[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.

[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.

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.

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.

[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.

[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.

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).

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.

[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 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)

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.

Acute hemodynamic effects of MDL 19205 in mild congestive heart failure.

MDL 19205 4-ethyl-1-,3-dihydro-5-(4-pyridinylcarbonyl)-2H-imidazol-2-one, a new cardioactive agent, has been shown to increase myocardial contractile force in animals. It is effective by both oral and intravenous routes. We studied 11 patients with congestive heart failure--in 10 cases owing to coronary artery disease, and in one to cardiomyopathy. All patients had symptoms of NYHA class II or III, left ventricular ejection fractions (LVEF) less than 55%, and left ventricular end-diastolic pressures (LVEDP) greater than 15 mm Hg. Following routine coronary angiography and ventriculography, 0.5 mg/kg MDL 19205 was administered intravenously over 5 min to six patients. Thirty minutes after injection, hemodynamic measurements and ventriculography were repeated. Mean LVEF increased from 42 to 49% (p less than 0.05 for baseline vs. 30 min). In five patients ventriculography was repeated 60 min after placebo administration: LVEF decreased from 45 to 40%. LVEDP decreased from 29 +/- 8 to 16 +/- 8 mm Hg after MDL 19205 administration (p less than 0.05) and remained constant at 24 mm Hg in the placebo group. The small although nonsignificant increase of LVdP/dt after MDL 19205 administration (10 +/- 33%), together with a considerable decrease in LVEDP, was consistent with a positive inotropic effect. LVdP/dt/total pressure developed (VPM), a measure of contractility relatively independent of changes in pre- and afterload, increased from 1.0 +/- 0.3 to 1.3 +/- 0.3 s-1 (p less than 0.05). Neither parameter of contractility (LVdP/dt and VPM) changed significantly in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

[Aortocoronary bypass operation in the elderly patient: favorable long-term course]. / Aortokoronare Bypass-Operation beim älteren Patienten: Günstiger Langzeitverlauf.

Age has been identified as an independent risk factor for coronary artery bypass grafting (CABG). We evaluated, therefore, the perioperative phase and long-term prognosis of all patients over the age of 64 (n = 80), who had been operated on for coronary heart disease at the University Hospital of Basel/Switzerland between 1979 and 1983. These elderly subjects were compared to 80 patients, 50 to 60 years old at the time of CABG, who were matched for degree of angina pectoris, coronary artery disease, left ventricular ejection fraction, sex and year of operation (matched-pairs analysis). Evaluation of long-term prognosis was based on regular clinical controls and on a questionnaire, sent to the patients in June 1984. During the perioperative phase 3 patients over 64 died versus 0 in the group of patients 50-60 years old. There were more complications in the older group (perioperative myocardial infarction 10 vs. 4, pulmonary embolism 2 vs. 0, cerebro-vascular insult 4 vs. 0). Three vs. one permanent pacemaker had to be implanted for irreversible AV-block. The difference in hospital stay, 21 vs. 19 days, was not significant. The cumulative survival rate was in both groups 95% after one year and 86 vs. 92% 5 years after CABG (difference not significant), despite the fact that significantly more elderly patients have had myocardial infarction prior to CABG. After an average follow-up of 28 months, 72% vs. 60% were without thoracic pain; 63 vs. 49% considered themselves in a good overall condition.(ABSTRACT TRUNCATED AT 250 WORDS)