RESUMO
We employ light-induced double Bragg diffraction of delta-kick collimated Bose-Einstein condensates to create three symmetric Mach-Zehnder interferometers. They rely on (i) first-order, (ii) two successive first-order, and (iii) second-order processes which demonstrate the scalability of the corresponding momentum transfer. With respect to devices based on conventional Bragg scattering, these symmetric interferometers double the scale factor and feature a better suppression of noise and systematic uncertainties intrinsic to the diffraction process. Moreover, we utilize these interferometers as tiltmeters for monitoring their inclination with respect to gravity.
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BACKGROUND: Docetaxel is a widely used cytotoxic agent. This study evaluates the impact of docetaxel toxicities on patient's health-related quality of life (QoL). PATIENTS AND METHODS: We conducted a multicenter, prospective, non-interventional trial, in which the QoL was assessed using the EORTC QLQ-C30 questionnaires at baseline and every 4 weeks up to 40 weeks in patients receiving a docetaxel-based chemotherapy for metastatic disease. Treatment-related adverse events were correlated with the corresponding QoL scores. Uni- and multivariate analyses were applied. RESULTS: From January 2008 to June 2011, a total of 2659 patients were included. The majority of patients (48.1%) had prostate cancer, followed by breast (17.1%) and non-small-cell-lung cancer (15.8%). Patients received a median of 5 docetaxel cycles with the median dose of 75 mg/m(2). The presence of grade 3/4 diarrhea showed the strongest effect on global health status/QoL average scores (50.91 versus 33.06), followed by vomiting (50.91 versus 35.17), dyspnea (50.94 versus 35.81), mucositis/stomatitis (50.88 versus 36.41), nausea (50.91 versus 36.68), infection (50.90 versus 37.14), fatigue (50.90 versus 43.82) and anemia (50.91 versus 41.03), P < 0.05 for all comparisons. Grade 3/4 leukopenia/neutropenia, alopecia, constipation, neurotoxicity and nail disorders had no significant impact on the global health status/QoL or other items. CONCLUSION: In this large non-interventional trial, docetaxel-associated grade 3 or 4 toxicities were shown to have a strong detrimental effect on patient's QoL. Notably, diarrhea and vomiting had the strongest negative impact on QoL measures. This has to be kept in mind while making therapeutic decisions and providing optimized supportive treatment measures. CLINICAL TRIALS NUMBER: This study was registered at Deutsches Krebsstudienregister (DKSR, primary registry in the WHO Registry Network) with the ID 527.
Assuntos
Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/psicologia , Neoplasias/tratamento farmacológico , Qualidade de Vida , Taxoides/efeitos adversos , Idoso , Diarreia/induzido quimicamente , Diarreia/psicologia , Docetaxel , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Feminino , Alemanha , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Neoplasias/patologia , Neoplasias/psicologia , Seleção de Pacientes , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Vômito/induzido quimicamente , Vômito/psicologiaRESUMO
BACKGROUND: People receiving hematopoietic stem cell transplantation (HSCT) endure long phases of therapy and immobility, which diminish their physical activity (PA) level leading to physical deconditioning. One of the reasons is a lack of clarity on the part of those who work in oncology clinical settings of their role in assessing, advising, and referring patients to exercise. Therefore, our study investigates reported physical activity counseling behavior of health care professionals (HCPs) and the patient perspective on this topic. METHODS: Physicians (N = 52), nurses (N = 52) physical therapists (N = 26), and patients receiving HSCT (N = 62) participated in a nationwide cross-sectional online-survey. Patients' preferred source of information concerning PA was determined. We examined HCPs self-assessed PA counseling behavior and patients' PA recall by assessing the use of the 5As (Ask, Advice, Agree, Assist, Arrange). Analysis of survey responses was descriptive. Univariate multinomial logistic regression examined whether sociodemographic factors and patient characteristics influence the response behavior. RESULTS: Physicians and PA specialists were patients' preferred source of information regarding PA. A large discrepancy between HCPs' perception and the degree to which HSCT patients recall advice became apparent; profound counseling steps like making referrals were less often recalled in our patient sample. Inactive patients reported to receive less basic PA counseling by physicians. CONCLUSION: Future research should identify the requirements to increase patients' recall concerning PA counseling in the setting of HSCT. Important messages about PA need to be made more salient to those who are less active and less engaged.
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Promoção da Saúde , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Transversais , Exercício Físico/fisiologia , Aconselhamento , Transplante de Células-TroncoRESUMO
Antibodies directed against the autoantigen p26 were detected in sera from 32 patients with acute Epstein-Barr virus (EBV) infection and clinical symptoms of infectious mononucleosis. P26 has now been identified as the enzyme manganese superoxide dismutase (MnSOD) by comparison of the NH2-terminal amino acid sequence. Antibodies against MnSOD belong to the immunoglobulin class M. They are not detectable in sera of patients with other herpesvirus infections. In the 32 patients investigated, the rise and fall of the autoantibodies coincides with the clinical symptoms. In vitro, the autoantibodies were shown to inhibit the dismutation of superoxide radicals by blocking MnSOD. As presented in the discussion this effect may contribute to the pathogenesis of acute EBV infection.
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Autoanticorpos/análise , Mononucleose Infecciosa/imunologia , Superóxido Dismutase/imunologia , Doença Aguda , Sequência de Aminoácidos , Autoanticorpos/imunologia , Humanos , Imunoglobulina M/análise , Imunoglobulina M/imunologia , Dados de Sequência MolecularRESUMO
Amino acid absorption was studied in chronic uremic rats. Intestinal transport of L-leucine appears to be inhibited with mild uremic intoxication, whereas severe uremia enhances absorption. Brush border activity of intestinal maltase and disaccharidases is higher in rats with chronic renal insufficiency. The same holds for gamma-glutamyl-transpeptidase activity.
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Absorção Intestinal , Mucosa Intestinal/metabolismo , Uremia/metabolismo , Animais , Dissacaridases/metabolismo , Mucosa Intestinal/enzimologia , Rim/fisiopatologia , Leucina/metabolismo , Masculino , Ratos , alfa-Glucosidases/metabolismo , gama-Glutamiltransferase/metabolismoRESUMO
BACKGROUND: Chronic hepatitis resulting from the hepatitis C virus (HCV) infection leads to cirrhosis in at least half the infected patients and increases the risk of hepatocellular carcinoma. There are indications that this pathogenic effect may result from the disturbance of intracellular signal cascades caused by the interaction with viral antigens. Although a great amount of data has been accumulated about functional regions in HCV proteins, relatively little is known about their intracellular targets. Previously, we have demonstrated that the full-length non-structural protein 3 of HCV (NS3) (Borowski P, Heiland M, Feucht H, Laufs R. Characterisation of non-structural protein 3 of hepatitis C virus as modulator of protein phosphorylation mediated by PKA and PKC. Evidences for action on the level of substrate and enzyme. Arch Virol 1999a; 144) and its NH2- and COOH-terminal truncated form (Borowski P, Heiland M, Oehlmann K, Becker B, Kornetzky L, Feucht HH, Laufs R. Non-structural protein 3 of hepatitis C virus inhibits phosphorylation mediated by cAMP-dependent protein kinase. Eur J Biochem 1996;237:611-618) associate to stable complexes with core histones H2B and H4. The changes of the properties of histones as substrate for cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) were found as a direct consequence of the interaction. OBJECTIVE: In the present study we further these observations, localize the histone binding domain of NS3 and investigate the mechanisms by which NS3 affects the functions of the histones in vitro. STUDY DESIGN: HCV protein exhibiting the mentioned histone binding activity was produced in a bacterial expression system, purified and binding to histones was biochemically characterized. The region of NS3 involved in the interaction with histones was defined by proteolytic fragmentation, microsequencing and a specific histone binding assay. Furthermore, a functional test to quantify the interaction of histones with DNA was established and the binding of DNA to histone as a function of NS3 concentration was analysed by means of graphical methods. RESULTS: The investigated fragment of HCV polyprotein consisting of amino acid residues 1189-1525 (HCV-polyprotein-(1189-1525)) displayed significant histone binding activity. The binding occurred at a molar ratio 1:1 of histone to HCV-polyprotein-(1189-1525) and was mediated by a linear stretch of amino acids located between the residues 1343 and 1379 of the HCV polyprotein. To demonstrate that HCV-polyprotein-(1189-1525) affects the binding of DNA to histones we used two independent methods: overlay assay and binding assay on Sepharose beads. Graphic analysis of the binding kinetics revealed an uncompetitive type of inhibition. CONCLUSIONS: Our results provide the first evidence that NS3 binds and affects the functions of core histones. The mechanism by which the NS3 interferes with the histone functions involves conformational changes of histone molecule.
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Hepacivirus/metabolismo , Histonas/metabolismo , Proteínas não Estruturais Virais/metabolismo , Sítios de Ligação , DNA/metabolismo , HumanosRESUMO
A novel enzyme-linked immunosorbent assay (ELISA) was developed for human cytomegalovirus (HCMV) utilizing a monoclonal anti-idiotype specific for CMVB1, an antibody to HCMV. Samples of HCMV were measured by their inhibition of the binding of CMVB1 to anti-idiotype. The ELISA detected HCMV in a concentration-dependent manner from 20 to 0.6 x 10(3) PFU/ml, with 50% inhibition at approx. 3 x 10(3) PFU/ml. These data demonstrate the potential of anti-idiotype antibodies as the basis of simple and rapid diagnostic tests for infectious agents.
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Anticorpos Anti-Idiotípicos , Anticorpos Antivirais , Antígenos Virais/análise , Citomegalovirus/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Afinidade de Anticorpos , Antígenos Virais/imunologia , Citomegalovirus/isolamento & purificação , Humanos , Sensibilidade e EspecificidadeRESUMO
A trial of operative cholangiomanometry was proposed as a guide to common duct exploration to see if this technique would help in reducing the incidence of unnecessary common bile duct explorations and the incidence of retained stones. The technique for operative cholangiomanometry as modified from White is described. This method was used in 21 patients. A very close correlation between manometry and cholangiography in predicting the presence of pathology within the common duct at the time of extrahepatic biliary surgery was shown. Flow was the most accurate diagnostic parameter. Seven patients who were found to have common duct stones had both abnormal manometry and cholangiography. Fourteen patients without stones included 12 with negative cholangiography and manometry, and two in which manometry was normal but cholangiography suggested pathology. Common duct manometry and cholangiography can be used to decrease the number of unnecessary common duct explorations and the incidence of retained stones. The theory that common duct pathology will increase pressure and decrease flow rates is supported by this study. Manometry and cholangiography should be used in combination as they are additive studies. Criteria for deciding when to explore the common duct are presented.
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Colangiografia/métodos , Ducto Colédoco , Cálculos Biliares/diagnóstico , Adulto , Idoso , Doenças do Ducto Colédoco/diagnóstico , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-IdadeRESUMO
The results of an investigation of adolescents with an attributional-style-questionnaire for real-life-situations are presented. Between the two clinical groups with neurotic respectively antisocial problems and the control group of adolescents with different somatic diseases only few significant differences were found corresponding to the attributional style; important differences were found according to the significance the groups ascribe to the different situations. The results are discussed and implications for the clinical therapeutic work are derived.
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Transtorno da Personalidade Antissocial/psicologia , Controle Interno-Externo , Transtornos Neuróticos/psicologia , Desenvolvimento da Personalidade , Adolescente , Feminino , Humanos , Masculino , Inventário de Personalidade , Papel do DoenteRESUMO
AIM: To correlate findings of hip ultrasound on day 4-10 of life with sex, intrauterine position and a positive family history for congenital hip anomalies. METHODS: The SNiP-study ( Survey of Neonates In Pommerania) registered 2256 neonates (2030 term, 226 preterm) between May 2002 and March 2004. Hip ultrasound results of 1043 term and since October 2003 33 preterm neonates were analysed. Time of ultrasound was day 4-10 after birth. Preterm neonates were examined when reaching their corrected term gestational age. Ultrasound was applied with a 7.5 MHz linear scanner and results were classified according to Graf. Chi-square and Fishers exact test were used for statistical analysis. RESULTS: 4.9 % of the screened hips were classified as IIc or higher, 3.1 % were unilateral and 1.7 % bilateral. Incidence was significantly higher (p < 0.023) in females (6.6 %) than in males (3.2 %). There was no significant difference in intrauterine position or positive family history for hip anomalies with 3.7 % for mothers, 1.2 % of fathers and 2.4 % of siblings positive. There was a higher incidence for congenital hip dysplasia in preterms with 6.1 %, which is not significant due to the limited number. DISCUSSION: Current screening methods miss up to 18 % of newborns with severe hip dysplasia. We were able to demonstrate that screening for congenital hip dysplasia with ultrasound is a diagnostic tool even during the first days of life. There is a significantly higher incidence of congenital hip dysplasia in females, but in contrast to other studies we found no significant difference in intrauterine position or familial history. Earlier diagnosis and therapy on the base of relevant risk factors might correspond with an improved prognosis and outcome. Further studies are warranted to evaluate the significance in preterm neonates.
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Luxação Congênita de Quadril/diagnóstico por imagem , Luxação Congênita de Quadril/genética , Feminino , Luxação Congênita de Quadril/embriologia , Luxação Congênita de Quadril/epidemiologia , Humanos , Incidência , Recém-Nascido , Masculino , Gravidez , Caracteres Sexuais , Irmãos , Ultrassonografia Pré-NatalRESUMO
A sample of 57 children aged 9 to 14 years with aggressive behavior disorders was compared with an unselected clinical control group of non-aggressive children with regard to personality traits and child psychiatric classifications. The children were divided into groups of more or less aggressive symptoms (mainly aggressive--partly aggressive--non aggressive patients) and after statistical grouping according to personality traits. Three type factors could be extracted, and their relationship to the principal symptoms was analyzed. Finally the relevance of the three type factors for an efficient classification and therapy of children with aggressive conduct disorders is discussed.
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Agressão/psicologia , Transtornos do Comportamento Infantil/psicologia , Desenvolvimento da Personalidade , Autoimagem , Adolescente , Criança , Feminino , Humanos , Masculino , Testes de PersonalidadeRESUMO
The diagnostic and therapeutic relevance of a questionnaire on action control. The present study deals with the applicability of the "theory of action control" (Kuhl, 1983) to psychiatric disorders in adolescents. A questionnaire on action vs state orientation in planning situations (HOP scale; Kuhl, 1985) was given to adolescent inpatients. The sample was subdivided into an anorectic group and by extreme-group clustering, a group with severe conduct disorders and a clinical control group. The hypothesis of high scores on action orientation on the HOP scale was confirmed for the anorectic patients but not for those with conduct disorders. A factor analysis of the HOP scale items yielded a three-factor solution. For two of the three factors differences between the clinical groups were found: The anorectic patients showed a high level of action orientation in situations with intense task commitment, whereas the patients with conduct disorders were mainly action-oriented in situations with forced decisions. With some restrictions the findings can be interpreted as clinical validation of the questionnaire.
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Anorexia Nervosa/diagnóstico , Anorexia Nervosa/psicologia , Transtorno da Personalidade Antissocial/diagnóstico , Transtorno da Personalidade Antissocial/psicologia , Hospitalização , Controle Interno-Externo , Motivação , Desenvolvimento da Personalidade , Adolescente , Anorexia Nervosa/terapia , Transtorno da Personalidade Antissocial/terapia , Feminino , Humanos , Masculino , Determinação da Personalidade , SocializaçãoRESUMO
Sera of 146 patients with acute EBV, HAV, HBV, CMV, HSV, and rubella virus infections, and sera from 35 healthy controls were tested for the antioxidant enzyme manganese superoxide dismutase (MnSOD). An enzyme immunoassay that detects all isomeres of the enzyme was developed. The mean MnSOD value of healthy controls was 107 ng/ml. In HAV, HBV and EBV infections characterized by viral replication in internal organs, there was an average 5-fold rise of serum MnSOD, whereas in viral infections with low direct cytopathogenity, such as rubella, CMV and HSV, the MnSOD levels showed only minor rises. These sera were also tested for autoantibodies against MnSOD using a novel sensitive indirect enzyme immunoassay. The average IgM anti-MnSOD concentration in sera of healthy controls was 112 GU. In sera of patients with acute HBV, CMV, HSV or rubella virus infections IgM anti-MnSOD values were only slightly raised above the cut-off level. In contrast, in some patients with acute EBV infections anti-MnSOD concentrations rose up to 20-fold of normal values. In HAV infections the same phenomenon was observed in patients who had reactivated EBV infections. These findings indicate that EBV may facilitate the B-cell response to MnSOD. These autoantibodies may inhibit the protective function of MnSOD and prolong the disease by oxygen injury. Our concept on the pathogenic effect of the autoantibodies against MnSOD emphasizes the importance of the antioxidant enzyme in viral infections.
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Autoanticorpos/sangue , Superóxido Dismutase/sangue , Viroses/enzimologia , Doença Aguda , Adulto , Autoantígenos/sangue , Autoantígenos/imunologia , Humanos , Imunoglobulina M/sangue , Superóxido Dismutase/imunologia , Viroses/sangue , Viroses/imunologiaRESUMO
Monoclonal antibodies of both the IgG and the IgM type were purified by hydroxylapatite HPLC (HA-HPLC) under very mild conditions. The IgM type antibodies, which were isolated from ascites fluid and separated from other proteins also by means of size exclusion HPLC. It was shown that the most frequently observed disadvantage of HA-HPLC, that is the relative short life of the columns (P. Steffen (1989) GIT Fachz. Lab., Suppl. 3/89 (Chromatogr.), 50-90), is due to microbial contamination rather than lower mechanical stability. In order to monitor column performance, a test was developed based on the use of standard proteins under isocratic separation conditions. This allows a direct comparison between the respective performances of columns made from different materials, hydroxylapatite or fluoroapatite, from different sources and with different particle sizes. A problem which often occurs with HA-HPLC in the case of IgM antibody isolation, namely precipitation of the antibodies at low salt concentrations at the beginning of a chromatographic run, was avoided by adding sodium chloride to both separation buffers.
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Anticorpos Monoclonais/isolamento & purificação , Soluções Tampão , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Eletroforese em Gel de Poliacrilamida , Humanos , Hidroxiapatitas , Imunoglobulina G/isolamento & purificação , Imunoglobulina M/isolamento & purificação , Controle de QualidadeRESUMO
Four monoclonal antibodies against HuIFN-alpha-1 and -alpha-2 were produced by the lymphocyte hybridoma technique. The screening for monoclonal anti-IFN antibodies was performed by two different procedures permitting the detection of neutralizing and non-neutralizing antibodies. The first antibody screening in the supernatants of hybridoma clones was carried out by an immunodot ELISA using a novel chromogen, 2-bromo-1-naphthol, for the immunoperoxidase reaction. The second screening was performed with a solid-phase bioassay. The monoclonal antibodies IIG11 and IVH2 react specifically with HuIFN-alpha-1 independently of its origin, natural or recombinant. The mAb IIG11 recognizes also an epitope on a 27 kDa interferon, probably HuIFN-alpha-8. The mAb IIG7 binds to HuIFN-alpha-2 only, whereas the mAb IIB2 binds to HuIFN-alpha-2 and also to the 27 kDa interferon and to a 25 kDa interferon, not yet further characterized. These antibodies can be used successfully for immunopurification as well as for quantification of the corresponding interferons.
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Anticorpos Monoclonais , Interferon Tipo I/análise , Anticorpos Monoclonais/isolamento & purificação , Reações Antígeno-Anticorpo , Bioensaio , Cromatografia de Afinidade , Ensaio de Imunoadsorção Enzimática , Humanos , Hibridomas/imunologia , Interferon Tipo I/imunologia , Leucócitos/imunologia , Peso Molecular , Testes de Neutralização , Proteínas RecombinantesRESUMO
A detergent extract isolated from the enriched fraction of integral membrane proteins of Jurkat cells showed an enhanced tyrosine phosphate level when phosphorylated in the presence of phorbol 12-myristate 13-acetate (TPA) and phorbol 12,13-dibutyrate (PDBu). The enhanced tyrosine phosphorylation was observed when the reaction time exceeded 6 min; at shorter incubation times, however, TPA inhibited tyrosine phosphorylation. When the reaction proceeded for a constant time period longer than 6 min and phorbol esters were added at different times after the start of the reaction, two phases of an enhanced tyrosine phosphorylation of a 50 kDa protein were observed. An increased phosphorylation of the 50 kDa protein was correlated with an enhanced phosphorylation of poly(Glu4,Tyr1). The two phases of enhanced phosphorylation differed in their TPA and PDBu requirement and in the proteins that were tyrosine phosphorylated. Studies with protein kinase C (PKC) inhibitors showed a negatively correlated effect on the enhanced tyrosine phosphorylation in phase I; tyrosine phosphorylation was further augmented. In phase II the regulation of tyrosine phosphorylation correlated with the efficiency of the PKC inhibitors on the alpha-isoform of PKC which was found in the cell extract. Separation of the proteins present in the investigated cell extract by gel filtration revealed a co-migration of the alpha-PKC and the 50 kDa protein. The metabolic labeling of intact Jurkat cells with 32Pi indicated that phorbol esters are also able to induce tyrosine phosphorylation of the 50 kDa protein underin vivo conditions. These data suggest an activation of two different tyrosine phosphorylation pathways by phorbol esters involving tyrosine phosphorylation/autophosphorylation of a 50 kDa kinase, as confirmed by 5'-p-fluorosulfonylbenzoyladenosine (FSBA) labeling, that are accurately regulated by alpha-PKC.