Mats Magnusson

Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin.

The aim of this study was to develop a model describing the carbamazepine autoinduction and the carbamazepine‐mediated induction of CYP3A4, CYP1A2, and P‐glycoprotein. Seven healthy volunteers were dosed with carbamazepine over 16 consecutive days. The CYP3A4, CYP1A2, and P‐glycoprotein activities were assessed, using midazolam, caffeine, and digoxin as probe substrates, on 12 occasions, covering the preinduced state and the onset and termination of the induction process. The data were evaluated using a mechanistic pharmacokinetic approach in NONMEM. The induction processes were described using turnover models, with carbamazepine and carbamazepine‐10,11‐epoxide as the driving force of the induction. The half‐lives of CYP3A4 and CYP1A2 were estimated to be 70 and 105 h, respectively. P‐glycoprotein was not affected by the carbamazepine treatment. The possibility of modeling the pharmacodynamics of enzyme induction using a turnover model was illustrated, and the time course of the process was estimated with good precision.

Outcome after percutaneous transluminal angioplasty of arterial stenosis in renal transplant patients

Background: Ensuring graft survival in renal transplant patients is of paramount importance. Early detection and treatment of complications such as transplant renal artery stenosis (TRAS) are essential. Purpose: To evaluate the technical and clinical success rate of renal transplant patients with stenosis in the transplant renal artery or in the iliac artery after percutaneous transluminal angioplasty (PTA). Material and Methods: PTA was carried out on 24 patients with TRAS or iliac artery stenosis. Altogether, 28 stenoses were treated with PTA. The immediate technical result and the clinical outcomes after 1 and 3 months were assessed as well as clinical adverse events. A reduction in serum creatinine and/or a reduction in the number of antihypertensive drugs were criteria for clinical success. Results: The immediate technical success rate after PTA was 93%. The clinical success rate after 1 month was 58%, increasing to 75% after 3 months. Conclusion: The technical success rate is not equivalent to the clinical success rate when treating TRAS with PTA. Furthermore, there is a delay in clinical response, sometimes of 3 months, after a technically successful PTA.

Survival time and period of catheterization in patients treated with percutaneous nephrostomy for urinary obstruction due to malignancy

Purpose: To assess patient mortality and survival time, period of catheterization, and indications for percutaneous nephrostomy (PCN) withdrawal in patients treated with PCN for urinary obstruction due to malignancy. Material and Methods: A retrospective analysis of 151 patients treated with 257 PCNs in a 5-year period was performed. Data on survival time, duration of catheterization, and clinical end-points for PCN treatment were collected. Results: The median survival time of the patients was 255 days, while median catheterization time was 62 days. The majority of patients (84) died with the catheter. Indications for PCN withdrawal were surgery, stent treatment, catheter displacement, and response to medical treatment. Conclusion: The majority of patients with malignancy treated with PCN have advanced disease and short life expectancy. Factors such as diagnosis, prognosis, economy, and the patients preference influence the choice of urinary diversion method. However, PCN should be considered in patients with malignancy on grounds of safety and low cost.

How Much Dose Can Be Saved in Three-Phase CT Urography? A Combination of Normal-Dose Corticomedullary Phase With Low-Dose Unenhanced and Excretory Phases

OBJECTIVE The purpose of this study was to investigate the degree to which the total radiation dose for CT urography can be lowered by selective reduction of the dose in the unenhanced and excretory phases when images in these phases are systematically evaluated alongside normal-dose corticomedullary phase images. SUBJECTS AND METHODS Twenty-seven patients (mean age, 74±9 years) underwent single-bolus CT urography with acquisition in the unenhanced, corticomedullary, and 5-minute excretory phases. The scanning parameters for normal-dose CT urography were as follows: 16×0.75 mm, 120 kV, and automatic exposure control technique reference tube loads of 100, 120, and 100 effective mAs (mAseff). The patients also underwent low-dose unenhanced and excretory phase scanning, in which the dose was escalated stepwise from a volume CT dose index (CTDIvol) of 1.7 to 6.6 mGy (reference 20-40-60-80 mAseff). Images were analyzed for quality and diagnostic confidence. If low-dose scans of three patients were inadequate, the study continued to the next dose level. When 20 patients were successfully included in the unenhanced and excretory phase groups, the study ended. Doses were calculated with a CT patient dosimetry calculator. RESULTS Combined with the normal dose for corticomedullary phase scanning, doses of CTDIvol 1.5 mGy for the unenhanced phase and CTDIvol 2.7 mGy for the excretory phase were sufficient. The effective dose for three-phase CT urography was lowered from 16.2 to 9.4 mSv, a decrease of 42%. Diagnostic confidence in low-dose images was equal to that in normal-dose images when low-dose unenhanced and excretory phase images were read along-side normal-dose corticomedullary phase images. CONCLUSION With a three-phase CT urographic protocol, significant dose reductions in the unenhanced and excretory phases can be achieved when these phases are combined with a normal-dose corticomedullary phase.

Three-dimensional rotational angiography of transplanted renal arteries : influence of an extended angle of rotation on beam-hardening artifacts

Purpose: To investigate whether three‐dimensional rotational angiography (3D‐RA) of the transplant renal artery performed with an extended angle of rotation can reduce beam‐hardening artifacts in 3D reconstructed images without image quality being lost or side effects to the transplanted kidney being increased. Material and Methods: 3D‐RA with a C‐arm rotation of 180° was performed consecutively in 12 renal transplanted patients with suspicion of renal artery stenosis. A 1.7‐mm balloon occlusion catheter was placed using the crossover technique and this was compared to a protocol with 160° rotation and a traditional 1.4‐mm catheter in 10 patients. The occurrence of beam‐hardening artifacts was registered and the effects of the reduced contrast load on image quality and of arterial occlusion on renal function were assessed. Results: The extended angle of rotation, from 160° to 180°, reduced the beam‐hardening artifacts. Artifacts were observed in 4/11 patients (36%) in the study group and in all 10 (100%) of the controls. There was no statistical difference regarding image quality between the two protocols. Renal function was equally affected in both protocols. Conclusion: 3D‐RA with an extended C‐arm rotation reduced the beam‐hardening artifacts. Image quality was not reduced despite the reduced contrast medium load. The different protocols had no effect on patient outcome.

Contrast enhancement in bladder tumors examined with CT urography using traditional scan phases.

Background Bladder assessment in an early contrast-enhancing computed tomography urography (CTU) phase requires that bladder tumors be enhanced using contrast material. Purpose To investigate the enhancement pattern in bladder tumors using a CTU protocol where the scan is enhancement triggered. Material and Methods Fifty patients diagnosed with bladder cancer were examined during the unenhanced (UP), corticomedullary (CMP), and excretory phases (EP). Twenty-one patients, all aged 50 years or older, were also examined during the nephrographic phase (NP). A ROI placed in the aorta was used to start the scan during the CMP when the attenuation reached 200 Hounsfield units (HU). The NP and EP were started with a 40 s and 300 s delay, respectively, after the CMP was finished. Attenuation and size measurements were made in the axial plane. Results Mean contrast enhancement of bladder tumors was 37, 25, and 17 HU in the CMP, NP, and EP, respectively. The differences in contrast enhancement were significant across all three phases. Eighty-eight percent of patients showed the highest contrast enhancement in the CMP. In 96% of the cases, contrast enhancement >20 HU was seen. The mean value of the shortest dimension of the bladder tumors was 22 ± 12 mm. Conclusion The contrast enhancement is significantly higher in the CMP than in the NP and EP, suggesting that the CMP is preferable when assessing the bladder in the early contrast enhancing phase.