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Biomedical subjects

E P Scott

Publications and source records attributed to E P Scott.

At least 19 recordsLinked to original sources

Thermal detection of embedded tumors using infrared imaging.

Breast cancer is the most common cancer among women. Thermography, also known as thermal or infrared imaging, is a procedure to determine if an abnormality is present in the breast tissue temperature distribution. This abnormality in temperature distribution might indicate the presence of an embedded tumor. Although thermography is currently used to indicate the presence of an abnormality, there are no standard procedures to interpret these and determine the location of an embedded tumor. This research is a first step towards this direction. It explores the relationship between the characteristics (location and power) of an embedded heat source and the resulting temperature distribution on the surface. Experiments were conducted using a resistance heater that was embedded in agar in order to simulate the heat produced by a tumor in the biological tissue. The resulting temperature distribution on the surface was imaged using an infrared camera. In order to estimate the location and heat generation rate of the source from these temperature distributions, a genetic algorithm was used as the estimation method. The genetic algorithm utilizes a finite difference scheme for the direct solution of the Pennes bioheat equation. It was determined that a genetic algorithm based approach is well suited for the estimation problem since both the depth and the heat generation rate of the heat source were accurately predicted.

Algorithms↗

Thiopurine methyltransferase activity in American white subjects and black subjects.

BACKGROUND: Thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme that preferentially catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds, including 6-mercaptopurine. TPMT exhibits genetic polymorphism in white populations, with 89% of individuals having high TPMT activity, 11% having intermediate activity, and one in 300 having extremely low or absent activity. TPMT activity is inversely correlated with formation of active 6-mercaptopurine metabolites (thioguanine nucleotides), thereby influencing 6-mercaptopurine toxicity and efficacy. METHODS: To investigate ethnic and gender differences in TPMT, we measured erythrocyte TPMT activity in 209 white healthy subjects and 196 black healthy subjects (202 women and 303 men). RESULTS: The black population had lower TPMT activity than the white population (median, 14.4 versus 16.8 units/ml packed erythrocytes; p < 0.001). Maximum likelihood estimation of TPMT activity distribution identified 91.9% and 93.9% with high activity and 7.7% and 6.1% with intermediate activity in the white and black groups, respectively. CONCLUSIONS: These data indicate that TPMT activity is similarly polymorphic in American black subjects and white subjects, although median TPMT activity is approximately 17% lower in black subjects.

Adolescent↗

Ethnic differences in erythrocyte catechol-O-methyltransferase activity in black and white Americans.

Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catecholamine and catechol drugs such as levodopa and methyldopa. Human COMT activity is inherited as an autosomal co-dominant trait; approximately 25% of white individuals have low activity consistent with homozygosity for a low activity allele, about 50% have intermediate activity (i.e., heterozygous genotype) and 25% have high activity. COMT activity has not been characterized in African-Americans or other black populations. To investigate potential ethnic and gender differences in COMT, we measured erythrocyte COMT activity in 195 unrelated black and 202 unrelated white healthy individuals living in the Southeast United States. Overall, the black population had significantly higher COMT activity than the white population (median 15.7 vs. 11.4 U/ml of packed red blood cell volume; P < .001). Maximum likelihood estimation of COMT activity distribution identified significant ethnic differences, with high activity in 23% of whites and 55% of blacks, intermediate activity in 50% of whites and 38% of blacks and low activity in 27% of whites and 7% of blacks. No greater differences in COMT activity were observed in either ethnic group. We conclude that red blood cell COMT activity is significantly higher in black subjects than white subjects. Hardy-Weinberg estimates indicate that this ethnic difference is due to a higher frequency of high activity COMT alleles in blacks vs. whites (0.74 vs. 0.48).

Adolescent↗

Genetic basis for a lower prevalence of deficient CYP2D6 oxidative drug metabolism phenotypes in black Americans.

Debrisoquin hydroxylase (CYP2D6) is a cytochrome P450 enzyme that catalyzes the metabolism of > 30 commonly prescribed medications. Deficiency in CYP2D6 activity, inherited as an autosomal recessive trait, was found to be significantly less common in American blacks (1.9%) than whites (7.7%). To determine the genetic basis for this difference, inactivating CYP2D6 mutations were assessed by allele-specific PCR amplification and RFLP analyses of genomic DNA from 126 unrelated whites and 127 unrelated blacks. Blacks had a twofold lower frequency (8.5 versus 23%, P = 0.001) of the CYP2D6(B) mutation (point mutation at intron 3/exon 4 splice site), while complete deletion of the CYP2D6 gene (5.5% blacks, 2.4% whites), and the CYP2D6(A) mutation (single nucleotide deletion in exon 5; 0.24% blacks, 1.4% whites) were not different between the two groups. The prevalence of heterozygous genotypes was significantly lower in blacks (25 versus 42% of extensive metabolizers, P = 0.009), consistent with the observed prevalence of the deficient trait in blacks and whites. We conclude that the same CYP2D6 mutations lead to a loss of functional expression in blacks and whites, but American blacks have a lower prevalence of the deficient trait due to a lower frequency of the CYP2D6(B) mutation. This could explain racial differences in drug effects and disease risk.

Base Sequence↗

Design and preliminary evaluation of an expert system for platelet request evaluation.

In spite of growing awareness of the potential risks associated with transfusion, the number of platelet units transfused in the United States continues to increase each year. There is a growing interest in ensuring that all transfusions are administered for appropriate reasons. Prospective review of requests for transfusions has been used to accomplish this goal. Although successful in reducing the number of inappropriate transfusions, this review method requires great time commitments by blood bank personnel and physicians. A knowledge-based system (ESPRE) that aids hospital blood bank personnel in the review of requests for platelet transfusions has been developed. The system automatically obtains most of the required patient data via a direct link to the hospital's main laboratory computers. The system generates a printed report that includes a list of patient-specific data, a list of the conditions for which a transfusion would be appropriate for the particular patient (given the clinical condition), and the conclusions drawn by the system. During a preliminary clinical evaluation of ESPRE, 73 randomly selected platelet transfusion requests were evaluated for approval by laboratory personnel and ESPRE. Overall, ESPRE would have approved 71 of the requests and laboratory staff would have approved 72. Forty-four percent of the requests would have been approved for the same reasons given by the staff. There were only three disagreements on final approval between ESPRE and blood bank personnel. This computerized expert system is a promising approach to the prospective review of all platelet transfusions.

Blood Banks↗

ESPRE--expert system for platelet request evaluation.

The expert system for platelet request evaluation (ESPRE) is being developed to support independent learning and decision making regarding the use of platelet transfusions while physicians are actively engaged in clinical practice. The knowledge of transfusion medicine incorporated in ESPRE has been largely gathered from blood bank physicians responsible for determining the appropriateness of blood product administration. Knowledge acquisition methods have included structured and unstructured interviews with protocol analysis using real and fabricated transfusion cases and critiques of an expert system prototype's conclusions. For knowledge representation, ESPRE uses frames with embedded production rules to provide processing efficiency and facilitate knowledge base development. ESPRE automatically acquires key laboratory findings from a laboratory information system. Systems such as ESPRE require careful evaluation and, if proven effective and accurate, present to laboratorians a new tool for delivering high-quality and individually adapted health care.

Decision Making, Computer-Assisted↗

ESPRE: a knowledge-based system to support platelet transfusion decisions.

ESPRE is a knowledge-based system which aids in the review of requests for platelet transfusions in the hospital blood bank. It is a microcomputer-based decision support system written in LISP and utilizes a hybrid frame and rule architecture. By automatically obtaining most of the required patient data directly from the hospital's main laboratory computers via a direct link, very little keyboard entry is required. Assessment of time trends computed from the data constitutes an important aspect of this system. To aid the blood bank personnel in deciding on the appropriateness of the requested transfusion, the system provides an explanatory report which includes a list of patient-specific data, a list of the conditions for which a transfusion would be appropriate for the particular patient (given the clinical condition), and the conclusions drawn by the system. In an early clinical evaluation of ESPRE, out of a random sample of 75 platelet transfusion requests, there were only three disagreements between ESPRE and blood bank personnel.

Decision Support Techniques↗

Effectiveness of a regional bone marrow donor program.

Because many potential bone marrow transplant patients lack HLA-matched siblings, there is growing interest in carrying out transplantations using matched, unrelated volunteer donors. We developed a local registry of 2147 informed donors who consented to be listed in the Bone Marrow Donor Registry. This registry was used to carry out 420 donor searches for 351 patients. The initial computer search involved matching for HLA-A and HLA-B locus antigens only because most donors had not been typed for HLA-DR antigens. Depending on the degree of HLA-A and HLA-B antigen mismatching allowed, suitably matched (HLA-DR-identical, mixed lymphocyte culture nonreactive) donors were located for 6% to 16% of patients. This resulted in 13 bone marrow transplants. This study shows that a small, local bone marrow donor registry can locate donors for a few patients; however, a large network involving an expanded number of donors will be necessary to allow an extensive evaluation of unrelated bone marrow transplantation.

Bone Marrow Transplantation↗

Conditioned saccharin aversions in rats as a result of cutaneous nicotine or intraperitoneal nicotine administered in divided doses.

Nicotine base was used in a conditioned taste aversion (CTA) paradigm to avert male Sprague-Dawley rats to saccharin solution (0.1%, w/v). Experiments investigated different dose routes of nicotine administration and duration of action as determinants in nicotine-induced CTA. In Experiment 1 nicotine was injected intraperitoneally (IP) at doses of 0.5, 1.0, or 3.0 mg/kg 30 min after drinking saccharin solution. Using a two-bottle choice test, no CTA was observed, although all nicotine animals showed obvious symptoms of malaise including seizures in the highest dose group. Experiment 2 showed dose-related CTA when nicotine (10.0, 30.0, or 50.0 mg/kg) was cutaneously applied 30 min following saccharin drinking. Experiment 2B showed that the aversions were due to associative rather than nonassociative factors such as sensitization or enhanced neophobia. In Experiment 3, the following group treatments were begun 30 min after saccharin drinking to distribute identical total nicotine doses over an extended period of time: One IP injection of 2.0 mg/kg nicotine (in a saline vehicle) and four injections of saline solution, three injections of 0.67 mg/kg nicotine and two injections of saline, five injections of 0.40 mg/kg nicotine, or five injections of saline. All injections were spaced 30 min apart. Compared with saline-injected controls, CTA occurred in the rats receiving either three or five injections of nicotine but the group receiving one injection did not differ from the control group. There was no difference in CTA between the groups receiving three or five injections.

Administration, Topical↗

Small lymphocytic lymphoma. Morphologic and immunologic progression.

The large cell lymphoma (LCL) that occurs in patients with chronic lymphocytic leukemia (Richter's syndrome) has generally been shown to be of the same light chain type as the original chronic lymphocytic leukemia (CLL). The authors now report on a patient with diffuse well-differentiated lymphocytic lymphoma (WDL) of the kappa light chain type who in the course of his illness first had the blood picture of CLL and then developed malignant lymphoma of large cell ("histiocytic") type, which expressed lambda light chains. Despite an extensive multiparameter investigation, we could not determine with certainty whether the presence of two morphologically and immunologically different lymphomas represented proliferation of two distinctly separate clones or whether it represented clonal evolution of the disease with an alteration in immunoglobulin light chain associated genes. The results of the study, however, suggest that the development of lymphoma with expression of a different immunoglobulin light chain may not necessarily indicate the occurrence of a second primary. This study also illustrates the necessity for sequential lymph node biopsies to document progression of disease in patients with low-grade lymphoproliferative disorders and indicates that the immunologic phenotype of a B-cell neoplasm in a given patient should not be assumed to remain constant.

Antigens, Surface↗

Automatic prediction of platelet utilization by time series analysis in a large tertiary care hospital.

The authors investigated the potential of various time series models to aid in the prediction of platelet utilization patterns at the authors' institution. During a seven-week feasibility study, prediction accuracy of time series models was slightly inferior to that of an experienced platelet transfusion coordinator. The models that adjusted for day-of-the-week variability were superior to simpler models in a prospective evaluation over a three-month period. Conversion to a time series model for platelet utilization prediction has resulted in significant savings in personnel costs for management of platelet concentrate inventory in the blood bank. Outdate rates have been lower than those achieved by the platelet transfusion coordinator, with no sacrifice in availability occurring during the evaluation period.

Blood Banks↗

Outcome of bone marrow transplantation in patients with extramedullary involvement of acute leukemia.

Infiltration of extrahemopoietic tissue with leukemic cells was evaluated as a prognostic indicator in 18 patients with acute leukemia undergoing bone marrow transplantation. When compared to 107 patients who did not have extramedullary leukemia at any time prior to marrow grafting, the patients with leukemic invasion into organs outside the hemopoietic system had a significant increase of leukemic recurrence and a significant decrease in survival after marrow transplantation. Extramedullary leukemia may be a negative prognostic indicator for bone marrow transplantation candidates.

Acute Disease↗

Platelet crossmatch tests using radiolabelled staphylococcal protein A or peroxidase anti-peroxidase in alloimmunized patients.

Refractoriness to random-donor platelets as a result of alloimmunization remains a major problem in long-term platelet transfusion therapy despite the use of HLA-matched platelets. We have therefore studied the use of two methods for detection of platelet associated IgG as platelet crossmatch tests for the selection of platelet donors. These methods use radiolabelled staphylococcal protein A (125I-SPA) and peroxidase anti-peroxidase (PAP), respectively. One hundred and ten crossmatch tests using 125I-SPA were performed retrospectively in 18 alloimmunized patients. The results indicated that the predictive value of a positive or a negative test was 87%; the sensitivity was 73% and the specificity was 95%. Results with the PAP test were similar. The HLA types were known for 48 donor-recipient pairs. With few exceptions, there was a correlation between the results of the platelet crossmatch tests and the effectiveness of platelet transfusion regardless of the degree of HLA match. These results indicate that platelet crossmatch tests may be valuable even when closely HLA matched donors are not available. A large-scale prospective study is warranted, particularly in highly immunized patients.

Anemia, Aplastic↗

Application of postcolumn ionization in the high-performance liquid chromatographic analysis of butabarbital sodium elixir.

A sensitive postcolumn ionization high-performance liquid chromatographic (HPLC) method for the quantitative determination of butabarbital sodium in butabarbital sodium elixir is described. The procedure employs a octadecylsilane column chemically bonded to porous silica microparticles. The mobile phase is a mixture of methanol and water (typically 35:65), adjusted to provide separation of butabarbital from two degradation compounds and other formulation ingredients. A buffer (pH 10) added between the column and detector provides for the primary ionization of the barbiturate necessary for optimum UV-detector sensitivity at approximately 240 nm. Determinations are made using the sodium salt; thus the need for extraction of the free base is eliminated. The procedure is linear over the 0.3-0.9-mg/ml concentration range of butabarbital sodium. Reproducibility values for 10 injections of a single reference standard range from 100.2 to 100.8% of theoretical with a mean of 100.5% and a coefficient of variation of 0.23%. An interlaboratory precision study for blind duplicates of one simulated product formulation and two commercial elixirs produced coefficients of variation of 1.4, 1.3, and 1.1%, respectively. Recovery determinations for the drug in simulated product formulations ranged from 98.4 to 99.0%, intralaboratory, and 97.7 to 102.2%, interlaboratory. The HPLC procedure is stability indicating with respect to two decomposition products.

Barbiturates↗

Successful second bone marrow transplantation in a patient with myositis ossificans progressiva and aplastic anemia.

Bone marrow transplantation has become the treatment of choice for patients with severe aplastic anemia who are fortunate enough to have allogeneic sibling donors. As patients have been transplanted earlier in the course of their disease, significant improvements have been obtained in long-term survival. However, in patients who have been sensitized by previous blood product transfusions, graft rejection continues to be a significant problem and second transplants when performed are frequently unsuccessful. This case report deals with a patient with myositis ossificans progressiva (MOP) who developed severe idiopathic aplastic anemia. He rejected his first graft after 160 days. However, he was successfully reingrafted with marrow from the same donor using a different conditioning regimen.

Anemia, Aplastic↗