Search PubMed⌕ Search

Biomedical subjects

A Campbell

Publications and source records attributed to A Campbell.

At least 127 records · Page 7Linked to original sources
PubMed1993

Developmental differences in acute nigrostriatal and mesocorticolimbic system response to haloperidol.

Dose-dependent effects of haloperidol (2.66 nmol/kg to 79.8 mmol/kg, IP) on levels of dopamine, homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) were assessed in the corpus striatum, nucleus accumbens, and medial prefrontal cortex (PFCTX) of 18-, 30-, and 110-day-old rats. Eighteen-day-old rats were 35% and 63% more sensitive than adults to the effects of haloperidol on striatal and accumbens turnover and had steeper dose-response curves. The dose-response function in the PFCTX was similar to striatum at 18 days, but became shallower and nonsigmoidal with age. Maximally effective doses of haloperidol produced, at all ages, a comparable percent rise in DOPAC levels in all regions. With maturation, the percent rise in HVA progressively outstripped DOPAC response in nucleus accumbens and striatum. Overall, prominent developmental differences emerged in these regions in their sensitivity and response to haloperidol, which are consistent with previously reported differences in behavioral sensitivity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Vascular complications after balloon and new device angioplasty.

BACKGROUND: Despite their potential advantages, new coronary angioplasty devices may be associated with more frequent vascular complications than noted after standard balloon angioplasty, theoretically due to the larger sheaths and prolonged periods of anticoagulation required by some of these devices. This study sought to identify the incidence, predictors, and clinical outcome of vascular complications after new device angioplasty. METHODS AND RESULTS: The clinical course of 1413 patients was reviewed after balloon or new device angioplasty. Vascular complications were defined as formation of a pseudoaneurysm, arteriovenous fistula, retroperitoneal hematoma, or groin hematoma associated with a > 15-point hematocrit drop or the need for surgical repair. Stepwise logistic regression was used to identify independent predictors for vascular complications. Vascular complications developed after 84 (5.9%) procedures; they occurred more frequently after intracoronary stenting (14.0%) and extraction atherectomy (12.5%) than after balloon angioplasty (3.2%) (odds ratios, 4.86; P < .001, and 4.26, P < .05, respectively). Independent predictors of vascular complications included the use of intraprocedural thrombolytic agents (P < .01), intracoronary stenting (P < .005), or extraction atherectomy (P < .05); high maximum creatinine level (P < .005); low nadir platelet count (P < .001); longer periods of excess anticoagulation (P < .05); and the need for repeat coronary angioplasty (P < .005). Vascular complications were not related to the size of the arterial sheath used. CONCLUSIONS: Vascular complications developed more frequently after new device angioplasty than after balloon angioplasty, with the risk for vascular complications directly related to the degree of periprocedural anticoagulation.

Aneurysm, False↗
PubMed1993

Cyclosporin A retention enemas in refractory distal ulcerative colitis and 'pouchitis'.

The aim of this study was to evaluate the use of cyclosporin enemas in patients with distal ulcerative colitis and 'pouchitis' resistant to all conventional medical therapy. In an trial 12 patients with distal ulcerative colitis unresponsive to treatment with topical and oral corticosteroids, 5-aminosalicylic acid, and oral immunosuppressive therapy together with 1 patient with 'pouchitis' unresponsive to repeated courses of antibiotics, topical corticosteroids, and oral mesalazine received 250 mg cyclosporin administered daily as a retention enema. Changes in symptoms and the sigmoidoscopic/histologic appearances of the rectal mucosa were assessed at monthly intervals. Seven of 12 patients with ulcerative colitis improved. There was a strong correlation between clinical and histologic improvement (p < 0.005). Four of 12 patients showed no response. Three of these required colectomy, two of whom had more extensive disease than had previously been documented. The patient with pouchitis showed improvement in symptoms and 'pouchoscopy' appearance but not in histologic score. Cyclosporin blood concentrations were very low and side effects negligible. Cyclosporin A retention enemas are safe and may be useful in the treatment of severe refractory distal ulcerative colitis. A controlled trial would now seem warranted.

Adult↗
PubMed1993

Teenage screening in a general practice setting.

Concern about the apparent lack of health awareness among local teenagers prompted practice nurse Anne Campbell and medical receptionist Sheila Edgar to launch a health promotion programme aimed at this age group. Here they report the success of the 'Teenscreen' project.

Adolescent↗
PubMed1992

Antagonism of limbic and extrapyramidal actions of intracerebrally injected dopamine by ergolines with partial D2 agonist activity in the rat.

Bromocriptine and a series of experimental ergoline D2 partial agonists (SDZ-208-911, SDZ-212-327, SDZ-208-912) were evaluated for their interactions with exogenous dopamine (DA, at ED50 = 16 micrograms) stereotaxically injected unilaterally into a limbic (superior-medial nucleus accumbens septi) or extrapyramidal (central corpus striatum) target site in rat brain. Behavioral measures to quantify responses were locomotor arousal induced by DA in accumbens and contralateral head turning with striatum. All agents, given systemically (i.p.), induced dose-dependent inhibition of behavioral responses to DA from both brain sites. In both accumbens and striatum, SDZ-212-327 was most potent and bromocriptine, least; however, bromocriptine was relatively much more potent in accumbens, and SDZ-208-912 somewhat more potent in striatum. These results add to the growing impression that agents with partial agonist actions at central DA receptors can show behaviorally inhibitory effects that may reflect paradoxical antidopaminergic actions against the full, natural agonist of DA receptors and that such effects can be regionally selective.

Animals↗
PubMed1992

Lambdoid phages as elements of bacterial genomes (integrase/phage21/Escherichia coli K-12/icd gene).

The lambdoid phages are a group of related temperate bacteriophages that lysogenize by site-specific recombination with the bacterial chromosome. Various members of the group have different specific chromosomal insertion sites, despite the fact that the enzymes catalyzing the insertion (integrases) appear to be all descended from a common ancestor. Insertion sites are not located randomly on the E. coli chromosome but are restricted to one segment of the map; also, most prophages are oriented in the same direction along the chromosome. Lambdoid phage 21 inserts within the isocitrate dehydrogenase gene and introduces an alternative 165 bp 3' end for that gene. A defective element (e14) inserts at the same position. We suggest that this mode of insertion arose from insertion of an ancestral phage to the right of icd which then picked up part of the icd gene by abnormal excision and speculate that, at an earlier time, phages may have arrived at their present locations by a process of chromosomal walking.

Bacterial Proteins↗
PubMed1992

Differences between antipsychotic drugs in persistence of brain levels and behavioral effects.

After a single dose of the butyrophenone neuroleptic haloperidol, behavioral effects and detectable drug levels in rat brain can last for several weeks. To determine if such persistence is a general property of neuroleptics, we compared drug levels and effects after IP administration of two butyrophenones (haloperidol and bromperidol), a high potency (fluphenazine) and a low potency (chlorpromazine) phenothiazine. Drug levels in brain tissue were measured by high pressure liquid chromatography and behavioral effects monitored as inhibition of apomorphine-induced stereotypy. Estimated near terminal elimination half-lives (t 1/2) from brain for acutely administered chlorpromazine (20 mg/kg) and fluphenazine (1 mg/kg) were 0.41 and 0.62 days, respectively, and neither drug was detectable after 4 days. Fluphenazine given daily for 5 days showed an only slightly slower elimination (t 1/2 = 1.1 days). In contrast, near-terminal elimination half-lives from brain for haloperidol and bromperidol (both at 1 mg/kg, IP) were much longer (6.6 and 5.8 days, respectively), and each was detectable for 21 days after dosing. Inhibition of apomorphine-induced stereotypy correlated highly (r = 0.95) with brain levels of haloperidol. For fluphenazine, given once or repeatedly, early inhibition was replaced within 1 week by supersensitivity to apomorphine which persisted for up to 3 weeks. These findings, indicating marked differences in clearance and recovery times after dosing with butyrophenones and phenothiazines, have clear implications for studies of the effects of neuroleptic drugs in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Indirect evidence of nasal inflammation assessed by titration of inflammatory mediators and enumeration of cells in nasal secretions of patients with chronic rhinitis.

Pathophysiologic mechanisms of perennial rhinitis are poorly understood. The characterization of inflammation was studied in nasal lavage of patients with perennial rhinitis by the enumeration of cells involved in the allergic inflammation and the measurement of six mediators released in nasal secretions to determine whether some mediators were relevant for the etiologic diagnosis and the occurrence of symptoms. Ten healthy subjects and 57 patients with perennial rhinitis were placed into four groups according to the symptoms they presented at the time of the study and the origin of the allergy. Allergy was characterized by the history, skin prick tests to standardized allergens, and RAST. Eosinophil protein X (EPX), tryptase, histamine, myeloperoxidase, prostaglandin D2, and leukotriene C4/D4 (LTC4/D4) were measured in nasal lavage by enzyme assay or radioimmunoassay. Eosinophils and neutrophils were enumerated after cytocentrifugation of the lavage fluid and May Grunwald Giemsa staining. Tryptase, myeloperoxidase and EPX but not histamine levels were increased in all four patient groups. Eosinophils, LTC4/D4, and prostaglandin D2 were significantly (p < 0.001, p < 0.03, and p < 0.01) increased in allergic and symptomatic patients. EPX was significantly increased in symptomatic allergic and nonallergic patients. This study suggests the involvement of mast cells, neutrophils, and eosinophils, but the latter cells appear to have a more prominent role. The importance of EPX and LTC4/D4 in the characterization of chronic symptomatic rhinitis was also observed.

Adolescent↗
PubMed1992

The driving advisement system: a computer-augmented quasi-simulation of the cognitive prerequisites for resumption of driving after brain injury.

No other activity so starkly pits the needs of the individual recovering from brain injury against the protection of society than does operating a motor vehicle. Cognitive abilities (e.g., response to complex processing demands, impulse control, ability to sustain performance, mental flexibility, and judgment), while evident only indirectly, are essential to performance, yet few are well sampled in currently used assessment procedures, which, instead, emphasize visuo-motor coordination and reaction time. In response to this need, a computerized quasi-simulation, the Driving Advisement System (DAS), was developed and is introduced here. The DAS incorporates a set of computer-based tasks for use by professionals charged with rendering advice concerning cognitive abilities necessary for driving safely. Normative data on DAS measures were obtained from a group of over 60 safe drivers free of significant neurological impairment. Preliminary validation findings are summarized. A sample DAS-generated report for a brain-injury survivor, who sought to resume driving, is used to illustrate the graphic norm-referenced presentation of an individual's performance together with self-appraisal ratings.

Automobile Driver Examination↗
PubMed1992

Controlled study of the effect of nicardipine and ceruletide on the sphincter of Oddi.

Although sphincter of Oddi dysfunction is a recognised cause of post cholecystectomy pain, the control mechanisms involved in sphincter of Oddi function are poorly understood. Pharmacological relaxation of the sphincter of Oddi may have a beneficial effect particularly in sphincter of Oddi dysfunction where basal sphincter pressure is high. The aim of this study was to investigate the effects of calcium channel blockade (nicardipine) and synthetic cholecystokinin (ceruletide) on sphincter of Oddi pressures. Nineteen patients (median age 49 years; range 21-75) attending for routine endoscopic retrograde cholangiopancreatographic (ERCP) examination were studied. No patients with evidence of sphincter of Oddi dysfunction were included in the study. Each patient was randomly allocated to receive a three minute intravenous infusion of nicardipine 3 mg (six) ceruletide 5 ng/kg (seven) or placebo (six). Endoscopic biliary manometry was done with recording of basal sphincter of Oddi pressures, sphincter of Oddi phasic wave amplitude and frequency before and after intravenous infusions. In the nicardipine group patients showed a decrease in both basal and phasic amplitude sphincter of Oddi pressure (mm Hg) from the preinfusion values (mean (SEM)) of 24.7 (3.6) and 112.3 (13.4) to 12.9 (2.9) (p less than 0.01) and 89.9 (12.4) (p less than 0.03) after infusion respectively. Ceruletide produced a decrease in sphincter of Oddi phasic wave frequency (c/min) from 3.4 (0.3) before infusion to 2.6 (0.5) after infusion (p less than 0.05). We conclude that nicardipine effectively decreases sphincter of Oddi pressure. This drug may therefore be of value in the treatment of sphincter of Oddi dysfunction where raised sphincter pressures are thought to be the primary pathogenic feature.

Adult↗
PubMed1992

Do central antiadrenergic actions contribute to the atypical properties of clozapine?

Full neuropharmacological understanding of the atypical antipsychotic agent clozapine remains elusive. Antidopaminergic actions of most neuroleptics probably contribute to their antipsychotic benefits, but also to neurological side-effects. Clinical evidence of abnormalities of dopamine (DA) and serotonin (5-HT) in psychotic disorders is inconsistent, but there is substantial metabolic and post-mortem evidence for hyperactivity of noradrenaline (NA). Clozapine is only weakly antidopaminergic but is a potent antagonist at brain alpha 1-adrenergic, 5-HT2-serotonergic, and muscarinic receptors. Its apparent limbic-over-extrapyramidal neurophysiological selectivity can be mimicked by combining a typical neuroleptic with a central alpha 1 antagonist. Clozapine strongly upregulates alpha 1, but not DA, receptor abundance, and may supersensitise alpha 1 but not DA receptors in rat brain. Clozapine also selectively increases activity of NA neurons and metabolic turnover in NA more than DA areas of rat brain, and also increases NA, but not DA or 5-HT, metabolites in human CSF. Potential psychotropic effects of selective central antiadrenergic agents may deserve reconsideration.

Clozapine↗
PubMed1992

Prolonged D2 antidopaminergic activity of alkylating and nonalkylating derivatives of spiperone in rat brain.

Alkyl and arylalkyl derivatives of the dopamine (DA) D2 antagonist spiperone were prepared and characterized chemically and pharmacologically. They included the N-methyl, N-phenethyl (NPS), and N-p-aminophenethyl (NAPS) derivatives, as well as the alkylating isothiocyanato (NIPS), bromacetamido, and ethylfumaramido p-substituted N-phenethylspiperones. These compounds showed high lipophilicity (log P up to 6.0 with NIPS), as well as very high in vitro D2 affinity (Ki = 35-280 pM) and D2 versus D1 selectivity (540-9000-fold) in radioreceptor assays with corpus striatum of rat brain. Of the alkylating series, NIPS showed the highest D2 affinity (57 pM) and D2 versus D1 selectivity (2040-fold) and so was selected for further evaluation. NPS, NAPS, and NIPS showed little or no affinity for 34 non-DA binding sites defined by radioligand assays for monoamine, amino acid, and peptide neurotransmitters, ion channels, peptide growth factors, and transmission mediators but did show low alpha 2 and moderate alpha 1 and 5-hydroxytryptamine (5-HT2) affinity with rat forebrain tissue in vitro; NIPS showed a marked gain in D2 versus 5-HT2 selectivity, compared with spiperone (1520- versus 26-fold). Systemic injections of NIPS induced marked decreases in rat striatal D2 binding sites 24 hr later, with little effect on D1, 5-HT2, or alpha 1 sites; NIPS and NAPS lowered apparent Bmax values at D2 receptors with little change in ligand affinity, ex vivo as well as in vitro. NPS, NAPS, and NIPS all induced dose-dependent lowering of D2 binding ex vivo (ID50 = 1-9 mumol/kg, intraperitoneally) and blocked the behavioral effects of the DA agonist apomorphine (0.9 mumol/kg) potently (ID50 = 0.3-0.5 mumol/kg) at 24 hr. Recovery from these anti-DA actions required about 1 week after equimolar (15 mumol/kg) and similarly effective doses of NPS and NAPS, as well as NIPS. Thus, highly selective and avidly bound lipophilic D2 affinity ligands with similarly avid in vitro and prolonged in vivo anti-DA activities can be derived from N-phenethylspiperones with or without an alkylating moiety present. Such affinity ligands may represent useful additions to previously used, generally less selective, D2 affinity ligands.

Alkylating Agents↗