RESUMEN
PURPOSE: The novel biplanar X-ray unit "EOS", EOS Imaging, allows to acquire simultaneously 2 perpendicular planes of full-length spine and limbs and to measure spatially correct angles based on the acquired image data sets. This is to be seen alongside with a low spatial resolution, high investment costs and high operating expenses. The use of the biplanar X-ray unit in morphology based scelettal radiography might improve the cost-benefit-relation. Thus, the purpose of this study was to compare image quality of the EOS-unit and the flat panel (FP)-technology as reference in a clinical setting. MATERIALS AND METHODS: All 114 patients of the Orthopedic Hospital Dept., who had a biplanar full-length lower limb radiograph and a FP-examination of the pelvis and/or the knee with maximum time interval of 3 months without changes in the clinical and radiological findings were included in the study. All X-ray examinations had been carried out due to clinical indications. Secondary captures comparable to the FP-images were extracted from the electronic EOS-image data sets. 4 radiologists independently from each other compared the visualization of normal anatomical structures of the pseudonymous EOS- and FP-images in a randomized order. RESULTS: In the overwiew of all readers and all sceletal regions image quality of the FP-images was considered being superior in a mean of 83â±â13â% standard deviation of the pair comparisons (minimum 48â%, maximum 100â%). Image quality of the EOS-images was assessed as being superior in 2â±â3â% of the cases (0â%, 10â%). Image quality of 0.8â±â3â% of the FP-images (0â%, 17â%) and 30â±â34â% (0â%, 100â%) of the EOS-images was estimated as diagnostically inadequate. 30â±â33â% of the pair comparisons (0â%, 100â%) showed a diagnostically inadequate image quality of the EOS-images and a diagnostically good image quality of the FP-images. CONCLUSION: Image quality of biplanar full-length lower limb X-ray examinations is not suitable to be used for the diagnostic assessment of the morphological bone structure using the currently available technological setting. KEY POINTS: ⶠbiplanar full-length lower limb X-ray examinations ⶠplat-panel radiography ⶠimage quality.
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Imagenología Tridimensional/instrumentación , Rodilla/diagnóstico por imagen , Pelvis/diagnóstico por imagen , Técnicas Estereotáxicas/instrumentación , Imagen de Cuerpo Entero/instrumentación , Pantallas Intensificadoras de Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Aumento de la Imagen/instrumentación , Masculino , Persona de Mediana Edad , Radiografía , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Our rationale was to evaluate whether a 64-slice CT scanner allows accurate measurement of computed tomographic (CT) changes in coronary artery flow profiles and whether CT flow measurements are suitable for classifying the significance and hemodynamic relevance of a stenosis and thereby supplement as a functional parameter for morphological stenosis analysis. METHODS: A total of 50 patients prospectively underwent computed tomography coronary angiography (coronary CTA) in a multidetector CT scanner (Brilliance 64, Philips)±1 day before or after invasive coronary angiography (ICA). Immediately thereafter, 2 radiologists reviewed the imaging data to detect any vessel segments with morphology poorly evaluable by coronary CTA. A locally constant cyclical measurement was acquired in these coronary arteries in breath-hold technique during the passage of a 50ml bolus of contrast media. For analysis, time-density curves of the bolus passage were registered in the coronary artery and the aorta (internal reference), the up-slopes were determined and correlated with each other. The results were compared with the ICA findings. RESULTS: 47 of 50 CT flow measurements were evaluable. A good correlation was found between the degrees of stenosis and slope ratios in aorta and coronary artery (R(2)=0.92). The threshold corridor was 0.55-0.77 for distinguishing hemodynamically (≥70%) from non-hemodynamically relevant stenoses. CONCLUSIONS: CT-based coronary artery flow measurements (CTFM) correlate well with the angiographically determined degree of stenosis and can elevate by non-invasive means the diagnostic accuracy of coronary CTA. From both a clinically diagnostic and scientific standpoint, CTFM proves a suitable method for quantifying coronary blood flow.
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Angiografía Coronaria/métodos , Estenosis Coronaria/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Anciano , Velocidad del Flujo Sanguíneo , Medios de Contraste , Femenino , Humanos , Yopamidol/análogos & derivados , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: A retrospective analysis of the long-term success rates of endoluminal therapy of renal artery stenosis in a university hospital was carried out. MATERIAL AND METHODS: Preinterventional and postinterventional data contained in the clinical records of all 104 patients who underwent percutaneous transluminal angioplasty (PTA, 25 patients) or stent PTA (79 patients) from 01 January 1994 to 31 December 2007, were documented using an electronically structured questionnaire and a time period classification. Subgroup analyses and statistical calculations were done using t-tests for joint random samples. RESULTS: At day 1 postintervention all patients showed a statistically significant decrease in mean systolic blood pressure (all patients: p=0.002, stent PTA group: p=0.023, PTA group: p=0.022). The significant decrease in mean systolic blood pressure persisted in years 1 and 2 postintervention (all patients: p=0.009 and 0.007, stent PTA group: p=0.039 and 0.015, respectively). Mean blood pressure values remained constant during the other time periods analyzed. In patients with a stent PTA carried out between 2001 and 2007 there was no significant reduction of prescribed antihypertonic drugs (p=0.023 and p=0.046, respectively). Mean serum creatinine concentrations decreased during years 1 and 2 postintervention and increased starting in year 3. In patients with elevated serum creatinine levels prior to the intervention the increase in mean serum creatinine level started in year 5. CONCLUSIONS: Endoluminal therapy of arteriosclerotic renal artery stenosis delays further deterioration of renal function and stabilizes blood pressure as well as the number of prescribed antihypertonic drugs. This can be considered a response to treatment in view of the mostly chronic progressive course of the disease.
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Procedimientos Endovasculares/estadística & datos numéricos , Hipertensión/epidemiología , Complicaciones Posoperatorias/epidemiología , Obstrucción de la Arteria Renal/epidemiología , Obstrucción de la Arteria Renal/cirugía , Insuficiencia Renal/epidemiología , Causalidad , Comorbilidad , Femenino , Alemania/epidemiología , Humanos , Incidencia , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Factores de Riesgo , EstreptonigrinaRESUMEN
We examined the safety and efficacy of vessel occlusion of the Amplatzer Vascular Plug 4 (AVP-4) in patients with arteriovenous fistulas after in-situ saphenous vein bypass grafts. We treated 18 fistulas of seven patients (four women, mean±standard deviation age 76±7 years, range 63-88 years). All fistulas were detected within 14 days after surgery. Initial diagnosis and follow-up was established by sonography. We measured the diameter of the feeding vessel and the time of vessel occlusion after plug deployment. Additionally, we recorded procedure time and the dose area product. Additional interventional procedures were necessary in three patients. We successfully used 19 AVP-4 for occlusion of all fistulas without thromboembolic complications. There was no need for recapturing the device, and we did not observe dislocation. Mean occlusion time was 9.6 min (range 5-22 min). Mean diameter of the feeding vessels was 3.5 mm (range 2.6-5.1 mm). Plug sizes ranged from 4-8 mm (mean 5.5 mm) resulting in an oversizing of 33-88%. Mean procedure time for patients with and without additional intervention was 91±38 min and 35±18 min, respectively. Mean dose area product was 11,790 cGy/cm2 (range 1,850-23,500 cGy/cm2). Permanent occlusion of the fistulas was confirmed by ultrasound after a mean follow-up of 4 months (1-6 months). Occlusion of arteriovenous fistulas with an AVP-4 seems to be effective and safe in patients with in-situ saphenous vein bypass grafts. The AVP-4 is well suited for this purpose because of the appropriate diameter of the feeding vessels.
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Fístula Arteriovenosa/terapia , Embolización Terapéutica/instrumentación , Arteria Poplítea/cirugía , Complicaciones Posoperatorias/terapia , Vena Safena/trasplante , Dispositivo Oclusor Septal , Anciano , Anciano de 80 o más Años , Angiografía , Femenino , Fluoroscopía , Humanos , Masculino , Persona de Mediana Edad , Arteria Poplítea/diagnóstico por imagen , Complicaciones Posoperatorias/diagnóstico por imagen , Radiografía Intervencional , Estudios Retrospectivos , Resultado del Tratamiento , UltrasonografíaRESUMEN
PURPOSE: In this study we examined the feasibility of portal vein embolization (PVE) by using the Amplatzer Vascular Plug (AVP-II). We measured the time of vessel occlusion after plug deployment and changes in plug length and diameter within 4 weeks of PVE. MATERIALS AND METHODS: In 10 consecutive patients (4 women, age 64 +/- 10 yrs, 48 - 82 yrs) an ipsilateral PVE of the right portal vein was performed prior to intended hemihepatectomy. After embolization with microparticles, the right portal vein was occluded using an AVP-II. We measured the time of complete vessel occlusion by angiography. Follow-up with computed tomography (CT) was performed within 72 h and after 4 weeks. RESULTS: PVE was performed in all 10 patients without acute complications. Complete vessel occlusion was achieved in 9.7 +/- 5.1 min (range 1 - 21 min). On follow-up CT we found enhanced arterial vascularization of the embolized liver segments in 5 / 5 patients within 72 hours and in 6 / 10 patients after 4 weeks. The plug showed a contraction of 20 +/- 9 % and a dilatation of 23 +/- 13 %. Thus, the AVP-II dilated to 94 +/- 8 % (78 - 100 %) of its nominal diameter. The plug diameter was significantly larger in men compared to women (17 +/- 1.7 mm vs. 14 +/- 1.4 mm, p < 0.02). We did not observe any recanalization or migration of the device. The volume of the left liver lobe increased significantly by 27 % (p < 0.001) after 4 weeks. CONCLUSION: PVE with the AVP-II is a feasible and effective method. The AVP-II can dilate within 4 weeks up to its nominal diameter dependent on the grade of oversizing. Dilatation of the diameter is associated with a shortening in length.
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Neoplasias de los Conductos Biliares/cirugía , Neoplasias Colorrectales/cirugía , Embolización Terapéutica/instrumentación , Hepatectomía , Conducto Hepático Común , Tumor de Klatskin/cirugía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Vena Porta , Dispositivo Oclusor Septal , Anciano , Anciano de 80 o más Años , Dilatación , Estudios de Factibilidad , Femenino , Humanos , Hígado/irrigación sanguínea , Masculino , Persona de Mediana Edad , Vena Porta/diagnóstico por imagen , Cuidados Preoperatorios , Estudios Retrospectivos , Factores Sexuales , Tomografía Computarizada por Rayos XRESUMEN
AIMS: To investigate the prognostic significance of chromosomal alterations in colorectal cancer patients. Histopathological tumour classification is still considered to be the gold standard for the characterization of solid tumours. However, it is well known that such established parameters do not satisfactorily predict the clinical outcome in individual cases. Markers that reliably predict survival are needed. These markers should guide the clinical treatment of neoplastic disease. METHODS AND RESULTS: Chromosomal imbalances in 61 colorectal carcinoma specimens in 37 patients determined by comparative genomic hybridization were correlated with patient survival using custom-made computer software which enabled the assessment of individual chromosomal loci. Kaplan-Meier analysis revealed that over-representations of 2p14-15, 6q23-6q24, 15q22-15q23, 22q11.2 and deletions of 1p36.1-36.2, 4q31.3, 4q35, 8q12-q21, 8p11.2 and 9p22 were significantly associated with shorter disease-specific survival, whereas over-expression of 20q13.3 and deletion of 18q11.2 were significantly associated with longer disease-specific survival in this collection of colorectal cancers. Multivariate Cox proportional hazards regression models consistently identified gains of 2p14-15, 15q22-23, 22q11.2 and losses of 1p36.1-36.2 and 4q35 as independent markers of shorter patient survival carrying greater significance than the classical clinicopathological parameters of nodal status and tumour grade. CONCLUSIONS: These five markers allow a molecular categorization of patients into high and low clinical risk groups. Thus, the genomic data have refined the histopathological classification highlighting the necessity for a supplementary genetically based stratification of colorectal cancer.
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Adenocarcinoma/genética , Aberraciones Cromosómicas , Neoplasias Colorrectales/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Estudios de Seguimiento , Marcadores Genéticos , Humanos , Procesamiento de Imagen Asistido por Computador , Cariotipificación , Hibridación de Ácido Nucleico/métodos , Modelos de Riesgos Proporcionales , Tasa de SupervivenciaRESUMEN
The lung resistance-related protein (LRP) was identified as the human major vault protein (MVP), and is overexpressed in various multidrug-resistant cancer cell lines and clinical samples. We characterized DNA sequences upstream to the transcription initiation site of the MVP gene in the human non-small cell lung cancer cell line SW-1573. A 1.9-kb and a shortened 0.7-kb fragment of the 5'-upstream genomic region show strong promoter activity in chloramphenicol acetyltransferase (CAT) reporter assays. The promoter is TATA-less and contains an inverted CCAAT-box and a Sp1 site located near to a p53 binding motif. An alternative 3'-splice site of intron 1 results in a splicing variant within the 5'-untranslated region of MVP mRNA.
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Resistencia a Múltiples Medicamentos/genética , Regiones Promotoras Genéticas , Regiones no Traducidas 5' , Empalme Alternativo , Secuencia de Bases , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Cloranfenicol O-Acetiltransferasa/metabolismo , Clonación Molecular , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Doxorrubicina/farmacología , Electroforesis en Gel de Agar , Ensayo de Inmunoadsorción Enzimática , Genes Reporteros , Humanos , Intrones , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Modelos Genéticos , Datos de Secuencia Molecular , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Plásmidos/metabolismo , ARN Mensajero , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Factor de Transcripción Sp1/genética , TATA Box , Transcripción Genética , Transfección , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba , Partículas Ribonucleoproteicas en Bóveda/genética , Partículas Ribonucleoproteicas en Bóveda/metabolismoRESUMEN
This protocol describes a PCR-based cDNA amplification technique of small total RNA quantities, optimized for determination and verification of gene expression variations in cells or tissue specimen. A proportional amplification of rare and abundant transcripts is thereby achieved by initial random hexamer-primed reverse transcription of total RNA. Compared to established oligo(dT)-primed techniques, this approach generates shorter than full length copies of long RNAs which leads to a normalized cDNA pool for a more adequate PCR-amplification. Subsequent double oligo(dA) tailing of the synthesized total cDNA strands and the utilization of heteropolymeric primers allow a highly specific, up to 500-fold PCR-amplification of the total cellular RNA amount. Thus, obstacles in availability of RNA from limited sources, such as human biopsies or microdissected histological sections, can be overcome. The amplified total cDNA (atcDNA) is shown to be applicable for confirmation of differential gene expression, as demonstrated in this protocol by expression analysis of the multidrug resistance-associated genes mdr1, mrp1 and lrp, using human cell lines as well as microdissected human tissue sections.
Asunto(s)
Expresión Génica , Reacción en Cadena de la Polimerasa/métodos , ARN/genética , Secuencia de Bases , Cartilla de ADN , ADN Complementario , Humanos , ARN/análisisRESUMEN
The effect of 1 - 3 intramuscular injections of the vitamin D3 metabolite 25-OHD3, synthetic 1 alpha-OHD3, and a combination of both on the plasma concentrations of calcium (Ca), inorganic phosphate (P(i)) and magnesium (Mg) was tested in 67 older dry dairy cows. Administering 4,0 mg 25-OHD3 reduced Ca and P(i) for some time while Mg blood levels remained constant. Injecting 210 micrograms 1 alpha-OHD3 plus 2.0 mg 25-OHD3 only brought a marked increase in P(i) concentrations, whereas 420 micrograms 1 alpha-OHD3 plus 4.0 mg 25-OHD3, and 350 micrograms 1 alpha-OHD3 alone significantly raised Ca and P(i) levels beginning on the 2nd day after injection and lasting for at least 6 days. These higher levels can be maintained by repeated injections. Another effect of injecting 1 alpha-OHD3 was to depress Mg blood levels, and a negative effect on the Ca and vitamin D3 metabolism is suggested which may cause hypocalcaemia when the effect of 1 alpha-OHD3 subsides. Metastatic calcifications of soft tissues were observed in some 1 alpha-OHD3-treated cows.
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Calcifediol/farmacología , Bovinos/sangre , Hidroxicolecalciferoles/farmacología , Minerales/sangre , Preñez/sangre , Animales , Calcifediol/administración & dosificación , Femenino , Hidroxicolecalciferoles/administración & dosificación , Inyecciones Intramusculares/veterinaria , Embarazo , Preñez/efectos de los fármacosRESUMEN
Analyses of different compounds in the plasma of healthy sheep before birth were conducted from day 70 to 43 (group 1), 42 to 22 (group 2), 21 to 15 (group 3), 14 to 8 (group 4) and 7 to 1 (group 5). There were significant differences in the concentration of ascorbic acid, total protein, total alpha-Amino-N, glucose, 3-hydroxybutyrate and of adenosine deaminase in the plasma between several groups, their significance is discussed. There was no difference in the concentration of cholesterol in the plasma of the sheep of the 5 groups. The content of ascorbic acid in 14 different tissues of sheep of the age of 6 and 12 months was analysed. There were significant differences between the 2 groups in the levels of ascorbic acid of the cerebrum and cerebellum, the hypophysis, the lungs, the kidneys and the spleen.
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Ácido Ascórbico/análisis , Preñez/sangre , Ovinos/sangre , Animales , Femenino , Embarazo , Preñez/metabolismo , Valores de Referencia , Ovinos/metabolismoRESUMEN
Of 55 patients with testicular cancer, treated by combination chemotherapy including cisplatin, 21 (mean age 35 [21-51] years) were reexamined for late sequelae of the chemotherapy 1-9 years later. No patient had a recurrence or second malignancy. They all had normal renal function (renal sequence scintigraphy; creatinine clearance). Seven of 20 patients had a polyneuropathy, nine of 18 had high-tone hearing loss. Two patients became fathers after treatment. In nine of 20 patients the serum concentration of follicle-stimulating hormone was raised to above 20 mU/ml, evidence of germ-cell damage. Six of 13 patients had an abnormal ejaculation following retroperitoneal lymphadenectomy or excision of a residual tumour. There was no evidence of any life-limiting toxicity of the chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Testiculares/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Sistema Cardiovascular/efectos de los fármacos , Cisplatino/efectos adversos , Fertilidad/efectos de los fármacos , Humanos , Riñón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Sistema Nervioso/efectos de los fármacos , Inducción de Remisión , Neoplasias Testiculares/fisiopatología , Factores de TiempoRESUMEN
We investigated the significance of X-ray element analysis of histological sections obtained from 26 patients with pneumoconiosis (occupations, etc. mining, quartz processing, metal polishing, exposure to aluminium dust, exposure to asbestos dust). Aluminium-containing or, in the case of asbestosis, magnesium-containing silicates were the most commonly found minerals. Iron and titanium were detected in particular in the sections obtained from metal polishers. X-ray micro-analysis permits a more accurate determination of dust exposure, and an improvement in the description of the pneumoconiosis presenting.
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Polvo/análisis , Microanálisis por Sonda Electrónica , Metales/análisis , Minerales/análisis , Neumoconiosis/patología , Asbestosis/patología , Biopsia , Humanos , Pulmón/patologíaRESUMEN
We determined ciprofloxacin levels in plasma, saliva, bronchial secretions, lavage fluid, and alveolar macrophages in 9 patients five hours following the last administration of the drug (2 x 750 mg ciprofloxacin daily over a period of at least 3 days). The ciprofloxacin concentration in the alveolar film was determined using urea as internal marker for the lavage. On average it was 2.51 micrograms/ml (= 186% of the plasma level), and clearly exceeded the minimal inhibition concentrations for the facultative pathogenic organism. This means that, in the alveolar film--which represents the barrier to descending pneumonia--an effective accumulation of the quinolone takes place.
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Bronquios/metabolismo , Ciprofloxacina/farmacocinética , Macrófagos/metabolismo , Alveolos Pulmonares/metabolismo , Saliva/metabolismo , Infecciones Bacterianas/sangre , Líquido del Lavado Bronquioalveolar/análisis , Humanos , Neumonía/sangreRESUMEN
We investigated the pharmacokinetic interaction of RMP (administered from the first day of treatment onwards), PZA (given from the second day onwards), and INH (day 17 onwards) in ten, previously untreated patients with pulmonary tuberculosis (five slow acetylators and five fast acetylators). In the case of the slow acetylators, higher INH and acetylhydrazine concentrations were measured than in the fast acetylators. RMP revealed the well-known autoinduction of its metabolism. During the course of continuing treatment, the PZA levels increased. No increased incidence of hepatoxic reactions was to be seen.
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Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Isoniazida/farmacocinética , Pirazinamida/farmacocinética , Rifampin/farmacocinética , Tuberculosis Pulmonar/sangre , Quimioterapia Combinada , Humanos , Infusiones Intravenosas , Isoniazida/efectos adversos , Tasa de Depuración Metabólica/fisiología , Pirazinamida/efectos adversos , Rifampin/efectos adversos , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
A specific direct method for determining the isoniazid derivative isonicotinoyl-hydrazine sodium glucuronide (INHG-Na) with the aid of high-pressure liquid chromatography has been developed, which permits the analysis of this derivative of isoniazid in addition to isoniazid itself and acetylisoniazid in the plasma of patients. In initial pharmacokinetic applications of the method, it has been shown that plasma INHG-Na is a stable substance that liberates only negligible concentrations of INH.
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Cromatografía Líquida de Alta Presión/métodos , Isoniazida/análogos & derivados , Isoniazida/farmacocinética , Tuberculosis Pulmonar/sangre , Acetilación , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Humanos , Isoniazida/efectos adversos , FenotipoRESUMEN
In a pilot study involving 62 patients with open pulmonary tuberculosis, we established that slow acetyators and patients receiving intravenous rifampicin treatment showed a tendency towards a more rapid negativisation of the sputum culture than did fast acetyators (lower levels of isoniazid) or patients receiving oral rifampicin therapy (decreasing bioavailability of the rifampicin during treatment).
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Etambutol/farmacocinética , Isoniazida/farmacocinética , Oxigenasas de Función Mixta/genética , Fenotipo , Rifampin/farmacocinética , Tuberculosis Pulmonar/tratamiento farmacológico , Acetilación , Administración Oral , Etambutol/administración & dosificación , Humanos , Isoniazida/administración & dosificación , Tasa de Depuración Metabólica/fisiología , Rifampin/administración & dosificaciónRESUMEN
We investigated the pharmacokinetics of rifampicin and its major metabolites, 25-desacetylrifampicin and 3-formylrifampicin, in two groups of six patients with active pulmonary tuberculosis, who received either multiple oral or intravenous rifampicin therapy in combination with intravenous isoniazid and ethambutol. Serum concentrations of rifampicin were each determined after a single oral and intravenous test dose of 600 mg rifampicin at the beginning and after 1 and 3 weeks of tuberculostatic treatment. Analysis of rifampicin and its metabolites was performed by high-pressure liquid chromatography. It was found that, due to autoinduction of its metabolizing hepatic enzymes, the systemic clearance of rifampicin increased from 5.69 to 9.03 l/h after 3 weeks of multiple dosing. The volume of distribution of the drug was constant over the period of this study. The bioavailability of the active, orally administered rifampicin decreased from 93% after the first single oral dose to 68% after 3 weeks of oral and intravenous rifampicin therapy. Relating to the increase in systemic (hepatic) clearance, a bioavailability no lower than 90% can be predicted. The reduction to 68% indicates that, in addition to an increase of hepatic metabolism, an induction of a prehepatic "first-pass" effect resulted from multiple rifampicin doses. Our study of rifampicin metabolites confirm that prehepatic metabolism was induced, since a higher metabolic ratio resulted after the oral doses than after the intravenous rifampicin test doses. A preabsorptive process can therefore be excluded as a cause of reduced bioavailability.