24-hour leg and forearm haemodynamics in transected spinal cord subjects.

OBJECTIVE: A circadian rhythm of blood pressure has been demonstrated both in subjects who are physically active during the day and in those confined to bed. The study of the circadian rhythm of arterial flow and peripheral resistance, on the other hand, is limited to pioneer experiments. This paper is aimed at demonstrating that leg peripheral resistance has circadian fluctuations which are modulated by spinal neural traffic. METHODS: Eleven normal (able-bodied) human subjects and 11 patients with spinal transection due to spinal cord injury (SCI) were studied. They were confined to bed for 24 h. Blood pressure and heart rate were monitored every 15 min with an automatic device and leg flow with an automatic strain-gauge plethysmograph synchronised to the pressurometer. Peripheral resistance was calculated at the same intervals. RESULTS: In able-bodied subjects leg resistance was significantly higher during waking hours (when the sympathetic system is more activated) than during sleep, while in subjects with spinal cord injury no difference was detected between day-time and night-time. CONCLUSIONS: The circadian rhythm is controlled by adrenergic fibres transmitted via the spinal cord.

Lack of influence of menopause on blood pressure and cardiovascular risk profile: a 16-year longitudinal study concerning a cohort of 568 women.

OBJECTIVE: To analyse the effect of menopause on blood pressure and cardiovascular risk. DESIGN: From an Italian general population, 568 women (408 pre- and 160 post-menopausal) were screened twice, in 1978 and 16 years later. METHODS: Cross-sectional analyses both in 1978 and in 1994, and longitudinal analysis in the 1978-1994 period. RESULTS: For the general analysis the cohort was reduced to 525 women with paired data in 1978 and 1994. In both cross-sectional studies, unadjusted blood pressure and cardiovascular risk were higher after than they were before menopause, but any difference disappeared after adjustment or matching for age. In 1994 we studied three groups of women: those who were still premenopausal, those who were fertile in 1978 but postmenopausal in 1994 and those who were already postmenopausal in 1978. The 16-year blood pressure increment was similar in all three groups. The incidence of myocardial infarction and angina pectoris was greater in those who were already postmenopausal than it was in those who had their menopause during the study period. An analysis of mortality was performed for all of the 568 women. Forty-three of them died, 14 from cardiovascular causes (six before and eight after menopause), 18 from neoplasia (two before and 16 after menopause) and 11 from other diseases. Menopausal status was rejected from the Cox equations both of overall and of cardiovascular mortality, showing a significantly predictive value only for neoplastic mortality. CONCLUSION: Menopause has no influence on high blood pressure and cardiovascular risk. The greater blood pressure levels, mortality and morbidity observed in postmenopausal women are simply attributable to their older age and are no longer detectable in an age-matched sample.

24 h rhythm of blood pressure and forearm peripheral resistance in normotensive and hypertensive subjects confined to bed.

OBJECTIVES: To define whether a diurnal rhythm of peripheral resistance exists in normotensive and hypertensive subjects, has any relationship with that of blood pressure and differs in dipper and non-dipper hypertensives. DESIGN AND METHODS: Forty-three subjects (13 normotensives and 30 mild-to-moderate essential hypertensives) confined for 24 h to bed were included. Blood pressure was recorded for 22 h at 15 min intervals, plethysmographic forearm flow was simultaneously measured and forearm resistance calculated. The analysis was performed for the whole 22 h period and for three 4 h truncated periods, two of certain wakefulness and one of certain sleep. RESULTS: A circadian rhythm of forearm resistance was shown in the normotensives, paralleling that of blood pressure. All the normotensives were dippers, with a nocturnal blood pressure dip (systolic/diastolic) of -4.5/-6.0%. In the hypertensives, the day/night blood pressure trends were not homogeneous: 21 showed higher blood pressure values during waking time, with a trend quite similar to that of the normotensives, whereas the other nine were non-dippers. Resistance was lower during sleep than during waking both in the normotensives and in the dipper hypertensives, whereas in the non-dippers it was higher during sleep. CONCLUSIONS: A sleep/waking rhythm of peripheral resistance with the highest values during daytime and the lowest during night-time does exist in normotensive as well as in the majority of hypertensive subjects resting continuously in bed, and therefore is largely independent of physical activity. Only in a minority of hypertensive patients are higher values of peripheral resistance present during sleep.

Effects of caffeine on glucose tolerance: a placebo-controlled study.

OBJECTIVE: The investigation was performed to study the effects of 200 mg oral caffeine on glucose tolerance. DESIGN: Single-blind Latin square with active treatment (caffeine) and placebo. SETTING: The University of Padova, Department of Internal Medicine. SUBJECTS: 30 nonsmoking healthy subjects aged 26-32 years who abstained not only from coffee but also from tea, chocolate and cola for 4 weeks and who had given their informed consent. INTERVENTIONS: A 75 g oral glucose tolerance test (OGTT) was performed after giving caffeine or placebo (highly decaffeinated coffee). RESULTS: The glycaemic curve was normal in all subjects and was similar in the two groups until the second hour; in subjects taking caffeine a shift towards the right was detected at the 2nd, 3rd and 4th hours in comparison to those taking the placebo. Blood insulin levels were comparable after caffeine and after placebo along the entire OGTT. CONCLUSIONS: The data suggest that caffeine intake induces a rise in blood glucose levels that is insulin independent.

Hemodynamics following real and hypnosis-simulated phlebotomy.

Forearm arterial flow was measured in 22 healthy first-time blood donors during a 300-ml. blood letting and during the subsequent recovery. Blood pressure (BP) was also taken simultaneously and forearm peripheral resistance calculated. Following a transient BP and flow increase due to tachycardia related to needle insertion, both systolic BP and flow progressively and significantly decreased, while resistance increased. In a further 22 sex- and aged-matched highly hypnotizable subjects, blood donation was simulated by means of verbal hypnotic suggestions. The BP, flow and resistance curves were similar to those obtained with the real blood letting, without any between-subject difference or group/time interaction. Mere hypnosis without suggestion of phlebotomy and the simple bed resting did not produce any effect. These results indicate that the hemodynamic changes observed during and after a blood loss are partly due to mental involvement rather than merely to the hydraulic effects of the removal of blood.

Vascular endothelial growth factor-A and Poly(A) binding protein-interacting protein 2 expression in human head and neck carcinomas: correlation and prognostic significance.

Vascular endothelial growth factor-A (VEGF-A) has been demonstrated to play an important role in tumour angiogenesis and to influence prognosis in many cancers. However its prognostic value in head and neck squamous cell carcinomas (HNSCCs) remains controversial. Therefore, we investigated the clinical relevance of VEGF-A expression in HNSCCs and analysed whether its expression was associated with PAIP2 protein levels, a VEGF-A mRNA-binding partner that strongly regulates VEGF-A expression in tissue culture. We determined the correlation of VEGF-A and PAIP2 protein levels, quantitatively evaluated in tumour tissue homogenates from 54 patients with HNSCC, to clinicopathological parameters. We showed that VEGF-A expression in HNSCC is correlated to the stage of tumour differentiation (P=0.050) and is an independent prognostic factor for progression-free survival (P=0.001) and overall survival (P=0.0004). In a pharynx carcinoma cell line, we demonstrated by RNA interference that VEGF-A expression is closely controlled by PAIP2. Moreover, in human HNSCCs, VEGF-A expression is significantly correlated to PAIP2 protein levels (P=0.0018). Nevertheless, PAIP2 expression is associated with neither clinicopathological factors nor patient's survival. Our data suggest that, in contrast to PAIP2 protein levels, which are unrelated to tumour prognosis, VEGF-A expression could serve as a prognostic marker in head and neck cancer and may be helpful for targeted therapies.

Lower blood pressure values in blood donors?

594 blood donors were studied to define the influence of regular blood donation on blood pressure. Blood pressures were compared at the first phlebotomy performed at the Padova Blood Unit, the 13-year phlebotomy, and the median between the two. As a control population, a cohort of 594 non-donors from the same general population similar to the blood donors was studied twice at a 15-year interval. Subjects had made on average 7.3 +/- 0.4 donations at the first step, 23 +/- 0.6 at the second, and 30.9 +/- 0.7 at the last step. Unadjusted systolic blood pressure regularly and significantly increased by 1.6% from the first phlebotomy to the second one and by 2.3% from the first to third. Adjusted systolic blood pressure, on the contrary, significantly decreased by 2.1% and by 2.7% respectively. Diastolic blood pressure tended to increase insignificantly, while the adjusted one did not change at all. The increase of systolic blood pressure from the first to second step directly correlated with the number of donations, and this also applied to differences between the first and the third. When the increase in age was introduced in the multiple regression analysis, systolic blood pressure rise from the first to third step showed an inverse correlation with the number of phlebotomies. Our data render suspect the results of epidemiological investigations which took into consideration cohorts of blood donors; although these cohorts may be anagraphically representative of a general population, repeated phlebotomies introduce a bias leading to the detection of misleadingly low blood pressure values in regular blood donors.

Characterisation of hypertensive patients according to 24 H peripheral resistance.

To clarify whether a circadian rhythm of peripheral resistance exists in humans and whether hypertensive patients represent a homogeneous category in this respect, 15 normotensives aged 31 +/- 4 years and 30 hypertensives aged 41 +/- 13 years were confined to bed for 22 h and forearm flow recorded automatically. Night-time BP values were higher in hypertensive patients (Group B) whose night/day ratios of mean BP were below the 95% C.I. of the normal regression of the normotensives, than in those falling within the 95% C.I. (Group A). Forearm resistance was lower during sleep than during waking in Group A and in the normotensive controls, paralleling the nocturnal blood pressure fall. On the contrary, in the Group B hypertensives, despite a comparable night-time BP decrease, forearm resistance was higher during sleep than during waking.

Should digoxin be proscribed in elderly subjects in sinus rhythm free from heart failure? A population-based study.

Increased mortality in digoxin-treated subjects has been demonstrated in patients with recent myocardial infarction. Those with congestive heart failure (CHF) due to causes other than myocardial infarction seem to be free from this effect. No information is currently available concerning mortality in elderly people who are frequently prescribed digitalis even in the absence of CHF. The aim of this study was to investigate whether subjects improperly receiving digoxin were worse off than those not receiving this drug. This analysis is a part of CASTEL, a population-based prospective study that has enrolled a cohort of 2,254 subjects aged > or = 65 years. CHF was diagnosed in 187 subjects and atrial fibrillation (AF) in 90. The remaining 1,977 were free from CHF and in sinus rhythm, but 447 were treated with digitalis. Cumulative mortality and morbid events by digitalis treatment were calculated in all these categories. Among subjects free from CHF and AF (improper use), all-cause and cardiovascular mortality was significantly higher among those taking digitalis than in those who did not. Non-fatal events including CHF were also more apparent in the former than in the latter. Cox analysis confirmed digitalis as a predictor of mortality in these subjects. No effect of digitalis on survival was found in patients with CHF or AF (proper use). In elderly subjects without atrial fibrillation or CHF, the use of digitalis worsens morbidity and mortality.

Effect of two different therapeutic approaches on total and cardiovascular mortality in a Cardiovascular Study in the Elderly (CASTEL).

Although limited numbers of elderly subjects have occasionally been included in population-based studies, only a few studies have been conducted specifically on elderly hypertensives, and practically none at a population level. We studied 655 hypertensive subjects from a cohort of 2,254 elderly subjects. The intervention consisted of the creation of a Hypertension Outpatients' Clinic under our auspices but with complete co-operation from general practitioners, randomizing the identified hypertensive patients into pre-established therapeutic drug regimens, and early follow-up recording of mortality for 7 years. The drugs used were clonidine (n = 61), nifedipine (n = 146) and the fixed combination of atenolol+chlorthalidone (n = 144); 304 subjects underwent "free therapy" by their personal physicians without any special intervention. There were 1,404 normotensive subjects. Overall 7-year follow-up mortality was 34.9% in the hypertensive subjects receiving "free therapy", 22.5% in those receiving "special care", and 24.2% in the normotensives. Cardiovascular mortality was respectively 23.7%, 12.2%, and 12.0%. Overall and cardiovascular annual cumulative mortality were significantly lower in the << special therapy >> than in the << free therapy >> group. The fixed combination of atenolol and chlorthalidone reduced mortality below that of the normotensives, independent of other cardiovascular risk factors.