Atypical heparin-induced thrombocytopenia complicated by intracardiac thrombus, effectively treated with ultra-low-dose rt-PA lysis and recombinant hirudin (Lepirudin).

A serious retroperitoneal bleeding occurred in a 56-year-old male patient receiving unfractionated heparin due to multiple pulmonary embolism. After reducing the heparin dose, the patient developed a new pulmonary embolism and a large thrombus in the right atrium. Concomitantly, the platelet count dropped to a value of 29 g/l. Heparin-induced thrombocytopenia (HIT) was confirmed by a functional assay, the heparin-induced platelet activation (HIPA) assay, whereas the results of a platelet factor 4/heparin complex ELISA were repeatedly negative. This indicated that the patient's HIT antibodies were directed towards an antigen other than platelet factor 4/heparin complexes. For treatment of the atrial thrombus, an ultra-low-dose lysis with rt-PA (2 mg/h, intravenously) was administered for a period of 52 h, overlapping with systemic treatment with recombinant hirudin (Lepirudin, Refludan, 0.06-0.14 mg/kg/h intravenously). The aim was to enhance lysis of the thrombus without increasing the haematoma, and at the same time keep the risk of fulminant pulmonary embolism due to thrombus fragmentation as low as possible. The cardiac thrombus disappeared within 48 h, without new signs of pulmonary embolism. Platelet counts normalized within nine days.

Which amino-acids do serum and hemofiltrate of critically ill patients with acute renal failure contain?

The removal of amino acids during continuous renal replacement therapies induces clinical problems. Previous studies on animals have shown nephroprotective (glycine, alanine) or negative effects (lysine) on renal function in occurrence of acute renal failure. Disturbed metabolism in acute renal failure needs adequate parenteral nutrition. On the other hand, experience with continuous renal replacement therapies of metabolic crises in inborn errors of metabolism indicate a good control of disturbed amino acid metabolism. The aim of our study was to find amino acids, that might play an important role in the pathogenesis, prognosis and detection of acute renal failure and severe illness, so far only estimated by lactic acid. Thirty-three probes (serum and hemofiltrate) were taken from patients, suffering with acute renal failure caused by septic shock, severe pancreatitis and hepatorenal syndrome, one hour after the beginning of extracorporal circulation, the conditions of treatment were standardized. The material was deproteinized and studied by the amino acid analyzer LBK 4251 Apha Plus (Pharmacia, Stockholm, Sweden), while the lactic acid concentration was determined in a standard laboratory. Proline, glycine, alanine, methionine and histidine showed a close relationship to the lactic acid levels, but these amino acids were an essential part of parenteral nutrition. A statistical relationship was also established in (amino acids with amide groups) asparagine, glutamine, citrulline, cystathionine and phosphoethanolamine. The mean values of most of the amino acids were higher than normal, but standard deviations were increased. The presence of these amino acids in hemofiltrate and the good sieving coefficients could mean that the better prognosis of critically ill patients in continuous renal replacement therapies may also be due to continuous control of amino acid levels (especially with amide groups).

[Mycotic complications in patients with chronic liver diseases and pancreatitis]. / Mykotische Komplikationen bei Patienten mit chronischen Lebererkrankungen und Pankreatitis.

UNLABELLED: We studied 15 patients with mostly alcoholic liver diseases and 25 patients with acute or chronic pancreatitis with regard to occurrence of yeasts in different microbiological samples and corresponding serological findings. In about a half of the patients with liver diseases yeast counts and serological titres were already raised in the first mycological investigation. Patients with pancreatitis, however, showed only little or negative cultural and serological results. This changed during the course of disease, where they developed significantly higher yeast counts and serotitres. Finally two case reports are presented: two patients with infected pancreatic pseudocysts (including a case of aspergillosis). CONCLUSIONS: in patients with decompensated chronic liver diseases an early search for mycological complications is recommended. In pancreatic diseases these complications are rather seen later in the course of the disease, especially under intensive care conditions. Therefore, we encourage surveillance cultures and control of serotitres in these patients.

Chronic cyclic strain reduces adenylate cyclase activity and stimulatory G protein subunit levels in coronary smooth muscle cells.

Previous studies from this laboratory have demonstrated that acute cyclic strain causes a reduction in adenylate cyclase activity in cultured coronary vascular smooth muscle cells. The objective of this study was to test the hypothesis that chronic cyclic strain of coronary vascular smooth muscle cells also causes inhibition of adenylate cyclase activity and that this may be related to changes in G protein steady-state levels. Cultured smooth muscle cells obtained from porcine coronary artery were subjected to 24 h of cyclic strain of 20 kPa (24% maximum strain) at 60 cycles/min. Unstretched cells served as controls. Basal, Gpp(NH)p, and forskolin plus Mn(2+)-stimulated adenylate cyclase activities were inhibited significantly in stretched versus unstretched vascular smooth muscle cells. The reduction in adenylate cyclase activity observed after 24 h of cyclic strain was associated with a significant (P < 0.05 vs controls) reduction in steady-state levels of Gs alpha 45, whereas Gi alpha 1,2 and G beta levels remained unchanged. The data support the hypothesis that adenylate cyclase activity and G protein steady-state levels in coronary smooth muscle are sensitive to chronic cyclic strain. It suggests that the G protein adenylate cyclase effector pathway may play an important role in the subacute adaptation of the coronary circulation to changes in intravascular pressure.

Sodium kinetics in salt-sensitive and salt-resistant normotensive and hypertensive subjects.

OBJECTIVE: To test the hypotheses that sodium kinetics are not affected by blood pressure, salt sensitivity, salt resistance or race, and that the kinetics of sodium balance are not a first-order process. DESIGN, PARTICIPANTS AND INTERVENTIONS: Two studies were conducted. In the first, 18 normotensive and 36 hypertensive men and women were given sodium at 120 mmol/day for 6 days, followed by 10 mmol/day for 8 days, then 400 mmol/day for 8 more days. Salt sensitivity was defined as an increase in diastolic blood pressure from the 10 to the 400 mmol/day intake. Salt resistance was defined as no increase, or a decrease in diastolic blood pressure with the increased sodium intake. In the second study, 12 white and 12 black normotensive men ingested sodium at 10, 200 or 400 mmol/day in random order, each for 7 days. All urine was collected in both protocols. SETTING: Metabolic ward at the University of Greifswald (Greifswald, Germany; study 1), and Clinical Research Center (Indiana University, Indianapolis, Indiana, USA; study 2). MAIN OUTCOME MEASURE: In addition to conventional statistics, a pharmacokinetic analysis was carried out to determine the elimination rate constant and half-life. RESULTS: In the Greifswald study, when the sodium intake was decreased, a longer half-life was determined for the salt-sensitive than the salt-resistant hypertensive subjects. The half-life for the normotensive salt-sensitive and salt-resistant subjects did not differ. When the sodium intake was decreased, a monoexponential equation fitted the data for all subjects; when the sodium intake was increased, only data for half the subjects could be fitted to the same equation. In the Indianapolis study, black race had a significant influence upon urinary sodium excretion. Furthermore, the half-life for sodium elimination was dependent upon sodium intake; namely, the greater the intake, the longer the elimination half-life. CONCLUSIONS: The time required to reach sodium balance may increase following salt-sensitive increases in blood pressure rather than precede them. Race influences the time required to achieve salt balance. Sodium kinetics are not a first-order process.

Pharmacokinetics of almitrine in healthy volunteers and patients with essential hypertension.

Pharmacokinetic studies with the arterial chemoreceptor stimulant almitrine (100 mg per os) were performed in 12 healthy volunteers and 8 patients with essential hypertension stage I in order to evaluate the suitability of the drug for physiological tests. The parent compound was determined gas-chromatographically. Almitrine was absorbed with maximal serum levels after 1.8 +/- 0.4 h in healthy volunteers and 1.5 +/- 0.3 h in patients. The elimination proceeded biexponentially with terminal half-lives from 14.6 to 43.4 h in volunteers and 12.5-45.0 h in patients. Further characteristics were large distribution volumes (16.1 +/- 4.5 ml/g in healthy volunteers, 13.9 +/- 4.7 ml/g in patients) and large interindividual variations of all pharmacokinetic parameters by a factor of 2 to 6. Significant differences between healthy individuals and patients were not observed. The drug was well tolerated. The pharmacokinetic properties of almitrine should be included into its evaluation as a test compound.

Hormonal and renal responses to arterial chemoreceptor stimulation by almitrine in healthy and normotensive men.

Healthy and normotensive men (n = 11) were hospitalized and kept under controlled fluid and sodium intake (120 mequ/d) for 5 days. Their systemic arterial blood pressures as well as heart and breathing rates were measured, and venous blood and urine samples were collected at intervals of 1-4 h. Diuresis was induced by scheduled drinking of tea (150 ml/h). Electrolytes, osmolality, and creatinine were determined in both plasma and urine samples. Aldosterone, cortisol, and vasopressin concentrations were measured only in the plasma. On the 2nd and 3rd day of the experiments the participants received orally either a placebo-pill or 100 mg almitrine bismesylate (Vectarion). Each subject was tested in a placebo- and an almitrine experiment. The subjects responded to the almitrine treatment with a suppression of the plasma aldosterone content, a transient rise of glomerular filtration rate, a natriuresis and an increase of renal concentrating ability. In the placebo-experiments, only the transient rise of filtration rate was significant. The data indicate that almitrine, by stimulating the peripheral arterial chemoreceptors, suppresses plasma aldosterone and inhibits renal proximal sodium reabsorption by so far unknown mechanisms. They also suggest that oral and intravenous almitrine administrations, respectively, might differently affect renal hemodynamics and excretory function.