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During the last deglaciation, the opposing patterns of atmospheric CO2 and radiocarbon activities (Δ(14)C) suggest the release of (14)C-depleted CO2 from old carbon reservoirs. Although evidences point to the deep Pacific as a major reservoir of this (14)C-depleted carbon, its extent and evolution still need to be constrained. Here we use sediment cores retrieved along a South Pacific transect to reconstruct the spatio-temporal evolution of Δ(14)C over the last 30,000 years. In ∼2,500-3,600 m water depth, we find (14)C-depleted deep waters with a maximum glacial offset to atmospheric (14)C (ΔΔ(14)C=-1,000‰). Using a box model, we test the hypothesis that these low values might have been caused by an interaction of aging and hydrothermal CO2 influx. We observe a rejuvenation of circumpolar deep waters synchronous and potentially contributing to the initial deglacial rise in atmospheric CO2. These findings constrain parts of the glacial carbon pool to the deep South Pacific.

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The antihypertensive and hormonal effects of the new angiotensin-converting enzyme (ACE) inhibitor, ramipril, were assessed by means of a single-blind trial in ten unselected patients with mild-to-moderate essential hypertension. After a 2-week period on placebo, 5 mg ramipril was administered once daily for 2 weeks. Blood pressure returned to normal in five patients and decreased in the remaining patients, without significant changes in heart rate or orthostatic hypotension. A fall in blood pressure was apparent within 1-2 h of the first dose; the maximum decrease was reached at 4-6 h and a fall in pressure was still detectable after 24 h. At 24 h post dose angiotensin-converting enzyme activity was suppressed to 40% of the baseline. Blood pressures for the 10 h interval post dosing showed smooth through-the-day control with minimal peak/trough difference in lowering effect. The magnitude of the blood pressure decrement achieved with the inhibitor did not correlate with baseline renin levels or the rise in renin following treatment. No side-effects were noted during the 2-week observation period. The study demonstrates that ramipril, given in a once-daily regimen over a period of 2 weeks, is well tolerated and provides smooth and effective blood pressure control throughout the 24-h interval between doses.

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A double-blind study was carried out in two parallel groups of patients with mild to moderate hypertension to assess the efficacy and tolerance of the combination 20 mg penbutolol plus 3 mg piretanide in comparison to 40 mg penbutolol alone over a period of 6 weeks. Active drug treatment in the 51 patients studied was preceded by a 2-week period of placebo. The results showed that in both groups there was an effective reduction in systolic and diastolic blood pressure compared with initial levels. Although there was no significant difference between the groups, the normalization of diastolic blood pressure (less than 95 mmHg) was achieved in 70% of the patients receiving the combination and in 59% of the patients treated with penbutolol alone. Pulse rate decreased in both groups, body weight only in the combination group. The biochemical and haematological parameters showed no clinically relevant changes during treatment with either drug regimens. Minor side-effects definitely or probably associated with the treatment were observed in both groups but were generally mild and did not interfere with treatment. No patient withdrew prematurely from the trial.

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In a randomized double-blind, parallel group study, the effects of piretanide on serum electrolytes and on symptoms of congestive heart failure were compared with those of the combination piretanide plus triamterene in out-patients with mild to severe congestive heart failure. A total of 60 patients entered the study; 13 patients were excluded from the statistical analysis (4 due to premature end of the study, 2 due to dose increase, 7 due to concomitant medication (antihypertensive or antihypotensive agents), so that the results of 47 patients were statistically analyzed, 26 of them in the piretanide and 21 of them in the piretanide plus triamterene group. Piretanide (6 mg once daily) and piretanide plus triamterene (6 mg + 50 mg once daily) both produced a significant reduction in certain symptoms of congestive heart failure which was evident at 2 weeks and was maintained and further enhanced over the ensuing 12-week trial period. Improvement in a number of symptoms of congestive heart failure was attained in 54% of the patients in the piretanide group and 67% in the piretanide plus triamterene group. This difference, however, was not clinically relevant, since the symptoms which are expected to improve in this short time showed no great difference between the two groups. There were no significant changes in serum potassium and serum magnesium within groups or differences between the groups. There were decreases in serum sodium, calcium and inorganic phosphorus in the piretanide plus triamterene group. In the piretanide group, only a temporary drop in inorganic phosphorus was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

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The efficacy and tolerability of penbutolol alone and in combination with piretanide at two dose levels were investigated in a double-blind parallel group study in patients with mild to moderate essential hypertension. All three treatments were given as a single daily dose. One hundred and eight patients entered the study; 82 completed a 7-day placebo run-in period followed by 3 weeks of active therapy. Penbutolol 20 mg plus piretanide 3 mg and penbutolol 40 mg plus piretanide 6 mg both produced a significantly greater reduction in supine diastolic blood pressure (16% and 19% respectively) than penbutolol 20 mg (9%). The reduction in supine diastolic blood pressure was significant for all three treatments with respects to the baseline reading. Side-effects were generally mild and transient and were similar in type and incidence in the three groups. Six patients did not complete the trial period because of an excessive response to the hypotensive medication: five in the high dose combination group, and one in the low dose combination group. Low doses of penbutolol (20 mg) and piretanide (3 mg) used in combination and in a once-daily administration provide a simple, effective and well tolerated regimen for patients with mild to moderate hypertension.

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