[Conventional school medicine--alternative medicine: one or both? A personal viewpoint]. / Schulmedizin--Alternativmedizin: eines oder beides? Eine persönliche Stellungnahme.

The demand for an alternative medical care is in fashion nowadays. The blessings of a science- and technology-oriented medicine are on suspicion. This essay deals with the current credo of scholastic medicine, the definition of alternative health care and with the methods of phytotherapy, homeopathy and acupuncture. The opinion is promoted that there is but one integral medicine. The different methods have to be subjected to cost-benefit analysis because society cannot afford to waste financial resources to ineffective diagnostic and therapeutic measures: however, traditional medical science should accept the challenge to accept interesting alternative methods. Health care is poorly provided, if only mercantile criteria are accepted as some health-insurers propose.

[To what extent do indications for or questioning of the 24-hour ECG in ambulatory practice correlate with established ECG findings?]. / Wie weit stimmen die Indikationen bzw. Fragestellungen in der ambulanten Praxis für das 24-Stunden-Ekg. mit den festgestellten Ekg.-Befunden überein?

In 1312 patients the Holter 24-h ECG method served to detect 3190 abnormalities of the cardiac rhythm (mean 2.43 different types of arrhythmia per patient), and were classified into 14 arrhythmia groups. The main groups of indications for Holter ECG were classified as follows: palpitation; syncopes, dizziness; life-threatening arrhythmias. The positivity of the test correlated extremely well with the severity of the clinical symptoms: if syncope or dizziness were the indications for Holter ECG, abnormalities were found in 57%; if life-threatening arrhythmias were suspected, abnormalities were found in 54.7% of the patients.

High salt intake blunts plasma catecholamine and renin responses to exercise: less suppressive epinephrine in borderline essential hypertension.

Graded physical exercise was associated with a parallel increase in plasma epinephrine and norepinephrine concentrations, and increments in the latter correlated directly with concurrent increases in plasma renin activity, heart rate, and blood pressure as studied in four normal subjects. With a high salt intake, plasma catecholamine levels were lower at each grade of exercise; the norepinephrine-renin response curve was shifted to the right and the norepinephrine-heart rate response curve to the left. In five patients with borderline essential hypertension, after salt loading epinephrine concentrations were higher and their responses during exercise greater than in normal subjects. A high salt intake suppresses the activity of the sympathetic nervous system as well as the renin system but increases cardiovascular responsiveness to pressor hormones. A high dietary salt intake may contribute to elevated concentrations of plasma epinephrine and to its cardiovascular effects in borderline essential hypertension.

'Variant' angina: evidence for small vessel coronary artery spasm?

A unique case of 'variant' angina pectoris has been observed in a patient with normal coronary arteries and typical chest pain appearing spontaneously at rest, and repeatedly provoked by ergonovine maleate (0.1 mg iv) associated with large transmural perfusion defects on 201Tl-imaging (after ergonovine) and a marked increase in T wave voltage despite no demonstrable spasm of a major coronary artery after the same doses of ergonovine. While saline solution could not provoke chest pain and treatment with a beta-blocking agent increased the frequency of ischemic attacks, a calcium antagonist therapy reduced and eventually eliminated the attacks. Thus, this case provides evidence for yet another aspect of a 'variant' form of angina pectoris: small vessel coronary artery spasm.

Decreased Beta-adrenoreceptor responsiveness as related to age, blood pressure, and plasma catecholamines in patients with essential hypertension.

The role of the sympathetic nervous system as it relates to adrenoreceptor-mediated hemodynamic responses was investigated in patients with essential hypertension and in normal subjects of similar age. An age-related increase in plasma norepinephrine (PNE) concentrations observed in 36 recumbent normal subjects (r = 0.623, p less than 0.001) was not found in 56 patients; the latter included some young patients with high values. Sympathetic overactivity in patients (n = 24) as compared with normotensive subjects (n = 20) was suggested by a greater increase in PNE upon standing (242 +/- 34 vs 155 +/- 25 pg/ml (SEM), p less than 0.05) and persistently higher plasma epinephrine (PE) concentrations at rest and during equieffective exercise (p less than 0.05). In patients, PNE was directly related to systolic (r = 0.57, p less than 0.01) and diastolic (r = 0.53, p less than 0.01) blood pressure. Older age was associated with diminished exercise tachycardia and increased blood pressure responses to exercise, which were both more pronounced in hypertensive patients. This higher pressure/lower heart rate pattern was paralleled by an age-related decrease in isoproterenol sensitivity in normal subjects (0.97 +/- 0.15 in six below age 34 years, 1.31 +/- 0.30 in eight between 35--49 years, and 1.82 +/- 0.12 microgra/m2 in six above 50 years), which was also more pronounced (p less than 0.05) in hypertensive patients (1.20 +/- 1.18 in seven below age 34 years, 2.42 +/- 0.30 in nine between 35--49 years, and 6.73 +/- 2.44 micrograms/m2 in eight above 50 years). Thus, an increase in the patients' blood pressure and age is associated with a progressive reduction in beta-adrenoreceptor sensitivity and/or reactivity. Defective beta-adrenoreceptor-mediated responses may result in unopposed alpha-adrenoreceptor-mediated vasoconstriction and thereby contribute to the development of hypertension.

Plasma catecholamines and cardiac, renal and peripheral vascular adrenoceptor-mediated responses in different age groups of normal and hypertensive subjects.

The role of the sympathetic nervous system in cardiac, renal and peripheral vascular adrenoceptor-mediated responses was investigated in patients with essential hypertension and age-matched normotensive subjects. Regardless of age plasma adrenaline was significantly higher in hypertensive when compared with normotensive subjects. This suggests a sympatho-adrenal factor in essential hypertension. Plasma noradrenaline tended to increase with age but its similarity between normotensive and hypertensive subjects points to similar postganglionic neural activity and/or similar overflow of noradrenaline into the circulation. On the other hand, beta-adrenoceptor-mediated tachycardia in response to exercise and intravenous isoproterenol as well as the forearm vasodilator response to intraarterial isoproterenol decreased in normal subjects with older age. In hypertensives this age-dependent beta-receptor-related effect tends to be enhanced as judged from the greater reduction of cardiac isoproterenol sensitivity and the blunted renin response to exercise stimulation. The dilator response to alpha-adrenoceptor blockade with phentolamine was not different in both groups. Therefore a qualitative rather than quantitative derangement of sympathetic control of vascular resistance - in which beta-dilator effects are reduced and alpha-constrictor mechanisms prevail - may contribute to the maintenance of established hypertension.

Activation of rat sympathetic ganglia SIF cell dopamine metabolism by muscarinic agonists.

The biochemical responsiveness of the dopamine-containing small intensely fluorescent (SIF) cells to cholinoceptive drugs was evaluated in rat superior cervical ganglion (SCG), middle-inferior cervical ganglion and celiac ganglion. Amines and metabolites were analyzed by mass fragmentography. The major metabolite of dopamine (DA) in all ganglia was 3,4-dihydroxyphenylacetic acid (DOPAC). Stimulation of muscarinic receptors with carbachol induced a 3-10 fold increase of DOPAC concentration in the ganglia, the celiac ganglion being the most responsive and the SCG being the least. Pretreatment with atropine blocked the rise of DOPAC. The rise of DOPAC after activation of muscarinic receptors was not the consequence of blocking the removal of this acid from the ganglion. We concluded that DA metabolism in SIF cells is enhanced by stimulation of muscarinic receptors and that the magnitude of the DOPAC increase in a ganglion may reflect the importance of DA in ganglionic transmission.

Haemodynamic responses to exercise and acute beta-receptor blockade in renin sub-types of essential hypertension.

1. Haemodynamic and renin responses to dynamic exercise before and after intravenous beta-adrenoreceptor blockade with propranolol were compared in twenty-one patients with essential hypertension and either high (n = 7), normal (n = 7) or low plasma renin activity (n = 7). 2. Renin and heart-rate responses to exercise and beta-receptor blockade diminished from high-renin to normal and to low-renin patients, effects which were blunted with increasing age. 3. Among the renin groups cardiac output, stroke volume, diastolic pulmonary artery pressure, systemic pressure and peripheral vascular resistance as well as their changes produced by exercise and acute beta-receptor blockade were not significantly different. 4. Long-term anti-hypertensive propranolol effects correlated with pre-treatment renin status, renin stimulation and its suppression by acute beta-receptor blockade as well as with the exercise tachycardia and the patient's age. 5. The results suggest different adrenergic control mechanisms in renin sub-types of essential hypertension, age being a modulating factor.

[Dynamics of plasma catecholamines and beta-adrenoreceptor functions. Use of a new radio-enzymatic micro-method]. / Dynamik von Plasmakatecholaminen und beta-Adrenozeptor-Funktionen. Anwendung einer neuen radioenzymatischen Mikromethode

The new method for simultaneous determination of noradrenaline (NA), adrenaline (A) and dopamine in 50 mul plasma has proved specific, sensitive and readily reproducible. In 6 healthy volunteers NA was 190 pg/ml and A 63 pg/ml in the supine position and rose during graded upright exercise to NA 819 pg/ml and A 161 pg/ml (150 watts; p less than 0.001 and less than 0.05 respectively). NA and A paralleled exercise tachycardia (r = 0.894; p less than 0.001) and renin stimulation (r = 0.620; p less than 0.001). 21 patients with essential hypertension exhibited relatively higher NA concentrations both at rest and during graded exercise (p less than 0.05 for both). Exercise-stimulated NA and A further rose following 0.15 mg/kg propranolol i.v. (p less than 0.01 and p less than 0.05 respectively). With increasing age and blood pressure, plasma catecholamine concentrations rise while the reactivity of heart rate and renin secretion decreases. Acute pharmacological blockade of beta-adrenoreceptors increases catecholamine overflow in similar fashion to the physiological dissociation of plasma catecholamines and adrenoceptor responsiveness.

A beta-blocker-based antihypertensive drug program guided by age and renin.

From analyses of the effectiveness of beta-blocker monotherapy in relation to the patient's age and to pre-treatment renin determinations an antihypertensive drug program is proposed in which beta-blockers form the cornerstone. Patients with essential hypertension can be subdivided into groups with low (19%), normal (59%), or high (23%) renin sodium index. The proportion with low renin hypertension increases with age. Patients with high renin fall into two categories: younger patients with fairly mild hypertension and older pateients with more severe hypertension and signs of renal disease. The antihypertensive efficacy of beta-blocker monotherapy is best in high renin forms, good but less consistent in normal renin patients and uniformly bad in low renin hypertensives. In relation to age, beta-blockers normalized blood pressure (larger than or equal to 95 mmHg diastolic) in three-quarters of the younger than 40-year-olds, in about half of those aged 40--60 years, but in only 20% of those aged over 60 years. On this basis, it is postulated that the older patients with a low renin exhibit a relatively hypoadrenergic state while those with a normal or high renin--for a given age and elevated pressure--have a relatively increased adrenergic nervous activity. Because the beta-blockers have a potent suppressive action on the renin-angiotensin system--and, as a consequence, on angiotensin vasoconstriction, aldosterone volume expansion and central stimulatory feedback mechanisms--their antihypertensive mode of action may be linked to an important extent, though not exclusively, to renin suppression.

Once daily dosage beta-blockade: antihypertensive efficacy of slow release oxprenolol as related to renin and age.

A single daily dose antihypertensive therapy with a new slow-release (SR) form of the beta-adrenoceptor blocking agent oxprenolol was as effective as a standard tid beta-blocker regimen in maintaining therapeutic effects over 24 hours. The good overall response rate (target larger than or equal to mmHg diastolic) of 67% was achieved in eight of the 11 high renin patients and 16 out of the 20 normal renin ones; the five low renin patients, who were also older, proved to be non-responsive. In terms of age, 83% of the patients aged under 40 years showed a reduction in diastolic pressure to larger than or equal to 95 mmHg, this percentage being significantly better than the 50% response rate in the 40--56-year-olds. In nine of the 12 beta-blocker non-responders the diastolic blood pressure was reduced to larger than 95 mmHg by adding a diuretic, and in four of the nine, all of them low renin patients, this effect persisted in response to diuretics alone. Oxprenolol SR suppresses renin acutely (59%) and chronically (62%), and it blunts the renin stimulatory effects of diuretics.

Renin and age as determinants of a predominantly betablocker-based antihypertensive drug program.

Patients with essential hypertension can be subdivided into groups with low (19%), normal (59%) or high (23%) renin sodium index. The proportion with low renin hypertension increases with age. Patients with high renin fall in two categories: younger patients with fairly mild hypertension and older patients with more severe hypertension and signs of renal disease. The antihypertensive efficacy of betablocker monotherapy is best in high renin forms, good but less consistent in normal renin patients and uniformly bad in low renin hypertensives. In relation to age, betablockers normalized blood pressure (less than or equal to 95 mm Hg diastolic) in three-quarters of the younger-than-40-year-olds, in about half of those 40-60 years of age but in only 20% of those over 60 years. On this basis, it is postulated that the older patients with a low renin exhibit a relatively hypoadrenergic state whereas those with a normal or high renin--for a given age and elevated pressure--have a relatively increased adrenergic nervous activity. Because the betablockers have a potent suppressive action on the renin-angiotensin system--and, as a consequence, on angiotensin vasoconstriction, aldosterone volume expansion and central stimulatory feedback mechanisms--their antihypertensive mode of action may be linked to an important extent, although not exclusively, to renin suppression.

Antihypertensive beta blocking action as related to renin and age: a pharmacologic tool to identify pathogenetic mechanisms in essential hypertension.

Three hundred fifteen patients with essential hypertension were classified according to low (18 percent), normal (59 percent) or high (23 percent) renin-sodium index. The proportion of patients with low renin hypertension progressively increased with increasing age and blood pressure, there being no difference between the sexes. Two high renin groups emerged: a younger group with early moderate hypertension, and an older group with severe hypertension consequent to possibly ischemic renal disease. Long-term beta blocking monotherapy in 137 patients resulted in a reduction of idastolic pressure to 95 mm Hg or less in 65 percent: 85 percent in those with high and 73 percent in those with normal renin activity; pressure was reduced to this level in only 1 of 24 patients (4 percent) with a low renin index. Antihypertensive efficacy was also related to age, since diastolic pressure was normalized in 80 percent of patients under age 40 years, in 50 percent of those aged 40 to 60 years, but in only 20 percent of those over age 60 years. Age may heolp in patient selection but is no substitute for the more reliable renin index, especially in patients over age 40 years, or with high pressure. Using studiew with propranolol as a standard, similar renin responses were obtained with two cardioselective beta1 type blocking drugs, atenolol and metoprolol, as well as with two nonselective beta2+1 receptor antagonists, LL21945 exhibiting prolonged receptor affinity and oxprenolol in slow release form. These long-acting drugs, which proved effective in single daily doses, could be of value in improving patient compliance...