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E L Madsen

Publications and source records attributed to E L Madsen.

At least 37 records · Page 2Linked to original sources
PubMed2000

A phase II trial of recombinant interferon alpha-2b and cisplatin in metastatic melanoma.

In this phase II study 37 patients with metastatic melanoma were treated with cisplatin 100 mg/m2 every three weeks and interferon alpha-2b 10 MU subcutaneously three times weekly; 125 cycles were administered. Thirty-four patients were evaluable for response and all 37 patients were assessable for toxicity. Four patients stopped treatment with cisplatin because of severe nephrotoxicity, and six patients stopped therapy because of other toxicities. Response rate was 6/34 = 18% (95%) CI (confidence interval): 7%-35%). One patient reached complete response lasting 27+ months. Five patients obtained partial responses with a median duration of response of 7 months (range 5-15+ ). Median time to progression was 2.3 months (range 1-27+). Median survival was 5 months (range 1-27+). We conclude that the combination of high-dose cisplatin 100 mg/m2 and interferon alpha-2b is associated with unacceptable toxicity. Haematological toxicity and nephrotoxicity were pronounced and the response rate was meagre and not encouraging.

Adult↗
PubMed2000

Naphthalene and donor cell density influence field conjugation of naphthalene catabolism plasmids.

We examined transfer of naphthalene-catabolic genes from donor microorganisms native to a contaminated site to site-derived, rifampin-resistant recipient bacteria unable to grow on naphthalene. Horizontal gene transfer (HGT) was demonstrated in filter matings using groundwater microorganisms as donors. Two distinct but similar plasmid types, closely related to pDTG1, were retrieved. In laboratory-incubated sediment matings, the addition of naphthalene stimulated HGT. However, recipient bacteria deployed in recoverable vessels in the field site (in situ) did not retrieve plasmids from native donors. Only when plasmid-containing donor cells and naphthalene were added to the in situ mating experiments did HGT occur.

Bacteria↗
PubMed1999

Nonlinearity parameter for tissue-mimicking materials.

A finite amplitude insert-substitution method has been used to determine the ultrasonic nonlinearity parameter B/A of nine versions of water-based, macroscopically uniform ultrasonically tissue-mimicking (TM) nonfat and fat materials. In this method, the amplitude of the second harmonic following transmission through degassed distilled water with known B/A (B/A = 5.2) and the amplitude of the second harmonic following transmission through the unknown sample are measured. The ratio of these amplitudes allows calculation of the B/A of the sample. Measured B/A values of the nonfat materials range from 5.6 to 6.6. These values compare favorably with published values for nonfat soft tissues. In contrast, the measured B/A values for two tissue-mimicking fat materials are 9.8 and 11.1; these two values represent the low and high end of B/A for most fresh fatty tissues. For comparison, B/A was measured for two commonly available uniform materials, corn oil and ethylene glycol, and the results are in good agreement with published values.

Adipose Tissue↗
PubMed1999

Doxorubicin versus methotrexate both combined with cyclophosphamide, 5-fluorouracil and tamoxifen in postmenopausal patients with advanced breast cancer--a randomised study with more than 10 years follow-up from the Danish Breast Cancer Cooperative Group. Danish Breast Cancer Cooperative Group (DBCG).

To evaluate the substitution of methotrexate with doxorubicin (Dox) in CMF-(cyclophosphamide, methotrexate, 5-fluorouracil) containing regimen for advanced breast cancer, 415 postmenopausal patients below the age of 66 years, naïve to chemotherapy, were accrued from 1980 to 1984 and followed-up until 1995. They received tamoxifen 30 mg daily orally and by randomisation either 400 mg/m2, cyclophosphamide, 25 mg/m2 doxorubicin and 500 mg/m2 5-fluorouracil (CAF) or 40 mg/m2 methotrexate instead of Dox (CMF) intravenously (i.v.) days 1 + 8 repeated every 4 weeks. Dox was substituted by methotrexate at a cumulative dose of 550 mg/m2. Among 341 eligible patients the response rate and median time to progression was significantly in favour of CAF: 53% CAF versus 36% CMF (P = 0.002) and 11.8 months CAF versus 6.5 months CMF (P = 0.001). Median duration of response was 19.5 CAF versus 18.0 CMF months, and survival 20.8 CAF versus 17.4 CMF months (non-significant). The two regimens were equimyelotoxic. There were no treatment-related fatalities but 1 patient with congestive heart failure on CAF was reported. Nausea/vomiting, stomatitis and infections were modest in both groups, whilst alopecia was more common with CAF. Regression analysis showed that long recurrence free interval, good performance status, and no visceral involvement was significantly related to long-term survival, whilst the treatment regimen was not. It is concluded that in chemotherapy-naïve patients with advanced breast cancer Dox-containing regimens are superior and remain the first choice of chemotherapy, especially in patients with visceral metastases, until newer drugs and combinations have been proven to be superior.

Adult↗
PubMed1999

The phenolic vir gene inducer ferulic acid is O-demethylated by the VirH2 protein of an Agrobacterium tumefaciens Ti plasmid.

Some or possibly all Ti plasmids of Agrobacterium tumefaciens encode a bicistronic operon designated virH, which encodes two proteins, VirH1 and VirH2, that resemble a family of cytochrome P450-type monooxygenases. Expression of this operon is induced by a family of phenolic compounds that induce all other operons within the vir regulon. We hypothesized that either or both of these proteins might metabolize some or all of these phenolic compounds. We therefore tested induction of a vir promoter by a variety of phenolic compounds in isogenic strains that express or lack virH1 and virH2. Although some compounds were equally effective inducers regardless of the virH status, other compounds induced vir expression far more effectively in the virH mutant than in the virH-proficient host. For all tested compounds, VirH2 appeared to be solely responsible for this effect. One such compound, ferulic acid, was chosen for biochemical analysis. Ferulic acid was degraded by a VirH-proficient host but not by a VirH mutant. The wild-type strain released large amounts of a more hydrophilic compound into the cell supernatant. This compound was tested by mass spectroscopy, nuclear magnetic resonance and UV spectroscopy and found to consist of caffeic acid. This indicates that wild-type strains convert virtually all added ferulic acid to caffeic acid, and that VirH2 is essential for this O-demethylation reaction. Ferulic acid was far more toxic than caffeic acid to the wild-type strain, although the wild-type strain was more resistant to ferulic acid than was the virH mutant. Caffeic acid was slowly removed from the broth, suggesting further metabolic reactions.

Agrobacterium tumefaciens↗
PubMed1999

Development of a unique phantom to assess the geometric accuracy of magnetic resonance imaging for stereotactic localization.

OBJECTIVE: To test the spatial accuracy of coordinates generated from magnetic resonance imaging (MRI) scans, using the Brown-Roberts-Wells head frame and localizer system (Radionics, Inc., Burlington, MA). METHODS: An anthropomorphic head phantom, consisting of a two-dimensional lattice of acrylic spheres (4-mm diameter) spaced 10 mm apart and embedded in a brain tissue-mimicking gelatin-agar gel, was constructed. The intersphere distances for the target lattice positions in MRI and computed tomographic scan sets were compared. The data sets were fused, and differences in fiducial marker and intraphantom target positions were measured. RESULTS: Intersphere distances were identical for the MRI and computed tomographic scan sets (10 +/- 0.1 mm). Differences in fiducial marker positions [maximal lateral difference, 0.97 mm; mean absolute lateral difference, 0.69 +/- 0.22 mm; maximal anteroposterior (AP) difference, 1.99 mm; mean absolute AP difference, 1.29 +/- 0.67 mm] were correlated with differences in intraphantom target positions (maximal lateral difference, 0.83 mm; mean absolute lateral difference, 0.28 +/- 0.24 mm; maximal AP difference, -1.97 mm; mean absolute AP difference, 1.63 +/- 25 mm; maximal vertical difference, -0.73 mm; mean absolute vertical difference, 0.34 +/- 0.21 mm). This suggested that improper fiducial rod identification and the subsequent transformation to stereotactic coordinate space were the greatest sources of spatial uncertainty. CONCLUSION: With computed tomographic data as the standard, these differences resulted in maximal and minimal composite uncertainties of 2.06 and 1.17 mm, respectively. The measured uncertainties exceed recommended standards for radiosurgery but allow the possible use of MRI-based stereotactic treatment planning for certain intracranial lesions, if the errors are corrected using appropriate software. Clinicians must recognize that error magnitudes vary for different systems, and they should perform systematic, scheduled, institutional error analyses as part of their ongoing quality assurance processes. This phantom provides one tool for measuring such variances.

Brain Mapping↗
PubMed1999

In situ, real-time catabolic gene expression: extraction and characterization of naphthalene dioxygenase mRNA transcripts from groundwater.

We developed procedures for isolating and characterizing in situ-transcribed mRNA from groundwater microorganisms catabolizing naphthalene at a coal tar waste-contaminated site. Groundwater was pumped through 0.22-microm-pore-size filters, which were then frozen in dry ice-ethanol. RNA was extracted from the frozen filters by boiling sodium dodecyl sulfate lysis and acidic phenol-chloroform extraction. Transcript characterization was performed with a series of PCR primers designed to amplify nahAc homologs. Several primer pairs were found to amplify nahAc homologs representing the entire diversity of the naphthalene-degrading genes. The environmental RNA extract was reverse transcribed, and the resultant mixture of cDNAs was amplified by PCR. A digoxigenin-labeled probe mixture was produced by PCR amplification of groundwater cDNA. This probe mixture hybridized under stringent conditions with the corresponding PCR products from naphthalene-degrading bacteria carrying a variety of nahAc homologs, indicating that diverse dioxygenase transcripts had been retrieved from groundwater. Diluted and undiluted cDNA preparations were independently amplified, and 28 of the resulting PCR products were cloned and sequenced. Sequence comparisons revealed two major groups related to the dioxygenase genes ndoB and dntAc, previously cloned from Pseudomonas putida NCIB 9816-4 and Burkholderia sp. strain DNT, respectively. A distinctive subgroup of sequences was found only in experiments performed with the undiluted cDNA preparation. To our knowledge, these results are the first to directly document in situ transcription of genes encoding naphthalene catabolism at a contaminated site by indigenous microorganisms. The retrieved sequences represent greater diversity than has been detected at the study site by culture-based approaches.

Bacteria↗
PubMed1999

Evaluation and optimization of DNA extraction and purification procedures for soil and sediment samples.

We compared and statistically evaluated the effectiveness of nine DNA extraction procedures by using frozen and dried samples of two silt loam soils and a silt loam wetland sediment with different organic matter contents. The effects of different chemical extractants (sodium dodecyl sulfate [SDS], chloroform, phenol, Chelex 100, and guanadinium isothiocyanate), different physical disruption methods (bead mill homogenization and freeze-thaw lysis), and lysozyme digestion were evaluated based on the yield and molecular size of the recovered DNA. Pairwise comparisons of the nine extraction procedures revealed that bead mill homogenization with SDS combined with either chloroform or phenol optimized both the amount of DNA extracted and the molecular size of the DNA (maximum size, 16 to 20 kb). Neither lysozyme digestion before SDS treatment nor guanidine isothiocyanate treatment nor addition of Chelex 100 resin improved the DNA yields. Bead mill homogenization in a lysis mixture containing chloroform, SDS, NaCl, and phosphate-Tris buffer (pH 8) was found to be the best physical lysis technique when DNA yield and cell lysis efficiency were used as criteria. The bead mill homogenization conditions were also optimized for speed and duration with two different homogenizers. Recovery of high-molecular-weight DNA was greatest when we used lower speeds and shorter times (30 to 120 s). We evaluated four different DNA purification methods (silica-based DNA binding, agarose gel electrophoresis, ammonium acetate precipitation, and Sephadex G-200 gel filtration) for DNA recovery and removal of PCR inhibitors from crude extracts. Sephadex G-200 spin column purification was found to be the best method for removing PCR-inhibiting substances while minimizing DNA loss during purification. Our results indicate that for these types of samples, optimum DNA recovery requires brief, low-speed bead mill homogenization in the presence of a phosphate-buffered SDS-chloroform mixture, followed by Sephadex G-200 column purification.

Centrifugation↗
PubMed1999

Analytical quality specifications for serum lactate dehydrogenase isoenzyme 1 based on clinical goals.

The aim of the study was to deduce analytical quality specifications for the determination of catalytic concentration of serum lactate dehydrogenase isoenzyme 1 (S-LD-1) according to clinical goals (the clinical utility model). We defined clinical goals for false positive and false negative S-LD-1 measurements in the monitoring of patients with testicular germ cell tumors (TGCT), clinical stage I, on a surveillance only program. The absolute S-LD-1 catalytic concentrations were routinely corrected for contamination from preanalytical hemolysis. A reference group of 37 men had a near In-Gaussian distribution for the absolute S-LD-1 catalytic concentration. The geometric mean was 76 U/l and an S-LD-1 >128 U/l (99.72 percentile, the decision limit) indicated a high risk of a relapse of TGCT. We have previously shown that an S-LD-1 >160 U/l (treatment limit) was associated with a suboptimal outcome from the treatment of metastatic TGCT. The maximum allowable analytical positive bias was 5 U/l, and the maximum allowable analytical negative bias was -32 U/l. The maximum allowable analytical coefficient of variation, CV(A), was 11% (approximately 14 U/l) at a bias = -5 U/l. For S-LD-1 measurements not corrected for hemolysis, the decision limit was 145 U/l, the maximum allowable negative bias -19 U/l, and CV(A) 8%(approximately 12 U/l). A routine correction for hemolysis had a large impact on the analytical quality specifications.

Catalysis↗
PubMed1999

Acoustic measurements in a tissue mimicking liquid.

A liquid has been developed that mimics soft tissue in terms of propagation speed, attenuation, and nonlinearity parameter B/A. Since the slope of the attenuation coefficient is nearly constant up to at least 18 MHz and the value can be anywhere in the range 0.1 through 0.7 dB/(cm MHz), the material is ideal for assessing the effectiveness of attenuation derating of output acoustic intensities and pressures measured in water. A clinical ultrasound system was used to transmit into the tissue mimicking liquid. The pulse intensity integral and rarefactional pressure at various field locations in the tissue mimicking liquid were computed and compared to the corresponding values measured in water with attenuation derating applied. The slope of the attenuation coefficient in the tissue mimicking liquid was used for the derating. From this data it is seen that the present practice of modeling in vivo exposure using linearly derated measurements made in water is not always conservative.

1-Propanol↗
PubMed1999

Interlaboratory comparison of ultrasonic backscatter, attenuation, and speed measurements.

In a study involving 10 different sites, independent results of measurements of ultrasonic properties on equivalent tissue-mimicking samples are reported and compared. The properties measured were propagation speed, attenuation coefficients, and backscatter coefficients. Reasonably good agreement exists for attenuation coefficients, but less satisfactory results were found for propagation speeds. As anticipated, agreement was not impressive in the case of backscatter coefficients. Results for four sites agreed rather well in both absolute values and frequency dependence, and results from other sites were lower by as much as an order of magnitude. The study is valuable for laboratories doing quantitative studies.

1-Propanol↗
PubMed1998

Oral treosulfan as second-line treatment in platinum-resistant ovarian cancer: a phase II study. The Danish Ovarian Cancer Study Group.

OBJECTIVE: To evaluate the effect of oral treosulfan in patients with platinum-resistant ovarian cancer. METHODS: A phase II trial of oral treosulfan 500 mg per day in 30 females with platinum resistant ovarian cancer. All patients had measurable or evaluable disease. RESULTS: The treatment was well tolerated. One patient (3%) achieved a partial response lasting 12+ months. Seven patients had stable disease for 5.3 months (median) range 4.4-7.5 months. Median time to progression was 11.5 weeks (95% C.L. 11-12 weeks). Median survival was 31 weeks (95% C.L. 30-35 weeks). CONCLUSION: Oral treosulfan in the present schedule is not recommended in platinum resistant ovarian cancer.

Adult↗
PubMed1998

Primitive neuroectodermal tumor (PNET) of the uterine cavity.

The occurrence of primitive neuroectodermal tumors located in the uterus is extremely rare. Eight cases have been described in the literature, and with the addition of this ninth case, we summarize treatment and outcome of PNET located in the uterine cavity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Liquid or solid ultrasonically tissue-mimicking materials with very low scatter.

A new tissue-mimicking material for ultrasound, using evaporated milk as the primary absorption component, is described. It has very low backscatter but still exhibits the 1540 m s-1 propagation speed and proportionality of attenuation coefficient and frequency over the diagnostic frequency range. The material can be produced in solid or liquid form with attenuation coefficient slopes spanning the range 0.1-0.7 dB cm-1 MHz-1. The liquid form is useful in phantoms where detailed beam patterns are to be determined, either involving translation of measurement devices in the liquid or phantoms with fibers present for causing the only detectable echoes. In the latter case, the liquid quality allows removal of liquid with one attenuation coefficient slope and replacement with another. The solid form may be more useful than the liquid for two reasons. First, many simulated lesions (including ones that produce essentially no internal echoes) can lie in the scan slice with positions extending over the entire image area without enhancement or shadowing effects being of concern. Second, the lack of significant backscatter from the material in the absence of added scatterers allows the backscatter coefficient to be varied over a considerable range. A critical result is that intrinsic material contrast between targets and surroundings can be accurately predicted in terms of the concentrations of added scatterers and, assuming all scatterers are of the same type, the contrast will be completely independent of frequency. Use of the fungicide thimerosal eliminates deterioration, and ultrasonic properties have been shown to be stable over 2.5 years.

Animals↗
PubMed1998

Estimating the spatial autocorrelation function for ultrasound scatterers in isotropic media.

The autocorrelation function pertaining to spatial distributions of ultrasonic scatterers in soft tissue is believed to contain useful information related to tissue morphology. A simple processing method applied to radio-frequency echo signals estimates this function for a sample having isotropic scattering conditions. It utilizes backscattered echo signals from the sample and echo signals from a reference object having defined scattering properties. The ratio of the echo signal power spectrum from the sample to the echo signal power spectrum from the reference object is obtained, and corrected for attenuation differences between the two media. This yields a "form factor" for the sample, whose inverse Fourier transform is the autocorrelation function. The method was tested using tissue-mimicking samples for which spatial autocorrelation functions could be modeled from the dimensions of embedded scatterers. The shapes of the measured autocorrelation functions were in reasonable agreement with those estimated, although measured functions overestimated the function at small lag distances. Scatterer diameters estimated from the zeros of the autocorrelation function agreed to within 6% of expected values when the measurement system bandwidth satisfied minimal criteria.

Humans↗
PubMed1998

Anthropomorphic 1H MRS head phantom.

An anthropomorphic 1H MRS head phantom has been developed which mimics the in vivo structure, metabolite concentrations, and relaxation times (for both water and metabolites) of human brain tissue. Different brain regions and two tumor types, fluid-containing ventricles, and air-filled sinus, and subcutaneous fat are all simulated. The main tissue-mimicking materials are gelatin/agar mixtures with metabolites and several other ingredients added. Their composition and method of production are thoroughly described. T1's and T2's of water in the phantom are very close to in vivo values, and metabolite T1's and T2's are considerably more realistic than those in aqueous solutions. Spectra and relaxation times for the pig brain were also acquired and compare well with those of the phantom. The realistic properties of this phantom should be useful for testing spectral quantitation and localization.

Animals↗
PubMed1997

[Reversible liver steatosis in patients treated with 5-fluorouracil and interferon-alpha].

Twenty-three patients with metastatic colorectal carcinoma were randomized as part of two multicenter Phase III trials to receive either 5-fluorouracil (5-FU)/interferon alpha-2A (INF-alpha) or 5-FU +/- leucovorin. The patients were evaluated regularly for response by CT of the abdomen when treatment began and then every six to eight weeks. incidentally, we found that four of 13 patients treated with 5-FU/INF-alpha and none of ten patients treated with 5-FU +/- leucovorin developed hepatic steatosis during treatment. The diagnoses were based on a decreased CT value of the liver parenchyma by the repeated CT, and histologically verified by liver biopsies. There was no relationship to cumulative 5-FU or INF-alpha dose. Based on posttreatment CT, the liver parenchyma changes were reversible after therapy was stopped. Recognition of this condition in patients receiving 5FU/INF-alpha is important to prevent a patient from being labeled as having progressive hepatic metastases.

Antimetabolites, Antineoplastic↗