Treatment of mild hypertension with progressive muscle relaxation. Predictive value of indexes of sympathetic tone.

Effects of progressive muscle relaxation (PMR) and of attention control were investigated in a prospective randomized trial of borderline or mild hypertensive patients. Both groups received placebo and had the same number of clinic return visits. After 22 weeks the average mean home BP in PMR decreased 3 mm Hg, whereas in controls BP increased 2 mm Hg. Progressive muscle relaxation had no significant effect on the clinic BP. The response to PMR was not uniform. Responders were characterized by faster heart rates and higher plasma norepinephrine levels. The responders also showed a decrease of anxiety scores during the trial. Progressive muscle relaxation is a time-consuming procedure. Blood pressure responses do not substantially exceed the placebo effects in unselected patients. However, relaxation may be suitable for young, anxious patients with mild hypertension who have a high resting sympathetic tone.

Role of cardiac factors in the initial hypotensive action by beta-adrenoreceptor blocking agents.

The blood pressure decrease after beta-blockade is delayed and there are little data on the hemodynamic events associated with the initial decrease in blood pressure. The present study measured the hemodynamics of the initial hypotensive action of timolol maleate, a nonselective beta-adrenoreceptor blocking agent, in 10 patients with essential hypertension. Frequent measurements were made for the first 30 hours of treatment, and follow-up measurements made at 3 and 6 weeks. Before treatment, mean arterial blood pressure, cardiac output, and arteriovenous oxygen difference were 115.9 +/- 9.1 mm Hg, 4.65 +/- 1.05 liter/min, and 55.0 +/- 9.6 ml/liter, respectively. At 3 hours after the first dose of timolol, blood pressure had fallen 13.5 +/- 8.2 mm Hg (p less than 0.05). This was preceded by an initial decrease in cardiac output, which was not associated with a simultaneous decrease in blood pressure, and by an increase of arteriovenous oxygen difference. The early, statistically significant, decrease in cardiac output was followed by a return to normal output, which coincided with the onset of blood pressure reduction. The magnitude of the initial decrease of cardiac output and of the initial increase in arteriovenous oxygen difference was significantly correlated to the later decrease in blood pressure (7 hours after first dose). These hemodynamic observations are consistent with the notion that early underperfusions of tissue play a role in the initial hypotensive action of beta-blockers. After 6 weeks, the blood pressure remained lower but the cardiac output was again decreased at that point. As with many antihypertensive agents, there was a difference between the early and late hemodynamic pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic factor in mild to moderate chronic renal failure.

The relationship between kidney function and plasma immunoreactive atrial natriuretic factor (irANF) levels as well as the effects of synthetic human ANF-(99-126) were investigated in 13 patients with mild to moderate chronic renal failure. Under basal conditions, glomerular filtration rate averaged 39 +/- 5 (SEM) ml/min/1.73 m2 and blood pressure (BP) averaged 166/107 +/- 7/2 mm Hg; 12 patients were hypertensive. Plasma irANF levels were significantly increased (98 +/- 16 vs 42 +/- 4 pg/ml in healthy control subjects; p less than 0.001) and correlated (p less than 0.05-0.005) inversely with hematocrit (r = -0.65) and positively with systolic BP (r = 0.75) or fractional sodium excretion (r = 0.75). Human ANF-(99-126) infusion for 45 minutes at 0.034 microgram/kg/min augmented (p less than 0.05-0.01) diuresis and urinary sodium, chloride, calcium, phosphate, and magnesium excretion. During the subsequent 45 minutes of human ANF-(99-126) infusion at a rate of 0.077 microgram/kg/min, diuresis and electrolyte excretion remained elevated (p less than 0.05-0.01). Glomerular filtration rate and effective renal plasma flow were not significantly modified, but filtration fraction rose progressively (p less than 0.01). Human ANF-(99-126) infusion decreased BP (p less than 0.05-0.01), produced hemoconcentration (hematocrit + 7%; p less than 0.01) without negative body fluid balance, and increased (p less than 0.01-0.001) plasma norepinephrine, insulin, and serum free fatty acids; plasma aldosterone and renin activity were unaltered during but rose after cessation of human ANF-(99-126) infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of cardiovascular receptors on the neural regulation of renin release in normal men.

Although factors influencing renin release have been studied extensively, one facet of renin release remains controversial, namely, neural regulation by arterial high-pressure receptors and cardiopulmonary low-pressure receptors. We therefore designed four studies to investigate systematically the separate and combined effects of unloading (decreased stretch) high- and low-pressure receptors on renin release in normal men. Selective unloading of cardiopulmonary receptors was induced by impeding the venous return with tourniquets around the thighs. A predominant unloading of arterial (carotid) baroreceptors was elicited with upright posture and simultaneously preventing the venous pooling in the legs. Unloading of both high- and low-pressure receptors was achieved by both upright standing and tilting. During postural experiments to predominantly unload arterial baroreceptors, the heart rate increased and the veins constricted, but renin failed to increase. The postural increase of renin occurred only if we allowed venous pooling in the legs. Selective unloading of cardiopulmonary receptors elicited substantial increases of renin. When both the cardiopulmonary and arterial baroreceptors were unloaded, renin increased more than with isolated unloading of cardiopulmonary receptors. We conclude that: 1) in intact humans it is possible to demonstrate an independent role of cardiopulmonary receptors in the control of renin release; 2) there Is evidence for interaction between the two receptor systems in renin control; but 3) an independent role for arterial baroreceptors in the control of renin release could not be demonstrated under the conditions of this experiment.

Performance of a new fibrin monomer assay to exclude deep vein thrombosis in symptomatic outpatients.

UNLABELLED: In this study we prospectively assessed the reliability of a new fibrin monomer assay in 106 outpatients with clinically suspected deep venous thrombosis of the lower limb. According to the results of the objective tests and using different cut-off points we calculated the sensitivity, specificity and negative predictive value of the fibrin monomer assay. The prevalence of deep vein thrombosis was 44.3% (31.1% proximal, 13.2% distal). Using a cut-off level of plasma fibrin monomer of 3.5 microg/ml, a sensitivity, specificity and negative predictive value of 100% (95% CI: 94-100%), 35.6% (95% CI: 23-48%) and 100% (95% CI: 86-100%), respectively, were obtained. The exclusion rate was 19.8% (95% CI: 12-27%) of all referred patients. These accuracy indices compared favourably with the respective results of a routine D-dimer ELISA used for comparison. CONCLUSION: This new fibrin monomer assay appears to be a reliable method for the exclusion of deep vein thrombosis in symptomatic outpatients.

Use of clonidine and propranolol as monotherapy in borderline hypertension.

The effect of clonidine (average 0.24 mg/day) and propranolol (average 105 mg/day) on home blood pressure readings in 16 patients with borderline hypertension was investigated in a randomized, double-blind, placebo crossover design. Patients could detect small but significant decreases of blood pressure with both active compounds (-8/-5 with propranolol and -11/-7 with clonidine). The larger mean blood pressure decrease from clonidine vs propranolol was significant (p less than 0.015). Small doses of sympatholytic agents might control the blood pressure in patients with borderline hypertension, and the home blood pressure technique is a convenient tool to detect and monitor such changes. Biochemical predictors of the responsiveness to clonidine were investigated. There was no difference in placebo norepinephrine and renin values between better and lesser responders to clonidine. Plasma norepinephrine fell with clonidine treatment, but with no relationship to the blood pressure response. Plasma norepinephrine response to clonidine might reflect not only the central withdrawal of sympathetic tone, but also, in part, the effect of clonidine on peripheral presynaptic alpha 2-receptors.

Multiple organ failure and coma as initial presentation of pheochromocytoma in a patient with multiple endocrine neoplasia (MEN) type II A.

The unusual case of a 65-year-old woman with intermittent hypotension, fever, pulmonary edema and coma as initial presentation of pheochromocytoma is reported. The patient developed respiratory, cardiac and renal failure, disseminated intravascular coagulation and liver dysfunction. She had to be defibrillated on multiple occasions, occurring in periods of severe hypertension. After successful surgical removal of a pheochromocytoma a thyroid medullary carcinoma was detected. Several members of the patients family had presented with multiple endocrine neoplasia (MEN II).

Rapid D-dimer testing and pre-test clinical probability in the exclusion of deep venous thrombosis in symptomatic outpatients.

We assessed the performance of three rapid D-dimer tests (Auto Dimertest, VIDAS and Tinaquant) in combination with a pretest clinical probability model for deep venous thrombosis (DVT) in 106 consecutive outpatients with suspected DVT. Contrast venography or colour-coded duplex ultrasonography demonstrated the presence of DVT in 47 patients (14 distal DVT and 33 proximal DVT). First, we assessed the accuracy indices for different cut-off levels of the rapid D-dimer tests. Sensitivity was found to be 97.9-100%, negative predictive value (NPV) was 96.3-100%, and the exclusion rate was 24.5-31.1%. Next, the patients were grouped according to the pre-test clinical probability model in categories with low, moderate or high probability. In patients with a low pre-test probability, DVT would have been directly ruled out and the patients would not have undergone further investigations. In patients with a moderate probability, D-dimer testing and, in the case of a positive result, objective testing would have been performed and, in the case of a negative result, they would have been ruled out of having DVT. Patients with high probability would directly have undergone objective tests for DVT. The combination with the pre-test clinical probability model improved the exclusion rate (43.5-44.6%), whereas sensitivity (97.5-100%) and NPV (97.6-100%) remained roughly unchanged. The combination of rapid D-dimer tests with a pre-test clinical probability model may help to reduce unnecessary work-up in patients with suspected DVT.

[Vasovagal syncope]. / Vasovagale Synkope.

Vasovagal syncope, also called neurocardiogenic syncope, is common with younger people. It results from an inappropriate, excessive autonomic reflex activity. In the elderly patient the syncope may be provoked by massage of the carotid bodies and is then known as carotid sinus syndrome. The pathogenesis of neurocardiogenic syncope is debated. Sudden vasodilation and/or bradycardia have been attributed to the activation of ventricular mechanoreceptors. The use of betablockers is based on this hypothesis. Head-up tilting at 60 degrees is helpful in the evaluation of syncope. In the therapy of recurrent vasovagal syncope, a thorough information of the patient and an adaptation of behaviour are often successful. Some authors have reported goods results with betablockade, etilefrin or mineralocorticoids. The patient with repeated severe syncopal attacks and asystole may benefit from an implantable DDD pacemaker.

[Acute digitoxin poisoning]. / Akute Digitoxinintoxikation.

We report a case of severe digitoxin poisoning with--as to our knowledge--the highest plasma concentration reported so far (376 ng/ml). On admission, the patient suffered from nausea and vomiting. The ECG showed a complete AV-block which was managed temporarily by pacing. Phenytoin was given for ventricular tachycardias. The plasma potassium level was 7.4 mmol/l. The elimination of the digitoxin was enhanced with cholestyramine and hemoperfusion. Because of persisting arrhythmias, hyperkalemia and a very high digitoxin level, purified Fab fragments of digoxin-specific antibodies (cross-reacting with digitoxin) were administered. After a first dose of 480 mg nausea disappeared readily, and with a second dose of 480 mg cardiac rhythm disturbances and hyperkalemia were overcome. There were no adverse reactions to treatment. We confirm the effectiveness of digoxin-specific Fab antibody fragments in life-threatening digitoxin intoxication.

Atrial antipressor natriuretic peptide: release mechanisms and vascular action in man.

Atrial natriuretic peptide (ANP) release into the human circulation, responses to cardiopulmonary volume changes and natriuretic and vasorelaxant effects were studied in 45 normal subjects and in 12 patients during diagnostic cardiac catheterization. A new radioreceptor assay with a detection limit of 2 fmol/tube for alpha-human ANP (alpha-hANP) was used. In normal subjects plasma ANP was 27.2 +/- 4 pmol/l (n = 45, range 2-80). Right atrial plasma ANP correlated with right atrial pressure (r = 0.813, P less than 0.01), and in four of the patients increases in ANP paralleled the rise in atrial pressure during bicycle ergometry. Reducing venous return by bilateral thigh-cuff occlusion decreased atrial ANP from 66.8 +/- 17.9 to 19.6 +/- 8.0 pmol/l (n = 6, P less than 0.05). Increasing cardiopulmonary volume during 3-h head-out water immersion was associated with an increase in ANP from 16.0 +/- 5.6 to 92.6 +/- 21.5 pmol/l (n = 7, P less than 0.01) followed by transient urinary sodium excretion. The natriuretic threshold plasma ANP concentration during intravenous ANP infusion was 70-80 pmol/l. Atrial natriuretic peptide infused intra-arterially at a maximal forearm vasodilator dose (0.75 micrograms/min per 100 ml forearm tissue) increased forearm blood flow by 7.0 +/- 1.44 ml/min per 100 ml whereas the increase in sodium nitroprusside was 11.1 +/- 1.47 ml/min per 100 ml. Thus, ANP is rapidly released in response to atrial volume and pressure changes and represents a powerful vasodilating and, at high concentrations, natriuretic hormone in man.

[Syncope in elderly patients--which studies are sensible?]. / Synkope beim älteren Patienten--Welche Untersuchungen sind sinnvoll?

In the elderly the cause of a syncope often is difficult to elucidate. A prospective study at the Kantonsspital Liestal (Switzerland) confirmed that history and physical examination together with an ECG at rest are the most important diagnostic tools in the investigation of a syncope. Further investigations such as 24-hour ECG, echocardiography or tilt test should be restricted to situations where history and physical examination support the suspicion of rhythm disturbances or valvular disorder or a vasovagal mechanism. Thus, if an arrhythmia is suspected a 24-hour ECG may produce useful information. Implantable pacemakers are particularly successful in bradycardic arrhythmias. Echocardiography and Doppler-ECG allow to quantify the severity of an aortic stenosis. The insertion of a prosthetic aortic valve is successfully performed also in the elderly. Tilt testing may elucidate the neurocardiogenic mechanism of a vasovagal syncope or a hypersensitive carotis sinus. In such cases a pacemaker or appropriate medication may be indicated.

[Syncope--is patient evaluation of value?]. / Synkope--lohnt sich die Abklärung?

History, physical examination and ECG allow to define the cause of syncope in about 50%. This initial assessment often, in addition, suggests a diagnosis, which is then confirmed with Holter-ECG or echocardiography, stress-ECG, tilt-test, carotissinus test or intracardial electrophysiological testing, rarely neurological or psychiatric evaluations. A stepwise approach is recommended.

[Fatal untoward effect of furosemide: immunocytopenic purpura and cerebral hemorrhage]. / Immunthrombozytopenische Purpura und letale zerebrale Blutung als unerwünschte Wirkung von Furosemid.

A 74 year old man was admitted to the hospital for purpura. The history revealed coronary heart disease. Bypass surgery had been performed 18 months ago. Furosemide had recently been prescribed for cardiac insufficiency and the patient had taken the drug intermittently over two weeks. Laboratory analysis showed severe thrombocytopenia. Despite immediate treatment with intravenous prednisolone and platelet transfusions the patient succumbed to cerebral hemorrhage. Autopsy confirmed a diffuse hemorrhagic diathesis and a cellular response of the bone marrow typical for an acute immune reaction. The start of the purpura nine to ten days after the first dose of furosemide, the exclusion of other possible causes for purpura and the focal proliferation of T-lymphocytes in the bone marrow render it highly probable, that furosemide was responsible for the fatal thrombocytopenia. Furosemide is discussed to have a potential for autoimmunological untoward effects due to its sulfonamide structure. Few case reports describe vasculitic and allergic phenomena. The generation of antibodies against thrombocytes and the depression of megakaryocytic function are thought to be involved. Our patient had been treated with furosemide during the bypass surgery 18 months before the development of purpura. A sensitization to furosemide probably took place at that time.

Glycerol and dextran combined in the therapy of acute stroke. A placebo-controlled, double-blind trial with a planned interim analysis.

The results of clinical trials investigating various therapies in acute ischemic stroke have been inconsistent. The effect of glycerol therapy and a combination therapy of glycerol and dextran was evaluated in a double-blind, placebo-controlled study. Repeated neurologic examinations (Day 0, Weeks 1, 6, 12, and 24) according to a modified Mathew score were performed on 62 patients. Statistical analysis showed no superiority of either treatment compared with placebo in acute ischemic stroke. A retrospective estimation of the Type II error of the study yielded approximately p = 0.25. A major side effect was hemolysis in 98% of patients treated with glycerol.

Cardiac evaluation of candidates for kidney transplantation: value of exercise radionuclide angiocardiography.

In view of the high incidence and mortality of coronary artery disease (CAD) in patients with kidney transplantation, a systematic cardiac evaluation was prospectively performed in 103 uraemic patients eligible for transplantation. After clinical examination, 28 patients with symptoms of CAD or diabetes mellitus were referred directly for coronary angiography, whereas the remaining 75 patients had rest and exercise radionuclide angiocardiography for evaluation of possible asymptomatic CAD. Among them, left ventricular ejection fraction was below 40% at rest or fell during exercise by at least 5 EF% in 12 patients; coronary angiography in nine showed CAD in four and hypertensive heart disease in five. In the remaining 63 (of 75) patients without severe resting left ventricular dysfunction or exercise ischaemia, the follow-up of 28 +/- 7 months revealed no clinical manifestation of CAD. Overall incidence of CAD in symptomatic and asymptomatic patients during a follow-up of 27 months after cardiac evaluation was 20 and 25% in nondiabetic and diabetic candidates for kidney transplantation, respectively (P = n.s.). Thus, clinical examination combined with exercise radionuclide angiocardiography in patients without signs or symptoms of heart disease had a high predictive accuracy for presence or absence of late manifestations of CAD. Exercise radionuclide angiocardiography is therefore a useful method for screening kidney transplantation candidates for asymptomatic CAD.