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1.
Nanotechnology ; 35(11)2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38081076

RESUMO

Laser-induced graphene (LIG) possesses desirable properties for numerous applications. However, LIG formation on biocompatible substrates is needed to further augment the integration of LIG-based technologies into nanobiotechnology. Here, LIG formation on cross-linked sodium alginate is reported. The LIG is systematically investigated, providing a comprehensive understanding of the physicochemical characteristics of the material. Raman spectroscopy, scanning electron microscopy with energy-dispersive x-ray analysis, x-ray diffraction, transmission electron microscopy, Fourier-transform infrared spectroscopy and x-ray photoelectron spectroscopy techniques confirm the successful generation of oxidized graphene on the surface of cross-linked sodium alginate. The influence of laser parameters and the amount of crosslinker incorporated into the alginate substrate is explored, revealing that lower laser speed, higher resolution, and increased CaCl2content leads to LIG with lower electrical resistance. These findings could have significant implications for the fabrication of LIG on alginate with tailored conductive properties, but they could also play a guiding role for LIG formation on other biocompatible substrates.

2.
Eur J Nucl Med Mol Imaging ; 49(2): 721-731, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34342669

RESUMO

PURPOSE: 68 Ga-FAPI (fibroblast activation protein inhibitor) is a rapidly evolving and highly promising radiotracer for PET/CT imaging, presenting excellent results in a variety of tumor entities, particularly in epithelial carcinomas. This retrospective analysis sought to evaluate the potential and impact of FAPI-PET/CT in rare cancer diseases with respect to improvement in staging and therapy, based on tracer uptake in normal organs and tumors. MATERIAL AND METHODS: Fifty-five patients with rare tumor entities, defined by a prevalence of 1 person out of 2000 or less, received a 68 Ga-FAPI-PET/CT scan. Fourteen women and 41 men (median age 60) were included within the following subgroups: cancer of unknown primary (n = 10), head and neck cancer (n = 13), gastrointestinal and biliary-pancreatic cancer (n = 17), urinary tract cancer (n = 4), neuroendocrine cancer (n = 4), and others (n = 7). Tracer uptake was quantified by standardized uptake values SUVmax and SUVmean and the tumor-to-background ratio (TBR) was determined (SUVmax tumor/SUVmean organ). RESULTS: In 20 out of 55 patients, the primary tumor was identified and 31 patients presented metastases (n = 88), characterized by a high mean SUVmax in primary (10.1) and metastatic lesions (7.6). The highest uptake was observed in liver metastases (n = 6) with a mean SUVmax of 9.8 and a high TBR of 8.7, closely followed by peritoneal carcinomatosis (n = 16) presenting a mean SUVmax of 9.8 and an excellent TBR of 29.6. In terms of the included subgroups, the highest uptake regarding mean SUVmax was determined in gastrointestinal and biliary-pancreatic cancer with 9.8 followed closely by urinary tract cancer with 9.5 and head and neck cancer (9.1). CONCLUSION: Due to excellent tumor visualization and, thereby, sharp contrasts in terms of high TBRs in primary and metastatic lesions in different rare malignancies, 68 Ga-FAPI-PET/CT crystallizes as a powerful and valuable imaging tool, particularly with respect to epithelial carcinomas, and therefore an enhancement to standard diagnostics imaging methodologies. The realization of further and prospective studies is of large importance to confirm the potential of FAP imaging in oncology.


Assuntos
Neoplasias Pancreáticas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Transporte Biológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Estudos Retrospectivos
3.
Eur Radiol ; 32(7): 4521-4526, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35118530

RESUMO

OBJECTIVE: Arterial spin labeling blood perfusion signal relies on the difference between a label and a control image. Background suppression pulses are commonly used to improve the contrast, yet these are based on estimates of tissue relaxation times. The aim of this study is to improve the perfusion contrast by individualizing the timing of these background suppression pulses by means of T1 mapping. METHODS: The optimized timing of the background suppression pulses is obtained by rapid T1 mapping employing the variable flip angle technique. Ten healthy volunteers were included in this study. To compare the results, visual grading and the Wilcoxon signed-rank test was used comparing three categories of image quality. RESULTS: The readers confirmed that the images of the proposed method generally show a higher signal-to-background ratio and cortical structures are better visible. Noise was mostly comparable to the standard method. Relative blood flow was statistically significant higher in the modified method. CONCLUSION: The individually optimized background suppression pulses improve the image appearance and allow for a better visualization of cortical structures. The proposed technique however prolongs scan time, which can be seen as negative result, yet needs to be further evaluated. KEY POINTS: • Background suppression timing in ASL can vary. • Both the label and control condition can be modified for T1 mapping. • Adapting the pulse timing improves the signal-to-background ratio.


Assuntos
Algoritmos , Artérias , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Perfusão , Razão Sinal-Ruído , Marcadores de Spin
4.
Eur J Nucl Med Mol Imaging ; 48(12): 3918-3924, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34018010

RESUMO

PURPOSE: A high expression of fibroblast activation protein (FAP) was observed in multiple sarcomas, indicating an enormous potential for PET/CT using 68Ga-radiolabeled inhibitors of FAP (FAPI). Therefore, this retrospective study aimed to evaluate the role of the novel hybrid imaging probe for sarcomas as a first clinical evaluation. METHODS: A cohort of 15 patients underwent 68Ga-FAPI-PET/CT for staging or restaging. The acquisition of PET scans was performed 60 min after administration of 127 to 308 MBq of the tracer. The uptake of 68Ga-FAPI in malignant tissue as well as in healthy organs was quantified by standardized uptake values SUVmean and SUVmax. RESULTS: Excellent tumor-to-background ratios (> 7) could be achieved due to low background activity and high SUVmax in primary tumors (median 7.16), local relapses (median 11.47), and metastases (median 6.29). The highest uptake was found for liposarcomas and high-grade disease (range 18.86-33.61). A high SUVmax (> 10) was observed for clinically more aggressive disease. CONCLUSION: These preliminary findings suggest a high potential for the clinical use of 68Ga-FAPI-PET/CT for patients diagnosed with sarcoma.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sarcoma , Humanos , Ligantes , Recidiva Local de Neoplasia , Estudos Retrospectivos , Sarcoma/diagnóstico por imagem
5.
Eur J Nucl Med Mol Imaging ; 48(4): 1178-1187, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33057927

RESUMO

PURPOSE: In cancer of unknown primary (CUP), positron emission tomography/computed tomography (PET/CT) with the glucose analog [18F]FDG represents the standard imaging approach for localization of the malignant primary. Frequently, however, [18F]FDG PET/CT cannot precisely distinguish between small occult tumors and chronic inflammation, especially in Waldeyer's tonsillar ring. To improve the accuracy for detecting primary tumors in the Waldeyer's tonsillar ring, the novel PET tracer [68Ga]Ga-FAPI-4 for specific imaging of fibroblast activation protein (FAP) expression was used as a more specific target for cancer imaging. METHODS: Eight patients with suspicion of a malignant tumor in Waldeyer's tonsillar ring or a CUP syndrome were examined. PET/CT scans with [18F]-FDG and [68Ga]Ga-FAPI-4 were performed for pre-operative tumor localization. After surgical resection, histopathological and immunohistochemical results were compared to PET/CT findings. RESULTS: Histopathology revealed a palatine or lingual tonsil carcinoma in all patients. In case of lymph node metastases smaller than 7 mm in size, the [18F]FDG PET/CT detection rate of cervical lymph node metastases was higher than that of [68Ga]FAPI PET/CT, while both tracers identified the primary tumors in all eight cases. The size of the primary and the lymph node metastases was directly correlated to the respective FAP expression, as detected by immunohistochemistry. The mean SUVmax for the primary tumors was 21.29 ± 7.97 for 18F-FDG and 16.06 ± 6.29 for 68Ga-FAPI, respectively (p = 0.2). The mean SUVmax for the healthy contralateral tonsils was 8.38 ± 2.45 for [18F]FDG and 3.55 ± 0.47 for [68Ga]FAPI (p < 0.001). The SUVmax ratio of [68Ga]FAPI was significantly different from [18F] FDG (p = 0.03). Mean TBRmax for the [68Ga]Ga-FAPI-4 tracer was markedly higher in comparison to [18F]FDG (10.90 vs. 4.11). CONCLUSION: Non-invasive imaging of FAP expression by [68Ga]FAPI PET/CT resulted in a better visual detection of the malignant primary in CUP, as compared to [18F]FDG imaging. However, the detection rate of lymph node metastases was inferior, presumably due to low FAP expression in small metastases. Nevertheless, by offering a detection method for primary tumors with the potential of lower false positive rates and thus avoiding biopsies, patients with CUP syndrome may benefit from [68Ga]FAPI PET/CT imaging.


Assuntos
Neoplasias Primárias Desconhecidas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Radioisótopos de Gálio , Humanos , Linfonodos , Neoplasias Primárias Desconhecidas/diagnóstico por imagem
6.
Nervenarzt ; 88(6): 607-615, 2017 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-28424823

RESUMO

Coma of unknown origin (CUO) is a frequent unspecific emergency symptom associated with a high mortality. A fast diagnostic work-up is essential given the wide spectrum of underlying diagnoses that are made up of approximately 50% primary central nervous system (CNS) pathologies and approximately 50% extracerebral, almost exclusively internal medical causes. Despite the high mortality associated with this symptom, there are currently no generally accepted management guidelines for adult patients presenting with CUO. We propose an interdisciplinary standard operating procedure (SOP) for patients with acute CUO as has been established in our maximum care hospital. The SOP is triggered by simple triage criteria that are sufficient to identify CUO patients before arrival in hospital. The in-hospital response team is led by a neurologist. Collaboration with nursing staff, internal medicine, anesthesiology, neurosurgery and trauma surgery is organized along structured pathways that include standardized laboratory tests, including cerebrospinal fluid (CSF), toxicology, computed tomography (CT) and CT angiography imaging (CTA). Our data suggest that neurologists and internists need to be placed at the beginning of the diagnostic work-up. Imaging should not just be carried out depending on the clinical syndrome because sensitivity, specificity and inter-rater reliability of the latter are not sufficient and because in many cases, multiple pathologies can be detected that could each explain CUO alone. Clinical examination, imaging and laboratory testing should be regarded as components of an integrative diagnostic approach and the final aetiological classification should only be made after the diagnostic work-up is complete.


Assuntos
Coma/diagnóstico , Coma/terapia , Estado Terminal/terapia , Técnicas de Diagnóstico Neurológico , Serviços Médicos de Emergência/métodos , Exame Físico/métodos , Coma/etiologia , Diagnóstico Diferencial , Serviço Hospitalar de Emergência/organização & administração , Humanos , Avaliação de Sintomas/métodos
7.
Parasitol Res ; 115(4): 1519-28, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26687969

RESUMO

Psoroptic mange is a skin disease which may result in serious health and welfare problems and important economic losses. Apart from the effect on weight gain, little information is available concerning other responses of the organism consequent to the successful therapy of bovine psoroptic mange. Accordingly, serum chemistry, hematology, organ weights, and leather quality of young bulls with experimentally induced clinical Psoroptes ovis mange and treated with either ivermectin long-acting injection (IVM LAI; IVOMEC(®) GOLD, Merial) or saline (n = 16 each) were examined 8 weeks after treatment when all IVM LAI-treated bulls were free of live P. ovis mites while the saline-treated bulls maintained clinical mange. IVM LAI-treated bulls had higher (p < 0.05) alkaline phosphatase, creatinine, cholesterol, glucose, and albumin levels and lower (p < 0.01) total protein and ß- and γ-globulin levels than the saline-treated bulls. Complete blood counts revealed higher leukocyte counts associated with higher eosinophil counts and higher platelet counts in the saline-treated compared to the IVM LAI-treated bulls (p < 0.01). Correlating with body weight, the warm carcass weight of the saline-treated bulls was lower than that of the IVM LAI-treated bulls (p < 0.05). Absolute and relative (organ weight divided by body weight) weights of the spleen, thymus, omental fat, and perirenal fat were higher (p < 0.01) for the IVM LAI-treated bulls than for the saline-treated bulls, while the IVM LAI-treated bulls had lower (p < 0.05) absolute and relative weights of the liver, adrenal glands, and selected lymph nodes than the saline-treated bulls. The leathers produced from the IVM LAI-treated bulls showed significantly (p < 0.001) less severe gouging or etching than leathers from the saline-treated bulls, and significantly (p < 0.05) more leather from the IVM LAI-treated bulls was of usable quality than the size of leather from the saline-treated bulls. Overall, these findings provided evidence that many changes, which are indicative of impaired protein and energy metabolism, immune system function, and performance resultant from clinical psoroptic mange, improved substantially within 8 weeks of successful treatment with injectable ivermectin.


Assuntos
Antiparasitários/uso terapêutico , Doenças dos Bovinos/tratamento farmacológico , Ivermectina/uso terapêutico , Infestações por Ácaros/veterinária , Tecido Adiposo/anatomia & histologia , Tecido Adiposo/efeitos dos fármacos , Animais , Peso Corporal , Bovinos , Doenças dos Bovinos/sangue , Doenças dos Bovinos/parasitologia , Masculino , Infestações por Ácaros/sangue , Infestações por Ácaros/tratamento farmacológico , Infestações por Ácaros/patologia , Ácaros/efeitos dos fármacos , Tamanho do Órgão , Psoroptidae/efeitos dos fármacos , Pele/parasitologia , Pele/patologia , Baço/anatomia & histologia , Baço/efeitos dos fármacos
8.
Internist (Berl) ; 57(10): 1022-1028, 2016 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-27357251

RESUMO

We report on the case of a 32-year-old female patient who initially presented with oliguric acute renal failure, hemolytic anemia with moderate thrombocytopenia and subsequently developed a transient ischemic attack in the cerebellum. The kidney biopsy revealed clinically suspected atypical hemolytic-uremic syndrome (aHUS), which was confirmed by intraglomerular thrombotic microangiopathy (TMA). Treatment with plasmapheresis and sustained administration of the C5 inhibitor eculizumab resulted in hematological remission but without improvement of kidney function. Further etiological investigations led to reduced plasma levels of inhibitory complement factor I on the basis of a heterozygous CFI mutation. In patients with aHUS molecular genetic investigations are indicated in order to determine the underlying cause, to regulate the therapeutic regimen and to allow prognostic statements with respect to a potential kidney transplantation.


Assuntos
Síndrome Hemolítico-Urêmica/diagnóstico , Síndrome Hemolítico-Urêmica/terapia , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/terapia , Insuficiência Renal/diagnóstico , Insuficiência Renal/terapia , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Terapia Combinada/métodos , Diagnóstico Diferencial , Feminino , Hemólise , Síndrome Hemolítico-Urêmica/sangue , Humanos , Ataque Isquêmico Transitório/sangue , Plasmaferese , Insuficiência Renal/sangue , Resultado do Tratamento
9.
Unfallchirurg ; 118(1): 53-68; quiz 69-70, 2015 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-25630884

RESUMO

Mild head injuries are one of the most frequent reasons for attending emergency departments and are particularly challenging in different ways. While clinically important injuries are infrequent, delayed or missed injuries may lead to fatal consequences. The initial mostly inconspicuous appearance may not reflect the degree of intracranial injury and computed tomography (CT) is necessary to rule out covert injuries. Furthermore, infants and young children with a lack of or rudimentary cognitive and language development are challenging, especially for those examiners not familiar with pediatric care. Established check lists of clinical risk factors for children and adults regarding traumatic brain injuries allow specific and rational decision-making for cranial CT imaging. Clinically important intracranial injuries can be reliably detected and unnecessary radiation exposure avoided at the same time.


Assuntos
Algoritmos , Lista de Checagem , Traumatismos Craniocerebrais/diagnóstico , Serviços Médicos de Emergência/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Adulto Jovem
10.
Klin Monbl Augenheilkd ; 232(12): 1386-91, 2015 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-26678901

RESUMO

The value of diffusion-weighted magnet resonance imaging (DWI-MRI) has been demonstrated for an ever growing range of clinical indications. DWI is sensitive to the diffusion of water molecules and probes their random displacement within tissue. DWI provides both qualitative and quantitative information on tissue characteristics, e.g. tissue cellularity. This review provides an overview of diffusion-weighted imaging and its emerging applications in ophthalmology. The basic physics and technical foundations of DWI are introduced. The emerging applications of DWI are surveyed, particularly in diseases of the eye, orbit and optical nerve.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Oftalmopatias/patologia , Aumento da Imagem/métodos , Doenças Orbitárias/patologia , Humanos
11.
Klin Monbl Augenheilkd ; 231(10): 1016-22, 2014 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-25178045

RESUMO

MR microscopy using an ultra high-field MR system is a novel non-invasive imaging technique to explore the human eye without optical distortions. This review aims to provide an insight into the technique. Normal MR microscopic anatomy of the human eye in vivo is demonstrated and clinical applications of MR microscopy are discussed.


Assuntos
Olho/citologia , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Microscopia/métodos , Oftalmoscopia/métodos , Humanos
12.
Klin Monbl Augenheilkd ; 231(12): 1187-95, 2014 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-25519506

RESUMO

This review documents technical progress in ophthalmic magnetic resonance imaging (MRI) at ultrahigh fields (UHF, B(0) ≥ 7.0 T). The review surveys frontier applications of UHF-MRI tailored for high spatial resolution in vivo imaging of the eye, orbit and optic nerve. Early examples of clinical ophthalmic UHF-MRI including the assessment of melanoma of the choroid membrane and the characterisation of intraocular masses are demonstrated. A concluding section ventures a glance beyond the horizon and explores research promises along with future directions of ophthalmic UHF-MRI.


Assuntos
Neoplasias Oculares/patologia , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Oftalmoscopia/métodos , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Avaliação da Tecnologia Biomédica
13.
Magn Reson Imaging ; 106: 18-23, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38042453

RESUMO

PURPOSE: Arterial Spin Labeling (ASL) allows for the non-invasive visualization of brain perfusion to detect abnormalities. In unilateral carotid artery stenosis, one hemisphere is less supplied with blood which results in a lower cerebral blood flow (CBF) compared to the healthy side. ASL can be performed time-resolved using multiple post labeling delay (PLD) times after labeling or static with a single delay, the latter allowing for a faster and more robust acquisition while bearing the risk of a falsely set delay resulting in unusable images. The purpose of this study is to compare the performance of multi-PLD and single-PLD ASL in patients with unilateral carotid artery stenosis both as means of diagnosis and therapeutic follow-up examination. METHODS: ASL perfusion data of 17 patients with known unilateral carotid artery stenosis was used to compare the diagnostic performance of the multi-PLD and single-PLD approach. Comparisons were made based on the CBF values and the added benefit of arrival time maps showing slower blood flow in multi-PLD ASL which might be overlooked in the individual delay images both before and after therapy. RESULTS: Both the multi-PLD and the single-PLD data could identify the side of the stenosis with hemispheric differences in each approach (p < 0.001) and depict the normalization of CBF after therapy (p > 0.05). There were no differences between the individual methods (p > 0.05). CONCLUSION: In this work, we could show that multi-PLD ASL in patients with unilateral carotid artery stenosis is beneficial as it provides both CBF and arrival time maps, however when only a single-PLD acquisition is available, this appears sufficient in a clinical setting to investigate the presence of a unilateral stenosis.


Assuntos
Estenose das Carótidas , Humanos , Estenose das Carótidas/diagnóstico por imagem , Constrição Patológica , Marcadores de Spin , Artérias , Encéfalo/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Imageamento por Ressonância Magnética/métodos
14.
Crit Care ; 17(4): R147, 2013 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-23880105

RESUMO

INTRODUCTION: Therapeutic hypothermia (TH) after out-of-hospital cardiac arrest (OHCA) was adopted early in Norway. Since 2004 the general recommendation has been to cool all unconscious OHCA patients treated in the intensive care unit (ICU), but the decision to cool individual patients was left to the responsible physician. We assessed factors that were associated with use of TH and predicted survival. METHOD: We conducted a retrospective observational study of prospectively collected cardiac arrest and ICU registry data from 2004 to 2008 at three university hospitals. RESULTS: A total of 715 unconscious patients older than 18 years of age, who suffered OHCA of both cardiac and non-cardiac causes, were included. With an overall TH use of 70%, the survival to discharge was 42%, with 90% of the survivors having a favourable cerebral outcome. Known positive prognostic factors such as witnessed arrest, bystander cardio pulmonary resuscitation (CPR), shockable rhythm and cardiac origin were all positive predictors of TH use and survival. On the other side, increasing age predicted a lower utilisation of TH: Odds Ratio (OR), 0.96 (95% CI, 0.94 to 0.97); as well as a lower survival: OR 0.96 (95% CI, 0.94 to 0.97). Female gender was also associated with a lower use of TH: OR 0.65 (95% CI, 0.43 to 0.97); and a poorer survival: OR 0.57 (95% CI, 0.36 to 0.92). After correcting for other prognostic factors, use of TH remained an independent predictor of improved survival with OR 1.91 (95% CI 1.18-3.06; P <0.001). Analysing subgroups divided after initial rhythm, these effects remained unchanged for patients with shockable rhythm, but not for patients with non-shockable rhythm where use of TH and female gender lost their predictive value. CONCLUSIONS: Although TH was used in the majority of unconscious OHCA patients admitted to the ICU, actual use varied significantly between subgroups. Increasing age predicted both a decreased utilisation of TH as well as lower survival. Further, in patients with a shockable rhythm female gender predicted both a lower use of TH and poorer survival. Our results indicate an underutilisation of TH in some subgroups. Hence, more research on factors affecting TH use and the associated outcomes in subgroups of post-resuscitation patients is needed.


Assuntos
Hipotermia Induzida/métodos , Unidades de Terapia Intensiva , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/terapia , Admissão do Paciente , Inconsciente Psicológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipotermia Induzida/tendências , Unidades de Terapia Intensiva/tendências , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/diagnóstico , Admissão do Paciente/tendências , Valor Preditivo dos Testes , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento
15.
Nat Genet ; 26(2): 163-75, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11017071

RESUMO

Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.


Assuntos
Calpaína/genética , Cromossomos Humanos Par 2 , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Variação Genética , Polimorfismo Genético , Adulto , Sequência de Aminoácidos , Calpaína/química , Mapeamento Cromossômico , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/epidemiologia , Finlândia , Frequência do Gene , Marcadores Genéticos , Genoma Humano , Haplótipos , Humanos , Americanos Mexicanos/genética , Dados de Sequência Molecular , Medição de Risco , Estados Unidos , População Branca/genética
16.
Nat Genet ; 13(2): 161-6, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8640221

RESUMO

Non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is a common disorder of middle-aged individuals characterized by high blood glucose levels which, if untreated, can cause serious medical complications and lead to early death. Genetic factors play an important role in determining susceptibility to this disorder. However, the number of genes involved, their chromosomal location and the magnitude of their effect on NIDDM susceptibility are unknown. We have screened the human genome for susceptibility genes for NIDDM using non-and quasi-parametric linkage analysis methods in a group of Mexican American affected sib pairs. One marker, D2S125, showed significant evidence of linkage to NIDDM and appears to be a major factor affecting the development of diabetes mellitus in Mexican Americans. We propose that this locus be designated NIDDM1.


Assuntos
Cromossomos Humanos Par 2 , Diabetes Mellitus Tipo 2/genética , Americanos Mexicanos/genética , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Ligação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Japão , População Branca
17.
Orthopade ; 41(10): 802-19, 2012 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-23052847

RESUMO

Instrumented 3-dimensional gait analysis is increasingly being used for the evaluation of movement disorders in orthopedic and neurological musculoskeletal diseases. Due to the high reliability of the measurements the procedures are appropriate for diagnostic purposes as well as for outcome assessment after conservative or surgical interventions. Contrary to conventional clinical assessments gait analysis parameters are able to demonstrate a normal physiological gait pattern that can be achieved with improved kinematic and kinetic parameters. For a suitable application in clinically relevant problems the limitations of the procedures should be taken into account. Due to the high instrumental involvement combined with time and cost expenditure instrumented gait analysis will probably not develop to a clinical routine procedure. Nevertheless, an excellent set of information for answering clinical questions is provided. The present contribution presents selected measurement procedures and technologies and illustrates the wide variety of possibilities with the use of selected clinical examples.


Assuntos
Actigrafia/instrumentação , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/fisiopatologia , Monitorização Ambulatorial/instrumentação , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/fisiopatologia , Desenho de Equipamento , Humanos
18.
Am J Transplant ; 11(1): 156-62, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21199355

RESUMO

In January 2005, an 18-year-old male patient with acute myeloid leukemia (AML) received a haploidentical hematopoietic stem cell transplantation (HSCT) from his father. He developed hemolytic uremic syndrome and end-stage renal disease (ESRD) requiring hemodialysis on day 357 after HSCT. On day 1020 after HSCT, a living kidney donation from the stem cell donor was carried out. The creatinine before kidney transplantation (KT) was ≈450 µmol/L, 268 µmol/L on day 2 after KT, 88 µM on day 38 and 89 µmol/L on day 960 (day 1980 after HSCT). Immunosuppression was gradually discontinued: cortisone on day 28, tacrolimus on day 32 and MMF on day 100 after KT (day 1120 after HSCT). As of June 2010, 66 months after HSCT and 32 months after KT, the patient has had neither rejection episodes nor clinical manifestations of transplantation-related complications. The patient reached 100% hematopoietic donor chimerism prekidney transplant and retained this state postkidney transplant. This unique case is the first report of a successful kidney transplant without immunosuppression after HSCT from the same haploidentical donor.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Falência Renal Crônica/cirurgia , Transplante de Rim , Doadores Vivos , Adolescente , Adulto , Humanos , Terapia de Imunossupressão , Falência Renal Crônica/induzido quimicamente , Leucemia Mieloide Aguda/terapia , Masculino , Quimeras de Transplante
19.
Diabet Med ; 28(11): 1373-80, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21711391

RESUMO

AIMS: Several polymorphisms of the melatonin receptor 1B gene (MTNR1B) have been shown to be associated with elevated fasting plasma glucose and impaired early insulin release. The aim of this study was to assess the effects of MTNR1B variants on traits related to the metabolic syndrome in the self-contained population of Sorbs from Germany. As comprehensive studies concerning the conservation of MTNR1B are lacking, we also evaluated natural selection in vertebrates and human populations at this locus. METHODS: Five single nucleotide polymorphisms representing all blocks of linkage disequilibrium within and surrounding the MTNR1B locus were genotyped in 937 Sorbs for association analyses on metabolic traits related to Type 2 diabetes. The associations were assessed by regression analyses, the conservation between species was investigated with phylogenetic analysis by maximum likelihood (PAML). In addition, various tests of population genetic measures (e.g. fixation index, Tajima's D) were performed. RESULTS: Previously reported association between MTNR1B variants (rs10830963, rs4753426) and oral glucose tolerance test-derived indices of ß-cell function (homeostasis model assessment-B, P = 3.7 × 10⁻6 and P = 0.004, respectively), as well as insulin (fasting insulin: P=2×10⁻³ and P=0.02; 30-min insulin: P = 2.1 × 10⁻4 and P=0.03, respectively) and fasting glucose (rs10830963, P=1.2×10⁻6) parameters could be replicated in the present study. Phylogenetic analysis by maximum likelihood analyses showed that the gene was strongly conserved between species (ω=0.2583). Structures important for the receptor function are also conserved. On the lineage leading to human adaptive selection was present (ω=1.1030). Population genetic measures further indicated natural selection. CONCLUSIONS: Our data support the physiologic importance of MTNR1B in the context of glucose homeostasis and suggest evidence of selection at this locus.


Assuntos
Diabetes Mellitus Tipo 2/genética , Etnicidade/genética , Resistência à Insulina/genética , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Receptor MT2 de Melatonina/genética , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/metabolismo , Evolução Molecular , Feminino , Alemanha/epidemiologia , Alemanha/etnologia , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/genética , Hemoglobinas Glicadas/metabolismo , Humanos , Resistência à Insulina/etnologia , Desequilíbrio de Ligação , Síndrome Metabólica/etnologia , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Filogenia , Receptor MT2 de Melatonina/metabolismo
20.
J Helminthol ; 85(4): 409-14, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21138608

RESUMO

Faecal samples of 250 horses from farms with a known history of tapeworm infection were examined comparatively for cestode eggs using a double centrifugation/combined sedimentation-floatation technique. From each faecal sample, three 5 g and three 15 g subsamples were processed, each using either saturated NaCl solution, specific gravity (sp. g.) 1.2 [NaCl]; concentrated sugar solution, sp. g. 1.26 [sugar]; or concentrated ZnSO4 solution, sp. g. 1.3 [ZnSO4] for floatation. In total, faeces from 187 horses ( = 74.8%) tested 'positive' for Anoplocephala eggs. Percentages of samples testing 'positive' for Anoplocephala ova were: 57.2% for 5 g faeces/NaCl, 66% for 15 g faeces/NaCl, 66% for 5 g faeces/sugar, 72.8% for 15 g faeces/sugar, 55.6% for 5 g faeces/ZnSO4, and 61.2% for 15 g faeces/ZnSO4, respectively. Processing of 15 g faecal samples resulted in a significant (P < 0.05; McNemar's χ2-test) increase in the percentage of Anoplocephala egg detection compared to processing of 5 g samples for all floatation solutions. By processing 15 g faecal samples using sugar solution for floatation, 97.3% of all samples that tested 'positive' for Anoplocephala eggs were identified; there was no significant difference between the rate of samples that tested 'positive' using 15 g faeces/sugar (72.8%) and the total rate of samples that tested 'positive' (74.8%). Conversely, percentages of 'positive' samples from other test combinations were significantly (P < 0.0001, McNemar's χ2-test) lower than the total rate of samples testing 'positive'. Processing faecal samples using sugar solution for floatation gave significantly (P < 0.05, Wilcoxon test) higher Anoplocephala egg counts than using NaCl and ZnSO4 solutions, for both 5 g and 15 g faecal samples. The double centrifugation technique using 15 g faecal samples and concentrated sugar solution for floatation appeared to offer an advantage for the detection of Anoplocephala eggs in horse faeces compared to the other test combinations.


Assuntos
Centrifugação/métodos , Cestoides/isolamento & purificação , Infecções por Cestoides/parasitologia , Infecções por Cestoides/veterinária , Fezes/parasitologia , Doenças dos Cavalos/parasitologia , Contagem de Ovos de Parasitas/veterinária , Animais , Cavalos , Contagem de Ovos de Parasitas/métodos , Parasitologia/métodos
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