485.1 ± 132.3 vs. 277.7 ± 143.7 %, cut-off < 140 %; p < 0.001). Six of seven (85.7 %) patients with inactive TED with recent onset DON versus one of four (25 %) with active post-DON were TSI-positive (p = 0.006). A discriminatory cut-point of 377 SRR % for TSI was determined based on a ROC analysis (sensitivity: 0.95, specificity: 0.8). CONCLUSIONS: Serum TSI levels identify patients with DON of recent onset requiring urgent therapy.


Assuntos
Oftalmopatia de Graves/sangue , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Clin Exp Immunol ; 178(1): 57-64, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24903731

RESUMO

Common autoimmune disorders tend to co-exist in the same subjects and cluster in families. The objective of this study was to determine the prevalence of autoimmune co-morbidity in patients with autoimmune thyroid disease (AITD) with and without thyroid-associated orbitopathy (TAO). This was a cross-sectional study conducted at an academic tertiary referral centre. Of 1310 patients with AITD [n = 777 or 59% with Graves' disease (GD) and n = 533, 41% with Hashimoto's thyroiditis (HT)] followed at a specialized joint thyroid-eye out-patient clinic, 176 (13·4%) had an adult type of the autoimmune polyglandular syndrome, 129 (9·8%) type 1 diabetes, 111 (8·5%) coeliac disease, 60 (4·6%) type A autoimmune gastritis, 57 (4·4%) vitiligo and 25 (1·9%) Addison's disease. Coeliac disease and autoimmune gastritis were associated positively with GD [odds ratio (OR) = 2·18; P = 0·002 and OR = 6·52; P < 0·001], whereas type 1 diabetes, Addison's disease, autoimmune primary hypogonadism, alopecia areata, rheumatoid arthritis and Sjögren's syndrome were 'protective' for GD and thus linked to HT, OR = 0·49 (P < 0·001), 0·06 (P < 0·001), 0·25 (P < 0·001), 0·50 (P = 0·090) and 0·32 (P = 0·003), respectively. Of 610 (46·6%) AITD patients with TAO, 584 (95·7%) and 26 (4·3%) had GD and HT, respectively (P < 0·001). TAO was most prevalent in GD patients with coeliac disease (94%, OR = 1·87, P < 0·001). Multivariate analysis showed high OR for coeliac disease and autoimmune gastritis (3·4 and 4·03, both P < 0·001) pertaining to the association with TAO while type 1 diabetes, Addison's disease and alopecia areata were protective for TAO. In patients with TAO, coeliac disease is the most prevalent co-morbid autoimmune condition and rates are increased compared to GD patients without TAO.


Assuntos
Doenças Autoimunes/imunologia , Trato Gastrointestinal/imunologia , Doenças Orbitárias/imunologia , Glândula Tireoide/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoimunidade/imunologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Oftalmopatia de Graves/imunologia , Oftalmopatia de Graves/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Orbitárias/patologia , Prevalência , Estudos Retrospectivos , Doenças da Glândula Tireoide/imunologia , Doenças da Glândula Tireoide/patologia , Glândula Tireoide/patologia , Adulto Jovem
7.
Stat Med ; 33(30): 5358-70, 2014 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-25345575

RESUMO

For determining a manageable set of covariates potentially influential with respect to a time-to-event endpoint, Cox proportional hazards models can be combined with variable selection techniques, such as stepwise forward selection or backward elimination based on p-values, or regularized regression techniques such as component-wise boosting. Cox regression models have also been adapted for dealing with more complex event patterns, for example, for competing risks settings with separate, cause-specific hazard models for each event type, or for determining the prognostic effect pattern of a variable over different landmark times, with one conditional survival model for each landmark. Motivated by a clinical cancer registry application, where complex event patterns have to be dealt with and variable selection is needed at the same time, we propose a general approach for linking variable selection between several Cox models. Specifically, we combine score statistics for each covariate across models by Fisher's method as a basis for variable selection. This principle is implemented for a stepwise forward selection approach as well as for a regularized regression technique. In an application to data from hepatocellular carcinoma patients, the coupled stepwise approach is seen to facilitate joint interpretation of the different cause-specific Cox models. In conditional survival models at landmark times, which address updates of prediction as time progresses and both treatment and other potential explanatory variables may change, the coupled regularized regression approach identifies potentially important, stably selected covariates together with their effect time pattern, despite having only a small number of events. These results highlight the promise of the proposed approach for coupling variable selection between Cox models, which is particularly relevant for modeling for clinical cancer registries with their complex event patterns.


Assuntos
Interpretação Estatística de Dados , Técnicas de Apoio para a Decisão , Modelos de Riscos Proporcionais , Análise de Regressão , Idoso , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Fatores de Confusão Epidemiológicos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Compostos de Fenilureia/farmacologia , Prognóstico , Sistema de Registros , Sorafenibe
8.
Trials ; 25(1): 368, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849916

RESUMO

BACKGROUND: Early identification of patients with chronic kidney disease (CKD) and advancing kidney insufficiency, followed by specialist care, can decelerate the progression of the disease. However, awareness of the importance and possible consequences of kidney insufficiency is low among doctors and patients. Since kidney insufficiency can be asymptomatic even in higher stages, it is often not even known to those belonging to risk groups. This study aims to clarify whether, for hospitalised patients with advanced chronic kidney disease, a risk-based appointment with a nephrology specialist reduces disease progression. METHODS: The target population of the study is hospitalised CKD patients with an increased risk of end-stage renal disease (ESRD), more specifically with an ESRD risk of at least 9% in the next 5 years. This risk is estimated by the internationally validated Kidney Failure Risk Equation (KFRE). The intervention consists of a specific appointment with a nephrology specialist after the hospital stay, while control patients are discharged from the hospital as usual. Eight medical centres include participants according to a stepped-wedge design, with randomised sequential centre-wise crossover from recruiting patients into the control group to recruitment to the intervention. The estimated glomerular filtration rate (eGFR) is measured for each patient during the hospital stay and after 12 months within the regular care by the general practitioner. The difference in the change of the eGFR over this period is compared between the intervention and control groups and considered the primary endpoint. DISCUSSION: This study is designed to evaluate the effect of risk-based appointments with nephrology specialists for hospitalised CKD patients with an increased risk of end-stage renal disease. If the intervention is proven to be beneficial, it may be implemented in routine care. Limitations will be examined and discussed. The evaluation will include further endpoints such as non-guideline-compliant medication, economic considerations and interviews with contributing physicians to assess the acceptance and feasibility of the intervention. TRIAL REGISTRATION: German Clinical Trials Register DRKS00029691 . Registered on 12 September 2022.


Assuntos
Progressão da Doença , Taxa de Filtração Glomerular , Falência Renal Crônica , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Fatores de Risco , Hospitalização , Medição de Risco , Fatores de Tempo , Resultado do Tratamento , Agendamento de Consultas
9.
Stat Med ; 32(10): 1778-91, 2013 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-22786659

RESUMO

When seeking prognostic information for patients, modern technologies provide a huge amount of genomic measurements as a starting point. For single-nucleotide polymorphisms (SNPs), there may be more than one million covariates that need to be simultaneously considered with respect to a clinical endpoint. Although the underlying biological problem cannot be solved on the basis of clinical cohorts of only modest size, some important SNPs might still be identified. Sparse multivariable regression techniques have recently become available for automatically identifying prognostic molecular signatures that comprise relatively few covariates and provide reasonable prediction performance. For illustrating how such approaches can be adapted to the specific features of SNP data, we propose different variants of a component-wise likelihood-based boosting approach. The latter links SNP measurements to a time-to-event endpoint by a regression model that is built up in a large number of steps. The variants allow for strategic choices in dealing with SNPs that differ in variance because of their variation in minor allele frequencies. In addition, we propose a heuristic that allows computationally efficient handling of millions of covariates, thus opening the door for incorporating SNP × treatment interactions. We illustrate this using data from patients with acute myeloid leukemia. We judge the resulting models according to prediction error curves and using resampling data sets. We obtain increased stability by moving interpretation from the SNP to the gene level. By considering these different aspects, we outline a more general strategy for linking SNP measurements to a time-to-event endpoint by means of sparse multivariable regression models.


Assuntos
Genômica/estatística & dados numéricos , Polimorfismo de Nucleotídeo Único , Algoritmos , Bioestatística , Frequência do Gene , Humanos , Leucemia Mieloide Aguda/genética , Funções Verossimilhança , Modelos Estatísticos , Análise Multivariada , Prognóstico , Análise de Regressão
10.
BMC Psychol ; 11(1): 245, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37626397

RESUMO

BACKGROUND: Stress-related disorders such as anxiety and depression are highly prevalent and cause a tremendous burden for affected individuals and society. In order to improve prevention strategies, knowledge regarding resilience mechanisms and ways to boost them is highly needed. In the Dynamic Modelling of Resilience - interventional multicenter study (DynaM-INT), we will conduct a large-scale feasibility and preliminary efficacy test for two mobile- and wearable-based just-in-time adaptive interventions (JITAIs), designed to target putative resilience mechanisms. Deep participant phenotyping at baseline serves to identify individual predictors for intervention success in terms of target engagement and stress resilience. METHODS: DynaM-INT aims to recruit N = 250 healthy but vulnerable young adults in the transition phase between adolescence and adulthood (18-27 years) across five research sites (Berlin, Mainz, Nijmegen, Tel Aviv, and Warsaw). Participants are included if they report at least three negative burdensome past life events and show increased levels of internalizing symptoms while not being affected by any major mental disorder. Participants are characterized in a multimodal baseline phase, which includes neuropsychological tests, neuroimaging, bio-samples, sociodemographic and psychological questionnaires, a video-recorded interview, as well as ecological momentary assessments (EMA) and ecological physiological assessments (EPA). Subsequently, participants are randomly assigned to one of two ecological momentary interventions (EMIs), targeting either positive cognitive reappraisal or reward sensitivity. During the following intervention phase, participants' stress responses are tracked using EMA and EPA, and JITAIs are triggered if an individually calibrated stress threshold is crossed. In a three-month-long follow-up phase, parts of the baseline characterization phase are repeated. Throughout the entire study, stressor exposure and mental health are regularly monitored to calculate stressor reactivity as a proxy for outcome resilience. The online monitoring questionnaires and the repetition of the baseline questionnaires also serve to assess target engagement. DISCUSSION: The DynaM-INT study intends to advance the field of resilience research by feasibility-testing two new mechanistically targeted JITAIs that aim at increasing individual stress resilience and identifying predictors for successful intervention response. Determining these predictors is an important step toward future randomized controlled trials to establish the efficacy of these interventions.


Assuntos
Resiliência Psicológica , Adolescente , Humanos , Adulto Jovem , Ansiedade , Transtornos de Ansiedade , Nível de Saúde , Saúde Mental , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Schweiz Arch Tierheilkd ; 154(3): 113-9, 2012 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-22378052

RESUMO

In order to expedite targeted interventions, mandatory notification of treated dog bite injuries for Swiss physicians and veterinarians was implemented in 2006. Since the number of notified cases was much lower than expected, the validity of the annually produced statistics with respect to the real situation in Switzerland was discussed controversially. In this study a questionnaire survey among physicians and veterinarians was carried out to evaluate the amount of and reasons for non-compliance with the mandatory notification. 81 % of the physicians and 97 % of the veterinarians reported the treatment of dog bite injuries in the year 2009. Among those, 60 % of the physicians and 41 % of the veterinarians indicated notification of less than 50 % of the treated cases. Our results indicate that the most relevant cases for targeted interventions seem to be notified, but that the statistical analyses have to be interpreted carefully.


Assuntos
Mordeduras e Picadas/epidemiologia , Cães , Animais , Humanos , Notificação de Abuso , Inquéritos e Questionários , Suíça/epidemiologia
12.
NPJ Precis Oncol ; 5(1): 64, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262104

RESUMO

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10-10, OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

13.
Stat Med ; 29(7-8): 808-17, 2010 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-20213721

RESUMO

When global techniques, based on fractional polynomials (FPs), are employed for modeling potentially nonlinear effects of several continuous covariates on a response, accessible model equations are obtained. However, local features might be missed. Therefore, a procedure is introduced, which systematically checks model fits, obtained by the multivariable fractional polynomial (MFP) approach, for overlooked local features. Statistically significant local polynomials are then parsimoniously added. This approach, called MFP + L, is seen to result in an effective control of the Type I error with respect to the addition of local components in a small simulation study with univariate and multivariable settings. Prediction performance is compared with that of a penalized regression spline technique. In a setting unfavorable for FPs, the latter outperforms the MFP approach, if there is much information in the data. However, the addition of local features reduces this performance difference. There is only a small detrimental effect in settings where the MFP approach performs better. In an application example with children's respiratory health data, fits from the spline-based approach indicate many local features, but MFP + L adds only few significant features, which seem to have good support in the data. The proposed approach may be expected to be superior in settings with local features, but retains the good properties of the MFP approach in a large number of settings where global functions are sufficient.


Assuntos
Bioestatística/métodos , Funções Verossimilhança , Análise Multivariada , Análise de Regressão , Alérgenos/efeitos adversos , Índice de Massa Corporal , Criança , Simulação por Computador/estatística & dados numéricos , Dispneia/epidemiologia , Feminino , Humanos , Masculino , Modelos Estatísticos , Dióxido de Nitrogênio/análise , Ozônio/análise , Pólen/efeitos adversos , Sistema Respiratório/fisiopatologia
14.
Reprod Domest Anim ; 45(1): 86-91, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18992117

RESUMO

Cryopreservation of cells and even tissue is feasible. New exciting findings arise in the promising field of cryobiology, e.g. the cryopreservation of whole ovaries. Uterus cryopreservation would be advantageous not only for experimental biology, but also for transplantation surgery. The objective of this study was to evaluate various cryopreservation protocols as well as various storage temperatures in cryopreservation of whole swine uteri. The used freezing protocol was slow (0.2 degrees C/min) after arterial perfusion with 1%, 5% or 10% dimethyl sulfoxide (DMSO) solution for 10 min and equilibration in this solution for 30 min. Viability of the organs was tested by histological examination, biochemical parameters and by the capability of rhythmical contractions in a perfusion system. Eighty swine uteri were cryopreserved. All uteri that were frozen with 10% and 5% DMSO were viable after thawing for at least 1 h, whereas only 40% survived with the use of 1% DMSO and 0% with the use of 0.5% DMSO, respectively. There was no difference regarding the survival rates after various cryostorage periods for up to 16 weeks or after cryostorage for 2 weeks in -70 degrees C or -130 degrees C. The cryopreservation of a whole organ such as the swine uterus is a valuable method for the study of cryoprotective agents and freezing protocols. This study demonstrates clearly that the perfusion of the organ with cryoprotectants is the only factor which allows the uterus to contract.


Assuntos
Criopreservação/veterinária , Suínos , Contração Uterina/fisiologia , Útero/fisiologia , Animais , Criopreservação/métodos , Crioprotetores/administração & dosagem , Dimetil Sulfóxido/administração & dosagem , Feminino , Soluções , Temperatura , Sobrevivência de Tecidos/fisiologia
15.
Science ; 179(4074): 700-2, 1973 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-4685042

RESUMO

Uptake of inorganic phosphate is impared in intestinal mucosa from hemizygous males and heterozygous females with X-linked familial hypophosphatemic rickets. Considerable intrafamilial and interfamilial variation in uptake of inorganic phosphate is observed in affected patients. Uptake by normal mucosa is concentrative and energy-dependent, and is mediated by at least two systems with widely different affinities. These results lend direct support to the thesis that the primary metabolic disturbance in this disease results from impaired transport of inorganic phosphate in kidney and gut.


Assuntos
Hipofosfatemia Familiar/metabolismo , Mucosa Intestinal/metabolismo , Fosfatos/metabolismo , Raquitismo/metabolismo , Transporte Biológico , Biópsia , Feminino , Heterozigoto , Homozigoto , Humanos , Técnicas In Vitro , Jejuno/metabolismo , Cinética , Masculino , Isótopos de Fósforo , Fatores Sexuais
16.
Acta Neuropathol Commun ; 7(1): 59, 2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023364

RESUMO

BACKGROUND: Diffuse lower WHO grade II and III gliomas (LGG) are slowly progressing brain tumors, many of which eventually transform into a more aggressive type. LGG is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the heterogeneity of the DNA methylome, its function in tumor biology, coupling with the transcriptome and tumor microenvironment and its possible impact for tumor development. METHODS: We here present novel DNA methylation data of an LGG-cohort collected in the German Glioma Network containing about 85% isocitrate dehydrogenase (IDH) mutated tumors and performed a combined bioinformatics analysis using patient-matched genome and transcriptome data. RESULTS: Stratification of LGG based on gene expression and DNA-methylation provided four consensus subtypes. We characterized them in terms of genetic alterations, functional context, cellular composition, tumor microenvironment and their possible impact for treatment resistance and prognosis. Glioma with astrocytoma-resembling phenotypes constitute the largest fraction of nearly 60%. They revealed largest diversity and were divided into four expression and three methylation groups which only partly match each other thus reflecting largely decoupled expression and methylation patterns. We identified a novel G-protein coupled receptor and a cancer-related 'keratinization' methylation signature in in addition to the glioma-CpG island methylator phenotype (G-CIMP) signature. These different signatures overlap and combine in various ways giving rise to diverse methylation and expression patterns that shape the glioma phenotypes. The decrease of global methylation in astrocytoma-like LGG associates with higher WHO grade, age at diagnosis and inferior prognosis. We found analogies between astrocytoma-like LGG with grade IV IDH-wild type tumors regarding possible worsening of treatment resistance along a proneural-to-mesenchymal axis. Using gene signature-based inference we elucidated the impact of cellular composition of the tumors including immune cell bystanders such as macrophages. CONCLUSIONS: Genomic, epigenomic and transcriptomic factors act in concert but partly also in a decoupled fashion what underpins the need for integrative, multidimensional stratification of LGG by combining these data on gene and cellular levels to delineate mechanisms of gene (de-)regulation and to enable better patient stratification and individualization of treatment.


Assuntos
Neoplasias Encefálicas/genética , Metilação de DNA/genética , Dosagem de Genes , Glioma/genética , Transcriptoma , Neoplasias Encefálicas/complicações , Biologia Computacional , Epigênese Genética , Humanos , Gradação de Tumores , Microambiente Tumoral/genética , Organização Mundial da Saúde
17.
Reprod Biomed Online ; 17(2): 249-58, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18682000

RESUMO

The aim of this study was to determine the correlation between three-dimensional power Doppler sonography (3D-PDS) of the (sub)endometrium and concentrations of angiogenic cytokines in patients attending an IVF programme. A total of 42 patients was included in a prospective, non-randomized clinical study. 3D-PDS of the (sub)endometrium was performed on the day of oocyte aspiration, with and without contrast agent. Quantitative assessment included the following 3D Doppler parameters: vascularization index, flow intensity, and vascularization flow index. On the same day, concentrations of oestradiol (serum only), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF) 1, IGF-binding protein 3 (IGFBP-3) and leptin were determined in the serum and in the follicular fluid. All 3D-PDS indices were significantly higher with contrast enhancement (P < 0.05). Follicular fluid concentrations of VEGF and IGFBP-3, as well as serum concentrations of leptin, showed significant P-values when correlated with (sub)endometrial Doppler indices. A weak linear dependency appeared between flow intensity and VEGF and leptin. Furthermore, weak dependencies were apparent between 3D Doppler parameters and high follicular fluid concentrations of VEGF and IGFBP-3. It is concluded that there is only little evidence for an association between (sub)endometrial Doppler indices as assessed by 3D-PDS and concentrations of angiogenic cytokines.


Assuntos
Proteínas Angiogênicas/análise , Citocinas/análise , Endométrio/diagnóstico por imagem , Imageamento Tridimensional , Ultrassonografia Doppler/métodos , Adolescente , Adulto , Citocinas/sangue , Endométrio/irrigação sanguínea , Estradiol/sangue , Feminino , Fertilização in vitro/métodos , Líquido Folicular/química , Humanos , Imageamento Tridimensional/métodos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Leptina/sangue , Projetos Piloto , Gravidez , Fator A de Crescimento do Endotélio Vascular/sangue
18.
Neurophysiol Clin ; 38(5): 289-95, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18940616

RESUMO

OBJECTIVES: Increasing evidence suggests that dysfunctions of the cortico-cerebello-thalamocortical circuit are involved in the pathophysiology of neuropsychiatric disorders. This study explores the effects of cerebellar repetitive transcranial magnetic stimulation (rTMS) on cerebello-thalamocortical pathways. METHODS: Ten healthy volunteers received MRI-guided rTMS in four separate sessions (120% motor threshold, 1000 stimuli) over either the medial or the right lateral cerebellum using frequencies of 1 and 10 Hz. Motor cortex excitability was assessed before and after the intervention by paired-pulse transcranial magnetic stimulation. RESULTS: Depending on stimulation frequency, cerebellar rTMS differentially modified intracortical inhibition. Low frequency rTMS increased short intracortical inhibition (SICI), whereas high frequency rTMS had no significant effect on SICI. CONCLUSIONS: These results suggest that rTMS over the cerebellum can modulate cerebello-thalamocortical pathways in a frequency-specific manner.


Assuntos
Cerebelo/fisiologia , Córtex Cerebral/fisiologia , Vias Neurais/fisiologia , Tálamo/fisiologia , Estimulação Magnética Transcraniana , Adulto , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Motor/fisiologia , Limiar Sensorial/fisiologia , Adulto Jovem
19.
Transfus Clin Biol ; 15(6): 395-401, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18757223

RESUMO

PURPOSE OF THE STUDY: Ovarian hyperstimulation syndrome is a potentially life-threatening complication during controlled ovarian stimulation for fertility treatment. Since no association of this condition with ABO blood groups was known, we compared ABO antigens with severity and onset of symptoms in a case-control study. PATIENTS AND METHODS: One hundred and twenty-one patients, mainly Caucasians, were hospitalized because of ovarian hyperstimulation syndrome after receiving in vitro fertilisation, in the period from January 2000 to February 2007. Severity of symptoms, pregnancy rate and ABO blood group were collated. The ABO blood group distribution was compared to four independent control groups. RESULTS: Blood group A was markedly more frequent and blood group O less frequent in patients with ovarian hyperstimulation syndrome compared to the blood group distribution in all control cohorts. The odds ratio for patients undergoing controlled ovarian stimulation with blood group A versus O to develop the early-onset form of this condition was 2.171 (p-value 0.002). No association for late-onset form could be found. The overall pregnancy rate was 50.4% and three times higher in the group of late-onset ovarian hyperstimulation syndrome compared to the early-onset form. Four patients developed thromboses in the jugular or subclavian vein, none of whom had blood group O. CONCLUSION: Blood group A may be associated with early-onset ovarian hyperstimulation syndrome in Caucasians. Depending on further studies, this possible association may be considered for an individualized hormone dosing in controlled ovarian stimulation.


Assuntos
Sistema ABO de Grupos Sanguíneos , Síndrome de Hiperestimulação Ovariana/sangue , Indução da Ovulação/efeitos adversos , Feminino , Fertilização in vitro/efeitos adversos , Alemanha/epidemiologia , Humanos , Razão de Chances , Síndrome de Hiperestimulação Ovariana/complicações , Síndrome de Hiperestimulação Ovariana/epidemiologia , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Fatores de Tempo , População Branca
20.
Orthop Traumatol Surg Res ; 104(6): 749-754, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29581067

RESUMO

BACKGROUND: The acromioclavicular (AC) joint is of great importance for shoulder stability and one of the most frequently injured regions of the shoulder. HYPOTHESIS: AC joint reconstruction with the ligament augmentation & reconstruction system (LARS™) leads to a good-to-excellent outcome at long-term follow-up. PATIENTS AND METHODS: This study was performed as a retrospective single-centre data analysis of a level-I trauma centre. All patients treated operatively for an acute AC dislocation with the LARS™ between 2003 and 2013 were included. RESULTS: The study group consisted of three female (6%) and 44 male patients (94%) with an average age of 37 years and a minimum follow-up of two years. The overall mean clinical outcomes at latest follow-up were: Constant 93, DASH 2.64, ASES 96, SST 97, UCLA 34 and VAS 0.4-representing a good-to-excellent outcome in all patients. Overall, 45 patients (96%) reported to be very satisfied with the achieved result at latest follow-up. In five patients, (11%) complications occurred during the follow-up period, requiring surgical revision in four of the five patients (80%). CONCLUSION: AC joint reconstruction with the LARS™ achieves good-to-excellent clinical and functional outcomes at long-term follow-up with a surgical revision rate of 8.5%. LEVEL OF EVIDENCE: Retrospective follow-up study, case series, level IV.


Assuntos
Articulação Acromioclavicular/cirurgia , Luxações Articulares/cirurgia , Instabilidade Articular/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Reoperação , Estudos Retrospectivos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA