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Biomedical subjects

T J Hall

Publications and source records attributed to T J Hall.

At least 19 recordsLinked to original sources

Low-reflection-coefficient liquid interfaces for system characterization.

The use of liquid brominated hydrocarbons to form a planar reflecting interface with water is described. Gravity-based planar reflecting surfaces with known reflection coefficients can be used in system characterization for quantitative ultrasonics, and a set of surfaces with a range of reflection coefficients allows calibration of the output power and receiver gain of ultrasonic imaging systems. The substances reported here are immiscible in water and form interfaces with water, resulting in a broad range of acoustic reflection coefficients. Reflection coefficients were measured at temperatures from 18-24 degrees C for "pure" substances and for mixtures of two brominated hydrocarbons. Results show that reflection coefficients are weakly dependent on temperature and that, at a specific temperature, a significant range of arbitrarily small reflection coefficients is available, in the case of the mixtures, by the appropriate choice of weight-percents of the two brominated hydrocarbons.

Hydrocarbons, Brominated↗

Ultrasonic properties of random media under uniaxial loading.

Acoustic properties of two types of soft tissue-like media were measured as a function of compressive strain. Samples were subjected to uniaxial strains up to 40% along the axis of the transducer beam. Measurements were analyzed to test a common assumption made when using pulse-echo waveforms to track motion in soft tissues--that local properties of wave propagation and scattering are invariant under deformation. Violations of this assumption have implications for elasticity imaging procedures and could provide new opportunities for identifying the sources of backscatter in biological media such as breast parenchyma. We measured speeds of sound, attenuation coefficients, and echo spectra in compressed phantoms containing randomly positioned scatterers either stiffer or softer than the surrounding gelatin. Only the echo spectra of gel media with soft scatterers varied significantly during compression. Centroids of the echo spectra were found to be shifted to higher frequencies in proportion to the applied strain up to 10%, and increased monotonically up to 40% at a rate depending on the scatterer size. Centroid measurements were accurately modeled by assuming incoherent scattering from oblate spheroids with an eccentricity that increases with strain. While spectral shifts can be accurately modeled, recovery of lost echo coherence does not seem possible. Consequently, spectral variance during compression may ultimately limit the amount of strain that can be applied between two data fields in heterogeneous media such as lipid-filled tissues. It also appears to partially explain why strain images often produce greater echo decorrelation in tissues than in commonly used graphite-gelatin test phantoms.

Animals↗

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↗

Ultrasonic and elasticity imaging to model disease-induced changes in soft-tissue structure.

Ultrasonic techniques are presented for the study of soft biological tissue structure and function. Changes in echo waveforms caused by microscopic variations in the mechanical properties of tissue can reveal disease mechanism, in vivo. On a larger scale, elasticity imaging describes the macroscopic mechanical properties of soft tissues. We summarize the approach and present preliminary results for studying disease-induced changes in renal tissue using these two acoustic imaging techniques.

Algorithms↗

Comparison of a cathode-ray-tube and film for display of computed radiographic images.

The goal of the study was to compare a cathode-ray-tube (CRT) digital display with film by using task-dependent image quality assessment methods. Contrast-detail analysis was utilized. Human observers performed a simple detection task, specifically, detecting a pillbox target in a uniform Poisson field, using either film or a digital display that employed a CRT monitor. Observers performed equally well on both film and CRT when the window settings of the digital display were established subjectively by a radiologist. Changing the window settings of the digital display to match the average background luminance of a film-illuminator combination decreased the luminance contrast of the targets and observer performance was reduced, though these effects were probably not linked. The "gold standard" film had lower luminance contrast than the CRT displayed images, yet observer performance was never lower for film than for the CRT. Therefore we concluded that luminance contrast was not a limiting factor for observer performance in this study. The CRT monitor changed fairly rapidly after it was calibrated. During a period of six months the gamma of the display increased from 1.82 to 2.42 and the maximum luminance decreased from 319 to 228 cd/m2. Low luminance output demonstrated a larger percentage decrease (approximately equal to 85%) than high luminance output (approximately equal to 29%) over the same time period. These observations suggest that standard window settings should be reviewed from time to time to ensure that the display is used optimally. No special look-up table setup such as perceptual linearization was used.

Calibration↗

Statistical analysis of strain images estimated from overlapped and filtered echo signals.

The visibility of soft-tissue lesions in strain imaging is currently limited by strain noise from waveform decorrelation. Attempts to balance noise reduction with concerns for contrast and spatial resolution rely on accurate models of time delay covariance for guidance. The most useful analytical models describe the covariance of time-varying time delay estimates in terms of experimental parameters and tissue deformation patterns. Assuming compressed tissue deforms linearly along the axis of the sound beam, we derived a delay covariance expression for echo data with Gaussian spectra that were filtered by a Gaussian window function before correlation. The Gaussian filter reduced the number of assumptions needed to obtain closed-form expressions and minimized the effects of strain within the correlation window. However, strain images are often made using uniformly weighted (sinc filtered) window functions. This paper compares time delay covariances for these two window functions, and describes an equivalent window duration at which delay variances for Gaussian and uniform windows are equal. At the equivalent window length, the analysis can be used to predict strain errors for either window function. Finally, this paper uses the delay covariance data to show how strain noise and image sharpness vary depending on the amount of overlap between correlation windows. For an applied strain less than 5%, an overlap near 50% offers an adequate compromise. These results can guide the selection of experimental parameters for improving the visibility of lesions in strain images.

Acoustics↗

Multiple synchronous primaries of the gastrointestinal tract: a molecular case report.

Six synchronous gastrointestinal primaries were identified in a 70 year old male with no known cancer predisposition syndrome or recognized risk factors except alcohol abuse. These specimens appeared to be independent and unrelated by gross and histopathological examination. In order to further evaluate the six tumors, we analyzed selected DNA sequences for alterations in the K-ras oncogene and p53 tumor suppressor gene. In addition, three loci were analyzed to determine microsatellite instability. Using the polymerase chain reaction, single stranded conformational polymorphism, and DNA sequencing, we demonstrated that each primary manifests genetic characteristics typical of the tissue of origin. In addition, one primary, a moderately differentiated colon adenocarcinoma, exhibited mutations not detected in the other specimens. This study suggests that these synchronous primaries arose independently and progressed along different carcinogenic pathways.

Adenocarcinoma↗

Gold salts inhibit osteoclastic bone resorption in vitro.

Loss of bone mass is commonly associated with rheumatoid arthritis (RA) and is increasingly considered to be due to the increased activity of bone-resorbing osteoclasts. Gold salts such as auranofin (AF), aurothioglucose (ATG) and aurothiomalate (ATM) have beneficial therapeutic effects in RA, but their mechanisms(s) of action is not well understood. In the present study we have examined the effects of these 3 gold salts on osteoclastic bone resorption in vitro, using the bone slice assay where bovine cortical bone slices are resorbed by osteoclasts disaggregated from the long bones of neonatal rats. All 3 gold salts inhibited osteoclastic bone resorption with IC50 values of AF = 0.1 microgram/ml, ATG and ATM = 1 microgram/ml. All 3 compounds caused a decreased survival of osteoclasts on bone slices at high concentrations indicating a cytotoxic effect that was also observed in a cytotoxicity assay with osteoblast-like UMR-106 cells. Preincubation of bone slices with various concentrations of AF followed by extensive washing prior to use in the bone slice assay also resulted in an inhibition of bone resorption (IC50 = 4 micrograms/ml) and osteoclast survival on the bone slices preincubated with high concentrations of AF was decreased. Since these effects were obtained with therapeutic concentrations of gold salts, these results indicate that inhibition of osteoclastic bone resorption by gold salts may, at least in part, account for their beneficial effects in RA.

Animals↗

Molecular aspects of osteoclast function.

In this article we have overviewed recent important advances in understanding the molecular mechanisms involved in osteoclastic bone resorption. Specifically, new findings relating to osteoclast activation and the process of bone resorption are reviewed and a current overall model of how osteoclasts resorb bone is presented. Controversial research topics concerning the regulation of osteoclast activity are also critically discussed.

Adenosine Triphosphatases↗

The analgesic drug buprenorphine inhibits osteoclastic bone resorption in vitro, but is proinflammatory in rat adjuvant arthritis.

We have examined the effect of the micro-opioid analgesic buprenorphine on osteoclastic bone resorption in vitro and in the rat adjuvant arthritis model. In the bone slice assay buprenorphine inhibited osteoclastic bone resorption with an IC50 of 1 microM. This effect was not mimicked by the micro-opioid agonist ([D-Ala, N-Me-Phe, Gly-ol]-enkephalin and was not prevented by the micro-opioid antagonist naloxone. Since other agents that inhibit osteoclastic bone resorption, such as bisphosphonates and calcitonin prevent bone erosion in the rat adjuvant arthritis model, we also examined the effect of buprenorphine in this model. Surprisingly, buprenorphine exacerbated inflammation measured by paw volume and increased joint destruction assessed by X-ray scores, in the injected paws and particularly in the non-injected paws. These studies also show that attempts to ameliorate animal suffering in this chronic model by using centrally acting analgesics such as buprenorphine may lead to complications in interpreting screening results obtained with novel, potential anti-arthritic compounds.

Analgesics↗

Phenothiazines are potent inhibitors of osteoclastic bone resorption.

1. We have previously shown that promethazine inhibits osteoclastic bone resorption in the in vitro bone slice assay (IC50 = 0.8 microM), but the mechanism(s) involved are unclear. 2. We have now tested the effects on osteoclast activity of five other structurally related compounds. Phenothiazine, chlorpromazine, amitriptyline, phenazine, and phenoxazine had IC50 values of 0.8, 0.9, 6, 7, and > 10 microM, respectively, in the bone slice assay, indicating that the basic phenothiazine structural element itself is important for osteoclast inhibitory activity. 3. The results are discussed in terms of the known effects of phenothiazines on plasma membrane fluidity, blocking of ion channels, and inhibition of calmodulin.

Animals↗

Laparoscopic surgery during pregnancy.

BACKGROUND: Animal studies have demonstrated fetal acidosis during carbon dioxide pneumoperitoneum. This finding suggests a potential adverse effect of CO2 pneumoperitoneum on fetal outcome in humans. PATIENTS AND METHODS: We reviewed our recent experience with laparoscopic surgery performed under general anesthesia and with the use of CO2 pneumoperitoneum, in pregnant women with appendicitis or cholecystitis. We compared these women's charts and pregnancy outcomes with those of pregnant women who underwent formal laparotomy during the same period of time. RESULTS: Seven pregnant patients underwent laparoscopic surgery, and there were 4 fetal deaths among them (3 during the first postoperative week, and another 4 weeks postoperatively). Five pregnant patients underwent formal laparotomy, of whom 4 subsequently progressed to term and 1 was lost to follow-up. CONCLUSIONS: Our recent experiences together with the available animal data suggest that caution should be used when considering nonobstetrical laparoscopic surgery in pregnant women. This experience suggests that additional clinical and laboratory investigations may be indicated to evaluate fetal risk associated with such surgery.

Abortion, Spontaneous↗

Ultrasonic measurement of glomerular diameters in normal adult humans.

The average size of acoustic scatterers and the integrated backscatter coefficient of kidney cortex were measured in vivo from 2-4 MHz for a group of 50 normal adult volunteers. Our goal was to determine the sensitivity of the ultrasonic measurements under clinical conditions by identifying biologic sources of estimation uncertainty. Based on 10 measurements on each kidney of each volunteer, the average glomerular diameter for the group was found to be 216 +/- 27 microns (SD). Glomerular size was found to correlate with body surface area (r = 0.4), and the ratio of glomerular surface area to body surface area (GSA/BSA) was found to be constant throughout normal adult life with GSA/BSA = (8.24 +/- 1.35) x 10(-8) (SD). These results are consistent with histologic analyses found in the literature. Within an individual, 7% standard errors in GSA/BSA are typical. Biologic variability dominates the variance in scatterer size estimates in a group not matched for BSA, where it accounts for 47% of the variance. In a group of individuals matched for BSA, biologic variability accounts for only 21% of the variance; day-to-day variability accounts for 35% of the variance; and experimental parameters account for the remainder. If a deviation greater than 2 x SD is considered abnormal, then this technique can potentially detect changes in glomerular diameter as small as 30 microns within an individual. To detect abnormal GSA/BSA values for an individual, GSA/BSA would have to differ from the mean for that group by about 3.6 x 10(-8) or about 40%. Therefore, at this time scatterer size estimates appear most reliable for tracking the progression of disease and treatment for an individual over time.

Adolescent↗

The effects of lossy compression on the detection of subtle pulmonary nodules.

We examined the ability of radiologists to detect pulmonary nodules in computed radiographic (CR) chest images subjected to lossy image compression. Low-contrast 1-cm diameter targets simulating noncalcified pulmonary nodules were introduced into clinical images and presented to ten radiologists in a series of two-alternative forced-choice (2AFC) observer experiments. The percentages of correct observer responses obtained while viewing noncompressed images (1:1) were compared with those obtained for the same images compressed 7:1, 16:1, 44:1, and 127:1. The images were compressed using a standard full-frame discrete cosine transform (DCT) technique. The degree of compression was determined by quantizing Fourier components in various frequency channels and then Huffman encoding the result. The data show a measurable decline in performance for each compression ratio. Through signal-to-noise ratio (SNR) analysis, we found that the reduction in performance was due primarily to the compression algorithm that increased image noise in the frequency channels of the signals to be detected.

Algorithms↗

K-ras mutation in a tubular adenoma originating at an ileostomy in a familial adenomatous polyposis patient.

Genetic alterations in a tubular adenoma with severe dysplasia arising in a Brooke ileostomy of a familial adenomatous polyposis patient were analyzed. Clinical and morphological characteristics suggest that ileal mucosa progressed to colonic metaplasia and then to dysplastic adenoma. Such changes at ileostomy sites are rare, and little is known about the associated genetic alterations. To determine whether metaplastic epithelium progression to adenoma in the ileum is subject to the same mutations identified in colon carcinogenesis, we evaluated somatic genetic alterations associated with sporadic colorectal cancer development. Sequences examined included mutation cluster regions of the p53 tumor suppressor gene and the k-ras oncogene. Using polymerase chain reaction and DNA sequencing, we identified a point mutation at codon 12 of the K-ras oncogene. To our knowledge, this is the first report of a ras mutation occurring in a tumor originating from ileal mucosa.

Adenoma↗

The bone-specific estrogen centchroman inhibits osteoclastic bone resorption in vitro.

There is considerable interest in identifying bone-specific estrogen-like compounds with beneficial activities on bone and the cardiovascular system, but lacking side effects on the reproductive system. Two such compounds are currently under clinical investigation -raloxifene (Lilly) and centchroman (Novo-Nordisk). There is evidence suggesting that 17 beta-estradiol can inhibit osteoclastic bone resorption although this is somewhat controversial. Therefore, we examined the effect of centchroman and raloxifene, as well as 17 beta-estradiol, in the in vitro bone slice assay, where the direct effect of compounds on osteoclast activity can be assessed. Centchroman (0.001 - 1 microM) dose-dependently inhibited osteoclastic bone resorption up to 70% at 1 microM (p = 0.007) with an IC50 = 0.1 microM, while in contrast, raloxifene had no significant effect on bone resorption over the same dose range. 17 beta-estradiol (0.0001 - 1 microM) had a modest but significant inhibitory effect on resorption (40%, p < 0.05) at 1 microM, but no effect at lower physiological/therapeutic concentrations. Centchroman (1 microM) inhibited osteoclast cytoplasmic spreading by 32%, while raloxifene and 17 beta-estradiol were without effect. These results show that centchroman at therapeutic concentrations (ED50 approximately 1 mg/kg in animal models) is a potent inhibitor of osteoclastic bone resorption in vitro, suggesting that bone-specific estrogen-like molecules may have different mechanisms of action.

Animals↗

The role of reactive oxygen intermediates in osteoclastic bone resorption.

Osteoclasts have been shown to produce reactive oxygen intermediates (ROI) and it has been suggested that ROI are involved in the process of bone resorption. ROI have also been shown to play a central role in the activation of the multisubunit transcription factor NF-kappa B that enhances the transcription of genes encoding defence and signaling proteins. Therefore, we have assessed the effect of pyrrolidine dithiocarbamate (PDTC), an oxygen-radical scavenger and metal chelator that is a selective and potent inhibitor of NF-kappa B activation, on osteoclastic bone resorption in the bone slice assay. PDTC (0.001-0.1 mM) dose-dependently and non-cytotoxically inhibited osteoclast activity with an IC50 of 0.01 mM. PDTC (0.01 mM) caused no change in the ratio of resorption pit area to resorption pit depth as measured by Lasertec confocal microscopy, indicating that ROI are not involved in the resorptive process per se. This view is supported by time-course studies showing that addition of PDTC or N-acetyl cysteine (NAC; an ROI scavenger, but not metal chelator), 6 hr after the start of the assay had no significant effect on subsequent bone resorption. Desferal (100 microM), a chelator of iron and other metal ions, had no significant effect on bone resorption, indicating (along with the results with NAC) that ROI-scavenging rather than metal chelation is responsible for inhibition of osteoclastic bone resorption by PDTC. Taken together these results indicate that ROI produced by osteoclasts in the bone slice assay are not involved in the process of bone resorption, but are important during osteoclast activation for bone resorption, possibly being involved in activation of the transcription factor NF-kappa B.

Acetylcysteine↗