Effects of Levosimendan on cardiac function, size and strain in heart failure patients.

Levosimendan improves cardiac function in heart failure populations; however, its exact mechanism is not well defined. We analysed the short-term impact of levosimendan in heart failure patients with ischemic and non-ischemic cardiomyopathy (CMP) using multiparametric cardiac magnetic resonance (CMR). We identified 33 patients with ischemic or non-ischemic CMP who received two consecutive CMR scans prior to and within one week after levosimendan administration. Changes in LV ejection fraction (LVEF) and LV volumes, as well as changes in strain rates, were measured prior to and within one week after levosimendan infusion. LV scarring, based on late gadolinium enhancement (LGE), was correlated to changes in LV size and strain rates. Both LV endiastolic (EDV) and endsystolic volumes (ESV) significantly decreased (EDV: p=0,001; ESV: p=0,002) after levosimendan administration, with no significant impact on LVEF (p=0.41), cardiac output (p=0.61), and strain rates. Subgroup analyses of ischemic or non-ischemic CMP showed no significant differences between the groups in terms of short-term LV reverse remodeling. The presence and extent of scarring in LGE did not correlate with changes in LV size and strain rates. CMR is able to monitor cardiac effects of levosimendan infusion. Short-term follow-up of a single levosimendan infusion using CMR shows a significant decrease in LV size, but no impact on LVEF or strain measurements. There was no difference between patients with ischemic or non-ischemic CMP. Quantification of LV scarring in CMR is not able to predict changes in LV size and strain rates in response to levosimendan.

[Dangerous intoxication from extreme serum concentrations of methaqualone metabolites. Detection and quantification of biosynthesis with gas chromatography-mass spectrometry]. / Lebensbedrohliche Intoxikation durch extreme Serum-konzentration eines Methaqualonmetaboliten. Nachweis und Quantifizierung mittels Biosynthese und Gaschromatographie-Massenspektrometrie.

CLINICAL COURSE: We present a potentially fatal case of acute methaqualone (M) poisoning with very low serum concentrations of M but extremely high levels of its metabolite, 2-methyl-3-(2-hydroxymethyl-phenyl)-4 (3H)-chinazoline (Met-1). A 23-year-old man was admitted to the intensive care unit 2 days after ingestion of 4-5 g M in an suicidal attempt. On admission he was somnolent and poorly responsive to painful stimuli. Physical examination revealed a heart rate of 95 bpm, a blood pressure of 125/65 mmHg, and a normal body temperature. His chest was clear to auscultation, respirations were shallow, and the skin was cyanotic. The electrocardiogram was unremarkable. The chest radiograph showed a normal heart size without pulmonary infiltrates or venous congestion. The pupils were dilated but reactive to light. The neurologic examination was further remarkable for increased limb reflexes, myoclonia, and positive pyramidal signs. During the next 2 days the patient became comatose and developed respiratory insufficiency due to non-cardiogenic pulmonary oedema, which was confirmed by chest radiograph and haemodynamic investigations by means of right heart catheterisation. He required mechanical ventilation for 6 days. Finally, he recovered completely and was discharged in good condition. DIAGNOSTICS: A lumbar puncture revealed neither blood nor pleocytosis in the cerebrospinal fluid. Cranial computed tomography was carried out on an emergency basis, but no abnormality was disclosed. An electroencephalogram did not exhibit any significant pathological findings. Testing for infectious diseases or porphyria gave negative results. Toxicological screening based on enzyme immunoassays (ELISA) was negative for alcohol, tricyclic antidepressants, benzodiazepines, barbiturates, and morphine, but gave a positive result for M. From the moment of admission daily blood samples were taken and analysed by combined gas chromatography and mass spectrometry. These showed very low levels of M but extremely high levels of Met-1. THERAPY: After gastric lavage, continuous enteric lavage with activated charcoal and mannitol was initiated to minimise intestinal absorption. Since M was hardly detectable in the serum, haemoperfusion was not regarded as indicated for drug elimination and treatment was restricted to general supportive measures. To rule out a central anticholinergic syndrome, an anticholinesterase drug (physostigmine) was administered but remained without therapeutic effect. CONCLUSIONS: The presented case is the first report of a life-threatening intoxication after M ingestion primarily caused by Met-1. It supports the significance of this metabolite for the toxic effects of the drug. A toxicological screening test based on ELISA proved helpful due to its cross-reactivity with metabolites. In cases similar to ours, resin haemoperfusion may be indicated to remove the metabolites despite low detectable concentrations of the parent substance in the serum.

Increased serum concentrations of adhesion molecules after coronary angioplasty.

1. Reocclusion is still a significant complication after percutaneous transluminal coronary angioplasty. The injury of coronary arteries resulting from PTCA plays an important role in the pathophysiology of both abrupt closure and late restenosis after an initially successful procedure. Cytokines play a pivotal role in the accumulation of circulating blood cells at the endothelium and are known to regulate their interaction with the vessel wall. 2. To obtain further information about this interaction, serum concentrations of soluble endothelial leukocyte adhesion molecule 1 (sELAM-1), leucocyte endothelial cell adhesion molecule 1 (sL-selectin), intercellular adhesion molecule 1 (sICAM-1), interleukin 2 receptor (sIL-2R) and interleukin 8 (IL-8) detected by enzyme-linked immunosorbent assay were monitored in 30 consecutive patients referred for elective PTCA. Fifteen patients who underwent elective coronary angiography without PTCA served as controls. 3. All patients underwent successful first PTCA. Within 24 h the serum concentrations of sELAM-1 increased gradually from 21.7 (SD 7.1) to 48.2 (SD 8.6) ng/ml (P < 0.01); levels of sL-selectin rose from 982.1 (SD 128.7) to 1541.3 (SD 104.6) ng/ml after 48 h (P < 0.01). Serum levels of IL-8 remained stable initially, but peaked at the end of the observation time of 72 h (9.4, SD 3.8, versus 16.1, SD 4.9 ng/ml; P < 0.05). A positive correlation was found between the number of dilatations and the rise in these parameters (P < 0.01). No significant changes were found in the serum concentrations of sICAM-1 and sIL-2R after PTCA or in any of the parameters in patients after coronary angiography. 4. We conclude that PTCA induces a significant rise in the concentration of certain adhesion molecules in serum. Thus, we provide preliminary data on the potential role of cytokines for blood cell-endothelium interaction after PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial infarction after chronic ergotamine abuse.

As a result of chronic ergotamine abuse, reversible arterial narrowing has been documented angiographically in peripheral, but not in coronary arteries. We report on a patient with no cardiovascular risk factors, but because of chronic ergotamine abuse suffered on acute myocardial infarction, complicated by ventricular fibrillation. Coronary angiography performed 3 days after resuscitation revealed a distal occlusion of the left anterior descending artery. Three months later, spontaneous recanalization had occurred, and no residual narrowing was seen angiographically. Thus, surveillance of patients with migraine headache to avoid chronic ergotamine abuse is recommended to prevent cardiovascular complications.

Serum concentrations of immune parameters during acute cardiogenic pulmonary edema.

OBJECTIVE: To evaluate the effect of acute cardiogenic pulmonary edema on the concentrations of immune parameters in serum. DESIGN: Prospective, controlled study. SETTING: Medical ICU. PATIENTS: Twenty-four consecutive patients with acute pulmonary edema who had significant clinical improvement within 30 mins and did not show any evidence of either tissue damage or infection. For comparison, 25 healthy, age-matched controls and 25 patients with mild chronic heart failure were also studied. INTERVENTIONS: Treatment with oxygen, nitrates, and loop diuretics. MEASUREMENTS: Lymphokines, acute-phase reactants, and cortisol concentrations were measured in serial serum and plasma samples. MAIN RESULTS: Serum concentrations of soluble CD-8 antigen (soluble CD-8) decreased from 928 +/- 124 (SEM) U/mL on admission to 712 +/- 112 and 579 +/- 67 U/mL after 2 and 6 hrs, respectively (p less than .05, p less than .01), and returned to baseline values within 48 hrs (853 +/- 109 U/mL). Concentrations of soluble interleukin-2 receptor increased from 721 +/- 71 to 1078 +/- 112 and 1226 +/- 128 U/mL 12 and 36 hrs, respectively, after admission (p less than .05, p less than .01). Plasma cortisol concentrations were markedly increased on admission (56.9 +/- 4.7 vs. 13.1 +/- 1.3 micrograms/dL after recovery, p less than .001). Increased cortisol concentrations coincided with the nadir of soluble CD-8. Tumor necrosis factor-alpha remained within normal limits in all patients. Neither acute-phase reactants nor angiotensin converting enzyme activity showed significant changes during the observation period. CONCLUSION: The present results indicate significant alterations in the serum concentrations of immune parameters as an effect of an uncomplicated acute cardiogenic pulmonary edema.

[Intensive care of cerebral hemorrhage]. / Intensivmedizinische Betreuung bei intrazerebraler Blutung.

Critically ill patients with intracerebral hemorrhage require immediate treatment in an intensive care unit. In the acute phase of the disease the patients are endangered from increased intracerebral pressure, respiratory disorders (aspiration!) and hypertension. An adequate intensive care management consisting of sedation, analgesia, intubation and mechanical ventilation, correct body positioning and treatment of hypertension is of decisive importance for the prognosis of these patients. The aim of this report is to discuss the most important therapeutic strategies and arising problems in the course of intracerebral hemorrhage.

Case report: acute renal failure, thrombocytopenia and nonhemolytic icterus probably caused by mefenamic acid (Parkemed)-dependent antibodies.

A 65-year-old, previously healthy man developed acute renal failure, severe thrombocytopenia and hepatic icterus after a small dose of mefenamic acid (Parkemed). Drug-dependent antibodies reacting against platelets could be identified as the most probable cause for this acute and rapidly reversible disorder. A concomitant hemolytic reaction was not observed and accordingly no drug-dependent red cell antibodies could be demonstrated. The drug-specific antibodies were found only during the acute phase using the platelet immunofluorescence test and a solid-phase immunoassay but not with the monoclonal antibody specific immobilization of platelet antigens assay. After discontinuation of the drug the patient steadily improved and fully recovered until day 22 after admission and drug removal. The clinical course strongly suggests that drug-dependent antibodies against mefenamic acid and/or its metabolites reacting by immune complex mechanism were responsible not only for the thrombocytopenia but also for the renal and hepatic failure.

Beta-2-microglobulin for differentiation between ciclosporin A nephrotoxicity and graft rejection in renal transplant recipients.

The clinical relevance of daily measurement of beta 2-microglobulin in serum and urine was evaluated in 49 patients undergoing renal transplantation. The changes in beta 2-microglobulin levels were compared to standard parameters for assessment of renal function. One hundred episodes of acute deterioration of renal function, clinically diagnosed as rejection, were analyzed retrospectively: (1) In 18 episodes renal malfunction did not respond to methylprednisone but improved immediately upon dose reduction of ciclosporin A, thus indicating a nephrotoxic effect of the drug. In these cases a mean increase of beta 2-microglobulin in urine as high as 7.9 mg/l was observed while serum values decreased. (2) Fifty episodes of apparent rejection (responsive to steroids) were preceded by a 3-day lasting continuous rise of beta 2-microglobulin in serum of up to 3.6 mg/l as a mean with only a moderate elevation in urine. (3) In 13 episodes antirejection treatment could have been avoided as continuously declining laboratory parameters indicated spontaneous improvement of renal function. We conclude that parallel determination of beta 2-microglobulin in serum and urine allows to differentiate between ciclosporin A nephrotoxicity and rejection in 91% of the cases.

Transient hyperoxaluria after ingestion of chocolate as a high risk factor for calcium oxalate calculi.

In 6 male subjects the diurnal variation of urinary oxalic acid excretion was studied after ingestion of chocolate, a food stuff rich in oxalic acid. The ingestion of chocolate caused a striking but transient increase in urinary oxalic acid excretion due to its absorption in the upper gastrointestinal tract. The peak excretion rates occurred 2-4 h after the intake of the chocolate. The peak values were 235% of the fasting excretion rate in the trial with 50 g chocolate and 289% in the trial with 100 g chocolate and reached the amounts found in cases with primary hyperoxaluria. The administration of ranitidine had no influence on oxalic acid absorption. The transient hyperoxaluria observed seems to be an important factor for the formation of calcium oxalate calculi in patients on risk for stone disorders.

[Prevention of stress hemorrhage in an internal medicine intensive care station: sucralfate versus ranitidine]. / Stressblutungsprophylaxe auf einer internen Intensivstation: Sucralfat versus ranitidin.

Stress ulcer bleeding is a serious complication of critical illness and is associated with increased morbidity and mortality. For the prophylaxis of stress ulcers, antacids, H2-blockers, or sucralfate are prescribed. While H2-blockers inhibit the secretion of gastric acid, sucralfate appears to provide protection without reducing levels of gastric acid. Inhibition of acid secretion increases gastric pH, allowing bacterial overgrowth of the stomach by Gram negative bacteria, which colonize the pharynx and trachea and increase the risk of nosocomial pneumonia. For this reason, H2 blockers appear disadvantageous, though they offer adequate prophylaxis for stress ulcer bleeding. As it does not increase gastric pH, sucralfate provides adequate protection against Gram negative gastric overgrowth, however its prophylactic efficacy is not generally accepted. Therefore, we compared the H2-blocker ranitidine to sucralfate in the prophylactic treatment of stress ulcer bleeding and studied the incidence of positive bacteriological findings in the blood and bronchial secretions of the two groups. In a randomized study, 84 patients undergoing general intensive care received either ranitidine (6 x 50 to 6 x 100 mg daily i.v.) or sucralfate (6 x 1 g via gastric tube or per os). Both groups were comparable with respect to age, underlying disorders, and factors predisposing to the development of stress ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of nephrotoxic cyclosporine peak concentrations by daily drug division in 3 equal oral portions.

Nephrotoxicity is the main side effect of cyclosporine therapy. In this study 2 groups consisting of 6 kidney transplant recipients were investigated. The oral cyclosporine daily dose was in the first group 13 mg/kg, in the second 11 mg/kg, respectively. In both groups, the daily dose was divided on the first day of investigation in 2 equal portions given at an interval of 12 hours. On the second day, the same dose was divided in 3 equal portions given at an interval of 8 hours. After cyclosporine administration twice a day very high blood cyclosporine peak concentrations (two to three times higher than the therapeutic range) were measured. These potential nephrotoxic cyclosporine concentrations could be prevented by cyclosporine application in 3 equal portions. A reduction of the daily dose in the early period after kidney transplantation to a starting daily dose of 12 mg/kg or even 10 mg/kg can be recommended.