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Biomedical subjects

K C Mills

Publications and source records attributed to K C Mills.

At least 19 recordsLinked to original sources
PubMed2001

The influence of stimulants, sedatives, and fatigue on tunnel vision: risk factors for driving and piloting.

A computerized task was used in two studies to examine the influence of stimulants, sedatives, and fatigue on single-target and divided-attention responses in different parts of the visual field. The drug effects were evaluated over time with repeated behavioral and subjective measures against ascending and descending drug levels. In the first study, 18 fully rested participants received placebo, alprazolam (0.5 mg), and dextroamphetamine (10 mg). Alprazolam impairs performance, whereas dextroamphetamine induces enhancement and tunnel vision. Study 2 exposed 32 participants to fatigue and no fatigue with a repeated-measures crossover design. Four independent groups subsequently received placebo, dextroamphetamine (10 mg), caffeine (250 mg), or alcohol (.07%). Under fatigue, stimulants have no performance-enhancing effects, whereas impairment from alcohol is severe. Under no fatigue, alcohol has a modest effect, caffeine has no effect, and dextroamphetamine significantly enhances divided-attention performance coincident with tunnel vision. Participants rate all drug effects more stimulating and less sedating while fatigued. Implications for transportation safety are discussed. Actual or potential applications of this research include driver and pilot training.

Alcohol Drinking↗
PubMed1997

Serotonin syndrome. A clinical update.

Serotonin syndrome is characterized by varied degrees of cognitive, autonomic, and neuromuscular dysfunction and can only be produced by drug therapy that increases central nervous system serotonin neurotransmission. Information gained from a retrospective review of 127 cases of serotonin syndrome is presented. It is not uncommon for severe cases of serotonin syndrome to be confused with neuroleptic malignant syndrome. Treatment is mainly supportive, but specific pharmacologic therapy with serotonin antagonists may be potentially beneficial.

Diagnosis, Differential↗
PubMed1996

A PC-based software test for measuring alcohol and drug effects in human subjects.

A new software-based visual search and divided-attention test of cognitive performance was developed and evaluated in an alcohol dose-response study with 24 human subjects aged 21-62 years. The test used language-free, color, graphic displays to represent the visuospatial demands of driving. Cognitive demands were increased over previous hardware-based tests, and the motor skills required for the test involved minimal eye movements and eye-hand coordination. Repeated performance on the test was evaluated with a latin-square design by using a placebo and two alcohol doses, low (0.48 g/kg/LBM) and moderate (0.72 g/kg/LBM). The data on 7 females and 17 males yielded significant falling and rising impairment effects coincident with moderate rising and falling breath alcohol levels (mean peak BrALs = 0.045 g/dl and 0.079 g/dl). None of the subjects reported eye-strain or psychomotor fatigue as compared with previous tests. The high sensitivity/variance relative to use in basic and applied research, and worksite fitness-for-duty testing, was discussed. The most distinct advantage of a software-based test that operates on readily available PCs is that it can be widely distributed to researchers with a common reference to compare a variety of alcohol and drug effects.

Adult↗
PubMed1996

Immunologic attributes of cytokine mobilized peripheral blood stem cells and recovery following transplantation.

The immunologic attributes of cytokine mobilized peripheral blood stem cell (PSC) products (n = 52) and the resulting reconstitution of the hematopoietic and immunologic system following autologous transplantation were examined in a consecutive population of non-Hodgkin lymphoma (NHL), or solid tumor patients at the University of Nebraska Medical Center. Granulocyte-monocyte colony stimulating factor (GM-CSF)-mobilized PSC products had a high frequency of monocytes (31%) and bands (15%) as compared to normal peripheral blood (PB) cells. The phenotypic analysis of the mobilized PSC product revealed that they had normal levels of CD4+ cells, an increased frequency of CD8+ cells and a corresponding decrease in the CD4+:CD8+ cell ratio as compared to the peripheral blood leukocytes (PBL) of normal individuals. PSC products also had an increase in CD34+ cells as compared to PB. Natural killer (NK) and T cell activity in the PSC products were also lower than that observed in PB. Post-transplantation there was an accelerated reconstitution of NK-cell function in the PB as compared to T cell function (PHA (phytohemagglutinin) mitogenesis) which did not return to normal by day 100 post-transplantation. We also report for the first time high levels of an irradiation resistant suppressor cell activity in the PSC product and in the PB post-transplantation. There was also a concomitant increase in CD4-, CD8-, TCR alpha/beta+ cells (phenotypic homolog of 'natural suppressor' (NS) cells) in the PB post-transplantation. The number of months of prior chemotherapy correlated with PHA response but the NS activity and frequency of CD4-, CD8- and TCR alpha/beta+ cells did not. Further, cytokine mobilization and apheresis appears to contribute to the loss of PHA responsiveness and the increased levels of suppressor cell activity.

Antigens, CD34↗
PubMed1996

Immunologic phenotype and function in human bone marrow, blood stem cells and umbilical cord blood.

The T cell-mediated antineoplastic activity observed following allogeneic transplantation and the suggestion of improved therapeutic efficacy by autologous peripheral stem cell transplantation (PSCT) as compared to autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma (NHL) stimulated our interest in the immunologic competence of stem cell products. We report the immune phenotype and function of normal peripheral blood (PB) cells, bone marrow (BM) cells from normal donors and cancer bearing patients, GM-CSF-mobilized and apheresed blood mononuclear cells from NHL patients, unmobilized apheresed mononuclear cells from normal volunteers and umbilical cord blood (CB). The analyses include three-color fluorescent cytometry of the major hematologic and immunologic phenotypes as well as natural killer (NK) activity, natural suppressor (NS) activity, and phytohemagglutinin (PHA) and pokeweed (PWM) mitogenesis. These studies demonstrated an increased frequency of T cells in apheresis products as compared to BM and CB products. Specifically, the mobilized PSC had significant increases in CD3+, CD4+, CD45RO+ and CD56+ cells relative to BM cells. In addition, the frequency of TCR gamma/delta + cells in all the stem cell products, with the exception of CB, were also increased compared to normal peripheral blood leukocytes (PBL). However, all the stem cell products had a significant depression in T (PHA mitogenesis) and B (PWM mitogenesis) cell function. The depression in immune cell functionality, in the PSC products was perhaps due to the high frequency of monocytes which appeared to be increased due to both mobilization and apheresis. The frequency of the NK cell phenotype (CD56) but not function was increased in the mobilized PSC products, while the NK cell function in the BM products from cancer patients but not normal donors was depressed as compared to normal PBL. In summary, there are significant differences in the cellular phenotypes and immunologic competence among the various stem cell products with potential therapeutic implications.

Bone Marrow↗
PubMed1995

Exogenous myeloperoxidase enhances bacterial phagocytosis and intracellular killing by macrophages.

It is well documented that myeloperoxidase (MyPo) contributes to the bacterial activities of neutrophils and monocytes. Since mature macrophages (M phi) are devoid of this enzyme, its participation in M phi-mediated phagocytes and bacterial killing has not been completely defined. The present study demonstrates the exogenously added MyPo, at physiological levels, enhances both phagocytosis and killing of Escherichia coli. Murine peritoneal M phi were exposed to various concentrations of MyPo for different time intervals. Viable opsonized E. coli was added either prior to or after addition of MyPo. Thioglycolate-induced but not resident M pho exhibited an increase in the number of phagocytizing cells. Both resident and thioglycolate-induced M phi demonstrated increased bactericidal activity. Physiological levels of soluble MyPo also induced a significant increase in chemiluminescence. Since luminol-dependent chemiluminescence measures reactive oxygen intermediate production, studies were done to determine whether superoxide anion or H2O2 was involved in MyPo-induced M pho killing. Both superoxide dismutase and catalase ablated MyPo-induced bactericidal activity. The above data suggest that soluble MyPo, released from neutrophils at a site of infection or inflammation, can enhance both phagocytosis and killing of microorganisms.

Animals↗
PubMed1995

Serotonin syndrome.

Serotonin syndrome is a potentially life-threatening complication of psychopharmacologic drug therapy. The syndrome is produced most often by the concurrent use of two or more drugs that increase brainstem serotonin activity and is often unrecognized because of the varied and nonspecific nature of its symptomatology. Serotonin syndrome is characterized by alterations in cognition, behavior, autonomic nervous system function and neuromuscular activity. Patients with serotonin syndrome usually respond to discontinuation of drug therapy and supportive care alone, but they may require treatment with a specific antiserotonergic drug such as cyproheptadine, methysergide and/or propranolol.

Adolescent↗
PubMed1994

Acute iron poisoning.

Acute iron poisoning continues to be one of the most common and deadly poisonings seen by emergency physicians. There are many potential pitfalls in the assessment, diagnosis, and treatment of iron-poisoned patients. This article reviews the pathophysiology of acute iron poisoning and describes a comprehensive management plan that will enable emergency physicians to provide appropriate emergency care to patients ingesting iron preparations. This article also addresses the common problems encountered by clinicians who care for iron-poisoned patients once they are admitted to the hospital.

Acute Disease↗
PubMed1993

Regulation of macrophage function by human recombinant myeloperoxidase.

Myeloperoxidase is an enzyme which is found in the azurophilic granules of neutrophils and is associated with bactericidal, fungicidal, and tumoricidal activity. The present studies show that human recombinant myeloperoxidase (rec-MyPo) can regulate a number of macrophage (M phi) capacities and functions. Macrophages from mice exposed to rec-MyPo in vitro released reactive oxygen intermediates, tumor necrosis factor alpha (TNF alpha), and interferon alpha/beta (IFN alpha/beta). Enhanced target cell killing was also demonstrated with TNF alpha sensitive but not TNF alpha insensitive cells. Intravenous injection of rec-MyPo induced high titers of systemic TNF alpha and IFN alpha/beta. These results indicate that MyPo can function as an immunomodulator both in vitro and in vivo. Because of these actions, it is apparent that MyPo represents a previously unrecognized endogenous immunomodulator.

Adjuvants, Immunologic↗
PubMed1984

Selective attenuation of ethanol-induced performance impairment by naloxone in humans.

Healthy human subjects performed a vigilance task involving decision making and motor responses under four drug conditions involving random assignment and double blind procedures. Naloxone (0.4 mg) or saline was injected intravenously before subjects consumed a drink of alcohol (0.56 gm ethanol per kg body weight) or a simulated alcoholic drink. Blood alcohol concentrations averaged 60 mg/dl. The impaired performance of the task by this blood alcohol concentration was ameliorated by prior administration of naloxone at one testing point in the study sequence (40 minutes after ingesting the alcohol). The effect was associated with a history of light drinking (mean intake 0.93 gm/kg of body weight/month). Further studies to characterize this phenomenon more fully are proposed.

Adult↗
PubMed1983

A residence hall tavern as a collegiate alcohol abuse prevention activity.

An alcohol abuse prevention program used community organization to install an experimental tavern in a university residence hall. Upperclass students enrolled in a course on alcohol education managed the tavern as a vehicle to increase resident participation in alcohol abuse prevention activities. Baseline and follow-up surveys assessed consumption levels, problem frequencies and attitudes about alcohol use. Attendance was high at project events. Students increased their use of nonalcoholic beverages, altered their perceptions of heavy drinking and drinking and driving, and saw the program as improving residence hall parties. Beer, wine and liquor consumption did not change as a result of the program. Similarly, self-reports of problems including hangover, drinking and driving, noise and litter were not influenced. Program goals that attempt to formally modify per capita alcohol consumption were discussed.

Adult↗
PubMed1983

Body sway and divided attention performance under the influence of alcohol: dose-response differences between males and females.

This study assessed women and men on a divided attention task, body sway, and subjective (self-report) estimates of impairment across different doses of alcohol. Twelve females and 12 males (mean age of 20.4 years) were given placebo, low, and high doses of alcohol in random order across sessions. Each subject was tested 3 times during each session. The study controlled for recent drinking history by restricting participation to light drinkers who were matched on age and education. Alcohol doses were adjusted for body fat and equivalent blood alcohol concentrations (BACs) were attained in the two gender groups. The results indicated that women and men did not differ in their extent of cognitive impairment at placebo and low alcohol doses. However, women showed significantly more cognitive impairment than their male counterparts at the high alcohol doses, even with equivalent BACs. The sway measure was influenced only by BAC and not by the gender of the subject. Sway observations were less sensitive and more variable than estimates of cognitive impairment. The subjective impairment data indicated that female subjects were less sensitive than males to the effects of alcohol at both the low and high doses. Implications for future research on cognitive impairment are discussed.

Adolescent↗
PubMed1983

Attitudes, beliefs and alcohol use. An analysis of relationships.

The relationships between attitudes toward alcohol and actual drinking behavior were examined. Attitudes toward specific drinking behaviors correlated better with those behaviors than did more global attitudes. Heavy drinkers believed that drinking heavily resulted in positive experiences.

Adolescent↗
PubMed1978

The caloric and intoxicating properties of fluid intake as components of stress-induced ethanol consumption in rats.

Rats housed continuously in a test environment for 25 days were offered water, 5% v/v ethanol, 10% v/v ethanol, and propylene glycol at 7.5% w/v. The propylene glycol concentration represented a caloric midpoint between the 5 and 10% ethanol. After 10 baseline sessions, during which preference for the four solutions was shown to be statistically equal, shock schedules were introduced. The consumption of ethanol at both concentrations showed significant peaks for the interval immediately following 12 min of shock each hour. Intake peaks were not observed for the water or propylene glycol. Baseline blood alcohol levels were negligible, but blood levels under shock averaged 143 mg/dl and ranged from 45.0 mg/dl to 295.0 mg/dl. After the shock sessions were terminated, baseline drinking indicated no significant change in preference relative to pre-shock baselines. but there was an elevation in preference for 5% ethanol relative to the other fluids. The preference for propylene glycol or water did not change.

Alcohol Drinking↗
PubMed1977

The temporal and volumetric components of stress induced drinking in rats.

Two experiments are presented which describe the temporal and volumetric changes in ethanol consumption with rats exposed to recurring schedules of inescapable random shock stress. The animals in Experiment I had an ethanol and water choice and the data demonstrated cumulative increases in voluntary ethanol consumption which occurred immediately after the shock schedule. The post shock changes occurred with both 5% and 10% V/V ethanol, were specific to the appearance of shock and were not reflected by measures of total daily ethanol intake. Experiment II exposed rats to extended 22 hr. stress sessions and each animal had four simultaneous fluid choices available: water, saccharin. 1% W/V, ethanol 5% V/V, and ethanol 10% V/V. Temporal intake patterns for both 5% and 10% ethanol showed pronounced peaks for the interval immediately following the shock schedule. A progressive shift of intake from 5% to 10% ethanol was also evidenced with increasing time under shock, while saccharin and water intake decreased. Blood ethanol levels during shock increased significantly from baseline for all animals and ranged from 30 to 162 mg/100 ml. The results are interpreted as a relationship between voluntary ethanol intake and escape from the consequences of stress.

Adaptation, Psychological↗