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Biomedical subjects

W Korte

Publications and source records attributed to W Korte.

At least 37 records · Page 2Linked to original sources
PubMed1998

DNA analysis in the case of Kaspar Hauser.

In 1828 a mysterious young man appeared in Nürnberg, Germany, who was barely able to speak or walk but could write down his name, Kaspar Hauser. He quickly became the centre of social interest but also the victim of intrigue. His appearance, his origin and assassination in 1833 were, and still are, the source of much debate. The most widely accepted theory postulates that Kaspar Hauser was the son of Grand Duke Carl von Baden and his wife Stephanie de Beauharnais, an adopted daughter of Napoleon Bonaparte. To check this theory, DNA analysis was performed on the clothes most likely worn by Kaspar Hauser when he was stabbed on December 14th, 1833. A suitable bloodstain from the underpants was divided and analysed independently by the Institute of Legal Medicine, University of Munich (ILM) and the Forensic Science Service Laboratory, Birmingham (FSS). Mitochondrial DNA (mtDNA) was sequenced from the bloodstain and from blood samples obtained from two living maternal relatives of Stephanie de Beauharnais. The sequence from the bloodstained clothing differed from the sequence found in both reference blood samples at seven confirmed positions. This proves that the bloodstain does not originate from a son of Stephanie de Beauharnais. Thus, it is becoming clear that Kaspar Hauser was not the Prince of Baden.

Base Sequence↗
PubMed1998

Preoperative values of molecular coagulation markers identify patients at low risk for intraoperative haemostatic disorders and excessive blood loss.

Conventional laboratory investigations of haemostasis like prothrombin time and activated partial thromboplastin time are not useful in predicting and managing intra-operative bleeding complications. In order to establish a possible "perioperative reference range" for thrombin generation prothrombin fragment F1+2 (F1+2) and fibrin degradation (D-dimer) markers, we measured F1+2 and D-dimer concentrations before surgery (but after induction of anaesthesia), 30 minutes into surgery, 10 minutes after the event expected to induce the maximal activation of the haemostatic systems, 90 minutes after surgery and on postoperative days 1 and 2 in 226 consecutive patients. Samples were collected from arterial lines. Twenty patients developed a clinically defined, intraoperative disorder of haemostasis, 206 did not. Patients with an intraoperative disorder of haemostasis had significantly higher preoperative F1+2 and D-dimer concentrations. Preoperative values for F1+2 and D-dimer concentrations above the 75th percentile of patients without an intraoperative disorder of haemostasis indicated a 2.70 to 2.88 fold risk of developing an intraoperative disorder of haemostasis (odds ratios were 3.04, 3.12 and 3.29 for D-dimer, ELISA, F1+2, and D-dimer latex tests, respectively with 95% confidence intervals from 1.20 to 8.46) with negative predictive values of 94%, but positive predictive values of only 16% to 26%. These data suggest that preoperative determination of molecular markers might be helpful in identifying a group of patients at high risk for intraoperative disorder of haemostasis by exclusion of low risk patients. Validation of such an approach requires a prospective trial.

Adult↗
PubMed1997

Plasma hypercoagulability in haemodialysis patients: impact of dialysis and anticoagulation.

BACKGROUND: Thrombotic complications are common in patients with endstage renal disease and contribute substantially to the morbidity and mortality in this population. The aim of the present study was to: i) determine the prevalence and the extent of hypercoagulability in patients undergoing dialysis treatment by measuring parameters that directly reflect thrombin concentrations; ii) assess changes in coagulation status during haemodialysis (HD); iii) quantify the relative impact of heparin, dialysis and their combined effects on coagulation status and iv) detect factors that modify coagulation haemostasis in dialysis patients. METHODS: A total of 39 patients (HD: n = 29, CAPD: n = 10) was analysed for procoagulatory and fibrinolytic activity determined by measurements of partial thromboplastin time, prothrombin fragments F1 + 2, thrombin-antithrombin complexes and D-dimer concentrations. HD patients were investigated prior to and during dialysis. A subgroup of patients was infused heparin alone without dialysis or was dialysed without heparin administration. Furthermore, subgroup and correlation analyses were performed for the type of dialysis (HD vs CAPD), dialyzer and shunt, Kt/V, underlying disease and treatment with recombinant erythropoietin (rhEPO). RESULTS: Baseline levels of all parameters-procoagulatory and fibrinolytic--were substantially elevated in all patients, but to a higher degree among those on CAPD. Moreover, haemodialysis treatment increased procoagulatory markers even further, suggesting stimulated coagulation and/or insufficient anticoagulation during dialysis. However, after 3 h of dialysis thrombin concentrations, determined by quantification of prothrombin fragments, were inversely correlated with Kt/V. Selective heparin infusion diminished procoagulatory activity only slightly and incompletely, whereas HD without heparin resulted in excess thrombin accumulation. Finally, subgroup analyses revealed more pronounced thrombin formation among patients treated with polysulfon dialyzers, whereas erythropoietin dosage was positively related with lower procoagulatory activity. CONCLUSION: A majority of patients on dialysis are in a hypercoagulable state, which is further aggravated by the haemodialysis procedure itself and may not be sufficiently controlled with current anticoagulation regimens. Intensified heparin treatment and the use of rhEPO are likely to improve coagulation haemostasis, whereas the type of dialyzer should be considered as a relevant procoagulatory factor.

Adult↗
PubMed1997

Veno-occlusive disease of the liver after bone marrow transplantation: is hypercoagulability really part of the problem?

Patients undergoing bone marrow transplantation (BMT) experience changes in various proteins with important functions in the coagulation and fibrinolysis system. Veno-occlusive disease (VOD) of the liver is a leading cause of non-relapse mortality after BMT. Because of the concurrent occurrence of changes in the coagulation and fibrinolysis system and development of VOD, most authors assume a causative relationship between these two observations, but the results leading to this conclusion are not unequivocal. Data currently available do not allow the conclusion that coagulation activation and local excess fibrin generation are key factors in the pathogenesis of VOD. One approach to deciding whether there is, in fact, excessive local fibrin generation during the development of VOD might be the monitoring of high risk patients with tools that enable differentiation of local and systemic hypercoagulability (e.g. anti-D-dimer immunoscintigraphy). Screening of patients at risk for VOD with special coagulation parameters pretransplant does not seem appropriate at present. However, markedly increased plasminogen activator inhibitor-1 levels (from baseline) seem to be appropriate tool to confirm the diagnosis of VOD when clinical suspicion exists. More research is needed in order to advance our understanding of the disease and to improve outcomes in both the prophylaxis and treatment of VOD.

Blood Coagulation↗
PubMed1996

Day-to-day titration to initiate transdermal fentanyl in patients with cancer pain: short- and long-term experiences in a prospective study of 39 patients.

Initial dose finding in patients with cancer pain who are started on TTS fentanyl (Duragesic, TTS-F) is often unsatisfactory with currently recommended doses and intervals. Acknowledging that studies reveal a "psuedo steady state" 15 to 20 hr after application of TTS-F, we prospectively investigated an increased initial dose and day-to-day titration of TTS-F in 39 (evaluable) patients with uncontrolled cancer pain. Significant pain reduction (P = 0.001) was seen after 24 hr, and satisfactory analgesia was achieved within 48 h and maintained for the rest of the study. Significant increases in TTS-F were necessary during weeks 1 through 4 to maintain pain control. Forty-nine percent of the patients needed one or more early dose increases. Only one patient had side effects partially due to the specific properties of the TTS. Other side effects seemed to be less common compared with usual morphine treatment. TTS-F can be titrated effectively and safely on a day-to-day basis with an increased initial dose and adequate patient monitoring, thus avoiding more complicated approaches. TTS-F seemed to induce less constipation than might be expected.

Administration, Cutaneous↗
PubMed1995

[Is the assessment of prothrombin fragment F1+2 for monitoring of heparin therapy in patients with deep vein thrombosis useful?].

Prothrombin fragments (F1+2) can be used to monitor oral anticoagulation; their generation is also suppressed by heparin. We studied the course of F1+2, aPTT, heparin doses administered and heparin concentrations, as well as prothrombin time, during the first 7 days of heparin therapy (target aPTT 70 s) and overlapping oral anticoagulation (target INR 2-3) in 26 patients routinely treated for deep venous thrombosis (deep venous thrombosis +/- pulmonary embolism, 23 patients) or pulmonary embolism with a history of recurring deep venous thrombosis (3 patients). Although we found significant suppression of F1+2 between all pre- and post-treatment values, a transient, significant increase was seen on days 2-4. The amount of heparin given was stable from day 1-5; the fact of a transient increase in F1+2 might thus indicate that heparin doses routinely used are too low for the treatment of hypercoagulability in deep venous thrombosis in patients. We also found a decrease in heparin concentration on day 2, which may be explicable by changed pharmacokinetics of heparin in individuals with deep venous thrombosis. In conclusion, F1+2 may be useful for monitoring heparin treatment and oral anticoagulation in deep venous thrombosis patients from a laboratory point of view. However, larger studies are necessary to confirm these results. It remains to be clarified whether monitoring of anticoagulation by molecular markers might improve therapy of deep venous thrombosis. Such studies are in progress.

Heparin↗
PubMed1994

Increased prothrombin activation in a patient with congenital afibrinogenemia is reversible by fibrinogen substitution.

We describe a patient with congenital afibrinogenemia who showed elevated prothrombin activation fragments (F1 + 2) indicating increased thrombin formation. This finding was unexpected since it has hitherto been thought that patients with congenital hypo- or afibrinogenemia have no evidence of increased utilization or accelerated consumption of coagulation factors. No other possible reasons for the elevation of F 1 + 2 were found. Upon fibrinogen substitution F1 + 2 decreased and were again increasing when fibrinogen concentration in plasma fell to very low levels. These findings raise the question of whether increased thrombin formation should be understood as a compensatory mechanism in congenital afibrinogenemia.

Adolescent↗
PubMed1994

Transdermal fentanyl in uncontrolled cancer pain: titration on a day-to-day basis as a procedure for safe and effective dose finding--a pilot study in 20 patients.

All communications on the use of transdermal fentanyl as well as the recommendations of the manufacturer include the direction that patients should be titrated with a short-acting narcotic to control their cancer pain before they are converted to a fentanyl transdermal therapeutic system (TTS). We investigated the possibility of avoiding this titration phase by immediate fentanyl TTS therapy in patients with uncontrolled cancer pain. Dose finding was performed by direct titration of fentanyl TTS according to clinical necessity on a day-to-day basis. Morphine solution for rescue medication was available. Short-term follow-up was 28 days, and 20 patients (10 in- and 10 outpatients) were evaluable. On the average, sufficient pain control [visual analogue scale (VAS) < 35 mm] was reached within 48 h of the start of fentanyl TTS. The mean VAS values before and during fentanyl TTS therapy were 53 mm (before), 27 mm (week 1), 21 mm (week 2), 18 mm (week 3) and 21 mm (week 4). There were statistically significant lower VAS values at all follow-up times compared to pretreatment values (e.g. pretreatment to day 1: P = 0.019; pretreatment to day 28: P = 0.002; Wilcoxon sign-rank test). The mean fentanyl TTS doses were 70 micrograms/h (week 1), 98 micrograms/h (week 2), 107 micrograms/h (week 3) and 116 micrograms/h (week 4). The differences of mean fentanyl TTS does were significantly different between days 1 and 7 (P < 0.001) and between days 8 and 14 (P = 0.006), but not between days 15 and 21 and days 22 and 28.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1994

Coincidence of familial platelet glycoprotein Ib/IX deficiency (Bernard-Soulier syndrome), idiopathic autoantibody against platelet glycoprotein Ib/IX, familial appearance of antiphospholipid antibodies, and familial factor XII deficiency.

The case of an 8-year-old boy with apparently homozygous Bernard-Soulier syndrome (platelet GP Ib/IX complex deficiency) and a transient idiopathic autoantibody against GP Ib/IX is described. He had been diagnosed with chronic autoimmune thrombocytopenia (due to the detection of antiplatelet autoantibodies) before Bernard-Soulier syndrome was proven. Both parents and his brother displayed intermediate deficiency of GP Ib/IX, thus indicating a heterozygote state for Bernard-Soulier syndrome. Alloimmunization as an explanation for the appearance of GP Ib/IX antiplatelet antibodies in the propositus can be excluded. A so-called pseudo Bernard-Soulier syndrome due to selective antibodies was also excluded. Flow cytometric analysis revealed residual expression of 2% GP Ib and 13% GP IX on the propositus' platelets. It seems that the propositus showed an idiopathic autoantibody against a platelet glycoprotein in which he is genetically deficient (but which is not completely lacking). Thus, in patients with untypical behavior upon therapy of "autoimmune thrombocytopenia", other differential diagnoses should also be considered even if antiplatelet antibodies are detected. In addition, all family members displayed elevated concentrations of antiphospholipid antibodies. These findings raise the question of a genetic predisposition for the development of autoantibodies. Moreover, an F. XII deficiency was found in all family members except the mother.

Adult↗
PubMed1994

Childhood stroke at three years of age with transient protein C deficiency, familial antiphospholipid antibodies and F. XII deficiency--a family study.

The unusual case of a boy with a stroke occurring at three years of age, transient reduction in protein C activity and high concentrations of antiphospholipid antibodies (APA) is described. APA or Lupus Anticoagulant (LA) were found in 7 of 11 relatives studied out of three different generations. In addition, antigenic Factor (F) XII deficiencies or borderline values were found in the propositus and 2 relatives. Evidence for F. XII inhibitors was found in the propositus, one of his brothers and both of his parents. Whether F. XII inhibitors in patients with APA and/or LA are pathophysiologically relevant in vivo or if they are only an in vitro phenomenon remains to be elucidated. It is reasonable to believe that the main laboratory pathology (APA and/or LA activity) in antiphospholipid syndrome is related to the clinical picture of a hypercoagulable state. There is evidence from the literature that deficiency or inhibition of F. XII might contribute to a prothrombotic state through impairment of the fibrinolytic system. There is also evidence that APA are able to reduce protein C activation. From a clinical point of view, it seems that hypercoagulability in our patient was controlled by low-dose aspirin therapy (75 mg/d). In conclusion, this case seems to support the idea of a genetic predisposition for the development of APA and/or LA. The related disturbances of the coagulatory, anticoagulatory and fibrinolytic systems might contribute in different ways to the prothrombotic state seen in patients with "antiphospholipid syndrome", eventually resulting in possible venous thrombosis or arterial thrombosis with corresponding ischaemic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antiphospholipid↗
PubMed1994

[Epidemiology of infectious diseases--analysis of an increase of infectious hepatitis in Hamburg].

In Hamburg, the incidence of reported cases of infectious hepatitis more than doubled from 1990 to 1991. The increase refers to hepatitis A, B and other forms of hepatitis. The seven public health offices and the local ministry for health, works and social affairs in Hamburg have analysed the development in a computer-based retrospective study comparing the 1990 and 1991 data. The predominantly affected age group of hepatitis A shifted from childhood to young adulthood. The importance of travelling to acquire hepatitis A was less than expected. In all forms of hepatitis the large number of IV-drug users and prisoners was striking.

Adolescent↗
PubMed1993

[Kasabach-Merritt syndrome. Intraoperative heparin therapy with follow-up combination therapy of heparin and ticlopidine for the control of intravascular coagulation].

A 39-year-old woman with Kasabach-Merritt syndrome (cavernous vascular malformations with disseminated intravascular coagulation) sustained a displaced fracture of the femoral shaft. Despite pronounced hypofibrinogenemia (< 0.1 g/l) there was no significant bleeding. The concentration of D dimer was raised to > 32 < 64 mg/l and that of prothrombin fragments F1 and F2 to > 10 nmol/l. The platelet count was 102,000/microliters and other coagulation parameters were normal or only slightly abnormal. The consumption coagulopathy was successfully controlled by continuous intravenous infusion of heparin (17,000 I.U./d) without need for clotting factor replacement, and was subsequently stabilized by combined treatment with low molecular weight heparin (5,000 I.U./d s.c.) and ticlopidine (250 mg twice daily by mouth). Oral therapy with acetylsalicylic acid alone or in combination with ticlopidine proved insufficient, being rapidly followed by a renewed fall in fibrinogen level and platelet count. The findings suggest that fibrin formation in the abnormal vascular territories was the principal pathogenetic factor in this case.

Abdominal Neoplasms↗
PubMed1990

Federal Republic of Germany: perspectives in school health.

In the Federal Republic of Germany, responsibilities for health and education are held by the 11 German states. Particularly in the health system, a number of tasks are delegated to private organizations under governmental control. In this review, general characteristics of both the public health and education systems are delineated. An overview of school health programs, including instruction, health services, environment, and school-community relations, and school-based research, also are presented.

Community Participation↗