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1.
Support Care Cancer ; 27(8): 2809-2818, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30539313

RESUMO

PURPOSE: Fatigue has found increasing attention as a debilitating and lasting condition of cancer patients. However, it has remained unclear to what degree long-term survivors of malignant melanoma suffer from fatigue. Therefore, this study aimed to determine fatigue and its link with quality of life, aftercare behavior, and mental and physical symptoms among melanoma survivors. METHODS: A register-based sample of 684 long-term survivors an average of 8.4 (SD = 1.72; range 5.67-12.17) years after diagnosis was compared to 2049 participants from a representative survey by the Multidimensional Fatigue Inventory. In a hierarchical linear regression, statistical predictors for fatigue were ascertained. RESULTS: Overall fatigue was not increased in melanoma survivors except for younger melanoma survivors under 40 years. As in the general population, fatigue increased with age, and it was higher in women compared to men. Fatigue was associated with decreased quality of life, reduced functioning, and increased physical and mental symptoms. Substantial predictors (30% explained variance) were higher age, additional chronic illness, self-blame, detrimental interactions and lack of social support, and also fear of recurrence. There was neither an effect of medical parameters (clinical stage, time since diagnosis) nor of participation in follow-up care. CONCLUSIONS: Fatigue needs to be taken seriously in the aftercare of melanoma survivors as it is associated with multiple functional and quality of life impairments and heightened distress. Reduction of fatigue in melanoma patients should address younger survivors (under 40 years) and older survivors (over 60 years) with additional chronic illness and focus on illness coping and social support.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Fadiga/epidemiologia , Melanoma/epidemiologia , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Sobreviventes de Câncer/psicologia , Estudos de Coortes , Fadiga/etiologia , Feminino , Humanos , Masculino , Melanoma/complicações , Melanoma/psicologia , Pessoa de Meia-Idade , Qualidade de Vida , Sistema de Registros , Fatores de Risco , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/psicologia , Apoio Social , Inquéritos e Questionários , Melanoma Maligno Cutâneo
2.
J Dtsch Dermatol Ges ; 16(5): 566-574, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29750454

RESUMO

BACKGROUND: Extemporaneous formulations broaden the spectrum of therapeutic options for topical treatment in particular and thus improve patient care. The latest amendment to the Regulation on the Operation of Pharmacies issued in 2012 brought about changes in prescribing and manufacturing practices. The aim of the present study was to assess the relevance of extemporaneous formulations in everyday clinical practice. METHODS: We used data from the German Institute for Drug Use Evaluation (DAPI) to analyze the prescribing practice for compounded preparations in Germany between the fourth quarter of 2011 and the third quarter of 2014. In doing so, we determined the total cost associated with extemporaneous formulations covered by statutory health insurance funds in the outpatient setting. RESULTS: Approximately three out of ten prescriptions (30.54 %) by German dermatologists during the observation period were extemporaneous formulations. While dermatologists make up only 2.7 % of physicians working in the statutory health care system in Germany, they prescribe more than half of all compounded preparations (53.6 %). Each dermatologist prescribed an average of 270.4 formulations per quarter; that number was 13.5 (1.3 %) for all other medical specialties. On average, 1,983,687 extemporaneous formulations overall (1.3 % of all prescriptions) were prescribed per quarter, corresponding to a total cost of € 40,944,982 (0.55 %). CONCLUSIONS: Apart from finished medicinal products, extemporaneous formulations play a key role in outpatient care. Based on the principles of evidence-based and patient-oriented medicine, the quality of compounded preparations and the prescribing practice of physicians (standardized vs. individual formulations) should be further investigated to optimize the quality of these preparations.


Assuntos
Composição de Medicamentos , Farmácias , Administração Tópica , Alemanha , Humanos
3.
Transfusion ; 57(5): 1152-1162, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28337761

RESUMO

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is an acute life-threatening microangiopathy with a tendency of relapse characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, and spontaneous von Willebrand factor-induced platelet clumping leading to microthrombi. The brain is frequently affected by microthrombi leading to neurologic abnormalities of varying severity. STUDY DESIGN AND METHODS: The aim of this observational cohort study was to investigate the prevalence of depression and cognitive deficits in 104 patients having survived acute TTP. TTP survivors were repeatedly assessed by means of different standardized questionnaires to evaluate depression (IDS-SR) and mental performance (FLei). We received answers of 104 individual TTP patients and 55 of them participated in both surveys. RESULTS: Seventy-one of the 104 responding TTP patients (68%) suffered from depression and the severity of depression was similar in both surveys performed 1 year apart. Furthermore, TTP patients had considerably lower cognitive performance than controls. There was no correlation between prevalence of depression and cognitive deficits and the number and the severity of acute episodes. Impairment of mental performance correlated with the severity of depression (rs  = 0.779). CONCLUSION: The prevalence of depression and cognitive deficits was significantly higher in TTP patients. Cognitive impairment seemed to be a consequence of depression, almost independently of number and severity of TTP episodes.


Assuntos
Disfunção Cognitiva/etiologia , Depressão/etiologia , Púrpura Trombocitopênica Trombótica/complicações , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Recidiva , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
4.
BMC Cancer ; 16: 94, 2016 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-26872727

RESUMO

BACKGROUND: The polyspecific organ cation transporter 1 (OCT1) is one of the most important active influx pumps for drugs like the kinase inhibitor sorafenib. The aim of this retrospective study was the definition of the role of intratumoral OCT1 mRNA expression in hepatocellular carcinoma (HCC) as a biomarker in systemic treatment with sorafenib. METHODS: OCT1 mRNA expression levels were determined in biopsies from 60 primary human HCC by real time PCR. The data was retrospectively correlated with clinical parameters. RESULTS: Intratumoral OCT1 mRNA expression is a significant positive prognostic factor for patients treated with sorafenib according to Cox regression analysis (HR 0.653, 95%-CI 0.430-0.992; p = 0.046). Under treatment with sorafenib, a survival benefit could be shown using the lower quartile of intratumoral OCT1 expression as a cut-off. Macrovascular invasion (MVI) was slightly more frequent in patients with low OCT1 mRNA expression (p = 0.037). Treatment-induced AFP response was not associated with intratumoral OCT1 mRNA expression levels (p = 0.633). CONCLUSIONS: This study indicates a promising role for intratumoral OCT1 mRNA expression as a prognostic biomarker in therapeutic algorithms in HCC. Further prospective studies are warranted on this topic.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Transportador 1 de Cátions Orgânicos/biossíntese , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Proteínas de Transporte de Cátions/biossíntese , Proteínas de Transporte de Cátions/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Transportador 1 de Cátions Orgânicos/genética , Compostos de Fenilureia/administração & dosagem , RNA Mensageiro/biossíntese , Sorafenibe
5.
Skin Pharmacol Physiol ; 29(1): 9-12, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26465879

RESUMO

BACKGROUND/AIMS: According to current guidelines, the emergency kit for patients with severe urticaria and/or angioedema should include a corticosteroid with a prednisolone-equivalent of 50-100 mg. Since severe dysphagia may occur in anaphylaxis, liquid corticosteroids are advantageous. Presently, only liquid preparations with less than 100 mg prednisolone equivalent are available worldwide. METHODS: We prepared a highly concentrated liquid prednisolone formula for oral administration (1 or 5 mg prednisolone per ml). We observed efficacy and safety of 100 mg or >250 mg liquid oral prednisolone in comparison to intravenous administration (250 mg prednisolone) in 53 patients with urticaria and/or angioedema. RESULTS: The symptom control achieved with oral administration was comparable to that obtained with intravenous therapy, with remission of at least 50% of the symptoms in less than 30 min. No side effects occurred during the treatment period. CONCLUSION: The liquid prednisolone formula is an additional therapeutic rescue medication in dermatological emergency medicine, filling a therapeutic niche for patients who need high-concentration liquid prednisolone. It is suitable for self-administration emergency kits in children and adults, in accordance with current guidelines.


Assuntos
Angioedema/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Prednisolona/administração & dosagem , Urticária/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Formas de Dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Resultado do Tratamento , Adulto Jovem
6.
Arch Gynecol Obstet ; 294(3): 599-606, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26993518

RESUMO

PURPOSE: New insights into the carcinogenesis of ovarian cancer (OC) lead to the definition of low-grade and high-grade serous OC. In this study, we validated the MD Anderson Cancer Center (MDACC) two-tier grading system and compared it with the traditional three-tier grading system as suggested by the International Federation of Gynecology and Obstetrics (FIGO). METHODS: Consecutive patients with serous OC were enrolled. These two grading systems were assessed independently from each other. Kaplan-Meier estimates and Cox-regression analyses were performed to validate and compare their prognostic impact. RESULTS: 143 consecutive patients entered the study. According to the Kaplan-Meier estimates, the MDACC grading system (p = 0.001) predicted the progression free survival (PFS) more precisely than the FIGO system (p = 0.025). The MDACC grading system (p = 0.008) but not the FIGO system (p = 0.329) showed a statistically significant difference in terms of disease specific survival (DSS). Multivariable Cox-regression analyses revealed an independent prognostic impact of the MDACC grading system but not of the FIGO system for PFS (HR 1.570; 95 % CI 1.007-2.449; p = 0.047, and HR 0.712; 95 % CI 0.476-1.066; p = 0.099, respectively). Concerning DSS, the two-tier grading system but not the FIGO system showed a prognostic impact in a univariable Cox-regression analysis (HR 2.152; 95 % CI 1.207-3.835; p = 0.009, and HR 1.258; 95 % CI 0.801-1.975; p = 0.319, respectively). CONCLUSIONS: We were able to validate the MDACC grading system in serous OC. Moreover, this grading system was stronger associated with survival than the FIGO system.


Assuntos
Cistadenocarcinoma Seroso/patologia , Neoplasias Ovarianas/patologia , Cistadenocarcinoma Seroso/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais
7.
BMC Bioinformatics ; 16: 294, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26374641

RESUMO

BACKGROUND: High-dimensional molecular measurements, e.g. gene expression data, can be linked to clinical time-to-event endpoints by Cox regression models and regularized estimation approaches, such as componentwise boosting, and can incorporate a large number of covariates as well as provide variable selection. If there is heterogeneity due to known patient subgroups, a stratified Cox model allows for separate baseline hazards in each subgroup. Variable selection will still depend on the relative stratum sizes in the data, which might be a convenience sample and not representative for future applications. Such effects need to be systematically investigated and could even help to more reliably identify components of risk prediction signatures. RESULTS: Correspondingly, we propose a weighted regression approach based on componentwise likelihood-based boosting which is implemented in the R package CoxBoost (https://github.com/binderh/CoxBoost). This approach focuses on building a risk prediction signature for a specific stratum by down-weighting the observations from the other strata using a range of weights. Stability of selection for specific covariates as a function of the weights is investigated by resampling inclusion frequencies, and two types of corresponding visualizations are suggested. This is illustrated for two applications with methylation and gene expression measurements from cancer patients. CONCLUSION: The proposed approach is meant to point out components of risk prediction signatures that are specific to the stratum of interest and components that are also important to other strata. Performance is mostly improved by incorporating down-weighted information from the other strata. This suggests more general usefulness for risk prediction signature development in data with heterogeneity due to known subgroups.


Assuntos
Expressão Gênica/genética , Análise de Regressão , Medição de Risco/métodos , Humanos , Modelos de Riscos Proporcionais
8.
Clin Lab ; 60(5): 783-90, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24839821

RESUMO

BACKGROUND: Among health-conscious individuals, including vegetarians, salads dressed with vinegar are frequently consumed. Dental erosion can also be caused by an acidic diet, and occurs with increasing tendency. The aim of this study was to analyze the erosive potential of vinegar varieties on human enamel samples. METHODS: A total of 30 vinegar varieties were selected. Enamel samples were prepared from human wisdom teeth, and the specially prepared enamel slices were incubated with 5 selected vinegars (Bio vinegar, pH = 3.1; raspberry vinegar, pH = 2.7; Condimento Balsamico, pH = 3.95; Ortalli Bianco Modena, pH = 2.7; Vinaigre de Jerez, pH = 2.9) for up to 8 hours. Controls were incubated with a 0.9% sodium chloride solution. The quantitative analysis of CaO, P2O5, F, MgO, Cl, and O in the enamel samples (incubation: 4, 8 hours) in various depths ranging from 7.5 - 105 microm was carried out using an electron probe micro-analyser (Jeol JXA 8900RL). Linear mixed models were fitted to analyze statistically relevant differences between the different vinegars at various depth levels. RESULTS: Incubating the enamel slices with the selected vinegars caused a release of minerals, which was dependent on time and type of vinegar. The vinegar Ortalli Bianco Modena led to a slight loss (1%) of the mineral CaO in a depth up to 20 microm, while the loss of minerals caused by raspberry vinegar in a depth of up to 30 microm was about 20% (4 hours). The greatest loss of the minerals was detected for the Bio Vinegar. After 8 hours incubation, a loss of minerals of about 20% in a depth of 45 microm and in a depth of 60 microm of 16% could be observed. Both, the Bio Vinegar and the raspberry vinegar led to a significantly higher loss of minerals (p < 0.0001) than all other tested vinegars. CONCLUSIONS: In this in vitro study, the erosive potential of different vinegar varieties on human enamel samples could be demonstrated. However, it must be considered that numerous modifying factors influence the enamel surface in vivo; therefore, a direct translation to in vitro conditions can only be done with caution.


Assuntos
Ácido Acético/efeitos adversos , Condimentos/efeitos adversos , Erosão Dentária/etiologia , Adulto , Microanálise por Sonda Eletrônica , Feminino , Humanos
9.
Odontology ; 102(2): 297-302, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23604464

RESUMO

Evidence from epidemiologic studies suggests that periodontal diseases may exert a weak to moderate influence on the severity and course of coronary heart disease. The aim of this study was to investigate whether an association between chronic oral infections and the presence of an acute myocardial infarction (AMI) exists. A total of 248 patients after AMI and 249 healthy controls were recruited for this study. The oral assessment included caries frequency (DMFT indices), number of teeth, probing pocket depths, bleeding on probing, clinical attachment level, as well as radiographs to diagnose apical lesions. The medical examination included a blood analysis, e.g. the determination of the serum concentration of C-reactive protein (CRP). The data analysis showed statistically significant differences between AMI patients and the controls with regard to number of missing teeth (p = 0.001), DMFT index (p = 0.001) and presence of apical lesions of endodontic origin (p = 0.001). Logistic regression showed that the probability of having lesions of endodontic origin was with an odds ratio of 1.54 (95% CI 1.10-2.16; p = 0.012) considerably higher in the AMI patient group. Likewise, the AMI patients had with an odds ratio of 1.21 (95% CI 1.14-1.28; p < 0.001) a higher number of missing teeth. The data from the blood analysis, in particular the CRP values, showed no significant correlation with the number of apical lesions. The results of the present study underline that patients, who have experienced a myocardial infarction, had more missing teeth and a higher number of inflammatory processes, especially of endodontic origin, than healthy patients.


Assuntos
Infarto do Miocárdio/complicações , Periodontite/complicações , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Periodontite/sangue
10.
J Neurochem ; 124(6): 757-69, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23145934

RESUMO

Photoreceptor cells face the challenge of adjusting their function and, possibly, their susceptibility to light damage to the marked daily changes in ambient light intensity. To achieve a better understanding of photoreceptor adaptation at the transcriptional level, this study aimed to identify genes which are under daily regulation in photoreceptor cells using microarray analysis and quantitative PCR. Included in the gene set obtained were a number of genes which up until now have not been shown to be expressed in photoreceptor cells, such as Atf3 (activating transcription factor 3) and Pde8a (phosphodiesterase 8A), and others with a known impact on phototransduction and/or photoreceptor survival, such as Grk1 (G protein-coupled receptor kinase 1) and Pgc-1α (peroxisome proliferator-activated receptor γ, coactivator 1alpha). According to their daily dynamics, the genes identified could be clustered in two groups: those with peak expression during the second part of the day which are uniformly promoted to cycle by light/dark transitions and those with peak expression during the second part of the night which are predominantly driven by a clock. Since Grk1 and Pgc-1α belong in the first group, the present results support a concept in which transcriptional regulation of genes by ambient light contributes to the functional adjustment of photoreceptor cells over the 24-h period.


Assuntos
Regulação da Expressão Gênica , Fotoperíodo , Células Fotorreceptoras/fisiologia , Transdução de Sinais/fisiologia , Transcrição Gênica/fisiologia , Percepção Visual/fisiologia , Animais , Masculino , Estimulação Luminosa/métodos , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley
11.
Int J Cancer ; 132(12): 2849-57, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23175270

RESUMO

Liquid-based cytology (LBC) has replaced conventional cytology (CC) for cervical cancer screening in some countries. However, it remains unclear whether LBC is superior to CC. A randomized controlled trial was conducted between August 2007 and March 2009 in Germany to compare LBC, alone and in combination with computer-assisted imaging technology (CAS), to CC in the detection of histologically confirmed cervical intraepithelial neoplasia (CIN). The main outcome measures were detection rates, relative sensitivities, positive predictive values (PPVs) and relative PPVs comparing LBC without and with CAS to CC. Primary histological outcome was CIN2 or higher. Included were 20,627 women participating in opportunistic cervical cancer screening at 20 gynecologic practices. The practices were randomized weekly to use LBC (n = 11,331) or CC (n = 9,296). Patients with positive findings were invited to expert colposcopy. The relative sensitivity of LBC versus CC using the CIN2+ cut-off was 2.74 (95% confidence interval [CI] 1.66-4.53). The relative sensitivity of LBC/CAS versus CC for CIN2+ was 3.17 (95% CI 1.94-5.19). The PPV of LBC and CC for CIN2+ was 48% and 38%, respectively. The PPV ratio did not differ significantly from unity. Differences between LBC and CC were smaller in some sensitivity and subgroup analyses; however, relative sensitivity of LBC remained increased. LBC without and with CAS compared with CC under the field conditions of an opportunistic screening system had a significantly higher sensitivity for the detection of CIN without deterioration of PPVs. Additional use of CAS did not further improve sensitivity of LBC. © 2012 Wiley Periodicals, Inc.


Assuntos
Citodiagnóstico/métodos , Detecção Precoce de Câncer/métodos , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
12.
Clin Lab ; 59(7-8): 747-55, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24133902

RESUMO

BACKGROUND: Ischemic-type biliary lesions (ITBL) are the most troublesome complications after liver transplantation. Their cause remains unknown and, although some risk factors have been identified, results from different research groups are often conflicting. The goal of this study was to investigate potential risk factors for ITBL. METHODS: 565 transplantations performed between September 1997 and August 2010 were identified and divided into two cohorts: 77 in which the patient developed ITBL and 488 in which no ITBL occurred. The following factors were analyzed: donor age, patient Child-Pugh score, cold ischemia time, total ischemia time, type of perfusion solution, shipped versus non-shipped organ, ABO-compatibility versus identity between donor and recipient, Rhesus-difference versus identity between donor and recipient, presence versus absence of HLA antibodies in the patient at the time of registration on the transplant waiting list, presence in the donor of at least one HLA-C group 1 allele versus at least one HLA-C group 2 allele. HLA-C is the major inhibitory ligand for killer immunoglobulin-like receptors (KIR) that regulate the cytotoxic activity of natural killer cells. HLA-C alleles can be allocated into two groups, HLA-C1 and HLA-C2, based on their KIR specificity. RESULTS: In a multivariate logistic regression analysis the donor age and patient Child-Pugh score C were found to be independent risk factors for ITBL (p < 0.001 and 0.007, respectively). However, the multivariate Cox regression analysis indicated that neither has an impact on graft survival. CONCLUSIONS: Donor age and patient Child-Pugh score predispose to ITBL, whereas other factors must intervene for their development.


Assuntos
Doenças Biliares/etiologia , Transplante de Fígado/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
14.
Neuroendocrinology ; 94(2): 113-23, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21474921

RESUMO

The cyclic nucleotide phosphodiesterase 10A (PDE10A) is highly expressed in striatal spiny projection neurons and represents a therapeutic target for the treatment of psychotic symptoms. As reported previously [J Biol Chem 2009; 284:7606-7622], in this study PDE10A was seen to be additionally expressed in the pineal gland where the levels of PDE10A transcript display daily changes. As with the transcript, the amount of PDE10A protein was found to be under daily and seasonal regulation. The observed cyclicity in the amount of PDE10A mRNA persists under constant darkness, is blocked by constant light and is modulated by the lighting regime. It therefore appears to be driven by the master clock in the suprachiasmatic nucleus (SCN). Since adrenergic agonists and dibutyryl-cAMP induce PDE10A mRNA, the in vitro clock-dependent control of Pde10a appears to be mediated via a norepinephrine → ß-adrenoceptor → cAMP/protein kinase A signaling pathway. With regard to the physiological role of PDE10A in the pineal gland, the specific PDE10A inhibitor papaverine was seen to enhance the adrenergic stimulation of the second messenger cAMP and cGMP. This indicates that PDE10A downregulates adrenergic cAMP and cGMP signaling by decreasing the half-life of both nucleotides. Consistent with its effect on cAMP, PDE10A inhibition also amplifies adrenergic induction of the cAMP-inducible gene arylalkylamine N-acetyltransferase (Aanat) which codes the rate-limiting enzyme in pineal melatonin formation. The findings of this study suggest that Pde10a expression is under circadian and seasonal regulation and plays a modulatory role in pineal signal transduction and gene expression.


Assuntos
Ritmo Circadiano/fisiologia , Diester Fosfórico Hidrolases/metabolismo , Glândula Pineal/enzimologia , Glândula Pineal/fisiologia , Estações do Ano , Transdução de Sinais/fisiologia , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Western Blotting , Ritmo Circadiano/efeitos dos fármacos , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Primers do DNA , Feminino , Imuno-Histoquímica , Imunoprecipitação , Masculino , Técnicas de Cultura de Órgãos , Papaverina/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/genética , Glândula Pineal/efeitos dos fármacos , RNA/biossíntese , RNA/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Núcleo Supraquiasmático/metabolismo , Núcleo Supraquiasmático/fisiologia
16.
Cornea ; 35(3): 342-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26751987

RESUMO

PURPOSE: To evaluate the reproducibility of Fourier domain anterior segment optical coherence tomography (RTVue) based on repeated measurements of corneal thickness (CT) and epithelial thickness (ET) and to test daytime-dependent changes of these parameters. METHODS: Twenty-three eyes from 23 healthy volunteers were included in this prospective study. Three clinical observers performed 3 consecutive measurements each of CT and ET in 3 sessions using RTVue, resulting in 9 measurements per session. Session 1 was performed at 9 AM ± 1 hour, session 2 at 4 PM ± 1 hour on the same day, and session 3 at 9 AM ± 1 hour 2 days later. CT and ET were assessed in 9 areas: corneal vertex, 4 paracentral zones, and 4 peripheral zones. RESULTS: The mean intraclass correlations (ICCs) for intraobserver and interobserver reproducibility were almost perfect (0.81-0.99) for CT in all corneal zones and for ET in all but 2 peripheral zones. Intraobserver ICC was substantial (0.61-0.8) for superior peripheral area and interobserver ICC for superior and inferior peripheral positions. CT and ET decreased significantly from morning to afternoon sessions [-3.15 µm (P < 0.0001) and -0.52 µm (P < 0.0001), respectively]. ET correlated weakly to moderately with CT. CONCLUSIONS: RTVue yields almost perfect reproducibility for CT and ET in central, paracentral, and peripheral lateral zones. Central CT and ET were significantly thinner in the afternoon compared with the morning.


Assuntos
Córnea/anatomia & histologia , Epitélio Corneano/anatomia & histologia , Tomografia de Coerência Óptica/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes
17.
Oncol Lett ; 12(3): 2001-2007, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27602128

RESUMO

The tyrosine kinase c-met alters signaling cascades such as the BRAF-MAPK and PI3K-PKB pathways. These alterations are involved in the carcinogenesis of type I but not type II ovarian cancer (OC). Therefore, the present study investigated the patterns of c-met expression in a cohort of consecutive patients with OC. c-met expression was determined by immunohistochemical analysis. Differences in c-met overexpression among subgroups of established clinicopathological features, including age, histological subtype, tumor stage, histological grading, post-operative tumor burden and completeness of chemotherapy, were determined by χ2 test. Cox regression analyses were performed to determine the prognostic effect of c-met. Survival rates were estimated using the Kaplan-Meier method. A total of 106 patients were enrolled into the study. c-met was overexpressed in 20.8% of the entire cohort; 35.7% of patients with type I OC and 8.6% of patients with type II OC showed overexpression (P=0.001). However, c-met overexpression was not associated with any other established clinicopathological features (all P-values >0.05). Univariate Cox regression analysis showed that overexpression of c-met was associated neither with progression-free survival (PFS) nor with disease-specific survival (DSS) (P=0.835 and P=0.414, respectively). Kaplan-Meier plots also failed to demonstrate an effect of c-met on the 5-year PFS and DSS rates (P=0.938 and P=0.412, respectively). These findings support the hypotheses that the overexpression of c-met is associated with type I but not type II OC, and that overexpression of c-met does not affect the prognosis of OC.

18.
Dig Liver Dis ; 48(3): 291-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26514736

RESUMO

BACKGROUND: Chronic hepatitis C is a major cause of liver-associated mortality caused by decompensated cirrhosis and hepatocellular carcinoma. With the approval of sofosbuvir, therapeutic efficacy has markedly increased. Early changes in non-invasive biomarkers of liver fibrosis under effective antiviral therapy are widely unknown. AIM: To evaluate early changes of fibrosis markers determined by enhanced liver fibrosis (ELF) scores and liver stiffness measurement (FibroScan(®)) in patients treated with sofosbuvir. METHODS: A total of 32 hepatitis C patients treated prospectively with sofosbuvir were included. The ELF-panel and FibroScan measurements were performed at baseline, week 4, end-of-treatment and 12 weeks thereafter. RESULTS: Antiviral therapy resulted in a biochemical and virological response within 4 weeks. Sustained virological response rate at 12-week follow-up (SVR12) was 93.8%; there was a significantly decrease from baseline to 12-week post-treatment follow-up in ELF (10.00 vs. 9.37; p=0.007) and FibroScan (8.0 vs. 6.8 kPa; p=0.016) measurements, indicating improvement of the dynamics of liver fibrosis. CONCLUSION: We observed a rapid decrease in non-invasive fibrosis markers measured by ELF-scores and FibroScan in hepatitis C-infected patients receiving sofosbuvir treatment. These initial results need to be histologically confirmed by liver biopsy in the future.


Assuntos
Antivirais/uso terapêutico , Aspartato Aminotransferases/sangue , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/diagnóstico por imagem , RNA Viral/sangue , Sofosbuvir/uso terapêutico , Técnicas de Imagem por Elasticidade , Feminino , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico por imagem , Humanos , Cirrose Hepática/enzimologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Carga Viral
19.
PLoS One ; 10(8): e0133586, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26317991

RESUMO

AIMS: To investigate the feasibility and to compare three devices measuring intraocular pressure (IOP) in mucopolysaccharidosis patients (MPS): iCare rebound tonometer (RT), Perkins applanation tonometer (PAT) and ocular response analyzer (ORA). METHODS: MPS patients who underwent at least two examinations out of: RT, PAT and ORA at the same visit were identified and retrospectively analyzed in this study. RESULTS: 17 patients fulfilled the inclusion criterion. In all 17 patients IOP measurements were performed with RT (34 eyes) and ORA (33 eyes), while PAT measurement was possible in only 12 (24 eyes) patients. The RT, corneal-compensated intraocular pressure (IOPcc) and Goldmann-correlated intraocular pressure (IOPg) differed relevantly from IOP assessed with PAT. Corneal clouding in MPS patients correlated positively with PAT, RT and IOPg (r = 0.3, 0.5, and 0.5 respectively), but not with IOPcc (r = 0.07). The MPS-related corneal clouding correlated positively with biomechanical corneal parameters assessed with ORA: corneal hysteresis (r = 0.77) and corneal resistance factor (r = 0.77) either. CONCLUSIONS: RT and ORA measurements were tolerated better than applanation tonometry in MPS patients. IOP measurements assessed with RT and ORA differed relevantly from PAT. Corneal-compensated IOP assessed with ORA seems to be less affected by the MPS-related corneal clouding than applanation or rebound tonometry. RT and ORA measurements should be preferred for IOP assessment in patients with MPS.


Assuntos
Córnea/fisiopatologia , Glaucoma/diagnóstico , Mucopolissacaridoses/fisiopatologia , Tonometria Ocular/instrumentação , Adolescente , Adulto , Criança , Córnea/patologia , Estudos de Viabilidade , Feminino , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Mucopolissacaridoses/complicações , Mucopolissacaridoses/patologia , Adulto Jovem
20.
PLoS One ; 10(8): e0132754, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26296089

RESUMO

Patients who have survived malignant melanoma for more than five years may lack the opportunity to talk about their burden. As a consequence their psychosocial care needs remain undetected and available supportive interventions may not be utilised. Therefore, the psychosocial burden of this patient group needs to be assessed using specific screening instruments. The aim of this study was to investigate the psychosocial burden of long-term melanoma survivors, their psychosocial care needs and the determinants of these needs. We wanted to find out if the use of professional support corresponds to the care needs defined by experts. Using the cancer registry of Rhineland-Palatinate, melanoma patients diagnosed at least 5 years before the survey were contacted by physicians. N = 689 former patients completed the Hornheide Questionnaire (short form HQ-S) to identify psychosocial support need (scale cut off ≥ 16 or item-based cut-off score) and the potential psychosocial determinants of these needs. Additionally, they were asked about their utilisation of the professional support system. More than one third (36%) of them was in need for professional psychosocial support. The highest burden scores concerned worry about tumour progression. Younger age (< 50), higher general fatigue, higher symptom burden, lower general health, negative social interactions and unfulfilled information needs were significant predictors of the need for psychosocial intervention. Related to the percentage of survivors identified as 'in need', the professional support system was underused. Further studies should investigate whether using the HQ-S to routinely identify burdened melanoma patients could lead to better fulfilment of their intervention needs, ultimately enhancing health-related quality of life.


Assuntos
Ansiedade/psicologia , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Melanoma/psicologia , Qualidade de Vida/psicologia , Sobreviventes/psicologia , Adulto , Idoso , Ansiedade/fisiopatologia , Feminino , Mau Uso de Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Melanoma/fisiopatologia , Pessoa de Meia-Idade , Neoplasias Cutâneas , Apoio Social , Inquéritos e Questionários , Melanoma Maligno Cutâneo
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