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1.
Proc Natl Acad Sci U S A ; 119(18): e2120241119, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35452330

RESUMO

SignificanceDue to active plate tectonics, there are no direct rock archives covering the first ca. 500 million y of Earth's history. Therefore, insights into Hadean geodynamics rely on indirect observations from geochemistry. We present a high-precision 182W dataset for rocks from the Kaapvaal Craton, southern Africa, revealing the presence of Hadean protocrustal remnants in Earth's mantle. This has broad implications for geochemists, geophysicists, and modelers, as it bridges contrasting 182W isotope patterns in Archean and modern mantle-derived rocks. The data reveal the origin of seismically and isotopically anomalous domains in the deep mantle and also provide firm evidence for the operation of silicate differentiation processes during the first 60 million y of Earth's history.

2.
Z Gerontol Geriatr ; 56(7): 573-579, 2023 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-36205776

RESUMO

BACKGROUND: In the event of a COVID-19-related absence from an outpatient treatment program, patients suffering from dementia and their caregivers were offered support from a distance. The aim was to examine the extent of the participants' burden as well as how the offer was accepted and evaluated. MATERIAL AND METHODS: All participants (n = 63) were offered supportive telephone contact over a period of 8 weeks at varying frequencies (weekly, fortnightly). In addition patients received cognitive and physical tasks by mail every 2 weeks. In order to examine the acceptance of the support, data collected from clinical routine were included in a treatment observation. Additionally, all participants were asked to evaluate the support retrospectively. RESULTS: Out of 63 contacted participants, 45 were included in the treatment observation. The telephone support was very well accepted and a tendency towards higher agreement could be ascertained by caregivers. The experience of burden remained stable at a moderate level for all participants; however, caregivers were significantly more burdened. CONCLUSION: The present treatment observation shows the acceptance of a location-independent psychosocial treatment program for dementia for future pandemics or treatment failure as well as for the routine care, e.g. for patients with restricted mobility or those living in rural areas without direct hospital connection. In particular, our data strengthen the importance of programs for caregivers in order to alleviate their burden.

3.
Phys Rev Lett ; 126(20): 207201, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34110224

RESUMO

We present a combined experimental and theoretical study of the mineral atacamite Cu_{2}Cl(OH)_{3}. Density-functional theory yields a Hamiltonian describing anisotropic sawtooth chains with weak 3D connections. Experimentally, we fully characterize the antiferromagnetically ordered state. Magnetic order shows a complex evolution with the magnetic field, while, starting at 31.5 T, we observe a plateaulike magnetization at about M_{sat}/2. Based on complementary theoretical approaches, we show that the latter is unrelated to the known magnetization plateau of a sawtooth chain. Instead, we provide evidence that the magnetization process in atacamite is a field-driven canting of a 3D network of weakly coupled sawtooth chains that form giant moments.

4.
Eur J Neurol ; 27(8): 1638-1646, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32337811

RESUMO

BACKGROUND AND PURPOSE: Although patient-centredness is considered a key component of high-quality neurological care, it is unclear to what extent it can or should be implemented during the acute phase. Using acute stroke as an example, the aim was to identify critical junctures for patient-centredness along the acute care pathway from the perspectives of patients, relatives and staff. METHODS: A qualitative multi-method study was conducted including 27 non-participant observations and 37 semi-structured interviews with patients, relatives and staff. Junctures were defined as critical when mentioned (as problematic) in two or three information sources (i.e. observations, staff interviews, or patient and relative interviews), as potentially critical when mentioned in one, and as uncritical when not mentioned. RESULTS: Post-procedure communication after thrombectomy, patients' stay at the stroke unit and decision-making around transfer, discharge and rehabilitation were identified as critical junctures for patient-centredness. Arrival at the emergency department and the (thrombectomy) treatment itself were identified as uncritical junctures, whilst history-taking and treatment preparation, the treatment decision and patients' stay at the intensive care unit were identified as potentially critical junctures. CONCLUSIONS: In acute stroke care, patients, relatives and staff prioritize fast over patient-centred decision-making in the most time-critical phases, especially before and during treatment. This is reversed after the procedure, when difficulties arise implementing a patient-centred approach in clinical practice. To improve patient-centredness where it is most needed, clear guidelines and accessible resources are recommended. Future research should investigate whether insights from acute phases of stroke care are applicable to other neurological conditions as well.


Assuntos
Assistência Centrada no Paciente , Acidente Vascular Cerebral , Cuidados Críticos , Humanos , Pesquisa Qualitativa , Qualidade da Assistência à Saúde , Acidente Vascular Cerebral/terapia
6.
Arch Gynecol Obstet ; 299(3): 847-855, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30607592

RESUMO

PURPOSE: Annual cervical cancer screening is recommended in Germany as a part of the statutory preventive care. Abnormal results can provoke psychological distress and anxiety, compromising women's adherence. Little is known about how a cervical dysplasia impacts adherence follow-up visits and prevention habits over time. To optimize care strategies, this study aims to identify women at risk for nonadherence to follow-up visits after a screening event. METHODS: Between November 2015 and May 2017, participants with an abnormal Pap smear at the Heidelberg and Leipzig University Hospitals received a four-part questionnaire (sociodemographic data, PHQ-D, self-designed fear and prevention habit questions) at the first consultation (T1) and subsequently after 3 (T2) and 6 (T3) months; healthy controls completed the questionnaire at T1. RESULTS: 132 women with an abnormal Pap smear [with conization: S1 (n = 68, 51.5%), without intervention: S2 (n = 64, 48.5%)] and healthy controls (K, n = 101) generally adhered to gynecological checkups, except S1 6 months after the first diagnosis (S1/T3 - 0.47, signed rank p < 0.0005). Knowledge of primary prevention information, i.e., HPV vaccination, was significantly higher among K (K 58%, S1 29%, S2 44%, Chi-squared p = 0.01) as was vaccine uptake (K 39% versus S1/S2 7% and 17%, respectively, Chi-squared p = 0.0004). Fear of upcoming Pap smears rose significantly over time (S1/T1-S1/T2-S1/T3, Wilcoxon signed-rank test p < 0.001) and was higher among those with conization at T2 (Chi-square test, p = 0.01) and partially accompanied by panic disorders at T1 (Chi-square test p = 0.035). Realization of general preventive habits rose significantly among women without an operative procedure (S2) over the study. CONCLUSION: This study advances the understanding of non-participation in follow-up visits after a dysplasia diagnosis, identifying post-conization women as a special risk group for decreased adherence.


Assuntos
Conização/métodos , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Adulto Jovem
7.
Br J Dermatol ; 178(1): 207-214, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28733990

RESUMO

BACKGROUND: Neutrophil (polymorphonuclear) granulocytes (PMN) have been shown to contribute to the pathogenesis of psoriasis by releasing interleukin-17 and LL37-DNA complexes via neutrophil extracellular traps (NETs), webs of chromatin strands decorated with antimicrobial peptides, in psoriatic skin. Fumaderm® , a fumaric acid ester (FAE) formulation consisting of different FAE salts, has been successfully used to treat psoriasis for decades. Most recently, FAE treatment was reported to inhibit NET formation in murine epidermolysis bullosa acquisita. OBJECTIVES: To elucidate the effect of FAE treatment on human psoriasis and healthy donor NET formation. RESULTS: Among the compounds present in the FAE formulation, dimethyl fumarate (DMF) pretreatment of human psoriasis and healthy donor PMN resulted in a consistent inhibitory effect on NET formation in response to phorbol 12-myristate 13-acetate but not to platelet activating factor and ionomycin. This effect was l-glutathione (GSH) dependent and involved a decrease in reactive oxygen species (ROS) production, a key event in NET formation. In contrast, G-protein-coupled signalling and protein synthesis were not involved. Monomethyl fumarate (MMF) was found to slightly reduce ROS production without affecting NET formation. CONCLUSIONS: We report DMF as a potent, stimulus-specific, GSH- and ROS-dependent modulator of NET formation. Our results support the notion that modulation of NET formation contributes to the beneficial effects of FAEs in a variety of inflammatory conditions.


Assuntos
Fármacos Dermatológicos/farmacologia , Fumarato de Dimetilo/farmacologia , Armadilhas Extracelulares/efeitos dos fármacos , Psoríase/tratamento farmacológico , Análise de Variância , Antioxidantes/farmacologia , Caspases/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Fumaratos/farmacologia , Proteínas de Ligação ao GTP/metabolismo , Glutationa/metabolismo , Humanos , Ionomicina/farmacologia , Fator de Ativação de Plaquetas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo , Acetato de Tetradecanoilforbol/farmacologia
8.
Br J Dermatol ; 179(2): 405-412, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29479687

RESUMO

BACKGROUND: The inflammatory tumour microenvironment is crucial for effective tumour control, and long-term immunosuppression has been identified as a major risk factor for skin carcinogenesis. In solid organ transplant recipients (OTRs) undergoing long-term pharmacological immunosuppression, an increased incidence of cutaneous squamous cell carcinoma (SCC) and more aggressive tumour growth compared with immunocompetent patients has been reported. OBJECTIVES: To determine the density and phenotype of immune cells infiltrating SCC and surrounding skin in OTRs, and to characterize the microanatomical distribution patterns in comparison with immunocompetent patients. METHODS: We analysed immune cell infiltrates within SCC and at defined regions of interest (ROIs) of tumour-surrounding skin in formalin-fixed paraffin-embedded tissue of 20 renal transplant patients and 18 carefully matched immunocompetent patients by high-resolution semiautomated microscopy on complete tissue sections stained for CD4, CD8, CD20 and CD68. RESULTS: The overall immune cell density of SCC arising in OTRs was significantly reduced compared with immunocompetent patients. Particularly CD4+ infiltrates at the directly invasive margin and tumour vicinity, intratumoral CD8+ T-cell densities and the overall density of CD20+ tumour-infiltrating B cells were significantly reduced in the tissue of OTRs. CONCLUSIONS: Immune cell infiltrates within SCC and at defined ROIs of tumour-surrounding skin in OTRs differ markedly in their composition and microanatomical distribution compared with tumours arising in immunocompetent patients. Our findings substantially broaden the understanding of how long-term systemic immunosuppression modulates the local inflammatory microenvironment in the skin and at the site of invasive SCC.


Assuntos
Carcinoma de Células Escamosas/imunologia , Terapia de Imunossupressão/efeitos adversos , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Cutâneas/imunologia , Pele/citologia , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Carcinoma de Células Escamosas/patologia , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Hospedeiro Imunocomprometido , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pele/imunologia , Pele/patologia , Neoplasias Cutâneas/patologia , Linfócitos T/imunologia , Transplantados , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
9.
Nature ; 485(7400): 627-30, 2012 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-22660324

RESUMO

Earth's lithosphere probably experienced an evolution towards the modern plate tectonic regime, owing to secular changes in mantle temperature. Radiogenic isotope variations are interpreted as evidence for the declining rates of continental crustal growth over time, with some estimates suggesting that over 70% of the present continental crustal reservoir was extracted by the end of the Archaean eon. Patterns of crustal growth and reworking in rocks younger than three billion years (Gyr) are thought to reflect the assembly and break-up of supercontinents by Wilson cycle processes and mark an important change in lithosphere dynamics. In southern West Greenland numerous studies have, however, argued for subduction settings and crust growth by arc accretion back to 3.8 Gyr ago, suggesting that modern-day tectonic regimes operated during the formation of the earliest crustal rock record. Here we report in situ uranium-lead, hafnium and oxygen isotope data from zircons of basement rocks in southern West Greenland across the critical time period during which modern-like tectonic regimes could have initiated. Our data show pronounced differences in the hafnium isotope-time patterns across this interval, requiring changes in the characteristics of the magmatic protolith. The observations suggest that 3.9-3.5-Gyr-old rocks differentiated from a >3.9-Gyr-old source reservoir with a chondritic to slightly depleted hafnium isotope composition. In contrast, rocks formed after 3.2 Gyr ago register the first additions of juvenile depleted material (that is, new mantle-derived crust) since 3.9 Gyr ago, and are characterized by striking shifts in hafnium isotope ratios similar to those shown by Phanerozoic subduction-related orogens. These data suggest a transitional period 3.5-3.2 Gyr ago from an ancient (3.9-3.5 Gyr old) crustal evolutionary regime unlike that of modern plate tectonics to a geodynamic setting after 3.2 Gyr ago that involved juvenile crust generation by plate tectonic processes.

10.
Internist (Berl) ; 59(10): 1106-1113, 2018 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-30046890

RESUMO

The examination of peripheral blood smears is not only essential for the differential diagnostics of hematological diseases but can also provide important indications for general internal diseases, infections, hereditary diseases and poisoning. By the systematic analysis of a blood smear for alterations to thrombocytes, erythrocytes and leukocytes, a blood smear investigation can make a decisive contribution to the formulation of a diagnosis. In this way evidence of rare diseases can also be gained when taking the corresponding clinical findings into consideration.


Assuntos
Doenças Hematológicas , Anomalia de Pelger-Huët , Doenças Raras/sangue , Diagnóstico Diferencial , Eritrócitos , Humanos
11.
NMR Biomed ; 30(2)2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28028862

RESUMO

Ultra-high field (UHF, ≥7 T) tight fit transceiver phased arrays improve transmit (Tx) efficiency (B1+ /√P) in comparison with Tx-only arrays, which are usually larger to fit receive (Rx)-only arrays inside. One of the major problems limiting applications of tight fit arrays at UHFs is the anticipated increase of local tissue heating, which is commonly evaluated by the local specific absorption rate (SAR). To investigate the tradeoff between Tx efficiency and SAR when a tight fit UHF human head transceiver phased array is used instead of a Tx-only/Rx-only RF system, a single-row eight-element prototype of a 400 MHz transceiver head phased array was constructed. The Tx efficiency and SAR of the array were evaluated and compared with that of a larger Tx-only array, which could also be used in combination with an 18-channel Rx-only array. Data were acquired on the Siemens Magnetom whole body 9.4 T human MRI system. Depending on the head size, positioning and the RF shim strategy, the smaller array provides from 11 to 23% higher Tx efficiency. In general, the Tx performance, evaluated as B1+ /√SAR, i.e. the safety excitation efficiency (SEE), is also not compromised. The two arrays provide very similar SEEs evaluated over 1000 random RF shim sets. We demonstrated that, in general, the tight fit transceiver array improves Tx performance without compromising SEE. However, in specific cases, the SEE value may vary, favoring one of the arrays, and therefore must be carefully evaluated.


Assuntos
Absorção de Radiação/fisiologia , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Imageamento por Ressonância Magnética/instrumentação , Exposição à Radiação/análise , Transdutores , Transferência de Energia , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Campos Magnéticos , Imagens de Fantasmas , Doses de Radiação , Exposição à Radiação/prevenção & controle , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
Unfallchirurg ; 120(6): 461-471, 2017 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-28540567

RESUMO

BACKGROUND: The increase in endoprosthetic and osteosynthetic surgical treatment is associated with a simultaneous increase in implant-associated infections (surgical site infections, SSI). Biofilms appear to play a significant role in the diagnosis and treatment of these infections and heavily contaminated wounds. This article aims to provide a current overview of biofilm and its relevance in orthopedic surgery. MATERIALS AND METHODS: A computer-assisted literature search of MedLine (PubMed) was performed using key word combinations with "biofilm" (as of March 2017). RESULTS: Biofilm, a polymicrobial organization and life form surrounded by a polysaccharide matrix, refers to an adaptation strategy of bacteria in unfavorable living conditions (e. g. under antibiotic therapy). Biofilms can develop after 6 h in highly contaminated wounds. In acute and chronic infections, biofilms can occur in 30-80 % of the cases. Only planktonic bacteria (high metabolic activity, cultivable) can be detected in standard microbiological cultures, biofilms, however, cannot. Molecular microscopic methods, such as fluorescence in situ hybridization (FISH), enable the detection of bacteria in biofilms. The core concepts of anti-biofilm therapy include the prevention of biofilm and early surgical debridement, followed by the local and/or systemic administration of antibiotics as well as the local application of antiseptics. CONCLUSIONS: The development of biofilm should be anticipated in strongly contaminated wounds as well as in acute and chronic infection sites. The best strategy to combat biofilms is to prevent their development. Standard microbiological culture methods do not enable the detection of biofilm. Therefore, the implementation of molecular biological detection methods (z. B. FISH) is important. Further anti-biofilm strategies are being investigated experimentally, but there are no real options for clinical use as of yet.


Assuntos
Antibacterianos/administração & dosagem , Infecções Bacterianas/terapia , Biofilmes/efeitos dos fármacos , Desbridamento/métodos , Tratamento de Ferimentos com Pressão Negativa/métodos , Procedimentos Ortopédicos/efeitos adversos , Infecção da Ferida Cirúrgica/terapia , Terapia Combinada/métodos , Medicina Baseada em Evidências , Humanos , Infecção da Ferida Cirúrgica/etiologia , Resultado do Tratamento
13.
Phys Rev Lett ; 116(4): 047202, 2016 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-26871354

RESUMO

Low-temperature neutron diffraction and NMR studies of field-induced phases in linarite are presented for magnetic fields H∥b axis. A two-step spin-flop transition is observed, as well as a transition transforming a helical magnetic ground state into an unusual magnetic phase with sine-wave-modulated moments ∥H. An effective J[over ˜]_{1}-J[over ˜]_{2} single-chain model with a magnetization-dependent frustration ratio α_{eff}=-J[over ˜]_{2}/J[over ˜]_{1} is proposed. The latter is governed by skew interchain couplings and shifted to the vicinity of the ferromagnetic critical point. It explains qualitatively the observation of a rich variety of exotic longitudinal collinear spin-density wave, SDW_{p}, states (9≥p≥2).

14.
Vox Sang ; 111(2): 178-86, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27509033

RESUMO

BACKGROUND AND OBJECTIVES: Biosimilars of the granulocyte colony stimulating factor (G-CSF) filgrastim were approved by the European Medicines Agency (EMA) for registered indications of the originator G-CSF, including prevention and treatment of neutropenia, as well as mobilization of peripheral blood stem cells in 2008. Nevertheless, there is still an ongoing debate regarding the quality, efficacy and safety of biosimilar G-CSF. MATERIALS AND METHODS: This article is a meta-analysis of clinical studies on the use of biosimilar G-CSF for mobilization and transplantation of haematopoietic stem cells as available in public databases. All data sets were weighted for the number of patients and parameters and then subjected to statistical meta-analysis employing the Mann-Whitney U-test followed by the Hodges-Lehmann estimator to assess differences between biosimilar and originator G-SCF. RESULTS: A total of 1892 individuals, mostly with haematological malignancies but also including 351 healthy donors have been successfully mobilized for autologous or allogeneic stem cell transplantation using biosimilar G-CSF (Zarzio(TM) : 1239 individuals; Ratiograstim(TM) /Tevagrastim(TM) : 653 individuals). A total of 740 patients with multiple myeloma, 491 with non-Hodgkin's lymphoma (NHL), 150 with Hodgkin's lymphoma (HL) and other diseases are included in this meta-analysis, as well as 161 siblings and 190 volunteer unrelated donors. For biosimilar and originator G-CSF, bioequivalence was observed for the yield of CD34+ stem cells as well as for the engraftment of the transplants. CONCLUSION: Biosimilar G-CSF has equivalent effects and safety as originator G-CSF.


Assuntos
Medicamentos Biossimilares/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico/citologia , Bases de Dados Factuais , Fator Estimulador de Colônias de Granulócitos/genética , Fator Estimulador de Colônias de Granulócitos/metabolismo , Mobilização de Células-Tronco Hematopoéticas , Humanos , Mieloma Múltiplo/terapia , Células-Tronco de Sangue Periférico/metabolismo , Transplante Autólogo , Transplante Homólogo
15.
Pneumologie ; 70(10): 630-637, 2016 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-27050448

RESUMO

Pulmonary arterial hypertension (PAH) is a rare disease characterised by vascular remodelling of the small lung arteries leading to a decrease of the vessel lumen and eventually to occlusion. According to the current guidelines, PAH is defined by a pulmonary arterial pressure ≥ 25 mmHg, an arterial wedge pressure ≤ 15 mmHg, and an elevated pulmonary vascular resistance (PVR > 3 WU). The current pathophysiological concepts include disturbances in the production, deposition and composition of the extracellular matrix, inflammatory processes, mutations in the BMPR2 gene as well as mutations in the KCNK3 gene. During the last few years, epigenetic and genetic investigations resulted in new findings which are highly relevant for the diagnosis, prognosis and therapy of PAH. These findings could lead to the development of new, individualised therapy strategies. Currently, several phase I and phase II studies are in progress, in which promising new substances are examined.


Assuntos
Terapia Genética/métodos , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/terapia , Terapia de Alvo Molecular/métodos , Medicina de Precisão/métodos , Medicina Baseada em Evidências , Predisposição Genética para Doença/genética , Humanos , Hipertensão Pulmonar/diagnóstico , Resultado do Tratamento
16.
Phys Rev Lett ; 115(24): 242502, 2015 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-26705628

RESUMO

Two short-lived isotopes ^{221}U and ^{222}U were produced as evaporation residues in the fusion reaction ^{50}Ti+^{176}Yb at the gas-filled recoil separator TASCA. An α decay with an energy of E_{α}=9.31(5) MeV and half-life T_{1/2}=4.7(7) µs was attributed to ^{222}U. The new isotope ^{221}U was identified in α-decay chains starting with E_{α}=9.71(5) MeV and T_{1/2}=0.66(14) µs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.

18.
Pathologe ; 36(3): 261-70, 2015 May.
Artigo em Alemão | MEDLINE | ID: mdl-25986886

RESUMO

Neuroendocrine neoplasms (NEN) of the breast are specific tumor entities. According to the literature up to 5% of breast neoplasms are malignant epithelial neoplasms of the breast. They are defined by a neuroendocrine (NE) architecture and cytology combined with an expression of the neuroendocrine vesicle markers chromogranin A and/or synaptophysin. The diagnosis is supplemented by the receptor status and the proliferative activity. According to the World Health Organization (WHO) classification of 2012 the following groups of NEN are distinguished: (1) invasive breast carcinoma with NE differentiation, (2) well-differentiated neuroendocrine tumor (NET) and (3) poorly differentiated small cell carcinoma (NEC). This review article focuses on (1) the definition and basic principles of diagnostics, (2) the history, nomenclature and WHO classification from 2003 and 2012, (3) the frequency of breast NEN, (4) the hereditary background and functional activity, (5) the expression of receptors and (6) the possible clinical implications. In addition, the first results of a retrospective single center study (n = 465 patients with breast cancer over a time period of 4 years) on the frequency of NEN of the breast at the Breast Center of the University Hospital Düsseldorf are presented. In this study a frequency of 4.5% of NEN was found based on a diagnostic cut-off of > 50% Chromogranin A and/or synaptophysin positive tumor cells.


Assuntos
Neoplasias da Mama/patologia , Tumores Neuroendócrinos/patologia , Biomarcadores Tumorais/análise , Mama/patologia , Proliferação de Células , Cromogranina A/análise , Feminino , Humanos , Invasividade Neoplásica , Prognóstico , Sinaptofisina/análise
19.
Ir Med J ; 108(10): 312-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26817292

RESUMO

DHPR deficiency is a rare autosomal recessively inherited metabolic disorder of tetrahydrobiopterin (BH4) regeneration. Clinical symptoms may comprise microcephaly, developmental delay, ataxia and seizures. BH4 is the cofactor for the enzyme phenylalanine (Phe)hydroxylase (PAH), and for tryptophan and tyrosine hydroxylases, both of which are essential for serotonin and dopamine biosynthesis. We present four patients in two families who are being treated at the National Centre for Inherited Metabolic Disorders (NCIMD). All are members of the Irish Traveller population. We have identified a homozygous mutation, c.353C>T, in the DHPR (QDPR) gene which, to the best of our knowledge, has not been previously described. The mainstay of treatment is a life-long Phe-restricted diet together with supplementation of L-dopa and 5-hydroxy tryptophan (5-HT) and folinic acid. In Ireland, there is neurological comorbidity in our adult DHPR patients, although the overall outcome is satisfactory and one affected female has three healthy children.


Assuntos
Di-Hidropteridina Redutase/genética , Fenilcetonúrias/genética , Adulto , Feminino , Humanos , Lactente , Masculino
20.
Phys Rev Lett ; 112(17): 172501, 2014 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-24836239

RESUMO

The superheavy element with atomic number Z=117 was produced as an evaporation residue in the (48)Ca+(249)Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-µs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope (294)117 and its decay products. A hitherto unknown α-decay branch in (270)Db (Z = 105) was observed, which populated the new isotope (266)Lr (Z = 103). The identification of the long-lived (T(1/2) = 1.0(-0.4)(+1.9) h) α-emitter (270)Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an "island of stability."

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