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1.
Int J Med Microbiol ; 305(8): 860-4, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26365168

RESUMO

Antibiotic resistance is an unsolved healthcare problem with increasing impact on patient management in the last years. In particular, multidrug resistance among Gram-negative bacterial strains has become the most pressing challenge. In order to deliver the most efficacious antimicrobial therapy with minimum delay, rapid diagnostic tests are required in order to detect multidrug resistant pathogens early during infection. In line with these efforts, we have developed a mass spectrometry-based assay for the rapid determination of ampicillin and cefotaxime resistance. The assay quantifies beta-lactamase activities towards ampicillin and cefotaxime within a turnaround time of 150 min, which is substantially faster than classical susceptibility testing.


Assuntos
Antibacterianos/metabolismo , Cefotaxima/metabolismo , Cromatografia Líquida/métodos , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Espectrometria de Massas/métodos , beta-Lactamases/análise , Ampicilina/metabolismo , Técnicas Bacteriológicas/métodos , Humanos , Fatores de Tempo , Resistência beta-Lactâmica
2.
Acta Chir Orthop Traumatol Cech ; 82(5): 327-31, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26516948

RESUMO

C-reactive protein (CRP) is a common laboratory infection marker in blood-serum of patients. In all diverse medical departments CRP is often used, and also in orthopaedics CRP is proved to be very helpful in diagnosis and monitor of infections. CRP in most fields is superior to conventional and newer infection parameter and is a basic parameter for inflammation. Especially for detection of an early postoperative infection CRP can be very helpful as an objective parameter easy to obtain. In uneventful operative treatment a similar evolution in CRP concentrations was found: the peak level occurred on the second or third postoperative day and reflected the extent of surgical trauma. A second rise of CRP in the postoperative course indicates a complication. Highest levels are reached in bacterial infection after the forth postoperative day with a cut-off level about 10 mg/dl. CRP can also be used as a preoperative marker for risk stratification and newer times CRP is reported as an independent fracture-risk-factor. In general CRP is the basic inflammatory parameter in orthopaedic surgery and is more significant and common than WBC or ESR. But CRP is only a laboratory parameter and must always be correlated with clinical signs of infection.


Assuntos
Proteína C-Reativa/metabolismo , Infecções/diagnóstico , Procedimentos Ortopédicos/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Biomarcadores/sangue , Humanos , Período Pós-Operatório , Cuidados Pré-Operatórios/métodos , Fatores de Risco
3.
Unfallchirurg ; 117(3): 274-80, 2014 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-23732615

RESUMO

Bouldering is a new trend sport which has become popular in recent years. From April 2011 to June 2012 a total of 5 patients with elbow dislocations from bouldering were admitted to our level 1 trauma center. The injuries varied from simple elbow dislocations to complex fracture dislocations. Elbow dislocations occurred during falling backwards when patients tried to protect themselves by retroversion of both arms. In all cases the falling height was less than 4 meters. The bouldering injury pattern, the diagnostic and therapeutic management as well as the rehabilitation program are described in detail in this article. To the best of our knowledge this is the first report on the special danger of bouldering for complex elbow injuries.


Assuntos
Acidentes por Quedas , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/terapia , Lesões no Cotovelo , Articulação do Cotovelo/cirurgia , Luxações Articulares/diagnóstico , Luxações Articulares/terapia , Adulto , Feminino , Humanos , Adulto Jovem
4.
Acta Chir Orthop Traumatol Cech ; 81(2): 118-21, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25105785

RESUMO

INTRODUCTION While plate fixation remains the gold standard for surgical treatment for displaced mid-shaft clavicle fractures (DMCF), intramedullary fixation has emerged as a promising alternative. However, due to its more demanding technique and depending on the fracture's nature, an open reduction can be necessary. Aim of this study was to compare the outcome of open reduction versus closed reduction of DMCF using ESIN. PATIENTS AND METHODS Titanium Elastic Nail (TEN) were used to treat 40 patients undergoing minimally invasive ESIN between December 2006 and July 2009. A total of 19 patients were treated with a closed reduction and 21 patients required open reduction. RESULTS Open reduction increases operative time and fluoroscopy time significantly versus closed reduction (open 80.8 ± 35.9 min; closed 30.5 ± 8.5 min). No significant differences were found regarding strength measurement (75.7 ± 22.0 N in the closed group and 74.2 ± 26.0 N in the open group), DASH score (5.1 ± 6.5 closed group vs. 5.8 ± 7.3 open group) and Constant score (87.4 ± 9 points closed group vs. 85.3 ± 7.2 points open group). No major complications were observed. CONCLUSION There was no significant difference comparing patients who were treated with an open versus a closed technique. If appropriately indicated we believe that using ESIN is an adequate and successful operative technique for DMCF. There were no significant differences in shoulder function after either procedure.


Assuntos
Pinos Ortopédicos , Clavícula/lesões , Fixação Intramedular de Fraturas/métodos , Fraturas Ósseas/cirurgia , Adulto , Clavícula/diagnóstico por imagem , Clavícula/cirurgia , Estética , Feminino , Fraturas Ósseas/diagnóstico por imagem , Humanos , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Radiografia , Estudos Retrospectivos , Titânio , Resultado do Tratamento
5.
Acta Chir Orthop Traumatol Cech ; 80(6): 407-10, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24750969

RESUMO

BACKGROUND: Fractures of the medial clavicle third are rare injuries. Even in case of significant fracture displacement, their therapeutic management has been nonoperative. Recently, surgical intervention has become mandatory for displaced fractures types to prevent non-union and functional complaints, but the optimal operative strategy is being discussed controversially. CASE PRESENTATION: We describe the case of a 63-year-old male patient with a significantly displaced medial clavicle fracture after failed conservative treatment resulting in restricted, painful shoulder function. The patient underwent open reduction and osteosynthesis with an anatomically precontoured locking compression plate (LCP). One year after surgery the patient is free of complaints and has returned to his preinjury activity level without any functional restrictions. CONCLUSION: As a not yet reported operative approach, anatomically preshaped locking plating seems to be an effective fixation method for displaced fractures of the medial clavicle third. The operative management is described in detail and discussed with the current literature. Based on the presented case, we underline the statement that displaced medial clavicle fractures should be surgically addressed to avoid late damage.


Assuntos
Placas Ósseas , Clavícula , Fixação Interna de Fraturas , Fraturas Ósseas , Desenho de Prótese/métodos , Clavícula/lesões , Clavícula/patologia , Clavícula/fisiopatologia , Clavícula/cirurgia , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Consolidação da Fratura , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fraturas Mal-Unidas/diagnóstico por imagem , Fraturas Mal-Unidas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Recuperação de Função Fisiológica , Resultado do Tratamento
6.
Eur Respir J ; 39(4): 919-26, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21965223

RESUMO

The aim of this study was to prospectively evaluate the accuracy of quantitative cardiac computed tomography (CT) parameters and two cardiac biomarkers (N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) and troponin I), alone and in combination, for predicting right ventricular dysfunction (RVD) in patients with acute pulmonary embolism. 557 consecutive patients with suspected pulmonary embolism underwent pulmonary CT angiography. Patients with pulmonary embolism also underwent echocardiography and NT-pro-BNP/troponin I serum level measurements. Three different CT measurements were obtained (right ventricular (RV)/left ventricular (LV)(axial), RV/LV(4-CH) and RV/LV(volume)). CT measurements and NT-pro-BNP/troponin I serum levels were correlated with RVD at echocardiography. 77 patients with RVD showed significantly higher RV/LV ratios and NT-pro-BNP/troponin I levels compared to those without RVD (RV/LV(axial) 1.68 ± 0.84 versus 1.00 ± 0.21; RV/LV(4-CH) 1.52 ± 0.45 versus 1.01 ± 0.21; RV/LV(volume) 1.97 ± 0.53 versus 1.07 ± 0.52; serum NT-pro-BNP 6,372 ± 2,319 versus 1,032 ± 1,559 ng · L(-1); troponin I 0.18 ± 0.41 versus 0.06 ± 0.18 g · L(-1)). The area under the curve for the detection of RVD of RV/LV(axial), RV/LV(4-CH), RV/LV(volume), NT-pro-BNP and troponin I were 0.84, 0.87, 0.93, 0.83 and 0.70 respectively. The combination of biomarkers and RV/LV(volume) increased the AUC to 0.95 (RV/LV(volume) with NT-pro-BNP) and 0.93 (RV/LV(volume) with troponin I). RV/LV(volume) is the most accurate CT parameter for identifying patients with RVD. A combination of RV/LV(volume) with NT-pro-BNP or troponin I measurements improves the diagnostic accuracy of either test alone.


Assuntos
Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Disfunção Ventricular Direita/complicações , Disfunção Ventricular Direita/diagnóstico por imagem , Doença Aguda , Idoso , Biomarcadores/sangue , Cuidados Críticos/métodos , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Índice de Gravidade de Doença , Troponina I/sangue
7.
J Clin Microbiol ; 50(5): 1727-9, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22322351

RESUMO

Early targeted antimicrobial therapy helps decrease costs and prevents the spread of antimicrobial resistance, including in Escherichia coli, the most frequent Gram-negative bacterium that causes sepsis. Therefore, rapid susceptibility testing represents the major prerequisite for knowledge-based successful antimicrobial treatment. To accelerate testing for antibiotic susceptibility, we have developed a new mass spectrometry-based assay for antibiotic susceptibility testing (MAAST). For proof of principle, we present an ampicillin susceptibility test for E. coli with a turnaround time of 90 min upon growth detection.


Assuntos
Resistência a Ampicilina , Ampicilina/farmacologia , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Espectrometria de Massas/métodos , Humanos , Testes de Sensibilidade Microbiana/métodos , Fatores de Tempo
8.
Orthopade ; 41(3): 212-6, 2012 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-22407096

RESUMO

BACKGROUND: Chronic and atraumatic groin pain may be due to a variety of pathologies local to and distal from the hip joint. Aside from frequent entities, such as inguinal hernia, impingement of the iliopsoas muscle by the anterior rim of the acetabular component leading to a hematoma can be a potential cause after total hip replacement (THR). MATERIAL AND METHODS: This article presents three cases of delayed groin pain after THR received due to osteoarthrosis of the hip joint several years prior to the onset of symptoms. In all three cases the patient suffered from chronic groin pain aggravated by active flexion without direct trauma. After thorough clinical, laboratory and radiological (ultrasound, x-ray, computed tomography) examination a hematoma of the iliopsoas muscle was detected. Furthermore, in all three cases the acetabular component appeared to be slightly malpositioned. Considering the least invasive procedure all cases were treated with an excavation of the hematoma. After recurrence the indications for revision of the malpositioned acetabular component were present. RESULTS: All patients clearly showed a reduction of pain after operative revision. There have been no further hematomas and the patients could be easily and rapidly remobilized. CONCLUSIONS: Persistent atraumatic groin pain connected to a deficit in hip flexion after THR needs thorough investigation by the treating physician. The differential diagnosis of a delayed hematoma due to impingement of the iliopsoas muscle is a rare but more complex entity. After careful consideration of the perioperative risks an early indication for revision of a malpositioned acetabular component is promising.


Assuntos
Artralgia/diagnóstico , Artralgia/etiologia , Artroplastia de Quadril/efeitos adversos , Hematoma/diagnóstico , Hematoma/etiologia , Neoplasias Musculares/diagnóstico , Neoplasias Musculares/etiologia , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Virilha , Humanos , Masculino , Pessoa de Meia-Idade
9.
Clin Chim Acta ; 520: 168-171, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34081934

RESUMO

The analysis of circulating cell free DNA is an important tool for the analysis of tumor resistance, tumor heterogeneity, detection of minimal residual disease and detection of allograft rejection in kidney or heart transplant patients. The proper use of this technique is important, and starts with considering pre-analytic aspects. The current paper addresses some important technical considerations to ensure the proper and harmonized use of cfDNA techniques.


Assuntos
Ácidos Nucleicos Livres , DNA Tumoral Circulante , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Testes Diagnósticos de Rotina , Humanos , Neoplasia Residual
10.
J Eur Acad Dermatol Venereol ; 24(12): 1400-5, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20384691

RESUMO

BACKGROUND AND OBJECTIVE: Tumescent local anaesthesia (TLA) with high prilocaine doses leads to formation of methemoglobin (MHb) which is known to be a potent activator of pro-inflammatory endothelial cell response in vitro. As TLA is widely used for large dermatological resections, the aim of this study was to investigate the effects of high prilocaine doses on the systemic inflammatory response in vivo and its clinical relevance. METHODS: This prospective study examines the influence of MHb on serum interleukin (IL)-6, IL-8 and tumour necrosis tumour necrosis (TNF)-α levels up to 72 h after application of TLA with prilocaine in doses higher than 600 mg. RESULTS: A total of 30 patients received prilocaine in a median dose of 1500 mg (range: 880-4160 mg) for large resections. Peak prilocaine serum concentration was reached 4 h (0.72 ± 0.07 µg/mL), the maximum concentration of MHb (7.43 ± 0.87%) and IL-6 (28.4 ± 4.1 U/L) 12 h after TLA application. TNF-α and IL-8 release were not found significantly increased. Three patients developed MHb concentrations >15%. CONCLUSIONS: This clinical study shows for the first time that a high prilocaine serum concentration leads in vivo to elevated systemic levels of IL-6 but not of IL-8 and TNF-α because of initial high MHb levels. Because of possible and unpredictable high MHb concentrations, TLA should only be performed with prilocaine in doses of 2.5 mg/kg. In general, new solutions of TLA are necessary to achieve adequate anaesthesia for large dermatological resections to decrease the risk of methemoglobinaemia.


Assuntos
Anestésicos Locais/administração & dosagem , Interleucina-6/sangue , Interleucina-8/sangue , Prilocaína/administração & dosagem , Fator de Necrose Tumoral alfa/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestésicos Locais/sangue , Proteína C-Reativa/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prilocaína/sangue , Estudos Prospectivos , Adulto Jovem
11.
J Chem Phys ; 131(12): 124306, 2009 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-19791880

RESUMO

In this letter, we report the first infrared spectrum of C(76)(2-). This multiply charged anion has been studied in an electrodynamic ion trap held at room temperature using tunable infrared radiation from a free-electron laser. Resonant vibrational excitation is found to cause electron detachment and the resulting singly negatively charged as well as the remaining doubly charged parent ion are monitored as a function of IR wavelength in an experimental scheme that we term infrared multiphoton electron detachment spectroscopy. The obtained IR spectra are contrasted to computed vibrational spectra using density functional theory. The dianionic molecule retains its overall symmetry (i.e., D(2) point group) with a (1)A(1) ground state with respect to the neutral fullerene. Spectral shifts of characteristic tangential modes relative to the neutral cage are shown to originate from the excess charge density.

12.
Clin Chim Acta ; 490: 181-185, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30194934

RESUMO

BACKGROUND: Copeptin acts as surrogate marker under stress stimuli, as well as an outcome predictor based on serum or plasma concentration in patients suffering intracranial hemorrhage, aneurysmal subarachnoid hemorrhage (aSAH), and stroke. The aim of this study was to establish a method for quantification of copeptin levels in cerebrospinal fluid (CSF) and to demonstrate its clinical applicability in patients following aSAH. METHODS: This assay was validated for CSF samples using a commercial immunoluminometric assay (IMLA). For the control group (10 patients), CSF copeptin levels were determined in patients without signs of acute neurological diseases and who underwent a diagnostic lumbar puncture. The pilot cohort included calculation of copeptin levels in CSF and in serum of patients following aSAH. RESULTS: The control group had CSF copeptin levels lower than 0.78 pmol/L-1. Among patients with aSAH, CSF copeptin values had a mean of 20.1 pmol/L-1 and serum copeptin concentrations had a mean of 61.39 pmol/L-1. CONCLUSIONS: This assay provides to best of our knowledge for the first time initial ranges values of CSF copeptin for patients without acute neurological disease and in patients with aSAH. Thus, it opens new doors to develop further calculations and relationships between diseases biomarker and outcome prediction.


Assuntos
Glicopeptídeos/líquido cefalorraquidiano , Imunoensaio/métodos , Humanos , Projetos Piloto , Hemorragia Subaracnóidea/líquido cefalorraquidiano
13.
Br J Dermatol ; 159(4): 871-80, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18652582

RESUMO

BACKGROUND: Diagnosis of Sézary syndrome (SS)-defining blood involvement is hampered by the lack of Sézary cell-specific markers and nonspecific morphology of the tumour cells. OBJECTIVES: To identify the most reliable and easy to use markers for the diagnosis of SS-defining blood involvement. METHODS: We studied 17 patients with SS and 11 control patients. We used flow cytometry for the detection of T-cell antigens (CD3, CD4, CD7 and CD8), expression of the Sézary cell-associated marker CD158k and T-cell receptor (TCR)-Vbeta chain. Additionally, Sézary cells were identified by peripheral blood smear for lymphocytes with cerebriform nuclei. RESULTS: It was not possible to diagnose blood involvement in all patients with SS by a single marker or method, although none of the markers was increased in the control population. Sézary cells were detected by blood smears in 13 of 17 (76%), by flow cytometry by their CD4+ CD7- CD3(dim) phenotype (> 1000 cells microL(-1)) in 13 of 17 (76%) and by expression of CD158k in 11 of 17 (65%) patients with SS. A specific T-cell clone was identified by identical TCR-Vbeta chain expression in 12 of 17 (71%) patients with SS. The identification of Sézary cells in individual patients varied for the different markers investigated. CONCLUSIONS: The combination of identifying CD4+ CD7- CD3(dim) cells, TCR-Vbeta chain and CD158k expression allowed a definite identification of SS-defining blood involvement in every individual patient. All of these markers can be measured by flow cytometry which would avoid time-consuming analysis of blood smears. These markers would also be suitable to monitor tumour cell load during therapy.


Assuntos
Antígenos CD/sangue , Biomarcadores Tumorais/sangue , Síndrome de Sézary/diagnóstico , Neoplasias Cutâneas/diagnóstico , Linfócitos T/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Citometria de Fluxo/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Sézary/metabolismo , Neoplasias Cutâneas/metabolismo
14.
Science ; 361(6399): 270-273, 2018 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-29903882

RESUMO

Air pollution is growing fastest in monsoon-affected South Asia. During the dry winter monsoon, the fumes disperse toward the Indian Ocean, creating a vast pollution haze, but their fate during the wet summer monsoon has been unclear. We performed atmospheric chemistry measurements by aircraft in the Oxidation Mechanism Observations campaign, sampling the summer monsoon outflow in the upper troposphere between the Mediterranean and the Indian Ocean. The measurements, supported by model calculations, show that the monsoon sustains a remarkably efficient cleansing mechanism by which contaminants are rapidly oxidized and deposited to Earth's surface. However, some pollutants are lofted above the monsoon clouds and chemically processed in a reactive reservoir before being redistributed globally, including to the stratosphere.


Assuntos
Poluentes Atmosféricos/química , Poluição do Ar , Vento , Ásia , Modelos Teóricos , Estações do Ano
15.
Cancer Res ; 57(12): 2354-7, 1997 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-9192807

RESUMO

Among the members of the carcinoembryonic antigen (CEA) family, CD66a (human C-CAM) and CGM2 (CEA gene family member 2) mRNAs are frequently down-regulated in colorectal cancer. In contrast, nonspecific cross-reactive antigen (NCA) mRNA is overexpressed in the majority of these carcinomas. In animal models, the rodent homologues of CD66a have been shown to act as tumor suppressors, suggesting an important role in carcinogenesis. Here we investigate the mRNAs of CD66a, CGM2, and NCA in 22 human colorectal adenomas and the respective normal mucosa specimens by Northern blots. The expression of both CD66a and CGM2 changed in a concomitant fashion. Using oligonucleotides specific for the N-terminal domains, two CD66a transcripts 3.9 and 1.5 kb in size were identified. These showed a greater than 50% down-regulation in 20 of 22 and 18 of 22 adenomas, respectively. Reduction of the CGM2 message was observed in 21 of 22 cases. Complete or near-complete losses of the CD66a 3.9-kb mRNA and the CGM2 message were found in 13 of 22 and 15 of 22 of the tumors, respectively. The medians of CD66a and CGM2 expressions were between 0.3 and 0.0, respectively. The tumor:normal ratio of NCA mRNA expression was increased up to 2.4-fold in 11 of 22 adenomas. Altogether, these results compare well to the changes reported previously for colorectal carcinomas. The high frequency and early appearance of dysregulation of members of the carcinoembryonic antigen family during colorectal tumorigenesis suggests that these changes may be important for the development of the malignant phenotype.


Assuntos
Adenoma/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciação/metabolismo , Neoplasias Colorretais/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/metabolismo , Northern Blotting , Antígeno Carcinoembrionário , Moléculas de Adesão Celular/metabolismo , Feminino , Proteínas Ligadas por GPI , Humanos , Mucosa Intestinal/metabolismo , Queratinas/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo
16.
Cancer Res ; 54(15): 4169-76, 1994 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-8033149

RESUMO

The tumor marker carcinoembryonic antigen (CEA) is predominantly expressed in epithelial cells along the gastrointestinal tract and in a variety of adenocarcinomas. As a basis for investigating its in vivo regulation and for establishing an animal model for tumor immunotherapy, transgenic mice were generated with a 33-kilobase cosmid clone insert containing the complete human CEA gene and flanking sequences. CEA was found in the tongue, esophagus, stomach, small intestine, cecum, colon, and trachea and at low levels in the lung, testis, and uterus of adult mice of independent transgenic strains. CEA was first detected at day 10.5 of embryonic development (embryonic day 10.5) in primary trophoblast giant cells and was found in the developing gut, urethra, trachea, lung, and nucleus pulposus of the vertebral column from embryonic day 14.5 onwards. From embryonic day 16.5 CEA was also visible in the nasal mucosa and tongue. Because this spatiotemporal expression pattern correlates well with that known for humans, it follows that the transferred genomic region contains all of the regulatory elements required for the correct expression of CEA. Furthermore, although mice apparently lack an endogenous CEA gene, the entire repertoire of transcription factors necessary for correct expression of the CEA transgene is conserved between mice and humans. After tumor induction, these immunocompetent mice will serve as a model for optimizing various forms of immunotherapy, using CEA as a target antigen.


Assuntos
Antígeno Carcinoembrionário/análise , Antígeno Carcinoembrionário/genética , Camundongos Transgênicos/genética , Camundongos Transgênicos/imunologia , Animais , Colo/química , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/análise , RNA Mensageiro/genética
17.
Cancer Res ; 50(7): 2128-34, 1990 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-2107969

RESUMO

Carcinoembryonic antigen (CEA) is one of the best characterized tumor-associated antigens and is extensively used in the in vitro immunodiagnosis of human colon adenocarcinomas. Among a number of anti-CEA monoclonal antibodies, the murine monoclonal antibody T84.66 shows the highest specificity and affinity for CEA and has been used successfully for in vivo tumor imaging in mice and humans. We report here the cloning and sequencing of the genes coding for monoclonal antibody T84.66 and the amino acid sequence of the variable regions for the heavy and light chains. We also report the construction of mouse/human chimeric IgG1 antibody genes using T84.66 variable region genes and human constant region genes. The resulting chimeric gene constructs were transfected into murine myeloma cells (Sp2/0) by electroporation and into Chinese hamster ovary cells by lipofection. The chimeric antibodies obtained exhibited the same specificity and affinity for CEA as that of the T84.66 immunoglobulin produced by the murine hybridoma cell line. Antibody concentrations in culture medium supernatants were clonally variable but similar (15-480 ng/ml) for both Sp2/0 and Chinese hamster ovary transfectants; the average production by Chinese hamster ovary transfectants was only 3-5-fold less than Sp2/0 transfectants. Ascites production of Sp2/0 transfectants is sufficiently high (900 micrograms/ml) for initial in vivo studies with humanized T84.66.


Assuntos
Anticorpos Monoclonais/genética , Antígeno Carcinoembrionário/imunologia , Genes de Imunoglobulinas , Sequência de Aminoácidos , Animais , Afinidade de Anticorpos , Sequência de Bases , Cricetinae , Cricetulus , Feminino , Vetores Genéticos , Humanos , Regiões Constantes de Imunoglobulina/genética , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Camundongos , Dados de Sequência Molecular , Ovário , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Transfecção
18.
Cancer Res ; 55(23 Suppl): 5929s-5934s, 1995 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-7493373

RESUMO

Chimeric T84.66 (cT84.66) is a high-affinity (5 x 10(10) M-1) anti-carcino-embryonic antigen (CEA) IgG1. In a recently completed pretherapy imaging trial, 111In-labeled cT84.66 demonstrated targeting of CEA-producing metastatic sites and low immunogenicity, with human antichimeric antibody (HACA) response in only 1 of 15 patients after a single administration. The purpose of the present study was to evaluate cT84.66-diethylenetriaminepentaacetic acid labeled with 90Y in a dose-escalation Phase I trial. Patients with metastatic CEA-producing malignancies received imaging doses of 5 mCi 111In-labeled cT84.66 first, followed 1-2 weeks later by 5 mg cT84.66 labeled with the therapeutic dose of 90Y. Immediately following the therapeutic infusion, diethylenetriaminepentaacetic acid was administered by continuous i.v. infusion over 3 days at 250 mg/m2 body surface area/24 h. Biodistribution, tumor targeting, absorbed radiation dose estimates, antibody clearance, and HACA response were evaluated through blood samples, 24-h urine collections, and nuclear images performed at serial time points after infusion. To date, three patients with metastatic colorectal cancer have been evaluated at the first dose level of 5 mCi/m2. No side effects were associated with antibody administration. Localization of the antibody to nonhepatic metastatic sites was observed. Size-exclusion high-performance liquid chromatography demonstrated the formation of CEA:antibody complexes in serum in all three patients. A significant variation among patients in the clearance rate of the antibody and complexes from blood to liver was seen, which resulted in a reciprocal relationship between estimated liver dose and red marrow dose. Patients who demonstrated faster clearance to liver demonstrated greater excretion of a low-molecular-weight metabolite through the urine. Two patients developed HACA response, which persisted at 4 months after therapy. At this first dose level, no tumor responses were seen and reversible grade 1 thrombocytopenia was observed in 2 patients. cT84.66 demonstrated effective localization in CEA-producing tumors. Its low immunogenicity after a single administration makes it attractive for further evaluation as a radioimmunotherapeutic agent. However, further evaluation is needed to determine whether its immunogenicity will remain low after multiple administrations. Additionally, in two of the three patients, we identified rapid clearance of the antibody to the liver. This underscores the need to identify, characterize, and understand further those factors that influence the biodistribution and clearance of anti-CEA antibodies to allow for better selection of patients for therapy and rational planning of radioimmunotherapy.


Assuntos
Neoplasias Colorretais/radioterapia , Radioimunoterapia , Radioisótopos de Ítrio/uso terapêutico , Antígeno Carcinoembrionário/imunologia , Neoplasias Colorretais/imunologia , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico
19.
Chem Sci ; 7(2): 1543-1547, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28808531

RESUMO

It caused a sensation eight years ago, when the first room temperature stable molecular compound with a Mg-Mg bond (LMgMgL, L = chelating ligand) containing magnesium in the oxidation state +1 was prepared. Here, we report the preparation of a [Mg16Cp*8Br4K]- cluster anion (Cp* = pentamethylcyclopentadiene) with 27 Mg-Mg bonds. It has been obtained through the reaction of KCp* with a metastable solution of MgBr in toluene. A highly-resolved Fourier transform mass spectrum (FT-MS) of this cluster anion, brought into vacuum by electrospraying its solution in THF, provides the title cluster's stoichiometry. This Mg16 cluster together with experiments on the metastable solution of MgBr show that: during the formation process of GRs (Grignard reagents) which are involved in most of sophisticated syntheses of organic products, not the highly reactive MgBr radical as often presumed, but instead the metalloid Mg16Cp*8Br4 cluster anion and its related cousins that are the operative intermediates along the pathway from Mg metal to GRs (e.g. Cp*MgBr).

20.
Eur J Med Res ; 21: 15, 2016 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-27072673

RESUMO

BACKGROUND: Isolated radial neck fractures occur only in rare cases. The majority of cases are non-displaced or minimally displaced and can be treated conservatively. Conservative treatment, however, might result in secondary displacement and/or malunion. On the other hand, open reduction and internal fixation (ORIF) as standard surgical approach in adults is associated with non-union, implant-related complications and reduced range of motion. For isolated radial neck fractures with an intact radial head, the procedure of centromedullary pinning--as widely used in the treatment of paediatric radial neck fractures--might be an alternative operative technique in adults as well. The purpose of this retrospective case series therefore was to evaluate the functional outcome of radial neck fractures treated by intramedullary pinning. METHODS: Between 02/2009 and 12/2014, a total of eight patients with isolated radial neck fractures (Mason type-III; Judet Type II and III) were treated with centromedullary pinning using titanium elastic nails (TEN). The mean age of the patients was 39 years (range 23-90 years) with a mean interval from injury to surgery of 2.9 days (range 1-7 days). Subjective and objective criteria included patient's satisfaction, pain rating on a visual analogue scale (VAS) and active range of motion (ROM) compared to the contralateral armside. Functional scoring included the Morrey Elbow Score (MEPS), the QuickDASH and the Elbow Self Assessment Score (ESAS). Furthermore, follow-up radiographs were evaluated. RESULTS: Seven of the eight patients were available for follow-up after a mean of 36 months (range 6-64 months). Patients' satisfaction was rated very good in four cases, good in two cases and sufficient in one case. An unrestricted active ROM compared to the contralateral side for extension-flexion arc and for pronation-supination-arc with full strength was rated in all cases. The Elbow Self Assessment Score was 98.52 ± 1.95 (range 96-100), the calculated Mayo elbow performance score was 95.71 ± 7.32 (range 85-100) and the QuickDASH score was 6.81 ± 10.42 (range 0-27). There were no complications as infection, non-union, heterotopic ossifications or secondary loss of reduction of the radial head. Only one patient complained about pain resulting from an affection of the superficial radial nerve. CONCLUSION: In the present cohort, good to excellent results without relevant complications were seen. The technique of intramedullary pinning as described in the treatment of isolated radial neck fractures in children represents a suitable and reliable method in adults as well. In selected cases, this technique can be recommended as an alternative, minimal-invasive approach to the radial head plate osteosynthesis.


Assuntos
Fixação Intramedular de Fraturas/métodos , Fraturas do Rádio/cirurgia , Rádio (Anatomia)/lesões , Rádio (Anatomia)/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Pinos Ortopédicos , Criança , Feminino , Fixação Intramedular de Fraturas/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Rádio (Anatomia)/fisiopatologia , Fraturas do Rádio/fisiopatologia , Amplitude de Movimento Articular , Reprodutibilidade dos Testes , Estudos Retrospectivos , Titânio , Resultado do Tratamento , Adulto Jovem
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