15 patients (4 females, 11 males, 21 to 55-year old) with mild to moderate essential hypertension (EH) were treated with placebo for two weeks and thereafter with increasing doses of prindolol (15 to 38 mg/day in the mean) and kept on a mean maintenance dosage of 32 mg/day for an average of 16 weeks in all. Blood pressure (BP), heart rate und plasma noradrenaline (PNA) concentrations were measured under standardized conditions (supine, standing, walking) at the end of two weeks on placebo and after the experimental treatment period. The results were compared to those of a group of 15 normotensive untreated control subjects (NS): after an average of 16 weeks on prindolol BP fell from 163/113 mm Hg to 129/91 mm Hg in the mean. PNA levels in EH before prindolol were significantly higher than in NS (supine: 272 +/- 22.0 ng/l (mean +/- SEM) vs. 135 +/- 15.1 ng/l, standing: 448 +/- 31.9 ng/l vs. 359 +/- 18.4 ng/l, walking: 388 +/- 22.5 ng/l vs. 234 +/- 22.1 ng/l). In EH chronic administration of prindolol led to a significant decrease in PNA concentrations under all the three test conditions to levels which did not differ significantly any more from those derived from NS. The adrenergic response to upright posture reflected in the percentage increase in PNA was significantly less in EH before prindolol when compared to the percentage increase in NS. On prindolol the adrenergic response was not abolidhed, yet it tended to approach the values found in NS. Before prindolol under resting conditions diastolic BP correlated closely with the corresponding PNA levels (p less than 0.01, r = 0.66, n = 15). This correlation could not be reestablished after prindolol treatment. The decrease in PNA after long-term treatment with prindolol was not correlated to the fall in blood pressure. The decrease in PNA indicates a lower activity of the sympathetic nervous system which may contribute to the antihypertensive effect of prindolol.

1. Plasma noradrenaline was measured in fiftynine patients with mild to severe essential hypertension and in fifteen normotensive control subjects under basal and orthostatic conditions. 2. In patients with essential hypertension mean plasma noradrenaline concentrations were significantly higher than in control subjects under basal and orthostatic conditions. 3. In patients with essential hypertension basal diastolic blood pressure correlated closely with the corresponding plasma noradrenaline concentrations. 4. Long-term treatment with prindolol of patients with essential hypertension led to a significant fall in diastolic and systolic blood pressure and heart rate and to a significant decrease in plasma noradrenaline concentrations under basal and orthostatic conditions. 5. The adrenergic response to upright posture, reflected by an increase in plasma noradrenaline, was not abolished by prindolol. 6. It is concluded that the anti-hypertensive effect of prindolol in patients with essential hypertension is at least partially mediated by a decrease of sympathetic nervous activity.

Since plasma exchange was introduced in the management of thrombotic thrombocytopenic purpura (TTP) in 1977, patient survival rate has increased from 10 to 80%. However, approximately 50 subsequent case reports in the literature provide no consensus as to the optimal therapy. We review here 4 episodes of TTP in 3 patients. In all cases, treatment was started with intensive FFP plasma exchange combined with administration of antiplatelet agents and corticosteroids. Remission was achieved in 3 out of 4 episodes although all required individualization of the medication regimen. In the remaining patient, cytotoxic therapy (vincristine) and ultimately splenectomy were required to achieve stable remission. The variable clinical response to these therapeutic protocols indicates that TTP may not represent a single homogeneous disease entity but rather may involve various underlying pathologies. We conclude that the most effective present therapy for the management of TTP is daily plasma exchange with fresh frozen plasma infusions combined with antiplatelet agents and steroids. Vincristine and splenectomy should only be employed if this protocol proves ineffective.

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