Biomedical subjects

C S Williams

Publications and source records attributed to C S Williams.

At least 55 records · Page 3Linked to original sources

PubMed1999

Home-based multicomponent rehabilitation program for older persons after hip fracture: a randomized trial.

OBJECTIVE: To determine whether a home-based systematic multicomponent rehabilitation strategy leads to improved outcomes relative to usual care. DESIGN: A randomized controlled trial with 12 months of follow-up. SETTING: General community; 27 home care agencies. PARTICIPANTS: Three hundred four nondemented persons at least 65 years of age who underwent surgical repair of a hip fracture at two hospitals in New Haven, CT, and returned home within 100 days. INTERVENTION: Systematic multicomponent rehabilitation strategy addressing both modifiable physical impairments (physical therapy) and activities of daily living (ADL) disabilities (functional therapy) versus usual care. MAIN OUTCOME MEASURES: A battery of self-report and performance-based measures of physical and social function. RESULTS: There was no significant difference in the proportion of participants in the two groups who recovered to prefracture levels in self-care ADL at 6 months (71% vs 75%) or 12 months (74% in both groups) or in home management ADL at 6 months (35% vs 44%) or 12 months (44% vs 48%). There also was no difference between the two groups in social activity levels, two timed mobility tasks, balance, or lower extremity strength at either 6 or 12 months. Compared with participants who received usual care, those in the multicomponent rehabilitation program showed slightly greater upper extremity strength at 6 months (p = .04) and a marginally better gait performance (p = .08). CONCLUSIONS: The systematic multicomponent rehabilitation program was no more effective in promoting recovery than usual home-based rehabilitation. Compared with previous cohorts, however, participants randomized to usual care in our study received more rehabilitative and home care services and experienced a higher rate of recovery. This finding is important given the current pressures to reduce home services. The challenge is to determine the composition and duration of rehabilitation and home services that will ensure optimal functional recovery most efficiently in older persons after hip fracture.

Activities of Daily Living↗

PubMed1999

Sulindac sulfide, but not sulindac sulfone, inhibits colorectal cancer growth.

Sulindac sulfide, a metabolite of the nonsteroidal antiinflammatory drug (NSAID) sulindac sulfoxide, is effective at reducing tumor burden in both familial adenomatous polyposis patients and in animals with colorectal cancer. Another sulindac sulfoxide metabolite, sulindac sulfone, has been reported to have antitumor properties without inhibiting cyclooxygenase activity. Here we report the effect of sulindac sulfone treatment on the growth of colorectal carcinoma cells. We observed that sulindac sulfide or sulfone treatment of HCA-7 cells led to inhibition of prostaglandin E2 production. Both sulindac sulfide and sulfone inhibited HCA-7 and HCT-116 cell growth in vitro. Sulindac sulfone had no effect on the growth of either HCA-7 or HCT-116 xenografts, whereas the sulfide derivative inhibited HCA-7 growth in vivo. Both sulindac sulfide and sulfone inhibited colon carcinoma cell growth and prostaglandin production in vitro, but sulindac sulfone had no effect on the growth of colon cancer cell xenografts in nude mice.

Animals↗

PubMed1999

The combined effects of baseline vulnerability and acute hospital events on the development of functional dependence among community-living older persons.

BACKGROUND: Many older persons who are highly vulnerable do not develop functional dependence, whereas some older persons with low vulnerability do develop functional dependence. We conducted this study to determine the combined effects of baseline vulnerability and precipitating events on the development of functional dependence. METHODS: We analyzed data from two prospective, population-based cohort studies. The development cohort included 799 community-living persons, 72 years of age and older, who were independent in their activities of daily living (ADLs). The validation cohort included 1,051 comparable persons. Participants were classified by baseline vulnerability, defined on the basis of physical performance, cognitive status, and age, and by exposure to potential precipitating events, determined from information gathered from acute care hospital admissions. The primary outcome was the onset of functional dependence, defined as a new disability in one or more of the seven ADLs at the 1-year follow-up interview or admission to a skilled nursing facility prior to the 1-year interview. RESULTS: Functional dependence developed in 109 (13.6%) participants in the development cohort and in 100 (9.3%) participants in the validation cohort. The rates of functional dependence for the low, intermediate, and high vulnerability groups were 7.1%, 17.2%, and 40.1% (p<.001) in the development cohort and 4.8%, 15.0%, and 28.0% (p<.001) in the validation cohort. For the four categories (none, mild, moderate, severe) of precipitating events, the rates of functional dependence were 9.0%, 19.4%, 27.3%, and 53.2% (p<.001 ) in the development cohort and 5.1%, 12.0%, 28.2%, and 53.3% (p<.001) in the validation cohort. For both cohorts, when baseline vulnerability and precipitating events were analyzed in cross-stratified format, the rate of functional dependence increased progressively from low-risk to high-risk groups in all directions (double-gradient phenomenon). The contributions of baseline vulnerability and precipitating events to the development of functional dependence were independent and statistically significant. CONCLUSIONS: Among community-living older persons, baseline vulnerability and precipitating hospital events contribute independently to the development of functional dependence and should each be targeted for intervention when developing strategies aimed at forestalling the onset of functional dependence.

Activities of Daily Living↗

PubMed1999

Mismatches between the home environment and physical capabilities among community-living older persons.

OBJECTIVE: To determine whether environmental hazards related to transfers, balance, and gait are any less prevalent in the homes of older persons with specific deficits in physical capabilities than they are in the homes of older persons without the same deficits. DESIGN: Cross-sectional study of a population-based cohort. SETTING: The general community in New Haven, Connecticut. PARTICIPANTS: A total of 1088 persons, aged 72 years and older, who had an environmental assessment of their homes. MEASUREMENTS: Each participant underwent a physical performance assessment and comprehensive interview to document the presence of underlying deficits in physical capabilities. Items from the environmental assessment that were potentially hazardous for participants with specific deficits in transfers, balance, or gait were identified. RESULTS: With the exception of no grab bars in the tub/shower, environmental hazards were as prevalent in the homes of participants with specific deficits in physical capabilities as they were in the homes of participants without the same deficits, and, in many cases, they were actually more prevalent. Among participants with and without observed difficulty standing from a chair, for example, the prevalence of a low lying chair was 24% versus 14% (chi2 = 13.4; P < .001), respectively. Among participants with and without an observed deficit in turning, the prevalence of an obstructed pathway was 47% versus 37% (chi2 = 8.7; P = .003), respectively; and the prevalence of loose throw rugs was 72% in both groups. CONCLUSIONS: If the epidemiologic link between environmental hazards and adverse functional outcomes can be strengthened, then interventions designed to enhance the everyday function of frail, older persons should focus on the environment as well as the individual.

Accidental Falls↗

PubMed1999

Alcohol use and functional disability among cognitively impaired adults.

BACKGROUND: The extent to which alcohol exposure increases risk for functional disability among older adults with cognitive impairment has not previously been assessed. OBJECTIVE: To examine the potential relationship between alcohol use and functional disability among older cognitively impaired adults. DESIGN: Retrospective medical record review. SETTING: Hospital-based geriatric assessment center. PARTICIPANTS: Two hundred forty-two consecutive participants with Mini-Mental Status Examination scores of < or = 24. MEASUREMENTS: Proxy-reported alcohol intake was classified in categories of never, former, light (< 1 drink/week), moderate (> or = 1 but < 14 drinks/week), and heavy (> or = 14 drinks/week) drinkers, and functional status was determined by proxy-reported performance in seven basic (BADL) and seven instrumental (IADL) activities of daily living (0 = poorest function and 14 = best function). RESULTS: Compared with never drinkers, moderate drinkers demonstrated higher mean BADL (12.2 vs 11.4, P = .033) and IADL scores (6.6 vs 5.6, P = .067), whereas heavy drinkers had higher BADL (12.8 vs 11.4, P = .019) but lower IADL scores (4.8 vs 5.6, P = .425). Former drinkers demonstrated both lower BADL (10.8 vs 11.4, P = .107) and IADL scores (3.9 vs 5.6, P = .011) compared with never drinkers. Evaluation of a potential dose-response effect was limited due to low numbers of light and heavy drinkers. CONCLUSIONS: Among cognitively impaired adults, moderate and heavy drinkers demonstrated better BADL function, whereas former drinkers had poorer IADL function, compared with never drinkers. Prospective studies that incorporate additional measures of exposure (e.g., cumulative lifetime consumption) and function (e.g., performance-based tests) may provide a more comprehensive understanding of alcohol's effects among older cognitively impaired adults.

Activities of Daily Living↗

PubMed1999

The role of COX-2 in intestinal cancer.

Cyclooxygenase (COX), the key regulatory enzyme for prostaglandin synthesis, is transcribed from two distinct genes. COX-1 is expressed constitutively in most tissues whereas COX-2 is induced by a wide variety of stimuli and was initially identified as an immediate-early growth response gene. In addition, COX-2 expression is markedly increased in 85-90% of human colorectal adenocarcinomas while COX-1 levels remain unchanged. Several epidemiological studies have reported a 40-50% reduction in the risk of developing colorectal cancer in persons who chronically take non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, which are classic inhibitors of COX. Genetic evidence also supports a role for COX-2, since mice null for COX-2 have an 86% reduction in tumour multiplicity in a background containing a mutated APC allele. These results strongly suggest that COX-2 contributes to the development of intestinal tumours and that inhibition of COX is chemopreventative. It is hoped that the chemopreventative effects of NSAIDs will be enhanced by the recent development of COX-2-specific inhibitors.

Journal Article↗

PubMed1999

A population-based study of environmental hazards in the homes of older persons.

OBJECTIVES: This study sought to estimate the population-based prevalence of environmental hazards in the homes of older persons and to determine whether the prevalence of these hazards differs by housing type or by level of disability in terms of activities of daily living (ADLs). METHODS: An environmental assessment was completed in the homes of 1000 persons 72 years and older. Weighted prevalence rates were calculated for each of the potential hazards and subsequently compared among subgroups of participants characterized by housing type and level of ADL disability. RESULTS: Overall, the prevalence of most environmental hazards was high. Two or more hazards were found in 59% of bathrooms and in 23% to 42% of the other rooms. Nearly all homes had at least 2 potential hazards. Although age-restricted housing was less hazardous than community housing, older persons who were disabled were no less likely to be exposed to environmental hazards than older persons who were nondisabled. CONCLUSIONS: Environmental hazards are common in the homes of community-living older persons.

Activities of Daily Living↗

PubMed1998

Depression and risk of coronary heart disease in elderly men and women: New Haven EPESE, 1982-1991. Established Populations for the Epidemiologic Studies of the Elderly.

BACKGROUND: Results of several recent studies suggest that depression is predictive of incident coronary disease. However, few studies have examined this relationship in the elderly, the age at which most coronary heart disease (CHD) becomes clinically manifest. METHODS AND RESULTS: Data are from the New Haven, Conn, cohort (N = 2812) of the Established Populations for the Epidemiologic Studies of the Elderly project. Baseline information on depressive symptoms and CHD risk factors was collected during an in-person interview in 1982. Nonfatal myocardial infarctions were identified through monitoring of admissions to local hospitals and were validated by medical chart review. Cause of death was obtained from death certificates for all deceased participants. Outcomes were defined as CHD deaths (n = 255) and total incident CHD events (n = 391) between January 1, 1982, and December 31, 1991. There was no association between depressive symptoms and CHD outcomes in men. Among women, depressive symptoms were associated with an age-adjusted relative risk of 1.03 (per unit increase on the symptom scale) for CHD mortality (P=.001) and total CHD incidence (P=.002). These associations were largely unaffected by adjustment for established CHD risk factors but were reduced to nonsignificant levels after additional adjustment for impaired physical function. Additional analysis showed a significant association for depressive symptoms among women who had no physical function impairments or who survived at least 3 years without an event. CONCLUSION: Depressive symptoms may not be independent risk factors for CHD outcomes in elderly populations in general but may increase risk among relatively healthy older women.

Activities of Daily Living↗

PubMed1998

The expression of epidermal growth factor and transforming growth factor-alpha mRNA in the small intestine of suckling rats: organ culture study.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are associated with regulation of various gastrointestinal functions. In order to better understand their role in developing small intestine EGF, TGF-alpha and EGF-R steady-state mRNA levels and transcript stability were determined. Reverse transcription (RT) competitive-polymerase chain reaction (PCR) revealed that intestinal TGF-alpha mRNA levels were 10-fold higher in comparison with EGF mRNA. The primary intestinal culture technique was used to evaluate mRNA stability. The stability of TGF-alpha mRNA was remarkably lower than the stability of EGF mRNA. High levels of TGF-alpha mRNA accompanied by high degradation rate of this mRNA suggested a rapid turnover of intestinal TGF-alpha mRNA.

Animals↗

PubMed1998

Induction of cyclooxygenase-2 by activated Ha-ras oncogene in Rat-1 fibroblasts and the role of mitogen-activated protein kinase pathway.

Elevated cyclooxygenase-2 (COX-2) expression and activity have been observed in several different transformed cell types that express mutated ras genes. To investigate the mechanism of increased COX-2 expression following Ras-mediated transformation, Rat-1:iRas cell line was transfected with an Ha-RasVal-12 cDNA expression vector that is under the transcriptional control of the lac operon and is inducible with isopropyl-1-thio-beta-D-galactopyranoside (IPTG). IPTG treatment caused parallel increases in the levels of Ha-Ras and COX-2 proteins in Rat-1:iRas cells. The increased expression of COX-2 was accompanied by increased prostaglandin E2 production. Selective inhibition of COX-2 activity suppressed the production of prostaglandin E2 by >90% but did not alter the progress of the morphological transformation. The level of COX-2 mRNA was up-regulated by activated Ha-Ras. Induction of Ras increased the transcription of COX-2 by 44.3 +/- 10.1% and increased the half-life of COX-2 mRNA by approximately 3.5-fold. A specific mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) inhibitor (PD 98059) caused a delay in both the activation of ERK1/2 and the induction of COX-2 in IPTG-induced Rat-1:iRas cells. Inhibition of ERK activity by PD 98059 also suppressed the induction of COX-2 by epidermal growth factor in intestinal epithelial cells and significantly reduced the expression of COX-2 in Ha-Ras-transformed rat intestinal epithelial cells. ERK activity appears to be required for induction of COX-2 by Ras.

Animals↗

PubMed1998

The mortality of elder mistreatment.

CONTEXT: Although elder mistreatment is suspected to be life threatening in some instances, little is known about the survival of elderly persons who have been mistreated. OBJECTIVE: To estimate the independent contribution of reported elder abuse and neglect to all-cause mortality in an observational cohort of community-dwelling older adults. DESIGN: Prospective cohort study with at least 9 years of follow-up. SETTING AND PATIENTS: The New Haven Established Population for Epidemiologic Studies in the Elderly cohort, which included 2812 community-dwelling adults who were older than 65 years in 1982, a subset of whom were referred to protective services for the elderly. MAIN OUTCOME MEASURES: All-cause mortality among (1) elderly persons for whom protective services were used for corroborated elder mistreatment (elder abuse, neglect, and/or exploitation), or (2) elderly persons for whom protective services were used for self-neglect. RESULTS: In the first 9 years after cohort inception, 176 cohort members were seen by elderly protective services for verified allegations; 10 (5.7%) of these were for abuse, 30 (17.0%) for neglect, 8 (4.5%) for exploitation, and 128 (72.7%) for self-neglect. At the end of a 13-year follow-up period from cohort inception, cohort members seen for elder mistreatment at any time during the follow-up had poorer survival (9%) than either those seen for self-neglect (17%) or other noninvestigated cohort members (40%) (P<.001). In a pooled logistic regression that adjusted for demographic characteristics, chronic diseases, functional status, social networks, cognitive status, and depressive symptomatology, the risk of death remained elevated for cohort members experiencing either elder mistreatment (odds ratio, 3.1; 95% confidence interval, 1.4-6.7) or self-neglect (odds ratio, 1.7; 95% confidence interval, 1.2-2.5), when compared with other members of the cohort. CONCLUSIONS: Reported and corroborated elder mistreatment and self-neglect are associated with shorter survival after adjusting for other factors associated with increased mortality in older adults.

Aged↗

PubMed1998

Prognostic importance of emotional support for elderly patients hospitalized with heart failure.

BACKGROUND: Several studies have indicated that a variety of social relationships are important predictors of morbidity and mortality in patients with coronary artery disease, but little attention has been focused on the prognostic importance of these factors in the growing population of elderly patients with heart failure. To address this issue, we sought to determine whether emotional support is associated with fatal and nonfatal cardiovascular events in elderly patients hospitalized with heart failure. METHODS AND RESULTS: We reviewed the medical records of 292 subjects aged > or =65 years who were hospitalized with clinical heart failure and were part of the New Haven, Conn, cohort of the Established Population for the Epidemiologic Study of the Elderly, a longitudinal, community-based study of aging that included a comprehensive assessment of psychosocial support. In the unadjusted analysis, lack of emotional support was significantly associated with the 1-year risk of fatal and nonfatal cardiovascular outcomes [odds ratio, 2.4; 95% confidence interval, 1.1 to 4.9]. After adjustment for demographic factors, clinical severity, comorbidity and functional status, social ties, and instrumental support, the absence of emotional support remained associated with a significantly higher risk (odds ratio, 3.2; 95% confidence interval, 1.4 to 7.8). The test for interaction between emotional support and sex was significant (P=.01). In the fully adjusted model, the odds ratio for women was 8.2 (95% confidence interval, 2.5 to 27.2) compared with 1.0 (95% confidence interval, 0.3 to 3.3) for men. CONCLUSIONS: Among elderly patients hospitalized with clinical heart failure, the absence of emotional support, measured before admission, is a strong, independent predictor of the occurrence of fatal and nonfatal cardiovascular events in the year after admission. In this cohort, the association is restricted to women.

Aged↗

PubMed1998

Regulation of androgen and estrogen receptors in male excurrent ducts of the goat: an immunohistochemical study.

BACKGROUND: Since androgens and/or estrogens must bind with specific receptors in order to elicit a response at the target organ(s), it is important to understand factors that regulate expression of androgen receptors (AR) and estrogen receptors (ER). Hence, the objective of the study is to determine the relative significance between circulating androgen (CA) and luminal androgen (LA) in maintaining normal expression of AR and ER in male excurrent ducts. METHODS: Mature Nubian goats were subjected for 15 days each to the following treatments: (1) bilateral orchidectomy, (2) bilateral orchidectomy and testosterone treatment, (3) unilateral ligation of the extratesticular rete, and (4) unilateral orchidectomy. Tissues from different segments of the excurrent ducts were fixed in 4% paraformaldehyde and embedded in Paraplast-plus. Antigenic sites for AR and ER were immunolocalized using PG-21 rabbit antirat/human antibody and H-222 rat antihuman monoclonal antibody, respectively. The avidin-biotin horseradish peroxidase procedure was used to identify positive immunoreactivity. Negative controls included incubation of sections with irrelevant IgG in place of primary antibody. RESULTS: In intact animals, whereas AR were found in epithelial, connective tissue, and peritubular smooth muscle cells of the efferent ductules, regions I-V of the epididymis, and ductus deferens, ER were confined to nonciliated cells of the efferent ductules. Bilateral orchidectomy caused a severe loss of both AR and ER staining. Testosterone replacement to orchidectomized animals restored staining of both AR and ER to the intact level. Neither unilateral ligation of the extratesticular rete nor unilateral orchidectomy had any effect on AR or ER immunostaining. CONCLUSION: Circulating androgen alone, without any input from luminal androgen or other rete fluid contents, can regulate expression of both androgen receptor and estrogen receptor.

Animals↗

PubMed1998

A population-based perspective of changes in health-related quality of life after myocardial infarction in older men and women.

This study analyzes changes in health-related quality-of-life (HQL) outcomes following myocardial infarction (MI) from a population-based perspective. Data came from a representative sample of 2812 men and women 65 years and older living in New Haven, CT. All subjects were interviewed at baseline in 1982, and again in 1985 and 1988. HQL outcomes included self-rated health, depressive symptoms, and physical and social functioning. Pooled logistic regression models were used to estimate the risk for decline in HQL outcomes due to MI. Of the 203 MIs during follow-up, 111 (55%) survived until the next interview to provide post-MI data on outcomes. In bivariate analysis, MI patients were more likely than subjects without MI to show a decline in physical functioning (26.4% vs. 11.9%, P = .001) and social functioning (31.4% vs. 20.8%), P = .06). There were no differences in self-rated health (26.3% vs. 26.9%), but MI patients were less likely to show an increase in depression (9.1%) vs. 15.8%, P = .08). These associations remained mostly unchanged after adjustment for CHD risk factors. The effect of MI on physical and social functioning was much stronger among patients with a recent MI (<1 year ago) than those whose MI had occurred more than a year before post-MI assessment. While a substantial proportion of MI patients experience a significant decline in quality of life-related outcomes, only some of these declines occur more frequently among MI patients than in the population at large. This effect may also be limited to the immediate post-MI period. Results from this analysis are discussed in terms of the "burden of illness" within a defined population due to MI.

Activities of Daily Living↗

PubMed1998

Meloxicam inhibits the growth of colorectal cancer cells.

Cyclooxygenase-2 has been reported to play an important role in colorectal carcinogenesis. The effects of meloxicam (a COX-2 inhibitor) on the growth of two colon cancer cell lines that express COX-2 (HCA-7 and Moser-S) and a COX-2 negative cell line (HCT-116) were evaluated. The growth rate of these cells was measured following treatment with meloxicam. HCA-7 and Moser-S colony size were significantly reduced following treatment with meloxicam; however, there was no significant change in HCT-116 colony size with treatment. In vivo studies were performed to evaluate the effect of meloxicam on the growth of HCA-7 cells when xenografted into nude mice. We observed a 51% reduction in tumor size after 4 weeks of treatment. Analysis of COX-1 and COX-2 protein levels in HCA-7 tumor lysates revealed a slight decrease in COX-2 expression levels in tumors taken from mice treated with meloxicam and no detectable COX-1 expression. Here we report that meloxicam significantly inhibited HCA-7 colony and tumor growth but had no effect on the growth of the COX-2 negative HCT-116 cells.

Animals↗

PubMed1998

Nuclear translocation of beta-catenin in hereditary and carcinogen-induced intestinal adenomas.

The physical interaction between beta-catenin and the adenomatous polyposis coli (APC) gene, and the ability of APC to regulate cytoplasmic levels of beta-catenin suggest a role for beta-catenin in colorectal carcinogenesis. In this study, we found that beta-catenin immunoreactivity was detected exclusively in the cell membrane and cytoplasm of morphologically normal intestinal epithelial cells with predominant distribution in the differentiated nonproliferative cell population. In contrast, beta-catenin was localized predominantly in the nucleus of adenomas from Min/+ mice and transgenic mice expressing a mutant truncated form of the APC gene (Apc(delta716) mice). Beta-catenin was expressed predominantly at the cell membrane and cytoplasm of the nontransformed rat intestinal epithelial (RIE-1) cells in culture, whereas predominantly nuclear localization of beta-catenin was observed in the human colon cancer cell line SW480. In the azoxymethane (AOM) treated rats, overexpression and nuclear localization of beta-catenin was observed in all adenomas. Previous studies have indicated the incidence of APC mutations amongst AOM-induced tumors to be 15% or less. These results demonstrate that nuclear localization of beta-catenin is a common event in colorectal tumorigenesis.

Adenoma↗

PubMed1998

The effect of falls and fall injuries on functioning in community-dwelling older persons.

BACKGROUND: Several preventive strategies have proven effective at reducing the occurrence and rate of falling. It remains to be determined, however, whether, and to what extent, falls and/or fall injuries are independent determinants of adverse functional outcomes in older persons. METHODS: A probability sample of 1,103 community-dwelling persons over age 71 years was followed for 3 years. The 957 cohort members (87%) who participated in at least one follow-up interview while residing in the community were included in this study. Outcome measures included one and three year change in basic and instrumental activities of daily living (BADLs-IADLs), social activities, and physical activities. Based on daily calendars and hospital surveillance, participants were placed into one of four levels of fall status: no falls, one fall without serious injury, at least two falls without serious injury, and one or more falls with serious injury. Hierarchical linear regression models, sequentially adding six domains of covariates, were constructed to examine fall status as a risk factor for change in function. RESULTS: One noninjurious fall (beta = -.437; p < .01), at least two noninjurious falls (beta = -.877; p < .001); and at least one injurious fall (beta = -1.254; p < .001) were each associated with decline in BADL-IADL function over 3 years after adjusting for covariates (model R2 = .2617). Experiencing two or more noninjurious falls (beta = -.538; p < .05) was associated with decline in social activities (model R2 = .2779) while experiencing at least one injurious fall (beta = -.580; p < .01) was associated with decline in physical activity (model R2 = .4231). CONCLUSIONS: Falls and fall injuries appear to be independent determinants of functional decline in community-dwelling older persons. Falling is a health condition meeting all criteria for prevention: high frequency, evidence of preventability, and high burden of morbidity.

Accidental Falls↗

PubMed1998

Luminal stability of insulin-like growth factors I and II in developing rat gastrointestinal tract.

BACKGROUND: Insulin-like growth factors (IGF)-I and -II are present in milk of a number of mammalian species. The stability of IGF-I and -II in the intestinal lumen was investigated by measuring the proteolytic degradation of 125I-labeled IGF-I and IGF-II by rat (suckling and adult) intestinal luminal flushings in vitro. METHODS: Degradation of 125I-labeled IGF-I and IGF-II was assessed by measuring the generation of acid-soluble radioactivity and the reduction of the amounts of peak activity (gel filtration). Degradation was confirmed by measuring the loss of immunoreactivity and receptor activity. RESULTS: Incubation of 125I-IGF-I with midjejunal luminal flushings from 12-day-old suckling rats generated acid-soluble radioactivity in a time- and dose-(flushing) dependent manner, whereas incubation of 125I-IGF-II produced only minor amounts of acid-soluble radioactivity. Degradation activity in luminal flushings from adult rat intestine was several times greater than that in luminal flushings from suckling rats. Degradation of 125I-IGF-II was several times lower than that of 125I-IGF-I in the intestinal luminal flushings from suckling and adult rats. The rate of decrease in immunoprecipitable 125I-IGF-I was considerably lower than the rate of decrease in receptor-active radioactivity. Except for immunoreactivity, analyses of acid-precipitable, peak-A, and receptor-active radioactivities demonstrate that IGF-II is relatively more stable than IGF-I in luminal flushings of suckling rat duodenum, jejunum, and midjejunum. CONCLUSIONS: These results show that the stability of IGF in the gastrointestinal lumen depends on the age of the animal and the segment of the gastrointestinal tract, as well as on the peptide isoform.

Aging↗