Multi-detector computed tomography and 3-dimensional imaging in a multi-vendor picture archiving and communications systems (PACS) environment

RATIONALE AND OBJECTIVES: To show the impact of the introduction of multi-detector computed tomography (CT) on radiologic workflow and to demonstrate how this reflects on picture archiving and communications systems (PACS) requirements. MATERIALS AND METHODS: Production measurements were obtained from different CT scanners (first two single-slice CT scanners; from December 2001 single and 4-slice CT; from April 2002 single and 16-slice CT) in number of patients from the radiologic information system. Implications on our PACS were recorded in terms of images and studies stored. Furthermore, our PACS design was made so that optimal use of 3-dimensional imaging within the radiologic workflow was possible. Finally, the number of non-diagnosed studies were recorded every day since the start of the transition to a filmless radiology department. RESULTS: This PACS design achieved a high level of integration between simple viewing and advanced 3-dimensional imaging and is optimized for handling large amounts of data. Overall increase of patients scanned with CT from January 2002-December 2003 was 54%. The number of series increased by 286% from December 2001-April 2003 and by 130% from April 2002-December 2003. From January 2002-February 2003, the number of images per patient increased from 175 to 450 (157%). Non-diagnosed studies decreased from about 100-120 before to practically zero after PACS implementation. CONCLUSION: PACS significantly increases productivity because of availability of the images and elimination of certain manual tasks. These results show that although the amount of examinations increases significantly with the introduction of MDCT, simultaneous introduction of PACS and filmless operation allows radiologists to handle the growth in workload.     

Kinetics of acetaminophen after single- and multiple-dose oral administration as a gradient matrix system to healthy male subjects

The in vivo characteristics of two formulations of a recently developed controlled-release system, the Gradient Matrix System (GMS-1 and GMS-2), with acetaminophen as a model drug compound have been determined in healthy volunteers both after separate single- and multiple-dose administration. Values for the mean residence time (MRT) were increased from 5.2 h for an oral solution to 10.2 and 13.3 h for two GMS formulations after single dosing. Peak plasma concentrations were lower for the two GMS formulations after single dosing compared to the oral solution. The bioavailability, relative to the oral solution, was 91 per cent and 84 per cent for the two GMS formulations tested. After multiple dosing of one of the GMS formulations over 5 days, no change in AUC compared to the single dose AUC occurred. Steady state was reached within 2-3 days of twice daily dosing of the GMS formulation. The peak-trough-fluctuation (per cent PTF) was 44 per cent. No signs of dose dumping were observed in fasted subjects. A plateau-like plasma drug concentration profile at steady state was maintained with the GMS formulation.     

Pharmacokinetic-pharmacodynamic modelling of the EEG effects of midazolam in individual rats: influence of rate and route of administration.

1. The purpose of the present investigation was to quantify the concentration-pharmacological effect relationship of midazolam in individual rats by use of effect parameters derived from aperiodic EEG analysis. By varying the rate and route of administration the role of (inter)active metabolites and development of acute tolerance was evaluated. 2. The pharmacokinetics and pharmacodynamics of midazolam were determined after intravenous administration of 10 mg kg-1 during 5, 30 and 60 min and oral administration of 15 mg kg-1. Following intravenous administration the pharmacokinetics were most adequately described by a bi-exponential equation. The values (mean +/- s.e. mean, n = 20) of clearance, volume of distribution at steady-state and terminal half-life were 67 +/- 2 ml min-1 kg-1, 1.61 +/- 0.071 kg-1 and 27 +/- 1 min, respectively. Following oral administration midazolam was rapidly absorbed with a systemic availability of 45 +/- 9%. 3. The averaged amplitudes in the 11.5-30 Hz (beta) frequency band of the fronto-central lead on the left-hemisphere, as derived by aperiodic EEG analysis, was selected as a measure of the pharmacological effect of midazolam. By pharmacokinetic-pharmacodynamic modelling the individual concentration-EEG effect relationships of midazolam were derived, which were successfully quantified by the sigmoidal Emax model. No marked and systematic differences in pharmacodynamic parameters were found between the rates and routes of administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dissolution profiles of mesalazine formulationsin vitro

In vitro dissolution profiles of three controlled-release mesalazine formulations were determined at pH 1.0, 6.0 and 7.5. A closed-column type dissolution apparatus was used. A reproducible gradual dissolution profile was seen for Pentasa^® at all pH values. Dissolution starts immediately and is complete after 20 h. Dissolution profiles at pH 1 and pH 7.5 are much alike and dissolution is faster than at pH 6. The behaviour of Asacol^® at different pH values corresponds with the expectations: no release at pH 6 and pH 1, fast release at pH 7.5. Dissolution starts after 1 h and is complete after 3 h. Mesalazine release from Salofalk^® tablets at pH 7.5 and pH 6.0 starts after 2 and 3 h, respectively, and is complete after 5 and 10 h. However, after a long lag-time (10 h) mesalazine is also released from Salofalksu^® tablets at pH 1 and dissolution is complete after 23 h.     

The bioavailability of seven commercially available rectal aminophylline suppositories

The bioavailability and thein vitro parameters of seven aminophylline 360 mg suppositories were compared with an oral hydroalcoholic solution of aminophylline as reference, using cross-over designs in groups of four subjects in single dose experiments. Plasma concentrations were followed for eight hours after drug administration. Four products gave extents of bioavailability of less than 80% of the reference solution. A dissolution test gave results which did not correlate well with the bioavailability results. It was concluded that no satisfactory plasma levels can be reached with the examined dose of aminophylline after single administration of one suppository.Calculation of the steady-state concentration was performed as well as a graphic simulation of the plasma concentration-time curves, after repeated administration; it was demonstrated that with most of the suppositories no sufficiently high level could be obtained after three doses per day.In honour of ProfessorHuizinga on the occasion of his retirement.     

Friction-based stabilization of juxtacellular recordings in freely moving rats

Virtually nothing is known about the activity of morphologically identified neurons in freely moving mammals. Here we describe stabilization and positioning techniques that allow juxtacellular recordings from labeled single neurons in awake, freely moving animals. This method involves the use of a friction-based device that allows stabilization of the recording pipette by friction forces. Friction is generated by a clamplike mechanism that tightens a sliding pipette holder to a preimplanted pipette guide. The interacting surfaces are smoothed to optical quality (<5-nm roughness) to enable micrometer stepping precision of the device during operation. Our method allows recordings from identified neurons in freely moving animals, and thus opens new perspectives for analyzing the role of identified neurons in the control of behavior.     

Comparison of in vitro and in vivo release characteristics of acetaminophen from gradient matrix systems

An effort was made to correlate the in vivo and in vitro release data of acetaminophen from two formulations of a recently developed controlled-release system, the Gradient Matrix System (GMS-1 and GMS-2). The in vivo release curves, obtained by deconvolution of the plasma concentration time plots, showed a small inter-subject variability. GMS-1 with fastest in vitro release also showed fastest in vivo release. A good relationship was only found after time-scaling of the release data.     

Study on motion artifacts in coronary arteries with an anthropomorphic moving heart phantom on an ECG-gated multidetector computed tomography unit

Acquisition time plays a key role in the quality of cardiac multidetector computed tomography (MDCT) and is directly related to the rotation time of the scanner. The purpose of this study is to examine the influence of heart rate and a multisector reconstruction algorithm on the image quality of coronary arteries of an anthropomorphic adjustable moving heart phantom on an ECG-gated MDCT unit. The heart phantom and a coronary artery phantom were used on a MDCT unit with a rotation time of 500 ms. The movement of the heart was determined by analysis of the images taken at different phases. The results indicate that the movement of the coronary arteries on the heart phantom is comparable to that in a clinical setting. The influence of the heart rate on image quality and artifacts was determined by analysis of several heart rates between 40 and 80 bpm where the movement of the heart was synchronized using a retrospective ECG-gated acquisition protocol. The resulting reformatted volume rendering images of the moving heart and the coronary arteries were qualitatively compared as a result of the heart rate. The evaluation was performed on three independent series by two independent radiologists for the image quality of the coronary arteries and the presence of artifacts. The evaluation shows that at heart rates above 50 bpm the influence of motion artifacts in the coronary arteries becomes apparent. In addition the influence of a dedicated multisector reconstruction technique on image quality was determined. The results show that the image quality of the coronary arteries is not only related to the heart rate and that the influence of the multisector reconstruction technique becomes significant above 70 bpm. Therefore, this study proves that from the actual acquisition time per heart cycle one cannot determine an actual acquisition time, but only a mathematical acquisition time.     

Accuracy, feasibility, and clinical impact of prospective Bayesian pharmacokinetically guided dosing of cyclophosphamide, thiotepa, and carboplatin in high-dose chemotherapy.

PURPOSE: Relationships between toxicity and pharmacokinetics have been shown for cyclophosphamide, thiotepa, and carboplatin (CTC) in high-dose chemotherapy. We prospectively evaluated whether variability in exposure to CTC and their activated metabolites can be decreased with pharmacokinetically guided dose administration and evaluated its clinical effect. EXPERIMENTAL DESIGN: Patients received multiple 4-day courses of cyclophosphamide (1,000-1,500 mg/m2/d), thiotepa (80-120 mg/m2/d), and carbop latin (area under the plasma concentration-time curve 3.3-5 mg x min/mL/d). Doses were adapted on day 3 based on pharmacokinetic analyses of cyclophosphamide, 4-hydroxycyclophosphamide, thiotepa, tepa, and carboplatin done on day 1 using a Bayesian algorithm. Doses were also adjusted before and during second and third courses. Observed toxicity was compared with that in patients receiving standard dose CTC (n = 43). RESULTS: A total of 46 patients (108 courses) were included. For cyclophosphamide, thiotepa, and carboplatin, a total of 39, 58, and 65 dose adaptations were done within courses and 17, 40, and 43 before courses. The precision within which the target exposure was reached improved compared with no adaptation, especially after within-course adaptations (precision for cyclophosphamide, thiotepa, and carboplatin is 19%, 16%, and 13%, respectively); >85% led to an exposure within +/-25% of the target compared with 60% without dose adjustments. Toxicity was similar to that in a reference population, although the incidence of veno-occlusive disease was reduced. CONCLUSIONS: Bayesian pharmacokinetically guided dosing for CTC was feasible and led to a marked reduction in variability of exposure.