Nutrition and immunity in older people.
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Biomedical subjects
Publications and source records attributed to M Cacciafesta.
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The epithelioid hemangioendothelioma of the liver has been recently characterized as a rare tumor with distinctive pathological features affecting young adults. Our report describes a case of histologically confirmed primary epithelioid hemangioendothelioma of the liver, diagnosed by clinical examination as well as radiological (CT/MR) and scintigraphic imaging (labelled red cells/ phytate-SPECT). This case highlights the usefulness of nuclear medicine techniques during the diagnostic of this rare tumor. Further it stresses the possibility of employing an easy and noninvasive method to adequately follow-up those patients who cannot be considered as disease-free even after orthotopic liver transplantation because of the recurrence of the disease in the transplanted liver.
Cortisol is the most important hormone secreted in response to acute and chronic stress. Thromboxane A2 (TxA2) is a potent eicosanoid with vasoconstricting and proaggregatory actions. Our earlier finding of a close correlation between plasma levels of TxB2, the stable metabolite of TxA2, and cortisol in subjects with major depression but without frank hypercortisolism prompted us to investigate a possible association between TxA2 and cortisol production in nondepressed subjects. The 24-hour urinary excretion values of 2,3-dinor-TxB2 (the urinary catabolite of TxA2) and cortisol were measured by radioimmunoassay in 50 subjects divided into three groups matched for age, sex distribution, and body mass index. Group 1 consisted of 19 healthy subjects; group 2 consisted of 15 patients with type IIa hypercholesterolemia, a condition associated with a high atherothrombotic risk, but without history of atherosclerosis or evidence of this disorder documented clinically or in noninvasive diagnostic tests; and group 3 consisted of 16 patients with regional atherosclerosis (8 with cerebrovascular disease, 6 with coronary artery disease, and 2 with peripheral vascular disease). Although the three groups had similar cortisol and 2,3-dinor-TxB2 urinary values, a significant direct correlation emerged between the two catabolites in the whole study sample (r = 0.63; p < 0.0001) and the three groups (r1 = 0.62, p < 0.01; r2 = 0.78, p < 0.0001; r3 = 0.63, p < 0.01). The close association between cortisol and thromboxane A2 biosynthesis thus appears to be a general phenomenon. These findings may be important in interpreting the well-described causative link between stress and atherothrombotic cardiovascular disease.
OBJECTIVE: The known association between systemic arterial hypertension in its initial stages and increased sympathetic nervous system drive prompted us to evaluate the influence of age on autonomic nervous system function in subjects with salt-sensitive arterial hypertension. DESIGN: In a randomized study, autonomic nervous system function was assessed by power spectral analysis of heart-rate variability calculated with an autoregressive algorithm in salt-sensitive hypertensives and controls at baseline and under sympathetic stress (passive head-up tilt). For 1 week before the study, all subjects kept to a diet supplying 120 mEq sodium. Sodium sensitivity was assessed by measuring and comparing arterial pressures after a 7-day controlled dietary sodium intake of 20 mEq per day after a 7-day period on 220 mEq sodium/day. SETTING: Geriatric division at the I Medical Clinic of the University of Rome "La Sapienza". PARTICIPANTS: Sixty-five patients with salt-sensitive hypertension (age range 19 to 89 years) and 64 age-matched normotensive controls, divided for data comparison into three age-groups: < 44 years; 44 to 64 years; and > or = 65 years. MEASUREMENTS: With an autoregressive algorithm in a power spectral analysis of heart rate variability, we detected four spectral frequency-domains: total power (0.0033 to 0.40 Hz), high-frequency power (0.16 to 0.40 Hz), low-frequency power (0.04 to 0.15 HZ) and very-low-frequency power (0.0033 to 0.04 Hz). To determine sodium sensitivity, for 1 week before the study all subjects kept to a diet supplying 120 mEq sodium. Sodium sensitivity was assessed by measuring and comparing arterial pressures after a 7-day controlled dietary intake of 20 mEq per day and after a 7-day period of 220 mEq sodium/day. RESULTS: Results were expressed as natural logarithms of power and normalized units. The hypertensive patients of all ages had significantly lower total power of heart rate variability than the normotensive controls (P < .05). At baseline, the youngest hypertensives had lower natural logarithms and low-frequency normalized units than controls (P < .001). After tilt, only their low-frequency normalized units exceeded those of controls (P < .001). The middle-aged hypertensive group had higher low-frequency normalized units than controls at baseline (P < .05) and after tilt (P < .001). At baseline and after tilt, the oldest hypertensives had lower low-frequency natural logarithms than controls (P < .05) and normalized units equal to those of controls. But the hypertensives of all ages were less able than controls (P < .001) to increase low-frequency power after head-up tilt. In the less than 44-year-old hypertensives, diastolic pressure correlated significantly with low-frequency power of heart rate variability, expressed in normalized units, at baseline (P < .05) and after head-tilt (P < .05). A significant inverse correlation was found between age and the natural logarithm of low-frequency power at baseline (r = -.682, P < .001) and after tilt (r = -.800; P < .001). Also, a significant inverse correlation was found to exist in normotensive subjects between the natural logarithm of low-frequency at baseline (r = -.595; P < .001) and after tilt (r = -.391; P < .001). The two regression line coefficients for age correlated significantly (P < .001) with the natural logarithm of low-power frequency after tilt. CONCLUSION: Whereas sodium chloride-sensitive hypertension appears to be associated with sympathetic hyperactivity in young and middle-aged subjects, in older people it is not. Sympathetic activity diminishes with age, declining faster in hypertensive subjects.
In salt-sensitive hypertension, a high sodium intake causes plasma catecholamines to rise and pulmonary baroreceptor plasticity to fall. In salt-sensitive and salt-resistant hypertensive subjects during low and high sodium intakes, we studied autonomic nervous system activity by power spectral analysis of heart rate and arterial pressure variabilities and baroreceptor sensitivity. In all subjects, high sodium intake significantly enhanced the low-frequency power of heart rate and arterial pressures at rest and after sympathetic stress. It also increased heart rate and arterial pressure variabilities. During high sodium intake, salt-sensitive hypertensive subjects had significantly higher low-frequency powers of systolic arterial pressure (7.5 mm Hg2, P < .05) and of heart rate at rest (59.2 +/- 2.4 normalized units [NU], P < .001) than salt-resistant subjects (6.6 +/- 0.3 mm Hg2, 55.0 +/- 3.2 NU) and normotensive control subjects (5.1 +/- 0.5 mm Hg2, 41.6 +/- 2.9 NU). In salt-sensitive subjects, low sodium intake significantly reduced low-frequency normalized units (P < .001) and the ratio of low- to high-power frequency (P < .001). High-sodium intake significantly increased baroreflex sensitivity in control subjects (from 10.0 +/- 0.7 to 17.5 +/- 0.7 ms/mm Hg, P < .001) and salt-resistant subjects (from 6.9 +/- 0.7 to 13.9 +/- 0.9, P < .05) but not in salt-sensitive subjects (7.4 +/- 0.3 to 7.9 +/- 0.4). In conclusion, a high sodium intake markedly enhances cardiac sympathetic activity in salt-sensitive and salt-resistant hypertension. In contrast, although reduced sodium intake lowers arterial pressure and sympathetic activity, it does so only in salt-sensitive subjects. Hence, in salt-resistant subjects, neither arterial pressure nor sympathetic activity depends on salt intake. During a high sodium intake in normotensive subjects and salt-resistant hypertensive subjects, increased sympathetic activity is probably compensated by enhanced baroreflex sensitivity.
Much evidence indicates an involvement of the sympathetic nervous system in the genesis of silent myocardial ischemia. The authors assessed autonomic system activity by power spectrum analysis of heart rate variability in 21 elderly hypertensive men with and without angiographically confirmed coronary artery disease and compared the results with those from an age-matched control group. In the analysis an autoregressive algorithm was used to determine the power spectrum from an electrocardiographic recording of 512 consecutive RR intervals. The autonomic nervous system induces two distinct sinusoids: a low-frequency signal attributable to sympathetic activity and a high-frequency vagal response. In the hypertensive patients with coronary disease the authors also evaluated sympathetic activation after double-blind, placebo-controlled administration of metoprolol (100 mg/day), followed by amlodipine (10 mg/day), quinapril (20 mg/day), and amlodipine (5 mg/day) plus quinapril (10 mg/day).
In a consecutive series of 62 hypertensive elderly subjects, the authors studied the relation of blood pressure circadian variations with echocardiographic parameters of left ventricular (LV) hypertrophy. All the subjects were submitted to an ambulatory blood pressure monitoring (ABPM) and to B- and M-mode echocardiography. In the elderly hypertensive group, LV mass index (LVMI) was more strongly related to twenty-four-hour, daytime and nighttime systolic ambulatory blood pressure (r = 0.52, r = 0.37, r = 0.51) than diastolic ambulatory blood pressures were (r = 0.32, r = 0.18, r = 0.33). Casual systolic and diastolic blood pressure (CBP) was found more weakly related to LVMI than ambulatory blood pressures were (r = 0.35, r = 0.26). Elderly hypertensive subjects were divided into two subgroups in relation to the presence (group 1) or absence (group 2) of blood pressure nocturnal decline. No differences were found between these two subgroups in regard to: casual blood pressure values, ambulatory blood pressures in the diurnal period, sex, body surface area, height, weight, and age. LVMIs were computed in all three groups and showed the following results: 89.32 +/- 19.76 in elderly normotensives, 91.21 +/- 31.32 in group 1, and 99.80 +/- 18.21 in group 2. Echocardiographic parameters of LV dimensions and LVMIs were different in group 1 and 2. An inverse correlation, statistically significant, was observed between LVMIs and the nocturnal blood pressure reduction (systolic: r = -0.36, P < 0.05; diastolic: r = -0.29, P < 0.05). These results suggest an association between a smaller LV mass and nocturnal blood pressure decline in elderly hypertensive patients.
OBJECTIVE: To investigate changes in sympathetic nervous system function in obesity. DESIGN: Cross-sectional clinical study. SUBJECTS: 18 middle-aged obese patients (43-55 years, BMI > 33 kg/m2) and 26 age- and sex-matched normal-weight controls (44-56 years, BMI < 26 kg/m2). MEASUREMENTS: Post-synaptic sympathetic response studied by power spectral analysis of heart rate variability at rest and during sympathetic stimulus obtained through passive head-up tilt. Spectral analysis comprised two frequency domain components: high-frequency power (HF), reflecting parasympathetic activity and low-frequency power (LF), in particular the LF: HF ratio, reflecting sympathetic function. Pre-synaptic sympatho-adrenal function was assessed by measurement of 8.00 am plasma noradrenaline. RESULTS: Obese patients had significantly lower spectral indexes of sympathetic response and higher spectral markers of parasympathetic activity than nonobese subjects both at rest (25.9 +/- 3.5 vs 38.6 +/- 1.7 LF NUs, P < 0.001) and after tilt (0.98 +/- 0.40 vs 2.30 +/- 0.39 LF: HF, P < 0.05; 62.7 +/- 6.9 vs 41.1 +/- 4.9 HF NUs, P < 0.05). By contrast, the obese subjects had higher noradrenaline levels (289.32 +/- 27.40 vs 159.80 +/- 19.20 pg/ml, P < 0.001). No relation was found between these neuroautonomic indexes and body mass index. CONCLUSION: Obese subjects seem to have increased pre-synaptic sympatho-adrenal function but a depressed end-organ cardiovascular response.
Both mean platelet volume (MPV) and left ventricular hypertrophy have been described as associated with increased risk for vascular events. Seventy-six hypertensive patients (37 M and 39 F) over 50 years of age were studied. They were divided into subgroups according to the presence of left ventricular hypertrophy (LVH = LV mass index > 125 g m-2, when LV mass was assessed by M-mode echocardiography according to Penn's Convention). MPV was 3% higher in hypertensive patients with LVH compared with those without LVH (P > 0.05) and it was associated with the occurrence of LVH (chi-square = 8.44, P = 0.042). MPV significantly correlated with left ventricular mass index (r = 0.298, P = 0.004) and interventricular septum thickness (r = 0.231, P = 0.022). Both correlations remained significant after adjustment for age, blood pressure and glycaemia. MPV seemed to be associated with increased left ventricular mass and interventricular septum thickness in middle-aged to elderly hypertensive patients.
OBJECTIVE: To evaluate whether the pulsatile component of blood pressure can be a risk factor independent of the steady component in elderly females. DESIGN: Fifty-two elderly hypertensive female patients were compared with 32 normotensive control subjects of the same age. According to the results of that first study, a cohort of 126 elderly females was studied over a 3-year period to evaluate whether the pulsatile and steady-state components of blood pressure correlated with the same parameters and could predict the occurrence of cardiovascular events. RESULTS: In the first study the hypertensive patients with elevated pulse pressure had significantly higher triglycerides level and lower urinary sodium excretion than the hypertensive patients with lower pulse pressure and than the control subjects of the same age. The incidence of cardiovascular events over a 3-year period was significantly higher in the elderly hypertensive females with increased pulse pressure. In the cohort of 126 females mean arterial pressure (MAP) and pulse pressure did not show the same degree of correlation with the biological parameters tested (plasma triglycerides: MAP r = 0.162, P < 0.05; pulse pressure r = 0.314, P < 0.0005; urinary sodium excretion: MAP r = -0.365, P < 0.0001; pulse pressure r = -0.257, P < 0.002). Furthermore, for the same MAP level, patients with cardiovascular accidents in a 3-year period had significantly higher pulse pressure values. Pulse pressure (and not MAP) was a strong predictor of cardiovascular accidents. CONCLUSIONS: In elderly hypertensive females the pulsatile and the steady-state components of blood pressure did not correlate with the same biological parameters. Furthermore, the pulsatile component, when explored by pulse pressure, seemed to be a strong independent cardiovascular risk factor.
The Na-K-Cl cotransport activity in red blood cells from essential hypertensive men with low (n = 8, mean age 42 +/- 4 years) or normal renin activity (n = 4, mean age 43 +/- 3 years), and in normotensive men with normal renin activity (n = 7, mean age 38 +/- 4 years) has been evaluated by means of a recently developed 23Na nuclear magnetic resonance (NMR) method. Sodium efflux was determined by relating the resonating frequency of the NMR signal from extracellular sodium to sodium concentration in the presence of the shift reagent Dy(PPP)2(7-). The maximum Na+ efflux driven by cotransport (Vmax) was measured in Na(+)-loaded erythrocytes in the presence of ouabain to block the Na-K-Cl pump activity. A significant difference (P < 0.05) was found in Vmax values of low renin patients (0.70 mmol/h/L cells, range 0.40 to 0.90 mmol/h/L cells) as compared with normotensive controls (0.39 +/- 0.08 mmol/h/L cells) and normal renin hypertensives (mean 0.49 +/- 0.04 mmol/h/L cells). In conclusion, this study showed an increased activity of the Na-K-Cl cotransport in red blood cells from low renin hypertensive men as compared with normal renin hypertensives and normotensives.
To evaluate the influence of atrial natriuretic factor (ANF) infusion on circulating prorenin, 20 essential hypertensive males, aged between 40 and 60 years, were studied. After 2 weeks under normal sodium intake (120 mmol NaCl per day), patients were randomly assigned to receive either ANF (0.01 fmol/Kg/min) (n.12 patients) or its vehicle (50 mL of isotonic saline) (n.8 patients) over a period of 60 minutes. Blood samples for plasma renin activity (PRA), prorenin and aldosterone (PAC) were taken at time -60, 0, 20, 40, 60, 120, 180, 240 minutes (infusion time: from 0 to 60 minutes). PRA and PAC decreased during the ANF infusion (PRA: from 0.33 +/- 0.05 ng/L/s at time 0 to 0.10 +/- 0.06 ng/L/s at 60 minutes, p < 0.0001; PAC: from 389.2 +/- 99.8 pmol/L at time 0 to 148.7 +/- 44.3 pmol/L at 60 minutes, p < 0.0001), while returned immediately to baseline levels after the infusion was stopped (PRA: 0.37 +/- 0.11 ng/L/s at 180 minutes, PAC: 251.6 +/- 72.1 pmol/L at time 180 minutes). On the contrary, plasma prorenin increased during ANF infusion (from 1.66 +/- 0.58 ng/L/s at time 0 to 2.44 +/- 0.72 ng/L/s at 60 minutes, p < 0.05), and returned to baseline levels after the end of the infusion (1.86 +/- 0.83 ng/L/s at 180 minutes). These data indicate that ANF infusion may alter only the circulating levels of active renin, without affecting plasma prorenin secretion.
Hypertension among the elderly generally represents a salt- sensitive state. However this salt-sensitivity does not appear to result from age-related increase in either sodium or salt intake. Since 20 years new trends seem to relate the role of sodium in the genesis of hypertension to a primary abnormality of electrolyte transport of cell membrane. Lipid abnormalities have also been described in untreated patients with high blood pressure. Plasma triglycerides were considerably higher (p < 0.01) in the hypertensives than in the controls. 24 hour sodium excretion was significantly lower (p < 0.0001) in hypertensives than in the controls. We have found a strong correlation among reduced sodium excretion, higher triglycerides and elevated blood pressure in the elderly. The blood pressure correlated negatively with 24 hour sodium excretion (p < 0.0001 for systolic and p < 0.002 for diastolic) and positively with plasma triglycerides (p < 0.0001 for systolic and p < 0.001 for diastolic). The poor literature regarding an association of these two alterations in human hypertensives makes our results provocative. We speculated that these alterations may be a facet of the insulin resistance commonly detectable in human hypertensives. However, further investigations are required to answer to this intriguing hypothesis.
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Erythrocytes from a patient with hypokalemic periodic paralysis (HPP) have been studied, in order to investigate the presence of alterations of membrane cation active transport systems. An original 23Na-NMR method has been used, capable of evaluating quantitatively the Na+ efflux due to the Na+/K+/Cl- cotransport. This method uses a loading system to increase internal cellular Na+ concentration: in the patient with HPP both the internal Na+ concentration after loading and the Na+/K+/Cl- cotransport activity were decreased in comparison to the controls. Our data seem to confirm that the fall of K+ serum levels during attacks in HPP must be ascribed to a shift of K+ from extra- to intracellular compartment (with consequent changes in the fibrocellular membrane polarity), due to an alteration of membrane cation transport system: which does not only consist in a hyperactivity of Na+/K+ ATPase (already described by other AA.), but also in a "secondary" decreased K+ efflux driven by the cotransport. The decrease of cotransport activity may be considered as "compensatory" (in fact, the intracellular Na+ content is normal), since this transport system can work as a kind of "emergency" system that can "help" the ATPase-dependent pump in extruding any excess of cell Na+ content, or can be depressed by any decrease of this value, caused by an hyperactivity of the Na+/K+ ATPase. The decreased cotransport activity results in a powerful contribution to the increase of intracellular potassium due to the hyperactivity of the Na+/K+ pump. This method could supply a useful diagnostic marker in all uncertain cases.
10 patients in perfect health, aged between 90 and 101 (mean age: 93 +/- 3), have been studied with echography in order to investigate the possible changes in volume and echo-pattern of abdominal organs, linked to the "physiological" aging. Our resulting data (reduced volume of liver and kidneys, changes in echo-pattern of pancreatic parenchyma, reduced thickness of renal cortical-medullary) seem to confirm the well known data of an atrophic change interesting the parenchyma of abdominal organs in aging: this latter, however, remains compatible with function preservation.
Hypertension is the leading cause of death in the elderly in Western countries. The Authors remark that hypertension is not only a purely hemodynamic phenomenon, but is a multifaceted disease frequently associated with metabolic disorders in the elderly. Among the latter, hyperinsulinism could be the linking pathogenetic factor with atherosclerosis progression. Then the Authors suggest a unitary pathogenetic hypothesis of hypertension and atherosclerosis. The crucial points are the inborn alteration of cellular sodium transport systems and the modulating action of environmental factors, first of all insulin. According to this hypothesis, the goal of the management of elderly hypertensives is the prevention of the fatal or invalidant cerebro- and cardiovascular event. To follow a good "pathogenetic" treatment of elderly hypertension and atherosclerotic process evolution, the first step is a dietetic approach avoiding acute load of sodium and lipids. Furthermore, the pharmacological treatment with calcium antagonists and ACE inhibitors is respectful of associated metabolic disorder and positively modulate the cellular sodium transport systems activity.
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