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Biomedical subjects

C A Anderson

Publications and source records attributed to C A Anderson.

At least 55 records · Page 3Linked to original sources

Blockade of GABA uptake with tiagabine inhibits audiogenic seizures and reduces neuronal firing in the inferior colliculus of the genetically epilepsy-prone rat.

Tiagabine is a new anticonvulsant drug that blocks the uptake of GABA, prolonging the action of this inhibitory transmitter. In the present study the effects of systemically administered tiagabine [30 mg/kg, ip (ED50)] were examined on audiogenic seizure (AGS) severity and neuronal firing in the inferior colliculus (IC) in the freely moving genetically epilepsy-prone rat (GEPR-9). The IC is known to be critical to AGS initiation. The effects of focal microinjection of tiagabine into the IC were also examined. Bilateral focal microinjection of tiagabine into the IC significantly reduced seizure severity in the GEPR-9. Systemically administered tiagabine also produced a significant reduction in seizure severity in the GEPR-9. Tiagabine produced a reduction in IC (central nucleus) neuronal firing, which was significant only at high acoustic intensities (90-105 dB), concomitant with the considerable reduction in seizure severity. These data are consistent with enhancement by tiagabine of gamma-aminobutyric acid (GABA)-mediated inhibition in IC, which is most prominent at high acoustic intensities. The time course of the reduction in neuronal firing of IC neurons paralleled the reduction in seizure severity. Previous studies have shown that two forms of GABA-mediated inhibition (intensity-induced and offset inhibition) in IC neurons are most prominent at high stimulus intensities, which are required to induce AGS. The blockade of GABA uptake by tiagabine may act to inhibit audiogenic seizures, in part, by intensifying these naturally occurring forms of acoustically evoked inhibition in inferior colliculus neurons.

Acoustic Stimulation↗

Mother-child interactions in ADHD and comparison boys: relationships with overt and covert externalizing behavior.

Reciprocal relationships between child characteristics and such familial factors as parental psychopathology and interaction style with the child characterize the development and maintenance of attention-deficit hyperactivity disorder (ADHD) as well as its comorbidity with antisocial behavior. Our goal was to ascertain the ability of negative maternal behavior exhibited during mother-son interactions to predict independently observed overt and covert externalizing behavior in the child, controlling for current maternal symptomatology and the boy's acting out behavior during the interaction. Participants were 49 boys with ADHD and 37 comparison boys, aged 6 to 12 years. Hierarchical multiple-regression analyses revealed that, even with maternal psychopathology and child negativity with the mother partialed, maternal negative behaviors predicted both observed noncompliance exhibited in class and play settings and laboratory stealing. Stealing was predicted from maternal negativity even with child interactional compliance controlled. Differential predictions of noncompliance were revealed in ADHD versus comparison families, yet similar patterns emerged for stealing within each group. Results are discussed in light of the high risk for antisocial behavior in ADHD children.

Acting Out↗

Behavioral and characterological attributional styles as predictors of depression and loneliness: review, refinement, and test.

The literature on self-blame and depression reveals two interrelated problems. First, although R. Janoff-Bulman's (1979) conceptualizations of self-blame are clear, empirical operationalization is difficult and has resulted in approaches that do not capture the richness of the constructs. Second, past research has produced inconsistent findings. A comprehensive literature review revealed that the inconsistencies are related to the method of assessing attributions. A correlational study designed to more accurately represent the self-blame conceptualization revealed that both behavioral and characterological self-blame contribute uniquely to depression and loneliness. Supplementary results regarding circumstantial attributions and regarding attributional styles for success were presented. Empirical issues regarding possible methodological refinements and effect size, as well as the value of categorical approaches to the study of attributional style were discussed.

Character↗

Induction of antigen-specific killer T lymphocyte responses using subunit SIVmac251 gag and env vaccines containing QS-21 saponin adjuvant.

Subunit vaccines based on recombinant proteins have proved useful for inducing antibody responses and they are safe for widespread use because they do not contain any live components. Unfortunately, they do not typically induce the types of cell-mediated immune responses required to control viral pathogens; specifically, they do not induce CD8+ cytotoxic T lymphocyte (CTL) responses. To increase the immunogenicity of recombinant proteins, we have used the QS-21 saponin adjuvant in subunit vaccine formulations. In the current study, experimental subunit vaccine formulations containing recombinant p55gag or gp120env proteins from the mac251 strain of the simian immunodeficiency virus (SIVmac251) and the QS-21 adjuvant were used to immunize rhesus macaques. These formulations induced SIV gag- or env-specific cellular immunity that was detectable in vitro and included killer cell activity. The induction of killer cells required prior vaccination and the responses were antigen specific for the immunogens contained in the vaccine formulations. Autologous target cells were required to detect these responses, suggesting genetic restriction, and effector cells appeared to be present in both the CD4+ and CD8+ T lymphocyte subpopulations. These data suggest that the vaccine-induced killer cell activity that was detected was mediated by both CD4+ and CD8+ lymphocytes. Despite the presence of these killer cells, all of the animals became infected with the SIVmac251 on experimental challenge. These findings demonstrated that antigen-specific killer cell responses could be induced by a subunit vaccine formulated with the QS-21 saponin adjuvant. The characteristics of the responses suggested that the effector cells were T lymphocytes, expressing either CD4 or CD8.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Use of fixed autologous stimulator cells to correctly present human immunodeficiency virus type 1 viral peptides to nonhuman primate lymphocytes in proliferation and cytotoxic T-lymphocyte assays.

Autologous, virus-transformed lymphoblastoid cell lines were established by using peripheral blood lymphocytes from rhesus monkeys that were previously immunized with recombinant human immunodeficiency virus type 1 strain IIIB glycoprotein 160. These autologous cell lines were used to present human immunodeficiency virus type 1 viral antigens in a processed and cell-associated manner to T lymphocytes. This was accomplished by either infecting the cells with recombinant vaccinia viruses or pulsing them with synthetic peptides and then subjecting them to a mild fixation step with glutaraldehyde. Fixed antigen-presenting cells were then used as stimulator cells in vitro to measure cell-mediated immune responses. Both the vaccinia virus-infected and peptide-pulsed autologous cells stimulated antigen-specific cellular proliferative responses. The magnitude of the responses correlated with the immunization histories of the animals and other measures of immunity, such as antibody titers. Autologous vaccinia virus-infected cells were also capable of inducing the in vitro maturation of CD4+ and CD8+ precursor cytotoxic T lymphocytes into antigen-specific mature cytotoxic T lymphocytes. The use of stimulator cells to present viral peptides in a cell-associated manner appeared to be a very sensitive and versatile manner in which to measure cell-mediated immune responses with peripheral blood lymphocytes from nonhuman primates. It is likely that a similar approach will function with peripheral blood lymphocytes from humans.

Amino Acid Sequence↗

Development of stenoses in transjugular intrahepatic portosystemic shunts.

PURPOSE: To evaluate the frequency and significance of stenoses or occlusions developing within transjugular intrahepatic portosystemic shunts (TIPS) and identify predictive factors. MATERIALS AND METHODS: Medical records of 52 patients who underwent TIPS placement between September 1991 and October 1993 were reviewed. Various shunt parameters were correlated with the development of shunt abnormalities. Findings at follow-up portography and frequency of variceal bleeding and paracentesis were also noted. RESULTS: Twenty-four patients were followed up for at least 6 months. In eight patients, stenoses developed within 6 months; one shunt occluded. No clear correlations were found between shunt parameters and development of shunt abnormalities. Two of four patients with recurrent variceal bleeding had associated shunt abnormalities. The frequency of stenosis of TIPS was high. CONCLUSION: Early detection and prompt revision of stenotic shunts may decrease the frequency of recurrent variceal bleeding and ascites.

Adolescent↗

Critical developmental periods for effects on male rat genitalia induced by finasteride, a 5 alpha-reductase inhibitor.

The conversion of testosterone to 5 alpha-dihydrotestosterone by the enzyme 5 alpha-reductase is inhibited by finasteride. In a study in which maternal dosing with finasteride commenced on Gestational Day 15 and terminated on Postpartum Day 21, there were 13 and 27% decreases in anogenital distance of male pups on Postnatal Day 1 at 0.03 and 3 mg/kg/day, respectively. These decreases were largely reversed by Postnatal Day 22 even though treatment of the dams continued. Treatment at 3 mg/kg/day also resulted in hypospadias with cleft prepuce and a 5-day delay in the separation of the prepuce from the glans penis in those animals without hypospadias. A second study in which 20 mg/kg/day finasteride was administered on successive 2-day periods during late gestation in rats demonstrated that the period of Gestational Days 16 to 17 was the most sensitive (critical period) for finasteride-induced hypospadias, cleft prepuce, decreased anogenital distance, reduced prostate weight, and nipple formation in F1 male offspring. This critical period is just prior to the appearance on Day 18 of gestation of a midline mesenchymal plate between the urogenital sinus and the rectum in normal male fetuses. This midline plate does not appear in finasteride-exposed fetuses destined to have hypospadias as demonstrated in a previous study. Based on these observations, we hypothesize that finasteride causes hypospadias by preventing the formation of the medial mesenchymal plate which is necessary for assisting the movement of the urogenital sinus from the base to the tip of the genital tubercle.

5-alpha Reductase Inhibitors↗

Stimulation or blockade of the dorsal nucleus of the lateral lemniscus alters binaural and tonic inhibition in contralateral inferior colliculus neurons.

Recent studies have demonstrated that several specific types of acoustically-evoked GABA-mediated inhibition occur in neurons of the central nucleus of inferior colliculus (ICc). The dorsal nucleus of the lateral lemniscus (DNLL) provides a major GABAergic projection to ICc. The present study examined the effects of electrical or chemical stimulation or reversible blockade within the DNLL on the discharge characteristics of ICc neurons in anesthetized rats. Microinjection of a local anesthetic (lidocaine) or a GABA-A agonist (THIP) via a cannula placed into DNLL reversibly blocked acoustically-evoked binaural inhibition and increased spontaneous firing in most contralateral ICc neurons. Trains of electrical pulses or microinjection of the excitant amino acid, kainate, into DNLL resulted in reduced acoustically-evoked firing, which was similar to binaural inhibition, in most contralateral ICc neurons examined. The effects of DNLL electrical stimulation were reversibly blocked by microinjection of THIP into the stimulation site, suggesting that the effect of the electrical stimulation is mediated by direct effects on cell bodies of DNLL neurons. These data support the idea that contralateral GABAergic input from the DNLL is inhibitory to ICc neurons. Thus, binaural inhibition and tonic inhibition in ICc neurons may be mediated, in part, by the GABAergic projection from the contralateral DNLL.

Acoustic Stimulation↗

Psychosocial outcomes of children of unipolar depressed, bipolar, medically ill, and normal women: a longitudinal study.

The psychosocial functioning of children of unipolar depressed, bipolar, medically ill, and psychiatrically normal women was studied over a 2-year period. Ninety-six children aged 8-16 years were assessed at 6-month intervals on Child Behavior Checklist behavior problems, social competence, internalizing and externalizing behaviors, academic performance, and school behavior. The children of unipolar mothers showed significantly poorer functioning on all measures as compared with the other 3 groups of children, including bipolar offspring. A greater proportion of children in the unipolar group also had relatively chronic, clinically significant problems in psychosocial functioning. Children of bipolar women did not differ from children of psychiatrically normal women. Results are discussed in terms of the consequences of children's continuing exposure to maternal depression and attendant stressors, as well as the contribution of social and academic difficulties to a vicious cycle of maladjustment.

Adolescent↗

Laparoscopic colostomy closure.

Perforated sigmoid diverticulitis often results in the patient undergoing a sigmoid resection, closure of the rectal stump, and an end sigmoid colostomy. To reestablish intestinal continuity, the patient must undergo a second major intra-abdominal operation. We have developed a technique of laparoscopic colostomy closure to reestablish intestinal continuity and have used it in two patients. Because of the reduced operative pain and shorter recovery period, this minimally invasive technique would be a better surgical alternative to colostomy closure.

Aged↗

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↗

Quality mind-set overcomes barriers to success.

To remove hindrances to fiscal strength, a healthcare facility needs a long-term, organization-wide strategy. Total quality management (TQM) can offer such a solution, but it requires a revised management philosophy. Under TQM, a hospital must adopt a workable definition of quality; develop a customer orientation; form organizational teams to study and revise work processes; involve all employees in quality efforts; and strive for continuous improvements.

Costs and Cost Analysis↗