Biomedical subjects
Publications and source records attributed to A Ciampi.
The personality dimensions related to risk-taking propensity in suicide patients were sought. Two dimensions, responsibility and self-esteem, were helpful in distinguishing between suicide involved patients, and non-suicide related cases.
Mice were given repeated injections, at 21 day intervals, of cyclophosphamide paired with a novel taste (saccharin) in the drinking water. Subsequent challenge with a syngeneic plasmacytoma tumor led to elevated tumor growth and mortality only in conditioned mice that were reexposed to saccharin. This effect was abolished by conditioned exposure to a histamine type II-receptor antagonist.
Expression of markers of differentiation was measured in a clone of the continuous cell line K562, derived originally from the cells of a patient with leukemia. Three of the markers were lineage specific, R18 for erythropoiesis and 80H.5 and My-1 for granulopoiesis. The fourth marker was the self-renewal capacity of clonogenic cells. The markers were measured as a function of time in pooled colonies from day 2 to day 12, and at a point of time in individual colonies. Evidence of an orderly pattern of marker appearance and disappearance was not seen. Rather, their expression appeared to occur at random during growth.
This study evaluated the reliability and sensitivity of laryngeal cancer patients' linear analogue self-assessments (LASA) of voice quality. Thirty patients completed LASA scales for a number of voice-related symptoms and abilities several times during a standard treatment programme. The study design allowed evaluation of the scales' reliability, both early and late in treatment, and sensitivity to the changes expected during irradiation. Another 29 post-treatment patients completed the same scales in interviews separated by several weeks. Results indicate that LASA scores were generally reliable, sensitive to clinical change, yet stable when clinical status is unaltered. Though further demonstrations of the validity of these scales are required, their possible use as outcome measures in future clinical trials comparing treatments for laryngeal cancer is feasible.
Although quantitative estimates of patients' attitudes toward the relative importance of different aspects of health are of great potential usefulness in medical decision making, there is little information about the stability of such values over time, particularly in patients whose clinical state is changing. To examine these questions, we selected a group of patients with laryngeal cancer undergoing treatment with radiotherapy. In this group of patients clinical problems are relatively circumscribed and related to the voice, and a temporary deterioration in voice-related symptoms and abilities is expected during treatment. Thirty patients were interviewed at the start and completion of a month's course of treatment. At each interview patients rated the quality of their own voices using a number of visual analogue scales and also provided both holistic and decomposed quantitative values for the importance of different aspects of voice function and sound. Although the analogue scales demonstrated the anticipated deterioration in the quality of the patients' voices, these changes in clinical state were not accompanied by any changes in the values the patients assigned to each aspect of voice sound and function. These results indicate that at least in the short term the values expressed by patients appear to be stable and uninfluenced by changes in their own clinical state. Longer term studies involving more systemic illnesses should now be carried out.
In health status index construction quantitative values for different states of health are frequently obtained by presenting written descriptions to raters whose values are elicited using one or more methods. In this study the authors examined the influence of several aspects of this measurement process upon the quantitative results obtained. They prepared a set of written descriptions of health states, each state being described in both a standard point-form and a narrative format. The narrative format was written in the first person singular, and listed all symptoms or problems associated with the state, whereas the point-form description included only the most severe symptom or problem. Values for these states were elicited from a group of 64 patients using two commonly employed methods, the standard gamble of Von Neumann and Morgenstern and category rating. The results indicate that the type of scenario presented to the rater and the sequence in which the methods of assessment were used had a major influence on the results. This work indicates that there is a need to examine systematically the process of obtaining quantitative values before reliance can be placed upon the results.
The voices of patients with laryngeal cancer following a specific radiotherapy regimen were subjected to perceptual evaluation. Interval scaling of the severity of perceived dysphonia was completed for the voices of male patients sampled before and 1 year following radiation therapy and for a set of male controls. Eight listeners did this quantitative rating and also specified the predominant quality in each voice. The results indicated that the degree of dysphonia in the pretreatment group was highest. Radiotherapy decreased this dysphonia but not to the point that posttreatment voices were indistinguishable from those of normal subjects. Also, the voice qualities of laryngeal cancer patients shifted toward those of the control group following radiotherapy with over one half of the irradiated patients judged to have rough or normal qualities.
Newborn CBA mice were inoculated i.p. with 1 X 10(8) adult (CBA X A)F1 lymphoid cells with 5 X 10(7) F1 hybrid lymphoid cells thereafter inoculated i.v. at 14-day intervals. The mice were subsequently grafted with A/J tail skin at 24 days of age. At 8 wk of age, individual tolerant males with intact skin grafts were each mated with similar tolerant skin-grafted females or with 8-wk-old control normal CBA females. Approximately 0.4 ml of peripheral blood from 7-wk-old progeny born to these crosses, along with the blood from age-matched progeny born to normal CBA incrosses, were used for in vitro mixed leukocyte cultures (MLC). All progeny received skin grafts of (CBA X A)F1 tail skin at 7 1/2 wk of age. In this study, we show i) that MLC hyporesponsiveness to histocompatible cells is an acquired phenotype expressed by lymphoid cells of the progeny of tolerant male mice, and ii) that these progeny also show delayed rejection of (CBA X A)F1 skin grafts. The continued breeding of the first generation animals established that a similar transmission of hyporesponsiveness can be observed in the second generation progeny. When putatively normal females, however, which had borne several litters after mating with neonatally tolerant males, were mated with "normal" (nontolerant) males; their offspring also exhibited a specific hyporesponsiveness in MLC to the initial tolerizing allodeterminants. This suggests that there may ultimately be a maternally derived origin for the transmission of characters from tolerant males.
A simple stem cell model of human tumor growth is presented. Three tumor cell populations are predicted: stem, transitional, and end cells. The properties of these cells are discussed in terms of their behavior in currently available technologies for investigation of cell kinetics and for their influence on clinical outcome. Stem cell renewal, transitional cell proliferation, and cell loss are analyzed mathematically to define their influence on the relative proportions of cell populations; it is demonstrated that stem cell renewal has a central role in determining the growth properties of tumors. The impact of a stem cell model on the use of tumor clonogenic assays as predictors of clinical outcome is discussed; opinions are expressed as to the definition of reasonable expectations for current experimental procedures.
A family of proportional- and additive-hazards models for the analysis of grouped survival data is developed. This family generalizes the unpublished work of F.J. Aranda-Ordaz and follows Holford (1976, Biometrics 32, 227-237). It contains the proportional-hazards model for grouped data, as well as additive-hazards models with time trends. The time trends prove to be useful in an example in which the hazards of the two groups cross.
A FORTRAN program is described which finds maximum likelihood estimates for the generalized log gamma model for survival time data. The model includes regression variables which are assumed to be linearly related to log survival time and handles censored data. The shape parameter is treated as fixed in the optimization procedure (a modification of Powell's hybrid method), but the program can find maximum likelihood estimates (MLE) for several different values of the shape parameter in one run. The other parameters can be optionally fixed so special cases of the generalized log gamma (GLG) model, such as the log exponential, extreme value and normal models, can be studied. A subroutine is included which calculates initial parameter estimates for a given shape parameter value which can be used to start the optimization procedure. After some background mathematics, a description of how to use the program is given, including input/output features, a description of the subroutines and an explanation of the flow of control. An application, using data from Princess Margaret Hospital, Toronto, is presented to illustrate the program's use.
The standard gamble, derived from decision theory, is considered a criterion method for obtaining patients' values for different health states. In this method, a rater's value for a health state is obtained by determining, in a hypothetical setting, his readiness to remain in that state or take a risky choice with different outcomes of known value. According to the expected utility criterion, a rater's utility or value for a particular state should not be influenced by changes in the gamble outcomes. The standard gamble was used to obtain 64 patients' judgments of a set of health states, first with the outcomes of perfect health or death, and subsequently with other health states as outcomes. The changes in gamble outcomes significantly influenced reported values for health states, indicating that the standard gamble is internally inconsistent. This observation poses a major limitation to its use as a value measurement method in medicine.
Women in two Ontario cities were asked to express their preferences about a medical decision: A fictitious patient with cancer was to be treated either conservatively without hope of cure, or radically, by a risky treatment having cure or immediate death as possible outcomes. Situation-specific variables were varied systematically across the sample by varying the levels of the fictitious patient's physical and psychosocial health and achievement motivation. The results obtained indicate that individual preferences shift in response to changes in the situation in which the decision is made. These findings raise questions about the uses to be made of measurements of preferences, especially in relation to what is meant by a "best decision."
As a result of many studies in descriptive and analytic epidemiology, in animal carcinogenesis, and in the direct examination of body fluids for mutagens/carcinogens, it is possible to develop a list of dietary factors that may be associated with the high rate of colon cancer and related cancers in Western countries. This paper is concerned with the design of intervention studies to clarify which of these factors is important. The size of such intervention trials is influenced primarily by two factors: the incidence of the disease outcome studied in a control population and the magnitude of risk reduction in a treated group. Calculations based on a variety of assumptions suggest that a randomized trial in which cancer mortality is measured as the outcome of the intervention in a healthy population is probably too costly to be justified by current evidence linking the disease to diet. However, precursor lesions can be considered as an alternative outcome. The choice of the precursor lesion depends on the link to the disease in question, the prevalence of the lesion in the population, and the ease of detection. Recent developments in the application of endoscopic methods and in the description of the pathologic process leading to cancer suggest the use of gastrointestinal polyps as "precursor lesions" as the outcome of a trial. We illustrate these points with a protocol for a study in progress, a randomized double-blind study of the effect of ascorbic acid and alpha-Tocopherol on the rate of recurrence of colorectal polyps.
The survival experience of 982 non-Hodgkin's lymphoma patients registered at Princess Margaret Hospital, Toronto, between 1967 and 1975, was studied. Prognostic groups were obtained by means of a classification procedure based on standard statistical techniques; the variables utilized in the classification were ones of known reproducibility which could be measured with little inconvenience to the patient. The results show that these prognostic groups give better information than the Ann Arbor staging classification in the sense that the survival curves are clearly separated and "good prognosis" and "poor prognosis" groups are clearly identified. Implications for therapy planning are briefly discussed.
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Analysis of a group of 79 patients with previously untreated Hodgkin's disease, whose HLA phenotypes were determined in 1972-73, shows that patients in a sub-group with the specificities collectively known as Aw19 have significantly poorer survival than patients without these specificities. The degree to which the serologically-detectable HLA antigens assist in determining the prognosis for survival has been analyzed using multiple regression analysis and retrospective stratification. Both approaches indicate that the association of HLA phenotype with survival is not accounted for by correlations between HLA antigens and other know prognostic factors, such as stage, histology, age, and sex. The greatest prognostic value of Aw19 appears to be for patients with relatively unfavorable age (greater than 40 years), stage (III and IV), or histology (lymphocyte depletion, mixed cellularity).
A framework is developed to take explicitly into account the conflicting demands of ethics and scientific rigor in the design of clinical trials. The framework recognizes the part played by the clinical-scientific community in the weighing of a new result provided by a clinical trial. To illustrate the usefulness of the framework, a value system is adopted which gives relatively high weight to ethical considerations. The analysis based on this value system reveals some limitations of the present clinical-trials mechanism, especially if success is defined exclusively in terms of cure, and other dimensions of the health system, such as explanatory, care, cost or prevention variables are neglected. On the basis of this analysis, it is suggested that: (a) If randomized clinical trials are to be ethically acceptable, they will necessarily yield a large proportion of null results. (b) Positive results from ethically acceptable clinical trials would be expected to have less impact than null results; unless this is the case, there will be a tendency to encourage false hopes. (c) Trials need not yield entirely null results, provided that attention is not focused exclusively on a single outcome variable. A trial of chemotherapy for acute myeloid leukaemia in adults is used to illustrate the need for new approaches to the planning and design of clinical trials.