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H J Sutherland

Publications and source records attributed to H J Sutherland.

At least 91 records · Page 5Linked to original sources
PubMed1990

Selective expression of CD45 isoforms on functional subpopulations of CD34+ hemopoietic cells from human bone marrow.

We have found that the small population of cells in human marrow that are characterized by their expression of CD34 can be readily subdivided into two apparently nonoverlapping subpopulations of approximate equal size, one expressing CD45RO and one CD45R. Functional studies of these subpopulations revealed that all of the primitive erythroid colony-forming cells (BFU-E) are CD34+ CD45RO+. Similarly, more primitive cells that give rise to both erythroid and granulopoietic colony-forming cells after being maintained for 5 wk on confluent irradiated long-term marrow culture feeder layers, also show this phenotype. In contrast, most granulopoietic colony-forming cells are CD34+ CD45RO- cells. The differential expression of CD45 isoforms on distinct functional subpopulations of hemopoietic cells is consistent with the concept that these molecules play an important role in the differentiation or activation of primitive, normally quiescent, hemopoietic cells. The presence of CD45RO and the lack of CD45R on human cells capable of initiating hemopoiesis in the long-term marrow culture system correspond to the reported lack of CD45R on transplantable hemopoietic stem cells in rodents and may be a useful addition to strategies for human stem cell purification, or for purging CD45R+ leukemic cells.

Antibodies, Monoclonal↗
PubMed1990

Ratings of the importance of quality of life variables: therapeutic implications for patients with metastatic breast cancer.

Metastatic breast cancer cannot be cured with currently available therapeutic agents, and the objectives of treatment must, therefore, be directed towards other goals that include the relief of symptoms and the preservation or restoration of function. The main objective of the study reported here was to examine the relative importance of 28 items concerned with general health or with disease and treatment to a group of patients with metastatic breast cancer. All items concerned aspects of quality of life whose relevance and importance to patients with metastatic breast cancer had been shown in previous work. Patients rated items according to importance using two methods, a Q sort and a linear analogue rating. General health items, notably self-care, mobility, and physical activity, appetite, sleep, and family relationships were ranked in the upper quartile of the group of items rated. By contrast, items concerned directly with the common side-effects of chemotherapy were given lower rankings. The ratings were shown to be reproducible. These results emphasize the importance of including in clinical trials of therapy that are palliative in intent, endpoints that include those aspects of quality of life that are of greatest importance to patients.

Adult↗
PubMed1990

Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers.

A major goal of current hematopoiesis research is to develop in vitro methods suitable for the measurement and characterization of stem cells with long-term in vivo repopulating potential. Previous studies from several centers have suggested the presence in normal human or murine marrow of a population of very primitive cells that are biologically, physically, and pharmacologically different from cells detectable by short-term colony assays and that can give rise to the latter in long-term cultures (LTCs) containing a competent stromal cell layer. In this report, we show that such cultures can be used to provide a quantitative assay for human "LTC-initiating cells" based on an assessment of the number of clonogenic cells present after 5-8 weeks. Production of derivative clonogenic cells is shown to be absolutely dependent on the presence of a stromal cell feeder. When this requirement is met, the clonogenic cell output (determined by assessment of 5-week-old cultures) is linearly related to the input cell number over a wide range of cell concentrations. Using limiting dilution analysis techniques, we have established the frequency of LTC-initiating cells in normal human marrow to be approximately 1 per 2 X 10(4) cells and in a highly purified CD34-positive subpopulation to be approximately 1 per 50-100 cells. The proliferative capacity exhibited by individual LTC-initiating cells cultured under apparently identical culture conditions was found to be highly variable. Values for the number of clonogenic cells per LTC-initiating cell in 5-week-old cultures ranged from 1 to 30 (the average being 4) with similar levels being detected in positive 8-week-old cultures. Some LTC-initiating cells are multipotent as evidenced by their generation of erythroid as well as granulopoietic progeny. The availability of a system for quantitative analysis of the proliferative and differentiative behavior of this newly defined compartment of primitive human hematopoietic cells should facilitate future studies of specific genetic or microenvironmental parameters involved in the regulation of these cells.

Bone Marrow Cells↗
PubMed1990

Are we getting informed consent from patients with cancer?

We developed a consent form for a hypothetical trial and asked patients to underline information that was pertinent to their decision to accept or refuse to participate in the proposed trial. We also investigated whether patients correctly interpreted statements describing the probability of certain events occurring. Of the 50 patients, 74% did not indicate that both risks and benefits were pertinent. Of the 20 patients who would not enter the trial, 70% focused on risks of therapy only. In contrast, of the 30 who agreed to enter, only 33% focused entirely on risks, while 10% did not note potential for either benefit or risk. For each of four probability statements, patients chose one of four possible interpretations, only one of which was correct. Depending on the statement, between 26 and 54% of the interpretations were incorrect. It appears that many decisions regarding trial entry may be based upon incomplete or incorrect information.

Adult↗
PubMed1989

Specific binding and release of cells from beads using cleavable tetrameric antibody complexes.

A two-step separation procedure is described for the positive selection of cells based on their reactivity with mouse monoclonal antibodies. In the first step cells are specifically cross-linked to hapten-modified glass beads using tetrameric monoclonal antibody complexes. In the second step bound cells are selectively eluted by reductive cleavage of the tetrameric antibody complexes. The latter are comprised of two mouse IgG1 monoclonal antibodies (one recognizing a cell surface antigen on target cells and the other a hapten coupled to the glass beads) bound together by two F(ab')2 fragments of rat anti-mouse IgG1 monoclonal antibody. The complexes provide a specific cleavable cross-link between cell and bead because the disulfide bonds between the two Fab' arms of the F(ab')2 fragments can be broken under relatively mild conditions using dithiothreitol. This specific cleavage of the cross-linker allows elution of the specifically absorbed cells without co-elution of non-specifically bound cells. This is shown in the purification of CD3+ T cells from human peripheral blood, where the removed fractions were over 90% pure and approximately 50% of the positive cells were recovered. Separation of cells labelled with limiting amounts of tetrameric antibody complexes demonstrated that this separation technique was also effective for the purification of cells expressing low amounts of antigens. This was confirmed by the purification of CD34-positive cells from human bone marrow. With this approach, colony-forming cells were enriched 15-24-fold over density separated marrow.

Antibodies, Monoclonal↗
PubMed1989

Measuring satisfaction with health care: a comparison of single with paired rating strategies.

One of the central problems in studies of patient satisfaction with health care is the development of reliable and valid methods to determine the relative importance of different aspects of health care. Two techniques, paired comparisons and rating on a visual analogue scale, were compared in terms of their consistency with logical assumptions, test-retest reliability, and convergent validity. Thirty women with breast cancer were asked to assess brief hypothetical scenarios describing out-patient clinic visits to a tertiary cancer care centre. Each scenario incorporated three variables related to satisfaction with care: staff attitude, control over treatment decisions, and continuity of medical supervision. The paired choice method showed marginally better reliability and logical consistency than the rating method. Of the three variables assessed, continuity of medical supervision was consistently ranked highest in importance, and control over treatment decisions lowest. These preference assessment techniques appear to be suitable for use in the development of patient satisfaction indices, and for studies designed to examine variations in the priority given to different aspects of satisfaction with care.

Attitude of Health Personnel↗
PubMed1989

Cancer patients: their desire for information and participation in treatment decisions.

The relationship between cancer patients' desire for information and their preference for participation in decision making has been examined. Approximately 77% of the 52 patients reported that they had participated in decision making to the extent that they wished, while most of the remaining 23% would have preferred an opportunity to have greater input. Although many of the patients actively sought information, a majority preferred the physician to assume the role of the primary decision maker. Ethically, the disclosure of information has been assumed to be necessary for autonomous decision making. Nevertheless, the results of this study indicate that patients may actively seek information to satisfy an as yet unidentified aspect of psychological autonomy that does not necessarily include participation in decision making.

Canada↗
PubMed1989

Measuring perceptions of the exemplary nurse.

Qualitative and quantitative data identifying and weighting the perceived importance of different attributes of the "exemplary" nurse were collected from nursing respondents at different points in their professional development. Statistically significant differences in the attribute weights reported by fourth-year students and graduate nurses were observed. Because their pool was qualitatively different, quantitative comparisons with first-year students were not possible. The results indicate that these methods may be useful in examining the processes whereby the members of different groups (eg, nursing students and faculty) formulate and modify their assumptions about their own and others' professional values.

Clinical Competence↗
PubMed1989

Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro.

To develop a purification strategy for isolating the most primitive hematopoietic stem cells present in normal human marrow we have combined cell separation techniques with an assay for cells that initiate sustained hematopoiesis in vitro in the presence of irradiated human marrow adherent cells. These "feeders" were established by subculturing 2- to 6-week-old primary long-term marrow culture adherent layers at a density of 3 x 10(4) irradiated cells per square centimeter. Test "long-term culture (LTC)-initiating cells" were plated on top of the feeders and the cocultures then maintained as standard long-term marrow cultures with half-media changes and removal of half of the nonadherent cells each week. The total number of myeloid, erythroid, and multilineage clonogenic progenitors present after 5 weeks was used to provide a quantitative assessment of the number of LTC-initiating cells originally added. Using this assay, the density, light scatter, and two cell surface antigen properties of LTC-initiating cells have been defined and compared with cells capable of directly forming colonies in methylcellulose. While the majority of the clonogenic cells were found in the high forward light scatter (FLS) "blast" window, LTC-initiating cells had significantly lower FLS properties and in this respect were more similar to lymphocytes. LTC-initiating cells also expressed less HLA-DR antigen than clonogenic cells. The majority of LTC-initiating cells were found in the top 2% of the CD34 (My10) fluorescence profile, whereas clonogenic cells were found throughout the top 5% of the CD34 fluorescence profile. By combining low FLS, low orthogonal light scatter (OLS), low HLA-DR expression, and high CD34 expression, a population could be obtained that was enriched for LTC-initiating cells approximately 800-fold over unseparated marrow. This population contains only 0.06% of the marrow cells and 2% of the total clonogenic cells, but retains 50% to 60% of the LTC-initiating cells present in the original marrow. The ability to purify these two populations independently shows that the LTC and clonogenic assays identify distinct, although not necessarily nonoverlapping cell types in human marrow. Since clonogenic cells are derived from LTC-initiating cells, the LTC assay clearly detects a more primitive population. The availability of a simple approach that allows the purification of such cells by three orders of magnitude in high yield should be useful for the investigation of early events in hematopoiesis as well as for the definitive isolation of human hematopoietic stem cells with long-term in vivo repopulating potential.

Bone Marrow Cells↗
PubMed1988

Measurement of the clinical status of patients with breast cancer: evidence for the validity of self assessment with linear analogue scales.

We have assessed the validity of a method of measurement for describing the clinical status of patients with breast cancer. One hundred and nine patients with breast cancer assigned numerical values to their own state of health using linear analogue scales. We have shown previously that this method of measurement is reliable and corresponds well with other methods of assessment. Validity was assessed in this study by examining the ability of measurements to distinguish between groups of patients who differed either in the presence of metastatic disease or in the treatments they were receiving. All patients completed the same set of 29 linear analogue scales that enquired about the severity of health related problems and symptoms. In general, patients with metastatic disease were clearly distinguished from patients without metastases by their scores on items related to physical function. Patients receiving chemotherapy were distinguished from those not receiving chemotherapy by their scores on treatment related toxicities. Measures of psychological and social health were similar in patients receiving chemotherapy regardless of disease status. These results provide further support for the validity of measurement of clinical status with linear analogue scales scored by patients.

Breast Neoplasms↗
PubMed1987

Why are (or are not) patients given the option to enter clinical trials?

Much attention has been paid to the use of ethical principles to guide the conduct of clinical trials. Less has been done to clarify and assess the "weights" assigned by clinicians (and others) to the values that come into conflict when patients are offered entry into trials. Quantitative techniques of value assessment were used to measure the relative importance of variables frequently identified as barriers to the entry of patients into clinical trials. Responses were obtained from 52 oncologists, 26 clinical trials and senior nurses, and 23 family physicians. The group of oncologists identified the scientific design of the trial as the most important factor. In contrast, the groups of nurses and family physicians gave higher weight to effects of the trial on the doctor-patient relationship. The results illustrate ways in which methods of value assessment may be used to clarify and rank values.

Clinical Trials as Topic↗
PubMed1985

Weight gain during adjuvant chemotherapy for breast cancer.

Weight gain during adjuvant chemotherapy has been reported by several authors. Because increased body weight at diagnosis is associated with an increased risk of disease recurrence, we have assessed the prevalence of weight gain in a series of patients receiving adjuvant treatment, as well as the association of weight gain with type of treatment and risk of recurrence. We first assembled an inception cohort of 237 patients who had all undergone pretreatment evaluation and treatment at one institution, and had already been followed for at least 12 months. Body weight at the start and completion of treatment was recorded, as was type of treatment and status at last followup. Ninety-six percent of patients gained weight during treatment and none lost weight (mean increase 4.3 kg). Weight gain was strongly associated with treatment, and was least in patients receiving single agent chemotherapy, greatest in patients treated with ovarian ablation and prednisone, and intermediate in those receiving combination chemotherapy. There was no association between weight gain and disease recurrence.

Adult↗
PubMed1984

Linear analogue self-assessment of voice quality in laryngeal cancer.

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.

Adult↗
PubMed1984

The assessment of values in laryngeal cancer: reliability of measurement methods.

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.

Adult↗
PubMed1984

Do patients and physicians agree on the assessment of voice quality in laryngeal cancer?

Information is available regarding tumor control rate and survival for patients with cancer of the larynx. Less well known are the effects of treatment upon the patient's quality of voice and way of life because there is at present no suitable method for the routine clinical assessment of these effects. This paper reports some results of the evaluation of one assessment technique using linear analogue scales, and it examines the agreement between patients' and physicians' assessment of severity of voice related function and sound. Each of 20 patients taped a voice recording and subsequently rated his overall functional ability and the sound of his voice. Twenty physicians rated the sound of the 20 patients' voices from the recording and judged functional ability from a written description. Agreement between the scores of patients and physicians indicated that despite being strongly correlated, they were often not the same. Implications of this technique are discussed.

Adult↗
PubMed1984

Describing health states. Methodologic issues in obtaining values for health states.

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.

Adult↗
PubMed1983

Measurement of values for states of health with linear analog scales.

Medical decisions may be greatly influenced by the values that patients place on different states of health. Previous attempts to obtain quantitative estimates of such values have assumed the numerical values assigned to different levels of health will remain constant regardless of the context in which the measurement is made. To examine this assumption, 64 ambulatory patients ranked five scenarios describing different states of health in order of preference. One of the scenarios was ranked as worse than death by 22 percent of raters, and two scenarios were ranked as worse than death by 31 percent of raters. The states were then rated using linear analog scales, first with the anchors or endpoints of perfect health and death, then with the anchor of perfect health replaced by each of the other health states, in descending order of preference, and finally with the anchor of death replaced by each of the other health states, in ascending order of preference. The numerical values assigned to scenarios were substantially and systematically influenced by the anchors on the scale. Relative to the values assigned to health states when anchors of perfect health and death were employed, the same states were assigned systematically higher values when the anchor of death was replaced by other health states, and systematically lower values when the anchor of perfect health was replaced. These findings persisted when states considered worse than death were excluded from the rating process. These results indicate that the quantitative values assigned health states are strongly influenced by the context in which the measurement is made, and that health cannot be regarded as a continuum with death as its lower boundary.

Analysis of Variance↗