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Biomedical subjects

T J Prihoda

Publications and source records attributed to T J Prihoda.

At least 19 recordsLinked to original sources

Cytogenetic studies in mice treated with the jet fuels, Jet-A and JP-8.

The genotoxic potential of the jet fuels, Jet-A and JP-8, were examined in mice treated on the skin with a single dose of 240 mg/mouse. Peripheral blood smears were prepared at the start of the experiment (t = 0), and at 24, 48 and 72 h following treatment with jet fuels. Femoral bone marrow smears were made when all animals were sacrificed at 72 h. In both tissues, the extent of genotoxicity was determined from the incidence of micronuclei (MN) in polychromatic erythrocytes. The frequency of MN in the peripheral blood of mice treated with Jet-A and JP-8 increased over time and reached statistical significance at 72 h, as compared with concurrent control animals. The incidence of MN was also higher in bone marrow cells of mice exposed to Jet-A and JP-8 as compared with controls. Thus, at the dose tested, a small but significant genotoxic effect of jet fuels was observed in the blood and bone marrow cells of mice treated on the skin.

Administration, Cutaneous↗

Combining ondansetron and naltrexone reduces craving among biologically predisposed alcoholics: preliminary clinical evidence.

RATIONALE: Previously, we have reported that the combination of ondansetron (a 5-HT3 antagonist) and naltrexone (a mu opioid antagonist) appears to act synergistically at improving the drinking outcomes of early onset alcoholics (EOA). a subtype of alcoholic characterized by developing problem-drinking earlier, antisocial behaviors, high familial loading, and biological disease predisposition. Presumably, this medication combination counteracts the interaction between activated central 5-HT3 receptors and the endogenous opioid system during the mediation of alcohol-induced reward. We now hypothesize further that an important mechanism by which the combination diminishes alcohol consumption is through a reduction in craving. OBJECTIVE: To determine whether the combination of naltrexone and ondansetron is superior to a placebo at reducing craving among EOA, and the relationship between craving and drinking behavior in both treatment groups. METHODS: We conducted an 8-week double-blind placebo-controlled clinical trial in which 10 EOA were randomized to receive ondansetron (4 microg/kg b.i.d.) + naltrexone (25 mg b.i.d.) and 10 EOA had a placebo (total n=20) as an adjunct to weekly standardized group cognitive behavioral therapy. Craving was measured by using the obsessive compulsive drinking scale (OCDS). RESULTS: Craving ratings were scored on four subscales which where derived empirically by principal component structure analysis of the OCDS. EOA who received the medication combination, compared with the placebo, had significantly lower scores on "automaticity of drinking" and "alcohol consumption ". Reduction in automaticity of drinking was correlated with self-reported drinking for only the medication combination group. CONCLUSIONS: By reducing automaticity of drinking, the medication combination presumably decreased drinking salience and intensity. Larger scale studies testing these medications, both alone and together, among alcoholic subtypes are needed to establish and extend these promising findings.

Adult↗

Micronuclei in the peripheral blood and bone marrow cells of rats exposed to 2450 MHz radiofrequency radiation.

PURPOSE: To determine the incidence of micronuclei in peripheral blood and bone marrow cells of rats exposed continuously for 24h to 2450 MHz continuous wave radiofrequency radiation (RFR) at an average whole-body specific absorption rate (SAR) of 12W/kg. MATERIALS AND METHODS: Eight adult male Sprague-Dawley rats were exposed to 2450 MHz RFR in circularly polarized waveguides. Eight sham-exposed rats were kept in similar waveguides without the transmission of RFR. Four rats were treated with mitomycin-C (MMC) and used as positive controls. All rats were necropsied 24h after the end of RFR and sham exposures, and after the 24h treatment with MMC. Peripheral blood and bone marrow smears were examined to determine the frequency of micronuclei (MN) in polychromatic erythrocytes (PCE). RESULTS: The results indicated that the incidence of MN/2000 PCE were not significantly different between RFR- and sham-exposed rats. The group mean frequencies of MN in the peripheral blood were 2.3+/-0.7 in RFR-exposed rats and 2.1+/-0.6 in sham-exposed rats. In bone marrow cells, the average MN incidence was 3.8+/-1.0 in RFR-exposed rats and 3.4+/-0.7 in sham-exposed rats. The corresponding values in positive control rats treated with MMC were 23.5+/-4.7 in the peripheral blood and 33.8+/-7.4 in bone marrow cells. CONCLUSION: There was no evidence for the induction of MN in peripheral blood and bone marrow cells of rats exposed for 24h to 2450 MHz continuous wave RFR at a whole body average SAR of 12 W/kg.

Animals↗

Agonist-dependent failure of neutrophil function in diabetes correlates with extent of hyperglycemia.

Inexplicable controversies with regard to possible functional defects of neutrophilic polymorphonuclear leukocytes (PMNs) in diabetes persist. The purpose of the present study was to elucidate the relative effectiveness of several PMN agonists in stimulating lysosomal-enzyme secretion and leukotriene (LT) B(4) production by PMNs isolated from diabetic subjects. Formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) induced significantly less lysosomal-enzyme secretion and LTB(4) production in diabetic-subject PMNs than in normal-subject PMNs. It is surprising that PMNs from these same diabetic subjects responded normally after stimulation with A23187, serum-opsonized zymosan, or phorbol myristate acetate. The in vitro responsiveness of PMNs stimulated with fMLP or PAF was inversely correlated with indices of in vivo glycemic control (fasting plasma glucose and glycated-hemoglobin levels). In combination, these results indicate that hyperglycemia is associated with sustained decreases in PMN function but only in response to agonists that initiate stimulus-response coupling via G-protein-coupled receptors. This agonist-selective reduction in PMN responsiveness may contribute to the compromised host defense associated with sustained hyperglycemia in diabetes.

Adult↗

Mass spectrometric analysis of platelet-activating factor after isolation by solid-phase extraction and direct derivatization with pentafluorobenzoic anhydride.

Platelet-activating factor is the term used to denote a class of extremely potent lipid mediators that consist predominantly of 1-O-alkyl- and 1-O-acyl-2-acetyl-sn-glycero-3-phosphocholines. A method has been devised for rapid isolation of these acetylated phospholipids by solid-phase extraction prior to direct derivatization with pentafluorobenzoic anhydride and analysis by gas chromatography (GC)/electron-capture mass spectrometry. Recovery through the entire method (lipid isolation, derivatization, and purification) typically ranged from 70% to 85%. Using the direct derivatization procedure described here, the practical limit of detection for each of the standard alkyl- and acyl-platelet-activating factor homologs was 1 fmol injected into the GC. Results from the application of the method to the analysis of alkyl and acyl homologs of platelet-activating factor isolated from stimulated human umbilical vein endothelial cells are presented, exhibiting excellent accuracy and precision for a wide range of tissue levels of this class of potent autacoids.

Anhydrides↗

Assessing quality of life in Mexican-American children with asthma: impact-on-family and functional status.

OBJECTIVE: To assess the internal consistency reliability and construct validity of two questionnaires, the Impact on Family (IOF) and the Functional Status II (R) (FSIIR), in a Mexican-American population of children with asthma. METHODS: We interviewed 115 Hispanic parents of children with asthma and compared the IOF and FSIIR scores and reliability coefficients for the following subgroups: English or Spanish language and high or low educational level. We assessed the construct validity of the IOF Total score and FSIIR Illness score by examining the relationship between these scores and other health status variables. RESULTS: The IOF Total score and FSIIR Illness score demonstrated acceptable construct validity and reliability for language and education subgroups, although several of the IOF subscales had low reliability. CONCLUSIONS: IOF Total score and FSIIR Illness score can be recommended for use by Spanish- and English-speaking Mexican-American respondents.

Adaptation, Psychological↗

Randomized controlled trial of the use of compensatory strategies to enhance adaptive functioning in outpatients with schizophrenia.

OBJECTIVE: Cognitive adaptation training is a novel psychosocial treatment approach designed to improve adaptive functioning by using compensatory strategies in the home or work environment to bypass the cognitive deficits associated with schizophrenia. The authors tested the effect of cognitive adaptation training on level of adaptive functioning in outpatients with schizophrenia. METHOD: Forty-five patients with DSM-IV schizophrenia or schizoaffective disorder were randomly assigned for 9 months to one of three treatment conditions: 1) standard medication follow-up, 2) standard medication follow-up plus cognitive adaptation training, and 3) standard medication follow-up plus a condition designed to control for therapist time and provide environmental changes unrelated to cognitive deficits. Comprehensive assessments were conducted every 3 months by raters who were blind to treatment condition. RESULTS: Significant differences were found between the three treatment groups in levels of psychotic symptoms, motivation, and global functioning at the end of the 9-month study period. Patients in the cognitive adaptation training group overall had higher levels of improvement, compared with those in the remaining treatment conditions. In addition, the three groups had significantly different relapse rates over the 9-month study: 13% for the cognitive adaptation training group, 69% for the group in which therapist time and environmental changes were controlled, and 33% for the group who received standard follow-up only. CONCLUSIONS: Compensatory strategies may improve outcomes for patients with schizophrenia.

Adult↗

Primary DNA damage in human blood lymphocytes exposed in vitro to 2450 MHz radiofrequency radiation.

Human peripheral blood samples collected from three healthy human volunteers were exposed in vitro to pulsed-wave 2450 MHz radiofrequency (RF) radiation for 2 h. The RF radiation was generated with a net forward power of 21 W and transmitted from a standard gain rectangular antenna horn in a vertically downward direction. The average power density at the position of the cells in the flask was 5 mW/cm(2). The mean specific absorption rate, calculated by finite difference time domain analysis, was 2.135 (+/-0.005 SE) W/kg. Aliquots of whole blood that were sham-exposed or exposed in vitro to 50 cGy of ionizing radiation from a (137)Cs gamma-ray source were used as controls. The lymphocytes were examined to determine the extent of primary DNA damage (single-strand breaks and alkali-labile lesions) using the alkaline comet assay with three different slide-processing schedules. The assay was performed on the cells immediately after the exposures and at 4 h after incubation of the exposed blood at 37 +/- 1 degrees C to allow time for rejoining of any strand breaks present immediately after exposure, i.e. to assess the capacity of the lymphocytes to repair this type of DNA damage. At either time, the data indicated no significant differences between RF-radiation- and sham-exposed lymphocytes with respect to the comet tail length, fluorescence intensity of the migrated DNA in the tail, and tail moment. The conclusions were similar for each of the three different comet assay slide-processing schedules examined. In contrast, the response of lymphocytes exposed to ionizing radiation was significantly different from RF-radiation- and sham-exposed cells. Thus, under the experimental conditions tested, there is no evidence for induction of DNA single-strand breaks and alkali-labile lesions in human blood lymphocytes exposed in vitro to pulsed-wave 2450 MHz radiofrequency radiation, either immediately or at 4 h after exposure.

Comet Assay↗

Combining ondansetron and naltrexone effectively treats biologically predisposed alcoholics: from hypotheses to preliminary clinical evidence.

BACKGROUND: Individuals considered to be early onset alcoholics (EOA) are characterized by an early onset age, a broad range of antisocial behaviors, high familial loading, and presumed biological disease predisposition. Ondansetron, a 5-HT3 antagonist, improves drinking outcomes and increases abstinence rates among EOA. Individuals with high familial loading for developing alcoholism have lower levels of beta-endorphin and demonstrate a more pronounced increase in beta-endorphin levels in response to alcohol administration compared with individuals who do not have alcoholic relatives. The propensity for naltrexone (a mu opioid antagonist) to reduce alcohol's rewarding effects and drinking in humans is greatest in individuals with high familial loading. Predicated on the added knowledge that 5-HT3 receptors may themselves mediate alcohol reward via activation of the endogenous opioid system, we hypothesized that the combination of ondansetron and naltrexone would act synergistically and would be an effective treatment in EOA. METHODS: We conducted an 8-week double-blind placebo controlled clinical trial in which 20 EOA were randomized to receive ondansetron (4 microg/kg twice a day) + naltrexone (25 mg twice a day) or placebo as an adjunct to weekly standardized group Cognitive Behavioral Therapy. RESULTS: At endpoint, subjects who received ondansetron + naltrexone (n = 10), compared with those who received placebo (n = 10), had fewer drinks/day (covariate adjusted mean 0.99 +/- 0.60 vs. 3.68 +/- 0.63; F1, 16 = 9.35,p = 0.008; effect size = 1.42), drinks/drinking day (covariate adjusted mean 3.14 +/- 0.87 vs. 6.76 +/- 0.71; F1, 13 = 10.45, p = 0.007; effect size = 1.71), and a trend toward increased percent days abstinent (covariate adjusted mean 69.76 +/- 8.64 vs. 48.24 +/- 9.12; F1, 16 = 3.58, p = 0.08; effect size = 0.88). CONCLUSIONS: Ondansetron plus naltrexone seems to synergistically improve the drinking outcomes of EOA. Larger scale studies that test these medications, both alone and together, among various alcoholic subtypes are needed to establish and extend these promising findings.

Adult↗

Securing meshed split-thickness skin grafts with 2-octylcyanoacrylate.

Meshed split-thickness skin grafts (STSGs) secured with 2-octylcyanoacrylate (2-OCA) were compared with meshed STSGs secured by suture and bolster (S&B). The 2 techniques were compared for graft survival, foreign-body giant cell response, inflammatory response, appearance, texture, and application time. Sixteen 2.5 x 2. 5 cm meshed STSGs were harvested from the dorsa of 2 pigs for a total of 32 grafts. On each pig 8 grafts were sprayed with 2-OCA, and the other 8 were secured with S&B. Evaluations were performed on postoperative days 14, 24, 48, and 56. Biopsy specimens were obtained on postoperative days 14 and 56. There were no significant differences in percent survival, foreign-body giant cell response, inflammatory response, and appearance between control and study grafts. The average time to apply the 2-OCA onto a graft was 3 seconds, compared with 8 minutes for S&B application. 2-OCA provides a quick and reliable means of securing meshed STSGs and would be especially useful in areas where it is difficult to use S&B, such as total maxillectomy defects.

Animals↗

Frequency of micronuclei in the blood and bone marrow cells of mice exposed to ultra-wideband electromagnetic radiation.

PURPOSE: To investigate the extent of genetic damage in the peripheral blood and bone marrow cells of mice exposed to ultra-wideband electromagnetic radiation (UWBR). MATERIALS AND METHODS: CF-1 male mice were exposed to UWBR for 15 min at an estimated whole-body average specific absorption rate of 37 mW x kg(-1). Groups of untreated control and positive control mice injected with mitomycin C were also included in the study. After various treatments, half of the mice were killed at 18 h, and the other half at 24 h. Peripheral blood and bone marrow smears were examined to determine the extent of genotoxicity, as assessed by the presence of micronuclei (MN) in polychromatic erythrocytes (PCE). RESULTS: The percentages of PCE and the incidence of MN per 2000 PCE in both tissues in mice killed at 18 h were similar to the frequencies observed in mice terminated at 24 h. There were no significant differences in the percentage of PCE between control and the mice with or without UWBR exposure; the group mean values (+/- standard deviation) were in the range of 3.1+/-0.14 to 3.2+/-0.23 in peripheral blood, and 49.0+/-3.56 to 52.3+/-4.02 in bone marrow. The mean incidence of MN per 2000 PCE in control and in mice with or without UWBR exposure ranged from 7.7+/-2.00 to 9.7+/-2.54 in peripheral blood and 7.4+/-2.32 to 10.0+/-3.27 in bone marrow. Pairwise comparison of the data did not reveal statistically significant differences between the control and mice with or without UWBR exposure groups (excluding positive controls). CONCLUSION: Under the experimental conditions tested, there was no evidence for excess genotoxicity in peripheral blood or bone marrow cells of mice exposed to UWBR.

Animals↗

Continuing medical education versus clinic-based STD and HIV education interventions for primary care service providers: replication and extension.

An evaluation of a 2-day sexually transmitted disease (STD) and HIV and AIDS curriculum for primary care providers is presented which compares large scale continuing medical education (CME) conferences with smaller clinic workshop (CW) models with regard to short-term (2-month) and long-term (10-month) program effects on STD and HIV knowledge, attitudes toward risk assessment, and frequency of both STD diagnosis and STD and HIV risk counseling. Data from interventions held in San Antonio, Texas (328 CME; 95 CW) replicate and extend earlier findings from a preliminary intervention, indicating nonsignificant CME-CW differences and dramatic and long-lasting gains from baseline among those with lower knowledge and experience levels preintervention. Similar program effect magnitudes were found for attitude and practice dimensions at 2 months postintervention, with the strongest consistent short and long-term program effects observed for STD and HIV knowledge among service providers.

Adult↗

Evaluation of the cardiac STATus CK-MB/myoglobin card test to diagnose acute myocardial infarctions in the ED.

A study was undertaken to evaluate a Card Test called "Spectral Diagnostics Inc Cardiac STATus CK-MB/Myoglobin" (Toronto, Canada), which is distributed by Dade International Inc, Miami, FL, for the simultaneous qualitative determination of CK-MB and myoglobin levels in human serum. The Card Test is advertised by the manufacturer as an aid in diagnosing acute myocardial infarction (AMI) in the emergency department (ED). Fifty-eight consecutive serum samples were obtained from 25 patients being evaluated for AMI in an ED. Qualitative CK-MB and myoglobin results from the Card Test were compared with quantitative CK-MB and myoglobin results using the ACS-180 instrument (Ciba Corning Diagnostics, Medfield, MA) and Stratus IIntellect T (Dade International Inc, Miami, FL), respectively. Qualitative results from the STATus CK-MB/Myoglobin Card Test were similar, diagnostically, to quantified results using these automated instruments.

Acute Disease↗

The relationship of methadone dose and other variables to outcomes of methadone maintenance.

The authors evaluated the relationship of methadone dose to retention in treatment and to urine tests for morphine and cocaine in a cohort of 610 opioid users admitted to methadone maintenance and followed for 1 year. Methadone dosing was flexible, with patient participation in dose decisions. The maximum dose during treatment ranged from 10 mg to 110 mg, with a mean of 52 mg. Higher doses were associated with increased retention through the dose range of 60 mg-69 mg. Dose was not related to the likelihood of a positive morphine test but was related to the likelihood of a positive cocaine test. In this study, with flexible dosing and patient participation in dose decisions, patients were retained on methadone about as well as was reported in a previous study with patients on a fixed dose of 80 mg.

Adult↗

Alkyl-PAF and acyl-PAF human neutrophil priming for enhanced fMLP- and rC5a-induced superoxide anion production.

Alkyl-PAF induced two components of polymorphonuclear leukocyte (PMN) priming for enhanced fMLP- and rC5a-induced superoxide anion (O2-) production. Component A priming had a shallow, linear alkyl-PAF concentration-response slope (10 pM-1 nM), and component B priming had a significantly steeper concentration-response slope (1-100 nM alkyl-PAF). Whereas the extent of component B priming decayed significantly within 5-10 min after pretreatment of PMNs with alkyl-PAF, component A priming was completely stable. WEB 2086, a specific and potent PAF receptor antagonist, abolished component A priming when PMNs were simultaneously stimulated with alkyl-PAF and either fMLP or rC5a but only partially reduced component B priming. However, whereas WEB 2086 also obliterated component A priming when PMNs were pretreated with alkyl-PAF for 2.5, 5, or 10 min prior to fMLP stimulation, WEB 2086 had little or no inhibitory effect on component B priming. Paradoxically, WEB 2086 significantly augmented alkyl-PAF-induced component B priming for enhanced rC5a-induced PMN O2. production yet concomitantly obliterated component A priming. PMN priming by acyl-PAF (1 nm-1 micron) had characteristics identical to those of alkyl-PAF-induced component A priming. These studies suggest that there are at least two effector pathways modulating alkyl-PAF-induced PMN respiratory burst priming. They are also consistent with the notion that component A priming is initiated via high-affinity PAF receptors and component B priming is mediated through low-affinity PAF receptors; and whereas alkyl-PAF interacts with both high- and low-affinity PAF receptors, both acyl-PAF and WEB 2086 preferentially bind to the high-affinity PAF receptors.

Adrenergic beta-Antagonists↗

Molecular heterogeneity of PAF in normal human mixed saliva: quantitative mass spectral analysis after direct derivatization of PAF with pentafluorobenzoic anhydride.

Platelet-activating factor (PAF), a family of phospholipid autacoids with potent pro-inflammatory activities, is present in saliva. The current study has quantitated various species of PAF isolated from normal human mixed saliva. Choline-containing, sn-2 acetylated phospholipids with sn-1 ether- or ester-linked fatty alcohol/acid moieties (alkyl-PAF or acyl-PAF, respectively) were evaluated after direct derivatization with pentafluorobenzoic (PFB) anhydride. Individual species of PFB-derivatized PAF were separated by gas chromatography prior to mass spectral analysis; quantitative estimates of six different species of PAF in saliva were made by comparison to corresponding authentic, synthetic PAF standards. In each saliva sample, all six species of PAF were readily detected by this facile procedure. The predominant PAF was 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine or 16:0-alkyl-PAF (0.75 +/- 0.09 pmol/ml saliva; mean +/- S.E.; n = 5) which represented only 30.4 +/- 1.5% of the total PAF. Substantial amounts of 18:1- and 18:0-alkyl-PAF and 16:0-acyl-PAF were also identified (0.52 +/- 0.07, 0.35 +/- 0.06, and 0.35 +/- 0.02 pmol/ml saliva, respectively). In summary, mass spectrometric analysis of PAF after direct derivatization with PFB anhydride has revealed that at least six different species of PAF are present in normal human mixed saliva. This structural diversity may represent an important aspect of homeostasis in the healthy oral cavity.

Anhydrides↗

Allelic imbalance in gastric cancer: an affected site on chromosome arm 3p.

In order to detect regions of DNA containing tumor suppressor genes involved in the development of gastric cancer, we performed an allelotype study on 78 gastric adenocarcinomas from a population composed largely of Texan Hispanics and Anglos, two ethnic groups that have a ratio of incidence rates of gastric cancer of approximately 2:1. In total, 42 microsatellite markers were employed, which detected at least one site per arm of each autosome in the human genome. These included several markers linked to known tumor suppressor genes (TP53, APC, DCC, RB1, and BRCA1). Sites showing quantitative allelic imbalance (AI) greater than 30% were located on 3p (36%), 11q (31%), 12q (38%), 13q (33%), 17p near TP53 (74%), and 17q near BRCAI (32%). Among the 22% of cases showing microsatellite instability (MI), a subset (4 of 17) showed instability at 59% or more of sites tested. No ethnic bias was detected in cases showing MI or in cases with AI at sites with rates of AI above 30%. Tumors of the intestinal subtype were significantly more likely than diffuse tumors to show AI at DI3S170 (P = 0.01). A deletion map of chromosome arm 3p was prepared for tumors with AI at D3S1478. These data indicate that a tumor suppressor gene on chromosome arm 3p is involved in the development of a subset of gastric cancers.

Adenocarcinoma↗