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Biomedical subjects

C B Nelson

Publications and source records attributed to C B Nelson.

35 records · Page 2Linked to original sources
PubMed1995

Synthesis of 1,4,7,8,9,10-hexahydro-9-methyl-6-nitropyrido[3,4-f]- quinoxaline-2,3-dione and related quinoxalinediones: characterization of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (and N-methyl-D-aspartate) receptor and anticonvulsant activity.

Four related series of substituted quinoxalinediones containing angular fused-piperidine rings have been synthesized as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists with potential as neuroprotective agents, primarily for acute therapy immediately following a stroke. The compounds were tested for their affinity to the AMPA, kainate, and strychnine-insensitive glycine receptor sites. In AMPA binding, the most potent compound was 27a (PNQX, IC50 = 63 nM), with affinity comparable to the literature standard 1 (NBQX, IC50 = 52 nM). Other 6-nitro analogs from the 9-aza series had comparable affinity at the AMPA receptor, as did 6-nitro-8-aza derivatives such as 13a (iPNQX, IC50 = 290 nM). The receptor binding profile of 27a differed from that of 1 in that 27a possessed significant affinity at the glycine site of the N-methyl-D-aspartate (NMDA) receptor, whereas 1 was essentially inactive. Three compounds, 26c, 26d, and 26e, demonstrated moderate selectivity for kainate relative to AMPA receptors. Selected analogs reported herein as well as in the literature were superimposed to generate an AMPA pharmacophore model, and 6-substituted compounds from the PNQX and iPNQX series were combined and analyzed via quantitative structure-activity relationship techniques. Compounds with high affinity at non-NMDA receptors were further characterized in functional assays in neuronal cell culture and in a cortical wedge preparation. Both 1 and 27a showed comparable effectiveness in an AMPA- and kainate-induced excitoxicity assay. Both inhibited AMPA-induced depolarizations in the cortical wedge. However, 27a also inhibited spontaneous epileptiform discharges in the cortical wedge (reversed by glycine), while 1 was ineffective. The combination of AMPA and NMDA antagonist activity may contribute to the 30-fold difference in potency between 27a and 1 in the maximal electroshock convulsant assay in mice. The significant in vivo potency of 27a suggests that it has potential clinical utility.

Animals↗
PubMed1995

Prevalence and correlates of drug use and dependence in the United States. Results from the National Comorbidity Survey.

OBJECTIVES: To analyze nationally representative data on the lifetime and 12-month prevalences of use of and dependence on illegal drugs (marijuana/hashish, cocaine/crack, heroin, hallucinogens), nonmedical prescription psychotropic drugs (sedatives, tranquilizers, stimulants, analgesics), and inhalants; and to examine data on the sociodemographic correlates of use and dependence. METHODS: The data come from the National Comorbidity Survey, a structured diagnostic interview administered to persons aged 15 to 54 years that generates reliable diagnoses according to the definitions and criteria of DSM-III-R. RESULTS: Of the respondents, 51.0% used one of the above drugs at some time in their lives, and 15.4% did so in the past 12 months. These estimates are similar to those obtained in the 1991 National Household Survey of Drug Abuse, where lifetime prevalence was 45.2% and 12-month prevalence was 16.7% among respondents in the age range 15 to 54 years. Of National Comorbidity Survey respondents, 7.5% (14.7% of lifetime users) were dependent at some time in their lives and 1.8% were dependent in the past 12 months. The prevalence estimate for lifetime dependence was reduced to 5.3% when calculated the percentage of respondents in the age range of 28 to 54 years who reported an onset of dependence as of 10 years earlier (ie, when they were 18 to 44 years old) was computed. This is similar to the Epidemiologic Catchment Area Study estimate of 5.1% among respondents in the age range 18 to 44 years, a comparison that matches the two studies on year of assessment, age of risk, and cohort. Males were significantly more likely to report both lifetime and 12-month use and dependence. Use and dependence were found to be more common in cohorts born after World War II than those born before the end of the war. The demographic predictors of lifetime use differed from the predictors of lifetime dependence among users, and these, in turn, differed from the predictors of recent dependence among people with a lifetime history of dependence. CONCLUSIONS: Drug use and dependence are highly prevalent in the general population. The fact that there are differences in the correlates of first use, dependence among users, and persistence of dependence means that future research aimed at pinpointing modifiable risk factors must be based on disaggregated analyses of separate stages of progression.

Adolescent↗
PubMed1995

Posttraumatic stress disorder in the National Comorbidity Survey.

BACKGROUND: Data were obtained on the general population epidemiology of DSM-III-R posttraumatic stress disorder (PTSD), including information on estimated life-time prevalence, the kinds of traumas most often associated with PTSD, sociodemographic correlates, the comorbidity of PTSD with other lifetime psychiatric disorders, and the duration of an index episode. METHODS: Modified versions of the DSM-III-R PTSD module from the Diagnostic Interview Schedule and of the Composite International Diagnostic Interview were administered to a representative national sample of 5877 persons aged 15 to 54 years in the part II subsample of the National Comorbidity Survey. RESULTS: The estimated lifetime prevalence of PTSD is 7.8%. Prevalence is elevated among women and the previously married. The traumas most commonly associated with PTSD are combat exposure and witnessing among men and rape and sexual molestation among women. Posttraumatic stress disorder is strongly comorbid with other lifetime DSM-III-R disorders. Survival analysis shows that more than one third of people with an index episode of PTSD fail to recover even after many years. CONCLUSIONS: Posttraumatic stress disorder is more prevalent than previously believed, and is often persistent. Progress in estimating age-at-onset distributions, cohort effects, and the conditional probabilities of PTSD from different types of trauma will require future epidemiologic studies to assess PTSD for all lifetime traumas rather than for only a small number of retrospectively reported "most serious" traumas.

Adolescent↗
PubMed1995

Estimates of radiogenic cancer risks.

A methodology recently developed by the U.S. EPA for estimating the carcinogenic risks from ionizing radiation is described. For most cancer sites, the risk model is one in which age-specific, relative risk coefficients are obtained by taking a geometric mean of the coefficients derived from the atomic bomb survivor data using two different methods for transporting risks from the Japanese to the U.S. population. The risk models are applied to estimate organ-specific risks per unit dose for a stationary population with mortality rates governed by 1980 U.S. vital statistics. With the exception of breast cancer, low-LET radiogenic cancer risk estimates are reduced by a factor of 2 at low doses and dose rates compared to acute high dose exposure conditions. For low dose (or dose rate) conditions, the risk of inducing a premature cancer death from uniform, whole body, low-LET irradiation is calculated to be 5.1 x 10(-2) Gy-1. Neglecting nonfatal skin cancers, the corresponding incidence risk is 7.6 x 10(-2) Gy-1. High-LET (alpha particle) risks are presumed to increase linearly with dose and to be independent of dose rate. High-LET risks are estimated to be 20 times the low-LET risks estimated under low dose rate conditions, except for leukemia and breast cancer where RBEs of 1 and 10 are adopted, respectively.

Adolescent↗
PubMed1994

Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey.

BACKGROUND: This study presents estimates of lifetime and 12-month prevalence of 14 DSM-III-R psychiatric disorders from the National Comorbidity Survey, the first survey to administer a structured psychiatric interview to a national probability sample in the United States. METHODS: The DSM-III-R psychiatric disorders among persons aged 15 to 54 years in the noninstitutionalized civilian population of the United States were assessed with data collected by lay interviewers using a revised version of the Composite International Diagnostic Interview. RESULTS: Nearly 50% of respondents reported at least one lifetime disorder, and close to 30% reported at least one 12-month disorder. The most common disorders were major depressive episode, alcohol dependence, social phobia, and simple phobia. More than half of all lifetime disorders occurred in the 14% of the population who had a history of three or more comorbid disorders. These highly comorbid people also included the vast majority of people with severe disorders. Less than 40% of those with a lifetime disorder had ever received professional treatment, and less than 20% of those with a recent disorder had been in treatment during the past 12 months. Consistent with previous risk factor research, it was found that women had elevated rates of affective disorders and anxiety disorders, that men had elevated rates of substance use disorders and antisocial personality disorder, and that most disorders declined with age and with higher socioeconomic status. CONCLUSIONS: The prevalence of psychiatric disorders is greater than previously thought to be the case. Furthermore, this morbidity is more highly concentrated than previously recognized in roughly one sixth of the population who have a history of three or more comorbid disorders. This suggests that the causes and consequences of high comorbidity should be the focus of research attention. The majority of people with psychiatric disorders fail to obtain professional treatment. Even among people with a lifetime history of three or more comorbid disorders, the proportion who ever obtain specialty sector mental health treatment is less than 50%. These results argue for the importance of more outreach and more research on barriers to professional help-seeking.

Adolescent↗
PubMed1994

Sex and depression in the National Comorbidity Survey. II: Cohort effects.

Data from a nationally representative sample of the general population are used to study cohort differences in the prevalence of DSM-III-R Major Depressive Episode (MDE). We document increasing lifetime prevalence of MDE among both men and women in more recent cohorts, but no major change in the sex ratio over the 40-year period retrospectively covered in the survey. We find a cohort difference in 12-month MDE, with older women much more likely than older men to have recurrent episodes. This sex difference in recurrence plays an important part in the elevated 12-month prevalence of depression among women compared to men in the 45-54 age range.

Adolescent↗
PubMed1994

The association of diabetic status, age, and race to withdrawal from dialysis.

Higher rates of withdrawal from dialysis have been shown among young diabetic patients. This study examined the hypothesis that diabetic status has a joint effect with age as the result of an age-related increase in co-morbid conditions among nondiabetic ESRD patients. Using data collected during the 1980s by the Michigan Kidney Registry, the experience of 4,753 white and 2,988 black Michigan dialysis patients (13,863 patient years) is analyzed. During follow-up, 364 white and 80 black patients withdrew from dialysis. By use of a Cox analysis, adjusted rates of withdrawal were shown to be higher among white than black patients (rate ratio (RR) = 3.34; P < 0.001), without significant differences by diabetic status. Rates increased with age (RR = 7.9 for 80+ versus 20 to 35 yr; P < 0.001), without significantly different patterns by race. Adjusted withdrawal rates among diabetics were 2.3 times that of nondiabetics overall (P < 0.001), with a statistically significant joint effect with age, the RR being highest among young patients. Among white patients, nondiabetics using continuous ambulatory peritoneal dialysis had a lower relative withdrawal rate than those using hemodialysis (RR = 0.73; P = 0.07), whereas diabetics using continuous ambulatory peritoneal dialysis showed slightly higher although statistically insignificant rates than their counterparts using hemodialysis (RR = 1.21; P = 0.50). Between 1980 and 1989, withdrawal rates for white patients aged 20 to 34 yr tended to decrease by 20% per year (P = 0.05), whereas they increased by 11% per year for patients aged 50 to 69 yr (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Bone cancer risk estimates.

Due to confusion between endosteal (bone surface) dose and average skeletal dose, ICRP 60 has substantially overestimated the risk of radiogenic bone cancer. This confusion apparently stems from an incorrect reading of the BEIR IV report, which does not clearly draw this distinction. It should also be noted that what appear to be summary numerical risk estimates for bone sarcoma induction in BEIR IV and BEIR V refer only to average skeletal dose as calculated for 224Ra.

Bone Neoplasms↗
PubMed1992

Comparison of continuous ambulatory peritoneal dialysis and hemodialysis patient survival with evaluation of trends during the 1980s.

To evaluate the mortality of continuous ambulatory peritoneal dialysis (CAPD) patients relative to hemodialysis (HD) patients, all Michigan residents 20 to 59 yr of age who initiated therapy for ESRD during the 1980s (N = 4,288) were studied. The study population was stratified by primary renal diagnosis (glomerulonephritis, hypertension, diabetes, other), and analyses were conducted within each group by Cox proportional hazards methods controlling for age, race, sex, and year in which chronic dialysis was initiated. Intent-to-treat (ITT) and treatment history (RxHx) censoring criteria were used. For patients with hypertension or other reported causes of ESRD, there was no significant difference in CAPD and HD patient mortality (relative risk (RR) = 0.99 and 1.05, respectively). In the ITT analysis, both glomerulonephritic (RR = 0.73; P = 0.10) and diabetic patients using CAPD experienced mortality rates lower than their HD counterparts. Among diabetics, this difference ranged from a RR of 0.40 to 0.70, being lowest for younger diabetics and statistically significant (P < or = 0.05) for ages 20 to 52 yr. Evaluation of mortality trends showed a significant (P < 0.01) decrease in diabetic CAPD mortality rates during the decade, whereas diabetic HD mortality rates increased (P = 0.06). Among diabetics, men had higher mortality rates than women (ITT--RxHx; RR = 1.22 to 1.27; P < 0.001) and white patients had higher mortality rates than black patients (ITT--RxHx, RR = 1.34 to 1.44; P < 0.001). Differences in mortality by sex and race were not found among nondiabetics, but mortality did increase significantly with age in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

EPA's perspective on risks from residential radon exposure.

Indoor radon has been judged to be the most serious environmental carcinogen which the EPA must address for the general public. The optimal strategy for dealing with this problem depends on the magnitude of the risk, how the risk is distributed within the population, as well as the effectiveness and costs of mitigation measures. Based on current exposure and risk estimates, radon exposure in single-family houses may be a causal factor in roughly 20,000 lung cancer fatalities per year. Most of these projected fatalities are attributable to exposures in houses with average or moderately elevated radon levels (below 10 pCi/L). Hence to appreciably reduce radon-induced lung cancers, remediation efforts must include houses not highly elevated in radon. From either an individual risk or a cost-benefit standpoint, reduction of a few pCi/L per home appears to be justified. The optimal strategy for dealing with the indoor radon problem depends on the magnitude of the risk per unit exposure, the distribution of exposures in houses, and the effectiveness and costs of mitigation. EPA's current views with respect to these factors and the associated uncertainties are discussed.

Carcinogens, Environmental↗
PubMed1986

An estimation of daily food usage factors for assessing radionuclide intakes in the U.S. population.

We have statistically analyzed data from the 1977-78 USDA Nationwide Food Consumption Survey to estimate the daily average food intakes by individuals in the general population and various subpopulations of the United States. These estimates are intended for use in assessing radionuclide intake by individuals through food consumption. We have also compared our results with those from other studies.

Age Factors↗
PubMedDate not supplied

Sex and depression in the National Comorbidity Survey. I: Lifetime prevalence, chronicity and recurrence.

Basic epidemiologic prevalence data are presented on sex differences in DSM-III-R major depressive episodes (MDE). The data come from the National Comorbidity Survey (NCS), the first survey in the U.S. to administer a structured psychiatric interview to a nationally representative sample of the general population. Consistent with previous research, women are approximately 1.7 times as likely as men to report a lifetime history of MDE. Age of onset analysis shows that this sex difference begins in early adolescence and persists through the mid-50s. Women also have a much higher rate of 12-month depression than men. However, women with a history of depression do not differ from men with a history of depression in either the probability of being chronically depressed in the past year or in the probability of having an acute recurrence in the past year. This means that the higher prevalence of 12-month depression among women than men is largely due to women having a higher risk of first onset. The implications of these results for future research are discussed in a closing section of the paper.

Adolescent↗