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1.
Matern Child Health J ; 26(3): 451-460, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35000072

RESUMEN

PURPOSE: There has been increasing awareness of perinatal health and organisation of maternal and child health care in the Netherlands as a result of poor perinatal outcomes. Vulnerable women have a higher risk of these poor perinatal outcomes and also have a higher chance of receiving less adequate care. Therefore, within a consortium, embracing 100 organisations among professionals, educators, researchers, and policymakers, a joint aim was defined to support maternal and child health care professionals and social care professionals in providing adequate, integrated care for vulnerable pregnant women. DESCRIPTION: Within the consortium, vulnerability is defined as the presence of psychopathology, psychosocial problems, and/or substance use, combined with a lack of individual and/or social resources. Three studies focussing on population characteristics, organisation of care and knowledge, skills, and attitudes of professionals regarding vulnerable pregnant women, were carried out. Outcomes were discussed in three field consultations. ASSESSMENT: The outcomes of the studies, followed by the field consultations, resulted in a blueprint that was subsequently adapted to local operational care pathways in seven obstetric collaborations (organisational structures that consist of obstetricians of a single hospital and collaborating midwifery practices) and their collaborative partners. We conducted 12 interviews to evaluate the adaptation of the blueprint to local operational care pathways and its' embedding into the obstetric collaborations. CONCLUSION: Practice-based research resulted in a blueprint tailored to the needs of maternal and child health care professionals and social care professionals and providing structure and uniformity to integrated care provision for vulnerable pregnant women.


Asunto(s)
Prestación Integrada de Atención de Salud , Partería , Niño , Femenino , Humanos , Embarazo , Mujeres Embarazadas/psicología , Psicopatología , Apoyo Social
2.
J Clin Pharm Ther ; 38(1): 3-11, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23281770

RESUMEN

BACKGROUND AND OBJECTIVE: Auron Misheil therapy (AMT) is a combination of widely used pharmaceuticals and herbal components that has been used since the 1980s as a supportive therapy, mainly in end-stage cancer patients on a compassionate basis. This phase I study was conducted to assess the safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) properties of AMT in a controlled trial environment. METHODS: The study was conducted in a single rising dose, double-blind, placebo-controlled design. Three groups of eight healthy male volunteers received one of three doses of AMT (0·011, 0·033 or 0·066 mL AMT/kg body weight intramuscularly; n = 6 per group) or placebo (n = 2 per group). RESULTS AND DISCUSSION: Auron Misheil therapy was shown to be well tolerated, revealing no severe or serious adverse events. There were no unexpected PK or PD results for any of the three components of AMT. CONCLUSIONS: These data provide important PK, PD and safety data for AMT, and support further controlled clinical investigation in patients with different types of cancer as an option for supportive care.


Asunto(s)
Calcio/administración & dosificación , Clorfeniramina/administración & dosificación , Insulina/administración & dosificación , Extractos Vegetales/administración & dosificación , Adulto , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Calcio/efectos adversos , Calcio/farmacocinética , Clorfeniramina/efectos adversos , Clorfeniramina/farmacocinética , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Humanos , Insulina/efectos adversos , Insulina/farmacocinética , Masculino , Extractos Vegetales/efectos adversos , Extractos Vegetales/farmacocinética , Adulto Joven
3.
Midwifery ; 127: 103855, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37890235

RESUMEN

OBJECTIVE: To evaluate the current practice of preconception care in the Netherlands and the perceptions of birth care professionals concerning preconception care. METHODS: We have developed a digital questionnaire and conducted a cross-sectional study by distributing the questionnaire among 102 organisations: 90 primary care midwifery practices and obstetric departments of 12 hospitals in the Southwest region of the Netherlands between December 2020 and March 2021. One birth care professional per organization was asked to complete the questionnaire. Descriptive statistics were used to present the results. FINDINGS: Respondents of eighty-three organisations (81.4 %) filled in the questionnaire, of whom 74 respondents were independent primary care midwives and 9 respondents were obstetricians. Preconception care mostly consisted of an individual consultation in which personalized health and lifestyle advice was given. Among the respondents, 44.4 % reported that the organization had a preconception care protocol. The way in which the consultation was carried out, as well as the health and lifestyle related questions asked, differed between respondents. More than 85 % of the respondents inquire about the following possible risk factors for complications: maternal illnesses, obstetric history, folic acid supplement intake, alcohol intake, smoking, substance abuse, hereditary disease, prescription medication, dietary habits, overweight, and birth defects in the family. The respondents acknowledged that preconception care should be offered to all couples who wish to become pregnant, as opposed to offering preconception care only to those with an increased risk of complications. Still, respondents do not receive many questions regarding the preconception period or requests for preconception care consultations. KEY CONCLUSION: Birth care professionals acknowledge the need for preconception care for all couples. In the Netherlands, preconception care consists mostly of an individual consultation with recommendations for health and lifestyle advice. However, the identification of risk factors varies between birth care professionals and less than half of the respondents indicate that they have a protocol available in their practice. Furthermore, the demand of parents-to-be for preconception care is low. More research, that includes more obstetricians, is necessary to investigate if there is a difference between the care provided by primary care midwives and obstetricians. IMPLICATIONS FOR PRACTICE: To increase the awareness and uptake of preconception care, it would be prudent to emphasize its importance to parents-to-be and professionals, and actively promote the use of widespread, standardized protocols for birth care professionals.


Asunto(s)
Partería , Atención Preconceptiva , Embarazo , Femenino , Humanos , Atención Preconceptiva/métodos , Países Bajos , Estudios Transversales , Encuestas y Cuestionarios
4.
Osteoarthritis Cartilage ; 20(9): 982-7, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22698441

RESUMEN

OBJECTIVE: To explore the associations between spinal morning stiffness and lumbar disc degeneration (LDD). DESIGN: Data from a cross-sectional general population-based study (Rotterdam Study-I) were used. Intervertebral disc spaces and osteophytes of people aged ≥55 years were scored on lumbar lateral radiographs (L1-2 through L5-S1 was scored). Logistic regression analysis was used to explore associations between spinal morning stiffness and two definitions of LDD (i.e., 'narrowing' and 'osteophytes'). Spinal morning stiffness combined with low back pain and its association with LDD was also analyzed. Similar analyses were performed for knee and hip pain, morning stiffness in the legs, and radiographic knee and hip osteoarthritis (OA) in order to compare these associations with those of LDD. All analyses were adjusted for age, gender, and body mass index (BMI). RESULTS: Lumbar lateral radiographs were scored for 2,819 participants. Both definitions of LDD were associated with spinal morning stiffness: adjusted odds ratio (aOR) 1.3; 95% confidence interval (CI): 1.1-1.6 for 'osteophytes' and aOR 1.8; 95% CI: 1.4-2.2 for 'narrowing'. Both the odds ratios increased when spinal morning stiffness was combined with low back pain: aOR 1.5; 95% CI: 1.1-2.0 for 'osteophytes' and aOR 2.5; 95% CI: 1.9-3.4 for 'narrowing'. When morning stiffness in the legs was combined with knee or hip pain, the associations with radiographic knee or hip OA were: aOR 3.0; 95% CI: 2.1-4.1 for knee OA and aOR 3.1; 95% CI: 1.9-5.0 for hip OA. CONCLUSIONS: Reported spinal morning stiffness is associated with LDD. The associations increased when we combined spinal morning stiffness with low back pain. The magnitude of the association for the definition 'narrowing' is similar to the association between morning stiffness in the legs and knee or hip OA.


Asunto(s)
Degeneración del Disco Intervertebral/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Osteofito/diagnóstico por imagen , Anciano , Artralgia/epidemiología , Estudios Transversales , Femenino , Articulación de la Cadera/diagnóstico por imagen , Humanos , Degeneración del Disco Intervertebral/epidemiología , Articulación de la Rodilla/diagnóstico por imagen , Dolor de la Región Lumbar/epidemiología , Masculino , Países Bajos/epidemiología , Osteoartritis de la Cadera/diagnóstico por imagen , Osteoartritis de la Cadera/epidemiología , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/epidemiología , Osteofito/epidemiología , Periodicidad , Radiografía
5.
Chemotherapy ; 57(5): 437-48, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22189340

RESUMEN

BACKGROUND: There are only limited data on tissue kinetics of ertapenem in colorectal tissue more than 3 h after administration of the drug. The purpose of this study was to assess the pharmacokinetics (PK) of ertapenem in colorectal tissue via population PK modeling. PATIENTS AND METHODS: Patients ≥18 years requiring surgical intervention at the colon and/or rectum were eligible (ClinicalTrials.gov identifier: NCT 00535652). Tissue and blood samples were taken during surgery after a single dose of 1 g ertapenem. Ertapenem concentration was determined by high-performance liquid chromatography/mass spectrometry. Population PK modeling was performed in S-ADAPT. RESULTS: Twenty-three patients were enrolled. The highest tissue concentration was 6.4 ± 2.3 mg/kg, the highest total plasma concentration 51.34 ± 9.4 mg/l, the highest unbound plasma concentration 7.05 ± 1.1 mg/l, and the unbound fraction in plasma was 14-15% for total ertapenem concentrations below approximately 22 mg/l, 19% at 100 mg/l, and 25% at 250 mg/l. The estimated geometric mean terminal half-life was 2.5 h for plasma and tissue. In the Monte Carlo simulation, a single dose of 1,000 mg ertapenem achieved robust (≥90%) probabilities of target attainment up to a minimum inhibitory concentration (MIC) of approximately 2 mg/l for the bacteriostasis target (free time above MIC, fT(>)(MIC) = 20%) and up to 0.25-0.5 mg/l for the near-maximal killing target (40% fT(>)(MIC)). CONCLUSION: Our data indicate an adequate penetration of ertapenem into uninfected colorectal tissue up to 8.5 h (35% of the dosing interval) after administration of 1 g intravenously.


Asunto(s)
Colon/metabolismo , Recto/metabolismo , beta-Lactamas/farmacocinética , Adulto , Anciano , Colon/efectos de los fármacos , Ertapenem , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos , Unión Proteica , Recto/efectos de los fármacos , Distribución Tisular
6.
Zentralbl Chir ; 135(4): 377-9, 2010 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-19842079

RESUMEN

BACKGROUND: Hemoperitoneum due to spontaneous rupture of a visceral vessel may result from a variety of underlying pathologies. However, its idiopathic form does not show evidence of any predisposition. PATIENT AND METHODS: An abdominal CT scan for acute abdominal pain yielded the unexpected diagnosis of a ruptured splenic artery in a 21-year-old patient. Hemostasis was achieved by endovascular coiling of a segmental splenic artery lacking any evidence of pathological transformation. An extensive intraabdominal hematoma was evacuated in a consecutive laparoscopy which, furthermore, confirmed interventional success. Despite extensive diagnostic efforts, the cause of the bleeding remained undefined. CONCLUSION: Spontaneous hemoperitoneum may occasionally be considered as a cause of acute abdomial pain and is diagnostically challenging. An interdisciplinary approach is desirable to meet the objective of modern organ-preserving therapy in splenic artery rupture.


Asunto(s)
Abdomen Agudo/etiología , Hemoperitoneo/etiología , Arteria Esplénica , Angiografía , Diagnóstico Diferencial , Embolización Terapéutica , Hemoperitoneo/terapia , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Masculino , Rotura Espontánea/diagnóstico , Rotura Espontánea/patología , Rotura Espontánea/terapia , Tomografía Computarizada por Rayos X , Adulto Joven
7.
Midwifery ; 86: 102708, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32289596

RESUMEN

OBJECTIVE: Vulnerability among pregnant women is an important and complex theme in the everyday practice of midwives. Exchanging knowledge and best practices about vulnerability between midwives in Europe can contribute to improving the knowledge and skills of midwives and as a result improve the care for vulnerable pregnant women. We therefore start a consortium with midwives, midwifery teachers, researchers and students from organizations of seven European cities with the aim to exchange knowledge and best practices concerning vulnerable pregnant women between midwives. To be able to effectively exchange knowledge and best practices, our consortium started with this study focuses on establishing a mutual definition of vulnerable pregnant women. Therefore, the aim of this study is to develop a mutual definition of vulnerable pregnant women and to identify aspects related to vulnerability. DESIGN: Delphi study with four rounds: (1) gathering existing knowledge from literature and definitions used by partners of the consortium, (2) and (3) two survey rounds and (4) an in-person consensus meeting. SETTING: Consortium of midwives, midwifery teachers, researchers and students from Antwerp (Belgium), Ghent (Belgium), Turku (Finland), Milan (Italy), Pila (Poland), Lisbon (Portugal) and Rotterdam (The Netherlands) PARTICIPANTS: We included all consortium members in the Delphi study. FINDINGS: Various aspects related to vulnerability and appropriate definitions were identified during the Delphi rounds. Consensus about the aspects related to vulnerability and the definition of vulnerable pregnant women was reached during the final consensus meeting. A vulnerable pregnant woman was defined as a woman who is threatened by physical, psychological, cognitive and/or social risk factors in combination with lack of adequate support and/or adequate coping skills. KEY CONCLUSION: We reached consensus about a mutual definition of vulnerable pregnant women and aspects related to vulnerability within this consortium. The Delphi approach led to interesting discussions and was a valuable method to define the concept of vulnerable pregnant women within our project . IMPLICATIONS FOR PRACTICE: In order to accomplish a project that aimed to improve care for vulnerable pregnant women it was important to first identify the population of vulnerable pregnant women with a mutual definition.


Asunto(s)
Mujeres Embarazadas/psicología , Poblaciones Vulnerables/clasificación , Técnica Delphi , Europa (Continente) , Humanos , Encuestas y Cuestionarios , Poblaciones Vulnerables/psicología
8.
Ann Hematol ; 88(4): 319-24, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18784923

RESUMEN

The 21-kD protein Ras of the low-molecular-weight GTP-binding (LMWG) family plays an important role in transduction of extracellular signals. Ras functions as a 'molecular switch' in transduction of signals from the membrane receptors of many growth factors, cytokines, and other second messengers to the cell nucleus. Numerous studies have shown that in multiple malignant tumors and hematopoietic malignancies, faulty signal transduction via the Ras pathway plays a key role in tumorigenesis. In this work, a non-radioactive assay was used to quantify Ras activity in hematologic malignancies. Ras activation was measured in six different cell lines and 24 patient samples, and sequence analysis of N- and K-ras was performed. The 24 patient samples comprised of seven acute myelogenous leukemia (AML) samples, five acute lymphocytic leukemia (ALL) samples, four myeloproliferative disease (MPD) samples, four lymphoma samples, four juvenile myelomonocytic leukemia (JMML) samples, and WBC from a healthy donor. The purpose of this study was to compare Ras activity determined by percentage of Ras-GTP with the mutational status of the Ras gene in the hematopoietic cells of the patients. Mutation analysis revealed ras mutations in two of the seven AML samples, one in codon 12 and one in codon 61; ras mutations were also found in two of the four JMML samples, and in one of the four lymphoma samples (codon 12). We found a mean Ras activation of 23.1% in cell lines with known constitutively activating ras mutations, which was significantly different from cell lines with ras wildtype sequence (Ras activation of 4.8%). Two of the five activating ras mutations in the patient samples correlated with increased Ras activation. In the other three samples, Ras was probably activated through "upstream" or "downstream" mechanisms.


Asunto(s)
Neoplasias Hematológicas/química , Neoplasias Hematológicas/genética , Proteínas ras/análisis , Proteínas ras/genética , Análisis Mutacional de ADN , Guanosina Difosfato/análisis , Guanosina Trifosfato/análisis , Neoplasias Hematológicas/etiología , Humanos , Leucemia Mieloide Aguda , Leucemia Mielomonocítica Juvenil , Linfoma , Mutación , Trastornos Mieloproliferativos , Oncogenes , Leucemia-Linfoma Linfoblástico de Células Precursoras , Transducción de Señal/genética , Células Tumorales Cultivadas
10.
Mol Cell Biol ; 15(7): 3786-95, 1995 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-7791786

RESUMEN

E2A-PBX1 is the oncogene produced at the t(1;19) chromosomal breakpoint of pediatric pre-B-cell leukemia. Expression of E2A-Pbx1 induces fibroblast transformation and myeloid and T-cell leukemia in mice and arrests differentiation of granulocyte macrophage colony-stimulating factor-dependent myeloblasts in cultured marrow. Recently, the Drosophila melanogaster protein Exd, which is highly related to Pbx1, was shown to bind DNA cooperatively with the Drosophila homeodomain proteins Ubx and Abd-A. Here, we demonstrate that the normal Pbx1 homeodomain protein, as well as its oncogenic derivative, E2A-Pbx1, binds the DNA sequence ATCAATCAA cooperatively with the murine Hox-A5, Hox-B7, Hox-B8, and Hox-C8 homeodomain proteins, which are themselves known oncoproteins, as well as with the Hox-D4 homeodomain protein. Cooperative binding to ATCAATCAA required the homeodomain-dependent DNA-binding activities of both Pbx1 and the Hox partner. In cotransfection assays, Hox-B8 suppressed transactivation by E2A-Pbx1. These results suggest that (i) Pbx1 may participate in the normal regulation of Hox target gene transcription in vivo and therein contribute to aspects of anterior-posterior patterning and structural development in vertebrates, (ii) that E2A-Pbx1 could abrogate normal differentiation by altering the transcriptional regulation of Hox target genes in conjunction with Hox proteins, and (iii) that the oncogenic mechanism of certain Hox proteins may require their physical interaction with Pbx1 as a cooperating, DNA-binding partner.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , ADN/metabolismo , Genes Homeobox , Proteínas de Homeodominio/metabolismo , Proteínas de Fusión Oncogénica/metabolismo , Oncogenes , Proteínas Proto-Oncogénicas/metabolismo , Animales , Secuencia de Bases , Western Blotting , Proteínas de Unión al ADN/genética , Proteínas de Homeodominio/genética , Metilación , Ratones , Datos de Secuencia Molecular , Proteínas de Fusión Oncogénica/genética , Factor de Transcripción 1 de la Leucemia de Células Pre-B , Unión Proteica , Biosíntesis de Proteínas , Conformación Proteica , Proteínas Proto-Oncogénicas/genética , Proteínas Recombinantes de Fusión/metabolismo , Secuencias Reguladoras de Ácidos Nucleicos , Relación Estructura-Actividad , Transcripción Genética , Activación Transcripcional , Transfección
11.
Chirurg ; 77(6): 490, 492-8, 2006 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-16773347

RESUMEN

Perioperative antimicrobial prophylaxis (PAP) leads to a reduction in surgical site infections. The aim of PAP is adequate serum and tissue concentrations of the antimicrobial drug in the field of operation. The antibiotic must be effective against the expected pathogens during the operation, safe, and have the fewest possible side effects. The indication for PAP should take into account the risks of the operative procedure and especially the individual risk factors of the patient. Depending on pharmacokinetics, the antibiotic should be administered within 60 min before incision. After closure of the wound, further applications of the antibiotic drug have no influence on the infection rate of the wound but do increase the side effects (resistance, CDT colitis, allergy). Operation-specific recommendations according to guidelines of the Paul Ehrlich Society are given.


Asunto(s)
Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Procedimientos Quirúrgicos Operativos , Infección de la Herida Quirúrgica/prevención & control , Adulto , Factores de Edad , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Hipersensibilidad a las Drogas/etiología , Urgencias Médicas , Femenino , Humanos , Masculino , Meticilina/farmacología , Resistencia a la Meticilina , Persona de Mediana Edad , Atención Perioperativa , Guías de Práctica Clínica como Asunto , Factores de Riesgo , Factores Sexuales , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Infección de la Herida Quirúrgica/microbiología , Factores de Tiempo , Gestión de la Calidad Total
12.
Cancer Res ; 55(23 Suppl): 5786s-5793s, 1995 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-7493347

RESUMEN

The goal of this study was to intraindividually compare a complete versus a fragmented, directly 99mTc-labeled, monoclonal anti-carcinoembryonic antigen (CEA) antibody, with respect to their antigen-targeting kinetics, sensitivity, and diagnostic accuracy in patients with CEA-expressing tumors. Twenty-five patients were investigated with the 99mTc-labeled anti-CEA IgG1 BW 431/26 and the F(ab')2/Fab' fragment mixture F023C5 within 7 days. For quantitative analysis, the region of interest technique was applied to planar scans, whole-body scans, and single photon emission computed tomography slices 10 min to 48 h postinjection (PI). Final correlations were performed according to the histopathology after surgery or biopsy. Earliest tumor detection was possible with complete IgG1 4 h PI (52% of finally positive lesions). Twenty-four- or even 48-h scans were necessary in 48% of finally positive lesions; tumor detection with fragments was possible in 17% at 1 h PI and in 94% at 4 h PI. With both monoclonal antibodies, in 35%, single photon emission computed tomography was necessary for tumor detection. Absolute antibody uptake in tumor lesions was higher with complete monoclonal antibodies than with fragments. The sensitivity of fragments was higher in detecting primary tumors, local recurrences, and lymph node metastases. For detection of liver metastases, sensitivity was also higher for fragments than for IgG (87 versus 73%), but in scintigraphically positive lesions, tumor:background ratios were significantly lower with fragments (1.26 +/- 0.12 versus 1.70 +/- 0.32; P < 0.01). Therefore, fragments seem to be more suitable for earlier detection of lesions known for their good vascularization, vascular permeability, and antigen accessibility, such as local recurrences, lymph node metastases, and peritoneal carcinomatoses. In liver metastases (high interstitial pressure, low vascular leakage), sensitivity of fragments is higher, but their rapid serum and whole-body clearance lead to a lower absolute antibody uptake, with the consequence of significantly lower tumor:background ratios than with IgG.


Asunto(s)
Adenocarcinoma/diagnóstico por imagen , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Endometriales/diagnóstico por imagen , Fragmentos de Inmunoglobulinas , Neoplasias Pulmonares/diagnóstico por imagen , Radioinmunodetección , Tecnecio , Adenocarcinoma/inmunología , Adulto , Anciano , Anticuerpos , Antígeno Carcinoembrionario/inmunología , Neoplasias Colorrectales/inmunología , Neoplasias Endometriales/inmunología , Femenino , Humanos , Neoplasias Pulmonares/inmunología , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad
13.
Oncogene ; 17(17): 2211-23, 1998 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-9811452

RESUMEN

Variant HL-60 cells resistant to differentiation induced by nitroprusside and cGMP analogs have normal guanylate cyclase and cGMP-dependent protein kinase (G-kinase) activity (J. Biol. Chem. 269, 32155-32161, 1994). We found decreased phosphorylation of a low molecular weight protein (pp23) in the variant cells and by co-migration on two-dimensional polyacrylamide gels, phosphopeptide mapping, immunoprecipitation and immunoblotting, we showed that pp23 was one of three post-translationally modified forms of Rap 1A expressed in HL-60 cells. Using an in vitro transcription/translation system, we studied each of the posttranslational processing steps of Rap 1A and we showed that pp23 represented fully processed Rap 1A. By immunoprecipitation, immunoblotting and 35S-methionine/cysteine incorporation, we showed that the variant cells were deficient in pp23, and thus in fully processed Rap 1A, but that these cells did express normal amounts of completely unprocessed Rap 1A and geranylgeranylated Rap 1A; the lack of Rap 1A processing beyond geranylgeranylation in the variant cells was not secondary to a change in Rap 1A's amino acid sequence. The variant cells had normal carboxyl methyltransferase activity suggesting they are deficient in proteolytic cleavage of Rap 1A. The deficient post-translational processing of Rap 1A had no effect on Rap 1A's subcellular distribution and we found no evidence for altered post-translational processing of H-Ras.


Asunto(s)
Células HL-60/química , Proteínas de Neoplasias/metabolismo , Fosfoproteínas/metabolismo , Procesamiento Proteico-Postraduccional , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacología , Proteína Quinasa Dependiente de GMP Cíclico Tipo I , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Activación Enzimática , Células HL-60/efectos de los fármacos , Humanos , Indicadores y Reactivos/farmacología , Peso Molecular , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Nitroprusiato/farmacología , Mapeo Peptídico , Fosfoproteínas/química , Fosfoproteínas/genética , Fosforilación , ARN Mensajero/análisis
14.
Int Immunopharmacol ; 5(1): 107-15, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15589468

RESUMEN

The aim of this study was to evaluate the impact of mycophenolate mofetil (MMF) on incidence, delay, severity and clinical course of early recurrent hepatitis C after liver transplantation (LT). A total of 21 hepatitis C virus (HCV)-positive patients after LT were prospectively enrolled in this study. All of them received a quadruple induction cyclosporine A (CsA)-based immunosuppression, augmented by MMF (n=12) or by azathioprine (n=9, AZA). MMF tended to delay recurrent disease (50+/-35 versus 35+/-35 weeks, P=0.5) with significantly lower levels of aminotransferases (P<0.05). Furthermore, patients under MMF revealed less severe allograft fibrosis at disease recurrence (stage of fibrosis: 1.5+/-0.5 versus 2.2+/-1.2; P=0.07). But stage of fibrosis significantly increased in the MMF-group (P<0.05) during 6 months of antiviral treatment. Three patients in the MMF-group and none of the controls suffered from severe fibrosing cholestatic recurrent hepatitis C. Initial post-LT administration of MMF tended to delay recurrent hepatitis C and to limit initial HCV-related biochemical and morphological graft dysfunction. But during clinical follow-up, its immunosuppressive capabilities exceeded possible antiviral properties, finally leading to significant progression of graft fibrosis. Thus, concomitant dose reduction of other basic immunosuppressants might be useful in this clinical setting.


Asunto(s)
Hepatitis C/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Hígado , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Adulto , Azatioprina/uso terapéutico , Ciclosporina/uso terapéutico , Femenino , Fibrosis/complicaciones , Rechazo de Injerto , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Índice de Severidad de la Enfermedad
17.
Transplantation ; 60(5): 515-7, 1995 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-7676504

RESUMEN

A microemulsion formulation of CsA, which was anticipated to be independent of bile for oral absorption, was compared with the currently marketed formulation in liver transplant patients with external biliary drainage. Eleven patients aged 47.6 +/- 13.1 years and weighing 75.8 +/- 5.7 kg received single 400-mg oral doses of each formulation in a randomized, crossover protocol on days 4 and 6 after transplant. Serial venous blood samples were collected over a 12-hr period after each administration and whole blood CsA concentrations were determined by a validated RIA specific for the parent compound. Systemic exposure to CsA was consistently higher from the microemulsion formulation in all patients, as judged by the peak concentration and the area under the curve. Specifically, the area under the concentration-time curve was 943 +/- 400 vs. 2378 +/- 911 ng.hr/ml, indicating an average 156% higher bioavailability from the microemulsion compared with the currently marketed formulation in liver transplant patients in the absence of bile.


Asunto(s)
Bilis/metabolismo , Ciclosporina/farmacocinética , Trasplante de Hígado , Absorción , Adulto , Anciano , Estudios Cruzados , Ciclosporina/administración & dosificación , Emulsiones , Femenino , Humanos , Masculino , Persona de Mediana Edad
18.
Transplantation ; 64(1): 162-3, 1997 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-9233718

RESUMEN

BACKGROUND: Recurrent hepatitis B infection after liver transplantation is associated with poor graft and patient survival. Famciclovir is a nucleoside with virostatic action in hepatitis B infection. We report the case of a 51-year-old patient who developed recurrent delta-positive hepatitis B infection after liver transplantation. After famciclovir treatment, he became seronegative for hepatitis B early and hepatitis B surface antigens and developed protective anti-hepatitis B surface antibody titers. METHODS: After recurrent hepatitis B was confirmed, treatment with famciclovir was initiated. RESULTS: Eighteen days after starting famciclovir, the patient became seronegative for hepatitis B early antigen and delta antigen, and hepatitis B virus DNA was no longer detectable in serum. Three months later, the patient became hepatitis B surface antigen negative and remains well 16 months later with increasing anti-hepatitis B surface levels. CONCLUSIONS: Antiviral treatment with famciclovir may be useful in treatment of delta-positive hepatitis B infection following liver transplantation. Further evaluation of famciclovir in treatment and prevention of hepatitis B in these patients is warranted.


Asunto(s)
2-Aminopurina/análogos & derivados , Antivirales/uso terapéutico , Hepatitis B/tratamiento farmacológico , Hepatitis D/sangre , Trasplante de Hígado/efectos adversos , 2-Aminopurina/uso terapéutico , Antígenos Virales/sangre , Famciclovir , Virus de la Hepatitis B/inmunología , Hepatitis D/etiología , Hepatitis D/prevención & control , Virus de la Hepatitis Delta/inmunología , Humanos , Masculino , Persona de Mediana Edad
19.
Transplantation ; 67(8): 1128-32, 1999 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-10232562

RESUMEN

BACKGROUND: Prostaglandins have been shown to protect against a variety of liver insults, including ischemia-reperfusion injury. Decreased graft injury and improved survival have been demonstrated in animal studies of liver transplantation after donor pretreatment with prostaglandin before organ retrieval. This potential clinical application has not been examined in human subjects. PATIENTS AND METHODS: One hundred and six liver donors were randomly assigned to receive either prostaglandin I2 (epoprostenol, 500 microg intravenous bolus) immediately before cold perfusion or no drug as control. Donor and recipient characteristics were recorded, and liver function tests were monitored after transplant to assess the effect of epoprostenol on graft injury. RESULTS: Donor pretreatment with epoprostenol significantly improved the rapidity and homogeneity of graft reperfusion. Epoprostenol pretreatment also significantly reduced peak values of transaminases after transplantation: serum glutamic-pyruvic transaminase, control (851+/-121 international units [IU]/L) and epoprostenol (463+/-78 IU/L); serum glutamic-oxalaacetic transaminase, control (870+/-127 IU/L) and epoprostenol (463+/-78 IU/L); serum glutamate dehydrogenase, control (458+/-95 IU/L) and epoprostenol (170+/-30 IU/L); P<0.01 for all, by t test. Serum levels of bilirubin and alkaline phospatase were not significantly altered by donor pretreatment with epoprostenol. CONCLUSIONS: Reduction of ischemia-reperfusion injury by administration of epoprostenol before graft retrieval may have important applications in liver transplantation. Further studies are required to establish the mechanism of this effect and to define its precise role in clinical practice.


Asunto(s)
Epoprostenol/uso terapéutico , Isquemia/prevención & control , Circulación Hepática , Trasplante de Hígado , Hígado/efectos de los fármacos , Daño por Reperfusión/prevención & control , Adolescente , Adulto , Niño , Frío , Femenino , Humanos , Hígado/fisiopatología , Circulación Hepática/efectos de los fármacos , Circulación Hepática/fisiología , Masculino , Persona de Mediana Edad , Perfusión , Cuidados Preoperatorios
20.
J Nucl Med ; 36(3): 430-41, 1995 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-7884505

RESUMEN

UNLABELLED: The goal of this study was to intraindividually compare complete versus fragmented directly labeled 99mTc monoclonal anti-CEA antibody with respect to antigen targeting and tumor uptake kinetics, sensitivity and diagnostic accuracy in colorectal cancer patients. METHODS: Twenty-five patients were investigated with 99mTc-labeled anti-CEA IgG1 BW 431/26 and the F(ab')2/Fab' fragment mixture F023C5 within 7 days. For quantitative analysis, an ROI technique was applied to planar scans, whole-body scans and SPECT slices 10 min to 48 hr postinjection. Final correlations were performed according to histology after surgery or biopsy. RESULTS: Earliest tumor detection with complete IgG1 was possible 4 hr postinjection (52% of finally positive lesions); imaging at 24 hr or even 48 hr was necessary in 48%. Tumor detection with fragments was possible in 17% at 1 hr postinjection and in 94% at 4 hr postinjection. In 35%, SPECT was necessary for tumor detection with both MAbs. Absolute antibody uptake in tumor lesions was higher with complete MAbs than with fragments. CONCLUSIONS: Lesions known for their good vascularization, vascular permeability and antigen accessibility were detected earlier and with higher sensitivity with fragments than with complete MAbs due to faster background clearance despite lower absolute antibody uptake.


Asunto(s)
Anticuerpos Monoclonales , Antígeno Carcinoembrionario/inmunología , Neoplasias Colorrectales/diagnóstico por imagen , Radioinmunodetección , Tecnecio , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad
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