Biomedical subjects
Publications and source records attributed to A Anderson.
Job satisfaction of the nursing staff at a 1,000-bed neuropsychiatric veterans administration (VA) facility was assessed, with results similar to those of other studies. The greatest source of stress was nurse/supervisor and nurse/physician interpersonal conflict. This article reports on a further study of this factor.
Advanced practice nurses have a unique opportunity to meet the health needs in our communities. Although laden with barriers and challenges, independent practice is a viable option for advanced practice nurses. This article reviews the critical steps to developing and implementing a budget and operational plan for a successful independent nursing practice.
Explore the source record for details and available documents.
Cytochrome P450 2B1, encoded by CYP2B1, and cytochrome P450 2B2, encoded by CYP2B2, are inducible in rat liver by phenobarbital (PB). We have used cultured adult rat hepatocytes to study molecular mechanisms regulating CYP2B1/CYP2B2 transcription. Northern blot analysis demonstrated that the endogenous CYP2B1/CYP2B2 genes were inducible by PB in such cultures. A PB-responsive element (PBRE) conferring PB inducibility on a reporter gene was identified in the CYP2B2 5'-flanking region. The PBRE was localized to a 163-bp Sau3AI fragment situated between 2155 and 2318 bp upstream from the CYP2B2 transcription start point (tsp). The PBRE also conferred PB responsiveness on an enhancerless heterologous promoter and was active in both orientations both upstream and downstream from the heterologous promoter; hence, it has the properties of a transcriptional enhancer. Gel-retardation assays showed that nuclear extracts of liver cells of untreated and PB-treated rats contained sequence-specific DNA-binding factors that interact with a PBRE-containing DNA fragment. These results may open the way to identifying one or more transcription factors mediating induction of CYP2B2 and CYP2B1 in rat liver.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Sheep infected with maedi visna virus were tested for immune reactivity to recombinant HSP65 and tuberculin PPD from mycobacteria. The results showed that both naturally and experimentally infected animals had elevated IgM but not IgG or IgA antibodies to HSP65 from Mycobacterium leprae or M. bovis. In experimentally infected animals, the elevated IgM antibodies appeared in blood from about 3 to 4 weeks postinfection. Increased T cell proliferative responses to HSP65 and PPD were also found in both naturally and experimentally infected sheep. The T cell responses to HSP65 were substantially inhibited by antibodies to ovine major histocompatibility complex class II molecules, indicating that the responses were class II restricted. Increased expression of a putative HSP65 molecule was observed in synovial membranes from sheep infected with maedi visna virus and goats infected with the related, caprine arthritis encephalitis virus. The results thus show that lentivirus infection induces T and B cell anti-HSP65 immune responses and suggest that synovial inflammation may be due, at least in part, to T and B cell recognition of HSP65-like molecules expressed in joints.
Synovial membranes and cartilage slices from sheep infected with the maedi-visna retrovirus were examined for immunoglobulin deposits by immunohistology. Granular deposits of IgM and IgG were observed in the synovial membranes and upper layers of cartilage from about 40% of virus-infected sheep. These deposits were present in animals with subclinical joint disease, as well as those affected clinically. No significant deposits were found in the synovial membrane or cartilage from normal sheep. Infected animals tended to have reduced cartilage proteoglycan staining. Altered expression of MHC class II, CD1 and adhesion molecules by chondrocytes in cartilage from infected sheep with clinical or subclinical synovitis was observed suggesting that in vivo cell activation is an early event in cartilage degradation in these infections. Exogenously derived antiviral antibodies exhibited molecular mimicry towards chondrocyte antigens, but no in vivo evidence for cross-reactivity was observed. The results showed that IgM and IgG deposits, putatively containing either virus/antivirus immune complexes or autoantibodies were formed in the joints of sheep with clinical or subclinical synovitis. These immune deposits may initiate and perpetuate chronic inflammation with concomitant activation of chondrocytes leading to pannus formation and cartilage destruction.
We used a microdialysis technique to monitor extracellular methotrexate (MTX) levels during the steady state in a rodent model. Microdialysis probes were implanted in the muscle, liver, and kidney of anesthetized male Wistar rats. MTX (18.75-500 mg/kg) was given as a continuous infusion through a venous catheter, and blood samples were obtained through a second venous catheter. Heparinized plasma, ultrafiltered plasma, microdialysis effluent from tissues, and tissue samples (obtained at the end of experiments) were analyzed for MTX content by high-performance liquid chromatography (HPLC). Steady state was demonstrated in the blood and tissues from 2 h until the end of the experiments (6 h). Extracellular drug levels in muscle and liver displayed a linear correlation with doses, whereas kidney levels reached a plateau at an MTX dose of 150 mg/kg per 6 h. Microdialysis-fluid endpoint levels for muscle, liver, and kidney were positively correlated to the endpoint total tissue levels (r2 = 0.80, 0.85, and 0.68, respectively). In the kidneys, the maximal relative tissue MTX accumulation was measured at a total dose of 75 mg/kg per 6 h. At higher doses, the relative drug sequestration declined to less than half of the values observed at this dose. This study demonstrates that the microdialysis technique can provide reproducible data on MTX tissue exposure in an animal model and that it offers a means of serial and reproducible monitoring of extracellular-tissue MTX levels at steady state and over a wide dose range. Pending additional studies, microdialysis may be a helpful technique for elucidating the kinetics of drug delivery to both targeted and toxicity-prone tissues during chemotherapy.
1. The study was undertaken in male patients aged 61-73 years with essential hypertension. 2. The patients had previously had their blood pressure controlled with the drug studied. 3. A randomized crossover study compared the effect of different drug doses on peak (3 h) and trough (24 h) blood pressure compared to placebo. 4. All drug doses used lowered blood pressure at peak response and the responses with different doses of angiotensin converting enzyme inhibitors were similar. The peak response to felodipine had some dose dependency. 5. Trough blood pressure was not different from placebo with enalapril, 5 and 10 mg, perindopril, 2 mg, felodipine, 2.5 mg but was different with enalapril, 20 and 40 mg, perindopril, 4 and 8 mg and felodipine, 5 and 10 mg. 6. Trough peak ratio was dose dependent, with the greatest dependency seen with enalapril which has the shortest half-life. 7. When low doses of enalapril (5 or 10 mg), perindopril (2 mg) or felodipine ER (2.5 mg) are used it is important to check blood pressure prior to the next dose to ensure that control is achieved and maintained.
This study examined whether a neurologic examination at 6 months of age is predictive of neurodevelopmental outcome at 12 months in very-low-birth-weight (VLBW) infants. A neurologic examination and the Bayley Scales of Infant Development were performed at 6 and 12 months with VLBW infants and full-term (FT) controls. VLBW infants were categorized based on early medical complications. High-risk (HR) infants had diagnoses of bronchopulmonary dysplasia, pulmonary immaturity, grade III or IV intraventricular hemorrhage, and/or periventricular leukomalacia. VLBW infants with other diagnoses were placed in the low-risk (LR) group. Total neurologic scores (NS) improved over time for all three groups but improved more for HR infants, who had more abnormal NS at both time points; NS at 6 months predicted neurologic and developmental scores at 12 months for all three groups, but the relation between 6- and 12-month outcomes was strongest for the HR infants. The neurologic examination may be helpful in assessing VLBW infants' need for referral to early childhood intervention programs.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Rat-liver microsomes were used to activate aflatoxin B1 for in vitro modification of the pS189 shuttle vector and the related signature vector pSP189, both of which carry the Escherichia coli supF gene as a mutational target. Plasmid degradation was minimized by carrying out the in vitro incubations in the absence of Mg2+ ions. Modified plasmids were transfected into human Ad293 cells, then recovered and electroporated into E. coli MBM7070 for mutant identification. Point mutation frequencies for in vitro modified plasmids were dramatically increased over the spontaneous background level. Mutant plasmids were characterized by DNA-sequence analysis. The vast majority of aflatoxin B1-induced mutations were base substitutions, mostly G:C to T:A transversions. The spectrum of aflatoxin B1-induced mutations in the pS189 supF gene was very similar to that observed previously for the pS189 supF gene with aflatoxin B1 activated by cytochrome P450 1A2 (CYP1A2) synthesized from a cDNA expression vector within transfected Ad293 cells. However, the spectrum for pSP189, which carries the same supF gene as pS189, but with different surrounding sequences, exhibited some notable differences from that of pS189; this suggests that sequence context effects on mutagenic specificity can operate over distances of tens of base pairs.
A recent official report on the Scottish Diet reviews evidence for poor health and poor diets among the Scots, and makes extensive and specific recommendations about dietary change. This paper examines the extent to which reported consumption of fifteen of the food groups discussed in that report vary among four neighbourhoods in Glasgow City. Some foods appear to be typical of a wider Glaswegian (or Scottish) diet and show little variation among neighbourhoods (e.g. semi-skimmed milk, white fish, confectionery, cakes and pastries, savoury snacks). Other foods however show marked differences between neighbourhoods after controlling for sex, age and social class; these include fruit, vegetables, meat (particularly processed meat products), bread, spreading fats, sugar, natural fruit juice and alcohol. This suggests that such intraurban variations in food consumption cannot be explained simply by socio-demographic or socio-economic factors in individuals and that cultural and supply factors also need to be taken into account.
The cytochrome P450 2B subfamily in the rat contains an estimated eight to eleven members at the genomic level. Synthesis in the liver of the prototypic forms P450 2B1 and P450 2B2 is dramatically induced by phenobarbital. The 1.9-kb mRNA for P450 2B3, a third member of the P450 2B subfamily, is constitutively present in rat liver but is not inducible by phenobarbital. We have now cloned and sequenced exonic sequences corresponding to the entire 2B3 mRNA and determined their exon-intron structure, which is identical to that of CYP2B1/CYP2B2 and other CYP2B genes. A putative CYP2B3 transcription start site was identified and CYP2B3 5'- and 3'-flanking sequences were compared to those of CYP2B1 and CYP2B2. CYP2B3, like CYP2B1 and CYP2B2, has a modified TATA box preceding the transcription start site and lacks the canonical polyadenylation signal preceding the poly(A) site. A 2B3 expression vector, pMT2-2B3, directed the synthesis in COS-1 cells of an approximately 50-kD protein detectable on Western blots with a polyclonal antibody and with one of four monoclonal antibodies raised against 2B1 but not with a polyclonal antibody raised against P450 PB6. The 2B3 protein migrated with a slightly higher electrophoretic mobility than 2B1 and comigrated with a protein detected by anti-2B1 antibodies in liver microsomes from untreated rats. The results indicate that a 2B3-like protein is present in rat liver and that it is distinct from P450 PB6 and other known constitutive rat hepatic P450s.
Ten patients who had their blood pressure controlled with enalapril (10 mg, n = 4; 20 mg, n = 6) and 10 control subjects on perindopril (4 mg, n = 6; 8 mg, n = 4) entered a double-blind crossover study. They received placebo or the active drug 1 week apart and had their blood pressure measured at 0, 2, 3, 4, and 24 h. Then they crossed over to the other angiotensin-converting enzyme inhibitors (4 mg perindopril congruent to 10 mg enalapril) and the double-blind study was repeated. Blood pressure control 2 to 4 h after drug administration was similar with both drugs (perindopril = 150 +/- 2/80 +/- 1; enalapril = 150 +/- 2/81 +/- 1). Twenty-four h after administration of perindopril blood pressure was lower than on enalapril (perindopril = 154 +/- 3/85 +/- 2; enalapril = 159 +/- 3/89 +/- 2). Enalapril, 2 to 4 h after administration, caused a greater decrease than placebo, whereas the change with perindopril did not differ from placebo. Twenty-four hours after receiving the active drug the blood pressure of subjects on perindopril did not differ from the peak effect when corrected for placebo and circadian variation, whereas the blood pressure on enalapril was higher. This study indicates that perindopril in the doses used has a longer duration of action than enalapril and is more suited to once daily use.