[Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) in 13 children: a case series]. / Thrombolyse mit rekombinantem Gewebe-Plasminogenaktivator (rt-PA) bei 13 Kindern: Eine Fallserie.

Since thromboembolic events (TE) are rare among children there is only limited information on the optimal choice of antithrombotic agents, dose and duration of antithrombotic therapy. Recombinant tissue plasminogen activator (rt-PA) is increasingly used for thrombolytic therapy of organ- and limb threatening thrombosis in children. We investigated retrospectively the efficacy and safety of rt-PA in 13 children treated consecutively between 1996-1999, following the same protocol. The median age was 3.9 years (3 days to 16 years). All children suffered from underlying diseases. In addition, 7 children had cardiac catheters and central venous catheters and two children suffered from Factor V Leiden mutation. Seven children presented with a TE in the arterial system, 6 with one in the venous system. All children were treated with continuous infusion of rt-PA (median dose 0.05; 0.0125-0.2 mg/kg/h) together with low-dose standard heparin (median dose 8; 5-15 IU/kg/h). Thrombolysis was performed for a median time period of 102 hours (6 hours to 16 days). Treatment effects on the thrombus were regularly confirmed by ultrasound. Plasma levels of fibrinogen and haemoglobin decreased moderately during treatment. No cumulative effect or increased dose requirement of rt-PA was detected during extended treatment. Patency of obstructed vessels was achieved in all children. One child developed severe gastrointestinal bleeding. Six children (46%) developed minor bleeding at the site of catheter puncture. One child developed rethrombosis at the site of the previous thrombus 2 weeks after completion of rt-PA treatment. Under rigorous laboratory and ultrasound control, our protocol using low dose rt-PA over a prolonged period of time was effective and safe.

Rebound increase of plasminogen activator inhibitor type I after cessation of thrombolytic treatment for acute myocardial infarction is independent of type of plasminogen activator used.

Plasma concentrations of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), and D-dimer were investigated in 50 patients treated intravenously for acute myocardial infarction with either streptokinase (n = 23), urokinase (n = 17), or recombinant t-PA (rt-PA, n = 10). The fibrinolytic variables were measured by enzyme immunoassay on admission; 1, 2, 4, 6, 8, 12, and 24 h later; and then daily until day 7 after admission. In each subgroup of patients treated with different thrombolytic agents, PAI-1 increased significantly (P < 0.01) approximately 3 h after cessation of thrombolytic therapy. PAI-1 peak concentrations did not differ significantly (P = 0.82) among these three subgroups. t-PA and D-dimer did not differ significantly (P > 0.14) among subgroups except for higher t-PA in the rt-PA group attributable to detection of the therapeutically administered exogenous rt-PA by the t-PA assay. Our findings demonstrate a marked PAI-1 increase after thrombolytic therapy for acute myocardial infarction, which seems to be a common, drug-independent antifibrinolytic rebound phenomenon in response to thrombolytic treatment.

Cardiac troponin I to diagnose percutaneous transluminal coronary angioplasty-related myocardial injury.

The purposes of the present study were to evaluate cardiac troponin 1 (cTnl) in the diagnosis of percutaneous transluminal coronary angioplasty (PTCA)-related myocardial injury in comparison with cardiac troponin T (cTnT) and creatine kinase (CK) MB mass concentration, and to investigate the frequency of myocardial injury, as indicated by myocardial protein release, after clinically symptomless side-branch occlusion (SBO) which may occur in the proximity of the attempted stenosis. The final study population comprised 80 patients undergoing elective, single vessel PTCA. Blood samples were drawn before, 6, 24 and 48 h after PTCA. cTnI, cTnT and CKMB mass baseline values were within the reference intervals in all patients (cTnI < 0.1 microgram/l, cTnT < 0.2 microgram/l, CKMB < 5 micrograms/l). Two patients presented with primary failure of PTCA, and visually successful PTCA was performed in all remaining patients. Seven patients (four with SBO) subsequently developed acute myocardial infarction (AMI). Symptomless SBO occurred in 16 patients. In controls (n = 55) there were no significant increases in cTnI, cTnT, or CKMB concentrations compared with baseline values, and all markers stayed within their reference intervals. In half the patients with symptomless SBO (n = 8) all markers were slightly to moderately increased, in two additional patients only CKMB was elevated (cTnI: 0.1-1.0 microgram/l; cTnT: 0.25-0.81 microgram/l and CKMB: 7.9-25.6 micrograms/l). In the majority of patients with primary failure or AMI we found pronounced increases in all tested markers (cTnI: 0.2-12.0 micrograms/l; cTnT: 0.44-12.10 micrograms/l; CKMB: 19.2-423.0 micrograms/l). The results of this study indicate that cTnI is comparably useful to cTnT or CKMB mass for diagnosing myocardial injury in PTCA patients. From our results a preference for one of the tested parameters cannot be clearly derived. Post-procedural cTnI, cTnT, and CKMB mass values are not higher than baseline values in uncomplicated cases, whereas AMI after PTCA leads to pronounced marker increases. SBO, even when symptomless, leads frequently (in about half the patients) to slight marker increases.

Markers of activated coagulation for early diagnosis of acute myocardial infarction.

Intracoronary thrombosis plays a key role in the pathogenesis of acute myocardial infarction (AMI), and the formation of an occlusive thrombus usually precedes the development of myocardial damage. Therefore we evaluated and compared the early sensitivities of thrombin-antithrombin III complex (TAT), D-dimer, myoglobin, creatine kinase (CK) MB mass concentration, and cardiac troponin T (cTnT) on admission to a coronary care unit (CCU) before heparin or thrombolytic therapy was started. We investigated 31 consecutive patients admitted to CCU for evolving AMI within 6 hours from the onset of infarct-related symptoms; the median delay from chest pain onset to CCU admission was 135 minutes. Of all biochemical markers tested TAT had the highest early sensitivity on admission to the CCU, and TAT was significantly more sensitive than cTnT, CKMB mass, myoglobin, and D-dimer. However, TAT increases give no information about the location of clot formation in the body, and the diagnosis of AMI must be subsequently verified by an increase in more cardiac specific proteins, such as troponins or CKMB.

Cardiac troponin I in the diagnosis of myocardial injury and infarction.

We used a cardiospecific enzymoimmunometric assay to measure cardiac troponin I (cTnI) in samples serially drawn from 78 patients with acute myocardial infarction (AMI), 7 patients with unstable angina (Braunwald class III), 22 multi-traumatized patients, and in 30 athletes after eccentric exercise, as well as in 101 non-traumatic chest pain patients on admission to the emergency department. cTnI assay crossreactivity with crude human skeletal muscle homogenates was < 0.1%. cTnI could not be detected in athletes or multi-traumatized patients except for 2 trauma patients with myocardial damage. Increased cTnI concentrations were found in 6 of 7 patients with unstable angina at rest and in all AMI patients. After AMI, cTnI increased about 3.5 h (median) after the onset of chest pain, reached peak values parallel to CKMB, and stayed increased for at least 4 days. Cardiac troponin T (cTnT) increased and mostly peaked parallel to cTnI. cTnT sensitivity on the 7th day after AMI was significantly higher than that of cTnI. In contrast to cTnI, cTnT mostly showed a second, usually smaller, peak about day 4 after AMI. During the first 4 h after the onset of chest pain and before thrombolytic therapy the sensitivities of myoglobin (0.43) and CKMB mass (0.56) were significantly higher than those of both troponins (cTnI, 0.29; cTnT, 0.25). Areas under receiver operator characteristic curves indicated only moderate diagnostic accuracies of bio-chemical markers for early AMI diagnosis in non-traumatic chest pain patients that cTnI is a highly sensitive and specific marker for myocardial damage which is suitable for early and late diagnosis.

Cardiac troponin T and creatine kinase MB mass concentrations in children receiving anthracycline chemotherapy.

Anthracyclines (doxorubicin, daunorubicin, and derivatives) are among the most effective antineoplastic drugs for pediatric cancer with dose-limiting acute and long-term cardiotoxicity. The exact mechanism of the development of cardiomyopathy is still not clear. Anthracyclines may induce subclinical acute myocardial injury leading to lysis of a limited number of myocytes. Alternatively, myocytes may experience a transient loss of cytoplasmic membrane integrity. Both conditions may lead to a transient efflux of small amounts of cytoplasmic enzymes and other proteins specific to the heart muscle fibers. To test these hypotheses we assayed plasma creatine kinase (CK) MB mass and cardiac specific troponin T (TnT). CKMB may be released even in case of reversible cell membrane injury, while prolonged elevation of TnT is the most sensitive and specific marker of limited myocardial necrosis. Thirty-five anthracycline-containing chemotherapy courses in 22 children with cancer were analyzed. CKMB mass and TnT concentrations were within the normal range in all children before anthracycline therapy. Within 72 hours from anthracycline therapy no increment of one of these two marker proteins was detected (ANOVA for repeated measures, P = 0.94 [TnT] and 0.25 [CKMB]). We conclude that only minimal if any acute necroses of cardiac myocytes occur after anthracycline therapy. Even membrane integrity appears to be maintained within the first 3 days after anthracycline therapy, in the absence of electrocardiographic or echocardiographic signs of acute cardiotoxicity.

Equivalent early sensitivities of myoglobin, creatine kinase MB mass, creatine kinase isoform ratios, and cardiac troponins I and T for acute myocardial infarction.

Early sensitivities of creatine kinase (CK), CKMB (activity and mass), CKMM and CKMB isoform ratios, myoglobin, cardiac troponin I (cTnI), and cardiac troponin T (cTnT) were compared to find the most sensitive serum marker for acute myocardial infarction (AMI) during the first hours after onset of chest pain. In a prospective study we investigated 37 consecutive patients with AMI who were admitted to the coronary care unit within 4 h after onset of chest pain. Blood samples were drawn every hour for the first 10 h after admission. CKMB mass concentrations, CKMM and CKMB isoform ratios, myoglobin, cTnI, and cTnT increased significantly (P < or = 0.0067) earlier than CK and CKMB activity and were also significantly (P < or = 0.046) and markedly more sensitive on admission. Differences in early sensitivities of myoglobin, CKMB mass, CK isoform ratios, cTnI, and cTnT were small and not significant. Therefore, turnaround time and practicality for emergency determination of methods, specificities of markers, the required specificity in the individual patient, and costs mainly determine the choice among myoglobin, CKMB mass, CK isoforms, cTnI, and cTnT.

[Viral hepatitis. Insurance medicine observations]. / Die Virushepatitiden. Versicherungsmedizinische Betrachtungen.

The major cause of liver diseases world-wide are the infectious hepatitis A-E which are due for different viruses. Most of the cases are clinically asymptomatic and without jaundice with a high rate of cure. The diagnosis and the differentiation of the various clinical syndromes are based mainly on serological markers of the involved antigen-antibody-systems. For insurance purposes the chronic hepatitis B, C and D are of great importance. Where chronic persistent hepatitis has a nearly normal life expectancy, chronic active hepatitis which may develop into cirrhosis and/or hepatocellular carcinoma has an increased mortality.

Bone mineral densitometry in dialyzed patients: quantitative computed tomography versus dual photon absorptiometry.

Reduced bone mineral density (BMD) increases risk of fractures, thus making it necessary to monitor patients suffering from chronic renal failure and consecutive disturbance of bone metabolism. In order to evaluate the reliability of available methods, bone mineral density of the lumbar spine assessed with single energy computed tomography (QCT) was compared with bone mineral density of the lumbar spine, femoral neck, Ward's triangle and trochanteric region measured by dual energy photon absorptiometry (DPA) in 45 hemodialyzed patients with a mean hemodialysis duration of 35 +/- 26 months (SD). Depending on the measurement site and method 4-34% of dialyzed patients suffered from reduced BMD (z-score < -2). The highest correlation (r = 0.61, p < 0.01) was found between QCT of the spine, trabecular bone, and DPA of Ward's triangle. One year after baseline measurement bone mineral density was reassessed after randomization to either QCT or DPA in 14 and 18 patients, respectively. Whereas lumbar spine and femoral neck did not change, mean BMD showed a decrease at the measurement sites of Ward's triangle (DPA), trochanteric region (DPA) and trabecular bone of the spine (QCT), which, however, was statistically not significant. Cortical BMD of the spine assessed with QCT showed an increase. Although there is some reduction in bone density at most sites in hemodialyzed patients, no significant bone loss could be demonstrated over the course of 1 year.

[Autoimmune diseases--principles and selected examples]. / Autoimmunkrankheiten--Grundlagen und ausgewählte Beispiele.

Autoimmune diseases present themselves as syndromes of different dysfunctions of the immune system due to multiple disturbances of immuninformation and regulation. Because of the lifelong persistence of the auto-antigen, chronic progredient diseases develop with a variety of symptoms and different stages within the clinical course. It may be that at first glance symptoms of lesser importance, like skin disorders or proteinuria, can be markers of a systemic manifestation of an immunopathy. The underwriting of proposal ought to be based on information of the own and family history as well as on recent clinical and serological findings and on the possible involvement of other organs.

Granulocyte elastase in acute myocardial infarction.

Plasma concentrations of polymorphonuclear granulocytes elastase (PMN elastase) in complex with alpha-1 proteinase inhibitor are a marker of neutrophil activation. The latter complex, creatine kinase and cardiac troponin T, were measured in peripheral venous blood samples serially drawn in 39 patients with acute myocardial infarction. Of the total, 29 received intravenous thrombolytic therapy either with streptokinase (n = 15), urokinase (n = 7) or recombinant tissue type plasminogen activator (n = 7). Creatine kinase activities and cardiac troponin T concentrations were used as markers of myocardial tissue injury. In all patients with acute myocardial infarction, PMN elastase was elevated (median 80 micrograms/l, interquartile range 71 to 100 micrograms/l). Peak and cumulative (area under curve) concentrations of PMN elastase did not correlate closely with determinants of myocardial injury (r < 0.2, n.s.). PMN elastase increased during the first 6 h after starting thrombolytic therapy, whereas it decreased in conventionally treated patients and 12 h later increased. Maximum concentrations of PMN elastase, however, were not significantly higher in patients with thrombolytic therapy than in those without. In acute myocardial infarction patients with complications such as cardiac arrest with subsequent resuscitation (n = 5), cardiac rupture (n = 1) or cardiogenic shock (n = 2), PMN elastase plasma concentrations were significantly higher (p = 0.04) than in uncomplicated infarctions. In the complicated patients, changes in elastase concentrations paralleled or even preceded changes in the clinical presentation. Therefore, thrombolytic treatment seems not to significantly influence the amount of systemic neutrophil activation, but plasma PMN elastase could be a useful marker to monitor and identify complications in acute myocardial infarction.

Plasma immunoreactive endothelin in the acute and subacute phases of myocardial infarction in patients undergoing fibrinolysis.

Endothelin is a potent vasoconstrictor of coronary arteries. We measured plasma concentrations of immunoreactive endothelin (irET) in 46 patients with confirmed acute myocardial infarction (AMI). When compared with irET concentrations in healthy individuals who served as controls, irET concentrations in patients were already significantly elevated at the time of admission (P = 0.002) and remained significantly elevated for at least 2 days after AMI (P < 0.01). IrET concentrations peaked 1 h (mean) after admission (8.5 +/- 3.9 ng/L, P = 0.02 compared with values at time of admission). Reperfusion of the infarct-related artery markedly influenced irET release. Before the start of thrombolytic therapy, irET concentration in patients with early reperfusion did not differ significantly from that of those without early reperfusion. However, irET time courses were significantly (P = 0.03 by analysis of variance) different in patients who did and did not have early reperfusion. In the latter, peak irET concentrations correlated closely with the angiographic left ventricular ejection fraction (r = -0.71, P = 0.03), maximum creatine kinase MB mass concentrations (r = 0.69, P = 0.01), and creatine kinase activities (r = 0.59, P = 0.03). Reflow and reversion of myocardial ischemia are associated with a reduced irET release in patients with AMI.

[Determining normal ultrasound values of the supra- and infraspinatus muscles]. / Sonographische Normalwertbestimmung der Mm. supra- et infraspinatus.

Sonographic investigations concerning thickness of tendons (in longitudinal sections) and muscles (in resting position and isometric contraction) were performed on 60 volunteers without shoulder complaints. Increase in muscle thickness within isometric contraction did not depend on thickness in resting position. There was no side difference in tendon thickness. Since the observed values (median 4-5 mm) were far below measurements cited in the greater part of literature, we tried to verify our data by sonographic and anatomic examination of shoulders of corpses. We conclude that, by standardising, thickness measurement of tendons and muscles might become more important in diagnosis of shoulder complaints.

Endothelin-1 in patients with complicated and uncomplicated myocardial infarction.

Endothelin-1 concentrations were measured in peripheral venous blood samples from 42 patients with acute myocardial infarction. In patients with ischemic or hemodynamic complications (n = 11), endothelin-1 concentrations were significantly higher already on admission (P = 0.008) and remained significantly higher until day 6 after admission compared to patients with uncomplicated infarctions (n = 31; P = 0.035). There were no close correlations between peak concentrations of endothelin-1 and creatine kinase or creatine kinase isoenzyme MB mass in either group. Only in complicated patients did left ventricular ejection fraction correlate closely and inversely with peak endothelin-1 concentrations (r = -0.71; P = 0.03). Therefore, plasma endothelin-1 concentrations in patients with acute myocardial infarction patients may reflect states of markedly depressed cardiac performance and recurrent myocardial ischemia.

Calcitonin gene-related peptide in patients with and without early reperfusion after acute myocardial infarction.

Plasma concentrations of calcitonin gene-related peptide (CGRP), a potent regulator of vascular tone, creatine kinase, myoglobin, and cardiac troponin T were assessed in 31 patients with acute myocardial infarction. In patients who had sustained acute myocardial infarctions, maximum CGRP concentrations (median, 3.2 pmol/L; interquartile range, 1.5 to 4.8 pmol/L) were markedly elevated as compared with healthy control subjects (n = 23; median, 1.02 pmol/L; p = 0.02). However, no marked differences in CGRP levels were observed between patients with early reperfusion (n = 19; median, 3.5 pmol/L) and patients without early reperfusion (n = 12; median, 2.6 pmol/L; p = 0.96), as well as between those with congestive heart failure (n = 8; median, 3.9 pmol/L) and those without congestive heart failure (n = 23; median, 3.2 pmol/L; p = 0.62). CGRP did not correlate closely with myocardial protein release or hemodynamic parameters (heart rate and blood pressure) or the occurrence of arrhythmias. Therefore we conclude that elevated peripheral venous CGRP concentrations in patients who have sustained an acute myocardial infarction are independent of successful reperfusion and hemodynamic state. Although the cause of CGRP increase is not yet identified, CGRP may play a role in the regulation of coronary vascular tone in patients after acute myocardial infarction.

Side-branch occlusion during percutaneous transluminal coronary angioplasty.

Concentrations of creatine kinase (CK) MB mass and cardiac troponin T were measured in serial peripheral venous blood samples from 21 patients who underwent percutaneous transluminal coronary angioplasty (PTCA). Angiography showed side-branch occlusion during PTCA without clinical signs of myocardial injury in 5 patients. After PTCA, CKMB mass concentrations were substantially higher than normal in all 5 patients with side-branch occlusion, and troponin T concentrations were high in 3. By contrast, only 2 patients and 1 patient, respectively, without side-branch occlusion had slight rises in CKMB and troponin T. Release of the contractile protein troponin T reflects more severe damage to myocytes than simple leakage of CKMB. Therefore, myocardial damage induced by side-branch occlusion can be graded by measurement of troponin T in plasma.