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Biomedical subjects

C A Anderson

Publications and source records attributed to C A Anderson.

At least 19 recordsLinked to original sources

Glutamate in the inferior colliculus plays a critical role in audiogenic seizure initiation.

Alterations of excitant amino acid (EAA) action are implicated in seizure susceptibility in the genetically epilepsy-prone rat (GEPR). The inferior colliculus (IC) is critical for audiogenic seizure (AGS) initiation in the GEPR. The present study observed that bilateral microinjection into the IC of L-canaline, a glutamate synthesis inhibitor, decreased AGS severity in the GEPR and also decreased potassium-evoked release of glutamate from IC slices. Bilateral microinjection of NMDA receptor antagonists, 2-amino-7-phosphonoheptanoate (AP7) or 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP) into IC blocked AGS, and an antagonist at non-NMDA EAA receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), also blocked AGS. NMDA receptor antagonists were 5-200 times more effective than CNQX. Microinjection of a non-competitive NMDA receptor antagonist, dizocilpine (MK-801), into IC had little effect except with very high doses. Microinjection of CPP or AP7 into the IC blocked AGS at considerably lower doses as compared to pontine reticular formation (PRF). However, MK-801 attenuated AGS when microinjected into PRF at doses that were ineffective in IC. Systemically administered CPP blocked AGS and significantly reduced IC neuronal firing in the behaving GEPR, suggesting an important action of systemically administered NMDA receptor antagonists on brainstem auditory nuclei critical to AGS. The present results support a critical role for glutamate acting, in part, through NMDA receptors in IC in initiation of AGS.

Acoustic Stimulation

Takayasu arteritis.

Takayasu Arteritis is a vasculitis of the giant cell type which affects young people. Complications of this disease can include myocardial infarction, stroke, limb loss, renal failure, and mesenteric ischemia. A case study demonstrates some of the complexities of diagnosis and treatment for this condition. Nursing care should be directed toward the alteration in tissue perfusion, prevention of infection in a patient on immunosuppressive therapy, and a variety of potential problems with coping.

Adult

Reversible effects of triamcinolone and lack of effects with aspirin or L-656,224 on external genitalia of male Sprague-Dawley rats exposed in utero.

Inhibitors of the arachidonic acid cascade were given to pregnant rats during the critical period for morphogenesis of the external genitalia. Groups treated subcutaneously (s.c.) with 0.1 or 0.25 mg/kg/day of triamcinolone acetonide (TA) on gestational days (GD) 14-19 had male fetuses on GD 20 with moderate decreases in absolute anogenital distance (AGD), but gross and histological examinations revealed no alterations to the genital tubercle (i.e., no hypospadias). The s.c. coadministration of arachidonic acid at 100 mg/kg/day had minimal to no effect on AGD in the TA-exposed groups. No effect on AGD was observed in male fetuses from groups administered aspirin orally at 150 mg/kg/day, and only a 6% decrease was observed in the 300-mg/kg/day group. Neither TA nor aspirin adversely affected AGD of female fetuses. In another study, TA was administered on GD 11-19 at dose levels of 0.05 and 0.1 mg/kg/day, and dams were allowed to deliver. High-dose male offspring examined on postcoitum day (PCD) 23, had moderate decreases in AGD. In both studies with TA, there were also significant decreases in offspring weights. The contribution of the decreased weight to the decrease in absolute AGD was examined by a variety of methods (ratio of AGD to cube root of weight or biparietal distance, comparison to weight-matched controls, and covariance analysis). We conclude that TA caused a specific decrease in AGD on GD 20 that was largely reversed by PCD 23. When examined as adults (8 weeks old), the external genitalia of TA-exposed offspring were normal. Thus, the TA-induced decreases in AGD on GD 20 did not predict irreversible malformation. TA also caused other effects, which included a somewhat flattened genital tubercle and apparently thinned and glossy skin between the tubercle and the anus in both sexes on GD 20 and PCD 23, but not as adults. In addition, there were high pup mortality and high incidences of micrognathia and omphalocele (in the 0.25-mg/kg/day group only). Aspirin at 75 or 150 mg/kg/day and a specific lipoxygenase inhibitor (L-656,224) at 1,000 or 2,000 mg/kg/day were also administered from GD 14 to 19, and no offspring effects were observed. Thus, of the three agents that potentially inhibit the arachidonic acid cascade, only triamcinolone produced moderate effects on rat external genitalia that were largely reversible.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Drug-Induced

Loss of intensity-induced inhibition in inferior colliculus neurons leads to audiogenic seizure susceptibility in behaving genetically epilepsy-prone rats.

The genetically epilepsy-prone rat (GEPR) exhibits elevated seizure sensitivity and audiogenic seizures (AGS). The inferior colliculus (IC) is the most critical brain region for AGS initiation. The present study evaluated IC neuronal firing and convulsive behavior simultaneously in freely moving GEPRs. High intensity acoustic stimulation produces neuronal firing reductions (intensity-induced inhibition) in about 50% of IC neurons in normal rats. However, in GEPR IC neurons, intensity-induced inhibition is significantly less effective than normal. Offset inhibition is also reduced in GEPR IC neurons, which leads to a greater than normal incidence of offset (afterdischarge) responses at high stimulus intensities. At AGS onset most IC neurons exhibit burst firing and reductions of acoustically evoked neuronal responses. Responsiveness to acoustic stimuli returns following AGS. This change in IC neuronal firing pattern suggests that the network that governs IC neuronal firing has temporarily changed from the auditory system to the network that mediates seizure propagation. GABA is strongly implicated in intensity-induced, binaural, and offset inhibition in IC neurons. The diminished efficacy of these forms of GABA-mediated acoustically evoked inhibition in the GEPR IC extends previous results, showing reduced effectiveness of exogenously applied GABA and benzodiazepine in GEPR IC neurons. This reduced effectiveness of GABA-mediated inhibition along with excess excitant amino acids in GEPR IC, previously reported, appear to be vital neurotransmitter mechanisms, subserving the exaggerated output of IC neurons at high acoustic intensities. This exaggerated IC firing may be instrumental in seizure initiation in this epilepsy model.

Acoustic Stimulation

Implementing continuous quality improvement (CQI) in hospitals: lessons learned from the International Quality Study.

Continuous Quality Improvement is in the process of being implemented in hospitals around the world. In an attempt to gain a better understanding of the "best management practices" the International Quality Study is being conducted in four countries--Canada, Germany, Japan and the United States--and across four industries--Health Care, Banking, Automotive and Computers. Information collected through a survey process will be analysed through causal modeling to determine correlations between management practices and achievement of quality objectives. Given both the complexity of the models and the number of key concepts involved, 400 hospitals have been invited to participate. The preliminary results show direct correlations between cultural influences and the concept of quality. The perceived definition of quality by the various countries varies and therefore the application of "quality concepts" differs. Once complete, this database of "best management practices" will serve as a worldwide benchmark for quality progress.

Canada

External genitalia of the rat: normal development and the histogenesis of 5 alpha-reductase inhibitor-induced abnormalities.

The normal histogenesis of the rat genital tubercle and the effect of exposure in utero to the 5 alpha-reductase inhibitor finasteride (L-652,931; MK-0906; Proscar) on that process were studied. In normal males and females, the genital tubercle was first seen on Day 14.25 of gestation. It contained a urethral plate which extended from the cloaca (and after Day 15.25, from the urogenital sinus) to the tip of the tubercle. On Day 18.25 the glans lamellae, which would separate the glans penis or the clitoris from the prepuce, began to develop in both sexes. Also on Day 18.25 a dense, midline plate of mesenchymal cells was first evident between the urogenital sinus and the rectum in normal males. This plate acted as a wedge, first increasing the separation between the rectum and the urogenital sinus, and subsequently separating the urethral plate from the surface epithelium in the genital tubercle. As a result, by Day 21.25 the urethra in males followed an "S"-shaped course, extending from the pelvis through the center of the glans penis to an orifice near the tip of the genital tubercle. In females, in which a mesenchymal plate did not develop, the urethral orifice remained at the base of the tubercle, and the clitoris contained the remnants of the urethral plate, extending as an open groove from the urethral orifice to the tip of the tubercle. Finasteride did not affect development of the genital tubercle in females. However, in males exposed to finasteride in utero, there was variable failure of the mesenchymal wedge to develop. As a result, the urethral plate remained in contact with the surface epithelium and eventually opened to form a groove on the ventral surface of the glans penis (hypospadias). Also, the persistence of the urethral plate along the ventral midline in finasteride-treated male fetuses and its subsequent opening as a groove interfered with development of the glans lamellae, causing displacement of the frenulum distally on the glans penis and the development of a cleft in the prepuce.

Androstenes

Army trauma research: tapping the potential.

Trauma management is the primary mission of military surgeons. Since the Vietnam War, however, military surgeons have relinquished leadership in clinical trauma care to the civilian sector, particularly to urban university surgeons. In this paper we explore whether the Army's contribution to trauma research has also diminished. Using standard bibliometric analysis of publication counts, we have shown that few recent publications related to trauma have originated from U.S. Army Medical Centers, compared with adjacent civilian universities. In 1988, 16 papers originating from the eight Army Medical Centers had key words related to trauma. In contrast, eight universities adjacent to the Army's medical centers published 139 articles on trauma. Problems including lack of clinical exposure to trauma patients, lack of funding, and inadequate emphasis on staff research training have contributed to this decline. We review these factors and describe solutions that could reverse this trend.

Humans

Protective effect of a synthetic peptide comprising the complete preS2 region of the hepatitis B virus surface protein.

A peptide was synthesized containing the entire 55 amino acid residue sequence of the hepatitis B virus (HBV) surface antigen preS2 region (ad subtype). The unconjugated peptide was inoculated into four chimpanzees. Following multiple injections, all of the animals developed specific antipeptide antibodies that reacted with intact surface antigen particles bearing the preS2 moiety. All four peptide-inoculated animals were found to be protected from infection after intravenous challenge with live HBV of either the ad or ay subtypes.

Animals

Temperature and aggression: ubiquitous effects of heat on occurrence of human violence.

Outlines 5 models of the temperature-aggression hypothesis: negative affect escape, simple negative affect, excitation transfer/misattribution, cognitive neoassociation, and physiological-thermoregulatory. Reviews relevant studies. Aggression measures include violent crime, spouse abuse, horn-honking, and delivery of electric shock. Analysis levels include geographic regional, seasonal, monthly, and daily variations in aggression, and concomitant temperature-aggression effects in field and laboratory settings. Field studies clearly show that heat increases aggression. Laboratory studies show inconsistencies, possibly because of several artifacts. Specific models have not been adequately tested, but the excitation transfer/misattribution and cognitive neoassociation approaches appear most promising, whereas the negative affect escape appears the least viable. Suggestions for future work are made.

Aggression

Temperature and aggression: effects on quarterly, yearly, and city rates of violent and nonviolent crime.

The hypothesized relation between uncomfortably hot temperatures and aggressive behavior was examined in two studies of violent and nonviolent crime. Data on rates of murder, rape, assault, robbery, burglary, larceny-theft, and motor vehicle theft were gathered from archival sources. The first three crimes listed are violent; the latter four are less violent (labeled nonviolent). On the basis of previous research and theory (Anderson & Anderson, 1984), it was predicted that violent crimes would be more prevalent in the hotter quarters of the year and in hotter years. Furthermore, it was predicted that this temperature-crime relation would be stronger for violent than for nonviolent crime. Study 1 confirmed both predictions. Also, differences among cities in violent crime were predicted to be related to the hotness of cities; this effect was expected to be stronger for violent than for nonviolent crimes. Study 2 confirmed both predictions, even when effects of a variety of social, demographic, and economic variables were statistically removed. Theoretical and practical implications are discussed.

Aggression

Neurovirulence of the UC-2 and UC-8 strains of bluetongue virus serotype 11 in newborn mice.

In vivo and in vitro experiments were done to investigate whether the difference in neurovirulence between the two strains of bluetongue virus 11, UC-2 and UC-8, is based on a different capability to gain access to the brain from the subcutaneous inoculation site or on a different tropism for neural cells. In newborn Balb/c mice subcutaneous inoculation of UC-8 at doses between 10(-0.2) plaque forming units (PFU) and 10(4.8) PFU caused a severe necrotizing encephalitis whereas UC-2 at doses of up to 10(4.4) PFU did not affect newborn Balb/c mice. However, intracranial inoculation of 10(2.4) PFU of either virus strain produced severe necrotizing encephalitis. In vitro both virus strains infected dissociated brain cell cultures similarly. Double labelling immunofluorescent staining with markers specific for neural cells did not reveal differences in the target cells for the two viruses. The difference in neurovirulence between UC-2 and UC-8, therefore, appears to be determined by the ability of UC-8 to infect the brain from a subcutaneous inoculation site.

Animals

Border disease. Virus-induced decrease in thyroid hormone levels with associated hypomyelination.

Border disease (BD) was induced in lambs by inoculation of their dams at 50 days gestation with Border disease virus (BDV) isolate #31. At birth, the clinically affected lambs had diffuse spinal cord hypomyelination, confirmed by immunocytochemical staining for myelin-associated glycoprotein and myelin basic protein. In the BD lambs, large numbers of thyroid follicular epithelial cells and scattered pituitary cells contained BDV antigen by immunofluorescence staining. Double labeling techniques demonstrated the BDV-infected pituitary cells to contain growth hormone, adrenocorticotrophic hormone, prolactin, or luteinizing hormone. Cells containing thyroid stimulating hormone were rare and were not positive for BDV antigen. Infection of the pituitaries and thyroid glands caused no detectable morphologic changes as compared to controls. The BD lambs had statistically significantly (p less than 0.05) lower mean serum concentrations of thyroxine and L-3,3',5-triiodothyronine as compared to age-matched uninfected controls. Similar significant differences in the mean plasma levels of growth hormone and thyroid stimulating hormone were not found. In addition, the BD lambs had a statistically significant (p less than 0.05) lower mean activity of the myelin-associated, thyroid hormone dependent enzyme, 2',3'-cyclic nucleotide-3'-phosphodiesterase in spinal cord tissue. Although not conclusive, these results indicate that the hypomyelination in BD may be due to depressed levels of circulating thyroid gland hormones secondary to a noninflammatory and noncytolytic infection of the thyroid gland by BDV. This is one of the first reports indicating that a virus-induced hormonal alteration may cause a congenital lesion in animals.

Animals

Experimentally induced ovine border disease: extensive hypomyelination with minimal viral antigen in neonatal spinal cord.

Border disease (BD) was experimentally induced in 9 lambs by inoculation of their dams with the BD-31 strain of border disease virus (BDV) at 50 days of gestation. These ewes developed serum-neutralizing antibody titers to BDV. The diagnosis of BD in their lambs was confirmed by hairy birthcoats, intrauterine growth retardation, tremors, and hypomyelination. Three clinically healthy age-matched control lambs, whose dams had been given an inoculum containing only BDV-free cell culture supernatant, were studied in parallel. There were significant differences in birth weights and in the lengths of the right tibiae and radii between the affected and the control lambs. There was a gradient in severity of clinical neurologic signs among the affected lambs, which directly correlated with the severity of hypomyelination in their spinal cords. However, the difference in severity of the neurologic deficits did not correlate with differences either in the precolostral serum-neutralizing antibody titers to BDV in these lambs or in the number of BDV antigen-containing cells in their spinal cords. Only approximately 0.01% to 0.3% of spinal cord cells, both in gray matter and white matter, were BDV antigen positive in the affected lambs. These results indicate that extensive infection of CNS cells with their subsequent destruction or functional alteration may not be a critical part of the pathogenesis of the hypomyelination in BD.

Animals

Enzyme-linked immunosorbent assay for the detection of antibodies to bovine virus diarrhea virus in sera from border disease virus-infected sheep.

An enzyme-linked immunosorbent assay (ELISA) was established for the rapid detection of specific antibodies against the causative agent of border disease in ovine sera. Polyethylene-glycol concentrated, equilibrium density gradient purified bovine virus diarrhea virus was used as test antigen. The optimal amount of antigen was 0.5 microgram/well, and the optimal concentration of conjugate was at 1/4,000 dilution. A total of 20 ovine serum samples, which had been collected from animals with or without border disease, were compared by ELISA and serum neutralization test for the detection of border disease-specific antibodies. ELISA was shown to be equally specific but less time-consuming and easier to perform than serum neutralization test. A positive correlation (r = 0.60) between the two tests was found.

Animals