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T A Stukel

Publications and source records attributed to T A Stukel.

52 records · Page 3Linked to original sources
PubMed1992

Predictive value of flow cytometric analyses of blast cells in assessing the phenotype of the leukemia colony-forming cell (L-CFC) population in acute myeloid leukemia.

Acute myeloid leukemia (AML) blast cells (BC) express antigens that are commonly found on their normal counterparts. The leukemia colony-forming cell (L-CFC) subpopulation, identified by its ability to form leukemia colonies in vitro, is thought to be the stem cell population that produces BC. To ascertain the association between myeloid antigens on the BC and the L-CFC from the same patient, we compared the expression of CD14, CD15, CD33, p124 and HLA class I from 17 cases of AML. These particular myeloid antigens were studied because they are suitable targets in purging bone marrow for autotransplantation. We found no significant difference in the expression of CD14, CD15, CD33, and HLA class I on the BC and L-CFC from the same patient, although we observed considerable heterogeneity among different AML cases. Analysis of the progenitor cell antigen p124 revealed significant within-patient differences on the BC and L-CFC (p = 0.007), with a greater tendency for expression on the L-CFC. This heterogeneity may be due to differences in maturation stage of the L-CFC and BC. This information is important when L-CFC phenotype is used to determine the appropriate selection of antibodies for purging of residual disease in the context of auto-transplantation.

Antigens, Differentiation↗
PubMed1991

Lack of effect of chronic administration of oral beta-carotene on serum cholesterol and triglyceride concentrations.

Previous studies suggest that chronic oral administration of retinol and other retinoids causes elevation of plasma triglyceride concentrations. The effects of chronic oral administration of beta-carotene, a carotenoid partially metabolized to retinol, on plasma lipid concentrations have not been well studied; therefore, we studied 61 subjects over 12 mo while they were enrolled in a skin-cancer-prevention study in which patients were randomly assigned to receive either placebo (n = 30) or 50 mg beta-carotene/d orally (n = 31). At study entry and 1 y later, fasting blood samples were obtained for measurement of triglycerides, total cholesterol, HDL cholesterol, retinol, and beta-carotene. Retinol concentrations changed minimally in both groups; beta-carotene concentration increased an average of 12.1 +/- 47 nmol/L in the placebo group and 4279 +/- 657 nmol/L in the active-treatment group. Both groups experienced similar small increases in triglyceride and total cholesterol concentrations and small decreases in HDL cholesterol. Daily oral administration of 50 mg beta-carotene/d did not affect plasma lipid concentrations.

Administration, Oral↗
PubMed1991

Determinants of increase in plasma concentration of beta-carotene after chronic oral supplementation. The Skin Cancer Prevention Study Group.

We studied the relationship between eight variables, including age, sex, baseline plasma beta-carotene (BC) concentration, and smoking status and the increase in plasma BC in 582 subjects receiving oral supplementation with 50 mg BC/d. Median plasma BC concentrations after 1 y of supplementation increased from 335 nmol/L at entry to 3163 nmol/L. Changes in plasma BC concentrations ranged widely from -313 to 16,090 nmol/L (median 2721 nmol/L). Multivariate analysis revealed that the subject's plasma BC concentration before supplementation was the most important indicator of the amount of increase after supplementation. Nonsmokers, women, and leaner subjects all had larger increases in plasma concentrations although the statistical model could account for relatively little of the variability in subjects' plasma response to BC supplementation (R2 = 0.14). We conclude that between-subject variability in response to daily supplementation with oral BC is very large and that the best predictor of this response is the initial plasma BC concentration.

Administration, Oral↗
PubMed1991

Ventilatory responses and entrainment of breathing during rowing.

The purpose of this investigation was to investigate the hypothesis that respiration was coupled with the mechanics of the rowing stroke. In the first part of the study, physiologic responses during incremental exercise on the variable-resistance rowing ergometer were compared in 16 untrained female subjects (U), 17 collegiate female rowers (C), and 21 elite oarswomen (E). Minute ventilation (VE) and frequency of respiration (fR) were examined on a log scale as their relationship with oxygen consumption (VO2) was exponential. The slopes for log VE/VO2 were similar for collegiate (0.65 +/- 0.02) and elite (0.59 +/- 0.01) rowers, but the slope was significantly higher for the untrained (0.87 +/- 0.01) subjects (P less than 0.001). Elite rowers utilized a higher tidal volume (VT) response per VO2 (0.68 +/- 0.04 vs 0.30 +/- 0.05; P = 0.01) and lower log fR response per VO2 (0.27 +/- 0.02 vs 0.50 +/- 0.03; P = 0.01) compared with collegiate rowers. The ratio of fR/strokes per minute (SPM) averaged 1.5 in E athletes but varied in the U and C groups. In the second part of the study, pattern and timing of respiration were recording using an inspiratory pneumotachygraph, analyzed, and compared with specific phases of the rowing stroke in ten untrained subjects and nine elite rowers. The ratio of inspiratory time (T1)/total respiratory time (TTOT) decreased during the drive phase and increased during the recovery phase in both untrained subjects and elite rowers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

A clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin. The Skin Cancer Prevention Study Group.

BACKGROUND: Beta carotene has been associated with a decreased risk of human cancer in many studies employing dietary questionnaires or blood measurements, and it has had protective effects in some animal models of carcinogenesis. METHODS: We tested the possible cancer-preventing effects of beta carotene by randomly assigning 1805 patients who had had a recent nonmelanoma skin cancer to receive either 50 mg of beta carotene or placebo per day and by conducting annual skin examinations to determine the occurrence of new nonmelanoma skin cancer. RESULTS: Adherence to the prescribed treatment was good, and after one year the actively treated group's median plasma beta carotene level (3021 nmol per liter) was much higher than that of the control group (354 nmol per liter). After five years of follow-up, however, there was no difference between the groups in the rate of occurrence of the first new nonmelanoma skin cancer (relative rate, 1.05; 95 percent confidence interval, 0.91 to 1.22). In subgroup analyses, active treatment showed no efficacy either in the patients whose initial plasma beta carotene level was in the lowest quartile or in those who currently smoked. There was also no significant difference between treated and control groups in the mean number of new nonmelanoma skin cancers per patient-year. CONCLUSIONS: In persons with a previous nonmelanoma skin cancer, treatment with beta carotene does not reduce the occurrence of new skin cancers over a five-year period of treatment and observation.

Aged↗
PubMed1990

Autologous bone marrow transplantation for acute myeloid leukemia using monoclonal antibody-purged bone marrow.

We report our experience from a clinical trial of autologous bone marrow transplantation (ABMT) in the treatment of 30 patients with acute myeloid leukemia (AML) using monoclonal antibody (MoAb) and complement-treated bone marrow. All patients were in complete remission (CR) at the time of transplant: 6 patients were in first CR, 18 in second CR, and 6 in third CR. The median age of all patients was 42 years (range 11 to 57 years). For marrow ablation, 28 patients were treated with cyclophosphamide and total body irradiation. One patient was treated with busulfan and cyclophosphamide and one was treated with busulfan and VP-16. Each patient was then transfused with autologous bone marrow that had been harvested previously and treated with two MoAbs, PM-81 and AML-2-23, and rabbit complement. Median time to recovery of neutrophils (500/microL) was 30 days, and platelets (20,000/microL) was 45 days. Median time for initial erythrocyte engraftment, assessed by a flow cytometric reticulocyte assay, was 13 days. Median overall and relapse-free survival of first CR patients was at least 17.4 months post-ABMT and the 2- and 3-year actuarial overall and relapse-free survival was 67% (+/- 19%). Median survival for the 24 patients in second or third CR was 6.8 months post-ABMT and 9.3 months since CR; however, six patients survived disease-free from 16 to 61 months post-ABMT. For the second and third CR group it was observed that six patients (5 of the 6 survivors) showed "inversions," when their post-ABMT remission lasted longer than any previous one. Actuarial 2- and 3-year disease-free and overall survival of patients in second and third CR was 25% (+/- 9%) and 18% (+/- 9%), and 29% (+/- 9%) and 23% (+/- 9%), respectively. ABMT avoids the problems of graft-versus-host disease and of finding suitable donors for allogeneic marrow transplantation.

Adolescent↗
PubMed1990

Induction of differentiation in blast cells and leukemia colony-forming cells from patients with acute myeloid leukemia.

The characteristic lesion in acute myeloid leukemia (AML) is the failure of myeloid cells to differentiate normally, leading to the accumulation of immature blast cells (BC) in the bone marrow. We determined whether BC and leukemia colony-forming cells (L-CFC) from AML patients could differentiate in vitro after short-term culture with interferon-gamma (IFN gamma), 1,25 dihydroxyvitamin D3 (D3), retinoic acid (RA), tumor necrosis factor-alpha (TNF alpha), and granulocyte-monocyte colony-stimulating factor (GM-CSF). Expression of myeloid differentiation antigens CD15, CD14, CD33, and p124 was determined on the BC by immunofluorescence and on the L-CFC by monoclonal antibody (MoAb) and complement (C')-mediated cytotoxicity followed by cloning in methylcellulose. We found that 26 of 39 (67%) cases demonstrated changes in the expression of myeloid differentiation antigens on the BC, and 6 of 7 (86%) cases showed an altered L-CFC myeloid antigen phenotype after short-term culture with differentiating agents. Alterations in myeloid antigen expression in the L-CFC population correlated with a reduction in L-CFC cloning potential. In the BC, alterations of myeloid differentiation antigens occurred in a manner consistent with those observed during normal myelopoiesis. For example, CD14 antigen expression (a late-stage monocyte antigen) increased on BC from 12 of 39 (31%) cases, and p124 (an antigen expressed both by myeloid progenitor cells and by a subset of monocytes) increased on 15 of 39 (38%) cases. Changes in the expression of CD33 antigens (expressed normally by myeloid progenitor cells and by mature monocytes) on the BC were variable, with 7 of 29 cases (24%) showing a decrease and 7 of 29 cases (24%) showing an increase. When comparisons were made between pairs of differentiation agents that caused the altered expression of an antigen on either the BC or L-CFC of a patient, the majority of changes were in the same direction (either both "increased" or both "decreased"). This suggests that the direction of antigen change is characteristic of the leukemia cell subpopulation for each patient and not of the stimulatory agent. This study demonstrates that cells from more than two thirds of AML cases examined responded to various differentiation agents in vitro as measured by changes in the expression of myeloid cell-associated surface antigens and by alterations in cloning potential of the L-CFC, a finding of potential clinical significance.

Antigens, CD↗
PubMed1989

The Skin Cancer Prevention Study: design of a clinical trial of beta-carotene among persons at high risk for nonmelanoma skin cancer.

We describe a randomized clinical trial of oral beta-carotene (50 mg/day) for preventing nonmelanoma skin cancer. It is a multicenter study conducted at sites in California, Minnesota, and New Hampshire. This report describes the design of the study, baseline characteristics of the 1805 randomized patients, changes in their plasma beta-carotene and retinol levels after 1 year of treatment, and plans for statistical analyses. Important features of this study are (1) a high proportion of potential subjects were found to be ineligible or chose not to enter the study, (2) the study agent is readily available over the counter and in common foods, and (3) nonmelanoma skin cancer is a relatively minor health concern for most patients. These considerations necessitated intensive efforts to encourage compliance with the study regimen. There are also some unusual statistical features of the study. One is that the study outcome is routinely assessed only at annual examinations, so the precise time of failure cannot be identified. Also, a secondary goal of the study is to determine whether beta-carotene decreases the average number of new skin cancers per patient per year, and there are no established statistical methods for analysis of data in this situation. Alternative approaches to the analysis are discussed.

Adult↗
PubMed1989

Determinants of plasma levels of beta-carotene and retinol. Skin Cancer Prevention Study Group.

The associations of retinol and beta-carotene plasma concentrations with eight personal variables and the use of seven classes of cardiovascular drugs were studied in over 1,750 patients with nonmelanoma skin cancer enrolled at four American study centers in a cancer prevention clinical trial. Dietary carotene and female sex were positively related to beta-carotene levels, while cigarette smoking and Quetelet index were negatively related. Use of vitamins, beta blockers, or other antihypertensive drugs were also related to beta-carotene levels, but were associated with much smaller changes in these levels. Age and use of other types of cardiovascular drugs were not associated with beta-carotene levels to a statistically significant extent. There was no statistically significant interaction of smoking and dietary carotene in predicting plasma beta-carotene levels. The multiple correlation coefficient between log plasma beta-carotene and the full model was R = 0.50. Retinol levels were positively related to male sex and use of vitamins, diuretics, beta blockers, other cardiovascular drugs, and menopausal estrogens, and negatively related to current cigarette smoking and use of nitrates. The multiple correlation coefficient between plasma retinol and the full model was R = 0.33. These findings confirm the importance of several previously reported predictors of plasma retinol and beta-carotene levels. They also identify several new predictors of these micronutrient levels.

Adult↗
PubMed1989

Laryngeal complications of prolonged intubation.

In this study, 82 patients who experienced translaryngeal intubation (TLI) for more than four days were prospectively evaluated for laryngeal complications. At the time of extubation or tracheostomy, direct laryngoscopy was performed in these patients and laryngeal damage evaluated. A typical pattern of laryngeal damage was seen, consisting of mucosal ulcerations along the posterior-medial aspects of both vocal cords and varying degrees of laryngeal edema in 77 patients (94 percent). Performance of a tracheostomy and presence of neuromotor activity were associated with the severity of laryngeal damage, but duration of TLI was not. Laryngoscopy was repeated at two-week intervals in 54 patients and laryngeal damage was resolved within four weeks in 63 percent. These 54 patients were evaluated for adverse clinical effects arising from TLI-induced laryngeal pathology and no relationship was found between laryngeal pathology seen at initial laryngoscopy and the development of adverse effects.

Hoarseness↗
PubMed1986

The effects of a required fourth-year clinical pharmacology course on student attitudes and subsequent performance.

Beginning with the class graduating June 1984, Dartmouth Medical School introduced a required clinical pharmacology course. Approximately 89% of the fourth-year students felt that the course was "essential" to their future careers as physicians. As interns, 80% found the course frequently useful or essential during their internships; 84% felt that they were either slightly or much better prepared than their fellow interns with respect to their therapeutic knowledge and skills. Average student performance on a pretest (33% correct answers) improved dramatically on a posttest (87% correct; P less than 0.001). Finally, although student performance on all sections of Part II of the national board examinations showed statistically nonsignificant trends toward improvement (from the 48th to the 52nd percentile), performance on questions testing core concepts in clinical pharmacology improved from the 38th percentile to the 74th percentile (P less than 0.0001). This required fourth-year course in clinical pharmacology was evaluated favorably by our students and resulted in objective improvement in their therapeutic knowledge and skills.

Attitude↗
PubMed1986

Comparison of membrane filter, multiple-fermentation-tube, and presence-absence techniques for detecting total coliforms in small community water systems.

Methods for detecting total coliform bacteria in drinking water were compared using 1,483 different drinking water samples from 15 small community water systems in Vermont and New Hampshire. The methods included the membrane filter (MF) technique, a 10-tube fermentation tube (FT) technique, and the presence-absence (P-A) test. Each technique was evaluated using a 100-ml drinking water sample. Of the 1,483 samples tested, 336 (23%) contained coliforms as indicated by either one, two, or all three techniques. The FT detected 82%, the P-A detected 88%, and the MF detected 64% of these positives. All techniques simultaneously detected 55% of the positives. Evaluation of the confirmation efficiency of the P-A technique showed 94% of the presumptive positives confirming as coliforms. Thirteen different species of coliforms were identified from the 37 tests in which the P-A was positive but the MF and FT were negative. The P-A test was simple to inoculate and interpret and was considerably more sensitive than the MF and slightly more sensitive than the FT in detecting coliforms in this type of drinking water supply.

Bacteriological Techniques↗
PubMedDate not supplied

A meta-analytic method for summarizing diagnostic test performances: receiver-operating-characteristic-summary point estimates.

The authors have devised a meta-analytic method to summarize diagnostic test performances, which they describe along with a clinical example wherein they analyze the performances of real-time ultrasonography in eight studies of the detection of proximal deep venous thrombosis of the lower extremity, selected on the basis of specific inclusion criteria. To evaluate the evidence for fitting a summary receiver operating characteristic (ROC) curve, a test of correlation between the estimates of true-positive rate (TPR) and false-positive rate (FPR) is performed. A high positive correlation argues for summarizing the studies with an ROC curve. In the absence of such correlation, a test of homogeneity is applied separately to the estimates of sensitivity (TPR) and specificity (TNR) to evaluate whether differences among studies are due to chance alone. If the estimates are homogeneous, a summary point estimate and confidence intervals (CIs) are calculated. As a final step, subgroup analyses can be performed to assess alternative explanations of variability in TPR and FPR. Within groups defined by the presence or absence of symptoms of venous thrombosis, a negative correlation between TPR and FPR and homogeneity among studies were found. For symptomatic patients, the summary TPR was 0.97 with a 95% CI of (0.94, 0.99) and the summary TNR was 0.97 (0.95, 0.99). For asymptomatic patients, the summary TPR was 0.66 (0.50, 0.81), and the summary TNR was 0.96 (0.90, 0.99). The difference in TPR between symptomatic and asymptomatic patients was statistically significant. There was no evidence that test referral bias or lack of independent interpretation of test results influenced these findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Confidence Intervals↗
PubMedDate not supplied

A randomized trial of the use of patient self-assessment data to improve community practices.

OBJECTIVE: Because of time constraints in the office environment, problems of concern to elderly patients may not be raised during clinic visits. To facilitate communication about geriatric health problems, we examined the impact of a strategy that used patient self-assessment data to improve community practices. DESIGN: Twenty-two primary care practices were randomized to participate in the intervention strategy (intervention practices) or to provide usual care (usual care practices). SETTING: Primary care practices in 16 towns in New Hampshire (total, 45 physicians). PATIENTS: 1651 patients 70 years of age or older. INTERVENTION: All patients received a mailed survey that asked about their health problems and about how well these problems were being addressed by their physicians. In the intervention practices, these data were used to generate a customized letter that directed the patient to specific sections in an 80-page modified version of the National Institute on Aging's Age Pages and were summarized and communicated to the patient's physician. MAIN OUTCOME MEASURE: Change from baseline in patients' overall assessment of health care. RESULTS: In 8 of 11 intervention practices, patients felt that their care had improved over the 2-year study period. This improvement occurred in only 1 of 11 usual care practices (P = 0.003). Patients in intervention practices reported receiving significantly more help with physical function, fall prevention, and assistance for memory problems. Self-assessed health status did not differ in the two groups. CONCLUSION: A standard, easy-to-implement strategy to improve the quality of provider--patient interactions can improve the satisfaction of older patients cared for in community practices.

Aged↗
PubMedDate not supplied

The uneven landscape of newborn intensive care services: variation in the neonatology workforce.

CONTEXT: In the past 30 years, the number of neonatologists has increased while total births have remained nearly constant. It is not known how equitably this expanded workforce is distributed. OBJECTIVE: To determine the geographic distribution of neonatologists in the United States. DATA SOURCES: 1996 American Medical Association physician masterfiles; 1999 survey of all U.S. neonatal intensive care units; 1995 American Hospital Association hospital survey; and 1995 U.S. vital records. MEASURES: The number of neonatologists and neonatal mid-level providers per live birth within 246 market-based regions. RESULTS: The neonatology workforce varied substantially across neonatal intensive care regions. The number of neonatologists per 10,000 live births ranged from 1.2 to 25.6 with an interquintile range of 3.5 to 8.5. The weakly positive correlation between neonatologists and neonatal mid-level providers per live birth is not consistent with substitution of neonatal mid-level providers for neonatologists (Spearman rank-correlation coefficient, 0.17; P < 0.01). There was no difference in the percentage of neonatal fellows in the lowest and highest workforce quintile (14% vs. 16%) or in the percentage of neonatologists engaged predominantly in research, teaching, or administration (14% in lowest and highest quintiles). CONCLUSIONS: The regional supply of neonatologists varies dramatically and cannot be explained by the substitution of neonatal mid-level providers or by the presence of academic medical centers. Further research is warranted to understand whether neonatal intensive care resources are located in accordance with risk and whether more resources improve newborn outcomes.

Age Distribution↗