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Biomedical subjects

L A Lipsitz

Publications and source records attributed to L A Lipsitz.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of age and gender on autonomic control of blood pressure dynamics.

Both age and gender influence cardiovascular autonomic control, which in turn may influence the ability to withstand adverse cardiac events and respond to orthostatic stress. The purpose of this study was (1) to quantify age- and gender- related alterations in autonomic control of blood pressure (BP) and (2) to examine the impact of these autonomic alterations on BP response to orthostatic stress. We measured continuous BP and R-R intervals and vasoactive peptide levels in the supine and 60 degrees head-up tilt positions during paced respiration (0.25 Hz) in 89 carefully screened healthy subjects (41 men, 48 women, aged 20 to 83 years). Data were analyzed by gender (age adjusted) and by age group (gender adjusted). During tilt, women had greater decreases in systolic BP than men (-10.2+/-2 versus -1.2+/-3 mm Hg; P=0.02) and smaller increases in low-frequency (sympathetically mediated) BP power (P=0.02). Upright plasma norepinephrine was lower in women (P=0.02). Women had greater supine high-frequency R-R interval power than men (P=0.0001). In elderly subjects, the tilt-induced increase in low-frequency BP power was also diminished (P=0.01), despite higher supine (P=0.02) and similar upright norepinephrine levels compared with younger subjects. Thus, healthy women have less sympathetic influence on BP and greater parasympathetic influence on R-R interval than men. Elderly subjects also have reduced sympathetic influence on BP, but this appears to be more consistent with a reduction in vasomotor sympathetic responsiveness.

Adult↗
PubMed1998

Complex demodulation of cardiorespiratory dynamics preceding vasovagal syncope.

BACKGROUND: The dynamic autonomic processes leading to vasovagal syncope are poorly understood. METHODS AND RESULTS: We used complex demodulation to continuously assess changes in respiration, R-R interval, and arterial pressure (blood pressure) variability during 60 degree head-up tilt in 25 healthy subjects with tilt-induced vasovagal syncope and 25 age-matched nonsyncopal control subjects. Coherence and transfer function analyses were used to examine the relation between respiration and R-R interval variability before syncope. Baseline blood pressure, R-R, and ventilation were similar between syncope subjects and control subjects. Syncope subjects experienced an increase in tidal volume and decrease in BP beginning 3 minutes before impending syncope (systolic blood pressure <80 mm Hg) necessitated termination of tilt. Approximately 90 seconds before syncope there was a sudden prolongation of R-R interval and increase in amplitude of high and low frequency R-R interval variability, indicating an abrupt enhancement of vagal tone. The increase in respiratory amplitude between 180 and 90 seconds before syncope was not accompanied by changes in R-R interval or R-R variability, suggesting a dissociation between respiration and the respiratory sinus arrhythmia. The coherence analysis showed fewer syncope subjects with coherence between respiratory and R-R interval variabilities and lower transfer magnitudes in syncope subjects compared with control subjects. Nonsyncopal subjects had no change in respiratory, R-R interval, or blood pressure dynamics during matched time periods before the time of syncope. CONCLUSIONS: Vasovagal syncope is preceded by a period of hyperpnea and cardiorespiratory decoupling followed by an abrupt increase in cardiovagal tone. Respiratory pumping without inspiratory cardiac slowing may partially counteract preload reduction until sudden bradycardia precipitates syncope.

Adult↗
PubMed1998

Biomechanical gait alterations independent of speed in the healthy elderly: evidence for specific limiting impairments.

OBJECTIVES: It is not known whether changes in the biomechanics of elderly gait are related to aging per se, or to reduced walking speed in this population. The goals of the present study were to identify specific biomechanical changes, independent of speed, that might impair gait performance in healthy older people by identifying age-associated changes in the biomechanics of gait, and to determine which of these changes persist at increased walking speed. DESIGN: Stereophotogrammetric and force platform data were collected. Differences in peak joint motion (kinematic) and joint moment and power (kinetic) values between healthy young and elderly subjects at comfortable and increased walking speed were measured. SETTING: A gait laboratory. SUBJECTS: Thirty-one healthy elderly (age 65 to 84 years) and 31 healthy young adult subjects (age 18 to 36 years), all without known neurologic, musculoskeletal, cardiac, or pulmonary problems. MAIN OUTCOME MEASURES: All major peak kinematic and kinetic variables during the gait cycle. RESULTS: Several kinematic and kinetic differences between young and elderly adults were found that did not persist when walking speed was increased. Differences that persisted at both comfortable and fast walking speeds were reduced peak hip extension, increased anterior pelvic tilt, and reduced ankle plantarflexion and ankle power generation. CONCLUSION: Gait performance in the elderly may be limited by both subtle hip flexion contracture and ankle plantarflexor concentric weakness. Results of the current study should motivate future experimental trials of specific hip flexor stretching and ankle plantarflexor concentric strengthening exercises to preserve and potentially improve walking performance in the elderly.

Adolescent↗
PubMed1998

Age-related changes in the initiation of gait: degradation of central mechanisms for momentum generation.

OBJECTIVE: To investigate cross-sectionally age-related changes in the expression and biomechanical efficiency of the gait-initiation motor program. DESIGN: Case-control study. PARTICIPANTS AND SETTING: Twenty healthy young research subjects and 20 healthy elderly subjects who volunteered from the community participated in this study at a university research laboratory. MAIN OUTCOME MEASURES: Participants performed gait-initiation trials at three speeds from a starting position on a force platform while ground reaction force data, 3-D motion analysis data, and electromyographic data were collected. Measures included: latency of tibialis anterior (TA) activation and soleus (SOL) and gastrocnemius (GA) inhibition, magnitude of center of pressure (COP) displacement, magnitude of momentum generated, and final walking velocity. RESULTS: The expression of the central motor program governing gait initiation, as evidenced by the invariant timing between TA activation and SOL/GA inhibition, was seen in both the young and elderly populations, but the frequency was diminished in the latter group. The momentum-generating capacity of the COP shift mechanism was present but significantly diminished in the elderly population. CONCLUSIONS: These findings suggest that the central nervous system uses stable, efficient mechanisms for dealing with the inherent instability of upright bipedalism and that the integrity of these mechanisms degrades with aging.

Adolescent↗
PubMed1998

Does artificial enteral nutrition prolong the survival of institutionalized elders with chewing and swallowing problems?

BACKGROUND: There is a lack of prognostic data regarding tube feeding of institutionalized elderly people. The objective of this study was to determine the impact of feeding tubes on the survival of nursing home residents with chewing and swallowing problems, and to follow the course of the tube-fed residents over one year. METHODS: We conducted a cohort study with 12-month follow-up using Minimum Data Set resident assessments from 1991. Participants included 5,266 nursing home residents over the age of 65 with chewing and swallowing problems living in 272 Washington state nursing homes. Residents who had a feeding tube were identified. Baseline clinical characteristics and 12-month survival were compared for residents with and without feeding tubes. The proportion of tube-fed residents who became tube-free during the follow-up period was determined, and clinical features that predicted this outcome were examined. RESULTS: Among the residents with chewing and swallowing problems, 10.5% had a feeding tube. After adjusting for potential confounding covariates, tube-fed residents had a significantly higher one-year mortality rate than those without feeding tubes (risk ratio, 1.44; 95% CI, 1.17-1.76). Of the 430 residents with feeding tubes who survived the follow-up period, 25.1% became free of a feeding tube. Age less than 87 years was associated with a significantly greater likelihood of becoming tube-free (odds ratio, 1.66; 95% CI, 1.03-2.6). CONCLUSIONS: Residents selected for feeding tube placement have poorer survival after one year than residents who are not tube-fed. However, the feeding tubes are removed in a significant proportion of residents who survive one year. Residents with a potentially reversible condition, for whom the feeding tubes are a temporary intervention, need to be identified.

Age Factors↗
PubMed1998

Identifying nursing home residents at risk for falling.

OBJECTIVES: To develop a fall risk model that can be used to identify prospectively nursing home residents at risk for falling. The secondary objective was to determine whether the nursing home environment independently influenced the development of falls. DESIGN: A prospective study involving 1 year of follow-up. SETTING: Two hundred seventy-two nursing homes in the state of Washington. PARTICIPANTS: A total of 18,855 residents who had a baseline assessment in 1991 and a follow-up assessment within the subsequent year. MEASUREMENTS: Baseline Minimum Data Set items that could be potential risk factors for falling were considered as independent variables. The dependent variable was whether the resident fell as reported at the follow-up assessment. We estimated the extrinsic risk attributable to particular nursing home environments by calculating the annual fall rate in each nursing home and grouping them into tertiles of fall risk according to these rates. RESULTS: Factors associated independently with falling were fall history, wandering behavior, use of a cane or walker, deterioration of activities of daily living performance, age greater than 87 years, unsteady gait, transfer independence, wheelchair independence, and male gender. Nursing home residents with a fall history were more than three times as likely to fall during the follow-up period than residents without a fall history. Residents in homes with the highest tertile of fall rates were more than twice as likely to fall compared with residents of homes in the lowest tertile, independent of resident-specific risk factors. CONCLUSIONS: Fall history was identified as the strongest risk factor associated with subsequent falls and accounted for the vast majority of the predictive strength of the model. We recommend that fall history be used as an initial screener for determining eligibility for fall intervention efforts. Studies are needed to determine the facility characteristics that contribute to fall risk, independent of resident-specific risk factors.

Accidental Falls↗
PubMed1997

Preliminary evidence for the evolution in complexity of heart rate dynamics during autonomic maturation in neonatal swine.

Previous studies suggest that the autonomic nervous system plays an important role in the generation of complex heart rate dynamics. Therefore, we hypothesized that the complexity (irregularity) of cardiac interbeat intervals would evolve with the maturation of autonomic innervation to the heart. Twelve healthy newborn piglets were implanted with ECG transmitters and studied at one or more different ages up to 33 days of age, the period during which pigs develop functional sympathetic innervation of the heart from the stellate ganglia. Three animals underwent right stellate ganglionectomy, two a left stellate ganglionectomy, two a right cardiac vagotomy and five a sham procedure. The statistic, approximate entropy (ApEn), was used to quantify the regularity of interbeat interval fluctuations. Sham-operated animals showed an increase in the standard deviation (SD) and irregularity (ApEn) of cardiac interval fluctuations with increasing age. Right stellate ganglionectomized piglets had lower interbeat interval ApEn values, but similar SD's by 26-27 days of age compared to sham-operated animals. Left stellate ganglionectomy, which affects cardiac inotropy rather than chronotropy, had no effect on cardiac interval irregularity, while vagotomy had an indeterminant effect. The increasing irregularity of interbeat interval dynamics during autonomic maturation and the apparent attenuation of heartbeat irregularity when right stellate ganglion innervation is interrupted, provides empirical support for the notion that complex heartbeat dynamics in the mature animal are the result of a network of autonomic neural pathways that enables an organism to adapt to stress.

Aging↗
PubMed1997

The risk factors and impact on survival of feeding tube placement in nursing home residents with severe cognitive impairment.

BACKGROUND: The provision of artificial enteral nutrition to an aged person with severe cognitive impairment is a complex dilemma in the long-term care setting. OBJECTIVE: To determine the risk factors and impact on survival of feeding tubes in nursing home residents with advanced cognitive impairment. METHODS: We conducted a cohort study with 24-month follow-up using Minimum Data Set resident assessments on 1386 nursing home residents older than 65 years with recent progression to severe cognitive impairment in the state of Washington. Residents within this population who underwent feeding tube placement were identified. Clinical characteristics and survival for a period of 24 months were compared for residents who were and were not tube fed. RESULTS: Among the residents with recent progression to severe cognitive impairment, 9.7% underwent placement of a feeding tube. Factors independently associated with feeding tube placement included age younger than 87 years (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.25-2.78), aspiration (OR, 5.46; 95% CI, 2.66-11.20), swallowing problems (OR, 3.00; 95% CI, 1.81-4.97), pressure ulcer (OR, 1.64; 95% CI, 1.23-2.95), stroke (OR, 2.12; 95% CI, 1.17-2.62), less baseline functional impairment (OR, 2.07; 95% CI, 1.27-3.36), no do-not-resuscitate order (OR, 3.03; 95% CI, 1.92-4.85), and no dementia (OR, 2.17; 95% CI, 1.43-3.22). Survival did not differ between groups of residents with and without feeding tubes even after adjusting for independent risk factors for feeding tube placement. CONCLUSIONS: There are specific risk factors associated with feeding tube placement in nursing home residents with severe cognitive impairment. However, there is no survival benefit compared with similar residents who are not tube fed. These prognostic data are important for health care providers, families, and patients making decisions regarding enteral nutritional support in long-term care.

Aged↗
PubMed1997

Exclusion of elderly subjects from clinical trials for Parkinson disease.

OBJECTIVES: To determine whether subjects older than 75 years are included in the randomized controlled trials of antiparkinsonian medications conducted during the last 30 years and to identify study characteristics that are associated with the exclusion of patients of advanced age. METHODS: A systematic search was conducted on MEDLINE from January 1966 until September 1996 of all randomized controlled trials of drugs used to treat the motor symptoms of Parkinson disease. Articles were abstracted for the age of subjects date of publication, geographic location, drug class studied, stage of Parkinson disease of subjects, and the number of subjects in each trial. RESULTS: One hundred twelve articles met the inclusion criteria. The weighted mean (+/- SD) age for subjects in all trials was 62.2 +/- 3.9 years. Forty-two studies (37.5%) included subjects older than 75 years. However, in 31 articles (27.7%) it could not be determined if subjects older than 75 years were included. Among the 8 studies that provided the actual number of subjects within specific age groups, only 8 (5.5%) of 145 subjects were older than 75 years. Publication in the last decade was significantly associated with a decreased likelihood of including subjects older than 75 years (odds ratio, 0.19; 95% confidence interval, 0.06-0.62). CONCLUSIONS: The relatively small number of subjects older than 75 years included in controlled trials of antiparkinsonian drugs seriously impedes our understanding of the efficacy and safety of these drugs in a large subgroup of frail patients for whom these products are prescribed. The tendency to exclude subjects of advanced age is highest in the most recently published articles that study new advances in pharmacotherapy. There is inadequate reporting of the age characteristics of subjects in clinical trials. This limitation hinders the synthesis of data regarding drug efficacy and toxicity relevant to older age groups.

Adult↗
PubMed1997

Syncope in the elderly.

Age-related physiologic changes and disease-related abnormalities predispose older adults to syncope. It is important to know the physiologic changes that occur with normal aging to understand better their interaction with disease processes and to facilitate better evaluation and treatment of syncope when it occurs. Attention to situational stresses, such as posture changes, meals, or medications, is also likely to increase the diagnostic yield and improve therapeutic strategies that can reduce morbidity and potential mortality of recurrent episodes. Therapy should be directed toward minimizing multiple factors that contribute to syncope, avoiding iatrogenic medication effects, and treating specific contributory diseases.

Adult↗
PubMed1997

Short-term functional outcomes of long-term care residents with pneumonia treated with and without hospital transfer.

OBJECTIVE: To determine 2-month mortality and functional status outcomes after resolution of pneumonia in older long-term care facility (LTCF) patients treated with and without hospital transfer. DESIGN: Retrospective cohort study. SETTING: Hebrew Rehabilitation Center for Aged, a 725-bed LTCF affiliated with an academic medical center, whose residents are cared for by staff physicians and geriatric fellows. PATIENTS: LTCF residents with an acute episode of pneumonia, defined as a new respiratory sign or symptom and a new infiltrate on chest radiograph. MEASUREMENTS: Functional decline or death in the 2 months after the resolution of pneumonia. RESULTS: Of 312 cases of pneumonia, 246 (79%) were treated in the LTCF and 66 (21%) were treated in the hospital. Equal proportions of patients died of their pneumonia (13% vs 12%), but a larger proportion of those hospitalized had either worsening in their functional status or had died at 2 months (P = .005, Mantel-Haenszel trend test). In a logistic regression model controlling for differences between patients treated at the two sites, hospital treatment remained associated with poorer 2-month outcome (AOR 3.02, 95% CI 1.32, 7.22), with a significant interaction between respiratory rate and treatment site. LTCF treatment was associated with better 2-month outcomes only among patients with a lower respiratory rate. For these patients, the difference in outcome between LTCF treatment and hospital treatment was greatest for patients who were independent or mildly dependent at baseline. CONCLUSIONS: In this academic LTCF, treatment for pneumonia without hospital transfer resulted in better 2-month outcomes compared with hospital treatment. Although the difference in outcome may be explained in part by differences between patients treated with and without hospital transfer, it persisted after correcting for these differences. The benefits of LTCF treatment appear to be greatest for those with less severe pneumonia and more independent functional status.

Activities of Daily Living↗
PubMed1997

Vasomotor instability preceding tilt-induced syncope: does respiration play a role?

This study aimed to determine whether alterations in cardiovascular dynamics before syncope are related to changes in spontaneous respiration. Fifty-two healthy subjects underwent continuous heart rate (HR), arterial blood pressure (BP), and respiratory measurements during 10-min periods of spontaneous and paced breathing (0.25 Hz) in the supine and 60 degrees head-up tilt positions. Data were evaluated by power spectrum and transfer function analyses. During tilt, 27 subjects developed syncope or presyncope and 25 remained asymptomatic. Subjects with tilt-induced syncope had significantly greater increases in low-frequency (0.04-0. 15 Hz) systolic BP, diastolic BP, and HR power during tilt than the asymptomatic subjects (P </= 0.01). This difference was present during spontaneous but not paced breathing. However, average tidal volume, respiratory rate, minute ventilation, proportion of breaths below 0.15 Hz, and low-frequency respiratory power during tilt did not differ between syncopal and nonsyncopal subjects. Transfer magnitudes between low-frequency respiration and BP, and between BP and interbeat interval, were also similar between groups. Thus vasomotor instability before syncope is not related to alterations in respiration or the cardiovagal baroreflex but may reflect oscillating central sympathetic outflow to the vasculature.

Baroreflex↗
PubMed1997

Effects of central muscarinic-1 receptor stimulation on blood pressure regulation.

Stimulation of central nervous system muscarinic-1 (M1) receptors in animals increases blood pressure, heart rate, and sympathetic outflow. In Alzheimer's disease, stimulation of central M1 receptors is reduced. When the oral formulation of the selective M1 agonist xanomeline was tested for the treatment of Alzheimer's disease, an increased incidence of syncope was observed. Therefore, we used Alzheimer's disease as a model of relative M1 deficiency to determine the effect of M1 receptor stimulation on blood pressure regulation in humans. Eight Alzheimer's patients and 6 healthy age- and sex-matched subjects underwent blood pressure, heart rate, forearm vascular resistance, plasma norepinephrine, and heart rate variability measurements during 90 minutes after ingestion of xanomeline or placebo, then during 45 minutes of head-up tilt. Alzheimer's patients were studied on three occasions: after placebo, the first dose of xanomeline, and 3 days of xanomeline. Normal subjects were studied after placebo and the first dose of xanomeline. A subset of 5 Alzheimer's patients was studied with the peripheral muscarinic antagonist methscopolamine. Oral xanomeline increased supine systolic and diastolic blood pressures in normal subjects and heart rate and plasma norepinephrine in all subjects. During the placebo tilt, 0 of 8 Alzheimer's patients and 2 of 6 healthy subjects developed near-syncope, and during the first-dose xanomeline tilt, 4 of 8 Alzheimer's patients and 3 of 6 healthy subjects had near-syncope. The maximal decrease in systolic blood pressure during tilt was greater with xanomeline than placebo in both groups (P<.03). Methscopolamine did not prevent xanomeline-induced hypotension. Central M1 receptor stimulation with the oral formulation of xanomeline in humans is associated with sympathetic stimulation under supine conditions and impaired baroreflex compensation during tilt. Alzheimer's patients, who presumably lack M1 receptor activity, may have a reduced risk of tilt-induced syncope compared with normal subjects. Both groups, however, have enhanced susceptibility to hypotension and syncope when M1 receptor activity is pharmacologically increased.

Aged↗
PubMed1996

Clinical and pathological correlates of apolipoprotein E epsilon 4 in Alzheimer's disease.

Inheritance of the apolipoprotein E (apoE) epsilon 4 allele is associated with a high likelihood of developing Alzheimer's disease (AD). The pathophysiologic basis of this genetic influence is unknown. We reasoned that understanding the influence of apoE epsilon 4 on the clinical course and neuropathological features of AD may provide tests of potential mechanisms. We carried out a prospective longitudinal study to compare the age of onset, duration, and rate of progression of 359 AD patients to apoE genotype. Thirty-one of the individuals who died during the study were available for quantitative neuropathological evaluation. Statistically unbiased stereological counts of neurofibrillary tangles (NFTs) and A beta deposits were assessed in a high-order association cortex, the superior temporal sulcus. Analysis of clinical parameters compared with apoE genotype showed that the epsilon 4 allele is associated with an earlier age of onset but no change in rate of progression of dementia. Quantitative neuropathological assessment revealed that NFTs were strongly associated with clinical measures of dementia duration and severity but not with apoE genotype. A beta deposition, by contrast, was not related to clinical features but was elevated in association with apoE epsilon 4. These results indicate that apoE epsilon 4 is associated with selective clinical and neuropathological features of AD and support hypotheses that focus on an influence of apoE epsilon 4 on amyloid deposition.

Adult↗
PubMed1996

Factors influencing subject willingness to participate in clinical gerontologic research.

To identify factors influencing willingness to participate (WTP) in clinical gerontologic research, a questionnaire containing descriptions of seven research projects with a corresponding set of questions about perceived intrusiveness (discomfort and inconvenience), stipend, and other incentive factors was sent to 1004 community-dwelling research subject registry members. There was an inverse relationship between perceived level of intrusiveness and WTP. The more intrusive the study, the greater the relative influence of a stipend on WTP. Male gender and a new experience with an opportunity to learn were independently related to WTP. Subject ratings of perceived intrusiveness for each study component were entered into a factor analysis to guide the development of a three-tier "Level of Intrusiveness" scale. Although prospective validation is necessary, the Level of Intrusiveness scale may be useful in predicting WTP, and determining when other incentives are needed to improve subject recruitment for clinical research.

Aged↗
PubMed1996

Cardiovascular adaptation to orthostatic stress during vasodilator therapy.

BACKGROUND: Orthostatic hypotension is a dangerous problem in elderly patients, often exacerbated by vasodilator medications. Age- and disease-related impairments in cardioacceleration and diastolic ventricular function may make older patients particularly vulnerable to the hypotensive effects of these drugs. Therefore we aimed to determine mechanisms of postural blood pressure regulation in elderly patients with coronary artery disease and to compare the effects of isosorbide dinitrate and nicardipine hydrochloride on postural blood pressure homeostasis in these patients. METHODS: Twenty elderly subjects with stable coronary artery disease (age, 76 +/- 4 [SD] years) underwent a baseline evaluation followed by a double-blind, randomized crossover comparison of nicardipine (20 mg by mouth t.i.d.) versus isosorbide (20 mg by mouth t.i.d.). Doppler echocardiography and a 15-minute 60-degree head-up tilt test were conducted on no study medications and then after successive 3-week treatment periods with nicardipine or isosorbide. Blood pressure, heart rate, vascular resistance, cardiac output, and spectral characteristics of heart rate and blood pressure variability were measured before and during each tilt. RESULTS: Isosorbide treatment was associated with a higher prevalence of symptoms of cerebral hypoperfusion and a failure to increase systemic vascular resistance during tilt. While taking isosorbide subjects were able to preserve cardiac output and maintain upright blood pressure through enhanced cardioacceleration. During nicardipine treatment systemic vascular resistance and low-frequency blood pressure variability were reduced, but the ability to increase systemic vascular resistance during tilt was preserved. CONCLUSIONS: Although nicardipine may decrease vascular responsiveness to sympathetic activation, the baroreflex-mediated vasoconstrictor response to upright tilt remains intact. In contrast, isosorbide impairs the systemic vascular response to orthostatic stress in elderly patients with stable coronary artery disease.

Aged↗