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Biomedical subjects

A Anderson

Publications and source records attributed to A Anderson.

At least 127 records · Page 7Linked to original sources
PubMed1992

Vitamin E in the treatment of chemotherapy-induced mucositis.

PURPOSE: To determine the efficacy of vitamin E in the treatment of chemotherapy-induced mucositis in patients with malignancy. PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled study was performed to evaluate the efficacy of topical vitamin E in the treatment of oral mucositis in patients receiving chemotherapy for various types of malignancy. A total of 18 patients, 17 of whom had solid tumors and one with acute leukemia, were included in this study. Lesions were observed daily prior to and 5 days after topical application of either vitamin E or placebo oil. RESULTS: Six of nine patients receiving vitamin E had complete resolution of their oral lesions. In eight of nine patients who received placebo, complete resolution of their oral lesions was not observed. This difference is statistically significant (p = 0.025 by Fisher's exact test). No toxicity was observed in this study. CONCLUSION: These results suggest that vitamin E may be an effective therapy in patients with chemotherapy-induced mucositis.

Administration, Topical↗
PubMed1992

The detection of promutagen activation by extracts of cells expressing cytochrome P450IA2 cDNA: preincubation dramatically increases revertant yield in the Ames test.

Two slightly different protocols, the plate incorporation method and the preincubation method, are used in the Ames Salmonella mutagen test. Using a preincubation method, we recently demonstrated efficient activation of a number of food-derived promutagens by extracts of mammalian cells expressing cDNAs of rat-liver cytochrome P450IA2 and of a P450IA2-IA1 hybrid. We report here that, for 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 1-aminoanthracene and several other promutagens, preincubation dramatically increased the number of revertant colonies in the Ames test when extracts of cytochrome P450IA2-containing transfected cells or low concentrations of rat-liver extracts were used as the source of activating enzymes. At higher concentrations of rat-liver extract protein, the effect of preincubation was less pronounced. The effect of preincubation was not due to the low protein concentrations in the assays since increasing the total protein concentration did not abolish the requirement for preincubation for the detection of MeIQ activation at low concentrations of rat-liver extract. In experiments where P450IA2 synthesized in transfected cells in culture is used to study promutagen activation, the plate incorporation protocol may seriously underestimate the capacity of cell extracts to activate promutagens. Thus, interlaboratory comparisons become difficult and unnecessarily large quantities of cell extract protein may be needed to detect promutagen activation. Whenever Ames test assays are carried out under conditions where P450 concentration limits revertant yield, it would be prudent to examine both the preincubation and plate incorporation protocol.

Aflatoxin B1↗
PubMed1992

Comparison and interaction of low dose felodipine and enalapril in the treatment of essential hypertension in elderly subjects.

The antihypertensive effect and tolerance of the combined low doses of felodipine and enalapril (5 + 5 mg daily) were compared with those of either drug at a higher dose level (10 mg daily). Our double-blind, three-way crossover study (balanced Latin square design) involved 36 elderly subjects (mean age 67 +/- 6 years) with essential hypertension. After a 4-week placebo run-in phase the subjects were randomized to the active treatment periods, starting with 5 mg felodipine plus 5 mg enalapril, 5 mg felodipine, or 5 mg enalapril daily for the first 4 weeks. The doses in the felodipine and enalapril periods were then doubled for another 2 weeks. All medication was given once daily in the morning, and blood pressure was measured 24 h after a previous dose. The supine blood pressure for subjects given placebo was 178/101 mm Hg. After 6 weeks' treatment systolic and diastolic supine blood pressures were significantly lower with 5 mg felodipine plus 5 mg enalapril (154/85 mg Hg) than with 10 mg felodipine (159/88 mm Hg) or with 10 mg enalapril (162/91 mm Hg), and the diastolic blood pressure was significantly lower with felodipine than with enalapril. At the end of the felodipine plus enalapril, felodipine, and enalapril treatment periods, 75, 69, and 56% of the subjects, respectively, had a supine diastolic blood pressure 90 mm Hg or less. The combination was tolerated better than either monotherapy. The most commonly reported adverse event was swollen ankles, which occurred in one, nine, and five subjects during felodipine plus enalapril, felodipine, and enalapril treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Clinical efficacy of perindopril in hypertension.

1. Perindopril's effectiveness in mild to moderate hypertension was evaluated in three studies. 2. Perindopril was more effective than sodium restriction in reducing blood pressure, and the effects were additive. 3. Perindopril was as effective as atenolol in reducing blood pressure, and was well tolerated. 4. Perindopril lowered blood pressure to the same extent as enalapril at peak drug levels but had a greater effect at the trough level of the drugs. 5. Perindopril is an effective antihypertensive agent with an acceptable side-effect profile in people with hypertension.

Aged↗
PubMed1992

Immunopathology of chronic experimental histoplasmic choroiditis in the primate.

A nonhuman primate model of ocular histoplasmosis was developed that enabled the authors to define the choroidal cellular immunopathology of both the acute and chronic phases of experimental histoplasmic choroiditis. Anti-human monoclonal antibodies were used to identify the inflammatory cell subsets and to calculate their relative percentages in the choroidal inflammatory lesions. Comparison of the acute (less than or equal to 65 days) and chronic (greater than or equal to 1 yr) phases suggested possible variations in the evolution of these lesions, resulting in the development of immunopathologically distinct chronic lesions. In this model, these late lesions could be differentiated by the presence or absence of dense lymphocytic foci, comprised predominantly of mature B-lymphocytes, located within the more diffuse inflammatory cell background. The chronic lesions containing these B-cell foci had significantly higher percentages of both mature B-cells (P less than 0.0001) and helper-inducer T-cells (P less than 0.05) than did the chronic lesions without B-cell foci. The increase in helper-inducer T-cells in the chronic lesions with B-cell foci resulted in a higher mean helper-suppressor T-cell ratio (mu = 0.60) than that seen in lesions lacking foci (mu = 0.33). These findings suggest that, even in the same eye, individual chronic histoplasmic choroidal lesions, which clinically resemble "histo spots" in humans, may have different immunopotentials.

Acute Disease↗
PubMed1992

Cellular proto-oncogene expression following exposure of mice to gamma rays.

Many studies have shown the importance of altered cellular proto-oncogene expression in contributing to changes in cell survival, cell transformation, and cell cycle progression. In these experiments we examined the effects of total-body exposure of BCF1 mice to gamma rays (3 Gy) in modulating expression of cellular oncogenes in both gut and liver tissues. We selected specific cellular oncogenes (c-fos, c-myc, c-src, and c-H-ras), based on their normal expression in liver and gut tissues from untreated mice. As early as 5 min following whole-body exposure of BCF1 mice to gamma rays we detected induction of mRNA specific for c-src and c-H-ras in both liver and gut tissues. Accumulation of c-fos-RNA was slightly decreased in gut but was unaffected in liver tissue from irradiated mice relative to untreated controls. Accumulation of c-myc mRNA was unaffected in all tissues examined. These experiments document that modulation of cellular proto-oncogene expression can occur as an early event in tissues following irradiation and suggest that this modulation may play a role in radiation-induced cellular changes.

Animals↗
PubMed1992

Hemodynamic comparisons of enalapril and felodipine and their combination.

Thirty-six patients (33 male, 3 female) with a mean age of 67 years and a diastolic blood pressure between 95 and 115 mm Hg, after a four-week placebo run-in period entered a double-blind crossover study comparing felodipine 5 and 10 mg with enalapril 5 and 10 mg and their combination (enalapril 5 mg + felodipine 5 mg). Combined therapy caused a fall in blood pressure of 24/16 mm Hg at trough level that was greater than the falls with the higher doses of monotherapy. The fall with felodipine was greater than with enalapril. Similar patients responded to felodipine and enalapril but more patients achieved blood pressure control with felodipine. When patients not controlled with enalapril 5 mg had felodipine 5 mg or enalapril 5 mg added, felodipine was more effective at lowering blood pressure than the increase in enalapril dosage. A similar effect occurred in those not controlled with felodipine 5 mg. Adverse effects occurred in 22 patients on felodipine, 14 patients on enalapril and 8 on combined therapy. The lipoprotein profile was not altered significantly. Glomerular filtration rates as assessed by 24-hour creatinine clearance were 90 ml/min at randomization, 125 ml/min on felodipine, 108 ml/min on enalapril and 120 ml/min on the combination. Felodipine and enalapril in low doses are effective antihypertensive agents in elderly people. Felodipine monotherapy is more effective than enalapril monotherapy but a greater blood pressure lowering effect can be obtained with the combination of low doses of enalapril and felodipine. This has the advantage that the number of side effects is less.

Aged↗
PubMed1991

Effect of the calmodulin inhibitor trifluoperazine on phosphorylation of P-glycoprotein and topoisomerase II: relationship to modulation of subcellular distribution, DNA damage and cytotoxicity of doxorubicin in multidrug resistant L1210 mouse leukemia cells.

The results from the present study using the sensitive and progressively DOX resistant L1210 model system demonstrated that the effects of TFP are not due to redistribution of DOX to the nucleus, and modulation of cytotoxicity is related to effects on DOX-induced DNA strand breaks. Although TFP affects phosphorylation of PGP and TOPO II (R2 greater than R1), the comparable DNA strand breaks at lower DOX levels with TFP in the resistant sublines suggest that modulation of TOPO II function related to drug-induced DNA damage by calmodulin-mediated events may be an important mode of action.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Epidemiology of non-fatal injuries due to external causes in Johannesburg-Soweto. Part II. Incidence and determinants.

A total of 3,535 trauma cases were enumerated in Johannesburg-Soweto between 1989 and 1990 in the course of 271 hospital ward rounds and 43 casualty watches. The overall trauma incidence was 2,886 new cases per annum per 100,000 population, rising to 19,872 for coloured males aged 20 - 24 years and to 8,761 for black males aged 20 - 24 years. Overall the male/female ratio was 2.9 rising to 6 or more in adolescence (15 - 19) for blacks and coloureds. There were some 156 new resident cases of trauma daily; half these were victims of interpersonal violence, and coloureds constituted 22% of this group, although forming only 8% of the denominator population. With regards to cause, most trauma among blacks and coloureds arose from interpersonal violence and significantly less from transport accidents. Among blacks injured in transport accidents (the majority of which involved motor vehicles) most were pedestrians, whereas most whites injured in such accidents were occupants of vehicles. For all groups trauma was most likely to be incurred 'in the street' although for white and coloured women the home was most dangerous. The implications of these and related findings for treatment and prevention and briefly reviewed.

Adolescent↗
PubMed1991

The Ah receptor, cytochrome P450IA1 mRNA induction, and aryl hydrocarbon hydroxylase in a human lymphoblastoid cell line.

The immunosuppressive and carcinogenic effects of aryl hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene (MC) on B lymphocytes of adult rodents and the induction of cytochrome P450IA1 and aryl hydrocarbon hydroxylase (AHH) in human mitogen-activated lymphocytes and B-lymphoblastoid cell lines are believed to be mediated by the Ah receptor. However, there has not been a direct demonstration or characterization of the Ah receptor in defined populations of any of these cells. We report here the detection and characterization of an abundant, high-affinity B lymphocyte Ah receptor in the AHH-inducible human B lymphoblastoid cell line BCR-5. Our results represent the first characterization of a human lymphocyte receptor in a well-defined lymphocyte population. Sucrose density gradient analysis of BCR-5 cytosols incubated with [3H]TCDD revealed a characteristic 9 S specific binding peak. The maximum concentration of Ah receptor was about 200 fmol/mg protein. Specific binding to the Ah receptor was also detected with [3H]MC and, to a lesser extent, with [3H]benzo[alpha]pyrene. The apparent binding affinity (Kd) for [3H]TCDD (determined by saturation analyses) was about 5 nM. A specific [3H]TCDD-Ah receptor complex which sedimented at 5 S was extracted from nuclei of BCR-5 cells incubated at 37 degrees with [3H]TCDD. The Ah receptor of BCR-5 cells is thus similar in characteristics to that identified in other cell lines. When BCR-5 cells were exposed in culture for 24 hr to increasing concentrations of benz[alpha]anthracene there was a concentration-dependent increase in induction and a good correlation (r = 0.98) between the level of induced AHH activity and the relative abundance of cytochrome P450IA1 mRNA. The human B lymphoblastoid cell line BCR-5, therefore, has a complete regulatory mechanism for Ah receptor-mediated induction of cytochrome P450IA1 that is essentially the same as that which has been well established in many rodent species. The accessibility of human blood lymphocytes and the ease of establishment of B lymphoblastoid cell lines from any donor provide a source of pure cultures of human B lymphocytes which can be grown continuously in vitro for the study of mechanisms related to Ah receptor-mediated cytochrome P450IA1 induction, immunosuppression and carcinogenesis.

Aryl Hydrocarbon Hydroxylases↗