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Biomedical subjects

C S Williams

Publications and source records attributed to C S Williams.

At least 73 records · Page 4Linked to original sources
PubMed1998

Health care utilization and costs in a Medicare population by fall status.

OBJECTIVES: The economic impact of trauma in older persons is a matter of increasing concern to public health practitioners and planners, yet it is an issue that has not been widely studied. Available evidence does suggest, however, that falls are the costliest category of injury among older persons. METHODS: This study used data from the Health Care Financing Administration and the Connecticut Long-Term Care Registry to isolate the effects of fall severity on hospital, nursing home, home health, and emergency room costs. Multivariate and logistic regression methods were used to control for the influence of a number of clinical and demographic factors believed to be independently related to health care costs. Health care costs of fallers were tracked for 1 year after the fall. The cost experience of this cohort was compared with nonfallers during the same time period. RESULTS: The results provide strong evidence that falls are associated with increased health care costs, and that this relation increases monotonically with the frequency and severity of falls. Incurring one or more injurious falls was associated with increased annual hospital costs of $11,042 (1996), nursing home costs of $5,325, and total health care costs of $19,440. Incurring two or more noninjurious falls increased costs substantially as well. CONCLUSIONS: The health care costs of falls are pervasive and substantial, and they increase with fall frequency and severity.

Accidental Falls↗
PubMed1998

Tuberculosis notifications in England: the relative effects of deprivation and immigration.

SETTING: Metropolitan areas of England, including London boroughs, in 1991. OBJECTIVE: To investigate the relative importance of deprivation, immigration and the elderly in explaining variations in tuberculosis rate. DESIGN: A retrospective study using multiple Poisson regression models to assess the interrelationship between various population parameters. RESULT: Significant differences ere observed between London and other metropolitan districts in the measures of tuberculosis, immigration and the elderly. In addition, all population parameters were significantly intercorrelated in London: areas with a high proportion of immigrants had high levels of deprivation and low proportions of elderly. In other metropolitan districts, only immigration and the Jarman index were significantly associated, and removing the immigration component from the index removed this statistical significance. Multiple Poisson regression models revealed that the immigrant index had the strongest explanatory power in explaining tuberculosis rates, but there were significant interactions between this and measures of urban deprivation indices. That is, there was a greater effect of increasing deprivation at lower levels of immigration than at higher levels. This phenomenon was more pronounced in London boroughs than other metropolitan districts. The elderly index had no significant influence on tuberculosis rates. CONCLUSION: Although the association between tuberculosis and deprivation previously reported for the city of Liverpool is confirmed across all urban areas of England, the immigrant proportion of the population has a greater statistical power in explaining variations in rates of urban tuberculosis. However, tuberculosis notifications can be most accurately predicted by combining both measures than by either one alone.

Aged↗
PubMed1997

Falls, injuries due to falls, and the risk of admission to a nursing home.

BACKGROUND: Falls warrant investigation as a risk factor for nursing home admission because falls are common and are associated with functional disability and because they may be preventable. METHODS: We conducted a prospective study of a probability sample of 1103 people over 71 years of age who were living in the community. Data on demographic and medical characteristics, use of health care, and cognitive, functional, psychological, and social functioning were obtained at base line and one year later during assessments in the participants' homes. The primary outcome studied was the number of days from the initial assessment to a first long-term admission to a skilled-nursing facility during three years of follow-up. Patients were assigned to four categories during follow-up: those who had no falls, those who had one fall without serious injury, those who had two or more falls without serious injury, and those who had at least one fall causing serious injury. RESULTS: A total of 133 participants (12.1 percent) had long-term admissions to nursing homes. In an unadjusted model, the risk of admission increased progressively, as compared with that for the patients with no falls, for those with a single noninjurious fall (relative risk, 4.9; 95 percent confidence interval, 3.2 to 7.5), those with multiple noninjurious falls (relative risk, 8.5; 95 percent confidence interval, 3.4 to 21.2), and those with at least one fall causing serious injury (relative risk, 19.9; 95 percent confidence interval, 12.2 to 32.6). Adjustment for other risk factors lowered these ratios to 3.1 (95 percent confidence interval, 1.9 to 4.9) for one noninjurious fall, 5.5 (95 percent confidence interval, 2.1 to 14.2) for two or more noninjurious falls, and 10.2 (95 percent confidence interval, 5.8 to 17.9) for at least one fall causing serious injury, but the association between falls and admission to a nursing home remained strong and significant. The population attributable risk of long-term admission to a nursing home for these three groups (the proportion of admissions directly attributable to the three categories of falls) was 13 percent, 3 percent, and 10 percent, respectively. CONCLUSIONS: Among older people living in the community falls are a strong predictor of placement in a skilled-nursing facility; interventions that prevent falls and their sequelae may therefore delay or reduce the frequency of nursing home admissions.

Accidental Falls↗
PubMed1997

Decreased transforming growth factor beta type II receptor expression in intestinal adenomas from Min/+ mice is associated with increased cyclin D1 and cyclin-dependent kinase 4 expression.

Tumor cells often become resistant to the growth-inhibitory effects of transforming growth factor beta (TGF-beta). Recent studies have identified TGF-beta type II receptor (RII) mutations in a subset of cancers, including colon cancer. To evaluate the expression of TGF-beta RII in premalignant intestinal adenomas and the relationship with cell cycle regulation, we investigated the expression of TGF-beta RII, cyclin D1, and cyclin-dependent kinase 4 (Cdk4) in Min/+ mouse intestinal adenomas. Immunohistochemistry indicated that TGF-beta RII cytoplasmic immunoreactivity was undetectable in the proliferative crypt zones of the normal small intestinal and normal colonic epithelium but was abundant toward the villus tips of the normal small intestine and the lumenal third of the colonic glands. As was observed in the proliferating crypt zones, TGF-beta RII immunoreactivity was dramatically decreased or undetectable in all adenomas examined in comparison to the abundant levels in adjacent normal differentiated intestinal epithelium. TGF-beta RII mRNA was also reduced in the adenomas in comparison to normal mucosa as determined by reverse transcription-PCR. In an inverse distribution to TGF-beta RII, Cdk4 nuclear immunoreactivity was restricted to the crypt regions of the small and large intestine, whereas cyclin D1 immunoreactivity was uniformly absent in normal intestinal epithelium. For both cyclin D1 and Cdk4, protein and mRNA levels were increased in intestinal adenomas but not in normal intestinal epithelium as determined by immunohistochemistry, in situ hybridization, and reverse transcription-PCR. In summary, the lack of TGF-beta RII expression was associated with increased cyclin D1 and Cdk4 expression in Min/+ mouse intestinal adenomas. We hypothesize that the former may enable tumor cells to escape from the normal growth-constraining influence of TGF-beta, whereas the latter promotes inappropriate cell proliferation and adenoma progression.

Adenoma↗
PubMed1997

A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro.

In earlier studies, we provided statistical evidence that individual differences in the angiotensinogen gene, the precursor of the vasoactive hormone angiotensin II, constitute inherited predispositions to essential hypertension in humans. We have now identified a common variant in the proximal promoter, the presence of an adenine, instead of a guanine, 6 bp upstream from the initiation site of transcription, in significant association with the disorder. Tests of promoter activity and DNA binding studies with nuclear proteins suggest that this nucleotide substitution affects the basal transcription rate of the gene. These observations provide some biological insight about the possible mechanism of a genetic predisposition to essential hypertension; they may also have important evolutionary implications.

Angiotensinogen↗
PubMed1997

ED use by older victims of family violence.

STUDY OBJECTIVE: To determine the nature and frequency of ED use by victims of physical elder abuse. METHODS: Community-dwelling victims of abuse were identified through a state elderly protective service program independent of the health care system in a geographic area served by two EDs. ED records were reviewed and abstracted to determine if and how victims used emergency services. RESULTS: During a 7-year period, 182 elderly victims of physical abuse were identified in the catchment area of the study, and 114 (62.6%) had been seen in one or both EDs at least once during a 5-year "window" surrounding the initial identification of abuse. These 114 individuals accounted for 628 visits (median 3, range 1-46); 30.6% of visits resulted in a hospital admission. An ordinal system was used that assigned a probability of any single ED visit being referable to abuse; 37.8% of subjects had at least one visit categorized as being of high probability, and 66% of subjects had at least one visit that resulted in an injury-related chief symptom or ICD-9 discharge diagnosis. CONCLUSION: Elder abuse victims have substantial interactions with EDs and these visits frequently result in admission. Strategies that identify elder abuse in less acute settings and effectively address the needs of victims would improve quality of life and likely result in substantial savings in health care expenditures.

Aged↗
PubMed1997

Biomechanical effects of operative nerve mobilization and transposition in a canine ulnar nerve model.

The purpose of this study was to evaluate the effects that operative mobilization and transposition of the ulnar nerve have on both neural excursion and mechanical properties. Twelve dogs underwent ulnar nerve transposition and postoperative casting. Four animals were killed at 3 weeks and four animals were killed at 6 weeks. Four animals had their casts removed at 3 weeks, were allowed to ambulate, and were killed at 6 weeks. Operated and contralateral control nerves were compared. Neural excursion was measured near the elbow and 12 cm proximally. The nerves were harvested and their mechanical properties determined. Repeated measures analysis of variance revealed significant differences in longitudinal excursion between control and experimental groups at both sites. Ultimate strain, ultimate strength, and modulus were significantly reduced in the experimental groups. No differences were seen in cross-sectional area or stiffness between control and experimental groups. Analysis revealed no independent effect of the rehabilitation method. Results of this study indicate that significant changes in neural excursion, ultimate strain, ultimate strength, and modulus occur following ulnar nerve mobilization and transposition and that these changes persist throughout the early postoperative period.

Analysis of Variance↗
PubMed1997

The role of change in physical performance in determining risk for dependence in activities of daily living among nondisabled community-living elderly persons.

Among community-living elderly persons, a single assessment of physical performance is a powerful predictor of dependence in activities of daily living (ADLs). The aim of this study was to determine whether an assessment of change in physical performance provides useful prognostic information beyond that available from a single assessment. Among a large representative cohort of elderly persons, we evaluated the 586 participants who were ADL independent at both the baseline and the one year interviews. For each of the three timed tests, participants who had a large decline in physical performance were significantly more likely to develop ADL dependence at three years than those who improved or showed no change. After adjusting for 1-year scores, however, change in physical performance was no longer associated with ADL dependence. However, among the 775 participants who were ADL independent at the baseline interview, change in physical performance was significantly associated with the onset of ADL dependence at one year, even after adjusting for baseline performance. When determining risk for ADL dependence, an assessment of change in physical performance over one year does not provide useful prognostic information beyond that available from a single assessment. Nevertheless, change in physical performance is independently associated with concurrent ADL dependence and may be useful in predicting future disability if measured over shorter intervals.

Activities of Daily Living↗
PubMed1997

Responses to exercise at 92% and 100% of the velocity associated with VO2max.

The purpose of this study was to evaluate the rationale for using the velocity associated with VO2max (vVO2max) and the time that vVO2max can be sustained (tMAX) in exercise prescription. Six male runners performed a 0%-slope incremental treadmill test to determine their VO2max (61.6 +/- 9.1 ml x kg(-1) x min(-1)) and the velocity at which it was elicited (vVO2max; 271 +/- 18 m x min(-1)). Then, they performed exhaustive tests at vVO2max and at 92% of vO2max. VO2max in these tests (4.56 +/- 0.55 and 4.57 +/- 0.50 l x min(-1)) were not different from the incremental value (4.31 +/- 0.83 l x min(-1)). At vVO2max, VO2max was attained after 299 +/- 74 s and sustained for 32 +/- 41 s. At 92% of vVO2max, it took longer to attain VO2max (491 +/- 156 s), but it was sustained longer (130 +/- 66 s). Since no athlete reached VO2max in the first 60% of the runs, the results did not provide a rationale to support the recommendation that athletes train at vVO2max for a fixed percentage of tMAX when the goal in the training session is to maintain VO2max.

Adult↗
PubMed1997

Driving cessation and increased depressive symptoms: prospective evidence from the New Haven EPESE. Established Populations for Epidemiologic Studies of the Elderly.

OBJECTIVES: The purpose of this study was to determine the association between driving cessation and depressive symptoms among older drivers. Previous efforts in this area have focused on the factors associated with cessation, not the consequences of having stopped. DESIGN: Cohort study. SETTING: Urban community. PARTICIPANTS: A driving survey was administered in 1989 to surviving noninstitutionalized members of the New Haven Established Populations for Epidemiologic Studies of the Elderly (EPESE) cohort. Of 1316 respondents, 502 were active drivers as of 1988, 92 had stopped driving between 1982 and 1987, and the remainder had either never driven or had stopped before 1982. MEASUREMENTS: Information about independent and dependent variables other than driving status came from the in person EPESE interviews in 1982, 1985, and 1988, except for medical conditions, which were updated yearly. Depressive symptoms were assessed by the Centers for Epidemiologic Studies-Depression (CES-D) scale. Analyses focused on the changes in depressive symptoms before and after driving cessation. Repeated measures multivariable analysis accounted for the effect of cessation on the outcome adjusting for the potential confounding due to sociodemographic and health-related factors. RESULTS: Individuals who stopped driving exhibited substantial increases in depressive symptoms during the 6-year interval. Driving cessation was among the strongest predictors of increased depressive symptoms (Coefficient 2.464, SE 0.758, P = .001) even when adjusting for sociodemographic and health-related factors. CONCLUSIONS: Driving cessation was associated with an increase in depressive symptoms even when accounting for sociodemographic and health-related factors. These consequences need to be taken into account when advising older drivers and when developing alternative transportation strategies.

Aged↗
PubMed1997

A predictive model for ADL dependence in community-living older adults based on a reduced set of cognitive status items.

OBJECTIVE: To develop and validate a simple tool, based on a reduced set of Mini-Mental State Examination (MMSE) items, that can be used to predict the onset of ADL dependence, and to compare the predictive accuracy of this new tool with that of the MMSE. DESIGN: Two prospective, population-based cohort studies, in tandem. The predictive model developed in the initial cohort was subsequently validated in a separate cohort. SETTING: General community in New Haven, Connecticut. PARTICIPANTS: For the development cohort, 775 community-living persons, 72 years of age and older, who were independent at baseline in their ADI, function. For the validation cohort, 1038 comparable subjects. MEASUREMENTS: All subjects underwent a baseline interview and cognitive assessment in their homes by a trained research nurse using standard instrument. Self-reported ADLs were ascertained at 1 year and 3 years for the development cohort and at 1 year and 21/2 years for the validation cohort. RESULTS: ADL dependence developed in 221 (28.5%) subjects in the development cohort. Although the rate of ADL dependence increased within each MMSE domain as the number of incorrect items increased, only orientation and short-term memory remained significantly associated with ADL dependence in multivariable analysis. A predictive model, based on the presence of impairments in these two domains, was developed that stratified subjects into three risk groups. Rates of ADL dependence were 22% (neither domain impaired), 44% (one domain impaired), and 68% (both domains impaired) (P < .001). The corresponding rates in the validation cohort, in which 191 (18.4%) subjects developed ADL dependence, were 15%, 26%, and 45% (P < .001). The area under the ROC curves for the MMSE and the reduced item strategy were nearly identical at 0.63 and 0.62, respectively. CONCLUSIONS: A simple and valid six-item strategy, based on the presence of impairments in orientation and short-term memory, predicts the onset of ADL dependence as effectively as does the 30-item MMSE. This new tool may be useful as part of a more comprehensive assessment when determining an older person's risk for developing ADL dependence.

Activities of Daily Living↗
PubMed1997

Growth of artificially fed infant rats: effect of supplementation with insulin-like growth factor I.

Insulin-like growth factor I (IGF-I), a potent mitogenic peptide, is present in considerable quantities in most mammalian milks, but its importance for the neonate is unknown. To test the hypothesis that milk-borne IGF-I is an important factor in the regulation of neonatal growth, as well as that of the gastrointestinal tract, rat pups were fed a rat milk substitute (RMS) devoid of growth factors via gastrostomy. These animals were compared with those given RMS supplemented with recombinant human IGF-I added at a concentration of 500 ng/ml. Animals given RMS + IGF-I gained mere weight than controls, although skeletal growth as represented by elongation of the tail was no different. Animals fed RMS + IGF-I had increased brain and liver wet weights as well as increased liver and small intestine protein contents. Serum IGF-I concentrations in the IGF-I-supplemented group were more than twofold above RMS controls and were similar to dam-fed rat pups. Semiquantification of serum IGF-binding proteins (IGFBP) in these animals documented that in IGF-I-supplemented pups the amount of 38- to 40-kDa molecular mass IGFBP species was also greater than in RMS controls. The rate of migration of enterocytes from crypts in duodenum and proximal jejunum was greater in IGF-I-supplemented animals than in rats fed RMS alone. These studies suggest that milk-borne IGF-I is important in modulation of somatic and gastrointestinal tract growth in the neonatal rat.

Animals↗
PubMed1996

Insulin-like growth factor-I (IGF-I) mRNA in the small intestine of suckling and adult rats.

The presence and cellular localization of insulin-like growth factor-I (IGF-I) mRNA in the small intestine of suckling and adult rats was studied. A sensitive reverse transcription (RT) competitive-polymerase chain reaction (PCR) revealed IGF-I gene expression in both age groups. Adult tissue contained 3-fold higher levels of IGF-I mRNA in comparison with sucklings. Using an in situ hybridization technique, IGF-I transcripts were localized mainly in enterocytes and goblet cells in the intestinal crypts of adult rats. By using this technique, IGF-I mRNA was not detected in jejunum of 12-day-old rats.

Animals↗
PubMed1996

Elevated cyclooxygenase-2 levels in Min mouse adenomas.

BACKGROUND & AIMS: Mutations in the APC gene result in an increased propensity to develop intestinal neoplasia; however, a complete understanding of the mechanisms resulting in tumor formation has remained elusive. Min mice possess a mutation in the APC gene and display a neoplastic phenotype similar to that observed in familial adenomatous polyposis coli in humans. Cyclooxygenase (COX) inhibitors decrease tumor multiplicity in the Min mouse intestine. The present study was designed to determine if there was an increase in COX-2 in adenomas harvested from Min mouse intestine. METHODS: COX-2 messenger RNA levels were determined by Northern blots and reverse-transcription polymerase chain reactions of B6Min x 129 mouse-derived tumors. Protein levels and localization were determined by Western blots and immunohistochemical staining. RESULTS: The Northern blots revealed an approximately threefold increase in the level of COX-2 messenger RNA in Min mouse adenoma compared with normal mucosa. COX-2 protein levels in adenomatous tissues were also approximately threefold higher compared with normal mucosa from the same mouse. Immunohistochemical staining with a monospecific COX-2 antibody confirmed that increases in COX-2 immunoreactivity were restricted to dysplastic and neoplastic foci within intestinal mucosa. CONCLUSIONS: These data show that COX-2 levels may be increased at an early stage in colorectal neoplasia during polyp formation and before invasion.

Adenoma↗
PubMed1996

Introduction to eicosanoids and the gastroenteric tract.

Eicosanoids are produced throughout the gastrointestinal tract and are significant mediators of physiologic and pathophysiologic processes. Understanding the precise role(s) of specific eicosanoid metabolites remains a significant challenge, but has led to the development of new pharmacologic strategies for treating NSAID-induced gastroenteropathy and IBD. Given the complex array of arachidonic acid metabolites, the development of more specific and potent inhibitors of these cyclooxygenase isoforms is important for future studies and possible therapeutic applications. Mice have been prepared that lack expression of COX-1 or COX-2. Once these animals have been carefully evaluated, understanding of the role of various pathways of eicosanoid formation in gastrointestinal function, development, and epithelial growth regulation might be improved. Considerable progress has been made in the understanding of arachidonic acid metabolism and in eicosanoid receptor biology. The identification and characterization of an inducible cyclooxygenase isoform has led to important studies evaluating the role of this enzyme in inflammation, neoplasia, and NSAID-induced gastrointestinal injury. The demonstration that COX-2 overexpression in intestinal epithelial cells leads to specific phenotypic changes, such as increased adhesion and inhibition of apoptosis, indicates that this enzyme may alter the tumorigenic potential of epithelial cells and offers hope for the future development of improved chemopreventive agents.

Animals↗
PubMed1996

Impairments in physical performance and cognitive status as predisposing factors for functional dependence among nondisabled older persons.

BACKGROUND: Little is known about the processes underlying the development of functional dependence. We set out to determine whether impairments in physical performance and cognitive status contribute independently to the risk of functional dependence in nondisabled older persons. METHODS: Among a probability sample of 1,103 community-living adults, aged 72 years and older, we evaluated the 945 subjects who reported no disability in the activities of daily living. Subjects underwent a comprehensive assessment, including physical performance and cognitive testing. RESULTS: Among the 775 subjects alive with complete outcomes data, 221 (28.5%) developed dependence in activities of daily living at either the 1- or 3-year follow-up interview. The rates of functional dependence were 18%, 20%, 26%, and 50% (p < .001) and 18%, 23%, 31%, and 47% (p < .001), respectively, across quarters of worsening physical performance and cognitive status. Compared with subjects in the best group, those with the worst physical performance and cognitive status were more than five times as likely to develop functional dependence (67% vs 13%; p < .001). After adjustment for age, gender, number of chronic conditions, and housing stratum, the risk of functional dependence increased across quarters of both worsening physical performance (relative risks [RR] 1.0, 1.1, 1.3, 2.1) and cognitive status (RR 1.0, 1.3, 1.5, 2.0), independent of the effect of the other. Similar results were found for subjects who developed functional dependence at one year, for those who developed functional dependence at three years, and for the combined endpoint of functional dependence or death. CONCLUSIONS: Impairments in physical performance and cognitive status contribute independently to the risk of functional dependence in nondisabled, community-living older adults. A better understanding of the processes underlying functional dependence may facilitate the design of effective and efficient strategies to prevent or slow functional decline.

Activities of Daily Living↗