Abundance of live ²44Pu in deep-sea reservoirs on Earth points to rarity of actinide nucleosynthesis.

Half of the heavy elements including all actinides are produced in r-process nucleosynthesis, whose sites and history remain a mystery. If continuously produced, the Interstellar Medium is expected to build-up a quasi-steady state of abundances of short-lived nuclides (with half-lives ≤100 My), including actinides produced in r-process nucleosynthesis. Their existence in today's interstellar medium would serve as a radioactive clock and would establish that their production was recent. In particular (244)Pu, a radioactive actinide nuclide (half-life=81 My), can place strong constraints on recent r-process frequency and production yield. Here we report the detection of live interstellar (244)Pu, archived in Earth's deep-sea floor during the last 25 My, at abundances lower than expected from continuous production in the Galaxy by about 2 orders of magnitude. This large discrepancy may signal a rarity of actinide r-process nucleosynthesis sites, compatible with neutron-star mergers or with a small subset of actinide-producing supernovae.

Salt intake, hypertension and diabetes mellitus.

Diabetes mellitus affects approximately 135 million people in the world. Diabetes and hypertension are both relatively common diseases in westernised countries. Both entities increase with age. Essential hypertension accounts for the majority of hypertension in people with type 2 diabetes, who constitute more than 90% of those with a dual diagnosis of diabetes and hypertension. The benefit conferred per mm Hg blood pressure reduction appears to be greater in persons with type 2 diabetes than in those with hypertension and non-coexistent diabetes mellitus. Similar to a subset of patients with essential hypertension, type 2 diabetic patients manifest dietary NaCl-induced exacerbation of hypertension. Recent guidelines have emphasised that the target blood pressure levels for patients with diabetes should be lower than in other hypertensive groups. An increased total body sodium and enhanced vascular reactivity are found in people with diabetes and most type 2 diabetic patients are salt sensitive. Type 2 diabetes with hypertension is associated with reduced renal plasma flow when dietary salt intake is high. Experimental, observational and interventional evidence support the benefits of sodium restriction in hypertensives. However, the full effects of sodium restriction are usually not obvious for at least 5 weeks. Other favourable effects of moderate reduction in sodium intake are a regress left ventricular hypertrophy, decrease in diuretic-induced potassium wastage, reduction in proteinuria, protection against stroke and from osteoporosis and renal stones, and enhancement of the antihypertensive effect of the antihypertensive agents.

Insulin resistance and hypertension in postmenopausal women.

The aim of the study was to elucidate the role of hyperinsulinaemia/insulin resistance in hypertension of lean postmenopausal women. Twenty-four women with essential hypertension (systolic/diastolic > or =140/90 mm Hg) and a body mass index (BMI) less than 26 kg/m(2) not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period, and 10 normotensive postmenopausal weight- and aged-matched controls were compared. Both groups were not receiving hormone replacement therapy. Hip and waist circumferences were measured and waist/hip ratios were calculated. Casual blood pressure was measured in triplicate. Neither the fasting plasma glucose nor serum insulin levels in hypertensive women and normotensives differed significantly. During 2 h oral glucose (75 g)-tolerance test the mean plasma glucose levels after 30 min (172.5 +/- 40.24 mg/dl vs. 143.67 +/- 20.16 mg/dl), 60 min (134.88 +/- 38.78 mg/dl vs. 112.33 +/- 5.44 mg/dl) and 120 min (116.08 +/- 26.65 mg/dl vs. 95.56 +/- 20.17 mg/dl) were significantly higher in hypertensives than that for normotensives (P < 0.05 for all three comparisons). The mean serum insulin levels of hypertensive women were significantly higher than that in normotensives after 15 min (92.04 +/- 59.90 microU/ml vs. 54.89 +/- 33.67 microU/ml) and 120 min (49.63 +/- 44.45 microU/ml vs. 19.22 +/- 24.10 microU/ml; P< 0.05 for both comparisons). The mean serum insulin: plasma glucose ratio for hypertensive women was significantly higher than that for normotensives after 15 min (0.596 +/- 0.46 vs. 0.359 +/- 0.20 microU/mg), 60 min (0.406 +/- 0.30 vs. 0.329 +/- 0.25 microU/mg) and 120 min (0.436 +/- 0.35 vs. 0.205 +/- 0.26 microU/mg) (P < 0.05 for all three comparisons). Significant correlations were observed between the daytime period and 24-h average ambulatory systolic blood pressure and the area under the serum insulin curve (r = 0.41 and 0.36, respectively). For non-dippers we found higher fasting insulinaemias but the AUC(insulin) did not differ. Plasma glucose levels did not differ either during fasting or during OGTT (AUC(glucose)). Insulinogenic index was higher in dippers than in non-dippers. We conclude that in lean, postmenopausal hypertensive women insulin resistance is increased compared with age- and weight-matched normotensive women. Also, hyperinsulinaemia correlates with ambulatory systolic blood pressure. Thus, insulin resistance may possibly be involved as a pathogenetic factor in lean, postmenopausal hypertensive women.

Altered circadian blood pressure profile in patients with active acromegaly. Relationship with left ventricular mass and hormonal values.

To determine the relationships between the circadian blood pressure profile and left ventricular mass, hormonal pattern and insulin sensitivity indices in patients with active acromegaly, ambulatory 24-h blood pressure monitoring (ABPM) was recorded in 25 subjects (47.0 +/- 15.1 years, range 23-72). Serum growth hormone (GH) and insulin-like growth factor-1, fasting and mean plasma glucose and insulin during oral glucose tolerance test (OGTT), insulinogenic index, the sum of the plasma insulin levels and the homeostasis model insulin resistance index (Homa's index) were determined. Left ventricular mass index (LVMI) was calculated from two-dimensional guided M-mode echocardiogram. The prevalence of hypertension was 56% (n = 14) and 40% (n = 10) according to sphygmomanometric measurements and ABPM, respectively. Non-dipping profile was observed in six of 10 hypertensives and in six of 15 normotensives. Serum growth hormone, fasting glucose, the area under the serum insulin curve and LVMI were higher for acromegalics with non-dipping profile than for dippers (all of them, P < 0.05). In non-dippers daytime heart rate was higher than night time (P < 0.001). In conclusion, the main observations in the present study suggested that both normotensive and hypertensive acromegalics had a highly prevalent non-dipping profile with a preserved circadian pattern of heart rate, that was associated with higher levels of serum GH. The disturbance in nocturnal blood fall in normotensives was associated with a decreased insulin sensitivity. The role of GH in blood pressure circadian rhythm regulation in essential hypertension deserves further studies.

Sibrafiban (Genentech).

Sibrafiban (G-7453) is an orally active non-peptide GPIIb/IIIa antagonist, under development by Genentech and Hoffmann-La Roche, and in phase III trials as an antithrombotic. Roche intends to file for marketing approval in 1999. Merrill Lynch predicts a product launch in 2001.

Relationship between hyperinsulinemia and ambulatory blood pressure monitoring of lean and overweight male hypertensives.

OBJECTIVE: To elucidate the role of hypertension as part of a state of insulin resistance. METHODS: Thirty-one uncomplicated hypertensive men not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period and 10 lean normotensive controls were compared. Hypertensive men were divided according to their body mass index into three groups. All subjects came to the clinic for measurements of height, weight, hip and waist circumferences, and sitting blood pressure, and to begin 24 h ambulatory blood pressure monitoring. Plasma glucose and insulin levels were measured during a 2 h oral glucose (75 g)-tolerance test. For the hypertensive population as a whole, behaviors of studied variables among dippers (n = 18) and nondippers (n = 13) were determined. RESULTS: During oral glucose-tolerance testing blood glucose levels after 60 min and 120 min were significantly higher (P < 0.05) in members of the high body mass index group than they were in members of the low body mass index group. Insulin levels of members of the high and middle body mass index groups were higher than those of members of the low body mass index group after 60 min (P < 0.05 for both comparisons) and 120 min (P < 0.05 for both comparisons). The mean serum insulin level in members of the low body mass index group was significantly higher than that in normotensives after 30 min, 60 min and 120 min (P < 0.05 for all three comparisons). The mean serum insulin: plasma glucose ratio for men in the low BMI group was significantly higher than that for normotensives after 60 min and 120 min (P < 0.05 for both comparisons). Correlations of blood pressure and insulin levels were not significant. Levels of high-density lipoprotein cholesterol and triglycerides were lower in members of the group with high body mass index than they were in members of the group with low body mass index. Total cholesterol: high-density lipoprotein cholesterol ratio was higher for members of the high body mass index group than it was for members of the middle body mass index group. Weight, body mass index, casual systolic blood pressure, 24 h average systolic blood pressure and diastolic blood pressure, 0700-2300 h systolic blood pressure, and 24 h average heart rate-systolic blood pressure product of dippers were significantly lower than those of nondippers. CONCLUSIONS: These results suggest that hypertension and being overweight have additive effects increasing insulinemia and that being overweight is associated with a significantly lower nocturnal fall in blood pressure.

[Arterial hypertension as a risk factor in the cardiovascular complications of diabetes mellitus]. / La hipertensión arterial como factor de riesgo en las complicaciones cardiovasculares de la diabetes mellitus.

Diabetic patients suffer from atherosclerosis and its complications more frequently and at an earlier stage than nondiabetic people. The factors predisposing diabetics to premature arteriosclerosis are not fully clarified. Data from a 5-year follow-up of 617 diabetics, 376 non-insulin dependent (NIDDM) and 241 insulin-dependent (IDDM), attending the Hospital de Clínicas José de San Martín at Buenos Aires city are reported. By the WHO criteria 55% of NIDDM and 29% of IDDM had hypertension. Hypertension was significantly (p less than 0.01) more common among NIDDM than among IDDM patients after adjustment for age, sex and obesity. The incidence of angor pectoris, acute myocardial infarction and heart failure was significantly greater in hypertensive patients of both types of diabetes than in the respective normotensive group. No sex differences were observed in both diabetic groups in the incidence rates of coronary heart disease. Overt diabetic nephropathy and diabetic retinopathy were more frequent in hypertensives than in normotensives of both groups of diabetics. Even though 63% of hypertensive patients with NIDDM and 57% with IDDM received antihypertensive treatment only 36% and 24% respectively had their blood pressure well controlled. Acute myocardial infarction was the most frequent cause of death in both NIDDM and IDDM hypertensive people.

Dynamics of the pulmonary circulation in systemic hypertension.

Pulmonary and systemic hemodynamics in 28 mild to moderate hypertensive patients (group II) with left ventricular (LV) hypertrophy (ECG and echo criteria) and 22 severe hypertensive patients with LV hypertrophy (group III) were compared with 20 patients with mild-to-moderate hypertension in WHO stage I (group I). Mean right atrial pressure was equivalent in groups II and III and significantly higher in the last group than in group I. An increased pulmonary arterial resistance (PAR) in group II and, to a large extent, in group III accounted for the elevation of diastolic and mean pulmonary arterial pressure in both groups in comparison with group I. Cardiac index (CI) was lower and systemic vascular resistance (SVR) higher in group III than in group I. Pulmonary capillary wedge pressure (PCWP) values were within the normal range and equivalent between groups II and III, and both significantly higher than in group I. PAR showed a positive relation with SVR (r = 0.30, P less than 0.01) and an inverse relation with CI (r = -0.561, P less than 0.001). Findings indicate that in systemic hypertension with LV hypertrophy there is an elevation of the right ventricular filling pressure and the pulmonary arterial pressure whose degree is even higher in severe hypertension. This increase is not necessarily a consequence of impairment of LV function as suggested by the normal range of PCWP values.

Comparison between the effects of urapidil and methyldopa on left ventricular hypertrophy and haemodynamics in humans.

In a randomised double-blind study the effects on left ventricular mass (LV mass) and cardiac haemodynamics of urapidil, an antihypertensive agent with a vascular postsynaptic alpha 1-blocking action and a central antihypertensive effect, were compared with those of methyldopa in 29 patients with essential hypertension. During a 3-month period, urapidil was initially given at 120 mg/day and increased to 180 mg/day if a satisfactory antihypertensive response was not achieved. Methyldopa was started at 100 mg/day and increased to 1500 mg/day if an adequate blood pressure response was not achieved. Echocardiographic measurements were obtained at baseline and after 12 weeks' active treatment. The frequency rates of responders (DBP less than 95 mm Hg) on urapidil and methyldopa were 54% and 62%, respectively, after 12 weeks. In the group as a whole there was a nonsignificant tendency for decreased LV mass on both active drugs. However, the haemodynamic changes were difficult to interpret because of baseline differences between the 2 treatment groups.

Antihypertensive treatment with metoprolol or hydrochlorothiazide in patients aged 60 to 75 years. Report from a double-blind international multicenter study.

In a randomized double-blind study (N = 562), a traditional treatment schedule, starting antihypertensive treatment in elderly hypertensive patients (60 to 75 years old) with 25 mg of hydrochlorothiazide once daily and doubling the dose if a satisfactory response was not achieved, was compared with antihypertensive treatment of 100 mg of metoprolol once daily, adding 12.5 mg of hydrochlorothiazide for patients whose response was not satisfactorialy achieved with metoprolol alone. Systolic and diastolic blood pressure was significantly reduced with both regimens. The frequency rates of responders (diastolic blood pressure, less than or equal to 95 mm Hg) in the metoprolol group and the hydrochlorothiazide group were 50% and 47% after four weeks and 65% and 61% after eight weeks, respectively. There were no significant differences in total symptom score or single symptoms between the regimens, but significantly more patients had hypokalemia and hyperuricemia with the hydrochlorothiazide regimen. Thus, we conclude that beginning antihypertensive treatment with 100 mg of metoprolol once daily and adding a small dose of hydrochlorothiazide (12.5 mg) in patients whose response is not satisfactory with metoprolol alone appears to be effective and safe in elderly hypertensive patients.

Hemodynamic effects of guanfacine in essential hypertension.

Hemodynamic evaluation of three men and eight women aged 20 to 58 years (mean, 44 years) with essential hypertension was performed before and after a single dose of guanfacine and before and after long-term administration of the drug, which is a stimulant of central alpha-adrenergic receptors. Mean (+/- SE) recordings of blood pressure before catheterization were 168/115 +/- 6/3 mmHg when supine and 168/112 +/- 8/4 mmHg when standing. Within two hours of oral administration of 3 mg of guanfacine, the heart rate decreased from a mean of 77 +/- 2 to 69 +/- 3 beats/min (P less than 0.05), and the pulmonary capillary wedge pressure (PCWP) decreased from a mean of 9 +/- 1 to 6 +/- 1 mmHg (P less than 0.02). The mean readings of pulmonary arterial pressure also decreased, as follows: systolic, from 22 +/- 2 to 18 +/- 0.14 mmHg (P less than 0.05); diastolic, from 9 +/- 1 to 7 +/- 1 mmHg (P less than 0.05); and mean, from 15 +/- 1 to 12 +/- 2 mmHg (P less than 0.05). No changes were observed in systemic blood pressure, the cardiac index, systemic vascular resistance, or total pulmonary vascular resistance. After a six-week course (mean dosage, 3.9 +/- 0.57 mg/day), the following variables decreased significantly: systemic blood pressure--systolic, diastolic, and mean, both supine and standing (P less than 0.001); heart rate (P less than 0.001); and systemic vascular resistance (P less than 0.01). The PCWP reached values similar to those measured during the control phase. Increases were noted in pulmonary artery systolic pressure (P less than 0.05), mean right atrial pressure (P less than 0.01), and in the stroke volume index (P less than 0.05). It is likely that the main hemodynamic mechanism underlying the long-term antihypertensive effect of guanfacine is a decrease in systemic vascular resistance.

Sympathetic nervous system response to graded exercise: effect of beta-blockade.

This study compares the sympathetic nervous system response to graded exercise in normotensive and essential hypertensive subjects with and without beta-adrenergic blockade. Blood pressure (BP), heart rate, and plasma norepinephrine (NE), epinephrine (E), and dopamine (DA) were measured just before starting the exercise (Pre-Ex), in the submaximal exercise (Sub-max),and after 8 minutes rest (Post-Ex). On placebo, Sub-max induced in both normotensives and hypertensives a similar increase in NE and E plasma levels. Plasma DA remained unchanged. Propranolol in controls and propranolol or mepindolol in hypertensives didn't modify significantly: 1) Pre-Ex plasma levels of E, NE, and DA; 2) response at Sub-max in controls; 3) plasma E and DA in hypertensive patients. In hypertensives on beta-blockade, submaximal exercise elicited a greater increase in plasma NE. Values for plasma NE in patients on propranolol were 1135 +/- 229 pg/ml higher than those obtained in the same patients on placebo (p less than 0.001). On mepindolol, the plasma NE increment was higher than that on placebo (p less than 0.05), but lower than that on propranolol (p less than 0.01). In controls, propranolol did not significantly modify BP at Pre-Ex or its response to exercise, whereas systolic and diastolic BP were significantly lower at Pre-Ex, Sub-max, and Post-Ex in hypertensives. On beta-blockade, heart rate decrease in Pre-Ex, Sub-max, and Post-Ex were not different in controls and hypertensives. The differences found on beta blockade would indicate that the effects of beta blockers are not identical in normotensive and hypertensive subjects.

Transducers for myocardial research.

Seven miniaturized transducers to measure force, displacement, and thickness--singly and in combination--in animal experiments are described. The transducers are lightweight and during an open-chest procedure can be inserted within a heartbeat, removed, and reinserted, with minimum trauma. Six or more transducers of various kinds can be used simultaneously without artifacts. For closed-chest experiments a combination force-displacement transducer can be catheter-borne. A trifunctional transducer was used successfully to measure force-displacement thickness in a small area. A single conductor can be added for ECG measurement in the area where the transducer is implanted.