Circadian variation in onset of epistaxis: analysis of hospital admissions.
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Circadian Rhythm↗
Biomedical subjects
F Portaluppi
Publications and source records attributed to F Portaluppi.
Dose and time effects of caffeine intake on human platelet adenosine A(2A) receptors : functional and biochemical aspects.
BACKGROUND-We determined whether repeated caffeine administration at different dosages and for different periods of time (400 or 600 mg/d for 1 week or 400 mg/d for 2 weeks) upregulates human platelet adenosine A(2A) receptors and is accompanied by increases in cAMP accumulation and decreases in aggregation and calcium levels after stimulation of A(2A) receptors by the selective agonist 2-hexynyl-5'-N-ethylcarboxamidoadenosine (HE-NECA). METHODS AND RESULTS-Platelets were obtained from peripheral venous blood of 45 healthy human volunteers at the end of 2 weeks of caffeine abstinence and at 12, 60, and 108 hours after the last dose of caffeine. The lowest dose of caffeine, when given for only 7 days, had no effect. Increasing the total dose, either by giving 400 mg/d for 14 days or giving 600 mg/d, resulted in binding assays performed with the adenosine A(2A) receptor radioligand [(3)H]SCH 58261 [5-amino-7(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1, 5-c]pyrimidine], in the upregulation of A(2A) receptors. Moreover, the potency of HE-NECA to produce antiaggregatory effects, a rise in cAMP accumulation, and a decrease in calcium levels was significantly increased. CONCLUSIONS-Chronic caffeine intake can lead to upregulation of adenosine A(2A) receptors, which is accompanied by sensitization, in a time- and dose-dependent manner, to the actions of the agonist HE-NECA.
Adenosine-5'-(N-ethylcarboxamide)↗
Seasonal variation in the occurrence of epistaxis.
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Adult↗
Circadian variation in onset of acute cardiogenic pulmonary edema is independent of patients' features and underlying pathophysiological causes.
BACKGROUND: The present study aimed to confirm the existence of a circadian pattern in the onset of acute pulmonary edema (APE) and to verify whether sex, age, preexisting diseases, and clinical causes determining the event may influence it. SUBJECTS AND METHODS: The study considered all consecutive cases of APE observed at the St. Anna General Hospital of Ferrara, Italy, during a 7-year period from January 1, 1992, to December 31, 1998. The sample population was divided into subgroups by sex, age (<75 and > or =75 years), presence or absence of diabetes and hypertension, clinical causes determining the event (i.e., acute myocardial infarction (AMI), pulmonary embolism, arrhythmias). The most important associated or concomitant diseases were also considered (i.e., coronary heart disease and angina, previous myocardial infarction, chronic cardiac failure, dilatative cardiopathy, chronic atrial fibrillation, valvular disease, chronic obstructive pulmonary disease, chronic cor pulmonale, malignancy, chronic renal failure). Time of symptom onset of each event was recorded accurately, then tabulated into 24 increments of 1h (e.g., 06:00 to 06:59 was reported as 6 A.M.). For statistical chronobiological analysis, partial Fourier series were used. RESULTS: During the 7-year period, 1321 consecutive cases of APE in 1014 different subjects were observed. The majority of events occurred at night, and statistical analysis showed a 24h rhythmicity both in the total sample population and in all considered subgroups, with the only exception being patients with pulmonary embolism and arrhythmias, for which the small number of cases made the study of rhythms in APE impossible. CONCLUSIONS: The nighttime preference in the occurrence of APE appears to be quite independent of all demographic features or underlying pathophysiological causes.
Acute Disease↗
Platelet alpha2-adrenoceptor alterations in patients with essential hypertension are normalized after treatment with doxazosin but not propranolol.
OBJECTIVE: Marked alterations have been demonstrated to occur in the platelet alpha2-adrenoceptors of patients with essential hypertension. The purpose of this study was to determine whether antihypertensive treatment with alpha-adrenergic blocker doxazosin or beta-adrenergic blocker propranolol can affect the affinity and the density of platelet alpha2-adrenoceptors in such patients. SUBJECTS AND METHODS: In two groups of 22 previously untreated, essential hypertensive patients, the mean affinity (Kd) and density (B(max)) of platelet alpha2-adrenoceptors were studied by [3H]-UK 14304 binding assays; the first assays were performed before any medication was begun, the second were performed after treatment for up to 13 weeks with doxazosin or propranolol. A third group of 22 healthy normotensive volunteers matched by age, sex and body mass index was used as control. RESULTS: Blood pressure did not differ significantly in the two hypertensive groups, and treatment with the two drugs resulted in closely similar, normal blood pressure levels. Kd and B(max) values were significantly higher in the two hypertensive groups than in controls. After treatment with propranolol the binding parameters did not change significantly, whereas after treatment with doxazosin Kd and B(max) returned to normotensive values. CONCLUSIONS: In previously untreated, essential hypertensive patients platelet alpha2-adrenoceptors have a lower affinity but a higher density than in normotensive subjects. Despite similar effects on blood pressure, the treatment with the alpha-adrenergic blocker doxazosin is followed by restoration of normal findings in the binding assays of platelet alpha2-adrenoceptors whereas the treatment with the beta-adrenergic blocker propranolol does not alter the Kd and B(max) values.
Adrenergic alpha-Agonists↗
[Respiratory disorders during sleep as cause of arterial hypertension].
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Humans↗
Caffeine alters A2A adenosine receptors and their function in human platelets.
BACKGROUND: Caffeine acts mainly via blockade of adenosine receptors, which have been classified into A1, A2A, A2B, and A3 subtypes. We determined whether repeated caffeine administration (750 mg/d for 1 week) upregulates the human platelet A2A adenosine receptor and is accompanied by sensitization of platelet responses (increase in cAMP accumulation and decrease in platelet aggregation) to selective stimulation of the A2A receptors. METHODS AND RESULTS: Platelets were obtained from peripheral venous blood of 9 human volunteers at the end of 1 week of caffeine abstinence (control) and at 12 and 60 hours after the last dose of caffeine (withdrawal). The A2A receptor radioligand [3H]SCH 58261 (5-amino-7(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1, 5-c]-pyrimidine) bound to a single affinity class of sites in platelet membranes from controls with a Bmax of 98+/-2 fmol/mg protein and a KD of 1.29+/-0.05 nmol/L. At 12 and 60 hours after caffeine withdrawal, the radioligand bound with similar affinity (KD=1.36+/-0.06 and 1.21+/-0.05 nmol/L, respectively), but the Bmax was increased (P<0.01) to 128+/-3 and 132+/-2 fmol/mg protein. The A2A receptor agonist 2-hexynyl-5'-N-ethylcarboxamidoadenosine (HE-NECA) increased cAMP accumulation (EC50=59+/-3 nmol/L) and inhibited (IC50=90+/-6 nmol/L) aggregation of control platelets. The EC50 values for HE-NECA to increase cAMP accumulation of platelets were reduced (P<0.01) at 12 and 60 hours after caffeine withdrawal (31+/-3 and 21+/-2 nmol/L, respectively). The IC50 values for HE-NECA to inhibit ADP-induced platelet aggregation were 50+/-5 and 30+/-2 nmol/L at 12 and 60 hours after caffeine withdrawal, respectively. CONCLUSIONS: Chronic caffeine intake leads to upregulation of A2A receptors and is accompanied by sensitization to the actions of the agonist HE-NECA.
Adenosine-5'-(N-ethylcarboxamide)↗
Circadian variation in spontaneous rupture of abdominal aorta.
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Aged↗
Chronopharmacology and chronotherapy of cardiovascular medications: relevance to prevention and treatment of coronary heart disease.
Biological functions and processes, including cardiovascular ones, exhibit significant circadian (24-hour) and other period rhythms. Ambulatory blood pressure assessment reveals marked circadian rhythms in blood pressure both in normotensive persons and hypertensive patients, whereas Holter monitoring substantiates day-night patterns in electrocardiographic events of patients with ischemic heart disease. The concept of homeostasis, that is, constancy of the milieu interne, which has dominated the teaching, research, and practice of medicine during the 20th century,is now being challenged by emerging concepts from the field of chronobiology-the science of biological rhythms. Epidemiologic studies document the heightened morning-time risk of angina, myocardial infarction, and stroke. Circadian rhythms in coronary tone and reactivity, plasma volume, blood pressure, heart rate, myocardial oxygen demand, blood coagulation, and neuroendocrine function plus day-night patterns in the nature and strength of environmental triggers all contribute to this morning vulnerability. Homeostatically devised pharmacotherapies, that is, medications formulated to ensure a near-constant drug concentration, may not be optimal to adequately control diseases that vary in risk and severity during the 24 hours. Moreover, circadian rhythms in the physiology of the gastrointestinal tract, vital organs, and body tissues may give rise to administration-time differences in the pharmacokinetics and effects of therapies. Thus the same medication consumed in the same dose under identical conditions in the evening and morning may not exhibit comparable pharmacokinetics and dynamics. New technology makes possible chronotherapy, that is, increase of the efficiency and safety of medications by proportioning their concentrations during the 24 hours in synchrony with biological rhythm determinants of disease. The chronotherapy of peptic ulcer disease achieved by the evening dosing of H 2-receptor antagonists and of asthma by the evening dosing of special drug delivery forms of theophylline and morning methylprednisolone administration has proven to be beneficial. Controlled-onset extended-release verapamil constitutes the first chronotherapy of essential hypertension and ischemic heart disease; once-a-day bedtime dosing results in a high drug concentration in the morning and afternoon and a reduced one overnight. Studies demonstrate effective 24-hour control of blood pressure, including the attenuation of its rapid rise in the morning, without induction of nighttime hypotension. Moreover, this formulation effectively controls angina, especially in the morning when the risk of ischemia is greatest. Determination of the role of verapamil chronotherapy in the primary prevention of cardiovascular morbidity and mortality awaits the results of the CONVINCE trial now in progress.
Adrenergic beta-Antagonists↗
Seasonal variation in the occurrence of nontraumatic rupture of thoracic aorta.
Research has identified circadian and seasonal patterns for several acute cardiovascular diseases. In order to investigate the possible existence of a seasonal variation in the onset of acute nontraumatic ruptures of thoracic aorta, this study considered all patients referred to the emergency department of St Anna Hospital of Ferrara, Italy, from January 1985 to December 1996. In the considered period, 85 patients (52 males, 33 females) of nontraumatic ruptures of thoracic aorta were observed. Cosinor analysis and partial Fourier series with up to 4 harmonics were applied to monthly data, and the best-fitting curves for circannual rhythmicity were calculated. A higher winter occurrence with a significant peak in January was found for the total population and the male subgroup. Although the underlying factors are not fully known, such patterns strictly resemble that of arterial blood pressure. Emergency doctors can put to practical use the recognition of a clearly identified chronorisk for aortic rupture, increasing alertness, and providing the most effective antihypertensive protection at the specific vulnerable periods.
Age Distribution↗
Platelet alpha2-adrenoceptor alterations in patients with essential hypertension.
AIMS: The purpose of this study was to determine whether human platelet alpha2-adrenoceptors were altered in essential hypertension. A systematic analysis was carried out on 165 normotensives and 124 untreated primary hypertensives. METHODS: The study was performed at different levels: i) density and affinity of platelet alpha2-adrenoceptors were determined by receptor binding assays using the full alpha2-adrenoceptor agonist [3H]-UK 14304 and a thermodynamic analysis of data was carried out to evaluate if binding mechanisms at the molecular level were altered during hypertension; ii) the functionality of Gi proteins coupled to alpha2-adrenoceptors and iii) forskolin-stimulated cAMP levels were measured. RESULTS: Platelet alpha2-adrenoceptors mean density (Bmax) and affinity (Kd) (+/-s.e.mean) were significantly lower and higher, respectively, in normotensive than in hypertensive subjects [Bmax=327+/-4 vs 435+/-5 fmol mg(-1) of protein (P<0.01) and Kd=3.76+/-10.05 vs 6.50+/-0.15 nM (P<0.01), respectively]. The 50% stimulating concentration of adrenaline on [35S]-GTPgammaS binding to Gi proteins was significantly (P<0.01) lower in normotensives (12+/-2 nM) than in hypertensives (110+/-10 nM). The 50% inhibiting concentration of adrenaline on forskolin-stimulated cAMP levels was significantly (P<0.01) lower in normotensive (22+/-2 nM) than in hypertensive subjects (200+/-25 nM). CONCLUSIONS: Present analysis, including receptorial and functional data, provides evidence that marked alterations occur in platelet alpha2-adrenoceptors of hypertensive subjects.
Adrenergic alpha-Antagonists↗
From a static to a dynamic concept of risk: the circadian epidemiology of cardiovascular events.
A growing body of evidence substantiates that the occurrence of cardiovascular events in unevenly distributed in time, especially during the 24 h. These temporal patterns are indicative of temporal variation in the (1) pathophysiological mechanisms that trigger cardiovascular events and (2) physiological status of the cardiovascular system, which combine to give rise to 24 h and other periodicities in the susceptibility to disease. The classic assumption of epidemiologic studies is constancy (or homeostasis) in one's risk to disease during the 24 h, as well as other, time domains. However, we propose a new concept, that of chronorisk since it takes into account the temporal variability in the pathophysiological mechanisms and their reciprocal temporal interactions that lead to day-night and other time-dependent patterns in cardiovascular events. This chronobiological approach, which is expected to contribute new insight into the prognostic and therapeutic assessment of cardiovascular events, is worthy of broader application in cardiovascular and other fields of medicine and warrants further investigation.
Cardiovascular Diseases↗
Circadian variation in the onset of acute critical limb ischemia.
Research has identified a circadian rhythm for several acute thrombotic cardiovascular and cerebrovascular diseases. We investigated the possible existence of a circadian variation in the onset of acute critical limb ischemia. Out of a consecutive series of 198 cases, precise determination (within 30 minutes) of the time of symptom onset was possible in 156 (78.8%). Partial Fourier series were applied to hourly data and the best-fitting curves for circadian rhythmicity were calculated. Both in the total population and in subgroups by gender and location of ischemia, a highly significant circadian pattern of occurrence was demonstrated with peak in the morning (approximately 0800) and nocturnal minimum around midnight. This study is the first demonstration of the circadian pattern of acute arterial occlusion of the limbs, in agreement with several studies showing a circadian pattern to the time of onset of acute myocardial infarction and other unfavorable acute events related to thrombosis. This opens up the potential for therapeutic implications, suggesting the need to adjust the dose of drugs based on the time of day. Further studies dealing with circadian variation in the efficacy of thrombolytic agents are so needed.
Acute Disease↗
In vitro versus in vivo assessment of vein wall properties.
Venous compliance reflects the mechanical properties of the vein wall. Clinical methods of measurement have not been validated by comparison with the accepted in vitro measurement. Despite this, clinical assessment of vein compliance may have a series of useful applications: (1) to assess the progression of chronic venous insufficiency and the related hemodynamic forces acting on the saphenous vein wall; (2) to determine the suitability of the saphenous vein for replacement of an arterial conduit by testing its mechanical properties; and (3) to select the saphenous vein with preferable mechanical performance for coronary artery bypass. The aim of this study is to assess the relationship between in vitro and two in vivo methods of compliance measurement. Compliance of the saphenous vein was determined in 20 patients, using both an invasive and a noninvasive (A and B, respectively) method. Duplex scanning was used for diameter measurement. Venous pressure was derived either intravenously with a needle transducer, or noninvasively with limb length measurement. Patients underwent saphenous excision with further in vitro compliance measurement of the same vein segment (method C). The compliance values obtained with the three methods showed different degrees of correlation (r= 0.516, p = 0.0001 for method A versus method C; r = 0.658, p = 0.0001 for method B versus method C; r = 0.993, p = 0.0001 for method A versus method B). The relationships with the in vitro measurements that were determined validate both in vivo methods for assessment of saphenous vein compliance. Due to its completely noninvasive design, method B appears to have potential use for clinical assessment of saphenous vein wall properties.
Biomechanical Phenomena↗
Clinical features of fatal familial insomnia: phenotypic variability in relation to a polymorphism at codon 129 of the prion protein gene.
Fatal Familial Insomnia is a hereditary prion disease characterized by a mutation at codon 178 of the prion protein gene cosegregating with the methionine polymorphism at codon 129 of the mutated allele. It is characterized by disturbances of the wake-sleep cycle, dysautonomia and somatomotor manifestations (myoclonus, ataxia, dysarthria, spasticity). PET studies disclose severe thalamic and additionally cortical hypometabolism. Neuropathology shows marked neuronal loss and gliosis in the thalamus, especially the medio-dorsal and anterior-ventral nuclei, olivary hypertrophy and some spongiosis of the cerebral cortex. Detailed analysis of 14 cases from 5 unrelated families showed that patients ran either a short (9.1 +/- 1.1 months) or a prolonged (30.8 +/- 21.3 months) clinical course according to whether they were homozygote met/met or heterozygote met/val at codon 129. Moreover, homozygotes had more prominent oneiric episodes, insomnia and dysautonomia at onset, whereas heterozygotes showed ataxia and dysarthria at onset, earlier sphincter loss and epileptic Grand Mal seizures; they also displayed more extensive cortical involvement on PET and at postmortem examination. Our data suggest that the phenotype expression of Fatal Familial Insomnia is related, at least partly, to the polymorphism at codon 129 of the prion protein-gene.
Adult↗
Chronobiological patterns of onset of acute cerebrovascular diseases.
There is a considerable amount of data indicating that several major unfavorable cerebrovascular events are not randomly distributed over time, but show a peculiar distribution along the day, the week, and the months of the year. The authors review the available evidence on the chronobiological (circadian, weekly, and seasonal) patterns of onset of acute cerebrovascular diseases and variations in their possible triggering mechanisms. The existence of a peculiar chronobiological pattern in the onset of acute cerebrovascular disease, characterized by both circadian (morning and evening occurrence), circaseptan (last and first days of the week), and circannual (especially in winter) is confirmed, although differences depending on biological (gender, age), pathological (diabetes, hypertension, smoke, alcohol), cultural, social, and environmental factors exist. A deeper knowledge of the underlying pathophysiologic mechanisms could provide more effective insights for both preventive strategies and optimization of therapeutic approach.
Age of Onset↗
Circadian rhythmicity in the occurrence of spontaneous acute dissection and rupture of thoracic aorta.
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Aged↗
Ultrasonographic assessment of ambulatory venous pressure in superficial venous incompetence.
PURPOSE: In spite of its invasiveness, measurement of ambulatory venous pressure (AVP) is widely considered the gold standard measurement of venous function. We studied a technique for noninvasive ultrasonographic AVP determination in superficial venous incompetence. METHODS: A linear relationship between venous pressure (measured by echo-guided venous puncture) and diameter (measured by transverse axis duplex imaging) was preliminarily demonstrated with multiple measurements in different conditions (supine, sitting, standing, and Trendelenburg positions, after exercise with and without cuff occlusion) in a saphenous tract at the thigh of 82 limbs in which reflux had been previously demonstrated. Then AVP was measured in another group of 44 patients who had demonstrated superficial venous incompetence, both with and without proximal occlusion, using again the same invasive method and a new noninvasive technique. The latter technique consisted in the construction of a linear diameter/pressure curve obtained after saphenous diameter (by high-resolution sonography) and noninvasive pressure (using hydrostatic values) determinations in the sitting and standing positions. Further measurement of saphenous diameter after standardized exercise permits extrapolation of the AVP values from the curve. RESULTS: Linear regression analysis demonstrates that (1) beginning from 20 mm Hg, the pressure/diameter relationship of the incompetent greater saphenous vein is linear; and (2) AVP values derived invasively and noninvasively are significantly correlated (r = 0.7347 and p < 0.0001 for AVP derived without occlusion; r = 0.7270 and p < 0.0001 for values recorded with occlusion). CONCLUSIONS: The proposed technique appears able to reliably assess noninvasively AVP values in superficial venous incompetence. In addition, it can be performed with equipment that is widely used for vascular investigations.
Exercise↗