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Biomedical subjects

R F Woolson

Publications and source records attributed to R F Woolson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Microcirculation architecture of metastases from primary ciliary body and choroidal melanomas.

PURPOSE: To describe the microcirculation architecture of metastatic choroidal and ciliary body melanoma. METHOD: Histologic sections of 35 metastases from 19 primary melanomas were stained to demonstrate microcirculation. RESULT: The appearance of microcirculatory networks in metastases is independent of the target organ but associated with the size of the metastatic deposit (estimated coefficient = 0.5959; SE = 0.3024; P = .0488). CONCLUSION: The microcirculatory patterns of primary uveal melanomas that are associated with metastatic behavior appear in foci of metastasis, regardless of the site of dissemination.

Choroid Neoplasms↗
PubMed1998

The dynamics of disease progression in sepsis: Markov modeling describing the natural history and the likely impact of effective antisepsis agents.

We conducted a 9-month prospective cohort study of 2,527 patients with systemic inflammatory response syndrome in three intensive care units and three general wards in a tertiary health care institution. Markov models were developed to predict the probability of movement to and from more severe stages--sepsis, severe sepsis, or septic shock--at 1, 3, and 7 days. For patients with sepsis, severe sepsis, and septic shock, the probabilities of remaining in the same category after 1 day were .65, .68, and .61, respectively. The probability for progression after 1 day was .09 for sepsis to severe sepsis and .026 for severe sepsis to shock. The probability of patients with sepsis, severe sepsis, and septic shock dying after 1 day was .005, .009, and .079, respectively. The model can be used to predict the reduction in end organ dysfunction and mortality with use of increasingly effective antisepsis agents.

Disease Progression↗
PubMed1997

Discriminant analysis using the unweighted sum of binary variables: a comparison of model selection methods.

Many clinical decision-making rules are equivalent to linear discriminant functions that involve the unweighted sum of binary variables (SBV). We briefly consider the geometry of this restriction and then propose a number of methods for forward stepwise selection of SBV models. Using a simulation study, we compare the performance of these methods under a wide range of plausible conditions and show that no single method is uniformly superior for selecting models of a fixed size. Factors of general importance in relative method performance are the ratio of sample size to the number of candidate variables and the class-conditional moment structure of the data. We conclude by offering some practical strategies for SBV model construction.

Computer Simulation↗
PubMed1997

Design of the Trial of Org 10172 in Acute Stroke Treatment (TOAST).

TOAST is a multicenter, randomized, placebo-controlled clinical trial testing the usefulness of a new antithrombotic drug in improving the outcome of persons with acute ischemic stroke. Until recently, no clinical trial testing a treatment for ischemic stroke had demonstrated efficacy in outcome. Design problems of previously conducted trials with inconclusive results may partly explain their failures. During the design of TOAST, the investigators addressed several issues so the trial could test the treatment accurately. We report the strategies used in designing, implementing, and coordinating the trial.

Adult↗
PubMed1997

Microbiological factors influencing the outcome of nosocomial bloodstream infections: a 6-year validated, population-based model.

All patients (n = 1,745) with nosocomial bloodstream infection identified between 1986 and 1991 at a single 900-bed tertiary care hospital were studied to identify microbiological factors independently associated with mortality due to the infection. Patients were identified by prospective, case-based surveillance and positive blood cultures. Mortality rates were examined for secular trends. Prognostic factors were determined with use of univariate and multivariate analyses, and both derivation and validation sets were used. A total of 1,745 patients developed nosocomial bloodstream infection. The 28-day crude mortality was 22%, and crude in-hospital mortality was 35%. Factors independently (all P < .05) associated with increased 28-day mortality rates were older age, longer length of hospital stay before bloodstream infection, and a diagnosis of cancer or disease of the digestive system. After adjustment for major confounders, Candida species were the only organisms independently influencing the outcome of nosocomial bloodstream infection (odds ratio [OR] for mortality = 1.84; 95% confidence interval [CI], 1.22-2.76; P = .0035). The two additional microbiological factors independently associated with increased mortality were pneumonia as a source of secondary infection (OR = 2.74; 95% CI, 1.87-4.00; P < .0001) and polymicrobial infection (OR = 1.68; 95% CI, 1.22-2.32; P = .0014). Our data suggest that microbiological factors independently affect the outcome of nosocomial bloodstream infection.

Adult↗
PubMed1996

Silent cerebral infarction in patients enrolled in the TOAST Study.

To determine the frequency, location, size, and risk factors for silent cerebral infarctions (SCIs) on brain CT, we identified 629 patients without a history of previous stroke who were enrolled in a multicenter clinical trial of therapy for acute ischemic stroke. On the baseline CT, 143 patients (22.7%) had SCIs; 34.3% of the lesions were in the right hemisphere, 38.5% in the left hemisphere, and 27.3% were bilateral. The lesion size was < 1 cm in 65.7%, and the most common site was the basal ganglia (48.3%). Patients with SCI were compared with controls without SCI to determine the odds ratios (ORs) for each risk factor. On univariate analysis, race (black versus white) had an OR of 1.80 (95% confidence interval [CI], 1.14 to 2.85), male sex an OR of 1.68 (95% CI, 1.12 to 2.51), and congestive heart failure an OR of 1.88 (95% CI, 1.07 to 3.31). Significant risk factors on multivariate analysis include age (OR 1.03 per year, p = 0.0070), male sex (OR 1.78, p = 0.0094), and race (OR 2.43, p = 0.0004). After including interaction terms with age and hypertension and age, sex, and race, hypertension was also a significant risk factor.

Adolescent↗
PubMed1996

A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease.

A 1-year, double-blind, placebo-controlled, randomized, parallel-group study compared the efficacy and safety of acetyl-L-carnitine hydrochloride (ALCAR) with placebo in patients with probable Alzheimer's disease (AD). Subjects with mild to moderate probable AD, aged 50 or older, were treated with 3 g/day of ALCAR or placebo (1 g tid) for 12 months. Four hundred thirty-one patients entered the study, and 83% completed 1 year of treatment. The Alzheimer's Disease Assessment Scale cognitive component and the Clinical Dementia Rating Scale were the primary outcome measures. Overall, both ALCAR- and placebo-treated patients declined at the same rate on all primary and most secondary measures during the trial. In a subanalysis by age that compared early-onset patients (aged 65 years or younger at study entry) with late-onset patients (older than 66 at study entry), we found a trend for early-onset patients on ALCAR to decline more slowly than early-onset AD patients on placebo on both primary endpoints. In addition, early-onset patients tended to decline more rapidly than older patients in the placebo groups. Conversely, late-onset AD patients on ALCAR tended to progress more rapidly than similarly treated early-onset patients. The drug was very well tolerated during the trial. The study suggests that a subgroup of AD patients aged 65 or younger may benefit from treatment with ALCAR whereas older individuals might do more poorly. However, these preliminary findings are based on past hoc analyses. A prospective trial of ALCAR in younger patients is underway to test the hypothesis that young, rapidly progressing subjects will benefit from ALCAR treatment.

Acetylcarnitine↗
PubMed1995

Relation between the microcirculation architecture and the aggressive behavior of ciliary body melanomas.

PURPOSE: To study the relation between vascular patterns and the biologically aggressive behavior of ciliary body melanomas. METHODS: The authors compared the frequency distribution of vascular patterns by location for 234 uveal melanomas (54 tumors involving the ciliary body, and 180 without ciliary body involvement). Stepwise Cox regressions (for the endpoint of time-to-death due to melanoma), performed separately for melanomas with and without ciliary body involvement, included the following variables: size, vascular patterns, cell type, mean of the largest nucleoli, mitoses, tumor infiltrating lymphocytes, age, and sex. A separate Cox regression procedure included the variable of tumor location. Kaplan-Meier survival curves were generated for time to melanoma death with ciliary body involvement and melanomas without ciliary body involvement for tumors containing or lacking vascular networks. RESULTS: These vascular patterns appear more often in the ciliary body than in the choroid: parallel vessels (P = 0.022), arcs (P = 0.003), and parallel with cross-linking, arcs with branching, and loops and networks (all P = 0.0001). Stepwise regression for tumors confined to the choroid indicated that the presence of networks was the most significant variable (P = 0.0001); stepwise regression for tumors with ciliary body involvement suggested that only one variable, networks, was significant (P = 0.0066). Kaplan-Meier survival estimates indicated that the survival of patients with tumors containing networks in the ciliary body was comparable to those containing networks in the choroid. CONCLUSION: Regardless of location, ciliary body or choroid, the presence of vascular networks shortens survival. The tumor location does not enter a stepwise Cox regression model when vascular patterns are included as variables. Therefore, the aggressive behavior of ciliary body melanomas appears to be related to the tendency for vascular networks to develop in this location.

Adolescent↗
PubMed1995

Using Kendall's tau b correlations to improve variable selection methods in case-control studies.

In this manuscript we evaluate the performance of a variable selection procedure that could be used in case-control studies. This method is based on selection statistics computed from a matrix of Kendall tau b correlation coefficients. A simulation study was performed to compare the performance of this method to logistic regression, discriminant analysis, and the rank-transformed versions of these methods. For most of the situations studied the method based on Kendall tau b correlation coefficients correctly selected the variables that were related to case-control status more often than any of the other methods. We discuss the implications of the results of this study for epidemiologic research.

Biometry↗
PubMed1994

A comparison of two methods of estimating a common risk difference in a stratified analysis of a multicenter clinical trial.

In this paper, we compare two methods of estimating the difference between the proportion of adverse events in a test treatment group and the proportion of adverse events in a control treatment group in a multicenter clinical trial. We used simulated data to compare the bias and mean squared error of the weighted least squares estimator to the bias and mean squared error of the Cochran-Mantel-Haenszel estimator. We also computed the coverage probabilities for confidence intervals derived from these estimators. We found that the weighted least squares method was often seriously biased. The coverage probabilities for the Cochran-Mantel-Haenszel estimators were often closer to their nominal values than were the coverage probabilities for the weighted least squares estimators. It also was found that these methods require a larger sample size to maintain coverage probabilities near their nominal values when unequal numbers of persons are assigned to the test and control treatments.

Anticoagulants↗
PubMed1994

Mean of the ten largest nucleoli, microcirculation architecture, and prognosis of ciliochoroidal melanomas.

BACKGROUND: Cytomorphometric measurements and the architecture of the microcirculation in tissue sections of eyes removed for ciliary body or choroidal melanomas have been identified independently as prognostically significant factors for survival. The relative significance of these two histologic features is addressed in this study. METHODS: The same 234 cases used to assess the prognostic significance of the microcirculatory patterns of choroidal and ciliary body melanomas were examined by two independent observers who measured the largest diameter of melanoma cell nucleoli from digitized images at a high magnification (x 3000) using the laser scanning confocal microscope. The mean of the ten largest nucleoli was calculated for each tumor according to previously published methods. Intraobserver and interobserver reproducibility was assessed for these measurements. Several Cox multiple regression models were constructed which included this cytomorphometric variable with and without the inclusion of the microcirculatory patterns. RESULTS: There is a high degree of intraobserver reproducibility but only a weak degree of interobserver reproducibility in measuring the mean of the ten largest nucleoli. Using multiple Cox regression models, the mean of the ten largest nucleoli from each observer failed to exert any effect on outcome after enucleation, regardless of whether the presence of networks of closed vascular loops was considered in the statistical formulation. The presence of networks of closed vascular loops was found to be the most statistically dominant histologic prognostic characteristic. CONCLUSION: The authors have not been able to confirm the use of the mean of the ten largest nucleoli as a significant prognostic factor in the outcome of patients whose eyes have been removed for ciliary body or choroidal melanomas. Further investigation of this cytomorphometric technique by other laboratories is warranted.

Adult↗
PubMed1994

Microcirculation architecture of melanocytic nevi and malignant melanomas of the ciliary body and choroid. A comparative histopathologic and ultrastructural study.

PURPOSE: This study was designed to (1) describe the vascular patterns of ciliary body and choroidal nevi by light microscopy, (2) compare the vascular ultrastructure of nevi with vessels of the normal uvea and uveal melanomas, and (3) compare the behavior of ciliochoroidal melanomas with and without a nevus-like vascular architecture. METHODS: After delineating the vascular patterns of 23 choroidal and ciliary body nevi by light microscopy, the authors identified 49 melanomas that had the same vascular patterns as nevi from a previously published series of 234 uveal melanomas. The survival of these 49 patients who had melanomas with a nevus-like vascular architecture was compared with the 185 patients who had melanomas that lacked this vascular profile. RESULTS: By light microscopy, the only vascular patterns identified in nevi are "normal" vessels, zones of avascularity ("silent" pattern), straight, and parallel vessels; closed vascular loops and networks were not detected in nevi. By transmission electron microscopy, the vascular basement membrane of malignant melanomas was multilaminar, fragmented, and significantly thicker than in normal eyes or nevi. None of the patients with nevi died of metastatic disease. Fourteen percent of patients whose melanomas had the same vascular profile as nevi died of metastatic disease, whereas 32% of patients whose melanomas had vascular patterns other than those seen in nevi died of metastatic melanoma (P = 0.012). CONCLUSIONS: The microcirculation architecture marks tumor progression in uveal melanocytic lesions by light and electron microscopy. In the spectrum of these lesions, nevi are benign, melanomas that have the same vascular profile as nevi have an intermediate biologic behavior, and melanomas with vascular networks are strongly associated with death due to metastatic disease.

Adolescent↗
PubMed1994

Residential radon exposure and lung cancer: evidence of an urban factor in Iowa.

An ecological study of lung cancer, cigarette smoking, and radon exposure was conducted in 20 Iowa counties. County-based lung cancer incidence data for white female residents of Iowa were stratified according to radon level and smoking status. Cancer incidence data for the period 1973-1990 were obtained from the State Health Registry of Iowa. Smoking level was determined from a randomly mailed survey. Radon level was determined according to an EPA supported charcoal canister survey. Within low smoking counties, rates for all lung cancer and small cell carcinoma were significantly lower (p < 0.05) in the high radon counties relative to the medium and low radon counties. However, within high smoking counties, rates for all lung cancer, adenocarcinoma, and small cell carcinoma were significantly higher (p < 0.05) in the high radon counties relative to the low radon counties. Variations in socioeconomic data for these counties, available through the 1980 and 1990 census, did not explain these results. Lung cancer rates also were significantly increased in urban counties even after holding smoking status constant. Multivariate analyses revealed significant interactions between smoking, urbanization, radon levels, and lung cancer. The results of this hypothesis generating study will be tested in a case/control study now ongoing in Iowa. Analysis will need to include separate evaluations by smoking status, radon level, and residence in urban or rural areas for the major morphologic types of lung cancer.

Adenocarcinoma↗
PubMed1994

Ensuring reliability of outcome measures in multicenter clinical trials of treatments for acute ischemic stroke. The program developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST).

BACKGROUND AND PURPOSE: Ensuring the reliability and validity of outcome measures used in clinical trials is essential to the success of the trial. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) is a multicenter clinical trial that is recruiting patients with acute ischemic stroke seen at medical centers across the United States. METHODS: This paper describes an approach to train physicians to use three clinical measures: the National Institutes of Health (NIH) Stroke Scale, a supplemental motor examination, and the Glasgow Outcome Scale. The program included education, certification, remediation when needed, monitoring, and reliability assessment. The goal was to ensure that interrater assessments were as equivalent to one another as possible. RESULTS: Of the first 95 clinicians who began the certification process, 75 passed during the first evaluation. Eighteen of the other physicians were able to complete the process after remediation. The intraclass correlations of both the NIH Stroke Scale and supplemental motor examination exceeded 0.95. The kappa values for the Glasgow Outcome Scale were 0.61 and 0.62 for the first and second ratings of the videotape, respectively. CONCLUSIONS: Our experience suggests that a program that includes educational and certification processes can be performed as part of the design of a multicenter clinical trial. The method of providing educational and testing videotapes to each site so that physicians can be trained and certified is an effective, inexpensive, and practical approach for enhancing and certifying the expertise of the large number of physicians involved in a multicenter study.

Brain Ischemia↗
PubMed1994

Slope estimation in the presence of informative right censoring: modeling the number of observations as a geometric random variable.

A method is proposed for the estimation of rate of change from incomplete longitudinal data where the number of observations made for each subject is assumed to vary depending on the level of the response variable. The proposed method involves a random slope model, in which the number of observations is modeled as a geometric distribution with its mean dependent on the individual subject's rate of change. The method adjusts for informative right censoring and provides estimates of the slopes of individual subjects as well as of the population. Under noninformative right censoring these estimators of the slopes are equivalent to Bayes estimators (Fearn, 1975, Biometrika 62, 89-100). The simulation study demonstrates that, in cases where the censoring process is informative, the proposed estimator is more efficient than either the unweighted or weighted estimator of slope. The method is illustrated by the analysis of renal transplant data.

Adult↗