Effects of temperature on the therapeutic efficacy and pharmacokinetics of ifosfamide.

The influence of tumor temperature (28, 32, 37, 39, 41, or 43 degrees C for 1 h) on the therapeutic efficacy of i.v. single bolus injections of ifosfamide (IFO) (32, 65, 125, or 250 mg/kg body weight) in human tumor xenografts (MX1 breast carcinoma) grown in nude mice (n = 240) was studied. Tumor temperature was controlled by water bath immersion. Sixty days after treatment the percentage of tumor-free survival was determined. For example, at 37 degrees C IFO in a dose of 65 mg/kg body weight led to 10% tumor-free survival in the treated animals. At 43 degrees C the same dose resulted in 60% tumor-free survival. A clear drug dose- and temperature-dependent increase of the therapeutic efficacy of an active oxazaphosphorine compound was also demonstrated in vitro. The concentrations of IFO and of 4-hydroxyifosfamide in blood and tumors at different body temperatures (controlled by water bath immersion) were determined over 120 min and WBC counts were obtained. The half-lives and the areas under the curve for IFO in blood were not significantly different at 37 degrees C and 41 degrees C. Since the half-life of IFO depends mainly on hepatic metabolism, the similarity of half-lives and of areas under the curve for IFO at 37 degrees C and 41 degrees C indicates a constant activation rate. However, significantly lower plasma concentrations of the activated drug at a liver (body) temperature of 41 degrees C, compared with 37 degrees C, were found, indicating a higher elimination rate. The concentration of the activated drug in the tumors within the initial 60 min at 41 degrees C, however, exceeded by > 2-fold that at 37 degrees C. The bone marrow toxicity of the same drug dose did not significantly increase with body temperature.

Detection of a hypercoagulable state in nonvalvular atrial fibrillation and the effect of anticoagulant therapy.

The purpose of the study was to evaluate alterations of the hemostatic system and the effect of anticoagulant therapy in nonvalvular atrial fibrillation. A set of molecular hematologic markers was measured prospectively in 69 patients with atrial fibrillation and 28 age-matched patients in sinus rhythm. Significantly elevated levels of thrombin-antithrombin III complex (8.5 +/- 1.6 vs. 2.5 +/- 0.3 micrograms/l; p < 0.001), fibrin monomers (27.1 +/- 3.2 vs. 13.4 +/- 3.7 nM; p < 0.001), D-dimers (788 +/- 76 vs. 405 +/- 46 micrograms/l; p < 0.005), and tissue-type plasminogen activator (9.6 +/- 0.5 vs. 7.2 +/- 0.5 micrograms/l; p < 0.05) were observed in patients with atrial fibrillation compared to those in sinus rhythm. In a subgroup of patients in whom anticoagulant therapy with oral coumadin or standard intravenous heparin was established after the initial study, hemostatic activation decreased significantly. In conclusion, molecular hematologic markers indicate a hypercoagulable state in atrial fibrillation which may characterized a group of patients at elevated risk of thromboembolic disease.

Intermittent regional therapy with rt-PA is not superior to systemic thrombolysis in deep vein thrombosis (DVT)--a German multicenter trial.

In a prospective and randomized multicenter trial the efficacy of intermittent regional and systemic thrombolytic therapy for DVT was evaluated. 137 patients with phlebographically confirmed acute DVT above the calf region were treated with 20 mg of rt-PA for 4 h each day. Thrombolysis was applied either locally via a dorsal pedal vein of the firmly bandaged affected leg or systemically using a cubital vein. Treatment lasted for 4-7 days, and during this time unfractionated heparin was applied continuously with the dosage adjusted according to aPTT (1.5-2.0 times the normal value). A second phlebography was performed within 24 h after the end of treatment. Results were evaluated by an independent radiologist who was unaware of the treatment given. Significant thrombolytic results (e.g. lysis of more than 50% of the original thrombus and complete recanalization of all affected veins) were reached in only 1/3 of all patients. Rates of recanalization did not differ in both groups and bleeding complications occurred in 26.5%. We conclude that intermittent local or systemic application of 20 mg rt-PA seems to be ineffective in the treatment of DVT.

Influence of induction of HSP70 on the cytotoxicity of oxazaphosphorine compounds and cisplatin.

Induction of HSP70 and thermotolerance may also decrease the cytotoxicity of cytostatic agents or their combination with hyperthermia in clinically used thermochemotherapy. HSP70 and thermotolerance were induced by hyperthermia (42 degrees C, 1 h) in two human tumor cell lines in vitro and in vivo. The influence of thermotolerance on the cytotoxicity of CDDP and the oxazaphosphorine compounds Mafo and Ifo and their combination with hyperthermia (42 degrees C or 43 degrees C, 1 h) were studied. The results show that neither thermotolerance nor HSP70 affects the tumor cell sensitivity to CDDP or oxazaphosphorine compounds. However, the additive effect of hyperthermia and CDDP was found to be attenuated in thermotolerant cells. The cytotoxicity of oxazaphosphorine compounds combined with hyperthermia was not altered after preheating, suggesting a different mechanism may be responsible for the drug-hyperthermia interaction of CDDP and oxazaphosphorine compounds. There were no differences between in vitro and in vivo results suggesting mechanisms at the cellular level being responsible for the influence of thermotolerance on drug- and drug-hyperthermia action.

First clinical application of the Medos-HIA ventricular support system: monitoring of the thrombotic risk by means of the biomarker prothrombin fragment F1 + 2 and scanning electron microscopy evaluation.

BACKGROUND: The medos-HIA ventricular support system was designed as an artificial heart assist device for intractable heart failure to act as a bridge for transplantation or recovery. The aim of this study is to report on the first clinical application of the system and to evaluate the thrombotic risk with the use of the biomarker prothrombin fragment F1 + 2 and scanning electron microscopy of the blood contacting surface. METHODS AND RESULTS: This device worked without any failure for 462 hours, and a sufficient output of 5.2 to 6 L was observed. No activation of the procoagulatory system occurred during pumping until the occurrence of the septicemia. Preseptic F1 + 2 levels were normal, at about 1 nmol/L. The blood contacting surfaces of the pump and the polyurethane valves were examined by means of scanning electron microscopy, and the surfaces were found to have smooth fibrin layers with no thrombogenic deposits. This fibrin layer is considered to prevent thrombotic adhesions, thereby minimizing the risk of thromboembolic complications. Post mortem examinations after pneumonia with septic shock showed no thrombus formation in this support system and around the inserted cannulas. CONCLUSIONS: The low risk for thromboembolic complications, no measurable activation of the coagulation system, and the excellent surface characteristics encourage further use of this inexpensive working device.

Fibrinolysis-adjusted perioperative low-dose aprotinin reduces blood loss in bypass operations.

BACKGROUND: Postoperative bleeding still remains a serious problem in bypass surgery. This study evaluated fibrinolysis and perioperative low-dose antifibrinolytic regimens adjusted to the time course of fibrinolysis. METHODS: In a prospective, randomized study of 42 patients undergoing bypass grafting, patients received low-dose aprotinin (group A; n = 14) or low-dose tranexamic acid (group TA; n = 14) intraoperatively and postoperatively, respectively, with no antifibrinolytics for comparison (group C; n = 14). Parameters of procoagulation, fibrinolysis, and activated factor VII were measured preoperatively, intraoperatively, and postoperatively. Blood loss was determined up to 24 hours. RESULTS: The level of thrombin-antithrombin III complex was significantly decreased postoperatively in the treatment groups (group A and TA versus C: 25 +/- 14 and 19 +/- 10 microg/L, respectively, versus 40 +/- 21 microg/L; p < 0.05). Levels of plasmin-antiplasmin complexes were significantly decreased postoperatively in group A (607 +/- 231 microg/L) versus group C (825 +/- 225 microg/L) (p < 0.05) but were increased in group TA (1,145 +/- 394 microg/L) versus group C (p < 0.05). At all times intraoperatively and postoperatively, levels of D-dimers were significantly decreased in group A and group TA versus control (p < 0.001), indicating that fibrinolysis persists after the operation. Intraoperatively, the factor VIIa level decreased significantly in group A (20 +/- 8 mU/mL) versus group C (31 +/- 15 mU/mL) (p < 0.05), but not in group TA (32 +/- 15 mU/mL). Blood loss was significantly lower in group A (135 +/- 37 mL) and group TA (155 +/- 71 mL) versus group C (354 +/- 170 mL) (p < 0.001). CONCLUSIONS: This low-dose aprotinin regimen adjusted to perioperative fibrinolysis reduces blood loss significantly in coronary bypass grafting. For further progress in this subject, clinical investigations of individual fibrinolysis-adjusted antifibrinolytic treatment seems warranted.

Antiphospholipid antibodies in children without and in adults with and without thrombophilia.

Antiphospholipid antibodies (APAs) are considered risk factors in patients with thromboembolic diseases. Although the incidence of such acquired coagulation disturbances in adults are well described, only few data exist for children. Therefore, in a first step to collect new data we analyzed the presence of different APAs in 202 consecutive children and compared them with two groups of adults. The children screened for APA were exclusively those who did not have any thromboembolic complications or a tendency for thrombophilia due to other underlying diseases such as systemic lupus or malignancy in their past or present medical history. Consecutive blood samples were evaluated from routine laboratory specimens. The two groups of adults comprised 200 patients after deep vein thrombosis and 200 patients without thromboembolic events that served as controls. Four lupus anticoagulant (LA) screening tests were determined: the dilute Russell's viper venom test; a lupus anticoagulant-sensitive activated partial thromboplastin time reagent; a second lupus-sensitive activated partial thromboplastin time; and the Kaolin clotting time. Furthermore, three different antiphospholipid antibodies ELISA assays against cardiolipin (ACA), beta2-glycoprotein I, and phosphatidyl-serine, were determined. The children had a much higher prevalence for LA than did the adults. On the other hand, their values for ACA were significantly lower than in adults with a history of thromboembolism. Findings in children were similar to the normal adult group. This has to be taken into account when evaluating children with thromboembolic diseases.

Asymptomatic circulating cerebral emboli and cerebral blood flow velocity under aspirin and ticlopidine in patients with cerebrovascular disease.

Aspirin and ticlopidine are two commonly used drugs in the prevention of cerebral embolic ischemic events. No direct comparisons in a cross-over design of the effects of ticlopidine and aspirin on asymptomatic circulating cerebral microemboli are available. We investigated 53 patients with cerebrovascular disease. Twenty-six patients were dosed for 2 weeks, 300 mg aspirin once daily and then for 2 weeks, 250 mg ticlopidine twice daily. In 27 other patients the scheme was reversed. Transcranial Doppler monitoring (both middle cerebral arteries simultaneously for 1 h were performed at the end of the two weeks. The signal was recorded on digitalised audio tapes and analyzed blinded off-line. The number of embolic signals per hour and vessel was 15.7 under aspirin and 11.7 under ticlopidine (difference not significant). The correlation between the number of emboli under the two medications was high. The highest number of embolic signals was found in high grade carotid stenosis. In patients with a low number of embolic signals, reproducibility was low. A minimum of 7 embolic signals in one treatment group is required for further therapeutic drug trials to allow reasonable comparisons. This study may help to plan further therapeutic trials using emboli detection.

Variability in occurrence of embolic signals in long term transcranial Doppler recordings.

Albeit still unproven, it is supposed that the presence and number of asymptomatic circulating cerebral microemboli detected by transcranial Doppler ultrasound (TCD) may be an indicator of stroke risk. Little research has been done to assess the reproducibility of these data and the required time for recording. We examined one middle cerebral artery in 7 subjects with carotid, aortic or cardiac embolic source for 24 h by TCD. Analysis for embolic signals was done off line completely blinded to the diagnosis and the time of the day during the recording. Embolic signals were found in all 7 subjects varying from 0 per h to 13 per h. Embolic signals occurred throughout the day with a nonsignificant tendency towards higher values in the early morning hours. Half an hour recording would not have been suitable to rule out or to confirm the presence of embolic signals as there were too many gaps between embolic signals of more than 1/2 h. One hour is the required minimum. Concerning the number of embolic signals, even a recording of four hours yielded variabilities of 0.25 and 8 embolic signals per hour in the same person. We recommend to perform follow-up studies the same time of the day. In patients with a low number of embolic signals longer recordings or a lower detection threshold with a higher number of detected embolic signals are necessary to compare frequencies of embolic signals.

Prothrombin fragments F1+2, thrombin-antithrombin III complexes, fibrin monomers and fibrinogen in patients with coronary atherosclerosis.

We determined the plasma levels of prothrombin fragment F1+2, thrombin-antithrombin III complexes (TAT), fibrin monomers (FM), D-dimers (DD) and fibrinogen in 57 patients with angiographically verified graded coronary artery disease (CAD) free of concomitant peripheral atherosclerosis, cerebrovascular disease or diabetes mellitus and a group of 21 apparently healthy controls. Blood was collected from the antecubital vein through atraumatic venipuncture prior to the angiographic procedure. Plasma levels of hemostatic markers were related to the presence and graded severity of CAD. The levels of prothrombin fragment F1+2 (1.74+/-0.11 vs. 1.0+/-0.07 nmol/l, P<0.001), FM (41.6+/-5.5 vs. 7.42+/-3.05 nmol/l, P<0.001), TAT (15.6+/-2.7 vs. 2.96+/-0.32 microg/l, P<0.001) and fibrinogen (3.64+/-1.3 vs. 3.08+/-0.33 g/l, P<0.01) were significantly higher in patients with CAD compared to controls, while there was no difference regarding the fibrinolytic system represented by DD (441.6+/-58.9 vs. 337.4+/-42.05 microg/l, n.s.). Within the CAD group, patients with extensive coronary atherosclerosis (> or =2 vessel disease) had significantly higher values for prothrombin fragment F1+2 (1.89 vs. 1.57 nmol/l, P = 0.04), FM (50.7 vs. 29.8 nmol/l, P = 0.03), and a trend to significance was noted for fibrinogen (3.9 vs. 3.3 g/l, P = 0.07) suggesting that blood coagulability was related to the severity of the disease and that hemostatic markers of thrombin activity represent a useful tool to identify patients with a latent hypercoagulable state with a higher susceptibility to sustain coronary thrombosis.

Course of molecular hemostatic markers during and after different surgical procedures.

STUDY OBJECTIVE: To establish the most vulnerable time of thrombi formation with regard to the plasmatic (noncellular) part of the coagulatory and fibrinolytic systems. DESIGN: Nonrandomized observational study. SETTING: A surgical and an orthopedic unit and the central laboratory of a university hospital. PATIENTS: 61 consenting ASA physical status I and II inpatients undergoing four different types of surgery: total hip replacement (THR): 16 patients; hemicolectomy: 15 patients; endoscopic cholecystectomy: 15 patients; subtotal thyroid resection: 15 patients. INTERVENTIONS: The time course of 11 procoagulatory and fibrinolytic parameters was examined during the different types of surgery. Blood samples were drawn on the day before surgery, directly before the induction of general anesthesia, 1 to 2 hours postoperatively, and on the mornings of postoperative days 1, 2, 3, 4, and 5. MEASUREMENTS AND MAIN RESULTS: The coagulation samples were centrifuged within 1 hour of collection at 2,300 g for 15 minutes at 4 degrees C. Hemoglobin, hematocrit, platelets, fibrinogen, prothrombin time, activated partial thromboplastin time, thrombin time, antithrombin III, and protein C were determined immediately on laboratory arrival of the samples. The samples were aliquoted at -70 degrees C. They were thawed within 2 weeks and prepared for the following assays: thrombin-antithrombin III complexes (TAT-complexes), D-dimers, and plasminogen activator inhibitor type 1. Maximum activation of coagulation is not reached until 2 hours postoperatively and slowly decreases until normal values are reached around the fifth postoperative day. Parameters displaying the greatest changes are TAT-complexes and D-dimers. The type of surgery with the most pronounced changes was total hip replacement, followed by hemicolectomy, cholecystectomy, and subtotal thyroid resection. CONCLUSION: The total hip replacement and hemicolectomy groups show similar and strong activation of the procoagulatory and fibrinolytic systems. Much less pronounced are the changes during endoscopic cholecystectomy and subtotal thyroid resection. Maximum activation occurs 1 to 2 hours postoperatively.

Resistance to activated protein C due to factor V Leiden mutation: high prevalence in patients with post-thrombotic leg ulcers.

BACKGROUND: Activated protein C (APC) resistance is the most frequently diagnosed heritable thrombophilic defect predisposing to thrombosis. OBJECTIVES: To determine the prevalence of APC resistance due to factor V Leiden mutation in patients with leg ulcers. METHODS: Within a 2-year-period 100 consecutive patients with leg ulcers were examined for factor V Leiden mutation. RESULTS: APC resistance due to factor V Leiden mutation was detected in 19 of 53 patients (36%) with post-thrombotic leg ulcers and in three of 47 patients (6%) with ulcers caused by primary varicosis. In a healthy control group APC resistance due to factor V Leiden mutation was found in five of 96 (5%) volunteers. CONCLUSIONS: In view of this high prevalence of APC resistance of 36%, which has never previously been reported, patients with post-thrombotic leg ulcers should be investigated for APC resistance.

[Increased prevalence of APC-resistance (factor V Leiden mutation) in patients with postthrombotic syndrome]. / Hohe Prävalenz der APC-Resistenz (Faktor-V-Leiden-Mutation) bei Patienten mit postthrombotischem Syndrom.

BACKGROUND AND OBJECTIVE: APC resistance (Factor V Leiden mutation) is the most often diagnosed hereditary thrombolytic defect. Data about the prevalence in patients with leg ulcers, especially postthrombosis, are limited of this defect. PATIENTS/METHODS: APC resistance was determined in 100 patients with venous leg ulcers. 53 patients had ulcers caused by postthrombotic syndrome and 47 patients ulcers associated with primary varicosities. A control group of 96 healthy volunteers was also studied. RESULTS: 19 of 53 patients (36%) with postthrombotic ulcers and 3 of 47 patients (6%) with varicosity-related ulcers had APC resistance. In the control group APC resistance was detected in 5 of 96 volunteers (5%). CONCLUSIONS: APC resistance should be considered as a risk factor for the development of venous leg ulcers.

Temporary vena cava filters and ultrahigh streptokinase thrombolysis therapy: a clinical study.

PURPOSE: To assess the efficacy of temporary vena cava filters in patients undergoing ultrahigh-dose streptokinase thrombolysis for iliocaval thrombosis and to determine therapy success and filter and therapy complications. METHODS: Forty-five patients were studied regarding extension and characteristics of thrombosis, duration, success, and complications of thrombolysis therapy, filter type, access route, pulmonary embolisms, and filter complications. RESULTS: Complete recanalization was achieved in 57% of cases. Filters were inserted predominantly via a transbrachial route. One fatal pulmonary embolism (2%) occurred 1 day after starting thrombolysis. No other pulmonary embolism was noted. Other complications were induced by thrombolysis alone (n = 12), thrombolysis and filter (n = 9), and filter alone (n = 11). CONCLUSION: Fatal pulmonary embolisms as a complication of ultrahigh-dose treatment of pelvic or caval thrombosis can not safely be prevented by the temporary vena cava filters currently available. Filter design needs to be improved.

Hemostaseologic and hematologic parameters with aspirin and ticlopidine treatment in patients with cerebrovascular disease: a cross-over study.

No direct comparisons of the effects of ticlopidine and aspirin on platelet aggregability, clotting parameters, and blood count are available in a cross-over study design in humans. We investigated 45 patients with cerebrovascular disease. Twenty-one patients received 300 mg aspirin once daily for 2 weeks and then for 2 more weeks received 250 mg ticlopidine twice daily. In 24 other patients, the scheme was reversed. ADP-induced aggregability was lower during ticlopidine treatment; epinephrine- and collagen-induced aggregabilities were lower with aspirin treatment. Platelet counts were higher during ticlopidine than during aspirin treatment (199.6/ nl with aspirin, 213.0/nl with ticlop dine, p = 0.008), probably reflecting less platelet activation and degradation and a longer platelet survival time induced by ticlopidine treatment.

[Successful partial lysis of a 4-level-thrombosis by rt-PA - case report]. / Erfolgreiche partielle Lyse einer 4-Etagen-Thrombose mit rt-PA - Fallbericht.

Thromboembolism of the vena cava, the venae iliaca communis, externa, femoralis, poplitea, and the fibular vein group of the left lower limb was diagnosed in a 13 year old girl. Several thrombogenic risk factors (APC-resistence, homocystinuria, contraception, smoking) were identified. Due to painful symptoms and for prevention of postthrombotic syndrome continuous systemic thrombolysis with rt-PA (0,5 mg/kg/d), in addition to heparine, was performed for 6 days. Diagnostic imaging at the end of therapy demonstrated complete and partial recanalization of the vena cava inferior, venae iliaca communis and externa. The distal veins of the leg remained occluded. After catheterization of the internal jugular vein and placement of a cava filter only mild pulmonary embolism occurred during systemic thrombolysis. No further complications were observed. All in all, therapy was tolerated well. Systemic thrombolysis with rt-PA in children and adolescents, although not established for regular treatment, is an effective therapeutic option in severe venous thrombosis.

Plasmids of human strains of Yersinia enterocolitica: molecular relatedness and possible importance for pathogenesis.

One-hundred fifteen strain of Yersinia enterocolitica were examined for plasmids and plasmid-mediated pathogenic properties. Human strains of serotypes O:3 and O:9 harbored plasmids of 46 and 44 megadaltons, respectively, with 90% homology of DNA sequences. The plasmid-mediated properties were calcium dependence, survival in human serum, conjunctivitis provocation in guinea pigs, and O agglutinogens. One strains of serotype O:8 harbored a 42-megadalton plasmid with 75% sequence homology with plasmids of serotypes O:3 and O:9. An additional plasmid-mediated property was lethality for white mice. Filter hybridization of restriction endonuclease-digested plasmid DNA indicated that a 5.6-megadalton fragment of the plasmid of serotype O:8 had virtually no sequence homology with plasmid DNA of serotypes O:3 and O:9 and therefore may be associated with the lethal factor for mice.

Evaluation of two new integrated adapters for blood drawing in closed blood bag systems: influence on different molecular coagulation markers.

We compared a conventional blood donation bag system (A) with two newly developed ones (B, C) with integrated Y-shaped adapters. The new systems facilitate the withdrawal of blood samples in a closed system under aseptic conditions. The purpose of the study was to determine whether disturbances during blood donation in the different tubings influence the quality of the donated plasma due to activation processes of the coagulation system. In all bag samples from 34 probands for each system, we found higher levels of the global tests (aPTT, TT) compared to intraindividual controls. This was due to a greater amount of anticoagulant in the bag samples. An increase of procoagulant activity was demonstrated for bags A and C. Concerning the fibrinolytic system, values were reduced in all three systems compared to controls. In summary, the quality of the plasma in the three different bag devices was comparable to controls concerning factor activities measured as global tests. The activation of the coagulation system was only slightly higher in the new system B and C than in the conventional one (A). Therefore, the new closed systems are suitable for blood donation and reveal a high coagulation quality of the plasma.

Bigated transcranial Doppler for the detection of clinically silent circulating emboli in normal persons and patients with prosthetic cardiac valves.

BACKGROUND AND PURPOSE: Detection of clinically silent circulating microemboli by transcranial Doppler sonography is now being widely investigated in the hope of identifying patients at increased risk for stroke. Automatic detection by bigated Doppler, which uses sampling from two different depths in the artery under study and considers the motion of the embolus, may help to define "periods of interest" that can be evaluated off-line. METHODS: In 12 normal volunteers and 10 patients with prosthetic aortic valves, we performed 1-hour recordings from one middle cerebral artery. In the normal subjects, we produced additional artifacts to use them as false-positives. Detection of microemboli was done off-line from digital audiotapes by an experienced blinded investigator (used as the gold standard) and was compared with on-line detection using specially designed software. RESULTS: With the setting used, 91.5% of all recorded artifacts could correctly be identified as such with the software. Embolic signals were detected by the software with a specificity of 59.9% and a sensitivity of 74.3%. CONCLUSIONS: Bigated Doppler adds a new dimension to the definition and detection of microembolic signals. It constitutes an important step forward toward automatic screening of stroke-prone patients. Assessing on-line periods of interest during the recording and going over the recorded data again off-line helps to save time for the discrimination of embolic signals from both the normal Doppler spectrum background and artifacts.

[Comparative studies on the rotavirus syndrome following infection with human rotavirus of the subgroup 1 or 2]. / Vergleichende Untersuchungen über das Rotavirussyndrom nach Infektion mit Humanrotavirus der Subgruppe 1 oder 2.

Human rotavirus infection which heals spontaneously causes gastroenteritis in newborns and infants. 150 pediatric patients infected with rotavirus as diagnosed by ELISA suffered from diarrhoea for an average of 3 days, from vomiting for 1 day, and/or fever for 1-2 days. Nowadays this disease is known as "human rotavirus syndrome". Human rotaviruses can be divided into at least 4 serotype antigens and some 3 further subgroup antigens. The serotype antigens are only detectable biologically (e.g. by neutralization test), whereas the subgroup antigens can be demonstrated as specific proteins by a solid-phase test (ELISA). This study investigated whether an infection with human rotavirus of subgroup 1 (21%) or 2 (77%), which occur most frequently causes different degrees of severity of the rotavirus syndrome. The clinical comparison of 27 (subgroup 1) and 98 (subgroup 2) infected patients shows that the disease is not significantly different. This means that the detection of subgroup antigens 1 and 2 does not result in a different prognosis for the disease. The diagnosis of subgroup antigens after human rotavirus infection is therefore clinically important only for the detection of nosocomial infections, especially due to the rarely occurring subgroups 1 and 3.