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Biomedical subjects

M Mancini

Publications and source records attributed to M Mancini.

At least 343 records · Page 19Linked to original sources

Calcium antagonists and thiazide diuretics in the treatment of hypertension.

The usefulness of the combination of nifedipine and chlorthalidone has been investigated in mild to moderate hypertensive patients (seven men, seven women; age range 39-62 years) by adding the diuretic to nifedipine monotherapy. After a 2 week washout, slow-release nifedipine 20 mg b.i.d. was given for 6 weeks, followed by addition of either chlorthalidone 25 mg (group A) or placebo (group B) q.d. for a further 6-week period. Blood pressure, heart rate, plasma renin activity, and 24-h urinary Na and K excretion were measured at baseline and at the end of each treatment period. Nifedipine decreased blood pressure in the two groups. A further significant fall was observed after chlorthalidone was added. No further change was detected after placebo in group B. Plasma renin activity after 1 h standardized walk significantly increased after combined treatment compared with baseline (3.3 +/- 1.2 to 9.4 +/- 5.3 ng/ml/h; p less than .05). No change was observed in 24 h urinary Na and K in the two groups. Venous distensibility measured by strain gauge plethysmography was slightly reduced during nifedipine monotherapy. Our data therefore suggest that chlorthalidone potentiates the antihypertensive effect of nifedipine despite an increase of renin activity.

Adult↗

Blood pressure during a combination of ketanserin and hydrochlorothiazide.

The antihypertensive effectiveness of a combination of ketanserin 20 mg plus hydrochlorothiazide 25 mg has been evaluated in 20 patients with arterial hypertension of mild to moderate degree in the age group over 50 years (age range 50-78 years). After a wash-out period of at least two weeks, patients were given a single oral dose of ketanserin 20 mg or thiazide 25 mg in a randomized order at two-day intervals and blood pressure, heart rate and cardiac workload (systolic blood pressure x heart rate) were measured during the following 24 h by an automatic recorder. Thereafter patients were given the combination of the two drugs for six weeks and 24 h blood pressure was assessed after the first dose and at the end of the treatment. A significant fall in systolic and diastolic blood pressure was rapidly induced by ketanserin from 2 to 8 h after dosing; thiazide on the other hand did not induce any change in these parameters (169 +/- 15/95 +/- 6 mmHg (22.5 +/- 2.0/12.7 +/- 0.8 kPa) at baseline versus 153 +/- 17/89 +/- 7 mmHg (20.4 +/- 2.3/11.9 +/- 0.9 kPa) at 2 h and 157 +/- 19/87 +/- 8 mmHg (20.9 +/- 2.5/11.6 +/- 1.1 kPa) at 8 h on ketanserin; 166 +/- 15/93 +/- 6 mmHg (22.1 +/- 2.0/12.4 +/- 0.8 kPa) at baseline versus 160 +/- 12/89 +/- 6 mmHg (21.3 +/- 1.6/11.9 +/- 0.8 kPa) at 2 h and 157 +/- 15/89 +/- 5 mmHg (20.9 +/- 2.0/11.9 +/- 0.7 kPa) at 8 h on thiazide).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Calcium metabolism and blood pressure in children.

Raised urinary calcium excretion has been reported in patients with essential hypertension, but it is not known whether this finding is an early expression of altered calcium metabolism or a consequence of longstanding high blood pressure (BP). BP and 24 h urinary excretion of calcium, sodium and creatinine were measured in a representative sample of healthy normotensive sixth grade school boys (n = 146: mean age 11.2 +/- 0.1 yrs, SEM). A significantly higher calcium output was found in children in the upper quarter of the BP distribution, even when differences due to body size, urinary creatinine and sodium excretion were excluded. The same result was obtained when students from the upper BP quartile were compared with age, height and weight-matched students from the rest of the study population (urinary calcium: 2.63 +/- 0.42 vs 1.54 +/- 0.23 mmol/24 h, P less than 0.02). Enhanced urinary calcium excretion is thus found in children in the upper part of the BP distribution for their age and sex and who are therefore at higher risk of hypertension in adulthood. This finding is compatible with the hypothesis of a primary abnormality of calcium metabolism in essential hypertension.

Blood Pressure↗

Reducing the risks of coronary heart disease in individuals and in the population.

Since moderately elevated levels of risk factors for coronary heart disease (CHD) are very common in the UK, a population strategy is the only practicable means of reducing risk in the large numbers of people affected. Even the most effective use of such a strategy is likely to leave a substantial minority of the population at high risk of CHD due to genetic and diet-resistant hyperlipidaemia. Hence the application of a high-risk strategy is equally essential and involves case-finding by widespread use of serum cholesterol measurement, followed by individual medical care. The two strategies are interdependent and additive and should be introduced in parallel to lessen the burden of CHD in the population as a whole and in the very-high-risk minority within the population. There will be a need for more lipid clinics, in addition to the introduction of population measures to combat CHD.

Adult↗

The binding of fibrinogen to platelets in diabetes mellitus.

Platelets from diabetics are known to be more sensitive in vitro to a variety of aggregating agents, to produce more prostaglandin endoperoxides and thromboxane and to bind more 125I-fibrinogen than platelets from normal controls Fibrinogen binding to platelets is a pre-requisite for platelet aggregation. Previous studies suggested a role for prostaglandins and/or thromboxane A2 in the exposure of fibrinogen receptors on platelets. The present study compares fibrinogen receptors on platelets. The present study compares fibrinogen binding to hyperaggregable platelets from diabetic patients and to normal platelets when prostaglandin/thromboxane formation is suppressed by aspirin. It was found that pre-treatment with aspirin reduced collagen or thrombin-induced binding to platelets from non-retinopathic diabetics to the values seen in controls. By contrast, aspirin did not normalize binding to platelets obtained from retinopathic diabetics. The combination of aspirin with apyrase (an ADP scavenger) almost completely inhibited binding and aggregation of platelets from normal controls or non-retinopathic diabetics exposed to collagen or thrombin, whereas it only partially affected binding and aggregation of platelets from retinopathics. By using a monoclonal antibody (B59.2) to the platelet receptor for fibrinogen, we determined that this receptor was quantitatively and qualitatively the same on platelets from normal controls and diabetics. We conclude that increased fibrinogen binding and hyperaggregability of platelets from non-retinopathic diabetics is related to their capacity to form more prostaglandin endoperoxides/thromboxane than normal platelets. In contrast, hyperaggregability and increased binding of platelets from retinopathics appear at least partly related to a mechanism independent of ADP release and thromboxane synthesis.

Blood Platelets↗

Effects of alpha-adrenergic and beta-adrenergic receptor blockade on lipid metabolism.

The role of lipoprotein lipase in the pathophysiology of lipid changes during alpha-receptor or beta-receptor blockade was evaluated in this clinical trial. Thirty hypertensive patients were given 2 mg of prazosin twice daily or 100 mg of metoprolol twice daily for 10 weeks, according to an open, randomized protocol. Both drugs were effective in reducing arterial blood pressure (from 153 +/- 16/102 +/- 6 mm Hg to 146 +/- 12/92 +/- 8 mm Hg with prazosin and from 158 +/- 17/103 +/- 8 to 144 +/- 14/94 +/- 10 mm Hg with metoprolol). Prazosin significantly reduced total plasma cholesterol from 202 +/- 39 to 188 +/- 36 mg/dl and increased high-density lipoprotein cholesterol from 36 +/- 8 to 40.5 +/- 11 mg/dl. Prazosin did not affect plasma triglycerides levels, whereas patients taking metoprolol had a slight rise in these levels, from 122 +/- 42 to 142 +/- 57 mg/dl, along with a decrease in high-density lipoprotein cholesterol from 37 +/- 10 to 31 +/- 8 mg/dl. The concentration of apoprotein B did not change significantly with either treatment. Lipoprotein lipase activity increased in the prazosin group from 28.4 +/- 16 to 37.7 +/- 14 mumol/liter per minute (p less than 0.01), but did not change significantly (29.9 +/- 12 versus 32.8 +/- 8 mumol/liter per minute) in patients treated with the beta blocker. These data, which confirm previous reports of serum lipid changes during antihypertensive therapy, suggest that alpha1 blockers may interfere with lipoprotein lipase, possibly by reducing its catecholamine-mediated inactivation.

Adolescent↗

Interference by sulphinpyrazone with the antihypertensive effects of oxprenolol.

The interfering effect of sulphinpyrazone, a uricosuric agent which reduces the activity of cyclo-oxygenase, with the antihypertensive activity of oxprenolol, a non-cardioselective beta-blocker with sympathomimetic activity, has been evaluated. Ten patients with primary arterial hypertension of mild to moderate degree entered a randomized double-blind cross-over study versus placebo. They were given oxprenolol + placebo or oxprenolol + sulphinpyrazone for 15 days, and then the treatments were crossed-over for a further 15 days. Oxprenolol significantly reduced blood pressure (161 +/- 3/101 +/- 1 vs 149 +/- 4/96 +/- 2 mmHg) and heart rate (72 +/- 3 vs 66 +/- 3 beats/min). During administration of the combination with sulphinpyrazone the blood pressure increased to its pretreatment level (156 +/- 5/101 +/- 2 mmHg). The effect of oxprenolol on heart rate was not influenced by the combined treatment (67 +/- 6 beats/min). The results may be explained by 1) sulphinpyrazone-induced inhibition of prostaglandin synthesis, which could interfere with the antihypertensive activity of oxprenolol, or 2) sulphinpyrazone-induced acceleration of the metabolism of oxprenolol.

Adult↗

A case of association between type I hyperlipoproteinemia and systemic lupus erythematosus (SLE). Effects of steroid treatment.

The case of a girl aged 19 yr with hypertriglyceridemia and systemic lupus erythematosus (SLE) is described. The girl had been admitted to a Lipid Outpatient Clinic in 1981 and diagnosed as having a Type I hyperlipidemia pattern. In November 1984 the patient acutely developed a SLE syndrome. Steroid treatment led to a dramatic fall of serum triglycerides from a starting value of 2100 mg/dl to 95 mg/dl. The role of steroids in completely correcting genetically deficient Lipoprotein Lipase Activity (LLA) is discussed.

Adult↗

Dietary interventions in north Karelia, Finland and south Italy. Modification of thromboxane B2 formation in platelets of male subjects only.

The effects of dietary interventions, based on changes of total fat, saturated fatty acids and cholesterol contents and of the polyunsaturated/saturated (P/S) fatty acid ratio of the diet, were studied in normal male and female subjects, living in North Karelia, Finland, and South Italy. In North Karelia the increase of P/S ratio (from 0.15 to 1.2) of the diet for a 6-week period resulted in reduced thromboxane B2 (TxB2) production by collagen-stimulated platelets only in male subjects, whereas plasma total, LDL and HDL cholesterol were reduced in both sexes. After a 6-week return to the original diet, plasma lipid levels were restored in all subjects. In the South Italy study, changes in platelet TxB2 production were observed only after return to the original diet in male subjects. Total and LDL cholesterol were significantly increased during the dietary intervention and returned toward baseline levels after switch back to the original diet. These data indicate that the increase of the P/S ratio in the diet reduces platelet TxB2 formation only in men.

Adult↗

Body fat distribution and cardiovascular risk in middle-aged people in southern Italy.

Skinfold thickness, % body fat content, body mass index, systolic and diastolic blood pressure, plasma glucose, serum cholesterol and triglycerides have been measured in 132 middle-aged men (mean age 39.8 +/- 9.9, range 20-59 yr) and in 114 middle-aged women (mean age 39.1 +/- 9.3, range 20-59 yr). Anthropometric data were related to blood pressure and biochemical parameters by using a straight-line regression analysis. Body mass index, % body fat content, subscapular and suprailiac skinfold thickness, consideral as indicative of splanchnic fat distribution, were positively correlated to blood pressure, plasma glucose, cholesterol and triglycerides. Triceps skinfold thickness, an index of peripheral fat distribution, showed weaker or no correlation with these parameters. These preliminary observations in the Neapolitan area support the hypothesis that, in addition to body mass index and % body fat content, preferential splanchnic fat distribution is associated with cardiovascular risk factors.

Adipose Tissue↗

Altered extracellular calcium homoeostasis in essential hypertension: a consequence of abnormal cell calcium handling.

A number of abnormalities in the extracellular and intracellular handling of calcium in arterial hypertension, namely an increased urinary calcium excretion, a reduced serum ionized calcium level and an enhanced intracellular free calcium concentration, have previously been reported by this and other laboratories. The present study aimed to investigate the handling of an exogenous calcium load in hypertensive and normotensive subjects in order to detect possible differences with regard to tissue calcium metabolism in vivo. A constant rate intravenous calcium infusion (0.2 mmol 2 h-1 kg-1 body wt.) was carried out in the participants. Serum calcium concentrations were determined at regular intervals during the infusion and in the 4 h after the end of the calcium load. Over the same period, urinary calcium excretion was evaluated in timed urine collections. Hypertensive subjects had lower serum ionized calcium levels compared with normotensive subjects at all the experimental points, a finding suggestive of a faster disappearance of calcium from the circulation. The total body calcium clearance, calculated from the area under the curve of the serum calcium concentrations, was enhanced in hypertensive patients (P less than 0.03). Although the renal calcium excretion was higher in hypertension, the renal calcium clearance accounted for only a minor fraction of the total body clearance, suggesting that the reduced serum calcium levels achieved by the hypertensive patients were not explained by the renal calcium leak. The enhanced total body calcium clearance found in hypertensive subjects is therefore due to an increased tissue calcium uptake. This finding provides indirect evidence of an altered cell calcium handling in hypertension.

Adult↗

Changing the Mediterranean diet: effects on blood pressure.

An increase in the polyunsaturated to saturated fatty acid ratio (P:S) in the diet has been reported to reduce blood pressure in man. We have investigated whether an increase in the percentage of saturated fatty acids in the typical Mediterranean diet would affect blood pressure in a sample of healthy rural population of southern Italy. Fifty-seven non-hospitalized normotensive volunteers (29 male, 28 female, aged 30-50 years) were studied. After a 2-week baseline period on their customary diet (P:S = 0.44), they underwent a 6-week isocaloric dietary intervention with a 70% increase in energy from saturated fatty acids and a corresponding decrease in carbohydrate and mono-unsaturated fat (P:S = 0.23). Thereafter they returned to their usual diet and were followed-up for 6 more weeks (switch-back period). By the end of the intervention period, systolic pressure was increased by 2.6 mmHg in men (P less than 0.05) and by 4.8 mmHg in women (P less than 0.01). Diastolic pressure was not significantly increased, although a significant linear regression of the group average blood pressure over time was observed for both systolic (0.161 mmHg, P less than 0.01) and diastolic pressure (0.107 mmHg, P less than 0.01). After returning to their customary diet, blood pressure returned to baseline (-0.212 mmHg, P less than 0.05 systolic and -0.226 mmHg, P less than 0.01 diastolic). No significant change in body weight occurred throughout the study. These findings suggest that changes in the saturated fatty acid content of the diet with moderate change in the dietary P:S ratio can influence blood pressure to a significant extent.

Adult↗

A role for steroid hormones in the variability of blood pressure determination.

Blood pressure variability was studied in eight patients with renovascular hypertension (group 1) and eight patients with hypertension and partial deficiency of adrenal zona fasciculata 11-hydroxylase (group 2). Systolic, diastolic and mean blood pressure were found to be higher in group 1 than in group 2 when measured at home (P less than 0.001), while no difference was measured when blood pressure was taken in the outpatient clinic. Heart rate was higher in group 1 than in group 2 both at home and in the clinic (P less than 0.005 and P less than 0.05, respectively); a significant increase was observed only in the hospital clinic for group 2 (P less than 0.001). No difference in systolic function and left ventricular mass was found between the two groups. Finally, group 2 exhibited a significant increase (P less than 0.0001) in systolic, diastolic and mean blood pressure in the clinic, compared with that found at home, while group 1 showed a poor increase (P less than 0.05) in systolic blood pressure only. It is suggested that the enzymatic impairment of adrenal glands in group 2 may play a role in the disparity of blood pressure levels determined at home and in the outpatient clinic. Furthermore, our data suggest that differences in blood pressure measurement at home and in the hospital clinic should be taken into account when screening patients with partial deficiency of 11-hydroxylase.

Adrenal Glands↗

Controlled trial of long-term oral calcium supplementation in essential hypertension.

A randomized, double-blind, placebo-controlled crossover trial of oral calcium supplementation was carried out in 18 patients with uncomplicated essential hypertension. After 15 weeks of oral calcium supplementation, 1 g/day, of the patients' habitual diet, the only blood pressure change (compared with the results of placebo treatment) was in the average standing systolic blood pressure, which was significantly reduced (-8.6 mm Hg; p less than 0.01). The 24-hour urinary calcium excretion and the total serum calcium concentration increased significantly during calcium supplementation (p less than 0.05), indicating good compliance with the treatment. The individual blood pressure changes with high calcium intake were found to be inversely related to basal 24-hour urinary calcium excretion (r = -0.69, p less than 0.001 for standing systolic pressure; r = -0.55, p less than 0.002 for standing diastolic pressure). This correlation was independent of age, basal blood pressure, serum calcium concentration, basal 24-hour urinary sodium excretion, and body weight changes during the trial. In particular, a subgroup of six patients, who had a basal 24-hour urinary calcium excretion higher than the mean + 2 SD of a reference healthy population previously described, showed a substantial average blood pressure fall at variance with the other patients in the study. These results do not support the usefulness of an oral calcium supplement in the majority of subjects with mild essential hypertension; however, they suggest that a group of patients with a previously reported abnormality of calcium metabolism may be responsive to this therapeutic measure.

Administration, Oral↗

A myeloma paraprotein with specificity for platelet glycoprotein IIIa in a patient with a fatal bleeding disorder.

Impaired platelet aggregation, normal shape change, and agglutination and normal ATP secretion and thromboxane synthesis in response to high concentrations of thrombin or arachidonic acid were found in a patient with multiple myeloma and hemorrhagic tendency. The purified IgG1 kappa or its F(ab1)2 fragments induced similar changes when added in vitro to platelet-rich plasma from normal subjects. In addition, the paraprotein inhibited adhesion to glass microbeads, fibrin clot retraction, and binding of radiolabeled fibrinogen or von Willebrand factor to platelets exposed to thrombin or arachidonic acid without affecting intraplatelet levels of cAMP. The radiolabeled para-protein bound to an average of 35,000 sites on normal platelets but it bound to less than 2,000 sites on the platelets from a patient with Glanzmann's thrombasthenia. Immunoprecipitation studies showed that the platelet antigen identified by the paraprotein was the glycoprotein IIIa. Furthermore, binding of radiolabeled prostaglandin E1 (PGE1) to resting platelets as well as binding of von Willebrand factor to platelets stimulated with ristocetin were entirely normal in the presence of patient's inhibitor. These studies indicate that bleeding occurring in dysproteinemia may be the result of a specific interaction of monoclonal paraproteins with platelets. In addition, our data support the concept that the interaction of fibrinogen and/or von Willebrand factor with the platelet glycoprotein IIb-IIIa complex is essential for effective hemostasis.

Antibodies, Monoclonal↗

Platelet fibrinogen binding in diabetes mellitus. Differences between binding to platelets from nonretinopathic and retinopathic diabetic patients.

While it is known that platelets from diabetic patients bind more fibrinogen than do platelets from normal subjects, there has been no study comparing this phenomenon in platelets from nonretinopathic and retinopathic patients. We have made such a comparison and have found the following. In agreement with previous reports, platelets from nonretinopathic diabetic patients bind abnormally high amounts of fibrinogen. No differences in the amount of fibrinogen bound to platelets (stimulated by collagen or thrombin) were found when data from nonretinopathic and retinopathic patients were compared. However, while aspirin (an inhibitor of thromboxane synthesis) reduced the abnormally high fibrinogen binding of platelets from nonretinopathic patients to normal control levels, it did not normalize the high fibrinogen binding of platelets from retinopathic diabetic patients. The combination of aspirin plus apyrase (an ADP scavenger) almost suppressed fibrinogen binding and aggregation of platelets from normal or nonretinopathic diabetic subjects, whereas it had a somewhat lesser effect on binding and aggregation of platelets from retinopathic subjects. By using a monoclonal antibody (B59.2) to the platelet receptor for fibrinogen, we determined that this receptor was the same in platelets from normal as well as nonretinopathic diabetic subjects and that this antibody could suppress the binding of fibrinogen and the aggregation of platelets from both types of patients just as it did in platelets from normal subjects. Thus, our data indicate that, while platelets from both retinopathic and nonretinopathic patients are hyperaggregable and show abnormally high binding of fibrinogen, they differ in that these abnormalities can be normalized in platelets from nonretinopathic patients by suppressing prostaglandin/thromboxane formation and scavenging ADP, but not in those from retinopathic patients.

Adolescent↗

Post prandial thermogenesis in different pathophysiological conditions.

Post Prandial Thermogenesis (PPT) is defined as the net increase in energy expenditure following the ingestion of a meal whereas diet-induced thermogenesis (DIT) indicates the overall influence of nutrients on energy expenditure. This paper reviews available data on PPT under specific clinical and dietetic conditions, e.g. the findings on PPT from pregnant and ovariectomized women, for elderly people, or the effects after MCT or LCT supplemented meals. PPT can be considered a suitable method to evaluate possible abnormalities of regulatory thermogenesis under certain clinical conditions and for the study of the acute effects of dietary components on energy expenditure.

Aging↗