Biomedical subjects

C H Morrell

Publications and source records attributed to C H Morrell.

16 recordsLinked to original sources

PubMed2001

Low levels of prostate-specific antigen predict long-term risk of prostate cancer: results from the Baltimore Longitudinal Study of Aging.

OBJECTIVES: To evaluate the relationship between low prostate-specific antigen (PSA) levels that are considered normal and the long-term risk of prostate cancer. METHODS: The relative risk of, and cumulative probability of freedom from, prostate cancer by PSA level and age decade was evaluated in male participants of a longitudinal aging study, the Baltimore Longitudinal Study of Aging (National Institute on Aging). The relative risk was estimated from a Cox proportional hazards regression model for men aged 40 to 49.9 (n = 351) and 50 to 59.9 (n = 445). The disease-free probability was determined by Kaplan-Meier survival analysis. RESULTS: The relative risk of prostate cancer for men aged 40 to 49.9 was 3.75 (range 1.6 to 8.6) when the PSA level was at or greater than the median (0.60 ng/mL) compared with men with PSA levels less than the median. This risk was similar for men aged 50 to 59.9 when comparing those with PSA levels greater than and less than the median (0.71 ng/mL). At 25 years, the cumulative probability of freedom from prostate cancer for men aged 40 to 49.9 was 89.6% (range 81% to 97%) and 71.6% (range 60% to 83%) when the PSA level was less than and greater than the median, respectively. The 25-year disease-free probability for men aged 50 to 59.9 was 83.6% (range 76% to 91%) and 58.9% (range 48% to 70%) when the PSA level was less than and greater than the median, respectively. CONCLUSIONS: The association between the baseline serum PSA level and the subsequent risk of prostate cancer suggests that the biologic events that predispose to prostate cancer begin early in middle age. Men who have baseline PSA levels that are "normal" but reflect a higher risk of prostate cancer may be the most appropriate candidates for future prevention trials. Those men with the lowest risk of prostate cancer on the basis of the baseline PSA measurements are unlikely to benefit from frequent PSA surveillance in an effort to detect prostate cancer early.

Adult↗

PubMed2001

Impact of donor/recipient traits independent of rejection on long-term renal function.

This study describes renal function at multiple points in time after transplantation and the influence of donor and recipient factors independent of rejection on this function. Donor and recipient records for 83 consecutive cadaveric renal transplants performed between 1992 and 1994 at Johns Hopkins Bayview Medical Center were reviewed retrospectively. Donor age, gender, weight, terminal serum creatinine (Cr), intensive care unit days, blood pressure, presence of cardiac arrest, kidney only versus multiple organ donation, and cold ischemia time and recipient age, gender, weight, pretransplant pregnancy status, and rejection episodes were recorded. The influences of each of these parameters on changes in recipient Cr clearance over time (derived using the Cockcroft-Gault formula from recipient serum Cr at 3 months and annually up to 5 years) were analyzed first individually, then together in an analysis with multiple explanatory variables. Parameters indicative of donor ischemia (ie, donor blood pressure, pressor administration, and occurrence of cardiac arrest) were not predictive of the course of recipient Cr clearance. With the inclusion of rejection, this analysis shows the magnitude of the independent effects that donor age, donor Cr clearance, and recipient gender have on the subsequent time course of recipient Cr clearance (P < 0.05). Recipient gender and the presence of rejection appear to have a fixed effect on the level of Cr clearance, whereas donor age and donor Cr clearance appear to influence the level and the time course of recipient Cr clearance. Of all these factors, donor age appears to have the greatest impact on recipient Cr clearance at all times. Analyzing renal function in this way may prove to be a more sensitive indicator than actuarial survival analysis for evaluating the early effects of changes in transplantation protocols and pharmacologic interventions.

Adolescent↗

PubMed2000

Today men with prostate cancer have larger prostates.

OBJECTIVES: To examine the relationship between prostate size and the method of cancer detection in men with organ-confined prostate cancer, and compare prostate size in men with and without cancer. METHODS: Prostate volume was evaluated in 720 men who had undergone radical prostatectomy for Stage T1c or Stage T2 cancer. Men with Stage T2 cancer were divided into those treated before 1989 (when widespread prostate-specific antigen [PSA] testing began), or not. Gland volume was also examined in 265 men participating in the Baltimore Longitudinal Study of Aging who had no clinical evidence of cancer. Volumes were compared using linear regression to allow for age. RESULTS: Prostate volume in men with Stage T1c cancer was statistically significantly larger than in men with Stage T2 cancer diagnosed in the pre-PSA era after adjusting for age (P = 0.0001), and statistically significantly larger than in men without cancer above age 47 years based on 95% confidence intervals. Prostate volumes in men with Stage T2 cancer diagnosed in the pre-PSA era and in men without cancer were not statistically significantly different. CONCLUSIONS: Prostate volume in men with PSA-detected, organ-confined cancer is larger than in men with palpable organ-confined cancer diagnosed in either the pre-PSA era or PSA era. These discrepancies may reflect a diagnostic bias due to the effect of benign prostatic hyperplasia on serum PSA that results in the selection of men with larger prostates for biopsy.

Adult↗

PubMed1999

The effect of gestational parity on FEV1 in a group of healthy volunteer women.

In the past, studies utilizing within-subject comparisons of small groups of pregnant women showed that forced expiratory volume in 1 s (FEV1) remained essentially unchanged during pregnancy. However, one of the findings from an epidemiological study was that women with greater number of children experienced a faster decline of FEV1. The aim of this study was to examine the effect of parity on FEV1 in a group of healthy volunteer women. To this end, cross-sectional multiple regression analyses of data from 397 healthy women participants in the Baltimore Longitudinal Study of Aging (BLSA) with a mean (range) age of 47.7 (18-92) years were performed. Similar analyses were done using the younger (50 years or less) and the older (> 50 years) subgroups. After controlling for age, height, weight, and smoking, parity as a dichotomous variable was associated with a higher FEV1 in women of child-bearing age (0.139 1; P = 0.02) but not in the older women. There was a modest link with the number of children (P = 0.05), with the first child possibly having the greatest effect on FEV1. We could not account for the effect of parity on FEV1 by the educational level, occupation, health status of the women, or by the presence of a cohort effect. Thus the nulliparous state is associated with lower FEV1 in this group of healthy adult women of child-bearing age.

Adult↗

PubMed1998

Likelihood ratio testing of variance components in the linear mixed-effects model using restricted maximum likelihood.

This paper reports the results of an extensive Monte Carlo study of the distribution of the likelihood ratio test statistic using the value of the restricted likelihood for testing random components in the linear mixed-effects model when the number of fixed components remains constant. The distribution of this test statistic is considered when one additional random component is added. The distribution of the likelihood ratio test statistic computed using restricted maximum likelihood is compared to the likelihood ratio test statistic computed from the usual maximum likelihood. The rejection proportion is computed under the null hypothesis using a mixture of chi-square distributions. The restricted likelihood ratio statistic has a reasonable agreement with the maximum likelihood test statistic. For the parameter combinations considered, the rejection proportions are, in most cases, less than the nominal 5% level for both test statistics, though, on average, the rejection proportions for REML are closer to the nominal level than for ML.

Analysis of Variance↗

PubMed1998

The relationship of obesity and the development of coronary heart disease to longitudinal changes in systolic blood pressure.

In an investigation of the relationship of obesity and the development of coronary heart disease (CHD) to longitudinal changes in systolic blood pressure (SBP), a sample of 1029 male participants from the Baltimore Longitudinal Study of Baltimore (BLSA), who were free of CHD at the beginning of the study, were examined with a total of 4111 examinations (mean of four examinations per person) conducted during the study period. The mean follow-up time was 8.1 years with a maximum of 16 examinations and 30.9 years of follow-up. During the follow-up period, 192 participants developed CHD, and these participants' data collected after the CHD event were excluded from the analysis. A proportional hazards regression model was used to calculate the relative risk of developing CHD for several CHD risk factors. Both simple and multiple proportional hazards regression models indicate a strong association between body mass index (BMI), cholesterol, cigarette smoking, and systolic blood pressure (SBP) with the risk of developing CHD. In addition, a linear mixed-effects model was used to examine changes in SBP measurements over time and to identify factors, including the age at first examination and time in study, that are related to that change. The results from the linear mixed-effects model analysis indicate that those in the obese group (BMI > or = 30 kg/m2) have SBP measurements that are on average 9.0 mm Hg higher than those in the normal group (20 < or = BMI < 25). Also, SPB measurements were on average 6.6 mm Hg higher in those who developed CHD during the study period than those who remained free of disease. In addition, SPB showed a quadratic relationship with time, and its patterns of change with time were different among the different age groups. Also, the relationship between changes in SBP with respect to cholesterol was dependent on time in the study as well.

Adult↗

PubMed1997

Construction of hearing percentiles in women with non-constant variance from the linear mixed-effects model.

Current age-specific reference standards for adult hearing thresholds are primarily cross-sectional in nature and vary in the degree of screening of the reference sample for noise-induced hearing loss and other hearing problems. We develop methods to construct age-specific percentiles for longitudinal data that have been modelled using the linear mixed-effects model. We apply these methods to construct percentiles of hearing level using data from a carefully screened sample of women from the Baltimore Longitudinal Study of Aging. However, the variation in the residuals and random effects from the linear mixed-effects model does not remain constant with age and frequency of the stimulus tone. In addition, the distribution of the hearing levels is not symmetric about the mean. We develop a number of methods to use the output from the linear mixed-effects model to construct percentiles that do not have constant variance. We use a transformation of the hearing levels to provide for skewness in the final percentile curves. The change in the variation of the residuals and random effects is modelled as a function of beginning age and frequency and we use this variance function to construct the hearing percentiles. We present a number of approaches. First, we use the absolute values of the population residuals to model the total deviation about the mean as a function of beginning age and frequency. Second, we model the standard deviation in the person-specific (cluster) residuals as well as the standard deviation in the estimated random effects. Finally, we use weighted least squares with the regressions on the absolute cluster residuals and absolute estimated random effects where the weights are the reciprocal of the standard deviations of their estimates.

Adolescent↗

PubMed1997

Age-associated changes in blood pressure in a longitudinal study of healthy men and women.

BACKGROUND: Current knowledge of age-associated increases in blood pressure is based primarily on unscreened population studies that may not be representative of healthy men and women. We examined longitudinal patterns of change in blood pressure in healthy male and female volunteers from the Baltimore Longitudinal Study of Aging (BLSA). METHODS: Longitudinal mixed-effects regression models are used to estimate the age-associated changes in blood pressure in 1307 men (age 17-97) and 333 women (age 18-93) who have been followed for up to 32 years (mean: 8.4 years for men and 3.4 years for women) and who have been screened for health problems or medications that affect blood pressure. RESULTS: On average, systolic pressure is relatively stable in men and women until approximately age 45, increases at 5-8 mm Hg per decade in middle age, then accelerates in men and stabilizes in women. Diastolic pressure increases at 1 mm Hg per decade at all ages in men, whereas in women the rate of change in diastolic pressure increases in middle age and then plateaus and may decline after age 70. Additional findings include: (a) BLSA cross-sectional and longitudinal findings are more similar than has been observed in studies of unscreened samples; (b) there is no evidence of a gender cross-over in this group of healthy men and women; and (c) compared to previous studies of unscreened samples, healthy BLSA men and women show a weaker association between baseline blood pressure and subsequent rate of blood pressure change. CONCLUSIONS: These findings suggest that several previously described age-associated patterns of blood pressure change partially reflect the effects of hypertension and its treatment, rather than intrinsic age changes in the blood pressure of healthy individuals.

Adolescent↗

PubMed1996

Age- and gender-specific reference ranges for hearing level and longitudinal changes in hearing level.

This paper presents age-specific reference ranges for hearing level and change in hearing level for men and women at 500, 1000, 2000, and 4000 Hz. The percentiles are constructed from data obtained from persons in the Baltimore Longitudinal Study of Aging who were rigorously screened for otological disorders and evidence of noise-induced hearing loss. The resulting percentile curves represent norms for changes in hearing level in the absence of any known otologic disease. These percentile curves provide a reference for detecting when a person deviates from a normal pattern of change, thus helping in diagnosing problems with hearing or in monitoring hearing in occupational settings. The smoothed means and standard deviations of the hearing levels were used to construct the longitudinal percentiles. The percentiles for cross-sectional change were constructed using the skew normal distribution to allow for the percentiles to be asymmetric on either side of the median level. These percentiles are the first reference curves that (1) provide standards for hearing level changes over periods of up to 15 years, (2) account for age differences in the distribution of hearing levels, and (3) are based on data from persons who have been systematically screened for otological disorders and evidence of noise-induced hearing loss.

Adult↗

PubMed1996

Risk factors related to age-associated hearing loss in the speech frequencies.

This paper examines the relationship between several risk factors and the development of age-associated hearing loss in the speech frequencies. Hearing loss is defined as an average threshold level of 30 dB HL or greater at the frequencies of 0.5, 1, 2, and 3 kHz. Hearing thresholds from 0.5 to 8 kHz using a pulse-tone tracking procedure were collected on participants of the Baltimore Longitudinal study of Aging since 1965. A proportional hazards regression model was used to study the relationship between several risk factors that have previously been found to be associated with numerous health-related outcomes and the length of follow-up time until the occurrence of unilateral or bilateral hearing loss in a screened group of 531 men. Risk factors considered are age, blood pressure, and alcohol and cigarette consumption. After controlling for age, only systolic blood pressure showed a significant relationship with hearing loss in the speech frequencies (p < .05). Since blood pressure is a modifiable risk factor, these results suggest that preventing hypertension might contribute to an effective program for the prevention of apparent age-associated hearing loss.

Adult↗

PubMed1995

Gender differences in a longitudinal study of age-associated hearing loss.

Current studies are inconclusive regarding specific patterns of gender differences in age-associated hearing loss. This paper presents results from the largest and longest longitudinal study reported to date of changes in pure-tone hearing thresholds in men and women screened for otological disorders and noise-induced hearing loss. Since 1965, the Baltimore Longitudinal Study of Aging has collected hearing thresholds from 500 to 8000 Hz using a pulsed-tone tracking procedure. Mixed-effects regression models were used to estimate longitudinal patterns of change in hearing thresholds in 681 men and 416 women with no evidence of otological disease, unilateral hearing loss, or noise-induced hearing loss. The results show (1) hearing sensitivity declines more than twice as fast in men as in women at most ages and frequencies, (2) longitudinal declines in hearing sensitivity are detectable at all frequencies among men by age 30, but the age of onset of decline is later in women at most frequencies and varies by frequency in women, (3) women have more sensitive hearing than men at frequencies above 1000 Hz but men have more sensitive hearing than women at lower frequencies, (4) learning effects bias cross-sectional and short-term longitudinal studies, and (5) hearing levels and longitudinal patterns of change are highly variable, even in this highly selected group. These longitudinal findings document gender differences in hearing levels and show that age-associated hearing loss occurs even in a group with relatively low-noise occupations and with no evidence of noise-induced hearing loss.

Adult↗

PubMed1992

Estimation of prostatic growth using serial prostate-specific antigen measurements in men with and without prostate disease.

Prostate growth curves were estimated from serial prostate-specific antigen (PSA) measurements on frozen sera in three groups of men: (a) 16 men with no prostatic disease by urological history and examination; (b) 20 men with a histological diagnosis of benign prostatic hyperplasia (BPH) who had undergone simple prostatectomy; and (c) 18 men with a histological diagnosis of prostate cancer. The median number of repeated PSA measurements over an 8- to 26-yr period prior to histological diagnosis or exclusion of prostate disease was eight and 11 for noncancer and cancer subjects, respectively. Predicted rates of change in PSA (PSA velocity) were linear and curvilinear for control and BPH subjects, respectively. Subjects with cancer demonstrated both a linear and an exponential phase of PSA velocity. Based on time to double PSA, we estimated the epithelial doubling time for men without prostate disease to range from 54 +/- 13 yr at age 40 to 84 +/- 13 yr at age 70. For men with BPH, doubling times ranged from 2 +/- 13 yr at age 40 to 17 +/- 5 yr at age 85. Subjects with local/regional and advanced/metastatic cancer had similar PSA doubling times of 2.4 +/- 0.6 yr and 1.8 +/- 0.2 yr, respectively. These data are consistent with what is known about prostatic growth with age in men without prostate disease and BPH, and the kinetics of prostate cancer growth. Estimates of prostatic growth rate from changes in PSA may be useful clinically in management of men with prostate disease.

Aged↗

PubMed1992

Two-sample nonparametric estimation and confidence intervals under truncation.

We consider point estimates and confidence intervals for the difference in location or scale between two populations when the observations are subject to truncation. We suggest procedures analogous to those for the complete-sample case. A rigorous justification is presented to support the proposed confidence interval procedure. Finally, some simulations verify the properties of the estimators and confidence intervals. We illustrate the procedure using data on tumor size.

Algorithms↗

PubMed1991

Modelling hearing thresholds in the elderly.

This paper concerns a linear mixed-effects repeated measures model in the analysis of a large data set with over 17,000 observations in a longitudinal study of pure-tone hearing perception in the elderly. The repeated measurements are described by fixed and random components in the model. The fixed effects include the age at entry, time of follow-up, a quadratic component in natural logarithm of frequency, a component to allow for participants with hearing impairments, as well as interaction terms between age and frequency and between impairment and frequency. The random factors include a term for subject, a time component and a frequency component. The analysis shows that hearing impaired individuals have similar patterns of hearing loss over time but, on average, have higher hearing thresholds than normal individuals. Estimation of the random effects in the model by restricted maximum likelihood (REML) using the Newton-Raphson method made possible the analysis of this large data set with speed and efficiency.

Aged↗

PubMed1991

Basal DNA damage in individual human lymphocytes with age.

A role for DNA damage is central to many theories of aging, but attempts to show an increase in DNA damage with age have yielded contradictory results. However, previous experiments have been of limited sensitivity, only able to examine induced (not basal) damage or pooled (not individual) cells. In this report, we apply a novel technique (Singh et al., 1988) to directly measure basal levels of DNA single-strand breaks and alkali-labile sites in individual human peripheral blood lymphocytes (PBL) obtained from young (less than 60 years) and old (more than 60 years) male donors. This approach shows that while average changes with age are small, changes in certain individuals and in certain cells may be large: the mean increase in damage was only 12%, but the increase in a subpopulation of highly damaged lymphocytes was 5-fold. However, most of this increase was contributed by just 3 of 17 older subjects. Further characterization of these individuals may shed light on the relationship between DNA damage and aging.

Adult↗

PubMedDate not supplied

Mixed-effects regression models for studying the natural history of prostate disease.

Although prostate cancer and benign prostatic hyperplasia are major health problems in U.S. men, little is known about the early stages of the natural history of prostate disease. A molecular biomarker called prostate specific antigen (PSA), together with a unique longitudinal bank of frozen serum, now allows a historic prospective study of changes in PSA levels for decades prior to the diagnosis of prostate disease. Linear mixed-effects regression models were used to test whether rates of change in PSA were different in men with and without prostate disease. In addition, since the prostate cancer cases developed their tumours at different (and unknown) times during their periods of follow-up, a piece-wise non-linear mixed-effects regression model was used to estimate the time when rapid increases in PSA were first observable beyond the background level of PSA change. These methods have a wide range of applications in biomedical research utilizing repeated measures data such as pharmacokinetic studies, crossover trials, growth and development studies, aging studies, and disease detection.

Aged↗