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Biomedical subjects

J Lasker

Publications and source records attributed to J Lasker.

11 recordsLinked to original sources
PubMed2002

Near-infrared diffuse optical tomography.

Diffuse optical tomography (DOT) is emerging as a viable new biomedical imaging modality. Using near-infrared (NIR) light, this technique probes absorption as well as scattering properties of biological tissues. First commercial instruments are now available that allow users to obtain cross-sectional and volumetric views of various body parts. Currently, the main applications are brain, breast, limb, joint, and fluorescence/bioluminescence imaging. Although the spatial resolution is limited when compared with other imaging modalities, such as magnetic resonance imaging (MRI) or X-ray computerized tomography (CT), DOT provides access to a variety of physiological parameters that otherwise are not accessible, including sub-second imaging of hemodynamics and other fast-changing processes. Furthermore, DOT can be realized in compact, portable instrumentation that allows for bedside monitoring at relatively low cost. In this paper, we present an overview of current state-of-the -art technology, including hardware and image-reconstruction algorithms, and focus on applications in brain and joint imaging. In addition, we present recent results of work on optical tomographic imaging in small animals.

Algorithms↗
PubMed1997

The effect of a psychological intervention program on the risk of a new coronary event after angioplasty: a feasibility study.

Restenosis after successful percutaneous coronary angioplasty (PTCA) is a major problem because it occurs in 25% to 35% of all patients. Because psychological factors, especially anger and vital exhaustion, have been found to increase the risk of new cardiac events after PTCA, a behavioral intervention might contribute to the reduction of the risk of restenosis. To investigate the operational and methodological aspects of a behavioral intervention, and to estimate the effect size of the risk reduction, we did a feasibility study of angioplasty patients who remained exhausted after PTCA. Breathing therapy was used as the main method for intervention. Thirty patients who participated in the intervention program and 65 controls were followed during an average period of 16 and 18 months, respectively. It was observed that the intervention resulted in a significant decrease of the mean exhaustion scores and reduced the risk of a new coronary event (cardiac death, coronary artery bypass grafting, myocardial infarction, rePTCA, restenosis) by 50% (chi = 2.19; p = 0.13). These results indicate that a clinical trial to test the hypothesis that a reduction of vital exhaustion and hostility reduces the risk of a new cardiac event after PTCA, is feasible and merits the efforts required.

Analysis of Variance↗
PubMed1992

The Roseto effect: a 50-year comparison of mortality rates.

OBJECTIVES: Earlier studies found striking differences in mortality from myocardial infarction between Roseto, a homogeneous Italian-American community in Pennsylvania, and other nearby towns between 1955 and 1965. These differences disappeared as Roseto became more "Americanized" in the 1960s. The present study extended the comparison over a longer period of time to test the hypothesis that the findings from this period were not due to random fluctuations in small communities. METHODS: We examined death certificates for Roseto and Bangor from 1935 to 1985. Age-standardized death rates and mortality ratios were computed for each decade. RESULTS: Rosetans had a lower mortality rate from myocardial infarction over the course of the first 30 years, but it rose to the level of Bangor's following a period of erosion of traditionally cohesive family and community relationships. This mortality-rate increase involved mainly younger Rosetan men and elderly women. CONCLUSIONS: The data confirmed the existence of consistent mortality differences between Roseto and Bangor during a time when there were many indicators of greater social solidarity and homogeneity in Roseto.

Adult↗
PubMed1990

Interaction of ethanol with enflurane metabolism and toxicity: role of P450IIE1.

Administration of enflurane (EF), a widely-used anesthetic agent, sometimes results in occult liver injury. As hepatic cytochromes P450 oxidize EF to a reactive intermediate, we assessed whether one such microsomal enzyme, ethanol-inducible P450IIE1, plays an obligatory role in EF metabolic activation and hepatotoxicity. Liver microsomes from rats fed ethanol (36% of total calories for 14 days) oxidized 1 mM EF (measured by its defluorination) at rates nearly 10-fold greater than those from control rats, reflecting the markedly enhanced content of immunoreactive microsomal P450IIE1 in the former animals. P450IIE1 involvement in hepatic EF oxidation was further suggested by the pronounced inhibition of microsomal defluorination noted with P450IIE1 antibodies and with ethanol, a specific substrate for this enzyme. EF administration to rats treated chronically with ethanol caused significant elevations in plasma levels of aspartate and alanine aminotransferases and glutamate dehydrogenase, indicative of hepatic injury, whereas concurrent treatment of naive rats with EF and ethanol failed to produce the same effect. Our results imply that ethanol-inducible P450IIE1 is the primary catalyst of hepatic EF bioactivation and that the increased bioactivation occurring in vivo secondary to chronic ethanol consumption is attendant with an increased incidence of EF hepatotoxicity.

Animals↗
PubMed1978

Absorption and glucuronylation of diethylstilbestrol by the rat small intestine.

1. The absorption and glucuronylation of [14C]diethylstilbestrol (DES) were studied in situ in segments of rat small intestine. 2. DES glucuronide accounted for nearly 50% of the methanol-soluble radioactive material appearing in the intestinal venous blood. 3. There was no difference between DES glucuronide formation in intestinal segments near the pyloric sphincter and in segments located near the ileo-caecal junction. 4. The appearance of DES and its glucuronide in the venous blood of aborally-located segments was dose-dependent from 0.1 to 5 mM, but in orally-located segments, an increase in DES concn. from 2 to 5 mM produced no increase in DES or its glucuronide in the venous blood. In neither of these intestinal regions was the rate of appearance of DES or DES glucuronide dependent upon intestinal blood flow. 5. The results indicate that intestinal glucuronylation of certain compounds during absorption may be significant over a wide range of concn. in all regions of the intestine.

Absorption↗
PubMedDate not supplied

Three-dimensional optical tomographic brain imaging in small animals, part 1: hypercapnia.

In this study, we explore the potential of diffuse optical tomography for brain oximetry. While several groups have already reported on the sensitivity of optical measurements to changes in oxyhemoglobin, deoxyhemoglobin, and blood volume, these studies were often limited to single source-detector geometries or topographic maps, where signals obtained from within the brain are projected onto 2-D surface maps. In this two-part study, we report on our efforts toward developing a volumetric optical imaging system that allows one to spatially resolve 3-D hemodynamic effects in rat brains. In part 1, we describe the instrumentation, optical probe design, and the model-based iterative image reconstruction algorithm employed in this work. Consideration of how a priori anatomical knowledge can be incorporated in the reconstruction process is presented. This system is then used to monitor global hemodynamic changes that occur in the brain under various degrees of hypercapnia. The physiologic cerebral response to hypercapnia is well known and therefore allows an initial performance assessment of the imaging system. As expected, we observe global changes in blood volume and oxygenation, which vary linearly as a function of the concentration of the inspired carbon dioxide. Furthermore, experiments are designed to determine the sensitivity of the reconstructions of only 1 mm to inaccurate probe positioning. We determine that shifts can significantly influence the reconstructions. In part 2 we focus on more local hemodynamic changes that occur during unilateral carotid occlusion performed at lower-than-normal systemic blood pressure. In this case, the occlusion leads to a predominantly monohemispherically localized effect, which is well described in the literature. Having explored the system with a well-characterized physiologic effect, we investigate and discuss the complex compensatory cerebrovascular hemodynamics that occur at normotensive blood pressure. Overall, these studies demonstrate the potential and limitations of our diffuse optical imager for visualizing global and focal hemodynamic phenomenon three dimensionally in the brains of small animals.

Algorithms↗
PubMedDate not supplied

Three-dimensional optical tomographic brain imaging in small animals, part 2: unilateral carotid occlusion.

This is the second part of a two-part study that explores the feasibility of 3-D, volumetric brain imaging in small animals by optical tomographic techniques. In part 1, we demonstrated the ability to visualize global hemodynamic changes in the rat head in response to elevated levels of CO(2) using a continuous-wave instrument and model-based iterative image reconstruction (MOBIIR) algorithm. Now we focus on lateralized, monohemispherically localized hemodynamic effects generated by unilateral common carotid artery (CCA) occlusion. This illustrates the capability of our optical tomographic system to localize and distinguish hemodynamic responses in different parts of the brain. Unilateral carotid occlusions are performed in ten rodents under two experimental conditions. In the first set of experiments the normal systemic blood pressure is lowered to 50 mmHg, and on unilateral carotid occlusion, we observe an ipsilateral monohemispheric global decrease in blood volume and oxygenation. This finding is consistent with the known physiologic response to cerebral ischemia. In a second set of experiments designed to observe the spatial-temporal dynamics of CCA occlusion at normotensive blood pressure, more complex phenomena are observed. We find three different types of responses, which can be categorized as compensation, overcompensation, and noncompensation.

Algorithms↗
PubMedDate not supplied

Effects of three recombinant human leukocyte interferons on drug metabolism in mice.

Three recombinant human leukocyte interferons (IFLrA, IFLrD, and a hybrid IFLrA/D) that differ markedly in their antiviral activity in murine L cells were examined for their effects on hepatic microsomal drug metabolism in adult female CD-1 mice. When administered for 1 or 3 consecutive days, IFLrA/D, which exhibited the highest antiviral activity in murine L cells, caused a dose-dependent decrease in cytochrome P-450 content and in the rate of metabolism in vitro of benzo[a]pyrene, hexobarbital, 7-ethoxycoumarin, benzphetamine, and zoxazolamine. The concentration of cytochrome b and the activity of NADPH-cytochrome c reductase were also depressed when IFLrA/D was administered for 3 days. Similar but somewhat smaller changes were observed following treatment of mice with IFLrD, which possessed approximately 1% of the antiviral activity of IFLrA/D in murine L cells. In contrast, IFLrA, which was essentially devoid of antiviral activity in the mouse cell line, failed to depress cytochrome P-450 levels and in vitro drug metabolism activity in a consistent or dose-dependent manner. Cytochrome P-450 content and the in vitro rate of metabolism of benzphetamine and zoxazolamine were maximally depressed 8-24 hr after a single intraperitoneal injection of 1.5 micrograms of interferon per mouse; at this time the interferons were no longer detectable in serum. Near-normal levels of cytochrome P-450 and in vitro drug metabolism activity were restored by 48 hr after a single injection of interferon. Treatment of mice with 1.5 micrograms of IFLrA/D once daily for 3 days prolonged hexobarbital sleeping time but not zoxazolamine paralysis time, whereas neither of these was influenced by treatment with IFLrA or D. The results indicate that an interferon-dependent process reduces the level of microsomal cytochrome P-450 in liver and potentiates the pharmacological actions of certain drugs in mice.

Animals↗