[Direct oral anticoagulants and acute stroke : Insights into translational research studies]. / Direkte orale Antikoagulanzien und akuter Schlaganfall : Einblicke in translationale Forschungsarbeiten.

In recent years a considerable number of translational research studies on intracerebral hemorrhage and ischemic stroke have been published, which are characterized by a particular proximity to practical clinical questions. Animal research has provided insights into the pathophysiological processes and therapy effects, which have so far only been insufficiently investigated in clinical studies. This includes the effectiveness of a rapid reversal of anticoagulation in cases of anticoagulation-associated intracerebral hemorrhage and the safety of thrombolytic treatment in ischemic stroke occurring during treatment with anticoagulants. With the approval of the direct oral anticoagulants these problems have become of particular contemporary relevance. Of course, results from experimental translational studies on stroke cannot be directly translated into clinical routine. Nevertheless, these investigations help to understand the underlying processes and mechanisms and provide proof of concept data for new treatment strategies. This review summarizes the most relevant results in this field of research with a particular focus on practical clinical questions.

Intraoperative assessment of kidney allograft perfusion by laser-assisted indocyanine green fluorescence videography.

BACKGROUND: Kidney allograft function crucially depends on the quality of organ perfusion. Duplex sonography, however, frequently reveals hypoperfused segments that remained undetectable to visual inspection intraoperatively. To date, no imaging system supplementing the surgeon's experience has achieved clinical acceptance. The present work examines whether laser-assisted indocyanine green (ICG) fluorescence-videography can be used as a safe and sensitive technique for the intraoperative assessment of renal allograft perfusion. METHODS: Intraoperative assessment of organ perfusion by laser-assisted ICG fluorescence videography (IC-VIEW) was performed in 10 consecutive de novo renal transplantations. The IC-VIEW system allows the visualization of graft perfusion by the fluorescein dye ICG that emits infrared light after exposure to laser light. RESULTS: Perfusion measurements were successful in all 10 transplant recipients. Fluorescence videography produced brilliant, sharply contrasted images of the organs, allowing the detection of even small perfusion deficits. Remarkably, this technique detected 1 large perfusion defect that had remained imperceptible to visual inspection. Repositioning of the graft led to a homogeneous overall perfusion. There were no complications with the ICG injection or the imaging device. CONCLUSION: Laser-assisted ICG fluorescence videography is a feasible and safe technique for the intraoperative assessment of renal allograft perfusion.

Pressure ulcer predictors in ICU patients: nursing skin assessment versus objective parameters.

OBJECTIVE: To evaluate objective parameters and subjective nursing assessment as pressure ulcer risk factors for intensive care unit (ICU) patients, and compared them with the performance of a general assessment tool (Waterlow scale). To validate the newly developed assessment method. METHOD: This prospective epidemiological study involved 698 patients admitted to an ICU between April 2001 and December 2004 without pressure ulcers and who stayed in the ICU for more than 72 hours. Objective parameters routinely determined during the first 24 hours in the ICU as well as subjective nursing assessment on admission were analysed for their significance as pressure ulcer risk predictors. RESULTS: Of the 698 patients 121 (17%) developed pressure ulcers in the ICU. With univariate analysis, a variety of objectively measurable parameters relating to organ dysfunction, circulatory impairment and sepsis showed significant association with the occurrence of pressure ulcers. When multiple logistic regression was performed, subjective nursing skin assessment parameters outweighed these parameters as pressure ulcer risk predictors. A risk function comprised of five skin-related and one other parameter yielded an overall correct pressure ulcer prediction proportion of 84.6%. With receiver-operator characteristic curve analysis, the area under the curve (AUC) was 0.82. Results were validated in 329 patients treated in the same ICU between January 2005 and May 2006, yielding an AUC of 0.80. CONCLUSION: Nursing skin assessment is an important pressure ulcer risk stratification tool in the ICU despite the availability of a large number of objectively measureable ICU specific parameters in these patients.

Nitric oxide in sepsis-syndrome: potential treatment of septic shock by nitric oxide synthase antagonists.

Nitric oxide (NO) is an effector molecule with multiple effects on various organ systems. The most prominent physiological actions of NO as a biological mediator include cGMP-dependent vasodilation and cytotoxicity against pathogens in the unspecific immune defense. Sepsis syndrome is a complex disease entity mostly caused by overwhelming bacterial infections. It has a high mortality rate of 40 to 60%. Catecholamine-resistant hypotension and myocardial depression are regarded as major factors contributing to death in septic patients. In septic shock, a pathophysiologically increased NO production occurs due to an excessive induction of the inducible NO synthase (iNOS). Inducible nitric oxide synthase up-regulation is probably caused by bacterial endo- and exotoxins as well as by an increase of circulating pro-inflammatory cytokines. It may be a key factor leading to pronounced vasodilation and myocardial toxicity. Experimental studies have confirmed that NO overproduction causes severe hypotension in septic animals. Treatment with competitive NOS-inhibitors abolishes this hypotension in animals as well as in septic patients. However, their use is complicated by concomitant decreases in cardiac index and oxygen delivery. Conclusive data on mortality in animals and patients with sepsis-syndrome treated by NOS antagonists are not available. This article discusses current concepts concerning the L-arginine/NO system in the pathophysiology of and as a potential therapeutic target in septic shock.

Prognostic indicators in fulminant hepatic failure.

Because of the inhomogeneous prognosis in fulminant hepatic failure, prognostic criteria are required which help to establish the indication for liver transplantation as a successful therapeutic procedure. In our study of 33 patients with fulminant hepatic failure (94% viral hepatitis, 67% hepatitis B), serum bilirubin > 320 or < 160 mumol/L, serum creatinine > 110 mumol/L, prothrombin time < 15% of the normal value and duration of jaundice until onset of encephalopathy > 7 days indicated a fatal outcome. When criteria described by O'Grady et al. were used, only limited predictability was achieved. This, as well as the frequently contradictory results of the few prognostic studies published so far, is probably due to the regional differences in the etiology and the different clinical courses of fulminant hepatic failure.

Alterations of purine metabolism in mononuclear cell populations of first degree relatives of insulin-dependent diabetic individuals with disturbed glucose tolerance.

In a T lymphocyte and macrophage-depleted mononuclear cell population of the peripheral venous blood of 10 of 41 first degree relatives of insulin-dependent diabetic individuals who had or had had disturbed glucose tolerance adenine uptake rates were significantly increased, the relative adenine incorporation rates into the adenine nucleotides, however, were diminished. Values were compared with those of 30 controls. In 7 of 9 investigated individuals with increased adenine uptake rates antibody-dependent cellular cytotoxicity against rat Langerhans islets (ADCC) was increased in the same cell population. In these individuals the number of diabetes manifestations was relatively high. Adenine uptake rates, ADCC and glucose tolerance changed with time.

Blood rheology in acute myocardial infarction: effects of high-dose i.v. streptokinase compared to placebo.

To compare the haemorheological effects of an i.v. infusion of 1.5 MU of streptokinase with placebo, we investigated the time course of plasma fibrinogen concentration and the haemorheologic parameters plasma viscosity, erythrocyte aggregation and whole blood viscosity at different shear rates during the early phase of acute myocardial infarction until week 3 in 38 unselected patients from the ISAM and ISIS-2 study. Within 3 h, streptokinase led to a near afibrinogenaemia lasting for more than 24 h. Concomitantly, with streptokinase we found a reduction of plasma viscosity, erythrocyte aggregation and whole blood viscosity, whereas with placebo, values showed a slight increase, resulting in significant differences between the groups within the first 2 days. Thereafter, both groups showed an increase in all parameters, values reaching a maximum after 1 week. The streptokinase-induced reduction in blood viscosity may lead to an improvement in microcirculation in the infarction area during the early phase, whereas the hyperviscosity observed independently of therapy after 1 week may lead to an impairment of microcirculation.

Outcome prediction models on admission in a medical intensive care unit: do they predict individual outcome?

Prospectively acquired data from 941 patients staying greater than 24 h in a medical ICU were analyzed to determine the relevance of scoring on ICU admission by the following methods of outcome prediction: Acute Physiology and Chronic Health Evaluation (APACHE II), Simplified Acute Physiology Score (SAPS), and Mortality Prediction Model (MPM). Analysis was performed separately for all patients (group A) and for a subsample (group B), obtained by excluding coronary care patients. Calculation of risk and classification of patients were carried out as recommended in the literature for MPM, APACHE II, and SAPS. In group A, sensitivities (correct prediction of hospital mortality) were 44.7%, 51.1%, and 21.2% and specificities (correct prediction of survival) were 84.5%, 85.4%, and 96.8%, respectively; overall correct classification rates were 73.3%, 75.8%, and 75.6%. In group B, sensitivities were slightly higher, but total correct classification rates did not reach group A levels. Goodness-of-fit testing showed low levels of fit for all methods in both groups. Application of APACHE II to diagnostic subgroups, using disease-adapted risk calculations, revealed marked inconsistencies between the estimated risk and the observed mortality. We conclude that the estimation of risk on admission by the three methods investigated might be helpful for global comparisons of ICU populations, although the lack of disease specificity reduces their applicability for severity grading of a given illness. The inaccuracy of these methods makes them ineffective for predicting individual outcome; thus, they provide little advantage in clinical decision-making.

Impairment of renal function in medical intensive care: predictability of acute renal failure.

Acute causes and chronic risk factors for the development of acute renal failure were analyzed in prospective acquired data of 261 patients in a medical ICU. The population was divided into a group requiring dialysis treatment for established renal failure (n = 95) and a collective maintaining mild renal insufficiency (n = 166). Bivariate and linear discriminant analyses revealed that, above all, variables related to bacterial infections (sepsis and administration of antibiotic agents) and pancreatitis contributed to the discrimination, followed by bleeding, volume depletion, and chronic liver disease in the discriminant function. Bivariate analysis also yielded significant results for mechanical ventilation, CNS depression, and surgery. The importance of the nephrotoxic properties of aminoglycosides may be outweighed by their role as an indicator of severe infectious disease. The overall correct classification rate of the discriminant function was 78.5%, which reflects the importance of the predictor variables, but does not allow individual predictions.

[The protease inhibitor gabexate mesilate in experimentally-induced acute pancreatitis with early gram-negative infection in the Göttingen minipig: therapeutic efficacy and effects on blood coagulation and fibrinolysis]. / Proteaseninhibitor Gabexat mesilat bei der experimentall induzierten akuten Pankreatitis mit früher gram-negativer Infektion am Göttinger Zwergschwein: Therapeutische Effizienz und Auswirkungen auf Blutgerinnung und Fibrinolyse.

Due to its biochemical properties, the newly developed low-molecular protease inhibitor gabexate mesilate is assumed to be efficient in the treatment of complicated acute pancreatitis. This thypothesis was tested using the model of the experimental taurocholate pancreatitis with early artificial E. coli infection in Göttingen mini pigs. Either gabexate mesilate or a placebo was given intravenously 150 min after induction of pancreatitis in a dosage of 2 mg/kg b.w. and h. Median survival time was 15 h in the gabexate mesilate treated animals (n = 7) as compared to 34 h in the placebo group (n = 7); this difference was not significant. The application of gabexate mesilate had no influence on the increased coagulation activity (decrease of prothrombin time, antithrombin III and platelet count) nor on the additional hyperfibrinolysis with concomitant decrease of plasminogen and antiplasmin. Prothrombin time and antithrombin III were less distinctly decreased in the placebo group; decrease of platelet count was more pronounced. On the basis of this study the hypothesis is not confirmed that treatment with gabexate mesilate for necrotizing experimental pancreatitis with additional gram-negative infection has a therapeutic efficiency.

Alterations of purine metabolism in mononuclear cells of individuals at risk of developing type I (insulin-dependent) diabetes mellitus.

For the metabolic characterization of immunocompetent cells which are involved in the development of an insulin-dependent diabetes, a method for measurement of adenine uptake by mononuclear and macrophage-depleted mononuclear cell populations and of incorporation rates into the ATP, ADP, AMP and hypoxanthine fractions of these cells is presented and examined for its informative value in a cross-sectional study of individuals at risk of developing insulin-dependent diabetes. Values of 30 controls were compared with those of 53 risk persons. In controls and in 28 of the risk persons the adenine uptake by mononuclear cells was two to three times higher than that by the macrophage-depleted mononuclear cell population, suggesting high adenine metabolic activity of phagocytic cells. This activity was significantly decreased in the phagocytic cells of the remaining 25 risk persons. Additionally, the adenine incorporation rates into the adenine nucleotides of mononuclear cells were reduced by approximately 50% in these 25 risk persons. The alterations of purine metabolism were found associated with clinical symptoms of transient alterations of glucose tolerance and in the case of manifestation with a mild (HLA DR 3) type of insulin-dependent diabetes.

[Acute myocardial infarct: aspects of changed mortality at the intensive care unit. Results of a prospective study from 1985 to 1987]. / Akuter Myokardinfarkt: Aspekte der veränderten Sterblichkeit auf der Intensivstation. Ergebnisse einer prospektiven Untersuchung der Jahre 1985 bis 1987.

Between 1975 and 1987 the mortality rate among 3143 patients with acute myocardial infarction admitted to an intensive care unit fell from 25% to below 10%. Among 829 patients examined prospectively during three consecutive years, the rate was 12.5% in 1985, 13.1% in 1986, and 9.3% in 1987 (mean of 11.6%). In addition to higher age, other risk factors were identified (mortality in brackets): female sex (14.6%), heart failure (20.6%), and diabetes (19.7%). Hypertension (11.2%) and previous infarct (12.8%) had no influence on mortality rate. The mortality rate was significantly reduced (P less than 0.0003) among 290 patients who had received intravenous fibrinolytic treatment, but this effect was marked only among women, elderly patients and those without risk factors. It is concluded that many measures had led to the observed reduction in acute death rate to about 10%. It is not yet possible to determine which of the different interventions played a part.

[Systemic thrombolysis with short-term streptokinase infusion in acute myocardial infarct]. / Systemische Thrombolyse mit Streptokinase-Kurzzeitinfusion bei akutem Myokardinfarkt.

Within 6 hours after the onset of acute myocardial infarction, 93 patients received a brief high-dose intravenous infusion of streptokinase, 49 patients received 500,000 IU within 30 min and 44 patients received 1,500,000 IU within 60 min. 26 patients had angiography in the acute phase, after 24 hours, and in the 4th week; 52 patients had angiography in the 4th week only; and 15 had no angiography. 7 patients died in hospital and 6 suffered a nonfatal reinfarction. There were no complications with bleeding. In 52% of cases, reopening of an occluded infarct vessel was achieved within 1 hour of the beginning of treatment. During the 4th week after infarction a patent infarct vessel was found in 84%, and 58% had a residual stenosis less than 70%. In contrast, in a control group that received no streptokinase treatment, 25% had a patent infarct vessel and 4% had a residual stenosis less than 70%. Indicative for salvage of ischemic myocardium are a significant improvement in local contraction disorders between the acute phase and the 4th week and a significant correlation between infarct size in the 4th week and beginning of treatment after onset of symptoms. 1. It may be concluded that: brief intravenous infusion of streptokinase results in restoration of blood flow in an infarcted coronary artery in a high percentage of cases; the shorter thrombus-lysis time with intracoronary streptokinase infusion could be made up for by the earlier initiation of intravenous streptokinase treatment; and a conclusive randomized trial is needed to ascertain the true impact of a brief high-dose intravenous infusion of streptokinase on mortality and morbidity following acute myocardial infarction.

[Retrospective evaluations on the importance of laparoscopy in the differentiation of acute oedematous and acute hemorrhagic necrotising pancreatitis in the early stage of the disease (author's transl)]. / Retrospektive Erhebungen zum Wert der Laparoskopie bei der Differenzierung von akuter ödematöser und akuter hämorrhagisch-nekrotisierender Pankreatitis in der Frühphase der Erkrankung.

Of 32 patients with acute pancreatitis on whom laparoscopy was performed within 3 days after the pain symptoms started, the type of inflammation could be assessed in 31 cases. Technically, the intervention did not cause any problems. In one case the examination had to be stopped prematurely due to hypotension, in another case the pain reaction led to premature discontinuance of the examination; other complications did not occur. The present experiences with this morphological diagnostic method have proven to be particularly useful for the indication regarding surgical interventions; it is, therefore, justifiable to compare the value of this method with that of noninvasive morphological methods (ultrasonography, and computer tomography).

[Aggressive aneurysmal bone cyst in childhood (author's transl)]. / Aggressive aneurysmale Knochencyste der Wirbelsäule im Kindesalter.

Case presentation of a four year old child with aggressive aneurysmal bone cyst of the fourth lumbar vertebra. Microscopic examination demonstrates a benign lesion. The roentgenographic pattern reflects a tumorlike bone destruction with signs of malignancy. Clinically, progression and invasion, similar to a semimalignant tumor, is noticed. The possible nature of this aggressive behaviour is discussed.

[Prognosis for patients of an intensive care unit. Myocardial infarct, pulmonary edema, reanimation and severe infections]. / Prognose von Patienten einer Intensivstation. Myokardinfarkt, Lungenödem, Reanimation und bedrohliche Infektionen.

The prognosis of patients should influence diagnostic and therapeutic measurements. For this reason the survival time is shown of 516 patients with acute myocardial infarction, 200 patients with pulmonary edema, 553 patients in which resuscitation had become necessary and 201 with life-threatening infections. The survival time is correlated to clinical signs easily obtainable on admission. Small groups can be selected which with a high degree of probability will die during their stay in hospital. Intensive therapy should be withheld from those patients. But prognostic indices without the probability of error cannot yet be constructed.