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Biomedical subjects

K Anderson

Publications and source records attributed to K Anderson.

At least 91 records · Page 5Linked to original sources

Comparison of polyvinyl alcohol fixative with three less hazardous fixatives for detection and identification of intestinal parasites.

Polyvinyl alcohol (PVA) containing the fixative mercuric chloride is considered the "gold standard" for the fixation of ova and parasites in the preparation of permanently stained smears of stool specimens. However, mercuric chloride is potentially hazardous to laboratory personnel and presents disposal problems. We compared three new alternative, nontoxic fixatives with PVA, analyzing ease of sample preparation and quality of smears. Sixty-eight fresh stool specimens were divided into aliquots and placed in each of four different fixatives: PARASAFE (PS) (Scientific Devices Laboratory, Inc., Des Plaines, Ill.), ECOFIX (EC) (Meridian Diagnostics, Inc., Cincinnati, Ohio), Proto-Fix (PF) (Alpha-Tec Systems, Inc., Vancouver, Wash.), and low-viscosity PVA fixative (PVA) (Meridian). Specimens were processed and stained according to each manufacturer's directions. Parasites were found in 31 of 68 slide preparations with PVA, 31 with PF, 30 with EC, and 30 with PS. Blastocystis hominis and Iodamoeba bütschlii were preserved in a readily identifiable state by all methods of fixation. However, some parasites were more easily identified with some of the fixatives because of differences in parasite distortion. For example, Entamoeba histolytica (Entamoeba dispar) was detected in 13 stools fixed with PF, 7 with PVA, and 6 with EC but none with PS. Likewise, Chilomastix mesnili was identified in 13 specimens fixed with PF, 8 with EC, and 5 with PVA but only 1 with PS, while Entamoeba coli was seen much less frequently with PS than with the other three fixatives. A dirty background was observed in 41% of specimens prepared with PS, whereas background quality was acceptable with other fixatives. Sample preparation was most rapid with PS, although the EC method involved the fewest steps. In conclusion, PVA and PF produced the least parasite distortion, while PS proved unsatisfactory for the identification of E. histolytica, E. coli, and C. mesnili. Both PF and EC appear to be acceptable, environmentally safe substitutes for PVA.

Animals↗

Manipulation of the phenotype of immortalised rat hepatocytes by different culture configurations and by dimethyl sulphoxide.

The liver-specific phenotype of immortalised rat hepatocytes is not irretrievably lost as they age in culture but can be manipulated by modifying the culture environment. Testosterone metabolism was used to investigate the profile of cytochrome P450 isoenzymes present in two immortalised cell lines, P9 and LQC, and in primary cultures of rat hepatocytes, cultured on collagen films, gels and double gel cultures (sandwich configuration). The extent of testosterone metabolism, and the range of metabolites produced, was increased in immortalised cells by the presence of collagen as a substratum film or gel but survival was poorer and the range of metabolites was reduced in sandwich culture. In contrast, testosterone metabolism was retained in primary hepatocytes in sandwich cultures at a higher level than in collagen film or gel cultures. Expression of alpha class glutathione-S-transferases (GSTs) increased and that of GSTP1 decreased (changes which indicate a recovery of normal liver GST phenotype) when the medium of immortalised cell cultures was supplemented with dimethyl sulphoxide (DMSO). DMSO also improved ethoxyresorufin O-deethylation (EROD) and testosterone metabolism in immortalised cells. It also markedly inhibited proliferation, DNA, RNA and protein synthesis. Maximal testosterone metabolism was observed in immortalised cells cultured on collagen gels in the presence of 1% (v/v) DMSO. Development of a protocol for treating immortalised liver cells cultured on collagen gels with DMSO to switch between proliferation and differentiation may provide a convenient system expressing the xenobiotic metabolising enzymes required for in vitro toxicity testing.

Animals↗

Cost of outpatient blood transfusion in cancer patients.

PURPOSE: To determine the cost of outpatient RBC transfusion from the provider's perspective at a major urban, academic cancer center. PATIENTS AND METHODS: We retrospectively studied 517 cancer patients with hematologic or solid tumors who received blood during fiscal year 1995 to 1996. A process-flow diagram was developed, and cost and utilization data for 12 months were collected and analyzed. A structured interview process was used to identify all direct and indirect costs from within the inpatient unit, blood bank, and outpatient clinic. Average costs were computed for the entire sample and for specific subgroups. RESULTS: In 1998 dollars, the average cost per RBC unit was $469 for adults and $568 for pediatric cancer patients. Adults and children generally received two and one RBC units per transfusion, respectively. Therefore, the average cost of a two-unit transfusion was $938 for adults. Patients with hematologic tumors required more RBC units (7.1 RBC units per year) at a higher average cost ($512 per RBC unit) than patients with solid tumors (4.7 RBC units per year, $474 per RBC unit). Further variations across tumor types were observed. Overhead, direct material, and direct labor represented 46%, 19%, and 35% of total costs respectively. CONCLUSION: The cost of outpatient RBC transfusions in cancer patients is higher than previously reported, in part because overhead costs and fixed costs might have been underestimated in previous studies. Furthermore, age, tumor type, and geographic variations in the cost of fixed assets and labor have a substantial impact on the cost of blood. The results indicate that the cost-effectiveness of alternatives to transfusions in the management of cancer patients may have been underestimated in the existing literature.

Adult↗

Limitations in the use of median frequency for lung sound analysis.

The aim of this paper is to investigate methods of standardizing lung sound analysis, with a view to supplementing traditional spirometric air flow measurements to help in the diagnosis of asthma and to provide a measure of the effectiveness of treatment. Lung sounds were measured in nine patients with asthma and five control subjects, alongside air flow measurements of forced expiratory volume (FEV1) and forced vital capacity (FVC). The patients were administered the bronchodilator, salbutamol, to assess how effective these measurement techniques were for quantifying its effect. The results agree with previous studies, that analysis of lung sounds is a potentially useful tool for indicating air flow changes. The results, however, also demonstrate that the emerging standard of 'F50' or 'median frequency' should be treated with great caution because of its high sensitivity to the measurement frequency range. F50 is very unlikely to provide a reliable single indicator of lung condition.

Adolescent↗

Interleukin-1 family expression in human breast cancer: interleukin-1 receptor antagonist.

We hypothesize that interleukin-1 alpha, beta, and receptor antagonist (IL-1 alpha, IL-1 beta, and IL-1 ra, respectively) are present and tumor cell associated in human breast cancer (HBC). We believe the levels of these cytokines in breast tumor homogenates relate to other known prognosticators of patient survival (i.e., estrogen receptor [ER] status). Our results demonstrated that, immunohistochemically, tumor cells express IL-1 alpha, IL-1 beta, and IL-1 ra in most specimens tested. In breast tissue homogenates, IL-1 alpha levels correlated inversely with ER levels (p < 0.06), whereas IL-1 ra levels correlated directly with both ER levels (p < 0.009) and IL-1 beta levels (p < 0.06). When analyzing cytokine levels for the ER (-) versus ER (+) patient groups, we found that in many instances these groups showed a different cytokine profile. These studies suggest that the IL-1 family of cytokines may be important in regulating protumorigenic activities within the HBC tumor microenvironment.

Biomarkers, Tumor↗

Handling criticism.

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Adaptation, Psychological↗

Are sealants doing more than preventing caries?

Dental sealants are among some of dentistry's most effective tools for preventing tooth decay when applied to pediatric patients' teeth. Yet, a quiet controversy is mounting about some of the chemicals that may be leaching from these powerhouses of prevention. Some scientists hint that sealants may require further study to rule out possible links between some of their components and breast cancer development, prostate enlargement and some as-yet-unknown biological effects. While sealants' preventive power ranks with fluoride, even a remote possibility that they may affect patients' systemic health creates concern.

Benzhydryl Compounds↗

Lifestyle and colon cancer: an assessment of factors associated with risk.

Studies of the etiology of colon cancer indicate that it is strongly associated with diet and lifestyle factors. The authors use data from a population-based study conducted in northern California, Utah, and Minnesota in 1991-1995 to determine lifestyle patterns and their association with colon cancer. Data obtained from 1,993 cases and 2,410 controls were grouped by using factor analyses to describe various aspects of lifestyle patterns. The first five lifestyle patterns for both men and women loaded heavily on dietary variables and were labeled: "Western," "moderation," "calcium/low-fat dairy;" "meat and mutagens," and "nibblers, smoking, and coffee." Other important lifestyle patterns that emerged were labeled "body size," "medication and supplementation," "alcohol," and "physical activity." Among both men and women, the lifestyle characterized by high levels of physical activity was the most marked lifestyle associated with colon cancer (odds ratios = 0.42, 95% confidence interval: 0.32, 0.55 and odds ratio = 0.52, 95% confidence interval: 0.39, 0.69, for men and women, respectively) followed by medication and supplementation (odds ratio = 1.68, 95% confidence interval: 1.29, 2.18 and odds ratio = 1.63, 95% CI 1.23, 2.16, respectively). Other lifestyles that were associated with colon cancer were the Western lifestyle, the lifestyle characterized by large body size, and the one characterized by calcium and low-fat dairy. Different lifestyle patterns appear to have age- and tumor site-specific associations.

Adult↗

Cytotoxic T lymphocytes to Ebola Zaire virus are induced in mice by immunization with liposomes containing lipid A.

An eight amino acid sequence (TELRTFSI) present in the carboxy terminal end (aa 577-584) of membrane-anchored GP, the major structural protein of Ebola virus, was identified as an H-2k-specific murine cytotoxic T cell epitope. Cytotoxic T lymphocytes (CTLs) to this epitope were induced by immunizing B10.BR mice intravenously with either irradiated Ebola virus or with irradiated Ebola virus encapsulated in liposomes containing lipid A. The CTL response induced by irradiated Ebola virus could not be sustained after the second round of in vitro stimulation of immune splenocytes with the peptide, unless the irradiated virus was encapsulated in liposomes containing lipid A. The identification of an Ebola GP-specific CTL epitope and the requirement of liposomal lipid A for CTL memory recall responses could prove to be a promising approach for developing a vaccine against Ebola virus infection.

Animals↗

Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant.

Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.

Adjuvants, Immunologic↗

Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis.

The functions of many open reading frames (ORFs) identified in genome-sequencing projects are unknown. New, whole-genome approaches are required to systematically determine their function. A total of 6925 Saccharomyces cerevisiae strains were constructed, by a high-throughput strategy, each with a precise deletion of one of 2026 ORFs (more than one-third of the ORFs in the genome). Of the deleted ORFs, 17 percent were essential for viability in rich medium. The phenotypes of more than 500 deletion strains were assayed in parallel. Of the deletion strains, 40 percent showed quantitative growth defects in either rich or minimal medium.

Culture Media↗

Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators.

BACKGROUND: The TIMI 14 trial tested the hypothesis that abciximab, the Fab fragment of a monoclonal antibody directed to the platelet glycoprotein (GP) IIb/IIIa receptor, is a potent and safe addition to reduced-dose thrombolytic regimens for ST-segment elevation MI. METHODS AND RESULTS: Patients (n=888) with ST-elevation MI presenting <12 hours from onset of symptoms were treated with aspirin and randomized initially to either 100 mg of accelerated-dose alteplase (control) or abciximab (bolus 0.25 mg/kg and 12-hour infusion of 0.125 microg. kg-1. min-1) alone or in combination with reduced doses of alteplase (20 to 65 mg) or streptokinase (500 000 U to 1.5 MU). Control patients received standard weight-adjusted heparin (70-U/kg bolus; infusion of 15 U. kg-1. h-1), whereas those treated with a regimen including abciximab received low-dose heparin (60-U/kg bolus; infusion of 7 U. kg-1. h-1). The rate of TIMI 3 flow at 90 minutes for patients treated with accelerated alteplase alone was 57% compared with 32% for abciximab alone and 34% to 46% for doses of streptokinase between 500 000 U and 1.25 MU with abciximab. Higher rates of TIMI 3 flow at both 60 and 90 minutes were observed with increasing duration of administration of alteplase, progressing from a bolus alone to a bolus followed by either a 30- or 60-minute infusion (P<0.02). The most promising regimen was 50 mg of alteplase (15-mg bolus; infusion of 35 mg over 60 minutes), which produced a 76% rate of TIMI 3 flow at 90 minutes and was tested subsequently in conjunction with either low-dose or very-low-dose (30-U/kg bolus; infusion of 4 U. kg-1. h-1) heparin. TIMI 3 flow rates were significantly higher in the 50-mg alteplase plus abciximab group versus the alteplase-only group at both 60 minutes (72% versus 43%; P=0.0009) and 90 minutes (77% versus 62%; P=0.02). The rates of major hemorrhage were 6% in patients receiving alteplase alone (n=235), 3% with abciximab alone (n=32), 10% with streptokinase plus abciximab (n=143), 7% with 50 mg of alteplase plus abciximab and low-dose heparin (n=103), and 1% with 50 mg of alteplase plus abciximab with very-low-dose heparin (n=70). CONCLUSIONS: Abciximab facilitates the rate and extent of thrombolysis, producing early, marked increases in TIMI 3 flow when combined with half the usual dose of alteplase. This improvement in reperfusion with alteplase occurred without an increase in the risk of major bleeding. Substantial reductions in heparin dosing may reduce the risk of bleeding even further. Modest improvements in TIMI 3 flow were seen when abciximab was combined with streptokinase, but there was an increased risk of bleeding.

Abciximab↗