Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 52
Filtrar
1.
Laryngorhinootologie ; 91 Suppl 1: S27-47, 2012 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-22456918

RESUMO

The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing and currently they account for 5% of all malignancies worldwide. Inspite of ongoing developments in diagnostic imaging and new therapeutic facilities, HNSCC still represents a multidisciplinary challenge. One of the most important prognostic factors in HNSCC is the presence of lymph node metastases. Patients with confirmed nodal involvement have a considerable reduction of their 5-year overall survival rate. In the era of individually optimised surgery, chemotherapy and intensity modulated radiotherapy, the main role of pre- and posttherapeutic imaging remains cancer detection at an early stage and accurate follow-up. The combined effort of early diagnosis and close patient monitoring after surgery and/or radio-chemotherapy influences disease progression and outcome prediction in patients with HNSCC. This review article focuses on currrent oncologic concepts and emerging tools in imaging of head and neck squamous cell cancer. Besides the diagnostic spectrum of the individual imaging modalities, their limitations are also discussed. One main part of this article is dedicated to PET-CT which combines functional and morphological imaging. Furthermore latest developments in MRT are presented with regard to lymph node staging and response prediction. Last but not least, a clinical contribution in this review explains, which information the head and neck surgeon requires from the multimodality imaging and its impact on operation planning.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Diagnóstico por Imagem , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias Otorrinolaringológicas/diagnóstico , Carcinoma de Células Escamosas/terapia , Hipóxia Celular/fisiologia , Terapia Combinada , Comportamento Cooperativo , Imagem de Difusão por Ressonância Magnética , Diagnóstico Precoce , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Interpretação de Imagem Assistida por Computador , Comunicação Interdisciplinar , Metástase Linfática/patologia , Imageamento por Ressonância Magnética , Imagem Multimodal , Estadiamento de Neoplasias , Neoplasias Otorrinolaringológicas/patologia , Neoplasias Otorrinolaringológicas/terapia , Patologia , Equipe de Assistência ao Paciente , Tomografia por Emissão de Pósitrons , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Tomografia Computadorizada por Raios X
2.
Radiologe ; 51(5): 397-402, 404, 2011 May.
Artigo em Alemão | MEDLINE | ID: mdl-21523450

RESUMO

INTRODUCTION: Documentation of a correct port placement is a routine investigation in radiology. This article describes typical complications of port catheters and minimally invasive treatment options which can guarantee further use without complications. MATERIAL AND METHODS: From January 2009 to May 2010 a surgical port placement was carried out on 174 patients at the University Clinic in Mannheim and of these, 52 patients were admitted to our institute for radiological imaging of the port. Minimally invasive treatment options are presented based on the observed port complications. RESULTS: Of the 52 patients 7 (13.5%) received a port catheter lysis. A successful port position correction was carried out in 3 (5.8%) patients with a malpositioned port catheter and port removal was recommended in 2 patients (3.8%) due to extensive arm venous thrombosis. A minimally invasive port catheter treatment allowed further use of the port system without operative revision in the corresponding patients. The measures were tolerated very well by the patients without postinterventional complications.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Migração de Corpo Estranho/diagnóstico por imagem , Migração de Corpo Estranho/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Radiografia Intervencionista/métodos , Feminino , Migração de Corpo Estranho/etiologia , Humanos , Masculino , Pessoa de Meia-Idade
3.
Unfallchirurg ; 111(6): 403-12, 2008 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-18470502

RESUMO

The aim of this study was to evaluate the reduction of pain, improvement of sagittal alignment, complications and intermediate term results of balloon kyphoplasty in the treatment of osteoporotic vertebral compression fractures (VCF). The study group consisted of 87 patients with 145 VCFs which were not responsive to non-operative treatment. All data were collected prospectively. Improvement of sagittal alignment (Cobb and kyphotic angles, anterior, middle and posterior height) was determined from CT scans. Pain was evaluated by means of a visual analogue scale (VAS). Postoperative CT scans revealed a significant reduction of the mean kyphotic angle of 5.7 degrees (range 2-24 degrees ) and a significant reduction of pain from 7.8+/-2.4 to 2.0+/-1.5 in the VAS (improvement of pain in 95.5% of patients). An asymptomatic leakage of cement was observed in 28 out of 145 vertebrae (19.3%). The outcome of 35 patients with 51 VCFs was evaluated after a mean of 13 (range 12-70) months (CT and VAS) and there was a persisting reduction of pain and no loss of reduction. In this group of patients new symptomatic fractures were evident in 4 and clinically asymptomatic (only seen on CT) fractures were detected in 5 out of 35 patients, 7 fractures were adjacent to and 2 fractures were remote from the initially treated level. In two patients an asymptomatic moderate loss of reduction was detected. These intermediate term results indicate that kyphoplasty reduces pain and improves sagittal alignment in patients with VCF. However, in 26% of patients new fractures occurred, predominantly in adjacent levels but approximately 50% of these fractures were clinically asymptomatic.


Assuntos
Cateterismo/métodos , Fraturas por Compressão/cirurgia , Fraturas Espontâneas/cirurgia , Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Vertebroplastia/instrumentação , Vertebroplastia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Consolidação da Fratura , Fraturas por Compressão/diagnóstico , Fraturas por Compressão/etiologia , Fraturas Espontâneas/diagnóstico , Fraturas Espontâneas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/diagnóstico , Fraturas da Coluna Vertebral/diagnóstico , Fraturas da Coluna Vertebral/etiologia , Resultado do Tratamento
5.
Kidney Int ; 71(1): 74-8, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17082757

RESUMO

The use of the colorimetric Jaffé method for the measurement of creatinine in mouse and rat plasma has been criticized as prior studies have shown a dramatic overestimation. We compared a colorimetric picric acid, an enzymatic, and a high-performance liquid chromatography (HPLC) method to assess their appropriateness for routine measurements of creatinine in plasma of healthy and diseased mice (n=61) and rats (n=56). For the colorimetric Jaffé method a pronounced overestimation is confirmed. Additionally the method showed interference with hemoglobin already in a very low, non-visible concentration range in rat plasma. The enzymatic measurement demonstrated a hemoglobin interference in mice, only when hemolysis was visible. The comparison between HPLC and the enzymatic measurement gave a good agreement between both methods in both species. Therefore the enzymatic method fulfills the requirements for a routine screening test for plasma creatinine in healthy as well as diseased mice and rats Kiover a broad concentration range.


Assuntos
Análise Química do Sangue/métodos , Creatinina/sangue , Amidoidrolases , Animais , Cromatografia Líquida de Alta Pressão , Colorimetria , Hemólise , Camundongos , Camundongos Mutantes , Picratos , Doenças Renais Policísticas/sangue , Doenças Renais Policísticas/genética , Ratos , Ratos Mutantes , Ratos Sprague-Dawley , Ureo-Hidrolases
6.
Rofo ; 178(8): 801-9, 2006 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-16862507

RESUMO

PURPOSE: To evaluate the value of MDCT in the monitoring of vertebral body architecture after balloon kyphoplasty and observe morphological changes of the vertebral body. MATERIAL AND METHODS: During a period of 26 months, 66 osteoporotic fractures of the vertebral bodies were treated with percutanous balloon kyphoplasty. The height of the vertebral body, width of spinal space, sagittal indices, kyphosis und COBB angle, and cement leakage were evaluated by computed tomography before and after treatment and in a long-term follow up. Statistical analysis was performed by calculating quantitative constant parameters of descriptive key data. In addition, parametric and distribution-free procedures were performed for all questions. RESULTS: After kyphoplasty, the treated vertebral bodies showed a significant gain in the height of the leading edge (0.15 cm; p < 0.0001) and in the central part of the vertebral body (0.17 cm; p < 0.0001). The height of the trailing edge did not change significantly. A corresponding gain in the sagittal index was found. The index remained stable during follow-up. Treated vertebral bodies as well as untreated references showed a comparable loss of height over the period of one year. The shape of the vertebral bodies remained stable. In comparison to these findings, treated vertebral bodies showed a reduced loss of height. A significant change in kyphosis und the COBB angle was noted. In total, pallacos leakage was detected in 71 % of cases. CONCLUSION: MDCT is an accurate method for evaluating vertebral body architecture after treatment with balloon kyphoplasty. Morphological changes in the vertebral bodies, and complications such as pallacos leakage and progression of osteoprosis can be accurately documented. The significant increase in the vertebral body height after treatment is closely correlated with a gain in the sagittal index and reduced kyphosis and COBB angle.


Assuntos
Cateterismo/métodos , Descompressão Cirúrgica/métodos , Laminectomia/métodos , Osteoporose/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fraturas da Coluna Vertebral/etiologia , Tomografia Computadorizada por Raios X/instrumentação , Resultado do Tratamento
8.
Kidney Int ; 69(1): 60-7, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16374424

RESUMO

Recombinant human erythropoietin (rhEPO) is used to treat anemia in chronic renal insufficiency. Erythropoietin (EPO) immunogenicity can lead to EPO-resistant anemia. Conjugating proteins with polyethylene glycol (PEG) can prolong elimination half-life and diminish protein immunogenicity. We investigated the efficacy of new erythropoietic agents, synthesized by single (Ro 50-3821) and multiple (MIX) integrations of PEG and succinimidyl butanoic acid with rhEPO, in rats with chronic renal insufficiency. Sprague-Dawley rats with surgically induced renal insufficiency received Ro 50-3821 or MIX subcutaneously (s.c.) over 4-12 weeks compared to rhEPO and NaCl. Hemoglobin and antibody levels served as primary efficacy and safety variables. Dosing intervals and dose-response characteristics were investigated. Ro 50-3821 (2.5 microg/kg once weekly) increased hemoglobin levels by 7 g/dl after 4 weeks compared to 1 g/dl in NaCl controls (P<0.05). MIX (2.5 microg/kg once weekly) and rhEPO (0.25 microg/kg three times weekly) increased hemoglobin levels by 3 g/dl. Ro 50-3821 administered for 12 weeks (0.75 microg/kg once weekly) increased hemoglobin levels (from 13 to 19 g/dl) more effectively than rhEPO (0.75 microg/kg once weekly, decline from 13 to 11 g/dl, P<0.05). No antibodies against Ro 50-3821 were detected after 12 weeks of treatment. Antibodies against rhEPO were seen in 69% of animals (P<0.00001). Ro 50-3821 increased hemoglobin levels with once weekly s.c. dosing. Multiple pegylated EPO is less effective. In rats, rhEPO failed to increase hemoglobin levels with once weekly long-term dosing. Antibody formation following rhEPO may explain this finding. Therefore, Ro 50-3821 may provide important clinical advantages compared to unpegylated EPO. It can be administered in longer dosing intervals and has a lower risk of unfavorable immunological responses.


Assuntos
Eritropoese/efeitos dos fármacos , Eritropoetina/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Animais , Eritropoetina/imunologia , Eritropoetina/toxicidade , Hemoglobinas/análise , Masculino , Polietilenoglicóis/toxicidade , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes , Sístole/efeitos dos fármacos
9.
Rofo ; 177(12): 1641-8, 2005 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-16333786

RESUMO

PURPOSE: The goal of this retrospective study was to evaluate the spectrum of abdominal injuries and the reliability of computed tomography-based diagnosis in patients after polytrauma. MATERIAL AND METHODS: CT findings and clinical reports for 177 patients after polytrauma were evaluated with regard to abdominal injuries. Clinical patient reports at the time of discharge from the hospital were utilized as the standard of reference. Abdominal injuries resulting from an accident, frequent additional traumas and following therapeutic procedures were recorded. In the case of discrepancies in the reports, the CT scans were viewed retrospectively. RESULTS: In 30 out of 177 patients, 42 abdominal injuries were detected. 69 % of the injuries were caused by traffic accidents while 31 % resulted from falls. Liver and spleen injuries were the most common. 50 % of the cases were treated surgically, and the other half of the cases underwent non-surgical conservative therapy. Massive chest traumas, pelvic injuries, cerebral traumas and injuries to extremities were commonly associated with abdominal injuries. Evaluation of the discrepancies in the clinical reports showed that injury to the pancreas and the small intestine were not successfully detected on CT, thus resulting in a false negative diagnosis. Early stages of organ parenchyma laceration were also initially misdiagnosed on CT. CONCLUSION: Contrast-enhanced whole-body MSCT is a reliable and rapid method for diagnosing abdominal injuries in patients after polytrauma. Only very few patterns of injury are not detected on CT. The appearance of fluid collection in the abdomen is an indicator of possible parenchyma injury and requires further evaluation in cases of clinically suspected organ trauma.


Assuntos
Traumatismos Abdominais/diagnóstico por imagem , Traumatismo Múltiplo/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Traumatismos Abdominais/etiologia , Acidentes por Quedas , Acidentes de Trânsito , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Meios de Contraste , Emergências , Feminino , Humanos , Iohexol/análogos & derivados , Fígado/lesões , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/etiologia , Padrões de Referência , Estudos Retrospectivos , Sensibilidade e Especificidade , Baço/lesões
10.
Rofo ; 177(12): 1649-54, 2005 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-16333787

RESUMO

PURPOSE: There is no gold-standard regarding the diagnostic work-up and therapy of an acute gastrointestinal (GI) hemorrhage. In most cases endoscopy provides the diagnosis but in a low percentage this modality is not feasible or negative. Purpose of this study was to evaluate the role of multi-phase Multi-Slice-Computertomography (MSCT) as a modality to diagnose and locate the site of acute GI hemorrhage in case of unfeasible or technically difficult endoscopy. MATERIALS AND METHODS: 58 patients, presenting with clinical signs of lower GI hemorrhage, were examined through a 24-month period. Preliminary endoscopy was either negative or unfeasible. Images were obtained with a four-detector row CT with an arterial (4 x 1 mm collimation, 0.8 mm increment, 1.25 mm slice width, 120 kV, 165 mAs) and portal venous series (4 x 2,5 mm collimation, 2 mm increment, 3 mm slice width, 120 kV, 165 mAs). Time interval between endoscopy and CT varied between 30 minutes and 3 hours. The results of the MSCT were correlated with clinical course and surgical or endoscopical treatment. RESULTS: 20 of the 58 patients (34 %) undergoing MSCT had a bleeding site identified, thus providing decisive information for the following intervention. In case of a following therapeutic intervention there was 100 % correlation regarding the bleeding site. In 38 of the 58 patients (66 %), a bleeding site was not identified by MSCT. Twenty of these 38 patients (53 %) were stable and required no further treatment. In 18 of these 38 patients further interventional therapy was required due to continuing hemorrhage and in all of those patients the bleeding site was detected by intervention. CONCLUSION: Compared to other diagnostic methods MSCT is a fast, widely-available and low-risk technique for the localization of active GI hemorrhage. The clinical use seems to be justified since in more than one third of the patients, MSCT demonstrates the site of bleeding and provides decisive information for further interventional therapy. Concerning those patients, in whom MSCT is negative (38 out of 58 patients), only every second patient requires any additional diagnostic work-up.


Assuntos
Angiografia/métodos , Hemorragia Gastrointestinal/diagnóstico por imagem , Tomografia Computadorizada Espiral/métodos , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoscopia , Feminino , Seguimentos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/cirurgia , Humanos , Laparotomia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
11.
Endocrinology ; 142(1): 165-73, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11145579

RESUMO

Insulin-like growth factor I (IGF-I) is a potent anabolic peptide that mediates most of its pleiotropic effects through association with the IGF type I receptor. Biological availability and plasma half-life of IGF-I are modulated by soluble binding proteins (IGFBPs), which sequester free IGF-I into high affinity complexes. Elevated levels of specific IGFBPs have been observed in several pathological conditions, resulting in inhibition of IGF-I activity. Administration of IGF-I variants that are unable to bind to the up-regulated IGFBP species could potentially counteract this effect. We engineered two IGFBP-selective variants that demonstrated 700- and 80,000-fold apparent reductions in affinity for IGFBP-1 while preserving low nanomolar affinity for IGFBP-3, the major carrier of IGF-I in plasma. Both variants displayed wild-type-like potency in cellular receptor kinase assays, stimulated human cartilage matrix synthesis, and retained their ability to associate with the acid-labile subunit in complex with IGFBP-3. Furthermore, pharmacokinetic parameters and tissue distribution of the IGF-I variants in rats differed from those of wild-type IGF-I as a function of their IGFBP affinities. These IGF-I variants may potentially be useful for treating disease conditions associated with up-regulated IGFBP-1 levels, such as chronic or acute renal and hepatic failure or uncontrolled diabetes. More generally, these results suggest that the complex biology of IGF-I may be clarified through in vivo studies of IGFBP-selective variants.


Assuntos
Cartilagem Articular/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Idoso , Substituição de Aminoácidos , Animais , Neoplasias da Mama , Cartilagem Articular/efeitos dos fármacos , Feminino , Variação Genética , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fator de Crescimento Insulin-Like I/farmacocinética , Cinética , Taxa de Depuração Metabólica , Mutagênese Sítio-Dirigida , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley , Receptor IGF Tipo 1/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacocinética , Especificidade por Substrato , Sulfatos/metabolismo , Distribuição Tecidual , Células Tumorais Cultivadas
12.
Hybridoma ; 19(3): 215-27, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10952410

RESUMO

The binding specificities of a panel of mouse monoclonal antibodies (MAbs) to human nerve growth factor (hNGF) were determined by epitope mapping using chimeric and point mutants of NGF. Subsequently, the MAbs were used to probe NGF structure-function relationships. Six MAbs, which recognize distinct or partially overlapping regions of hNGF, were evaluated for their ability to block the binding of hNGF to the TrkA and p75 NGF receptors in various in vitro assays, which included blocking of TrkA autophosphorylation and blocking of NGF-dependent survival of dorsal root ganglion sensory neurons. Three MAbs (911,912,938) were potent blockers of all activities. Potent blocking of p75 binding occurs only with MAb 909, which recognizes an NGF region identified by mutagenesis as important for NGF-p75 binding. These results are consistent with recently proposed models of binding regions involved in NGF-TrkA and NGF-p75 interactions generated through mutagenic analysis and structure determination of the NGF-TrkA complex. These studies provide insight to the epitope specificities and potency of MAbs that would be useful for physiological NGF blocking studies.


Assuntos
Alanina/genética , Anticorpos Monoclonais/metabolismo , Sítios de Ligação de Anticorpos/genética , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Animais , Western Blotting , Células CHO , Cricetinae , Humanos , Mutagênese Sítio-Dirigida , Fator de Crescimento Neural/biossíntese , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Mutação Puntual , Estrutura Secundária de Proteína/genética , Ratos , Receptor de Fator de Crescimento Neural/genética , Receptor de Fator de Crescimento Neural/metabolismo , Receptor trkA/antagonistas & inibidores , Receptor trkA/genética , Receptor trkA/imunologia , Receptor trkA/metabolismo , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Transfecção , Células Tumorais Cultivadas
13.
Drug Metab Dispos ; 28(5): 590-7, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10772640

RESUMO

The purpose of this investigation was to characterize the stability, activity, and interactions of recombinant human nerve growth factor (rhNGF) in various biological matrices in vitro and in vivo. rhNGF (10 microg/ml) remained stable in human plasma for up to 4 days at 37 degrees C. There was a decrease in the recovery of rhNGF after incubation at lower concentrations (20 ng/ml) and for longer time periods (3 and 5 days at 37 degrees C). Size exclusion HPLC analysis indicated that rhNGF forms high molecular weight (HMW) complexes after long incubation periods. We confirmed that alpha(2)-macroglobulin (alpha(2)M) is the major plasma component that binds to rhNGF. Furthermore, this interaction was considerably increased by treatment of plasma with primary amines such as CH(3)NH(2). Changes in the pH environment did not affect the interaction of rhNGF with alpha(2)M. We also determined that the binding of rhNGF to CH(3)NH(2)-treated pure alpha(2)M or alpha(2)M present in human plasma substantially diminished its immunoreactivity and bioactivity detection. The interaction of rhNGF with activated alpha(2)M was reversed and inhibited by coincubation with dimethyl sulfoxide. Released rhNGF under these conditions was fully bioactive. (125)I-rhNGF also binds to alpha(2)M by forming similar (125)I-rhNGF/HMW complexes in plasma after i.v. administration in rats and mice. Sixty minutes after dosing in rats, most of the labeled material was in the form of a (125)I-rhNGF/HMW complex. These studies have provided a better understanding of the nature of the interactions of rhNGF with plasma components as well as methods to enhance, reverse, and inhibit these interactions.


Assuntos
Fatores de Crescimento Neural/metabolismo , Animais , Proteínas Sanguíneas/efeitos dos fármacos , Proteínas Sanguíneas/metabolismo , Cromatografia em Gel , Dimetil Sulfóxido/farmacologia , Ensaio de Imunoadsorção Enzimática , Humanos , Concentração de Íons de Hidrogênio , Radioisótopos do Iodo , Camundongos , Fatores de Crescimento Neural/sangue , Fatores de Crescimento Neural/farmacologia , Células PC12 , Ligação Proteica/efeitos dos fármacos , Ratos , Proteínas Recombinantes/sangue , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , alfa-Macroglobulinas/metabolismo
14.
Drug Metab Dispos ; 28(5): 598-607, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10772641

RESUMO

In this study, we have characterized the metabolism, tissue disposition, excretion routes, and plasma pharmacokinetics of recombinant human nerve growth factor after single and multiple s.c. administration in male cynomolgus monkeys. Unlabeled nerve growth factor (NGF; 2 mg/kg) was administered three times a week for 4 weeks and a full pharmacokinetic profile was obtained for doses 1 and 12. For the tissue distribution studies, 0.8 microg/kg of trace (125)I-labeled recombinant human nerve growth factor was dosed. Histological analysis of emulsion-microautoradiography indicated that specific (125)I-NGF labeling was confined to sections of nerves most frequently localized adjacent to large vessels in sections of kidney, spleen, liver, and salivary gland. A small percentage of large neurons within the sympathetic ganglia were intensely labeled, as well as large neurons within the dorsal root ganglia. We found an increased disposition of (125)I-NGF in parts of the peripheral nervous system (including sympathetic ganglia) from 8 to 24 h postdose. In contrast, radioactivity in most non-neuronal tissues declined. This suggests specific uptake in these target tissues known to express specific receptors for NGF. We also identified changes in pharmacokinetic parameters after single versus chronic s. c. administration. These studies demonstrated that s.c. administration of NGF at 0.8 microg/kg doses in monkeys is capable of accessing and localizing in the target tissues.


Assuntos
Fatores de Crescimento Neural/farmacocinética , Animais , Área Sob a Curva , Autorradiografia , Células CHO , Cricetinae , Nefropatias Diabéticas/tratamento farmacológico , Eletroforese em Gel de Poliacrilamida , Fezes/química , Meia-Vida , Humanos , Injeções Subcutâneas , Radioisótopos do Iodo , Macaca fascicularis , Masculino , Fatores de Crescimento Neural/administração & dosagem , Testes de Precipitina , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacocinética , Distribuição Tecidual
15.
Am J Respir Crit Care Med ; 161(3 Pt 1): 1030-6, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10712359

RESUMO

Reexpansion of a collapsed lung induces increased microvascular permeability leading to reexpansion pulmonary edema (REPE). This study was designed to prove the hypothesis that local overproduction of interleukin-8 (IL-8) induces inflammatory cell accumulation which leads to the induction of REPE. Initially, we examined the detailed characteristics of a rabbit model of REPE in association with IL-8 production and its mRNA expression. The lung tissue to plasma ratio of radiolabeled albumin (T/P ratio), the lung wet to dry ratio, and bronchoalveolar lavage (BAL) neutrophil counts were significantly increased in the reexpanded lung. IL-8 concentrations and mRNA expression were significantly increased in the reexpanded lung homogenate. Immunohistochemically, alveolar macrophages (AMs) and epithelial cells in the reexpanded lung and AMs in the collapsed lung were positive for IL-8. Second, we examined the effect of pretreatment with a specific monoclonal anti-IL-8 antibody (Ab) or control IgG on the development of REPE. The T/P ratio and BAL neutrophil counts were conspicuously decreased by pretreatment with anti-IL-8 Ab, but not with control IgG. On a histopathological study, lung injury and leukocyte infiltration were attenuated by the pretreatment with anti-IL-8 Ab. In conclusion, IL-8 production is enhanced in the reexpanded lung, and contributes to the development of REPE. The pretreatment with anti-IL-8 antibody may be useful as a novel protective therapy for this disease.


Assuntos
Interleucina-8/fisiologia , Atelectasia Pulmonar/imunologia , Edema Pulmonar/imunologia , Síndrome do Desconforto Respiratório/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Líquido da Lavagem Broncoalveolar/imunologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Neutrófilos/imunologia , Atelectasia Pulmonar/patologia , Edema Pulmonar/patologia , Coelhos , Síndrome do Desconforto Respiratório/patologia
16.
Invest Radiol ; 35(2): 111-7, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10674455

RESUMO

RATIONALE AND OBJECTIVES: To evaluate the diagnostic value of breath-hold contrast-enhanced 3D magnetic resonance angiography (MRA) for assessment of the visceral abdominal arteries and veins in patients with suspected abdominal neoplasms. METHODS: Twenty-one patients underwent MR imaging on a 1.5 T unit using a body phased-array coil. MRA was performed with a 3D-FLASH sequence (TR 3.8 ms, TE 1.3 ms, flip angle 25 degrees, acquisition time 20 seconds), 8 to 12 seconds after an intravenous bolus injection of Gd-DTPA. The acquisition delay between the arterial and the portal venous phase was 12 seconds. The image quality and the degree of vascular involvement were evaluated using coronal source images and maximum intensity projection reconstructions. Diagnosis was confirmed by surgery/histology. RESULTS: Image quality was optimal in more than 85% of the patients (19/21 arterial phase and 17/21 portal venous phase). MRA correctly predicted vascular status in 20 of 21 patients (95%), with complete concordance between MRA results and surgical findings. In one patient with chronic pancreatitis, MRA demonstrated a false-positive finding that could not be confirmed surgically. CONCLUSIONS. Breath-hold contrast-enhanced 3D-MRA is a valuable technique for assessing visceral abdominal arteries and veins.


Assuntos
Abdome/irrigação sanguínea , Angiografia por Ressonância Magnética/métodos , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico
17.
Dev Biol Stand ; 97: 121-33, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10463538

RESUMO

We have developed a novel strategy for a rapid bioassay that is accurate, precise, sensitive, and high capacity. It is capable of quantifying ligand bioactivity by measuring ligand-induced receptor tyrosine kinase activation in terms of receptor-phosphorylation. The assay, termed << Kinase Receptor Activation>> or KIRA, uses two separate microtiter plates, one for ligand stimulation of intact cells, and the other for receptor capture and phosphotyrosine ELISA. The assay makes use of either endogenously expressed receptors or stably transfected receptors with a polypeptide flag. KIRA assays for the ligands IGF-I and NGF were compared to their corresponding endpoint bioassays (3T3 cell proliferation for IGF-I and PC12 cell survival for NGF). The KIRA assays showed excellent correlation with the more classical endpoint bioassays. Further, they were highly reproducible, minimizing the requirement for repeat assays. The KIRA assay format has great potential as a rapid, accurate and precise bioassay, both for potency determination as well as stability-indicating analyses.


Assuntos
Bioensaio/métodos , Receptores Proteína Tirosina Quinases/metabolismo , Células 3T3 , Animais , Bioensaio/estatística & dados numéricos , Células CHO , Divisão Celular , Linhagem Celular , Cricetinae , Ativação Enzimática , Ensaio de Imunoadsorção Enzimática , Humanos , Ligantes , Camundongos , Células PC12 , Fosforilação , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Ratos , Receptores Proteína Tirosina Quinases/genética , Receptor IGF Tipo 1/metabolismo , Receptor trkA , Receptores de Fator de Crescimento Neural/genética , Receptores de Fator de Crescimento Neural/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Transdução de Sinais , Transfecção
18.
J Pharm Biomed Anal ; 19(6): 883-91, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10698554

RESUMO

We have developed a novel strategy for a rapid bioassay that is accurate, precise, sensitive, and high capacity. It is capable of quantifying ligand bioactivity by measuring ligand-induced receptor tyrosine kinase activation in terms of receptor phosphorylation. The assay, termed a 'kinase receptor activation' or KIRA, utilizes two separate microtiter plates, one for ligand stimulation of intact cells, and the other for receptor capture and phosphotyrosine ELISA. The assay makes use of either endogenously expressed receptors or stably transfected receptors with a polypeptide flag. KIRA assays for the ligands IGF-I and NGF were compared to their corresponding endpoint bioassays (3T3 cell proliferation for IGF-I and PC12 cell survival for NGF). The KIRA assays showed excellent correlation with the more classical endpoint bioassays. Further, they were highly reproducible, minimizing the requirement for repeat assays. The KIRA assay format has great potential as a rapid, accurate and precise bioassay, both for potency determination as well as stability-indicating analyses.


Assuntos
Bioensaio/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Receptores Proteína Tirosina Quinases/análise , Ativação Enzimática , Humanos , Fator de Crescimento Insulin-Like I/análise , Fosforilação , Receptores Proteína Tirosina Quinases/metabolismo , Receptor trkA/análise , Células Tumorais Cultivadas , Proteínas do Envelope Viral/análise
19.
Biochemistry ; 37(25): 8870-8, 1998 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-9636028

RESUMO

IGF-1 (insulin-like growth factor 1) is a 70-residue protein hormone which has both metabolic and mitogenic activities mediated through IGF-1 binding to cell surface receptors. However, an unrelated class of proteins, the IGF-binding proteins (IGFBPs) also bind IGF-1 in the serum and tissues and block or modulate its activity in vivo. Therefore, inhibitors of the IGFBPs can alter the distribution between free and bound IGF-1 [Loddick, S. A., Liu, X.-J., Lu, Z.-X., Liu, C., Behan, D. P., Chalmers, D. C., Foster, A. C., Vale, W. W., Ling, N., and De Souza, E. B. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 1894-1898] and potentially affect the distribution of IGF-1 among body tissues. We report here that phage-displayed peptide libraries have yielded a peptide that binds IGFBP-1 and produces IGF-like activity at sub-micromolar concentrations. The 14-residue peptide has an extremely well-defined solution conformation that can aid in the design of smaller, orally active compounds. Interestingly, the peptide structure contains a helix, as does one region of IGF-1 previously implicated in IGFBP binding, yet displays side chains different from those of the IGF-1 helix I. Furthermore, an IGF-1 variant lacking receptor-signaling activity in vitro is shown here to produce IGF-like mitogenic and metabolic activity in vivo. These results suggest that small antagonist mimetics of protein ligands, identified by binding selection to otherwise inhibitory factors, may be useful as indirect agonists for a variety of therapeutic applications.


Assuntos
Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , Fator de Crescimento Insulin-Like I/metabolismo , Mimetismo Molecular , Sequência de Aminoácidos , Animais , Bacteriófago M13/metabolismo , Ligação Competitiva/efeitos dos fármacos , Insulina/farmacologia , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/antagonistas & inibidores , Fator de Crescimento Insulin-Like I/química , Fator de Crescimento Insulin-Like I/farmacologia , Ligantes , Masculino , Modelos Moleculares , Dados de Sequência Molecular , Biblioteca de Peptídeos , Peptídeos/síntese química , Peptídeos/farmacologia , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Ratos Zucker , Receptor IGF Tipo 1/deficiência
20.
Radiology ; 206(2): 373-8, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9457188

RESUMO

PURPOSE: To evaluate the use of dual-phase helical computed tomography (CT) (with or without CT angiography) to assess resectability in patients suspected to have pancreatic cancer. MATERIALS AND METHODS: Tumor resectability was prospectively evaluated in 89 patients who later underwent surgery for suspected pancreatic cancer. Helical CT scans were obtained in the vascular phase and a phase of maximal hepatic enhancement. CT angiograms were produced with multiprojection volume reconstruction and maximum-intensity projection. CT results were correlated with surgical and histopathologic results. RESULTS: Helical CT allowed detection of pancreatic cancer in 74 of 76 cases (97%). There were six false-positive results (positive predictive value, 92%). For prediction of irresectability, helical CT had an accuracy of 91%, negative predictive value of 79%, and sensitivity of 91%. Helical CT allowed detection of liver metastases in 21 of 28 cases (75%), nodal involvement in 13 of 24 cases (54%), and vascular invasion in 35 of 40 cases (88%). CT angiography demonstrated 30 of the 35 cases of vascular invasion detected with helical CT (86%). CONCLUSION: Use of dual-phase helical CT improves prediction of resectability in patients with pancreatic cancer. CT angiography cannot show all of the findings seen on helical scans.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma/epidemiologia , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Angiografia/métodos , Meios de Contraste , Estudos de Avaliação como Assunto , Feminino , Humanos , Iohexol/análogos & derivados , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...