Mode of action of psoralens, benzofurans, acridinons, and coumarins on the ionic currents in intact myelinated nerve fibres and its significance in demyelinating diseases.

The actions of psoralens, benzofurans, acridinons and coumarins on the ionic currents in intact myelinated nerve fibres were investigated. All 6 substances blocked the potassium currents in a time-dependent manner, producing so-called K+ transients. Only 5-methoxypsoralen is a largely selective blocker of predominantly the axolemmal potassium channels, which is the characteristic required by our previously proposed working hypothesis for the mechanism of potassium-channel blockers in demyelinating diseases, in particular multiple sclerosis. If the observed K+ transients were to arise by blocking of the potassium channels of the Schwann cell, that is, by the periaxonal accumulation of K+ and a resulting collapse of the electromotive driving force for potassium-ions, according to a modified version of our previous hypothesis the other substances tested could also have a beneficial effect on the impaired impulse conduction in demyelinated axons. In this case a large number of new potential drugs would be available for the symptomatic therapy of MS.

Insulin glulisine: a faster onset of action compared with insulin lispro.

AIM: This randomized, single-centre, double-blind, crossover study compared the pharmacodynamic and pharmacokinetic properties of two different doses of insulin glulisine (glulisine) and insulin lispro (lispro) in lean to obese subjects. METHODS: Eighty subjects without diabetes, stratified into four body mass index (BMI) classes (<25, >or=25 to <30, >or=30 to <35 and >or=35 kg/m(2)), were randomized to receive single injections of glulisine and lispro (0.2 and 0.4 U/kg) on four study days under glucose clamp conditions. Glucose infusion rates (GIR) and insulin (INS) concentrations were assessed for 10 h postdose. RESULTS: Glulisine showed a greater early metabolic action than lispro [GIR-area under the curve (GIR-AUC) between 0 and 1 h (0.2 U/kg: 102.3 +/- 75.1 vs. 83.1 +/- 72.8 mg/kg, p < 0.05; 0.4 U/kg: 158.0 +/- 100.0 vs. 112.3 +/- 70.8 mg/kg, p < 0.001)], with an earlier time to 10% of total GIR-AUC (0.2 U/kg: 1.4 +/- 0.4 vs. 1.5 +/- 0.4 h; 0.4 U/kg: 1.4 +/- 0.3 vs. 1.5 +/- 0.3 h, p < 0.05). The total metabolic effect was not different between the two insulins. In accordance with these findings, the time to 10% of total INS-AUC was faster with glulisine compared with lispro at either dose (0.2 U/kg: 0.7 +/- 0.2 vs. 0.8 +/- 0.2 h; 0.4 U/kg: 0.8 +/- 0.2 vs. 0.9 +/- 0.2 h, p < 0.001). The faster rise in insulin concentrations and the earlier onset of activity of glulisine vs. lispro was consistently observed in each individual BMI class. CONCLUSIONS: Glulisine shows a faster onset of action than lispro, independent of BMI and dose.

[Purulent pericardial effusion with tamponade: a rare initial manifestation of o pneumococcal infection]. / Purulenter Perikarderguss mit Tamponade. Seltene Primärmanifestation einer Pneumokokkeninfektion.

HISTORY AND FINDINGS: A 70-year-old man, admitted for a haemorrhoid operation, suddenly went into circulatory shock (heart rate 150/min, blood pressure 100/70 mm Hg), necessitating transfer to an intensive care unit. His neck veins were prominent and he had a paradoxical pulse. Heart sounds were distant and there was an arrhythmia (atrial fibrillation in the ECG). No murmurs were heard. Breath sounds were decreased, especially in the lung bases. INVESTIGATIONS: Differential blood count showed 30% stab cells with 12,200 white cells per microliter. Erythrocyte sedimentation rate was 118 mm in the first hour, C-reactive protein was raised to 11.8 mg/dl. There was a partially compensated respiratory acidosis (pH 7.12; pO 93.4 mm Hg; pCO 16.3 mm Hg; base deficit -22.6 mmol/l). In the chest radiogram the cardiac silhouette was greatly enlarged bilaterally. The echocardiogram demonstrated a large pericardial perfusion with a "swinging heart". TREATMENT AND COURSE: At pericardial needle puncture 700 ml of amber-coloured fluid, containing pneumococci, were aspirated with immediate circulatory improvement. Penicillin, 10 mill.U twice daily for 13 days, was administered intravenously, followed by amoxycillin, 1 g three times daily by mouth, for a further 15 days. In addition he was given anti-inflammatory treatment with diclofenac and methylprednisolone. Despite this pericardial effusion recurred after 14 days and 600 ml of sterile fluid were removed. Subsequently the inflammatory signs disappeared. Three months later no effusion was present and there were no signs of constrictive pericarditis.

[A catheter for imaging the persistent ductus arteriosus]. / Ein Katheter zur Darstellung des Ductus arteriosus persistens.

Nonsurgical techniques for patent ductus closure require precise knowledge of ductus diameter, length and shape. Angiographic visualization, especially in adults, may be difficult, due to the high flow and overlap of the aorta or the pulmonary artery. We have developed a new catheter for visualizing a patent ductus without intraarterial injection of contrast dye. A smooth latex balloon is mounted near the tip of this catheter and when it is filled with dye, the balloon fits the contours of the ductus. Ductus diameter may be established by measuring the diameter of the balloon. Furthermore, the hemodynamic consequences of ductus closure may be observed with the balloon occluding the ductus.

Transfemoral plug closure of patent ductus arteriosus.

A patent ductus arteriosus should be closed because of its hemodynamic significance and/or the risk of infective endocarditis. Mortality of surgery is low. In adults, however, technical problems can arise due to calcification of the ductus walls. Using the transfemoral plug technique, developed by Porstmann, we attempted a ductus closure without surgery on 35 patients. The youngest was an 11-year-old girl, the oldest a 63-year-old woman (mean age of all patients: 37 years). The pressure in the pulmonary artery ranged from 15/5 to 70/27 mmHg, the diameter of the ductus from 2 to 9 mm (mean: 4.4 mm). According to the size and shape of the ductus, a plug of polyvinyl alcohol (Ivalon) with an inner steel wire frame was prepared. Threaded over a long arterio-transductal venous track wire, the plug was introduced into the femoral artery and advanced into the ductus by a pushing catheter. After removal of the track wire the plug remained wedged in the ductus. In all 35 patients, transfemoral ductus closure was possible. Patients with complaints improved remarkably within some days. Heart size and pulmonary congestion decreased considerably. All patients were followed for a period of 1-46 months. In two of them, the ivalon plug embolized into a side branch of the left pulmonary artery 7 and 2 weeks after the procedure, but without serious consequences.(ABSTRACT TRUNCATED AT 250 WORDS)

[Trans-femoral ductus Botalli occlusion in patients over 60 years of age]. / Transfemoraler Ductus-Botalli-Verschluss nach dem 60. Lebensjahr.

A persistent ductus arteriosus was occluded with an ivalon-plug introduced through the femoral artery in 14 patients over 60 years old (61 to 70 years). Two patients had previous surgery. The maximum left-to-right shunt was 53%, the maximum pulmonary artery pressure 54/24 mm Hg. In all patients ductus occlusion was successful and permanent. Bleeding at the puncture site in two patients could be stopped by manual compression. During a follow-up period of up to 5 years there were no instances of recanalization.

[Transfemoral closure of the duct of Botallo. Acute and long-term results]. / Transfemoraler Ductus-Botalli-Verschluss. Akut- und Langzeitergebnisse.

A persistent ductus arteriosus was occluded with an Ivalon plug via a catheter delivery system, introduced through the femoral artery, in 38 patients, aged 11-72 years (mean 39). The mean diameter of the ductus was 4.5 +/- 1.2 (2-9) mm, mean pulmonary artery pressure 30/12 (15/5-70/27) mm Hg. In two patients the plug became dislocated after two and seven weeks, respectively, without serious consequences. In all others the occlusion was successful and permanent. There were only a few complications and none was serious. During a follow-up period of up to four years there were no instances of recanalization or further plug dislocation.