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R Cha

Publications and source records attributed to R Cha.

16 recordsLinked to original sources
PubMed2003

MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD.

OBJECTIVE: To assess the feasibility of using MRI measurements as a surrogate endpoint for disease progression in a therapeutic trial for AD. METHODS: A total of 362 patients with probable AD from 38 different centers participated in the MRI portion of a 52-week randomized placebo-controlled trial of milameline, a muscarinic receptor agonist. The therapeutic trial itself was not completed due to projected lack of efficacy on interim analysis; however, the MRI arm of the study was continued. Of the 362 subjects who underwent a baseline MRI study, 192 subjects underwent a second MRI 1 year later. Hippocampal volume and temporal horn volume were measured from the MRI scans. RESULTS: The annualized percent changes in hippocampal volume (-4.9%) and temporal horn volume (16.1%) in the study patients were consistent with data from prior single-site studies. Correlations between the rate of MRI volumetric change and change in behavioral/cognitive measures were greater for the temporal horn than for the hippocampus. Decline over time was more consistently seen with imaging measures, 99% of the time for the hippocampus, than behavioral/cognitive measures (p < 0.001). Greater consistency in MRI than behavioral/clinical measures resulted in markedly lower estimated sample size requirements for clinical trials. The estimated number of subjects per arm required to detect a 50% reduction in the rate of decline over 1 year are: AD Assessment Scale-cognitive subscale 320; Mini-Mental Status Examination 241; hippocampal volume 21; temporal horn volume 54. CONCLUSION: The consistency of MRI measurements obtained across sites, and the consistency between the multisite milameline data and that obtained in prior single-site studies, demonstrate the technical feasibility of using structural MRI measures as a surrogate endpoint of disease progression in therapeutic trials. However, validation of imaging as a biomarker of therapeutic efficacy in AD awaits a positive trial.

Adolescent↗
PubMed2001

Functional inferences vary with the method of analysis in fMRI.

Neuroanatomic substrates of specific cognitive functions have been inferred from anatomic distributions of activated pixels during fMRI studies. With declarative memory tasks, interest has focused on the extent to which various medial temporal lobe anatomic structures are activated while subjects encode new information. The aim of this project was to examine how commonly used variations in fMRI data processing methods affect the distribution of activation in anatomically defined medial temporal lobe regions of interest (ROIs) during a complex scene-encoding task. ROIs were drawn on an MRI anatomic template formed from 3D SPGR scans of eight subjects combined in Talairach space. Separate ROIs were drawn for the posterior and anterior hippocampal formation, parahippocampal gyrus, and entorhinal cortex. Twelve different activation maps were created for each subject by using four correlation coefficients and three cluster volumes. Friedman's two-way ANOVA by ranks was used to test the hypothesis that the distribution of activated pixels among defined anatomic ROIs varied as a function of the data processing method. By simply varying the combination of correlation coefficient and cluster volume, significantly different distributions of activation within named medial temporal lobe structures were obtained from the same fMRI datasets (P < 0.015; P < 0.001). The number of subjects studied (n = 8) is in a range commonly found in the literature yet this clearly resulted in spurious associations between processing parameter variations and activation distribution. Using data processing methods that are independent of the arbitrary selection of cutoff values for thresholding activation maps may reduce the likelihood of obtaining spurious results.

Adult↗
PubMed1999

Serial prostate specific antigen screening for prostate cancer: a computer model evaluates competing strategies.

PURPOSE: We compare prostate specific antigen (PSA) screening strategies in terms of expected years of life saved with screening, number of screens, number of false-positive screens and rates of over diagnosis, defined as detection by PSA screening of patients who would never have been diagnosed without screening. MATERIALS AND METHODS: A computer model of disease progression, clinical diagnosis, PSA growth and PSA screening was used. Under baseline conditions, when screening is not considered, the model replicates clinical diagnosis and disease mortality rates recorded by the Surveillance, Epidemiology and End Results Program of the National Cancer Institute in the mid 1980s. RESULTS: Biannual screening with PSA greater than 4.0 ng./ml. was projected to reduce the number of screens and false-positive tests by almost 50% relative to annual screening while retaining 93% of years of life saved. With annual screening use of an age specific bound for PSA to consider a test positive instead of the standard 4.0 ng./ml. was projected to reduce false-positive screens by 27% and over diagnosis by a third while retaining almost 95% of years of life saved. Sensitivity analyses did not change the relative efficacy of biannual screening. CONCLUSIONS: Under the model assumptions biannual PSA screening is a cost-effective alternative to annual PSA screening for prostate cancer. With annual screening use of an age specific bound for PSA positivity appears to reduce false-positive results and over diagnosis rates sharply relative to a bound of 4 ng./ml. while retaining most of the survival benefits.

Adult↗
PubMed1998

Asymptomatic incidence and duration of prostate cancer.

Prostate cancer is known as a disease with an extremely high prevalence relative to its clinical incidence in the population. The combination of preclinical incidence and duration that could yield this phenomenon is of tremendous interest to researchers trying to understand the natural history of the disease and to develop efficient screening strategies. In this article, the authors present estimates of the age-specific asymptomatic incidence and average preclinical duration of prostate cancer. The methodological approach is to first estimate the age-specific incidence of new (stage AI) prostate cancers using preclinical prevalence data from autopsy studies performed between 1941 and 1964 and clinical incidence data for the years 1960-1986 from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. Then, the preclinical prevalence estimates are divided by the derived preclinical incidence estimates to yield estimates of the average duration of asymptomatic disease. The estimated mean duration among white men is between 11 and 12 years and appears to be approximately 1 year shorter for blacks than for whites. Comparison of the lifetime risks of preclinical and clinical disease suggests that approximately 75% of prostate cancers will never become diagnosed if clinical incidence remains at levels observed in 1984-1986, prior to the introduction of prostate-specific antigen (PSA) screening in the population.

Adult↗
PubMed1997

Risk of dementia among persons with diabetes mellitus: a population-based cohort study.

It is unclear whether persons with diabetes are at increased risk for dementia, including Alzheimer's disease. Existing studies are limited by small sample size, selection bias, and case-control designs. This population-based historical cohort study provides estimates of the risk of dementia and Alzheimer's disease associated with adult onset diabetes mellitus (AODM). The sample included all persons with AODM residing in Rochester, Minnesota, on January 1, 1970, plus all persons diagnosed in Rochester or who moved to Rochester with the diagnosis between January 1, 1970, and December 31, 1984. Individuals were followed through review of their complete medical records from AODM diagnosis until dementia onset, emigration, death, or January 1, 1985. Standardized morbidity ratios for dementia and Alzheimer's disease were calculated, using an expected incidence based on age- and sex-specific rates for the Rochester population. Poisson regression was used to estimate risks for persons with AODM relative to those without. Of the 1,455 cases of AODM followed for 9,981 person-years, 101 developed dementia, including 77 who met criteria for Alzheimer's disease. Persons with AODM exhibited significantly increased risk of all dementia (Poisson regression relative risk (RR) = 1.66, 95% confidence interval (CI) 1.34-2.05). Risk of Alzheimer's disease was also elevated (for men, R = 2.27, 95% CI 1.55-3.31; for women, RR = 1.37, 95% CI 0.94-2.01). These findings emphasize the importance of AODM prevention and prompt additional investigation of the relation between AODM and dementia.

Age Distribution↗
PubMed1996

The small aortic root and the Medtronic Hall valve: ultrafast computed tomography assessment of left ventricular mass following aortic valve replacement.

BACKGROUND AND AIMS OF THE STUDY: The selection of an appropriate size aortic valve substitute with respect to patient size and life-style, in the presence of a small aortic root, is problematic, and a decision to enlarge the aortic annulus is often arbitrary. An aortic valve substitute-patient mismatch may place an excessive load on the left ventricle resulting in residual left ventricular mass with attendant patient morbidity and mortality. The aim of this study was to assess the adequacy of the Medtronic Hall valve in the small aortic root using ultrafast computed tomography analysis of left ventricular mass. MATERIALS AND METHODS: In 13 patients the smallest Medtronic Hall valves (size 20 and 21; measured internal orifice area of 2.01 cm2 for both) were used to replace the native aortic valve. All patients had aortic stenosis, and left ventricular hypertrophy was established by echocardiography. The mean body surface area was 1.8 +/- 0.2 m2 (range 1.50-2.06 m2) and the mean weight was 75 +/- 15 Kg (range 50-97 Kg). The mean preoperative New York Heart Association functional class was 3.54 +/- 0.5. RESULTS: There was no operative or late mortality. At a mean follow up of 22 months after aortic valve replacement, the mean left ventricular mass index was 89 +/- 11.4 g/m2 (normal left ventricular mass index by ultrafast computed tomography = 97 +/- 14 g/m2) and mean New York Heart Association functional class was 1.6 +/- 0.8 (p (Binomial) = 0.0001 compared to preoperative). Doppler echocardiogram demonstrated a mean gradient across the prosthetic valve of 17 +/- 7 mmHg. There was no trend towards greater left ventricular mass index in patients with greater body surface area or weight. In no patient was the aortic annulus enlarged. CONCLUSIONS: Trends from this preliminary data suggest that implanting the smallest Medtronic-Hall aortic valves (sizes 20 and 21) results in normal left ventricular mass following aortic valve replacement in patients up to a body surface area of 2.06 m2 and provides support for the notion that an aortic annulus enlarging procedure was not necessary in this group of patients.

Adult↗
PubMed1995

Normothermic retrograde cardioplegia is effective in patients with left ventricular hypertrophy. A prospective and randomized study.

Twenty patients with left ventricular hypertrophy (LVH) undergoing isolated aortic valve replacement were prospectively randomized to receive either continuous retrograde normothermic (n = 8) or intermittent retrograde hypothermic (n = 12) methods of myocardial protection. Biopsies of the left ventricular septum were evaluated for ultrastructure and assayed for ATP. There was no mortality, no requirement for intra-aortic balloon pump nor neurological events in any of the patients from either group. Myocardial ATP (warm 23.2 +/- 1.8 nmol/mg protein; cold 22.4 +/- 1.2 nmol/mg protein; p = 0.72) and myocardial CPK-MB (warm 43.6 +/- 5.2 U/l; cold 39.0 +/- 2.5 U/l; p = 0.67) were not significantly different. Ultrastructure was generally well preserved in the biopsies from both groups, with the exception of one patient in the normothermic group. Systemic lactate sampled after 40 minutes of cardiopulmonary bypass was significantly higher in the normothermic group (warm 3.4 +/- 0.27 mmol/l; cold 2.3 +/- 0.21 mmol/l; p = 0.01), however, the myocardial lactate production was not significantly different between the two groups (extraction ratio; warm 0.01 +/- 0.3; cold 0.13 +/- 0.1; p = 0.45). We conclude that the continuous normothermic retrograde method of myocardial protection is effective in patients with left ventricular hypertrophy; however, the higher systemic lactate levels using this technique raises concerns regarding the adequacy of systemic perfusion at 37 degrees C.

Aged↗
PubMed1994

Doppler echocardiography in normal functioning valve prostheses.

Even though there has been some criticism regarding the Doppler evaluation in prosthetic valves because of inter-observer and intra-observer variability, among other factors, and Doppler study has a tendency to have falsely high gradients compared to invasive studies, especially mechanical aortic prostheses, Doppler evaluation can provide reliable hemodynamic information about valve function. This test may be particularly useful if used serially, when baseline values are known. Doppler measurement of gradient and valve area has an expected normal range that is specific for the prosthetic type, size, anatomical position, and chronological age. Clearly, a database involving these aspects is needed to provide a more accurate normal range. This study is intended to provide guidance for echocardiographers.

Adult↗
PubMed1993

Review article: transesophageal echocardiography.

Since 1990, we have performed transesophageal echocardiography (TEE) on 508 patients. This procedure has provided valuable information. The author reviews the indications and usage of TEE in various clinical settings and the need for further evaluation.

Echocardiography, Transesophageal↗
PubMed1987

Prolonged electrocardiographic monitoring in patients with syncope. Importance of frequent or repetitive ventricular ectopy.

The purposes of this study were to document the findings on prolonged electrocardiographic monitoring in patients with syncope, correlate these findings with symptoms during monitoring, and define the prognostic importance of these findings. A total of 235 patients with syncope in whom a cause was not assigned or suggested by the initial history, physical examination, and electrocardiography were studied. Although a variety of arrhythmias were documented during monitoring, the vast majority of arrhythmias were of short duration and did not produce symptoms. At two years, the patients with frequent or paired premature ventricular contractions (PVCs) when compared with patients with rare PVCs, had a higher incidence of sudden death (18.2 percent versus 4.0 percent; p less than 0.001) and higher overall mortality (28.3 percent versus 10.8 percent; p less than 0.003). Similarly, patients with ventricular tachycardia, when compared with patients with rare PVCs, had a higher incidence of sudden death (18.7 percent versus 4.0 percent; p less than 0.0001) and higher overall mortality (36.5 percent versus 10.8 percent; p less than 0.00001). Cox regression analyses revealed that frequent or repetitive PVCs and sinus pauses were independent electrocardiographic predictors of sudden death and mortality in patients presenting with syncope. Therefore, patients with syncope and frequent or repetitive ventricular ectopy or sinus pauses constitute a high-risk subgroup and may be candidates for more extensive diagnostic evaluation.

Adolescent↗
PubMed1986

Syncope in the elderly.

This report describes the evaluation of syncope in 210 elderly patients as compared with 190 younger patients. The elderly group had a mean age of 71 years (range 60 to 90) and the younger group had a mean age of 39 years (range 15 to 59). A cardiovascular cause was found in 33.8 percent of the elderly and in 16.8 percent of the young (p = 0.0001), a noncardiovascular cause in 26.7 percent of the elderly and 37.9 percent of the young (p = 0.02), and unknown cause in 38.5 percent of the elderly and 45.3 percent of the young (NS). Prolonged electrocardiographic monitoring established the diagnosis in 17 percent of the elderly but in only 8 percent of the young (p = 0.008). Syncope resulted in trauma in 39 percent of the elderly and in 32 percent of the young, but the elderly more often had major trauma. The two-year overall mortality was 26.9 +/- 3.4 percent in the elderly and 8.3 +/- 2.1 percent in the young (p less than 0.0001). The overall mortality and incidence of sudden death in the elderly with a cardiovascular diagnosis were similar to those in the young; however, in the elderly with a noncardiovascular diagnosis and syncope of unknown cause, the mortality and incidence of sudden death were higher. Multivariate analyses using mortality and sudden death as endpoints revealed that a cardiovascular cause of syncope was a very strong risk factor. In patients with a noncardiovascular cause or unknown cause of syncope, a history of congestive heart failure, older age, and male sex are important prognostic factors.

Adolescent↗