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1.
Anaesthesist ; 60(8): 735-9, 2011 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-21647666

RESUMEN

A patient reported anxiety and sleeping problems 9 months after reconstruction of the anterior floor of the mouth following tumor surgery. These symptoms had been initiated by a postoperative delirium with hallucinations, which had not been detected during its occurrence. One session of psychotherapy 9 months later reduced the symptoms. Patients in intensive care units should be asked and informed about delirium symptoms. This might prevent long-term psychological distress.


Asunto(s)
Delirio/complicaciones , Delirio/etiología , Complicaciones Posoperatorias/psicología , Ansiedad/etiología , Ansiedad/psicología , Ansiedad/terapia , Carcinoma de Células Escamosas/cirugía , Delirio/terapia , Diagnóstico Diferencial , Miedo , Femenino , Alucinaciones/etiología , Alucinaciones/terapia , Humanos , Persona de Mediana Edad , Neoplasias de la Boca/cirugía , Complicaciones Posoperatorias/terapia , Psicoterapia , Resultado del Tratamiento
2.
Eur J Clin Microbiol Infect Dis ; 29(5): 563-70, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20213255

RESUMEN

We report the first outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in Germany. The presence of KPC was confirmed by polymerase chain reaction (PCR). The KPC-encoding plasmid was analysed by transconjugation experiments, DNA sequencing, Southern blotting and isoelectric focussing. Typing was performed by pulsed-field gel electrophoresis (PFGE). An ertapenem-resistant K. pneumoniae with low minimum inhibitory concentrations (MIC) to other cabapenems (tested by the Vitek system) was isolated from the index patient in January 2008. A KPC-2 was identified after K. pneumoniae with identical susceptibility patterns had been isolated from two more patients. Despite the introduction of infection control measures, transmission occurred in five additional patients and three of the patients died from infections. The source of the outbreak strain remained unclear; however, the Tn4401-containing bla (KPC-2) gene was similar to previously described isolates from Greece. Five months after the end of the outbreak, a KPC-K. pneumoniae was isolated from a patient who had been treated in Greece previously. Retrospectively, this patient was treated in November 2007 on the same unit as the index case. Typing revealed that all patients were colonised by the same strain. KPC-K. pneumoniae has been introduced to Germany possibly from Greece and transmission to other institutions is likely.


Asunto(s)
Proteínas Bacterianas/biosíntesis , Brotes de Enfermedades , Infecciones por Klebsiella/epidemiología , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/enzimología , beta-Lactamasas/biosíntesis , Adulto , Anciano , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Electroforesis en Gel de Campo Pulsado , Femenino , Alemania/epidemiología , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Resistencia betalactámica , beta-Lactamasas/genética
3.
Antimicrob Resist Infect Control ; 9(1): 22, 2020 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-32005223

RESUMEN

BACKGROUND: The relevance of vancomycin resistance in enterococcal blood stream infections (BSI) is still controversial. Aim of this study was to outline the effect of vancomycin resistance of Enterococcus faecium on the outcome of patients with BSI after orthotopic liver transplantation (OLT). METHODS: The outcome of OLT recipients developing BSI with vancomycin-resistant (VRE) versus vancomycin-susceptible Enterococcus faecium (VSE) was compared based on data extraction from medical records. Multivariate regression analyses identified risk factors for mortality and unfavourable outcomes (defined as death or prolonged intensive care stay) after 30 and 90 days. RESULTS: Mortality was similar between VRE- (n = 39) and VSE- (n = 138) group after 30 (p = 0.44) or 90 days (p = 0.39). Comparable results occurred regarding unfavourable outcomes. Mean SOFANon-GCS score during the 7-day-period before BSI onset was the independent predictor for mortality at both timepoints (HR 1.32; CI 1.14-1.53; and HR 1.18; CI 1.08-1.28). Timely appropriate antibiotic therapy, recent ICU stay and vancomycin resistance did not affect outcome after adjusting for confounders. CONCLUSION: Vancomycin resistance did not influence outcome among patients with Enterococcus faecium bacteraemia after OLT. Only underlying severity of disease predicted poor outcome among this homogenous patient population. TRIAL REGISTRATION: This study was registered at the German clinical trials register (DRKS-ID: DRKS00013285).


Asunto(s)
Bacteriemia , Enterococcus faecium/efectos de los fármacos , Trasplante de Hígado/efectos adversos , Resistencia a la Vancomicina , Adulto , Antibacterianos/farmacología , Bacteriemia/etiología , Bacteriemia/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Vancomicina/farmacología
4.
BJS Open ; 3(6): 793-801, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31832586

RESUMEN

Background: Liver resection is the only curative therapeutic option for intrahepatic cholangiocarcinoma (ICC), but the approach to recurrent ICC is controversial. This study analysed the outcome of liver resection in patients with recurrent ICC. Methods: Demographic, radiological, clinical, operative, surgical pathological and follow-up data for all patients with a final surgical pathological diagnosis of ICC treated in a tertiary referral centre between 2001 and 2015 were collected retrospectively and analysed. Results: A total of 190 patients had liver resection for primary ICC. The 1-, 3- and 5-year overall survival (OS) rates were 74·8, 56·6 and 37·9 per cent respectively. Independent determinants of OS were age 65 years or above (hazard ratio (HR) 2·18, 95 per cent c.i. 1·18 to 4·0; P = 0·012), median tumour diameter 5 cm or greater (HR 2·87, 1·37 to 6·00; P = 0·005), preoperative biliary drainage (HR 2·65, 1·13 to 6·20; P = 0·025) and local R1-2 status (HR 1·90, 1·02 to 3·53; P = 0·043). Recurrence was documented in 87 patients (45·8 per cent). The mean(s.d.) survival time after recurrence was 16(17) months. Independent determinants of recurrence were median tumour diameter 5 cm or more (HR 1·71, 1·09 to 2·68; P = 0·020), high-grade (G3-4) tumour (HR 1·63, 1·04 to 2·55; P = 0·034) and local R1 status (HR 1·70, 1·09 to 2·65; P = 0·020). Repeat resection with curative intent was performed in 25 patients for recurrent ICC, achieving a mean survival of 25 (95 per cent c.i. 16 to 34) months after the diagnosis of recurrence. Patients deemed to have unresectable disease after recurrence received chemotherapy or chemoradiotherapy alone, and had significantly poorer survival. Conclusion: Patients with recurrent ICC may benefit from repeat surgical resection.


Antecedentes: La resección hepática es la única opción terapéutica curativa para el colangiocarcinoma intrahepático (intrahepatic colangiocarcinoma, iCCA), pero el enfoque terapéutico de la recidiva del iCCA es controvertido. En este estudio se analizaron los resultados de la resección hepática en pacientes con recidiva de un iCCA. Métodos: Se recopilaron de forma retrospectiva y se analizaron los datos demográficos, radiológicos, clínicos, quirúrgicos, de anatomía patológica y de seguimiento de todos los pacientes con diagnóstico anatomopatológico definitivo de iCCA en un centro de referencia terciario entre 2001 y 2015. Resultados: En total, 190 pacientes se sometieron a resección hepática por iCCA primario. La supervivencia global (overall survival, OS) a 1, 3 y 5 años fue del 75%, 57% y 38%, respectivamente. La edad de ≥ 65 años (cociente de riesgos instantáneos, hazard ratio, HR 2,2, i.c. del 95% 1,2­4,0, P = 0,012), la mediana del diámetro del tumor ≥ 5 cm (HR 2,9, i.c. del 95% 1,4­6,0, P = 0,005), el drenaje biliar preoperatorio (HR 2,6, i.c. del 95% 1,3­6,2, P = 0.025) y el estado local R1/2 (HR 1,9, i.c. del 95% 1,0­3,5, P = 0,043) fueron factores pronósticos independientes de la OS. La recidiva se documentó en 87 (45,8%) pacientes. El tiempo medio de supervivencia después de la recidiva fue de 16 ± 2 meses. Los factores pronósticos independientes de recidiva fueron la mediana del diámetro del tumor ≥ 5 cm (HR 1,7, i.c. del 95% 1,1­2,7, P = 0,020), el tumor de alto grado (G3­G4) (HR 1,6, i.c. del 95% 1,0­2,5, P = 0,034) y el estado local R1 (HR 1,7, i.c. del 95% 1,1­2,6, P = 0,020). La resección repetida con intención curativa se realizó en 25 pacientes con iCCA recidivado, con una supervivencia media de 25 meses (i.c. del 95% 16­34 meses) tras el diagnóstico de recidiva. Los pacientes que se consideraron no resecables después de la recidiva se sometieron a quimioterapia o quimiorradioterapia y presentaron una supervivencia significativamente peor. Conclusión: Los pacientes con recidiva de un iCCA pueden beneficiarse de la resección quirúrgica repetida.


Asunto(s)
Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/cirugía , Colangiocarcinoma/cirugía , Hepatectomía , Recurrencia Local de Neoplasia/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Modelos de Riesgos Proporcionales , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Centros de Atención Terciaria/estadística & datos numéricos , Adulto Joven
5.
Leukemia ; 21(9): 2025-34, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17581612

RESUMEN

In multiple myeloma, the overexpression of receptor activator of nuclear factor kappa B (NF-kappaB) ligand (RANKL) leads to the induction of NF-kappaB and activator protein-1 (AP-1)-related osteoclast activation and enhanced bone resorption. The purpose of this study was to examine the molecular and functional effects of proteasome inhibition in RANKL-induced osteoclastogenesis. Furthermore, we aimed to compare the outcome of proteasome versus selective NF-kappaB inhibition using bortezomib (PS-341) and I-kappaB kinase inhibitor PS-1145. Primary human osteoclasts were derived from CD14+ precursors in presence of RANKL and macrophage colony-stimulating factor (M-CSF). Both bortezomib and PS-1145 inhibited osteoclast differentiation in a dose- and time-dependent manner and furthermore, the bone resorption activity of osteoclasts. The mechanisms of action involved in early osteoclast differentiation were found to be related to the inhibition of p38 mitogen-activated protein kinase pathways, whereas the later phase of differentiation and activation occurred due to inhibition of p38, AP-1 and NF-kappaB activation. The AP-1 blockade contributed to significant reduction of osteoclastic vascular endothelial growth factor production. In conclusion, our data demonstrate that proteasomal inhibition should be considered as a novel therapeutic option of cancer-induced lytic bone disease.


Asunto(s)
Antineoplásicos/farmacología , Resorción Ósea/tratamiento farmacológico , Ácidos Borónicos/farmacología , Mieloma Múltiple/complicaciones , Osteoclastos/efectos de los fármacos , Pirazinas/farmacología , Apoptosis/efectos de los fármacos , Resorción Ósea/etiología , Resorción Ósea/patología , Bortezomib , Diferenciación Celular/efectos de los fármacos , Linaje de la Célula/efectos de los fármacos , Femenino , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Técnicas In Vitro , Masculino , FN-kappa B/metabolismo , Osteoclastos/citología , Osteoclastos/metabolismo , Piridinas/farmacología , Ligando RANK/metabolismo , Transducción de Señal/efectos de los fármacos , Células Madre/citología , Células Madre/efectos de los fármacos , Factor de Transcripción AP-1/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
6.
Chirurg ; 87(1): 73-83; quiz 84-5, 2016 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-26643155

RESUMEN

Due to the comprehensive establishment of modern techniques, tracheostomy has become a routine procedure in intensive care units (ICU). The negative effects of prolonged translaryngeal intubation on the laryngeal and tracheal mucosa up to tracheal stenosis can be reduced by tracheostomy. Furthermore, long-term ventilation is facilitated; however, there is no clear evidence on the optimal timing of tracheostomy in critically ill patients. The specific indications and contraindications of surgical as well as percutaneous tracheostomy must be strictly observed for a safe and successful intervention. Exchanging the tracheostomy tube may lead to potentially dangerous situations especially after percutaneous tracheostomy. A standardized and structured approach is therefore recommended.


Asunto(s)
Unidades de Cuidados Intensivos , Traqueotomía/métodos , Manejo de la Vía Aérea/métodos , Adhesión a Directriz , Humanos , Intubación Intratraqueal/efectos adversos , Cuidados a Largo Plazo , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Traqueotomía/normas
7.
Chirurg ; 76(3): 284-300, 2005 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-15448932

RESUMEN

During the observation period between 2001 and 2003, all outpatient surgical therapy, including degrees of urgency, surgical care volume, regional provenance of patients, diagnoses, and referral channels were prospectively analysed at the Surgical Department of the University of Heidelberg, Germany. The data gathered do not merely describe the volume and characteristics of care encountered at this academic surgical institution but also provide further insight into the variability of resource utilisation and associated patient flow. Additionally, a retrospective evaluation using structured interviews and questionnaires was performed to differentiate and quantify patient care, teaching, and research activities. This study illustrates the high relevance of academic outpatient institutions to regional provision of general surgical care in Germany. There is a clear dominance of medical support functions, while research and teaching activities are of only minor relevance and realised particularly in subspecialty clinics. These data should give important stimuli for the future planning of health care in Germany. Outpatient clinics for general surgery appear to be an excellent basis for regional models of integrated health care delivery in the future.


Asunto(s)
Centros Médicos Académicos/estadística & datos numéricos , Procedimientos Quirúrgicos Ambulatorios/estadística & datos numéricos , Reforma de la Atención de Salud/estadística & datos numéricos , Programas Nacionales de Salud/estadística & datos numéricos , Centros Médicos Académicos/economía , Centros Médicos Académicos/legislación & jurisprudencia , Procedimientos Quirúrgicos Ambulatorios/economía , Procedimientos Quirúrgicos Ambulatorios/legislación & jurisprudencia , Ritmo Circadiano , Ahorro de Costo/legislación & jurisprudencia , Análisis Costo-Beneficio , Prestación Integrada de Atención de Salud/economía , Prestación Integrada de Atención de Salud/legislación & jurisprudencia , Prestación Integrada de Atención de Salud/estadística & datos numéricos , Episodio de Atención , Alemania , Reforma de la Atención de Salud/economía , Reforma de la Atención de Salud/legislación & jurisprudencia , Programas Nacionales de Salud/economía , Programas Nacionales de Salud/legislación & jurisprudencia , Garantía de la Calidad de Atención de Salud/economía , Garantía de la Calidad de Atención de Salud/legislación & jurisprudencia , Garantía de la Calidad de Atención de Salud/estadística & datos numéricos , Asignación de Recursos/economía , Asignación de Recursos/legislación & jurisprudencia , Asignación de Recursos/estadística & datos numéricos , Especialidades Quirúrgicas/economía , Especialidades Quirúrgicas/legislación & jurisprudencia , Especialidades Quirúrgicas/estadística & datos numéricos , Revisión de Utilización de Recursos/estadística & datos numéricos , Carga de Trabajo/estadística & datos numéricos
8.
Chirurg ; 73(10): 1043-52, 2002 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-12395164

RESUMEN

Expansion of ambulatory surgical care is a major focus in United States health politics. In 1996 a total of 31.5 million ambulatory operations were performed, currently accounting for 45% of yearly procedures. Operations in ophthalmology and gastroenterology are predominant. Ambulatory surgery is organized in different forms: "office-based surgery," "hospital outpatient departments," and "ambulatory surgery centers" (ASC). The numbers of ASCs are rapidly increasing. The current proportion of ASCs is 16% of all operations. The type of ambulatory surgery is primarily defined by payors. Medicare standards are the benchmark for private organizations. Recovery care centers now offer postoperative care beyond the former 23-h threshold. This may lead to a further expanded ASC access. Revenues for ambulatory surgery were so far mostly based on fees for service. The implementation of an outpatient prospective payment system ("OPPS") is planned by Medicare, using fixed package prices within a newly defined ambulatory payment classification ("APC"). The dimension of structural changes could be enormous and possibly be compared with the implementation of DRGs in 1983.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios/métodos , Comparación Transcultural , Procedimientos Quirúrgicos Ambulatorios/economía , Procedimientos Quirúrgicos Ambulatorios/estadística & datos numéricos , Análisis Costo-Beneficio/organización & administración , Grupos Diagnósticos Relacionados/economía , Grupos Diagnósticos Relacionados/organización & administración , Alemania , Humanos , Sistema de Pago Prospectivo/economía , Sistema de Pago Prospectivo/organización & administración , Estados Unidos
9.
Chirurg ; 71(3): 281-91, 2000 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-10789045

RESUMEN

Surgical hospitals can be seen as operational or even industrial production systems. Doctors have a major impact on both medical performance and costs. For active participation in the management process, knowledge of industrial controlling mechanisms is required. German hospitals currently receive no procedure-related financial revenues, such as prices or tariffs for defined medical treatment activities. Maximum clinical revenues are, furthermore, limited by principles of planned economy and can be increased only slightly by greater medical performance. Costs are the only target that can be autonomously influenced by the management. Operative controlling in hospitals aims at horizontal and vertical coordination of subunits and decentralization of process regulations. Hospital medical performance is not clearly defined, its quantitative measurement very problematic. Process-orientated clinical activities are not taken into account. A high percentage of hospital costs are fixed and can be influenced only by major structural interventions in the long term. Variable costs are primarily dependent on the quantity of clinical activities, but also heavily influenced by patient structure (comorbidity and risk profile). The various forms of industrial cost calculations, such as internal budgeting, internal markets or flexible plan-cost balancing, cannot be directly applied in hospital management. Based on these analyses, current operational concepts and strategic trends are listed to describe cost-management options in hospitals with focus on the German health reforms.


Asunto(s)
Cirugía General/economía , Costos de Hospital/estadística & datos numéricos , Planificación Hospitalaria/economía , Hospitales Especializados/economía , Comercialización de los Servicios de Salud/economía , Programas Nacionales de Salud/economía , Control de Costos/tendencias , Predicción , Alemania , Humanos
10.
Chirurg ; 73(5): 492-9, 2002 May.
Artículo en Alemán | MEDLINE | ID: mdl-12089835

RESUMEN

INTRODUCTION: The forthcoming introduction of a DRG-based account system in Germany aims at higher transparency and economic efficiency, particularly in the sector of in-patient health care. The availability of documentation of the highest quality, taking into account all potentially relevant diagnoses, appears to be the best method for achieving maximum revenue in individual surgical units. The aim of the study was to determine the relevance of various degrees of documentation depth on calculated DRG-based revenue. Furthermore, we evaluated whether improvements in the quality of documentation can be realized in current hospital organization. METHODS: In a prospective study, clinical data from 402 in-patients were collected and revenues were calculated based on the Australian-Refined DRG system. Various qualities of documentation were defined. In order to find the medical sectors most sensitive to "under-documentation", homogenous cases were classified into 23 treating groups, according to diagnosis. RESULTS: In 267 cases, maximum revenue was determined only by one main diagnosis, while better results could be achieved in 137 cases (34%) by extended documentation quality. Half of this gain could only be achieved by an independent medical documentation specialist. An upper limit of documentation intensity (number of diagnoses) could be defined. Maximum gain did not require maximum number of diagnoses. CONCLUSIONS: Documentation depth has an important influence on the calculated revenue of surgical therapy based on AR-DRG system. The quality and depth of the documentation is not, in itself, sufficient. In order to be really effective, it requires the highest degree of professionalism from hospital staff.


Asunto(s)
Grupos Diagnósticos Relacionados/economía , Documentación/métodos , Garantía de la Calidad de Atención de Salud/economía , Mecanismo de Reembolso/economía , Servicio de Cirugía en Hospital/economía , Análisis Costo-Beneficio , Alemania , Humanos , Programas Nacionales de Salud/economía
11.
Arch Soc Esp Oftalmol ; 79(2): 75-9, 2004 Feb.
Artículo en Español | MEDLINE | ID: mdl-14988786

RESUMEN

PURPOSE: To introduce a new type of therapy for corneal rejection after keratoplasty with the microinjection of intrastromal depot cortisone in single or multiple doses. METHODS: Thirty-three consecutive eyes with corneal graft rejection were diagnosed and treated by one of the authors (EA) between January 1998 and November 2000. RESULTS: Of the 33 eyes, 26 were submitted to Penetrating Keratoplasty (PK), five to lamellar, and two to homoplastic keratoplasty. The most common rejection type was epithelial in 20 eyes, 11 eyes showed mixed rejection types and two eyes, endothelial. In 18 of the cases (54.54%) treatment consisted solely of intraestromal injection; in the other 15 cases some other medications were added mostly because of patient anxiety. The vast majority of the cases (81%) improved clinically within a few days after the injection. Fifty-four percent of the cases required a number of doses ranging from one to five; the rest of the cases had a greater number of sessions. Thirty-one cases have been followed up for a period longer than six months without showing increase in intraocular pressure or development of steroid lens opacities. CONCLUSION: Intrastromal depot cortisone injection is a new alternative for the treatment of corneal graft rejections after keratoplasty.


Asunto(s)
Betametasona/administración & dosificación , Sustancia Propia/efectos de los fármacos , Glucocorticoides/administración & dosificación , Rechazo de Injerto/prevención & control , Queratoplastia Penetrante , Complicaciones Posoperatorias , Administración Tópica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Rechazo de Injerto/tratamiento farmacológico , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza Visual
12.
Br J Pharmacol ; 169(1): 21-33, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23387445

RESUMEN

BACKGROUND AND PURPOSE: Hepatic uptake (e.g. by OATP1B1), phase I and II metabolism (e.g. by CYP3A4, UGT1A1) and subsequent biliary excretion (e.g. by MRP2) are key determinants for the pharmacokinetics of numerous drugs. However, stably transfected cell models for the simultaneous investigation of transport and phase I and II metabolism of drugs are lacking. EXPERIMENTAL APPROACH: A newly established quadruple-transfected MDCKII-OATP1B1-CYP3A4-UGT1A1-MRP2 cell line was used to investigate metabolism and transcellular transport of the endothelin receptor antagonist bosentan. KEY RESULTS: Intracellular accumulation of bosentan equivalents (i.e. parent compound and metabolites) was significantly lower in all cell lines expressing MRP2 compared to cell lines lacking this transporter (P < 0.001). Accordingly, considerably higher amounts of bosentan equivalents were detectable in the apical compartments of cell lines with MRP2 expression (P < 0.001). HPLC and LC-MS measurements revealed that mainly unchanged bosentan accumulated in intracellular and apical compartments. Furthermore, the phase I metabolites Ro 48-5033 and Ro 47-8634 were detected intracellularly in cell lines expressing CYP3A4. Additionally, a direct glucuronide of bosentan could be identified intracellularly in cell lines expressing UGT1A1 and in the apical compartments of cell lines expressing UGT1A1 and MRP2. CONCLUSIONS AND IMPLICATIONS: These in vitro data indicate that bosentan is a substrate of UGT1A1. Moreover, the efflux transporter MRP2 mediates export of bosentan and most likely also of bosentan glucuronide in the cell system. Taken together, cell lines simultaneously expressing transport proteins and metabolizing enzymes represent additional useful tools for the investigation of the interplay of transport and metabolism of drugs.


Asunto(s)
Citocromo P-450 CYP3A/metabolismo , Glucuronosiltransferasa/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Transportadores de Anión Orgánico/metabolismo , Sulfonamidas/metabolismo , Animales , Antihipertensivos/metabolismo , Transporte Biológico , Bosentán , Cromatografía Líquida de Alta Presión , Cromatografía Liquida/métodos , Citocromo P-450 CYP3A/genética , Perros , Antagonistas de los Receptores de Endotelina , Glucurónidos/metabolismo , Glucuronosiltransferasa/genética , Humanos , Transportador 1 de Anión Orgánico Específico del Hígado , Células de Riñón Canino Madin Darby , Espectrometría de Masas/métodos , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Transportadores de Anión Orgánico/genética , Pirimidinas/metabolismo , Transfección
13.
Chirurg ; 83(1): 54-64, 2012 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-22246074

RESUMEN

The spectacular increase in liability processes in the field of surgery and in particular in visceral surgery, necessitates an objectification of the conflict between surgical medical professionals and medico-legal institutions, firms of solicitors and courts. Out of court settlements assisted by expert opinion commissions of the Medical Council can avoid many legal conflicts. For improvement of the legal standpoint of a defendant medical professional an unambiguous, extensive and detailed documentation of medical examination findings, the indications for the planned operative intervention, extensive and detailed documentation on disclosure and informed consent of the patient for the planned operative intervention, an extensive, detailed careful and responsibly guided report of the operation as well as a systematic, orderly well-planned postoperative complication management are necessary to counter the accusation of an organizational failure of medical professionals and the accused hospital. The mutual building of confidence between surgical medical professionals and legal institutions is safeguarded by a comprehensive documentation and an unambiguous description and formulation of the medical discharge report on termination of inpatient treatment.


Asunto(s)
Benchmarking/legislación & jurisprudencia , Procedimientos Quirúrgicos del Sistema Digestivo/legislación & jurisprudencia , Testimonio de Experto/legislación & jurisprudencia , Responsabilidad Legal , Mala Praxis/legislación & jurisprudencia , Compensación y Reparación/legislación & jurisprudencia , Servicios Contratados/legislación & jurisprudencia , Documentación/normas , Alemania , Humanos , Consentimiento Informado/legislación & jurisprudencia , Errores Médicos/legislación & jurisprudencia , Registros Médicos/legislación & jurisprudencia , Manejo de Atención al Paciente/legislación & jurisprudencia
14.
Chirurg ; 83(7): 661-6, 2012 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-22782174

RESUMEN

The committee draft for the new patient rights act was approved by the Federal Cabinet on 23 May 2012. Both the demands of the patient representative of the Federal government and some of the demands from the cornerstone paper of the State commission were taken into consideration.The draft of the new act contains comprehensive amendments to the Civil Code with the subtitle"Treatment contract in accordance with §630" and encompasses §§630a-h. The valid legal situation is therefore to all intents and purposes now codified.


Asunto(s)
Mala Praxis/legislación & jurisprudencia , Programas Nacionales de Salud/legislación & jurisprudencia , Defensa del Paciente/legislación & jurisprudencia , Procedimientos Quirúrgicos Operativos/legislación & jurisprudencia , Comités Consultivos/legislación & jurisprudencia , Testimonio de Experto/legislación & jurisprudencia , Alemania , Humanos , Consentimiento Informado/legislación & jurisprudencia , Registros Médicos/legislación & jurisprudencia , Acceso de los Pacientes a los Registros/legislación & jurisprudencia , Grupo de Atención al Paciente/legislación & jurisprudencia , Educación del Paciente como Asunto/legislación & jurisprudencia , Gestión de Riesgos/legislación & jurisprudencia , Procedimientos Quirúrgicos Operativos/efectos adversos
15.
Br J Pharmacol ; 165(6): 1836-1847, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21923755

RESUMEN

BACKGROUND AND PURPOSE: The coordinate activity of hepatic uptake transporters [e.g. organic anion transporting polypeptide 1B1 (OATP1B1)], drug-metabolizing enzymes [e.g. UDP-glucuronosyltransferase 1A1 (UGT1A1)] and efflux pumps (e.g. MRP2) is a crucial determinant of drug disposition. However, limited data are available on transport of drugs (e.g. ezetimibe, etoposide) and their glucuronidated metabolites by human MRP2 in intact cell systems. EXPERIMENTAL APPROACH: Using monolayers of newly established triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells as well as MDCK control cells, single- (OATP1B1) and double-transfected (OATP1B1-UGT1A1, OATP1B1-MRP2) MDCK cells, we therefore studied intracellular concentrations and transcellular transport after administration of ezetimibe or etoposide to the basal compartment. KEY RESULTS: Intracellular accumulation of ezetimibe was significantly lower in MDCK-OATP1B1-UGT1A1-MRP2 triple-transfected cells compared with all other cell lines. Considerably higher amounts of ezetimibe glucuronide were found in the apical compartment of MDCK-OATP1B1-UGT1A1-MRP2 monolayers compared with all other cell lines. Using HEK cells, etoposide was identified as a substrate of OATP1B1. Intracellular concentrations of etoposide equivalents (i.e. parent compound plus metabolites) were affected only to a minor extent by the absence or presence of OATP1B1/UGT1A1/MRP2. In contrast, apical accumulation of etoposide equivalents was significantly higher in monolayers of both cell lines expressing MRP2 (MDCK-OATP1B1-MRP2, MDCK-OATP1B1-UGT1A1-MRP2) compared with the single-transfected (OATP1B1) and the control cell line. CONCLUSIONS AND IMPLICATIONS: Ezetimibe glucuronide is a substrate of human MRP2. Moreover, etoposide and possibly also its glucuronide are substrates of MRP2. These data demonstrate the functional interplay between transporter-mediated uptake, phase II metabolism and export by hepatic proteins involved in drug disposition.


Asunto(s)
Azetidinas/metabolismo , Etopósido/metabolismo , Glucurónidos/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Animales , Línea Celular , Perros , Ezetimiba , Glucuronosiltransferasa/genética , Células HEK293 , Humanos , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteína 1 de Transporte de Anión Orgánico/genética , ARN Mensajero/metabolismo , Transfección
18.
Leukemia ; 22(9): 1767-72, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18580957

RESUMEN

Several prognostic markers, including parameters of tumor burden and cytogenetics, were adopted to identify high-risk patients in multiple myeloma (MM). Recently, the International Staging System (ISS), including beta2-microglobulin (beta2M) and albumin, was introduced for patients with symptomatic MM. As bone disease is a hallmark of MM, we investigated the prognostic impact of the bone resorption marker carboxy-terminal telopeptide of type-1 collagen (ICTP) in combination with ISS, beta2M, albumin, deletion of chromosome 13 and high-dose therapy (HDT) in 100 patients with newly diagnosed symptomatic MM. beta2M alone, albumin alone, ISS, HDT, del(13q14) and ICTP were significant prognostic factors for overall survival (OS). In a multivariate analysis, ICTP was the most powerful prognostic factor (log-rank P<0.001, hazard ratio: ninefold increase). ICTP clearly separated two subgroups with a good and a worse prognosis within each of the three ISS stages (ISS I: P=0.027, ISS II: P=0.022, ISS III: P=0.013). Incorporation of ICTP in a combined ICTP-ISS score significantly (P<0.001) separated four risk groups with a 5-year OS rate of 95, 64, 46 and 22%, [corrected] respectively. These data demonstrate for the first time that the inclusion of the collagen-I degradation product ICTP, as a biomarker of bone resorption, adds to the prognostic value of ISS.


Asunto(s)
Colágeno Tipo I/análisis , Mieloma Múltiple/diagnóstico , Estadificación de Neoplasias/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Resorción Ósea/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Estadificación de Neoplasias/normas , Péptidos/análisis , Pronóstico , Análisis de Supervivencia
19.
Int J Biomed Comput ; 37(3): 237-47, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-7705905

RESUMEN

We present a simple, formal, lexicon-based method for automated indexing of diagnoses based on the Systematized Nomenclature of Medicine (SNOMED II), called the LBI-method. Part 1 gives an introduction to the LBI-method and presents its realization as application system SALBIDH. The underlying model states that a diagnosis is represented by a set of indices of any nomenclature. The LBI-method is defined as a composition of functions, which in turn define the 3 steps of the LBI-method: preprocessing, morphological analysis, and semantic analysis. Part 2 will focus on the design and the results of an evaluation study to judge the quality of the LBI-method. In this evaluation study the quality of automated indexing was examined as well as the quality of the retrieval of patient data by using automated indexed diagnoses.


Asunto(s)
Indización y Redacción de Resúmenes , Diagnóstico , Procesamiento de Lenguaje Natural , Programas Informáticos , Descriptores , Procesamiento Automatizado de Datos , Humanos , Almacenamiento y Recuperación de la Información , Terminología como Asunto
20.
Int J Biomed Comput ; 38(2): 101-8, 1995 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7729926

RESUMEN

We present a simple, formal, lexicon-based method for automated indexing of diagnoses based on the Systematized Nomenclature of Medicine (SNOMED), called LBI-method. Part 1 gave an introduction to the LBI-method and presented its realisation as application system SALBIDH. Part 2 presents the design and the results of an evaluation study to judge the quality of the LBI-method. In this evaluation study the quality of automated indexing as well as the quality of the retrieval of patient data by using automated indexed diagnoses was examined. The results show that the retrieval based on SNOMED indices is at least as good as the retrieval based on ICD classes despite a lot of indexing errors. From this we gather that our system is not yet good enough for immediate routine use but that an appropriate indexing quality and, as a result, a higher retrieval quality can be achieved after few improvements of the LBI-method, especially after revision of the lexicons.


Asunto(s)
Indización y Redacción de Resúmenes , Diagnóstico , Procesamiento de Lenguaje Natural , Descriptores , Procesamiento Automatizado de Datos , Estudios de Evaluación como Asunto , Humanos , Almacenamiento y Recuperación de la Información , Registros Médicos , Alta del Paciente , Validación de Programas de Computación , Terminología como Asunto
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