Biomedical subjects

C Martens

Publications and source records attributed to C Martens.

At least 19 recordsLinked to original sources

PubMed2003

Monte Carlo model of the Elekta SLiplus accelerator: validation of a new MLC component module in BEAM for a 6 MV beam.

A new component module (CM), called MLCE, has been implemented in the BEAM program. The CM takes into account the particular 'tongue-and-groove' design of the Elekta multi-leaf collimator (MLC) and the air gap between the leaves. The model was validated by two series of measurements and simulations. The first benchmarking series focuses on the interleaf leakage and the intraleaf transmission. The measurement showed a total transmission through the MLC of 1.42% of the open field dose. Two Monte Carlo (MC) simulations were made, the first with the new CM MLCE (inclusive of air gap) and the second with the CM MLCQ (exclusive of air gap), which is available in the BEAM distribution. When the air gap between the leaves was determined by varying the parameters of the leaf geometry within tolerance limits on the technical drawing, the total measured transmission of 1.42% was well reproduced by the CM MLCE. In contrast, MC simulations with MLCQ showed that the transmission through the MLC calculated without the interleaf leakage is only 44% of the total transmitted radiation. The relevance of the detailed MLC modelling was demonstrated also by studying the 'adjacent' tongue-and-groove effect, where two adjacent (not opposing) leaves are complementary, opened or closed. The two complementary leaf settings were simulated both with the CM MLCE and MLCQ. A comparison with measurements was made. In regions covered by two or more leaves, the dose increased by 14% for two leaves and by 40% for more than two leaves when the interleaf leakage was included in the transmission. The tongue-and-groove effect was perfectly reproduced by the MLCE module.

Algorithms↗

PubMed2002

The value of radiographic film for the characterization of intensity-modulated beams.

In this paper the performance of radiographic film (KODAK X-Omat V) for analysing intensity-modulated (IM) beams in a plane at reference depth (5 cm for 6 MV, 10 cm for 18 MV) was investigated. The field size dependence of the film response was studied for small and medium field sizes. The dose rate dependence of the response and possible effects of fractionating the dose were assessed. In the end, profiles were measured for two clinically delivered IM beams, and the results were compared with diamond detector data. We found that the response of the radiographic film increases with field size, but for field sizes up to 15 x 15 cm the deviations remain within 3% for measurements with the films in a plane at reference depth. We found that the response of the films decreases with decreasing dose rate, and that the extent of this effect differs from film batch to film batch. For clinical IM beams the effect can amount to about 9% at the location of shielded organs at risk. Also, fractionating the dose reduces the net optical density, but this effect is normally small when assessing IM beams. In low-dose regions low-energy photons have an important contribution, resulting in a higher response at these positions. This may counteract the dose rate dependence of the response. In the high-dose regions of the two IM beams that were studied, the relative dose measurements with film are within 1% of those obtained with a diamond detector, when the results of three films are averaged. In shielded organs at risk the deviations can mount to about 3%, depending on the film batch. In conclusion, radiographic film is a suitable detector for characterizing IM beams in a plane at reference depth.

Dose-Response Relationship, Radiation↗

PubMed2002

Outpatient total body irradiation as a component of a comprehensive outpatient transplant program.

Outpatient total body irradiation (TBI) as part of a comprehensive outpatient transplant program was delivered to 142 of 167 (85%) consecutive patients receiving TBI-based conditioning therapy. Outpatients received either a single fraction of 500 cGy (110 patients) or 1200 cGy in six fractions over 3 days (32 patients). Patients were assessed daily and were administered oral ondansetron and dexamethasone for prophylaxis of nausea and vomiting as well as i.v. hydration. Accommodation during outpatient TBI-based conditioning was either the patient's home if within 30 min of the hospital, a hotel on the hospital grounds or on a closed hospital ward. None of the 142 patients required admission to the inpatient program during their TBI. There was no difference in 100-day mortality between those receiving TBI as an outpatient (9%) vs as an inpatient (16%). Of four deaths occurring within the first 14 days post transplant, none could be attributed to receiving TBI as an outpatient. Two hundred and six inpatient days were saved through the delivery of outpatient TBI. A comprehensive outpatient program, appropriate patient selection, daily hydration, the use of prophylactic 5HT3 antagonist anti-emetic therapy all contribute to the safe delivery of outpatient TBI.

Adolescent↗

PubMed2002

Underdosage of the upper-airway mucosa for small fields as used in intensity-modulated radiation therapy: a comparison between radiochromic film measurements, Monte Carlo simulations, and collapsed cone convolution calculations.

Head-and-neck tumors are often situated at an air-tissue interface what may result in an underdosage of part of the tumor in radiotherapy treatments using megavoltage photons, especially for small fields. In addition to effects of transient electronic disequilibrium, for these small fields, an increased lateral electron range in air will result in an important extra reduction of the central axis dose beyond the cavity. Therefore dose calculation algorithms need to model electron transport accurately. We simulated the trachea by a 2 cm diameter cylindrical air cavity with the rim situated 2 cm beneath the phantom surface. A 6 MV photon beam from an Elekta SLiplus linear accelerator, equipped with the standard multileaf collimator (MLC), was assessed. A 10 x 2 cm2 and a 10 x 1 cm2 field, both widthwise collimated by the MLC, were applied with their long side parallel to the cylinder axis. Central axis dose rebuild-up was studied. Radiochromic film measurements were performed in an in-house manufactured polystyrene phantom with the films oriented either along or perpendicular to the beam axis. Monte Carlo simulations were performed with BEAM and EGSnrc. Calculations were also performed using the pencil beam (PB) algorithm and the collapsed cone convolution (CCC) algorithm of Helax-TMS (MDS Nordion, Kanata, Cahada) version 6.0.2 and using the CCC algorithm of Pinnacle (ADAC Laboratories, Milpitas, CA, USA) version 4.2. A very good agreement between the film measurements and the Monte Carlo simulations was found. The CCC algorithms were not able to predict the interface dose accurately when lateral electronic disequilibrium occurs, but were shown to be a considerable improvement compared to the PB algorithm. The CCC algorithms overestimate the dose in the rebuild-up region. The interface dose was overestimated by a maximum of 31% or 54%, depending on the implementation of the CCC algorithm. At a depth of 1 mm, the maximum dose overestimation was 14% or 24%.

Air↗

PubMed2001

Combining the advantages of step-and-shoot and dynamic delivery of intensity-modulated radiotherapy by interrupted dynamic sequences.

PURPOSE: A hybrid between step-and-shoot and dynamic operation, called interrupted dynamic sequences, was investigated for prostate intensity-modulated radiotherapy (IMRT) delivered by a multisegment close-in technique. The new delivery mode was compared to the step-and-shoot mode concerning dose distribution. METHODS AND MATERIALS: Segments suitable for dynamic transition were selected using a system of segment classes. Transitions were only allowed between two segments of the same class, keeping intended sharp in-field dose gradients unchanged. Delivery was performed by an Elekta SLiplus (Crawley, UK) linear accelerator equipped with a dynamic multileaf collimator (MLC). Because no modeling of the dose during the transitions is made, accurate dose measurements were performed. Dose profiles were measured using a linear ion chamber array (LA48, PTW-Freiburg). The suitability of this detector for measurements in sharp dose gradients was investigated first. In addition, field flatness was examined for segments with a low monitor unit (MU) count. Uncertainties in dose output were investigated using an ionization chamber (30001, PTW-Freiburg). RESULTS: Because linear array measured penumbrae are only slightly broader (< or = 0.4 mm for MLC collimated field) than those obtained using a diamond detector, the array is a good device for profile measurements. Uncertainties related with the use of low MU beam segments are very small (< 1% for segments of minimum 3 MU), giving no contra-evidence for the step-and-shoot mode. Interrupted dynamic sequences are shown to introduce only small dosimetric differences as compared to the step-and-shoot delivery. CONCLUSION: Both delivery modes, step-and-shoot and interrupted dynamic sequences, result in similar dose distributions for the forward planned prostate class solution.

Humans↗

PubMed2001

RNA polymerase II and TBP occupy the repressed CYC1 promoter.

Saccharomyces cerevisiae CYC1 gene expression has been studied in great detail with regard to the response to oxygen availability and carbon source. In the absence of oxygen and the presence of glucose, the CYC1 gene is completely repressed. Chromatin structure is thought to play an important role in CYC1 gene regulation, as nucleosome depletion results in 94-fold derepression. In addition, the CYC1 core promoter has been used extensively in hybrid constructs to study activation by heterologous transcription factors. Therefore, we set out to map the chromatin structure of the CYC1 promoter and determine its role in CYC1 gene regulation. We report here that the repressed CYC1 promoter contains no positioned nucleosomes over the core promoter. However, we did find TFIID and RNA polymerase II bound in a complex on the repressed promoter. These results indicate that recruitment of TFIID and RNA polymerase II are not rate-limiting steps in CYC1 activation.

Chromatin↗

PubMed2001

Improved delivery efficiency for step and shoot intensity modulated radiotherapy using a fast-tuning magnetron.

The delivery efficiency of step and shoot intensity modulated radiotherapy (IMRT) has been improved by the installation of fast-tuning magnetrons into three travelling wave linear accelerators. The IMRT delivery efficiency and the beam start-up performance have been compared before and after installation. Start-up and inter sub-field times were reduced by an average of 3.0 s. A typical start-up time from depression of the start button to beam on is now around 4 s. Delivery efficiency for a variety of clinical and quality control prescriptions was improved by an average of 30.7% (range 7.4-60.9%), depending on a complex combination of the number of sub-fields, distance moved by leaves and dose rate. For the oldest accelerator (7 years old), dosimetric accuracy was significantly improved for low dose sub-fields. The dose output was within 2% for a 1 monitor unit (MU) sub-field and 1% for a 2 MU sub-field. The two newer accelerators displayed similar or better dose characteristics even before fast-tuning magnetron installation. Beam symmetries and flatnesses were acceptable at all energies and dose rates, and showed no obvious degradation in low dose sub-fields. It is recommended that fast-tuning magnetrons are adopted for accelerators of this design performing step and shoot IMRT.

Magnetics↗

PubMed2001

The value of the LA48 linear ion chamber array for characterization of intensity-modulated beams.

In this paper the performance of the LA48 linear ion chamber array (PTW, Freiburg, Germany) for characterization of intensity-modulated (IM) beams was investigated. First, some elementary properties were explored. A series of beam penumbras and output factors for small rectangular fields were measured at 6 and 18 MV, and the results were compared with data obtained using a diamond detector. The energy and dose rate dependence of the array response were examined, and the leakage current was assessed. In a second step, profiles were measured for two clinically delivered IM beams and for a dynamic wedge. The interplay between the sharpening of the penumbra by the upper metal electrode plate of the array and the volume averaging of the 4 x 4 mm ion chamber elements results in precise measurements, even in regions of high dose gradient. It is true, however, that the metal electrodes imply a small energy spectrum dependence in the array response. The dose rate dependence is found to be negligible. All of this makes, the LA48 linear array a suitable device for analysing dose distributions of clinical IM beams.

Dose-Response Relationship, Radiation↗

PubMed2000

Benefit of emergency haemorrhoidectomy: a comparison with results after elective operations.

OBJECTIVE: To compare the outcome of emergency and elective haemorrhoidectomy. DESIGN: Retrospective study. SETTING: Teaching hospital, Belgium. SUBJECT: 104 patients who had haemorrhoidectomy for acutely ulcerated or strangulated haemorrhoids, and 545 who had elective haemorrhoidectomy. RESULTS: Early complications (26/104, 25%), reoperation (7/104, 7%) and late anal stenosis (7/104, 7%) were more common after emergency than elective haemorrhoidectomy, for which the corresponding figures were 74/545 (3.6%), 9 (1.7%) and 1/545 (0.2%). Late outcome was similar for the two groups. CONCLUSIONS: Emergency haemorrhoidectomy is indicated for the treatment of the acute complications of haemorrhoids.

Acute Disease↗

PubMed2000

The value of the PinPoint ion chamber for characterization of small field segments used in intensity-modulated radiotherapy.

Volume averaging and lack of electronic equilibrium complicate accurate dosimetry of small photon fields. In this paper the performance of the PinPoint ion chamber for characterizing small fields used in intensity-modulated radiotherapy (IMRT) was investigated and the results were compared with those obtained using the Markus ion chamber and a diamond detector. Sharp beam penumbras were measured for a 5 x 5 cm field defined using a cerrobend block mounted on the accelerator head. In addition, output factors were measured for a 6 MV photon beam and a variety of small rectangular fields collimated widthwise using the multileaf collimator (MLC) in combination with the back-up jaws. From this study, a reference field of 5 x 5 cm and a measuring depth of 5 cm are recommended. This is related to the over-response of the PinPoint chamber to low-energy Compton scattered photons, an effect that was investigated rigorously and turned out to limit the scope of this ionization chamber. However, taking into account some limitations, the PinPoint chamber is an excellent detector for output measurements in small fields down to 2 cm. In profile measurements the chamber causes a broadening of the measured penumbras but its spatial resolution is superior to that of the Markus chamber.

Calibration↗

PubMed1999

A generic particle-based nonradioactive homogeneous multiplex method for high-throughput screening using microvolume fluorimetry.

We have developed a novel fluorescence-based homogeneous binding assay for high-throughput screening of chemical compounds. In this assay, a Cy5- or Cy5.5-labeled ligand binds to receptor immobilized on a particle, either a bead or a cell. The resulting localized signal can be detected by a modified microvolume fluorimeter (MVF). When a molecule which competes with the labeled ligand is present, the localized fluorescence on cells or beads is reduced. Image processing software enumerates events and analyzes fluorescence intensity. We describe MVF assays for the IL-1 and IL-5 receptors. Using synthetic peptides with a range of affinities for the IL-1 receptor, we obtained IC(50) data consistent with those determined by radioligand binding assays. Because the image processing software can discriminate among events with different diameters, we were able to develop a multiplex assay, in which the IL-1R and IL-5R assays were carried out in the same well with each receptor immobilized on a different size of bead. IC(50) values generated in the multiplex assay for ligands specific to each receptor were comparable to those determined independently. Finally, similar IC(50) values were obtained in a 16-microl volume in an 864-well plate. This homogeneous, nonradioactive, miniaturizable, and multiplex-capable assay holds much promise for screening of combinatorial libraries and compound collections.

Animals↗

PubMed1999

Heterodimerization between members of the Nur subfamily of orphan nuclear receptors as a novel mechanism for gene activation.

We have recently shown that the orphan nuclear receptor Nur77 (NGFI-B) is most active in transcription when it is interacting with a cognate DNA sequence as a homodimer. Further, we have shown that the target for Nur77 dimers, the Nur response element (NurRE), is responsive to physiological stimuli in both endocrine and lymphoid cells, whereas other DNA targets of Nur77 action are not. The Nur77 subfamily also includes two related receptors, Nur-related factor 1 (Nurr1) and neuron-derived orphan receptor 1 (NOR-1). Often, more than one member of this subfamily is induced in response to extracellular signals. We now show that Nur77 and Nurr1 form heterodimers in vitro in the presence or absence of NurRE, and we have documented interactions between these proteins in vivo by using a two-hybrid system in mammalian cells. These heterodimers synergistically enhance transcription from NurRE reporters in comparison to that seen with homodimers. The naturally occurring NurRE from the pro-opiomelanocortin gene preferentially binds and activates transcription in the presence of Nur77 homo- or heterodimers, while a consensus NurRE sequence does not show this preference. Taken together, the data indicate that members of the Nur77 subfamily are most potent as heterodimers and that different dimers exhibit target sequence preference. Thus, we propose that a combinatorial code relying on specific NurRE sequences might be responsible for the activation of subsets of target genes by one of the members of the Nur77 subfamily of transcription factors.

Corticotropin-Releasing Hormone↗

PubMed1997

Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia.

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of ischemic heart disease. An open-label study was conducted to test the efficacy and safety of atorvastatin, a new synthetic HMG-CoA reductase inhibitor in proven FH. After a 4-week placebo phase, 22 subjects were randomized to either 80 mg atorvastatin at night (n = 11) or 40 mg twice a day for 6 weeks. The two dosage groups were well matched and had no difference in lipoprotein responses. After 6 weeks, the LDL cholesterol concentration was reduced by 57%, from 8.16 +/- 1.15 to 3.53 +/- 0.99 mmol/L (P < .001). The total cholesterol concentration decreased from 9.90 +/- 1.32 to 5.43 mmol/L (P < .001). HDL cholesterol concentration increased from 1.19 +/- 0.31 to 1.49 +/- 0.43 mmol/L (P < .001). Triglyceride concentrations decreased from 1.34 +/- 0.66 to 0.88 +/- 0.36 mmol/L (P < .01). Three subjects had single, transient increases of serum transaminase of up to twice the upper limit of normal. Apolipoprotein B concentration decreased significantly by 42%. Changes in apolipoproteins AI and (a) were not statistically significant. Nondenaturing gradient gel electrophoresis revealed increases in the size of smaller LDL particles in four subjects. Plasma fibrinogen concentration increased by 44%. The drug was well tolerated. One subject withdrew for personal reasons. Atorvastatin is a powerful and safe lipid-modifying agent for LDL cholesterol; it also modifies HDL cholesterol and triglyceride concentrations, and may suffice as a single agent for many subjects with heterozygous FH.

Adult↗

PubMed1997

Surgical treatment of distal biceps tendon ruptures results of a multicentric BOTA-study and review of the literature. Belgian Orthopedic Trauma Association.

Distal biceps tendon ruptures (DBTR) are relatively uncommon. This multicentric study, conducted on behalf of BOTA (Belgian Orthopedic Trauma Association), documents the complications and results after surgical treatment of 18 DBTR's. In the current series a repair with Mitek anchors was found to be a simple and reliable fixation that could be performed through a single anterior approach with minor risks of radial nerve damage. If a two-incision technique following Boyd and Anderson is used, the ulna should not be exposed in order to avoid a radioulnar synostosis; splitting the extensor muscle mass is preferable to a subperiostal ulna dissection, and the wound should always be drained to decrease the likelihood of hematoma formation.

Adult↗

PubMed1995

Florid reactive periostitis.

Florid reactive periostitis (FRP) is a benign entity, mostly involving the tubular bones of the hands and feet. It is important to distinguish FRP from malignant processes such as periosteal osteosarcoma and parosteal osteosarcoma, to give an adequate treatment and to avoid amputation of the total digit. The final diagnosis of FRP is usually based on the combination of clinical, radiological, and pathological findings. The pattern seen on the isotope bone scan can be very helpful in orienting the differential diagnosis.

Bone Neoplasms↗

PubMed1995

Bilateral posterior four-part fracture-dislocation of the shoulder.

A case of a bilateral posterior four-part fracture dislocation of the shoulder after a convulsive seizure was treated conservatively on one side, while the other shoulder was replaced by a hemiarthroplasty. A review of the literature and a treatment protocol for managing these injuries are presented. In four-part fracture-dislocations good results can be achieved with conservative treatment, but when avascular necrosis is likely to occur (delay in diagnosis or dubious relationship of the fragments after reduction) it is better to replace the humeral head.

Bone Nails↗

PubMed1995

Modulation of vindesine and doxorubicin resistance in multidrug-resistant pleural mesothelioma cells by tumor necrosis factor-alpha.

Tumor necrosis factor-alpha (TNF-alpha) has been shown to enhance the cytotoxicity of a variety of antineoplastic agents. To examine whether multidrug-resistant cells are targets of TNF-alpha, and whether TNF-alpha is capable of modulating chemoresistance of these cells, a pleural mesothelioma cell line (PXF1118L) and two multidrug-resistant sublines thereof were used as experimental models. Drug resistance of these cells was due to P-glycoprotein expression, as confirmed by (1) staining with a monoclonal antibody (MRK16) specific for human P-glycoprotein, (2) decreased accumulation of [3H]vinblastine that was reversed by verapamil, and (3) enhanced cytotoxicity of vindesine in the presence of verapamil. Parental and multidrug-resistant cells exhibited little but comparable sensitivity to TNF-alpha alone. Combining TNF-alpha with vindesine or, to a lesser extent, with doxorubicin, but not with cisplatin, resulted in greater cytotoxicity towards multidrug-resistant cells than seen for each compound alone, indicating a synergism. In contrast, TNF-alpha failed to modulate vindesine or doxorubicin cytotoxicity in parental cells. [3H]Vinblastine accumulation was unaffected by TNF-alpha, and chemoresistance was reduced by TNF-alpha also in the presence of verapamil (10 microM), indicating that TNF-alpha was acting in a way different from calcium-channel blockers. Though the molecular mechanism by which TNF-alpha was enhancing vindesine and doxorubicin cytotoxicity remained undefined in this study, the numbers of TNF-alpha binding sites on parental and on multidrug-resistant cells were similar, and P-glycoprotein expression was unmodulated during the entire 48 h incubation period. In conclusion, we show that TNF-alpha increases the cytotoxicity of anticancer drugs in multidrug-resistant tumor cells by a mechanism that differs from most chemosensitizing agents, including verapamil. Further studies will be needed to clarify the mechanism by which TNF-alpha synergizes with anticancer drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1990

Abnormal T cells from lpr mice down-regulate transcription of interferon-gamma and tumor necrosis factor-alpha in vitro.

We have studied the ability of isolated T cell subpopulations from the autoimmune mouse MRL/MPJ/lpr/lpr (lpr) to proliferate and to undergo changes in cytokine gene transcription in vitro, in the presence or absence of cytokines. The lpr mouse develops lupus-like symptoms and massive lymphadenopathy due to accumulation of abnormal CD4-/CD8- T lymphocytes, which are unusual in coexpressing Thy1 and B220. FACS-purified B220+/Thy1+ lpr lymph node cells showed little proliferative response to cytokines, even in the presence of PMA, and failed to proliferate in response to stimulation through the CD3/TcR complex. Polymerase chain reaction was used to examine the presence of cytokine gene transcripts in B220-/Thy1+ and B220+/Thy1+ ("abnormal") T cells, before and after in vitro culture. The high level of transcripts of IFN-gamma and TNF-alpha genes observed in freshly isolated B220+/Thy1+ cells decreased after 10 hr of in vitro culture, while levels of TNF-beta, IL-6 and TGF-beta transcripts were maintained. These results suggest that a positive stimulus for IFN-gamma and TNF-alpha gene transcription by lpr B220+/Thy1+ cells may exist in vivo but is removed upon purification of this abnormal T cell subset.

Animals↗