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Biomedical subjects

L Ferrucci

Publications and source records attributed to L Ferrucci.

At least 109 records · Page 6Linked to original sources

Effect of age and severity of disability on short-term variation in walking speed: the Women's Health and Aging Study.

Standardized objective measures of human performance have been introduced in clinical and epidemiologic studies of older populations. Reliability of these measures has usually been estimated by comparing two measures obtained in the same person. However, no information is available on variability of multiple measures collected serially over short time intervals. This study uses data from the Weekly Disability Study, a component of the Women's Health and Aging Study, to describe fluctuations in physical performance over multiple, consecutive time intervals. Walking speed was measured weekly over a 6-month period in 99 older women affected by mild to severe disability. Overall, 2120 observations were explored using techniques developed for the analysis of repeated measures. Results showed that the correlations between observations in the same person were inversely related to their separation in time. The decay in the autocorrelation function was steeper in the least disabled. However, even with 20-week separations in assessments, correlations remained above 0.6 in all age and severity of disability subgroups. Changes over time in performance differed somewhat between disability subgroups, but the relative performance across subgroups remained stable over the entire course of the study. A clear learning effect was found only in those in the middle disability subgroup. Results support the utilization of repeated measures of physical performance in research that evaluates older persons over time.

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Progressive versus catastrophic disability: a longitudinal view of the disablement process.

BACKGROUND: There is little epidemiologic data on the development of disability over time in older persons. This study uses prospective data from cohorts followed annually for 6 to 7 years to identify persons who developed severe disability and to characterize the time course of their disabling process and subsequent mortality. METHODS: Incidence rates of severe disability, defined as need for help in three or more activities of daily living (ADLs), were estimated for 6,640 persons who had not reported severe disability at baseline and at the first four annual follow-up visits. Among persons developing severe disability, those who reported no need for help in ADLs in previous interviews were defined as cases of catastrophic disability, and those who had previously reported some disability in ADLs were defined as cases of progressive disability. RESULTS: Overall, 212 subjects developed progressive and 227 developed catastrophic disability. The rates of progressive disability and catastrophic disability were 11.3 and 12.1 cases per 1,000 person-years, respectively. For both types of disability, incidence rates increased exponentially with age, but the increase was steeper for progressive disability. At ages 70-74, less than 25% of severe disability was progressive, while over age 85 progressive disability represented more than half of severe disability. Incidence rates of total and both types of severe disability were similar in men and women. Mortality after severe disability onset was extremely high. Survival was unrelated to age at disability onset and type of disability but was significantly longer in women than in men (median 3.44 vs 2.12 years; p < .0001). CONCLUSION: Tracking the development of disability provides new and important insights into the disability experience in older men and women that are potentially relevant in planning preventive, intervention, and long-term care strategies.

Activities of Daily Living↗

Cognitive impairment and risk of stroke in the older population.

OBJECTIVE: Recent studies have suggested that vascular dementia in older persons is more common than previously hypothesized. A substantial proportion of dementia in old age may be an early manifestation of cerebrovascular disease (CVD), that eventually becomes clinically evident as an acute cerebrovascular accident. This study was aimed at assessing whether cognitive impairment and cognitive decline in older persons free of stroke are associated with higher risk of future stroke, independently of other risk factors. DESIGN: Population-based prospective study. PARTICIPANTS: A total of 5024 subjects from the Established Populations for Epidemiologic Studies of the Elderly, who were alive and had no history of previous stroke at the sixth follow-up visit. Subjects who had reported a stroke in a previous interview or with a diagnosis of cerebrovascular disease in a hospitalization record during the previous 3 years were excluded. MEASUREMENTS: Cognitive function was assessed by the Short Portable Mental Status Questionnaire (SPMSQ). Occurrence of a stroke was prospectively assessed by examining hospital discharge diagnoses and death certificates. RESULTS: During 19,533 person-years of follow-up, 259 strokes were recorded (13.3/1000 person-years). Stroke incidence was lowest in those with normal SPMSQ score (12.1/1000 person-years), intermediate in those with moderate impairment (16.3/1000 person-years), and highest in those with severe impairment (30.9/1000 person-years). Adjusting for age, education, smoking, history of hypertension, blood pressure, heart attack, diabetes, and disability, the relative risks of stroke for moderate and severe cognitive impairment were 1.2 (0.9-1.6) and 2.2 (1.2-3.8), respectively. The association between cognitive impairment and incident stroke was not mediated by hypertension or diabetes. Compared with subjects with stable or improved SPMSQ score in the previous 3 years, those who declined had higher risk of stroke. CONCLUSIONS: The elevated risk of subsequent strokes in older persons with cognitive impairment suggests that CVD may play larger role in causing cognitive impairment then previously suspected. It remains to be demonstrated whether reducing modifiable risk factors for CVD decreases the burden of cognitive impairment in older persons without stroke.

Age Distribution↗

Does the Clock Drawing Test predict cognitive decline in older persons independent of the Mini-Mental State Examination? The FINE Study Group. Finland, Italy, The Netherlands Elderly.

OBJECTIVE: To evaluate the value of the Clock Drawing Test (CDT) in predicting cognitive deterioration over a 4-year period, independent of baseline cognitive status evaluated by the Mini-Mental State Examination (MMSE). DESIGN: A preplanned analysis of data collected during the second (1991) and the third (1995) follow-up of the Italian rural cohorts of the FINE Study (Finland, Italy, the Netherlands Elderly). SUBJECTS: Of the 427 men (mean age 77.6 +/- 4.1 years; range 72-90 years) interviewed in 1991, 264 survived and were reinterviewed in 1995. The study population included 247 persons who were interviewed and received a complete cognitive evaluation in both 1991 and in 1995. MEASUREMENTS: Cognitive assessment in 1991 included the MMSE, the Dementia Rating Scale (DRS), and the CDT. The CDT was classified as normal or pathological, based on previously established criteria. The MMSE and the DRS were repeated in 1995. RESULTS: Independent of age and baseline MMSE, score, subjects with pathological CDT compared with normal CDT had lower MMSE scores at follow-up (P < .01). These results were also confirmed by evaluating cognitive decline through its impact on change over time in daily life autonomy, as measured by the DRS (P < .01). Among persons scoring more than 21 on the MMSE, compared with persons with a normal CDT, those with pathological CDT performance were 5.4 (95% CI: 2.1-14.2) and 5.5 (95% CI: 1.6-19.6) times more likely to have a MMSE score below 21 and 18, respectively, 4 years later, independent of age and baseline MMSE score. CONCLUSIONS: Findings suggest that the CDT identifies older persons at high risk of cognitive decline and adds prognostic information that supplements the standard MMSE test.

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Protective effect of chronic NSAID use on cognitive decline in older persons.

OBJECTIVE: To verify whether chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) has a protective effect against cognitive decline in older persons. DESIGN: Prospective study with a 3-year observation period. SETTING: Three communities of the Established Populations for Epidemiologic Studies of the Elderly (EPESE). SUBJECTS: A population-based sample of 7671 subjects who received an in-person interview at the sixth annual follow-up. Persons with documented NSAID use at the time of the interview and 3 years before were considered chronic users (21%), while all other persons were considered as nonusers. MAIN OUTCOME MEASURE: Change over time in cognitive function assessed as the number of correct answers to a 9-item version of the Short Portable Mental Status Questionnaire (SPMSQ). RESULTS: For every level of SPMSQ score measured at the beginning of the observation period, the mean SPMSQ score after 3 years was higher in chronic NSAID users than in nonusers. Cognitive function at the end of the observation period was significantly higher in chronic NSAID users than in controls, adjusting for initial SPMSQ score and potential confounders. Older age, female gender, education, and history of cerebrovascular disease were also independent predictors of lower SPMSQ score. In the multivariate analysis, the magnitude of the protective effect estimated for NSAID use was comparable to a difference in age of 3.5 years. The percentage of persons who started above a specific SPMSQ score cut-point and deteriorated below that cut-point over a 3-year period was significantly lower in chronic NSAID users than in nonusers (30.2% vs 34.3%, P = .03, for decline below SPMSQ score of 8 and 12.3% vs 14.4% for decline below SPMSQ score of 6, P = .04). After controlling for potential confounders, the relative risk of cognitive declining in chronic NSAID users compared with nonusers was 0.82 (95% Confidence Interval: 0.69-0.98) for a decline below a score of 8, and 0.80 (95% CI: 0.66-0.98) for a decline below a score of 6. CONCLUSIONS: These results support the association between NSAID use and reduction in cognitive decline in older persons. Ultimately, randomized controlled trials must be done to prove a beneficial effect definitively.

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Alcohol consumption and risk of deep venous thrombosis and pulmonary embolism in older persons.

OBJECTIVES: To assess whether low to moderate alcohol consumption decreases the risk of deep venous thrombosis and pulmonary embolism. DESIGN: Prospective cohort study. SETTING: Three communities of the Established Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS: A total of 7959 persons aged 68 years or older. MEASUREMENTS: The incidence of deep venous thrombosis and pulmonary embolism was assessed by surveying hospital discharge diagnoses and deaths from 1985 through 1992. Those participants who estimated they used alcohol less than 1 time, on average, in the past month, less than 1 ounce per day, and 1 ounce or more per day were compared with those who reported no alcohol intake in the past year. Age, gender, race, body mass index, smoking, education, income, disability, cognitive function, arterial pressure, medication use, baseline chronic conditions, number of hospital admissions in past year, and occurrence of disease during follow-up were examined as possible confounders. RESULTS: During 48,038 person-years of follow-up, 155 events were observed (35 deep venous thromboses and 123 pulmonary emboli). Compared with non-drinkers, after adjusting for potential confounding variables, the relative risks (95% confidence interval) for deep venous thrombosis and pulmonary embolism associated with increasing alcohol consumption levels were 0.7 (0.4-1.1), 0.6 (0.4-0.9), and 0.5 (0.2-1.1), respectively (P for trend = .004). The results were unchanged after stratifying on health status and disability. CONCLUSIONS: Low to moderate alcohol consumption is associated with a decreased risk of deep venous thrombosis and pulmonary embolism in older persons.

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Self-report of difficulty in performing functional activities identifies a broad range of disability in old age.

OBJECTIVE: To describe a broad range of physical disability by examining the association between a four-level measure of disability, based on self-report of difficulty in performing functional activities, and previously identified risk factors for disability. DESIGN: Cross-sectional. SETTING: Community-based. PARTICIPANTS: A total of 2373 noninstitutionalized men and women aged 65 and older from the Veneto Region of Italy. MEASUREMENTS: Odds ratios for the association of the four levels of disability (none, mild, moderate, and ADL disability) differentiated by this new measure with known risk factors for physical disability. MAIN RESULTS: This summary measure of physical disability distinguished older persons with disability from the population typically classified as nondisabled. Twenty-one percent of study participants were identified as having Activities of Daily Living (ADL) disability (defined as self-report of difficulty in one or more ADLs), and an additional 40% had mild or moderate disability based on degree of difficulty in Instrumental Activities of Daily Living (IADLs) and physical functional activities. Hip fracture and lower extremity performance were strongly independently associated with each level of disability. The association of a range of established risk factors for disability and health care utilization measures with the levels of disability identified in our study, and the trend toward increasing odds with increasing disability, provide evidence of the construct validity of this measure. CONCLUSIONS: Self-report of difficulty in performing functional activities identifies older persons with physical disability not ascertained by self-report of the need for help, the measure typically used to identify disability in older populations. Further studies should evaluate the potential for self-reported difficulty in functional activities to predict important disability-related outcomes.

Activities of Daily Living↗

Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability.

BACKGROUND: Functional assessment is an important part of the evaluation of elderly persons. We conducted this study to determine whether objective measures of physical function can predict subsequent disability in older persons. METHODS: This prospective cohort study included men and women 71 years of age or older who were living in the community, who reported no disability in the activities of daily living, and who reported that they were able to walk one-half mile (0.8 km) and climb stairs without assistance. The subjects completed a short battery of physical-performance tests and participated in a follow-up interview four years later. The tests included an assessment of standing balance, a timed 8-ft (2.4-m) walk at a normal pace, and a timed test of five repetitions of rising from a chair and sitting down. RESULTS: Among the 1122 subjects who were not disabled at base line and who participated in the four-year follow-up, lower scores on the base-line performance tests were associated with a statistically significant, graduated increase in the frequency of disability in the activities of daily living and mobility-related disability at follow-up. After adjustment for age, sex, and the presence of chronic disease, those with the lowest scores on the performance tests were 4.2 to 4.9 times as likely to have disability at four years as those with the highest performance scores, and those with intermediate performance scores were 1.6 to 1.8 times as likely to have disability. CONCLUSIONS: Among nondisabled older persons living in the community, objective measures of lower-extremity function were highly predictive of subsequent disability. Measures of physical performance may identify older persons with a preclinical stage of disability who may benefit from interventions to prevent the development of frank disability.

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Food intake and mortality in the frail elderly.

BACKGROUND: Adequate qualitative and quantitative food intake is a major determinant of health. However, nutritional requirements in the elderly are unknown, and even more so in the frail elderly. The aim of the study was to evaluate the influence of energy and macro-nutrients on health in the frail nursing home elderly. METHODS: Food intake of 72 not severely diseased elderly patients was assessed with direct weighing method. Outcome measure was survival over 28-month follow-up period. Confounders of the association of food intake with survival were: age, gender, body-mass index, daily function, somatic health, anergy, and nutritional status. Crude association of food intake with survival was assessed with Kaplan-Meyer method, and adjusted association with multiple Cox regression models. RESULTS: Patients of the study had good average food intake. Mortality rate was relatively low (.20 per year). Low levels of energy, protein, lipid, and carbohydrate intake were negatively associated with survival even after adjustment for confounders. When compared to high intake, adjusted relative risks for mortality of low intake were 4.74, 3.75, 4.71, and 2.04, respectively. Medium levels of energy, protein, and lipid, but not carbohydrate, intake yielded intermediate mortality risk. CONCLUSIONS: Food intake is a strong predictor of survival even in moderately diseased elderly patients, suggesting possible low-cost interventions.

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Immediate and long-term survival after intra-aortic balloon pumping: is advanced age an independent, unfavorable prognostic factor?

OBJECTIVE: To determine whether advanced age is an independent prognostic factor that may increase the risk of complications and reduce the immediate and long-term survival after treatment with intra-aortic balloon pumping (IABP) for acute ischemic heart disease. DESIGN: Retrospective analysis of a clinical series and long-term follow-up study. PATIENTS: A total of 142 patients (age range 23-86 years) in whom IABP was indicated following a standardized protocol. MEASUREMENTS: Univariate analysis of the association between age and anamnestic, clinical, and hemodynamic data significantly affecting prognosis; multivariate logistic regression analysis of variables showing significant associations. RESULTS: IABP-related complications were independent of age. At univariate analysis, pre-existing, noncardiac, associated conditions (chronic renal failure, stroke, bronchopulmonary disease) (P < .001), an indication to IABP for hemodynamic complications of acute myocardial infarction rather than for medically refractory myocardial ischemia (P < .001), a lack in hemodynamic response to IABP (P < .002), a prolonged delay to IABP initiation (P < .003), and advanced age (P < .025) were all predictors of in-hospital mortality. However, older patients were also more frequently affected by chronic comorbid conditions and by acute left ventricular failure as an indication to IABP. When these variables were entered into logistic regression models, the association between age and mortality was no longer statistically significant. Similarly, advancing age was associated (P < .012) with an increased mortality rate during an average follow-up of 94 +/- 9 months, but, again, such a significant association disappeared when simultaneously adjusting for New York Heart Association functional class, which was the single most important predictor of long-term mortality. CONCLUSIONS: Several anamnestic and clinical variables, rather than advanced age itself, are independent, prognostic factors negatively affecting the outcome of treatment with IABP. Technique-related complications are independent of age. Thus, old age should not be considered as a criterion to exclude any patient, a priori, from the potential benefits of this type of cardiocirculatory assistance.

Acute Disease↗

Foot pain and disability in older persons: an epidemiologic survey.

OBJECTIVE: To investigate the prevalence of foot pain in older people and its association with pathological conditions of the feet and with disability in basic and instrumental activities of daily living. DESIGN: Cross-sectional survey of a community-dwelling older population. PARTICIPANTS: A total of 459 subjects, 73% of the population aged 65 years and older living in Dicomano, Florence, Italy. MEASUREMENTS: A standardized medical examination was performed by a geriatrician to collect information on the presence of pain, specific problems of the feet, gait, and several indicators of physical health status. Disability in basic and instrumental activities of daily living was evaluated by self-report. RESULTS: The prevalence of foot pain was very high, especially in subjects affected by calluses or corns, hallux deformities, hammer toes, pes planus, and edema and among those who complained of difficulty in looking after the basic needs of the feet. Patients with foot pain needed a greater number of steps and longer time to walk the same distance. Foot pain was associated with a higher prevalence of disability in instrumental activities of daily living, particularly those related to standing and ambulation capacities, but it was not related to higher prevalence of disability in basic activities of daily living. CONCLUSIONS: Foot pain is associated with specific conditions of the feet and disability in instrumental activities of daily living. Adequate assessment and treatment of foot problems may prevent foot pain and potentially reduce risk of disability. This hypothesis needs to be tested in longitudinal studies and specific intervention trials.

Activities of Daily Living↗

Improved exercise tolerance by cardiac rehabilitation after myocardial infarction in the elderly: results of a preliminary, controlled study.

Elderly patients are commonly excluded from cardiac rehabilitation after myocardial infarction (MI). The present controlled, non-randomized trial was undertaken as a preliminary study to compare some effects of cardiac rehabilitation between patients younger and older than 65 years without contraindications to physical exercise. Baseline total work capacity (TWC) was assessed by a maximal ergometric stress testing 4 weeks after MI. Patients were then prospectively enrolled into an 8-week ambulatory rehabilitation program (R-group: age < or = 65 N = 16; age > 65 N = 16). Those who refused or who could not participate in the program because of logistic difficulties served as controls (NR-group: age < or = 65 N = 16; age > 65 N = 14). In spite of non-randomized allocation, clinical characteristics did not differ between either treatment groups or age groups. TWC was re-assessed at 8 weeks from baseline evaluation in all patients. The number of completed training sessions in the R-group, and the proportion of sessions which were suspended for physiological or pathological (adverse events during exercise) causes were similar under and over 65 years. TWC increased (p < 0.001) in the R-group, the improvement being similar in the two age cohorts (< or = 65: +55% vs > 65: +65%, NS). A spontaneous enhancement of TWC (+37%, p < 0.001) occurred among younger controls as well. Only older controls did not improve their TWC; moreover, their +16% change was significantly (p < 0.05) less than the +65% increase obtained by the R-group of the same age.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission.

BACKGROUND: A short battery of physical performance tests was used to assess lower extremity function in more than 5,000 persons age 71 years and older in three communities. METHODS: Balance, gait, strength, and endurance were evaluated by examining ability to stand with the feet together in the side-by-side, semi-tandem, and tandem positions, time to walk 8 feet, and time to rise from a chair and return to the seated position 5 times. RESULTS: A wide distribution of performance was observed for each test. Each test and a summary performance scale, created by summing categorical rankings of performance on each test, were strongly associated with self-report of disability. Both self-report items and performance tests were independent predictors of short-term mortality and nursing home admission in multivariate analyses. However, evidence is presented that the performance tests provide information not available from self-report items. Of particular importance is the finding that in those at the high end of the functional spectrum, who reported almost no disability, the performance test scores distinguished a gradient of risk for mortality and nursing home admission. Additionally, within subgroups with identical self-report profiles, there were systematic differences in physical performance related to age and sex. CONCLUSION: This study provides evidence that performance measures can validly characterize older persons across a broad spectrum of lower extremity function. Performance and self-report measures may complement each other in providing useful information about functional status.

Activities of Daily Living↗

A nutritional index predicting mortality in the nursing home.

OBJECTIVE: To define a sensitive and specific index, based on nutritional indicators, predicting mortality in nursing home patients. DESIGN: A prospective cohort study. SETTING: A nursing home. MEASUREMENTS: Anthropometric and laboratory nutritional indicators were assessed in 104 nursing home elderly residents (20 males, 84 females). Patients were aged 60 years and older and had relatively good somatic health and nutritional status. Mortality data were collected over an 18-month follow-up period. Discriminant analysis was used to compute an adimensional measure (index) that could predict mortality with the highest sensitivity and specificity. RESULTS: Mortality was 0.20/year. A nonlinear, "U-shaped" relationship of cholesterol levels with mortality was found. A prognostic index based on cholesterol, lymphocyte count, mid-arm circumference, hemoglobin, age, and gender was obtained. Higher values of this index were associated with progressively higher risks at 12 months and 18 months. Sensitivity and specificity calculated on 18-month mortality were 80% and 78.4%, respectively. CONCLUSIONS: This index, based on simple measures, can be a useful tool in the evaluation of health status of the elderly living in nursing homes.

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Relationship between health status, fluid intelligence and disability in a non demented elderly population.

This study examines the impact of overall health status and common chronic medical conditions on cognitive performance in an older population and the effect of poor cognitive performance on functional disability. The study population consisted of 485 subjects who were 77 and 78 years old, and residing in district No. 6 of the city of Florence; all participants underwent a structured interview to collect information on demographics, education, physical health, disability, and cognitive status. Data from 94 subjects, who were previously diagnosed as affected by dementia or other conditions known to be direct causes of cognitive impairment, and from 6 subjects, who scored less than 20 in the Mini-Mental State Examination, were excluded from the analysis. The number of chronic conditions, drugs used, contacts with the physician, days in bed, and days of hospitalization in the last 6 months were considered as indicators of physical health. Functional disability was assessed evaluating both ADLs and IADLs. The Mini-Mental State and the "Blocks" test, a component of the Wechsler Adult Intelligence Scale Revised, were used for the assessment of cognitive status. After adjusting for the level of formal education, physical health status and several specific chronic conditions were predictors of cognitive performance. A significant association was found between a low "Blocks" test score and a decreased level of functional status. In a multivariate model, better performance on the "Blocks" test was associated with a higher score in the disability scale. This association was independent of the effect of education. The results suggest that in the elderly, poor health status is associated with a cognitive impairment that can be measured by the "Blocks" test. However, the role of this association in the pathway from disease to disability remains unclear.

Activities of Daily Living↗

Commission of the European Communities "Europe Against Cancer" Programme. European school of oncology advisory report. Cancer treatment in the elderly.

Within the EC approximately one million cases of cancer are diagnosed every year. At present, more than 55% of cancers occur in subjects aged over 65 years. There has been little clinical attention to the problem of neoplasia in the elderly. They are not receiving the same standard of specialised oncological care as younger patients. Other diseases (co-morbidity conditions) associated with cancer, and influencing its treatment and outcomes are not being properly considered. Information on surgery, radiotherapy and chemotherapy in younger patients exists for all cancers and could be adapted for the elderly. Controversial aspects of neoplasia in the elderly concern the intensity of chemotherapy, extent of surgery and the relative roles of specialised cancer centres, community hospitals and primary care providers. Future research should aim to replace subjective opinions on presence of frailty with objective instruments such as the multidimensional geriatric assessment scale. New trials could then seek to improve treatment in well-defined populations in terms of both efficacy and quality of life. Funding priorities should firstly consider that clinical trials for tumours in the elderly must be organised from cancer institutes and specialised referral centres in collaboration with geriatricians, primary care and community hospital physicians. Continuing education of doctors should be reported. A document such as this with appropriate modifications might be used as an initial message on neoplasia in the elderly to be published for information to clinicians and the public throughout Europe. Specific measures of quality assurance need financial support to evaluate the improvements in patterns of care. The 10 points of the 'Europe Against Cancer Guidelines' need reemphasising.

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Acute and long-term effects of flosequinan in patients with chronic cardiac failure.

The acute and long-term effects of the orally active vasodilator flosequinan were assessed in 10 patients with New York Heart Association class II to IV cardiac failure. Baseline hemodynamics, exercise capacity, left and right ventricular ejection fraction, and pulmonary transit time were measured by right cardiac catheterization, bicycle ergometer stress testing, and nuclear angiocardiography during a run-in period on placebo. Acute hemodynamic effects of flosequinan were monitored for 48 hours; the drug was then given as a single 100 mg daily dose for 6 weeks. Exercise capacity was reevaluated every 2 weeks, and right cardiac catheterization and nuclear angiocardiography were repeated at the end of the 6-week period. Placebo did not exert any effect. Flosequinan reduced right atrial, pulmonary artery, and pulmonary artery wedge pressures from 60 minutes to 48 hours after dosing. Heart rate was minimally increased. Cardiac index, mean systemic arterial pressure, and systemic and pulmonary vascular resistance were substantially unaffected. These effects were maintained after 6 weeks. Exercise capacity was enhanced after 2, 4, and 6 weeks. Left ventricular ejection fraction was unchanged, whereas right ventricular ejection fraction and pulmonary transit time were improved. In conclusion, flosequinan exerted a potent, long-lasting, venodilating effect that was maintained long-term, without evidence of tolerance.

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Distribution of TaqI sites along human chromosomes revealed by in situ enzyme-nick translation.

We have studied the relative richness of TaqI sites along human chromosomes by means of a nonradioactive in situ enzyme-nick translation procedure. Regions with a higher content of these sequences are shown to be the noncentromeric heterochromatin blocks, whereas within euchromatin, terminal R-bands are the domains more enriched in these sites. Results obtained suggest that the method of performing enzyme digestions using time as a variable, and then in situ nick translation, provides much more complete information about the distribution of enzyme sequences along chromosomes than standard enzyme digestions.

Binding Sites↗