Analysis of early changes in the articular cartilage transcriptisome in the rat meniscal tear model of osteoarthritis: pathway comparisons with the rat anterior cruciate transection model and with human osteoarthritic cartilage.

OBJECTIVE: The purpose of this study was to use microarray technology to: (1) understand the early molecular events underlying the damage of articular cartilage initiated by this surgical procedure, and (2) determine whether these changes mimic those that are occurring in human osteoarthritic (OA) cartilage. DESIGN: Cartilage was harvested from both medial and lateral sides of the tibial plateaus and femoral condyles of both meniscal tear (MT) and sham surgery groups on days 3, 7 and 21 post-surgery. mRNA prepared from these rat cartilage samples was used for microarray analysis. RESULTS: Statistical analysis identified 475 genes that were differentially expressed between the sham and MT groups, at one or more of the time points that were analyzed. By integrating these genes with OA-related genes reported previously in a rat OA model and in human OA array studies, we identified 20 commonly changed genes. Six out of these 20 genes (Col5A1, Col6A2, INHBA, LTBP2, NBL1 and SERPINA1) were differentially expressed in two animal models and in human OA. Pathway analysis identified some key features of OA pathology, namely cartilage extracellular matrix remodeling, angiogenesis, and chondrocyte cell death that were recapitulated in the animal models. The rat models suggested increased inflammation and cholesterol metabolic pathways may play important role in early cartilage degeneration. CONCLUSION: We identified a large number of differentially expressed genes in the articular cartilage of the MT model. While there was lack of overall identity in cartilage gene expression between the rat models and human OA, several key biological processes were recapitulated in the rat MT OA model.

Certified reference material for radionuclides in fish flesh sample IAEA-414 (mixed fish from the Irish Sea and North Sea).

A certified reference material (CRM) for radionuclides in fish sample IAEA-414 (mixed fish from the Irish Sea and North Seas) is described and the results of the certification process are presented. Nine radionuclides (40K, 137Cs, 232Th, 234U, 235U, 238U, 238Pu, 239+240Pu and 241Am) were certified for this material. Information on massic activities with 95% confidence intervals is given for six other radionuclides (90Sr, 210Pb(210Po), 226Ra, 239Pu, 240Pu 241Pu). Less frequently reported radionuclides (99Tc, 129I, 228Th, 230Th and 237Np) and information on some activity and mass ratios are also included. The CRM can be used for quality assurance/quality control of the analysis of radionuclides in fish sample, for the development and validation of analytical methods and for training purposes. The material is available from IAEA, Vienna, in 100 g units.

Pulmonary ferritin: differential effects of hyperoxic lung injury on subunit mRNA levels.

Ferritin is an iron storage protein that is regulated at the transcriptional and transcriptional levels, resulting in a complex mixture of tissue- and condition-specific isoforms. The protein shell of ferritin is composed of 24 subunits of two types (heavy or light), which are encoded by two distinct and independently regulated genes. In the present studies, the isoform profile for lung ferritin differed from other tissues (liver, spleen, and heart) as determined by isoelectric focusing (IEF) and polyacrylamide gel electrophoresis (PAGE). Lung ferritin was composed of equal amounts of heavy and light subunits. Differences in isoform profiles were the result of tissue-specific differential expression of the ferritin subunit genes as demonstrated by Northern blot analyses. Like heart ferritin, lung ferritin exhibited a low iron content that did not increase extensively in response to iron challenge, which contrasts with ferritins isolated from liver or spleen. When animals were exposed to hyperoxic conditions (95% oxygen for up to 60 h), ferritin heavy subunit mRNA levels did not markedly change at any of the investigated time points. In contrast, ferritin light subunit mRNA increased severalfold in response to hyperoxic exposure. Investigation of the cytoplasmic distribution of ferritin mRNA showed that a substantial portion was associated with the ribonucleoprotein (RNP) fraction of the cytosol, suggesting that a pool of untranslated ferritin mRNA exists in the lung. Upon hyperoxic insult, all ferritin light subunit mRNA pools (RNP, monosomal, polysomal) were elevated, although a specific shift from RNP to polysomal pools was not evident. Therefore, the increase in translatable ferritin mRNA in response to hyperoxia resulted from transcriptional rather than specific translational activation. The observed pattern of light chain-specific transcriptional induction of ferritin is consistent with the hypothesis that hyperoxic lung injury is at least partially iron mediated.

Comparison of six microwave antennas for hyperthermia treatment of cancer: sar results for single antennas and arrays.

Interstitial techniques of inserting catheters into tumors for the purpose of applying therapeutic irradiation and hyperthermia are in widespread use. Several miniature microwave antenna designs are currently used for these treatments. These include multisection, hot-tip, 2- and 3-node, dipole and helical antennas, all of which are commercially available. The antenna designs are diverse enough to have a dramatic effect on the power deposition patterns either as single antennas or when used in arrays. Aside from the dipole antenna, most of the antennas have never been evaluated experimentally or theoretically in arrays, although the array configuration is used in the vast majority of all clinical treatments. Power deposition or SAR (specific absorption rate) tests were run in muscle equivalent phantom. Single antennas were evaluated at 400 points in a plane and isoSAR contours drawn, normalized to maximum SAR. Single antennas were also compared in large and small diameter catheters to evaluate catheter dependent antenna performance. The dipole, multisection, hot-tip and helical antennas were evaluated in arrays of four antennas located at the corners of a square, spaced 2.0 cm apart. Arrays of antennas were evaluated at 441 points in three planes orthogonal to the antenna axes. Results in the single antenna studies showed that the dipole was less affected by snugness of catheter fit than the multisection, hot-tip or helical antennas. In large catheters, the latter three antennas showed more extreme tip heating performance. The 2- and 3-node antennas deposited only 20% SAR in the distal 30 mm of antenna length. In arrays, the multisection, hot-tip, and dipole antennas all yielded 80-90% SAR centrally in the central measurement plane. Comparing the three antennas, the dipole array deposited 20% more power centrally in a plane near the insertion point, and the multisection and hot-tip antenna designs deposited 10% more central power in a plane near the antenna tips. The helical antenna array deposited only 30% SAR centrally in the plane near the antenna tips and in the central plane. Only 10% SAR was measured centrally near the insertion point, as expected for tip-heating antennas. Finally, the clinical significance of the results is discussed as applied to human tumors undergoing hyperthermia treatments.

Interstitial microwave hyperthermia and brachytherapy for malignancies of the vulva and vagina. I: Design and testing of a modified intracavitary obturator.

A vaginal obturator was fabricated to be used in combination with implanted catheters to provide microwave hyperthermia and brachytherapy to the vulva and vaginal wall. This site is difficult to heat or irradiate solely with interstitial techniques. The obturator was modified to provide grooves for the mounting of interstitial catheters into the outer wall and was matched with a template for circumferential implants. Power deposition tests were done using arrays of three microwave antenna designs: dipole (hA = hB = 3.9 cm), helical (3.9 cm coil, shorted), and modified dipole (1.0 cm helix on dipole tip) to test the performance of the obturator. The obturator and four non-obturator catheters were positioned in muscle-equivalent phantom. Two obturator catheters along with two free-standing catheters formed the obturator array. Four freestanding catheters formed the non-obturator array. Power deposition or specific absorption rate (SAR) measurements were made along the central axis, bisect, and diagonal transect of each array. SAR results showed that antennas in the obturator wall radiated as dipole theory predicts, although with less power density when compared to antennas in the same catheters spaced 1.8 cm from the obturator. This could be compensated for by increasing the power to the antennas in the obturator by 42%. Adjacent pairs of antennas were placed 90 degrees out of phase for 0.25 sec and rotated around the array. Phase rotation demonstrated that the central array SAR peaks could be lowered from 100% to 50% SAR, with dipole antennas thus resulting in lowered peak temperatures and the ability to heat larger volumes by improving the distribution of power. With helical antennas, there was 50% SAR at the array center when operated coherently without phase rotation. Three patients were treated with the obturator and a custom-made template using dipole antennas, and temperatures were measured in five obturator catheters. Therapeutic heating was measured in the catheters on the obturator between antennas in contact with the vaginal mucosa.

Three-dimensional theoretical temperature distributions produced by 915 MHz dipole antenna arrays with varying insertion depths in muscle tissue.

Interstitial microwave antenna array hyperthermia (IMAAH) systems are currently being used in the treatment of cancer. The insertion depth of an interstitial microwave antenna, defined as the length of the antenna from the tip to the point of insertion in tissue, affects its ability to produce uniform power deposition patterns in tumor volumes. The effect of varying insertion depths on the ability of an IMAAH system to heat two theoretical tumor models was examined. Four dipole microwave antennas were implanted in a 2 x 2 cm array and driven at 915 MHz in muscle tissue. The explicit power deposition patterns were calculated for each insertion depth using known theory. The bioheat transfer equation was solved for the 3-dimensional steady-state temperature distributions in cylindrical and ellipsoidal tumor models using a finite element method. Homogeneous and nonhomogeneous blood flow models were considered. As a basis of comparison of the various temperature distributions, the volume of tumor heated to greater than or equal to 43 degrees C was calculated. Under the conditions of this study, the insertion depth was shown to have a significant effect on the ability of an IMAAH system to heat the tumor volumes. A sharp decrease in the percentage of tumor volume heated to greater than or equal to 43 degrees C was seen for insertion depths between 7.8 and 14.6 cm. At an insertion depth of 11.7 cm (3/4 lambda) there was virtually no heating of the tumor. Regions of elevated power occurred outside of the desired treatment volume, stressing the importance of adequate thermometry techniques and demonstrating the need for hyperthermia treatment planning prior to implantation of an antenna array. Plots of the power deposition patterns and the corresponding temperatures produced in the diagonal plane of the antenna arrays are present.

Absorbed power deposition for various insertion depths for 915 MHz interstitial dipole antenna arrays: experiment versus theory.

Dipole antennas are commonly used in interstitial clinical hyperthermia treatments because of their compatibility with brachytherapy techniques and their good power deposition patterns when used in arrays. For accurate treatment planning, however, there must be a comprehensive knowledge base to predict the power deposition patterns when insertion depth is a non-resonant length. This is especially true for insertion depths that result in significant power deposition outside of the antenna junction plane and presumably outside of the tumor volume. A computer controlled measurement system was used with a muscle equivalent phantom to make measurements of specific absorption rate (SAR) or absorbed power per unit mass of tissue at 598 points in a plane. The diagonal plane was the measurement plane of choice because it characterized the SAR profiles at the array center as well as areas in the proximity of the antennas. Dartmouth dipole antennas were used (0.9 mm O.D.) in brachytherapy catheters with inner catheters (2.2 mm O.D./1.2 mm I.D.). The resonant half-wavelength of this dipole antenna/catheter combination is 7.8 cm. A choke modification of the dipole was also investigated. Four antennas were used in a boxlike configuration with 2.0 cm separation. Insertion depths of 5.9, 7.8, 9.8, 12.7, 15.6 and 17.6 cm were used. The hA subsection (junction to tip) was held constant at 3.9 cm. Plots were made of the experimental SAR data normalized to the maximum SAR measured in the plane. Theoretical plots were calculated in the same plane for each of the insertion depths. SAR comparisons were also made longitudinally along the central axis of the array and through the antenna junctions in the diagonal plane for resonant half-wavelength insertion depth. Experimental results verified theoretical predictions of the existence of a secondary hot-spot in the center of the array, but outside of the antenna junction plane and approximately a quarter-wavelength from the insertion point. This secondary hot-spot appears for all insertion depths greater than 10 cm. At longer insertion depths approaching a full wavelength, however, this secondary peak is not dominant. Choke antennas demonstrated a solution to the problem of shifting SAR patterns with varying insertion depths by restricting the active length of the antenna.

Brain hyperthermia: I. Interstitial microwave antenna array techniques--the Dartmouth experience.

PURPOSE: Microwave antennas of various designs were inserted into arrays of nylon catheters implanted in brain tumors with the goal of raising temperatures throughout the target volume to 43.0 degrees C. METHODS AND MATERIALS: All antennas were flexible, and included dipole, choke dipole, modified dipole, and helical designs driven at 915 or 2450 MHz. Antennas were tested in brain-equivalent phantom in arrays. Phase shifting and phase rotation techniques were incorporated into the treatment system to steer power in the tumor, assisted by a treatment planning computer that predicted power deposition patterns and temperature distributions. Choke antennas were designed and tested to reduce a dependence of the central power location on depth of insertion into tissue. Temperature data analysis used only central and orthogonal axes mapping data measured at 2.0 mm intervals. RESULTS: A total of 23 patients were treated, using from one to six microwave antennas. Minimum tumor temperatures, averaged over the 60 min treatment, ranged from 37.2-44.3 degrees C (mean 40.0 degrees C) and maximum average tumor temperatures ranged from 46.5-60.1 degrees C (mean 49.1 degrees C). The percentage of all measured temperatures reaching therapeutic levels (> or = 43.0 degrees C) was 70.9. T90, the temperature at which 90% of all measured temperatures equaled or exceeded, was 40.8 degrees C, and T50 was 44.2 degrees C. CONCLUSION: Patient data analysis showed that the array of four dipole antennas spaced 2.0 cm apart were capable of heating a volume of 5.9 cm (along the central array axis) x 2.8 cm x 2.8 cm.

Experimental brain hyperthermia: techniques for heat delivery and thermometry.

An experimental canine brain model was developed to assess the effects of hyperthermia for a range of time and temperature endpoints, delivered within a specified distance of an interstitial microwave antenna in normal brain. The target temperature location was defined radially at 5.0 or 7.5 mm from the microwave source at the longitudinal location of maximum heating along the antenna in the left cerebral cortex. Temperatures were measured with fiberoptic probes in a coronal plane at this location in an orthogonal catheter at 1.0 mm intervals. Six antennas were evaluated, including dipole, modified dipole, and four shorted helical antennas with coil lengths from 0.5 to 3.9 cm. Antenna performance evaluated in tissue equivalent phantom by adjusting frequency at a fixed insertion depth of 7.8 cm or adjusting insertion depth at 915 MHz showed dipoles to be much more sensitive to insertion depth and frequency change than helical antennas. Specific absorption rate (SAR) was measured in a brain/skull phantom and isoSAR contours were plotted. In vivo temperature studies were also used to evaluate antenna performance in large and small canine brain tissues. A helical antenna with a 2.0 cm coil length driven at 915 MHz was chosen for the beagle experiments because of tip heating characteristics, well-localized heating along the coil length, and heating pattern appropriate to the smaller beagle cranial vault. Verification of lesion dimensions in 3-D was obtained by orthogonal MRI scans and histology to document the desired heat effect, which was to obtain an imagable lesion with well-defined blood-brain-barrier breakdown and necrotic zones. The desired lesion size was between 1.5 to 2.5 cm diameter radially, in the coronal plane with the greatest diameter.

Thermal conduction effects associated with temperature measurements in proximity to radiofrequency electrodes and microwave antennas.

The smearing effects due to thermal conduction along various, nonenergized, interstitial devices were quantified in a flow cell-thermal step gradient. An insulated cylindrical flow cell with a high (ca 45 degrees C, 1.12 cm i.d., 1.6 cm o.d.) temperature region surrounded by a low (ca 37 degrees C) temperature region was used to compare temperature profiles measured with a thermocouple sensor inside a Stanford radiofrequency (RF) hyperthermia/brachytherapy catheter, a BSD instrumented microwave (MW) antenna (i.e., thermistor integrated into a dipole antenna) and a Dartmouth MW antenna with a juxtaposed optical sensor. Two parameters were used to quantify the thermal smearing of each interstitial device in the flow cell: (a) the maximum temperature difference (MTD) and (b) the full- width- half-maximum (FWHM) of the high temperature region. The "true" temperature maximum (45.4 degrees C) and distribution (FWHM = 1.65 +/- 0.06 cm) were measured with an optical sensor. These data indicate that the BSD instrumented MW antenna significantly smeared the true temperature profile (MTD = 2.7 degrees C, FWHM = 2.1 cm), as did the Dartmouth MW antenna (MTD = 1.5 degrees C, FWHM = 1.7 cm). The Stanford RF catheter, when insulated, resulted in minimal smearing (MTD = 0.3 degrees C, FWHM = 1.9 cm). Moreover, when the insulation was removed so the RF electrode was exposed to the thermal step gradient, smearing was again minimal (MTD = 0.3 degrees C, FWHM = 1.9 cm).

Diquat-dependent protein carbonyl formation. Identification of lipid-dependent and lipid-independent pathways.

In a previous report on diquat-dependent oxidative damage in rat hepatic microsomes, protein oxidation, as measured by protein carbonyl (PC) formation, was observed in addition to lipid peroxidation (LP). Both phenomena were antioxidant sensitive. Inhibition of PC formation was somewhat surprising given the proposed mechanism of metal-catalyzed protein oxidation. Studies reported here examined diquat-dependent PC formation in greater detail. In rat hepatic microsomes, diquat-dependent thiobarbituric acid-reactive substances (TBARS) and PC formation were time and concentration dependent. In this system, LP was inhibited completely by U-74006F or U-78517G, whereas PC formation was inhibited only partially by these antioxidants. In an essentially lipid-free system consisting of purified rat hepatic cytochrome P450 reductase, BSA and an NADPH-generating system, PC formation was also observed, but was not antioxidant-sensitive. Under these conditions, minimal diquat-dependent TBARS formation was observed. The observation of relative antioxidant insensitivity is consistent with H2O2 (generated during the diquat redox cycle) catalyzing protein oxidation via a site-specific, metal-catalyzed mechanism. Thus, different pathways would appear to be involved in diquat-dependent PC formation in lipid-containing and lipid-free systems. Carbon tetrachloride induces LP following reductive activation to the trichloromethyl free radical, a pathway not directly involving H2O2 generation. In the microsomal system, CCl4 induced TBARS and PC formation, both of which were completely inhibitable by antioxidants. Taken together, these data suggest that diquat induces PC formation by lipid-dependent (antioxidant-sensitive) and lipid-independent (antioxidant-insensitive) pathways. In microsomes, both pathways contribute to diquat-dependent PC formation. Data for the lipid-independent pathway are consistent with the mechanism of metal-catalyzed protein oxidation proposed by Stadtman and colleagues (reviewed in Free Radic Biol Med 9: 315-325, 1990), while the lipid-dependent pathway is likely secondary to LP itself--via a Michael-type addition reaction between hydroxyalkenals and protein sulfhydryl groups, amino groups or other protein nucleophiles. The latter pathway is also responsible for carbon tetrachloride-dependent PC formation. Additional studies are in progress to further characterize the lipid-independent mechanism.

Inhibition of in vitro lipid peroxidation by 21-aminosteroids. Evidence for differential mechanisms.

In a previous report (Ryan and Petry, Arch Biochem Biophys 300: 699-704, 1993), the effects of two 21-aminosteroids (U-74500A and U-74006F) on the oxidation and reduction of iron in a buffer/organic solvent system were investigated. In those studies, U-74500A was found to be an efficient iron reductant and potential iron chelator, whereas U-74006F had little effect on iron redox chemistry. As an extension of those studies, we now report the effects of U-74006F and U-74500A on lipid peroxidation in systems that are dependent upon iron oxidation/reduction. In liposomes, U-74500A inhibited ADP:Fe(II)-dependent lipid peroxidation in a concentration-dependent manner, whereas U-74006F was minimally effective in this system. The mechanism of U-74500A-dependent inhibition probably involved interactions with iron, as iron oxidation was inhibited in the presence of this compound. No effects on iron oxidation were observed in the presence of U-74006F. Addition of Ferrozine to liposomal incubation mixtures indicated that at least two iron pools were present in samples containing U-74500A, one immediately bound by Ferrozine, and another that was bound more slowly. Furthermore, ADP:Fe(III)/ascorbate-dependent lipid peroxidation was blocked completely by U-74500A, presumably by formation of a redox inert complex upon reduction of the iron. U-74500A partially protected ADP:Fe(II) from oxidation by H2O2 and lipid hydroperoxides, indicating that the U-74500A:iron complex was stable in the presence of biologically relevant oxidants. U-74006F did not markedly affect iron oxidation or reduction when incorporated into phospholipid liposomes. In microsomal lipid peroxidation systems containing ADP:Fe(III) and NADPH, both U-74500A and U-74006F inhibited lipid peroxidation. U-74006F-dependent inhibition of microsomal lipid peroxidation was dependent on both NADPH and Fe(III). Further, it was enhanced when U-74006F was allowed to preincubate in this system prior to iron addition. Preincubation of U-74006F with microsomes, NADPH, and ADP:Fe(III) produced several metabolites detectable by HPLC. These results suggest that U-74500A inhibits lipid peroxidation by directly affecting iron redox chemistry, whereas U-74006F-mediated inhibition is enhanced by preincubation with a metabolically competent microsomal system.

Gene expression analysis of the acute phase response using a canine microarray.

The safety of pharmaceuticals is typically assessed in the dog and rat prior to investigation in humans. As a result, a greater understanding of adverse effects in these preclinical testing species would improve safety assessment. Despite this need, there is a lack of tools to examine mechanisms and identify biomarkers in the dog. To address this issue, we developed an Affymetrix-based oligonucleotide microarray capable of monitoring the expression of thousands of canine genes in parallel. The custom canine array contains 22,774 probe sets, consisting of 13,729 canine and 9045 human-derived probe sets. To improve cross-species hybridization with human-derived probes, the detection region was moved from the variable 3' UTR to the more homologous coding region. Testing of this strategy was accomplished by comparing hybridization of naive dog liver RNA to the canine array (coding region design) and human U133A array (standard 3' design). Although raw signal intensity was greater with canine-specific probe sets, human-derived probes detected the expression of additional liver transcripts. To assess the ability of this tool to detect differential gene expression, the acute phase response was examined in beagle dogs given lipopolysaccharide (LPS). Hepatic gene expression 4 and 24 h post-LPS administration was compared to gene expression profiles of vehicle-treated dogs (n=3/group). Array data was consistent with an acute inflammatory response, with transcripts for multiple cytokines and acute phase proteins markedly induced 4 h after LPS challenge. Robust changes in the expression of transcripts involved with glucose homeostasis, biotransformation, and extracellular matrix remodeling were observed 24 h post-dose. In addition, the canine array identified several potential biomarkers of hepatic inflammation. Strong correlations were found between gene expression data and alterations in clinical chemistry parameters such as serum amyloid A (SAA), albumin, and alkaline phosphatase (ALP). In summary, this new genomic tool successfully detected basal canine gene expression and identified novel aspects of the acute phase response in dog that shed new light on mechanisms underlying inflammatory processes.

Quantitative assessment of variables that influence soft-tissue electrovaporization in a fluid environment.

OBJECTIVES: To evaluate the process of soft-tissue electrovaporization and to study variables that affect tissue clearance rates in a laboratory setting, in order to identify parameters that can optimize transurethral electrovaporization of the prostate. METHODS: Fresh bovine skeletal muscle, equivalent in impedance and surface properties to the human prostate, was submerged in 3.3% sorbitol solution and electrovaporized with a grooved monopolar electrode attached to the weighted arm of a linear actuator. The effects of excursion rate, applied mechanical load, power setting, electrode configuration, and generator performance on the volume of tissue removed, were assessed. RESULTS: Tissue removal increased significantly when electrode excursion rate was slowed from 25 to 15 mm/s (P < 0.05) and then to 10 mm/s (P < 0.05); when the load was increased from 20 to 50 g (P < 0.005); and when dial power was increased from 120 to 150 W (P < 0.01). Tissue removal was generator dependent. There was no significant difference between the Force 40 and the Force 2 (P > 0.4), but a new computer-controlled constant power output generator (Force FX) did significantly improve tissue vaporization at an equivalent power setting (P < 0.005 and P < 0.01, respectively). Tissue removal was also dependent upon electrode configuration, with the VaporTrode-Grooved Bar removing significantly more tissue than either an ungrooved roller bar of equivalent size or 2-mm smooth roller ball, respectively, both after a single pass (P < 0.001 and P < 0.05) and after five repeated passes (P < 0.05 and P < 0.005). The histologic depth of tissue thermal effect was less than 1 mm, but it was 38% greater for the VaporTrode-Grooved Bar (0.68 mm) than for the standard cutting loop (0.5 mm, P < 0.01). CONCLUSIONS: Using a novel method to quantify tissue removal, we have demonstrated that electrode configuration, excursion rate, applied load, power setting, and generator performance are interdependent factors that influence the efficacy of the electrovaporization process in a fluid environment.

Theoretical and experimental analysis of air cooling for intracavitary microwave hyperthermia applicators.

An intracavitary microwave antenna array system has been developed and tested for the hyperthermia treatment of prostate cancer at Thayer School of Engineering and Dartmouth-Hitchcock Medical Center. The antenna array consists of a choked dipole antenna inserted into the urethra and a choked dipole antenna eccentrically embedded in a Teflon obturator inserted into the rectum. To prevent unnecessary heating of the healthy tissue that surrounds each applicator, an air cooling system has been incorporated into the rectal applicator. The air cooling system was designed and modeled theoretically using a numerical solution of heat and momentum equations within the applicator, and an analytical solution of the Pennes bioheat equation in tissue surrounding the applicator. The 3-D temperature distribution produced by the air-cooled rectal applicator was measured in a perfused canine prostate.

Use of a flexible epidural stimulating electrode for intraoperative monitoring of spinal somatosensory evoked potentials.

The use of an epidural stimulating spinal electrode has been adapted for recording spinal somatosensory evoked potentials (SSEP) during spinal surgery. This technique utilizes a flexible, 1 mm diameter electrode with four platinum contacts that is easily slipped into the epidural space both rostral and caudal to the exposed surgical field. The flexibility of the electrode assembly ensures against dural penetration. Incoming somatosensory spinal evoked potentials recorded using the lumbosacral electrode are compared with the SSEP recorded above the surgical site (rostral electrode). The spinal SEPs were generally triphasic (thoracic) or polyphasic (lumbosacral) with an amplitude of 5 microV. This system has been used for intraoperative monitoring during 33 major spinal operations. Waveform morphology, as well as the latencies and amplitudes of the component peaks of the spinal SEPs remained relatively constant compared with the cortical SEPs.

Spinal and cortical somatosensory evoked potential monitoring during corrective spinal surgery with 108 patients.

To reduce the incidence of neurologic complications following spinal surgery, somatosensory evoked potentials (SEPs) were monitored in 108 patients. An electrode with four in-line contacts was used to record spinal SEPs in the epidural space in 33 patients at locations both rostral and caudal to the surgical site. Cortical SEPs were successfully monitored in 107/108 patients and spinal SEPs in all 33 attempted epidurally. Spinal conduction velocities were found to range from 43.9 to 110.5 m/s depending on vertebral level and the time location of the measured peak in the response waveform. Frequency power spectra of the SEP waveforms were found to be a reliable adjunct to peak latency amplitude analysis in the time domain. Use of caudal and rostral epidural, subcortical, and cortical electrode sites were found to be the most reliable technique for the maximum patient safety.

Transuranic biokinetic parameters for marine invertebrates--a review.

A catalogue of biokinetic parameters for the transuranic elements plutonium, americium, curium, neptunium, and californium in marine invertebrates is presented. The parameters considered are: the seawater-animal concentration factor (CF); the sediment-animal concentration ratio (CR); transuranic assimilation efficiency; transuranic tissue distribution and transuranic elimination rates. With respect to the seawater-animal CF, authors differ considerably on how they define this parameter and a seven-point reporting system is suggested. Transuranic uptake from sediment by animals is characterised by low CRs. The assimilation efficiencies of transuranic elements in marine invertebrates are high compared to vertebrates and mammals in general and the distribution of transuranics within the body tissue of an animal is dependent on the uptake path. The elimination of transuranics from most species examined conformed to a standard biphasic exponential model though some examples with three elimination phases were identified.

Technetium-99 in the Irish marine environment.

Technetium-99 activity concentrations in seawater and biota from Irish coastal waters are presented. Time series measurements of 99Tc in seawater and Fucus vesiculosus from the western Irish Sea show that activity concentrations have increased in line with the increase in discharges of 99Tc from Sellafield. The peak in activity concentrations in both seawater and Fucus vesiculosus occurred in 1997 approximately two years after the peak in 99Tc discharges. The highest activity concentration recorded in Fucus vesiculosus showed a 29-fold increase over the mean concentration for the period 1988-1993. Technetium-99 activity concentrations were measured in fish, lobsters, prawns, mussels and oysters landed at major fishing ports on the east and northeast coasts of Ireland between 1996 and 1998. Concentration factors for 99Tc in the brown seaweed Fucus vesiculosus and certain species of fish, crustaceans and molluscs from the Irish Sea were estimated. In general, these concentration factors were higher than those in the literature which were derived from laboratory studies, but agreed well with values which were based on field studies. The mean committed effective doses to Irish typical and heavy seafood consumers due to 99Tc in the period 1996-1998 were 0.061 and 0.24 microSv, respectively.

Determination of self-absorption corrections for gamma analysis of environmental samples: comparing gamma-absorption curves and spiked matrix-matched samples.

Accurate determination of the massic activity of gamma-emitting radionuclides in environmental samples, particularly sediments and soils, cannot be achieved without taking into account sample self-absorption. The extent of self-absorption in the sample will depend on a number of factors including sample composition, density, sample size and gamma-ray energy. The preferred method for correcting for this effect is to use spiked or natural matrix reference materials that match each sample type to be analysed. However, for laboratories that must measure a wide variety of sample matrices this method is too costly and time-consuming. Another technique commonly used is to make direct gamma-ray transmission measurements for each sample. This method, while more practical, still requires a minimum of three measurements to be made for each sample analysed. A more convenient method is to prepare sets of gamma-absorption curves. This approach involves making a series of direct transmission measurements for samples of varying densities but similar type. Sets of matching samples, both spiked and unspiked, were prepared and density correction factors determined using the direct transmission method and the spiked sample approach. It was found that, for soil and sediment samples, these two methods typically differed by 5-9% for higher energy gamma rays and by 12-15% for the 59.54 keV 241Am peak. Gamma-absorption curves were also derived and, for the admittedly limited dataset, 95% confidence intervals of +/-7% for the curve generated using the spiked samples method were obtained.