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Biomedical subjects

E L Madsen

Publications and source records attributed to E L Madsen.

At least 19 recordsLinked to original sources

Cellular effects of piezoelectric versus electrohydraulic high energy shock waves.

High energy shock waves produced by a piezoelectric lithotripter, (EDAP LT.01) and an electrohydraulic lithotripter, (Dornier HM3) were examined for their effects on Chinese hamster ovary cells in suspension. The EDAP caused acute lactate dehydrogenase release, consistent with severe membrane disruption in a proportion of cells, with the remaining proportion of cells replicating normally as measured by clonogenic assay. Similarly, the Dornier also caused lactate dehydrogenase release. However, a significant proportion of cells which remained "viable" after Dornier treatment, (intact to lactate dehydrogenase), did not replicate by clonogenic assay. The Dornier HM3 lithotripter has been reported to produce free radicals in aqueous solution. In the current investigation, we could not detect significant free radical formation from the EDAP LT.01. Chinese hamster ovary cell killing by the Dornier HM3 was significantly augmented by radiosensitizers, 5-iodo-2-deoxyuridine or buthionine sulfoximine, while radioprotectors cysteamine and WR-1065 had no protective effect. EDAP cell killing was not influenced by either radioprotectors or radiosensitizers. The mechanism of in vitro cytotoxicity differs between piezoelectric and electrohydraulic high energy shock wave delivery.

Animals

Serum lactate dehydrogenase isoenzyme 1 and tumour volume are indicators of response to treatment and predictors of prognosis in metastatic testicular germ cell tumours.

44 patients with metastatic testicular germ cell tumours treated with cisplatin-based chemotherapy were evaluated for prognostic implications of clinical characteristics. 22 obtained complete remission by the initial chemotherapy, and 30 are disease-free. S-LDH-1 had an overall predictive value regarding the response of 80%, S-LDH of 64%, S-AFP of 62%, and S-hCG of 62%. In multivariate analysis regarding response, only tumour volume classified according to the Royal Marsden system (P = 0.0036) and S-LDH-1 (P = 0.0069) yielded information. Regarding survival, S-LDH-1 (P = 0.0141) and an estimate of total tumour mass (P = 0.0171) had most impact with additional information from S-hCG only (P = 0.0536). We conclude that S-LDH-1 may be used as a tumour marker in addition to S-hCG and S-AFP in patients with metastatic testicular germ cell tumour.

Adolescent

Microscopic mechanism of attenuation of compressional ultrasonic waves in tissue-mimicking phantom materials.

An investigation was performed to determine whether the sound-attenuation-insuspensions theory of Allegra and Hawley can be used to explain the compressional (longitudinal wave) attenuation of ultrasonically tissue-mimicking materials commonly used in phantoms for testing the performance of medical ultrasound systems. These materials are composed of microscopic graphite particles suspended in a gel. The theory was first tested using materials containing spherical glass beads instead of graphite particles because these materials more closely fit the geometric conditions assumed in the theory. For the glass bead type materials as well as the graphite particle type materials, the attenuation coefficients predicted using the Allegra and Hawley model agreed rather well with experimental measurements over the diagnostic frequency range.

Biocompatible Materials

Weekly oral idarubicin in advanced prostatic cancer. A phase II study.

Twenty-five patients with advanced prostatic cancer progressing after one course of endocrine treatment entered a phase II study of weekly administration of 30 mg Idarubicin orally. Twenty-two patients were evaluable for response and partial response (PR) was noted in 2 patients and stable disease (NC) in 10 patients. Median survival was 31 weeks and median time to progression was 14 weeks. Twenty-three patients were eligible in a score system combining analgetic consumption and pain reduction measured on a Visual Analogue Scale (VAS) and 30% achieved a subjective response. Fifteen patients fulfilled treatment with the planned dose and 10 patients had dose reduction to a median of 23.8 mg Idarubicin. Haematological toxicity was greater than or equal to grade 3 (WHO) in 20% of the patients. Non-haematological toxicity was dominated by nausea/vomiting with 48% grade 3 (WHO). In conclusion, Idarubicin seems of limited value in the treatment of patients refractory to first line endocrine treatment.

Administration, Oral

Method for determining the SATA and SAPA intensities for real-time ultrasonographic scanning modes.

Determination of a complete set of sonographic exposure parameters is desirable for any clinical ultrasound unit and is particularly important in controlled studies of biologic effects. When the exposure system is a diagnostic real-time scanner operating in autoscan mode, the determination of two of these parameters, the spatial average-temporal average (SATA) and the spatial average-pulse average (SAPA) intensities, is not straightforward because of the spatial overlap of successive propagating pulses. A method is described for determining these intensities for autoscan operation. The primary tool in the method is a digital oscilloscope, which supports pretrigger recording and configuring of the oscilloscope's memory into segments that can record rapidly occurring successive pulses, each segment recording one pulse. Results for a few commercially available real-time scanning systems are presented.

Ultrasonics

In situ biodegradation: microbiological patterns in a contaminated aquifer.

Conventional approaches for proving in situ biodegradation of organic pollutants in aquifers have severe limitations. In the approach described here, patterns in a comprehensive set of microbiological activity and distribution data were analyzed. Measurements were performed on sediment samples gathered at consistent depths in aquifer boreholes spanning a gradient of contaminant concentrations at a buried coal tar site. Microbial adaptation to polyaromatic hydrocarbons (PAHs) was demonstrated by mineralization of naphthalene and phenanthrene in samples from PAH-contaminated, but not adjacent pristine, zones. Furthermore, contaminant-stimulated in situ bacterial growth was indicated because enhanced numbers of protozoa and their bacterial prey were found exclusively in contaminated subsurface samples. The data suggest that many convergent lines of logically linked indirect evidence can effectively document in situ biodegradation of aquifer contaminants.

Animals

A teaching phantom for sonographers.

An anthropomorphic torso section phantom is described that is intended for use during initial stages of ultrasonographer training. The phantom represents a section of the upper abdomen, with simulated ribs, liver, kidney with fat pad, gallbladder, aorta, and bowel gas. Positioned in the liver are ten simulated soft tissue masses, which produce a variety of typical echographic patterns. All simulated soft tissue components are formed of tissue-mimicking materials that match their corresponding tissue counterparts in terms of speed of sound, ultrasonic attenuation, and density. Construction details are presented and examples of images are shown.

Abdomen

Ultrasound transmission measurements through the os calcis.

A method of measuring ultrasonic propagation in the os calcis was devised for assessing bone properties in humans. Speed-of-sound (SOS) and broadband ultrasound attenuation (BUA) were measured using broadband acoustic pulses transmitted and received by a pair of focused transducers. The transducers are mounted coaxially in a water tank with the subject's heel in between. Reproducibility of results in an adult male was 10% for the BUA and 1.2% for the SOS. Both SOS and BUA changed when the transmission path through the os calcis was varied. For a population of normal male subjects, SOS and BUA were correlated with densitometry results on the os calcis, but less well correlated to area density at remote sites.

Absorptiometry, Photon

Statistical uncertainty in ultrasonic backscatter and attenuation coefficients determined with a reference phantom.

Uncertainties in measured attenuation and backscatter coefficients due to statistical fluctuations in echo signal data from a randomly scattering medium are estimated. The uncertainties are computed for the special case in which a reference phantom is employed to account for transducer and instrumentation factors when measuring attenuation and backscatter coefficients. The resultant uncertainty in the attenuation is inversely proportional to the 3/2 power of the depth range. The error in the backscatter coefficient arises both from the local fluctuation in the data and from the uncertainty in the attenuation estimate. The first of these is inversely proportional to the square root of the number of independent data points, while the second results in a contribution that is depth dependent. Predicted errors were tested by scanning tissue mimicking phantoms and estimating attenuation and backscatter coefficients for subsets of the digitized echo data. Standard deviations of the experimental results were in agreement with those predicted.

Models, Structural

Experimental verification of a model for predicting transient temperature distributions by focused ultrasound.

A thermal model for predicting time-dependent temperature distributions during ultrasound heating was tested quantitatively. The relevant thermal processes incorporated in the model are heat conduction and ultrasound power absorption, and the required input parameters include the absolute ultrasound power, the shape and frequency of the ultrasound transducer, and the thermal and acoustical properties of the medium. Testing was done by heating an ultrasonically tissue-mimicking phantom with a 525 kHz, single element, focused source. The phantom has muscle-like acoustical properties and contains an array of copper-constantan thermocouples. Time-dependent temperature changes predicted with the thermal model were in very good agreement with those measured in the phantom, verifying the validity of the model for use in optimizing an ultrasound applicator design for a specific treatment situation.

Humans

A method for in vitro mapping of ultrasonic speed and density in breast tissue.

A method has been developed for mapping density and ultrasonic speed in 1 mm thick slices of soft tissue with a resolution of about 1 mm. Tests using phantom sections have verified the accuracy and resolution of the ultrasonic speed maps. The method has been applied to breast tissues of three patients including tumors and surrounding tissue. Fixing a specimen in 5% formaldehyde did not change the degree of local variation in ultrasonic speeds, and raised mean speeds by less than 0.8%. The densities with fixing remained almost unchanged at low tissue densities (0.93 g/cm3), but rose 1.5% for higher tissue density (greater than 1.00 g/cm3).

Female

Improved resolution backscatter coefficient imaging.

This paper reports the extension of a method for imaging acoustic backscatter coefficients that allows for greater spatial resolution in the resulting images. This is done by using a broad-band excitation pulse and short-duration time gates in the analysis. The images produced had better spatial resolution than the previously reported technique [Ultrasonic Imaging 10, 121-138]. Furthermore, the pixel values were based upon quantitatively accurate backscatter coefficients at given spatial locations. The paper also discusses the additional computational requirements of greater spatial resolution and proposes a least-squares fit to a smoothly varying set of sparse data to generate the data points in between.

Ultrasonics

Surveillance alone versus radiotherapy after orchiectomy for clinical stage I nonseminomatous testicular cancer. Danish Testicular Cancer Study Group.

From December 1980 to January 1984, all patients with stage I nonseminomatous testicular cancer in Denmark entered a randomized trial comparing surveillance only with radiotherapy after orchiectomy. One hundred fifty patients were assessable for the final analysis. Relapse occurred in 23 patients in the surveillance group and in 11 patients in the radiotherapy group. Radiotherapy completely prevented retroperitoneal relapse; 14 retroperitoneal relapses occurred in the surveillance-only group. All relapsing patients in the surveillance-only group are without evidence of disease with a median observation time after chemotherapy of 67 months. Two of the patients with relapse in the radiotherapy group died with disease; the others are alive without evidence of disease, with a median observation time after relapse treatment of 72 months. In the surveillance group, four relapses occurred later than 2 years after orchiectomy; only one such late relapse occurred in the radiotherapy group. Four of the retroperitoneal relapses occurred without concomitant increase in the serum marker levels (alpha-fetoprotein [AFP] and human chorionic gonadotropin [HCG]). It is concluded that surveillance only should replace radiotherapy after orchiectomy as standard treatment for clinical stage I nonseminomatous testicular cancer. Improved methods for control of retroperitoneal relapses, especially of embryonal carcinomas, are needed.

Adolescent

Method of cavitation-suppressed exposure of cells and explant mouse embryos to clinical real-time and pulsed Doppler ultrasound.

An apparatus and procedure for well-controlled exposure of cells or explant mouse embryos to clinical real-time ultrasound are described. Cells or embryos to be exposed are suspended in media made sufficiently viscous through inclusion of methylcellulose that cavitation is suppressed but thermal effects remain negligible. During exposure, the scanning beam is precisely centered in a 2 mm x 20 mm slot in a 20 cm diameter agar disc containing the suspension. The high viscosity causes the cells to remain distributed uniformly throughout the exposure; this fact, along with precision beam alignment, ensures that exposure is well defined. Exposure data are acquired with a 0.6 mm diameter hydrophone.

Animals

Diagnostic ultrasound is unable to enhance the rate of neoplastic transformation in cultured mammalian cells.

The ability of diagnostic pulsed ultrasound to induce heritable genetic damage of the type that could result in neoplasia was assayed using BHK21/cl 13 hamster cells or normal human fibroblasts as targets. Using an exposure apparatus carefully designed to minimize beam attenuation and reflection, cavitation, and heating, cells were exposed from 20 seconds to 40 minutes either to clinical machines operating at maximum power, or to a highly focused nonclinical transducer at 2900 W/cm2, or to 200 shocks from a lithotripter. No evidence of an increase in the frequency of neoplastically transformed BHK cells or in the frequency of mutant human cells was seen over those found in matched sham-exposed controls.

Animals

The role of preimplantation sonographic exposure in postimplantation development and pregnancy outcome.

To determine what, if any, effects exposure to ultrasonic beams has on preimplantation embryos we isolated mouse blastocysts and assessed resorption rate, pregnancy rate, decidual swelling volume, and live birth rate after in vitro exposure with subsequent transfer to surrogate mothers. The blastocyst stage embryos were isolated by flushing the uteri of pregnant animals with a phosphate buffered medium. Blastocysts at a discrete stage of development were pooled and transferred to a PB1-methylcellulose medium. This medium is specifically designed to maintain the embryos in a high viscosity solution during the sonographic exposure to prevent microcavitation. After the exposure, the embryos were washed free of methylcellulose and transferred to the uteri of pseudopregnant surrogate mothers. A total of 660 blastocyst stage embryos were distributed among seven treatment groups. After exposure, the embryos were transferred to 54 surrogate mothers. A total of 199 embryos were implanted successfully for postimplantation evaluation. An additional 427 blastocysts were distributed among four treatment groups and transferred to 46 surrogate mothers to assess the effect of sonographic exposure on birth rate. The results indicate possible deleterious effects (decreased implantation rate, increased resorption rate, decreased decidual swelling volume, and increased stillbirth rate) of short ultrasonic exposures (1 min and 5 min) on mouse blastocyst function.

Animals

Sister chromatid exchange analysis of human cells exposed to diagnostic levels of ultrasound.

Lymphocyte and lymphoblastoid cells were exposed in vitro to diagnostic levels of ultrasonic beams delivered by a Hewlett-Packard CE 30001 and a GE system with a 5 MHz linear transducer for 20 sec, 1 min, 5 min, and 20 min. Temperature and cavitation effects were controlled and there were matched sham exposures. The synergistic effects of theophylline with ultrasonography also were investigated. Small increases in sister chromatid exchange levels were observed after ultrasonic exposure, but increases were so small as to be unlikely to have clinical relevance. Theophylline was found to have no effect and ultrasonography had no effect on cell viability.

Adult