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Biomedical subjects

J F Potter

Publications and source records attributed to J F Potter.

At least 37 records · Page 2Linked to original sources

Changes in baroreceptor sensitivity for heart rate during normotensive pregnancy and the puerperium.

Normal pregnancy is associated with marked changes in cardiovascular haemodynamics, which in part may be due to changes in autonomic control mechanisms. Baroreflex sensitivity for heart rate (BRS) was calculated in the supine and standing positions using power spectral analysis of pulse interval (PI) and systolic blood pressure (SBP) in 16 normotensive pregnant women and 10 normotensive non-pregnant controls. The pregnant women were studied on three occasions during their pregnancy (early, mid- and late gestation) and once during the puerperium. Supine total SBP variability increased between early and late pregnancy by 79% [95% confidence intervals (CI) 30%, 145%; P<0. 001], and supine high-frequency PI variability decreased by 75% (CI 51%, 88%; P<0.001). Supine BRS fell by 50% (P<0.001), with values returning to early-pregnancy levels in the puerperium, which were similar to those recorded in the control group. Standing SBP variability and BRS values were unchanged during pregnancy and post partum. The low/high frequency ratio of PI variability, taken as a surrogate measure of sympathovagal balance, increased by 137% (CI 42%, 296%; P<0.01) in the supine but not the standing position from early to late pregnancy. This was due to a decrease in high-frequency variability rather than to an increase in low-frequency variability, suggesting that these changes may have been due to vagal withdrawal rather than increased sympathetic activity. Normotensive pregnancy is associated with a marked decrease in supine BRS, although the exact mechanisms for these changes remain unclear. Further studies are required to define whether changes in BRS and sympathovagal tone in early pregnancy can be used to predict the onset of pregnancy-induced hypertension.

Adolescent↗

Insights into the neurodegenerative process of Alzheimer's disease: a role for mononuclear phagocyte-associated inflammation and neurotoxicity.

Since the first description of Alzheimer's disease (AD) in 1907, significant progress was made into understanding disease pathophysiology. The enormous effort in AD research has translated into the discovery of genetic linkages for disease, into elucidating the structure and function of the etiologic beta-amyloid protein, and into unraveling the seemingly complex neuroimmunological cascade that affects neuronal dysfunction. Although effective therapies do not currently exist, many are being developed. We propose that the neuropathogenesis of AD, in measure, revolves around the immunological activation of glial cells, which in turn leads to alterations in inflammatory neurotoxin production, and ultimately to neuronal injury and death. Elucidating the mechanisms involved in such glial cell immune activation should provide valuable insights into understanding the disease process and in providing effective therapeutics to prevent and/or retard the devastating neurodegeneration that afflicts so many of our elderly.

Alzheimer Disease↗

Baroreflex sensitivity changes with calcium antagonist therapy in elderly subjects with isolated systolic hypertension.

In order to study the effects of calcium-blocking therapy on cardiovascular homeostasis in elderly subjects with isolated systolic hypertension, we performed a randomised double-blind placebo-controlled crossover study of 6 weeks therapy with modified-release nifedipine or placebo. Changes with calcium-blocker treatment in clinic and 24-h blood pressure (BP), heart rate, BP variability, baroreflex sensitivity (BRS) by three methods (Valsalva manoeuvre, phenylephrine and sodium nitroprusside injection), and in baroreflex- and non-baroreflex-mediated reflexes (tilt and cold face stimulus) were studied in 14 elderly subjects (mean age [+/- SEM] 70 +/- 1 years) with sustained isolated systolic hypertension (clinic BP 179 +/- 3/85 +/- 1 mm Hg). Clinic systolic BP, but not diastolic BP, was reduced with treatment (by 14 +/- 6 mm Hg, P = 0.03, diastolic BP 4 +/- 3 mm Hg, P = 0.16). Twenty-four hour BP was also reduced by nifedipine treatment (by 18 +/- 3/9 +/- 2 mm Hg, both P < 0.001). Clinic and 24-h heart rate, and daytime BP variability, were unchanged with treatment. BRS was significantly increased during nifedipine therapy by all three measurement methods (all P < 0.05). With 60 degrees tilt during active treatment, subjects exhibited a greater heart rate increase (P < 0.01), and a reduced fall in systolic (P < 0.05) and diastolic BP (P < 0.05). Thus despite the arteriosclerosis and reductions in large artery compliance described in elderly patients with isolated systolic hypertension, clinically important improvements in clinic and ambulatory BP and some aspects of cardiovascular homeostasis can be achieved with calcium-channel blocking therapy.

Age Factors↗

Older subjects show no age-related decrease in cardiac baroreceptor sensitivity.

OBJECTIVE: To examine the relationship between age, blood pressure and cardiac baroreceptor sensitivity derived from spectral analysis, the Valsalva manoeuvre and impulse response function. METHODS: We studied 70 healthy normotensive volunteers who were free from disease and not taking medication with cardiovascular or autonomic effects. We measured beat-to-beat arterial blood pressure and used standard surface electrocardiography to record pulse interval under standardized conditions with subjects resting supine as well as during three Valsalva manoeuvres. We performed single, multiple and stepwise regression of patient characteristics against cardiac baroreceptor sensitivity results. RESULTS: There is a non-linear decline in cardiac baroreceptor sensitivity with advancing age, increasing systolic blood pressure and heart rate values (except for the Valsalva-derived result), but little further decline after the fourth decade. Only age significantly influenced values derived using the Valsalva manoeuvre and impulse response analysis. Using spectral analysis, age, systolic and diastolic blood pressure and heart rate influenced cardiac baroreceptor sensitivity, age contributing to 50% of the variability. Age also influenced the relationship between pulse interval and blood pressure, possibly indicating more non-baroreceptor-mediated changes with advancing age. CONCLUSIONS: Although age is the dominant factor influencing cardiac baroreceptor sensitivity in this normotensive population, there is little change in mean values after 40 years of age. The differences in the relationship between pulse interval and blood pressure with advancing age have implications for the calculation of cardiac baroreceptor sensitivity using spectral analysis.

Adult↗

Orthostatic blood pressure changes and arterial baroreflex sensitivity in elderly subjects.

BACKGROUND: orthostatic hypotension in elderly people is often attributed to diminished afferent baroreflex sensitivity, but this has not been demonstrated. We examined the hypothesis that postural change in blood pressure is related to baroreflex sensitivity, independent of the confounding effect of baseline blood pressure. METHODS: we studied 25 active, untreated elderly subjects free of postural symptoms (mean age 70 +/- 1 years): 16 with hypertension (clinic blood pressure 194 +/- 6/98 + 3 mmHg) and nine normotensive controls (clinic blood pressure 134 + 3/77 + 3 mmHg). We assessed baroreflex sensitivity from the heart rate and blood pressure responses to the Valsalva manoeuvre and a pressor and depressor stimulus (bolus phenylephrine injection or sodium nitroprusside infusion respectively). Subjects were then passively tilted to 60 degrees and maximum changes in systolic blood pressure, heart rate, forearm blood flow and forearm vascular resistance recorded. RESULTS: maximum change in systolic blood pressure with head-up tilt was correlated with supine systolic blood pressure (r = 0.60, P = 0.001). Maximum change in systolic blood pressure with orthostasis was greater in the hypertensive subjects (45 +/- 4 mmHg versus 29 +/- 6, P = 0.04) and the heart rate increment was less (16 +/- 2 bpm versus 24 +/- 4, P = 0.02). The increase in forearm vascular resistance with tilt was similar in the two groups (47 +/- 11 versus 38 +/- 7 units, P = 0.52). All three methods of assessing baroreflex sensitivity showed a reduction in the hypertensive subjects (all P < or = 0.02). Lower values of baroreflex sensitivity were related to greater falls in systolic blood pressure with tilt, after adjustment for the baseline level of systolic blood pressure. CONCLUSIONS: we found a relationship between baroreflex sensitivity and the systolic blood pressure fall with orthostasis, even after adjustment for prevailing systolic blood pressure. Despite equivalent changes in forearm vascular resistance with tilt, greater falls in systolic blood pressure were seen in hypertensive subjects than in normotensive controls, due in part to an inadequate baroreflex-mediated heart rate response. The postural fall in blood pressure often observed in elderly hypertensive subjects may be related to the reduced baroreflex sensitivity seen in this condition.

Aged↗

Measuring postural changes in blood pressure in the healthy elderly.

BACKGROUND: Background The reproducibility of postural changes in blood pressure of a healthy elderly population determined using standard clinical measurements is not known. OBJECTIVE: To assess the differences in reproducibility of postural changes in blood pressure in healthy elderly subjects 1 and 3 min after standing within a day and between visits spaced 6 weeks apart. METHODS: Casual readings of blood pressures of supine and standing subjects were measured twice during the day by the same observer on two occasions 6 weeks apart using a semi-automatic syphgmomanometer. Twenty-two subjects with no known risk factors for orthostatic hypotension (13 men) aged 69+/-3 years (mean+/-SD) with a mean initial screening supine blood pressure of 153+/-19/88+/-11 mmHg were recruited. RESULTS: There were significant differences(P<0.001) between the postural changes both for systolic and for diastolic blood pressure between 1 and 3 min of standing, the largest falls occurring after 1 min of standing, though we found no variation between morning and afternoon measurements and between visits. The coefficients of reproducibility between visits for the postural changes in blood pressure after 1 and 3 min of standing were large both for systolic and for diastolic blood pressure, ranging from 9.8 to 29.3 mmHg. CONCLUSIONS: There was a consistent and significant difference between the postural changes in blood pressure after 1 and 3 min of standing for this healthy elderly population, but there was no significant difference between the postural changes in morning and afternoon measurements and between visits. This marked variability in the postural change in blood pressure with duration of standing must be taken into account when assessing the prevalence of orthostatic hypotension and the effects of treatment in patients with orthostatic falls in blood pressure.

Aged↗

The effect of visual and hearing impairments on functional status.

OBJECTIVES: To describe the prevalence of visual and auditory impairment in frail older persons and to evaluate the association between sensory impairment and overall functional status. DESIGN: Prospective patient evaluation and retrospective analysis of data. SETTING: The outpatient geriatric assessment clinic of a university medical center. PARTICIPANTS: Consecutive patients seen in the University of Nebraska Medical Center Outpatient Geriatric Assessment Clinic from 1986 to 1992 for whom both vision and hearing information were available (n = 576). MEASUREMENTS: Visual acuity was measured by the Lighthouse Near Visual Acuity Test, and auditory acuity was evaluated with the whisper test. Functional status was determined by Lawton-Brody activities of daily living (ADL) and instrumental activities of daily living (IADL) scales. Comorbid illness was classified by the Cumulative Illness Rating Scale, and mental status was assessed by the Folstein Mini-Mental State Exam. RESULTS: Eighteen percent of patients had visual impairment of 20/70 or worse. Hearing impairment was found in 64%. The mean ADL and IADL scores were 20/24 and 12/23, respectively, for patients with visual acuity better than 20/70, compared with 18/24 and 8/23 for visually impaired patients (P < .001 for both comparisons). ADL and IADL scores were also higher in hearing intact patients compared with those with hearing impairment: respectively, 21/24 vs 19/24 (P < .001) and 13/23 vs 11/23 (P < .001). The effects of visual acuity and hearing acuity on IADL score are independent of mental status and comorbid illness (P < .001). The effect of visual acuity on ADL score is independent of mental status and comorbid illness (P < .001), whereas the effect of hearing on ADL score is not. Subjects with both hearing and vision impairment had mean IADL (P < = .05) and ADL (P < = .05) scores significantly lower than those with no impairment CONCLUSIONS: Impairments of vision and hearing are common in this frail older outpatient population. Functional status, as measured by IADL and ADL scores, is diminished for sensory impaired subjects. Combined vision and hearing impairments have a greater effect on function than single sensory impairments and influence functional status independent of mental status and comorbid illness. Overall, these results suggest that interventions to improve sensory function may improve functional independence.

Activities of Daily Living↗

Linear and nonlinear analysis of human dynamic cerebral autoregulation.

The linear dynamic relationship between systemic arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) was studied by time- and frequency-domain analysis methods. A nonlinear moving-average approach was also implemented using Volterra-Wiener kernels. In 47 normal subjects, ABP was measured with Finapres and CBFV was recorded with Doppler ultrasound in both middle cerebral arteries at rest in the supine position and also during ABP drops induced by the sudden deflation of thigh cuffs. Impulse response functions estimated by Fourier transfer function analysis, a second-order mathematical model proposed by Tiecks, and the linear kernel of the Volterra-Wiener moving-average representation provided reconstructed velocity model responses, for the same segment of data, with significant correlations to CBFV recordings corresponding to r = 0.52 +/- 0.19, 0.53 +/- 0.16, and 0.67 +/- 0.12 (mean +/- SD), respectively. The correlation coefficient for the linear plus quadratic kernels was 0.82 +/- 0.08, significantly superior to that for the linear models (P < 10(-6)). The supine linear impulse responses were also used to predict the velocity transient of a different baseline segment of data and of the thigh cuff velocity response with significant correlations. In both cases, the three linear methods provided equivalent model performances, but the correlation coefficient for the nonlinear model dropped to 0.26 +/- 0.25 for the baseline test set of data and to 0.21 +/- 0.42 for the thigh cuff data. Whereas it is possible to model dynamic cerebral autoregulation in humans with different linear methods, in the supine position a second-order nonlinear component contributes significantly to improve model accuracy for the same segment of data used to estimate model parameters, but it cannot be automatically extended to represent the nonlinear component of velocity responses of different segments of data or transient changes induced by the thigh cuff test.

Adult↗

Critical closing pressure explains cerebral hemodynamics during the Valsalva maneuver.

The Valsalva maneuver (VM), a voluntary increase in intrathoracic pressure of approximately 40 mmHg, has been used to examine cerebral autoregulation (CA). During phase IV of the VM there are pronounced changes in mean arterial blood pressure (MABP), pulse interval, and cerebral blood flow (CBF), but the changes in CBF are of a much greater magnitude than those seen in MABP, a finding to date attributed to either a delay in activation of the CA mechanism or the inability of this mechanism to cope with the size and speed of the blood pressure changes involved. These changes in CBF also precede those in MABP, a pattern of events not explained by the physiological process of CA. Measurements of CBF velocity (transcranial Doppler) and MABP (Finapres) were performed in 53 healthy volunteers (aged 31-80 yr). By calculating beat-to-beat values of critical closing pressure (CCP) during the VM, we have found that this parameter suddenly drops at the start of phase IV, providing a coherent explanation for the large increase in CBF. If CCP is included in the estimation of cerebrovascular resistance, a temporal pattern more consistent with an autoregulatory response to the MABP overshoot is also found. CCP is intricately involved in the control of CBF during the VM and should be considered in the assessment of CA.

Adult↗

Evidence of defective cardiovascular regulation in insulin-dependent diabetic patients without clinical autonomic dysfunction.

(1) Autonomic dysfunction is a well recognised complication of diabetes mellitus and early detection may allow therapeutic manoeuvres to reduce the associated mortality and morbidity. We sought to identify early cardiovascular autonomic neuropathy using spectral analysis of heart rate and systolic blood pressure variability. (2) Thirty patients with Type 1 (insulin-dependent) diabetes mellitus (DM) and 30 matched control subjects were studied. In addition to standard tests of autonomic function, heart rate and systolic blood pressure variability were assessed using power spectral analysis. From the frequency domain analysis of systolic blood pressure and R-R interval, the overall gain of baroreflex mechanisms was assessed. (3) Standard tests of autonomic function were normal in both groups. Total spectral power of R-R interval was reduced in the Type 1 DM group for low-frequency (473 +/- 63 vs. 747 +/- 78 ms2, mean +/- S.E.M., P = 0.002) and high-frequency bands (125 +/- 13 vs. 459+/-90 ms2, P < 0.0001). Systolic blood pressure low-frequency power was increased in the diabetic group (9.3 +/- 1.2 vs. 6.6+/-0.7 mmHg2, P < 0.05). The low frequency/high frequency ratio for heart rate variability was significantly higher in the Type 1 DM patients (4.6+/-0.5 vs. 2.9+/-0.5, P = 0.002), implying a relative sympathetic predominance. When absolute powers were expressed in normalised units, these differences persisted. There were significant reductions in baroreceptor-cardiac reflex sensitivity in Type 1 DM patients compared to controls while supine (9.7+/-0.7 vs. 18.5 +/- 1.7 ms/mmHg, P < 0.0001) and standing (2.9+/-0.9 vs. 7.18+/-1.9 ms/mmHg, P < 0.001). (4) Spectral analysis of cardiovascular variability detects autonomic dysfunction more frequently in Type 1 DM patients than conventional tests, and is suggestive of an abnormality of parasympathetic function. The abnormality of baroreceptor-cardiac reflex sensitivity could be explained by this impairment of parasympathetic function and this may predispose to the development of hypertension and increase the risk of sudden cardiac death. Using spectral analysis methods may allow detection of early diabetic cardiac autonomic neuropathy and allow therapeutic intervention to slow the progression.

Adult↗

Transcutaneous monitoring of blood gases: is it comparable with arterialized earlobe sampling?

Researchers are increasingly looking for reliable non-invasive methods of assessing blood gas concentrations, and several new techniques have recently become available. Values derived using arterialized earlobe samples have been found to be comparable with conventional arterial samples, and recent studies have compared transcutaneous blood gas analysis with the traditional arterial samples and found a reasonable level of agreement in particular for the partial pressure of carbon dioxide. There are no data comparing oxygen and carbon dioxide partial pressures (pO2, pCO2) derived from arterialized samples with one of the newer transcutaneous techniques. We therefore simultaneously studied arterialized earlobe blood gas samples and values for pO2 and pCO2 obtained by a transcutaneous monitor (TINA, Radiometer, Copenhagen) in 26 subjects with varying blood gas values. There was a close agreement between the two methods for assessment of pCO2 [mean difference (95% C.I.) between transcutaneous and earlobe values 0.25 kPa (-0.004, 0.5 kPa)], but not for pO2 [1.71 kPa (0.35, 3.07 kPa)]. Similarly, the limits of agreement were narrow for pCO2 compared to those for pO2 (-0.98, 1.47 kPa and -6.44, 3.02 kPa respectively). We conclude that transcutaneous measurement of pCO2 using the TINA is acceptable in the research setting, whereas assessment of pO2 cannot reliably be made using this technique.

Adult↗

Applicability of new techniques in the assessment of arterial baroreflex sensitivity in the elderly: a comparison with established pharmacological methods.

1. There has been considerable interest in techniques recently developed for the study of arterial baroreceptor-cardiac reflex sensitivity based on analysis of spontaneous baroreflex sequences and on spectral analysis. This study examined how these newer techniques agreed with the established pharmacological methods in elderly subjects. 2. In 20 elderly subjects [10 hypertensive (clinic blood pressure 180 +/- 4/88 +/- 2 mmHg) and 10 normotensive (clinic blood pressure 136 +/- 3/73 +/- 2 mmHg)], we assessed baroreflex sensitivity from spontaneous sequences of increasing and decreasing blood pressure and pulse interval and their mean, and from spectral analysis to derive alpha, the index of overall baroreflex gain. Pharmacological baroreflex sensitivity was derived from the blood pressure and pulse interval responses to depressor (sodium nitroprusside) and pressor (phenylephrine) stimuli, and their mean. 3. Baroreflex sensitivity was significantly lower in the hypertensive group by the pharmacological, sequence and spectral methods (all P < 0.05). 4. There was acceptable agreement between pharmacological baroreflex sensitivity and sequences of the same direction, but with some systematic bias. There was also reasonable agreement between pharmacological and spectral baroreflex sensitivity and close agreement without bias between sequence and spectral methods. 5. The newer and established techniques demonstrate acceptable agreement in the elderly, albeit with some systematic bias. Pharmacological methods have enjoyed historical precedence but newer techniques give equivalent results, and are preferable in some circumstances. The newer techniques may be more descriptive of the spontaneous behaviour of the arterial baroreflex at rest rather than under artificially stimulated conditions.

Aged↗

Diurnal blood pressure change varies with stroke subtype in the acute phase.

BACKGROUND AND PURPOSE: It is unclear whether acute stroke is associated with a loss of the normal diurnal blood pressure (BP) change and whether stroke type influences this. Some of this confusion results from the use of fixed time definitions of day and night, which can be overcome by the use of cumulative sums analysis (cusums). METHODS: Ninety-eight stroke patients had 24-hour BP monitoring (Spacelabs 90207) performed within 48 hours of ictus. Three subgroups were identified: cortical infarct, n=50; subcortical infarct, n=29; and primary intracerebral hemorrhage [PICH], n= 19. An age-matched control group of 74 subjects was also studied. Diurnal change was assessed by both day-night differences (absolute and percentage) and cusums (cusums plot height [CPH] and circadian alteration magnitude [CDCAM]); ANCOVA was used to compare groups. RESULTS: Compared with control subjects, cortical infarct and PICH subgroups had significantly reduced mean diurnal systolic changes using day-night differences (absolute, -12 and -17 mm Hg; percentage, -10 and -12, respectively; P < 0.0001) and cusums (CDCAM, -6.96 and -8.6 mm Hg; CPH, -32.05 and -46.04 mm Hg, respectively; P < 0.005), only the subcortical infarct subgroup demonstrated reduced percentage differences (-4.4%, P < 0.02). Mean diastolic differences were significantly reduced in all stroke subgroups(CPH, -24.84, -17.31, and -36.92 mm Hg; absolute, -8.26, -4.04, and -11.44 mm Hg; percentage, -10.65, -5.81, and -15.23%, for cortical infarct, subcortical infarct, and PICH subgroups, respectively; P < 0.05), except for CDCAM, which was not reduced in subcortical infarcts (-4.78 and -7.70 mm Hg for cortical infarct and PICH subgroups, respectively; P < 0.001). CONCLUSIONS: Diurnal BP change was reduced in the 3 stroke subgroups studied, especially in patients with cortical infarcts and PICH. This may reflect damage to the central modulation of autonomic BP control. The implications in terms of prognosis and therapy in the acute period require further study.

Acute Disease↗

Disagreement in the reporting of depressive symptoms between patients with dementia of the Alzheimer type and their collateral sources.

The authors investigated sources of disagreement on the Geriatric Depression Scale (GDS) between patients and their collateral sources (CSs). There were 198 subjects with possible or probable Alzheimer's disease (DAT) and 64 cognitively intact subjects evaluated at an outpatient geriatric assessment center. The 30-item GDS was completed by the patient and the CS version of the GDS by the CS. A sizable discrepancy was found in the reporting of depressive symptoms by the subjects vs. the CSs. Multiple-regression analyses revealed that both level of insight and level of physical illness in the subjects with DAT significantly influenced the discrepancy. An increased sense of burden in the CSs was associated with a larger symptom gap in both DAT and control subjects. CSs consistently perceived more depressive symptoms than subjects, especially subjects with DAT who had no insight into their cognitive impairment.

Aged↗