Omitting covariates from the proportional hazards model.
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Analysis of Variance↗
Biomedical subjects
T M Morgan
Publications and source records attributed to T M Morgan.
Combined recombinant human interferon alpha 2 and cytotoxic agents studied in a clonogenic assay.
A human tumor clonogenic assay has been used to test the antiproliferative effect of recombinant human leukocyte interferon alpha 2 alone and in combination with each of 8 cytotoxic agents. Cell lines derived from 6 human tumors and primary tumor cells from 13 patients have been used in these clonogenic assay studies. Results show that interferon as a single agent causes insignificant reduction in tumor cell colony survival if the short-term 1-hr cell exposure method is used; only high concentrations of interferon used in continuous cell exposure in the clonogenic assay can demonstrate a reduction in colony survival to below 50% of control values. Combinations of interferon with either doxorubicin or cisplatin frequently show additive and occasionally synergistic antiproliferative effects on tumor cell colony formation. Variations in drug concentrations and sequencing of drugs have been tested, showing that optimal antiproliferative effects of combined interferon and doxorubicin are realized when maximal concentrations of interferon and prolonged cell exposure time of both interferon and doxorubicin are employed. Combinations of interferon and doxorubicin tested in the clonogenic assay demonstrate cytotoxicity superior to that of either agent tested alone.
Antineoplastic Combined Chemotherapy Protocols↗
Planning the duration of accrual and follow-up for clinical trials.
In clinical trials, the duration of accrual and follow-up are chosen to ensure an adequate power to detect a specified difference at a given level of significance, but appropriate choices for durations of accrual and follow-up are not unique. Methods of determining appropriate combinations for the accrual and follow-up periods are given and the unique cost effective choice of accrual and follow-up periods is presented. The accrual period can be substantially decreased by including a short follow-up period. The unique cost effective duration of follow-up depends on the ratio of the cost of accruing patients to the cost of following patients for end point determination.
Clinical Trials as Topic↗
Synergistic antitumor activity of vincristine and VP-16-213.
The potential interaction of the antitumor agents vincristine and VP-16-213 was investigated in vivo. DBA/2 mice were inoculated with 10(6) P388 murine leukemia cells, after which single IP injections of saline only, vincristine only, VP-16-213 only, or a combination of vincristine and VP-16-213 were administered. Long-term survival (greater than 60 days) was observed in 0/45, 1/45 (2%), 9/135 (7%), and 44/135 (33%) mice, respectively (P less than 0.001). Treatment was most effective when VP-16-213 was administered 0-72 h after vincristine. A similar trend was observed in mice bearing P1534 murine leukemia. These data demonstrate synergistic antitumor activity between vincristine and VP-16-213 in a murine model.
Animals↗
Analysis of non-response in a prospective study of depression in Los Angeles County.
The occurrence of depression in a probability sample of 1003 Los Angeles County adults was measured in a 1979-80 prospective cohort study. The primary measure of depression was the 20-item Center for Epidemiologic Studies-Depression (CES-D) scale. Of the original 1003 adults, 893 were successfully re-interviewed at a second time period (reasons for not being interviewed originally and at the second time period are given). Demographic data on those not re-interviewed are contrasted with data from those who did respond. The mean depression level and percentage classified as depressed at the first interview were higher in non-respondents than in respondents to the second interview. Techniques are given for assessing whether discontinued participation is due to exposure or disease factors. For this study, it was shown that dropping out of the study was mainly due to exposure (or demographic) factors and not to depression as such. Two methods for estimating the level of disease at the second time period for respondents and dropouts are illustrated.
Adolescent↗
Analysis of effects of sex and age in response to items on the CES-D scale.
Analyses of differences in response to individual items in the Center for Epidemiologic Studies Depression (CES-D) scale based on sex and age breakdown are reported for a sample of 1,000 adults from Los Angeles County. Overall, results are comparable to those obtained in other population studies. Analyses performed separately for age and sex groups show response differences on individual items which affect the summated score. The interitem correlations are shown to be much higher for women that men, but overall the index assesses a comparable underlying dimension of depression for the two sexes.
Adolescent↗
Characterization and properties of phage B33, a female-specific phage of Pseudomonas aeruginosa.
The morphology and physico-chemical properties of a temperate phage, B33, of Pseudomonas aeruginosa have been determined. This phage is similar in size and structure to the previously described and serologically related phage B3 (Holloway, Egan & Monk, 1960), but differs from it in its plating properties on bacteria harbouring R plasmids. The plasmid RP1-1 causes a reduction in e.o.p. of B33 of 10(-6), and the mechanism whereby this occurs has been studied. The interaction is a specfic one since other plasmids either fail to affect plating or completely abolish it. The mechanism by which the latter occurs is different from that mediated by RP1-1, since mutants of B33 insensitive to RP1-1 nevertheless fail to plaque on these hosts.
Adsorption↗
Effect of covariate measurement error in randomized clinical trials.
Prognostic factors often appear as covariates in clinical trials designed to estimate treatment effects. These factors are usually subject to measurement error and lead to decreased efficiency in the estimation of the treatment effect. We use Weibull regression models and asymptotic theory to derive the efficiency of estimation obtained by adjusting for one dichotomous and one continuous covariate measured with error. An application to a clinical trial involving advanced lung cancer patients illustrates the results.
Antineoplastic Agents↗
Lessons from overviews of cardiovascular trials.
Overviews of clinical trials in the cardiovascular field have been critically reviewed. Six reasons for the overviews were identified. An impression, at least from a scientific viewpoint, is that the pooled analyses have been valuable. Six potential problems are discussed and recommendations given based on lessons learned. These include the avoidance of three types of biases--publication bias, overviewer bias and investigator bias. The role of time-dependent treatment effects, the complex issue of 'mixing of apples and oranges' and the problem of errors are also addressed.
Cardiovascular Agents↗
Demonstration of an association among dietary cholesterol, central serotonergic activity, and social behavior in monkeys.
Epidemiologic studies link plasma cholesterol reduction to increased mortality rates as a result of suicide, violence, and accidents. Deficient central serotonergic activity is similarly associated with violence and suicidal behavior. We investigated the relationship among dietary and plasma cholesterol, social behavior, and the serotonin system as a possible explanation for these findings. Juvenile cynomolgus monkeys (eight female and nine male) were fed a diet high in fat and either high or low in cholesterol. We then evaluated their behavior over an 8-month period. Plasma lipids and cerebrospinal fluid metabolites of serotonin, norepinephrine, and dopamine were assessed on two occasions, at 4 and 5.5 months after the initiation of behavioral observations. Animals that consumed a low-cholesterol diet were more aggressive, less affiliative, and had lower cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid than did their high-cholesterol counterparts (p < .05 for each). The association among dietary cholesterol, serotonergic activity, and social behavior was consistent with data from other species and experiments and suggested that dietary lipids can influence brain neurochemistry and behavior; this phenomenon could be relevant to our understanding of the increase in suicide and violence-related death observed in cholesterol-lowering trials.
Aggression↗
Age and dietary polyunsaturated fat alter high density lipoprotein subfraction cholesterol concentrations in a pediatric population of African green monkeys.
African green monkeys were raised from birth to 60 months of age on diets containing cholesterol (0.8 mg/kcal) and enriched in polyunsaturated (polyunsaturated to saturated fat ratio [P:S] = 2.5) or saturated (P:S = 0.3) fat. Lipoproteins were isolated from plasma of a group of animals (N = 123) and were separated by gel filtration chromatography at 9, 14, 26, 38, and 50 months of age, which covered a period through adolescence into young adulthood. Total plasma cholesterol (TPC) concentrations were 16% lower (p = 0.01) in the polyunsaturated fat-fed group, and high density lipoprotein (HDL) cholesterol concentrations averaged 20% lower (p = 0.008) in this group between 14 and 50 months of age, while plasma apolipoprotein A-I (apo A-I) averaged 7% lower (p = 0.06) over this age interval in the animals. The HDL cholesterol to apo A-I ratio was found to be significantly lower (p = 0.006) in the animals fed the polyunsaturated fat diet. This suggested that the HDL subfraction distribution might differ between groups. In a subset of animals (n = 105, 64 male and 41 female), HDL was subfractionated by density gradient ultracentrifugation into six subfractions, HDL-I to HDL-VI, from lowest to highest density. The saturated fat-fed animals had significantly higher cholesterol concentrations in HDL-I and significantly lower cholesterol concentrations in HDL-III, HDL-IV, and HDL-V. These effects held across all ages studied; therefore, these diet effects were not age dependent. In both diet groups, the HDL subfraction pattern changed with age such that the HDL-I and HDL-II cholesterol concentrations decreased, and those of HDL-IV, HDL-V, and HDL-VI increased as the animals matured. The decrease in HDL-I with age appeared to result primarily from a decrease in HDL-I in males, while the HDL-I cholesterol concentration in females did not change with age. We conclude that diet, age, and gender all affect HDL subfraction distribution and therefore can potentially modify the relative atherogenicity of the plasma HDL populations. It remains for future studies to demonstrate the effectiveness of each subfraction in promoting or preventing the cholesterol deposition of atherosclerosis.
Aging↗
Atherosclerosis of cynomolgus monkeys hyper- and hyporesponsive to dietary cholesterol. Lack of effect of vasectomy.
A moderately atherogenic diet was fed to young adult cynomolgus macaque males that were observed to be either hypo- or hyperresponsive to dietary cholesterol and who were randomized into groups to be either vasectomized or sham-vasectomized. The extent of atherosclerosis was found to be considerably greater at all arterial sites studied for the monkeys that were hyperresponsive to dietary cholesterol. The differences in atherosclerosis development among the hyperresponder monkeys occurred primarily in the proximal portions of the coronary arteries, the proximal and distal portions of the common carotid arteries, and only in the most proximal portions of the femoral arteries. There were no significant effects of vasectomy or sham vasectomy on atherosclerosis extent in either the hyper- or the hyporesponding groups, although there was a suggestion of somewhat larger lesions in the left circumflex coronary artery of hyperresponder monkeys that were vasectomized and somewhat smaller atherosclerotic lesions in the left common carotid arteries of vasectomized monkeys. The data presented here do not support our first report of worsened atherosclerosis among cynomolgus monkeys fed diets high in cholesterol. The findings of the current study are consistent with recent epidemiological studies of vasectomized and nonvasectomized human males.
Animals↗
Comparison of 50% dextrose water, 25% mannitol, and 23.5% saline for the treatment of hemodialysis-associated muscle cramps.
Hypertonic solutions of dextrose (D), mannitol (M), and saline (S) are effective treatments for hemodialysis-associated muscle cramps, but have not been directly compared to one another. Concern exists that postdialysis retention of M and S may lead to increased thirst, interdialytic weight pain (IDWG), and elevated blood pressure. The authors performed a prospective, randomized, double-blind crossover study to compare the efficacy of D, M, and S in 24 chronic hemodialysis patients. Cramps were treated with 50 ml (126 mOsm) D, 100 ml (138 mOsm) M, and 16 ml (126 mOsm) S. All patients were assigned to each regimen for a 2 week period. For the entire patient group (n = 24), mean cramp duration (+/- SD) was less for M compared to D (9 +/- 5 vs 13 +/- 12 min, p less than 0.05), but not to S (10 +/- 6, p = NS) although not every patient had a cramp episode during each 2 week period of study. In a subgroup of 11 patients with a mean of 3.7 (range 1-6) cramps during each 2 week period, the efficacy of D, M, and S was similar. In both patient groups, IDWG, blood pressure control, and the frequency of adverse effects was similar with the use of all three agents. Mild postdialysis hyperglycemia and hypernatremia during D and S, respectively, were the only significant laboratory abnormalities. The authors conclude: 1) the safety and efficacy of D, M, and S are equivalent, and 2) the nonmetabolized osmotic agents M and S do not lead to increased IDWG or decreased blood pressure control.
Blood Pressure↗
Improving physicians' and nurses' clinical breast examination: a randomized controlled trial.
Health professionals' clinical breast examination accuracy and skills are not optimal. We conducted a randomized trial to evaluate changes in physicians' and nurses' lump detection accuracy and examination skills after a training program emphasizing development of tactile skills and using silicone breast models containing lumps of varying sizes, degrees of hardness, and depth of placement. Sensitivity, specificity, and examination technique were measured before and four months after training in 43 experimental group and 46 control group participants. Mean sensitivity increased from 57% to 63% in the experimental group but decreased from 57% to 56% in the control group (P less than or equal to .05). The experimental group's posttest sensitivity was better for each lump characteristic, with statistically significant improvement for the very small (0.3 cm) and medium hard lumps. Duration of examination independently predicted sensitivity. Specificity decreased from 56% to 41% in the experimental group while it increased from 56% to 68% in the control group (P less than or equal to .05). Physicians had significantly higher mean sensitivity than nurses overall, as well as for the larger (1.0 cm), very small (0.3 cm), and softer lumps, but significantly lower mean specificity (33% versus 57%, P = .03). The experimental group improved significantly in five of six technique components while the control group improved in only one. To determine the effect of training on specificity in the clinical setting, we examined medical records of women seen by a subset of experimental and control physicians during the six months following training. There were no significant differences in the proportion of abnormal breast examinations reported or the number of mammograms ordered by experimental and control physicians. Our results show health professionals can be taught successfully to improve their clinical breast examination accuracy and skills.
Adult↗
Is breast self-examination predicted by knowledge, attitudes, beliefs, or sociodemographic characteristics?
The relationship of women's sociodemographic characteristics, knowledge, attitudes, and beliefs to breast self-examination (BSE) practice is not clear. We therefore studied these variables among older women at risk for developing breast cancer to determine which might be associated with the sensitivity, specificity, and frequency of BSE practice. We interviewed 300 women 40 to 68 years of age and measured BSE sensitivity and specificity using manufactured silicone breast models containing lumps. Of 54 variables and 10 scales examined univariately, six were associated with BSE sensitivity, one was negatively associated with specificity, and 10 were associated with frequency. No variable was associated with more than one component of BSE practice, and BSE frequency was not associated with BSE sensitivity or specificity. Using multivariate analysis, BSE sensitivity was best explained by type of employment, health interest, and perceived vulnerability to breast cancer, which accounted for approximately 16% of the variance. BSE frequency was best explained by intention to perform BSE, knowing how to perform BSE, using the correct method of BSE, self-confidence in the ability to perform BSE monthly, and self-confidence in the ability to find small lumps. These variables accounted for 27% of the variance. Sociodemographic characteristics, knowledge, attitudes, and beliefs poorly predicted how accurately women practiced BSE but somewhat better predicted how often women practiced BSE.
Adult↗