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Biomedical subjects

D T Lowenthal

Publications and source records attributed to D T Lowenthal.

At least 37 records · Page 2Linked to original sources

Tau protein in cerebrospinal fluid: a new diagnostic and prognostic marker in Alzheimer disease?

Tau is the main protein of paired helical filaments. It can be detected and measured in cerebrospinal fluid (CSF) and for this reason it has been proposed as a possible in vivo marker of Alzheimer disease (AD). To evaluate the usefulness of CSF tau in the diagnosis of AD we measured it in patients with AD, frontal lobe dementia (FLD), vascular dementia (VD), and in healthy controls by means of a specific enzyme-linked immunosorbent assay test. Individuals with AD had significantly higher tau levels than FLD, VD, and controls. Individuals with late onset AD had significantly higher levels than those with early onset disease. In AD, CSF tau level did not correlate with age, duration, or severity of the disease, whereas a correlation with age was found in FLD and controls. In the nine AD patients in whom CSF tau measurement was repeated after 2 years, mean levels did not differ from baseline, although a worsening of cognitive performances occurred. The overlap among the different groups and the absence of any modification over time suggest that CSF tau measurement, more than in confirming or staging overt AD, might be useful in revealing the disease at its preclinical phase.

Aged↗

Evaluation and treatment of hypertension in active individuals.

Hypertension is a very common vascular disease. It is seen in adolescents, obese persons, postmenopausal women, and the elderly. A nonpharmacologic approach to treatment is a critical first step in management. The modalities include a diet low in salt and saturated fat, exercise, less than 2 ounces of alcohol daily, and abstinence from smoking. Dynamic (aerobic) exercise is effective in lowering blood pressure (BP) only if performed regularly. Weight reduction by diet must be combined with exercise if there is to be a reduction in BP. Strength training is not to be considered as an alternative to aerobic training for reducing BP. Antihypertensive mediation can be added to nonpharmacologic interventions for additional BP reduction. Beta-blockade is not a contraindication to exercise training.

Adolescent↗

Effects of delapril in combination with indapamide on blood pressure and left ventricular mass in elderly hypertensive patients.

We present a single-blinded, placebo-controlled trial of the effects on blood pressure and left ventricular mass and of the safety of a combined antihypertensive treatment with delapril, a new nonsulfhydryl angiotensin-converting enzyme inhibitor, and indapamide, a sulfonamide diuretic. We studied 28 elderly patients aged 65-85 years (mean age, 69 +/- 1) with sitting systolic/diastolic blood pressure of 160-200/95-115 mm Hg (at the end of the placebo period). After a 2-week placebo run-in, patients took 30 mg delapril in combination with 1.25 mg indapamide once daily for 24 weeks. Twenty-four-hour ambulatory blood pressure was monitored and M- and B-mode echocardiography were performed before and after 24 weeks of treatment. Blood pressure decreased from 156 +/- 1.5/101 +/- 1 mm Hg before treatment to 133 +/- 1/73 +/- 1 mm Hg after treatment. The total blood pressure burden also decreased; the percentage of measurements with a systolic blood pressure > or = 140 mm Hg and a diastolic blood pressure > or = 90 mm Hg decreased from 48.7% +/- 5%/31.5% +/- 4.3% to 23.5% +/- 4%/20.5% +/- 2.9% (p < 0.0005 and p < 0.05). The area under the curve of the 24-hour blood pressure decreased from 250 +/- 41/103 +/- 21 mm Hg to 97 +/- 21/37 +/- 8.5 mm Hg (p < 0.001 and p < 0.005). The left ventricular mass index (LVMI) in the 15 patients with pretreatment left ventricular hypertrophy was reduced after therapy from 167.5 +/- 8.5 g/m 2 to 152.2 +/- 7.6 g/m 2 (p < 0.05). A positive correlation was observed between percent changes of the area under the curve of the 24-hour diastolic blood pressure and percent changes of LVMI (r = 0.6; p < 0. 05) in the 15 patients with left ventricular hypertrophy. Only 2 patients reported side effects: 1 developed skin rash and 1 developed headache. The safety of the treatment was confirmed by laboratory tests. In elderly hypertensive patients, the combination of delapril and indapamide at low doses reduced blood pressure and had favorable effects on LVMI with few side effects.

Age Factors↗

Pharmacokinetic and pharmacodynamic changes in the elderly. Clinical implications.

Age-related changes in pharmacokinetics principally affect drug absorption, distribution, metabolism and elimination. Changes in pharmacodynamics are primarily seen in the cardiovascular and neuroendocrine system. Age-dependent changes in the kinetics and dynamics of drugs acting on the cardiovascular system and central nervous system are common, and this review, while by no means exhaustive of the effects of drugs on all organ systems, is reflective of the principles and gives examples of the effects of age on these 2 major systems. While pharmacokinetic changes in the elderly are usually well characterised, pharmacodynamic changes are understood only in the most preliminary way. There has been relatively little research in this area of geriatric clinical pharmacology, and pharmacodynamic changes are still an area of investigation.

Aged↗

Role of IGF-I in muscular atrophy of aging.

Loss of muscle mass and strength are well-known consequences of aging. The growth hormone/IGF-I pathway is both impaired with aging and essential for growth and maintenance of skeletal muscle. Despite this, growth hormone (GH) replacement has not been effective in increasing muscle mass and strength in the elderly. Possible explanations for this failure include 1. The presence of other age-related impairments in muscle that prevent the actions of GH and IGF-I and 2. Complications arising from a failure to deliver GH and IGF-I in the physiologically correct manner. This article summarizes the results of clinical trials of GH and IGF-I in the elderly and discusses the current status of strategies for safely and effectively stimulating the GH/IGF-I pathway in this population.

Adult↗

Proton magnetic resonance spectroscopy can differentiate Alzheimer's disease from normal aging.

In order to evaluate the pattern of proton magnetic resonance spectroscopy (1H-MRS) in the gray and white matter of patients with Alzheimer's disease (AD) and healthy controls, a cross-sectional study was carried out on 13 consecutive AD patients and 7 healthy older subjects who were referred to the Day-Hospital for diagnostic assessment. All examinations were performed on a 1.5 Tesla whole-body scanner. Volumes of interest were selected in both the gray (temporal region) and the white (frontal region) matter. N-acetyl group, total creatine, total choline and myo-inositol were quantified referring the metabolite peak area to the unsuppressed water peak area acquired under the same conditions, and the ratio was expressed in arbitrary units. A significant decrease in N-acetyl-aspartate (NAA) in both gray and white matter and an increase in myo-inositol (mI) in gray matter of AD patients were observed. The gray matter NAA/mI ratio clearly separated the two groups. White matter mI was significantly associated with severity and duration of dementia. No association with age was documented. It can be concluded that in vivo 1H-MRS can contribute to the knowledge of pathophysiology of AD, giving neurochemical details of both gray and white matter. In particular, the gray matter NAA/ml ratio seems to be able to differentiate normal cerebral aging from Alzheimer's disease.

Aged↗

Nocturnal polyuria in the elderly person.

Aging often disturbs the normal circadian rhythm of urine production. The nocturia commonly seen with aging may result from the loss of nighttime vasopressin production or release that develops by childhood. Restoring the nocturnal increase in vasopressin can have a dramatic clinical response: improved quality of life and less risk of nighttime falls in carefully selected and accurately diagnosed patients.

Aged↗

Effects of age, physical training, and physical fitness on coronary heart disease risk factors in older track athletes at twenty-year follow-up.

OBJECTIVE: To compare current coronary heart disease (CHD) risk factor values in older athletes with mid-life measures and to examine the associations between changes in CHD risk factors with aging, physical training, and physical fitness. DESIGN: Prospective study with three longitudinal evaluation points: initial (T1), 10-year (T2), and 20-year (T3). Subjects were selected because of their elite status in Masters track competition. SETTING: University and medical center laboratories. PARTICIPANTS: Participants were 60 to 92 years of age and included 21 of the initial 27 subjects. At T3, subjects were divided into three groups, based on physical activity levels: high intensity (H), remained elite in national and international competition (n = 9); moderate intensity (M) continued frequent rigorous endurance training but rarely competed (n = 10); and low intensity (L) greatly reduced their training volume and intensity (n = 2). MEASUREMENTS: Smoking history; family history of coronary or cerebrovascular disease; resting blood pressure; resting electrocardiogram (ECG); serum total cholesterol, plasma glucose; body weight, % body fat, body mass index, waist:hip ratio; training pace and mileage; maximal oxygen consumption VO2 max). MAIN RESULTS: Several risk factors (smoking, diabetes, obesity) were never present, and the prevalence of other risk factors (family history of cardiovascular disease, abnormal resting ECG) remained low through T3 (< or = 14% of subjects). Mean systolic and diastolic blood pressure remained low without medication, but diastolic blood pressure measurements had the greatest redistribution between evaluation periods of any risk factor (r = .16, P = .479, T1 to T2). Mean total cholesterol was lower at T2 (-13%, P = .005) and T3 (-14%, P = .019) compared with T1. Change in VO2 max was correlated with changes in body weight (r = -.44, P = .048) and % fat (r = -.52, P = .015) from T1 to T2, whereas age was correlated to changes in systolic blood pressure (r = -.61, P = .003) and total cholesterol (r = -.49, P = .023) from T2 to T3. CONCLUSIONS: The prevalence of CHD risk factors remained low, and mean risk factor values remained low and generally stable in older athletes who had maintained habitual exercise training.

Age Factors↗

Twenty-year follow-up of aerobic power and body composition of older track athletes.

The purpose was to determine the aerobic power (maximal oxygen uptake) and body composition of older track athletes after a 20-yr follow-up (T3). At 20 yr, 21 subjects [mean ages: 50.5 +/- 8.5 yr at initial evaluation (T1), 60.2 +/- 8.8 yr at 10-yr follow-up (T2), and 70.4 +/- 8.8 yr at 20-yr follow-up (T3)] were divided into three intensity groups: high (H; remained elite; n = 9); moderate (M; continued frequent moderate-to-rigorous endurance training; n = 10); and low (L; greatly reduced training; n = 2). All groups decreased in maximal oxygen uptake at each testing point (H, 8 and 15%; M, 13 and 14%; and L, 18 and 34% from T1 to T2 and T2 to T3, respectively). Maximal heart rate showed a linear decrease of approximately 5-7 beats.min-1.decade-1 and was independent of training status. Body weight remained stable for the H and M groups and percent fat increased approximately 2-2.5%/decade. Although fat-free weight decreased at each testing point, there was a trend for those who began weight-training exercise to better maintain it. Cross-sectional analysis at T3 showed that leg strength and bone mineral density were generally maintained from age 60 to 89 yr. Those who performed weight training had a greater arm region bone mineral density than those who did not. These longitudinal data show that the physiological capacities of older athletes are reduced despite continued vigorous endurance exercise over a 20-yr period (approximately 8-15%/decade). Changes in body composition appeared to be less than those shown for the healthy sedentary population and were related to changes in training habits.

Aged↗

Pharmacokinetic profile and endocrine effects of posatirelin treatment in healthy elderly subjects.

The pharmacokinetics and endocrine effects of a therapeutic dose (10 mg/day) of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide) were investigated in healthy elderly subjects. Posatirelin was given once daily by intramuscular injection for 7 days. Pharmacokinetic parameters were estimated using a model-independent approach. The plasma concentrations of free triiodotyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) and the circadian rhythms of prolactin and cortisol were considered as indicator variables of endocrine response to posatirelin administration. Posatirelin was well tolerated and no significant adverse effects were observed during the study. Peak plasma concentration (Cmax), time of peak plasma concentration (tmax), area under the plasma concentration-time curve from time zero to infinity (AUC0-infinity), elimination half-life (t1/2), and total clearance (CI/F) were measured after single-dose intramuscular injection (day 1) and after multiple-dose administration (day 7). There were no significant changes in these parameters after multiple-dose administration (day 7). Posatirelin induced a progressive reduction in basal TSH levels and maximum response. There were no significant changes during treatment in the time at which basal levels of FT3 and FT4 occurred, and these levels remained within the normal range throughout the study. The circadian rhythms of cortisol and prolactin were not influenced by posatirelin treatment. The pharmacokinetics of posatirelin were not time dependent, and the drug did not accumulate after multiple-dose administration. Short-term treatment with posatirelin did not induce clinically relevant endocrine consequences in healthy elderly subjects.

Aged↗

Relative heart rate, heart rate reserve, and VO2 during submaximal exercise in the elderly.

BACKGROUND: The purpose of this study was to examine the relationships among relative maximal heart rate (%HRmax), maximal heart rate reserve (%HRmax reserve), and maximal oxygen uptake (%VO2max) during submaximal exercise by elderly subjects. METHODS: VO2max and HRmax were determined on 36 women and 19 men, 60 to 80 yrs of age, by a maximal treadmill test to volitional exhaustion. On a separate day, subjects underwent a submaximal treadmill protocol consisting of three 6-min exercise stages at treadmill speeds and grades estimated to elicit 40%, 60%, and 80% of HRmax reserve. Cardiorespiratory responses were determined during mins 4-5 and 5-6 of each stage. RESULTS: Measured exercise intensities expressed by the three methods were: %HRmax reserve = 36, 55, and 79%; %HRmax = 65, 75, and 88%; %VO2max = 53, 69, and 88%. %HRmax was greater (p < .05) than %VO2max at 53 and 69% of VO2max. %HRmax reserve was less (p < .05) than %VO2max for all three intensities. Slopes and intercepts for the linear regression equations relating %VO2max with %HRmax and with %HRmax reserve differed between men and women (p < .05). The regression equation relating %VO2max and %HRmax was y = -22.8 + 1.2 (%HRmax) -13.0 (Gender) + 0.2 (%HRmax x Gender): standard error of the estimate (SEE) = 9.7% and R2 = .71. The regression equation relating %VO2max and %HRmax reserve was y = 32.4 + 0.7 (%HRmax reserve) -10.9 (Gender) + 0.2 (%HRmax reserve x Gender): SEE = 9.8% and R2 = .70 (Gender: F = 0; M = 1). CONCLUSIONS: The data indicate that there is considerable variability among methods of expressing exercise intensity and that %HRmax more closely represents %VO2max than does %HRmax reserve (p < .05) in older adults. These results are in contrast to what has been shown with younger subjects and with American College of Sports Medicine guidelines for exercise prescription.

Aged↗