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Biomedical subjects

D T Lowenthal

Publications and source records attributed to D T Lowenthal.

At least 19 recordsLinked to original sources
PubMed1992

Influence of exercise and age on myocardial beta-adrenergic receptor properties.

The bradycardia following physical training may be mediated by an alteration in beta-adrenergic receptor number or agonist affinity. We characterized the interaction between age and exercise on myocardial beta-adrenergic receptor number and agonist affinity in 4- and 24-month-old F344 rats to test the hypothesis that the effects of training should be blunted in older rats. beta-adrenergic receptor density was unchanged with age or training. The total number of receptors per heart increased with age due to increased ventricle weight. With training, in the senescent rats the total number of receptors decreased due to a reduced amount of homogenate protein recovered from the ventricle, the significance of which is unknown. The receptor agonist dissociation constant for isoproterenol was determined in both the absence and presence of beta,gamma-imidoguanosine 5'-triphosphate [Gpp(NH)p] and did not change with age or training. Neither training nor age influenced beta-adrenergic receptor characteristics, suggesting that training bradycardia is not mediated by an alteration in beta-adrenergic receptors.

Aging↗
PubMed1992

Incidence of injury during moderate- and high-intensity walking training in the elderly.

To evaluate the effect of 26 weeks of moderate- and high-intensity walking training on injury rates in the elderly, 68 healthy volunteers (31 men, 37 women) were assigned to moderate intensity (MOD, n = 26) or high-intensity (HI, n = 24) training, or to a control (CONT, n = 18) group. To achieve prescribed training intensity, many subjects walked uphill on a treadmill. Seven of 50 subjects who trained (14%) suffered a training-related orthopedic injury; one subject was injured during treadmill testing. Four training injuries (lower leg and foot) occurred during weeks 1-13; three training injuries (leg and groin) occurred during weeks 14-26. Six of the injuries were to women. Because only one training injury occurred during uphill treadmill walking, injuries appeared related to fast walking and not exercise intensity. The higher incidence of injury in females is consistent with our earlier work, indicating the importance of further research to determine the underlying cause.

Aged↗
PubMed1992

Drug therapy in the elderly.

The segment of the population older than 65 accounts for about 25% of the total drug expenditures in developed countries. This figure is predicted to reach 40% by the year 2030. Drug therapy in the elderly can be complicated by many factors. The pharmacokinetic processes of absorption, distribution, metabolism, and elimination are altered by the physiologic changes of aging involving body composition and organ function. While the extent of drug absorption is not affected by age, few drugs have delayed rates of absorption after oral administration. Changes in body composition, protein binding, and blood flow do affect the concentrations of free unbound drug, the volume of distribution, and elimination half-life of a number of drugs. The primary goal of drug therapy in the elderly is to improve the quality of life. When medical therapy is required, the physician must be aware of the potential effect of age and disease on pharmacokinetics and pharmacodynamics and of the possible ramifications for adverse drug reactions or interactions. By increasing our knowledge of the action and effects of drugs in the elderly, and by enhancing communication and understanding between physician and patient, we can significantly improve the overall quality of care for the elderly patient.

Aged↗
PubMed1992

Health status of the aged: medical profile of a group of functional elderly.

By studying a group of very elderly but generally functional people, we have compiled a medical profile that helps describe health-related characteristics of effective aging. We obtained functional, nutritional, and biochemical information regarding 61 men and women (mean age 86.8 years) attending a veterans' convention. Twenty-three out of 60 (38%) reported a fall in the previous year, with those who were less physically active falling more than the most active. Many of the men were thin or had lost weight, but at most 3 of the 25 male subjects were clinically malnourished. Many of the women were heavy but were otherwise healthy. Of the 36 women, 6 (17%) had an elevated level of thyroid-stimulating hormone (TSH). Five of 58 (9%) had low vitamin B12 levels. Even in the older old who seem to be aging well, falling is relatively common, and screening for certain laboratory abnormalities has a reasonably high yield.

Accidental Falls↗
PubMed1992

Abnormal neuroendocrine responses during exercise in heart transplant recipients.

BACKGROUND: Osmotic and neural factors stimulate neuroendocrine activity during exercise. In contrast to excitatory mechanisms, afferent information from cardiac mechanoreceptors inhibits integrative centers in the hypothalamus and medula oblongata, which serves to buffer neuroendocrine activity. Orthotopic cardiac transplantation results in the loss of afferent information from cardiac mechanoreceptors. Thus, transplantation possibly results in exaggerated neuroendocrine responses when patients are physically active. METHODS AND RESULTS: We measured the neuroendocrine response to moderate and strenuous exercise performed at the same relative intensity in 11 heart transplant recipients (50 +/- 14 years old) 18 +/- 12 months after transplantation and 11 control subjects matched with respect to sex, age, and body size. Plasma levels of norepinephrine, vasopressin, renin activity, atrial natriuretic peptide, angiotensin II, and aldosterone were measured at rest, during a maximal graded exercise test, and during submaximal exercise at 40% and 70% of peak power output on a cycle ergometer (W). Plasma renin activity and atrial natriuretic peptide were elevated at rest in heart transplant recipients (p < or = 0.05). Heart rate (%HRmax reserve), rating of perceived exertion, and reductions in plasma volume (% delta from rest) at the conclusion of the three exercise conditions did not differ between heart transplant recipients and control (p > or = 0.05). Relative changes in neuroendocrine hormones were similar (p > or = 0.05) in heart transplant recipients and control during exercise at 40% of peak power output. Relative changes in plasma norepinephrine, vasopressin, atrial natriuretic peptide, and plasma renin activity were greater (p < or = 0.05) in heart transplant recipients during exercise at 70% of peak power output and the graded exercise test. CONCLUSIONS: We interpret these data as a possible indication of ablation of cardiac mechanoreceptor afferents and unopposed neuroendocrine stimulation in heart transplant recipients. Furthermore, chronic neuroendocrine hyperactivity is likely in ambulatory heart transplant recipients. Although cyclosporine nephrotoxicity is implicated in the development of hypertension, our data suggest that chronic neuroendocrine hyperactivity, which alters renal volume regulation, also contributes to the incidence and severity of hypertension in heart transplant recipients.

Afferent Pathways↗
PubMed1992

Drug use among functionally active, aged, ambulatory people.

BACKGROUND AND METHODS: Only a few pharmacoepidemiology studies have included very old subjects and most studies included both healthy and very ill people. Interpretation of data from these investigations is limited because of the mix of health status in the populations studied. We examined drug use in a group of active, relatively healthy, older people. Sixty-one attendees at a national convention, aged 76-96 years, volunteered to participate in a study on health status in a very old, ambulatory population. Medication histories, selected blood biochemistry analyses, a mental status examination, and other data were collected. RESULTS: The mean number of prescription and nonprescription drugs used per person was 2.02 and 1.85, respectively. More than a quarter of the sample population took no prescription medications and two-thirds used two or fewer prescription drugs. Sixteen percent of those taking prescription medications experienced adverse effects from their current drug regimens. Although falling was prevalent among our study subjects, there were similar drug-use patterns in those who did and who did not fall. CONCLUSIONS: In a group of relatively healthy and functional very old people, we found that drug use was not excessive, although adverse effects were still prevalent. In addition, most subjects were knowledgeable about their medications. These studies demonstrate that extreme age alone does not always result in sickness, frailty, and overuse of medications.

Aged↗
PubMed1991

Response to mental and physical stress before and during adrenoreceptor blocker and angiotensin-converting enzyme inhibitor treatment in essential hypertension.

The effects of mental, static and dynamic stresses on physiologic parameters before and after beta-blocker (n = 24) and angiotensin-converting enzyme inhibitor (n = 29) treatment were examined. Mental stress induced similar elevation in systolic and diastolic blood pressures (BPs) with and without beta-blocker treatment. During angiotensin-converting enzyme inhibitor treatment, the change in systolic BP was significantly greater (p less than 0.05). Heart rate response was attenuated by beta blockers and unchanged by the angiotensin-converting enzyme inhibitor. Skin temperature and galvanic skin resistance significantly decreased (p less than 0.05) with mental stress. Beta blockers did not change the response pattern, whereas the angiotensin-converting enzyme inhibitor attenuated the stress-induced reduction of both skin temperature and galvanic skin response. After handgrip exercise, increases in systolic and diastolic BPs and heart rate were similar before and after beta-blocker treatment, whereas the angiotensin-converting enzyme inhibitor induced small but significantly fewer (p less than 0.05) changes in diastolic BP and heart rate. Treadmill exercise induced similar changes in systolic and diastolic BPs with both treatments compared with no treatment. The angiotensin-converting enzyme inhibitor appears to provide additional protection to that seen with beta blockers during mental and static stressors by blunted changes in skin temperature and galvanic skin resistance.

Adrenergic beta-Antagonists↗
PubMed1988

Clinical pharmacokinetics of clonidine.

Clonidine is a centrally active antihypertensive agent effective in the treatment of mild, moderate and severe hypertension, alone or in combination with other drugs. Use of oral clonidine has often been limited by side effects which include dry mouth and drowsiness. Transdermal clonidine was therefore developed as an alternative to oral therapy. Ideally, a drug administered at a constant rate into the systemic circulation should attain steady-state concentrations with less peak-to-trough fluctuation than that associated with intermittent oral dosing. In theory, transdermal administration should thus minimise the adverse effects associated with peak plasma drug concentration, while avoiding the potential for decreased efficacy associated with trough levels. Clonidine has been incorporated into a small, pliable adhesive cutaneous delivery device designed to provide therapeutically effective doses of drug at a constant rate for at least 7 days. The transdermal therapeutic system is a laminate consisting of an external film impermeable to moisture and to the drug, a thin layer of active drug dispersed within a highly drug-permeable matrix, a membrane with a controlled intrinsic permeability regulating the rate of delivery of drug to the skin, and an adhesive coating that attaches the system to the skin surface. The permeation of drug through the skin occurs primarily by diffusion. Application of the clonidine transdermal system to both normotensive and hypertensive subjects has consistently reduced systolic and diastolic blood pressures. Maximum reduction in blood pressure occurs 2 to 3 days after initial application, and is maintained for at least 7 days or until the system is removed. The rate at which clonidine is presented to the skin surface is controlled by the microporous membrane: this rate is the same for all strengths of transdermal clonidine, the amount of clonidine released being proportional to its surface area. Thus, the daily dose is regulated by the area of skin covered. Typically, steady-state plasma concentrations are reached on the fourth day after initial transdermal system application. The lack of dose dependency in half-life and renal clearance estimates emphasise that the transdermal absorption of clonidine is linear. The plasma clonidine concentration produced by a particular transdermal dose varies considerably between individuals as a result of interindividual variation in renal clearance. For this reason, it is recommended that dosages be titrated up from the smallest system (3.5 cm2) until the desired pharmacological effect has been obtained.(ABSTRACT TRUNCATED AT 400 WORDS)

Clonidine↗
PubMed1988

Coordinating drug use and exercise in elderly hypertensives.

In the elderly hypertensive who maintains an active lifestyle, exercise and medication can interact due to age-related changes, resulting in reduced therapeutic effect. Underlying physiologic principles and indications for exercise therapy in geriatric hypertension are discussed as an aid toward deriving the greatest benefit and fewest side effects from concomitant drug therapy in non-sedentary elderly hypertensives, an expanding patient subgroup.

Aged↗
PubMed1987

Esmolol-digoxin drug interaction.

An open-label baseline-controlled study was conducted in 11 healthy male subjects to study the possible interaction between the cardioselective, short-acting beta blocker esmolol and digoxin when administered concurrently under steady-state conditions. Steady-state concentration, elimination half-life, and the total body clearance of esmolol were not changed significantly (P greater than .05) by digoxin. Digoxin peak concentration and the time to reach the peak concentration were not affected by esmolol. However, the digoxin AUC during the six-hour esmolol infusion increased from 2.60 +/- 0.59 to 2.88 +/- 0.75 ng.hr/mL (P less than .05). There were no clinically significant changes in the heart rate and blood pressure during this drug interaction study. The PR intervals were similar between digoxin monotherapy and esmolol plus digoxin combined treatment. Although digoxin did not influence the kinetics of esmolol, the small increase seen in digoxin serum concentration during the combination therapy warrants that caution be exercised during concurrent administration of esmolol and digoxin to patients.

Adolescent↗