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Biomedical subjects

R F Woolson

Publications and source records attributed to R F Woolson.

18 recordsLinked to original sources

A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer's disease. The Tacrine Collaborative Study Group.

BACKGROUND: In Alzheimer's disease, there is a marked decline in the function of cholinergic neurons in the brain. However, studies of treatment with cholinesterase inhibitors have produced conflicting results. We conducted a multicenter trial to evaluate whether the cholinesterase inhibitor tacrine (1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate) could improve cognition in patients with Alzheimer's disease. METHODS: Of 632 eligible patients with probable Alzheimer's disease, 215 improved while receiving tacrine during a preliminary crossover phase to determine responsiveness and the best dose. The 215 patients were randomly assigned to receive either placebo or their best dose of tacrine (10 or 20 mg four times a day) in a six-week, double-blind trial. The primary measures of efficacy were the cognitive subscale of the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change scale; the secondary measures included the Mini-Mental State Examination and the assessment of the activities of daily living. RESULTS: At the end of the six-week trial, the patients receiving tacrine had a mean adjusted cognitive-subscale score of 30.3 (Alzheimer's Disease Assessment Scale) as compared with 32.7 in patients receiving placebo. This represents a smaller decline (by 2.4 points) in cognitive performance in the tacrine group (P < 0.001). There were no differences between the groups in their global-rating scores. The tacrine group had a significantly smaller decline in the activities of daily living. The results of the Mini-Mental State Examination favored tacrine, but the differences were small and not statistically significant (a score of 16.0 with tacrine vs. 15.3 with placebo; P = 0.08). Gastrointestinal symptoms, elevation of aminotransferase levels, and headache were the most frequent side effects; all could be reversed by reducing the dose or discontinuing treatment. CONCLUSIONS: In this short-term study in patients with Alzheimer's disease who were selected for apparent responsiveness to tacrine, treatment with tacrine resulted in a statistically significant reduction in the decline of cognitive function, although this reduction was not large enough to be detected by the study physicians' global assessments of the patients.

Activities of Daily Living

A comparison of several tests for censored paired data.

This paper reviews several tests for censored paired data and uses Monte Carlo methods to evaluate their sizes and powers. Each of the tests maintains its size. The Akritas test and the paired Prentice-Wilcoxon test are somewhat more powerful than the Gehan statistic or the generalized signed rank test for most of the distributions studied. If the survival times follow an exponential distribution, then the Gehan and the generalized signed rank tests are more powerful against a location shift alternative.

Computer Simulation

Application of empirical Bayes inference to estimation of rate of change in the presence of informative right censoring.

We apply parametric empirical Bayes inference of Morris to the estimation of rate of change from incomplete longitudinal studies where the right censoring process is considered informative, that is, the length of time the subjects participate in the study is associated with level of the study variable. Ignoring such an association can result in a biased estimate of rate of change. The proposed method provides estimates of rate of change for individual subjects as well as for the entire group, adjusted for informative right censoring. The method is considered more robust than those based on a specific parametric model for the censoring distribution. Under non-informative right censoring these estimators of slopes are equivalent to the Bayes estimators derived by Fearn. We illustrate the method with an example involving renal transplant data. We evaluate the method's performance through a simulation study.

Bayes Theorem

The morphologic characteristics of tumor blood vessels as a marker of tumor progression in primary human uveal melanoma: a matched case-control study.

Nine morphologic patterns of tumor vessels were identified in eyes removed for ciliary body or choroidal melanoma by the examination of tissue sections stained with fluorescein-conjugated Ulex europaeus I using laser scanning confocal microscopy. This technique also highlights intravascular tumor invasion. Each of these nine morphologic patterns of tumor vessels also may be demonstrated by a modification of the periodic acid-Schiff reaction, viewed with a green narrow band pass filter, but this modified histochemical technique does not accurately identify intravascular tumor invasion. Most tumors have a heterogeneous distribution of vascular patterns. Melanomas in two groups of 20 tumors each were matched by tumor size and location (one group of tumors from patients who survived at least 15 years free of metastatic melanoma after enucleation and one group of tumors from patients who died of metastatic melanoma). A matched case-control analysis indicates that the presence of at least one closed vascular loop in a uveal melanoma is the most significant vascular pattern associated with death from metastatic melanoma after enucleation. Closed loops are associated with other histologic features that are predictive of an unfavorable outcome after enucleation: epithelioid cells and mitotic figures. In this preliminary study the formation of closed vascular loops is a marker of tumor progression in ciliary body and choroidal melanomas.

Adult

Studies of Org 10172 in patients with acute ischemic stroke. TOAST Study Group.

This report presents data from pilot studies of Org 10172 in the management of patients with acute ischemic stroke. The studies have established a potentially optimal dosage and treatment regimen and have provided information for the development of a large randomized trial. The trial of Org 10172 in acute stroke treatment is now underway in the United States.

Brain Ischemia

Dietary habits, prepregnancy weight, and weight gain during pregnancy. Risk of pre term rupture of amniotic sac membranes.

BACKGROUND: Premature rupture of amniotic sac membranes (PROM) is associated with perinatal morbidity and mortality. A matched case-control study was undertaken to determine whether dietary habits, prepregnancy weight, and weight gain during pregnancy were associated with increased risks for PROM. METHODS: Three study groups were defined, consisting of women delivering pre term with PROM (PP), full term with PROM (FP), and pre term without PROM (PWP). Cases were singly matched by race, age, and parity with women having full term deliveries without PROM. Data were collected by face-to-face structured interviews with eligible subjects and by medical records abstraction. RESULTS: Conditional multiple logistic regression indicated that during pregnancy, PP cases were significantly more likely to have gained less than 21 pounds (9.5 kg) (OR = 2.7, CI = 1.14-6.36) and were only half as likely as controls to have improved their diet (OR = 0.43, CI = 0.18-0.99) while controlling for cigarette smoking, urinary tract infection, chorioamnionitis, chlamydia, and a history of previous PROM. FP cases were significantly less likely than controls to have gained 31-40 pounds (14-18 kg) while pregnant (OR = 0.56, CI = 0.33-0.94) and were significantly more likely than controls to have a somewhat inadequate pregnancy diet (OR = 2.05, CI = 1.11-3.77) while controlling for a history of previous PROM. PWP cases were significantly less likely to have gained 31-40 pounds (14-18 kg) (OR = 0.42, CI = 0.21-0.84) or greater than 40 pounds (18 kg) (OR = 0.37, CI = 0.17-0.80) while pregnant or to have had adequate dairy products intake (OR = 0.60, CI = 0.36-0.99) while controlling for cigarette usage. CONCLUSION: Maternal dietary habits, weight gain during pregnancy, and supplement intake are associated with the occurrence of both pre term and full term PROM and pre term delivery without PROM.

Adult

Quantification of visual fields for statistical analysis.

The importance of visual fields in the study of ocular vascular disorders prompted the development of a method to convert visual fields plotted on a Goldmann perimeter into a digital form so that the data could be analyzed and stored by a computer. An instrument called a scotometer was designed to measure the visual fields and the various scotomata, and a data coding form was developed to facilitate the entry of the data into the computer. After extensive testing, this method is now being used in several clinical trials. Statistics have been computed that support the reliability of the coding process.

Computers

Long-term outcome of major psychoses. I. Schizophrenia and affective disorders compared with psychiatrically symptom-free surgical conditions.

We conducted a 30- to 40-year field follow-up of 685 patients with schizophrenia, affective disorders, and nonpsychiatric conditions. Long-term outcome was analyzed in terms of the patients' marital, residential, occupational, and psychiatric status. On the whole, psychiatric patients showed a significantly poorer outcome than the surgical controls. On the basis of long-term outcome, schizophrenia, and affective disorders, selected according to the specified research criteria, were significantly different: schizophrenia definitely showed poorer outcome than affective disorders. However, no significant differences in all four outcome variables were found between mania and depression. We hope that the present data on long-term outcome of the typical cases can be used to compare outcome of other psychiatric disorders, such as undiagnosed psychoses, having mixtures of schizophrenic and affective features. In doing this, we hope to charify our understanding of undiagnosed psychoses and their relationship to schizophrenia and affective disorders.

Adult

Comparing psychological and pharmacological treatments for hyperkinetic boys and their classmates.

This study compares the short-term effects of methylphenidate and of teacher consultation on the on-task behavior of diagnosed hyperkinetic outpatient boys and selected classmates. Statistically significant treatment effects were found for both drug-treated and behaviorally treated hyperkinetic boys; the size of these effects did not differ between the two types of treatment. Within the behavioral group, the treatment effect spilled over, so that there was also a significant treatment effect on overactive classmates of the behaviorally treated hyperkinetic children and a trend toward a significant treatment effect on their average classmates. Some implications of the findings are discussed.

Attention

Direct and indirect laser photocoagulation of central serous choroidopathy.

A 3 1/2-year prospective randomized clinical trial showed a definite superiority of direct argon laser photocoagulation to the fluorescein leaking site compared to indirect treatment away from the leak in patients with central serous choroidopathy. One patient in each treatment group developed a subretinal neovascular membrane after photocoagulation to the fluorescein leak. Moderate prolongation of the neurosensory detachment did not adversely influence the final visual acuity in the indirect treatment group. Although direct laser photocoagulation reduces the duration of central serous choroidopathy, there is a risk of producing subretinal neovascularization. The principles of risk vs benefit should be explained to all patients and treatment should be advised only for compelling reasons.

Adolescent

A computer program for survival comparisons to a standard population.

PROPHAZ is a computer program created for the analysis of survival data using the general proportional hazards model. It was designed specifically for the situation in which the underlying hazard function may be estimated from the mortality experience of a large reference population, but may be used for other problems as well. Input for the program includes the variables of interest as well as the information necessary for estimating the hazard function (demographic and mortality data). Regression coefficients for the variables of interest are obtained iteratively using the Newton-Raphson method. Utilizing large sample asymptotic theory, x2 statistics are derived which may be used to test hypotheses of the form C beta = 0. Input format is completely flexible for the variables of interest as well as the mortality data.

Computers

Excess mortality in schizophrenia and affective disorders. Do suicides and accidental deaths solely account for this excess?

Excess mortality was found in the first decade of follow-up for schizophrenia and affective disorders. This trend continued for schizophrenia throughout the entire four decades of the follow-up period. Suicides were higher than expected for all psychiatric groups except female schizophrenics and male manics. Accidental deaths were higher in these two groups, which did not show significantly excessive suicide rates. Suicides and accidental deaths were then excluded from the mortality analysis to determine their contribution to excess nortality. We conclude that death due to suicides and accidental deaths is not the sole cause for excess mortality, especially in schizophrenia.

Accidents

Mortality in patients with schizophrenia, mania, depression and surgical conditions. A comparison with general population mortality.

Mortality data are presented from a four-decade follow-up study of 200 schizophrenic, 100 manic, 225 depressive patients, and 160 surgical controls (80 appendicectomy; 80 herniorrhaphy). Data for this analysis were available on 648 (95 per cent) members of the study population. Using sex-age standardized mortality ratios (SMR), the mortality experience of the study population was compared with that of the state of Iowa, the geographical area served by the admitting medical facility for the study group. Results are presented for a four-decade period beginning 1935-44, and ending 1965-74. All three psychiatric groups had a significant increase in mortality risk. This was most pronounced in the first decade following admission, although schizophrenic patients, especially females, continued to show a significant excess of deaths throughout the entire four decades of the follow-up period. During no decade of the follow-up period did the mortality of the surgical controls differ significantly from that of the Iowa population.

Adult

Osmoltye and tryptophan receptors controlling gastric emptying in the dog.

The effect of three monosaccharides, three disaccharides, two dipeptides, combinations of tryptophan with two hexoses, one hexitol, and two amino acids ongastric emptying was studied in dogs to further define the samll intestinal receptors responsive to osmolytes and tryptophan. On a molar basis the disacchardies and dipeptides were almost twice as potent as their respective constituent monosaccharides or amino acids implying that the osmoreceptor is deep to the brush border disaccharidases and cytosol dipeptidases. Tryptophan probably acts by a mechanism different from the osmoreceptor since slowing of gastric emptying by tryptophan was inhibited by methionine which has no effect on a stimulant of the osmoreceptor mechanism. Lysine unlike methionine does not share the neutral amino acid transport pathway with tryptophan. Lysine did not change the inhibitory effect of tryptophan on gastric emptying. This imples that transport of tryptophan into the intestinal cell is necessary for its slowing effect. Glucose and galactose also inhibited the tryptophan effect whereas a nonabsorbed hexitor, mannitol, was without effect. Interference by the hexoses was also probably by competition with tryptophan for transport into the cell. These studies further indicate that the tryptophan receptor is different from the osmoreceptor.

Alanine

The relative risk of spontaneous complete atrioventricular block in elderly patients with impaired intra-ventricular conduction.

We reviewed 144 consecutive patients with symptomatic high grade atrioventricular block. Cases due to congenital heart disease, acute myocardial infarction, cardiac surgery or digitalis toxicity were excluded. Of the remaining, we chose 71 patients in whom atrioventricular conduction was observed either intermittently during complete heart block (CHB) or in electrocardiograms taken within two years prior to documentation of CHB. The mean age was 69 years, with the peak incidence in the seventh decade in 43 men and eight decade in 28 women. Bundle branch block (BBB) was present in 76% of patients as follows: 47% had right BBB (20% with normal QRS axis, 20% with left axis deviation and 7% with right axis deviation), 17% had left BBB (11% with normal QRS axis and 6% with left axis deviation) and 12% had either alternating BBB, right BBB with alternating axis deviation or atypical BBB. "Trifascicular block" patterns accounted for 21% of the total group of CHB. We also studied the prevalence of various patterns of BBB in a group of 2000 random hospital patients of comparable age and sex exclusive of those with acute myocardial infarction and heart surgery. The risk of CHB for the various patterns of BBB was calculated relative to normal intraventricular conduction. All patterns of BBB carried a considerably increased relative risk of CHB, (P smaller than .01). The relative risk was highest for RBBB with left axis deviation and lowest for LBBB with normal or left axis deviation. In the men, 74% had QRS patterns of "bifascicular" or "trifascicular" block during atrioventricular conduction. By contrast, 71% women had atrioventricular beats showing either no BBB or right BBB with normal QRS axis. QRS pattern during CHB was unchanged from that during atrioventricular conduction in 52% if cases (rabge 38%-76% with different QRS patterns) suggesting idiojunctional pacemaker. CHB in these cases was thought to be due probably to coexistent disease in the AV node or His bundle. Although the concept of uni-, bi- and trifascicular block patterns has been useful in identifying patients at greater risk of CHB, the predictability of the electrocardiogram has obvious limitations, particularly in women.

Aged

Effects of essential and nonessential amino acids on gastric emptying in the dog.

Five dogs with gastric fistulas were studied to assess the effect on gastric emptying of two potent cholecystokinin (CCK) releasers (tryptophan and phenylalanine) and six other essential amino acids; the nonessential amino acids alanine, beta-alanine, arginine, asparagine, aspartic acid, citrulline, cysteine, cystine, glutamic acid, glutamine, D-glutamine, histidine, hydroxyproline, ornithine, proline, serine, tyrosine, and D-tryptophan; four peptide and amino acid preparations; and solutions of glucose, glycine, and mannitol. Of the essential amino acids, only tryptophan significantly slowed emptying and it was above 4 mM that there was a difference between control and test meal. The delay in response to tryptophan was dose-related and approached maximum at 40 mM; D-tryptophan had no effect at these concentrations. In concentrations up to 80 mM, none of the nonessential amino acids slowed emptying significantly. The four peptide and amino acid preparations in concentrations ranging from 80 to 700 milliosmoles had dose responses identical to those of D-glucose, glycine, and mannitol at similar osmolalities. It is concluded that L-tryptophan is a uniquely potent delayer of gastric emptying in the dog which is dose-dependent and stereospecific. Phenylalanine, a potent CCK releaser, did not slow emptying, which suggests that CCK release may not be the only mechanism by which tryptophan acts. The peptide and amino acid preparations (casein hydrolysate, Bacto-peptone, Amigen, FreAmine) seem to delay emptying by stimulation of osmoreceptors which is distinct from the mechanism of action of tryptophan.

Amino Acids